[{"id":"herpes-simplex-and-zoster-antiviral-prophylaxis","kind":"protocol","name":"Aciclovir prophylaxis against herpes simplex and shingles during cancer treatment","aka":["acyclovir prophylaxis","aciclovir prophylaxis","valaciclovir prophylaxis","HSV prophylaxis","VZV prophylaxis","shingles prevention bortezomib","herpes zoster prophylaxis"],"tldr":"The viruses behind cold sores and shingles stay in the body for life and can flare when cancer treatment weakens the immune system. People having intensive leukaemia treatment, a stem cell transplant, or myeloma drugs such as bortezomib are usually given an antiviral tablet, aciclovir or valaciclovir, to prevent this. Most people having ordinary chemotherapy for a solid tumour do not need it.","summary":"ASCO/IDSA (2018) recommend nucleoside analogue prophylaxis such as aciclovir for HSV-seropositive patients having allogeneic stem cell transplant or leukaemia induction. AGIHO (2022, adults) recommends oral aciclovir 400 mg twice or four times daily against oral HSV disease (AIIr), valaciclovir as an alternative (BI), and intravenous aciclovir 250 mg/m2 three times daily if oral medication is not tolerated (AIIr). Against VZV, oral aciclovir from 400 mg once daily to 400 mg three times daily (AII). Indications: acute leukaemia on intensive chemotherapy, from induction through neutropenia (BIIr); ALL throughout treatment (BI); acute promyelocytic leukaemia on arsenic trioxide, during treatment and 6 months after (BIIr); any proteasome inhibitor-based myeloma regimen, bortezomib strongly (AII); idelalisib (BIII); selected lymphoma and CLL by individual risk. Not generally indicated for VZV in solid tumours (DIII), where 5-year cumulative zoster incidence is about 5%; consider it with long-term corticosteroids (CIIu), continued up to 6 months after steroids stop. Serology is optional because about 90% of adults are HSV-1 and VZV seropositive, so universal prophylaxis is equally appropriate. Recombinant (non-live) zoster vaccine is recommended, with aciclovir still added in high-risk groups until comparative data exist; live zoster vaccine is contraindicated. All three nucleoside analogues need dose adjustment in renal impairment. Brivudin is contraindicated with fluoropyrimidines.","asOf":"2026-11-11","links":[],"tags":["protocol","antiviral-prophylaxis","infection-prevention"],"related":["lymphoma-tx-pjp-and-infection-prophylaxis"],"cancers":["aml","all-leukemia","multiple-myeloma","cll"],"sections":["supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant"],"targets":[],"drugs":["bortezomib","idelalisib"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["lymphoma-tx-pjp-and-infection-prophylaxis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer treatments make cold sores and shingles more likely. For those treatments, your team may give you a daily antiviral tablet to stop them coming back.","domain":"infection-prevention","setting":{"who":["doctor","pharmacist","nurse"],"where":["outpatient-clinic","ward","chemotherapy-day-unit"]},"population":"Adults with solid tumours or haematological cancers outside the transplant setting (AGIHO 2022, whose literature search was restricted to adults), and adults having allogeneic transplant or leukaemia induction (ASCO/IDSA 2018). Prophylaxis after allogeneic and autologous transplant is referred by AGIHO to its transplant guidelines. Children are not covered by either source.","trigger":"A treatment with a known high risk of HSV or VZV reactivation is about to start.","steps":[{"action":"Before intensive leukaemia induction or allogeneic transplant, start a nucleoside analogue such as aciclovir in anyone who has had herpes simplex","why":"Without it, herpes simplex flares in a third to two thirds of people on intensive leukaemia treatment, mostly as painful mouth ulcers.","source":"asco-idsa-2018","quote":"Herpes simplex virus-seropositive patients undergoing allogeneic hematopoietic stem-cell transplantation or leukemia induction therapy should receive nucleoside analog-based antiviral prophylaxis, such as acyclovir."},{"action":"Do not wait for serology if it is not available: treat everyone with an indication as at risk","why":"About nine in ten adults already carry these viruses, so testing first changes the decision for few people.","source":"agiho-2022","quote":"We consider a universal prophylactic strategy for all patients with indication for prophylaxis of HSV as equally appropriate, because seroprevalence of HSV-1 is about 90% for adults."},{"action":"In acute leukaemia on intensive chemotherapy, give aciclovir or valaciclovir from the start of induction through the neutropenic phase","why":"In trials aciclovir cut symptomatic herpes simplex to a tenth of the rate with placebo.","source":"agiho-2022","quote":"Considering the high risk of reactivation prophylactic acyclovir or valacyclovir should be applied in patients with acute leukaemia receiving intensive chemotherapy to reduce HSV stomatitis, and to reduce other HSV reactivations (BIIr) (Table 6).","grade":"BIIr"},{"action":"Use oral aciclovir 400 mg twice or four times daily against herpes simplex, or intravenous aciclovir 250 mg/m2 three times daily if tablets cannot be taken","why":"A network analysis of thirteen trials found these the most effective regimens, and twice daily worked almost as well as four times daily.","source":"agiho-2022","quote":"We recommend oral acyclovir 400 mg BID or 400 mg QID as prophylaxis of oral HSV disease (AIIr).","grade":"AIIr"},{"action":"In acute lymphoblastic leukaemia, continue prophylaxis against both viruses for as long as treatment lasts","why":"ALL treatment is long and includes steroids and sometimes anti-CD20 antibodies, all of which raise the risk.","source":"agiho-2022","quote":"antiviral prophylaxis to reduce reactivation of HSV and VZV is recommended for patients with acute lymphoblastic leukaemia while on treatment (BI) (Table 6).","grade":"BI"},{"action":"Give aciclovir to everyone on a bortezomib-based myeloma regimen, and to those on other proteasome inhibitors","why":"Shingles affected 13% of people on bortezomib in the VISTA trial, and about 3% when they also took an antiviral.","source":"agiho-2022","quote":"Therefore, we strongly recommend acyclovir prophylaxis in patients receiving bortezomib-based treatment regimens (AII) (Table 7).","grade":"AII"},{"action":"For shingles prevention use oral aciclovir between 400 mg once daily and 400 mg three times daily","why":"All these doses have worked; no trial has compared them.","source":"agiho-2022","quote":"We recommend oral acyclovir to reduce clinical VZV reactivation; dosages from 400 mg once daily to 400 mg TID have been shown to be effective (AII).","grade":"AII"},{"action":"Do not give routine shingles prophylaxis with ordinary chemotherapy for a solid tumour","why":"Without prophylaxis only about 5 in 100 people with solid tumours get shingles within five years.","source":"agiho-2022","quote":"Pharmacological prophylaxis to prevent disease by reactivation of VZV in patients with solid tumours is not generally indicated (DIII) (Table 5).","grade":"DIII"},{"action":"Consider prophylaxis for people on high-dose corticosteroids for a long time, and continue it for up to 6 months after the steroids stop","why":"Steroids at 10 mg prednisolone a day or more for two weeks or longer raise the risk of shingles.","source":"agiho-2022","quote":"Antiviral prophylaxis might be continued for up to 6 months after corticosteroids have been terminated [76].","grade":"CIIu"},{"action":"Offer the recombinant (non-live) shingles vaccine, and keep aciclovir going in high-risk groups alongside it","why":"The vaccine is safe in cancer but works less well during treatment, and no trial has yet shown it can replace the tablet.","source":"agiho-2022","quote":"Until more data are available, particularly of comparative trials for vaccination versus pharmacological prophylaxis, it is suggested to apply acyclovir additionally in high risk patient groups (for recommendations see below)."},{"action":"Adjust the dose of aciclovir, valaciclovir or famciclovir to kidney function","why":"All three are cleared by the kidneys and build up when kidney function is poor.","source":"agiho-2022","quote":"Of note, all three nucleoside analogues (acyclovir, valacyclovir, famciclovir) require dose adjustment in patients with renal impairment."}],"bestInClass":{"statement":"ASCO/IDSA (2018) and AGIHO (2022) agree that HSV prophylaxis with aciclovir belongs in leukaemia induction and allogeneic transplant. AGIHO is the more detailed and more recent: oral aciclovir 400 mg twice or four times daily for HSV (AIIr), 400 mg once to three times daily for VZV (AII), for intensive leukaemia treatment, ALL throughout therapy, arsenic trioxide in acute promyelocytic leukaemia, and every proteasome inhibitor regimen in myeloma, but not routinely for solid tumours (DIII). The recombinant zoster vaccine is recommended but does not yet replace aciclovir in high-risk groups. Duration is the main unsettled point: AGIHO gives 28 to 100 days in AML trials, the whole of ALL treatment, 6 months after arsenic trioxide or after steroids, and individual extension in lymphoma where reactivations occurred up to 51 months after treatment began.","sources":["agiho-2022","asco-idsa-2018"]},"variants":[{"name":"Valaciclovir instead of aciclovir","differs":"Uses valaciclovir, a better absorbed prodrug, at 250 or 500 mg twice daily for HSV, or for VZV in myeloma.","evidence":"AGIHO grades valaciclovir for HSV BI, and for VZV CIIu in general and BIIu with proteasome inhibitors; the best valaciclovir dose for HSV is not defined.","sources":["agiho-2022"]},{"name":"Low-dose aciclovir with proteasome inhibitors","differs":"Uses 400 mg once daily, or lower, for shingles prevention during bortezomib, carfilzomib or ixazomib.","evidence":"Mainly retrospective series; AGIHO's 2015 edition noted that the risk of aciclovir resistance with low doses has not been assessed.","sources":["agiho-2022","agiho-2015"]}],"grades":[{"claim":"Oral aciclovir 400 mg twice or four times daily against oral HSV disease","grade":"AIIr","source":"agiho-2022"},{"claim":"Valaciclovir as an alternative against oral HSV disease","grade":"BI","source":"agiho-2022","quote":"Oral valacyclovir can be used alternatively (BI), but the best regimen (250 mg BID or 500 mg BID) has not yet been defined."},{"claim":"Prophylaxis in acute leukaemia on intensive chemotherapy","grade":"BIIr","source":"agiho-2022"},{"claim":"Prophylaxis in ALL throughout treatment","grade":"BI","source":"agiho-2022"},{"claim":"Aciclovir with bortezomib-based regimens","grade":"AII","source":"agiho-2022"},{"claim":"No routine VZV prophylaxis in solid tumours","grade":"DIII","source":"agiho-2022"},{"claim":"Consider prophylaxis with long-term high-dose corticosteroids","grade":"CIIu","source":"agiho-2022"}],"sources":[{"key":"agiho-2022","label":"Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus","publisher":"AGIHO/DGHO, Annals of Hematology","year":2022,"url":"https://europepmc.org/article/PMC/PMC8810475","doi":"10.1007/s00277-021-04746-y","gradingScheme":"Strength of recommendation A (strongly supports use) to D (supports a recommendation against use), quality of evidence I (randomised trial) to III (expert opinion), with an index for level II (r meta-analysis, t transferred evidence, h historical control, u uncontrolled trial), printed together, for example AIIr.","read":"full-text","accessed":"2026-11-11"},{"key":"agiho-2015","label":"Antiviral prophylaxis in patients with solid tumours and haematological malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)","publisher":"AGIHO/DGHO, Annals of Hematology","year":2015,"url":"https://europepmc.org/article/PMC/PMC4525190","doi":"10.1007/s00277-015-2447-3","read":"full-text","accessed":"2026-11-11"},{"key":"asco-idsa-2018","label":"Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update","publisher":"ASCO and IDSA, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/abstract/MED/30179565","doi":"10.1200/JCO.18.00374","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ASCO/IDSA 2018 guideline was read only as an abstract, so its doses, durations and grades for antiviral prophylaxis are not stated here.","Neither source covers children; paediatric doses and indications come from local or national paediatric protocols not read for this page.","Prophylaxis after allogeneic and autologous transplant, and against cytomegalovirus, is set by transplant guidelines (ECIL, EBMT, AGIHO's transplant guidelines) not read for this page.","How long to continue prophylaxis is not settled outside the situations named, and no trial has compared the recombinant zoster vaccine with aciclovir.","Influenza antiviral prophylaxis after exposure, which the census row also names, is not covered by these sources and is not addressed here."]},{"id":"acute-oncology-telephone-triage","kind":"protocol","name":"Acute oncology telephone triage: the 24-hour helpline and the UKONS red, amber and green grading","aka":["UKONS triage tool","24-hour SACT helpline","chemotherapy helpline","oncology triage line","acute oncology advice line","Cancer Treatment Helpline"],"tldr":"During cancer treatment you should have a phone number answered day and night. A trained nurse asks set questions about each symptom and grades it green, amber or red. Green means advice for home, one amber a review within 24 hours, and red (or two ambers) being seen in person as soon as possible. A temperature of 37.5 °C or more, or below 36 °C, always means urgent assessment.","summary":"The UK model: everyone on systemic anticancer therapy (SACT) or radiotherapy has a 24-hour number for specialist advice, and calls are triaged with the UKONS Triage Assessment Tool, now version 3. Each symptom is graded from 0 to 4 against NCI-CTCAE-based descriptors and assigned a colour: all green is self-care advice; one amber is a review within 24 hours; two or more ambers escalate to red; red is a face-to-face assessment as soon as possible. Some symptoms are red at any grade: chest pain (stop SACT, advise 999, disconnect an infusion pump), and fever on SACT, where a temperature of 37.5 °C or above, below 36.0 °C, or feeling generally unwell means urgent assessment on the neutropenia pathway, with a caution that analgesia, steroids or dehydration can mask a temperature. Version 3 includes prompts for checkpoint inhibitor toxicity at any time, for ICANS and CRS after cell therapy, for MSCC with back pain and for SVCO with breathlessness.\n\nThe UKAOS four-nations review (June 2025) found 99% of UK providers support 24/7 access and 90% use the UKONS tool, but variation in who answers (41 providers used non-clinical staff first), in cut-off periods after treatment, and in records; it recommends a national framework, trained and competency-assessed triage staff, and standardised data. In Clatterbridge's year of calls, 45.2% of clinical calls were red, and 72.3% of out-of-hours reds went to the emergency department against 38.3% in hours. Scotland's Cancer Treatment Helpline routes out-of-hours calls through NHS24 call handlers using UKONS questions. Canada's COSTaRS practice guides (updated 2020 and 2026) are the main national alternative.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency","telephone-triage"],"related":["febrile-neutropenia-first-hour","metastatic-spinal-cord-compression-emergency","icans-grading-and-management","idea-acc-acute-oncology-assessment-units"],"cancers":[],"sections":[],"technologies":["epro-symptom-monitoring"],"targets":[],"drugs":[],"companies":[],"institutions":["clatterbridge","leicester-cancer-research-centre"],"pathways":[],"terms":["febrile-neutropenia","ctcae-grading","superior-vena-cava-obstruction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-basch-epro-survival-jama-2017"],"journals":[],"dependsOn":[],"notes":[],"simple":"Keep your cancer helpline number with you. Ring it if you feel unwell during treatment. A nurse will ask questions and tell you whether you need to come in.","domain":"emergencies","setting":{"who":["nurse","patient-or-carer","doctor"],"where":["telephone-triage","acute-oncology-service","home"]},"population":"Adults receiving, or recently given, systemic anticancer therapy or radiotherapy, and people who have had immune checkpoint inhibitors or cell therapy at any time, who call a specialist helpline. Haematology patients may follow local policy for bleeding. Children's services use separate tools (a paediatric toolkit is noted in gaps) and are not covered here.","trigger":"A patient, carer or health professional rings the 24-hour helpline about a symptom during or after cancer treatment.","steps":[{"action":"Give every person starting anticancer treatment a 24-hour contact number, an alert card, and guidance on which symptoms to report","why":"Problems from treatment can become dangerous within hours, often at night or at weekends.","source":"ukaos-2025","quote":"All SACT patients and/or carers should receive a 24-hour contact number for specialist advice, along with guidance on symptom recognition and when to seek help."},{"action":"Have calls triaged only by staff trained and assessed as competent in telephone triage","why":"A structured assessment by someone trained to use it is what makes advice over the phone safe.","source":"ukaos-2025","quote":"Best practice dictates that only staff who have successfully completed formal telephone triage training to assess treatment and disease related symptoms and are deemed competent should perform triage duties."},{"action":"Ask whether the person has ever had an immune checkpoint inhibitor, and if the regimen is unclear, triage by symptoms with caution","why":"Immunotherapy side effects can start months or years after the last dose.","source":"ukons-v3","quote":"CAUTION! Please note patients who are receiving or have received IMMUNE CHECK POINT INHIBITORS may present with treatment related problems at anytime during treatment or even months to years after treatment has been completed."},{"action":"Grade each symptom the caller reports against the tool, using the current NCI-CTCAE criteria for severity","why":"A shared grading scale means every nurse reaches the same decision for the same symptom.","source":"ukons-v3","quote":"Practitioners are advised to refer to the latest version of NCI-CTCAE common toxicity criteria to assess the severity of the problem and seek further clinical advice regarding management."},{"action":"If the person has had anticancer treatment in the last 6 to 8 weeks or is immunocompromised and has a temperature of 37.5 °C or above, below 36.0 °C, or feels generally unwell, arrange urgent assessment on the neutropenic sepsis pathway","why":"Infection with a low white cell count can kill within hours, and a normal temperature does not rule it out.","source":"ukons-v3","quote":"IF TEMPERATURE 37.5˚C OR ABOVE OR BELOW 36.0˚C OR GENERALLY UNWELL - URGENT ASSESSMENT AND CLINICAL REVIEW - FOLLOW NEUTROPENIA PATHWAY."},{"action":"Do not be reassured by a normal temperature in someone who has taken paracetamol, ibuprofen or steroids, or may be dehydrated","why":"These can hide a fever while an infection is developing.","source":"ukons-v3","quote":"ALERT - patients who have taken analgesia or steroids or who may be dehydrated may not present with an abnormal temperature but may still have an infection and be at risk of sepsis - if in doubt do a count."},{"action":"For chest pain, advise 999 and urgent emergency assessment, stop oral and intravenous anticancer treatment until reviewed, and arrange disconnection of any infusion pump","why":"Chest pain during treatment can be a heart problem, a clot in the lung or a drug reaction.","source":"ukons-v3","quote":"STOP oral and intravenous Systemic Anti-Cancer Treatment (SACT) until reviewed by oncology or haematology team."},{"action":"With back pain, think of spinal cord compression; with breathlessness, think of superior vena cava obstruction, clots, pneumonitis and infection","why":"These are emergencies that can first be described over the phone as an ordinary symptom.","source":"ukons-v3","quote":"Back pain consider metastatic spinal cord compression (MSCC)."},{"action":"Act on the overall result: all green is self-care advice; one amber is a review within 24 hours; two or more ambers count as red; red is a face-to-face assessment as soon as possible","why":"Several moderate problems together can add up to someone who is seriously unwell.","source":"ukons-v3","quote":"Red = arrange for a face to face assessment as soon as possible"},{"action":"Record every call on the log sheet and share it with the treating team, so that it can be audited and acted on","why":"The next nurse or doctor needs to know what was said and advised.","source":"ukaos-2025","quote":"A robust local system for documenting helpline activity is essential for audit, continuity of care, and service improvement."}],"bestInClass":{"statement":"In the UK the UKONS Triage Assessment Tool, version 3, is the national standard in practice: 90% of providers use it and a further 9 use versions based on it (UKAOS 2025). Its rules are a symptom-by-symptom 0 to 4 grade with a colour, one amber for review within 24 hours, two ambers escalating to red, and red for face-to-face assessment as soon as possible, with fever at 37.5 °C or more (or below 36 °C) on treatment always triggering the neutropenia pathway. The UKAOS 2025 review, written with UKONS, is the current UK statement on how the service around the tool should run (trained and competency-assessed staff, 24-hour access, records and audit). It is not a graded guideline: the tool is an expert consensus instrument, and its outcomes have been described in service evaluations rather than tested in a trial. The strongest trial evidence for structured symptom reporting comes from patient-reported outcome monitoring (Basch 2016: fewer emergency visits and better quality of life), which complements rather than replaces the phone line.","sources":["ukons-v3","ukaos-2025","clatterbridge-2023","basch-2016"]},"variants":[{"name":"Non-clinical call handlers out of hours (Scotland's Cancer Treatment Helpline)","differs":"Out of hours, calls go to NHS24, where a trained non-clinical handler asks the UKONS questions and routes the caller; in hours a trained oncology nurse triages. The UKAOS review found 41 UK providers relied on non-clinical staff to answer first.","evidence":"NHS Tayside service review of 8385 calls, 2016 to 2020: 35% advice only, 41% review, 24% review and admission; 85% handled by oncology alone. A descriptive single-centre review without a comparison group.","sources":["tayside-2021","ukaos-2025"]},{"name":"COSTaRS practice guides (Canada)","differs":"Symptom-specific practice guides for nurses giving remote support (17 after the 2020 update, with a guide for difficulty swallowing added in 2026), with assessment, triage, medicines and self-care sections, CTCAE grades added in 2020, and a requirement to review three or more self-care strategies.","evidence":"Built from systematic reviews of guidelines (86 new sources in 2020; 175 in the 2026 update) and validated by Canadian oncology nurses. Read only as abstracts.","sources":["costars-2020","costars-2026"]},{"name":"Digital daily symptom check-ins mapped to the UKONS tiers (Leicester)","differs":"Patients report symptoms in an app each day; answers are mapped to green, amber or red, and red tells the patient to ring the 24-hour line. Alerts are grouped into episodes for clinician review in weekday working hours only.","evidence":"A 10-week single-centre service evaluation of 32 patients: 91.7% of check-ins completed, median 47 minutes to first response for in-hours red alerts, no safety signal found. Not a trial.","sources":["jmir-2026"]}],"grades":[{"claim":"One amber: review within 24 hours","grade":"not graded (expert consensus tool)","source":"ukons-v3","quote":"1 Amber = review within 24 hours"},{"claim":"Two or more ambers: escalate to red","grade":"not graded (expert consensus tool)","source":"ukons-v3","quote":"2 or more amber = escalate to red"},{"claim":"Use of a national triage tool supports standard competency, training and data","grade":"recommendation (service review; not graded)","source":"ukaos-2025","quote":"The use of a national triage tool would support the development of standard competency, training and education programmes, and support the collection of detailed presentation data using a universal toxicity grading standard."}],"sources":[{"key":"ukons-v3","label":"Oncology/Haemato-oncology Triage Line: Triage Assessment Tool, version 3 (A3 poster)","publisher":"UK Oncology Nursing Society (UKONS), hosted by the UK Acute Oncology Society","year":2025,"url":"https://www.ukacuteoncology.co.uk/application/files/4217/3799/3595/UKONS_Triage_tool_poster_A3_V10.pdf","gradingScheme":"An expert consensus triage instrument: each symptom graded 0 to 4 with a colour; the recommendations are not graded. The poster carries no publication date; the year given is the PDF's own creation date (21 January 2025).","read":"full-text","accessed":"2026-11-11"},{"key":"ukaos-2025","label":"A UK Review of Systemic Anti-cancer Therapy Helplines: Getting it right first time for cancer patients","publisher":"UK Acute Oncology Society (UKAOS) with UKONS and UKSB","year":2025,"url":"https://www.ukacuteoncology.co.uk/application/files/7117/5260/7575/UKAOS_4_Nations_Report_v7_003_PDF_2.pdf","gradingScheme":"A four-nations survey and scoping review with recommendations; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"clatterbridge-2023","label":"Evaluation of an established oncology triage hotline in a model of emergency department avoidance: assessing the UKONS triage tool and call outcomes","publisher":"Supportive Care in Cancer","year":2023,"url":"https://europepmc.org/abstract/MED/38051438","doi":"10.1007/s00520-023-08167-7","read":"abstract","accessed":"2026-11-11"},{"key":"tayside-2021","label":"Cancer Treatment Helpline: a retrospective study of the NHS Tayside experience","publisher":"BMJ Open Quality","year":2021,"url":"https://europepmc.org/article/PMC/PMC8211038","doi":"10.1136/bmjoq-2021-001488","read":"full-text","accessed":"2026-11-11"},{"key":"jmir-2026","label":"Implementing UK Oncology Nursing Society-Informed Digital Symptom Triage With Episode-Based Review in Routine NHS Acute Oncology: Service Evaluation","publisher":"JMIR Cancer","year":2026,"url":"https://europepmc.org/article/PMC/PMC13237529","doi":"10.2196/92586","read":"full-text","accessed":"2026-11-11"},{"key":"costars-2020","label":"Pan-Canadian Oncology Symptom Triage and Remote Support (COSTaRS) practice guides: what's changed in Version 2020?","publisher":"Canadian Oncology Nursing Journal","year":2020,"url":"https://europepmc.org/abstract/MED/33165347","doi":"10.5737/23688076304269276","read":"abstract","accessed":"2026-11-11"},{"key":"costars-2026","label":"Leveraging co-production in the systematic review of evidence to update the Pan-Canadian Oncology Symptom Triage and Remote Support (COSTaRS) practice guides","publisher":"Canadian Oncology Nursing Journal","year":2026,"url":"https://europepmc.org/abstract/MED/42621903","doi":"10.5737/23688076362128","read":"abstract","accessed":"2026-11-11"},{"key":"basch-2016","label":"Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial","publisher":"Journal of Clinical Oncology","year":2016,"url":"https://europepmc.org/abstract/MED/26644527","doi":"10.1200/JCO.2015.63.0830","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-acc-electronic-pro-monitoring-standard"],"gaps":["The UKONS tool's own guidance document (training, competency and the full log sheet) was not found publicly; only the version 3 poster was read. ukons.org does not list the tool among its public resources.","No randomised trial has compared telephone triage with a structured tool against unstructured advice; the evidence for the UKONS tool is service evaluations (Clatterbridge, Tayside) and the expert consensus behind it.","Cut-off periods after treatment differ between UK providers (6 weeks, 8 weeks or 3 to 6 months), and the tool itself uses 6 to 8 weeks for fever; no source read sets one national cut-off.","The COSTaRS practice guides and their 2026 update were read only as abstracts; their triage thresholds are not compared with UKONS here.","A paediatric oncology telephone triage toolkit exists (J Pediatr Hematol Oncol Nurs 2026, linguistic validation) but was not read; children are not covered."]},{"id":"ambulatory-chemotherapy-pumps-at-home","kind":"protocol","name":"Ambulatory chemotherapy pumps at home: set-up, checks, spills and disconnection","aka":["chemo pump at home","5-FU pump","fluorouracil infusor","elastomeric pump","balloon pump","46-hour infusion","baby bottle pump","CADD pump","pump disconnection","infusor"],"tldr":"Some chemotherapy, such as fluorouracil for bowel cancer, runs for about two days from a small pump you carry home, connected to your port or PICC. The rate is set in the pharmacy or checked by two nurses before you leave. You will be told how to carry it, what to do if it leaks or the line comes apart, and who to call day or night.","summary":"Home infusion pumps carry a particular hazard: a programming or calculation error delivers days of chemotherapy in hours. ISMP Canada's root cause analysis of a 2006 death, in which fluorouracil intended to run over 4 days ran over 4 hours, found that the order lacked the volume and rate to programme, the rate had to be calculated through several steps, the label carried a confusing 'mL/24 h' figure, the pump gave little feedback, and checks were not truly independent. Its recommendations: put the critical administration details (total volume, rate) in standard order sets; standardise volumes or concentrations so the calculation is built into the order; express rates only in mL per hour; use pumps with safeguards such as pharmacy-controlled rates (elastomeric pumps) or preset maximum rates; and embed independent double checks with documented calculations.\n\nASCO-ONS (2024) requires a second verification at preparation and a final check before administration that includes pump settings and rate, confirmation with the patient of the drug, infusion time and symptoms to report, and education on home handling: storage, waste, body fluids and spill clean-up. Elastomeric pumps fail too: in 205 incident reports from one pharmacy, 44% were leaks, 30% flow anomalies and 20% injection difficulties, and fluorouracil residue has been found around the catheter connection. A closed-system device reduced contamination at disconnection in a laboratory study, and a small pilot found patients could be trained to disconnect their own pump.","asOf":"2026-11-11","links":[],"tags":[],"related":["oral-anticancer-medicines-at-home","hazardous-drug-handling-in-clinical-areas","sact-administration-checks-at-the-chair"],"cancers":[],"sections":[],"technologies":["ambulatory-chemotherapy-pumps","closed-system-transfer-devices","implanted-ports","picc-lines"],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["chemotherapy-side-effects-pancreatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"You go home with a small pump giving your treatment slowly over a day or two. Know who to call, keep the spill kit handy, and phone if it leaks, comes apart or seems to be running too fast or too slow.","domain":"chemotherapy-administration","setting":{"who":["nurse","pharmacist","patient-or-carer"],"where":["chemotherapy-day-unit","home","community","aseptic-unit"]},"population":"Adults receiving continuous infusional chemotherapy at home through an elastomeric or electronic ambulatory pump connected to a central line, most often fluorouracil-based regimens for gastrointestinal, head and neck and other cancers. Paediatric home infusion and subcutaneous syringe drivers for symptom control are not covered.","trigger":"A continuous infusion is to start in clinic and continue at home, or a home pump is due to be disconnected.","steps":[{"action":"Write the total volume, duration and rate in mL per hour into the standard order, so no one has to work them out at the chair","why":"A fatal overdose happened when nurses had to calculate the rate from the dose themselves and made an error.","source":"ismp-canada-2007","quote":"Include critical information required for medication administration as part of standardized order sets in manual and electronic medication orders."},{"action":"Use a pump with a built-in safeguard where possible: an elastomeric pump with a fixed rate set in the pharmacy, or an electronic pump with preset limits","why":"If the rate cannot be programmed wrongly at the bedside, the error that killed a patient in 2006 cannot happen.","practice":"ISMP Canada recommends pumps with safeguards such as pharmacy-controlled rate delivery (elastomeric pumps) or preset maximum rates, but its recommendation tables are set in columns that the extracted text interleaves, so the sentence cannot be quoted verbatim."},{"action":"Have a second clinician independently check the pump, its programming or flow rate and the rate against the order before it is connected","why":"A truly independent check, done without being told the answer, catches calculation and programming slips.","source":"asco-ons-2024","quote":"Infusion pump (if applicable) settings, including rate"},{"action":"Before starting, confirm with the person the drug, how long it should run, the route and the symptoms to report","why":"A person who knows the pump should run for about two days will notice if it empties in hours.","source":"asco-ons-2024","quote":"Before initiation of antineoplastic therapy, personnel approved by the health care organization who is administering the antineoplastic(s) confirms the therapy with the patient, including, at a minimum, the name of the drug, the infusion time, route of infusion, symptoms to report, for example: hypersensitivity symptoms or pain at infusion"},{"action":"Teach safe handling at home: storage, waste, body fluids, and how to clean up a spill, with a spill kit and a 24-hour contact number","why":"Pumps can leak, and fluorouracil residue has been found around the connection.","source":"asco-ons-2024","quote":"Procedures for safe handling medications in the home, including disposal of waste, handling body secretions, storage, safe handling, and management of unused medication, and clean-up of drug spills"},{"action":"Ask the person to call at once if the pump leaks, the line disconnects, or it seems to be emptying too fast or not at all","why":"Leaks and flow problems are the commonest pump failures.","source":"chefchaouni-2023","quote":"The main technical failures were: chemotherapy product leakage (44%), flow rate anomalies (30%) and injection difficulties (20%)."},{"action":"At disconnection, wear protective gloves and treat the pump and tubing as hazardous waste; then flush and lock the line as for any access","why":"Drug residue on the pump and connection can expose nurses, patients and family.","source":"cardoso-2025","quote":"The detection of 5-FU residues highlights the critical need for safe handling practices and the consistent use of personal protective equipment (PPE) to protect healthcare workers, especially nursing staff involved in the removal of the infusion pumps, after treatment."}],"bestInClass":{"statement":"No graded guideline on home chemotherapy pumps could be read. The strongest open source is ISMP Canada's root cause analysis (2007): critical administration details in the standard order, standardised volumes or concentrations, rates in mL per hour only, pumps with rate safeguards, and truly independent double checks. ASCO-ONS (2024) adds verification of pump settings and rate before administration, confirmation with the patient of the infusion time, and home safe-handling education. Disconnection with a closed-system device and patient self-disconnection are promising but rest on small studies.","sources":["ismp-canada-2007","asco-ons-2024"]},"variants":[{"name":"Closed-system transfer device at the pump connection","differs":"Connects the pump line to the port needle through a closed-system device instead of a standard Luer lock or needle-free connector.","evidence":"In a laboratory study of 30 elastomeric pumps, overall 5-FU contamination at disconnection was significantly lower with the closed device (Qimono) than with Luer lock or a needle-free connector; wipes showed 43 to 61% less contamination.","sources":["raphaelle-2023"]},{"name":"Patient self-disconnection at home","differs":"Trains selected patients to disconnect their own pump and do basic line care instead of a nurse visit.","evidence":"A six-month pilot of nine patients reported time savings of 102 minutes per cycle for patients and 64 for home care nurses, with stable satisfaction. Too small to judge safety.","sources":["al-fartousi-2026"]}],"grades":[],"sources":[{"key":"ismp-canada-2007","label":"Fluorouracil Incident Root Cause Analysis","publisher":"Institute for Safe Medication Practices Canada","year":2007,"url":"https://www.ismp-canada.org/download/reports/FluorouracilIncidentMay2007.pdf","gradingScheme":"Root cause analysis; recommendations classed by strategy (eliminate, control, accept), not graded by evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and ONS (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded; developed from a systematic review (2015 to 2023), expert panel consensus and public comment.","read":"full-text","accessed":"2026-11-11"},{"key":"chefchaouni-2023","label":"Retrospective analysis of failures of ambulatory elastomeric pumps containing 5-FU in a hospital pharmacy unit","publisher":"Journal of Oncology Pharmacy Practice (Chefchaouni et al.)","year":2023,"url":"https://doi.org/10.1177/10781552211060290","doi":"10.1177/10781552211060290","read":"abstract","accessed":"2026-11-11"},{"key":"cardoso-2025","label":"Safeguarding Patients, Relatives, and Nurses: A Screening Approach for Detecting 5-FU Residues on Elastomeric Infusion Pumps Using HPLC-DAD","publisher":"Toxics (Cardoso et al.)","year":2025,"url":"https://doi.org/10.3390/toxics13050416","doi":"10.3390/toxics13050416","read":"abstract","accessed":"2026-11-11"},{"key":"raphaelle-2023","label":"Safe disconnection of 5-fluorouracil elastomeric pumps: The benefit of a closed-system-transfer device designed for cytotoxic drug administration/perfusion","publisher":"Journal of Vascular Access","year":2023,"url":"https://doi.org/10.1177/11297298211044017","doi":"10.1177/11297298211044017","read":"abstract","accessed":"2026-11-11"},{"key":"al-fartousi-2026","label":"Reducing staff workload through patient involvement in oncology: A pilot study on self-disconnection of 5-fluorouracil elastomeric pumps at home","publisher":"Annales Pharmaceutiques Françaises (Al Fartousi et al.)","year":2026,"url":"https://doi.org/10.1016/j.pharma.2026.03.007","doi":"10.1016/j.pharma.2026.03.007","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No graded guideline on ambulatory chemotherapy pumps could be read; the INS and ISOPP standards, which cover them, were not reachable.","How temperature, height and position change the flow of elastomeric pumps, and what to tell patients about carrying them, comes from manufacturers' instructions, none of which were read.","The ISMP Canada analysis dates from 2007; whether its recommendations (rates in mL per hour, rate-limited pumps) are now universal is not known.","The disconnection and self-disconnection studies are a laboratory study and a nine-patient pilot, read as abstracts."]},{"id":"chemotherapy-induced-anaemia-esa-and-iron","kind":"protocol","name":"Anaemia during chemotherapy: investigation, iron and erythropoiesis-stimulating agents","aka":["chemotherapy-induced anaemia","ESA in cancer","epoetin for anaemia in cancer","darbepoetin","iron for anaemia during chemotherapy","cancer-associated anaemia"],"tldr":"Chemotherapy often lowers the red blood cells, causing tiredness and breathlessness. Your team should first look for other causes such as low iron or blood loss. If the treatment is not aimed at cure, injections that stimulate red cell production (ESAs) or a blood transfusion are options; if the aim is cure, ESAs are not used because of their risks.","summary":"ASCO/ASH (2019) ask clinicians first to look for and treat other causes of anaemia (drug history, blood film, iron studies including ferritin and transferrin saturation, folate, vitamin B12, reticulocytes, occult blood loss, renal function, erythropoietin level, thyroid where indicated). ESAs may be offered for chemotherapy-associated anaemia when treatment is not curative in intent and haemoglobin has fallen below 10 g/dL, with red cell transfusion as an alternative (evidence based, high quality, strong); they should not be offered when treatment is curative (strong), nor to most people whose anaemia is not chemotherapy-associated (strong), except lower-risk myelodysplastic syndromes with erythropoietin 500 IU/L or below.\n\nESAs raise the risk of venous thromboembolism (high quality, strong), so the risk is weighed for each person. Doses follow the product's licence; haemoglobin is raised only to the lowest level that avoids transfusion; ESAs stop if there is no response in 6 to 8 weeks, prompting a search for progression or iron deficiency (strong). Iron replacement may be used with an ESA, with baseline and periodic iron studies (weak). In myeloma, non-Hodgkin lymphoma and CLL the response to cancer treatment is observed before an ESA is considered. NICE TA323 recommends ESAs within their licences for anaemia in people having chemotherapy, choosing the cheapest suitable product. Epoetin alfa and beta, darbepoetin and biosimilar epoetin alfa are considered equivalent.","asOf":"2026-11-11","links":[],"tags":["protocol","anaemia","supportive-care"],"related":["mds","red-cell-and-platelet-transfusion-thresholds"],"cancers":[],"sections":["supportive-care"],"technologies":["transfusion-support"],"targets":[],"drugs":["epoetin-alfa","darbepoetin-alfa","epoetin-theta"],"companies":[],"institutions":["asco","nice"],"pathways":[],"terms":["anaemia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Chemotherapy can lower red blood cells and make you tired. Doctors check for other causes first. They may give iron, an injection to make more red cells, or a blood transfusion.","domain":"supportive-care","setting":{"who":["doctor","pharmacist","nurse"],"where":["outpatient-clinic","chemotherapy-day-unit"]},"population":"Adults with cancer and anaemia during or related to myelosuppressive chemotherapy. Children, people with chronic kidney disease (who have their own ESA guidance) and red cell transfusion thresholds (covered in the transfusion protocol) are not covered here.","trigger":"Haemoglobin falls during chemotherapy, or symptoms of anaemia appear.","steps":[{"action":"Before any ESA, look for other causes: take a drug history, review a blood film, check iron studies, folate, vitamin B12, reticulocytes, kidney function and signs of blood loss, and treat what you find","why":"Anaemia during cancer care often has a treatable cause, such as iron deficiency or bleeding, that an ESA would not fix.","source":"asco-ash-2019","quote":"Before offering an ESA, clinicians should conduct an appropriate history, physical examination, and diagnostic tests to identify alternative causes of anemia aside from chemotherapy or an underlying hematopoietic malignancy.","grade":"informal consensus; evidence quality intermediate; strength strong"},{"action":"If treatment is not aimed at cure and haemoglobin is below 10 g/dL, offer an ESA or a red cell transfusion, depending on how severe the anaemia is and the circumstances","why":"ESAs reduce the need for transfusions; a transfusion works faster when symptoms are severe.","source":"asco-ash-2019","quote":"Depending on clinical circumstances, ESAs may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin (HgB) has declined to < 10 g/dL.","grade":"evidence based; evidence quality high; strength strong"},{"action":"Do not offer an ESA when the treatment is curative in intent","why":"ASCO/ASH judged the possible harms of ESAs not worth taking when the aim of treatment is cure.","source":"asco-ash-2019","quote":"ESAs should not be offered to patients with chemotherapy-associated anemia whose cancer treatment is curative in intent","grade":"evidence based; evidence quality intermediate; strength strong"},{"action":"Do not offer an ESA to most people whose anaemia is not caused by chemotherapy; the exception is lower-risk myelodysplastic syndromes with a low erythropoietin level","why":"ASCO/ASH found no case for routine use outside chemotherapy and lower-risk MDS.","source":"asco-ash-2019","quote":"ESAs should not be offered to most patients with nonchemotherapy-associated anemia","grade":"informal consensus; evidence quality low; strength strong"},{"action":"Weigh the risk of blood clots before starting an ESA","why":"ESAs increase the risk of venous thromboembolism, which is already raised in cancer.","source":"asco-ash-2019","quote":"ESAs increase the risk of thromboembolism, and clinicians should carefully weigh the risks of thromboembolism and use caution and clinical judgment when considering use of these agents","grade":"evidence based; evidence quality high; strength strong"},{"action":"Raise haemoglobin only to the lowest level that avoids transfusion","why":"ASCO/ASH set no fixed target; the aim is to avoid transfusion, not to reach a normal count.","source":"asco-ash-2019","quote":"HgB may be increased to the lowest concentration needed to avoid or reduce the need for RBC transfusions, which may vary by patient and condition","grade":"informal consensus; evidence quality intermediate; strength moderate"},{"action":"Give iron alongside an ESA where it helps, and check iron studies at the start and during treatment","why":"Iron improves the response to an ESA and reduces transfusions, with or without measured iron deficiency.","source":"asco-ash-2019","quote":"Iron replacement may be used to improve HgB response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency.","grade":"evidence based; evidence quality intermediate; strength weak"},{"action":"Stop the ESA if there is no response after 6 to 8 weeks, and look again for progression or iron deficiency","why":"If it has not worked by then, continuing adds risk and cost without benefit.","source":"asco-ash-2019","quote":"ESAs should be discontinued in patients who do not respond within 6 to 8 weeks.","grade":"informal consensus; evidence quality intermediate; strength strong"}],"bestInClass":{"statement":"ASCO/ASH (2019), read in full, is the most detailed current guideline: investigate other causes first, offer an ESA or transfusion for chemotherapy-associated anaemia below 10 g/dL only when treatment is not curative, weigh the clot risk, aim for the lowest haemoglobin that avoids transfusion, stop after 6 to 8 weeks without response, and consider iron alongside. NICE TA323 (2014) recommends ESAs within their marketing authorisations for people having chemotherapy and does not repeat ASCO/ASH's restriction to non-curative treatment; the licences themselves were not read. ESMO's 2018 guideline, which covers intravenous iron in more detail, could not be read.","sources":["asco-ash-2019","nice-ta323","esmo-2018"]},"variants":[{"name":"ESAs within their licences, cheapest suitable product (NICE TA323)","differs":"Recommends epoetin alfa, beta, theta and zeta and darbepoetin alfa within their marketing authorisations for anaemia in people having chemotherapy, and the product with the lowest acquisition cost where several are suitable.","evidence":"A NICE technology appraisal of cost-effectiveness; NICE does not grade it. ASCO/ASH likewise consider the products equivalent (informal consensus, moderate).","sources":["nice-ta323","asco-ash-2019"]},{"name":"Wait for the response to treatment in myeloma, lymphoma and CLL (ASCO/ASH)","differs":"In myeloma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia, observes the blood count response to cancer treatment before considering an ESA.","evidence":"ASCO/ASH recommendation 3; the response to treatment may correct the anaemia without an ESA.","sources":["asco-ash-2019"]}],"grades":[{"claim":"ESA or transfusion for chemotherapy-associated anaemia below 10 g/dL, non-curative treatment","grade":"evidence based; high; strong","source":"asco-ash-2019"},{"claim":"No ESA when treatment is curative","grade":"evidence based; intermediate; strong","source":"asco-ash-2019"},{"claim":"ESA for lower-risk MDS with erythropoietin 500 IU/L or below","grade":"evidence based; intermediate; moderate","source":"asco-ash-2019","quote":"ESAs may be offered to patients with lower risk myelodysplastic syndromes and a serum erythropoietin level ≤ 500 IU/L"},{"claim":"ESAs increase thromboembolism risk","grade":"evidence based; high; strong","source":"asco-ash-2019"},{"claim":"Iron with an ESA","grade":"evidence based; intermediate; weak","source":"asco-ash-2019"}],"sources":[{"key":"asco-ash-2019","label":"Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update","publisher":"ASCO and the American Society of Hematology, Blood Advances (also published in J Clin Oncol)","year":2019,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6482353/","doi":"10.1182/bloodadvances.2018030387","gradingScheme":"Each recommendation printed with type (evidence based or informal consensus), evidence quality (high, intermediate, low) and strength (strong, moderate, weak).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ta323","label":"Erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating anaemia in people with cancer having chemotherapy (TA323)","publisher":"NICE","year":2014,"url":"https://www.nice.org.uk/guidance/ta323/chapter/1-Guidance","gradingScheme":"NICE technology appraisals are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2018","label":"Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical Practice Guidelines","publisher":"ESMO, Annals of Oncology","year":2018,"url":"https://doi.org/10.1093/annonc/mdx758","doi":"10.1093/annonc/mdx758","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2018 guideline could not be read: Europe PMC holds no abstract and the publisher refused a script. Its recommendations on intravenous iron without an ESA, and its ferritin and transferrin saturation thresholds, are not given here.","ASCO/ASH 2019 does not set iron-deficiency thresholds or choose between oral and intravenous iron in the text read; it recommends monitoring iron, transferrin saturation or ferritin.","ASCO/ASH ask that ESA doses follow FDA labelling; UK practice follows the SmPC under NICE TA323. Neither label was read.","No guideline after 2019 was found in Europe PMC; newer agents for anaemia in MDS are outside this protocol."]},{"id":"antibacterial-prophylaxis-in-neutropenia","kind":"protocol","name":"Antibacterial (fluoroquinolone) prophylaxis during expected severe neutropenia","aka":["fluoroquinolone prophylaxis","levofloxacin prophylaxis","ciprofloxacin prophylaxis","antibiotic prophylaxis in neutropenia","neutropenic antibacterial prophylaxis"],"tldr":"Some people on intensive chemotherapy, such as for acute leukaemia, are offered an antibiotic tablet while their white cells are lowest,. Guidelines disagree on who should have it: NICE offers it to more adults; children's and Australian guidelines limit it to the highest risk, as it breeds resistant germs. It does not replace calling the team at once with a fever.","summary":"Guidelines agree that prophylaxis is a fluoroquinolone given only for the period of severe neutropenia, and differ on who gets it. NICE CG151 offers fluoroquinolone prophylaxis to adults with acute leukaemias, stem cell transplants or solid tumours in whom a neutrophil count of 0.5 × 10⁹/L or lower is anticipated, noting that only ciprofloxacin was licensed for it in September 2024 and pointing to the MHRA January 2024 restrictions; units using it should monitor resistance. ASCO/IDSA (2018) recommend antibacterial prophylaxis for patients at high risk, including those expected to have profound, protracted neutropenia (under 100 neutrophils/µL for more than 7 days). For children, the international paediatric guideline (2020, endorsed by COG) says consider prophylaxis only in AML and relapsed ALL on intensive chemotherapy expected to cause neutrophils under 500/µL for at least 7 days (weak, high quality), not routinely in ALL induction or after autologous or allogeneic HSCT (weak), and not at all when severe neutropenia for 7 days is not expected (strong, moderate); levofloxacin is preferred (strong, moderate), ciprofloxacin an alternative with weaker gram-positive cover. Prophylaxis halved bacteraemia in children with AML or relapsed ALL but increased resistance and did not reduce overall mortality. The 2025 Australian and New Zealand consensus concludes that in most circumstances the harms outweigh the benefit.","asOf":"2026-11-11","links":[],"tags":["protocol","antimicrobial-prophylaxis","paediatric"],"related":["febrile-neutropenia-first-hour","paediatric-fever-and-neutropenia"],"cancers":["aml","all-leukemia","childhood-cancers"],"sections":["supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["nice","asco"],"pathways":[],"terms":["neutropenia","febrile-neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"During some very strong chemotherapy, doctors may give an antibiotic tablet to prevent infection while white cells are very low. It is only for some people, because it can make germs resistant. If you get a fever, still ring the team at once.","domain":"infection-prevention","setting":{"who":["doctor","pharmacist","patient-or-carer"],"where":["outpatient-clinic","ward","home"]},"population":"Adults (NICE: 18 or over) with acute leukaemias, stem cell transplants or solid tumours in whom significant neutropenia is expected; children with cancer and child HSCT recipients (the 2020 paediatric guideline). People already on a fluoroquinolone and those with fluoroquinolone contraindications need an individual decision.","trigger":"A course of chemotherapy or a transplant is planned that is expected to cause severe neutropenia.","steps":[{"action":"Before each intensive course, estimate how deep and how long the neutropenia will be","why":"Prophylaxis helps only when neutrophils will be very low for long enough; for shorter, milder neutropenia it adds harm without benefit.","source":"paed-abp-2020","quote":"Do not use systemic antibacterial prophylaxis for children whose therapy is not expected to result in severe neutropenia (absolute neutrophil count <500/μL) for at least 7 days.","grade":"Strong recommendation, moderate-quality evidence"},{"action":"In adults expected to have neutrophils of 0.5 × 10⁹/L or lower from treatment for acute leukaemia, stem cell transplant or a solid tumour, offer a fluoroquinolone for the expected period of neutropenia (NICE)","why":"NICE judged that preventing infections in this group outweighs the costs; other guidelines limit prophylaxis to people at higher risk (see variants).","source":"nice-cg151"},{"action":"In children, consider prophylaxis only for AML or relapsed ALL on intensive chemotherapy expected to cause neutrophils below 500/µL for at least 7 days","why":"In these children prophylaxis halved bloodstream infections, but it also raised resistance and did not lower overall deaths, so the panel kept it to the highest-risk group.","source":"paed-abp-2020","quote":"Consider systemic antibacterial prophylaxis administration in children with AML and relapsed ALL receiving intensive chemotherapy expected to result in severe neutropenia (absolute neutrophil count <500/μL) for at least 7 days.","grade":"Weak recommendation, high-quality evidence"},{"action":"Do not give routine prophylaxis to children in induction for newly diagnosed ALL, or to children having autologous or allogeneic stem cell transplant","why":"Their baseline risk of bloodstream infection is lower, so the smaller benefit was judged not to outweigh the resistance it causes.","source":"paed-abp-2020","quote":"We suggest that systemic antibacterial prophylaxis not be used routinely for children receiving induction chemotherapy for newly diagnosed ALL.","grade":"Weak recommendation, low-quality evidence"},{"action":"Where prophylaxis is used in children, use levofloxacin","why":"Levofloxacin was tested in the large paediatric trial and covers the streptococci that ciprofloxacin covers less well. The 2026 update kept this strong recommendation.","source":"paed-abp-2020","quote":"Levofloxacin is the preferred agent if antibacterial prophylaxis is planned.","grade":"Strong recommendation, moderate-quality evidence"},{"action":"If a child cannot have levofloxacin, consider giving no antibacterial prophylaxis rather than another drug","why":"New in the 2026 update; the 2020 edition had named ciprofloxacin as the alternative, with weaker cover against streptococci.","source":"paed-prophylaxis-2026","quote":"A new conditional recommendation was introduced to consider using no antibacterial prophylaxis in patients unable to receive levofloxacin.","grade":"conditional (as described in the abstract)"},{"action":"Tell patients and families about the short- and long-term side effects of fluoroquinolones before starting, and follow the MHRA restrictions","why":"Fluoroquinolones can cause disabling and long-lasting side effects, such as tendon damage; knowing this, some families choose not to have prophylaxis.","source":"paed-abp-2020","quote":"Patients and families should be informed about potential short- and long-term fluoroquinolone-related adverse effects prior to administration and this information may lead to some families choosing against prophylaxis."},{"action":"Give it only during the expected period of severe neutropenia, and stop it when the count recovers","why":"Limiting the time on the antibiotic limits resistance and side effects; the trials gave it only during severe neutropenia.","source":"paed-abp-2020","quote":"If antibacterial prophylaxis is planned, we suggest that administration be restricted to the expected period of severe neutropenia (absolute neutrophil count <500/μL).","grade":"Weak recommendation, low-quality evidence"},{"action":"Monitor antibiotic resistance and infection patterns in any unit that uses fluoroquinolone prophylaxis","why":"Widespread prophylaxis can make the germs that cause infections resistant to the same drugs used to treat them.","source":"nice-cg151","quote":"Rates of antibiotic resistance and infection patterns should be monitored in treatment facilities where patients are having fluoroquinolones for the prophylaxis of neutropenic sepsis."},{"action":"Tell the patient that prophylaxis does not replace urgent assessment for a fever or feeling unwell","why":"Infections still happen on prophylaxis, and the first-hour fever pathway applies in full.","practice":"Every guideline read assumes that febrile neutropenia on prophylaxis is managed as an emergency; none states it as a separate recommendation. The first-hour protocol covers it."}],"bestInClass":{"statement":"Give a fluoroquinolone only to people expected to have severe, prolonged neutropenia, only for that period, with resistance monitored. The guidelines differ on who qualifies. NICE CG151 offers it to all adults with acute leukaemia, stem cell transplant or a solid tumour in whom neutrophils of 0.5 × 10⁹/L or lower are expected, and does not grade recommendations. ASCO/IDSA (2018) limit it to adults at high risk, including profound, protracted neutropenia (under 100/µL for more than 7 days). The paediatric guideline (2020, endorsed by COG; its 2026 update maintains these recommendations and adds a conditional recommendation to consider no prophylaxis where levofloxacin cannot be used) limits it to AML and relapsed ALL with neutrophils under 500/µL for at least 7 days (weak, high quality) and prefers levofloxacin (strong, moderate). The Australian and New Zealand consensus (2025) concludes that in most circumstances the harms of resistance, side effects and microbiome disruption outweigh a benefit that does not include lower mortality.","sources":["nice-cg151","asco-idsa-2018","paed-abp-2020","paed-prophylaxis-2026","cog-abp-2020","anz-2025"]},"variants":[{"name":"Broad adult eligibility (NICE CG151)","differs":"Offers fluoroquinolone prophylaxis to any adult with acute leukaemia, stem cell transplant or a solid tumour in whom neutrophils of 0.5 × 10⁹/L or lower are anticipated, including solid tumour chemotherapy, rather than only profound and protracted neutropenia.","evidence":"NICE does not grade recommendations. It notes that in September 2024 only ciprofloxacin was licensed for this use and refers to the MHRA January 2024 advice on fluoroquinolone restrictions.","sources":["nice-cg151"]},{"name":"High-risk adults only (ASCO/IDSA 2018)","differs":"Recommends antibacterial prophylaxis for patients at high risk of infection, including those expected to have profound, protracted neutropenia, defined as fewer than 100 neutrophils/µL for more than 7 days, or other risk factors.","evidence":"Read as an abstract only; the grade is not given here.","sources":["asco-idsa-2018"]},{"name":"Against routine prophylaxis in most circumstances (Australia and New Zealand, 2025)","differs":"The updated consensus for adults and children concludes that the potential harm of resistance, adverse effects and microbiome disruption outweighs the reduction in infection in most circumstances, given no mortality benefit and better sepsis pathways.","evidence":"Read as an abstract only; its specific recommendations and grades were not read.","sources":["anz-2025"]}],"grades":[{"claim":"Consider prophylaxis in children with AML or relapsed ALL with neutrophils under 500/µL for at least 7 days","grade":"Weak recommendation, high-quality evidence","source":"paed-abp-2020"},{"claim":"No routine prophylaxis in induction for newly diagnosed ALL","grade":"Weak recommendation, low-quality evidence","source":"paed-abp-2020"},{"claim":"No prophylaxis when severe neutropenia for 7 days is not expected","grade":"Strong recommendation, moderate-quality evidence","source":"paed-abp-2020"},{"claim":"No routine prophylaxis for children having autologous HSCT","grade":"Weak recommendation, moderate-quality evidence","source":"paed-abp-2020","quote":"We suggest that systemic antibacterial prophylaxis not be used routinely for children undergoing autologous HSCT."},{"claim":"No routine prophylaxis for children having allogeneic HSCT","grade":"Weak recommendation, moderate-quality evidence","source":"paed-abp-2020","quote":"We suggest that systemic antibacterial prophylaxis not be used routinely for children undergoing allogeneic HSCT."},{"claim":"Levofloxacin preferred","grade":"Strong recommendation, moderate-quality evidence","source":"paed-abp-2020"},{"claim":"Effect of levofloxacin on bacteraemia in children with AML and relapsed ALL","grade":"RR 0.50, 95% CI 0.32 to 0.78 (trial result reported by the guideline)","source":"paed-abp-2020","quote":"Levofloxacin prophylaxis significantly reduced bacteremia in this group (RR, .50; 95% CI, .32–.78)."}],"sources":[{"key":"nice-cg151","label":"Neutropenic sepsis: prevention and management in people with cancer (CG151), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg151/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'do not offer', 'consider'). Recommendation 1.2.1.1 was updated in January 2020 and September 2024.","read":"full-text","accessed":"2026-11-11"},{"key":"paed-abp-2020","label":"Guideline for Antibacterial Prophylaxis Administration in Pediatric Cancer and Hematopoietic Stem Cell Transplantation","publisher":"Pediatric Oncology Group of Ontario panel (Lehrnbecher et al.), Clinical Infectious Diseases","year":2020,"url":"https://europepmc.org/article/PMC/PMC7312235","doi":"10.1093/cid/ciz1082","gradingScheme":"GRADE: strong or weak recommendation with high, moderate, low or very low quality evidence, printed together.","read":"full-text","accessed":"2026-11-11"},{"key":"cog-abp-2020","label":"Antibacterial prophylaxis in pediatric cancer and HSCT (COG endorsement, version date 21 July 2020)","publisher":"Children's Oncology Group","year":2020,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_Antibacterial_Prophylaxis_Guideline_Document_21JULY2020-new-logo.pdf","gradingScheme":"Reprints the source guideline's GRADE strength and quality.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-idsa-2018","label":"Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update","publisher":"ASCO and IDSA, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/article/MED/30179565","doi":"10.1200/JCO.18.00374","read":"abstract","accessed":"2026-11-11"},{"key":"paed-prophylaxis-2026","label":"Clinical Practice Guideline for Systemic Antibacterial and Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Cell Transplant Recipients: 2026 Update","publisher":"Pediatric Oncology Group of Ontario panel, Journal of Clinical Oncology","year":2026,"url":"https://europepmc.org/article/MED/42826360","doi":"10.1200/jco-26-00720","gradingScheme":"GRADE (strong or conditional, with evidence quality), with good practice statements; the individual grades were not read.","read":"abstract","accessed":"2026-11-11"},{"key":"anz-2025","label":"Consensus guidelines for antibacterial prophylaxis in patients with neutropenia","publisher":"Internal Medicine Journal (Australian and New Zealand consensus)","year":2025,"url":"https://europepmc.org/article/MED/41521409","doi":"10.1111/imj.70250","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ASCO/IDSA 2018 guideline and the 2025 Australian and New Zealand consensus were read as abstracts only, so their grades, drug choices and exact eligibility rules are not given here.","No guideline read reports a mortality benefit from antibacterial prophylaxis; the paediatric synthesis found none.","ECIL guidance on fluoroquinolone prophylaxis in adult haematology was not read for this protocol.","The 2026 paediatric update could only be read as an abstract (the publisher refused a script and there is no open full text); its three new good practice statements on drug interactions, infection prevention and infection epidemiology are not given in detail, and the COG page still lists the 2020 endorsement.","The paediatric panel names as research gaps the value of prophylaxis in ALL induction and other intensive ALL phases, in solid tumours on intensive chemotherapy, and levofloxacin against ciprofloxacin head to head.","The dose and duration of fluoroquinolone used come from local protocols and the product licence, which were not read here."]},{"id":"sact-administration-checks-at-the-chair","kind":"protocol","name":"Anticancer treatment administration checks at the chair: assessment, independent double checks and line tracing","aka":["chemotherapy bedside checks","chemotherapy double check","independent double check","two-nurse check chemotherapy","fourth verification","tracing the lines","pre-administration checks","chemotherapy time out"],"tldr":"On each treatment day a nurse checks how you are, your temperature, pulse, blood pressure, allergies and side effects. Before the drip starts, two trained staff check the bag against your prescription and against you, using two identifiers such as your name and date of birth, and follow the tubing from bag to line. You will be told the drug's name, how long it takes and what to report at once.","summary":"The ASCO-ONS Antineoplastic Therapy Administration Safety Standards (2024) replaced the 2016 ASCO/ONS standards' three verifications with four: before preparation (order elements and dose calculation), at preparation (a second clinician checks vials, concentration, volume, diluent and tubing), after preparation and before administration (two licensed clinicians independently verify drug, dose, volume, rate, route, expiry and appearance), and a new fourth verification in the presence of the patient, in which two licensed clinicians, at least one on site and the other in person or by approved video, check two patient identifiers, the drug, dose, rate and duration, route, administration set and pump settings. The panel added the fourth check because drugs are now often prepared away from where they are given, and added visual inspection of the administration set ('tracing the lines').\n\nOn each treatment day staff assess and record performance status, vital signs, date of birth, allergies and previous reactions, toxicities and pain, and update the medication list; the nurse confirms the drug, infusion time, route and symptoms to report with the patient before starting. A practitioner certified in basic life support must be present and a licensed practitioner on site, with hypersensitivity, extravasation and, where relevant, cytokine release order sets and drugs to hand.\n\nThe standards are not graded. The panel notes that remote video verification looks feasible but that no well-designed research has evaluated its effect on safety.","asOf":"2026-11-11","links":[],"tags":[],"related":["sact-prescribing-and-pharmacy-verification","chemotherapy-extravasation-management"],"cancers":[],"sections":[],"technologies":["smart-infusion-pumps","infusion-devices-vascular-access","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["extravasation-infusion-reaction","crs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before your drip starts, two staff check the drug, the dose and you. You will be asked your name and date of birth more than once. That is on purpose. Tell them at once if you feel itchy, breathless, flushed or have pain where the drip goes in.","domain":"chemotherapy-administration","setting":{"who":["nurse","pharmacist","pharmacy-technician"],"where":["chemotherapy-day-unit","ward","home"]},"population":"Adults and children receiving parenteral anticancer therapy in a health care facility or at home. Intrathecal treatment has further rules of its own. Oral treatment is ordered and labelled under the same standards but has no chair-side verification.","trigger":"A prepared anticancer drug is ready to be given.","steps":[{"action":"On each treatment day, assess and record performance status, vital signs, date of birth, allergies and previous reactions, side effects and pain, and act on what you find","why":"A patient who is unwell on the day may need treatment delayed or the dose changed, whatever the prescription says.","source":"asco-ons-2024","quote":"On each clinical encounter or day of treatment, staff performs and documents a patient assessment that includes at least the following six elements and takes appropriate action:"},{"action":"Update the list of all medicines, including over-the-counter, herbal products and supplements, at every visit","why":"A new medicine or supplement started since the last cycle can interact with the treatment.","source":"asco-ons-2024","quote":"The patient's medication list inclusive of prescribed and over-the-counter medications, herbal products, and supplements is updated and documented in the medical record at every encounter and reviewed by a licensed practitioner when a change occurs"},{"action":"Do not give anything that has not been verified by pharmacy","why":"The chair-side check confirms what was prepared matches the order; it does not replace the clinical check of the order itself.","source":"bopa-2025","quote":"SACT must not be administered by a HCP, or taken by a patient until an appropriately trained RPP has verified the prescription."},{"action":"At preparation, have a second clinician check the vials, concentration, volume or weight, diluent, and route, filters and tubing","why":"Most preparation errors are a wrong vial strength, a wrong volume drawn up or a wrong diluent.","source":"asco-ons-2024","quote":"Upon preparation of the antineoplastic medication, a second licensed clinician approved by the health care organization to prepare antineoplastic therapy verifies:"},{"action":"After preparation and before giving it, have two licensed clinicians independently verify drug name, dose, volume, rate, route, expiry and the drug's appearance, and record it","why":"Two people checking separately are less likely to share the same mistake than one person checking twice.","source":"asco-ons-2024","quote":"After preparation and before each antineoplastic therapy administration, at least two licensed clinicians approved by the health care organization to administer or prepare antineoplastic therapy independently verify and document the accuracy of the following elements in the patient's medical record:"},{"action":"At the patient's side, have two licensed clinicians confirm the patient's identity with two identifiers, then the drug, dose, rate and duration, route, administration set and pump settings","why":"This last check, with the patient present, catches a right drug going to the wrong person or a pump set to the wrong rate.","source":"asco-ons-2024","quote":"In the presence of the patient: At least two licensed clinicians approved by the health care organization to administer or prepare antineoplastic therapy in person or through appropriate institutionally approved video-enabled technology, with at least one person on site, verify the patient's identification using at least two identifiers and document accuracy in the patient's medical record."},{"action":"Trace each line by eye from the bag through the pump to the patient before starting","why":"Following the tubing finds clamps left closed, loose connections, the wrong drug on the wrong pump and the wrong filter.","source":"asco-ons-2024","quote":"“Tracing the lines” immediately prior to administration reduces errors related to unclamped tubing, loose or disconnected lines, ensures multiple lines are infusing at the prescribed rate, the right drug is connected to the right pump, and the proper tubing or filters are used."},{"action":"Before starting, tell the patient the drug's name, how long it will run, the route, and what to report straight away, such as signs of an allergic reaction or pain at the drip site","why":"The patient is the last check, and often the first to notice a reaction or a leak into the tissues.","source":"asco-ons-2024","quote":"Before initiation of antineoplastic therapy, personnel approved by the health care organization who is administering the antineoplastic(s) confirms the therapy with the patient, including, at a minimum, the name of the drug, the infusion time, route of infusion, symptoms to report, for example: hypersensitivity symptoms or pain at infusion site"},{"action":"Make sure someone certified in basic life support is present, a licensed practitioner is on site, and allergy and extravasation drugs and order sets are within reach","why":"Severe allergic reactions and leaks of drug into the skin need treatment within minutes.","source":"asco-ons-2024","quote":"Hypersensitivity and anaphylactoid management policy is present and aligns with current literature and guidelines. Hypersensitivity order sets and medications are accessible within the appropriate timeframe for optimal treatment"},{"action":"Record that all four verifications were done, and the patient's condition during and at the end of treatment","why":"The record shows each check happened and gives the next team a baseline if a reaction comes later.","source":"asco-ons-2024","quote":"Documentation in the patient's medical record confirms the four verifications prior to parenteral antineoplastic administration and the patient's clinical status during and upon completion of antineoplastic therapy"}],"bestInClass":{"statement":"The ASCO-ONS standards (2024): four separate verifications, the last two by two licensed clinicians independently, and the fourth at the patient's side with two identifiers, pump settings and the administration set traced; a day-of-treatment assessment; the drug, time, route and warning symptoms confirmed with the patient; a basic life support provider present and reaction drugs to hand. No other current standard covering the chair-side check could be read, so there is no disagreement to report; BOPA (2025) adds that nothing may be given before a trained pharmacy professional has verified the prescription.","sources":["asco-ons-2024","bopa-2025"]},"variants":[{"name":"Three verifications (ASCO/ONS 2016)","differs":"The earlier standards required three independent verifications, at order verification, drug preparation and administration, without a separate check at the patient's side of a drug prepared elsewhere.","evidence":"Replaced in 2024. The panel added the fourth verification because many drugs are now prepared away from where they are given, such as at home or in a stand-alone unit.","sources":["asco-ons-2024"]},{"name":"Second check by video","differs":"One clinician is with the patient and the second joins the fourth verification by an approved video link, as at home.","evidence":"Allowed by ASCO-ONS 2024. The panel cites a review finding remote verification feasible and possibly similar to a live two-person check, but says no well-designed research has evaluated its effect on safety, and cautions that technology can still lead to errors.","sources":["asco-ons-2024"]}],"grades":[{"claim":"Four separate verifications, in person or by approved video","grade":"Standard (not graded)","source":"asco-ons-2024","quote":"Personnel approved by the health care organization to prepare or administer antineoplastic therapy perform four separate verifications in person or by institutionally approved video-enabled technology:"},{"claim":"A practitioner certified in basic life support present during administration","grade":"Standard (not graded)","source":"asco-ons-2024","quote":"At least one practitioner who maintains current certification in (age-appropriate) basic life support is present during antineoplastic therapy administration"},{"claim":"Remote verification: effect on safety not yet studied","grade":"Panel statement (not graded)","source":"asco-ons-2024","quote":"Authors of a review of literature and synthesis of practice interviews regarding remote verification of high-risk medications report remote verification at the point of administration is feasible and may be alike live two-person checks; however, no well-designed research has evaluated the impact on safety as of this writing."}],"sources":[{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and the Oncology Nursing Society (JCO Oncology Practice; Oncology Nursing Forum)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded. They were developed from a systematic review (PubMed January 2015 to January 2023, CINAHL to April 2023) combined with the expert panel's opinion and public comment.","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-video-second-check-safety-study"],"gaps":["The standards are not graded and no trial compares two-person checks with one-person checks, barcode scanning or smart-pump drug libraries for anticancer drugs; none of those technologies is required by the standards read.","No UK or European standard for the chair-side check could be read: the ONS Chemotherapy and Immunotherapy Guidelines are a priced book and no current UKONS or RCN document was found.","Remote (video) verification is allowed by ASCO-ONS, but its effect on safety has not been studied, in the panel's own words.","The ASCO-ONS text was read from an archived copy of the publisher's page because the publisher refuses a script."]},{"id":"sact-prescribing-and-pharmacy-verification","kind":"protocol","name":"Anticancer treatment prescribing and pharmacy verification before each cycle","aka":["chemotherapy order verification","SACT prescription verification","clinical screening of chemotherapy prescriptions","pharmacist chemotherapy check","chemotherapy order set","first verification","SACT clinical check"],"tldr":"Before any cancer drug is made up for you, the prescription is written from an agreed treatment plan and then checked by a specially trained pharmacist or pharmacy technician: that it is the right treatment for your cancer, that the dose is worked out correctly from your height, weight and kidney function, and that your blood results are good enough for treatment that day.","summary":"The US standard is the ASCO-ONS Antineoplastic Therapy Administration Safety Standards (2024), which replaced the 2016 ASCO/ONS standards; the UK standard for the pharmacy step is BOPA's Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0 (June 2025). Neither grades its standards: ASCO-ONS combined a systematic review (2015 to 2023) with panel opinion and public comment.\n\nBoth require prescribing from approved, standard regimens on electronic or preprinted order sets, by authorised prescribers. ASCO-ONS bans verbal orders except to hold or stop treatment, requires a supporting reference or a second practitioner for orders that depart from the standard regimen, and asks that height and weight be measured in metric units and verified by two people before a new plan. Its order must state the calculation method and variables, and how often they are rechecked.\n\nThe two differ on who verifies. BOPA says no anticancer treatment may be given or taken until a trained registered pharmacy professional has verified the prescription, and sets out checks for cycle 1 (consent, the regimen against the treatment plan, eligibility, allergies, interactions, critical tests such as cardiac function or genomic results) and for every cycle (dose calculation and units, blood results, renal and hepatic function, cumulative doses, supportive medicines, then a signature). ASCO-ONS requires a licensed pharmacist to verify all parenteral orders only where children under 18 are treated; for adults its first verification, before preparation, may be done by any personnel the organisation approves to prepare or give the treatment. BOPA asks for adult doses to be banded where national bands exist.","asOf":"2026-11-11","links":[],"tags":[],"related":["dpyd-testing-before-fluoropyrimidines","sact-administration-checks-at-the-chair"],"cancers":[],"sections":[],"technologies":["body-surface-area-dosing","carboplatin-calvert-dosing","chemotherapy-dosing-in-obesity","pharmacy-automation","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dose-modification"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your cancer drugs are checked by a trained pharmacy person before they are made, every cycle. It is normal to be asked your weight, your other medicines and any allergies again.","domain":"pharmacy","setting":{"who":["doctor","pharmacist","pharmacy-technician"],"where":["outpatient-clinic","aseptic-unit","chemotherapy-day-unit","ward"]},"population":"Adults and children prescribed systemic anticancer therapy by any route, in hospital, clinic or at home. BOPA excludes hormonal treatments and radiopharmaceuticals, and intrathecal treatment, which has its own national guidance. Children need extra checks (BOPA tables 2, 3 and 5; ASCO-ONS pharmacist verification).","trigger":"A cycle of anticancer treatment is prescribed, whether the first cycle of a new regimen or a later one.","steps":[{"action":"Prescribe only from a standard regimen that the organisation has defined for the diagnosis, with its references","why":"Building each prescription from an agreed, referenced plan removes most of the room for a wrong drug, dose or schedule.","source":"asco-ons-2024","quote":"The health care organization defines standard antineoplastic therapy regimens by diagnosis with references"},{"action":"Prescribe on an electronic prescribing system, within an approved protocol","why":"Electronic order sets calculate doses and carry the protocol's supportive medicines, so less is written by hand.","source":"bopa-2025","quote":"All SACT must be prescribed in the context of an approved protocol and prescribed via an electronic prescribing system."},{"action":"Do not accept verbal orders, except to hold or stop treatment","why":"A spoken dose or drug name is easily misheard and leaves no record to check.","source":"asco-ons-2024","quote":"Verbal orders are not allowed except to hold or stop antineoplastic therapy administration"},{"action":"For any order that departs from the standard regimen, record the reason and get a supporting reference or a second prescriber's authorisation","why":"Changes from the usual plan are where unusual doses and wrong combinations slip through.","source":"asco-ons-2024","quote":"The policy requires a supporting reference and/or authorization by a second licensed practitioner prior to ordering, signing, or administration of an exception order"},{"action":"Measure height and weight in kilograms and centimetres and have two people, one a licensed clinician, verify them before a new treatment plan is prepared","why":"Most doses are calculated from height and weight, so a mistake in either is carried into every drug.","source":"asco-ons-2024","quote":"Weight and height are measured and documented in the medical record in metric units (eg, kg and cm). Both the measurement and documentation are verified by two individuals, one of whom is a licensed clinician, prior to preparation and administration of a newly prescribed antineoplastic treatment plan."},{"action":"Write doses without unapproved abbreviations, without trailing zeros and with leading zeros","why":"\"1.0 mg\" can be read as 10 mg and \".5 mg\" as 5 mg; these are known causes of tenfold errors.","source":"asco-ons-2024","quote":"Doses are written following health care organization policy for preventing the use of unapproved abbreviations, omitting trailing zeros, and including leading zeros"},{"action":"Do not give or hand over any anticancer treatment until a trained pharmacist or pharmacy technician has verified the prescription","why":"A separate trained check before preparation catches errors the prescriber did not see.","source":"bopa-2025","quote":"SACT must not be administered by a HCP, or taken by a patient until an appropriately trained RPP has verified the prescription."},{"action":"At cycle 1, check consent, and check that the regimen matches the documented treatment plan or clinic letter","why":"The first cycle is where a wrong regimen or a regimen for a different stage of disease is most likely to be caught.","source":"bopa-2025","quote":"Check that the regimen prescribed matches the intended documented treatment plan and/or clinic letter."},{"action":"At cycle 1, check for interactions and duplication between the anticancer drugs, the supportive medicines and everything else the patient takes","why":"Some cancer drugs interact dangerously with common medicines, herbal products or other cancer drugs.","source":"bopa-2025","quote":"Check for potential interactions, contra-indications and duplication between all planned SACT & supportive medication and patient’s concurrent medication."},{"action":"At cycle 1, make sure the critical pre-treatment tests are done and reported, such as heart function, cumulative doses or genomic results","why":"Some results decide whether a drug can be given at all or at what dose, such as a heart scan before an anthracycline or a DPD test before fluorouracil.","source":"bopa-2025","quote":"Ensure that relevant pre-treatment critical tests have been completed and reported prior to treatment (e.g. Cardiac function, cumulative dosing, genomic testing) as these may impact eligibility for, or dosing of SACT."},{"action":"Every cycle, check the dose calculation (flat, body surface area, weight or AUC) and its units","why":"Doses change as weight and kidney function change, and a unit error can mean a dose a thousand times too large.","source":"bopa-2025","quote":"Check drug dose calculations (Flat, BSA, weight, AUC) and units are appropriate."},{"action":"Every cycle, check the blood results set by the protocol, and adjust for kidney and liver function","why":"Low blood counts or poor kidney or liver function can make a normal dose dangerous.","source":"bopa-2025","quote":"Check laboratory values (e.g.: FBC, U&Es LFTs) as defined within SACT protocol"},{"action":"Every cycle, check that lifetime maximum doses, such as for anthracyclines, will not be exceeded","why":"Some drugs damage the heart or lungs once a total amount has been given over all cycles.","source":"bopa-2025","quote":"Ensure maximum lifetime cumulative doses for e.g. anthracyclines will not be exceeded."},{"action":"Every cycle, check premedication and supportive medicines, adjusted for side effects recorded at earlier cycles","why":"Anti-sickness medicines, steroids and fluids are part of giving the treatment safely, and may need changing after a reaction.","source":"bopa-2025","quote":"Check pre-medications has been prescribed if appropriate, and adjusted if necessary in response to recorded toxicities"},{"action":"Sign and date the prescription as the record of verification","why":"The signature shows the check was done, by whom and when.","source":"bopa-2025","quote":"When satisfied that the prescription is correct sign and date prescription as a record of verification."}],"bestInClass":{"statement":"Prescribe from standard, referenced regimens on electronic order sets; no verbal orders except to hold or stop; a reference or second prescriber for exception orders; height and weight in metric units verified by two people; and a trained pharmacy professional's verification of every prescription before anything is prepared or given, with a fuller check at cycle 1 (BOPA 2025; ASCO-ONS 2024). On who verifies, the two standards differ: BOPA requires a trained registered pharmacy professional for every prescription, adult or child, while ASCO-ONS requires a licensed pharmacist only where children are treated and otherwise allows the first verification by any staff the organisation approves to prepare or give the treatment. Neither standard is graded.","sources":["asco-ons-2024","bopa-2025"]},"variants":[{"name":"Dose banding","differs":"Rounds a calculated dose to the nearest standard band of pre-made doses, rather than making each dose to the milligram.","evidence":"BOPA asks for adult doses to be banded where bands are available, by the national dose banding tables in England, Wales and Northern Ireland or the SOPPG tables in Scotland, and says banding is not usually used in children. No outcome data were read.","sources":["bopa-2025"]},{"name":"Capping body surface area","differs":"Some clinicians cap the body surface area used to calculate doses, usually in people with obesity.","evidence":"BOPA describes capping as individual or local practice and asks only that the decision be documented in the treatment plan. ASCO's guideline on dosing in obesity, not read here, is linked from the technology record on chemotherapy dosing in obesity.","sources":["bopa-2025"]},{"name":"Pharmacy technician verification","differs":"A trained pharmacy technician verifies simple prescriptions for later cycles, such as flat-dosed or well-tolerated drugs, instead of a pharmacist.","evidence":"BOPA version 5.0 sets the training and experience required and places technician verification within its level 2a; it is a governance standard, not a trial.","sources":["bopa-2025"]}],"grades":[{"claim":"Standard regimens defined by diagnosis, with references","grade":"Standard (not graded)","source":"asco-ons-2024"},{"claim":"A licensed pharmacist verifies all parenteral orders where children under 18 are treated","grade":"Standard (not graded)","source":"asco-ons-2024","quote":"A licensed pharmacist verifies all orders before dispensing parenteral antineoplastics in the health care organization that treats pediatric patients under age 18 years"},{"claim":"Cumulative doses tracked for drugs with cumulative toxicity","grade":"Standard (not graded)","source":"asco-ons-2024","quote":"Cumulative doses of antineoplastic therapy are tracked for agents associated with cumulative toxicity"},{"claim":"No anticancer treatment given or taken before verification by a trained pharmacy professional","grade":"Standard (not graded)","source":"bopa-2025"},{"claim":"Adult doses banded where bands exist","grade":"Standard (not graded)","source":"bopa-2025","quote":"Note: SACT for adult patients should be dose banded where bands are available."}],"sources":[{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and the Oncology Nursing Society (JCO Oncology Practice; Oncology Nursing Forum)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded. They were developed from a systematic review (PubMed January 2015 to January 2023, CINAHL to April 2023) combined with the expert panel's opinion and public comment.","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded; BOPA calls them the gold standard for verification and asks for a local risk assessment where a service departs from them.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["Neither standard is graded, and ASCO-ONS says several of its sections rest mainly on expert experience; no trial compares one verification process with another.","ASCO-ONS and BOPA differ on whether a pharmacist (or trained pharmacy professional) must verify every adult prescription; ASCO-ONS requires a licensed pharmacist only where children are treated.","The ASHP guidelines on preventing medication errors with chemotherapy (2015) could not be read and are not cited.","How often weight should be rechecked, and the percentage change that triggers a recalculated dose, are left to local policy by both standards.","The ASCO-ONS text was read from an archived copy of the publisher's page because the publisher refuses a script; the ONS version of the same standards served only a preview."]},{"id":"anticipatory-nausea-and-vomiting","kind":"protocol","name":"Anticipatory nausea and vomiting before chemotherapy: prevention and treatment","aka":["anticipatory nausea","ANV","conditioned nausea before chemotherapy","anticipatory emesis","feeling sick before chemotherapy"],"tldr":"Some people feel sick, or are sick, before a chemotherapy session, set off by the hospital or a smell: a learned reaction to sickness in earlier cycles. The best protection is good anti-sickness medicine from the first cycle. If it happens, tell your team: relaxation training helps, and a calming tablet such as lorazepam the night before and on the morning of treatment can be offered.","summary":"Anticipatory nausea and vomiting is a conditioned response that follows poorly controlled nausea in earlier cycles. MASCC/ESMO (2016, unchanged from 2009 and still the latest statement) recommend preventing it by optimal control of acute and delayed chemotherapy-induced nausea and vomiting, and treating it with benzodiazepines and behavioural therapies, in particular progressive muscle relaxation, systematic desensitisation and hypnosis; their 2016 search found no new trial meeting its criteria. eviQ (reviewed 2024) gives lorazepam 0.5 to 1 mg orally the night before and 1 to 2 hours before treatment. A 2024 meta-analysis for the Japanese antiemesis guideline found that systematic desensitisation reduced anticipatory nausea (risk ratio 0.60) and vomiting (0.54) in a few small, mostly high-risk-of-bias studies. In a randomised trial of 474 people, 20-minute nurse-delivered mindfulness relaxation or relaxing music reduced anticipatory nausea at the midpoint of chemotherapy but not at the end. The 2023 MASCC/ESMO update suggests progressive muscle relaxation, alone or with guided imagery, as an adjunct for chemotherapy-induced nausea generally [II, B].","asOf":"2026-11-11","links":[],"tags":["protocol","nausea-and-vomiting","supportive-care"],"related":["antiemetic-prophylaxis-by-emetic-risk"],"cancers":[],"sections":["supportive-care"],"technologies":["antiemetic-therapy","relaxation-guided-imagery","hypnosis-cancer-care"],"targets":[],"drugs":[],"companies":[],"institutions":["mascc","esmo"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some people feel sick before chemo because of bad sickness last time. Good sickness medicine from the start helps stop this. Relaxing exercises and a calming tablet can help.","domain":"symptom-management","setting":{"who":["nurse","doctor","pharmacist","patient-or-carer"],"where":["chemotherapy-day-unit","outpatient-clinic","home"]},"population":"Children and adults receiving chemotherapy (the MASCC/ESMO statement covers both); the lorazepam dose given is for adults. Most trial participants were women with breast cancer.","trigger":"Before the first cycle (prevention); and whenever a person reports nausea or vomiting starting before a treatment session.","steps":[{"action":"Give guideline antiemetic prophylaxis for the emetic risk of the regimen from the first cycle, and treat breakthrough nausea promptly","why":"Anticipatory nausea is learned from bad experiences in earlier cycles; preventing that first bad experience is the most effective protection.","source":"eviq-7","quote":"The best management of anticipatory emesis is to ensure good control of acute and delayed emesis, starting from the initial anti-cancer treatment cycle."},{"action":"Before each cycle, ask whether nausea or vomiting starts before treatment, for example on the way to hospital or at the sight or smell of the unit","why":"It is easily missed unless asked about, and recognising it early allows treatment before it becomes entrenched.","source":"eviq-7","quote":"Anticipatory emesis: occurring before receiving next treatment of anti-cancer therapy. It is a conditioned response, typically occurring after a previous negative experience with anti-cancer therapy."},{"action":"Offer a behavioural therapy: progressive muscle relaxation training, systematic desensitisation or hypnosis","why":"These techniques help unlearn the link between the treatment setting and feeling sick.","source":"mascc-esmo-2016-anv","quote":"Benzodiazepines and behavioral therapies, in particular progressive muscle relaxation training, systematic desensitization and hypnosis, continue to be recommended for the treatment of anticipatory nausea and vomiting."},{"action":"Offer a benzodiazepine, for example lorazepam 0.5 to 1 mg by mouth the night before and again 1 to 2 hours before treatment","why":"A benzodiazepine reduces anxiety and the learned nausea that comes with it.","source":"eviq-7","quote":"For patients who do develop anticipatory emesis, non-pharmacologic methods such as behavioural/psychological techniques may be useful and/or benzodiazepines e.g. lorazepam 0.5 mg to 1 mg orally on the night before and then repeated the next day 1-2 hours before anti-cancer treatment."},{"action":"Suggest progressive muscle relaxation, alone or with guided imagery, alongside antiemetics during chemotherapy","why":"Relaxation reduces nausea after chemotherapy as well, which helps prevent the bad experiences that anticipatory nausea grows from.","source":"mascc-esmo-2023","quote":"The adjunctive use of PMRT (alone or with GI) is suggested for the management of CINV [II, B].","grade":"[II, B]"}],"bestInClass":{"statement":"MASCC/ESMO 2016 remains the latest international statement (the 2023 update did not revisit anticipatory nausea): prevent it through optimal control of acute and delayed nausea from the first cycle, and treat it with benzodiazepines and behavioural therapy (progressive muscle relaxation, systematic desensitisation, hypnosis). eviQ (2024) agrees and gives the lorazepam dose. The evidence under the treatment recommendations is thin: MASCC/ESMO found no new trial meeting its criteria in 2016, and the Japanese guideline's 2024 meta-analysis supports systematic desensitisation from small, mostly high-risk-of-bias studies.","sources":["mascc-esmo-2016-anv","mascc-2023-committees","eviq-7","jsco-2024-anv"]},"variants":[{"name":"Brief nurse-delivered mindfulness relaxation or relaxing music before chemotherapy","differs":"A 20-minute session given by an oncology nurse, of mindfulness relaxation or relaxing music, rather than a course of behavioural therapy from a psychologist.","evidence":"Randomised trial of 474 people (mostly women with early breast cancer): both reduced anticipatory nausea at the midpoint of chemotherapy against standard care (odds ratios 0.44 and 0.40) but not at the end, and did not change anticipatory vomiting or nausea after chemotherapy.","sources":["hunter-2020"]},{"name":"Systematic desensitisation as the preferred behavioural therapy (Japanese antiemesis guideline 2023)","differs":"Singles out systematic desensitisation among behavioural methods; hypnotherapy and yoga could not be pooled.","evidence":"Meta-analysis of two studies: risk ratio 0.60 for anticipatory nausea and 0.54 for anticipatory vomiting; most included studies at high or unclear risk of bias. The authors call for further research before routine use.","sources":["jsco-2024-anv"]},{"name":"Sublingual lorazepam for anticipatory or anxiety-related nausea in palliative care (Scotland)","differs":"In palliative care, gives lorazepam 500 micrograms to 1 mg sublingually (an unlicensed route), with diazepam or midazolam as second line, and pairs antiemetics with assessment and treatment of anxiety.","evidence":"National palliative care guideline (2025), based on an evidence review and expert opinion; not graded for this point.","sources":["scottish-palliative-nv-2025"]}],"grades":[{"claim":"Anticipatory nausea is best prevented by optimal control of acute and delayed nausea","grade":"MASCC/ESMO consensus recommendation (grade not shown in the abstract read)","source":"mascc-esmo-2016-anv","quote":"The guideline panel continues to recommend that anticipatory nausea and vomiting are best prevented through optimization of acute and delayed phase chemotherapy-induced nausea and vomiting control."},{"claim":"Systematic desensitisation reduced anticipatory nausea","grade":"meta-analysis, RR 0.60 (95% CI 0.49 to 0.72)","source":"jsco-2024-anv","quote":"Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02)."},{"claim":"Progressive muscle relaxation, alone or with guided imagery, as an adjunct for chemotherapy-induced nausea","grade":"[II, B]","source":"mascc-esmo-2023","quote":"The adjunctive use of PMRT (alone or with GI) is suggested for the management of CINV [II, B]."}],"sources":[{"key":"mascc-esmo-2016-anv","label":"2016 updated MASCC/ESMO consensus recommendations: Anticipatory nausea and vomiting in children and adults receiving chemotherapy","publisher":"MASCC/ESMO, Supportive Care in Cancer","year":2017,"url":"https://europepmc.org/abstract/MED/27510314","doi":"10.1007/s00520-016-3330-z","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-esmo-2023","label":"2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting","publisher":"MASCC/ESMO, ESMO Open","year":2024,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10937211/","doi":"10.1016/j.esmoop.2023.102195","gradingScheme":"ESMO levels of evidence (I to V) and grades of recommendation (A to E), in square brackets.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-2023-committees","label":"MASCC/ESMO Antiemetic Guideline 2023: committee slide set","publisher":"MASCC","year":2025,"url":"https://mascc.org/wp-content/uploads/2025/04/Antiemetic-guidelines-2023-slides-v2.pdf","gradingScheme":"Slide summary of the 2023 update; lists the ten committees, none on anticipatory nausea.","read":"full-text","accessed":"2026-11-11"},{"key":"eviq-7","label":"Prevention of anti-cancer therapy induced nausea and vomiting (AINV) (ID 7)","publisher":"eviQ, Cancer Institute NSW","year":2024,"url":"https://www.eviq.org.au/p/7","gradingScheme":"Evidence-based summary built on ASCO 2020, NCCN 2024 and MASCC/ESMO 2023; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"jsco-2024-anv","label":"Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023","publisher":"International Journal of Clinical Oncology","year":2024,"url":"https://europepmc.org/abstract/MED/38722486","doi":"10.1007/s10147-024-02536-w","read":"abstract","accessed":"2026-11-11"},{"key":"hunter-2020","label":"A randomized trial of nurse-administered behavioral interventions to manage anticipatory nausea and vomiting in chemotherapy","publisher":"Cancer Medicine","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7050098/","doi":"10.1002/cam4.2863","read":"full-text","accessed":"2026-11-11"},{"key":"scottish-palliative-nv-2025","label":"Scottish Palliative Care Guidelines: Nausea and vomiting","publisher":"Healthcare Improvement Scotland (Right Decision Service)","year":2025,"url":"https://www.palliativecareguidelines.scot.nhs.uk/scottish-palliative-care-guidelines/symptoms/non-pain-symptoms/nausea-and-vomiting/","gradingScheme":"Evidence review with SIGN methodology ratings for references; recommendations are not individually graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 2016 MASCC/ESMO statement was read only as an abstract; its levels of evidence, its dose recommendations and its advice for children are not shown here.","The ASCO (2020) and NCCN antiemesis guidelines' sections on anticipatory nausea were not read.","No trial in the sources read compares a benzodiazepine with a behavioural therapy, or tests either in the era of olanzapine and NK1 antagonists, which may have made anticipatory nausea less common.","Advice on drowsiness, driving and falls with lorazepam is not given in the sources read, and should come from the prescriber.","How many people are offered behavioural therapy, and who delivers it, has not been measured in any source read."]},{"id":"anticoagulants-and-antiplatelets-before-endoscopy","kind":"protocol","name":"Anticoagulants and antiplatelet drugs around elective endoscopy and endoscopic biopsy","aka":["stopping blood thinners before endoscopy","warfarin before colonoscopy","DOAC before endoscopy","apixaban before endoscopy","rivaroxaban before colonoscopy","clopidogrel before endoscopy","aspirin before endoscopy","heparin bridging endoscopy","antithrombotics and polypectomy"],"tldr":"If you take a blood thinner or a drug like aspirin or clopidogrel, tell the team well before an endoscopy or colonoscopy. For a simple look with small biopsies most people carry on, perhaps missing one morning dose. For riskier procedures, such as removing polyps, the team will say which drug to stop, for how long, and when to restart. Never stop a heart or clot medicine on your own.","summary":"BSG/ESGE 2021 (GRADE) sorts procedures by bleeding risk (low: diagnostic endoscopy with or without biopsy, stenting, EUS without sampling; high: polypectomy, endoscopic resection, ERCP with sphincterotomy, EUS-guided sampling, PEG and others) and patients by thrombotic risk. Everyone is told both the thrombotic risk of stopping and the bleeding risk of continuing (strong, low). Aspirin continues for all procedures except ampullectomy (strong, low). Low-risk procedures: continue P2Y12 inhibitors, single or dual (strong, low); continue warfarin with an INR within range in the week before (weak, low); omit the morning DOAC dose (weak, low). High-risk procedures, low thrombotic risk: stop P2Y12 inhibitors 7 days before (strong, moderate) keeping aspirin; stop warfarin 5 days before with INR below 1.5 (strong, high); last DOAC dose 3 days before (strong, low), 5 days for dabigatran with clearance 30 to 50 ml/min. High thrombotic risk: keep aspirin and discuss P2Y12 interruption with an interventional cardiologist (strong, high); bridge warfarin with LMWH (strong, low). Restart within 2 to 3 days (strong, moderate). ACG-CAG 2022 (GRADE, all conditional) differs: it suggests continuing warfarin for elective endoscopy generally and suggests against heparin bridging when warfarin is held, suggests interrupting DOACs rather than continuing them, suggests not interrupting aspirin for secondary prevention, interrupting the P2Y12 inhibitor but not aspirin on dual therapy, and could not recommend on resumption timing.","asOf":"2026-11-11","links":[],"tags":[],"related":["antithrombotic-interruption-around-surgery"],"cancers":[],"sections":[],"technologies":["cancer-associated-thrombosis","endoscopic-resection"],"targets":[],"drugs":["aspirin"],"companies":[],"institutions":[],"pathways":[],"terms":["endoscopy","colonoscopy","vte"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Tell the team about any blood thinner. Usually you keep taking aspirin. For a simple test you may skip one morning dose of some blood thinners. For bigger procedures you may stop for a few days, as the team tells you. Do not stop on your own.","domain":"screening-diagnostics","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","ward","home"]},"population":"Adults taking an anticoagulant (warfarin, a direct oral anticoagulant, or low molecular weight heparin) or an antiplatelet drug (aspirin, clopidogrel, prasugrel, ticagrelor) who need elective gastrointestinal endoscopy, including people with cancer and cancer-associated thrombosis. Acute GI bleeding is a different setting (both guidelines address it separately). Image-guided percutaneous biopsy (liver, lung, bone, kidney) is not covered: its guidelines could not be read. Children are not covered.","trigger":"An elective endoscopy or colonoscopy is booked for someone taking an anticoagulant or antiplatelet drug.","steps":[{"action":"When booking, record every anticoagulant and antiplatelet drug, why it is taken, and the planned procedure, and judge both the bleeding risk of the procedure and the clot risk of stopping","why":"Whether to stop depends on both: how likely the procedure is to bleed, and how dangerous a pause is for the heart or a clot.","source":"bsg-esge-2021","quote":"We recommend that all patients are advised of the thrombotic risks of discontinuing antiplatelets or anticoagulants, as well as the haemorrhagic risks of continuing therapy (strong recommendation, low quality evidence).","grade":"strong recommendation, low quality evidence"},{"action":"Keep taking aspirin for all endoscopic procedures, except ampullectomy","why":"Aspirin adds little bleeding risk to endoscopy, and stopping it can trigger a heart attack or stroke.","source":"bsg-esge-2021","quote":"For all endoscopic procedures we recommend continuing aspirin (strong recommendation, low quality evidence), with the exception of ampullectomy (weak recommendation, low quality evidence).","grade":"strong recommendation, low quality evidence"},{"action":"For low-risk procedures such as diagnostic endoscopy with biopsy, continue clopidogrel, prasugrel or ticagrelor","why":"Ordinary biopsies rarely bleed enough to matter.","source":"bsg-esge-2021","quote":"For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (DAPT) (strong recommendation, low quality evidence).","grade":"strong recommendation, low quality evidence"},{"action":"For low-risk procedures, continue warfarin and check that the INR has not been above range in the week before","why":"Warfarin can be kept going for simple procedures as long as the blood is not thinner than intended.","source":"bsg-esge-2021","quote":"It should be ensured that the international normalised ratio (INR) does not exceed the therapeutic range in the week prior to the procedure (strong recommendation, low quality evidence).","grade":"strong recommendation, low quality evidence"},{"action":"For low-risk procedures on a direct oral anticoagulant (apixaban, rivaroxaban, edoxaban, dabigatran), omit only the morning dose on the day","why":"Skipping one dose lowers the drug level at the time of the biopsy without leaving a long gap in protection.","source":"bsg-esge-2021","quote":"For low-risk endoscopic procedures we suggest omitting the morning dose of direct oral anticoagulants (DOACs) on the day of the procedure (weak recommendation, low quality evidence).","grade":"weak recommendation, low quality evidence"},{"action":"For high-risk procedures in people at low clot risk, stop clopidogrel, prasugrel or ticagrelor 7 days before, keeping aspirin if on dual therapy","why":"These drugs affect platelets for about a week, and procedures such as polyp removal can bleed.","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists 7 days before the procedure (strong recommendation, moderate quality evidence).","grade":"strong recommendation, moderate quality evidence"},{"action":"For high-risk procedures in people at low clot risk, stop warfarin 5 days before and check the INR is below 1.5","why":"Warfarin takes several days to wear off; the INR confirms it has.","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing warfarin for 5 days before the procedure (strong recommendation, high quality evidence).","grade":"strong recommendation, high quality evidence"},{"action":"For high-risk procedures on a direct oral anticoagulant, take the last dose 3 days before (5 days for dabigatran with reduced kidney function), and ask a haematologist if kidney function is falling fast","why":"These drugs clear in a few days, faster or slower depending on the kidneys.","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients on DOACs, we recommend that the last dose of DOACs be taken 3 days before the procedure (strong recommendation, low quality evidence).","grade":"strong recommendation, low quality evidence"},{"action":"For people at high clot risk (recent coronary stents, mechanical heart valves, recent clots), keep aspirin and plan any pause with the cardiologist; bridge warfarin with low molecular weight heparin","why":"For them a pause in treatment can cause a stent to block or a clot to form, which may be worse than bleeding.","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a consultant interventional cardiologist about the risk/benefit of discontinuing P2Y12 receptor antagonists (strong recommendation, high quality evidence).","grade":"strong recommendation, high quality evidence"},{"action":"Restart any drug that was stopped within 2 to 3 days after the procedure, and tell the person that bleeding afterwards is more likely while on these drugs","why":"The longer the pause, the higher the risk of a clot; the timing balances that against bleeding from the site.","source":"bsg-esge-2021","quote":"If antiplatelet or anticoagulant therapy is discontinued, then we recommend this should be resumed up to 2–3 days after the procedure depending on the perceived haemorrhagic and thrombotic risks (strong recommendation, moderate quality evidence).","grade":"strong recommendation, moderate quality evidence"}],"bestInClass":{"statement":"BSG/ESGE 2021 for UK and European practice: classify the procedure's bleeding risk and the patient's thrombotic risk; continue aspirin; for low-risk procedures continue P2Y12 inhibitors and warfarin (INR in range) and omit the morning DOAC dose; for high-risk procedures at low thrombotic risk stop P2Y12 inhibitors 7 days, warfarin 5 days (INR below 1.5) and DOACs 3 days before; at high thrombotic risk involve cardiology and bridge warfarin; restart within 2 to 3 days. The North American ACG-CAG guideline (2022) disagrees on two points, both on conditional recommendations: it suggests continuing warfarin for elective endoscopy rather than interrupting it, and suggests against heparin bridging when warfarin is held. Both agree on continuing aspirin for secondary prevention and on interrupting DOACs, rather than continuing them, for procedures that need it.","sources":["bsg-esge-2021","acg-cag-2022"]},"variants":[{"name":"ACG-CAG: continue warfarin and do not bridge","differs":"Suggests continuing warfarin for elective endoscopic procedures rather than interrupting it for 1 to 7 days, and, where it is held, suggests against heparin bridging; it excludes patients at high thromboembolic risk, for whom elective procedures should be deferred.","evidence":"Conditional recommendations: very low certainty for continuing warfarin, low certainty against bridging. BSG/ESGE itself notes studies showing more post-polypectomy bleeding with LMWH bridging without fewer clots, while still advising bridging for those at high thromboembolic risk.","sources":["acg-cag-2022","bsg-esge-2021"]},{"name":"ACG-CAG: no recommendation on single P2Y12 inhibitor or on restart timing","differs":"For patients on a P2Y12 inhibitor alone, ACG-CAG could not recommend for or against interruption, and it could not recommend a time to resume warfarin, a DOAC or a P2Y12 inhibitor (same day versus 1 to 7 days). BSG/ESGE gives 7 days off before high-risk procedures and restart within 2 to 3 days.","evidence":"ACG-CAG found one randomised trial and one cohort study for P2Y12 interruption and no comparative studies of resumption timing.","sources":["acg-cag-2022","bsg-esge-2021"]}],"grades":[{"claim":"Bridge warfarin with LMWH for high-risk procedures in people at high thrombotic risk","grade":"strong recommendation, low quality evidence","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend that warfarin should be temporarily discontinued and substituted with low molecular weight heparin (LMWH) (strong recommendation, low quality evidence)."},{"claim":"Check INR below 1.5 before a high-risk procedure after stopping warfarin","grade":"strong recommendation, low quality evidence","source":"bsg-esge-2021","quote":"Check INR prior to the procedure to ensure <1.5 (strong recommendation, low quality evidence)."},{"claim":"Dabigatran with creatinine clearance 30 to 50 ml/min: last dose 5 days before","grade":"strong recommendation, low quality evidence","source":"bsg-esge-2021","quote":"For patients on dabigatran with a creatinine clearance (CrCl) (or estimated glomerular filtration rate (eGFR)) of 30–50 mL/min we recommend that the last dose be taken 5 days prior to the procedure (strong recommendation, low quality evidence)."},{"claim":"Continue warfarin rather than interrupt it for elective endoscopy (US and Canada)","grade":"conditional recommendation, very low certainty of evidence","source":"acg-cag-2022","quote":"For patients on warfarin undergoing elective/planned endoscopic GI procedures, we suggest warfarin be continued, as opposed to temporarily interrupted (1–7 days) (conditional recommendation, very low certainty of evidence)."},{"claim":"No heparin bridging when warfarin is held (US and Canada)","grade":"conditional recommendation, low certainty of evidence","source":"acg-cag-2022","quote":"For patients on warfarin, who hold warfarin in the periprocedural period for elective/planned endoscopic GI procedures, we suggest against bridging anticoagulation (conditional recommendation, low certainty of evidence)."},{"claim":"Interrupt DOACs rather than continue them (US and Canada)","grade":"conditional recommendation, very low certainty of evidence","source":"acg-cag-2022","quote":"For patients on direct oral anticoagulants (DOACs) who are undergoing elective/planned endoscopic GI procedures, we suggest temporarily interrupting DOACs rather than continuing DOACs (conditional recommendation, very low certainty of evidence)."},{"claim":"Do not interrupt aspirin for secondary prevention (US and Canada)","grade":"conditional recommendation, very low certainty of evidence","source":"acg-cag-2022","quote":"For patients on ASA 81–325 mg/d (monotherapy) for secondary cardiovascular prevention, we suggest against interruption of ASA (conditional recommendation, very low certainty of evidence)."}],"sources":[{"key":"bsg-esge-2021","label":"Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update","publisher":"BSG and ESGE (Veitch et al., Gut; also published in Endoscopy, 10.1055/a-1547-2282)","year":2021,"url":"https://doi.org/10.1136/gutjnl-2021-325184","doi":"10.1136/gutjnl-2021-325184","gradingScheme":"GRADE: strong or weak recommendation; high, moderate, low or very low quality evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"acg-cag-2022","label":"American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period","publisher":"ACG and CAG (Abraham et al., American Journal of Gastroenterology)","year":2022,"url":"https://doi.org/10.14309/ajg.0000000000001627","doi":"10.14309/ajg.0000000000001627","gradingScheme":"GRADE: strong or conditional recommendation; high, moderate, low or very low certainty of evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"sir-2019","label":"Society of Interventional Radiology Consensus Guidelines for the Periprocedural Management of Thrombotic and Bleeding Risk in Patients Undergoing Percutaneous Image-Guided Interventions, Part II: Recommendations","publisher":"Society of Interventional Radiology (Journal of Vascular and Interventional Radiology)","year":2019,"url":"https://doi.org/10.1016/j.jvir.2019.04.017","doi":"10.1016/j.jvir.2019.04.017","read":"not-reachable","accessed":"2026-11-11"},{"key":"cirse-2021","label":"CIRSE Standards of Practice on Peri-operative Anticoagulation Management During Interventional Radiology Procedures","publisher":"Cardiovascular and Interventional Radiological Society of Europe (Cardiovascular and Interventional Radiology)","year":2021,"url":"https://doi.org/10.1007/s00270-020-02763-4","doi":"10.1007/s00270-020-02763-4","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-pu-lmwh-plan-around-endoscopy"],"gaps":["Image-guided percutaneous biopsy and other interventional radiology procedures are not covered: the SIR 2019 consensus guidelines (no abstract in Europe PMC, paywalled) and the CIRSE 2021 Standards of Practice (paywalled; abstract states only the aim) could not be read.","Neither guideline read gives specific advice for low molecular weight heparin used to treat cancer-associated thrombosis, which many people with cancer take; BSG/ESGE discusses LMWH only as a bridge for warfarin.","Most recommendations rest on low or very low quality evidence, and the two guidelines disagree on continuing warfarin and on bridging.","Thrombocytopenia from chemotherapy or marrow disease, which also changes bleeding risk, is outside both guidelines."]},{"id":"cancer-associated-vte-treatment","kind":"protocol","name":"Anticoagulation for a blood clot in a person with cancer: choice of drug, duration and special situations","aka":["cancer-associated thrombosis treatment","CAT treatment","DVT in cancer","pulmonary embolism in cancer","DOAC or LMWH in cancer","apixaban for cancer clot","dalteparin","anticoagulation duration cancer"],"tldr":"Clots in a leg vein or the lungs are common in cancer. They are treated with blood thinners, either daily injections (low-molecular-weight heparin) or tablets (such as apixaban, rivaroxaban or edoxaban), usually for at least six months and often while the cancer is active. Tablets suit most people, but injections may be safer with some stomach, bowel or bladder cancers and some cancer drugs.","summary":"ITAC (2022) recommends LMWH for initial treatment when creatinine clearance is at least 30 mL/min (1A), or rivaroxaban or apixaban from the start, or edoxaban after at least 5 days of parenteral anticoagulation, in patients not at high risk of gastrointestinal or genitourinary bleeding (1A). For maintenance, LMWH is preferred over vitamin K antagonists (1A) and DOACs are recommended in the absence of strong drug interactions or impaired gastrointestinal absorption (1A), with caution in gastrointestinal, especially upper gastrointestinal, cancers. Treat for at least 6 months (1A); after 6 months, continue or stop by individual assessment of benefit and risk and cancer activity (guidance). ASCO (2023) is concordant: LMWH, edoxaban, rivaroxaban or apixaban for at least 6 months, preferred over VKAs (strong, high-quality evidence), noting less recurrence but more clinically relevant non-major bleeding with factor Xa inhibitors and checking drug interactions first.\n\nNICE NG158 (2020) differs on emphasis and duration: it suggests considering a DOAC first and, if unsuitable, LMWH alone or with a VKA, and gives 3 to 6 months then review, saying evidence on duration in active cancer is very limited. ASH (2021, abstract) makes conditional recommendations for LMWH or DOAC initially, a DOAC for short-term treatment and LMWH or DOAC long term. ITAC treats incidental clots like symptomatic ones. For special situations ITAC gives guidance, not graded evidence: full-dose anticoagulation if platelets are above 50 x 10^9/L without bleeding, case-by-case below that; unfractionated heparin then early VKA, or anti-Xa-adjusted LMWH, when creatinine clearance is below 30 mL/min; LMWH or DOAC with a brain tumour (2A); LMWH in pregnancy. For recurrence on treatment, increase LMWH by 20 to 25% or switch class (guidance). Vena cava filters only when anticoagulation is contraindicated or a PE recurs despite optimal treatment (guidance).","asOf":"2026-11-11","links":[],"tags":[],"related":["catheter-related-thrombosis-in-cancer"],"cancers":[],"sections":[],"technologies":["cancer-associated-thrombosis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["vte","thrombocytopenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A clot in someone with cancer is treated with blood thinners, as injections or tablets, usually for six months or more. Your team picks the one that is safest with your cancer and your other medicines.","domain":"supportive-care","setting":{"who":["doctor","pharmacist","nurse"],"where":["acute-oncology-service","emergency-department","ward","outpatient-clinic"]},"population":"Adults with active cancer and a confirmed deep vein thrombosis or pulmonary embolism, symptomatic or found incidentally on a scan. Clots related to a central venous catheter have their own protocol. Children follow paediatric guidance; ITAC gives separate recommendations for children with central lines. NICE's recommendations for active cancer apply to proximal DVT or PE.","trigger":"A deep vein thrombosis or pulmonary embolism is confirmed in a person with active cancer.","steps":[{"action":"Start anticoagulation with low-molecular-weight heparin, or with rivaroxaban or apixaban from day one, if kidney function allows (creatinine clearance 30 mL/min or more)","why":"Both injections and tablets prevent the clot growing or coming back; the choice depends on the person's bleeding risk, cancer and other medicines.","source":"itac-2022","quote":"Low-molecular-weight heparin (LMWH) is recommended for the initial treatment of established VTE in patients with cancer when creatinine clearance is ≥30 mL/min (grade 1A).","grade":"1A"},{"action":"Use a tablet (DOAC) only where the risk of gut or bladder bleeding is not high; edoxaban needs at least 5 days of injections first","why":"In trials, the tablets caused more bleeding from tumours of the stomach, bowel and urinary tract.","source":"itac-2022","quote":"For patients who do not have a high risk of gastrointestinal or genitourinary bleeding, rivaroxaban or apixaban (in the first 10 days), or edoxaban (started after at least 5 days of parenteral anticoagulation) can also be used for the initial treatment of established VTE in patients with cancer when creatinine clearance is ≥30 mL/min (grade 1A).","grade":"1A"},{"action":"Before choosing, take into account the tumour site, interactions with cancer drugs, and the person's bleeding risk","why":"Some cancer drugs change blood levels of the tablets, and some tumours bleed easily.","source":"nice-ng158","quote":"When choosing anticoagulation treatment for people with active cancer and confirmed proximal DVT or PE, take into account the tumour site, interactions with other drugs including those used to treat cancer, and the person's bleeding risk.","grade":"[2020]"},{"action":"Check for drug interactions before starting a factor Xa inhibitor tablet","why":"Interactions with cancer treatments can make the tablet too strong (bleeding) or too weak (new clots).","source":"asco-2023","quote":"Drug-drug interaction should be checked before using a direct factor Xa inhibitor (Type: Evidence based; Evidence quality: High; Strength of recommendation: Strong).","grade":"Evidence based; Evidence quality: High; Strength of recommendation: Strong"},{"action":"Treat for at least 6 months, with low-molecular-weight heparin or a DOAC rather than warfarin","why":"Clots often come back in people with active cancer; six months was the length tested in the trials.","source":"itac-2022","quote":"LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer (grade 1A).","grade":"1A"},{"action":"At 6 months, decide with the patient whether to continue, based on cancer activity, bleeding, tolerability and preference","why":"The risk of another clot stays high while the cancer is active, but so does the risk of bleeding.","source":"itac-2022","quote":"After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit–risk ratio, tolerability, drug availability, patient preference, and cancer activity (guidance, in the absence of data).","grade":"guidance"},{"action":"Treat a clot found incidentally on a staging scan the same way as one that causes symptoms","why":"Clots found by chance carried the same risks as symptomatic ones in the trials.","source":"itac-2022","quote":"These findings further support managing patients with incidental cancer-associated thrombosis in a similar manner as symptomatic cancer-associated thrombosis."},{"action":"If platelets are low, give full-dose anticoagulation only above a platelet count of 50 x 10^9/L without bleeding; below that, decide case by case with great caution","why":"Chemotherapy can lower platelets, and anticoagulation with very low platelets risks serious bleeding.","source":"itac-2022","quote":"decisions on treatment and dose should be made on a case-by-case basis with the utmost caution (guidance, in the absence of data and a balance between desirable and undesirable effects depending on the bleeding risk vs VTE risk).","grade":"guidance"},{"action":"If creatinine clearance is below 30 mL/min, use unfractionated heparin followed by early warfarin, or LMWH adjusted by anti-Xa levels","why":"LMWH and the tablets build up when the kidneys are failing.","source":"itac-2022","quote":"In the presence of severe renal failure (creatinine clearance <30 mL/min), we suggest using unfractionated heparin followed by early vitamin K antagonists (possible from day 1) or LMWH adjusted to anti-Xa concentration for the treatment of established VTE (guidance, in the absence of data and an unknown balance between desirable and undesirable effects).","grade":"guidance"},{"action":"If a clot recurs despite treatment, increase LMWH by 20 to 25%, or switch between LMWH and a DOAC","why":"A clot that recurs on treatment may need a stronger dose or a different drug.","source":"itac-2022","quote":"In the event of VTE recurrence, three options can be considered: (1) increase LMWH by 20–25% or switch to direct oral anticoagulants; (2) for direct oral anticoagulants, switch to LMWH; and (3) for vitamin K antagonist, switch to LMWH or direct oral anticoagulants (guidance, based on evidence of very low quality and an unknown balance between desirable and undesirable effects).","grade":"guidance"},{"action":"Consider a vena cava filter only if anticoagulation cannot be given, or a pulmonary embolism recurs despite optimal treatment, and restart anticoagulation when safe","why":"A filter can stop clots reaching the lungs but does not treat the clot and can cause its own problems.","source":"itac-2022","quote":"In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation.","grade":"guidance"}],"bestInClass":{"statement":"For most people with active cancer: LMWH or a DOAC (apixaban, rivaroxaban, or edoxaban after 5 days of parenteral treatment), for at least 6 months, rather than a vitamin K antagonist (ITAC 2022, 1A; ASCO 2023, strong, high-quality evidence), with LMWH favoured where gastrointestinal or genitourinary bleeding risk is high or strong drug interactions exist, and a decision at 6 months on continuing. The guidelines differ on duration and order of preference: ITAC and ASCO set a minimum of 6 months; NICE NG158 (2020) treats for 3 to 6 months then reviews, and suggests considering a DOAC first; ASH 2021 (read as abstract) conditionally favours a DOAC for short-term treatment. ESMO 2023 could not be read.","sources":["itac-2022","asco-2023","nice-ng158","ash-2021"]},"variants":[{"name":"DOAC first (NICE)","differs":"Considers a DOAC as the first choice and LMWH (alone or with a VKA) only if a DOAC is unsuitable, for 3 to 6 months and then review.","evidence":"NICE NG158 [2020]. Its committee found evidence on duration in active cancer very limited and judged apixaban the most cost-effective option on a small number of people with cancer in the trials. Most anticoagulants were off label for cancer-associated VTE in the UK in March 2020.","sources":["nice-ng158"]},{"name":"LMWH alone for the whole course","differs":"Uses daily LMWH injections throughout, the standard before DOACs.","evidence":"ITAC: LMWH for 6 months was more effective than VKAs in five randomised trials without more bleeding; DOACs reduce recurrence compared with LMWH (pooled RR 0.62, 95% CI 0.43 to 0.91) without a significant increase in major bleeding, but with more clinically relevant non-major bleeding, and one meta-analysis in gastrointestinal cancers found more major bleeding with DOACs (RR 2.3).","sources":["itac-2022"]}],"grades":[{"claim":"LMWH for initial treatment (creatinine clearance 30 mL/min or more)","grade":"1A","source":"itac-2022"},{"claim":"Rivaroxaban, apixaban or edoxaban for initial treatment, without high gastrointestinal or genitourinary bleeding risk","grade":"1A","source":"itac-2022"},{"claim":"DOACs for maintenance in the absence of strong drug interactions or impaired gastrointestinal absorption","grade":"1A","source":"itac-2022","quote":"Direct oral anticoagulants (edoxaban, rivaroxaban, or apixaban) are recommended for patients with cancer when creatinine clearance is ≥30 mL/min in the absence of strong drug–drug interactions or gastrointestinal absorption impairment (grade 1A)."},{"claim":"Minimum 6 months of LMWH or DOAC","grade":"1A","source":"itac-2022"},{"claim":"LMWH, edoxaban, rivaroxaban or apixaban for at least 6 months, preferred over VKAs","grade":"Evidence based; Evidence quality: High; Strength of recommendation: Strong","source":"asco-2023","quote":"For long-term anticoagulation, LMWH, edoxaban, rivaroxaban, or apixaban for at least 6 months are preferred over vitamin K antagonists (VKAs) because of improved efficacy."},{"claim":"Brain tumour: LMWH or DOAC","grade":"2A","source":"itac-2022","quote":"For the treatment of established VTE in patients with a brain tumour, low-molecular-weight heparin (LMWH) or direct oral anticoagulants can be used (grade 2A)."},{"claim":"Active cancer: 3 to 6 months, then review","grade":"[2020] (NICE does not grade recommendations)","source":"nice-ng158","quote":"Offer people with active cancer and confirmed proximal DVT or PE anticoagulation treatment for 3 to 6 months."},{"claim":"Consider a DOAC for active cancer with proximal DVT or PE","grade":"[2020] (NICE does not grade recommendations)","source":"nice-ng158","quote":"Consider a direct-acting oral anticoagulant (DOAC) for people with active cancer and confirmed proximal DVT or PE."}],"sources":[{"key":"itac-2022","label":"2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19","publisher":"International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.)","year":2022,"url":"https://doi.org/10.1016/S1470-2045(22)00160-7","doi":"10.1016/S1470-2045(22)00160-7","gradingScheme":"GRADE: evidence A (high) to D (very low); recommendation grade 1 (strong) or 2 (weak); 'guidance' (best clinical practice) where there is no clear evidence, based on expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2023","label":"Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update","publisher":"ASCO (Journal of Clinical Oncology, Key et al.)","year":2023,"url":"https://doi.org/10.1200/JCO.23.00294","doi":"10.1200/JCO.23.00294","gradingScheme":"Each recommendation has a type (evidence based or consensus), evidence quality (high to low) and strength (strong or moderate or weak).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng158","label":"Venous thromboembolic diseases: diagnosis, management and thrombophilia testing (NG158), last updated 2 August 2023","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng158/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written ([2020]).","read":"full-text","accessed":"2026-11-11"},{"key":"ash-2021","label":"American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer","publisher":"American Society of Hematology (Blood Advances, Lyman et al.)","year":2021,"url":"https://doi.org/10.1182/bloodadvances.2020003442","doi":"10.1182/bloodadvances.2020003442","gradingScheme":"GRADE; recommendations strong or conditional.","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2023","label":"Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline","publisher":"ESMO (Annals of Oncology, Falanga et al.)","year":2023,"url":"https://doi.org/10.1016/j.annonc.2022.12.014","doi":"10.1016/j.annonc.2022.12.014","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO Clinical Practice Guideline on VTE in cancer (2023) could not be read: the publisher refused a script, no archived copy was found and Europe PMC holds no abstract. Its positions are not represented here.","The ASH 2021 guideline was read as an abstract only, so its specific drug and duration recommendations beyond the abstract's summary are not given.","Only the 2023 ASCO update (recommendations 3.7, 4.1 and 4.2) was read; ASCO's unchanged 2019 recommendations on duration beyond 6 months, incidental clots and brain metastases were not.","Guidance for low platelets, severe kidney failure and recurrence on treatment rests on expert consensus without trial data (ITAC 'guidance').","NICE NG158 recommendations for active cancer date from 2020, before the apixaban trial CARAVAGGIO was weighed by the other guidelines."]},{"id":"antiemetic-prophylaxis-by-emetic-risk","kind":"protocol","name":"Antiemetic prophylaxis for chemotherapy by emetic risk","aka":["CINV prophylaxis","chemotherapy-induced nausea and vomiting prevention","antiemetic regimen by emetogenicity","anti-sickness medicines with chemotherapy"],"tldr":"Sickness from chemotherapy is now largely preventable. The anti-sickness medicines you are given depend on how likely your chemotherapy is to cause sickness: for the strongest regimens that is four medicines before treatment and some for the days after, for the mildest none at all. If you are still sick, tell your team: there is a next step.","summary":"Prophylaxis is chosen by the emetic risk of the regimen, defined as the chance of vomiting in the first 24 hours without prophylaxis (high, above 90 per cent; moderate; low; minimal), adjusted for patient factors such as female sex and younger age. MASCC/ESMO (2023) recommend for high emetic risk a four-drug regimen before chemotherapy: a 5-HT3 receptor antagonist, dexamethasone, an NK1 receptor antagonist (aprepitant, fosaprepitant, netupitant or fosnetupitant with palonosetron, or rolapitant) and olanzapine (I, A). For delayed nausea after cisplatin and other non-anthracycline-cyclophosphamide regimens, dexamethasone and olanzapine continue on days 2 to 4 (II, B); after anthracycline with cyclophosphamide, dexamethasone stops after day 1 and olanzapine alone continues on days 2 to 4 (II, B). Olanzapine 10 mg is the best investigated dose; 5 mg or a bedtime dose is an option where sedation matters (II, B).\n\nFor moderate emetic risk, MASCC/ESMO add an NK1 receptor antagonist for carboplatin at AUC 5 or more and for women under 50 having oxaliplatin, use a 5-HT3 receptor antagonist with a steroid for other regimens, and limit the steroid to day 1. Low emetic risk gets a single agent before treatment and nothing for the delayed phase; minimal risk gets none. ASCO (2020) keeps dexamethasone when checkpoint inhibitors are given with chemotherapy and gives no routine prophylaxis for checkpoint inhibitors alone. For breakthrough nausea and vomiting the evidence favours olanzapine 10 mg once daily for 3 days (II, B); for high-dose chemotherapy before stem cell transplant, a 5-HT3 receptor antagonist with dexamethasone and aprepitant (I, A), with olanzapine to be considered.","asOf":"2026-11-11","links":[],"tags":["protocol","nausea-and-vomiting","supportive-care"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["antiemetic-therapy"],"targets":[],"drugs":["aprepitant","netupitant-palonosetron","palonosetron","ondansetron","granisetron","rolapitant","dexamethasone","cisplatin","carboplatin","oxaliplatin","cyclophosphamide"],"companies":[],"institutions":["mascc","esmo","asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer medicines make people sick. Doctors give anti-sickness medicines before treatment to stop it happening. The stronger the treatment, the more of these medicines you get.","domain":"supportive-care","setting":{"who":["doctor","pharmacist","nurse","patient-or-carer"],"where":["chemotherapy-day-unit","ward","outpatient-clinic","home"]},"population":"Adults having intravenous anticancer treatment. The MASCC/ESMO recommendations on which most steps rest are written for adults; children (ASCO 2020 adds fosaprepitant to its paediatric recommendations), radiotherapy-induced nausea and nausea in advanced cancer not caused by treatment are covered by separate guidance and are not covered here. Oral anticancer drugs taken daily are a gap in every guideline read.","trigger":"A chemotherapy regimen is prescribed, before the first cycle.","steps":[{"action":"Before the first cycle, classify the regimen by its emetic risk: high, moderate, low or minimal","why":"The emetic risk of the most sickness-causing drug in the regimen decides which anti-sickness medicines are needed.","source":"mascc-esmo-2023-hec","quote":"High emetic risk is defined as a risk of more than 90% of vomiting."},{"action":"Take the person's own risk factors into account as well, such as being female and younger","why":"Two people on the same regimen do not have the same risk; women and younger people are sick more often.","source":"mascc-esmo-2023-hec","quote":"patient demographics such as sex (women are at a higher risk than men) and age (younger patients have a higher risk than older)"},{"action":"For high emetic risk, give four drugs before chemotherapy: a 5-HT3 receptor antagonist, dexamethasone, an NK1 receptor antagonist and olanzapine","why":"Large trials showed that adding olanzapine to the older three-drug combination prevents more nausea, so it is now part of the standard set.","source":"mascc-esmo-2023-hec","quote":"Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC.","grade":"I, A"},{"action":"After cisplatin or other high-risk regimens that are not anthracycline with cyclophosphamide, continue dexamethasone and olanzapine on days 2 to 4","why":"Sickness after cisplatin often peaks a few days later; the evidence for stopping the steroid after day 1 in these regimens is not yet conclusive.","source":"mascc-esmo-2023-hec","quote":"DEX and olanzapine on days 2 to 4 is suggested to prevent delayed nausea and vomiting","grade":"II, B"},{"action":"After anthracycline with cyclophosphamide, stop dexamethasone after day 1 and continue olanzapine alone on days 2 to 4","why":"Trials showed the extra days of steroid add nothing after this regimen, so they can be spared.","source":"mascc-esmo-2023-hec","quote":"There is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC.","grade":"II, B"},{"action":"Give olanzapine 10 mg; consider 5 mg or a bedtime dose where drowsiness is a concern, for example in older people","why":"10 mg is the dose most studied; 5 mg works better than nothing but has not been shown equal to 10 mg.","source":"mascc-esmo-2023-hec","quote":"If sedation is a concern, a starting daily dose of 5 mg and/or administration at bedtime is an option","grade":"II, B"},{"action":"For moderate emetic risk, add an NK1 receptor antagonist to the 5-HT3 receptor antagonist and steroid for carboplatin at AUC 5 or more, and for women under 50 having oxaliplatin","why":"These two groups are sick more often than others on moderate-risk treatment, and the third drug helps them.","source":"mascc-esmo-2023-mec","quote":"for patients undergoing carboplatin (AUC ≥ 5) and women < 50 years of age receiving oxaliplatin-based treatment"},{"action":"For other moderate-risk regimens, give a 5-HT3 receptor antagonist with a steroid, and give the steroid on day 1 only","why":"Trials found a single day of steroid as good as several days for these regimens, with fewer steroid side effects.","source":"mascc-esmo-2023-mec","quote":"it is recommended that the administration of steroids should be limited to day 1 in moderately emetogenic chemotherapy regimens"},{"action":"For low emetic risk, give one anti-sickness drug before treatment and none for the following days; for minimal risk, give none routinely","why":"Most people on these treatments are not sick, so routine medicines would add side effects without benefit.","source":"mascc-esmo-2023-low","quote":"No antiemetic prophylaxis is recommended for minimal emetic potential therapy, and single agents recommended for low emetic potential chemotherapy for acute emesis, but no prophylaxis is recommended for delayed emesis."},{"action":"Keep dexamethasone in the regimen when a checkpoint inhibitor is given with chemotherapy; give no routine prophylaxis for a checkpoint inhibitor alone","why":"There is no evidence that the steroid weakens immunotherapy in these combinations, and the immunotherapy drugs on their own rarely cause sickness.","source":"asco-2020","quote":"There is no clinical evidence to warrant omission of dexamethasone from guideline-compliant prophylactic antiemetic regimens when CPIs are administered to adults in combination with chemotherapy."},{"action":"For high-dose chemotherapy before a stem cell transplant, give a 5-HT3 receptor antagonist, dexamethasone and aprepitant, and consider olanzapine","why":"High-dose conditioning causes sickness over several days; this combination is the best supported.","source":"mascc-esmo-2023-multiday","quote":"Olanzapine could be considered part of the antiemetic regimen."},{"action":"For cisplatin given over several days, give all four drugs on each treatment day, with olanzapine 5 mg at bedtime, and continue olanzapine, aprepitant and dexamethasone for 2 days after the last dose","why":"Each day of cisplatin brings its own sickness, and the delayed phase follows the last dose.","source":"mascc-esmo-2023-multiday","quote":"Olanzapine (in a dose of 5 mg at bedtime), aprepitant, and dexamethasone should be given once daily on the days of chemotherapy and until 2 days post-chemotherapy","grade":"I/A"},{"action":"If nausea or vomiting breaks through despite prophylaxis, give olanzapine 10 mg once daily for 3 days, and step up the next cycle","why":"Olanzapine has the best evidence for rescue; rescue medicines are usually those used for the next higher level of risk.","source":"mascc-esmo-2023-multiday","quote":"The available evidence for breakthrough nausea and vomiting suggests the use of 10-mg olanzapine, once daily for 3 days","grade":"II/B"}],"bestInClass":{"statement":"The MASCC/ESMO 2023 update is the most recent international guideline and the only one read here in full. It makes olanzapine a fixed part of a four-drug regimen for all high emetic risk chemotherapy (I, A), which it notes is in line with ASCO, keeps dexamethasone on days 2 to 4 after cisplatin and other non-anthracycline-cyclophosphamide regimens, and drops it after day 1 for anthracycline with cyclophosphamide. ASCO's latest update (2020) was read only as an abstract: it left its adult recommendations unchanged apart from adding olanzapine as an option in stem cell transplant and a 5 mg olanzapine dose, and it is the source for keeping dexamethasone with chemotherapy plus checkpoint inhibitors. Where the two differ is the dose of olanzapine: ASCO offers 5 mg as an option, while MASCC/ESMO say 10 mg is the best investigated and that 5 mg has not been shown to be as effective. NCCN (2023) and Cancer Care Ontario (2019) were not read; a 2024 comparison of all four says they share many fundamental similarities and that evidence is thin for low and minimal risk regimens.","sources":["mascc-esmo-2023-hec","mascc-esmo-2023-mec","mascc-esmo-2023-low","mascc-esmo-2023-multiday","asco-2020","comparison-2024"]},"variants":[{"name":"Olanzapine 5 mg as a standard dose (ASCO 2020)","differs":"ASCO's 2020 update added a 5 mg olanzapine dose for adults as an option alongside 10 mg.","evidence":"MASCC/ESMO (2023) found that 5 mg is better than placebo but that no adequately powered study has compared it with 10 mg, so they keep 10 mg as the best investigated dose and 5 mg as an option where sedation is a concern (II, B).","sources":["asco-2020","mascc-esmo-2023-hec"]},{"name":"Dexamethasone on day 1 only after cisplatin (steroid-sparing)","differs":"Stops dexamethasone after day 1 for cisplatin as well as for anthracycline with cyclophosphamide, to spare steroid side effects such as poor sleep, high blood sugar and indigestion.","evidence":"MASCC/ESMO judged the trials inconclusive for cisplatin and kept the 3 to 4 day regimen; they note that a few studies have tested a 1-day regimen in cisplatin, one showing comparable efficacy, and that none of the trials it considered included olanzapine. The 2025 review by members of the committee lists this as an open question.","sources":["mascc-esmo-2023-hec","beyond-2025"]},{"name":"Non-drug approaches alongside medicines (MASCC/ESMO integrative review)","differs":"Adds acupuncture or electroacupuncture, food-based approaches, or progressive muscle relaxation with or without guided imagery to the drug regimen.","evidence":"MASCC/ESMO (2023) could make recommendations for these three, found major methodological flaws in many trials, could make no recommendation for ginger because the evidence conflicts, and none for aromatherapy, hypnosis in adults, music therapy or reflexology.","sources":["mascc-esmo-2023-integrative"]}],"grades":[{"claim":"Four-drug regimen with olanzapine before high emetic risk chemotherapy, both cisplatin-type and anthracycline with cyclophosphamide","grade":"I, A","source":"mascc-esmo-2023-hec","quote":"Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC."},{"claim":"Dexamethasone and olanzapine on days 2 to 4 after non-anthracycline-cyclophosphamide high emetic risk chemotherapy","grade":"II, B","source":"mascc-esmo-2023-hec","quote":"DEX and olanzapine on days 2 to 4 is suggested to prevent delayed nausea and vomiting"},{"claim":"Olanzapine alone on days 2 to 4 after anthracycline with cyclophosphamide","grade":"II, B","source":"mascc-esmo-2023-hec"},{"claim":"Olanzapine 10 mg, with 5 mg or a bedtime dose as an option where sedation is a concern","grade":"II, B","source":"mascc-esmo-2023-hec","quote":"The best investigated dose is 10 mg."},{"claim":"Four drugs for multiple-day cisplatin","grade":"I/A (acute); II/B for the number of days","source":"mascc-esmo-2023-multiday"},{"claim":"5-HT3 receptor antagonist, dexamethasone and aprepitant for high-dose chemotherapy before stem cell transplant","grade":"I/A","source":"mascc-esmo-2023-multiday"},{"claim":"Olanzapine for breakthrough nausea and vomiting","grade":"II/B","source":"mascc-esmo-2023-multiday"}],"sources":[{"key":"mascc-esmo-2023-hec","label":"2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high-emetic-risk antineoplastic agents","publisher":"MASCC and ESMO, Supportive Care in Cancer","year":2023,"url":"https://europepmc.org/article/PMC/PMC10739516","doi":"10.1007/s00520-023-08221-4","gradingScheme":"Each recommendation printed with a level of evidence (Roman numeral) and a grade of recommendation (letter), for example I A; the definitions of the levels and grades were not in the text read.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-esmo-2023-multiday","label":"2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting","publisher":"MASCC and ESMO, Supportive Care in Cancer","year":2023,"url":"https://europepmc.org/article/PMC/PMC10725845","doi":"10.1007/s00520-023-08224-1","gradingScheme":"Level of evidence and grade of recommendation printed together, for example I/A.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-esmo-2023-mec","label":"2023 updated MASCC/ESMO Consensus recommendations: Prevention of nausea and vomiting following moderately emetic risk antineoplastic agents","publisher":"MASCC and ESMO, Supportive Care in Cancer","year":2023,"url":"https://europepmc.org/abstract/MED/38114821","doi":"10.1007/s00520-023-08222-3","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-esmo-2023-low","label":"2023 updated MASCC/ESMO consensus recommendations: controlling nausea and vomiting with chemotherapy of low or minimal emetic potential","publisher":"MASCC and ESMO, Supportive Care in Cancer","year":2023,"url":"https://europepmc.org/abstract/MED/38110581","doi":"10.1007/s00520-023-08223-2","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-esmo-2023-integrative","label":"2023 MASCC/ESMO consensus antiemetic guidelines related to integrative and non-pharmacological therapies","publisher":"MASCC and ESMO, Supportive Care in Cancer","year":2023,"url":"https://europepmc.org/abstract/MED/38102373","doi":"10.1007/s00520-023-08225-0","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-esmo-2023-esmo-open","label":"2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting","publisher":"MASCC and ESMO, ESMO Open","year":2024,"url":"https://doi.org/10.1016/j.esmoop.2023.102195","doi":"10.1016/j.esmoop.2023.102195","read":"not-reachable","accessed":"2026-11-11"},{"key":"asco-2020","label":"Antiemetics: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2020,"url":"https://europepmc.org/abstract/MED/32658626","doi":"10.1200/JCO.20.01296","read":"abstract","accessed":"2026-11-11"},{"key":"comparison-2024","label":"2020 ASCO, 2023 NCCN, 2023 MASCC/ESMO, and 2019 CCO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients","publisher":"Supportive Care in Cancer","year":2024,"url":"https://europepmc.org/abstract/MED/38594320","doi":"10.1007/s00520-024-08462-x","read":"abstract","accessed":"2026-11-11"},{"key":"beyond-2025","label":"Going beyond the 2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting","publisher":"European Journal of Cancer","year":2025,"url":"https://europepmc.org/abstract/MED/40288116","doi":"10.1016/j.ejca.2025.115451","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-moon-olanzapine-antiemetic-everywhere"],"gaps":["The moderate and low emetic risk updates were read only as abstracts, so their grades, their lists of which drugs fall in which risk group, and their preferred single agent for low risk are not given here.","The ESMO Open summary of the 2023 MASCC/ESMO guideline could not be read: the publisher page refused a script and Europe PMC holds no abstract.","ASCO 2020 was read only as an abstract; its full table of regimens, its paediatric recommendations and its doses are not given here. No ASCO antiemetic update after 2020 was found in Europe PMC.","NCCN Antiemesis guidelines require a login and were not read; Cancer Care Ontario's 2019 guidance was not located.","The emetic risk of several newer drugs is not settled: MASCC/ESMO say experience with sacituzumab govitecan and trastuzumab deruxtecan suggests a risk comparable to carboplatin at AUC above 5, and call for trials.","No guideline read here covers nausea from daily oral anticancer drugs or long-delayed nausea, which the 2025 review lists as open questions.","Whether dexamethasone can be limited to day 1 after cisplatin when olanzapine is added is unresolved; MASCC/ESMO did not consider the SPARED study, published then as an abstract only."]},{"id":"antifungal-prophylaxis-in-haematology","kind":"protocol","name":"Antifungal prophylaxis for people at high risk of invasive fungal infection","aka":["mould-active prophylaxis","mold-active prophylaxis","posaconazole prophylaxis","primary antifungal prophylaxis","azole prophylaxis","invasive aspergillosis prevention"],"tldr":"People on the most intensive leukaemia treatment, or a stem cell transplant from a donor, are at risk of serious mould infections in the lungs. Most are offered a preventive antifungal medicine, usually posaconazole, while their immunity is lowest. Other cancer treatments usually do not need one. These drugs interact with many medicines, so the pharmacist checks every combination.","summary":"Give systemic antifungal prophylaxis only to groups at high risk of invasive fungal disease, and make it mould-active. In children (POGO 2020, endorsed by COG; the 2026 update maintains these): strong recommendations for AML expected to cause profound and prolonged neutropenia (high quality) and for allogeneic HSCT pre-engraftment and during systemic immunosuppression for GVHD (moderate); consider it in newly diagnosed or relapsed ALL at high risk (weak, low); do not use it routinely in low-risk ALL or in most lymphomas and solid tumours (strong); not routinely in autologous HSCT (weak). If warranted, use a mould-active agent (strong, high), an echinocandin or a mould-active azole (strong, moderate), and not amphotericin routinely (strong, low). In adults, ECIL-10 (2025) grades posaconazole A-I during remission induction for AML and MDS, gives isavuconazole, micafungin and caspofungin B-II, does not indicate prophylaxis in ALL, Hodgkin lymphoma, myeloma or autologous HSCT, endorses mould-active prophylaxis for high-risk CAR-T recipients, and now counts children with ALL aged 12 or older or with insufficient treatment response as high risk. Mould-active azoles are not recommended with vincristine (D-II). ASCO/IDSA (2018) recommend antifungal prophylaxis for patients expected to have profound, protracted neutropenia.","asOf":"2026-11-11","links":[],"tags":["protocol","antimicrobial-prophylaxis","antifungal","paediatric"],"related":["paediatric-fever-and-neutropenia","antibacterial-prophylaxis-in-neutropenia","neutropenic-precautions-and-daily-life","vincristine","venetoclax"],"cancers":["aml","all-leukemia","childhood-cancers"],"sections":["supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["asco"],"pathways":[],"terms":["neutropenia","lymphoma-tx-pjp-and-infection-prophylaxis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Very strong leukaemia treatment and donor stem cell transplants can let moulds cause lung infections. A preventive antifungal medicine is often given during that time. It can clash with other medicines, so the team checks them.","domain":"infection-prevention","setting":{"who":["doctor","pharmacist","nurse","patient-or-carer"],"where":["ward","outpatient-clinic","home"]},"population":"Adults and children with haematological cancers, and recipients of allogeneic or autologous haematopoietic cell transplant or CAR-T cells (ECIL-10 covers adults and children with haematological malignancies; POGO covers children with cancer and HSCT recipients). Most people with solid tumours or lymphoma are low risk and are not covered by a prophylaxis recommendation.","trigger":"Treatment is planned that is expected to cause profound and prolonged neutropenia, or an allogeneic transplant, or systemic immunosuppression for graft-versus-host disease.","steps":[{"action":"Before each phase, decide whether the person is at high risk of invasive fungal disease, by disease, treatment and expected neutropenia","why":"The benefit of prophylaxis grows with the risk; in low-risk people side effects, cost and drug interactions outweigh it.","source":"paed-afp-2020","quote":"Do not routinely administer systemic antifungal prophylaxis to children and adolescents with cancer at low risk for IFD, such as most pediatric patients with lymphomas and solid tumors (Evidence quality: moderate; Strength of recommendation: strong).","grade":"Evidence quality: moderate; Strength of recommendation: strong"},{"action":"Give antifungal prophylaxis to children and adolescents having AML treatment expected to cause profound and prolonged neutropenia","why":"Children with AML are at high risk of fungal infection, and prophylaxis reduced it most in those at highest risk.","source":"paed-afp-2020","quote":"Administer systemic antifungal prophylaxis to children and adolescents receiving treatment of acute myeloid leukemia that is expected to result in profound and prolonged neutropenia (Evidence quality: high; Strength of recommendation: strong).","grade":"Evidence quality: high; Strength of recommendation: strong"},{"action":"Give it to children having an allogeneic transplant before engraftment, and during systemic immunosuppression for graft-versus-host disease","why":"These are two separate periods of high fungal risk; in transplant recipients prophylaxis also lowered deaths from fungal infection.","source":"paed-afp-2020","quote":"Administer systemic antifungal prophylaxis to children and adolescents undergoing allogeneic HSCT pre-engraftment and to those receiving systemic immunosuppression for the treatment of graft-versus-host disease (GVHD; Evidence quality: moderate; Strength of recommendation: strong).","grade":"Evidence quality: moderate; Strength of recommendation: strong"},{"action":"Consider it for children with ALL at high risk, including those aged 12 or older and those with an insufficient response to induction","why":"Risk in ALL varies by protocol and phase; a large European trial found older children and poor responders were at higher risk, and ECIL now recommends prophylaxis for them.","source":"ecil-10","quote":"Consequently, older children (≥ 12 years) with ALL and those with insufficient treatment response are identified as being at elevated risk for IFD and are now recommended to receive antifungal prophylaxis."},{"action":"In adults with AML or high-risk MDS having remission induction chemotherapy, give mould-active prophylaxis, with posaconazole the best-supported choice","why":"Posaconazole is the only agent ECIL grades A-I in this setting; isavuconazole, micafungin and caspofungin are B-II alternatives.","source":"ecil-10","quote":"Regarding acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients undergoing remission induction chemotherapy, a B-II grading has been assigned to isavuconazole, micafungin, and caspofungin, based on non-randomized studies that have shown efficacy in preventing invasive fungal diseases (IFD).","grade":"posaconazole A-I; isavuconazole, micafungin, caspofungin B-II"},{"action":"When prophylaxis is warranted, use a mould-active drug: an echinocandin or a mould-active azole, not routine amphotericin","why":"Compared with fluconazole, mould-active drugs reduced fungal infection and deaths from it; amphotericin was no better than fluconazole and caused more side effects.","source":"paed-afp-2020","quote":"In choosing a mold-active agent, administer an echinocandin or a mold-active azole (Evidence quality: moderate; Strength of recommendation: strong).","grade":"Evidence quality: moderate; Strength of recommendation: strong"},{"action":"Do not give voriconazole or posaconazole with vincristine; consider isavuconazole with caution or another option","why":"These azoles slow the breakdown of vincristine and can cause severe nerve damage.","source":"ecil-10","quote":"Antifungal prophylaxis with a mold-active triazole, such as voriconazole or posaconazole, is not recommended because of interactions which could increase the toxicity of vincristine (D-II).","grade":"D-II"},{"action":"Check every other medicine for interactions before starting an azole, including venetoclax and other targeted drugs","why":"Azoles raise the levels of many drugs; in its section on chronic lymphocytic leukaemia, ECIL says that with venetoclax prophylaxis should be avoided or used cautiously, adjusting the venetoclax dose and monitoring antifungal levels.","source":"ecil-10","quote":"In the case of co-administration of venetoclax, antifungal prophylaxis should be avoided or used cautiously because of drug-drug interactions (i.e. adjustment of venetoclax dosing is needed with therapeutic drug monitoring of the antifungal agent)"},{"action":"Do not give routine antifungal prophylaxis for autologous transplant, ALL in adults, Hodgkin lymphoma or myeloma","why":"The risk of fungal infection in these groups is too low for prophylaxis to help; ECIL suggests fluconazole against Candida in the neutropenic phase of autologous transplant (B-III).","source":"ecil-10","quote":"Prophylaxis is not indicated in patients treated for myeloproliferative neoplasms (NPM), acute lymphoid leukemia (ALL), and Hodgkin lymphoma (HL)."},{"action":"For CAR-T recipients, give mould-active prophylaxis to those at high risk and anti-yeast prophylaxis to those at low risk","why":"Fungal infections after CD19 CAR-T run at 1 to 15%, higher with cytokine release syndrome and the steroids used to treat it.","source":"ecil-10","quote":"The expert panel proposes to endorse the use of anti-mold prophylaxis in high-risk patients during pre-infusion and post-infusion, while in low-risk patients, anti-yeast prophylaxis can be recommended (B-II).","grade":"B-II"},{"action":"In children, give prophylaxis during observed or expected severe neutropenia, and in allogeneic transplant during immunosuppression for GVHD","why":"These are the periods of highest risk; no trial has compared start and stop rules.","source":"paed-afp-2020","quote":"If systemic antifungal prophylaxis is warranted, consider administration during periods of observed or expected severe neutropenia.","grade":"Evidence quality: low; Strength of recommendation: weak"}],"bestInClass":{"statement":"Prophylaxis targeted to high-risk groups and mould-active. For children, the POGO guideline (2020, endorsed by COG; its 2026 update keeps the strong recommendations for AML and allogeneic HSCT and for an echinocandin or mould-active azole, and adds good practice statements on drug interactions, infection prevention and local epidemiology). For adults and children with haematological cancers, ECIL-10 (2025): posaconazole A-I during AML and MDS induction, isavuconazole, micafungin and caspofungin B-II, and new recommendations for CAR-T and for older or poorly responding children with ALL. The guidelines differ on ALL: ECIL does not indicate prophylaxis for ALL in general but now recommends it for children aged 12 or older or with insufficient response, while POGO makes a weak recommendation to consider it for high-risk ALL without defining the subgroup. They also differ on choice: POGO puts echinocandins and mould-active azoles side by side (echinocandins where hepatotoxicity matters, azoles where oral dosing matters), while ECIL ranks posaconazole highest in AML induction.","sources":["ecil-10","paed-afp-2020","cog-afp-2020","paed-prophylaxis-2026","asco-idsa-2018"]},"variants":[{"name":"Fluconazole where mould risk is low","differs":"Uses fluconazole, which covers yeasts but not moulds, in units where mould infection is rare, or as part of a strategy with mould-directed diagnostic tests.","evidence":"POGO says fluconazole may be appropriate where the mould risk is sufficiently low; ECIL grades fluconazole B-I in AML only where the incidence of mould infections is low.","sources":["paed-afp-2020","ecil-10"]},{"name":"Echinocandin rather than azole in children","differs":"Uses daily intravenous caspofungin or micafungin rather than an oral azole, accepting the need for intravenous access to avoid azole interactions and liver toxicity.","evidence":"POGO strong recommendation for either class (moderate quality); ECIL-10 raised caspofungin to B-I in children after a randomised trial in paediatric allogeneic HSCT found it as effective as triazoles.","sources":["paed-afp-2020","ecil-10"]},{"name":"Haploidentical transplant with post-transplant cyclophosphamide","differs":"ECIL treats haploidentical allogeneic HSCT with post-transplant cyclophosphamide as low risk for mould infection before engraftment.","evidence":"B-II in the ECIL-10 allogeneic HSCT table.","sources":["ecil-10"]}],"grades":[{"claim":"Prophylaxis in children with AML expected to have profound and prolonged neutropenia","grade":"Evidence quality: high; Strength of recommendation: strong","source":"paed-afp-2020"},{"claim":"Prophylaxis in children having allogeneic HSCT pre-engraftment and during GVHD treatment","grade":"Evidence quality: moderate; Strength of recommendation: strong","source":"paed-afp-2020"},{"claim":"Consider prophylaxis in high-risk ALL in children","grade":"Evidence quality: low; Strength of recommendation: weak","source":"paed-afp-2020","quote":"Consider administering systemic antifungal prophylaxis to children and adolescents with newly diagnosed and relapsed acute lymphoblastic leukemia at high risk for IFD (Evidence quality: low; Strength of recommendation: weak)."},{"claim":"Use a mould-active agent when prophylaxis is warranted","grade":"Evidence quality: high; Strength of recommendation: strong","source":"paed-afp-2020","quote":"If systemic antifungal prophylaxis is warranted, administer a mold-active agent (Evidence quality: high; Strength of recommendation: strong)."},{"claim":"No routine amphotericin prophylaxis","grade":"Evidence quality: low; Strength of recommendation: strong","source":"paed-afp-2020","quote":"Do not use amphotericin routinely as systemic antifungal prophylaxis (Evidence quality: low; Strength of recommendation: strong)."},{"claim":"No routine prophylaxis in children having autologous HSCT","grade":"Evidence quality: low; Strength of recommendation: weak","source":"paed-afp-2020"},{"claim":"Posaconazole tablets during AML and MDS remission induction","grade":"A-I","source":"ecil-10"},{"claim":"Mould-active azoles with vincristine","grade":"D-II","source":"ecil-10"},{"claim":"Caspofungin as mould-active prophylaxis in children","grade":"B-I","source":"ecil-10","quote":"Hence, the caspofungin grade of recommendation has been updated to a B-I."}],"sources":[{"key":"ecil-10","label":"Primary antifungal prophylaxis in hematological malignancies. Updated clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL-10)","publisher":"European Conference on Infections in Leukaemia, Leukemia","year":2025,"url":"https://europepmc.org/article/PMC/PMC12208874","doi":"10.1038/s41375-025-02586-7","gradingScheme":"ESCMID system: strength A (strongly supports) to D (supports against); quality I (randomised trial), II (non-randomised, cohort or case-control; index r, t, h, u or a for the source), III (expert opinion); printed as, for example, B-II.","read":"full-text","accessed":"2026-11-11"},{"key":"paed-afp-2020","label":"Clinical Practice Guideline for Systemic Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients","publisher":"Pediatric Oncology Group of Ontario panel (Lehrnbecher et al.), Journal of Clinical Oncology","year":2020,"url":"https://europepmc.org/article/PMC/PMC7499615","doi":"10.1200/jco.20.00158","gradingScheme":"GRADE: evidence quality high to very low and strength strong or weak, printed in brackets after each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"cog-afp-2020","label":"Systemic antifungal prophylaxis in pediatric patients with cancer and HSCT recipients (COG endorsement, version date 31 August 2020)","publisher":"Children's Oncology Group","year":2020,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_Antifungal_Prophylaxis_Guideline_Document_31AUG2020-new-logo.pdf","gradingScheme":"Reprints the source guideline's GRADE strength and quality.","read":"full-text","accessed":"2026-11-11"},{"key":"paed-prophylaxis-2026","label":"Clinical Practice Guideline for Systemic Antibacterial and Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Cell Transplant Recipients: 2026 Update","publisher":"Pediatric Oncology Group of Ontario panel, Journal of Clinical Oncology","year":2026,"url":"https://europepmc.org/article/MED/42826360","doi":"10.1200/jco-26-00720","read":"abstract","accessed":"2026-11-11"},{"key":"asco-idsa-2018","label":"Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update","publisher":"ASCO and IDSA, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/article/MED/30179565","doi":"10.1200/JCO.18.00374","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 2026 paediatric update was read only as an abstract; any change in wording or grade beyond what the abstract states is not reflected here, and the COG page still lists the 2020 endorsement.","ASCO/IDSA 2018 was read only as an abstract; its choice of agent and grades are not given.","Doses and therapeutic drug monitoring targets are in the ECIL-10 tables and the product licences; they are not reproduced here.","ECIL-10 says knowledge of fungal infection with bispecific antibodies is too limited for any recommendation.","Neither guideline defines precisely which children with ALL are at high risk; POGO calls for protocol-specific and phase-specific recommendations."]},{"id":"aseptic-compounding-of-hazardous-anticancer-drugs","kind":"protocol","name":"Aseptic compounding of hazardous anticancer drugs in the pharmacy","aka":["chemotherapy compounding","cytotoxic reconstitution","aseptic preparation of chemotherapy","chemotherapy isolator","biological safety cabinet","USP 800 compounding","pharmacy chemotherapy preparation"],"tldr":"Cancer drugs given by drip or injection are usually made up in a hospital pharmacy, inside a sealed cabinet that protects both the drug from germs and the staff from the drug. Staff wear chemotherapy gloves and gowns, use sealed transfer devices, and prepare the drip lines in the cabinet so that nurses do not have to open the drug on the ward.","summary":"Compounding hazardous drugs carries the highest exposure risk of any handling task. The NIOSH Alert (2004), endorsed by ASCO (2019) alongside USP chapter 800, OSHA and ONS, is the most detailed open standard. Drugs on the NIOSH list (2024 update) are prepared in a ventilated cabinet: where asepsis is needed, a Class II biological safety cabinet (type B2 preferred), a Class III cabinet or an aseptic containment isolator, exhausting filtered air outside where feasible. Staff wear double chemotherapy-tested gloves, changed every 30 minutes or when damaged, and a disposable, non-absorbent, closed-front gown with cuffs; the outer glove goes over the cuff. Closed-system transfer devices may reduce contamination but are not a substitute for a cabinet and are used inside one. Intravenous tubing is primed in the cabinet or in-line with drug-free fluid, never at the bedside. Work surfaces are cleaned with a deactivating agent where available and a cleaning agent before and after each activity and at the end of the shift, with protective gloves.\n\nThe evidence is weak throughout. ASCO's standards are consensus based; on external ventilation of cleanrooms it found no long-term clinical evidence and leaves it to institutions; on CSTDs it found low-quality evidence and called for a testing protocol. The Cochrane review (24 observational cluster studies, 359 hospitals, mostly PhaSeal) could draw no firm conclusions. In the UK, COSHH makes the employer responsible for assessing and controlling exposure, with monitoring where carcinogens are handled.","asOf":"2026-11-11","links":[],"tags":[],"related":["hazardous-drug-handling-in-clinical-areas","sact-prescribing-and-pharmacy-verification"],"cancers":[],"sections":[],"technologies":["closed-system-transfer-devices","pharmacy-automation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your cancer drugs are made up in a special sealed cabinet in the pharmacy, by staff in protective gloves and gowns, so the drug stays clean and the staff stay safe.","domain":"hazardous-drug-safety","setting":{"who":["pharmacist","pharmacy-technician"],"where":["aseptic-unit"]},"population":"Pharmacy staff preparing injectable hazardous drugs, chiefly antineoplastics on the NIOSH list, in hospital aseptic units or compounding pharmacies. Oral and clinical-area handling are covered by the hazardous-drug handling and oral anticancer medicine protocols.","trigger":"A prescription for an injectable hazardous anticancer drug has been verified and is to be prepared.","steps":[{"action":"Identify which drugs are hazardous using the current NIOSH list, and keep a facility-specific list","why":"Handling precautions only work if everyone knows which drugs need them, including new drugs not yet on the national list.","source":"niosh-2024","quote":"Therefore, this list may not be all-inclusive, and employers should consider creating a facility-specific hazardous drug list."},{"action":"Prepare hazardous drugs only inside a ventilated cabinet designed to contain them","why":"Opening vials and drawing up drug releases droplets and vapour that a cabinet captures.","source":"niosh-2004","quote":"Use a ventilated cabinet designed to reduce worker exposures while preparing hazardous drugs (see following section entitled Ventilated Cabinets)."},{"action":"When the drug must stay sterile, use a cabinet designed for both containment and aseptic work: a Class II (type B2 preferred) or Class III biological safety cabinet or an aseptic containment isolator, exhausted outside where feasible","why":"The cabinet must protect the drug from germs and the staff from the drug at the same time.","source":"niosh-2004","quote":"Therefore, when asepsis is required or recommended, use ventilated cabinets designed for both hazardous drug containment and aseptic processing."},{"action":"Wear double chemotherapy-tested gloves and a protective gown while reconstituting and mixing","why":"Some drugs pass through ordinary gloves and fabric; tested gloves and a non-absorbent gown block them.","source":"niosh-2004","quote":"Wear PPE (including double gloves and protective gowns) while reconstituting and admixing drugs:"},{"action":"Change gloves every 30 minutes, or at once if torn, punctured or contaminated","why":"Gloves become more permeable with time and damage.","source":"niosh-2004","quote":"Change gloves every 30 minutes or when torn, punctured, or contaminated."},{"action":"If closed-system transfer devices are used, use them inside the cabinet, never instead of it","why":"A closed device can cut leaks but has not been shown to replace the cabinet's protection.","source":"niosh-2004","quote":"Remember that a closed-system transfer device is not an acceptable substitute for a ventilated cabinet and should be used only within a ventilated cabinet."},{"action":"Prime the infusion tubing in the cabinet, or in-line with drug-free fluid, so it is never primed with drug at the bedside","why":"Priming with drug outside a cabinet sprays droplets where nurses and patients are.","source":"niosh-2004","quote":"Have pharmacy personnel prime the IV tubing and syringes inside the ventilated cabinet, or prime them in-line with nondrug solutions—never in the patient’s room."},{"action":"Clean work surfaces with a deactivating agent, where one is available, and a cleaning agent before and after each activity and at the end of the shift","why":"Drug residue on surfaces is a main route of staff exposure, and some residues need deactivating, not just wiping.","source":"niosh-2004","quote":"Clean work surfaces with an appropriate deactivation agent (if available) and cleaning agent before and after each activity and at the end of the work shift."},{"action":"Assess the risks under the applicable workplace law, control them, and monitor where needed","why":"Employers are legally responsible for keeping exposure as low as possible.","source":"hse-cytotoxics","quote":"Under COSHH, employers must assess the risks from handling cytotoxic drugs for employees and anyone else affected by this type of work, and take suitable precautions to protect them."}],"bestInClass":{"statement":"Prepare drugs on a current hazardous-drug list inside a ventilated cabinet suited to aseptic containment (Class II BSC, type B2 preferred, Class III BSC or aseptic containment isolator, externally exhausted where feasible), with double chemotherapy gloves changed every 30 minutes, a closed-front non-absorbent gown, CSTDs used only within the cabinet, priming in the cabinet or in-line with drug-free fluid, and deactivation and cleaning of surfaces before and after each task (NIOSH 2004, endorsed by ASCO 2019). USP chapter 800, which ASCO reports requires CSTDs for administration and recommends them for compounding, could not be read. The sources agree in direction but none is graded, and the evidence for CSTDs (Cochrane 2018, very low certainty) and external ventilation (ASCO 2019, no long-term clinical evidence) is weak.","sources":["niosh-2004","niosh-2024","asco-2018","cochrane-cstd-2018","hse-cytotoxics"]},"variants":[{"name":"Closed-system transfer devices for all compounding (USP 800, as reported by ASCO)","differs":"Uses a CSTD for every transfer from vial to bag or syringe in compounding, rather than only where local risk assessment favours it.","evidence":"ASCO 2019 reports that USP 800 recommends CSTDs for sterile compounding and requires them for administration, and that some studies found fewer contaminated wipe samples after CSTDs were introduced, but rated the evidence low quality and called for a testing protocol. Cochrane 2018: very low certainty, no firm conclusions.","sources":["asco-2018","cochrane-cstd-2018"]},{"name":"External ventilation of the cleanroom or segregated compounding area","differs":"Vents the room around the cabinet to the outside rather than recirculating its air through HEPA filters.","evidence":"ASCO 2019 found no long-term clinical evidence and leaves it to each institution as part of a suite of protective measures.","sources":["asco-2018"]}],"grades":[],"sources":[{"key":"niosh-2004","label":"NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings (DHHS (NIOSH) Publication No. 2004-165)","publisher":"National Institute for Occupational Safety and Health (CDC)","year":2004,"url":"https://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf","gradingScheme":"Not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"niosh-2024","label":"NIOSH List of Hazardous Drugs in Healthcare Settings, 2024 (DHHS (NIOSH) Publication No. 2025-103)","publisher":"National Institute for Occupational Safety and Health (CDC)","year":2024,"url":"https://doi.org/10.26616/NIOSHPUB2025103","doi":"10.26616/NIOSHPUB2025103","gradingScheme":"Not graded; advisory.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2018","label":"Safe Handling of Hazardous Drugs: ASCO Standards","publisher":"ASCO (Journal of Clinical Oncology, Celano et al.)","year":2019,"url":"https://doi.org/10.1200/JCO.18.01616","doi":"10.1200/JCO.18.01616","gradingScheme":"Consensus-based standards developed by weighing benefits and harms, because the evidence base was limited; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"hse-cytotoxics","label":"Safe handling of cytotoxic drugs in the workplace","publisher":"Health and Safety Executive (UK)","year":2026,"url":"https://www.hse.gov.uk/healthservices/safe-use-cytotoxic-drugs.htm","gradingScheme":"Regulatory guidance under COSHH; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"cochrane-cstd-2018","label":"Closed-system drug-transfer devices plus safe handling of hazardous drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff","publisher":"Cochrane Database of Systematic Reviews (Gurusamy et al.)","year":2018,"url":"https://doi.org/10.1002/14651858.CD012860.pub2","doi":"10.1002/14651858.CD012860.pub2","gradingScheme":"GRADE certainty of evidence: high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["USP General Chapter <800> and the ISOPP Standards (2022), the main current compounding standards, could not be read; the UK aseptic standards (QAAPS) and PIC/S guidance were not read.","The NIOSH Alert dates from 2004; NIOSH moved its protective-equipment tables to a 2023 document that could not be retrieved.","No source read sets a deactivating agent or method; NIOSH says 'if available'.","Environmental wipe sampling and staff biological monitoring are recommended in some settings, but ASCO found the value of routine medical surveillance unclear."]},{"id":"checkpoint-inhibitor-baseline-and-monitoring","kind":"protocol","name":"Baseline tests and monitoring before and during checkpoint inhibitor treatment","aka":["baseline tests before immunotherapy","ICI pre-treatment screening","checkpoint inhibitor monitoring bloods","thyroid and cortisol monitoring on immunotherapy","pre-immunotherapy checklist"],"tldr":"Before immunotherapy such as pembrolizumab or nivolumab starts, your team checks your blood count, kidney and liver tests, thyroid and often cortisol and sugar levels, and asks about autoimmune and lung conditions. Some tests are repeated before each dose, because immunotherapy side effects are often found on a blood test before you feel them.","summary":"SITC 2021: before starting, full blood count with differential, a comprehensive metabolic panel, TSH and free T4; consider urinalysis for baseline kidney disease; consider an ECG for people at higher risk of myocarditis (cardiac disease, diabetes, combined anti-PD-(L)1 and anti-CTLA-4), and baseline troponin may be considered. Liver tests before every infusion; blood count, metabolic panel, TSH and free T4 intermittently throughout, with thyroid tests every 4 to 6 weeks on treatment and every 6 to 12 months after it ends. Education on irAEs, contraception and fertility; a careful risk-benefit discussion for people with autoimmune disease (LE: 1) and specialist referral with lung function tests for autoimmune interstitial lung disease (LE: 3).\n\nESE 2022 sets a baseline minimum for everyone of morning (08:00 to 09:00) TSH, free T4, cortisol, glucose and electrolytes (sodium, potassium, calcium), repeated every 4 to 6 weeks, preferably before each cycle, and adds ACTH, LH, FSH, oestradiol or testosterone, prolactin and HbA1c where hypophysitis risk is higher, such as with ipilimumab. ESMO 2022 and the ESC 2022 cardio-oncology guideline could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","irae"],"related":["irae-hypophysitis-adrenal","irae-hepatitis","irae-pneumonitis","irae-colitis"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","cardiac-biomarker-monitoring"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","dostarlimab","tremelimumab","avelumab"],"companies":[],"institutions":["sitc","esmo"],"pathways":[],"terms":["irae","immune-endocrinopathy","myocarditis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before immunotherapy, you will have blood tests to check your liver, kidneys, thyroid and hormones. They are repeated during treatment to catch side effects early.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit"]},"population":"Adults about to start, or receiving, an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1 or anti-CTLA-4, alone or combined, with or without chemotherapy). Monitoring for chemotherapy or targeted drugs given alongside follows those drugs' own requirements. Children are not addressed.","trigger":"A decision to start checkpoint inhibitor treatment, and each treatment cycle after it.","steps":[{"action":"Give dedicated education on immune-related side effects, with a booklet or alert card","why":"Most side effects start between visits; knowing what to report and carrying a card speeds up treatment elsewhere.","source":"sitc-2021","quote":"Patients should receive dedicated education on irAEs by a medical professional and may receive additional materials such as informational booklets or reference cards."},{"action":"Discuss fertility before treatment and advise contraception during it","why":"The effects of these drugs on pregnancy and fertility are not fully known.","source":"sitc-2021","quote":"Patients should be encouraged to use contraception while receiving immunotherapy. Fertility should be discussed prior to treatment."},{"action":"Take a full blood count with differential, a comprehensive metabolic panel, TSH and free T4 before the first dose, and consider urinalysis","why":"A baseline makes it possible to tell later whether a change is a side effect.","source":"sitc-2021","quote":"The following tests should be performed prior to beginning ICI therapy: complete blood count (CBC) with differential, comprehensive metabolic panel (CMP), thyroid-stimulating hormone (TSH), free thyroxine (fT4). Urinalysis should be considered to evaluate for baseline kidney disease."},{"action":"Add a morning cortisol, glucose and electrolytes to the baseline, and ACTH, sex hormones, prolactin and HbA1c where hypophysitis risk is higher, such as with ipilimumab","why":"Hormone problems are common with these drugs and can be dangerous if missed; a morning baseline makes later results interpretable.","source":"ese-2022","quote":"Baseline minimum tests : Morning (8:00–9:00 h) thyroid-stimulating hormone (TSH), free thyroxine (fT4), cortisol (with attention to any recent or current glucocorticoid treatment), glucose, and electrolytes (Na, K, Ca)."},{"action":"Consider a baseline ECG for people at higher risk of myocarditis, and consider a baseline troponin","why":"Myocarditis is rare but often fatal; a baseline helps interpret a later rise.","source":"sitc-2021","quote":"Consider performing a baseline electrocardiogram (EKG) on patients deemed at a higher risk for myocarditis (eg, cardiac comorbidities, diabetes mellitus, anti-PD-(L)1 with anti-CTLA-4 ICI combination therapy, etc). Baseline troponin testing may also be considered to provide information for evaluating potential future cardiac toxicity."},{"action":"For people with autoimmune disease, discuss the risk of a flare against the expected benefit before deciding, and arrange specialist monitoring","why":"Checkpoint inhibitors can flare existing autoimmune disease, but for many cancers the survival benefit outweighs that risk.","source":"sitc-2021","quote":"For patients with life-threatening autoimmune disorders, the decision to initiate ICI therapy should only be considered after a careful risk-benefit discussion between patient and provider, and consideration of alternative therapies.","grade":"LE: 1"},{"action":"Refer people with existing autoimmune interstitial lung disease to a lung specialist for lung function tests before starting","why":"Existing lung disease raises the risk of pneumonitis.","source":"sitc-2021","quote":"Patients with pre-existing autoimmune ILD should be referred to a specialist where possible before initiation of ICI therapy for the consideration of pulmonary function tests (PFTs) and risk assessment","grade":"LE: 3"},{"action":"Check liver tests before every infusion","why":"Immune hepatitis is usually silent and found on the blood test.","source":"sitc-2021","quote":"Liver biochemical tests (aka liver function tests (LFTs)) should be checked prior to each ICI infusion."},{"action":"Repeat the hormone baseline (TSH, free T4, cortisol, glucose, electrolytes) every 4 to 6 weeks, preferably before each cycle","why":"Thyroid, pituitary and adrenal problems and diabetes can start at any time on treatment.","source":"ese-2022","quote":"These tests should be repeated every 4–6 weeks, preferably before each treatment cycle starts."},{"action":"After treatment ends, keep checking thyroid function every 6 to 12 months","why":"Thyroid problems can appear months after the last dose.","source":"sitc-2021","quote":"Thyroid function (TSH, fT4) should be tested every 4–6 weeks during ICI treatment, and should continue to be tested every 6–12 months following the conclusion of ICI treatment."}],"bestInClass":{"statement":"SITC 2021 and ESE 2022 agree on a baseline blood count, metabolic panel and thyroid function, liver tests before each dose and thyroid tests every 4 to 6 weeks on treatment and every 6 to 12 months after. ESE goes further, asking for a morning cortisol, glucose and electrolytes in everyone and a full pituitary panel where hypophysitis risk is higher, while SITC asks for cortisol only when symptoms or other results point to it. SITC adds risk-based ECG and optional troponin, urinalysis, and specialist review for autoimmune disease and interstitial lung disease. The cardiac baseline in the 2022 ESC cardio-oncology guideline and the ESMO 2022 baseline list could not be read and are not compared.","sources":["sitc-2021","ese-2022","esmo-2022","esc-2022"]},"variants":[{"name":"Morning cortisol in everyone, with a full pituitary panel for ipilimumab (ESE 2022)","differs":"Adds cortisol, glucose and electrolytes to every baseline and repeat, drawn at 08:00 to 09:00, and a comprehensive panel (ACTH, LH, FSH, oestradiol or testosterone, prolactin, HbA1c) when hypophysitis risk is higher, such as ipilimumab alone or with a PD-1 inhibitor.","evidence":"Guideline consensus; the testing schedule is not a graded recommendation.","sources":["ese-2022"]}],"grades":[{"claim":"Risk-benefit discussion before checkpoint inhibitors in life-threatening autoimmune disease","grade":"LE: 1","source":"sitc-2021"},{"claim":"Specialist referral and lung function tests for autoimmune interstitial lung disease","grade":"LE: 3","source":"sitc-2021"},{"claim":"Mild thyroid dysfunction may be monitored without treatment, with TSH and free T4 every 3 to 6 weeks early on","grade":"good clinical practice","source":"ese-2022","quote":"We suggest that cases of clinically and biochemically mild thyrotoxicosis or hypothyroidism can be monitored without treatment (good clinical practice)."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"ese-2022","label":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline","publisher":"European Society of Endocrinology, European Journal of Endocrinology","year":2022,"url":"https://europepmc.org/article/PMC/PMC9641795","doi":"10.1530/EJE-22-0689","gradingScheme":"GRADE: quality of evidence printed as +000 (very low), ++00 (low), +++0 (moderate) or ++++ (strong); 'recommend' is a strong and 'suggest' a weak recommendation; recommendations not formally graded are marked good clinical practice.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"},{"key":"esc-2022","label":"2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)","publisher":"European Society of Cardiology, European Heart Journal","year":2022,"url":"https://doi.org/10.1093/eurheartj/ehac244","doi":"10.1093/eurheartj/ehac244","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The 2022 ESC cardio-oncology guideline, which gives the European position on a baseline ECG and troponin before checkpoint inhibitors, has no open full text in Europe PMC and was not read.","The ASCO 2021 guideline's baseline list is in its full text, which could not be read; its abstract gives none.","Whether to test for hepatitis B, hepatitis C, HIV or tuberculosis at baseline is not settled by the sources read; SITC asks for these tests before infliximab or vedolizumab, not before the checkpoint inhibitor.","No trial read here shows that routine cortisol or troponin screening improves outcomes."]},{"id":"anti-vegf-drugs-around-surgery","kind":"protocol","name":"Bevacizumab and other anti-VEGF drugs around surgery: pausing before and restarting after","aka":["holding bevacizumab before surgery","anti-angiogenic drugs and wound healing","VEGF inhibitor surgery interval","stopping TKI before surgery","Avastin before surgery"],"tldr":"Drugs that block blood vessel growth, such as bevacizumab (Avastin), ramucirumab, aflibercept and tablets like cabozantinib, lenvatinib or sunitinib, slow the healing of wounds. Before planned surgery they are paused, for between 2 days and 4 weeks depending on the drug, and restarted only once the wound has healed, usually at least 2 to 4 weeks after a big operation.","summary":"Every anti-VEGF agent's label carries a wound-healing warning with an interval, and the intervals track the drug's half-life. US labels: bevacizumab withhold at least 28 days before elective surgery and do not give for at least 28 days after major surgery (half-life about 20 days); ramucirumab 28 days before, at least 2 weeks after; ziv-aflibercept at least 4 weeks before and after (minor surgery such as port placement, biopsy or tooth extraction: resume once healed); cabozantinib and sunitinib at least 3 weeks before; tivozanib at least 24 days; regorafenib and fruquintinib 2 weeks; sorafenib at least 10 days; lenvatinib and pazopanib at least 1 week; axitinib at least 2 days; for all the TKIs, at least 2 weeks after major surgery and until the wound has healed. EU SmPCs are less specific: Avastin says therapy 'should be withheld for elective surgery' and not started for at least 28 days after major surgery; Lenvima says interruption 'should be considered'. In the Avastin colorectal trials, surgery 28 to 60 days before starting carried no extra risk, while operating during treatment gave wound or bleeding complications in 10 to 20%. A meta-analysis of 7 randomised trials (5147 people) found bevacizumab doubled wound complications (OR 2.32), mainly in colon cancer. No label establishes the safety of restarting after a wound-healing complication.","asOf":"2026-11-11","links":[],"tags":[],"related":["surgical-site-infection-prevention","routine-preoperative-tests"],"cancers":[],"sections":[],"technologies":["antiangiogenic"],"targets":[],"drugs":["bevacizumab","ramucirumab","ziv-aflibercept","cabozantinib","lenvatinib","sunitinib","pazopanib","sorafenib","regorafenib","axitinib","fruquintinib","tivozanib"],"companies":[],"institutions":[],"pathways":[],"terms":["antiangiogenic-toxicities"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you take one of these drugs and need an operation, tell both the surgeon and the cancer team. The drug is usually paused beforehand and restarted once the wound has healed. Do not stop or restart it yourself.","domain":"surgery-perioperative","setting":{"who":["doctor","surgical-team","pharmacist","nurse","patient-or-carer"],"where":["outpatient-clinic","ward","home"]},"population":"Adults receiving bevacizumab (including biosimilars), ramucirumab, ziv-aflibercept or a VEGF receptor tyrosine kinase inhibitor (cabozantinib, lenvatinib, sunitinib, pazopanib, sorafenib, regorafenib, axitinib, fruquintinib, tivozanib) who need elective surgery or are recovering from it. Emergency surgery cannot wait for these intervals; the label warnings still tell the team what to watch for. Intravitreal anti-VEGF injections for eye disease are outside scope.","trigger":"Planned surgery, including dental surgery, in someone on an anti-VEGF drug, or starting an anti-VEGF drug soon after an operation.","steps":[{"action":"Tell the surgeon and the oncology team about the anti-VEGF drug as soon as surgery is planned, including dental surgery","why":"The pause has to start weeks ahead for some of these drugs, so it needs planning.","source":"fotivda-us","quote":"Advise patients to contact their healthcare provider before any planned surgeries, including dental surgery","grade":"Label instruction (no grade)"},{"action":"Withhold bevacizumab for at least 28 days before elective surgery","why":"Bevacizumab stays in the body for weeks (its half-life is about 20 days), and wounds heal less well while it is active.","source":"avastin-us","quote":"Withhold for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days following a major surgery, and until adequate wound healing.","grade":"Label instruction (no grade)"},{"action":"Withhold ramucirumab for 28 days and ziv-aflibercept for at least 4 weeks before elective surgery","why":"Both are antibodies or fusion proteins that last for weeks, like bevacizumab.","source":"zaltrap-us","quote":"Withhold ZALTRAP for at least 4 weeks prior to elective surgery. Do not administer ZALTRAP for at least 4 weeks after major surgery and until wounds have adequately healed.","grade":"Label instruction (no grade)"},{"action":"Stop a VEGF receptor tablet for the interval on its own label before elective surgery: cabozantinib or sunitinib 3 weeks, tivozanib 24 days, regorafenib or fruquintinib 2 weeks, sorafenib 10 days, lenvatinib or pazopanib 1 week, axitinib 2 days","why":"Each tablet leaves the body at a different speed, so each label sets its own pause.","source":"cabometyx-us","quote":"Impaired Wound Healing: Withhold CABOMETYX for at least 3 weeks before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing.","grade":"Label instruction (no grade)"},{"action":"After major surgery, do not restart for at least 2 weeks (TKIs, ramucirumab) or 4 weeks (bevacizumab, ziv-aflibercept), and not until the wound has healed","why":"Restarting too early can make a wound or a bowel join break down.","source":"cyramza-us","quote":"Impaired Wound Healing : Withhold CYRAMZA for 28 days prior to elective surgery. Do not administer CYRAMZA for at least 2 weeks following a major surgical procedure and until adequate wound healing.","grade":"Label instruction (no grade)"},{"action":"After minor surgery such as port placement, a biopsy or a tooth extraction, restart once the wound has fully healed","why":"Small wounds heal faster, so the gap after them can be shorter.","source":"zaltrap-us","quote":"For minor surgery such as central venous access port placement, biopsy, and tooth extraction, ZALTRAP may be initiated/resumed once the surgical wound is fully healed.","grade":"Label instruction (no grade)"},{"action":"If a wound-healing problem develops during treatment, withhold the drug until the wound has healed and decide case by case whether to restart","why":"No study has shown that restarting after a wound complication is safe.","source":"avastin-us","quote":"Withhold AVASTIN until adequate wound healing.The safety of resumption of AVASTIN after resolution of wound healing complications has not been established.","grade":"Label instruction (no grade)"}],"bestInClass":{"statement":"Follow the interval on the drug's own current label; there is no guideline that sets a different one. The US labels give explicit numbers before and after surgery for every agent; the EU SmPCs for Avastin and Lenvima give the post-surgery interval or a 'consider interrupting' instruction but no pre-surgery number, so a UK or EU team may use the US figure or its own policy. The evidence behind the bevacizumab interval is the colorectal trial experience reported in the labels (no extra wound or bleeding complications when surgery was 28 to 60 days before starting; 10 to 20% when operating during treatment) and a meta-analysis of randomised trials (OR 2.32 for wound complications).","sources":["avastin-us","avastin-eu","lenvima-eu","zhang-2016"]},"variants":[{"name":"EU Avastin wording: withhold for elective surgery, interval not stated","differs":"Says therapy should be withheld for elective surgery and not started for at least 28 days after major surgery or until the wound is fully healed, without a number of days before surgery.","evidence":"EU SmPC section 4.4; the same trial experience as the US label is reported in section 4.8.","sources":["avastin-eu"]},{"name":"EU Lenvima wording: consider interruption","differs":"Temporary interruption 'should be considered' before major surgery; the US label says withhold for at least 1 week.","evidence":"EU SmPC: no formal studies of lenvatinib on wound healing; limited experience on when to restart.","sources":["lenvima-eu","lenvima-us"]},{"name":"Sorafenib: two different intervals in one label","differs":"The US label's dosing and warnings sections say at least 10 days before elective surgery; one line of its patient information says at least 2 weeks.","evidence":"Both appear in the current DailyMed text; the prescriber sections give 10 days.","sources":["nexavar-us"]}],"grades":[{"claim":"Bevacizumab doubles wound-healing complications","grade":"Meta-analysis of 7 randomised trials, 5147 participants","source":"zhang-2016","quote":"The pooled estimate of odds ratio (OR) was 2.32, and the 95 % confidence intervals (CI) was 1.43 to 3.75. (P < 0.001)."},{"claim":"No extra risk when major surgery was 28 to 60 days before starting bevacizumab","grade":"Clinical trial experience reported in the SmPC","source":"avastin-eu","quote":"In clinical trials of metastatic carcinoma of the colon or rectum, there was no increased risk of post-operative bleeding or wound healing complications observed in patients who underwent major surgery 28-60 days prior to starting Avastin."},{"claim":"Bevacizumab half-life","grade":"Pharmacokinetics (label)","source":"avastin-us","quote":"The estimated half-life is 20 days (11 to 50 days)."},{"claim":"Axitinib: shortest pre-surgery interval","grade":"Label instruction","source":"inlyta-us","quote":"Withhold INLYTA for at least 2 days prior to elective surgery."},{"claim":"Lenvatinib and pazopanib: one week","grade":"Label instruction","source":"lenvima-us","quote":"Withhold LENVIMA for at least 1 week prior to elective surgery."},{"claim":"Regorafenib: two weeks","grade":"Label instruction","source":"stivarga-us","quote":"Withhold STIVARGA for at least 2 weeks prior to elective surgery."},{"claim":"Sunitinib: three weeks","grade":"Label instruction","source":"sutent-us","quote":"Impaired Wound Healing : Withhold SUTENT for at least 3 weeks prior to elective surgery."},{"claim":"Tivozanib: 24 days","grade":"Label instruction","source":"fotivda-us","quote":"Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery."},{"claim":"Fruquintinib: two weeks before major surgery","grade":"Label instruction","source":"fruzaqla-us","quote":"Impaired Wound Healing: Withhold FRUZAQLA for 2 weeks before major surgery."},{"claim":"Pazopanib: one week","grade":"Label instruction","source":"votrient-us","quote":"Withhold VOTRIENT at least 1 week prior to elective surgery."},{"claim":"Sorafenib: ten days","grade":"Label instruction","source":"nexavar-us","quote":"Risk of Impaired Wound Healing : Withhold NEXAVAR for at least 10 days prior to elective surgery."},{"claim":"Ramucirumab EU SmPC: at least 4 weeks","grade":"Label instruction","source":"cyramza-eu","quote":"Ramucirumab therapy should be temporarily discontinued for at least 4 weeks prior to elective surgery."}],"sources":[{"key":"avastin-us","label":"Avastin (bevacizumab) US prescribing information, DailyMed (Genentech, version of 8 January 2025)","publisher":"Genentech / US FDA (DailyMed)","year":2025,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=939b5d1f-9fb2-4499-80ef-0607aa6b114e","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"avastin-eu","label":"Avastin summary of product characteristics (EMA EPAR product information, as downloaded; the PDF prints no revision date)","publisher":"European Medicines Agency","year":2026,"url":"https://www.ema.europa.eu/en/documents/product-information/avastin-epar-product-information_en.pdf","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"cyramza-us","label":"Cyramza (ramucirumab) US prescribing information, DailyMed (Eli Lilly, version of 10 June 2026)","publisher":"Eli Lilly / US FDA (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c6080942-dee6-423e-b688-1272c2ae90d4","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"cyramza-eu","label":"Cyramza summary of product characteristics (EMA EPAR product information, as downloaded; the PDF prints no revision date)","publisher":"European Medicines Agency","year":2026,"url":"https://www.ema.europa.eu/en/documents/product-information/cyramza-epar-product-information_en.pdf","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"zaltrap-us","label":"Zaltrap (ziv-aflibercept) US prescribing information, DailyMed (Sanofi, version of 17 November 2025)","publisher":"Sanofi / US FDA (DailyMed)","year":2025,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6725df6-50ee-4b0a-b900-d02ba634395d","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"cabometyx-us","label":"Cabometyx (cabozantinib) US prescribing information, DailyMed (Exelixis, version of 17 November 2025)","publisher":"Exelixis / US FDA (DailyMed)","year":2025,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3850cce2-6137-42e5-a792-d318c4a4b3b5","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"stivarga-us","label":"Stivarga (regorafenib) US prescribing information, DailyMed (Bayer, version of 18 February 2026)","publisher":"Bayer / US FDA (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=824f19c9-0546-4a8a-8d8f-c4055c04f7c7","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"inlyta-us","label":"Inlyta (axitinib) US prescribing information, DailyMed (Pfizer, version of 21 February 2025)","publisher":"Pfizer / US FDA (DailyMed)","year":2025,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=84137882-e000-47da-bd5b-fa76ab3c76f9","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"lenvima-us","label":"Lenvima (lenvatinib) US prescribing information, DailyMed (Eisai, version of 22 October 2026)","publisher":"Eisai / US FDA (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4bedd21-efde-44c6-9d9c-b48b78d7ed1e","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"lenvima-eu","label":"Lenvima summary of product characteristics (EMA EPAR product information, as downloaded; the PDF prints no revision date)","publisher":"European Medicines Agency","year":2026,"url":"https://www.ema.europa.eu/en/documents/product-information/lenvima-epar-product-information_en.pdf","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"sutent-us","label":"Sutent (sunitinib) US prescribing information, DailyMed (Pfizer, version of 23 February 2026)","publisher":"Pfizer / US FDA (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=43a4d7f8-48ae-4a63-9108-2fa8e3ea9d9c","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"votrient-us","label":"Votrient (pazopanib) US prescribing information, DailyMed (Novartis, version of 17 December 2025)","publisher":"Novartis / US FDA (DailyMed)","year":2025,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eeaaaf38-fb86-4d9f-a19d-0f61daac2fd7","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"nexavar-us","label":"Nexavar (sorafenib) US prescribing information, DailyMed (Bayer, version of 18 November 2024)","publisher":"Bayer / US FDA (DailyMed)","year":2024,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b50667e4-5ebc-4968-a646-d605058dbef0","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"fruzaqla-us","label":"Fruzaqla (fruquintinib) US prescribing information, DailyMed (Takeda, version of 12 August 2026)","publisher":"Takeda / US FDA (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=186d786e-dc8a-45f2-b5e1-01ac0201879f","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"fotivda-us","label":"Fotivda (tivozanib) US prescribing information, DailyMed (AVEO, version of 21 September 2026)","publisher":"AVEO / US FDA (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de77155c-ecf2-4f15-9758-21d271449d83","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"zhang-2016","label":"Zhang et al., Bevacizumab and wound-healing complications: a systematic review and meta-analysis of randomized controlled trials (Oncotarget 2016)","publisher":"Oncotarget","year":2016,"url":"https://doi.org/10.18632/oncotarget.12666","doi":"10.18632/oncotarget.12666","gradingScheme":"Meta-analysis; no recommendation grade.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No national or international guideline sets these intervals independently of the labels; the ESMO metastatic colorectal cancer guideline (2023) could not be read in full to check whether it states one for liver surgery after bevacizumab.","The intervals before surgery are set from half-life and trial exclusion rules rather than from trials comparing intervals; whether a shorter pause is safe is not known.","The EU product information for Zaltrap and Cabometyx could not be downloaded (rate limit) and was not read; the US labels were used.","No label establishes when it is safe to restart after a wound-healing complication.","Biosimilars of bevacizumab carry the same instructions as the reference product; their labels were not read one by one."]},{"id":"prostate-radiotherapy-bladder-and-rectal-preparation","kind":"protocol","name":"Bladder filling and rectal preparation for prostate radiotherapy","aka":["bladder filling protocol","full bladder for radiotherapy","drinking water before radiotherapy","rectal preparation for radiotherapy","micro-enema before radiotherapy","bowel preparation for prostate radiotherapy","empty bowel radiotherapy","bladder scan before radiotherapy"],"tldr":"For prostate radiotherapy you are usually asked to empty your bladder and then drink a set amount of water before the planning scan and every treatment. A comfortably full bladder pushes the bowel away from the radiation. Some centres also ask for a small enema or laxatives to empty the back passage, but newer studies suggest this is not needed for everyone when daily scans check the position.","summary":"No guideline grades bladder or rectal preparation for prostate radiotherapy, and practice varies. Bladder: a comfortably full bladder lifts small bowel out of the pelvis and lowers bowel dose, but drinking protocols give inconsistent volumes from day to day (Nasser 2021 review). In a randomised trial of 110 men, 540 ml of water gave more reproducible bladder volumes than 1080 ml (median variation 76 against 105 ml) with no more toxicity; a 2021 meta-analysis of 11 studies (417 patients) found 300 to 400 ml gave the best reproducibility and that reproducibility fell as the volume rose. Checking the bladder on imaging before each fraction is the practical safeguard.\n\nRectum: a 2014 systematic review of 18 studies found no robust evidence for one rectal emptying method over another; randomised trials of simethicone (SPoRT, 30 men) and an antiflatulent (78 men) found no reduction in rectal volume or rescans; a small trial found an osmotic laxative gave less rectal gas than a bulking laxative with probiotic. In 295 Royal Marsden patients with daily cone-beam CT, micro-enema preparation reduced the share with a large rectum on the planning CT by only 10 to 15% and did not change intrafraction motion; the authors conclude preparation is not universally needed and recommend intervention where a large rectum coincides with seminal vesicle involvement or risk. A published comment reads the same data as support for risk-adapted, not universal, omission. The ESTRO ACROP IGRT guideline (2019) is cited by Alexander et al. as not recommending routine preparation; its full text could not be read.","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["in-room-imaging-systems","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiotherapy","prostate-radiotherapy-fractionation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Empty your bladder, then drink the amount of water your team tells you, at the same time before every treatment. Some people are also asked to empty their bowel first.","domain":"radiotherapy","setting":{"who":["radiographer","patient-or-carer"],"where":["radiotherapy-department","home"]},"population":"Adults having external beam radiotherapy to the prostate or prostate bed, with or without the pelvic lymph nodes, using daily image guidance. Bladder and rectal preparation for cervical, bladder, rectal and gynaecological radiotherapy, and for brachytherapy, use different volumes and rules and are not covered.","trigger":"Booking of the radiotherapy planning CT; then before each treatment.","steps":[{"action":"Ask the patient to empty their bladder, then drink a set, moderate volume of water (in trials 300 to 540 ml) a fixed time before the planning CT and before every treatment","why":"A comfortably full bladder lifts the bowel away from the radiation; a moderate drink is easier to repeat the same way every day than a large one.","source":"chen-water-volume-2021","quote":"Consuming 300-400 ml of water potentially leads to the best bladder volume reproducibility; moreover, the higher the water consumption volume, the lower the bladder volume reproducibility.","grade":"Systematic review and meta-analysis (10 cohort studies, 1 randomised trial)"},{"action":"Do not ask for very large drinks: 540 ml was more reproducible than 1080 ml and caused no more side effects","why":"Drinking more fills the bladder more on the planning day than on treatment days, so the shapes stop matching.","source":"mullaney-2014","quote":"The 540 mL bladder-filling arm resulted in reproducible BVs throughout a course of RT, without any deterioration in QoL or increase in toxicities for prostate patients.","grade":"Randomised trial (110 patients)"},{"action":"When the pelvic lymph nodes are treated, aim for a full bladder","why":"With a larger area treated, a full bladder matters more for keeping the small bowel out of the high-dose region.","source":"nasser-bladder-2021","quote":"While treating prostate only with empty bladder could be feasible, treating the prostate and pelvic lymph nodes should be preferably done with a full bladder, to limit the radiation dose to the small bowel.","grade":"Narrative review"},{"action":"Check bladder filling on the pre-treatment cone-beam CT, and wait or ask the patient to drink more if it differs from the plan","why":"Even with a drinking routine the bladder fills differently on different days, and the scan shows it before the dose is given.","source":"nasser-bladder-2021","quote":"CBCT prior each fraction of RT is useful for urine volume estimation in order to ensure consistent bladder filling for RT.","grade":"Narrative review"},{"action":"Do not prescribe rectal preparation to everyone by default where daily 3D image guidance is used; decide case by case","why":"With a daily scan before each treatment, enemas changed the position of the prostate very little and only modestly reduced the number of people with a full rectum.","source":"alexander-rectal-2026","quote":"Findings suggest rectal preparation is not universally required with contemporary IGRT.","grade":"Retrospective cohort (295 patients), single centre"},{"action":"Where the planning CT shows a large rectum and the seminal vesicles are involved or at high risk, intervene: repeat the scan after rectal preparation, or adapt the plan","why":"A changing rectum can push the seminal vesicles out of the treated area, so these patients are the ones preparation or adaptation helps.","source":"alexander-rectal-2026","quote":"Interfraction changes in rectal volume can lead to significant underdosing of seminal vesicles therefore we do recommend further intervention for patients with both a large rectum on pCT and seminal vesicle involvement, or a high risk of seminal vesicle involvement.","grade":"Retrospective cohort (295 patients), single centre"},{"action":"If rectal preparation is used, choose the method locally and say to the patient that no method has been shown best","why":"Enemas, laxatives, diet and anti-wind medicines have all been tried, and none has proved better than another.","source":"mcnair-rectal-review-2014","quote":"There is no robust evidence to recommend one rectal emptying strategy over another.","grade":"Systematic review (18 studies)"}],"bestInClass":{"statement":"No guideline sets a best practice; the evidence supports a moderate, timed drink after emptying the bladder (300 to 540 ml in the trials; Chen 2021, Mullaney 2014), a full bladder when the pelvic nodes are treated, and confirmation of bladder filling on the pre-treatment scan. For the rectum, with daily 3D image guidance, routine preparation for everyone is not supported (Alexander 2026; ESTRO ACROP 2019 as cited there); preparation or plan adaptation is targeted at people with a large rectum on the planning CT and seminal vesicle involvement or risk. Where the sources differ: Alexander et al. read their data as showing preparation is not universally required, while the published comment on it reads them as support for risk-adapted omission only, pending prospective study. No method of rectal emptying is better than another (McNair 2014).","sources":["chen-water-volume-2021","mullaney-2014","nasser-bladder-2021","alexander-rectal-2026","gupta-comment-2026","mcnair-rectal-review-2014"]},"variants":[{"name":"Empty bladder, then 350 ml of water one hour before (Royal Marsden)","differs":"Patients empty their bladder an hour before planning and treatment and drink 350 ml of water; micro-enema use depends on the prescription.","evidence":"Described as the routine for 295 patients in the Alexander 2026 cohort; within the volume range the meta-analysis found most reproducible.","sources":["alexander-rectal-2026","chen-water-volume-2021"]},{"name":"Drinking until the bladder feels comfortably full","differs":"No set volume; the patient drinks until they feel full.","evidence":"In the meta-analysis this was less reproducible than 300 to 400 ml (mean bladder volume difference against planning of about 46 ml). The Nasser review cites a study where patients reporting a comfortably full bladder had an adequately full bladder only 76.5% of the time.","sources":["chen-water-volume-2021","nasser-bladder-2021"]},{"name":"Bladder ultrasound scan before treatment, with biofeedback","differs":"A portable bladder scanner measures the volume before each treatment, and the patient waits or drinks until a target is reached.","evidence":"The Nasser review cites one study where 93% of patients on a scan protocol were ready after the cone-beam CT against 75% without, and another where feedback did not improve filling; overall it judges protocols, ultrasound and biofeedback to fall short of consistent filling.","sources":["nasser-bladder-2021"]},{"name":"Empty bladder for prostate-only treatment","differs":"The bladder is kept empty, in some single-fraction schedules with a catheter.","evidence":"Described as feasible for prostate-only treatment in the Nasser review, citing a non-inferiority report; not recommended when the pelvic nodes are treated.","sources":["nasser-bladder-2021"]},{"name":"Antiflatulent (simethicone) as bowel preparation","differs":"Patients take simethicone during treatment to reduce rectal gas.","evidence":"Two randomised trials found no overall reduction in rectal volume, gas or planning rescans (78 and 30 patients); SPoRT found less rectal volume variability from week three onwards with simethicone, which its authors say needs a larger study.","sources":["mcguffin-antiflatulent-2018","ward-sport-2022"]},{"name":"Laxatives with a low-gas diet","differs":"Patients follow a low-gas diet and take a laxative during treatment.","evidence":"A trial of 17 patients found an osmotic laxative gave lower rectal gas than a bulking laxative with probiotic (OR 3.2 for a higher gas rating with the bulking regimen); the authors call for larger studies.","sources":["weston-laxative-2020"]}],"grades":[{"claim":"540 ml gave less bladder volume variation than 1080 ml","grade":"Randomised trial (110 patients)","source":"mullaney-2014","quote":"There was significantly less BV variation in the 540 mL arm when compared with 1080 mL (median: 76 mL vs 105 mL, P = .003)."},{"claim":"Rectal preparation reduced large rectum on planning CT by only 10 to 15%","grade":"Retrospective cohort (295 patients)","source":"alexander-rectal-2026","quote":"Results do not justify blanket use of rectal preparation for individuals undergoing radiotherapy to their prostate."},{"claim":"The findings support risk-adapted, not universal, omission of rectal preparation","grade":"Published correspondence","source":"gupta-comment-2026","quote":"The findings are therefore best viewed as supporting risk-adapted deimplementation rather than universal omission of rectal preparation."},{"claim":"No consensus on bladder filling protocols","grade":"Narrative review","source":"nasser-bladder-2021","quote":"There is no consensus on what bladder filling protocols should be used for prostate external beam radiotherapy."}],"sources":[{"key":"alexander-rectal-2026","label":"Is rectal preparation necessary in contemporary image-guided prostate radiotherapy?","publisher":"Clinical and Translational Radiation Oncology (Alexander et al., Royal Marsden)","year":2026,"url":"https://doi.org/10.1016/j.ctro.2026.101207","doi":"10.1016/j.ctro.2026.101207","read":"full-text","accessed":"2026-11-11"},{"key":"gupta-comment-2026","label":"Comment on \"Is rectal preparation necessary in contemporary image-guided prostate radiotherapy?\"","publisher":"Clinical and Translational Radiation Oncology (Gupta et al.)","year":2026,"url":"https://doi.org/10.1016/j.ctro.2026.101255","doi":"10.1016/j.ctro.2026.101255","read":"full-text","accessed":"2026-11-11"},{"key":"nasser-bladder-2021","label":"Maintaining consistent bladder filling during external beam radiotherapy for prostate cancer","publisher":"Technical Innovations and Patient Support in Radiation Oncology (Nasser et al.)","year":2021,"url":"https://doi.org/10.1016/j.tipsro.2021.01.002","doi":"10.1016/j.tipsro.2021.01.002","read":"full-text","accessed":"2026-11-11"},{"key":"mullaney-2014","label":"A randomized trial comparing bladder volume consistency during fractionated prostate radiation therapy","publisher":"Practical Radiation Oncology (Mullaney et al.)","year":2014,"url":"https://doi.org/10.1016/j.prro.2013.11.006","doi":"10.1016/j.prro.2013.11.006","read":"abstract","accessed":"2026-11-11"},{"key":"chen-water-volume-2021","label":"Bladder volume reproducibility after water consumption in patients with prostate cancer undergoing radiotherapy: a systematic review and meta-analysis","publisher":"Biomedical Journal (Chen et al.)","year":2021,"url":"https://doi.org/10.1016/j.bj.2020.11.004","doi":"10.1016/j.bj.2020.11.004","read":"abstract","accessed":"2026-11-11"},{"key":"mcnair-rectal-review-2014","label":"A systematic review: effectiveness of rectal emptying preparation in prostate cancer patients","publisher":"Practical Radiation Oncology (McNair et al.)","year":2014,"url":"https://doi.org/10.1016/j.prro.2014.06.005","doi":"10.1016/j.prro.2014.06.005","read":"abstract","accessed":"2026-11-11"},{"key":"mcguffin-antiflatulent-2018","label":"To prep or not to prep: a randomized trial on the use of antiflatulent medication as part of bowel preparation for patients having image guided external beam radiation therapy to the prostate","publisher":"Practical Radiation Oncology (McGuffin et al.)","year":2018,"url":"https://doi.org/10.1016/j.prro.2017.10.012","doi":"10.1016/j.prro.2017.10.012","read":"abstract","accessed":"2026-11-11"},{"key":"ward-sport-2022","label":"Randomised controlled trial on the effect of simethicone bowel preparation on rectal variability during image-guided radiation therapy for prostate cancer (SPoRT study)","publisher":"Journal of Medical Imaging and Radiation Oncology (Ward et al.)","year":2022,"url":"https://doi.org/10.1111/1754-9485.13404","doi":"10.1111/1754-9485.13404","read":"abstract","accessed":"2026-11-11"},{"key":"weston-laxative-2020","label":"Effects of a laxation and probiotic bowel preparation regimen: a randomized controlled trial in patients undergoing prostate radiation therapy","publisher":"Nutrition and Cancer (Weston et al.)","year":2020,"url":"https://doi.org/10.1080/01635581.2019.1669675","doi":"10.1080/01635581.2019.1669675","read":"abstract","accessed":"2026-11-11"},{"key":"estro-acrop-prostate-igrt-2019","label":"ESTRO ACROP consensus guideline on the use of image guided radiation therapy for localized prostate cancer","publisher":"ESTRO (Radiotherapy and Oncology; Ghadjar et al.)","year":2019,"url":"https://doi.org/10.1016/j.radonc.2019.08.027","doi":"10.1016/j.radonc.2019.08.027","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-pelvic-filling-protocol","idea-pu-rectal-spacer-prostate"],"gaps":["No guideline with graded recommendations covers bladder filling or rectal preparation for prostate radiotherapy. The ESTRO ACROP IGRT guideline (2019) was read only as an abstract (the open repository copy is restricted and the publisher returned a bot page); its position on preparation is reported here only as Alexander et al. cite it.","The water-volume trial, the meta-analysis and the rectal preparation trials were read as abstracts; all are small or single-centre.","No source read gives the best timing between drinking and treatment; centres use 30 minutes to an hour.","The Alexander 2026 cohort is retrospective, and its preparation and no-preparation groups differed by prescription, a limitation the published comment sets out.","Whether rectal spacers change the need for preparation was not examined; spacers are an upgrade idea of their own (idea-pu-rectal-spacer-prostate).","Bladder and rectal preparation for cervical, rectal, bladder and gynaecological radiotherapy and for brachytherapy is not covered."]},{"id":"bleeding-precautions-when-platelets-are-low","kind":"protocol","name":"Bleeding precautions at home when platelets are low","aka":["thrombocytopenia precautions","low platelet precautions","bleeding precautions","low platelets during chemotherapy","bruising and bleeding on chemotherapy"],"tldr":"When chemotherapy lowers the platelets that help blood clot, small changes at home lower the chance of bleeding: a very soft toothbrush, an electric shaver, shoes on, no aspirin or ibuprofen unless the team agrees, and firm pressure on any cut. Some signs need a call to the team straight away, such as bleeding that will not stop, blood in urine or stools, or a bad headache or change in vision.","summary":"The home advice comes from national patient guidance: NCI's Chemotherapy and You (2023) and its thrombocytopenia page (reviewed 2022), and Macmillan (2018, under review). They agree on a very soft toothbrush, an electric shaver, care with sharp objects, shoes at all times, gentle nose-blowing, avoiding aspirin, ibuprofen and supplements without the team's agreement, firm pressure on bleeding, treating constipation, and calling about named warning signs. They differ on flossing: NCI's booklet says not to use dental floss but suggests a water flosser, its mouth-care section says to ask before flossing, and Macmillan says not to floss. None of this has been tested in a trial and none of it is graded. Platelet support is a clinical decision: NICE NG24 offers prophylactic platelet transfusion below 10 x 10^9 per litre to people who are not bleeding and not having a procedure, with exceptions (chronic bone marrow failure, autoimmune thrombocytopenia, HIT, TTP), and transfusion for clinically significant bleeding below 30 x 10^9 per litre. ASCO 2018 allows adults after autologous stem cell transplant at experienced centres to be transfused at the first sign of bleeding rather than prophylactically.","asOf":"2026-11-11","links":[],"tags":[],"related":["oral-mucositis-prevention-and-oral-care","diet-alcohol-and-weight-during-cancer-treatment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["thrombocytopenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Chemotherapy can lower your platelets, the cells that stop bleeding. Use a very soft toothbrush and an electric shaver, wear shoes, and ask before taking any painkiller or supplement. Press firmly on a cut until it stops. Call your team if bleeding will not stop, if you see blood in your urine or stools, or if you get a bad headache or blurred vision.","domain":"supportive-care","setting":{"who":["patient-or-carer","nurse","doctor"],"where":["home","telephone-triage","chemotherapy-day-unit"]},"population":"Adults having chemotherapy or targeted therapy whose platelet count is low or is expected to fall. The sources do not set a platelet count at which the home precautions start; the treating team says when they apply. Children, people after stem cell transplant, and people on anticoagulants have their own team-specific advice.","trigger":"The team says the platelet count is low, or a treatment known to lower platelets is starting.","steps":[{"action":"Brush teeth with a very soft toothbrush, softened under hot water, and ask the team before flossing","why":"Gums bleed easily when platelets are low; a soft brush cleans without cutting them.","source":"nci-chemo-and-you","quote":"Brush your teeth with a very soft toothbrush.","grade":"Not graded (patient booklet)"},{"action":"Use an electric shaver rather than a razor, and take care with scissors, knives and other sharp objects","why":"Small cuts bleed for longer when platelets are low.","source":"nci-chemo-and-you","quote":"Use an electric shaver instead of a razor.","grade":"Not graded (patient booklet)"},{"action":"Wear shoes at all times, blow the nose gently, and avoid contact sports or activities where an injury is likely","why":"Knocks and falls cause bruising and bleeding that may be hard to stop.","source":"nci-chemo-and-you","quote":"Wear shoes all the time, even inside the house or hospital.","grade":"Not graded (patient booklet)"},{"action":"Do not use tampons, enemas, suppositories or rectal thermometers, or wear clothes with tight collars, wrists or waistbands","why":"These can damage delicate linings and cause bleeding. NCI lists them under 'Things not to do'.","source":"nci-chemo-and-you","quote":"Use tampons, enemas, suppositories, or rectal thermometers.","grade":"Not graded (patient booklet; listed under 'Things not to do')"},{"action":"Check with the team before taking aspirin, ibuprofen, other over-the-counter medicines, vitamins, herbs or supplements, or drinking alcohol","why":"Aspirin and ibuprofen make bleeding more likely, and some supplements change how treatment works.","source":"nci-bleeding-page","quote":"Many over-the-counter medicines contain aspirin or ibuprofen, which can increase your risk of bleeding.","grade":"Not graded (patient information)"},{"action":"Tell the team about constipation, so a stool softener can be prescribed","why":"Straining can make the back passage bleed.","source":"nci-chemo-and-you","quote":"They may prescribe a stool softener to prevent straining and rectal bleeding when you go to the bathroom.","grade":"Not graded (patient booklet)"},{"action":"If bleeding starts, press firmly on the place with a clean cloth and keep pressing until it stops; put ice on a bruise","why":"Steady pressure helps a clot form when there are fewer platelets to make one.","source":"nci-bleeding-page","quote":"If you start to bleed, press down firmly on the area with a clean cloth. Keep pressing until the bleeding stops.","grade":"Not graded (patient information)"},{"action":"Call the team straight away for bleeding that does not stop after a few minutes, blood in urine, black or bloody stools, vomiting blood, unusual vaginal bleeding, a bad headache, a change in vision, or new confusion or sleepiness","why":"These can be signs of serious bleeding, including bleeding in the brain, and need checking the same day.","source":"nci-bleeding-page","quote":"Head or vision changes such as bad headaches or changes in how well you see, or if you feel confused or very sleepy.","grade":"Not graded (patient information)"},{"action":"Expect the team to check the platelet count often, and to decide on medicine, a platelet transfusion or a delay in chemotherapy if it is too low","why":"A platelet transfusion or a treatment delay is the team's decision, made on the count and on whether there is bleeding.","source":"nci-chemo-and-you","quote":"You may need medication, a platelet transfusion, or a delay in your chemotherapy treatment if your platelet count is too low.","grade":"Not graded (patient booklet)"}],"bestInClass":{"statement":"No guideline grades home bleeding precautions; the best available version is the national patient guidance from NCI (2023 booklet, 2022 web page), with Macmillan (2018) agreeing on every point except flossing. Where they differ, NCI's booklet allows a water flosser but not dental floss, and Macmillan says not to floss. The clinical side is graded by its own guidelines: NICE NG24 (2015, updated 2026) offers prophylactic platelet transfusion below 10 x 10^9 per litre to people who are not bleeding or having a procedure, and transfusion for clinically significant bleeding below 30 x 10^9 per litre; ASCO 2018 agrees on prophylactic thresholds and allows transfusion at the first sign of bleeding, rather than prophylactically, for adults after autologous stem cell transplant at experienced centres.","sources":["nci-chemo-and-you","nci-bleeding-page","macmillan-chemo-side-effects","nice-ng24-platelets","asco-platelet-2018"]},"variants":[{"name":"No flossing at all (Macmillan)","differs":"Says to use a soft toothbrush and not to floss, with no mention of a water flosser.","evidence":"Patient information, not graded: 'Use a soft toothbrush to protect your gums from bleeding and do not floss.' NCI's booklet instead suggests a water flosser and, in its mouth-care section, says to ask about flossing when platelets are low.","sources":["macmillan-chemo-side-effects","nci-chemo-and-you"]},{"name":"Gloves for housework and gardening (Macmillan)","differs":"Adds protective gloves for household and garden work to prevent cuts.","evidence":"Patient information, not graded: 'Wear protective gloves when doing work around the house or in the garden.'","sources":["macmillan-chemo-side-effects"]},{"name":"Platelet transfusion only when bleeding, after autologous stem cell transplant (ASCO 2018)","differs":"Adults after autologous stem cell transplant at experienced centres are transfused at the first sign of bleeding rather than at a set count.","evidence":"ASCO 2018, from randomised trials, as stated in the abstract; prophylactic thresholds still apply to children after autologous transplant and to everyone after allogeneic transplant.","sources":["asco-platelet-2018"]}],"grades":[{"claim":"Home bleeding precautions","grade":"Not graded: patient booklets and web pages give expert advice without a grading scheme","source":"nci-chemo-and-you"},{"claim":"Prophylactic platelet transfusion below 10 x 10^9 per litre for people who are not bleeding or having a procedure, except in chronic bone marrow failure, autoimmune thrombocytopenia, HIT and TTP","grade":"Not graded (NICE NG24 1.7.3, 'offer'); the threshold's superscript does not survive in the page text, so it is given here in prose","source":"nice-ng24-platelets"},{"claim":"No routine prophylactic platelet transfusion in chronic bone marrow failure, autoimmune thrombocytopenia, HIT or TTP","grade":"Not graded (NICE NG24 1.7.7)","source":"nice-ng24-platelets","quote":"Do not routinely offer prophylactic platelet transfusions to people with any of the following:"},{"claim":"No prophylactic platelet transfusion before low-bleeding-risk procedures such as central venous cannulation","grade":"Not graded (NICE NG24 1.7.8, 'do not offer')","source":"nice-ng24-platelets","quote":"Do not offer prophylactic platelet transfusions to people having procedures with a low risk of bleeding, such as adults having central venous cannulation or any people having bone marrow aspiration and trephine biopsy."},{"claim":"Adults after autologous stem cell transplant may be transfused at the first sign of bleeding","grade":"Based on randomised controlled trials (as stated in the ASCO 2018 abstract; the graded recommendation table was not read)","source":"asco-platelet-2018","quote":"Based on data from randomized controlled trials, adult patients who undergo autologous stem-cell transplantation at experienced centers may receive a platelet transfusion at the first sign of bleeding, rather than prophylactically."}],"sources":[{"key":"nci-chemo-and-you","label":"Chemotherapy and You: Support for People with Cancer","publisher":"National Cancer Institute (US)","year":2023,"url":"https://www.cancer.gov/publications/patient-education/chemotherapy-and-you.pdf","gradingScheme":"Patient booklet; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nci-bleeding-page","label":"Bleeding and Bruising (Thrombocytopenia) and Cancer Treatment","publisher":"National Cancer Institute (US)","year":2022,"url":"https://www.cancer.gov/about-cancer/treatment/side-effects/bleeding-bruising","gradingScheme":"Patient information page; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-chemo-side-effects","label":"Side effects of chemotherapy","publisher":"Macmillan Cancer Support","year":2018,"url":"https://www.macmillan.org.uk/cancer-information-and-support/treatment/types-of-treatment/chemotherapy/side-effects-of-chemotherapy","gradingScheme":"Patient information page; not graded. Reviewed September 2018, next review was due 2021, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng24-platelets","label":"Blood transfusion (NG24): platelet transfusion recommendations","publisher":"NICE","year":2015,"url":"https://www.nice.org.uk/guidance/ng24/chapter/Platelet-transfusion","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider', 'do not offer') signals strength. Last updated 26 February 2026.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-platelet-2018","label":"Platelet Transfusion for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update","publisher":"ASCO (Journal of Clinical Oncology)","year":2018,"url":"https://doi.org/10.1200/JCO.2017.76.1734","doi":"10.1200/JCO.2017.76.1734","gradingScheme":"ASCO evidence quality and recommendation strength; the graded table was not read, only the abstract.","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No trial has tested whether home bleeding precautions prevent bleeding; every home step here is expert advice, and none is graded.","The sources do not say at what platelet count the precautions should start or stop; that is left to the treating team.","The flossing advice differs between NCI and Macmillan, and neither cites evidence for its position.","Macmillan's chemotherapy side effects page was last reviewed in 2018 and is marked as under review.","Only the abstract of the ASCO 2018 platelet transfusion guideline was read; its graded recommendation table, including its numerical thresholds, was not.","Advice for people taking anticoagulants or antiplatelet drugs while their platelets are low is specific to each team and is not covered by these sources."]},{"id":"central-line-occlusion-management","kind":"protocol","name":"Blocked central line or port: assessment and clearing with a thrombolytic","aka":["blocked PICC","blocked port","CVAD occlusion","line will not bleed back","withdrawal occlusion","Cathflo","alteplase line lock","urokinase lock","persistent withdrawal occlusion"],"tldr":"If your line or port will not give blood back or will not flush, the nurse first checks for simple causes such as a kink, a closed clamp or a needle that has slipped. If a clot is the likely cause, a small dose of clot-dissolving medicine can be left in the line for half an hour to two hours. It should never be forced.","summary":"Occlusion is partial (fluid goes in but blood will not come back) or complete. ESMO (2015) groups causes as mechanical (a kink, a tight suture, a dislodged or blocked port needle, the tip against the vein wall, pinch-off between the first rib and clavicle), thrombotic (fibrin sheath, clot in the lumen, mural or venous thrombosis) and drug-related (precipitates from incompatible drugs or parenteral nutrition). The alteplase label asks that malposition, mechanical failure, suture constriction and precipitates be considered first, and warns against vigorous suction or excessive pressure, which can damage the catheter or push a clot into the circulation. If thrombosis of the vein is suspected (swelling, pain), ESMO recommends Doppler ultrasound [III, A].\n\nFor a suspected clot in the lumen, alteplase 2 mg in 2 ml (for people of 30 kg or more) is instilled and left; function is checked at 30 minutes and again at 120 minutes, and a second dose may be given if function has not returned at 120 minutes. In the label's trials, 75% of 995 patients had function restored 120 minutes after the first dose and 85% overall after up to two doses. Once restored, 4 to 5 ml of blood is aspirated to remove the drug and clot before a saline flush. The Cochrane review (2012) found low-quality evidence that urokinase restores patency better than placebo (RR 2.09; number needed to treat 4) and very low-quality evidence for alteplase, and could not judge safety. Regular saline flushing after every use is the main prevention (ESMO [II, B]).","asOf":"2026-11-11","links":[],"tags":[],"related":["catheter-related-thrombosis-in-cancer","picc-and-tunnelled-line-care","implanted-port-access-and-care"],"cancers":[],"sections":[],"technologies":["picc-lines","implanted-ports","catheter-lock-solutions","huber-needles-port-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access","vte"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If your line or port is blocked, the nurse checks for kinks and clamps first, then may put a clot-dissolving medicine in it for a while. Tell the team if your arm, neck or face swells.","domain":"vascular-access","setting":{"who":["nurse","doctor"],"where":["chemotherapy-day-unit","ward","outpatient-clinic","community"]},"population":"Adults with cancer who have a PICC, tunnelled central catheter or implanted port that will not aspirate or flush. Children are dosed by lumen volume (alteplase label). Dialysis catheters were excluded from the alteplase trials and are not covered.","trigger":"Blood cannot be withdrawn, or the line or port is sluggish or will not flush.","steps":[{"action":"Look for mechanical causes first: a closed clamp, a kink, a tight suture, a port needle that has slipped, the tip against the vein wall or the catheter pinched under the collarbone","why":"Many blocked lines are not clotted, and a clot-dissolving drug will not fix a kink or a misplaced needle.","source":"esmo-2015","quote":"Several mechanical causes can lead to a blockage: kink in catheter, tight suture, huber needle dislodge or occlusion, the catheter tip being blocked by the vessel wall and pinch-off syndrome (compression of the catheter, caused by its passage through the narrow angle between the first rib and the lateral portion of the clavicle)."},{"action":"Consider a drug or nutrition precipitate if the blockage followed incompatible infusions or parenteral nutrition","why":"Precipitates need a different solution from clots.","source":"esmo-2015","quote":"Inappropriate concentration or inadequate mixture can cause the precipitation of medications in the catheter lumen (low or high pH, calcium phosphate precipitate, lipid emulsion, high-osmolarity and high-protein nutrition formulas) [ 109 ]."},{"action":"Never force a flush or pull hard on the syringe","why":"Force can split the catheter or push a clot into the lungs.","source":"alteplase-label","quote":"Because of the risk of damage to the vascular wall or collapse of soft‑walled catheters, vigorous suction should not be applied during attempts to determine catheter occlusion."},{"action":"If the arm, neck or face is swollen or painful, arrange a Doppler ultrasound for thrombosis","why":"A clot in the vein around the catheter needs anticoagulant treatment, not just clearing of the line.","source":"esmo-2015","quote":"Although venography is considered the gold standard for the diagnosis of CRT, Doppler ultrasound is usually carried out [III, A]","grade":"[III, A]"},{"action":"For a suspected clot in the lumen, instil alteplase 1 mg/ml: 2 mg in 2 ml for people weighing 30 kg or more, without excessive pressure","why":"A small dose left in the catheter dissolves the clot in most cases.","source":"alteplase-label","quote":"Patients weighing ≥30 kg: 2 mg in 2 mL"},{"action":"Try to aspirate after 30 minutes and, if still blocked, after 120 minutes; if function has not returned at 120 minutes, a second dose may be instilled","why":"Most clots clear within two hours; a second dose clears some of the rest.","source":"alteplase-label","quote":"If catheter function is not restored at 120 minutes after 1 dose of Cathflo Activase, a second dose may be instilled"},{"action":"Once the line works, withdraw 4 to 5 ml of blood to remove the drug and clot, then flush gently with saline","why":"The drug and the loosened clot should come out rather than be pushed into the bloodstream.","source":"alteplase-label","quote":"If catheter function has been restored, aspirate 4–5 mL of blood in patients ≥10 kg or 3 mL in patients <10 kg to remove Cathflo Activase and residual clot, and gently irrigate the catheter with 0.9% Sodium Chloride Injection, USP"},{"action":"If two doses fail, do not keep trying: get imaging of the catheter and decide with the team whether to reposition, exchange or remove it","why":"A line that still will not work after two doses is likely misplaced, damaged or sheathed, and further doses have not been studied.","practice":"The alteplase label gives no safety or efficacy data beyond two 2 mg doses, and ESMO's comparison table lists removal of a non-functional catheter among the options in other guidelines; no guideline read sets out the imaging step."},{"action":"Prevent recurrence by flushing with saline after every infusion and every blood sample","why":"Leaving blood or drug in the catheter is the commonest cause of clotting and precipitate.","source":"esmo-2015","quote":"Routine flushing with saline, after the completion of any infusion or blood sampling, is recommended [II, B]","grade":"[II, B]"}],"bestInClass":{"statement":"No graded oncology guideline sets out an occlusion algorithm that could be read. The best-supported sequence combines ESMO 2015 (rule out mechanical and precipitate causes; Doppler ultrasound for suspected thrombosis [III, A]; saline flushing after every use [II, B]) with the alteplase label (2 mg in 2 ml, check at 30 and 120 minutes, a second dose if needed, aspirate before flushing, no force). The evidence for thrombolytics is weak: the Cochrane review (2012) rated urokinase low quality and alteplase very low quality for efficacy, and could not judge safety.","sources":["esmo-2015","alteplase-label","cochrane-patency-2012"]},"variants":[{"name":"Urokinase instead of alteplase","differs":"Uses urokinase as the catheter thrombolytic, as some countries do where alteplase for catheters is not licensed.","evidence":"Cochrane 2012: low-quality evidence from two studies that urokinase restores patency better than placebo (RR 2.09, 95% CI 1.47 to 2.95; number needed to treat 4), with insufficient evidence on safety. Doses vary by product and country and were not read from a label here.","sources":["cochrane-patency-2012"]}],"grades":[{"claim":"Urokinase more effective than placebo for restoring patency","grade":"Low-quality evidence","source":"cochrane-patency-2012","quote":"There was low quality evidence from a meta-analysis of two studies suggesting that urokinase (various strengths) was more effective than placebo for restoring patency to occluded CVC lumens in adults and children with underlying medical conditions (relative risk (RR) 2.09, 95% confidence interval (CI) 1.47 to 2.95), with a number needed to treat of 4 (95% CI 2 to 8)."}],"sources":[{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I (large good-quality RCT or meta-analysis) to V (no control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"},{"key":"alteplase-label","label":"Cathflo Activase (alteplase) for catheter clearance, US prescribing information","publisher":"US National Library of Medicine, DailyMed (Genentech)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=91ecdef2-95ff-42dd-a31c-c8a09cab3ad9","read":"full-text","accessed":"2026-11-11"},{"key":"cochrane-patency-2012","label":"Interventions for restoring patency of occluded central venous catheter lumens","publisher":"Cochrane Database of Systematic Reviews (van Miert et al.)","year":2012,"url":"https://doi.org/10.1002/14651858.CD007119.pub2","doi":"10.1002/14651858.CD007119.pub2","gradingScheme":"GRADE quality of evidence: high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"ins-2024","label":"Infusion Therapy Standards of Practice, 9th Edition","publisher":"Infusion Nurses Society (Journal of Infusion Nursing)","year":2024,"url":"https://doi.org/10.1097/NAN.0000000000000532","doi":"10.1097/NAN.0000000000000532","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No graded national or international guideline on occlusion could be read; the INS Standards (2024), which address it in detail, were not reachable, and NCCN is cited only through ESMO's 2015 comparison table.","The Cochrane review dates from 2012 (searches to 2011) and was read as an abstract; no newer systematic review of thrombolytics for catheter occlusion was found.","Management of drug or lipid precipitates (for example with acid or ethanol) is not covered: no source read gives a regimen.","There is no OnCo drug record for alteplase, so the drug is named here without a link."]},{"id":"vte-prophylaxis-after-cancer-surgery","kind":"protocol","name":"Blood clot prevention around cancer surgery, including extended prophylaxis after major abdominal and pelvic operations","aka":["VTE prophylaxis","thromboprophylaxis","extended thromboprophylaxis","28 days of heparin injections after surgery","DVT prevention after cancer surgery","blood thinner injections after surgery","anti-embolism stockings"],"tldr":"Cancer and major surgery both raise the risk of blood clots in the legs and lungs. Before the operation the team should assess your risk of clots and of bleeding, use stockings or leg pumps, and usually give blood-thinning injections. After major cancer surgery in the abdomen or pelvis these are often continued at home for four weeks, because many clots happen after discharge.","summary":"NICE NG89 (2018, updated 2019) asks for every surgical patient's VTE and bleeding risk to be assessed on admission with a published tool and reassessed at consultant review or when their condition changes. For abdominal (gastrointestinal, gynaecological, urological) surgery at increased risk, mechanical prophylaxis (anti-embolism stockings or intermittent pneumatic compression) starts on admission and continues until mobility returns, and LMWH or fondaparinux is added for at least 7 days where clot risk outweighs bleeding risk. NICE says to consider extending pharmacological prophylaxis to 28 days after major cancer surgery in the abdomen. For thoracic surgery the same pattern is 'consider'. ASCO (2023 update) added apixaban and rivaroxaban as options for extended prophylaxis after cancer surgery, with a weak recommendation. The Cochrane review (2019; 7 RCTs, 1728 participants, benign and malignant disease) found extended LMWH reduced VTE after major abdominal or pelvic surgery from 13.2% to 5.3% (OR 0.38, 95% CI 0.26 to 0.54, moderate-quality evidence), mostly clots found by scanning, with no difference in bleeding or mortality. Before discharge, people should be shown how to inject and dispose of needles, told how long to continue, and told the signs of DVT, pulmonary embolism and bleeding.","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":["colorectal","ovarian","endometrial","gastric","pancreatic"],"sections":[],"technologies":["cancer-associated-thrombosis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["vte"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After a big cancer operation you may be asked to keep giving yourself a small blood-thinning injection each day for about four weeks. It lowers the chance of a clot. Tell your team about calf pain or swelling, sudden breathlessness or chest pain, or any unusual bleeding.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","pharmacist","patient-or-carer"],"where":["ward","theatre","home"]},"population":"Adults and young people aged 16 and over having surgery for cancer, as NICE NG89 scopes it; the extended 28-day course applies to major cancer surgery in the abdomen (NICE) or abdomen and pelvis (Cochrane, ASCO). Thoracic, head and neck, orthopaedic and neurosurgical operations have their own sections in NG89; children under 16 are outside it. People already on anticoagulants need a bridging plan instead.","trigger":"Admission for cancer surgery.","steps":[{"action":"Assess every surgical patient's risk of VTE and of bleeding on admission or by the first consultant review, using a published tool","why":"Prevention is only worth its bleeding risk in people whose clot risk is high enough, and a structured tool means nobody is missed.","source":"nice-ng89","quote":"Assess all surgical and trauma patients to identify the risk of VTE and bleeding:","grade":"[2018, amended 2021]"},{"action":"Explain the risk of clots, why prevention is offered and its side effects, how to use stockings or leg pumps, and how to lower risk by drinking enough and moving","why":"People who understand why they need the injections and stockings are more likely to keep using them.","source":"nice-ng89","quote":"For people admitted to hospital who are at increased risk of VTE, give them and their family members or carers (as appropriate) verbal and written information on the following before offering VTE prophylaxis:","grade":"[2018]"},{"action":"Start mechanical prophylaxis, anti-embolism stockings or intermittent pneumatic compression, on admission and continue until mobility is back to normal","why":"Squeezing the legs keeps blood moving while you are less active, without any bleeding risk.","source":"nice-ng89","quote":"Start mechanical VTE prophylaxis on admission for people undergoing abdominal surgery. Choose either:","grade":"[2018]"},{"action":"Do not use anti-embolism stockings where they could damage the skin or circulation; measure the legs, fit the right size and check the skin daily","why":"Badly fitting stockings can cause pressure sores, and they are unsafe with some skin and arterial conditions.","source":"nice-ng89","quote":"Ensure that people who need anti-embolism stockings have their legs measured and that they are provided with the correct size of stocking. Anti-embolism stockings should be fitted and patients shown how to use them by staff trained in their use.","grade":"[2010]"},{"action":"Add LMWH or fondaparinux for at least 7 days after abdominal surgery when clot risk outweighs bleeding risk","why":"Blood-thinning injections reduce clots after major surgery more than stockings alone.","source":"nice-ng89","quote":"Add pharmacological VTE prophylaxis for a minimum of 7 days for people undergoing abdominal surgery whose risk of VTE outweighs their risk of bleeding, taking into account individual patient factors and according to clinical judgement.","grade":"[2018]"},{"action":"If regional anaesthesia such as an epidural is used, time the anticoagulant doses to keep the risk of a spinal bleed low","why":"A blood thinner given too close to placing or removing an epidural catheter can cause bleeding around the spinal cord.","source":"nice-ng89","quote":"If regional anaesthesia is used, plan the timing of pharmacological VTE prophylaxis to minimise the risk of epidural haematoma.","grade":"[2010]"},{"action":"After major cancer surgery in the abdomen or pelvis, consider continuing pharmacological prophylaxis for 28 days after the operation","why":"Cancer keeps clot risk high for weeks after surgery, and many clots appear after people have gone home.","source":"nice-ng89","quote":"Consider extending pharmacological VTE prophylaxis to 28 days postoperatively for people who have had major cancer surgery in the abdomen.","grade":"[2018]"},{"action":"Reassess clot and bleeding risk at consultant review and whenever the person's condition changes","why":"A new bleed, a return to theatre or a fall in platelets can change whether blood thinners are still safe.","source":"nice-ng89","quote":"Reassess all medical, surgical and trauma patients for risk of VTE and bleeding at the point of consultant review or if their clinical condition changes.","grade":"[2018]"},{"action":"Before discharge on prophylaxis, teach how to give the injections and dispose of needles, how long to continue, the side effects to watch for, and whom to contact","why":"Four weeks of daily injections at home only work if people know how to do them and why to finish the course.","source":"nice-ng89","quote":"Give people discharged with VTE prophylaxis and their family members or carers (as appropriate) verbal and written information on:","grade":"[2018]"},{"action":"Tell everyone going home the signs of a deep vein thrombosis and a pulmonary embolism, and to seek help at once if they appear","why":"Calf pain or swelling, sudden breathlessness or chest pain need urgent treatment.","source":"nice-ng89","quote":"the importance of seeking help if DVT, pulmonary embolism or other adverse events are suspected.","grade":"[2018]"}],"bestInClass":{"statement":"Risk assessment for VTE and bleeding on admission, mechanical prophylaxis from admission, LMWH or fondaparinux for at least 7 days after abdominal surgery, and extended pharmacological prophylaxis to 28 days after major abdominal or pelvic cancer surgery (NICE NG89 'consider' [2018]; Cochrane 2019, moderate-quality evidence that it reduces VTE without increasing bleeding or mortality). ASCO 2023 adds apixaban or rivaroxaban tablets as options for the extended course, with a weak recommendation, where NICE names only LMWH or fondaparinux. Most of the reduction in the trials is in clots found by scanning; symptomatic VTE fell from 1.0% to 0.1%, a difference that did not reach significance.","sources":["nice-ng89","cochrane-extended-lmwh-2019","asco-vte-2023"]},"variants":[{"name":"Apixaban or rivaroxaban tablets for the extended course","differs":"Replaces four weeks of daily injections with an oral factor Xa inhibitor after cancer surgery.","evidence":"ASCO 2023 added both as options with a weak strength of recommendation, on two randomised trials that its abstract describes as having important limitations but suggesting safety and effectiveness. NICE NG89 does not list them for abdominal surgery.","sources":["asco-vte-2023","nice-ng89"]}],"grades":[{"claim":"Offer VTE prophylaxis for abdominal surgery at increased risk","grade":"[2018] (NICE does not grade)","source":"nice-ng89","quote":"Offer VTE prophylaxis to people undergoing abdominal (gastrointestinal, gynaecological, urological) surgery who are at increased risk of VTE."},{"claim":"Consider extending pharmacological prophylaxis to 28 days after major abdominal cancer surgery","grade":"[2018] (NICE does not grade)","source":"nice-ng89"},{"claim":"Extended LMWH reduced VTE from 13.2% to 5.3% after major abdominal or pelvic surgery","grade":"moderate-quality evidence","source":"cochrane-extended-lmwh-2019"},{"claim":"Apixaban and rivaroxaban as options for extended prophylaxis after cancer surgery","grade":"weak strength of recommendation","source":"asco-vte-2023","quote":"Apixaban and rivaroxaban were added as options for extended pharmacologic thromboprophylaxis after cancer surgery, with a weak strength of recommendation."},{"claim":"Consider prophylaxis for thoracic surgery at increased risk","grade":"[2018] (NICE does not grade)","source":"nice-ng89","quote":"Consider VTE prophylaxis for people undergoing thoracic surgery who are at increased risk of VTE."}],"sources":[{"key":"nice-ng89","label":"Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism (NG89), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng89/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended. Published March 2018, last updated August 2019.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-vte-2023","label":"Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update","publisher":"ASCO (Journal of Clinical Oncology)","year":2023,"url":"https://doi.org/10.1200/JCO.23.00294","doi":"10.1200/JCO.23.00294","gradingScheme":"ASCO: strength of recommendation (strong or weak) and quality of evidence (high, intermediate, low).","read":"abstract","accessed":"2026-11-11"},{"key":"cochrane-extended-lmwh-2019","label":"Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery","publisher":"Cochrane Database of Systematic Reviews","year":2019,"url":"https://doi.org/10.1002/14651858.CD004318.pub5","doi":"10.1002/14651858.CD004318.pub5","gradingScheme":"GRADE quality of evidence: high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-vte-2023","label":"Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline","publisher":"ESMO (Annals of Oncology)","year":2023,"url":"https://doi.org/10.1016/j.annonc.2022.12.014","doi":"10.1016/j.annonc.2022.12.014","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-pu-extended-clot-prevention-after-surgery"],"gaps":["The ESMO 2023 VTE guideline could not be read (no abstract in Europe PMC, the publisher refused a script), and the ASCO 2023 update and the Cochrane review were read as abstracts only. What ASCO and ESMO define as the high-risk features that call for extended prophylaxis is not on this page.","NICE NG89 (2018, updated 2019) names LMWH or fondaparinux; whether it will add oral factor Xa inhibitors for surgical prophylaxis is not known.","The Cochrane review counted clots confirmed by objective tests, including scans, and ran a sensitivity analysis limited to open surgery. Whether the benefit holds for symptomatic clots, and after laparoscopic or robotic surgery with enhanced recovery, is not settled in the sources read; some centres stop prophylaxis at discharge after minimally invasive surgery, but no source read states that as policy.","Doses of LMWH and adjustments for kidney function and body weight come from the product information and local policy and are not given here.","Use is low where it has been measured: the linked upgrade idea cites a US claims study in which 4.7% of eligible older patients received extended prophylaxis after colorectal cancer resection."]},{"id":"vte-risk-assessment-and-thromboprophylaxis-ambulatory","kind":"protocol","name":"Blood clot risk assessment and preventive anticoagulation during outpatient cancer treatment","aka":["Khorana score","ambulatory thromboprophylaxis","primary VTE prophylaxis in cancer outpatients","cancer-associated thrombosis prevention","blood thinners to prevent clots during chemotherapy"],"tldr":"Cancer and its treatment raise the chance of a blood clot in a leg or lung. Most people having treatment as outpatients do not need a blood thinner, but some do: your team can work out your risk with a simple score from your blood count, weight and type of cancer. Everyone should know the signs of a clot: a swollen, painful leg or sudden breathlessness or chest pain.","summary":"Routine thromboprophylaxis is not recommended for all outpatients with cancer (ITAC 2022; ASCO 2020; NICE NG89 for mobile people on anticancer treatment). Risk is assessed at the start of systemic treatment and periodically, with a validated model: the Khorana score gives 2 points for a very high-risk cancer site and 1 point each for a high-risk site, platelets of 350 × 10⁹/L or more, haemoglobin below 100 g/L or use of an erythropoiesis-stimulating agent, white cells above 11 × 10⁹/L and a body mass index of 35 or more.\n\nThe guidelines differ on who should be offered prophylaxis. ITAC (2022) recommends rivaroxaban or apixaban for ambulatory patients on systemic anticancer therapy with a Khorana score of 2 or more who are not bleeding or at high bleeding risk (grade 1B); ASCO (2020) says clinicians may offer apixaban, rivaroxaban or low-molecular-weight heparin to selected high-risk outpatients. NICE NG89 (2018) does not use a score: it advises against prophylaxis for mobile people on cancer treatment except for myeloma on thalidomide, pomalidomide or lenalidomide with steroids (aspirin or low-molecular-weight heparin) and pancreatic cancer on chemotherapy (low-molecular-weight heparin), continued for as long as chemotherapy lasts. ITAC also recommends prophylaxis in locally advanced or metastatic pancreatic cancer with low bleeding risk (low-molecular-weight heparin grade 1A, rivaroxaban or apixaban grade 1B) and in myeloma on immunomodulatory drugs (grade 1A), and does not recommend low-molecular-weight heparin prophylaxis outside a trial in advanced lung cancer.","asOf":"2026-11-11","links":[],"tags":["protocol","thrombosis","supportive-care"],"related":["thalidomide","lenalidomide","pomalidomide"],"cancers":["pancreatic","multiple-myeloma"],"sections":["supportive-care"],"technologies":["cancer-associated-thrombosis"],"targets":[],"drugs":["aspirin"],"companies":[],"institutions":["nice","asco","esmo"],"pathways":[],"terms":["vte"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer can make blood clots more likely. Your team checks how likely a clot is. If your risk is high, they may offer a blood thinner. Tell them at once about a swollen leg or sudden breathlessness.","domain":"supportive-care","setting":{"who":["doctor","pharmacist","nurse","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","home"]},"population":"Adults with cancer having systemic anticancer treatment as outpatients. People admitted to hospital, people having cancer surgery, people with a central venous catheter and the treatment of an established clot are covered by separate recommendations in the same guidelines and are not covered here. NICE NG89 covers people aged 16 or over.","trigger":"Systemic anticancer treatment is about to start, and periodically during it.","steps":[{"action":"Do not give preventive blood thinners routinely to every outpatient with cancer","why":"For most people the chance of a clot is lower than the chance of a bleed from the blood thinner.","source":"asco-2020","quote":"Thromboprophylaxis is not routinely recommended for all outpatients with cancer."},{"action":"Assess clot risk when systemic treatment starts and again during it, with a validated score such as the Khorana score","why":"Risk changes with the cancer, the treatment and the blood count, and a score picks out the minority at high risk.","source":"asco-2020","quote":"Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE."},{"action":"Score the cancer site, platelet count, haemoglobin or use of an erythropoiesis-stimulating agent, white cell count and body mass index","why":"These five items were the ones that predicted clots in a large group of outpatients on chemotherapy; a score of 3 or more marked a risk of about 7 per cent over the first few months.","source":"khorana-2008","quote":"Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 x 10(9)/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 x 10(9)/L, and body mass index of 35 kg/m(2) or more (1 point each)."},{"action":"Check bleeding risk and medicine interactions before offering an anticoagulant","why":"Prophylaxis is only for people who are not bleeding and not at high risk of bleeding; some anticancer drugs interact with the newer oral anticoagulants.","source":"itac-2022","quote":"and not actively bleeding or not at a high risk for bleeding (grade 1B)."},{"action":"For a Khorana score of 2 or more and low bleeding risk, offer rivaroxaban or apixaban (ITAC) or, under ASCO, apixaban, rivaroxaban or low-molecular-weight heparin","why":"In a meta-analysis ITAC cites, preventive anticoagulation cut clots by about two fifths at a score of 2 or more, and by more at 3 or more, without a rise in major bleeding.","source":"itac-2022","quote":"Primary prophylaxis with direct oral anticoagulant (rivaroxaban or apixaban) is recommended in ambulatory patients who are receiving systemic anticancer therapy and are at intermediate-to-high-risk of VTE, identified by a validated risk assessment model (ie, a Khorana score ≥2), and not actively bleeding or not at a high risk for bleeding (grade 1B).","grade":"1B"},{"action":"In locally advanced or metastatic pancreatic cancer on systemic treatment with low bleeding risk, offer prophylaxis with low-molecular-weight heparin or rivaroxaban or apixaban","why":"Pancreatic cancer carries one of the highest clot risks, and two randomised trials support prophylaxis.","source":"itac-2022","quote":"Primary pharmacological prophylaxis of VTE with LMWH (grade 1A) or with direct oral anticoagulants (rivaroxaban or apixaban; grade 1B) is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer treated with systemic anticancer therapy and who have a low risk of bleeding.","grade":"1A (LMWH); 1B (rivaroxaban or apixaban)"},{"action":"In myeloma treated with thalidomide, lenalidomide or pomalidomide with steroids, give prophylaxis: aspirin or low-molecular-weight heparin, or under ITAC also a prophylactic-dose anticoagulant","why":"These drugs combined with steroids raise the risk of clots substantially.","source":"itac-2022","quote":"In patients with myeloma treated with immunomodulatory drugs combined with steroids or other systemic anticancer therapies, VTE primary pharmacological prophylaxis is recommended (grade 1A)","grade":"1A"},{"action":"Do not use low-molecular-weight heparin prophylaxis in advanced lung cancer outside a clinical trial","why":"The trials in lung cancer did not show a net benefit large enough to recommend it.","source":"itac-2022","quote":"Primary pharmacological prophylaxis of VTE with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer treated with systemic anticancer therapy, including patients who have a low risk of bleeding (guidance).","grade":"guidance"},{"action":"Where prophylaxis is given, continue it for as long as the chemotherapy continues","why":"The raised risk lasts as long as the treatment that causes it.","source":"nice-ng89","quote":"If giving VTE prophylaxis to people with cancer (see recommendations 1.6.2 and 1.6.3), continue for as long as they are receiving chemotherapy."},{"action":"Teach every patient the signs of a clot and to report them the same day","why":"A swollen painful leg, or new breathlessness or chest pain, can be a clot that needs treatment straight away.","source":"asco-2020","quote":"Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE."}],"bestInClass":{"statement":"The guidelines agree that routine prophylaxis for all outpatients is not recommended and that pancreatic cancer and myeloma on immunomodulatory drugs are exceptions; they disagree on whether a risk score should decide it for everyone else. ITAC (2022, GRADE) recommends rivaroxaban or apixaban at a Khorana score of 2 or more with low bleeding risk (grade 1B); ASCO (2020) allows apixaban, rivaroxaban or low-molecular-weight heparin for selected high-risk outpatients, and its 2023 update did not change this; NICE NG89 (2018) does not use a score and limits prophylaxis in mobile people on cancer treatment to myeloma on thalidomide, pomalidomide or lenalidomide with steroids and to pancreatic cancer on chemotherapy. The ESMO 2023 guideline could not be read.","sources":["itac-2022","asco-2020","asco-2023","nice-ng89","esmo-2023"]},"variants":[{"name":"No risk score; prophylaxis only in myeloma and pancreatic cancer (NICE NG89)","differs":"Advises against prophylaxis for mobile people on chemotherapy, radiotherapy or immunotherapy unless they have another reason for raised risk, and considers it only for myeloma on thalidomide, pomalidomide or lenalidomide with steroids (aspirin 75 mg or 150 mg, or low-molecular-weight heparin) and pancreatic cancer on chemotherapy (low-molecular-weight heparin).","evidence":"NICE does not grade recommendations; NG89's cancer recommendations date from 2018, before the direct oral anticoagulant trials in outpatients were reflected in ITAC 2022.","sources":["nice-ng89"]},{"name":"Low-molecular-weight heparin as an option at high Khorana risk (ASCO 2020)","differs":"Includes low-molecular-weight heparin, as well as apixaban and rivaroxaban, for selected high-risk outpatients, where ITAC's Khorana recommendation names the two oral drugs only.","evidence":"Read as an abstract; the abstract does not give the score threshold or the grade.","sources":["asco-2020"]},{"name":"Aspirin 100 mg in myeloma (ITAC)","differs":"Lists low-dose aspirin 100 mg daily, prophylactic low-molecular-weight heparin, low or therapeutic-dose vitamin K antagonists and prophylactic apixaban as options in myeloma on immunomodulatory drugs, where NICE names aspirin 75 or 150 mg or low-molecular-weight heparin.","evidence":"ITAC grades the choice among these 2B, saying they have shown similar effects in preventing clots.","sources":["itac-2022","nice-ng89"]}],"grades":[{"claim":"Rivaroxaban or apixaban for ambulatory patients on systemic anticancer therapy with a Khorana score of 2 or more and low bleeding risk","grade":"1B (GRADE)","source":"itac-2022"},{"claim":"Low-molecular-weight heparin in locally advanced or metastatic pancreatic cancer on systemic treatment, low bleeding risk","grade":"1A (GRADE)","source":"itac-2022"},{"claim":"Rivaroxaban or apixaban in the same pancreatic cancer setting","grade":"1B (GRADE)","source":"itac-2022"},{"claim":"Prophylaxis in myeloma on immunomodulatory drugs with steroids or other systemic therapy","grade":"1A (GRADE)","source":"itac-2022"},{"claim":"Choice among anticoagulants and low-dose aspirin in myeloma","grade":"2B (GRADE)","source":"itac-2022","quote":"or low-dose aspirin (100 mg daily) can be used, and have shown similar effects with regard to preventing VTE (grade 2B)."},{"claim":"No low-molecular-weight heparin prophylaxis outside a trial in advanced lung cancer","grade":"guidance (no GRADE rating)","source":"itac-2022"}],"sources":[{"key":"itac-2022","label":"2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19","publisher":"International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology","year":2022,"url":"https://europepmc.org/article/PMC/PMC9236567","doi":"10.1016/S1470-2045(22)00160-7","gradingScheme":"GRADE methodology, printed as grade 1A, 1B, 2A and so on; 'guidance' where data are absent and the panel gives its own advice.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng89","label":"Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism (NG89), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng89/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'consider', 'do not offer') and each is dated, for example [2018]. Published March 2018, last updated August 2019.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2020","label":"Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2020,"url":"https://europepmc.org/abstract/MED/31381464","doi":"10.1200/JCO.19.01461","read":"abstract","accessed":"2026-11-11"},{"key":"asco-2023","label":"Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2023,"url":"https://europepmc.org/abstract/MED/37075273","doi":"10.1200/JCO.23.00294","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2023","label":"Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline","publisher":"ESMO, Annals of Oncology","year":2023,"url":"https://doi.org/10.1016/j.annonc.2022.12.014","doi":"10.1016/j.annonc.2022.12.014","read":"not-reachable","accessed":"2026-11-11"},{"key":"khorana-2008","label":"Development and validation of a predictive model for chemotherapy-associated thrombosis","publisher":"Blood","year":2008,"url":"https://europepmc.org/abstract/MED/18216292","doi":"10.1182/blood-2007-10-116327","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-clot-risk-score-and-preventive-anticoagulation"],"gaps":["The ESMO 2023 guideline could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its position on the Khorana score and on direct oral anticoagulants is not stated here.","ASCO 2020 and 2023 were read only as abstracts, so ASCO's Khorana threshold, grades and doses are not given here.","The Khorana abstract does not list which cancer sites count as very high or high risk; the ITAC text read does not list them either.","None of the sources read gives doses for prophylactic apixaban, rivaroxaban or low-molecular-weight heparin in this setting; these come from the product label and the local formulary.","No source read settles prophylaxis for people on immunotherapy alone or on oral targeted drugs, whose clot risk the Khorana score was not built for.","NICE NG89's cancer recommendations date from 2018 and predate the outpatient trials of direct oral anticoagulants that ITAC 2022 draws on."]},{"id":"blood-sampling-from-a-central-line","kind":"protocol","name":"Blood sampling from a central line or port","aka":["taking blood from a PICC","bloods from a port","CVAD blood sampling","discard volume","line bloods","blood cultures from a central line","paired blood cultures"],"tldr":"Blood can often be taken from your line or port so you do not need a needle in your arm. The nurse cleans their hands and the end of the line, usually draws off a little blood first and throws it away, takes the samples and then flushes the line with salt water. If an infection is suspected, a sample is also taken from a vein in your arm.","summary":"Every access is a chance for infection, so the line is opened no more often than needed: a 2026 scoping review of six studies found that more frequent access for blood draws is associated with more line infections and that standard sampling times, phlebotomy teams and peripheral cultures reduce it. Hand hygiene (CDC IB), scrubbing the hub or needleless connector with an antiseptic and using only sterile devices (CDC IA) apply as for any access. For blood cultures, IDSA (2009) asks for the hub to be cleaned with alcohol, tincture of iodine or alcoholic chlorhexidine above 0.5%, allowed to dry (A-I), and, when line infection is suspected, paired cultures from the catheter and a peripheral vein before antibiotics, labelled by site (A-II); ESMO 2015 agrees ([II, A]). After any sample the line is flushed with saline (ESMO [II, B]).\n\nHow much blood to discard first, to avoid diluted or drug-contaminated results, is not set by any guideline that could be read; the INS Standards address it but were not reachable. Local policies commonly discard a few millilitres; an intensive-care study in 105 patients found 2 ml gave results agreeing with venepuncture for electrolytes and blood counts.","asOf":"2026-11-11","links":[],"tags":[],"related":["suspected-central-line-infection","picc-and-tunnelled-line-care","implanted-port-access-and-care"],"cancers":[],"sections":[],"technologies":["picc-lines","implanted-ports","needleless-connector-disinfecting-caps"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Blood can be taken from your line instead of your arm. The nurse cleans the line end first and flushes it after.","domain":"vascular-access","setting":{"who":["nurse"],"where":["chemotherapy-day-unit","ward","outpatient-clinic","community"]},"population":"Adults with cancer who have a PICC, tunnelled central catheter or accessed implanted port. The discard-volume studies were done in intensive care. Children need their own local rules.","trigger":"Blood tests or blood cultures are due in a person with a central line.","steps":[{"action":"Take blood from the line only when it is needed, grouping tests to limit how often the line is opened","why":"Each time a line is opened, germs have a chance to get in.","source":"davis-2026","quote":"Increased frequency of CVC access is associated with a higher risk of CLABSI."},{"action":"Clean your hands before and after touching the line","why":"Hands are the commonest route by which germs reach a line.","source":"cdc-hicpac-2011","quote":"Hand hygiene should be performed before and after palpating catheter insertion sites as well as before and after inserting, replacing, accessing, repairing, or dressing an intravascular catheter.","grade":"Category IB"},{"action":"Scrub the hub or needleless connector with an antiseptic and access it only with sterile devices","why":"The connector is touched many times and is a main route for germs into the line.","source":"cdc-hicpac-2011","quote":"Minimize contamination risk by scrubbing the access port with an appropriate antiseptic (chlorhexidine, povidone iodine, an iodophor, or 70% alcohol) and accessing the port only with sterile devices","grade":"Category IA"},{"action":"For routine tests, withdraw and discard a small volume first, as local policy sets, then take the samples","why":"The first blood drawn is mixed with the flush or drugs in the catheter and can give wrong results.","practice":"No guideline that could be read sets a discard volume; the INS Standards do but were not reachable. A 2026 intensive-care study found 2 ml enough for electrolytes and blood counts (see variants)."},{"action":"For blood cultures, clean the hub with alcohol, tincture of iodine or alcoholic chlorhexidine above 0.5% and let it dry before drawing","why":"Skin and hub bacteria can contaminate the bottle and give a false result.","source":"idsa-2009","quote":"If a blood sample is obtained through a catheter, clean the catheter hub with either alcohol or tincture of iodine or alcoholic chlorhexidine (>0.5%), allowing adequate drying time to mitigate blood culture contamination (A-I).","grade":"A-I"},{"action":"When line infection is suspected, take paired cultures from the line and from a vein before antibiotics, and label each bottle with where it came from","why":"Comparing the two shows whether the line is the source of the infection.","source":"idsa-2009","quote":"For suspected CRBSI, paired blood samples, drawn from the catheter and a peripheral vein, should be cultured before initiation of antimicrobial therapy, and the bottles should be appropriately marked to reflect the site from which the samples were obtained (A-II).","grade":"A-II"},{"action":"Flush the line with 0.9% saline after every sample","why":"Blood left in the catheter can clot and block it or feed germs.","source":"esmo-2015","quote":"Routine flushing with saline, after the completion of any infusion or blood sampling, is recommended [II, B]","grade":"[II, B]"}],"bestInClass":{"statement":"Open the line only when needed, with hand hygiene (CDC IB), a scrubbed hub and sterile devices (CDC IA), hub antisepsis allowed to dry before cultures (IDSA A-I), paired line and peripheral cultures before antibiotics when infection is suspected (IDSA A-II; ESMO [II, A]) and a saline flush after every sample (ESMO [II, B]). The discard volume for routine bloods is set by local policy: no guideline that could be read specifies it.","sources":["cdc-hicpac-2011","idsa-2009","esmo-2015","davis-2026"]},"variants":[{"name":"A 2 ml discard","differs":"Discards 2 ml before routine sampling from a central catheter, rather than 3 ml or more, to reduce blood loss.","evidence":"In 105 intensive-care patients, results from the proximal lumen after a 2 ml discard agreed well with venepuncture for sodium, potassium, calcium and blood counts except white cells; acidosis explained some differences (Pushparaj 2026). Not studied in cancer outpatients or ports.","sources":["pushparaj-2026"]},{"name":"Peripheral venepuncture or phlebotomy teams instead of line sampling","differs":"Takes routine bloods and cultures by venepuncture, or by a phlebotomy team, to keep the central line closed.","evidence":"A 2026 scoping review of six hospital studies found standard sampling times, phlebotomists for peripheral cultures and avoiding the line for both cultures and routine bloods lowered line infection rates. In cancer care this trades against repeated needle sticks in people with poor veins.","sources":["davis-2026"]}],"grades":[{"claim":"If no peripheral sample can be drawn, take at least two samples through different lumens","grade":"B-III","source":"idsa-2009","quote":"If a blood sample cannot be drawn from a peripheral vein, it is recommended that ≥2 blood samples should be drawn through different catheter lumens (B-III)."}],"sources":[{"key":"cdc-hicpac-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"idsa-2009","label":"Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America","publisher":"IDSA (Clinical Infectious Diseases, Mermel et al.)","year":2009,"url":"https://doi.org/10.1086/599376","doi":"10.1086/599376","gradingScheme":"Strength A (good evidence) to C (poor evidence); quality I (at least one randomised trial), II (non-randomised trials, cohort or case-control studies) or III (expert opinion), from the Canadian Task Force scheme.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I to V; grades A to E, adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"},{"key":"davis-2026","label":"Limiting central venous catheter access for blood sampling and its impact on central line-associated bloodstream infection: A scoping review","publisher":"American Journal of Infection Control (Davis et al.)","year":2026,"url":"https://doi.org/10.1016/j.ajic.2025.11.001","doi":"10.1016/j.ajic.2025.11.001","read":"abstract","accessed":"2026-11-11"},{"key":"pushparaj-2026","label":"Minimizing discard volume to 2 ml before blood sampling from a central venous catheter: a prospective observational study in India","publisher":"Acute and Critical Care (Pushparaj et al.)","year":2026,"url":"https://doi.org/10.4266/acc.000792","doi":"10.4266/acc.000792","read":"abstract","accessed":"2026-11-11"},{"key":"ins-2024","label":"Infusion Therapy Standards of Practice, 9th Edition","publisher":"Infusion Nurses Society (Journal of Infusion Nursing)","year":2024,"url":"https://doi.org/10.1097/NAN.0000000000000532","doi":"10.1097/NAN.0000000000000532","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-central-line-discard-volume-in-cancer-outpatients"],"gaps":["No guideline that could be read sets a discard volume, a discard method (discard, push-pull mixing or reinfusion) or the order of tubes when sampling from a central line; the INS Standards (2024), which do, were not reachable.","Whether blood for cultures should be drawn with or without a discard is not stated in any source read.","Whether drug levels may be taken from the lumen used to give the same drug is not addressed by any source read, so no rule is given.","The discard-volume and access-frequency studies were done in intensive care and read as abstracts only."]},{"id":"irae-haematological","kind":"protocol","name":"Blood side effects of checkpoint inhibitors: low platelets, haemolysis, neutropenia and marrow failure","aka":["haematological irAEs","hematologic immune-related adverse events","checkpoint inhibitor immune thrombocytopenia","ICI-related ITP","checkpoint inhibitor haemolytic anaemia","immune-related neutropenia","checkpoint inhibitor aplastic anaemia","ICI-related HLH"],"tldr":"Rarely, immunotherapy makes the immune system attack blood cells, causing low platelets (easy bruising or bleeding), destruction of red cells (tiredness, breathlessness, yellow skin, dark urine) or low white cells (infections). These are found on blood tests and treated with steroids and other medicines, usually with a haematologist involved.","summary":"Uncommon (under 1% in one series of 745 patients on PD-(L)1 inhibitors) but potentially life-threatening (SITC 2021). The commonest are immune thrombocytopenia (median onset 41 days) and autoimmune haemolytic anaemia (median 50 days, more frequent on PD-(L)1 than CTLA-4 inhibitors). Neutropenia appears at a median of 10.5 weeks; aplastic anaemia is rare, hard to treat and often does not resolve; HLH (median 26 days) is the most dangerous. In a small series, 43% of patients rechallenged after a haematological irAE had a recurrence.\n\nSITC 2021: work up each with a blood count, film and the relevant tests (clotting and LDH for thrombocytopenia; reticulocytes, Coombs test, LDH and ADAMTS13 for haemolysis; ferritin and soluble IL-2 receptor for HLH), separate immune causes from chemotherapy, and treat by haematological standard of care: prednisone 1 mg/kg for ITP (LE: 1) with IVIG for severe ITP (LE: 1) and rituximab as an option (LE: 2); prednisone 1 mg/kg for haemolysis (LE: 3) with IVIG if refractory (LE: 3); prednisone with G-CSF for immune neutropenia (LE: 3); ciclosporin or ATG for aplastic anaemia (LE: 4); steroids with etoposide or tocilizumab for HLH, under haematology (LE: 3). ASCO 2021 (abstract) makes haematological toxicity an exception to continuing treatment at grade 1.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","haematology"],"related":["irae-rechallenge"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab","prednisone","human-normal-immunoglobulin","rituximab","etoposide","tocilizumab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["irae","thrombocytopenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Very rarely, immunotherapy can lower your blood counts. Tell your team about unusual bruising or bleeding, yellow skin or dark urine, or a fever.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","patient-or-carer","multidisciplinary-team"],"where":["outpatient-clinic","chemotherapy-day-unit","acute-oncology-service","ward"]},"population":"Adults receiving or who have received an immune checkpoint inhibitor, alone or with chemotherapy, whose blood counts fall without another explanation. People with haematological cancers or pre-existing autoimmunity have more causes of low counts to exclude. Children are not addressed by this source.","trigger":"A new fall in platelets, haemoglobin or neutrophils, a positive Coombs test, signs of haemolysis, bruising or bleeding, or unexplained fever with cytopenias and a high ferritin, during or after checkpoint inhibitor treatment.","steps":[{"action":"Record a baseline platelet count before immunotherapy and watch for falls below it","why":"Cancer and other treatments often lower platelets, so a baseline makes a new immune drop easier to see.","source":"sitc-2021","quote":"Because patients may already be experiencing thrombocytopenia as a result of cancer or due to a number of oncological treatment regimens, it may be prudent to establish a baseline platelet count and monitor for additional drops below this value when beginning ICI therapy."},{"action":"For possible immune thrombocytopenia, send a full blood count with differential, a blood film, clotting tests (PT, PTT, fibrinogen, D-dimer) and LDH","why":"These separate immune destruction from clotting disorders such as DIC.","source":"sitc-2021","quote":"Diagnostic workup for patients with possible ICI-related ITP should include CBC with differential, blood smear evaluation, DIC labs (PT/partial thromboplastin time (PTT)/fibrinogen/d-dimer), and LDH."},{"action":"Treat immune thrombocytopenia as a haematologist would, typically with prednisone 1 mg/kg","why":"Steroids stop the immune system destroying platelets.","source":"sitc-2021","quote":"For patients with ICI-related ITP, treatment should follow hematological standard of care. Typically, this includes steroids (prednisone dose of 1 mg/kg oral or equivalent","grade":"LE: 1"},{"action":"For possible haemolysis, send reticulocytes, a blood film, a direct antiglobulin (Coombs) test, LDH and ADAMTS13","why":"These confirm red cells are being destroyed and exclude a clotting-related cause that needs different treatment.","source":"sitc-2021","quote":"Diagnostic workup for patients with possible ICI-related HA should include CBC with differential, reticulocyte count, blood smear evaluation, direct antiglobulin test (Coomb’s), and LDH with ADAMTS13 level."},{"action":"Treat autoimmune haemolytic anaemia with prednisone 1 mg/kg, adding IVIG if it does not respond","why":"Steroids are the standard first treatment for immune haemolysis.","source":"sitc-2021","quote":"For patients with ICI-related AIHA, treatment should follow hematological standard of care. Typically, this includes steroids (prednisone dose of 1 mg/kg oral or equivalent)","grade":"LE: 3"},{"action":"In patients on chemotherapy with immunotherapy, distinguish immune neutropenia from chemotherapy marrow suppression","why":"The treatments differ: immune neutropenia needs steroids, chemotherapy neutropenia does not.","source":"sitc-2021","quote":"For patients being treated with chemo-immunotherapy who develop neutropenia, it is important to differentiate between immune-related neutropenia and chemotherapy-induced myelosuppression."},{"action":"Treat immune neutropenia with prednisone 1 mg/kg and G-CSF","why":"Steroids stop the immune attack and G-CSF lifts the white cell count to lower infection risk.","source":"sitc-2021","quote":"For patients with immune-related neutropenia, treatment should follow hematological standard of care. Typically, this includes steroids (prednisone 1 mg/kg oral or equivalent) with G-CSF","grade":"LE: 3"},{"action":"For aplastic anaemia, add an immunosuppressant beyond steroids such as ciclosporin, and consider ATG","why":"Immune marrow failure rarely responds to steroids alone.","source":"sitc-2021","quote":"For patients with ICI-related AA, additional immunosuppressive therapies beyond steroids should be used, such as cyclosporine.","grade":"LE: 4"},{"action":"Suspect HLH early, send ferritin and soluble IL-2 receptor, and involve a haematologist","why":"HLH is life-threatening and needs specialist treatment such as etoposide or tocilizumab with steroids.","source":"sitc-2021","quote":"Diagnostic workup for patients with possible ICI-related HLH should include CBC with differential, blood smear evaluation, ferritin, and soluble IL-2 receptor. Because this condition is life-threatening, it should be suspected when symptoms arise and warrants early consultation with a specialist."}],"bestInClass":{"statement":"SITC 2021 is the only guideline read in full with a haematological section, and its rule is to treat each condition by the haematological standard of care for the same disease without immunotherapy: prednisone 1 mg/kg for immune thrombocytopenia (LE: 1) with IVIG for severe cases (LE: 1) and rituximab as an option (LE: 2); prednisone 1 mg/kg for haemolysis (LE: 3) with IVIG if refractory (LE: 3); prednisone with G-CSF for immune neutropenia (LE: 3); ciclosporin or ATG for aplastic anaemia (LE: 4); and steroids with etoposide or tocilizumab for HLH (LE: 3). The higher grades come from the evidence in the non-immunotherapy diseases. ASCO 2021 (abstract) agrees that haematological toxicity is an exception to continuing treatment at grade 1. ESMO 2022 could not be read.","sources":["sitc-2021","asco-2021","esmo-2022"]},"variants":[],"grades":[{"claim":"Immune thrombocytopenia: prednisone 1 mg/kg","grade":"LE: 1","source":"sitc-2021"},{"claim":"Severe immune thrombocytopenia: IVIG 0.5 g/kg/day for 5 days with steroids; rituximab may be considered","grade":"LE: 1 (IVIG); LE: 2 (rituximab)","source":"sitc-2021"},{"claim":"Autoimmune haemolytic anaemia: prednisone 1 mg/kg; IVIG if steroid-refractory","grade":"LE: 3","source":"sitc-2021","quote":"For patients with severe ICI-related AIHA that do not respond to steroids, IVIG (0.5 g/kg/day for 5 days)"},{"claim":"Immune neutropenia: prednisone 1 mg/kg with G-CSF","grade":"LE: 3","source":"sitc-2021"},{"claim":"Aplastic anaemia: ciclosporin; ATG may be considered","grade":"LE: 4","source":"sitc-2021"},{"claim":"HLH: steroids and immunosuppressives such as etoposide or tocilizumab, with haematology","grade":"LE: 3","source":"sitc-2021","quote":"For patients with ICI-related secondary HLH, hematological consultation is required as this is a challenging condition to manage. Standard of care treatment typically involves steroids and immunosuppressives, such as etoposide or tocilizumab"},{"claim":"Haematological toxicity is an exception to continuing treatment at grade 1","grade":"expert consensus","source":"asco-2021"}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline was read only as its abstract and its haematological table is not compared here.","Only one guideline with a haematological section could be read; the steps rest on SITC 2021 alone, and no second guideline is compared.","Whether and when to restart a checkpoint inhibitor after a haematological irAE is not addressed beyond SITC's note that 3 of 7 rechallenged patients in one series had a recurrence.","This protocol does not cover haematological toxicity after CAR T-cell therapy, which has its own grading (ICAHT)."]},{"id":"antithrombotic-interruption-around-surgery","kind":"protocol","name":"Blood thinners around cancer surgery, biopsy and endoscopy: when to stop, whether to bridge, when to restart","aka":["perioperative anticoagulation management","bridging anticoagulation","heparin bridging","stopping warfarin before surgery","stopping DOAC before surgery","periprocedural antithrombotic management","stopping clopidogrel before biopsy"],"tldr":"If you take a blood thinner and need an operation, biopsy or endoscopy, your team will make a written plan saying exactly when to take your last dose and when to restart. Aspirin is often continued. Warfarin is usually stopped five days before, and the newer tablets (apixaban, rivaroxaban, edoxaban, dabigatran) one to three days before. Most people do not need heparin injections in the gap.","summary":"The CHEST 2022 guideline (44 recommendations, GRADE) makes two strong recommendations: against heparin bridging in atrial fibrillation, and to continue a vitamin K antagonist for pacemaker or defibrillator implantation; the rest are conditional, and the panel states that most perioperative questions remain uncertain. BRIDGE (n=1884, AF, warfarin) found no bridging noninferior for arterial thromboembolism (0.4% vs 0.3%) with less major bleeding (1.3% vs 3.2%). PAUSE (n=3007, AF, apixaban, dabigatran, rivaroxaban) omitted the DOAC 1 day before a low-bleeding-risk and 2 days before a high-bleeding-risk procedure, resumed 1 day or 2 to 3 days after, without bridging or coagulation testing, with low rates of bleeding and stroke. ASH 2018 recommends strongly against periprocedural LMWH bridging for people on anticoagulation for VTE. For endoscopy, BSG/ESGE 2021 continue aspirin for all procedures (strong, low), continue P2Y12 inhibitors and warfarin for low-risk procedures, stop P2Y12 inhibitors 7 days and warfarin 5 days before high-risk procedures in people at low thrombotic risk (INR below 1.5), take the last DOAC dose 3 days before a high-risk procedure (5 days for dabigatran with CrCl 30 to 50), and resume up to 2 to 3 days after (strong, moderate). Unlike CHEST, BSG/ESGE still bridge with LMWH for warfarin in high thrombotic risk (mechanical valves, AF with mitral stenosis, VTE within 3 months). Coronary stents: liaise with a cardiologist before stopping a P2Y12 inhibitor.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","routine-preoperative-tests","anticoagulants-and-antiplatelets-before-endoscopy"],"cancers":[],"sections":[],"technologies":["cancer-associated-thrombosis"],"targets":[],"drugs":["aspirin"],"companies":[],"institutions":[],"pathways":[],"terms":["biopsy","core-needle-biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Do not stop or change a blood thinner on your own before a procedure. Ask for a written plan with the date of your last dose and the date to restart, and bring the list of all your medicines.","domain":"surgery-perioperative","setting":{"who":["doctor","surgical-team","anaesthetist","pharmacist","nurse","patient-or-carer"],"where":["outpatient-clinic","ward","home"]},"population":"Adults on long-term warfarin, a direct oral anticoagulant (apixaban, rivaroxaban, edoxaban, dabigatran) or an antiplatelet (aspirin, clopidogrel, prasugrel, ticagrelor) who need elective cancer surgery, a biopsy or an endoscopic procedure. Not for emergency surgery, people with a recent coronary stent without cardiology input, or neuraxial anaesthesia timing, which follows anaesthetic guidance. People on therapeutic LMWH for cancer-associated thrombosis are covered only where a source names LMWH.","trigger":"A planned operation, biopsy or endoscopic procedure in someone taking an anticoagulant or antiplatelet.","steps":[{"action":"Weigh the bleeding risk of the procedure against the person's clot risk, and explain both to them before deciding","why":"Stopping a blood thinner raises the risk of a stroke or clot; continuing it raises the risk of bleeding. The balance differs for each person and each procedure.","source":"bsg-esge-2021","quote":"We recommend that all patients are advised of the thrombotic risks of discontinuing antiplatelets or anticoagulants, as well as the haemorrhagic risks of continuing therapy (strong recommendation, low quality evidence).","grade":"Strong recommendation, low quality evidence"},{"action":"Give a written personal plan with the date and time of the last dose of each drug and of the first dose on restarting","why":"Mistakes in timing are common when several drugs or injections are involved; a written plan prevents them.","source":"bsg-esge-2021","quote":"Once the decision to modify antithrombotic medication is made, then a personal plan for that patient should be made. This should include written as well as verbal information regarding the precise timing of any changes.","grade":"Not graded (guideline text)"},{"action":"Continue aspirin through most procedures; if stopping it is considered, decide case by case","why":"Aspirin taken to prevent a second heart attack or stroke protects more than it harms around most procedures.","source":"bsg-esge-2021","quote":"For all endoscopic procedures we recommend continuing aspirin (strong recommendation, low quality evidence), with the exception of ampullectomy (weak recommendation, low quality evidence).","grade":"Strong recommendation, low quality evidence (endoscopy)"},{"action":"For a high-bleeding-risk procedure in someone at low clot risk, stop clopidogrel, prasugrel or ticagrelor 7 days before; with a coronary stent, keep aspirin and ask the cardiologist first","why":"These drugs affect platelets for about a week; stopping them too soon after a stent can cause the stent to block.","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists 7 days before the procedure (strong recommendation, moderate quality evidence). In patients on DAPT, we recommend continuing aspirin (strong recommendation, low quality evidence).","grade":"Strong recommendation, moderate quality evidence"},{"action":"For a high-bleeding-risk procedure, stop warfarin 5 days before and check that the INR is below 1.5","why":"Warfarin takes several days to wear off; the INR blood test shows when clotting is back to a safe level for surgery.","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing warfarin for 5 days before the procedure (strong recommendation, high quality evidence). Check INR prior to the procedure to ensure <1.5 (strong recommendation, low quality evidence).","grade":"Strong recommendation, high quality evidence (stop 5 days); strong, low (INR check)"},{"action":"Do not bridge with heparin injections in people with atrial fibrillation whose warfarin is paused","why":"In a large randomised trial, heparin injections in the gap did not prevent strokes and more than doubled major bleeding.","source":"chest-2022","quote":"of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation","grade":"Strong recommendation (GRADE)"},{"action":"Stop a DOAC by the bleeding risk of the procedure and kidney function, without heparin bridging or routine clotting tests: omit 1 day before low-risk and 2 days before high-risk procedures","why":"These tablets wear off within a day or two in people with normal kidneys, so a short planned gap is enough.","source":"pause-2019","quote":"The DOAC regimens were omitted for 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure.","grade":"Prospective cohort study (not a guideline grade)"},{"action":"For a high-risk endoscopic procedure, take the last DOAC dose 3 days before (5 days for dabigatran with creatinine clearance 30 to 50 ml/min)","why":"The endoscopy guideline counts the gap from the last dose taken, which is the same as missing two full days of tablets.","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients on DOACs, we recommend that the last dose of DOACs be taken 3 days before the procedure (strong recommendation, low quality evidence).","grade":"Strong recommendation, low quality evidence"},{"action":"Restart the blood thinner once bleeding is controlled, usually within 2 to 3 days of the procedure","why":"Leaving it off for longer exposes the person to clots; DOACs work within hours of the first dose, warfarin takes days.","source":"bsg-esge-2021","quote":"If antiplatelet or anticoagulant therapy is discontinued, then we recommend this should be resumed up to 2–3 days after the procedure depending on the perceived haemorrhagic and thrombotic risks (strong recommendation, moderate quality evidence).","grade":"Strong recommendation, moderate quality evidence"}],"bestInClass":{"statement":"For surgery, CHEST 2022 is the most recent full guideline (GRADE): no heparin bridging in atrial fibrillation (strong), on the evidence of BRIDGE, and a pharmacokinetic DOAC interruption schedule without bridging, on the evidence of PAUSE; ASH 2018 recommends strongly against bridging for people on anticoagulation for VTE. For endoscopy and endoscopic biopsy, BSG/ESGE 2021 is the current specialty standard. The two disagree on one point: BSG/ESGE still substitute LMWH for warfarin in people at high thrombotic risk (mechanical heart valves, atrial fibrillation with mitral stenosis or recent stroke, VTE within 3 months), while CHEST's strong recommendation against bridging covers atrial fibrillation; CHEST's position for mechanical valves could not be read beyond its abstract.","sources":["chest-2022","bridge-2015","pause-2019","ash-2018","bsg-esge-2021"]},"variants":[{"name":"Heparin bridging for warfarin in high thrombotic risk (BSG/ESGE)","differs":"Stops warfarin 5 days before, starts a daily therapeutic LMWH dose 2 days later, gives the last LMWH dose at least 24 hours before the procedure and restarts LMWH the day after until the INR is in range.","evidence":"A strong recommendation in BSG/ESGE 2021 (the quality of evidence is printed as low in the summary and moderate in the section text) for high-risk endoscopic procedures in people at high thrombotic risk, as defined in its table 3. CHEST 2022 recommends strongly against bridging in atrial fibrillation.","sources":["bsg-esge-2021","chest-2022"]},{"name":"Continuing warfarin or P2Y12 inhibitors for low-risk procedures","differs":"Does not stop warfarin (INR checked in the week before, not above range) or clopidogrel for diagnostic endoscopy and biopsy; omits only the morning DOAC dose.","evidence":"BSG/ESGE 2021: warfarin continued (weak, low), P2Y12 inhibitors continued (strong, low), morning DOAC dose omitted (weak, low).","sources":["bsg-esge-2021"]},{"name":"Longer interruption after very high bleeding risk procedures","differs":"Delays restarting antithrombotics for about a week after procedures such as endoscopic submucosal dissection of an early cancer.","evidence":"BSG/ESGE 2021 says it 'may be desirable' on the basis of a meta-analysis of post-ESD bleeding; thrombosis was not analysed.","sources":["bsg-esge-2021"]}],"grades":[{"claim":"Strong recommendations in CHEST 2022","grade":"Two strong of 44; the rest conditional","source":"chest-2022","quote":"A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations"},{"claim":"No bridging is as safe for strokes and causes less bleeding (BRIDGE)","grade":"Randomised, double-blind trial, n=1884","source":"bridge-2015","quote":"The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority)."},{"claim":"No LMWH bridging for people on anticoagulation for VTE","grade":"Strong recommendation (GRADE)","source":"ash-2018","quote":"Strong recommendations included using patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy and against using periprocedural low-molecular-weight heparin (LMWH) bridging therapy."},{"claim":"DOAC resumption after the procedure (PAUSE schedule)","grade":"Prospective cohort study","source":"pause-2019","quote":"The DOAC regimens were resumed 1 day after a low-bleeding-risk procedure and 2 to 3 days after a high-bleeding-risk procedure."},{"claim":"Stents: liaise with an interventional cardiologist before stopping a P2Y12 inhibitor","grade":"Strong recommendation, high quality evidence","source":"bsg-esge-2021","quote":"For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a consultant interventional cardiologist about the risk/benefit of discontinuing P2Y12 receptor antagonists (strong recommendation, high quality evidence)."},{"claim":"Uncertainty remains","grade":"Panel statement","source":"chest-2022","quote":"Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions."}],"sources":[{"key":"chest-2022","label":"Douketis et al., Perioperative Management of Antithrombotic Therapy: an American College of Chest Physicians Clinical Practice Guideline (CHEST 2022)","publisher":"American College of Chest Physicians","year":2022,"url":"https://doi.org/10.1016/j.chest.2022.07.025","doi":"10.1016/j.chest.2022.07.025","gradingScheme":"GRADE: strong or conditional recommendations; high, moderate, low or very low certainty of evidence.","read":"abstract","accessed":"2026-11-11"},{"key":"bridge-2015","label":"Douketis et al., Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation (BRIDGE, NEJM 2015)","publisher":"New England Journal of Medicine","year":2015,"url":"https://doi.org/10.1056/NEJMoa1501035","doi":"10.1056/NEJMoa1501035","gradingScheme":"Randomised controlled trial; no recommendation grade.","read":"abstract","accessed":"2026-11-11"},{"key":"pause-2019","label":"Douketis et al., Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant (PAUSE, JAMA Intern Med 2019)","publisher":"JAMA Internal Medicine","year":2019,"url":"https://doi.org/10.1001/jamainternmed.2019.2431","doi":"10.1001/jamainternmed.2019.2431","gradingScheme":"Prospective management cohort; no recommendation grade.","read":"abstract","accessed":"2026-11-11"},{"key":"ash-2018","label":"Witt et al., American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy (Blood Adv 2018)","publisher":"American Society of Hematology","year":2018,"url":"https://doi.org/10.1182/bloodadvances.2018024893","doi":"10.1182/bloodadvances.2018024893","gradingScheme":"GRADE: strong or conditional recommendations.","read":"abstract","accessed":"2026-11-11"},{"key":"bsg-esge-2021","label":"Veitch et al., Endoscopy in patients on antiplatelet or anticoagulant therapy: BSG and ESGE guideline update (Gut 2021)","publisher":"British Society of Gastroenterology and European Society of Gastrointestinal Endoscopy","year":2021,"url":"https://doi.org/10.1136/gutjnl-2021-325184","doi":"10.1136/gutjnl-2021-325184","gradingScheme":"GRADE: strength (strong or weak) and quality of evidence (high, moderate, low, very low), printed after each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"sir-2019","label":"Patel et al., Society of Interventional Radiology Consensus Guidelines for the Periprocedural Management of Thrombotic and Bleeding Risk in Patients Undergoing Percutaneous Image-Guided Interventions, Part II (JVIR 2019)","publisher":"Society of Interventional Radiology","year":2019,"url":"https://doi.org/10.1016/j.jvir.2019.04.017","doi":"10.1016/j.jvir.2019.04.017","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["CHEST 2022 could be read only as its abstract: its DOAC intervals, its position on bridging for mechanical heart valves and VTE, and its minor-procedure recommendations are not reproduced here.","The SIR 2019 consensus and CIRSE 2021 standards for image-guided biopsy (the usual route to a cancer diagnosis), the BSH 2016 guideline, NICE CKS and the ACC/AHA perioperative guideline could not be read (publisher or site refused a script); bleeding-risk categories for percutaneous biopsy are therefore not given here.","BRIDGE and PAUSE enrolled people with atrial fibrillation; how far their results apply to people anticoagulated for cancer-associated thrombosis, whose clot risk stays high while the cancer is active, is not settled by these sources.","Timing of anticoagulants around spinal or epidural anaesthesia follows separate anaesthetic guidance not read here."]},{"id":"body-size-based-dose-calculation","kind":"protocol","name":"Body surface area and weight-based dose calculation for anticancer drugs, including full doses in obesity","aka":["BSA dose calculation","body surface area dosing","mg/m2 dosing","chemotherapy dose calculation","dosing in obesity","dose capping","BSA capping","actual body weight dosing","re-weighing during chemotherapy","chemotherapy dosing for obese patients"],"tldr":"Most chemotherapy doses are worked out from your height and weight. Both are measured in metric units and checked by two people before a new treatment starts, and your weight is rechecked during treatment. If you are a larger person, the American guideline says you should get the full dose for your actual size, not a reduced or 'capped' one.","summary":"Most cytotoxic doses are expressed per square metre of body surface area (BSA), calculated from height and weight (DuBois or Mosteller), or per kilogram. Errors start at the scales: ASCO-ONS (2024) cites a study of 10,000 records in which 20% held height or weight errors, and now requires height and weight in metric units, measured and documented and verified by two people, one licensed, before a new treatment plan is prepared. The order must state the calculation method, the variables, how often they are re-evaluated and what change prompts recalculation. BOPA (2025) requires an up-to-date height, weight and BSA on the first prescription and a local policy on when weight change triggers a new dose; it bands adult doses where national bands exist and asks that any BSA capping be documented.\n\nFor people with obesity, ASCO (2012, updated 2021) recommends full weight-based cytotoxic doses, especially when the aim is cure, and the 2021 update adds full approved doses of immunotherapy and targeted therapy; toxicity is handled the same way as in anyone else. The 2012 guideline found that up to 40% of obese patients received limited doses and that fears of toxicity were unfounded. Capping persists: in a German cohort of 730 women with early breast cancer capped at BSA 2.0 m2, those above 2.1 m2 had lower dose intensity and worse survival, with obesity a possible confounder. How often to re-weigh is unsettled; a 2,276-patient study found a 10% BSA change in at most 7.6% of patients and suggested three- to six-monthly weighing for most.","asOf":"2026-11-11","links":[],"tags":[],"related":["body-surface-area-dosing","carboplatin-dose-calculation","sact-prescribing-and-pharmacy-verification"],"cancers":[],"sections":[],"technologies":["chemotherapy-dosing-in-obesity"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your dose comes from your height and weight, so the team measures them carefully. Bigger bodies get the full dose, because cutting it can make treatment work less well.","domain":"pharmacy","setting":{"who":["doctor","pharmacist","nurse"],"where":["outpatient-clinic","chemotherapy-day-unit","aseptic-unit","ward"]},"population":"Adults prescribed anticancer drugs dosed by body surface area or weight, including people with obesity. Children are weighed before every cycle and dosed by protocol (BOPA); carboplatin is dosed by kidney function (see the carboplatin protocol), and flat-dosed drugs need no calculation.","trigger":"A new treatment plan is prescribed, or weight changes during a course.","steps":[{"action":"Measure height and weight in metric units, record them, and have two people, one a licensed clinician, verify both before a new treatment plan is prepared","why":"Mistyped numbers, decimal slips and pounds written as kilograms are common, and each one changes the dose.","source":"asco-ons-2024","quote":"Weight and height are measured and documented in the medical record in metric units (eg, kg and cm). Both the measurement and documentation are verified by two individuals, one of whom is a licensed clinician, prior to preparation and administration of a newly prescribed antineoplastic treatment plan."},{"action":"Write the calculation on the order: the method, the variables used, how often they will be rechecked and what change prompts recalculation","why":"Anyone checking the dose later can repeat the sum and see when it should change.","source":"asco-ons-2024","quote":"The dose calculation, including: 3.9.8.1. The calculation methodology 3.9.8.2. The variables used to calculate the dose 3.9.8.3. The frequency at which variables are re-evaluated, such as weight or laboratory data 3.9.8.4. The changes in the values that prompt confirmation or recalculation of doses"},{"action":"Put an up-to-date height, weight and body surface area on the first prescription","why":"The pharmacist needs the same numbers the prescriber used to check the dose independently.","source":"bopa-2025","quote":"Ensure an up-to-date height, weight and BSA (where relevant) is calculated and documented on the prescription."},{"action":"Use the person's actual weight and give full weight-based cytotoxic doses to people with obesity, especially when treatment aims to cure","why":"Reducing doses for larger people lowers the chance the treatment works, and full doses are not more toxic for them.","source":"asco-obesity-2021","quote":"The Panel continues to recommend that full, weight-based cytotoxic chemotherapy doses be used to treat obese adults with cancer."},{"action":"Give full approved doses of immunotherapy and targeted therapy to people with obesity","why":"There is no evidence that these drugs need reducing for body size, and the 2021 guideline extended full dosing to them.","source":"asco-obesity-2021","quote":"New to this version of the guideline, the Panel also recommends that full, approved doses of immunotherapy and targeted therapies be offered to obese adults with cancer."},{"action":"If side effects occur, reduce or delay doses in a person with obesity in the same way as in anyone else","why":"Toxicity, not body size, is the reason to change a dose.","source":"asco-obesity-2021","quote":"In the event of toxicity, the consensus of the Panel is that dose modifications of systemic antineoplastic therapies should be handled similarly for obese and nonobese patients."},{"action":"Recheck weight during treatment as often as local policy says, and recalculate the dose when it changes beyond the local threshold","why":"Weight loss or gain during treatment can make the original dose too high or too low.","source":"bopa-2025","quote":"There must be a local policy in place which determines when treatment doses should be recalculated if the patients’ weight changes during the course of treatment."},{"action":"Have the pharmacist check every calculation and its units at each cycle, and band adult doses where national bands exist","why":"A second, independent calculation catches arithmetic and unit errors before the drug is prepared.","source":"bopa-2025","quote":"Check drug dose calculations (Flat, BSA, weight, AUC) and units are appropriate."}],"bestInClass":{"statement":"Metric height and weight, measured and verified by two people before a new plan (ASCO-ONS 2024); the calculation method, variables and recalculation triggers written on the order (ASCO-ONS 2024); an independent pharmacist check of every calculation (BOPA 2025); and full doses for actual body size in obesity, for cytotoxics and, since 2021, immunotherapy and targeted therapy (ASCO 2021). The sources do not set a re-weighing interval or a weight-change threshold; both are left to local policy, and BOPA tolerates documented BSA capping as individual practice, which ASCO recommends against routinely.","sources":["asco-ons-2024","bopa-2025","asco-obesity-2021","asco-obesity-2012"]},"variants":[{"name":"Capping body surface area (often at 2.0 m2)","differs":"Doses are calculated from a maximum BSA, commonly 2.0 m2, for larger patients. BOPA allows it as individual or local practice if documented in the treatment plan.","evidence":"ASCO 2012 found up to 40% of obese patients received limited doses and recommended against it. In 730 women with early breast cancer at Tübingen, capping at 2.0 m2 meant those above 2.1 m2 received median relative dose intensity of 83.9% against 92.6%, and had worse 5-year overall survival (85.5% against 94.3%); the authors could not separate obesity itself from underdosing.","sources":["bopa-2025","asco-obesity-2012","tubingen-capping-2026"]},{"name":"Less frequent re-weighing","differs":"Weighs every three months for acute leukaemia, lymphoma, pancreatic cancer and people under 20, and every six months for others, rather than monthly or every cycle.","evidence":"In 2,276 adults, a BSA change of 10% or more occurred in at most 7.6% and after a median of 84 days (Kemps 2024, Dutch hospital data). ASCO-ONS cites the same study and leaves the interval to the organisation.","sources":["kemps-2024","asco-ons-2024"]},{"name":"Dose banding instead of individual BSA dosing","differs":"Patients are grouped into BSA bands and given a standard prepared dose per band, so doses can be made in advance.","evidence":"Using clearance data from 1,012 patients and six drugs, banding changed individual doses by minus 14% to plus 22% with no significant loss of precision in reaching the target exposure, except for paclitaxel (Chatelut 2012). BOPA asks for adult doses to be banded where national tables exist.","sources":["chatelut-2012","bopa-2025"]}],"grades":[],"sources":[{"key":"asco-obesity-2021","label":"Appropriate Systemic Therapy Dosing for Obese Adult Patients With Cancer: ASCO Guideline Update","publisher":"American Society of Clinical Oncology (Journal of Clinical Oncology, Griggs et al.)","year":2021,"url":"https://doi.org/10.1200/JCO.21.00471","doi":"10.1200/JCO.21.00471","gradingScheme":"ASCO rates evidence quality and recommendation strength in the full text; not read here.","read":"abstract","accessed":"2026-11-11"},{"key":"asco-obesity-2012","label":"Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline","publisher":"American Society of Clinical Oncology (Journal of Clinical Oncology, Griggs et al.)","year":2012,"url":"https://doi.org/10.1200/JCO.2011.39.9436","doi":"10.1200/JCO.2011.39.9436","read":"abstract","accessed":"2026-11-11"},{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and ONS (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded; developed from a systematic review (2015 to 2023), expert panel consensus and public comment.","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"kemps-2024","label":"Frequency of measuring body weight in (sub)populations of patients with cancer treated with chemotherapy","publisher":"European Journal of Hospital Pharmacy (Kemps et al.)","year":2024,"url":"https://doi.org/10.1136/ejhpharm-2021-003215","doi":"10.1136/ejhpharm-2021-003215","read":"abstract","accessed":"2026-11-11"},{"key":"tubingen-capping-2026","label":"Impact of chemotherapy dose capping on treatment intensity and survival in early breast cancer patients with high body surface area","publisher":"Archives of Gynecology and Obstetrics","year":2026,"url":"https://doi.org/10.1007/s00404-026-08317-2","doi":"10.1007/s00404-026-08317-2","read":"abstract","accessed":"2026-11-11"},{"key":"chatelut-2012","label":"Dose banding as an alternative to body surface area-based dosing of chemotherapeutic agents","publisher":"British Journal of Cancer (Chatelut et al.)","year":2012,"url":"https://doi.org/10.1038/bjc.2012.357","doi":"10.1038/bjc.2012.357","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The full ASCO 2021 guideline, with its evidence ratings and its drug-by-drug notes on immunotherapy and targeted therapy, could not be read; the steps rest on its abstract.","No guideline read sets how often to re-weigh or what weight change should trigger a new dose; both are local policy. The NHS England national dose banding principles, which set UK rounding rules, returned a bot challenge and were not read.","No national standard on rounding doses to vial sizes could be read.","Body composition (sarcopenia) may explain toxicity better than BSA; ASCO 2021 names it as a research priority."]},{"id":"bone-health-on-hormone-therapy","kind":"protocol","name":"Bone health on aromatase inhibitors, ovarian suppression and androgen deprivation therapy","aka":["bone density scan on aromatase inhibitor","DEXA on hormone therapy","cancer treatment-induced bone loss","osteoporosis on androgen deprivation therapy","bone protection on letrozole or anastrozole"],"tldr":"Some hormone treatments for breast and prostate cancer thin the bones and raise the chance of a fracture. When you start an aromatase inhibitor or treatment that stops the ovaries working, a bone density scan is offered; on prostate hormone therapy your fracture risk may be checked. Exercise, a good diet and not smoking help, and bone-strengthening medicine is offered if the bones are thin.","summary":"Aromatase inhibitors, treatment-induced menopause, ovarian suppression and androgen deprivation therapy (ADT) accelerate bone loss. NICE NG101 offers a baseline DEXA scan to women with invasive breast cancer not receiving adjuvant bisphosphonates who start an aromatase inhibitor, have treatment-induced menopause or start ovarian suppression, and not to those on tamoxifen alone; bisphosphonates are offered to those identified by the 2008 UK expert group algorithms. Men with breast cancer starting testicular suppression with an aromatase inhibitor also have bone density assessed (NG101, 2025). Separately, adjuvant bisphosphonates for postmenopausal women with node-positive disease are offered to reduce recurrence, and also protect bone.\n\nFor prostate cancer on ADT, NICE NG131 advises against routine bisphosphonates to prevent osteoporosis, suggests considering fracture risk assessment in line with NICE's osteoporosis guidance, offers bisphosphonates to those with osteoporosis and suggests denosumab if bisphosphonates are not suitable. ASCO (2019) asks clinicians to assess fracture risk with established tools, to measure bone density where the risk is substantial, to advise nutrition, exercise and lifestyle for everyone, and, where a drug is needed, to use bisphosphonates or denosumab at osteoporosis doses. Before starting a bone-modifying drug, see the protocol on dental assessment and jaw osteonecrosis.","asOf":"2026-11-11","links":[],"tags":["protocol","bone-health","survivorship"],"related":["letrozole","anastrozole","exemestane","goserelin"],"cancers":["breast-cancer","prostate"],"sections":["supportive-care"],"technologies":["bone-modifying-agents","androgen-deprivation"],"targets":[],"drugs":["zoledronic-acid","denosumab"],"companies":[],"institutions":["nice","asco"],"pathways":[],"terms":["treatment-induced-bone-loss","aromatase-inhibitor","adt"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some hormone treatments make bones weaker. Your team may check your bones with a scan. Exercise and good food help. Some people need medicine to protect their bones.","domain":"survivorship","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","community"]},"population":"Adults with non-metastatic breast cancer starting an aromatase inhibitor, ovarian suppression or with treatment-induced menopause, and adults with prostate cancer on androgen deprivation therapy. Bone-modifying drugs for bone metastases, given at higher doses to prevent skeletal events, are a different use and not covered here.","trigger":"Starting an aromatase inhibitor, ovarian suppression or androgen deprivation therapy, or treatment causing early menopause.","steps":[{"action":"When hormone therapy starts, assess fracture risk with an established tool","why":"Treatment adds to the person's own risk from age, previous fractures, steroids, smoking and family history; a tool puts these together.","source":"asco-2019","quote":"Clinicians are advised to assess fracture risk using established tools."},{"action":"Offer a baseline DEXA bone density scan to women with breast cancer starting an aromatase inhibitor or ovarian suppression, or with treatment-induced menopause, unless they are having adjuvant bisphosphonates","why":"These treatments lower oestrogen, which speeds bone loss; a baseline scan shows who needs protection.","source":"nice-ng101","quote":"Offer a baseline dual-energy X-ray absorptiometry (DEXA) scan to assess bone mineral density in women with invasive breast cancer who are not receiving bisphosphonates as adjuvant therapy and who:"},{"action":"Do not offer a DEXA scan to people on tamoxifen alone","why":"NICE found no need for a routine scan in people taking tamoxifen on its own.","source":"nice-ng101","quote":"Do not offer a DEXA scan to people with invasive breast cancer who are receiving tamoxifen alone."},{"action":"Assess bone density in men with breast cancer starting testicular function suppression with an aromatase inhibitor","why":"The combination lowers sex hormones and puts bone at risk in the same way.","source":"nice-ng101","quote":"On starting testicular function suppression in combination with an aromatase inhibitor, assess bone mineral density in people with ER-positive invasive breast cancer who have male reproductive organs"},{"action":"For men on androgen deprivation therapy, consider a fracture risk assessment in line with NICE's osteoporosis guidance","why":"ADT lowers testosterone, which speeds bone loss over years of treatment.","source":"nice-ng131","quote":"Consider assessing fracture risk in people with prostate cancer who are having androgen deprivation therapy, in line with the NICE guideline on osteoporosis: risk assessment ."},{"action":"Advise everyone on diet, exercise and lifestyle for bone health","why":"These help bone in everyone and cost little.","source":"asco-2019","quote":"The bone health of all patients may benefit from optimizing nutrition, exercise, and lifestyle."},{"action":"Do not give bisphosphonates routinely to every man on ADT; offer them to those with osteoporosis","why":"Treatment is aimed at people whose bones are already thin, where it prevents fractures.","source":"nice-ng131","quote":"Offer bisphosphonates to people who are having androgen deprivation therapy and have osteoporosis."},{"action":"If bisphosphonates are not suitable or not tolerated in men on ADT with osteoporosis, consider denosumab","why":"Denosumab is an injection that strengthens bone by another route.","source":"nice-ng131","quote":"Consider denosumab for people who are having androgen deprivation therapy and have osteoporosis if bisphosphonates are contraindicated or not tolerated."},{"action":"Where a drug is needed, use a bisphosphonate or denosumab at the osteoporosis dose","why":"These are the drugs with evidence for preventing fractures; the doses used for bone metastases are higher and carry more risk.","source":"asco-2019","quote":"When a pharmacologic agent is indicated, bisphosphonates or denosumab at osteoporosis-indicated dosages are the preferred interventions."},{"action":"Before a bisphosphonate or denosumab, discuss the risk of jaw osteonecrosis and arrange a dental check","why":"These drugs rarely cause bone in the jaw to break down; a dental check before starting is part of preventing it.","source":"nice-ng101","quote":"Discuss the benefits and risks of bisphosphonate treatment with women, particularly the risk of osteonecrosis of the jaw, atypical femoral fractures and osteonecrosis of the external auditory canal."}],"bestInClass":{"statement":"NICE (NG101 for breast, last updated 2025; NG131 for prostate) and ASCO (2019) agree on assessing risk when bone-thinning hormone therapy starts, on lifestyle measures for all, and on bisphosphonates or denosumab when the bones are thin. They differ in how the risk is measured: NICE offers a baseline DEXA scan to every woman starting an aromatase inhibitor or ovarian suppression who is not already on adjuvant bisphosphonates, whereas ASCO starts with a fracture risk tool and measures bone density only where the risk is substantial; for men on ADT, NICE suggests a fracture risk assessment rather than a routine scan and advises against routine bisphosphonates. The ESMO 2020 bone health guideline could not be read.","sources":["nice-ng101","nice-ng131","asco-2019","esmo-2020"]},"variants":[{"name":"Risk tool first, bone density only at substantial risk (ASCO 2019)","differs":"Uses an established fracture risk tool for everyone and orders a bone density test only for those at substantial risk, rather than a baseline scan for all women starting an aromatase inhibitor.","evidence":"ASCO built its recommendations on the US Preventive Services Task Force review in the general population plus 61 studies in people with cancer; read as an abstract, so grades are not given.","sources":["asco-2019"]},{"name":"Adjuvant bisphosphonates for postmenopausal women with node-positive breast cancer (NICE NG101)","differs":"Offers zoledronic acid or sodium clodronate after surgery to reduce recurrence in postmenopausal women with node-positive disease, and considers them in node-negative disease at high risk; women on these do not need the baseline DEXA scan.","evidence":"NICE recommendation [2018]; the use was off-label in March 2025, as NICE notes.","sources":["nice-ng101"]},{"name":"Cancer Care Ontario guideline endorsed by ASCO for prostate cancer (2020)","differs":"A prostate-specific bone health guideline covering fracture risk on ADT through to bone metastases, endorsed in full by ASCO.","evidence":"Read as an abstract; its individual recommendations are not given here.","sources":["asco-cco-prostate-2020"]}],"grades":[{"claim":"Baseline DEXA for women starting an aromatase inhibitor, ovarian suppression or with treatment-induced menopause, not on adjuvant bisphosphonates","grade":"not graded (NICE); dated [2009, amended 2018]","source":"nice-ng101"},{"claim":"No routine bisphosphonates to prevent osteoporosis on ADT","grade":"not graded (NICE); dated [2008]","source":"nice-ng131","quote":"Do not routinely offer bisphosphonates to prevent osteoporosis in people with prostate cancer having androgen deprivation therapy."},{"claim":"Bisphosphonates for people on ADT with osteoporosis","grade":"not graded (NICE); dated [2014]","source":"nice-ng131"}],"sources":[{"key":"nice-ng101","label":"Early and locally advanced breast cancer: diagnosis and management (NG101), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'consider', 'do not') and each is dated. Published July 2018, last updated April 2025.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng131","label":"Prostate cancer: diagnosis and management (NG131), recommendations","publisher":"NICE","year":2019,"url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is dated, for example [2014]. Published May 2019, last updated December 2021.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2019","label":"Management of Osteoporosis in Survivors of Adult Cancers With Nonmetastatic Disease: ASCO Clinical Practice Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2019,"url":"https://europepmc.org/abstract/MED/31532726","doi":"10.1200/JCO.19.01696","read":"abstract","accessed":"2026-11-11"},{"key":"asco-cco-prostate-2020","label":"Bone Health and Bone-Targeted Therapies for Prostate Cancer: ASCO Endorsement of a Cancer Care Ontario Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2020,"url":"https://europepmc.org/abstract/MED/31990618","doi":"10.1200/JCO.19.03148","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2020","label":"Bone health in cancer: ESMO Clinical Practice Guidelines","publisher":"ESMO, Annals of Oncology","year":2020,"url":"https://doi.org/10.1016/j.annonc.2020.07.019","doi":"10.1016/j.annonc.2020.07.019","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2020 bone health guideline could not be read: Europe PMC holds no abstract and the publisher refused a script. Its thresholds for starting bone protection are not given here.","NG101 refers to the algorithms of a 2008 UK expert group position statement for deciding who gets bisphosphonates; that statement was not read, so its T-score thresholds are not given here.","ASCO 2019 was read only as an abstract; which tool, which bone density threshold and how often to repeat the scan are not given here.","No source read sets how often to repeat a DEXA scan during an aromatase inhibitor or ADT.","No source read gives calcium or vitamin D doses or an exercise prescription; the step on lifestyle rests on ASCO's general statement."]},{"id":"bone-marrow-aspirate-and-trephine-biopsy","kind":"protocol","name":"Bone marrow aspirate and trephine biopsy: preparation, pain control and aftercare","aka":["bone marrow biopsy","bone marrow test","bone marrow aspiration","BMAT","trephine biopsy","iliac crest biopsy","bone marrow aspirate"],"tldr":"A bone marrow test takes a small sample of liquid marrow and a thin core of bone, usually from the back of the hip, to look for blood cancers or check treatment. It is done awake with local anaesthetic, sometimes with sedation or gas and air. Serious problems are rare (about 1 in 1,250 tests in a UK survey). Call the hospital for fever, a red or oozing wound, or pain that gets worse.","summary":"No society guideline sets out how to do or prepare for the procedure; this page is built from the evidence that exists. Safety: British Society for Haematology surveys recorded 26 adverse events, including one death, in an estimated 54,890 biopsies from 1995 to 2001, and 16 adverse events in 19,259 procedures in 2003 (0.08%). Haemorrhage was the commonest and most serious, with myeloproliferative disorders, aspirin, other platelet dysfunction and thrombocytopenia the risk factors most often present (warfarin, disseminated intravascular coagulation and obesity also named). No source sets platelet or anticoagulant thresholds; plans are local.\n\nPain: under local anaesthetic, 70% report pain and 35% severe pain (methoxyflurane trial background). A 2024 meta-analysis of 18 randomised trials (1,017 people) found distraction (SMD -0.85), a powered biopsy system (SMD -0.27) and acupoint stimulation reduced pain, while hypnosis did not reach significance. Virtual reality was not significantly different from nitrous oxide/oxygen in REVEH (mean pain 3.0 against 3.5 of 10, n = 126). Inhaled methoxyflurane lowered worst pain against placebo (4.9 against 6.0). Sedation and gas and air (Entonox) are used in some UK hospitals. Rapid aspiration gave better specimens than slow aspiration at a cost of 1 point more pain on a 10-point scale.\n\nAftercare, as UK patient information describes it: eat and drink normally unless sedated, a dressing for 24 hours, pressure on any bleeding, mild painkillers for a few days' ache, no driving or alcohol for 24 hours after sedation with someone at home overnight, and a call to the 24-hour line for fever, a red or oozing site, feeling unwell or worsening pain.","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":["multiple-myeloma","aml","mds","myeloproliferative-neoplasms"],"sections":[],"technologies":["bone-marrow-biopsy-devices","music-therapy-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bone-marrow","biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A needle takes some marrow from inside your hip bone. You get a numbing injection. It can hurt for a short time, so ask about gas and air or medicine to relax you. Tell the team if you take blood thinners. Keep the plaster on for a day. Call the hospital if you get a fever, a red or leaking wound, or worse pain.","domain":"screening-diagnostics","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","ward","home"]},"population":"Adults having a bone marrow aspirate with or without trephine biopsy, usually from the posterior iliac crest, to diagnose, stage or monitor leukaemia, lymphoma, myeloma or other blood and marrow disorders. Children (who usually have sedation or general anaesthesia) and sternal aspiration are outside scope.","trigger":"A bone marrow examination is requested.","steps":[{"action":"Before the test, ask about blood thinners, aspirin and bleeding disorders, and look at the platelet count and diagnosis","why":"Bleeding is the main serious risk, and it was seen mostly in people on aspirin, with low platelets or with certain marrow disorders.","source":"bain-2005","quote":"The major risk factors for haemorrhage, in order of frequency, were diagnosis of a myeloproliferative disorder, aspirin treatment, other putative platelet dysfunctions, and thrombocytopenia.","grade":"National adverse event survey (ungraded)"},{"action":"Explain the test and its risks, including how rare serious complications are, and take written consent","why":"Knowing that serious problems are rare, and which ones to watch for, helps people decide and cope.","source":"bain-2005","quote":"Sixteen adverse events were reported, representing 0.08% of total reported procedures.","grade":"National adverse event survey (ungraded)"},{"action":"Let the person eat and drink as normal unless they are having sedation, in which case follow the unit's fasting instructions","why":"Local anaesthetic alone does not need an empty stomach; sedation does.","source":"cruk-2025","quote":"You are usually able to eat and drink before your test.","grade":"Patient information (ungraded)"},{"action":"Give local anaesthetic, and offer something more for pain or anxiety, such as sedation, gas and air or inhaled methoxyflurane where available","why":"Many people still feel pain with local anaesthetic alone, and a third describe it as severe.","source":"meof-2014","quote":"Pain during bone marrow biopsy (BMB) under local anaesthesia (LA) is reported in 70% of patients, of whom 35% rate the pain as severe.","grade":"Randomised trial background statement (ungraded)"},{"action":"Offer distraction, such as virtual reality, music or conversation, during the procedure","why":"In trials, distraction lowered pain without drugs or side effects.","source":"jcn-sr-2024","quote":"Distraction, powered bone marrow biopsy system and acupoint stimulation are effective in reducing pain among patients undergoing bone marrow aspiration and biopsy.","grade":"Systematic review and meta-analysis of randomised trials (GRADE certainty not stated in the abstract)"},{"action":"Aspirate rapidly rather than slowly to get a good specimen, warning the person of a brief pulling pain","why":"A fast pull draws up more marrow and gives a better sample, so the test is less likely to need repeating.","source":"aspiration-rct-2016","quote":"We propose that the R-technique is preferable to the S-technique due to better specimen quality.","grade":"Randomised trial (ungraded)"},{"action":"Cover the site with a dressing to stay on for 24 hours, and tell the person to press on it if it bleeds and call if bleeding does not stop","why":"Most oozing stops with firm pressure; bleeding that continues needs checking.","source":"cruk-2025","quote":"You have a dressing over the site, which you should keep on for 24 hours. If you notice any bleeding apply pressure to the area. If it doesn't stop, contact your hospital 24 hour advice line.","grade":"Patient information (ungraded)"},{"action":"After sedation, make sure someone takes the person home and stays overnight, and advise no driving, alcohol or machinery for 24 hours","why":"Sedatives affect judgement and reactions for longer than people feel.","source":"cruk-2025","quote":"If you have sedation, you’ll need someone to take you home and stay with you overnight. Also, for 24 hours after, you shouldn’t drive, drink alcohol, or operate heavy machinery.","grade":"Patient information (ungraded)"},{"action":"Tell the person to call the 24-hour line for a temperature, a red or sore site, fluid oozing, feeling unwell, or pain that is severe or getting worse","why":"These are signs of infection or bleeding under the skin, which are rare but need treatment.","source":"cruk-2025","quote":"If you have severe pain or it's getting worse then you should contact the hospital.","grade":"Patient information (ungraded)"}],"bestInClass":{"statement":"There is no graded guideline for performing or preparing for bone marrow biopsy; the best-supported elements are: a bleeding history focused on aspirin, other antiplatelet and anticoagulant drugs, thrombocytopenia and myeloproliferative disorders (BSH surveys, where these were the commonest factors in haemorrhage, the main serious complication at about 0.08% of procedures); local anaesthetic with an offer of additional analgesia or sedation, since most people still feel pain; and distraction, which a 2024 meta-analysis of randomised trials found effective. Virtual reality and nitrous oxide/oxygen were similar in one phase 3 trial. Aftercare as described by UK patient information is consensus practice without trial evidence.","sources":["bain-2005","bain-2003","jcn-sr-2024","reveh-2023","meof-2014","cruk-2025"]},"variants":[{"name":"Nitrous oxide/oxygen (Entonox or MEOPA) for pain","differs":"An inhaled gas mixture breathed by the patient during the procedure, used in some UK and French centres instead of or alongside sedation.","evidence":"REVEH (126 patients): mean pain 3.5 of 10 with nitrous oxide/oxygen and 3.0 with virtual reality, not significantly different; all also had lidocaine. Cancer Research UK notes some hospitals use gas and air instead of sedation.","sources":["reveh-2023","cruk-2025"]},{"name":"Inhaled methoxyflurane (Penthrox)","differs":"A self-administered handheld inhaler licensed in Australia for short procedures.","evidence":"Randomised, double-blind trial of 100 patients with cancer: worst pain 4.90 against 6.0 with placebo (p = 0.011).","sources":["meof-2014"]},{"name":"Powered biopsy drivers","differs":"A battery-powered driver turns the needle into the bone instead of manual pressure and rotation.","evidence":"In the 2024 meta-analysis, powered systems reduced pain modestly (SMD -0.27, 95% CI -0.53 to -0.003).","sources":["jcn-sr-2024"]},{"name":"Follow-up telephone calls (nurse practitioner model)","differs":"The operator calls each patient the day after and a week after to ask about adverse events.","evidence":"Described as a competency measure in a training guideline; no outcome evidence.","sources":["jadpro-2012"]}],"grades":[{"claim":"Adverse events, including one death, in UK biopsies 1995 to 2001","grade":"National postal survey (ungraded)","source":"bain-2003","quote":"A total of 26 adverse events, including one death directly attributable to the procedure, were reported among an estimated 54 890 biopsies."},{"claim":"Distraction reduced pain","grade":"Meta-analysis of randomised trials","source":"jcn-sr-2024","quote":"The pooled results revealed statistically significant pain reduction effects using distraction (SMD: -.845, 95% CI: -1.344 to -.346, p < .001)"},{"claim":"Virtual reality and nitrous oxide/oxygen gave similar pain","grade":"Phase 3 randomised trial","source":"reveh-2023","quote":"The average pain intensity was 3.5 (SD 2.6, 95% CI -1.6 to 8.6) for the MEOPA group and 3.0 (SD 2.4, 95% CI -1.7 to 7.7) for the VR group"}],"sources":[{"key":"bain-2005","label":"Bone marrow biopsy morbidity: review of 2003","publisher":"Bain, Journal of Clinical Pathology (British Society for Haematology survey)","year":2005,"url":"https://doi.org/10.1136/jcp.2004.022178","doi":"10.1136/jcp.2004.022178","gradingScheme":"Adverse event survey; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"bain-2003","label":"Bone marrow biopsy morbidity and mortality","publisher":"Bain, British Journal of Haematology","year":2003,"url":"https://doi.org/10.1046/j.1365-2141.2003.04329.x","doi":"10.1046/j.1365-2141.2003.04329.x","gradingScheme":"Adverse event survey; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"jcn-sr-2024","label":"The effectiveness of non-pharmacological interventions on reducing pain in patients undergoing bone marrow aspiration and biopsy: a systematic review and meta-analysis of randomized controlled trials","publisher":"Journal of Clinical Nursing","year":2024,"url":"https://doi.org/10.1111/jocn.17121","doi":"10.1111/jocn.17121","gradingScheme":"Meta-analysis with GRADE certainty assessment (certainty per outcome not given in the abstract).","read":"abstract","accessed":"2026-11-11"},{"key":"reveh-2023","label":"A New Option for Pain Prevention Using a Therapeutic Virtual Reality Solution for Bone Marrow Biopsy (REVEH Trial): Open-Label, Randomized, Multicenter, Phase 3 Study","publisher":"Journal of Medical Internet Research","year":2023,"url":"https://doi.org/10.2196/38619","doi":"10.2196/38619","gradingScheme":"Randomised trial; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"meof-2014","label":"A randomised, double-blind, placebo-controlled study to assess the safety and efficacy of methoxyflurane for procedural pain of a bone marrow biopsy","publisher":"BMJ Supportive & Palliative Care","year":2014,"url":"https://doi.org/10.1136/bmjspcare-2013-000447","doi":"10.1136/bmjspcare-2013-000447","gradingScheme":"Randomised trial; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"aspiration-rct-2016","label":"Bone Marrow Aspiration: A Randomized Controlled Trial Assessing the Quality of Bone Marrow Specimens Using Slow and Rapid Aspiration Techniques and Evaluating Pain Intensity","publisher":"Acta Haematologica","year":2016,"url":"https://doi.org/10.1159/000438480","doi":"10.1159/000438480","gradingScheme":"Randomised trial; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"icsh-2008","label":"ICSH guidelines for the standardization of bone marrow specimens and reports","publisher":"International Council for Standardization in Hematology (International Journal of Laboratory Hematology)","year":2008,"url":"https://doi.org/10.1111/j.1751-553x.2008.01100.x","doi":"10.1111/j.1751-553x.2008.01100.x","read":"abstract","accessed":"2026-11-11"},{"key":"jadpro-2012","label":"Bone Marrow Aspiration and Biopsy: A Guideline for Procedural Training and Competency Assessment","publisher":"Jackson et al., Journal of the Advanced Practitioner in Oncology","year":2012,"url":"https://doi.org/10.6004/jadpro.2012.3.4.7","doi":"10.6004/jadpro.2012.3.4.7","gradingScheme":"Training guideline; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"cruk-2025","label":"Bone marrow test (patient information, last reviewed 8 April 2025)","publisher":"Cancer Research UK","year":2025,"url":"https://www.cancerresearchuk.org/about-cancer/tests-and-scans/bone-marrow-test","gradingScheme":"Patient information describing usual UK practice; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No society guideline for performing or preparing for bone marrow aspirate and trephine biopsy was found; the ICSH 2008 guideline covers specimens and reports and was read as an abstract only.","No source read sets platelet thresholds or intervals for stopping anticoagulants or antiplatelet drugs before the procedure; UK practice follows local policy.","The BSH adverse event surveys date from 1995 to 2003 and were read as abstracts; no more recent national figure was found.","The aftercare steps come from patient information describing usual practice, not from trials: the 24-hour dressing and the 24-hour restrictions after sedation have no evidence behind their exact timings.","The trials of pain relief were read as abstracts; certainty of evidence per intervention in the 2024 meta-analysis was not available."]},{"id":"pelvic-radiation-disease-bowel-symptoms","kind":"protocol","name":"Bowel effects after pelvic radiotherapy (pelvic radiation disease): assessment and management","aka":["pelvic radiation disease","radiation proctitis","radiation proctopathy","radiation enteritis","bowel problems after radiotherapy","late bowel effects of radiotherapy","rectal bleeding after radiotherapy","bile acid malabsorption after radiotherapy"],"tldr":"Radiotherapy to the pelvis (for prostate, bladder, cervix, womb, rectal or anal cancer) can change how the bowel works for months or years: urgency, loose stools, wind, leakage or bleeding. Most of it has a cause that can be found and treated, often more than one, so ask for a proper assessment rather than being told it is just something to live with.","summary":"The reference is the 2015 Frontline Gastroenterology guidance (Andreyev et al.), the algorithm used in the ORBIT randomised trial, in which an algorithmic approach helped and trained nurses managed patients as well as a gastroenterologist; 65 clinicians reviewed it and agreed 27 of 28 sections. Its principles: patients can have many symptoms at once, each with more than one cause, so investigate systematically and order all first-line tests at the first visit; irritable bowel syndrome is rarely the right diagnosis here; endoscopy or surgery in irradiated tissue carries more risk, and irradiated areas are not biopsied. Common treatable causes are bile acid malabsorption (SeHCAT; a sequestrant for moderate or severe), small intestinal bacterial overgrowth (breath test or aspirate), carbohydrate intolerance, exocrine pancreatic insufficiency after para-aortic fields, and pelvic floor dysfunction (at least six weeks of exercises). Faecal calprotectin is not recommended in this group. Bleeding from telangiectasia usually starts 6 to 12 months after treatment and settles by 8 to 10 years: reassure if it is not affecting life; otherwise stop anticoagulants if possible and consider sucralfate enemas, then hyperbaric oxygen (RCT support; MASCC/ISOO suggests it, level II), formalin or thermal ablation such as argon plasma coagulation, which the guidance says is absolutely contraindicated after brachytherapy. The ASGE (2019) found argon plasma coagulation and other endoscopic methods effective from small observational studies. MASCC/ISOO suggests Lactobacillus probiotics to prevent radiation diarrhoea (level III).","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":["prostate","cervical","endometrial","rectal-cancer","anal"],"sections":[],"technologies":["bowel-after-pelvic-radiotherapy","hyperbaric-oxygen-radiation-injury","probiotics-treatment-diarrhoea","rejuv-rehab-pelvic-floor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bennett-cochrane-database-syst-rev","paper-wei-cochrane-database-syst-rev"],"journals":[],"dependsOn":[],"notes":[],"simple":"After radiotherapy to the lower tummy, the bowel can work differently for a long time. Tell your team about diarrhoea, urgency, leaking, bleeding or waking at night to open your bowels. There are tests and treatments that help.","domain":"radiotherapy","setting":{"who":["nurse","doctor","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","community","home"]},"population":"Adults with bowel symptoms during or after pelvic radiotherapy for any cancer (prostate, bladder, cervix, uterus, rectum, anus), including brachytherapy. The guidance was written mainly for clinical nurse specialists working with a gastroenterologist, and for general practitioners. Acute diarrhoea during treatment is covered only by the MASCC/ISOO probiotic suggestion; children are not covered.","trigger":"A person who has had pelvic radiotherapy reports a change in bowel function (frequency, urgency, loose stools, leakage, wind, pain, bleeding, waking at night to open the bowels), at any time after treatment.","steps":[{"action":"Take a structured history of every bowel symptom, using a Bristol Stool Chart and, where possible, a questionnaire the patient fills in beforehand","why":"People often have several symptoms at once, and words like 'diarrhoea' mean different things to different people.","source":"andreyev-prd-2015","quote":"Tools such as a Bristol Stool Chart can often clarify exactly what patients mean."},{"action":"Ask specifically about oily, pale, floating or hard-to-flush stools, waking at night to open the bowels, rapid weight loss and links to food or new medicines","why":"These point to causes that can be treated, such as fat malabsorption, and are easily missed.","source":"andreyev-prd-2015","quote":"Patients and clinicians alike often miss the presence of intermittent steatorrhoea—ask:"},{"action":"Investigate every symptom systematically, and order all first-line tests at the first visit","why":"Each symptom can have more than one cause; testing everything at once means treatment can start sooner and fewer visits are needed.","source":"andreyev-prd-2015","quote":"Arranging all investigations at the first consultation reduces follow-up and allows directed treatment at all causes for symptoms at the earliest opportunity."},{"action":"Do not settle for a diagnosis of irritable bowel syndrome","why":"In people who have had pelvic radiotherapy, specialist units almost always find a specific cause instead.","source":"andreyev-prd-2015","quote":"Specialist centres only very rarely reach a new diagnosis of ‘irritable bowel syndrome’ in this patient group."},{"action":"Do not use faecal calprotectin to look for bowel inflammation in this group","why":"It is too unspecific after radiotherapy to guide care.","source":"andreyev-prd-2015","quote":"Note: faecal calprotectin as a marker for bowel inflammation is too non-specific and hence not recommended in this population."},{"action":"Test for bile acid malabsorption (SeHCAT scan) in loose stools, and treat moderate or severe malabsorption with a bile acid sequestrant and a lower-fat diet","why":"Radiotherapy can damage the part of the small bowel that reabsorbs bile, and the bile then causes diarrhoea; binding it often helps a great deal.","source":"andreyev-prd-2015","quote":"For severe BAM developing after radiotherapy, most patients need a bile acid sequestrant and advice about long-term reduction in dietary fat intake."},{"action":"In moderate or severe bile acid malabsorption, check trace elements and fat-soluble vitamins periodically and replace them","why":"Long-term malabsorption and sequestrant treatment can leave people short of vitamins and minerals.","source":"andreyev-prd-2015","quote":"Many patients with moderate/severe BAM will be deficient in trace elements and fat-soluble vitamins. These should be checked periodically and supplemented as appropriate."},{"action":"For frequency or leakage with radiation proctopathy, start pelvic floor and toileting exercises for at least six weeks, with a stool bulking agent; refer faecal incontinence to a specialist team","why":"Radiotherapy weakens the muscles and stiffens the rectum; exercises and firmer stools reduce urgency and leakage.","source":"andreyev-prd-2015","quote":"Pelvic floor and toileting exercises (page 18)—min. 6 weeks."},{"action":"Investigate rectal bleeding with flexible endoscopy, and do not biopsy irradiated bowel","why":"The bleeding is usually from small fragile vessels the radiotherapy has caused, but other causes must be ruled out; biopsy of irradiated tissue can cause ulcers or fistulas that do not heal.","source":"andreyev-prd-2015","quote":"Do not biopsy irradiated areas."},{"action":"If the bleeding is minor and not affecting daily life, reassure and do nothing more","why":"Radiation bleeding usually starts 6 to 12 months after treatment, is worst at about 4 years and has gone by 8 to 10 years.","source":"andreyev-prd-2015","quote":"If bleeding is not staining clothes, causing anaemia or interfering with daily activities, reassure and do nothing."},{"action":"If bleeding affects quality of life, stop anticoagulants if possible and consider sucralfate enemas, with or without metronidazole","why":"Sucralfate coats and protects the lining of the rectum; stopping blood thinners lets it heal.","source":"andreyev-prd-2015","quote":"If bleeding affects quality of life, stop anticoagulants if possible and consider sucralfate enemas ± metronidazole 400 mg tds for 4 weeks."},{"action":"For persistent bleeding, discuss ablation at a specialist centre: hyperbaric oxygen, formalin, or thermal treatment such as argon plasma coagulation, which must not be used after brachytherapy","why":"Each option has trade-offs: hyperbaric oxygen has trial support but takes eight weeks of daily sessions; heat treatments are simple but can cause ulcers that do not heal in irradiated tissue.","source":"andreyev-prd-2015","quote":"Any thermal therapy (eg, APC): Advantages: easily available and simple; disadvantages: significant risk of non-healing ulceration/perforation as the tissue is ischaemic and unproven efficacy in heavy bleeding. Absolutely contraindicated in patients treated with brachytherapy."},{"action":"Treat anything the guidance marks as an emergency (for example severe colitis, heavy bleeding from another source, or very abnormal blood tests) by discussing it at once with a suitably qualified clinician","why":"Some findings need same-day action rather than the routine pathway.","source":"andreyev-prd-2015","quote":"Where it is stated that ‘this is an emergency’, the user of this guide must discuss the issue with a suitably qualified person for immediate action."}],"bestInClass":{"statement":"The 2015 Frontline Gastroenterology guidance (Andreyev et al.), the algorithm tested in the ORBIT randomised trial, is the most complete readable protocol: systematic investigation of every symptom with all first-line tests at the first visit, active search for bile acid malabsorption, bacterial overgrowth, carbohydrate intolerance, pancreatic insufficiency and pelvic floor dysfunction, no biopsy of irradiated tissue, and a stepped approach to bleeding (reassure, stop anticoagulants, sucralfate enemas, then ablation). On ablation the sources differ in emphasis: the guidance prefers hyperbaric oxygen for its randomised evidence and warns that thermal therapy such as argon plasma coagulation risks non-healing ulceration and is absolutely contraindicated after brachytherapy, while the ASGE (2019) found argon plasma coagulation, bipolar electrocoagulation, heater probe and radiofrequency ablation effective from small observational studies. MASCC/ISOO 2020 suggests hyperbaric oxygen for radiation proctitis (level II).","sources":["andreyev-prd-2015","mascc-isoo-2020","asge-2019"]},"variants":[{"name":"Endoscopic thermal therapy first for bleeding (United States)","differs":"Treats bleeding radiation proctopathy with argon plasma coagulation or another endoscopic method as the usual first ablative step.","evidence":"ASGE 2019 (abstract read): from mostly small observational studies, argon plasma coagulation, bipolar electrocoagulation, heater probe and radiofrequency ablation were effective; the evidence was limited by a lack of controlled and comparative trials. The UK guidance warns of non-healing ulceration and perforation, and contraindicates thermal therapy after brachytherapy.","sources":["asge-2019","andreyev-prd-2015"]},{"name":"Hyperbaric oxygen","differs":"About eight weeks of daily sessions in a pressure chamber for bleeding or other late radiation damage.","evidence":"MASCC/ISOO 2020 suggests it for radiation proctitis in pelvic cancers (level II). The UK guidance notes randomised evidence and possible benefit for urinary symptoms, against time, cost and travel.","sources":["mascc-isoo-2020","andreyev-prd-2015"]},{"name":"Probiotics to prevent diarrhoea during pelvic radiotherapy","differs":"Gives a probiotic containing Lactobacillus during treatment to prevent acute radiation diarrhoea.","evidence":"MASCC/ISOO 2020 suggests (level III) that probiotics containing Lactobacillus may help prevent diarrhoea from radiotherapy or chemoradiotherapy in pelvic cancers.","sources":["mascc-isoo-2020"]}],"grades":[{"claim":"Agreement with the guidance sections (defined as 60% or more of panellists agreeing)","grade":"Consensus reached for 27 of 28 sections","source":"andreyev-prd-2015","quote":"Consensus (defined prospectively as 60% or more panellists selecting ‘strongly agree’ or ‘agree’) was reached for 27 of the original 28 sections in the guide, with a median of 75% of panellists agreeing with each section."},{"claim":"An algorithmic approach helps and trained nurses can manage patients as well as a gastroenterologist","grade":"One randomised trial (ORBIT), as described by the guidance","source":"andreyev-prd-2015","quote":"A recent randomised trial suggested that an algorithmic approach to investigating and managing gastrointestinal symptoms of pelvic radiation disease (PRD) is beneficial and that specially trained nurses can manage patients as effectively as a gastroenterologist."},{"claim":"Hyperbaric oxygen to treat radiation proctitis in pelvic cancers","grade":"II (suggestion)","source":"mascc-isoo-2020","quote":"The panel suggests that hyperbaric oxygen is an effective way to treat RT‐induced proctitis in patients with pelvic malignancy."},{"claim":"Lactobacillus probiotics to prevent radiation diarrhoea in pelvic cancers","grade":"III (suggestion)","source":"mascc-isoo-2020"}],"sources":[{"key":"andreyev-prd-2015","label":"Guidance: The practical management of the gastrointestinal symptoms of pelvic radiation disease","publisher":"Frontline Gastroenterology (BMJ and British Society of Gastroenterology; Andreyev et al.)","year":2015,"url":"https://doi.org/10.1136/flgastro-2014-100468","doi":"10.1136/flgastro-2014-100468","gradingScheme":"Not graded: an algorithm reviewed by 65 clinicians in two rounds, consensus defined as 60% or more agreeing with a section.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-isoo-2020","label":"MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy (Table 3, gastrointestinal mucositis)","publisher":"MASCC and ISOO (Cancer; Elad et al.)","year":2020,"url":"https://doi.org/10.1002/cncr.33100","doi":"10.1002/cncr.33100","gradingScheme":"Level of evidence I to V; each statement a recommendation, a suggestion or no guideline possible.","read":"full-text","accessed":"2026-11-11"},{"key":"asge-2019","label":"ASGE guideline on the role of endoscopy for bleeding from chronic radiation proctopathy","publisher":"American Society for Gastrointestinal Endoscopy (Gastrointestinal Endoscopy)","year":2019,"url":"https://doi.org/10.1016/j.gie.2019.04.234","doi":"10.1016/j.gie.2019.04.234","read":"abstract","accessed":"2026-11-11"},{"key":"ascrs-2018","label":"The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Chronic Radiation Proctitis","publisher":"ASCRS (Diseases of the Colon and Rectum)","year":2018,"url":"https://doi.org/10.1097/DCR.0000000000001209","doi":"10.1097/DCR.0000000000001209","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-pu-nurse-led-pelvic-radiation-disease-clinic"],"gaps":["The main guidance dates from 2015 and no newer UK or European guideline on pelvic radiation disease was found; its steps rest on panel agreement and one randomised trial of the algorithm as a whole, not on graded evidence for each step.","The ASCRS 2018 clinical practice guideline on chronic radiation proctitis could not be read (no abstract or text available to a script), and the ASGE 2019 guideline was read as an abstract only, so their grades are not given here.","The MASCC/ISOO 2014 statements carried into 2020 unchanged on sucralfate enemas, octreotide, amifostine and sulfasalazine sit in a supplement that was not read.","The ORBIT trial itself was not read; it is described here only as the guidance describes it.","Rectal bleeding after pelvic radiotherapy can also be a new cancer; the guidance's algorithm sends unexplained bleeding and other findings for endoscopy and specialist review, which this summary does not reproduce in full."]},{"id":"bowel-preparation-for-colonoscopy","kind":"protocol","name":"Bowel preparation for colonoscopy","aka":["bowel prep","colonoscopy prep","split-dose bowel preparation","laxative before colonoscopy","PEG bowel prep","Moviprep","low-fibre diet before colonoscopy","clear liquid diet before colonoscopy"],"tldr":"A colonoscopy can only find polyps and early cancers if the bowel is clean. Eat low-fibre food the day before, drink the laxative in two halves (the evening before and the morning of the test, or all on the day for an afternoon test), and finish the last dose at least two hours before the test. Follow your unit's written instructions, which come first.","summary":"ESGE 2019 (GRADE): a low-fibre diet on the day before (strong, moderate); enhanced instructions, verbal or written, for patients and for ward staff caring for inpatients (strong, moderate); split-dose preparation for elective colonoscopy (strong, high), with same-day dosing an acceptable alternative for afternoon lists (strong, high); start the last dose within 5 hours of the procedure and finish it at least 2 hours before (strong, moderate); high- or low-volume PEG or clinically validated non-PEG agents, individualised where fluid and electrolyte disturbance is a risk (strong, moderate); simethicone suggested (weak, moderate); no routine enemas (strong, moderate), no routine oral sodium phosphate (strong, low) and no routine prokinetics (weak, low). After an inadequate preparation, repeat within a year (strong, moderate). PEG in inflammatory bowel disease and urgent bleeding; insufficient evidence in pregnancy. The US Multi-Society Task Force (2025) agrees on split dosing (and suggests 2 litres may be enough), same-day dosing for afternoon procedures (an inferior alternative in the morning), restriction limited to the day before with clear liquids or low-fibre food for early meals, and simethicone, and sets a target of more than 90% adequate preparations per endoscopist and per unit; ESGE's quality committee sets a minimum standard of 90% or more, assessed on validated scales.","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["colonoscopy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before a colonoscopy you eat plain low-fibre food the day before and drink a strong laxative in two parts. The last part is on the morning of the test and must be finished at least two hours before it. A clean bowel means nothing is missed.","domain":"screening-diagnostics","setting":{"who":["patient-or-carer","nurse","doctor"],"where":["home","outpatient-clinic","ward"]},"population":"Adults having elective colonoscopy, including screening after a positive stool test, diagnosis of suspected bowel cancer and surveillance after cancer or polyps. People with kidney or heart failure, or otherwise at risk of fluid and salt disturbance, need an individualised laxative choice; inpatients, inflammatory bowel disease, urgent colonoscopy for bleeding and pregnancy are named where ESGE addresses them. Children are not covered.","trigger":"A colonoscopy is booked.","steps":[{"action":"Give the person clear, specific instructions, spoken and written, and give them to ward staff too when the person is an inpatient","why":"Most poor preparations come from instructions that were unclear or not followed.","source":"esge-2019","quote":"ESGE recommends specific verbal or written instructions to patients and to clinic staff caring for hospitalized patients, to improve the quality of bowel preparation.","grade":"Strong recommendation, moderate quality evidence."},{"action":"Check whether the person is at risk of fluid or salt imbalance (kidney or heart failure, frailty) and choose the laxative with them in mind","why":"Some laxatives shift fluid and salts, which matters most for weak kidneys or hearts.","source":"esge-2019","quote":"ESGE recommends the use of high volume or low volume PEG-based regimens as well as that of non-PEG-based agents that have been clinically validated for routine bowel preparation. In patients at risk for hydroelectrolyte disturbances, the choice of laxative should be individualized.","grade":"Strong recommendation, moderate quality evidence."},{"action":"Do not use oral sodium phosphate routinely","why":"It can damage the kidneys and upset blood salts.","source":"esge-2019","quote":"ESGE recommends against the routine use of oral sodium phosphate for bowel preparation.","grade":"Strong recommendation, low quality evidence."},{"action":"Eat a low-fibre diet on the day before the colonoscopy","why":"Less fibre leaves less residue in the bowel to hide the lining.","source":"esge-2019","quote":"ESGE recommends a low fiber diet on the day preceding colonoscopy.","grade":"Strong recommendation, moderate quality evidence."},{"action":"Take the laxative as a split dose: half the evening before and half on the day","why":"Splitting the dose cleans the bowel better than taking it all the day before.","source":"esge-2019","quote":"ESGE recommends split-dose bowel preparation for elective colonoscopy.","grade":"Strong recommendation, high quality evidence."},{"action":"For an afternoon colonoscopy, the whole dose may be taken on the same day instead","why":"Same-day dosing works as well for afternoon lists and avoids an evening dose.","source":"esge-2019","quote":"ESGE recommends, for patients undergoing afternoon colonoscopy, a same-day bowel preparation as an acceptable alternative to split dosing.","grade":"Strong recommendation, high quality evidence."},{"action":"Start the last dose within 5 hours of the colonoscopy and finish it at least 2 hours before","why":"The bowel is cleanest a few hours after the last dose; finishing 2 hours before keeps the stomach empty for sedation.","source":"esge-2019","quote":"ESGE recommends to start the last dose of bowel preparation within 5 hours of colonoscopy, and to complete it at least 2 hours before the beginning of the procedure.","grade":"Strong recommendation, moderate quality evidence."},{"action":"Consider adding simethicone to the preparation","why":"It reduces bubbles that can hide small polyps.","source":"esge-2019","quote":"ESGE suggests adding oral simethicone to bowel preparation.","grade":"Weak recommendation, moderate quality evidence."},{"action":"Do not add enemas or prokinetic drugs routinely","why":"In trials, adding an enema did not clean the bowel better and made preparation harder to bear.","source":"esge-2019","quote":"ESGE recommends against the routine use of enemas for bowel preparation.","grade":"Strong recommendation, moderate quality evidence."},{"action":"If the preparation was inadequate, repeat the colonoscopy within a year, or sooner after extra preparation, with the next regimen adjusted to the reason it failed","why":"A poorly prepared bowel can hide polyps and cancers, so the examination needs doing again.","source":"esge-2019","quote":"ESGE recommends early repetition of colonoscopy within 1 year in the case of inadequate bowel preparation, unless clinically contraindicated.","grade":"Strong recommendation, moderate level of evidence."}],"bestInClass":{"statement":"Split-dose preparation (ESGE strong, high quality; US Multi-Society Task Force 2025 recommends), or same-day dosing for afternoon procedures; the last dose started within 5 hours and finished at least 2 hours before; a validated PEG or non-PEG laxative chosen individually for people at risk of fluid and salt disturbance, without routine oral sodium phosphate, enemas or prokinetics; low-fibre food on the day before only; enhanced instructions; simethicone suggested. The two guidelines differ in emphasis: the US Task Force allows clear liquids or low-fibre food for early meals on the day before, suggests a 2-litre regimen may be sufficient, and calls same-day dosing an inferior alternative for morning procedures, where ESGE addresses same-day dosing only for afternoon lists.","sources":["esge-2019","usmstf-2025"]},"variants":[{"name":"Clear liquids all day before the colonoscopy","differs":"Restricts the person to clear liquids for the whole day before, rather than low-fibre food.","evidence":"ESGE recommends a low-fibre diet and notes that adherence to diet restriction is low in real life; the US Task Force (2025) allows either clear liquids or a low-fibre or low-residue diet for the early and midday meals of the day before.","sources":["esge-2019","usmstf-2025"]},{"name":"Low-volume (2 litres or less) regimens","differs":"Uses a lower-volume PEG with ascorbate, or a non-PEG agent such as sodium picosulfate with magnesium citrate or oral sulfate solution, instead of 4 litres of PEG.","evidence":"ESGE accepts both high- and low-volume PEG and validated non-PEG agents (strong, moderate) and individualises the choice where fluid and salt disturbance is a risk; the US Task Force suggests a 2-litre regimen may be sufficient. The relative safety of each agent in kidney or heart failure was not read in full here.","sources":["esge-2019","usmstf-2025"]}],"grades":[{"claim":"Enhanced instructions for bowel preparation","grade":"Strong recommendation, moderate quality evidence.","source":"esge-2019","quote":"ESGE recommends the use of enhanced instructions for bowel preparation."},{"claim":"PEG regimens in inflammatory bowel disease","grade":"Strong recommendation, high quality evidence.","source":"esge-2019","quote":"ESGE recommends high volume or low volume PEG-based bowel preparation in patients with inflammatory bowel disease (IBD)."},{"claim":"PEG regimens for urgent colonoscopy for lower gastrointestinal bleeding","grade":"Strong recommendation, moderate quality evidence.","source":"esge-2019","quote":"ESGE recommends PEG regimens for bowel preparation if urgent colonoscopy is scheduled for lower gastrointestinal bleeding (LGIB)."},{"claim":"No routine prokinetic agents","grade":"Weak recommendation, low quality evidence.","source":"esge-2019","quote":"ESGE does not suggest the routine use of prokinetic agents for bowel preparation."},{"claim":"Pregnancy and breastfeeding: insufficient evidence for a specific regimen","grade":"Insufficient evidence to determine net benefits or risks.","source":"esge-2019","quote":"ESGE found insufficient evidence to determine for or against the use of specific regimens in pregnant/breastfeeding women."},{"claim":"Split dosing recommended; same-day an inferior alternative for morning colonoscopy (US)","grade":"recommend / suggest (GRADE terms in abstract; full grades not read)","source":"usmstf-2025","quote":"We recommend the use of a split-dose bowel preparation regimen and suggest that a 2 L regimen may be sufficient."}],"sources":[{"key":"esge-2019","label":"Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, Update 2019","publisher":"ESGE (Hassan et al., Endoscopy)","year":2019,"url":"https://www.esge.com/assets/downloads/pdfs/guidelines/2019_a_0959_0505.pdf","doi":"10.1055/a-0959-0505","gradingScheme":"GRADE: strong or weak recommendation; high, moderate, low or very low quality evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"usmstf-2025","label":"Optimizing Bowel Preparation Quality for Colonoscopy: Consensus Recommendations by the US Multi-Society Task Force on Colorectal Cancer","publisher":"US Multi-Society Task Force on Colorectal Cancer (Jacobson et al., Gastroenterology)","year":2025,"url":"https://doi.org/10.1053/j.gastro.2025.02.002","doi":"10.1053/j.gastro.2025.02.002","gradingScheme":"Consensus statements worded 'recommend' or 'suggest'; the grading detail is in the full text, which was not read.","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESGE guideline dates from 2019; no newer ESGE bowel preparation guideline was found. The US Task Force update (2025) was read as an abstract only, so its grades and its advice for people at high risk of inadequate preparation are not stated.","Neither source read gives specific advice for people having chemotherapy, with a stoma, or after bowel resection for cancer; their preparation follows local policy and the endoscopist's advice.","How to manage diabetes medicines (insulin, SGLT2 inhibitors, GLP-1 receptor agonists) and anticoagulants around colonoscopy is outside these sources; anticoagulants are covered by the protocol on holding blood thinners before biopsy and endoscopy.","The Thieme publisher page returned a bot challenge to a script; the ESGE-hosted copy of the same article was read instead."]},{"id":"breast-radiotherapy-positioning-and-setup","kind":"protocol","name":"Breast radiotherapy positioning, immobilisation and daily set-up verification","aka":["breast radiotherapy set-up","breast board","breast positioning for radiotherapy","radiotherapy skin marks","radiotherapy tattoos","breast IGRT","breast image guidance","prone breast radiotherapy","chest wall radiotherapy set-up"],"tldr":"For breast or chest wall radiotherapy you usually lie on your back on a sloping board with both arms above your head, in the same position every day. Skin marks or a camera that maps your skin help line you up, and X-ray images, ideally daily, check your position before treatment. If lifting both arms is too hard, one arm up is an option; some departments treat larger breasts lying face down.","summary":"The ESTRO-ACROP guideline (2023) is the only international guideline on breast set-up. Its recommendations: supine as the standard position for most treatments (it works with surface guidance); prone considered for larger breasts or more lung sparing where the equipment, expertise and patient tolerance allow; both arms up as more stable (one randomised study), one arm up for those who cannot tolerate it; flat or inclined boards both acceptable if collision risk is managed. There is insufficient evidence for any breast immobilisation device; bras or thermoplastic moulds may help selected patients with large or pendulous breasts, with skin dose evaluated locally.\n\nWithout surface-guided imaging, skin marks are required; the options (permanent tattoo, temporary marks) should be discussed with the patient, and the guideline notes that temporary marks may affect wellbeing less. For verification it recommends daily 2D-2D or 3D online imaging where available, matching on the bony anatomy under the treated volume and the breast tissue or contour, and warns against using surface guidance as the only verification without local validation, especially for partial-breast or boost treatment. Most of its statements rest on small studies; several are labelled considerations because the evidence could not support a recommendation. Breath-hold for left-sided treatment is a separate protocol.","asOf":"2026-11-11","links":[],"tags":[],"related":["breath-hold-left-breast-radiotherapy"],"cancers":["breast-cancer"],"sections":[],"technologies":["surface-guided-radiotherapy","in-room-imaging-systems","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiotherapy","imrt-term","post-mastectomy-radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"You lie the same way every day, usually on your back with your arms above your head. Small marks or cameras help line you up, and quick X-rays check you are in the right place.","domain":"radiotherapy","setting":{"who":["radiographer","patient-or-carer"],"where":["radiotherapy-department"]},"population":"Adults having external beam photon radiotherapy to the whole breast, partial breast or chest wall, with or without regional lymph nodes, after lumpectomy or mastectomy. Proton therapy, upright radiotherapy, MR-linac treatment and intrafraction motion are outside the guideline's scope and are not covered.","trigger":"The planning CT appointment and each treatment session.","steps":[{"action":"Position the patient lying on their back for most breast and chest wall treatments","why":"Lying on the back is the simplest position to repeat each day and lets surface cameras see the breast.","source":"estro-acrop-breast-positioning-2023","quote":"Based on the literature and the current equipment we recommend the supine position as the standard for most treatments, see the recommendations when prone positioning is advised below.","grade":"Recommendation"},{"action":"Consider lying face down (prone) for larger breasts or when more lung sparing is needed, if the department has the equipment and experience and the patient can tolerate it","why":"Lying face down lets a large breast fall away from the chest, which can even out the dose and spare the lung and skin folds.","source":"estro-acrop-breast-positioning-2023","quote":"For patients with larger breasts or patients that require a higher degree of lung sparing, prone may be considered if the equipment and expertise are available, and the patient can tolerate the position.","grade":"Recommendation"},{"action":"Raise both arms above the head where the patient can; use one arm up if they cannot","why":"Both arms up is steadier from day to day, but after surgery some people cannot lift both arms for long.","source":"estro-acrop-breast-positioning-2023","quote":"Both arms up are considered more stable from one randomised study, in this study significantly lower translational displacements were found.","grade":"Recommendation"},{"action":"Use a breast board indexed to the couch, flat or inclined, with the patient stable and comfortable","why":"A board that clicks into the same place on the couch every day makes the position easier to repeat.","source":"estro-acrop-breast-positioning-2023","quote":"While lacking formal evidence, anecdotally the authors strongly advise the use of positioning aids, e.g., supine breast boards, which can be indexed to both the treatment couch and skin reference marks for efficient and accurate patient positioning.","grade":"Consideration (no formal evidence)"},{"action":"Do not adopt a breast immobilisation device routinely; consider a treatment bra or mould only for selected patients with large or pendulous breasts, and check its effect on skin dose","why":"No device has been shown to help most people, and anything resting on the breast can raise the skin dose and make skin reactions worse.","source":"estro-acrop-breast-positioning-2023","quote":"There is currently insufficient evidence to support the widespread adoption of any specific type of immobilisation device of the breast.","grade":"Recommendation"},{"action":"Without surface-guided imaging, use skin marks for set-up, and discuss with the patient whether these are permanent tattoos or temporary marks","why":"Marks are needed to line the body up before imaging; permanent tattoos stay for life, and some people find them a lasting reminder of their cancer.","source":"estro-acrop-breast-positioning-2023","quote":"The available options for skin marking should be discussed taking into account long-term patient experience and patient preference.","grade":"Recommendation"},{"action":"Verify the position with 2D-2D or 3D imaging online, every day where available","why":"Daily images before treatment catch a shift in position and allow it to be corrected before the radiation is given.","source":"estro-acrop-breast-positioning-2023","quote":"Where available, 2D-2D or 3D imaging daily is recommended for online position verification.","grade":"Recommendation"},{"action":"Where only single 2D images are available, allow for the errors they cannot show with suitable margins","why":"A single flat image cannot see a shift towards or away from the camera.","source":"estro-acrop-breast-positioning-2023","quote":"If 2D-2D or 3D position verification is not available, the limitations of 2D position verification (online or offline) in visualising out-of-plane setup errors should be considered and appropriate target volume margins employed.","grade":"Recommendation"},{"action":"Match the images on both the bones under the treated area and the breast tissue or breast outline","why":"The breast can move and change shape relative to the ribs, so matching on bone alone can miss it.","source":"estro-acrop-breast-positioning-2023","quote":"Image-matching should evaluate bony anatomy directly underlying the treated volume as well as breast tissue or external breast contour.","grade":"Recommendation"},{"action":"Do not use surface guidance as the only check until the department has shown locally that it agrees with X-ray imaging, and take particular care with partial-breast or boost treatment","why":"Cameras see the skin, not the surgical bed inside the breast, which is what a partial-breast or boost treatment aims at.","source":"estro-acrop-breast-positioning-2023","quote":"SGRT should not be used as a sole means of position verification without centres first conducting a local study to validate consistent agreement with the pre-existing IGRT modality.","grade":"Recommendation"},{"action":"For left-sided treatment, add breath-hold to reduce the heart dose (see the breath-hold protocol)","why":"Holding a deep breath moves the heart away from the treated area.","source":"nice-ng101","quote":"Use a deep inspiratory breath-hold radiotherapy technique for people with left-sided breast cancer to reduce the dose to the heart.","grade":"[2018]"}],"bestInClass":{"statement":"Supine on an indexed breast board with both arms up where tolerated, no routine breast immobilisation device, skin marks (permanent or temporary, chosen with the patient) unless surface guidance replaces them, and daily online 2D-2D or 3D imaging matched on bone and breast tissue, with surface guidance used alone only after local validation (ESTRO-ACROP 2023). Prone treatment is an option for larger breasts or extra lung sparing where expertise exists; for left-sided cancer the heart is better spared by supine breath-hold (HeartSpare IB, in the breath-hold protocol). ESTRO-ACROP is the only guideline read on this subject, so there is no second guideline to set beside it; its authors say most of the underlying studies are small and old.","sources":["estro-acrop-breast-positioning-2023","estro-acrop-breath-hold-2023"]},"variants":[{"name":"Prone positioning","differs":"The patient lies face down on a dedicated board with the treated breast hanging through an opening.","evidence":"ESTRO-ACROP: improves dose homogeneity and can reduce lung and skin-fold dose, but is harder to implement and needs a dedicated team; most supine-prone comparisons are more than 10 years old; no predictor tells which patients do better prone.","sources":["estro-acrop-breast-positioning-2023"]},{"name":"One arm up","differs":"Only the arm on the treated side is raised, the other resting at the side or across the waist.","evidence":"Cohort studies report it as more comfortable; one randomised study found both arms up more stable. ESTRO-ACROP allows one arm up for patients who cannot tolerate both.","sources":["estro-acrop-breast-positioning-2023"]},{"name":"Temporary skin marks instead of permanent tattoos","differs":"Set-up marks are drawn or applied semi-permanently and renewed during the course, so no lifelong tattoo remains.","evidence":"ESTRO-ACROP cites a randomised study (176 against 166 patients) that found no significant difference in random or systematic set-up error between tattoos and non-permanent marks on weekly portal imaging, and a qualitative study (SuPPORT 4 All) reporting that permanent tattoos may affect wellbeing. It lists temporary marks as a consideration.","sources":["estro-acrop-breast-positioning-2023"]},{"name":"Surface-guided set-up without skin marks","differs":"An optical surface imaging system positions the patient against their planning surface, with no tattoos or marks.","evidence":"ESTRO-ACROP: SGRT may improve set-up accuracy and allow marks to be omitted, but must be validated in the department's own workflow, and should not replace X-ray verification without local validation.","sources":["estro-acrop-breast-positioning-2023"]},{"name":"Treatment bra or thermoplastic breast mould","differs":"A fabric bra or moulded shell holds a large or pendulous breast in a fixed shape.","evidence":"ESTRO-ACROP: may benefit selected patients; in one free-breathing study a bra reduced mean heart dose from 4.9 to 1.4 Gy but phantom measurements found skin dose about 1.5 times higher with it; the effect on skin toxicity must be evaluated locally.","sources":["estro-acrop-breast-positioning-2023"]}],"grades":[{"claim":"Supine as the standard position for most treatments","grade":"Recommendation","source":"estro-acrop-breast-positioning-2023"},{"claim":"Without surface guided imaging, skin marking is required","grade":"Recommendation (summary table)","source":"estro-acrop-breast-positioning-2023","quote":"In the absence of surface guided imaging, the use of skin marking is required."},{"claim":"Temporary skin marks may be an alternative to permanent tattoos with less impact on wellbeing","grade":"Consideration","source":"estro-acrop-breast-positioning-2023","quote":"Temporary skin marks may be an alternative to permanent tattoos with a lesser impact on patient well-being"},{"claim":"Daily 2D-2D or 3D online position verification where available","grade":"Recommendation","source":"estro-acrop-breast-positioning-2023"},{"claim":"SGRT should not replace standard image guidance without local validation, with particular caution for partial-breast and integrated-boost treatment","grade":"Recommendation (summary table)","source":"estro-acrop-breast-positioning-2023","quote":"SGRT should not replace standard image-guidance without local validation and particular caution to partial-breast/integrated-boost treatments."}],"sources":[{"key":"estro-acrop-breast-positioning-2023","label":"ESTRO-ACROP guideline for positioning, immobilisation and setup verification for local and loco-regional photon breast cancer irradiation","publisher":"ESTRO (Technical Innovations and Patient Support in Radiation Oncology; Mast et al.)","year":2023,"url":"https://doi.org/10.1016/j.tipsro.2023.100219","doi":"10.1016/j.tipsro.2023.100219","gradingScheme":"Two labels, no levels: recommendations, proposed where the evidence supported them, and considerations, practice the authors judged relevant but the evidence could not support.","read":"full-text","accessed":"2026-11-11"},{"key":"estro-acrop-breath-hold-2023","label":"ESTRO-ACROP guideline: Recommendations on implementation of breath-hold techniques in radiotherapy","publisher":"ESTRO (Radiotherapy and Oncology; Aznar et al.)","year":2023,"url":"https://doi.org/10.1016/j.radonc.2023.109734","doi":"10.1016/j.radonc.2023.109734","gradingScheme":"Not graded: expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng101","label":"Early and locally advanced breast cancer: diagnosis and management (NG101), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or updated.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-tattoo-free-set-up"],"gaps":["Only one guideline addresses breast set-up (ESTRO-ACROP 2023), and its literature search closed in January 2019; its authors describe the evidence as limited and the studies as small. No ASTRO or RCR guideline on the same subject was found.","No action threshold (how many millimetres of shift should trigger a correction) is given by the guideline; departments set their own, and none was read.","The RCR guidance on image-guided radiotherapy (On Target 2) could not be found on the RCR website on 11 November 2026 (the expected page returned 404) and was not read; AAPM Task Groups 142 and 179 are paywalled and were not read.","Whether permanent tattoos can be dropped without loss of accuracy rests, in the guideline, on one randomised study with weekly portal imaging and one qualitative study; neither was read directly.","Intrafraction motion and respiratory motion were excluded from the guideline's scope."]},{"id":"breast-screening-after-chest-radiotherapy-at-a-young-age","kind":"protocol","name":"Breast screening after chest radiotherapy at a young age","aka":["breast cancer surveillance after Hodgkin lymphoma","breast MRI after mantle radiotherapy","very high risk breast screening after radiotherapy","IGHG breast surveillance","BARD referral"],"tldr":"Women who had radiotherapy to the chest as children, teenagers or young adults, for example for Hodgkin lymphoma, have a much higher chance of breast cancer at a young age. They should be offered yearly breast MRI and mammograms, starting at 25 or 30 or 8 years after the radiotherapy, whichever is later. In England this is arranged through the NHS very high risk screening programme.","summary":"Female survivors of childhood, adolescent and young adult cancer treated with chest radiotherapy of 10 Gy or more have a cumulative breast cancer incidence of 13 to 20 per cent by 40 to 45 years, and up to 35 per cent by 50 (IGHG 2020). IGHG recommends annual mammography and breast MRI from age 25 or 8 years after radiotherapy, whichever is later, up to at least age 60 (level A, strong), and annual surveillance from 25 to be reasonable after upper abdominal radiotherapy exposing breast tissue at a young age (level B, moderate). Surveillance should come with counselling on its benefits and harms.\n\nIn England the NHS Breast Screening Programme very high risk service takes women irradiated to breast tissue between 10 and 35 years of age, identified for lymphoma by the BARD dataset or referred by oncologists: annual MRI from 25 (irradiated at 10 to under 20) or 30 (irradiated at 20 to under 36), or 8 years after radiotherapy if later; annual MRI with mammography from 40 to under 51; annual mammography with or without MRI from 51 to under 71. Girls irradiated below 10 are not tested by the programme, unlike IGHG. For anthracyclines without chest radiotherapy, IGHG's 2026 update considers surveillance reasonable after 200 mg/m² of doxorubicin or more, from 30 or 8 years after exposure.","asOf":"2026-11-11","links":[],"tags":["protocol","survivorship","late-effects","screening"],"related":["doxorubicin"],"cancers":["hodgkin-lymphoma"],"sections":["supportive-care"],"technologies":["mammography"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-effects","lymphoma-living-hodgkin-survivorship-screening","lymphoma-tx-hodgkin-late-effects"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Radiotherapy to the chest when young raises the chance of breast cancer later. Yearly breast scans should start in your mid-twenties or thirties.","domain":"survivorship","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","community"]},"population":"Women who as children, adolescents or young adults had radiotherapy exposing breast tissue (chest, mantle, mediastinal, axillary, whole-lung or total body fields, or upper abdominal fields extending above the diaphragm), above all for Hodgkin lymphoma; and, under the 2026 IGHG update, women treated with 200 mg/m² or more of doxorubicin without chest radiotherapy. Women with a genetic predisposition follow separate genetic surveillance protocols.","trigger":"A survivor treated with chest radiotherapy when young reaches age 25, or 8 years have passed since radiotherapy, whichever is later.","steps":[{"action":"Identify women who had radiotherapy exposing breast tissue when young and tell them about their raised risk","why":"Survivors may not know they need earlier screening unless someone tells them.","source":"ighg-2020","quote":"Female survivors of childhood, adolescent, and young adult (CAYA) cancer treated with radiation to fields that expose breast tissue—hereafter referred to as chest radiation—are at increased risk of developing breast cancer at a young age."},{"action":"Counsel the survivor on the benefits and harms of surveillance before starting","why":"Surveillance finds cancers earlier but also brings false alarms, biopsies and anxiety; the choice is hers.","source":"ighg-2020","quote":"A survivor information form was developed to counsel survivors about the potential harms and benefits of surveillance."},{"action":"After chest radiotherapy of 10 Gy or more, offer yearly mammography and breast MRI from age 25 or 8 years after radiotherapy, whichever is later, until at least 60","why":"MRI and mammography together find more cancers than either alone in young women with dense breasts.","source":"ighg-2020","quote":"Therefore, annual breast cancer surveillance with both mammography and MRI is recommended for survivors of CAYA cancer treated with 10 Gy or more chest radiation with an attained age of 25 years or 8 years after radiation, whichever occurs last, for at least up to age 60 years (level A, strong recommendation).","grade":"level A, strong recommendation"},{"action":"After upper abdominal radiotherapy that exposed breast tissue at a young age, consider yearly surveillance from 25, deciding with the woman","why":"The risk is raised but less clearly than after chest radiotherapy, so it is an individual decision.","source":"ighg-2020","quote":"annual surveillance is reasonable at age 25 years for survivors treated with upper abdominal radiation—that can extend above the diaphragm—at a young age (level B, moderate recommendation).","grade":"level B, moderate recommendation"},{"action":"In England, refer eligible women to the NHS Breast Screening Programme very high risk service; women treated for lymphoma are found through BARD, others through the BARD non-lymphoma referral form","why":"The programme organises the MRI and mammography schedule and the recall of women who would otherwise be lost to follow-up.","source":"nhs-bsp-protocols-2026","quote":"BARD - for women who received radiotherapy to sites involving breast tissue during treatment for lymphoma and non-lymphomas (where appropriate)"},{"action":"In the NHS programme, follow the age bands: annual MRI first, adding mammography from 40, and annual mammography with or without MRI from 51 to under 71","why":"The programme sets which test is used at which age, and the start depends on the age at radiotherapy.","source":"nhs-bsp-frequency-2026","quote":"Surveillance starts at age 25 or 8 years after first irradiation, whichever is the later"},{"action":"After 200 mg/m² or more of doxorubicin without chest radiotherapy, consider routine surveillance from 30 or 8 years after exposure, whichever is later","why":"Newer evidence shows a moderate rise in breast cancer risk at these doses even without radiotherapy.","source":"ighg-2026","quote":"Routine breast cancer surveillance after ≥200 mg/m 2 doxorubicin in the absence of chest radiation is reasonable from age 30 years onward or ≥8 years from exposure (whichever occurs last)."}],"bestInClass":{"statement":"IGHG (2020) is the international standard: annual mammography plus breast MRI from 25 or 8 years after chest radiotherapy of 10 Gy or more, whichever is later, until at least 60 (level A, strong), with counselling on benefits and harms. The NHS very high risk programme in England (updated 11 November 2026) implements the same principle with age bands and differs in three ways: it starts at 30 for women irradiated at 20 or older, uses MRI alone before 40 and mammography with or without MRI from 51, and does not screen women irradiated before age 10. IGHG's 2026 update extends surveillance to survivors of 200 mg/m² or more of doxorubicin without chest radiotherapy; the NHS programme pages read do not include them.","sources":["ighg-2020","nhs-bsp-frequency-2026","nhs-bsp-protocols-2026","ighg-2026"]},"variants":[{"name":"NHS Breast Screening Programme very high risk protocol (England)","differs":"Irradiated at 10 to under 20: annual MRI from 25 to under 40. Irradiated at 20 to under 36: annual MRI from 30 to under 40. Both: annual MRI with mammography from 40 to under 51, annual mammography with or without MRI from 51 to under 71, starting no earlier than 8 years after radiotherapy. Girls irradiated below 10 are not tested by the programme.","evidence":"A national screening protocol; not graded.","sources":["nhs-bsp-frequency-2026"]},{"name":"Surveillance after anthracyclines without chest radiotherapy (IGHG 2026)","differs":"Adds routine surveillance from 30 or 8 years after exposure for survivors treated with 200 mg/m² or more of doxorubicin; makes no recommendation for daunorubicin, epirubicin or idarubicin without chest radiotherapy.","evidence":"GRADE: moderate-quality evidence of no association below 100 mg/m², high-quality evidence of a weak association at 100 to 199 mg/m² and a moderate risk at 200 mg/m² or more. Read as an abstract.","sources":["ighg-2026"]}],"grades":[{"claim":"Annual mammography and MRI after 10 Gy or more chest radiotherapy, from 25 or 8 years after, to at least 60","grade":"level A, strong recommendation","source":"ighg-2020"},{"claim":"Annual surveillance after upper abdominal radiotherapy exposing breast tissue at a young age","grade":"level B, moderate recommendation","source":"ighg-2020"}],"sources":[{"key":"ighg-2020","label":"Updated Breast Cancer Surveillance Recommendations for Female Survivors of Childhood, Adolescent, and Young Adult Cancer From the International Guideline Harmonization Group","publisher":"International Late Effects of Childhood Cancer Guideline Harmonization Group, Journal of Clinical Oncology","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7723685/","doi":"10.1200/JCO.20.00562","gradingScheme":"GRADE Evidence-to-Decision framework; recommendations printed with a level (for example A or B) and a strength (for example strong or moderate).","read":"full-text","accessed":"2026-11-11"},{"key":"ighg-2026","label":"International Guideline Harmonization Group Recommendations for Breast Cancer Surveillance in Childhood, Adolescent, and Young Adult Cancer Survivors After Anthracyclines","publisher":"IGHG, JCO Oncology Practice","year":2026,"url":"https://europepmc.org/abstract/MED/41499731","doi":"10.1200/OP-25-01017","read":"abstract","accessed":"2026-11-11"},{"key":"nhs-bsp-protocols-2026","label":"Protocols for surveillance of women at higher risk of developing breast cancer","publisher":"NHS Breast Screening Programme (GOV.UK)","year":2026,"url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/protocols-for-surveillance-of-women-at-higher-risk-of-developing-breast-cancer","gradingScheme":"National programme protocol; not graded. Page updated 11 November 2026; applies to England.","read":"full-text","accessed":"2026-11-11"},{"key":"nhs-bsp-frequency-2026","label":"Tests and frequency of testing for women at very high risk","publisher":"NHS Breast Screening Programme (GOV.UK)","year":2026,"url":"https://www.gov.uk/government/publications/breast-screening-higher-risk-women-surveillance-protocols/tests-and-frequency-of-testing-for-women-at-very-high-risk--2","gradingScheme":"National programme protocol; not graded. Applies to England.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The IGHG 2026 anthracycline update was read only as an abstract.","The NHS programme pages read do not say whether survivors of high-dose doxorubicin without chest radiotherapy are eligible.","IGHG's upper limit of at least 60 and the NHS programme's age bands differ, and no source read compares outcomes between them.","Surveillance outside England (Scotland, Wales, Northern Ireland and other countries) was not read.","Women who also carry a genetic predisposition follow a case-by-case protocol under the NHS programme, which is not given here."]},{"id":"respiratory-motion-management-4d-ct-and-gating","kind":"protocol","name":"Breathing motion in lung and upper abdominal radiotherapy: 4D CT, gating, breath-hold and compression","aka":["respiratory motion management","4D CT","4DCT","four-dimensional CT","respiratory gating","abdominal compression","internal target volume","ITV","tumour tracking","TG-76","breath-hold for lung"],"tldr":"Tumours in the lung, liver and upper abdomen move as you breathe. At the planning scan the team usually records the whole breathing cycle (4D CT) to see how far the tumour moves. They then plan to cover that movement, or reduce it by asking you to hold your breath, pressing gently on your tummy, or switching the beam on only at one point in each breath. They practise the breathing with you first.","summary":"AAPM Task Group 76 (Report 91, 2006) recommends measuring three-dimensional tumour motion for each patient where breathing motion may matter, over several breathing cycles; if motion cannot be measured, the prudent course is to assume it is significant and use motion management. Motion management is recommended for consideration when the range of motion exceeds 5 mm in any direction, or when it gives significant normal tissue sparing; the 5 mm threshold may be lower for SBRT. A measured motion should be built into the margin: the whole range if no device is used (an internal target volume), only the residual motion if one is. The patient is coached at simulation and on the first treatment day; a back-up CT without breathing requirements is taken in case the patient cannot comply. TG-76 recommends a qualified physicist at simulation sessions using motion devices and at least the first treatment, the most accurate dose calculation available in lung, written QA for every step, and frequent verification images of the diaphragm or tumour (daily for the first few treatments, then at least weekly). MPPG 9.b (2025) requires 4D CT for thoracic and abdominal SBRT and end-to-end testing with a moving phantom. In the TG-324 survey of AAPM members (2020), 95% used motion management for thoracic and abdominal sites, 60% the internal target volume method, 25% breath-hold or compression and 13% gating or tracking. TG-76 is 20 years old and predates routine cone-beam CT and surface guidance; no newer AAPM report replaces it.","asOf":"2026-11-11","links":[],"tags":[],"related":["breath-hold-left-breast-radiotherapy","stereotactic-radiosurgery-and-sbrt-delivery-safeguards","radiotherapy-planning-ct-simulation"],"cancers":["nsclc","lung-cancer","hcc"],"sections":[],"technologies":["respiratory-motion-management","respiratory-gating-tumour-tracking-systems","ct","in-room-imaging-systems","surface-guided-radiotherapy","sbrt","cyberknife"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiotherapy","planning-target-volume","fiducial-markers"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your breathing moves tumours in the chest and tummy. A special scan measures how much. The team may ask you to breathe in a set way or hold your breath, and will practise it with you.","domain":"radiotherapy","setting":{"who":["radiographer","doctor","patient-or-carer"],"where":["radiotherapy-department"]},"population":"Adults having external beam radiotherapy to the lung, oesophagus, liver, pancreas, kidney or other sites that move with breathing, including SBRT. Left-sided breast breath-hold is covered by its own protocol. Particle therapy has separate guidance (AAPM TG-290) not read here.","trigger":"Planning radiotherapy to a site where breathing may move the target.","steps":[{"action":"Measure the tumour's movement for each patient where breathing motion may matter, over several breathing cycles, usually with a 4D CT at the planning scan","why":"How much a tumour moves differs from person to person, so it must be measured rather than guessed.","source":"aapm-tg76-2006","quote":"When measuring tumor motion, the motion should be observed over several breathing cycles if possible.","grade":"Task group recommendation (ungraded)"},{"action":"If motion cannot be measured, assume it is significant and treat with a motion management technique","why":"Assuming no movement could mean part of the tumour is missed.","source":"aapm-tg76-2006","quote":"If no method exists for measuring motion, for example, with a standard respiratory-gated CT procedure, the prudent approach is to assume that motion is significant and treat with respiratory management (box 6).","grade":"Task group recommendation (ungraded)"},{"action":"Consider breath-hold, compression, gating or tracking when the tumour moves more than 5 mm in any direction, or when it would spare significant normal tissue; use a lower threshold for SBRT","why":"Small movements are lost among other set-up errors; larger ones are worth controlling to spare healthy lung and organs.","source":"aapm-tg76-2006","quote":"The Task Group recommends that respiratory management techniques be considered if either of the following conditions occur:","grade":"Task group recommendation (ungraded)"},{"action":"Build the measured motion into the margin: the whole range of motion if no device is used, only the motion during beam-on if one is","why":"The margin is what makes sure the tumour stays inside the beam wherever it is in the breath.","source":"aapm-tg76-2006","quote":"If a respiratory management device is not used, the entire range of motion should be considered when establishing the internal margin.","grade":"Task group recommendation (ungraded)"},{"action":"Coach the patient in the breathing technique at the planning scan and again on the first treatment day","why":"Practice makes breathing more regular and breath-holds more repeatable.","source":"aapm-tg76-2006","quote":"Coaching the patient at simulation and on the first day of treatment is fairly common and recommended.","grade":"Task group recommendation (ungraded)"},{"action":"If the patient may not manage the breathing technique, take a back-up planning CT without it at the same appointment","why":"It avoids a second planning visit if breath-hold or gating turns out not to be possible.","source":"aapm-tg76-2006","quote":"If the potential exists that the patient will be unable to comply with breathing or breath-hold techniques for treatment, a backup CT scan without such a requirement is recommended during simulation.","grade":"Task group recommendation (ungraded)"},{"action":"Have a qualified medical physicist present at simulation sessions using motion management devices and at least the first treatment","why":"The equipment is complex, and problems are easiest to fix at the start.","source":"aapm-tg76-2006","quote":"The Task Group recommends that, due to the complexity of the management of the respiratory motion problem and the technology used, a qualified medical physicist be present at all treatment-simulation (virtual or otherwise) imaging sessions in which respiratory management devices are used and also for at least the first treatment for each patient.","grade":"Task group recommendation (ungraded)"},{"action":"Use the most accurate dose calculation available for treatment in the lung","why":"Radiation behaves differently in air-filled lung, and simpler calculations get the dose wrong there.","source":"aapm-tg76-2006","quote":"Due to the complex nature of radiation transport in low-density regions such as the lung, the Task Group recommends that the most accurate dose calculation available be used.","grade":"Task group recommendation (ungraded)"},{"action":"Image the diaphragm or tumour at the breathing phase used for treatment, daily for the first few treatments and at least weekly after that","why":"The link between an outside breathing signal and the tumour inside can change from day to day.","source":"aapm-tg76-2006","quote":"Daily verification is recommended for the first few treatments, followed by (at least) weekly verification to ensure that the anatomy at the respiratory position used for treatment remains constant.","grade":"Task group recommendation (ungraded)"},{"action":"For stereotactic treatment of moving targets, test the whole chain (4D CT, planning, delivery) end to end with a moving phantom","why":"It checks that the system actually hits a moving target before any patient is treated with it.","source":"aapm-mppg-9b-2025","quote":"If the planned scope of clinical services includes treatments affected by respiratory motion, the entire treatment chain (CT simulation, treatment planning, treatment delivery) should be assessed with E2E testing using a dynamic phantom setup with clinically relevant motion parameters (amplitude, cycle time).","grade":"Minimum practice guideline (ungraded)"},{"action":"Keep written quality assurance procedures for imaging, planning and delivery with motion devices, and record the results","why":"Each device adds steps that can go wrong; checking them regularly keeps treatment accurate.","source":"aapm-tg76-2006","quote":"Strict QA procedures for the imaging, planning, and delivery of radiotherapy using respiratory management devices are required to ensure the safe and effective use of these devices.","grade":"Task group recommendation (ungraded)"}],"bestInClass":{"statement":"Measure each patient's tumour motion (4D CT over several breathing cycles); consider active motion management when motion exceeds 5 mm or when it spares significant normal tissue, with a lower threshold for SBRT; otherwise cover the full measured range with an internal margin (AAPM TG-76). Coach the patient at simulation and the first treatment, keep a back-up CT, use the most accurate lung dose calculation, verify the breathing position by imaging, and run written QA (TG-76); for SBRT, test the chain end to end with a moving phantom (MPPG 9.b 2025). Which technique (internal target volume, breath-hold, compression, gating or tracking) is chosen depends on the patient's tolerance and the equipment; no guideline read ranks them and no randomised trial read compares them for outcomes.","sources":["aapm-tg76-2006","aapm-mppg-9b-2025","aapm-tg324-survey-2022"]},"variants":[{"name":"Internal target volume (free breathing, margin covers all motion)","differs":"The patient breathes freely and the target volume is drawn over all phases of the 4D CT. The commonest approach in the TG-324 survey (60% of respondents).","evidence":"TG-76 accepts it when the full range of motion is in the margin; it irradiates more normal tissue than techniques that reduce motion.","sources":["aapm-tg76-2006","aapm-tg324-survey-2022"]},{"name":"Breath-hold or abdominal compression","differs":"Motion is reduced by a voluntary or device-assisted breath-hold, or by a plate or belt pressing on the upper abdomen. Used by 25% of TG-324 respondents.","evidence":"TG-76 describes both and recommends verifying stability within and between breath-holds; tolerance varies and few factors predict who can manage it.","sources":["aapm-tg76-2006","aapm-tg324-survey-2022"]},{"name":"Gating or real-time tracking","differs":"The beam is switched on only in a chosen phase of breathing, or follows the moving target (for example robotic or MLC tracking, often with implanted markers). Used by 13% of TG-324 respondents.","evidence":"TG-76: internal markers give the most accurate position but need an invasive procedure and can migrate; external surrogates need their relation to the tumour established.","sources":["aapm-tg76-2006","aapm-tg324-survey-2022"]}],"grades":[{"claim":"Motion management is very widely used in thoracic and abdominal radiotherapy","grade":"Practice survey (AAPM members, 2020)","source":"aapm-tg324-survey-2022","quote":"Overall, 95% of respondents used respiratory motion management for thoracic and abdominal sites, with 36% of respondents using respiratory motion management for at least 90% of thoracic and abdominal patients."},{"claim":"The internal target volume method is the commonest approach","grade":"Practice survey (AAPM members, 2020)","source":"aapm-tg324-survey-2022","quote":"The majority (60%) of respondents used the internal target volume method to treat thoracic and abdominal cancer patients, with 25% using breath hold or abdominal compression and 13% using gating or tracking."},{"claim":"The 5 mm threshold may be lowered for SBRT","grade":"Task group recommendation (ungraded)","source":"aapm-tg76-2006","quote":"The recommended 5-mm motion-limit criterion value may be reduced for special procedures, such as stereotactic body radiotherapy."}],"sources":[{"key":"aapm-tg76-2006","label":"The Management of Respiratory Motion in Radiation Oncology: report of AAPM Task Group 76 (AAPM Report 91)","publisher":"American Association of Physicists in Medicine (Keall et al.; also Medical Physics 2006)","year":2006,"url":"https://www.aapm.org/pubs/reports/RPT_91.pdf","doi":"10.1118/1.2349696","gradingScheme":"Task group recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"aapm-tg324-survey-2022","label":"Results from the AAPM Task Group 324 respiratory motion management in radiation oncology survey","publisher":"Journal of Applied Clinical Medical Physics","year":2022,"url":"https://doi.org/10.1002/acm2.13810","doi":"10.1002/acm2.13810","read":"full-text","accessed":"2026-11-11"},{"key":"aapm-mppg-9b-2025","label":"AAPM-RSS Medical Physics Practice Guideline 9.b: SRS-SBRT","publisher":"American Association of Physicists in Medicine and Radiosurgery Society (Journal of Applied Clinical Medical Physics)","year":2025,"url":"https://doi.org/10.1002/acm2.14624","doi":"10.1002/acm2.14624","gradingScheme":"Minimum practice guideline using 'must' and 'should'; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["AAPM TG-76 dates from 2006, before routine cone-beam CT, surface guidance and MR-guided treatment; its verification advice (radiographs daily for the first few treatments, then weekly) is older than current daily volumetric imaging practice. No newer AAPM report on photon motion management was found; TG-324 published a survey, not a replacement report.","No European or UK guideline on motion management for lung or abdominal radiotherapy was read; ESTRO-ACROP lung SBRT guidance was read only as an abstract (see the stereotactic protocol).","No randomised trial read compares the techniques (internal target volume, breath-hold, compression, gating, tracking) for cancer control or side effects; choice rests on dosimetry, tolerance and equipment.","The 5 mm threshold was chosen because that much motion causes imaging artefacts and systematic errors, not because of outcome data."]},{"id":"car-t-bridging","kind":"protocol","name":"Bridging therapy while CAR T cells are manufactured","aka":["bridging therapy","CAR-T bridging","bridging chemotherapy","holding therapy before CAR T","bridging radiotherapy"],"tldr":"Making CAR T cells from your own blood takes several weeks. During that wait many people have a short course of treatment, called bridging, to keep the cancer under control so they are well enough for the CAR T cells. It is given only after the blood cells have been collected, and is chosen so it will not cause infections or organ problems that could delay the infusion.","summary":"EBMT/JACIE 2019: bridging maintains disease control between collection and infusion; the aim is control rather than remission. Give it only after leukapheresis; avoid regimens that cause infection, bleeding or organ dysfunction; omit it for stable, low-burden disease when turnaround is short; avoid long half-life immunotherapies that may impair CAR T-cell expansion (alemtuzumab, daratumumab, checkpoint inhibitors, brentuximab vedotin). Lymphoma options include rituximab, gemcitabine, oxaliplatin, bendamustine, pixantrone, oral regimens such as PEP-C or cyclophosphamide 100 mg daily, lenalidomide or ibrutinib, high-dose steroids, or radiotherapy to bulky or symptomatic masses. In ALL, CRS risk tracks blast burden, so bridging matters more, usually with reduced-dose B-ALL agents. Frequent monitoring is mandatory, at the treating or referring centre.\n\nMyeloma (Rasche 2026, industry-funded expert consensus, anti-BCMA CAR T): bridging for the large majority; target at least partial response; switch regimen if not reached; usually 6 to 8 weeks; about 2 weeks' washout before lymphodepletion; avoid agents the patient was refractory to and anti-BCMA agents before anti-BCMA CAR T; consider radiotherapy for extramedullary disease; talquetamab for heavily pretreated patients. SITC 2020: assess disease burden by imaging, marrow or lumbar puncture before starting CAR T-cell therapy. The adult B-ALL Delphi consensus (Blood 2026) covers bridging and pre-CAR T leukaemia staging, but only its abstract was read.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t"],"related":["car-t-apheresis","car-t-lymphodepletion"],"cancers":["dlbcl","primary-mediastinal-b-cell-lymphoma","mantle-cell-lymphoma","follicular-lymphoma","all-leukemia","multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["rituximab","gemcitabine","oxaliplatin","bendamustine","pixantrone","cyclophosphamide","etoposide","procarbazine","lenalidomide","ibrutinib","dexamethasone","methylprednisolone","talquetamab","venetoclax","carfilzomib","pomalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":["bridging-therapy","lymphoma-tx-car-t-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"While your CAR T cells are being made, you may have a short treatment to keep the cancer in check. It starts after your cells are collected.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","multidisciplinary-team","nurse"],"where":["outpatient-clinic","chemotherapy-day-unit","ward"]},"population":"Adults and children with B-cell lymphoma, B-cell acute lymphoblastic leukaemia or multiple myeloma waiting for an autologous CAR T-cell product. Choice of regimen depends on the disease; the myeloma consensus covers triple-class exposed patients before anti-BCMA CAR T only.","trigger":"After leukapheresis, while the CAR T-cell product is being manufactured.","steps":[{"action":"Give bridging therapy only after the T cells have been collected","why":"Chemotherapy before collection can damage the T cells the product is made from.","source":"ebmt-2019","quote":"Whatever treatment is chosen, bridging therapy should only be given after leukapheresis so that the quality of the CAR T-cell product is not affected."},{"action":"Aim for disease control, not remission","why":"The goal is to arrive at the infusion well enough, with organs working, rather than to cure the cancer beforehand.","source":"ebmt-2019","quote":"In brief, the aim is not so much to achieve disease remission as to establish adequate disease control prior to the CAR T-cell infusion."},{"action":"Choose a regimen unlikely to cause infection, bleeding or organ damage","why":"Lymphodepletion and CAR T cells follow soon after, and complications from bridging can delay or prevent them.","source":"ebmt-2019","quote":"Bridging therapy should therefore ideally not induce major complications, such as infections, bleeding or any organ dysfunction that might interfere with the planned lymphodepleting therapy and CAR T-cell infusion."},{"action":"Consider omitting bridging when lymphoma is stable and low-burden and the product will arrive soon","why":"Treatment that is not needed only adds side effects.","source":"ebmt-2019","quote":"Bridging therapy can be omitted in the presence of stable, low burden disease if the turn-around time for the CAR T cells is expected to be short."},{"action":"Avoid long half-life immunotherapies such as alemtuzumab, daratumumab, checkpoint inhibitors and brentuximab vedotin","why":"They may still be in the body at infusion and stop the CAR T cells expanding or persisting.","source":"ebmt-2019","quote":"Importantly, certain agents, especially immunotherapeutic drugs with a longer half-life, may interfere with the expansion or persistence of the infused CAR T cells and should be avoided."},{"action":"For lymphoma, choose from chemo-immunotherapy, oral regimens, targeted drugs, high-dose steroids or radiotherapy to bulky or symptomatic sites, guided by prior response and where the disease is","why":"What worked before, how much disease there is and where it sits decide what will control it fastest with least harm.","source":"ebmt-2019","quote":"When choosing bridging therapy for lymphoma patients, factors to be considered include the prior response to chemotherapy and chemo-immunotherapy, the overall tumor burden and the distribution and sites of tumor involvement."},{"action":"In acute lymphoblastic leukaemia, use bridging to lower the blast count, usually with reduced-dose leukaemia drugs","why":"The more leukaemia at infusion, the higher the risk of severe cytokine release syndrome.","source":"ebmt-2019","quote":"In ALL, the risk of CRS has been found to correlate with the leukemic blast burden at the time of the CAR T-cell infusion."},{"action":"In myeloma, aim for at least a partial response, and switch to a different bridging regimen if it is not reached","why":"Lower tumour burden at infusion is linked with better results and fewer toxicities after anti-BCMA CAR T.","source":"rasche-mm-2026","quote":"We agreed that patients who do not achieve ≥partial response after initial BT should switch to a different (second-line) BT regimen; the objectives of this may differ."},{"action":"In myeloma, do not bridge with an anti-BCMA agent before anti-BCMA CAR T","why":"Short exposure to the same target could encourage resistance; the effect is unknown.","source":"rasche-mm-2026","quote":"Avoid anti-BCMA BT before anti-BCMA CAR-T therapy due to unknown effects of short-term use and resistance concerns."},{"action":"Where feasible, leave about two weeks between the end of bridging and lymphodepletion","why":"A gap lets bridging side effects settle and drugs wash out before conditioning.","source":"rasche-mm-2026","quote":"If feasible, we recommend an approximate 2-week wash-out period between BT and lymphodepleting chemotherapy, regardless of BT regimen."},{"action":"Monitor closely with blood tests and imaging during bridging, with clear communication between referring and treating centres","why":"Problems need to be caught early while waiting for the product.","source":"ebmt-2019","quote":"Frequent monitoring, including laboratory testing and imaging, is mandatory in order to prevent or rapidly treat complications that might arise while awaiting the arrival of the CAR T-cell product."},{"action":"Restage the disease by imaging, marrow or lumbar puncture as appropriate before starting CAR T-cell therapy","why":"Disease burden at infusion predicts the risk of severe toxicity and guides monitoring.","source":"sitc-iec-2020","quote":"Disease burden should be assessed via imaging and bone marrow evaluation and/or lumbar puncture, as appropriate, before initiating CAR T cell therapy."}],"bestInClass":{"statement":"EBMT/JACIE 2019 is the only general best practice text read in full and is the backbone here: bridging after collection, for control rather than remission, with low-toxicity agents, avoiding long half-life immunotherapies. It is ungraded, as are the other sources. The 2022 EBMT/JACIE/EHA update, which supersedes it, could be read only as its abstract. For myeloma the 2026 expert consensus differs from EBMT 2019 in two places: it recommends bridging for the large majority regardless of disease pace (EBMT 2019 allows omission in stable low-burden lymphoma), and it lists anti-CD38 antibody combinations as bridging options where EBMT 2019 names daratumumab among agents to avoid. The myeloma panel was funded by the manufacturer of the bispecific it recommends.","sources":["ebmt-2019","ebmt-eha-2022","rasche-mm-2026","sitc-iec-2020"]},"variants":[{"name":"Bridging for nearly everyone before anti-BCMA CAR T in myeloma (Rasche et al., 2026)","differs":"Uses bridging for the vast majority, including slowly progressing relapse; targets at least partial response; 6 to 8 weeks; switches regimen if no partial response; radiotherapy for extramedullary disease; anti-CD38, proteasome inhibitor, chemotherapy, venetoclax for t(11;14), or talquetamab in heavily pretreated patients.","evidence":"Qualitative interviews and a consensus workshop of 10 European experts, funded by Johnson & Johnson; supported by retrospective data such as the CARTITUDE-4 finding that a 25% or greater paraprotein fall after bridging went with longer progression-free survival.","sources":["rasche-mm-2026"]},{"name":"Adult B-ALL Delphi consensus (Blood 2026)","differs":"33 consensus statements on CAR T-cell administration in adult B-ALL, including bridging and pre-CAR T-cell leukaemia staging, from the ROCCA consortium.","evidence":"Modified Delphi with a 27-member validation group; only the abstract was read, so its specific bridging statements are not given here.","sources":["rocca-all-2026"]}],"grades":[{"claim":"EBMT/JACIE 2019 recommendations","grade":"not graded (consensus)","source":"ebmt-2019","quote":"Given the absence of randomized trial evidence in this field, a decision was made not to grade these recommendations."},{"claim":"Myeloma bridging recommendations","grade":"expert consensus, not graded","source":"rasche-mm-2026"}],"sources":[{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-eha-2022","label":"Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)","publisher":"EBMT, JACIE and EHA, Annals of Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/34923107","doi":"10.1016/j.annonc.2021.12.003","read":"abstract","accessed":"2026-11-11"},{"key":"rasche-mm-2026","label":"Experiences and expert panel consensus on bridging therapy before anti-BCMA CAR-T cell therapy in multiple myeloma (Rasche et al.)","publisher":"Bone Marrow Transplantation","year":2026,"url":"https://europepmc.org/article/PMC/PMC13349869","doi":"10.1038/s41409-026-02905-1","gradingScheme":"Expert panel consensus from interviews and a workshop with voting; recommendations are not graded. Funded by Johnson & Johnson Research & Development.","read":"full-text","accessed":"2026-11-11"},{"key":"rocca-all-2026","label":"Consensus recommendations for CAR T-cell administration in adult acute lymphoblastic leukemia: a modified Delphi study","publisher":"Blood","year":2026,"url":"https://europepmc.org/abstract/MED/42154904","doi":"10.1182/blood.2026033559","gradingScheme":"Modified Delphi consensus statements; the abstract gives no grades.","read":"abstract","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The EBMT/JACIE/EHA 2022 recommendations, the current European edition, were read only as an abstract; whether they changed the 2019 bridging advice is not stated here.","The adult B-ALL Delphi consensus (Blood 2026) was read only as an abstract; its bridging and staging statements are not reproduced.","The EBMT 2019 washout table before leukapheresis is an image and was not read.","No randomised trial compares bridging regimens, or bridging against no bridging, in any of the sources read.","The International Myeloma Working Group guidance cited by the myeloma panel was not read directly."]},{"id":"cancer-related-fatigue-screening-and-management","kind":"protocol","name":"Cancer-related fatigue: screening, treatable causes and management","aka":["cancer-related fatigue","CRF management","fatigue during chemotherapy","tiredness after cancer treatment","exercise for cancer fatigue","CBT for cancer fatigue"],"tldr":"Tiredness that rest does not fix is one of the commonest effects of cancer and its treatment, for months or years. Your team should ask about it and look for treatable causes such as anaemia, low thyroid, pain, poor sleep, low mood or a medicine. What helps most is exercise suited to you, cognitive behavioural therapy and mindfulness. Modafinil is not recommended, nor methylphenidate routinely.","summary":"The ASCO-SIO guideline update (2024) covers adults from diagnosis onward and sorts recommendations by phase. During treatment, clinicians should recommend exercise (aerobic, resistance or both), CBT, mindfulness-based programmes and tai chi or qigong (each moderate evidence, strong recommendation); psychoeducation and American ginseng 2,000 mg daily may be recommended (conditional). After treatment, exercise, CBT and mindfulness-based programmes are strong recommendations, and yoga, acupressure and moxibustion conditional. In advanced cancer or at the end of life, CBT and corticosteroids may be offered (low evidence, conditional). In every phase, wakefulness agents (modafinil, armodafinil) should not be recommended, and psychostimulants (methylphenidate) should not be used routinely; during treatment, L-carnitine and antidepressants such as paroxetine are also recommended against.\n\nScreening and assessment were not re-examined in 2024; the panel referred readers to the 2014 ASCO adaptation, which recommends that everyone be evaluated for fatigue after primary treatment and that those with moderate to severe fatigue have a comprehensive assessment with medical and treatable contributing factors addressed. The APTA guideline (2022) grades the tools: the EORTC QLQ-C30 is the only screening tool graded A, and the Piper Fatigue Scale-Revised, FACIT-Fatigue and PROMIS Fatigue short forms are graded A for fuller assessment. The ESMO 2020 guideline could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","fatigue","supportive-care","survivorship"],"related":["exercise-during-and-after-cancer-treatment","dexamethasone"],"cancers":[],"sections":["supportive-care"],"technologies":["cancer-related-fatigue-management","exercise-oncology","exercise-during-chemotherapy","cbt-fatigue-distress","mindfulness-based-interventions","tai-chi-qigong","american-ginseng-fatigue","yoga-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":["asco","mascc","esmo"],"pathways":[],"terms":["cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Feeling very tired is common with cancer. Tell your team. Gentle exercise and talking therapies help most.","domain":"symptom-management","setting":{"who":["nurse","doctor","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","community","home"]},"population":"Adults with cancer from diagnosis onward, during and after treatment and in advanced disease (ASCO-SIO 2024). Children and adolescents are covered by a separate paediatric guideline, not read here. The 2024 recommendations were built from randomised trials in which most participants had breast cancer; the panel did not set separate recommendations by cancer type.","trigger":"At the first visit, at intervals during treatment, at the end of treatment and at follow-up; and whenever a person reports tiredness.","steps":[{"action":"Ask about fatigue at the start of care, at intervals and after primary treatment, and give everyone information about managing it","why":"Fatigue is often thought to be unavoidable and goes unreported; asking routinely finds the people who could be helped.","source":"asco-2014","quote":"It is recommended that all patients with cancer be evaluated for the presence of fatigue after completion of primary treatment and be offered specific information and strategies for fatigue management."},{"action":"Screen with a validated tool: the EORTC QLQ-C30 (graded A) or the MD Anderson Symptom Inventory (graded B); follow a positive screen with a fuller assessment","why":"A short standard questionnaire catches tiredness that a general question misses, and shows change over time.","source":"apta-2022","quote":"Only 1 screening tool rises to the level of grade A evidence for screening CRF. The EORTC-QLQ-C30 is a general symptom inventory that can be used to screen for fatigue and other problems those with cancer may have. The MDASI, also a general symptom inventory in which the individual with cancer assesses their present symptom burden, is graded B.","grade":"A (EORTC QLQ-C30); B (MDASI)"},{"action":"For moderate to severe fatigue, look for and treat contributing causes first: anaemia, thyroid and other hormone problems, pain, low mood, anxiety, poor sleep, poor nutrition, inactivity and medicines","why":"Several of these can be corrected directly, and fatigue rarely improves while they are untreated.","source":"asco-sio-2024","quote":"patients experiencing fatigue should also be evaluated and treated for contributing comorbid conditions that commonly cluster with fatigue, including pain, depression, anxiety, and sleep disturbance, as well as nutritional deficit, activity level, anemia, medication adverse effects."},{"action":"On immune checkpoint inhibitors, check for immune side effects that cause fatigue (thyroid, adrenal and pituitary problems among them) when fatigue is new or worse","why":"Fatigue can be the first sign of a hormone gland being damaged by immunotherapy, which needs its own treatment.","source":"asco-sio-2024","quote":"Fatigue can also be a symptom of other forms of immunotherapy toxicity, including adrenal insufficiency, hypothyroidism, hypophysitis, hepatitis, renal insufficiency, pneumonitis, neurologic toxicities, and anemia."},{"action":"Recommend exercise (aerobic, resistance or both), tailored to the person and supervised or not, during and after treatment","why":"Exercise has the most consistent evidence of any treatment for cancer-related fatigue.","source":"asco-sio-2024","quote":"1.1. Clinicians should recommend exercise (aerobic, resistance, or a combination) to reduce the severity of fatigue during cancer treatment. Exercise should be tailored according to the individual patient’s abilities and may be either supervised or unsupervised Moderate Strong","grade":"Evidence quality moderate; recommendation strong"},{"action":"Offer cognitive behavioural therapy (in person or online) and mindfulness-based programmes, during and after treatment","why":"Both reduce fatigue in randomised trials, and after treatment they have worked for people with moderate to severe fatigue.","source":"asco-sio-2024","quote":"2.2. Clinicians should recommend cognitive behavioral therapy (CBT) to manage symptoms of cancer-related fatigue in adults who have completed cancer treatment. CBT may be delivered in person or via a web-based program Moderate Strong","grade":"Evidence quality moderate; recommendation strong"},{"action":"During treatment, tai chi or qigong at low to moderate intensity may also be recommended","why":"These gentle movement practices reduced fatigue in trials of people on treatment.","source":"asco-sio-2024","quote":"1.4. Clinicians should recommend tai chi or qigong, practiced at a low to moderate intensity, to reduce the severity of cancer-related fatigue in adults undergoing cancer treatment Moderate Strong","grade":"Evidence quality moderate; recommendation strong"},{"action":"Do not prescribe modafinil or armodafinil for fatigue, and do not prescribe methylphenidate routinely","why":"Trials have not shown these drugs help cancer-related fatigue enough to outweigh their side effects.","source":"asco-sio-2024","quote":"1.7. Clinicians should not recommend wakefulness agents, such as modafinil or armodafinil, to manage symptoms of cancer-related fatigue in adults undergoing cancer treatment Moderate Strong","grade":"Evidence quality moderate; recommendation strong (against), during treatment"},{"action":"In advanced cancer or at the end of life, consider CBT, and corticosteroids where there is no contraindication, reviewing the balance of benefit and harm over time","why":"A short course of a steroid can lift fatigue near the end of life, but its side effects build up with time.","source":"asco-sio-2024","quote":"3.2. Clinicians may recommend corticosteroids to manage symptoms of cancer-related fatigue in patients at the end of life where no contraindications exist. The risk-benefit ratio of corticosteroid use should be assessed over time Low Conditional","grade":"Evidence quality low; recommendation conditional"}],"bestInClass":{"statement":"ASCO-SIO 2024 is the most recent graded guideline read, and MASCC endorsed it in 2026 (endorsement not read). It puts exercise, CBT and mindfulness-based programmes first in every phase before and after the end of treatment (moderate evidence, strong recommendation), adds tai chi or qigong during treatment, and recommends against wakefulness agents and routine psychostimulants. For screening and choosing a tool, the 2014 ASCO adaptation (screen everyone; assess and correct causes in moderate to severe fatigue) and the APTA 2022 tool grades are the sources read. Where these differ from ESMO 2020 cannot be said, because the ESMO guideline could not be read.","sources":["asco-sio-2024","asco-2014","apta-2022","esmo-2020","mascc-2026"]},"variants":[{"name":"American ginseng during treatment","differs":"Adds a supplement, Panax quinquefolius 2,000 mg a day, for fatigue during treatment.","evidence":"ASCO-SIO 2024 grades the evidence low and the recommendation conditional; after treatment it found the evidence on ginseng insufficient to recommend for or against. It suggests twice-daily dosing, morning and before noon, to avoid disturbing sleep. Supplements can interact with cancer drugs, so a pharmacist should check.","sources":["asco-sio-2024"]},{"name":"Yoga, acupressure or moxibustion after treatment","differs":"Mind-body or traditional Chinese medicine approaches offered after treatment instead of or alongside exercise and CBT.","evidence":"Each conditional on low-quality evidence in ASCO-SIO 2024 after treatment (yoga especially in women with breast cancer). During treatment, the panel found the evidence on yoga and acupressure insufficient.","sources":["asco-sio-2024"]}],"grades":[{"claim":"Mindfulness-based programmes reduce fatigue after treatment","grade":"Moderate; Strong","source":"asco-sio-2024","quote":"2.3. Clinicians should recommend mindfulness-based programs to reduce the severity of fatigue in adults who have completed cancer treatment."},{"claim":"Psychostimulants are not recommended routinely during treatment","grade":"Moderate; Conditional (against)","source":"asco-sio-2024","quote":"1.9. Clinicians should not routinely recommend psychostimulants, such as methylphenidate, to manage symptoms of cancer-related fatigue in adults undergoing cancer treatment Moderate Conditional"},{"claim":"Antidepressants are not recommended for fatigue during treatment","grade":"Moderate; Conditional (against)","source":"asco-sio-2024","quote":"1.10. Clinicians should not recommend antidepressants, such as paroxetine, to manage symptoms of cancer-related fatigue in adults undergoing cancer treatment Moderate Conditional"},{"claim":"Exercise in advanced cancer or at the end of life","grade":"Insufficient; no recommendation","source":"asco-sio-2024","quote":"There is insufficient evidence to make recommendations for or against collaborative care intervention, exercise, melatonin, or protocolized patient-tailored treatment to manage symptoms of cancer-related fatigue among adults with advanced cancer or at the end of life"},{"claim":"Multidimensional assessment tools","grade":"A","source":"apta-2022","quote":"Grade A scales of the PFS-R, the FACIT–Fatigue, and the PROMIS Fatigue–Short Forms."}],"sources":[{"key":"asco-sio-2024","label":"Management of Fatigue in Adult Survivors of Cancer: ASCO-Society for Integrative Oncology Guideline Update","publisher":"ASCO and SIO, Journal of Clinical Oncology","year":2024,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12082589/","doi":"10.1200/JCO.24.00541","gradingScheme":"Evidence quality high, moderate, low, very low or insufficient; strength of recommendation strong or conditional (weak), for or against.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2014","label":"Screening, Assessment, and Management of Fatigue in Adult Survivors of Cancer: an ASCO Clinical Practice Guideline Adaptation","publisher":"ASCO, Journal of Clinical Oncology","year":2014,"url":"https://europepmc.org/abstract/MED/24733803","doi":"10.1200/JCO.2013.53.4495","read":"abstract","accessed":"2026-11-11"},{"key":"apta-2022","label":"Screening and Assessment of Cancer-Related Fatigue: A Clinical Practice Guideline for Health Care Providers","publisher":"Academy of Oncologic Physical Therapy of APTA, Physical Therapy","year":2022,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9525018/","doi":"10.1093/ptj/pzac120","gradingScheme":"Tools graded A (should be used in clinical practice), B (may be used), P (limited evidence, one study) or R (not recommended or limited evidence).","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2020","label":"Cancer-related fatigue: ESMO Clinical Practice Guidelines for diagnosis and treatment","publisher":"ESMO, Annals of Oncology","year":2020,"url":"https://doi.org/10.1016/j.annonc.2020.02.016","doi":"10.1016/j.annonc.2020.02.016","read":"not-reachable","accessed":"2026-11-11"},{"key":"mascc-2026","label":"MASCC endorsement and global perspectives on implementation of the ASCO-SIO fatigue in adult cancer survivors guideline","publisher":"MASCC, Supportive Care in Cancer","year":2026,"url":"https://doi.org/10.1007/s00520-026-10855-z","doi":"10.1007/s00520-026-10855-z","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2020 cancer-related fatigue guideline could not be read (no abstract in Europe PMC; the publisher refused a script), so where ESMO differs from ASCO-SIO is not shown.","The 2014 ASCO adaptation was read only as an abstract: its screening intervals, the 0 to 10 cut-offs it uses for moderate and severe fatigue, and its list of laboratory tests are not given here.","The MASCC 2026 endorsement was not read; Europe PMC holds only its title.","NCCN's cancer-related fatigue guideline is not reproducible and was not read.","The 2024 evidence base is drawn mostly from women with breast cancer; how well the recommendations carry to other cancers is not settled.","Children and adolescents have a separate guideline (2023 update) that was not read here."]},{"id":"carboplatin-dose-calculation","kind":"protocol","name":"Carboplatin dose calculation by the Calvert formula and kidney function","aka":["Calvert formula","carboplatin AUC dosing","carboplatin dose by GFR","AUC 5 carboplatin","carboplatin GFR","EDTA GFR for carboplatin","carboplatin Cockcroft-Gault"],"tldr":"Carboplatin is not dosed by your size but by how well your kidneys clear it. The team picks a target exposure (the 'AUC', often 5 or 6) and multiplies it by your kidney filtration rate plus 25. Your kidney function is either measured with a special test or estimated from a blood test, and the newest international guidance prefers the measured test when treatment aims to cure.","summary":"The Calvert formula (1989) gives the total dose in mg as target AUC x (GFR + 25). It was derived and validated with GFR measured by 51Cr-EDTA clearance, and the US label prints it with that note. The kidney function fed into it is where practice differs.\n\nADDIKD (2025), the first international consensus on anticancer drug dosing in kidney dysfunction, prefers directly measured GFR, not standardised to body surface area, especially with curative intent, extremes of body size or muscle mass, amputation or paraplegia, or an eGFR above 125 or at or below 45 ml/min/1.73 m2. Where measured GFR is not feasible, it recommends eGFR by CKD-EPI de-indexed to the patient's own BSA (clinical consensus; strong). KDIGO 2024 says non-indexed eGFR may be indicated at extremes of body weight for narrow-therapeutic-range drugs, and its text names carboplatin. Much of the world still uses Cockcroft-Gault creatinine clearance, which overestimates GFR by 10 to 20% and, with modern IDMS-standardised creatinine assays, can overdose: in a UK cohort of 2,471 patients, 25.5% of Cockcroft-Gault doses were more than 20% off against 18.6% for BSA-adjusted CKD-EPI (Janowitz 2017).\n\nADDIKD advises against lowering the target AUC because of reduced kidney function, and against recalculating each cycle unless kidney function changes by more than 20% or the patient's condition changes. In the UK, adult doses are then banded to national tables (BOPA 2025) and the pharmacist checks the AUC calculation at verification.","asOf":"2026-11-11","links":[],"tags":[],"related":["paper-calvert-j-clin-oncol","sact-prescribing-and-pharmacy-verification","iohexol"],"cancers":[],"sections":[],"technologies":["carboplatin-calvert-dosing"],"targets":[],"drugs":["carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Carboplatin doses come from a sum using your kidney function. A blood test, or a special kidney scan or injection test, tells the team how fast your kidneys work, and the dose is worked out from that.","domain":"pharmacy","setting":{"who":["doctor","pharmacist"],"where":["outpatient-clinic","aseptic-unit","chemotherapy-day-unit"]},"population":"Adults prescribed carboplatin, alone or in combination, for any cancer. ADDIKD notes that eGFR CKD-EPI is unsuitable in kidney replacement therapy, pregnancy and people under 18; children are dosed by protocol, often from a measured GFR (BOPA notes the AUC dose is usually calculated from the DTPA half life).","trigger":"Carboplatin is prescribed for a first cycle, or kidney function or weight changes during a course.","steps":[{"action":"Calculate the total carboplatin dose in mg as target AUC x (GFR + 25), not in mg per square metre","why":"Carboplatin leaves the body almost entirely through the kidneys, so the dose that gives a predictable exposure depends on kidney function rather than body size.","source":"calvert-1989","quote":"Dose (mg) = target AUC x (GFR + 25) is now the recommended formula."},{"action":"Take the target AUC from the regimen protocol; for single-agent carboplatin in previously treated patients the label range is 4 to 6","why":"Higher AUC gives more blood count toxicity, and combination regimens use their own targets.","source":"carboplatin-label","quote":"The target AUC of 4 mg/mL•min to 6 mg/mL•min using single agent carboplatin appears to provide the most appropriate dose range in previously treated patients."},{"action":"Use directly measured GFR (for example an isotope or iohexol clearance), not standardised to body surface area, where it is available, and especially when treatment aims to cure","why":"The formula was built on measured GFR; estimates drift furthest from the truth in people with very high or low kidney function or unusual body build.","source":"addikd-integration-2025","quote":"ADDIKD proposes that directly measured GFR (not standardised to body surface area [BSA]) as the preferred kidney function value to be used to mirror the original Calvert formula study.","grade":"clinical consensus; strong"},{"action":"If measured GFR is not feasible, use eGFR from the CKD-EPI equation adjusted to the patient's own body surface area (in ml/min), rather than Cockcroft-Gault creatinine clearance","why":"BSA-adjusted CKD-EPI is closer to measured GFR than Cockcroft-Gault in people with cancer, so the dose is closer to the intended one.","source":"addikd-part1-2025","quote":"BSA-adjusted eGFR CKD-EPI is a suitable alternative to directly measured GFR for use in the Calvert formula when dosing carboplatin, especially where eGFR CKD-EPI 45–125 mL/min/1.73 m 2 , treatment intent is non-curative and the patient is neither an amputee, paraplegic or has conditions of skeletal muscle and is without extremes of body size or muscle mass.","grade":"clinical consensus; strong"},{"action":"Use a creatinine result taken while kidney function is stable and as close as possible to the treatment day","why":"A creatinine estimate assumes steady kidney function; after an acute kidney injury the blood level can lag one to three days behind.","source":"addikd-part1-2025","quote":"eGFR CKD-EPI requires stable kidney function and should be performed as close as possible to the time of administering the anticancer drug(s) to ensure it is a reflective estimation of the patient’s steady state kidney function.","grade":"clinical consensus; strong"},{"action":"Do not lower the target AUC because kidney function is reduced; the formula already lowers the dose","why":"Reducing both the GFR and the AUC would cut the dose twice and may cost treatment benefit.","source":"addikd-integration-2025","quote":"This includes a recommendation against lowering target AUC in reduced kidney function, as it may compromise clinical benefit."},{"action":"Recalculate during the course when kidney function changes by more than 20% from baseline or the patient's condition changes","why":"Small cycle-to-cycle wobbles in creatinine do not need a new dose; a real change in kidney function does.","source":"addikd-integration-2025","quote":"The recalculation of carboplatin doses at each cycle was also deemed unnecessary, except when baseline kidney function (e.g., eGFR) alters by > 20% or when there is a change in the clinical status of the patient."},{"action":"Have the pharmacist check the AUC calculation and units at verification, and band the final adult dose where national bands exist","why":"An independent check catches arithmetic and unit errors before the drug is made.","source":"bopa-2025","quote":"Check drug dose calculations (Flat, BSA, weight, AUC) and units are appropriate."},{"action":"When rechecking a banded carboplatin dose, recalculate from the new kidney function; do not work out a percentage change from the old banded dose","why":"A banded dose is already rounded, so comparing against it can hide or exaggerate a real change.","source":"bopa-2025","quote":"Warning: it is NOT appropriate to use the previous banded dose to work out a percentage dose change threshold as this risks under or overestimating the actual carboplatin dose when banding."}],"bestInClass":{"statement":"Dose = target AUC x (GFR + 25), with GFR measured directly (not BSA-indexed) where available and always for curative treatment, extremes of body size or muscle mass, or an eGFR above 125 or at or below 45 ml/min/1.73 m2 (ADDIKD 2025, clinical consensus, strong). Where measured GFR is not feasible, ADDIKD and KDIGO 2024 favour CKD-EPI eGFR de-indexed to the patient's BSA over Cockcroft-Gault, supported by the 2,471-patient Cambridge cohort (Janowitz 2017) and the UK gynaecological cohorts of Samani 2022. Do not lower the AUC for kidney function; recalculate when kidney function changes by more than 20%. Guidance disagrees on the estimate: the US label and much software still use creatinine clearance, and the Gynecologic Oncology Group recommended Cockcroft-Gault with adjusted body weight above a BMI of 25.","sources":["addikd-part1-2025","addikd-integration-2025","kdigo-2024","janowitz-2017","samani-2022","calvert-1989"]},"variants":[{"name":"Cockcroft-Gault creatinine clearance in the formula","differs":"Estimates GFR as creatinine clearance by Cockcroft-Gault, sometimes with ideal or adjusted body weight, and puts that into the formula. The US label's renal dose table for single-agent carboplatin is set in creatinine clearance bands.","evidence":"Cockcroft-Gault was built on 249 hospitalised men with a creatinine assay that predates IDMS standardisation, and overestimates GFR by 10 to 20% (ADDIKD). In 2,471 UK patients it gave a dose more than 20% off in 25.5% against 18.6% for BSA-adjusted CKD-EPI (Janowitz 2017). In two UK centres, unadjusted Cockcroft-Gault and Wright performed worst and adjusted-body-weight Cockcroft-Gault among the best (Samani 2022).","sources":["addikd-part1-2025","janowitz-2017","samani-2022","carboplatin-label"]},{"name":"Adjusted body weight in Cockcroft-Gault above a BMI of 25 (Gynecologic Oncology Group)","differs":"Uses adjusted rather than actual body weight in Cockcroft-Gault for patients with a BMI of 25 or more, to avoid overestimating clearance in larger people.","evidence":"Recommended by the GOG after the switch to IDMS creatinine assays, as cited by Samani 2022, where CG with adjusted body weight was among the most accurate estimators against nuclear medicine GFR in two UK cohorts. The GOG document itself was not read.","sources":["samani-2022"]},{"name":"AUC 6 with an estimate, converted to AUC 5 with measured GFR","differs":"Some UK centres and trials dose at AUC 6 when GFR is estimated and AUC 5 when it is measured, on the reasoning that estimates run low.","evidence":"Samani 2022 found this practice in its survey and that dosing on AUC 6 with an estimate carried a risk of overdosing compared with measured GFR at AUC 5; it advises centres to avoid it.","sources":["samani-2022"]},{"name":"A cancer-specific GFR model (CamGFR)","differs":"Estimates GFR with a model developed in people with cancer at Cambridge University Hospitals rather than CKD-EPI.","evidence":"In 2,471 patients it reduced doses more than 20% off to 14.2% (Janowitz 2017), and version 2 was the most accurate estimator in the UK gynaecological cohorts (Samani 2022). Not adopted by ADDIKD or KDIGO.","sources":["janowitz-2017","samani-2022"]}],"grades":[{"claim":"eGFR by CKD-EPI to assess kidney function, except where measured GFR is clinically necessary","grade":"Evidence quality/certainty: clinical consensus; strength of recommendation: strong","source":"addikd-part1-2025","quote":"We recommend the use of estimated glomerular filtration rate calculated via the Chronic Kidney Disease—Epidemiology Collaboration (eGFR CKD-EPI ) equation to guide the assessment of kidney function, except where directly measured glomerular filtration rate (GFR) is clinically necessary."},{"claim":"eGFR CKD-EPI to guide dosing of kidney-dependent anticancer drugs, with measured GFR preferred for carboplatin, cisplatin and others in specific situations","grade":"Evidence quality/certainty: clinical consensus; strength of recommendation: strong","source":"addikd-part1-2025","quote":"We recommend eGFR CKD-EPI to guide the dosing of anticancer drugs whose dose is dependent on kidney function, except in specific clinical situations or for a select group of anticancer drugs where eGFR CKD-EPI may be unsuitable."},{"claim":"Non-BSA-indexed eGFR at extremes of body weight, for narrow-therapeutic-range drugs","grade":"Practice Point 4.2.4","source":"kdigo-2024","quote":"In people with extremes of body weight, eGFR nonindexed for body surface area (BSA) may be indicated, especially for medications with a narrow therapeutic range or requiring a minimum concentration to be effective."}],"sources":[{"key":"addikd-part1-2025","label":"Aligning kidney function assessment in patients with cancer to global practices in internal medicine (ADDIKD, Part 1)","publisher":"eClinicalMedicine (Sandhu et al., ADDIKD Working Group, eviQ / Cancer Institute NSW)","year":2025,"url":"https://doi.org/10.1016/j.eclinm.2025.103102","doi":"10.1016/j.eclinm.2025.103102","gradingScheme":"GRADE-informed consensus: evidence quality or certainty (here 'clinical consensus') and strength of recommendation, strong or conditional.","read":"full-text","accessed":"2026-11-11"},{"key":"addikd-integration-2025","label":"Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practice","publisher":"eClinicalMedicine (Sandhu et al.)","year":2025,"url":"https://doi.org/10.1016/j.eclinm.2025.103161","doi":"10.1016/j.eclinm.2025.103161","read":"full-text","accessed":"2026-11-11"},{"key":"kdigo-2024","label":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","publisher":"KDIGO (Kidney International)","year":2024,"url":"https://doi.org/10.1016/j.kint.2023.10.018","doi":"10.1016/j.kint.2023.10.018","gradingScheme":"Recommendations graded 1 (we recommend) or 2 (we suggest) with evidence quality A to D; practice points are ungraded expert judgement.","read":"full-text","accessed":"2026-11-11"},{"key":"carboplatin-label","label":"Carboplatin injection, US prescribing information (Accord Healthcare)","publisher":"US National Library of Medicine, DailyMed","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=48aa7ef3-9f44-2a08-e054-00144ff88e88","read":"full-text","accessed":"2026-11-11"},{"key":"calvert-1989","label":"Carboplatin dosage: prospective evaluation of a simple formula based on renal function","publisher":"Journal of Clinical Oncology (Calvert et al.)","year":1989,"url":"https://doi.org/10.1200/JCO.1989.7.11.1748","doi":"10.1200/JCO.1989.7.11.1748","read":"abstract","accessed":"2026-11-11"},{"key":"janowitz-2017","label":"New Model for Estimating Glomerular Filtration Rate in Patients With Cancer","publisher":"Journal of Clinical Oncology (Janowitz et al.)","year":2017,"url":"https://doi.org/10.1200/JCO.2017.72.7578","doi":"10.1200/JCO.2017.72.7578","read":"abstract","accessed":"2026-11-11"},{"key":"samani-2022","label":"Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers","publisher":"ESMO Open (Samani et al.)","year":2022,"url":"https://doi.org/10.1016/j.esmoop.2022.100401","doi":"10.1016/j.esmoop.2022.100401","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-carboplatin-gfr-estimate-outcome-study"],"gaps":["No ESMO, ASCO or NICE guideline on carboplatin dose calculation exists to compare with ADDIKD; ADDIKD is a consensus (its carboplatin recommendations rest on clinical consensus), and its uptake outside Australia is not yet known.","Many trial protocols cap the GFR entered into the formula; the NCI CTEP letter that is the usual source could not be read, so no cap figure is given here. ADDIKD handles high estimates differently, asking for measured GFR when eGFR is above 125 ml/min/1.73 m2.","The Gynecologic Oncology Group's adjusted-body-weight guidance is cited only through Samani 2022; the original was not read.","The Calvert and Janowitz papers were read as abstracts only.","Which estimate to use in obesity, cachexia and after amputation is not settled by trials; ADDIKD asks for measured GFR in these people, which many centres cannot provide quickly."]},{"id":"care-in-the-last-days-of-life","kind":"protocol","name":"Care in the last days of life: recognising dying, hydration, symptom control and anticipatory medicines","aka":["end of life care","last days of life","care of the dying","just in case medicines","anticipatory prescribing","anticipatory medicines","death rattle","noisy respiratory secretions","terminal agitation","terminal delirium","dying phase"],"tldr":"When someone may be in their last days, the team should say so honestly, plan care with them and their family, stop medicines that no longer help, keep their mouth moist and offer drinks if they want them, and prescribe 'just in case' medicines for pain, breathlessness, sickness, agitation and noisy breathing so that help is at hand without delay, including at home.","summary":"NICE NG31 (2015) sets out the process: gather and document the person's needs, signs and wishes when dying is suspected; look for the signs that suggest it (agitation, Cheyne-Stokes breathing, falling consciousness, mottled skin, noisy secretions) while staying alert to recovery; reassess at least every 24 hours; discuss the prognosis honestly unless the person does not want to know; name a lead professional; and make an individualised care plan. Hydration is supported by mouth, with frequent mouth care; clinically assisted hydration is an individual decision, with a therapeutic trial considered for distressing signs of dehydration, monitored at least every 12 hours. MASCC (2024) adds that anyone with a prognosis of a week or more and insufficient intake should be considered for assisted hydration, and that a blanket policy either way is not justifiable. NICE gives no named doses; it advises the lowest effective dose, a syringe pump when more than 2 or 3 as-needed doses are given in 24 hours, no intramuscular injections, no routine oxygen, and specialist advice when symptoms do not settle. The drug classes it names are opioids or benzodiazepines for breathlessness, benzodiazepines for anxiety and agitation, antipsychotics for delirium, hyoscine butylbromide then octreotide for nausea from bowel obstruction, and atropine, glycopyrronium or hyoscine for distressing noisy secretions. Anticipatory medicines are prescribed early and individually, with indications and doses stated. The Korean guideline (2020) grades its parallel recommendations, for example opioids for dyspnoea B IIa and antipsychotics for delirium B IIb. One randomised trial (SILENCE, 2021) found that giving scopolamine butylbromide prophylactically once dying was recognised halved the rate of death rattle; no guideline read recommends prophylaxis.","asOf":"2026-11-11","links":[],"tags":[],"related":["strong-opioids-for-cancer-pain","palliative-sedation-for-refractory-suffering"],"cancers":[],"sections":[],"technologies":["syringe-drivers","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["last-days-of-life-care","palliative-sedation","advance-care-planning","respect-process"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"In the last days of life, care is about comfort. The team should talk with you honestly, ask what matters to you, stop medicines that no longer help and leave medicines in the home in case they are needed. Noisy breathing near the end is common and is not usually distressing for the person.","domain":"palliative","setting":{"who":["doctor","nurse","multidisciplinary-team","patient-or-carer"],"where":["ward","home","community"]},"population":"Adults (18 and over) who are dying during the last 2 to 3 days of life, as NICE NG31 scopes it, with cancer or any other condition (NICE NG31 and the Korean guideline are not cancer specific). Children and young people are outside this record. Palliative sedation for refractory symptoms is a separate record.","trigger":"The team thinks the person may be entering the last days of life.","steps":[{"action":"When dying is suspected, gather and record the person's needs, current signs and symptoms, history, goals and wishes, and the views of those important to them","why":"Recognising dying is uncertain, and a complete picture helps the team judge whether the person is dying, stable or improving.","source":"nice-ng31","quote":"If it is thought that a person may be entering the last days of life, gather and document information on:","grade":"Not graded (NICE 1.1.1)"},{"action":"Look for the changes that suggest the last days of life, and reassess at least every 24 hours, staying alert to signs of stabilising or recovery","why":"Signs such as agitation, changed breathing, drowsiness and mottled skin suggest dying, but some people improve, and the plan must change if they do.","source":"nice-ng31","quote":"Monitor for further changes in the person at least every 24 hours and update the person's care plan.","grade":"Not graded (NICE 1.1.6)"},{"action":"Avoid tests that are unlikely to change care in the last days","why":"Blood tests and scans cause discomfort and rarely change what is done for comfort; a blood count may still help where it guides a platelet transfusion to prevent catastrophic bleeding.","source":"nice-ng31","quote":"Avoid undertaking investigations that are unlikely to affect care in the last few days of life unless there is a clinical need to do so, for example, when a blood count could guide the use of platelet transfusion to avoid catastrophic bleeding.","grade":"Not graded (NICE 1.1.4)"},{"action":"Talk about the prognosis with the person as soon as dying is recognised, unless they do not want to know, and include those important to them if the person wishes","why":"People and families need time and honest information to say what matters and to make choices.","source":"nice-ng31","quote":"Discuss the dying person's prognosis with them (unless they do not wish to be informed) as soon as it is recognised that they may be entering the last days of life and include those important to them in the discussion if the dying person wishes.","grade":"Not graded (NICE 1.2.3)"},{"action":"Ask about any advance statement, advance decision to refuse treatment or lasting power of attorney, and build an individualised care plan including preferred place of care","why":"Plans made earlier, such as a ReSPECT form or an advance decision, should shape care when the person can no longer say.","source":"nice-ng31","quote":"In discussion with the dying person, those important to them and the multiprofessional team, create an individualised care plan. The plan should include the dying person's:","grade":"Not graded (NICE 1.3.5)"},{"action":"Name a lead professional and give the person and family contact details, including out of hours","why":"Families caring at home at night need to know whom to call.","source":"nice-ng31","quote":"Identify a named lead healthcare professional, who is responsible for encouraging shared decision‑making in the person's last days of life.","grade":"Not graded (NICE 1.3.3)"},{"action":"Help the person drink if they want to and can swallow safely, and offer frequent mouth and lip care; family can help if they wish","why":"A dry mouth is one of the commonest discomforts at the end of life, and mouth care relieves it whether or not fluids are given.","source":"nice-ng31","quote":"Offer frequent care of the mouth and lips to the dying person, and include the management of dry mouth in their care plan, if needed.","grade":"Not graded (NICE 1.4.2)"},{"action":"Decide on clinically assisted hydration individually; consider a trial if there are distressing signs of dehydration such as thirst or delirium, monitor at least every 12 hours, and stop if there are signs of harm","why":"Drip fluids may ease thirst or confusion but can cause swelling or fluid on the lungs, and it is not known whether giving or withholding them changes when death comes.","source":"nice-ng31","quote":"Consider a therapeutic trial of clinically assisted hydration if the person has distressing symptoms or signs that could be associated with dehydration, such as thirst or delirium, and oral hydration is inadequate.","grade":"Not graded (NICE 1.4.8)"},{"action":"Review all medicines and, with agreement, stop those that no longer relieve symptoms or may cause harm","why":"Tablets for long-term prevention no longer help and become hard to swallow.","source":"nice-ng31","quote":"When it is recognised that a person may be entering the last days of life, review their current medicines and, after discussion and agreement with the dying person and those important to them (as appropriate), stop any previously prescribed medicines that are not providing symptomatic benefit or that may cause harm.","grade":"Not graded (NICE 1.5.1)"},{"action":"Give medicines subcutaneously or intravenously rather than intramuscularly when swallowing fails, and consider a syringe pump if more than 2 or 3 as-needed doses are given in 24 hours","why":"Injections into muscle hurt; a pump under the skin gives steady relief without repeated injections.","source":"nice-ng31","quote":"Consider using a syringe pump to deliver medicines for continuous symptom control if more than 2 or 3 doses of any 'as required' medicines have been given within 24 hours.","grade":"Not graded (NICE 1.5.6)"},{"action":"For breathlessness, treat reversible causes, use non-drug measures such as a fan, consider an opioid, a benzodiazepine or both, and give oxygen only where low oxygen is known or suspected","why":"Oxygen does not ease breathlessness unless oxygen levels are low, and the mask can add discomfort; opioids reduce the feeling of breathlessness.","source":"nice-ng31","quote":"Do not routinely start oxygen to manage breathlessness. Only offer oxygen therapy to people known or clinically suspected to have symptomatic hypoxaemia.","grade":"Not graded (NICE 1.5.16)"},{"action":"For agitation or delirium, look first for a cause such as pain or a full bladder or bowel, treat what can be reversed, then consider a benzodiazepine for anxiety or agitation or an antipsychotic for delirium","why":"Restlessness near death is sometimes discomfort that can be fixed, such as a full bladder, rather than something that needs sedation.","source":"nice-ng31","quote":"Be aware that agitation in isolation is sometimes associated with other unrelieved symptoms or bodily needs for example, unrelieved pain or a full bladder or rectum.","grade":"Not graded (NICE 1.5.23)"},{"action":"For noisy breathing, reassure the family that it is unlikely to cause the person discomfort, reposition, and if it distresses the person consider atropine, glycopyrronium or hyoscine, reviewing at least every 12 hours","why":"The rattle comes from secretions the person can no longer clear; it is often harder for those listening than for the person, and the medicines dry secretions but can cause a dry mouth or confusion.","source":"nice-ng31","quote":"Reassure them that, although the noise can be distressing, it is unlikely to cause discomfort.","grade":"Not graded (NICE 1.5.29)"},{"action":"Prescribe anticipatory medicines early, individually, with the indication and dose stated, for the symptoms likely to occur (pain, breathlessness, nausea, agitation, noisy secretions), taking account of place of care and how long it takes to get medicines","why":"Symptoms often come at night or at weekends; having the medicines and the authority to give them already in place avoids hours of distress.","source":"nice-ng31","quote":"Ensure that suitable anticipatory medicines and routes are prescribed as early as possible. Review these medicines as the dying person's needs change.","grade":"Not graded (NICE 1.6.3)"},{"action":"Seek specialist palliative care advice if symptoms do not improve promptly or treatment causes unwanted sedation","why":"Specialist teams have more options and experience with hard-to-control symptoms.","source":"nice-ng31","quote":"Seek specialist palliative care advice if the dying person's symptoms do not improve promptly with treatment or if there are undesirable side effects, such as unwanted sedation.","grade":"Not graded (NICE 1.5.9)"}],"bestInClass":{"statement":"NICE NG31 (2015) is the most complete readable standard: recognise and document, reassess every 24 hours, honest communication, a named lead and an individual care plan, oral fluids and mouth care with assisted hydration decided individually, no routine oxygen, subcutaneous or intravenous rather than intramuscular routes, a syringe pump when as-needed doses mount up, and anticipatory medicines prescribed early with indications and doses. NICE does not grade its recommendations or name doses. The Korean guideline (2020) agrees on the same points and grades them: opioids for dyspnoea (B IIa), oxygen only for hypoxia (C IIa), drugs for secretions (C IIb), antipsychotics for delirium (B IIb), minimising restraints and lines in delirium (B I). On hydration, MASCC (2024) leans further towards offering it than NICE where prognosis is a week or more, and both reject a blanket policy. On noisy breathing, guidelines treat once it is distressing; one randomised trial (SILENCE 2021) supports prophylaxis, which no guideline read has adopted.","sources":["nice-ng31","korea-2020","mascc-cah-2024","silence-2021"]},"variants":[{"name":"Prophylactic anticholinergic for death rattle","differs":"Gives subcutaneous scopolamine (hyoscine) butylbromide 20 mg four times a day from the moment dying is recognised, rather than waiting for noisy breathing to start.","evidence":"SILENCE (157 patients in 6 Dutch hospices, double blind): death rattle in 13% with scopolamine butylbromide against 27% with placebo (difference 14%, 95% CI 2% to 27%); restlessness 28% against 23%, dry mouth 10% against 15%. One trial; NICE (2015) and the Korean guideline (2020) predate or do not adopt prophylaxis.","sources":["silence-2021","nice-ng31"]},{"name":"Assisted hydration offered more readily","differs":"Considers clinically assisted hydration for everyone with insufficient intake and a prognosis of a week or more, and in shorter prognoses for thirst, opioid toxicity or family distress, usually by subcutaneous infusion (hypodermoclysis), including at home.","evidence":"MASCC expert opinion (2024), based on a literature review that found a lack of evidence for or against. The CHELsea II cluster randomised trial (1600 patients planned) is testing assisted hydration in the last days of life against usual care; no results were found.","sources":["mascc-cah-2024","chelsea-ii-2022"]},{"name":"Suction for secretions","differs":"Uses suction to clear secretions from the mouth or throat.","evidence":"The Korean guideline notes suction can be burdensome from catheter irritation and asks for benefits and harms to be weighed (D IIa); NICE asks for non-drug measures to be considered without naming suction.","sources":["korea-2020","nice-ng31"]}],"grades":[{"claim":"Weigh benefits and risks before giving intravenous fluids and nutrition in the dying process","grade":"B I","source":"korea-2020","quote":"We recommend that before providing intravenous (IV) fluids and nutrition to patients in the dying process, benefits and risks should be evaluated in terms of the patient’s degree of thirst, whether the patient is dehydrated, the possibility of oral feeding, the risk of aspiration, cardiovascular function, and comorbidities."},{"claim":"Opioids for dyspnoea, adding benzodiazepines if needed","grade":"B IIa","source":"korea-2020","quote":"Opioids can be considered to improve dyspnea in patients in the dying process. If their effect is insufficient, and especially if symptoms deteriorate due to anxiety, benzodiazepines can be added."},{"claim":"Oxygen not given routinely; considered for known or suspected hypoxia","grade":"C IIa","source":"korea-2020","quote":"Oxygen is not conventionally administered to patients in the dying process to improve dyspnea. If the cause of dyspnea is known to be hypoxia or if hypoxia is clinically suspected, oxygen can be considered."},{"claim":"Drugs to suppress respiratory secretions may be considered","grade":"C IIb","source":"korea-2020","quote":"Pharmacological treatments to suppress respiratory secretions can be considered for patients in the dying process."},{"claim":"Antipsychotics first line for delirium in the dying process","grade":"B IIb","source":"korea-2020","quote":"Antipsychotics may be considered as the first-line pharmacological treatment for delirium in patients in the dying process."},{"claim":"Minimise restraints, catheters and intravenous lines in delirium; non-drug measures recommended","grade":"B I","source":"korea-2020"},{"claim":"Consider assisted hydration where the person may die of dehydration before the cancer","grade":"Expert opinion statement 5","source":"mascc-cah-2024","quote":"Clinically assisted hydration should be considered in patients at risk of dying from dehydration before dying from their cancer"},{"claim":"Prophylactic scopolamine butylbromide reduced death rattle (13% against 27%)","grade":"One randomised, double-blind, placebo-controlled trial","source":"silence-2021"}],"sources":[{"key":"nice-ng31","label":"Care of dying adults in the last days of life (NG31), recommendations","publisher":"NICE","year":2015,"url":"https://www.nice.org.uk/guidance/ng31/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider', 'do not') signals strength. Several drug uses were off label in December 2015, as the guideline notes.","read":"full-text","accessed":"2026-11-11"},{"key":"korea-2020","label":"Clinical Practice Guideline for Care in the Last Days of Life","publisher":"Korean Journal of Hospice and Palliative Care (Korean Society for Hospice and Palliative Care and partners)","year":2020,"url":"https://doi.org/10.14475/kjhpc.2020.23.3.103","doi":"10.14475/kjhpc.2020.23.3.103","gradingScheme":"Each recommendation is printed with an evidence level (A to D) and a recommendation class (I, IIa, IIb), in that order.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-cah-2024","label":"MASCC expert opinion/guidance on the use of clinically assisted hydration in patients with advanced cancer","publisher":"Supportive Care in Cancer (MASCC Palliative Care Study Group)","year":2024,"url":"https://doi.org/10.1007/s00520-024-08421-6","doi":"10.1007/s00520-024-08421-6","gradingScheme":"Twelve expert opinion statements after a literature review; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"silence-2021","label":"Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of Life: the SILENCE Randomized Clinical Trial","publisher":"JAMA (van Esch et al.)","year":2021,"url":"https://doi.org/10.1001/jama.2021.14785","doi":"10.1001/jama.2021.14785","read":"abstract","accessed":"2026-11-11"},{"key":"chelsea-ii-2022","label":"Clinically assisted hydration in patients in the last days of life ('CHELsea II' trial): a cluster randomised trial (protocol)","publisher":"BMJ Open","year":2022,"url":"https://doi.org/10.1136/bmjopen-2022-068846","doi":"10.1136/bmjopen-2022-068846","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-prophylactic-antimuscarinic-when-dying-recognised"],"gaps":["NICE NG31 names drug classes but no doses; anticipatory medicine doses come from local formularies and were not read here. The common UK set (an opioid, midazolam, an antiemetic such as levomepromazine or haloperidol, and an antimuscarinic) is local practice and is not stated as such in NG31.","NICE NG31 dates from December 2015 and has not been updated; the Korean guideline is from 2020. No newer national guideline on the last days of life was read.","Whether assisted hydration helps or harms in the last days is unknown; the CHELsea II trial is testing it and no results were found.","Prophylaxis of death rattle rests on one trial (SILENCE), read as an abstract only.","Non-drug care (repositioning, fans, presence, spiritual care) is acknowledged by NICE as important but was outside the scope of NG31."]},{"id":"catheter-related-thrombosis-in-cancer","kind":"protocol","name":"Catheter-related thrombosis in people with cancer: diagnosis, anticoagulation and whether the line can stay","aka":["CRT","line clot","PICC clot","port thrombosis","upper extremity DVT from a line","central line thrombosis","catheter-associated thrombosis"],"tldr":"A blood clot can form around a central line, such as a port or a PICC. Signs include a swollen, painful or red arm, neck or face, swollen veins on the chest, or a line that will not flush or give blood. An ultrasound scan confirms it. It is treated with blood thinners for at least three months, and the line can often stay in if it still works and is not infected.","summary":"Symptomatic catheter-related thrombosis (CRT) is reported in about 4 to 8% of people with cancer and lines (ESMO 2015), and many more clots are found on screening. Signs are often non-specific; the first is often difficulty aspirating or infusing, with local pain, redness, swelling or oedema. Doppler ultrasound is the usual first test [III, A]; venography or other imaging follows when ultrasound is normal but suspicion remains or central occlusion is suspected [III, A].\n\nITAC (2022, guidance) recommends anticoagulation for at least 3 months and for as long as the catheter is in place, suggesting LMWH, and notes that LMWH, DOACs and VKAs have not been compared directly in CRT. The catheter can stay if it is functional, well positioned and not infected, with symptoms resolving under close surveillance. ESMO (2015) adds that where the line is no longer needed or long-term anticoagulation is contraindicated, 3 to 5 days of anticoagulation before removal is recommended [I, A], and that the line should come out if symptoms progress or the clot extends into the superior vena cava. Routine anticoagulant prophylaxis against CRT is not recommended (ITAC 1A); right-sided jugular insertion with the tip at the cavoatrial junction is (1B), and ITAC suggests ports over PICCs where a central line is needed (guidance).","asOf":"2026-11-11","links":[],"tags":[],"related":["cancer-associated-vte-treatment","implanted-port-access-and-care"],"cancers":[],"sections":[],"technologies":["implanted-ports","picc-lines","cancer-associated-thrombosis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["vte","central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If your arm, neck or face swells or aches, or your line stops working, tell your team the same day. A scan checks for a clot, which is treated with blood thinners, often without taking the line out.","domain":"vascular-access","setting":{"who":["doctor","nurse"],"where":["chemotherapy-day-unit","acute-oncology-service","ward","outpatient-clinic"]},"population":"Adults with cancer and a central venous catheter (implanted port, PICC, tunnelled or non-tunnelled central line). ITAC gives separate recommendations for children with central lines; they are not covered here. Line occlusion without a venous clot (a blocked lumen or fibrin sheath) is a separate problem.","trigger":"Arm, shoulder, neck or face swelling or pain on the side of a central line, distended chest wall veins, or a line that will not flush or aspirate.","steps":[{"action":"Suspect a clot when the line becomes hard to aspirate or flush, or the arm, neck or face on that side is painful, red or swollen","why":"Line clots often cause vague symptoms; a line that stops working can be the first sign.","source":"esmo-2015","quote":"Frequently in clinical practice, the first signs are: difficulty aspirating or infusing through the lumen of the catheter, and complaints of local pain or a burning sensation during injection."},{"action":"Confirm with Doppler ultrasound","why":"Ultrasound is quick, painless and finds most line clots.","source":"esmo-2015","quote":"Although venography is considered the gold standard for the diagnosis of CRT, Doppler ultrasound is usually carried out [III, A], because it is readily available and non-invasive (sensitivity 56%–100%; specificity 94%–100%)","grade":"[III, A]"},{"action":"If ultrasound is normal but suspicion remains, or a central vein blockage is suspected, arrange venography, CT or MR venography","why":"Ultrasound cannot see the veins inside the chest well.","source":"esmo-2015","quote":"In patients with suspected CRT and a normal ultrasound, or suspected central venous occlusion, venography or alternative imaging should be carried out [magnetic resonance imaging, computed tomography (CT), gadolinium-enhanced magnetic resonance venography or contrast-enhanced CT] [III, A]","grade":"[III, A]"},{"action":"Anticoagulate for at least 3 months and for as long as the catheter stays in, preferably with low-molecular-weight heparin","why":"Treatment stops the clot growing or travelling to the lungs while the line, which caused it, is still there.","source":"itac-2022","quote":"For the treatment of symptomatic catheter-related thrombosis in patients with cancer, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place; in this setting, LMWHs are suggested and direct comparisons between LMWHs, direct oral anticoagulants, and vitamin K antagonists have not been made (guidance).","grade":"guidance"},{"action":"Keep the line if it works, is in the right place and is not infected, and watch closely while anticoagulated","why":"Removing a working line is often unnecessary, and a new line carries its own risks.","source":"itac-2022","quote":"In patients with cancer and with catheter-related thrombosis, the central venous catheter can be kept in place if it is functional, well positioned, and not infected, with good resolution of symptoms under close surveillance while anticoagulation therapy is administered.","grade":"guidance"},{"action":"If the line is no longer needed, or long-term anticoagulation cannot be given, anticoagulate for 3 to 5 days before taking it out","why":"A short course first lowers the chance that pulling the line dislodges the clot.","source":"esmo-2015","quote":"When the CVC is no longer necessary, or if long-term anticoagulation is contraindicated, a short course (3–5 days) of anticoagulation therapy is recommended before removing the catheter, in order to avoid clot embolisation [I, A]","grade":"[I, A]"},{"action":"Remove the line if symptoms get worse or the clot extends into the superior vena cava","why":"A spreading clot despite treatment, or one in the main vein to the heart, outweighs the value of keeping the line.","source":"esmo-2015","quote":"Additionally, if symptoms progress or the blood clot extends into the SVC, the CVC should be removed."},{"action":"Do not give routine anticoagulant prophylaxis to prevent line clots","why":"In trials the bleeding risk outweighed the small reduction in clots for most people.","source":"itac-2022","quote":"Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended (grade 1A).","grade":"1A"}],"bestInClass":{"statement":"Confirm with Doppler ultrasound (ESMO 2015 [III, A]); anticoagulate for at least 3 months and while the line remains, LMWH suggested (ITAC 2022, guidance); keep a functional, well-positioned, uninfected line; anticoagulate 3 to 5 days before removing a line that is no longer needed (ESMO [I, A]); no routine prophylaxis (ITAC 1A). The two sources differ on what follows removal: ITAC sets 3 months as a minimum while the catheter is in place; ESMO says the length after removal is uncertain and 3 months is usually advised [I, C]. Neither has trial data comparing DOACs with LMWH for line clots.","sources":["itac-2022","esmo-2015"]},"variants":[{"name":"Prophylactic-dose anticoagulation while the line stays","differs":"After the treatment course, continues anticoagulation at a prophylactic dose until the catheter is removed.","evidence":"ESMO 2015 recommends continuing at a prophylactic dose while the catheter is in place [I, C]; ITAC 2022 recommends treatment for as long as the catheter is in place without specifying a step-down dose.","sources":["esmo-2015","itac-2022"]},{"name":"A DOAC instead of LMWH","differs":"Treats the line clot with apixaban, rivaroxaban or edoxaban.","evidence":"Not compared directly with LMWH in CRT (ITAC 2022). ESMO 2015 said there were no data for the newer oral anticoagulants in CRT at the time.","sources":["itac-2022","esmo-2015"]}],"grades":[{"claim":"Doppler ultrasound as the usual diagnostic test","grade":"[III, A]","source":"esmo-2015"},{"claim":"Short anticoagulation before removing a line that is no longer needed","grade":"[I, A]","source":"esmo-2015"},{"claim":"About 3 months of anticoagulation after removal","grade":"[I, C]","source":"esmo-2015","quote":"According to the severity of thrombosis, 3 months of therapy is usually advised, with some authors suggesting even shorter courses [I, C]"},{"claim":"Anticoagulation for at least 3 months and while the line is in place, LMWH suggested","grade":"guidance","source":"itac-2022"},{"claim":"No routine anticoagulant prophylaxis for CRT","grade":"1A","source":"itac-2022"},{"claim":"Right-sided jugular insertion with the tip at the cavoatrial junction","grade":"1B","source":"itac-2022","quote":"Catheters should be inserted on the right side, in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium (grade 1B)."},{"claim":"Implanted ports suggested over PICCs where a central line is needed","grade":"guidance","source":"itac-2022","quote":"In patients requiring central venous catheters, we suggest the use of implanted ports over peripherally inserted central catheter lines (guidance)."}],"sources":[{"key":"itac-2022","label":"2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19","publisher":"International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.)","year":2022,"url":"https://doi.org/10.1016/S1470-2045(22)00160-7","doi":"10.1016/S1470-2045(22)00160-7","gradingScheme":"GRADE: evidence A (high) to D (very low); recommendation grade 1 (strong) or 2 (weak); 'guidance' (best clinical practice) where there is no clear evidence, based on expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology, Sousa et al.)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I (large good-quality RCT or meta-analysis) to V (no control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No randomised trial compares anticoagulants or durations for catheter-related thrombosis in cancer; ITAC's treatment recommendations are 'guidance' (expert consensus), and ITAC found no new studies since 2019.","The ESMO guideline on central venous access dates from 2015; ESMO's 2023 VTE guideline could not be read.","Line occlusion from a fibrin sheath or blocked lumen, and its treatment with a thrombolytic lock, is not covered here."]},{"id":"community-care-of-vascular-access-devices","kind":"protocol","name":"Central line and port care in the community and at home","aka":["district nurse line care","community PICC care","PICC care at home","port flush in the community","line care after discharge","home line care"],"tldr":"If you go home with a PICC, tunnelled line or port, a community or district nurse may look after it, or you or a carer may be taught to. You should be shown what to do before you leave hospital, have someone to ask afterwards, and the nurse should clean their hands, use a clean no-touch technique, change the clear dressing weekly and clean the end of the line before and after use.","summary":"NICE CG139 (2012, updated 2017) is the UK guideline for infection prevention in primary and community care, and NICE QS61 (2014) statement 5 makes vascular access device care a quality standard: people with a device should have their infection risk minimised by completing specified procedures for insertion and maintenance, and by removal as soon as it is no longer needed, with a written protocol as the structure measure. Before discharge, patients and carers are taught any techniques they need to prevent infection and manage the device, with follow-up training and support available; community staff are trained and assessed as competent. The care itself is the hospital standard: hand decontamination before access or dressing; aseptic technique (ANTT named as one framework); a sterile transparent dressing over a central line changed every 7 days or sooner if lifting or damp; chlorhexidine in 70% alcohol on the hub before and after access (QS61 adds a 15-second clean, from epic3); saline to flush and lock; and daily inspection of central line sites. Many of these recommendations date from 2003 and none is graded.","asOf":"2026-11-11","links":[],"tags":[],"related":["picc-and-tunnelled-line-care","implanted-port-access-and-care","blood-sampling-from-a-central-line","central-line-occlusion-management","central-line-maintenance-bundle"],"cancers":[],"sections":[],"technologies":["picc-lines","implanted-ports","catheter-securement-devices"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before you go home with a line, you should be taught how to look after it and who to call. The nurse who looks after it at home should clean their hands and the line end every time.","domain":"vascular-access","setting":{"who":["nurse","patient-or-carer"],"where":["community","home"]},"population":"Adults with cancer living at home with a PICC, tunnelled central catheter or implanted port, cared for by community or district nurses, practice nurses or themselves and their carers. NICE CG139 covers primary and community care in England.","trigger":"A person is discharged, or starts treatment as an outpatient, with a central venous access device that will be cared for outside hospital.","steps":[{"action":"Before discharge, teach the person and their carer any techniques they will need to prevent infection and manage the device safely","why":"Most of the time with a line is spent at home, and problems start there.","source":"nice-cg139","quote":"Before discharge from hospital, patients and their carers should be taught any techniques they may need to use to prevent infection and safely manage a vascular access device.","grade":"[2003, amended 2012]"},{"action":"Make sure follow-up training and support are available to the person and carer after discharge","why":"Skills fade and questions arise once people are home.","source":"nice-cg139","quote":"Follow-up training and support should be available to patients with a vascular access device and their carers.","grade":"[2003, amended 2012]"},{"action":"Have community staff who care for lines trained and assessed as competent in the infection-prevention practices","why":"Community nurses may care for central lines only occasionally, so training and checks keep standards consistent.","source":"nice-cg139","quote":"Healthcare workers caring for a patient with a vascular access device should be trained, and assessed as competent, in using and consistently adhering to the infection prevention practices described in this guideline.","grade":"[2003, amended 2012]"},{"action":"Clean your hands before accessing or dressing the line","why":"Hands are the commonest route by which germs reach a line.","source":"nice-cg139","quote":"Hands must be decontaminated (see section 1.1.2 on hand decontamination ) before accessing or dressing a vascular access device.","grade":"[new 2012]"},{"action":"Use an aseptic technique, such as ANTT, for site care and whenever the line is accessed","why":"Keeping key parts untouched stops germs entering the line in a home setting without hospital facilities.","source":"nice-cg139","quote":"An aseptic technique must be used for vascular access device catheter site care and when accessing the system","grade":"[new 2012]"},{"action":"Change the transparent dressing over a central line every 7 days, or sooner if it lifts or moisture collects under it","why":"A sealed dressing keeps germs out; a loose or damp one lets them in.","source":"nice-cg139","quote":"Change the transparent semipermeable membrane dressing covering a central venous access device insertion site every 7 days, or sooner if the dressing is no longer intact or moisture collects under it.","grade":"[2012]"},{"action":"Clean the hub or injection port with chlorhexidine in 70% alcohol before and after each access","why":"The hub is touched every time the line is used and is a main route for infection.","source":"nice-cg139","quote":"Decontaminate the injection port or vascular access device catheter hub before and after accessing the system using chlorhexidine gluconate in 70% alcohol.","grade":"[new 2012]"},{"action":"Flush and lock the lumens with sterile 0.9% saline unless the device maker requires otherwise","why":"Flushing keeps the line open; saline avoids the risks of heparin for most devices.","source":"nice-cg139","quote":"Preferably, a sterile 0.9 percent sodium chloride injection should be used to flush and lock catheter lumens.","grade":"[2003]"},{"action":"Inspect a central line site daily, and have it removed as soon as it is no longer needed","why":"Daily checks catch infection early; a line that is not needed only adds risk.","source":"nice-qs61","quote":"Central venous catheter insertion sites should be inspected daily."},{"action":"Work to a written local protocol covering insertion, maintenance and removal, and audit against it","why":"QS61 measures quality by whether every specified step is done for every person with a device.","source":"nice-qs61","quote":"People who need a vascular access device have their risk of infection minimised by the completion of specified procedures necessary for the safe insertion and maintenance of the device and its removal as soon as it is no longer needed."}],"bestInClass":{"statement":"In the UK, NICE CG139 and QS61 statement 5 set the standard for line care outside hospital: patient and carer teaching before discharge with follow-up support, trained and assessed staff, hand decontamination, aseptic technique, a transparent dressing changed every 7 days on central lines, hub decontamination with chlorhexidine in alcohol before and after access, saline flush and lock, daily site inspection and removal when no longer needed, all under a written protocol. The clinical steps match the hospital guidelines (CDC, epic3, ESMO) set out in the port and PICC care protocols; the community-specific additions are the teaching, support and competence recommendations, which date from 2003 and are ungraded.","sources":["nice-cg139","nice-qs61"]},"variants":[],"grades":[],"sources":[{"key":"nice-cg139","label":"Healthcare-associated infections: prevention and control in primary and community care (CG139), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg139/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended ([2003], [2012], [new 2012]).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-qs61","label":"Infection prevention and control (QS61), quality statement 5: vascular access devices","publisher":"NICE","year":2014,"url":"https://www.nice.org.uk/guidance/qs61/chapter/Quality-statement-5-Vascular-access-devices","gradingScheme":"Quality statements are not graded; each comes with structure, process and outcome measures.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["NICE CG139 was last updated in 2017 and several of its line-care recommendations date from 2003; no newer UK community guideline on central line care was found.","No source read sets how often a community nurse should see a person with a line, who keeps the care record across hospital and community, or how out-of-hours problems are handled; these are local arrangements.","Whether patients and carers can safely flush or dress their own lines, and with what training, is not addressed beyond NICE's teaching recommendation.","The RCN infusion standards and Queen's Nursing Institute community standards could not be found in a readable current edition."]},{"id":"central-line-removal","kind":"protocol","name":"Central line and port removal: when, how and what to watch for afterwards","aka":["PICC removal","port removal","Hickman line removal","CVAD removal","taking out a central line","line removal air embolism","port explant"],"tldr":"A central line or port is taken out when treatment is finished or if it causes a problem such as an infection or clot. The usual precautions, lying flat as it comes out, a sealed dressing afterwards and being watched for a while, aim to prevent a rare but serious problem: air getting into the vein.","summary":"Lines come out when no longer essential (CDC Category IA) or for complications. ESMO (2015) lists the infective indications: severe sepsis, septic thrombophlebitis, endocarditis, tunnel infection, port abscess, bloodstream infection persisting beyond 48 to 72 hours of adequate treatment, or infection with Staphylococcus aureus, fungi or mycobacteria [II, A]. For catheter-related thrombosis, where the line is no longer needed or anticoagulation cannot continue long term, ESMO recommends 3 to 5 days of anticoagulation before removal to avoid clot embolisation [I, A]; the separate catheter-related thrombosis protocol sets out where ITAC and ASCO differ. Catheter tips are cultured only when the line is removed for suspected infection, not routinely (IDSA A-II); for a port, the reservoir contents are cultured too.\n\nThe removal technique itself (lying flat or head down, breath-holding or Valsalva as the catheter leaves, firm pressure and an occlusive dressing over the tract, and a period of observation) comes from nursing standards that could not be read. The reason is air embolism: a 2026 systematic review of 28 case reports of delayed air embolism after removal found symptoms began 10 minutes to over 2 hours afterwards, a persisting skin-to-vein channel in over 90% of those imaged, permanent neurological harm in 18% and death in 32%. ESMO's management of air embolism is to lay the patient head down on their side and give 100% oxygen.","asOf":"2026-11-11","links":[],"tags":[],"related":["suspected-central-line-infection","catheter-related-thrombosis-in-cancer","central-venous-catheter-insertion-for-anticancer-therapy"],"cancers":[],"sections":[],"technologies":["picc-lines","implanted-ports"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"When you no longer need your line, it is taken out. Afterwards, keep the dressing on and tell someone at once if you feel breathless, dizzy or unwell.","domain":"vascular-access","setting":{"who":["nurse","doctor","surgical-team"],"where":["chemotherapy-day-unit","ward","outpatient-clinic","theatre"]},"population":"Adults with cancer who have a PICC, tunnelled cuffed central catheter or implanted port that is no longer needed or must come out because of a complication. Non-tunnelled lines in intensive care and dialysis catheters are covered by their own protocols.","trigger":"Treatment through the line has ended, or infection, thrombosis, malfunction or malposition makes removal necessary.","steps":[{"action":"Review at every contact whether the line is still needed, and arrange removal as soon as it is not","why":"A line that stays in after it is needed adds risk of infection and clots with no benefit.","source":"cdc-hicpac-2011","quote":"Promptly remove any intravascular catheter that is no longer essential [69–72].","grade":"Category IA"},{"action":"Remove the line for severe infection: sepsis, septic thrombophlebitis, endocarditis, tunnel infection, port abscess, persistent bacteraemia, or Staphylococcus aureus, fungal or mycobacterial infection","why":"These infections rarely clear while the line remains, because germs live on it.","source":"esmo-2015","quote":"Indications to remove the CVC are: severe sepsis, suppurative (septic) thrombophlebitis, endocarditis, tunnel infection, port abscess, BSI which continues despite 48–72 h of adequate coverage or infections with S. aureus , fungi or mycobacteria [II, A]","grade":"[II, A]"},{"action":"If the line has a clot around it and is coming out, give a few days of anticoagulation first, as the treating team directs","why":"Pulling the line through a fresh clot can break pieces off into the lungs.","source":"esmo-2015","quote":"When the CVC is no longer necessary, or if long-term anticoagulation is contraindicated, a short course (3–5 days) of anticoagulation therapy is recommended before removing the catheter, in order to avoid clot embolisation [I, A]","grade":"[I, A]"},{"action":"Send the catheter tip for culture only if the line is removed for suspected infection","why":"Routine tip cultures are often contaminated and lead to unnecessary treatment.","source":"idsa-2009","quote":"Catheter cultures should be performed when a catheter is removed for suspected catheter-related bloodstream infection (CRBSI); catheter cultures should not be obtained routinely (A-II).","grade":"A-II"},{"action":"When a port is removed for suspected infection, send the reservoir contents as well as the catheter tip","why":"The reservoir culture is more sensitive than the tip.","source":"esmo-2015","quote":"For subcutaneous ports, a culture of the material inside the port reservoir should be included, as it is more sensitive than the catheter tip culture."},{"action":"Remove the catheter with the person lying flat, ask them to hold their breath or bear down as it comes out, press firmly on the site and seal it with an occlusive dressing","why":"As the catheter leaves, air can be sucked into the vein through the track; lying flat, breath-holding and a seal stop this.","practice":"No guideline that could be read describes the removal technique; the INS Standards do but were not reachable. The 2026 systematic review found a persisting skin-to-vein channel in over 90% of imaged cases of delayed air embolism, which is what the seal and pressure aim to close."},{"action":"Watch the person after removal and tell them to report breathlessness, chest pain, dizziness, confusion or weakness at once, even hours later","why":"Air embolism after removal can appear late, and most people had brain symptoms.","source":"pacini-2026","quote":"Symptoms developed between ten minutes and one hour after removal of CVC in 54% of cases, between one and two hours in 14%, and after more than two hours in 32%."},{"action":"If air embolism is suspected, lay the person on their left side, head down, give 100% oxygen and call for emergency help","why":"This position and oxygen help while the air is absorbed and emergency treatment is arranged.","source":"esmo-2015","quote":"Air embolism: immediately place the patient in the lateral decubitus head down position and deliver 100% oxygen [ 29 ]."}],"bestInClass":{"statement":"Remove lines promptly when no longer essential (CDC IA) and for the infective indications ESMO lists [II, A]; anticoagulate for 3 to 5 days before removing a thrombosed line where removal is planned (ESMO [I, A], with ITAC and ASCO differing on whether removal is needed at all, see the catheter-related thrombosis protocol); culture tips only for suspected infection (IDSA A-II) and port reservoirs when ports are explanted for infection. The removal technique and the observation period rest on nursing standards that could not be read; the 2026 systematic review of delayed air embolism supports vigilance for at least two hours and sealing the tract.","sources":["cdc-hicpac-2011","esmo-2015","idsa-2009","pacini-2026"]},"variants":[],"grades":[{"claim":"Culture the catheter tip, not the subcutaneous segment, for CVCs","grade":"B-III","source":"idsa-2009","quote":"For CVCs, culture the catheter tip, not the subcutaneous segment (B-III)."}],"sources":[{"key":"cdc-hicpac-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I to V; grades A to E, adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"},{"key":"idsa-2009","label":"Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America","publisher":"IDSA (Clinical Infectious Diseases, Mermel et al.)","year":2009,"url":"https://doi.org/10.1086/599376","doi":"10.1086/599376","gradingScheme":"Strength A (good evidence) to C (poor evidence); quality I (at least one randomised trial), II (non-randomised trials, cohort or case-control studies) or III (expert opinion).","read":"full-text","accessed":"2026-11-11"},{"key":"pacini-2026","label":"Delayed presentation of air embolism after removal of central venous catheters: A systematic review","publisher":"Journal of Critical Care (Pacini et al.)","year":2026,"url":"https://doi.org/10.1016/j.jcrc.2026.155606","doi":"10.1016/j.jcrc.2026.155606","read":"abstract","accessed":"2026-11-11"},{"key":"ins-2024","label":"Infusion Therapy Standards of Practice, 9th Edition","publisher":"Infusion Nurses Society (Journal of Infusion Nursing)","year":2024,"url":"https://doi.org/10.1097/NAN.0000000000000532","doi":"10.1097/NAN.0000000000000532","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No guideline that could be read describes how to remove a PICC, tunnelled line or port (position, breath-holding, dressing, observation time); the INS Standards (2024), which do, were not reachable. The removal step here is common practice, marked as such.","How long to observe someone after removal is not set by any source read; the 2026 review of 28 case reports found a third of delayed air emboli began more than two hours after removal.","Surgical removal of ports and cuffed tunnelled catheters (dissection, cuff release) is not covered.","Whether a thrombosed line needs to come out at all is disputed between ESMO 2015 and later guidance; see the catheter-related thrombosis protocol."]},{"id":"central-line-insertion-bundle","kind":"protocol","name":"Central line insertion bundle: preventing bloodstream infection at the time of placement","aka":["CLABSI insertion bundle","central line insertion checklist","CVC insertion bundle","maximal sterile barrier precautions","line insertion asepsis"],"tldr":"When a central line is put in, the team follows a checklist: clean hands, a cap, mask, sterile gown and gloves for the person inserting it, a sterile drape over the whole body, and chlorhexidine in alcohol on the skin, left to dry. Someone watches and can stop the procedure if a step is missed. For long treatments such as chemotherapy, a tunnelled line or a port is usually the right kind of line.","summary":"The insertion bundle in SHEA/IDSA/APIC 2022 is a set of essential practices: an evidence-based list of indications (low quality), education and competency of inserters (moderate), a process such as a checklist with an empowered observer (moderate), hand hygiene (moderate), an all-inclusive cart or kit (moderate), ultrasound guidance (high), maximum sterile barrier precautions with cap, mask, sterile gown, sterile gloves and a full-body drape (moderate; CDC IB; epic3 Class C), and alcoholic chlorhexidine skin preparation of at least 2% allowed to dry (high; epic3 Class A; CDC IA at more than 0.5%). Site choice: subclavian preferred for non-tunnelled lines in the ICU (high) and avoid the femoral vein in adults (CDC IA); in children the femoral site may be considered when upper sites are contraindicated. Use the fewest lumens needed (CDC IB, epic3 Class A); for long-term access use a tunnelled line or implanted port (epic3 Class A); PICCs are not a strategy to lower infection risk (SHEA). No systemic antibiotic prophylaxis at insertion (SHEA high, CDC IB, epic3 Class A). Replace a line placed in an emergency without assured asepsis within 48 hours (CDC IB). Antiseptic- or antimicrobial-impregnated catheters are an additional approach where rates stay high.","asOf":"2026-11-11","links":[],"tags":["protocol","clabsi","vascular-access"],"related":["central-line-maintenance-bundle","implanted-port-access-and-care","central-venous-catheter-insertion-for-anticancer-therapy"],"cancers":[],"sections":["supportive-care"],"technologies":["implanted-ports","picc-lines"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Putting in a central line opens a path for germs into a big vein. The team cleans their hands, wears sterile clothes, covers you with a sterile sheet and cleans your skin well. A checklist makes sure nothing is missed.","domain":"infection-prevention","setting":{"who":["doctor","nurse","anaesthetist","surgical-team"],"where":["ward","theatre","intensive-care","outpatient-clinic"]},"population":"Adults and children having a central venous catheter placed (non-tunnelled CVCs, tunnelled lines, PICCs and implanted ports), as SHEA, CDC and epic3 scope it. SHEA's site preference is for ICU placement; chlorhexidine skin preparation in infants under 2 months and in neonatal intensive care is weighed case by case.","trigger":"A decision has been made that the person needs a central venous catheter.","steps":[{"action":"Check the line is needed against an agreed list of indications before placing it","why":"The surest way to prevent a line infection is not to place a line that is not needed.","source":"shea-2022","quote":"Provide easy access to an evidence-based list of indications for CVC use to minimize unnecessary CVC placement (Quality of Evidence: LOW)","grade":"Quality of Evidence: LOW"},{"action":"Choose the device for the length of treatment: a tunnelled line or implanted port for long-term access, with the fewest lumens needed","why":"Cancer treatment often lasts months; devices built for long use, with fewer openings, carry less infection risk over that time.","source":"epic3","quote":"Use a tunnelled or implanted central venous access device with a subcutaneous port for patients in whom long-term vascular access is required.","grade":"Class A"},{"action":"Only let trained staff assessed as competent put in central lines","why":"Infection and mechanical complications fall with experience and a consistent technique.","source":"cdc-2011","quote":"Designate only trained personnel who demonstrate competence for the insertion and maintenance of peripheral and central intravascular catheters.","grade":"Category IA"},{"action":"Use a checklist, completed by an observer other than the inserter, who can stop the procedure if asepsis is broken","why":"A second person catches missed steps that the busy inserter will not.","source":"shea-2022","quote":"HCP should be empowered to stop the procedure if breaches in aseptic technique are observed.","grade":"Quality of Evidence: MODERATE"},{"action":"Have an all-inclusive cart or kit with everything needed for aseptic insertion","why":"Leaving the sterile field to fetch an item is a common way asepsis is broken.","source":"shea-2022","quote":"A catheter cart or kit that contains all necessary components for aseptic catheter insertion should be available and easily accessible in all units where CVCs are inserted.","grade":"Quality of Evidence: MODERATE"},{"action":"Clean hands with alcohol rub or soap and water before insertion; gloves do not replace this","why":"Hands carry the skin germs that cause most early line infections.","source":"shea-2022","quote":"Perform hand hygiene prior to catheter insertion or manipulation (Quality of Evidence: MODERATE)","grade":"Quality of Evidence: MODERATE"},{"action":"Choose the site weighing infection against mechanical risk: in adults avoid the femoral vein, and for non-tunnelled ICU lines prefer the subclavian","why":"Groin lines carry more infection in adults; the subclavian has the lowest infection risk but more risk of lung puncture and is avoided in people who may need dialysis.","source":"cdc-2011","quote":"Avoid using the femoral vein for central venous access in adult patients","grade":"Category IA"},{"action":"Use ultrasound to guide the needle, if the operator is trained in it","why":"Ultrasound cuts the number of attempts and mechanical complications.","source":"shea-2022","quote":"Use ultrasound guidance for catheter insertion (Quality of Evidence: HIGH)","grade":"Quality of Evidence: HIGH"},{"action":"Use maximum sterile barrier precautions: everyone involved wears a cap, mask, sterile gown and sterile gloves, and the patient is covered with a full-body sterile drape","why":"A large sterile field stops the guidewire and catheter touching anything unclean.","source":"shea-2022","quote":"A mask, cap, sterile gown, and sterile gloves are to be worn by all HCP involved in the catheter insertion procedure.","grade":"Quality of Evidence: MODERATE"},{"action":"Apply the same precautions for a PICC and for a guidewire exchange","why":"A PICC is a central line and carries a similar infection risk in hospital patients.","source":"cdc-2011","quote":"Use maximal sterile barrier precautions, including the use of a cap, mask, sterile gown, sterile gloves, and a sterile full body drape, for the insertion of CVCs, PICCs, or guidewire exchange","grade":"Category IB"},{"action":"Prepare the skin with an alcoholic chlorhexidine solution of at least 2% and let it dry completely before the puncture","why":"Chlorhexidine in alcohol is the most effective skin antiseptic for line insertion, and it works only once it has dried.","source":"shea-2022","quote":"Before catheter insertion, apply an alcoholic chlorhexidine solution containing at least 2% chlorhexidine gluconate to the insertion site.","grade":"Quality of Evidence: HIGH"},{"action":"Do not give antibiotics to prevent infection at insertion","why":"Preventive antibiotics at insertion do not lower line infections and they breed resistance.","source":"epic3","quote":"Do not routinely administer intranasal or systemic antimicrobials before insertion or during the use of an intravascular device to prevent catheter colonisation or bloodstream infection.","grade":"Class A"},{"action":"Replace a line put in during an emergency, when asepsis could not be assured, within 48 hours","why":"A line placed in a rush is more likely to have been contaminated.","source":"cdc-2011","quote":"When adherence to aseptic technique cannot be ensured (i.e., catheters inserted during a medical emergency), replace the catheter as soon as possible, i.e., within 48 hours","grade":"Category IB"}],"bestInClass":{"statement":"The SHEA/IDSA/APIC 2022 essential practices at insertion, which CDC/HICPAC 2011 and epic3 broadly share: indication check, competent inserters, a checklist with an empowered observer, hand hygiene, an all-inclusive kit, ultrasound guidance, maximum sterile barrier precautions with a full-body drape, alcoholic chlorhexidine skin preparation allowed to dry, and no antibiotic prophylaxis. The sources differ in the strength and detail: chlorhexidine concentration is at least 2% in SHEA (high) and epic3 (Class A, 2% in 70% isopropyl alcohol) but more than 0.5% with alcohol in CDC (IA); maximum sterile barriers are moderate quality in SHEA, Category IB in CDC and Class C in epic3, and SHEA notes one randomised trial in surgical patients found no added benefit; SHEA prefers the subclavian site only for ICU placement and calls the site risk outside the ICU unclear. For people having long cancer treatment, epic3 recommends a tunnelled line or an implanted port (Class A), and SHEA warns that a PICC is not a way to lower infection risk.","sources":["shea-2022","cdc-2011","epic3"]},"variants":[{"name":"Antiseptic- or antimicrobial-impregnated catheters where rates stay high","differs":"Uses chlorhexidine with silver sulfadiazine or minocycline with rifampin catheters for lines expected to stay more than 5 days, in units whose CLABSI rate is above target despite the essential practices, or for patients with limited access and recurrent infection.","evidence":"SHEA additional approach, quality of evidence high in adults and moderate in children; CDC Category IA under the same conditions; epic3 Class A for adults. SHEA notes many of the trials predate routine bundles and the benefit on top of them is unknown.","sources":["shea-2022","cdc-2011","epic3"]},{"name":"Femoral or tunnelled femoral lines in children","differs":"In children and infants the femoral vein may be considered if upper body sites are contraindicated; a tunnelled femoral line with an exit site in the mid-thigh, outside the nappy area, may be safer.","evidence":"Stated by SHEA without a separate grade; CDC's femoral avoidance (Category IA) is for adults.","sources":["shea-2022","cdc-2011"]},{"name":"Povidone-iodine in alcohol for chlorhexidine sensitivity","differs":"Uses povidone-iodine in alcohol instead of chlorhexidine where the patient is sensitive to chlorhexidine; CDC also allows tincture of iodine, an iodophor or 70% alcohol.","evidence":"epic3 Class A within the skin preparation recommendation; CDC Category IA within its recommendation; CDC lists the comparison of chlorhexidine and povidone-iodine, both in alcohol, as unresolved.","sources":["epic3","cdc-2011"]}],"grades":[{"claim":"Alcoholic chlorhexidine skin preparation","grade":"Quality of Evidence: HIGH","source":"shea-2022","quote":"Use an alcoholic chlorhexidine antiseptic for skin preparation (Quality of Evidence: HIGH)"},{"claim":"2% chlorhexidine in 70% isopropyl alcohol, single use, allowed to dry, before CVC insertion","grade":"Class A","source":"epic3","quote":"Decontaminate the skin at the insertion site with a single-use application of 2% chlorhexidine gluconate in 70% isopropyl alcohol (or povidone iodine in alcohol for patients with sensitivity to chlorhexidine) and allow to dry prior to the insertion of a central venous access device."},{"claim":"More than 0.5% chlorhexidine with alcohol before CVC insertion","grade":"Category IA","source":"cdc-2011"},{"claim":"Maximum sterile barrier precautions","grade":"Quality of Evidence: MODERATE","source":"shea-2022","quote":"Use maximum sterile barrier precautions during CVC insertion (Quality of Evidence: MODERATE)"},{"claim":"Maximal sterile barrier precautions","grade":"Category IB","source":"cdc-2011"},{"claim":"Maximal sterile barrier precautions","grade":"Class C","source":"epic3","quote":"Use maximal sterile barrier precautions for the insertion of central venous access devices."},{"claim":"A checklist or similar process at insertion","grade":"Quality of Evidence: MODERATE","source":"shea-2022","quote":"In ICU and non-ICU settings, a facility should have a process in place, such as a checklist, to ensure adherence to infection prevention practices at the time of CVC insertion (Quality of Evidence: MODERATE)"},{"claim":"Subclavian site preferred for ICU placement","grade":"Quality of Evidence: HIGH","source":"shea-2022","quote":"The subclavian site is preferred to reduce infectious complications when the catheter is placed in the ICU setting (Quality of Evidence: HIGH)"},{"claim":"Minimum number of lumens","grade":"Class A","source":"epic3","quote":"Use a catheter with the minimum number of ports or lumens essential for management of the patient."}],"sources":[{"key":"shea-2022","label":"Strategies to prevent central line-associated bloodstream infections in acute-care hospitals: 2022 Update","publisher":"SHEA, IDSA, APIC (Infection Control and Hospital Epidemiology)","year":2022,"url":"https://europepmc.org/article/PMC/PMC9096710","doi":"10.1017/ice.2022.87","gradingScheme":"Quality of evidence HIGH, MODERATE or LOW; each recommendation classed as an essential practice, an additional approach, not routine, or unresolved.","read":"full-text","accessed":"2026-11-11"},{"key":"cdc-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","doi":"10.1093/cid/cir257","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"epic3","label":"epic3: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England","publisher":"Journal of Hospital Infection (Loveday et al., commissioned by the Department of Health)","year":2014,"url":"https://europepmc.org/article/PMC/PMC7114876","doi":"10.1016/S0195-6701(13)60012-2","gradingScheme":"SIGN-style classes A (1++ or consistent 1+ evidence) to D (level 3 or 4 evidence), GPP (good practice point), H&S (health and safety legislation).","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["None of the guidelines read asks for a mask on the patient; the full-body sterile drape covers the patient, and masks are named for the staff doing the insertion.","The INS Infusion Therapy Standards of Practice (2024) could not be read and are not cited here.","No guideline read is specific to children with cancer; the paediatric points (femoral site, chlorhexidine in infants) come from the general guidelines.","Outside the ICU, SHEA says the infection risk of different insertion sites remains unclear, and it is unclear whether ultrasound-guided subclavian insertion reduces infection.","The comparison of chlorhexidine and povidone-iodine, both in alcohol, is an unresolved issue in CDC 2011."]},{"id":"central-line-maintenance-bundle","kind":"protocol","name":"Central line maintenance bundle: preventing bloodstream infection after insertion","aka":["CLABSI maintenance bundle","central line care bundle","Hickman line care","PICC line care","CVC maintenance","line infection prevention","CRBSI prevention"],"tldr":"A central line (a Hickman, PICC or port) lets germs straight into the blood, so every touch is planned. Hands are cleaned, the connector is scrubbed with antiseptic each time, the dressing is kept clean and dry and changed weekly, and every day someone asks whether the line is still needed. Families caring for a line at home are taught the same steps before they leave hospital.","summary":"Maintenance rests on the SHEA/IDSA/APIC 2022 compendium (essential practices for all acute hospitals, graded by quality of evidence), CDC/HICPAC 2011 (updated 2017), epic3 (England, 2014) and NICE CG139 for care at home. Essential: hand hygiene before any contact (epic3 Class A); aseptic technique; scrub hubs, needleless connectors and injection ports before each access (SHEA moderate; CDC IA), with alcoholic chlorhexidine preferred and friction for at least 5 seconds (SHEA) or 15 seconds (epic3 Class D/GPP); access only with sterile devices; chlorhexidine in alcohol for site care at dressing changes (epic3 Class A); transparent dressings changed at least every 7 days and gauze every 2 days, or sooner if soiled, loose or damp (SHEA moderate); chlorhexidine-containing dressings over 2 months of age (SHEA high), which CDC 2017 recommends at IA only from age 18 and leaves unresolved in children; daily review and removal of non-essential lines (SHEA moderate, CDC IA); administration sets up to 7 days (SHEA high) or 96 hours (epic3 Class A); no systemic antimicrobial prophylaxis, routine antibiotic locks or routine line replacement; and unit surveillance of CLABSI per 1,000 catheter days.\n\nDaily chlorhexidine bathing is graded high for ICU patients over 2 months, but SHEA notes benefit in adult haematology-oncology was not seen in children, and a Children's Oncology Group randomised trial (2021) found more CLABSI with chlorhexidine bathing in children with cancer, concluding it does not support routine use. Antiseptic caps, antimicrobial lock therapy for recurrent CLABSI and vascular access teams are additional approaches where rates stay high.","asOf":"2026-11-11","links":[],"tags":["protocol","clabsi","vascular-access","paediatric"],"related":["implanted-port-access-and-care","central-line-insertion-bundle","picc-and-tunnelled-line-care","community-care-of-vascular-access-devices"],"cancers":["childhood-cancers"],"sections":["supportive-care"],"technologies":["implanted-ports","picc-lines","allogeneic-hsct"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":["central-venous-access","febrile-neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A central line is a thin tube into a big vein. Germs on hands or on the end of the tube can cause a serious blood infection. Clean hands, scrub the end of the tube each time, keep the dressing dry and take the line out when it is no longer needed.","domain":"infection-prevention","setting":{"who":["nurse","doctor","patient-or-carer"],"where":["ward","chemotherapy-day-unit","intensive-care","home","community"]},"population":"Adults and children with a central venous catheter (tunnelled lines such as Hickman and Broviac, PICCs, implanted ports and short-term non-tunnelled lines) during cancer treatment, in hospital and at home. SHEA scopes acute-care hospitals; NICE CG139 covers primary and community care. Infants under 2 months and premature neonates are named exceptions for chlorhexidine. Port needle access is covered in its own protocol.","trigger":"A central venous catheter is in place, from the first dressing after insertion until the line is removed.","steps":[{"action":"Train and check the competence of every person who cares for the line, and teach the patient and family before discharge","why":"Most line infections come from how the line is handled, so every pair of hands that touches it needs the same technique.","source":"nice-cg139","quote":"Before discharge from hospital, patients and their carers should be taught any techniques they may need to use to prevent infection and safely manage a vascular access device."},{"action":"Clean hands with alcohol rub, or soap and water if soiled, before and after any contact with the line or its site","why":"Hands carry the skin germs that most often cause line infections; gloves do not replace hand cleaning.","source":"epic3","quote":"Hands must be decontaminated, with an alcohol-based hand rub or by washing with liquid soap and water if soiled or potentially contaminated with blood or body fluids, before and after any contact with the intravascular catheter or insertion site.","grade":"Class A"},{"action":"Use an aseptic technique for site care and every time the line is accessed","why":"An aseptic technique keeps the parts that enter the blood untouched by anything unclean.","source":"cdc-2011","quote":"Maintain aseptic technique for the insertion and care of intravascular catheters","grade":"Category IB"},{"action":"Before every access, scrub the hub, needleless connector or injection port with alcoholic chlorhexidine or 70% alcohol, with friction","why":"About half of hubs and connectors carry germs in ordinary practice; scrubbing removes them before they are pushed into the line.","source":"shea-2022","quote":"Before accessing catheter hubs, needleless connectors, or injection ports, vigorously apply mechanical friction with an alcoholic chlorhexidine preparation, or 70% alcohol.","grade":"Quality of Evidence: MODERATE"},{"action":"Scrub for at least 5 seconds (SHEA), or 15 seconds and let it dry (epic3), and follow the local policy on which","why":"The two guidelines set different minimum times; neither has been tested on every connector type.","source":"shea-2022","quote":"Apply mechanical friction for a minimum of 5 seconds to reduce contamination."},{"action":"Access the port or connector only with sterile devices","why":"A non-sterile syringe tip undoes the scrub.","source":"cdc-2011","quote":"Minimize contamination risk by scrubbing the access port with an appropriate antiseptic (chlorhexidine, povidone iodine, an iodophor, or 70% alcohol) and accessing the port only with sterile devices","grade":"Category IA"},{"action":"At each dressing change, clean the site with 2% chlorhexidine in 70% alcohol from a single-use applicator and let it air dry","why":"Chlorhexidine in alcohol kills skin germs and keeps working after it dries.","source":"epic3","quote":"Use a single-use application of 2% chlorhexidine gluconate in 70% isopropyl alcohol (or povidone iodine in alcohol for patients with sensitivity to chlorhexidine) to clean the central catheter insertion site during dressing changes, and allow to air dry.","grade":"Class A"},{"action":"Change transparent dressings at least every 7 days and gauze every 2 days, and at once if the dressing is soiled, loose or damp","why":"A lifted or wet dressing lets germs track along the line into the vein.","source":"shea-2022","quote":"For nontunneled CVCs in adults and children, change transparent dressings and perform site care with a chlorhexidine-based antiseptic at least every 7 days or immediately if the dressing is soiled, loose, or damp.","grade":"Quality of Evidence: MODERATE"},{"action":"Use a chlorhexidine-containing dressing for patients over 2 months old, where the local policy and the child's age allow","why":"These dressings reduce line infections in adults; in children the evidence is thinner and CDC makes no recommendation under 18 (see variants).","source":"shea-2022","quote":"Use chlorhexidine-containing dressings for CVCs in patients over 2 months of age (Quality of Evidence: HIGH)","grade":"Quality of Evidence: HIGH"},{"action":"Do not let the line go under water; shower only with the line and connector covered by an impermeable cover","why":"Bath water and swimming pools can carry germs into the line; a cover makes showering possible.","source":"cdc-2011","quote":"Do not submerge the catheter or catheter site in water.","grade":"Category IB"},{"action":"Ask every day whether the line is still needed, and take out any line that is not","why":"Every day a line is in is a day it can become infected.","source":"shea-2022","quote":"Assess the need for continued intravascular access on a daily basis during multidisciplinary rounds.","grade":"Quality of Evidence: MODERATE"},{"action":"Change administration sets not used for blood, blood products or lipids no more often than every 96 hours to 7 days; change blood sets after each transfusion episode or every 12 hours","why":"More frequent changes add handling without reducing infection. SHEA allows up to 7 days and epic3 96 hours (Class A); blood and lipids support germ growth, so epic3 changes blood sets when the transfusion ends or every 12 hours, and lipid sets every 24 hours.","source":"shea-2022","quote":"Routine replacement of administration sets not used for blood, blood products, or lipid formulations can be performed at intervals up to 7 days (Quality of Evidence: HIGH)","grade":"Quality of Evidence: HIGH"},{"action":"Do not give antibiotics to prevent line infection while the line is in","why":"Preventive antibiotics do not lower line infections and they breed resistance.","source":"shea-2022","quote":"Do not use antimicrobial prophylaxis for short-term or tunneled catheter insertion or while catheters are in situ (Quality of Evidence: HIGH)","grade":"Quality of Evidence: HIGH"},{"action":"Do not replace central lines on a schedule","why":"Routine replacement adds insertion risks without preventing infection.","source":"epic3","quote":"Do not routinely replace central venous access devices to prevent catheter-related infection.","grade":"Class A"},{"action":"Count line infections per 1,000 catheter days on each unit and report them back to the unit and its leaders","why":"A unit that measures its rate can see whether the bundle is working and when to add more.","source":"shea-2022","quote":"Measure unit-specific incidence of CLABSI (eg, CLABSI per 1,000 catheter days) and report the data on a regular basis to the units, physician and nursing leadership, and hospital administrators overseeing the units.","grade":"Quality of Evidence: HIGH"},{"action":"If the rate stays high despite these steps, consider antiseptic caps on connectors, and antimicrobial lock solutions for patients with long-term lines and recurrent infection","why":"These are additional approaches with costs or risks, kept for where the essentials are not enough.","source":"shea-2022","quote":"Use an antiseptic-containing hub/connector cap/port protector to cover connectors (Quality of Evidence: MODERATE)","grade":"Quality of Evidence: MODERATE"}],"bestInClass":{"statement":"Run the essential practices of the SHEA/IDSA/APIC 2022 compendium as one bundle, with the UK guidelines filling in detail: hand hygiene and aseptic technique, hub and connector scrubbing before every access with alcoholic chlorhexidine, chlorhexidine in alcohol for site care, transparent dressings changed at least weekly or when compromised, chlorhexidine-containing dressings in adults, a daily review of need, no preventive antibiotics or scheduled line changes, and unit surveillance. Where the guidelines differ, both are stated: hub scrub time is at least 5 seconds in SHEA and at least 15 seconds with drying in epic3 (Class D/GPP); administration sets may run up to 7 days in SHEA (high quality) but up to 96 hours in epic3 (Class A); chlorhexidine dressings are recommended from 2 months in SHEA (high quality) but from 18 years in CDC 2017 (Category IA), with no recommendation for children and a recommendation against them for premature neonates. Daily chlorhexidine bathing is an essential practice for ICU patients in SHEA, but it is not established for children with cancer: SHEA records no benefit in them and the Children's Oncology Group trial found more infections with it.","sources":["shea-2022","cdc-2011","epic3","nice-cg139","zerr-2021"]},"variants":[{"name":"Hub scrub of at least 15 seconds, then drying (epic3, England)","differs":"Decontaminates the hub with 2% chlorhexidine in 70% alcohol for a minimum of 15 seconds and lets it dry before access, against SHEA's minimum of 5 seconds of friction. NICE CG139 asks for decontamination before and after access, with no time.","evidence":"epic3 grades it Class D/GPP (good practice); SHEA's 5 seconds rests on laboratory studies and it notes the time may not apply to untested connectors.","sources":["epic3","shea-2022","nice-cg139"]},{"name":"Chlorhexidine dressings by age (CDC/HICPAC 2017 update)","differs":"Recommends chlorhexidine-impregnated dressings with an FDA-cleared label for short-term non-tunnelled CVCs in patients aged 18 and over, recommends against them in premature neonates because of skin reactions, and makes no recommendation for other children. SHEA recommends them from 2 months.","evidence":"CDC Category IA for adults, IC against in premature neonates, unresolved issue for other children; SHEA quality of evidence high.","sources":["cdc-2011","shea-2022"]},{"name":"Daily chlorhexidine bathing, and why it is not routine for children with cancer","differs":"SHEA makes daily chlorhexidine bathing an essential practice for ICU patients over 2 months, and CDC 2011 suggests a 2% chlorhexidine wash for daily skin cleansing (Category II). In a Children's Oncology Group double-blind trial of 174 evaluable children with cancer or allogeneic transplant, CLABSI was 5.44 per 1,000 line days with chlorhexidine cloths against 3.10 with control cloths, and staphylococci with reduced chlorhexidine susceptibility were more often acquired.","evidence":"SHEA quality of evidence high for ICU patients; it calls the role outside the ICU unclear and notes benefit in adult haematology-oncology was not seen in children. The paediatric trial stopped early for poor accrual; its authors concluded that the data do not support routine chlorhexidine bathing in these children.","sources":["shea-2022","cdc-2011","zerr-2021"]},{"name":"Ethanol locks in children with cancer","differs":"Some paediatric centres fill the line with 70% ethanol between uses to prevent infection, especially after a line infection.","evidence":"A randomised double-blind trial in 94 children and young people with cancer or haematological disorders and a new CLABSI stopped for futility: treatment failure was 44% with ethanol and 43% with placebo, and line blockage needing a clot-dissolving drug was more common with ethanol (58% against 33%); its authors do not recommend routine ethanol locks for treatment or secondary prophylaxis. A 2023 meta-analysis, mostly of before-and-after studies, reported fewer infections with ethanol locks and more thrombosis and catheter breakage. SHEA lists antimicrobial lock therapy as an additional approach for recurrent CLABSI and asks that the adverse effects of ethanol locks be carefully considered.","sources":["wolf-2018","ethanol-meta-2023","shea-2022"]}],"grades":[{"claim":"Disinfect hubs, needleless connectors and injection ports before access","grade":"Quality of Evidence: MODERATE","source":"shea-2022","quote":"Disinfect catheter hubs, needleless connectors, and injection ports before accessing the catheter (Quality of Evidence: MODERATE)"},{"claim":"Decontaminate the hub for at least 15 seconds and allow to dry","grade":"Class D/GPP","source":"epic3","quote":"The hub should be cleaned for a minimum of 15 s and allowed to dry before accessing the system."},{"claim":"Chlorhexidine-containing dressings over 2 months of age","grade":"Quality of Evidence: HIGH","source":"shea-2022"},{"claim":"Bathe ICU patients over 2 months daily with chlorhexidine","grade":"Quality of Evidence: HIGH","source":"shea-2022","quote":"Bathe ICU patients >2 months of age with a chlorhexidine preparation on a daily basis (Quality of Evidence: HIGH)"},{"claim":"Promptly remove any line that is no longer essential","grade":"Category IA","source":"cdc-2011","quote":"Promptly remove any intravascular catheter that is no longer essential"},{"claim":"Administration sets in continuous use need not be replaced more often than every 96 hours","grade":"Class A","source":"epic3","quote":"Administration sets in continuous use do not need to be replaced more frequently than every 96 h, unless device-specific recommendations from the manufacturer indicate otherwise, they become disconnected or the intravascular access device is replaced."},{"claim":"Use bundled performance improvement initiatives","grade":"Category IB","source":"cdc-2011"},{"claim":"Antimicrobial lock therapy for long-term lines (additional approach)","grade":"Quality of Evidence: HIGH","source":"shea-2022","quote":"Use antimicrobial lock therapy for long-term CVCs (Quality of Evidence: HIGH)"},{"claim":"Antibiotic lock solutions should not be used routinely","grade":"Class D/GPP","source":"epic3","quote":"Antimicrobial lock solutions should not be used routinely to prevent catheter-related bloodstream infections."}],"sources":[{"key":"shea-2022","label":"Strategies to prevent central line-associated bloodstream infections in acute-care hospitals: 2022 Update","publisher":"SHEA, IDSA, APIC (Infection Control and Hospital Epidemiology)","year":2022,"url":"https://europepmc.org/article/PMC/PMC9096710","doi":"10.1017/ice.2022.87","gradingScheme":"Quality of evidence HIGH, MODERATE or LOW; each recommendation classed as an essential practice (all acute-care hospitals), an additional approach (where rates stay high), not routine, or unresolved.","read":"full-text","accessed":"2026-11-11"},{"key":"cdc-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","doi":"10.1093/cid/cir257","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"epic3","label":"epic3: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England","publisher":"Journal of Hospital Infection (Loveday et al., commissioned by the Department of Health)","year":2014,"url":"https://europepmc.org/article/PMC/PMC7114876","doi":"10.1016/S0195-6701(13)60012-2","gradingScheme":"SIGN-style classes A (1++ or consistent 1+ evidence) to D (level 3 or 4 evidence), GPP (good practice point), H&S (health and safety legislation).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-cg139","label":"Healthcare-associated infections: prevention and control in primary and community care (CG139), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg139/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended.","read":"full-text","accessed":"2026-11-11"},{"key":"zerr-2021","label":"Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double-blinded randomized controlled trial from the Children's Oncology Group","publisher":"Cancer","year":2021,"url":"https://europepmc.org/article/MED/33079403","doi":"10.1002/cncr.33271","read":"abstract","accessed":"2026-11-11"},{"key":"wolf-2018","label":"Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial","publisher":"The Lancet Infectious Diseases","year":2018,"url":"https://europepmc.org/article/MED/29884572","doi":"10.1016/s1473-3099(18)30224-x","read":"abstract","accessed":"2026-11-11"},{"key":"ethanol-meta-2023","label":"Ethanol Lock for Prevention of CVC-Related Bloodstream Infection in Pediatric Patients: A Systematic Review and Meta-Analysis","publisher":"Journal of Pediatric Pharmacology and Therapeutics","year":2023,"url":"https://europepmc.org/article/MED/38130502","doi":"10.5863/1551-6776-28.5.386","read":"abstract","accessed":"2026-11-11"},{"key":"ins-2024","label":"Infusion Therapy Standards of Practice, 9th Edition","publisher":"Infusion Nurses Society (Journal of Infusion Nursing)","year":2024,"url":"https://doi.org/10.1097/NAN.0000000000000532","doi":"10.1097/NAN.0000000000000532","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The INS Infusion Therapy Standards of Practice (9th edition, 2024), the main nursing standard for line care, could not be read: it is paywalled and no open copy was found.","No current guideline specific to central line care in children with cancer was found. The Children's Oncology Group archived its central venous catheter care guideline in August 2018, and the UK Children's Cancer and Leukaemia Group guidance could not be found at a public address.","The paediatric chlorhexidine bathing and ethanol lock trials were read as abstracts only.","The guidelines set different minimum hub scrub times (5 or 15 seconds) and SHEA notes the 5-second figure may not apply to connectors not tested; no trial compares them in patients.","How often to change intermittently used administration sets is unresolved in SHEA.","None of these guidelines asks for a mask on the patient or the patient turning their head away during dressing changes or hub access; masks appear only for line insertion."]},{"id":"central-venous-catheter-insertion-for-anticancer-therapy","kind":"protocol","name":"Central venous catheter insertion for anticancer treatment: PICC, tunnelled line and implanted port","aka":["PICC insertion","port insertion","portacath insertion","Hickman line insertion","tunnelled CVC insertion","central line insertion bundle","CVAD insertion","chest port implantation","SIC-Port"],"tldr":"A PICC, a tunnelled line or a port is put in by a trained doctor, nurse or radiologist under local anaesthetic, using an ultrasound scan to find the vein, full sterile precautions and a check that the tip sits just above the heart before it is used. Afterwards your breathing and blood pressure are checked, and you should say if you feel short of breath or have chest pain.","summary":"The insertion bundle is the same for all three devices and comes from infection-prevention and oncology guidelines. A checklist (SHEA 2022, moderate), hand hygiene, alcoholic chlorhexidine skin preparation (ESMO [I, A]; SHEA high quality) and maximal sterile barrier precautions with cap, mask, sterile gown and gloves and a full body drape (CDC Category IB; SHEA moderate); ultrasound-guided venepuncture (SHEA high; CDC IB, by trained operators); the fewest lumens needed (CDC IB); no systemic antibiotic prophylaxis (ESMO [I, A]; CDC IB). Avoid the femoral vein (ESMO [I, A]); ITAC 2022 asks for right-sided jugular insertion with the tip at the junction of the superior vena cava and right atrium to reduce catheter-related thrombosis (grade 1B).\n\nESMO asks for implanted ports to be placed under strict sterile conditions in an operating room [II, B], and for the tip position to be confirmed by intraoperative fluoroscopy or post-operative chest X-ray [II, B], with intracavitary ECG as an alternative [V, D]. Newer practice moves tip location into the procedure: NICE HTG368 supports an ECG-based tip confirmation system for PICCs in adults, avoiding a chest X-ray unless there is no P wave, and the Italian GAVeCeLT SIC-Port bundle (2026) adds ultrasound vein assessment, a preference for the axillary vein, ultrasound exclusion of pneumothorax, ultrasound tip navigation, intracavitary ECG or echo tip location, and pocket closure with intradermal sutures and glue. After insertion ESMO asks for four-hourly observations and a chest X-ray for breathlessness or chest wall pain [II, C].","asOf":"2026-11-11","links":[],"tags":[],"related":["venous-access-device-selection-for-anticancer-therapy","picc-and-tunnelled-line-care","implanted-port-access-and-care","catheter-related-thrombosis-in-cancer","central-line-insertion-bundle"],"cancers":[],"sections":[],"technologies":["picc-lines","implanted-ports","picc-tip-location-systems","infusion-devices-vascular-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"The line or port is put in under local anaesthetic, using an ultrasound scan and very clean, sterile conditions. Its tip is checked before treatment goes through it.","domain":"vascular-access","setting":{"who":["doctor","nurse","radiographer","surgical-team"],"where":["theatre","outpatient-clinic","ward"]},"population":"Adults with cancer needing a long-term central venous access device for anticancer treatment: a PICC, a tunnelled cuffed catheter or an implanted chest or arm port. Device choice is covered in the device-selection protocol. Children, dialysis catheters and short-term non-tunnelled lines in intensive care follow their own protocols; SHEA's recommendations are written for acute-care hospitals and much of their evidence is from intensive care.","trigger":"A long-term central venous device has been chosen and is to be inserted.","steps":[{"action":"Assess the person before the procedure: history (previous lines, clots, difficult access), examination, blood tests and an ultrasound survey of the veins","why":"Knowing the veins and the clotting risk beforehand lets the operator choose a safe vein of the right size and avoid complications.","source":"esmo-2015","quote":"Careful preoperative assessment is advised. This should include the patient's medical history, a physical examination and the appropriate laboratory and radiological tests (discussed below)."},{"action":"Use a checklist at insertion, completed by someone other than the operator, to confirm each infection-prevention step","why":"Checklists make it much more likely every step is done every time.","source":"shea-clabsi-2022","quote":"In ICU and non-ICU settings, a facility should have a process in place, such as a checklist, to ensure adherence to infection prevention practices at the time of CVC insertion (Quality of Evidence: MODERATE)","grade":"Quality of Evidence: MODERATE"},{"action":"Choose a catheter with the fewest lumens the treatment needs","why":"Each extra lumen is another route for infection and clots.","source":"cdc-hicpac-2011","quote":"Use a CVC with the minimum number of ports or lumens essential for the management of the patient [65–68]. Category IB","grade":"Category IB"},{"action":"Avoid the femoral vein; where possible insert on the right, in the jugular vein, aiming the tip at the junction of the superior vena cava and right atrium","why":"Groin lines carry more infection and clot risk, and a right-sided line with its tip in the right place is less likely to cause a clot.","source":"itac-2022","quote":"Catheters should be inserted on the right side, in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium (grade 1B).","grade":"1B"},{"action":"Clean hands, prepare the skin with chlorhexidine in alcohol, and use maximal sterile barrier precautions: cap, mask, sterile gown, sterile gloves and a full body drape","why":"Most early line infections come from skin germs carried in at insertion, and full barriers cut that risk.","source":"cdc-hicpac-2011","quote":"Use maximal sterile barrier precautions, including the use of a cap, mask, sterile gown, sterile gloves, and a sterile full body drape, for the insertion of CVCs, PICCs, or guidewire exchange","grade":"Category IB"},{"action":"Find and puncture the vein under real-time ultrasound guidance, by an operator trained in it","why":"Ultrasound means fewer attempts and fewer punctures of arteries or lung.","source":"shea-clabsi-2022","quote":"Use ultrasound guidance for catheter insertion (Quality of Evidence: HIGH)","grade":"Quality of Evidence: HIGH"},{"action":"Do not give antibiotics routinely before insertion","why":"Trials have not shown that preventive antibiotics stop line infections, and they encourage resistance.","source":"esmo-2015","quote":"Antimicrobial prophylaxis to prevent catheter colonisation, before insertion or during maintenance of CVCs, is not recommended [I, A]","grade":"[I, A]"},{"action":"Place an implanted port under strict sterile conditions, in an operating room, under local anaesthetic with or without sedation","why":"A port sits in a surgical pocket under the skin, so it is inserted with surgical sterility.","source":"esmo-2015","quote":"Insertion of an implantable venous access device should be carried out under strict sterile conditions, in the operating room [II, B]","grade":"[II, B]"},{"action":"Confirm the tip position before use: by fluoroscopy during the procedure or a chest X-ray afterwards, or by an intracavitary ECG method","why":"A tip in the wrong place can cause clots, irregular heartbeats or a line that does not work.","source":"esmo-2015","quote":"Catheter tip position should be verified radiologically with an intraoperative fluoroscopy, or a post-operative chest X-ray [II, B]","grade":"[II, B]"},{"action":"After the procedure, check temperature, pulse, blood pressure and breathing four-hourly, and get a chest X-ray if the person is breathless or has chest wall pain","why":"These are the early signs of a collapsed lung, bleeding or a misplaced line.","source":"esmo-2015","quote":"After the procedure, patients require 4 hourly observations including: temperature, pulse, blood pressure and respiratory rate. A chest X-ray is required if the patient has dyspnoea or chest wall pain [II, C]","grade":"[II, C]"},{"action":"If air embolism is suspected, lay the person on their left side, head down, and give 100% oxygen","why":"This position helps keep air from blocking the outflow of the heart while help arrives.","source":"esmo-2015","quote":"Air embolism: immediately place the patient in the lateral decubitus head down position and deliver 100% oxygen [ 29 ]."}],"bestInClass":{"statement":"Insertion checklist (SHEA moderate), hand hygiene, alcoholic chlorhexidine (ESMO [I, A]; SHEA high), maximal sterile barrier precautions (CDC IB), real-time ultrasound guidance (SHEA high; CDC IB), fewest lumens (CDC IB), no antibiotic prophylaxis (ESMO [I, A]), no femoral site (ESMO [I, A]), right jugular with the tip at the cavoatrial junction (ITAC 1B), ports in a sterile operating environment (ESMO [II, B]) and confirmed tip position before use. On tip confirmation the sources differ by date: ESMO 2015 prefers fluoroscopy or chest X-ray [II, B] and rates intracavitary ECG [V, D], while NICE (2015, updated 2019) supports ECG-based tip confirmation for PICCs in adults and the 2026 GAVeCeLT bundle uses intracavitary ECG or echocardiography during the procedure instead of X-ray. ESMO also notes the open cephalic cut-down avoids immediate complications [IV, D], where newer bundles use ultrasound-guided puncture.","sources":["esmo-2015","cdc-hicpac-2011","shea-clabsi-2022","itac-2022","nice-htg368","sic-port-2026"]},"variants":[{"name":"SIC-Port bundle for chest ports (GAVeCeLT, 2026)","differs":"Eight steps: a systematic ultrasound survey of the neck and chest veins (RaCeVA), chlorhexidine 2% in 70% alcohol with maximal barriers, ultrasound-guided puncture preferring the axillary vein to avoid tunnelling over the collarbone, ultrasound to exclude pneumothorax, ultrasound tip navigation, tip location by intracavitary ECG or echocardiography with a bubble test, a pocket made by hydro-dissection over the pectoral muscle, and closure with absorbable intradermal sutures and cyanoacrylate glue. It also advises micro-introducer kits and a vein at least three times the catheter's diameter.","evidence":"A society consensus bundle drawn from the recent literature, adopted in GAVeCeLT training courses; not tested as a bundle in a trial.","sources":["sic-port-2026"]},{"name":"ECG-based tip confirmation for PICCs instead of chest X-ray (NICE HTG368)","differs":"Uses an ECG-based tip confirmation system during PICC insertion so the line can be used without a confirmatory chest X-ray; an X-ray is still needed if there is no P wave, as in atrial fibrillation.","evidence":"NICE found the case for adoption supported by the evidence, with cost similar to blind insertion plus X-ray outside intensive care and an estimated saving of 109 pounds per patient against fluoroscopy. ESMO 2015 graded the intracavitary ECG method [V, D].","sources":["nice-htg368","esmo-2015"]},{"name":"Open surgical cut-down of the cephalic vein for ports","differs":"Exposes the cephalic vein in the shoulder groove surgically instead of puncturing a vein with a needle.","evidence":"ESMO calls it the best approach to avoid immediate complications, graded [IV, D]. Newer guidance makes ultrasound-guided puncture the standard (SHEA high quality; SIC-Port).","sources":["esmo-2015","shea-clabsi-2022","sic-port-2026"]}],"grades":[{"claim":"Avoid the femoral vein unless other sites are contraindicated","grade":"[I, A]","source":"esmo-2015","quote":"There is insufficient evidence to recommend a specific insertion site, but the femoral vein should be avoided unless there is a contraindication to the other sites (e.g. SVC syndrome), due to the increased risk of infection and concerns about thrombosis [I, A]"},{"claim":"Chlorhexidine solutions with alcohol at insertion","grade":"[I, A]","source":"esmo-2015","quote":"Chlorhexidine solutions with alcohol should be used [I, A]"},{"claim":"Alcoholic chlorhexidine for skin preparation","grade":"Quality of Evidence: HIGH","source":"shea-clabsi-2022","quote":"Use an alcoholic chlorhexidine antiseptic for skin preparation (Quality of Evidence: HIGH)"},{"claim":"Maximum sterile barrier precautions during CVC insertion","grade":"Quality of Evidence: MODERATE","source":"shea-clabsi-2022","quote":"Use maximum sterile barrier precautions during CVC insertion (Quality of Evidence: MODERATE)"},{"claim":"Ultrasound guidance, if available, by fully trained operators","grade":"Category IB","source":"cdc-hicpac-2011","quote":"Use ultrasound guidance to place central venous catheters (if this technology is available) to reduce the number of cannulation attempts and mechanical complications."},{"claim":"No routine systemic antimicrobial prophylaxis before insertion","grade":"Category IB","source":"cdc-hicpac-2011","quote":"Do not administer systemic antimicrobial prophylaxis routinely before insertion or during use of an intravascular catheter to prevent catheter colonization or CRBSI [114]."},{"claim":"Intracavitary ECG as an alternative to radiological tip confirmation","grade":"[V, D]","source":"esmo-2015","quote":"An alternative to radiologic confirmation is the intracavitary electrocardiogram (ECG) method, where arrhythmia is documented during insertion of the wire [V, D]"},{"claim":"Open cephalic cut-down to avoid immediate complications","grade":"[IV, D]","source":"esmo-2015","quote":"The open technique (cephalic vein cut-down) is the best approach to avoid the risk of immediate complications [IV, D]"}],"sources":[{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I (large good-quality RCT or meta-analysis) to V (no control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"},{"key":"cdc-hicpac-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"shea-clabsi-2022","label":"Strategies to prevent central line-associated bloodstream infections in acute-care hospitals: 2022 Update","publisher":"SHEA, IDSA, APIC (Infection Control and Hospital Epidemiology)","year":2022,"url":"https://doi.org/10.1017/ice.2022.87","doi":"10.1017/ice.2022.87","gradingScheme":"Quality of evidence HIGH, MODERATE or LOW, with each recommendation classed as an essential practice, an additional approach or an unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"itac-2022","label":"2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19","publisher":"International Initiative on Thrombosis and Cancer (ITAC), The Lancet Oncology","year":2022,"url":"https://doi.org/10.1016/S1470-2045(22)00160-7","doi":"10.1016/S1470-2045(22)00160-7","gradingScheme":"GRADE: evidence A (high) to D (very low); recommendation grade 1 (strong) or 2 (weak); 'guidance' (best clinical practice) where there is no clear evidence, based on expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"sic-port-2026","label":"A GAVeCeLT bundle for chest-port insertion: The SIC-Port protocol","publisher":"Journal of Vascular Access (Brescia et al., GAVeCeLT)","year":2026,"url":"https://doi.org/10.1177/11297298251375833","doi":"10.1177/11297298251375833","read":"full-text","accessed":"2026-11-11"},{"key":"nice-htg368","label":"The Sherlock 3CG Tip Confirmation System for placement of peripherally inserted central catheters (HTG368, formerly MTG24)","publisher":"NICE","year":2019,"url":"https://www.nice.org.uk/guidance/htg368/chapter/1-Recommendations","gradingScheme":"NICE does not grade recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"lamperti-2012","label":"International evidence-based recommendations on ultrasound-guided vascular access","publisher":"Intensive Care Medicine (Lamperti et al.)","year":2012,"url":"https://doi.org/10.1007/s00134-012-2597-x","doi":"10.1007/s00134-012-2597-x","gradingScheme":"GRADE and GRADE-RAND.","read":"abstract","accessed":"2026-11-11"},{"key":"ins-2024","label":"Infusion Therapy Standards of Practice, 9th Edition","publisher":"Infusion Nurses Society (Journal of Infusion Nursing)","year":2024,"url":"https://doi.org/10.1097/NAN.0000000000000532","doi":"10.1097/NAN.0000000000000532","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No guideline read is specific to inserting tunnelled cuffed (Hickman type) catheters; the steps here are the general central line bundle, and tunnelling technique and cuff position are not covered. OnCo has no technology record for tunnelled catheters.","The INS Standards (2024) and the GAVeCeLT PICC insertion bundle could not be read.","ESMO's 2015 guideline predates ultrasound tip navigation and routine ECG tip location; whether intra-procedural ECG or echo should replace chest X-ray for ports and tunnelled lines rests on the 2026 GAVeCeLT consensus, not a guideline graded since.","SHEA's recommendations are written for acute-care hospitals and lean on intensive-care evidence; outpatient insertion of ports and PICCs in cancer services is less studied.","Whether a mask on the patient is needed during insertion is not stated by the guidelines read, which list the mask among the operator's barriers."]},{"id":"irae-hypophysitis-adrenal","kind":"protocol","name":"Checkpoint inhibitor hypophysitis and adrenal insufficiency: emergency treatment, replacement and steroid emergency card","aka":["immune checkpoint inhibitor hypophysitis","ICI adrenal insufficiency","adrenal crisis on immunotherapy","cortisol deficiency immunotherapy","steroid sick day rules immunotherapy","ipilimumab hypophysitis"],"tldr":"Immunotherapy can damage the pituitary or adrenal glands so the body stops making cortisol, a hormone needed to survive illness. Anyone on immunotherapy who becomes very unwell should be treated for low cortisol at once while tests are done. Most then need hydrocortisone tablets for life, a steroid emergency card, and to know how to double the dose when ill. Immunotherapy can usually carry on.","summary":"Hypophysitis affects up to 17% of people on checkpoint inhibitors, mostly with CTLA-4 blockade (70% of published cases) and at ipilimumab doses above 3 mg/kg; ACTH deficiency is present in about 95% of anti-CTLA-4 cases (ESE 2022). Primary adrenal insufficiency is rare. Both usually cause permanent hormone loss.\n\nThe emergency (Society for Endocrinology 2018; ESE 2022): any severely unwell patient on a checkpoint inhibitor is assumed to have cortisol deficiency until proven otherwise. Take blood for cortisol (and ACTH) and give hydrocortisone 100 mg intravenously or intramuscularly, then 50 mg every 6 hours, with fluids; check glucose. A pre-treatment cortisol above 450 nmol/L excludes deficiency. Methylprednisolone does not replace cortisol and is kept for pituitary compression (visual loss, cranial nerve palsy, severe headache); ESE recommends against high-dose steroids for hypophysitis otherwise. Never start levothyroxine until cortisol deficiency is excluded or treated.\n\nMaintenance: hydrocortisone 15 to 25 mg a day in two or three doses (ESE) or 10, 5 and 5 mg (Society for Endocrinology), fludrocortisone for primary adrenal insufficiency only, a steroid emergency card, sick day rules and an injection kit, and no abrupt stop. A controlled endocrinopathy is not a reason to stop the checkpoint inhibitor (ESE, ASCO). SITC 2021 differs in advising interruption of immunotherapy and corticosteroids for acute hypophysitis.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","acute-oncology","endocrine"],"related":["irae-colitis","irae-pneumonitis","hyponatraemia-siadh"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["ipilimumab","nivolumab","pembrolizumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab","hydrocortisone"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["immune-endocrinopathy","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can stop your body making cortisol, a hormone you need when you are ill. Signs include tiredness, headache, feeling faint or being sick. It is treated with hormone tablets. Carry your steroid card and learn the sick day rules.","domain":"immunotherapy-toxicity","setting":{"who":["patient-or-carer","nurse","doctor","emergency-team","pharmacist"],"where":["emergency-department","acute-oncology-service","telephone-triage","ward","outpatient-clinic","home"]},"population":"Adults treated with an immune checkpoint inhibitor (most often ipilimumab, alone or with nivolumab) who present unwell, or who have symptoms or screening results suggesting cortisol deficiency. Covers secondary (pituitary) and primary (adrenal) insufficiency. People already on high-dose steroids for another immune side effect need interpretation by an endocrinologist; children are not covered.","trigger":"A person on or after checkpoint inhibitor treatment presents severely unwell, or reports fatigue, headache, nausea, dizziness or visual change, or a routine test shows low cortisol or a low TSH with low or normal free T4.","steps":[{"action":"Treat any severely unwell patient on a checkpoint inhibitor as having cortisol deficiency until proven otherwise","why":"Low cortisol can kill quickly and its signs are vague; giving steroids while waiting for the result is safe.","source":"sfe-2018","quote":"Any patient receiving a CPI who presents severely unwell should be assumed to have acute cortisol deficiency until proven otherwise and treated with glucocorticoids until serum cortisol result available"},{"action":"Take blood for cortisol (and ACTH if possible), then give hydrocortisone 100 mg intravenously or intramuscularly, followed by 50 mg every 6 hours, with fluid resuscitation","why":"The blood sample before treatment is what later confirms or excludes the diagnosis; the hydrocortisone and fluids treat the crisis.","source":"ese-2022","quote":"We recommend the use of high-dose glucocorticoids in case of an acutely unwell patient ICI-treated with suspected adrenal crisis, more specifically 100 mg hydrocortisone intravenously or intramuscularly followed by 50 mg every 6 h and fluid resuscitation","grade":"good clinical practice"},{"action":"Measure blood glucose in every unwell patient on a checkpoint inhibitor","why":"Checkpoint inhibitors can also cause sudden insulin-dependent diabetes, and steroid treatment raises glucose.","source":"sfe-2018","quote":"Plasma glucose should be measured in all unwell patients treated with a CPI."},{"action":"Stop the emergency steroids only if the pre-treatment cortisol was above 450 nmol/L and there is no other reason for them","why":"A cortisol above that level before treatment excludes deficiency; if in doubt, steroids continue and an endocrinologist is asked.","source":"sfe-2018","quote":"A baseline (pre-glucocorticoid treatment) serum cortisol of >450 nmol/L excludes cortisol deficiency"},{"action":"In a mildly unwell or symptom-free patient, start oral hydrocortisone if the 09:00 cortisol is under 200 nmol/L or a random cortisol under 100 nmol/L, and refer to endocrinology","why":"These cut-offs deliberately err towards treating; the diagnosis is confirmed later by a specialist.","source":"sfe-2018","quote":"If low serum cortisol levels (09:00 h <200 nmol/L or random cortisol <100 nmol/L) are detected in a mildly symptomatic/asymptomatic patient start oral hydrocortisone."},{"action":"If there is headache, double vision or a cranial nerve palsy, arrange an urgent contrast MRI of the pituitary","why":"A swollen pituitary can press on the optic nerves, and brain metastases can look the same.","source":"sfe-2018","quote":"Headache, diplopia and cranial nerve palsies (CTCAE grade 3–4) should trigger an urgent MRI scan of the pituitary; to assess the potential need for treatment with IV methylprednisolone and to distinguish intracranial metastases as a differential diagnosis."},{"action":"Do not give high-dose steroids for hypophysitis unless there is compression of the optic chiasm or other severe pressure symptoms","why":"There is no evidence that high doses restore pituitary function, and one study linked them with shorter survival; replacement-dose hydrocortisone treats the hormone loss.","source":"ese-2022","quote":"We recommend against the use of high-dose glucocorticoids for treatment of hypophysitis, with exception of optic chiasm compression or other severe compressive symptoms.","grade":"++00 (low quality evidence), strong recommendation"},{"action":"Do not start levothyroxine until cortisol deficiency has been excluded or treated","why":"Thyroid hormone speeds up cortisol use and can tip someone with untreated adrenal insufficiency into crisis.","source":"sfe-2018","quote":"Thyroxine should never be instigated unless cortisol deficiency is excluded as it can trigger an adrenal crisis."},{"action":"Once recovered, continue replacement with hydrocortisone, usually 15 to 25 mg a day split into two or three doses","why":"Pituitary and adrenal damage from checkpoint inhibitors rarely recovers, so replacement is usually lifelong.","source":"ese-2022","quote":"Most patients are managed well on a daily dose of 15–25 mg hydrocortisone split into two or three doses","grade":"good clinical practice"},{"action":"For primary adrenal insufficiency, add fludrocortisone; it is not needed for pituitary causes","why":"Damage to the adrenal gland itself also removes aldosterone, which keeps salt and blood pressure up.","source":"ese-2022","quote":"We recommend standard mineralocorticoid replacement for patients with proven primary adrenal insufficiency (good clinical practice).","grade":"good clinical practice"},{"action":"Before discharge, give a steroid emergency card, teach the sick day rules and supply a hydrocortisone injection kit","why":"Most adrenal crises can be prevented if the person doubles their dose when ill and anyone treating them knows they depend on steroids.","source":"sfe-2018","quote":"Prior to discharge, patients should be provided with a Steroid Emergency Card, education with regards to ‘sick day rules’, and an hydrocortisone emergency injection kit as per Society for Endocrinology guidance"},{"action":"Never stop glucocorticoid replacement abruptly, even if immunotherapy has stopped, without a formal test of pituitary and adrenal function","why":"Stopping suddenly can cause an adrenal crisis.","source":"ese-2022","quote":"We recommend against stopping high-dose glucocorticoid replacement abruptly without formal assessment of pituitary–adrenal function, even if ICI treatment was stopped (good clinical practice).","grade":"good clinical practice"},{"action":"Continue or restart the checkpoint inhibitor once the patient is stable on replacement","why":"A controlled hormone deficiency is not a reason to give up an effective cancer treatment.","source":"ese-2022","quote":"We recommend that a controlled endocrinopathy is not a contraindication for initiation and/or continuation of ICI therapy (++00).","grade":"++00 (low quality evidence), strong recommendation"}],"bestInClass":{"statement":"The endocrine guidelines agree on the emergency: assume cortisol deficiency in any severely unwell patient on a checkpoint inhibitor, take blood, and give hydrocortisone 100 mg then 50 mg 6-hourly with fluids (Society for Endocrinology 2018; ESE 2022, good clinical practice). They agree that replacement-dose hydrocortisone, not high-dose methylprednisolone, treats the hormone loss, keeping high doses for pituitary compression (ESE, ++00), and that a controlled endocrinopathy does not stop immunotherapy (ESE ++00; ASCO 2021 exempts controlled endocrinopathies from permanent discontinuation after grade 4). SITC 2021, an oncology guideline, differs: for symptoms of acute hypophysitis it advises interrupting immunotherapy and giving corticosteroids (LE: 4), and replaces with hydrocortisone 10 to 12 mg/m2 a day. Maintenance doses differ in form but not much in total: ESE 15 to 25 mg a day in two or three doses, Society for Endocrinology 10, 5 and 5 mg or prednisolone 3 to 5 mg once a day.","sources":["sfe-2018","ese-2022","sitc-2021","asco-2021"]},"variants":[{"name":"Interrupt immunotherapy and give corticosteroids for acute hypophysitis (SITC 2021)","differs":"Advises interrupting immunotherapy and giving corticosteroids when symptoms of acute hypophysitis appear, then hydrocortisone replacement at 10 to 12 mg/m2/day with a medical alert device and stress-dose education; withholds immunotherapy temporarily for adrenal insufficiency of any grade.","evidence":"LE: 4 for interruption and corticosteroids; the rest without a level (expert consensus).","sources":["sitc-2021"]},{"name":"Fixed three-dose replacement (Society for Endocrinology 2018)","differs":"Tapers treatment-dose glucocorticoids after 48 to 72 hours of recovery to hydrocortisone 10 mg on waking, 5 mg at lunchtime and 5 mg in the early evening, or prednisolone 3 to 5 mg once a day; warns that a short Synacthen test may be falsely reassuring within 6 to 12 weeks of hypophysitis.","evidence":"Expert consensus endorsed by the Society for Endocrinology Clinical Committee.","sources":["sfe-2018"]}],"grades":[{"claim":"Hydrocortisone 100 mg intravenously or intramuscularly then 50 mg every 6 hours with fluids for suspected adrenal crisis","grade":"good clinical practice","source":"ese-2022"},{"claim":"No high-dose glucocorticoids for hypophysitis except compression","grade":"++00 (low), strong","source":"ese-2022"},{"claim":"A controlled endocrinopathy is not a contraindication to checkpoint inhibitors","grade":"++00 (low), strong","source":"ese-2022"},{"claim":"Sick day rules training for ACTH and vasopressin deficiency","grade":"good clinical practice","source":"ese-2022","quote":"We recommend that patients with pituitary hormone deficiencies, more particularly ACTH and vasopressin deficiencies, are provided with appropriate and regular training on managing their glucocorticoid and/or desmopressin treatment during period of illness (‘Sick Day Rules’) (good clinical practice)."},{"claim":"Interrupt immunotherapy and give corticosteroids for symptoms of acute hypophysitis","grade":"LE: 4","source":"sitc-2021","quote":"If symptoms of acute hypophysitis are observed, immunotherapy should be interrupted and corticosteroids administered"},{"claim":"Endocrinopathies controlled by hormone replacement are exempt from permanent discontinuation after grade 4","grade":"expert consensus","source":"asco-2021"}],"sources":[{"key":"sfe-2018","label":"Society for Endocrinology Endocrine Emergency Guidance: acute management of the endocrine complications of checkpoint inhibitor therapy","publisher":"Society for Endocrinology, Endocrine Connections","year":2018,"url":"https://europepmc.org/article/PMC/PMC6013692","doi":"10.1530/EC-18-0068","gradingScheme":"Expert consensus of endocrinologists, oncologists and an acute physician, endorsed by the Society for Endocrinology Clinical Committee; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ese-2022","label":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline","publisher":"European Society of Endocrinology, European Journal of Endocrinology","year":2022,"url":"https://europepmc.org/article/PMC/PMC9641795","doi":"10.1530/EJE-22-0689","gradingScheme":"GRADE: quality of evidence printed as +000 (very low), ++00 (low), +++0 (moderate) or ++++ (strong); 'recommend' is a strong and 'suggest' a weak recommendation; recommendations not formally graded are marked good clinical practice.","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The NHS England National Patient Safety Alert on the steroid emergency card, and the Society for Endocrinology's 2016 adrenal crisis guidance it builds on, were not read for this page; the card is cited here through the 2018 guidance only.","No trial read here tests whether high-dose steroids change pituitary recovery; ESE cites a retrospective study in which patients given high doses had shorter survival, and says it is unclear whether the steroids or a worse prognosis explain it.","Routine screening for cortisol deficiency during treatment (how often to test morning cortisol) differs between centres; the guidelines read here set the thyroid testing interval but not a cortisol interval."]},{"id":"chemotherapy-induced-peripheral-neuropathy-assessment-and-prevention","kind":"protocol","name":"Chemotherapy nerve damage (peripheral neuropathy): assessment, dose changes and prevention","aka":["CIPN assessment","chemotherapy-induced peripheral neuropathy","frozen gloves during paclitaxel","surgical glove compression during taxanes","cryotherapy for neuropathy","duloxetine for chemotherapy neuropathy"],"tldr":"Some chemotherapy drugs, such as paclitaxel, docetaxel, oxaliplatin, vincristine and bortezomib, can damage the nerves in the hands and feet, causing tingling, numbness or pain. Tell your team at every visit: the dose can be lowered or delayed before the damage lasts. No medicine is proven to prevent it; cooling or compressing the hands is being tested. Duloxetine can help painful nerve damage.","summary":"ASCO (2020) found that no agent is recommended to prevent CIPN and discourages acetyl-L-carnitine. Clinicians should consider dose delay, dose reduction, substitution or stopping the drug in people who develop intolerable neuropathy or loss of function; duloxetine is the only drug with appropriate evidence for established painful CIPN, and its benefit is limited. Assessment rests on asking at every cycle: an Australian Delphi consensus (2022) agreed on education before treatment, a history to find risk factors, closer monitoring or a baseline neurological assessment for people with existing neuropathy, screening with a short patient-reported questionnaire at every treatment cycle and at follow-up, and encouraging physical activity.\n\nOn prevention by cooling or compression, randomised evidence has grown since ASCO 2020. In POLAR (2025, 122 women on weekly paclitaxel or nab-paclitaxel, one hand treated and the other as control), a frozen glove or two surgical gloves one size too small, worn from 30 minutes before to 30 minutes after the infusion, each reduced grade 2 or higher sensory CIPN (cooling 29 against 50 per cent; compression 24 against 38 per cent). In CryoPac (2026, 268 randomised, frozen gloves and socks), cryotherapy did not significantly reduce CIPN at the end of treatment (74 against 84 per cent) but reduced patient-reported tingling and numbness, with 67 per cent compliance. No guideline read has yet graded these trials.","asOf":"2026-11-11","links":[],"tags":["protocol","neuropathy","supportive-care"],"related":["idea-moon-neuropathy-prevention-programme"],"cancers":[],"sections":["supportive-care"],"technologies":["frozen-gloves-compression-taxane","limb-cryocompression-devices"],"targets":[],"drugs":["paclitaxel","nab-paclitaxel","docetaxel","oxaliplatin","vincristine","bortezomib"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["peripheral-neuropathy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some chemotherapy can hurt the nerves in hands and feet. Tell your team about tingling or numbness each time. They may change the dose.","domain":"symptom-management","setting":{"who":["nurse","doctor","pharmacist","patient-or-carer"],"where":["chemotherapy-day-unit","outpatient-clinic"]},"population":"Adults having neurotoxic chemotherapy: taxanes, platinum drugs (above all oxaliplatin), vinca alkaloids, bortezomib and others. The cooling and compression trials were in women with breast cancer on weekly paclitaxel or nab-paclitaxel (POLAR) or taxane chemotherapy (CryoPac). POLAR excluded people with previous chemotherapy, existing neuropathy or conditions linked with neuropathy.","trigger":"A neurotoxic chemotherapy regimen is planned, and at every cycle.","steps":[{"action":"Before treatment, explain the symptoms of nerve damage and ask the person to report them","why":"Tingling and numbness are easy to dismiss; people who know to report them help the team act early.","source":"cipn-path-2022","quote":"Patients should receive education about CIPN prior to treatment"},{"action":"Take a history for risk factors, and plan closer monitoring or a neurological assessment for people who already have neuropathy","why":"Diabetes, existing neuropathy and some other conditions make nerve damage more likely or worse.","source":"cipn-path-2022","quote":"Patients with preexisting peripheral neuropathy or who are at high risk should be considered for pretreatment neurological assessment or closer monitoring"},{"action":"Screen for neuropathy at every treatment cycle, using a short patient-reported questionnaire, and continue at follow-up","why":"Doctors' grading alone misses symptoms that the person notices; asking every cycle catches them early.","source":"cipn-path-2022","quote":"Screening for CIPN should occur at every treatment cycle"},{"action":"When neuropathy becomes intolerable or affects function, consider delaying, reducing, substituting or stopping the drug","why":"Nerve damage can become permanent; changing the dose in time can prevent lasting harm.","source":"asco-2020","quote":"Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment."},{"action":"Do not offer a drug to prevent neuropathy; in particular, do not use acetyl-L-carnitine","why":"No drug has been shown to prevent it, and ASCO specifically discourages acetyl-L-carnitine.","source":"asco-2020","quote":"The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged."},{"action":"For painful established neuropathy, offer duloxetine and explain that the benefit is modest","why":"It is the only drug with good evidence for nerve pain after chemotherapy.","source":"asco-2020","quote":"Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited."},{"action":"Encourage physical activity during treatment, and refer people with pain, balance problems or falls for further help","why":"Staying active helps keep physical function; balance problems from nerve damage raise the risk of falls.","source":"cipn-path-2022","quote":"All patients should be encouraged to be physically active during treatment to minimise impairments to physical function"},{"action":"During weekly paclitaxel or nab-paclitaxel, consider a frozen glove or tight surgical gloves on the hands from 30 minutes before to 30 minutes after the infusion","why":"Cooling or squeezing the hands during the drip is thought to reduce how much drug reaches the small nerves; in one randomised trial both lowered moderate or worse nerve damage.","source":"polar-2025","quote":"Cooling was performed with a frozen glove and compression was applied by 2 surgical gloves (1 size smaller than the tight-fitting size) 30 minutes before, after, and during taxane administration."}],"bestInClass":{"statement":"ASCO 2020 remains the latest graded guideline read: no drug prevents CIPN, dose modification is the main tool, and duloxetine is the only treatment with adequate evidence for painful CIPN. Assessment at every cycle with patient-reported tools is consensus practice (Australian CIPN-path, 2022). On cooling and compression the evidence has moved since ASCO 2020 and is mixed: POLAR (2025) found that both a frozen glove and surgical-glove compression reduced grade 2 or higher sensory CIPN, while CryoPac (2026) found that frozen gloves and socks did not significantly reduce CIPN on its primary measure but reduced sensory symptoms. Offering them during weekly taxanes is reasonable where tolerated, and is not yet a guideline recommendation in any source read. The ESMO-EONS-EANO 2020 guideline could not be read.","sources":["asco-2020","cipn-path-2022","polar-2025","cryopac-2026","esmo-eons-eano-2020"]},"variants":[{"name":"Frozen gloves and socks during all taxane infusions (CryoPac)","differs":"Cools both hands and feet during each taxane infusion, rather than one hand as in POLAR.","evidence":"Randomised trial of 268 people: CIPN at end of treatment 74 per cent with cryotherapy against 84 per cent with usual care, not significant (P = 0.071); fewer hand tingling and numbness and foot numbness on patient report; compliance 67 per cent; no effect on dose modifications. Read as an abstract.","sources":["cryopac-2026"]},{"name":"Compression with surgical gloves instead of cooling (POLAR)","differs":"Two surgical gloves one size smaller than a tight fit, worn from 30 minutes before to 30 minutes after the taxane infusion, with no cooling.","evidence":"In POLAR compression lowered grade 2 or higher sensory CIPN from 38 to 24 per cent in the compressed hand against the untreated hand (P = .008); cooling lowered it from 50 to 29 per cent (P = .002). The trial compared each method with the person's other hand, not the two methods with each other.","sources":["polar-2025"]}],"grades":[{"claim":"Hand cooling reduced grade 2 or higher sensory CIPN in POLAR","grade":"single randomised trial (within-patient control), P = .002","source":"polar-2025","quote":"Both interventions significantly reduced the incidence of grade 2 or higher CIPN (cooling: 15 participants experiencing high-grade CIPN in the cooling arm [29%] vs 26 in the control arm [50%]; P = .002;"},{"claim":"Frozen gloves and socks did not significantly reduce CIPN incidence at end of treatment in CryoPac","grade":"single randomised trial, P = 0.071","source":"cryopac-2026","quote":"Cryotherapy did not significantly reduce CIPN incidence (TNS ≥ 2) at EoT but cryotherapy-treated patients reported fewer sensory symptoms and demonstrated reduced tactile disturbance."}],"sources":[{"key":"asco-2020","label":"Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2020,"url":"https://europepmc.org/abstract/MED/32663120","doi":"10.1200/JCO.20.01399","read":"abstract","accessed":"2026-11-11"},{"key":"cipn-path-2022","label":"Development and consensus process for a clinical pathway for the assessment and management of chemotherapy-induced peripheral neuropathy","publisher":"Supportive Care in Cancer","year":2022,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9135801/","doi":"10.1007/s00520-022-07024-3","gradingScheme":"Two-stage Delphi of 70 Australian respondents; consensus defined as 80 per cent or more agreeing; statements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"polar-2025","label":"Efficacy of Hand Cooling and Compression in Preventing Taxane-Induced Neuropathy: The POLAR Randomized Clinical Trial","publisher":"JAMA Oncology","year":2025,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11886872/","doi":"10.1001/jamaoncol.2025.0001","read":"full-text","accessed":"2026-11-11"},{"key":"cryopac-2026","label":"Efficacy of cryotherapy in preventing taxane-induced neuropathy: the CryoPac randomised controlled trial","publisher":"Annals of Oncology","year":2026,"url":"https://europepmc.org/abstract/MED/42838271","doi":"10.1016/j.annonc.2026.09.014","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-eons-eano-2020","label":"Systemic anticancer therapy-induced peripheral and central neurotoxicity: ESMO-EONS-EANO Clinical Practice Guidelines for diagnosis, prevention, treatment and follow-up","publisher":"ESMO, EONS and EANO, Annals of Oncology","year":2020,"url":"https://doi.org/10.1016/j.annonc.2020.07.003","doi":"10.1016/j.annonc.2020.07.003","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-hand-foot-cooling-compression-during-taxanes","idea-mach-cold-or-compression-by-adherence"],"gaps":["ASCO 2020 was read only as an abstract; its grades, its position on cryotherapy, compression and exercise, and its dose-modification detail by drug are not given here.","The ESMO-EONS-EANO 2020 guideline could not be read: Europe PMC holds no abstract and the publisher refused a script.","No guideline read has graded POLAR (2025) or CryoPac (2026), and the two trials point in somewhat different directions on the main measure.","No source read sets dose-reduction rules by drug and grade; these come from each regimen's protocol and product information.","Who should be excluded from cooling (for example people with Raynaud's phenomenon or cold intolerance) is not stated in the parts of the trials read.","The evidence behind ASCO's advice against acetyl-L-carnitine is not in the abstract read."]},{"id":"venous-access-device-selection-for-anticancer-therapy","kind":"protocol","name":"Choosing a venous access device for anticancer treatment: port, PICC, tunnelled line or cannula","aka":["port or PICC","PICC versus port","Hickman versus port","choice of central line for chemotherapy","vascular access device selection","CAVA trial","MAGIC-ONC"],"tldr":"If you need many months of treatment into a vein, a central line saves repeated needles. For most people with solid tumours, a randomised trial found an implanted port under the skin had fewer problems than a PICC in the arm or a tunnelled line in the chest. For urgent treatment of leukaemia and similar cancers, a PICC or tunnelled line with two channels may suit better.","summary":"The CAVA trial (UK, 1061 adults, 2021) compared Hickman-type tunnelled catheters, PICCs and implanted ports for at least 12 weeks of anticancer therapy. Ports had fewer complications (a composite of infection, venous thrombosis, pulmonary embolus, inability to aspirate, mechanical failure and others) than Hickman lines (29% against 43%, OR 0.54) and than PICCs (32% against 47%, OR 0.52); PICCs and Hickman lines had similar rates, with non-inferiority not confirmed. The authors concluded that most patients receiving anticancer therapy for solid tumours should receive a port in the NHS.\n\nMAGIC-ONC (2025, RAND/UCLA appropriateness method, 1422 scenarios) rated a single-lumen tunnelled CVC or a port appropriate for chemotherapy for solid tumours regardless of intensity, urgency or duration, and a double-lumen PICC or tunnelled CVC appropriate for urgent chemotherapy in acute haematological cancers; in advanced chronic kidney disease it advises coordinating with a nephrologist to preserve veins. ITAC (2022) suggests ports over PICCs where a central line is needed (guidance) and right-sided jugular insertion with the tip at the cavoatrial junction (1B). ESMO (2015) notes that PICCs' main limitation is shorter longevity from a higher risk of thrombosis and advises avoiding the femoral vein [I, A].","asOf":"2026-11-11","links":[],"tags":[],"related":["implanted-port-access-and-care","picc-and-tunnelled-line-care","catheter-related-thrombosis-in-cancer"],"cancers":[],"sections":[],"technologies":["implanted-ports","picc-lines","infusion-devices-vascular-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"For long treatment, a port under the skin usually causes fewer problems than a PICC or a line in the chest. Ask which device you will have and why.","domain":"vascular-access","setting":{"who":["doctor","nurse","multidisciplinary-team"],"where":["outpatient-clinic","chemotherapy-day-unit"]},"population":"Adults starting intravenous anticancer treatment expected to last weeks to months. CAVA enrolled adults receiving at least 12 weeks of treatment for solid or haematological cancers in UK oncology units. Children, people needing apheresis or transplant lines, and dialysis patients have other considerations.","trigger":"A course of intravenous anticancer treatment is planned, or peripheral veins are becoming hard to use.","steps":[{"action":"Plan the device before treatment starts, taking into account the cancer type, how urgent treatment is, how long the device must stay in and the person's other conditions","why":"The best device differs between an urgent leukaemia course and months of outpatient treatment for a solid tumour.","source":"magic-onc-2025","quote":"Appropriateness of VAD selection varied by type of cancer, treatment urgency, and planned dwell time."},{"action":"For most people with solid tumours needing central access, offer an implanted port","why":"In a randomised trial ports had about a third fewer complications than PICCs or tunnelled lines.","source":"cava-2021","quote":"For most patients receiving SACT, PORTs are more effective and safer than both Hickman and PICCs."},{"action":"For urgent chemotherapy in acute leukaemia and similar cancers, consider a double-lumen PICC or tunnelled central line","why":"These can be placed quickly and give two channels for chemotherapy, blood products and antibiotics at the same time.","source":"magic-onc-2025","quote":"For patients with acute hematologic cancers requiring urgent chemotherapy, placement of a double-lumen peripherally inserted central catheter (PICC) or a tunneled central venous catheter (CVC) was rated as appropriate, regardless of treatment intensity or infusate characteristics."},{"action":"Where a central line is needed, prefer a port to a PICC, inserted on the right in the jugular vein with the tip at the junction of the superior vena cava and right atrium","why":"PICCs in the arm are more prone to clots, and the right jugular route with a correctly placed tip lowers clot risk.","source":"itac-2022","quote":"Catheters should be inserted on the right side, in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium (grade 1B).","grade":"1B"},{"action":"Avoid the femoral vein unless the other sites cannot be used","why":"Lines in the groin carry more infection and clot risk.","source":"esmo-2015","quote":"There is insufficient evidence to recommend a specific insertion site, but the femoral vein should be avoided unless there is a contraindication to the other sites (e.g. SVC syndrome), due to the increased risk of infection and concerns about thrombosis [I, A]","grade":"[I, A]"},{"action":"In advanced chronic kidney disease, involve a kidney specialist before placing a PICC or line, to protect veins needed for dialysis","why":"Arm veins used for a PICC may be needed later for dialysis access.","source":"magic-onc-2025","quote":"In patients with advanced chronic kidney disease, coordination of care with a nephrologist to ensure vein preservation in the context of cancer prognosis was recommended."}],"bestInClass":{"statement":"For solid tumours needing central access, an implanted port: the CAVA randomised trial found fewer complications than with PICCs or Hickman lines, ITAC (2022) suggests ports over PICCs (guidance), and MAGIC-ONC (2025) rates a port or single-lumen tunnelled line appropriate. For urgent treatment of acute haematological cancers, a double-lumen PICC or tunnelled line (MAGIC-ONC). Right-sided jugular insertion with the tip at the cavoatrial junction (ITAC 1B); avoid the femoral vein (ESMO [I, A]). The sources agree in direction; MAGIC-ONC rates the tunnelled line alongside the port for solid tumours, while CAVA found ports superior to Hickman lines.","sources":["cava-2021","magic-onc-2025","itac-2022","esmo-2015"]},"variants":[{"name":"PICC as the default device","differs":"Places a PICC for most courses because it is quick, done by nurses at the bedside and needs no surgery.","evidence":"CAVA: PICCs had more complications than ports (47% against 32%, OR 0.52 for ports) and similar rates to Hickman lines; ESMO 2015 notes their shorter longevity from higher thrombosis risk; ITAC suggests ports over PICCs. The trial abstract does not report patient preference or waiting times, which can favour PICCs in practice.","sources":["cava-2021","esmo-2015","itac-2022"]}],"grades":[{"claim":"Ports superior to Hickman lines for complications","grade":"Randomised trial result (OR 0.54, 95% CI 0.37 to 0.77)","source":"cava-2021","quote":"PORTs were superior to Hickman with a complication rate of 29% (73 of 253) versus 43% (131 of 303; OR 0·54 [95% CI 0·37-0·77])."},{"claim":"Ports superior to PICCs for complications","grade":"Randomised trial result (OR 0.52, 95% CI 0.33 to 0.83)","source":"cava-2021","quote":"PORTs were superior to PICCs with a complication rate of 32% (47 of 147) versus 47% (93 of 199; OR 0·52 [0·33-0·83])."},{"claim":"Ports suggested over PICCs where a central line is needed","grade":"guidance","source":"itac-2022","quote":"In patients requiring central venous catheters, we suggest the use of implanted ports over peripherally inserted central catheter lines (guidance)."},{"claim":"Solid tumours: single-lumen tunnelled CVC or port appropriate for chemotherapy","grade":"Rated appropriate (RAND/UCLA)","source":"magic-onc-2025","quote":"For patients with malignant solid tumors, a single-lumen tunneled CVC or implanted port was rated as appropriate for delivering chemotherapy, regardless of treatment intensity, urgency, or duration."}],"sources":[{"key":"cava-2021","label":"Central venous access devices for the delivery of systemic anticancer therapy (CAVA): a randomised controlled trial","publisher":"The Lancet (Moss et al.)","year":2021,"url":"https://doi.org/10.1016/S0140-6736(21)00766-2","doi":"10.1016/S0140-6736(21)00766-2","read":"abstract","accessed":"2026-11-11"},{"key":"magic-onc-2025","label":"The Michigan Appropriateness Guide for Intravenous Catheters in Adult Patients With Cancer (MAGIC-ONC): Results From a Multispecialty Panel Using the RAND/UCLA Appropriateness Method","publisher":"Annals of Internal Medicine (Major et al.)","year":2025,"url":"https://doi.org/10.7326/ANNALS-25-02523","doi":"10.7326/ANNALS-25-02523","gradingScheme":"RAND/UCLA appropriateness method: each scenario rated appropriate, neutral or uncertain, or inappropriate by a 9-member panel.","read":"abstract","accessed":"2026-11-11"},{"key":"itac-2022","label":"2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19","publisher":"International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.)","year":2022,"url":"https://doi.org/10.1016/S1470-2045(22)00160-7","doi":"10.1016/S1470-2045(22)00160-7","gradingScheme":"GRADE: evidence A (high) to D (very low); recommendation grade 1 (strong) or 2 (weak); 'guidance' (best clinical practice) where there is no clear evidence, based on expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology, Sousa et al.)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I (large good-quality RCT or meta-analysis) to V (no control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["CAVA and MAGIC-ONC were read as abstracts only; CAVA's subgroup results (haematological cancers, treatment mode) and MAGIC-ONC's full appropriateness tables, including when a peripheral cannula or midline is appropriate, were not read.","When a peripheral cannula is enough, and whether midlines have any role for anticancer drugs, are not settled by the sources read here.","The INS Infusion Therapy Standards of Practice (2024), which address device selection, could not be read.","The ESMO guideline on venous access dates from 2015."]},{"id":"chronic-pain-in-cancer-survivors","kind":"protocol","name":"Chronic pain in cancer survivors: assessment, non-opioid treatment first and careful opioid use","aka":["chronic pain after cancer","persistent pain in survivors","post-treatment pain","aromatase inhibitor joint pain","opioids in cancer survivors","chronic cancer-related pain"],"tldr":"Pain can last for years after cancer treatment. Tell your team about any pain, especially new pain, which should be checked for cancer coming back. Most long-lasting pain is best managed first with exercise, talking therapies, physiotherapy and non-opioid medicines; acupuncture helps joint pain from aromatase inhibitors. Opioids can be tried with care, because long-term use carries real risks.","summary":"ASCO (2016) recommends screening for pain at each encounter, evaluating new pain for recurrence, a second cancer or a late effect of treatment, involving other professionals for complex needs, and using systemic non-opioid and adjuvant analgesics; a trial of opioids may be given to carefully selected survivors who do not respond to more conservative management and remain distressed or impaired, with assessment of risk and universal precautions against misuse. Many of its recommendations rest on expert consensus because high-quality evidence was scarce. The SIO-ASCO integrative guideline (2022) recommends acupuncture for aromatase inhibitor joint pain, and says acupuncture, reflexology or acupressure may be recommended for general cancer or musculoskeletal pain, hypnosis for procedural pain and massage in palliative or hospice care. For pain from active cancer or its treatment, ASCO's opioid guideline (2023) says opioids should be offered for moderate to severe pain unless contraindicated, started as needed at the lowest dose with early assessment and titration.\n\nThe Japan Society of Pain Clinicians (2025) goes further for survivors: not all survivor pain is cancer pain; pain that is not should be treated without opioids where possible, and when opioids are needed they follow the country's non-cancer chronic pain rules (up to 60 mg oral morphine equivalent a day, not above 90 mg, for a target of 3 months). It grades psychosocial approaches [1B] and exercise [1B] most highly, NSAIDs, paracetamol, gabapentinoids for cancer-related neuropathic pain and duloxetine for CIPN pain as weak recommendations [2B], and advises against long-term corticosteroids for pain [2D].","asOf":"2026-11-11","links":[],"tags":["protocol","pain","survivorship","supportive-care"],"related":["chemotherapy-induced-peripheral-neuropathy-assessment-and-prevention","exercise-during-and-after-cancer-treatment"],"cancers":[],"sections":["supportive-care"],"technologies":["pain-management","acupuncture-aromatase-inhibitor-arthralgia","cbt-fatigue-distress","exercise-oncology","hypnosis-cancer-care","massage-therapy-cancer","reflexology-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":["asco","esmo"],"pathways":[],"terms":["peripheral-neuropathy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Pain after cancer treatment is common. Tell your team. New pain needs checking. Many treatments help besides strong painkillers.","domain":"survivorship","setting":{"who":["doctor","nurse","pharmacist","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","community"]},"population":"Adults after cancer treatment, or living long term with cancer, who have chronic pain (ASCO 2016; JSPC 2025). Pain from active cancer or active treatment is covered by ASCO's opioid guideline (2023). SIO-ASCO found the evidence insufficient for recommendations in children.","trigger":"Every follow-up encounter; and any report of new or persisting pain.","steps":[{"action":"Ask about pain at every encounter","why":"Long-lasting pain after cancer is common and often goes unmentioned unless someone asks.","source":"asco-2016","quote":"Clinicians should screen for pain at each encounter."},{"action":"Evaluate any new pain for recurrence, a second cancer or a late effect of treatment before treating it as chronic pain","why":"New pain can be the first sign that the cancer has come back, which changes everything that follows.","source":"asco-2016","quote":"Recurrent disease, second malignancy, or late-onset treatment effects in any patient who reports new-onset pain should be evaluated, treated, and monitored."},{"action":"Decide whether the pain is caused by cancer or not, and manage pain that is not cancer pain without opioids where possible","why":"Pain after treatment is often not caused by cancer, and long-term opioids for such pain carry risks without clear benefit.","source":"jspc-2025","quote":"Pain that is not cancer pain should be managed with analgesics other than opioids and nerve blocks, and pain that persists despite this approach should be treated as non-cancer chronic pain so as to prevent opioid overuse."},{"action":"Offer psychosocial treatment (CBT, self-management, psychoeducation) and exercise therapy, and bring in other professionals when needs are complex","why":"These improve pain, mood and quality of life; complex pain usually needs a team rather than one prescriber.","source":"jspc-2025","quote":"Psychosocial approaches such as psychotherapy, self-management, and psychoeducation are effective in treating chronic pain in cancer survivors.【1B】","grade":"1B"},{"action":"Use non-opioid and adjuvant analgesics: NSAIDs or paracetamol, a gabapentinoid for neuropathic pain caused by cancer, duloxetine for painful chemotherapy nerve damage","why":"These can relieve pain and improve function without the risks of long-term opioids.","source":"asco-2016","quote":"Systemic nonopioid analgesics and adjuvant analgesics may be prescribed to relieve chronic pain and/or to improve function."},{"action":"For joint pain from aromatase inhibitors, recommend acupuncture; acupuncture, reflexology or acupressure may also be offered for general cancer or musculoskeletal pain","why":"Acupuncture reduced aromatase inhibitor joint pain in trials, which can help people keep taking their hormone treatment.","source":"sio-asco-2022","quote":"Among adult patients, acupuncture should be recommended for aromatase inhibitor-related joint pain. Acupuncture or reflexology or acupressure may be recommended for general cancer pain or musculoskeletal pain."},{"action":"Consider a trial of opioids only for carefully selected survivors whose pain has not responded to other treatment and still causes distress or impaired function, after assessing the risks","why":"Opioids can help some people, but long-term use brings risks of dependence, falls, hormone problems and overdose.","source":"asco-2016","quote":"Clinicians may prescribe a trial of opioids in carefully selected patients with cancer who do not respond to more conservative management and who continue to experience distress or functional impairment. Risks of adverse effects of opioids should be assessed."},{"action":"When opioids are used, apply universal precautions against misuse, and involve palliative care, pain or addiction specialists for anyone with a substance use disorder","why":"Structured safeguards lower the chance of harm; people with addiction still deserve pain relief and need specialist planning.","source":"opioids-2023","quote":"For patients with a substance use disorder, clinicians should collaborate with a palliative care, pain, and/or substance use disorder specialist to determine the optimal approach to pain management."}],"bestInClass":{"statement":"No single recent graded guideline covers chronic pain in survivors. ASCO 2016 remains the US reference (screen every visit, rule out recurrence, non-opioid and adjuvant analgesics, opioids as a selective trial with precautions), mostly on expert consensus. SIO-ASCO 2022 adds the strongest integrative recommendation, acupuncture for aromatase inhibitor joint pain. The Japan Society of Pain Clinicians statement (2025) is the most recent and most explicit: it separates cancer pain from non-cancer pain in survivors, ranks psychosocial approaches and exercise first [1B], and caps opioid doses and duration as for non-cancer chronic pain. ASCO does not set a dose cap for survivors in the parts read; JSPC does. ESMO 2018 could not be read.","sources":["asco-2016","sio-asco-2022","jspc-2025","opioids-2023","esmo-2018"]},"variants":[{"name":"Japanese opioid limits for non-cancer pain in survivors","differs":"Opioids only when non-opioid analgesics and nerve blocks fail, with a recommended maximum of 60 mg a day oral morphine equivalent, an upper limit of 90 mg, and reassessment with withdrawal or dose reduction considered after a target of 3 months and at most 6 months.","evidence":"JSPC 2025 consensus, applying Japan's guideline for opioids in chronic non-cancer pain; tramadol is weakly recommended in carefully selected survivors [2B]. No comparable numerical limits appear in the ASCO abstracts read.","sources":["jspc-2025"]},{"name":"Nerve blocks and intrathecal analgesia","differs":"Interventional treatment for pain from cancer in internal organs (for example a coeliac plexus block) or intractable cancer pain.","evidence":"JSPC 2025: neurolytic nerve blocks may be considered because they can reduce opioid use [2C]; intrathecal analgesia may be considered for intractable cancer pain [2C].","sources":["jspc-2025"]},{"name":"Hypnosis and massage","differs":"Hypnosis for pain during procedures; massage for pain in palliative or hospice care.","evidence":"SIO-ASCO 2022: each may be recommended, on an intermediate level of evidence with moderate strength.","sources":["sio-asco-2022"]}],"grades":[{"claim":"Exercise therapy for chronic pain in survivors","grade":"1B","source":"jspc-2025","quote":"Consider exercise therapy because of its potential to improve health-related quality of life in cancer survivors. [1B]"},{"claim":"Duloxetine for chronic pain, especially painful CIPN","grade":"2B","source":"jspc-2025","quote":"Duloxetine is weakly recommended for chronic pain in cancer survivors because it is more effective for pain due to chemotherapy-induced peripheral neuropathy (CIPN) than other adjuvant analgesics. [2B]"},{"claim":"No long-term corticosteroids for chronic pain alone","grade":"2D","source":"jspc-2025","quote":"Corticosteroids should not be used long term in cancer survivors for the sole purpose of relieving chronic pain. [2D]"},{"claim":"SIO-ASCO integrative recommendations","grade":"intermediate evidence; benefit outweighs risk; moderate strength","source":"sio-asco-2022","quote":"These recommendations are based on an intermediate level of evidence, benefit outweighing risk, and with moderate strength of recommendation."},{"claim":"Opioids for moderate to severe pain from active cancer or its treatment","grade":"not given in the abstract","source":"opioids-2023","quote":"Opioids should be offered to patients with moderate-to-severe pain related to cancer or active cancer treatment unless contraindicated."}],"sources":[{"key":"asco-2016","label":"Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2016,"url":"https://europepmc.org/abstract/MED/27458286","doi":"10.1200/JCO.2016.68.5206","read":"abstract","accessed":"2026-11-11"},{"key":"sio-asco-2022","label":"Integrative Medicine for Pain Management in Oncology: Society for Integrative Oncology-ASCO Guideline","publisher":"SIO and ASCO, Journal of Clinical Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/36122322","doi":"10.1200/JCO.22.01357","read":"abstract","accessed":"2026-11-11"},{"key":"opioids-2023","label":"Use of Opioids for Adults With Pain From Cancer or Cancer Treatment: ASCO Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2023,"url":"https://europepmc.org/abstract/MED/36469839","doi":"10.1200/JCO.22.02198","read":"abstract","accessed":"2026-11-11"},{"key":"jspc-2025","label":"Consensus statement on chronic pain treatment in cancer survivors","publisher":"Japan Society of Pain Clinicians, Journal of Anesthesia","year":2025,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11937162/","doi":"10.1007/s00540-024-03427-0","gradingScheme":"GRADE-based (Minds Manual 2020): certainty A (high) to D (very low) combined with strength 1 (strong) or 2 (weak), for example [2B].","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2018","label":"Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines","publisher":"ESMO, Annals of Oncology","year":2018,"url":"https://doi.org/10.1093/annonc/mdy152","doi":"10.1093/annonc/mdy152","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["ASCO 2016, SIO-ASCO 2022 and ASCO 2023 were read only as abstracts; their individual evidence ratings, drug choices and doses are not given here.","The ESMO 2018 cancer pain guideline could not be read (no abstract in Europe PMC; the publisher refused a script).","The 2026 update of the Australian guideline for cancer pain in adults was found but its body text is not released by PubMed Central to a script; not read.","No source read sets an opioid dose limit for survivors outside Japan; whether US or European survivors should follow non-cancer chronic pain opioid guidance is not settled in the sources read.","The JSPC statement is a national consensus; its recommendations draw on studies mostly from other countries and on expert agreement."]},{"id":"paediatric-clostridioides-difficile","kind":"protocol","name":"Clostridioides difficile infection in children with cancer or after stem cell transplant","aka":["C. difficile in children with cancer","C diff paediatric oncology","CDI children","Clostridium difficile children cancer"],"tldr":"C. difficile is a gut germ that can cause bad diarrhoea, often after antibiotics. In children having cancer treatment it is treated with an antibiotic by mouth, chosen by how severe it is. Children with it are kept apart from others to stop it spreading, and probiotics and faecal transplants are not used routinely during treatment.","summary":"The 2024 update from an international panel led by the Pediatric Oncology Group of Ontario (96 randomised trials in any population, GRADE), endorsed by the Children's Oncology Group in August 2024, covers children and adolescents aged 1 to 18 with cancer or undergoing haematopoietic cell transplant; infants under 1 are excluded because C. difficile in them is usually colonisation. Treat non-severe infection with oral metronidazole or oral vancomycin (strong, low) and severe infection (colitis, pneumatosis, pseudomembranous colitis, ileus or surgery) with oral vancomycin or, new in 2024, oral fidaxomicin (strong, low), after a trial including children with cancer showed higher cure at follow-up and fewer recurrences with fidaxomicin. Consider fidaxomicin for recurrence (conditional, moderate). Do not use faecal microbiota transplantation routinely (strong, low), though it may be reasonable once treatment is over and the child is no longer immunosuppressed. Do not use probiotics routinely for prevention or treatment (conditional, low), because of documented invasive infections from probiotics in children with cancer, nor bezlotoxumab (conditional, moderate). Two new good practice statements: isolate according to local policy, and minimise systemic antibiotics, especially after a previous episode.","asOf":"2026-11-11","links":[],"tags":["protocol","paediatric","infection"],"related":["paediatric-fever-and-neutropenia"],"cancers":["childhood-cancers"],"sections":["supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Antibiotics can let a gut germ called C. difficile cause diarrhoea. The child gets a medicine by mouth and is kept in a single room. Teams try not to give antibiotics the child does not need.","domain":"paediatric","setting":{"who":["doctor","nurse","pharmacist"],"where":["ward","outpatient-clinic"]},"population":"Children and adolescents aged 1 to 18 with cancer and those undergoing haematopoietic cell transplant. Infants under 1 year are excluded by the guideline. Adults are not covered.","trigger":"A child having cancer treatment or a transplant has diarrhoea and C. difficile toxin is detected, or is at risk because of antibiotics.","steps":[{"action":"Isolate a child with C. difficile infection and follow the local infection control policy","why":"Isolation limits spread of C. difficile to other children; the exact rules differ by country and hospital.","source":"patel-cdi-2024","quote":"In pediatric patients with cancer and HCT recipients experiencing CDI, follow infection control practices including isolation according to jurisdictional policies.","grade":"Good practice statement"},{"action":"Keep systemic antibiotics to those the child needs, especially after a previous episode","why":"Exposure to antibiotics is a known risk factor for C. difficile in children with cancer.","source":"patel-cdi-2024","quote":"In pediatric patients with cancer and HCT recipients, especially those who have experienced CDI, minimize systemic antibacterial administration where feasible.","grade":"Good practice statement"},{"action":"Do not give probiotics routinely to prevent C. difficile","why":"There are no trials in children having cancer treatment, and probiotics have caused bloodstream and fungal infections in such children.","source":"patel-cdi-2024","quote":"We suggest that probiotics not be used routinely for the prevention of CDI in pediatric patients with cancer and HCT recipients","grade":"conditional recommendation, low quality evidence"},{"action":"Treat non-severe infection with oral metronidazole or oral vancomycin","why":"The trials found similar cure and relapse rates with the two.","source":"patel-cdi-2024","quote":"Use either oral metronidazole or oral vancomycin for the treatment of non-severe CDI in pediatric patients with cancer and HCT recipients","grade":"strong recommendation, low quality evidence"},{"action":"Treat severe infection with oral vancomycin or oral fidaxomicin","why":"Vancomycin cured more severe cases than metronidazole; fidaxomicin, tested in a trial that included children with cancer, cured more at follow-up and halved relapses compared with vancomycin.","source":"patel-cdi-2024","quote":"Use either oral vancomycin or oral fidaxomicin for the treatment of severe CDI in pediatric patients with cancer and HCT recipients","grade":"strong recommendation, low quality evidence"},{"action":"Consider fidaxomicin for a recurrence","why":"Fidaxomicin reduces further relapses, though it has not been tested specifically in recurrent infection.","source":"patel-cdi-2024","quote":"Consider fidaxomicin for the treatment of recurrent CDI in pediatric patients with cancer and HCT recipients","grade":"conditional recommendation, moderate quality evidence"},{"action":"Do not use faecal microbiota transplantation routinely during treatment","why":"Its benefit in children is uncertain, the products vary, and the safety concern is highest while the child is neutropenic or immunosuppressed.","source":"patel-cdi-2024","quote":"Do not use FMT routinely for the treatment of CDI in pediatric patients with cancer and HCT recipients","grade":"strong recommendation, low quality evidence"},{"action":"Do not use bezlotoxumab or probiotics routinely as treatment","why":"Bezlotoxumab did not help in the trial of children with cancer and needs a drip; probiotics carry the infection risk above.","source":"patel-cdi-2024","quote":"We suggest that monoclonal antibodies not be used routinely for the treatment of CDI in pediatric patients with cancer and HCT recipients","grade":"conditional recommendation, moderate quality evidence"}],"bestInClass":{"statement":"The 2024 international paediatric guideline (Patel et al.), endorsed by the Children's Oncology Group, is the only guideline written for children with cancer and transplant recipients: oral metronidazole or vancomycin for non-severe infection, oral vancomycin or fidaxomicin for severe infection, fidaxomicin considered for recurrence, isolation and antibiotic stewardship, and no routine probiotics, faecal transplant or bezlotoxumab. Its evidence is mostly from adult trials, which is why most grades are low; adult guidelines (IDSA and SHEA 2021) were not read here beyond their abstract, so no comparison with them is made on this page.","sources":["patel-cdi-2024","cog-cdi-2024"]},"variants":[{"name":"Faecal microbiota transplantation after treatment ends","differs":"Uses faecal transplant for recurrent infection once the child has finished cancer treatment and is no longer immunosuppressed.","evidence":"The guideline's strong recommendation is against routine use during treatment; its rationale says faecal transplant may be a reasonable option once patients have completed therapy and are no longer immunosuppressed. No paediatric oncology trial supports it.","sources":["patel-cdi-2024"]}],"grades":[{"claim":"Oral metronidazole or vancomycin for non-severe infection","grade":"strong recommendation, low quality evidence","source":"patel-cdi-2024"},{"claim":"Oral vancomycin or fidaxomicin for severe infection","grade":"strong recommendation, low quality evidence","source":"patel-cdi-2024"},{"claim":"Fidaxomicin for recurrence","grade":"conditional recommendation, moderate quality evidence","source":"patel-cdi-2024"},{"claim":"No routine faecal microbiota transplantation","grade":"strong recommendation, low quality evidence","source":"patel-cdi-2024"},{"claim":"No routine probiotics for prevention","grade":"conditional recommendation, low quality evidence","source":"patel-cdi-2024"},{"claim":"No routine probiotics for treatment","grade":"conditional recommendation, low quality evidence","source":"patel-cdi-2024","quote":"We suggest that probiotics not be used routinely for the treatment of CDI in pediatric patients with cancer and HCT recipients"},{"claim":"No routine monoclonal antibodies (bezlotoxumab)","grade":"conditional recommendation, moderate quality evidence","source":"patel-cdi-2024"}],"sources":[{"key":"patel-cdi-2024","label":"Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update","publisher":"International panel (Pediatric Oncology Group of Ontario), eClinicalMedicine","year":2024,"url":"https://europepmc.org/article/PMC/PMC11046252","doi":"10.1016/j.eclinm.2024.102604","gradingScheme":"GRADE: recommendations strong or conditional, evidence high, moderate, low or very low, printed after each recommendation; good practice statements are ungraded.","read":"full-text","accessed":"2026-11-11"},{"key":"cog-cdi-2024","label":"Guideline for the Management of Clostridioides difficile Infection in Pediatric Patients with Cancer and Hematopoietic Cell Transplantation Recipients (COG endorsement, version date 10 September 2024)","publisher":"Children's Oncology Group","year":2024,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_C_diff_Guideline_Document_10SEPT2024-new-logo.pdf","gradingScheme":"Reprints the source guideline's GRADE strength and quality for each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"idsa-shea-2021","label":"Clinical Practice Guideline by IDSA and SHEA: 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults","publisher":"IDSA and SHEA, Clinical Infectious Diseases","year":2021,"url":"https://europepmc.org/abstract/MED/34164674","doi":"10.1093/cid/ciab549","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The guideline sets no paediatric criteria for diagnosing C. difficile infection (which test, and which symptoms); the panel names this as needed.","Doses and treatment length are not given in the guideline and come from local formularies.","Most evidence is from adult trials; few trials include neutropenic children.","The adult IDSA and SHEA 2021 focused update was read only as an abstract, which does not state its recommendations, so how adult and paediatric advice differ on fidaxomicin and metronidazole is not set out here."]},{"id":"consent-and-education-before-anticancer-treatment","kind":"protocol","name":"Consent and education before anticancer treatment","aka":["chemotherapy consent","SACT consent","informed consent for chemotherapy","chemotherapy education session","pre-chemotherapy teaching","chemo school","new patient chemotherapy talk"],"tldr":"Before cancer drug treatment starts, you should be told what the treatment is for, what it involves, its likely benefits and side effects, what the other options are (including no treatment), and given time to decide. You should also get written information and a 24-hour number, and be told which symptoms mean you must call straight away.","summary":"Consent is a process, not a form. The GMC's standard (2020, updated 2026) sets seven principles: patients are involved in decisions, given the information they need and the time and support to understand it; professionals find out what matters to the patient and share the benefits and harms of the options and reasonable alternatives, including taking no action; adults are presumed to have capacity. Information usually includes diagnosis and prognosis and their uncertainties, the options, what each involves and the likely benefits, risks of harm and chance of success, with recognised risks anyone in the patient's position would want to know, tailored to the individual. A consent form is a useful prompt and record but no substitute for dialogue, and the decision should be reviewed immediately before treatment and regularly during it. NICE NG197 adds time to decide, teach-back and a written summary afterwards.\n\nThe cancer-specific standard is ASCO-ONS (2024): an organisational policy for consent for anticancer treatment by any route, consent documented before the regimen starts, and education, verbal and written or electronic and in the patient's preferred language, before the first dose of each treatment plan. Its minimum content: diagnosis; goals of treatment (cure, longer life or symptom control); duration, schedule, missed doses, drug names, supportive medicines and interactions; current medicines including herbal products; short- and long-term side effects including infertility; pregnancy prevention; symptoms needing a call or urgent care; when to stop oral treatment; safe handling at home; follow-up; contact details and when to call; and the missed-appointment policy, involving family and carers as needed. BOPA (2025) asks pharmacists to confirm consent at the first-cycle check and that consent is taken by a trained professional.","asOf":"2026-11-11","links":[],"tags":[],"related":["oral-anticancer-medicines-at-home","sact-prescribing-and-pharmacy-verification","anticancer-drug-interaction-review"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["informed-consent"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before treatment, the team should explain why you are having it, what it is like, the risks and the other choices, and give you time and written information. You can ask questions and change your mind.","domain":"consent-and-communication","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit"]},"population":"Adults starting a new course of systemic anticancer treatment by any route; children and young people need assent and the consent of those with parental responsibility (ASCO-ONS and GMC, which points to its separate guidance for under-18s). People who may lack capacity are assessed and decided for under the law that applies where they are.","trigger":"A new anticancer treatment plan is proposed, including a change to a new regimen.","steps":[{"action":"Share the information the person wants or needs: diagnosis and outlook and their uncertainties, the options including no treatment, what each involves, and its likely benefits, harms and chance of success","why":"A decision is only informed if the person knows the alternatives and what matters about each.","source":"gmc-2020","quote":"You must give patients the information they want or need to make a decision."},{"action":"Tailor the discussion of risks to what matters to the person, always including recognised risks that anyone in their position would want to know","why":"Listing every possible side effect overwhelms; leaving out ones that matter to the person is not informed consent.","source":"gmc-2020","quote":"Recognised risks of harm that you believe anyone in the patient’s position would want to know."},{"action":"State the goal of treatment plainly: cure, longer life or relief of symptoms","why":"People often overestimate the chance of cure; the aim changes how much side effect is worth accepting.","source":"asco-ons-2024","quote":"Goals of treatment, that is, cure disease, prolong life, or reduce symptoms"},{"action":"Give the person the time and support they need to decide, and check understanding, for example by asking them to explain it back","why":"Rushed decisions are more often regretted, and teach-back shows what has really been understood.","source":"nice-ng197","quote":"1.2.12 Give people (and their family members, friends or carers, as appropriate) the time they need to make decisions about tests, treatments and interventions."},{"action":"Document informed consent before the regimen starts, following the organisation's standard process, and have consent taken by a trained professional","why":"A clear record, made by someone who knows the treatment, protects the person and lets every later checker confirm it.","source":"asco-ons-2024","quote":"Informed consent and assent (if applicable) for antineoplastic therapy, as appropriate to the treatment population, is documented before initiation of the regimen"},{"action":"Before the first dose, give verbal and written or electronic education in the person's preferred language, and record what was covered","why":"People remember little of a single conversation; written material in their own language lets them go back to it.","source":"asco-ons-2024","quote":"Patients are provided with verbal and written or electronic information as part of an education process before the first administration of antineoplastic agents in each treatment plan. The content of this educational material will be documented and should be administered in the patient's preferred language."},{"action":"Cover short- and long-term side effects, including effects on fertility, and pregnancy prevention","why":"Some effects, such as infertility, can only be prevented before treatment starts.","source":"asco-ons-2024","quote":"Potential long-term and short-term adverse effects of therapy, including infertility risks for appropriate patients"},{"action":"Tell the person which symptoms mean they must call the team or seek urgent care, and give contact details, with when and whom to call","why":"Infection and other emergencies during treatment need treating within hours.","source":"asco-ons-2024","quote":"Symptoms or adverse effects that require the patient to contact the health care organization or to seek immediate attention"},{"action":"Explain safe handling of medicines and body fluids at home, including storage, disposal and spills","why":"Anticancer drugs at home can harm carers, children and pets if handled or thrown away wrongly.","source":"asco-ons-2024","quote":"Procedures for safe handling medications in the home, including disposal of waste, handling body secretions, storage, safe handling, and management of unused medication, and clean-up of drug spills"},{"action":"Include family or carers in the education according to the person's ability to manage treatment, and match teaching to their needs and readiness","why":"Carers often give oral medicines and spot problems first.","source":"asco-ons-2024","quote":"Education includes family, caregivers, or others on the basis of the patient's ability to assume responsibility for managing therapy."},{"action":"Review the decision immediately before treatment and regularly during a course, giving the chance to ask questions","why":"Consent can change as side effects, results and circumstances change.","source":"gmc-2020","quote":"You should review a patient’s decision immediately before providing treatment or care and, if treatment is ongoing, make sure there are clear arrangements in place to review decisions regularly, allowing patients opportunity to ask questions and discuss any concerns."}],"bestInClass":{"statement":"Consent as a dialogue built on what matters to the person, covering the options including no treatment and the recognised risks anyone would want to know, with time to decide and a review before and during treatment (GMC 2020, updated 2026; NICE NG197). For anticancer treatment, ASCO-ONS (2024) adds documented consent before the regimen starts and a defined minimum of verbal and written education in the person's language before the first dose, including goals of treatment, fertility, pregnancy prevention, when to call, safe handling at home and contact details. None of these standards is graded; ASCO-ONS rests on a systematic review and panel consensus.","sources":["gmc-2020","nice-ng197","asco-ons-2024","bopa-2025"]},"variants":[{"name":"Consent form as the record (UK practice)","differs":"Uses a written consent form, often specific to the regimen, signed before the first cycle and checked by the pharmacist at verification.","evidence":"The GMC says forms are a helpful prompt and record that make review easier but are no substitute for a meaningful dialogue. BOPA requires the pharmacist to check consent before the first cycle. Regimen-specific UK forms were not read.","sources":["gmc-2020","bopa-2025"]}],"grades":[],"sources":[{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and ONS (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded; developed from a systematic review (2015 to 2023), expert panel consensus and public comment.","read":"full-text","accessed":"2026-11-11"},{"key":"gmc-2020","label":"Decision making and consent (professional standards, in effect 9 November 2020, last updated 3 August 2026)","publisher":"General Medical Council","year":2020,"url":"https://www.gmc-uk.org/professional-standards/the-professional-standards/decision-making-and-consent","gradingScheme":"Professional standards; 'must' marks a duty and 'should' an explanation of how to meet it. Not graded by evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng197","label":"Shared decision making (NG197), recommendations","publisher":"NICE","year":2021,"url":"https://www.nice.org.uk/guidance/ng197/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["None of the standards read is graded, and no trial shows which form of pre-treatment education prevents most harm.","The GMC standard binds UK doctors and associates; nurses and pharmacists who take consent follow their own regulators' codes, which were not read.","Healthcare Improvement Scotland's guidance on consent for SACT and UK regimen-specific consent forms were not read.","Fertility preservation is named here only as a topic to raise; the referral pathway belongs to a fertility protocol."]},{"id":"radiotherapy-consent","kind":"protocol","name":"Consent for radiotherapy: who takes it, when, and what it must cover","aka":["radiotherapy consent form","consent for radiation therapy","RCR consent forms","site-specific radiotherapy consent","informed consent radiotherapy","Montgomery consent","e-consent radiotherapy"],"tldr":"Before radiotherapy starts you are asked to agree to it in writing, after someone trained in your kind of treatment has explained what it aims to do, its likely and rare side effects, the other options including no treatment, and anything that matters to you in particular. You should have time to think, you are asked to confirm before treatment begins, and you can change your mind at any point.","summary":"In the UK, consent for radiotherapy follows the GMC's Decision making and consent (2020) and the Montgomery judgment (2015): the patient must be told of any material risk, judged by what a reasonable person in their position, or this particular patient, would think significant, and of reasonable alternatives including no treatment. The Royal College of Radiologists (RCR) publishes national site-specific consent forms (most sites, plus SRS, brachytherapy and a blank form; current versions from 2025, with Welsh-language versions), written with lawyers, patients and risk communication specialists, which list expected (50% to 100%), common (10% to 50%), less common (under 10%) and rare (under 1%) early and late side effects. The RCR recommends but does not mandate them.\n\nThe RCR implementation guidance (2021): consent is taken by a consultant clinical oncologist, a trained clinical oncology doctor, or an expert radiographer or specialist nurse trained in consent for that site; it is documented before the first fraction, ideally days before; it is confirmed before treatment starts (for example at planning); a patient in doubt is offered a second consultation; consent is renewed after a material change such as a new site or diagnosis; and withdrawal is documented. The forms are for adults with capacity only, not for children or adults who lack capacity. Patient-specific risks (job, health, activities, previous radiotherapy, radiosensitising drugs) are written in, and alternatives including no treatment are recorded in the notes. Separately, IR(ME)R 2017 requires employers' procedures to give the person, wherever practicable and before exposure, adequate information on the benefits and risks of the radiation dose. The RCR endorses no commercial e-consent platform and warns that some do not transfer the full signed form to the electronic record.","asOf":"2026-11-11","links":[],"tags":[],"related":["radiotherapy-pregnancy-and-breastfeeding-enquiry","radiotherapy-patient-identification-and-time-out"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["astro"],"pathways":[],"terms":["informed-consent"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before radiotherapy a doctor, or a specially trained radiographer or nurse, explains the treatment, its side effects and the other choices, including not having it. You sign a form and get a copy. You can ask for more time or a second talk, and you can stop at any time.","domain":"consent-and-communication","setting":{"who":["doctor","radiographer","nurse","patient-or-carer"],"where":["outpatient-clinic","radiotherapy-department"]},"population":"Adults with capacity having external beam radiotherapy or brachytherapy, as the RCR forms are scoped (the forms say over 16). Children and young people, and adults who lack capacity, need the hospital's alternative consent process and are not covered by the RCR forms. The pregnancy check is a separate protocol.","trigger":"A decision to offer a course of radiotherapy; again at the planning appointment or before the first fraction; and whenever the planned treatment changes materially.","steps":[{"action":"Have consent taken by someone trained and experienced in this treatment site: a consultant clinical oncologist, a clinical oncology doctor trained in consent for that plan, or an expert radiographer or specialist nurse trained in consent for that site","why":"The person explaining has to know the treatment well enough to answer your questions about it.","source":"rcr-implementation-2021","quote":"Consent should be taken by a healthcare professional with sufficient training and experience who is also experienced in the management of the radiotherapy treatment site and protocol."},{"action":"Discuss the alternatives, including no treatment, before taking consent, and record that discussion in the notes","why":"Agreeing to a treatment only means something if you know what else you could choose.","source":"rcr-implementation-2021","quote":"In light of the Montgomery judgment it is essential that alternative treatments are discussed with the patient prior to the process of taking consent."},{"action":"Explain every risk that a reasonable person in the patient's position, or this patient, would think significant, even if it is rare","why":"The law in the UK since 2015 is that you are told what matters to you, not only what doctors usually mention.","source":"rcr-development-2021","quote":"The test of materiality is whether, in the circumstances of the particular case, a reasonable person in the patient’s position would be likely to attach significance to the risk, or the doctor is or should reasonably be aware that the particular patient would be likely to attach significance to it."},{"action":"Use the site-specific form for this treatment, and write in risks particular to this person (their job, health, activities, earlier radiotherapy, radiosensitising medicines)","why":"A side effect that is minor for most people can matter a great deal to one person, such as a voice change for a singer.","source":"rcr-implementation-2021","quote":"Discussions should be personalised and must include any specific risks that are likely to be significant to that patient."},{"action":"Give information on the benefits and risks of the radiation dose before the exposure, wherever practicable, as the department's IR(ME)R procedures require","why":"UK radiation law requires that people know why they are being exposed and what the dose may do.","source":"irmer-2017","quote":"providing that wherever practicable, and prior to an exposure taking place, the individual to be exposed or their representative is provided with adequate information relating to the benefits and risks associated with the radiation dose from the exposure;"},{"action":"Take and document consent before the first treatment, leaving days, not hours, to reconsider where possible (emergencies such as spinal cord compression excepted)","why":"Time to think, talk to family and come back with questions makes the decision your own.","source":"rcr-implementation-2021","quote":"Ideally there should be time (measured in days rather than hours) for the patient to reconsider their decision to undergo treatment before the first fraction is administered."},{"action":"When consent was taken in advance, ask the person to confirm it before treatment starts, for example at the planning appointment, and record this on the form","why":"Weeks may pass between the clinic and the first treatment; a person may have new questions or a change of mind.","source":"rcr-implementation-2021","quote":"When consent is taken in advance of treatment the patient should be asked to confirm consent before the start of treatment, for example, at their planning appointment."},{"action":"If the person has doubts, offer a second consultation with a suitably trained professional before treatment begins","why":"Doubts deserve a proper conversation, not a signature under pressure.","source":"rcr-implementation-2021","quote":"Where a patient expresses doubt about proceeding with the treatment, the opportunity to have a second consultation with a suitably trained and experienced healthcare professional prior to commencing treatment should be offered."},{"action":"Seek consent again if the treatment changes materially from what was discussed, such as a different site or a new diagnosis","why":"Agreement to one treatment is not agreement to a different one.","source":"rcr-implementation-2021","quote":"Renewed consent should be sought where there is material change in the radiotherapy which will be delivered, which was not discussed at the initial consent."},{"action":"Accept withdrawal of consent at any time, discuss it, and record it fully","why":"You can stop treatment whenever you choose; the team should talk through what stopping means and write it down.","source":"rcr-implementation-2021","quote":"A patient can withdraw consent at any time. Where consent is withdrawn this should be discussed and documented in full in the patient notes."},{"action":"Do not use the RCR adult forms for children or for adults who lack capacity; use the hospital's alternative process","why":"Decisions for children and for adults who cannot decide for themselves follow different legal rules.","source":"rcr-implementation-2021","quote":"The RCR SSR consent forms should not be used in situations where a patient lacks capacity. In this situation the hospital should provide an appropriate alternative form. The RCR SSR consent forms should not be used for children/minors who are undergoing radiotherapy."},{"action":"Give the person a copy of the completed form and file it in their record; have a local way for people to opt out of their treatment data being used for research, audit and teaching","why":"You keep a record of what you agreed to, and you have a say in how your information is used beyond your care.","source":"rcr-implementation-2021","quote":"It is important that departments also have a local policy for patients to opt out of the use of information collected during radiotherapy being used in research, audit and teaching."},{"action":"If an electronic consent system is used, check locally that it reproduces the current RCR form exactly and transfers the whole signed form into the electronic record","why":"Some e-consent systems have been found to drop important details when the form is saved to the patient record.","source":"rcr-econsent-2026","quote":"There is some evidence showing that with certain commercial e-consent forms, critical details of the e-consent are not transcribed when the signed e-consent is transferred to the patient’s electronic patient record."}],"bestInClass":{"statement":"In the UK: consent by a professional trained in that site, after a discussion of alternatives including no treatment and of every risk material to this patient (Montgomery 2015; GMC 2020), recorded on the RCR national site-specific form with patient-specific risks written in, taken days before the first fraction where possible, confirmed before treatment begins, renewed after any material change, and withdrawable at any time (RCR implementation guidance 2021; forms reissued 2025). IR(ME)R 2017 separately requires information on the benefits and risks of the radiation dose before exposure wherever practicable. These are consensus and legal standards; no trial compares consent processes for radiotherapy on outcomes. Practice outside the UK (the ACR-ASTRO practice parameter in the United States) could not be read here.","sources":["rcr-implementation-2021","rcr-development-2021","rcr-forms-page","irmer-2017"]},"variants":[{"name":"Locally written consent forms instead of the RCR national forms","differs":"Many UK centres had their own site-specific forms before the national set; the RCR found no consensus on which side effects they listed. The RCR forms are recommended, not mandatory, and adoption goes through each hospital's consent or governance committee.","evidence":"RCR Development (2021): 54% of centres had a site-specific consent form for prostate cancer, with no consensus between them on the side effects included.","sources":["rcr-development-2021","rcr-implementation-2021"]},{"name":"Electronic consent platforms","differs":"Commercial e-consent systems present the consent form on a screen and save it to the electronic record. The RCR endorses none of them, says it knows of none that faithfully reproduces its forms, and asks organisations using them to risk-assess content accuracy, transfer to the record, updates and version control.","evidence":"RCR position statement (2026), citing some evidence that critical details are lost on transfer to the electronic record.","sources":["rcr-econsent-2026"]},{"name":"Sending the form to the patient before the appointment","differs":"The RCR FAQs discuss sending forms in advance; the forms carry the patient's own initials on each page of side effects and a statement that alternatives were discussed.","evidence":"No trial; RCR practice advice.","sources":["rcr-forms-page","rcr-breast-form-2025"]}],"grades":[{"claim":"The RCR recommends but does not mandate its site-specific forms","grade":"ungraded (college guidance)","source":"rcr-implementation-2021","quote":"The RCR supports and advises that hospitals use the SSR consent forms for radiotherapy. However, the RCR does not mandate the use of these forms."},{"claim":"A form does not replace the conversation","grade":"ungraded (college guidance)","source":"rcr-implementation-2021","quote":"The consent form does not replace the need for a conversation and dialogue around the consent process."},{"claim":"Information on benefits and risks of the dose before exposure","grade":"statutory requirement (IR(ME)R 2017, Schedule 2)","source":"irmer-2017"},{"claim":"The RCR endorses no commercial e-consent platform","grade":"ungraded (position statement)","source":"rcr-econsent-2026","quote":"The RCR does not currently endorse ANY commercial e-consent platform for the delivery of radiotherapy consent forms."}],"sources":[{"key":"rcr-implementation-2021","label":"National standard site-specific radiotherapy consent forms: Implementation","publisher":"The Royal College of Radiologists","year":2021,"url":"https://www.rcr.ac.uk/media/1econldf/implementation-of-the-national-site-specific-radiotherapy-consent-forms.pdf","gradingScheme":"College guidance; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"rcr-development-2021","label":"National standard site-specific radiotherapy consent forms: Development (quotes Montgomery v Lanarkshire Health Board [2015] UKSC 11 and GMC Decision making and consent 2020)","publisher":"The Royal College of Radiologists","year":2021,"url":"https://www.rcr.ac.uk/media/45jjjpaj/development-of-the-national-site-specific-radiotherapy-consent-forms.pdf","gradingScheme":"College guidance; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"rcr-forms-page","label":"National radiotherapy consent forms (current forms, FAQs and supporting documents)","publisher":"The Royal College of Radiologists","year":2025,"url":"https://www.rcr.ac.uk/our-services/management-service-delivery/national-radiotherapy-consent-forms/","read":"full-text","accessed":"2026-11-11"},{"key":"rcr-breast-form-2025","label":"Radiotherapy consent form for breast cancer, January 2025 version 4","publisher":"The Royal College of Radiologists","year":2025,"url":"https://www.rcr.ac.uk/media/ajnh3df2/250116_dc23013b-rcr-breast-cancer-consent-form-5.pdf","read":"full-text","accessed":"2026-11-11"},{"key":"rcr-econsent-2026","label":"Position Statement on radiotherapy consent forms and e-consent","publisher":"The Royal College of Radiologists","year":2026,"url":"https://www.rcr.ac.uk/news-policy/latest-updates/rcr-position-statement-on-radiotherapy-consent-forms-and-e-consent/","read":"full-text","accessed":"2026-11-11"},{"key":"irmer-2017","label":"The Ionising Radiation (Medical Exposure) Regulations 2017 (SI 2017/1322), Schedule 2: Employer's procedures","publisher":"UK legislation (legislation.gov.uk)","year":2017,"url":"https://www.legislation.gov.uk/uksi/2017/1322/schedule/2/made","gradingScheme":"Statute; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"gmc-consent-2020","label":"Decision making and consent","publisher":"General Medical Council","year":2020,"url":"https://www.gmc-uk.org/professional-standards/the-professional-standards/decision-making-and-consent","read":"not-reachable","accessed":"2026-11-11"},{"key":"acr-astro-practice-parameter","label":"ACR-ASTRO Practice Parameter for Radiation Oncology","publisher":"American College of Radiology and American Society for Radiation Oncology","year":2023,"url":"https://www.acr.org/Clinical-Resources/Clinical-Tools-and-Reference/Practice-Parameters-and-Technical-Standards","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The GMC's Decision making and consent (2020) could not be read: the GMC site returned 403 to a script. Its content appears only as the RCR documents quote it.","The Montgomery judgment was not read from the court's own text; its words are quoted as the RCR Development document gives them.","Consent practice outside the UK was not read: the ACR-ASTRO practice parameter served an HTML shell to a script, and no European consensus on radiotherapy consent was found.","No trial evidence was found comparing consent processes for radiotherapy (forms, timing, e-consent, decision aids) on understanding, regret or outcomes; the standards here are legal and consensus.","Consent for children and for adults who lack capacity is outside the RCR forms and is not detailed here.","The RCR implementation and development documents date from April 2021; the forms themselves were reissued in 2025, and no newer version of the implementation guidance was found on the RCR page."]},{"id":"contrast-reaction-history-and-premedication","kind":"protocol","name":"Contrast scans after a previous contrast reaction: allergy referral, switching agent and premedication","aka":["contrast allergy","contrast premedication","steroid premedication before CT","allergy to CT dye","iodine contrast allergy","gadolinium allergy","contrast hypersensitivity","recurrent contrast reaction prevention"],"tldr":"If you have reacted to a scan dye before, tell the team every time, and ask that the name of the dye goes in your records. European radiologists now advise using a different dye, chosen with an allergy specialist where possible, rather than taking steroid tablets beforehand, which have not been shown to prevent serious reactions. A needed scan should not be refused because of an old reaction.","summary":"ESUR (2025 paper; 2026 handbook) has moved away from routine premedication. Corticosteroid and H1-antihistamine premedication has no evidence of reducing severe immediate reactions and weak, conflicting evidence for mild or moderate ones; it is not recommended after non-immediate reactions; and in comparative studies changing the culprit agent was more effective (in one multivariate analysis, OR 0.329 for recurrence after changing the iodinated agent against 0.907, not significant, for steroid premedication). The sequence is: document the agent, dose, timing and severity of the index reaction; measure serum tryptase within 4 hours of a moderate or severe immediate reaction (and a baseline at 24 hours or more); refer moderate and severe reactions, reactions to more than one agent and recurrent reactions to a drug allergy specialist for skin testing of the culprit and alternatives, ideally within 6 months; and for the next scan consider unenhanced or other imaging but never deny a well-indicated contrast examination. When contrast is given, use the agent the allergist advises, or a different one if the culprit is known, and observe for at least 30 minutes with the line in place. Elective scans after moderate or severe reactions wait for the allergy result. Premedication remains optional only for an emergency after a severe reaction to an unknown agent (ESUR quoting EAACI: prednisolone 50 mg IV or equivalent and clemastine 2 mg IV or equivalent, at least 30 minutes before). After a severe non-immediate skin reaction with danger signs, the whole class (all iodinated or all gadolinium agents) is avoided. North American practice, in the ACR Manual, still includes corticosteroid premedication regimens; that manual could not be read here.","asOf":"2026-11-11","links":[],"tags":[],"related":["iodinated-contrast-kidney-and-metformin"],"cancers":[],"sections":[],"technologies":["iodinated-contrast-media","gadolinium-based-contrast-agents","ct","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Had a reaction to scan dye before? Tell the team. They should note which dye it was, may send you to an allergy clinic, and will usually use a different dye next time. You will be watched for at least 30 minutes after the dye with a drip line left in.","domain":"screening-diagnostics","setting":{"who":["doctor","radiographer","nurse","patient-or-carer"],"where":["outpatient-clinic","ward","emergency-department"]},"population":"Adults with a history of a hypersensitivity reaction to an iodine-based or gadolinium-based contrast agent who need a contrast-enhanced scan. Children are outside the ESUR paper (it excluded paediatric studies). Treating a reaction as it happens is a separate emergency protocol; the ESUR handbook covers it.","trigger":"A contrast-enhanced CT or MRI is requested for someone whose record or history mentions a previous contrast reaction.","steps":[{"action":"Find out which contrast agent caused the previous reaction, how severe it was and how soon it came on, and record it in the allergy section of the health record","why":"Knowing the exact dye and how bad the reaction was decides what is safe next time.","source":"esur-2026","quote":"If the patient has experienced a previous hypersensitivity reaction, identify the specific agent that elicited the previous reaction, and if the injection is mandatory, choose an alternative contrast agent."},{"action":"After a moderate or severe immediate reaction, take blood for serum tryptase within 4 hours, and again after 24 hours or more as a baseline","why":"Tryptase shows whether the reaction was a true allergic-type release from mast cells, which the allergy clinic needs to know.","source":"esur-2026","quote":"Measure serum tryptase within 4 hours from the start of all moderate to severe immediate hypersensitivity reactions to contrast agents."},{"action":"Refer moderate and severe reactions, reactions to more than one agent, and any repeat reaction to a drug allergy specialist, naming the agent used","why":"Skin testing can show which dyes are safe for this person, which is better than guessing.","source":"esur-2025-hsr-part2","quote":"Serum tryptase should be measured within 1–4 h after a moderate or severe reaction, and at least all moderate or severe hypersensitivity reactions should be referred to an allergologist."},{"action":"Consider an unenhanced scan or another kind of imaging, but do not refuse a contrast scan that is clearly needed when there is no alternative","why":"An old reaction should not cost someone a scan their cancer care depends on.","source":"esur-2026","quote":"Never deny a patient a clinically well-indicated enhanced examination if alternative imaging strategies are not available."},{"action":"For an elective scan after a moderate or severe reaction, wait for the allergy assessment and use the agent it advises","why":"The allergy result is the most reliable guide to a safe dye.","source":"esur-2026","quote":"Postpone imaging to wait for the results of the allergy analysis"},{"action":"Where no allergy advice is available, use a different contrast agent from the one that caused the reaction, rather than relying on premedication","why":"Switching to a different dye prevented repeat reactions better than steroid tablets in comparative studies.","source":"esur-2025-hsr-part2","quote":"Changing from the culprit contrast agent to another molecule with differing side-chains is more effective than premedication."},{"action":"Do not give routine premedication; reserve it for an emergency scan after a severe reaction to an unknown agent","why":"Steroids and antihistamines beforehand have not been shown to prevent serious reactions, and steroids can raise blood sugar.","source":"esur-2025-hsr-part2","quote":"Premedication is optional in emergency situations where an unidentified culprit CM led to a severe HR, as recommended by the EAACI"},{"action":"If premedication is used in that emergency, give prednisolone 50 mg IV (or equivalent) and clemastine 2 mg IV (or equivalent) at least 30 minutes before, with a resuscitation-trained team member nearby","why":"This is the short intravenous regimen ESUR prints from the European allergy guideline for when there is no time for testing.","source":"esur-2026","quote":"Consider administration of premedication (EAACI guidelines)"},{"action":"After the contrast, keep the person under observation for at least 30 minutes with the drip line still in","why":"Most immediate reactions start within this time, and the line lets treatment be given at once.","source":"esur-2026","quote":"When the contrast medium is administered: observe the patient at least 30 minutes with IV line in place"},{"action":"After a severe delayed skin reaction with danger signs (blistering, skin loss, mouth or eye involvement, fever or organ involvement), do not give any agent of the same class again; choose other imaging and refer urgently","why":"Severe delayed skin reactions can be life-threatening and can recur with related dyes.","source":"esur-2026","quote":"Avoid all iodine-based contrast media after a severe non-immediate hypersensitivity reaction to an iodine-based contrast medium"},{"action":"After a mild or moderate delayed reaction, give the person written advice on what to do if it happens again","why":"Delayed reactions, usually a rash, can appear hours to days later, after the person has gone home.","source":"esur-2026","quote":"Give the patient written instructions for a possible repeat non-immediate hypersensitivity reaction"}],"bestInClass":{"statement":"ESUR 2025/2026: document the culprit agent and severity, measure tryptase within 4 hours of a moderate or severe immediate reaction, refer to a drug allergy specialist for testing of the culprit and alternatives, and use the agent the allergist advises or, without that, a different agent; observe for at least 30 minutes with the line in place; never deny a well-indicated contrast examination. No routine premedication: there is no evidence that it reduces severe immediate reactions, the evidence for mild and moderate ones is weak and conflicting, and it is not recommended after non-immediate reactions; it stays optional for an emergency after a severe reaction to an unknown agent, as EAACI recommends. The ACR Manual on Contrast Media, the main North American reference, keeps corticosteroid premedication regimens; it could not be read here, so its exact recommendations are not stated.","sources":["esur-2026","esur-2025-hsr-part2"]},"variants":[{"name":"Corticosteroid and antihistamine premedication before each contrast scan","differs":"Gives oral or intravenous corticosteroid, often with an H1-antihistamine, before the contrast to anyone with a previous reaction, frequently scaled to the severity of that reaction, and often with the same contrast agent.","evidence":"ESUR (2025): the regimens date from the era of high-osmolar contrast and early low-osmolar agents and remain widely used; there are no comparative randomised trials; premedication may mainly reduce mild reactions and does not significantly affect severe ones; in a large retrospective study recurrence was 19% (80 of 423) with the same agent and steroid premedication against 3% (10 of 322) with a different agent and no premedication (OR 0.14). Corticosteroids can raise blood glucose transiently. The ACR Manual's current regimens could not be read.","sources":["esur-2025-hsr-part2","acr-manual-contrast"]}],"grades":[{"claim":"Routine premedication not recommended (no grade printed)","grade":"ungraded consensus","source":"esur-2025-hsr-part2","quote":"In summary, there is no evidence that premedication reduces the risk of severe IHR to CM."},{"claim":"Change the culprit agent rather than premedicate (no grade printed)","grade":"ungraded consensus","source":"esur-2025-hsr-part2","quote":"Comparative studies have shown that an alternative ICM was more effective than premedication in preventing HR"},{"claim":"Emergency premedication regimen quoted from EAACI","grade":"ungraded (handbook)","source":"esur-2026","quote":"50 mg prednisolone IV (or equivalent) – ≥ 30min before contrast administration"}],"sources":[{"key":"esur-2026","label":"Contrast Media Safety Committee Guidelines 2026: hypersensitivity reactions to contrast agents (in adults)","publisher":"European Society of Urogenital Radiology (ESUR) Contrast Media Safety Committee","year":2026,"url":"https://www.esur.org/wp-content/uploads/2026/10/Guidelines-2026.pdf","gradingScheme":"The handbook prints no grades.","read":"full-text","accessed":"2026-11-11"},{"key":"esur-2025-hsr-part2","label":"Hypersensitivity reactions to contrast media: Part 2. Prevention of recurrent hypersensitivity reactions in adults. Updated guidelines by the ESUR Contrast Media Safety Committee","publisher":"ESUR Contrast Media Safety Committee (van der Molen et al., European Radiology)","year":2025,"url":"https://doi.org/10.1007/s00330-025-11676-0","doi":"10.1007/s00330-025-11676-0","gradingScheme":"Recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"acr-manual-contrast","label":"ACR Manual on Contrast Media","publisher":"American College of Radiology","year":2024,"url":"https://www.acr.org/Clinical-Resources/Contrast-Manual","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-pu-contrast-switch-agent-after-reaction"],"gaps":["The ACR Manual on Contrast Media could not be read (the address served a JavaScript shell to a script), so the North American premedication regimens and their indications are not stated here; the page names the disagreement without the detail.","There are no randomised trials comparing switching agent with premedication; the evidence for switching is retrospective and observational (ESUR 2025).","Drug allergy services able to test contrast agents are not available everywhere; ESUR makes referral after mild reactions optional where capacity is short.","Neither ESUR document grades its recommendations.","Children are not covered by the ESUR paper."]},{"id":"crs-grading-and-management","kind":"protocol","name":"Cytokine release syndrome after CAR T-cell therapy: ASTCT grading, tocilizumab and steroids","aka":["CRS management","cytokine release syndrome grading","ASTCT CRS grading","tocilizumab for CRS","CAR-T fever"],"tldr":"After CAR T-cell therapy, the immune cells can release a flood of chemical messengers, causing fever, low blood pressure and breathing trouble: cytokine release syndrome. Any fever after CAR T-cell therapy needs the treating centre at once. Teams grade it from 1 to 4 and treat with tocilizumab and, if needed, steroids; infection is treated at the same time because the two look alike.","summary":"CRS usually starts within 1 to 2 weeks of infusion (median 2 to 3 days for tisagenlecleucel and axicabtagene ciloleucel, sometimes within 24 hours) (SITC 2020). ASTCT 2019 grading: fever of 38 °C or more not attributable to another cause, with grade set by the worse of hypotension (grade 2 no vasopressor, grade 3 one vasopressor with or without vasopressin, grade 4 several) and hypoxia (grade 2 low-flow oxygen up to 6 L/min, grade 3 high-flow, face mask or non-rebreather, grade 4 positive pressure). Once antipyretics, tocilizumab or steroids are given, fever is no longer needed to grade.\n\nSITC 2020: tocilizumab may be considered at grade 2 in adults (LE: 3) and earlier for older or comorbid patients; in children, at grade 3 (LE: 3). If one dose does not work, give steroids with a second dose (LE: 3); after two doses, consider anakinra, siltuximab or high-dose methylprednisolone (LE: 4). EBMT/JACIE 2019 limits tocilizumab to four doses per episode and names siltuximab as second line. Presume infection and treat it while investigating; neutropenic fever antibiotics are not delayed for a presumed CRS. Daily blood count, metabolic panel, magnesium, phosphate, CRP and ferritin while in hospital; cardiac assessment for prolonged severe CRS; hold G-CSF and avoid GM-CSF during CRS.\n\nThe ASTCT 2026 update to the grading and the 2022 EBMT/JACIE/EHA recommendations were read only as abstracts.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t","acute-oncology"],"related":["febrile-neutropenia-first-hour"],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["tocilizumab","siltuximab","dexamethasone","axicabtagene-ciloleucel","tisagenlecleucel","lisocabtagene-maraleucel","brexucabtagene-autoleucel","idecabtagene-vicleucel","ciltacabtagene-autoleucel","obecabtagene-autoleucel","methylprednisolone"],"companies":[],"institutions":["sitc"],"pathways":[],"terms":["crs","lymphoma-tx-crs-icans"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"CAR T-cell therapy can cause a high temperature and low blood pressure in the first weeks. Ring the treating hospital at once if you get a fever. There are drugs that work well when given early.","domain":"cell-therapy-toxicity","setting":{"who":["nurse","doctor","pharmacist","patient-or-carer","multidisciplinary-team"],"where":["ward","intensive-care","outpatient-clinic","telephone-triage","home"]},"population":"Adults and children treated with CAR T-cell therapy or another immune effector cell therapy. Thresholds for tocilizumab differ for children (SITC). Cytokine release syndrome after bispecific T-cell engagers is graded on the same ASTCT scale but managed under product-specific step-up dosing protocols, not set out here.","trigger":"A temperature of 38 °C or more, low blood pressure, low oxygen saturation or feeling unwell in the weeks after CAR T-cell infusion.","steps":[{"action":"Before infusion, check CRP, ferritin, LDH, full blood count, a metabolic panel with magnesium and phosphate, and an echocardiogram or MUGA scan","why":"These give a baseline to compare with when CRS starts and show whether the heart can cope.","source":"sitc-iec-2020","quote":"Prior to CAR T cell therapy, treating physicians should order CRP, ferritin, lactate dehydrogenase (LDH), complete blood counts, comprehensive metabolic panel (including Mg/Pho), and transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) scan.","grade":"LE: 4"},{"action":"Make sure tocilizumab is on hand for every patient during the CRS risk period, with staff trained to give it","why":"Severe CRS can come on within hours, and the drug that treats it must be available on site.","source":"sitc-iec-2020","quote":"However, adequate staff and supportive care resources are an absolute prerequisite for proceeding with CAR T cell therapy, and it is important to ensure that tocilizumab—which, along with other interleukin (IL)-6-modulating agents, was used as an investigational intervention for COVID-19—is available for the management of CRS."},{"action":"Give the patient and carer written information on the symptoms of CRS and neurotoxicity and tell them to report any immediately","why":"Patients treated as outpatients, or after discharge, are the first to notice a fever.","source":"ebmt-2019","quote":"This should include information and education on the symptoms of CRS and serious neurological adverse reactions, the need to report any symptoms immediately to their treating physician and the need to remain in close proximity to the center in which the CAR T cells were administered for at least 4 weeks following the infusion."},{"action":"If treated as an outpatient, admit at the first sign of fever, low blood pressure or confusion","why":"CRS can worsen quickly and needs monitoring that only a ward can give.","source":"sitc-iec-2020","quote":"If patients are treated with CAR T cell products in the outpatient setting, admission should be strongly considered at the first signs of toxicity, including fever, hypotension or altered mental status."},{"action":"In hospital, check full blood count, metabolic panel, magnesium, phosphate, CRP and ferritin daily","why":"Trends help track CRS and spot organ damage, although no blood test alone decides treatment.","source":"sitc-iec-2020","quote":"In the inpatient setting, complete blood counts, comprehensive metabolic panel (CMP), Mg, Phos, CRP, and ferritin should be ordered daily for patients treated with CAR T cell therapies.","grade":"LE: 3"},{"action":"Call the doctor for a first temperature above 38 °C, heart rate over 120 or under 60, breathing rate over 25 or under 12, oxygen saturation under 92% on air, tremor or confusion","why":"These are the early warnings SITC names for physician review.","source":"sitc-iec-2020","quote":"Events requiring physician notification should include deviations from baseline in systolic blood pressure, heart rate of >120 or <60 beats/min, arrhythmia, respiratory rate of >25 or <12 breaths/min (or values outside the normal range in pediatric patients), arterial oxygen saturation of <92% on room air, upward trend in blood creatinine levels or liver function tests, tremors or jerky movements in extremities, altered mental status, and first occurrence of temperature greater than 38°C, as per the ASTCT definition of fever."},{"action":"Presume infection as well, and start empiric antibiotics by local protocol without waiting for CRS to be confirmed","why":"CRS and sepsis look alike and can happen together; many patients are also neutropenic.","source":"ebmt-2019","quote":"Empiric antimicrobial therapy based on symptoms and institutional protocols should not be delayed based on the presumption of CRS and clinicians should consider the prior duration of neutropenia."},{"action":"Grade CRS by the ASTCT scale: fever of 38 °C or more, graded by the worse of hypotension and hypoxia","why":"One shared scale lets teams and trials compare like with like and links grade to treatment.","source":"astct-2019","quote":"CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause."},{"action":"Once antipyretics, tocilizumab or steroids have been given, keep grading on blood pressure and oxygen alone","why":"Treatment can switch off the fever while CRS continues.","source":"astct-2019","quote":"In patients who have CRS then receive antipyretics or anti-cytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity."},{"action":"In adults with grade 2 CRS, consider tocilizumab, and consider it earlier for older patients or those with significant comorbidities","why":"Blocking IL-6 early can stop CRS from progressing; frailer patients tolerate low blood pressure and hypoxia less well.","source":"sitc-iec-2020","quote":"For elderly patients or patients with extensive comorbidities, tocilizumab should be considered earlier in the course of CRS. For adults who develop ASTCT grade 2 CRS, tocilizumab may be considered","grade":"LE: 3"},{"action":"In children, give tocilizumab at grade 3 CRS, and consider it for prolonged grade 2 or fever that cannot be tolerated","why":"SITC sets a different threshold for children based on paediatric experience.","source":"sitc-iec-2020","quote":"For pediatric patients, tocilizumab should be administered at ASTCT grade 3 CRS","grade":"LE: 3"},{"action":"If CRS does not improve after one dose of tocilizumab, give a corticosteroid with a second dose","why":"Steroids add a second, broader brake on the inflammation.","source":"sitc-iec-2020","quote":"In both adults and children, if CRS does not improve after 1 dose of tocilizumab, then steroids should be administered with a second dose of tocilizumab","grade":"LE: 3"},{"action":"If CRS does not improve after two doses of tocilizumab and steroids, consider anakinra, siltuximab or high-dose methylprednisolone","why":"Refractory CRS needs drugs that act on other parts of the cytokine cascade.","source":"sitc-iec-2020","quote":"If CRS does not improve after 2 doses of tocilizumab (and steroids), third-line agents, including anakinra, siltuximab, and high-dose methylprednisolone, should be considered","grade":"LE: 4"},{"action":"Do not give tocilizumab more than four times in one episode of CRS","why":"Further doses add risk without evidence of benefit; EBMT names siltuximab as the second-line IL-6 drug.","source":"ebmt-2019","quote":"Tocilizumab should be administered no more than four times during one episode of CRS."},{"action":"For severe CRS lasting 72 hours without response, assess the heart with troponin and an echocardiogram","why":"Prolonged CRS can strain or inflame the heart.","source":"sitc-iec-2020","quote":"In patients with prolonged severe CRS (persisting for 72 hours without response to interventions), a cardiac assessment should be considered as described in the cardiology section; this may include measurement of cardiac biomarkers such as troponin or the performance of a TTE","grade":"LE: 4"},{"action":"Consider holding G-CSF during CRS and avoid GM-CSF","why":"Growth factors may feed the inflammation while CRS is active.","source":"sitc-iec-2020","quote":"Consider holding G-CSF during CRS. GM-CSF should be avoided during CRS.","grade":"LE: 5"}],"bestInClass":{"statement":"Grade with the ASTCT 2019 consensus scale, which all the sources read here use; ASTCT published an update in 2026 whose changes could not be read. For treatment, SITC 2020 is the most detailed graded guideline that could be read: tocilizumab may be considered at grade 2 in adults and earlier in older or comorbid patients (LE: 3), at grade 3 in children (LE: 3), steroids with a second dose if one fails (LE: 3), and anakinra, siltuximab or high-dose methylprednisolone after two doses (LE: 4). EBMT/JACIE 2019 agrees on tocilizumab with steroids for severe cases, caps tocilizumab at four doses per episode and names siltuximab as second line. ASCO 2021 (abstract) treats prolonged or severe CRS with tocilizumab with or without a corticosteroid. All rest on expert consensus and non-randomised data; no randomised comparison of thresholds for tocilizumab was read.","sources":["astct-2019","astct-2026","sitc-iec-2020","ebmt-2019","asco-cart-2021"]},"variants":[{"name":"Tocilizumab for persistent fever in grade 1 (axicabtagene ciloleucel trial algorithm)","differs":"SITC reports that the algorithm from the axicabtagene ciloleucel trials advised considering tocilizumab 8 mg/kg intravenously for fever lasting more than 3 days and refractory in grade 1 CRS, and anti-IL-6 therapy for all grade 2 or higher CRS.","evidence":"A trial management algorithm reported in SITC's review, not a panel recommendation.","sources":["sitc-iec-2020"]},{"name":"Steroids only as second line (tisagenlecleucel trials)","differs":"Managed early CRS with tocilizumab and used corticosteroids only for refractory hypotension or severe symptoms not responding to the first dose.","evidence":"Trial practice reported by SITC.","sources":["sitc-iec-2020"]},{"name":"Pre-emptive or prophylactic tocilizumab (single-centre studies)","differs":"Gives tocilizumab, with or without dexamethasone, before CRS develops or at its earliest signs in high-risk patients. SITC cites a Fred Hutchinson study reporting a modest decrease in severe CRS and a Children's Hospital of Philadelphia study in children with high disease burden.","evidence":"Non-randomised studies reported by SITC; not recommended routinely.","sources":["sitc-iec-2020"]},{"name":"No regulatory requirement for on-site tocilizumab in the US since June 2025","differs":"The FDA ended the risk-management programme for BCMA- and CD19-directed autologous CAR T-cell products, removing the requirement that dispensing hospitals be specially certified and have on-site, immediate access to tocilizumab. SITC 2020 still treats tocilizumab availability as a prerequisite, and the clinical need for it has not changed.","evidence":"Regulatory decision; FDA cites established management guidelines and stable adverse event reporting.","sources":["fda-rems-2025","sitc-iec-2020"]}],"grades":[{"claim":"Baseline CRP, ferritin, LDH, blood count, metabolic panel and echocardiogram before CAR T cells","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Daily blood count, metabolic panel, magnesium, phosphate, CRP and ferritin in hospital","grade":"LE: 3","source":"sitc-iec-2020"},{"claim":"Tocilizumab may be considered for adult grade 2 CRS","grade":"LE: 3","source":"sitc-iec-2020"},{"claim":"Tocilizumab at grade 3 CRS in children","grade":"LE: 3","source":"sitc-iec-2020"},{"claim":"Steroids with a second tocilizumab dose if one dose fails","grade":"LE: 3","source":"sitc-iec-2020"},{"claim":"Anakinra, siltuximab or high-dose methylprednisolone after two tocilizumab doses","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Prolonged or severe CRS treated with tocilizumab with or without a corticosteroid","grade":"expert consensus","source":"asco-cart-2021","quote":"Management of patients with prolonged or severe CAR T-cell-associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid."}],"sources":[{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"astct-2019","label":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","publisher":"American Society for Transplantation and Cellular Therapy, Biology of Blood and Marrow Transplantation","year":2019,"url":"https://europepmc.org/article/PMC/PMC12180426","doi":"10.1016/j.bbmt.2018.12.758","gradingScheme":"A consensus grading system (grades 1 to 4), not a set of graded recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"astct-2026","label":"ASTCT Consensus Grading for Toxicities after Immune Effector Cell Therapy","publisher":"American Society for Transplantation and Cellular Therapy, Transplantation and Cellular Therapy","year":2026,"url":"https://europepmc.org/abstract/MED/42711241","doi":"10.1016/j.jtct.2026.05.020","gradingScheme":"Consensus definitions and grading criteria; the abstract gives no grades.","read":"abstract","accessed":"2026-11-11"},{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-eha-2022","label":"Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)","publisher":"EBMT, JACIE and EHA, Annals of Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/34923107","doi":"10.1016/j.annonc.2021.12.003","read":"abstract","accessed":"2026-11-11"},{"key":"asco-cart-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724386","doi":"10.1200/JCO.21.01992","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus.","read":"abstract","accessed":"2026-11-11"},{"key":"fda-rems-2025","label":"FDA Eliminates Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies (FDA Safety Communication, 26 June 2025)","publisher":"US Food and Drug Administration","year":2025,"url":"https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-eliminates-risk-evaluation-and-mitigation-strategies-rems-autologous-chimeric-antigen-receptor","gradingScheme":"A regulatory safety communication; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ASTCT 2026 update of the consensus grading for CRS, ICANS and IEC-HS was read only as its abstract, which says the panel considered updating the 2019 criteria but does not say what changed. The 2019 grading is used here; check the 2026 paper before relying on a grade boundary.","The EBMT/JACIE/EHA 2022 recommendations (the current European edition) and the ASCO 2021 CAR T-cell guideline were read only as abstracts; the 2019 EBMT/JACIE edition was read in full and is cited where the steps rest on EBMT.","No randomised trial read here compares tocilizumab thresholds (grade 1 against grade 2) or prophylactic against reactive tocilizumab.","The tocilizumab dose and maximum per dose are product-label matters (SmPC or US prescribing information), which were not read for this page; SITC mentions 8 mg/kg only in describing a trial algorithm.","How much steroid for CRS affects CAR T-cell efficacy is uncertain; SITC cites a trend to shorter progression-free survival with prolonged corticosteroids in one axicabtagene ciloleucel cohort."]},{"id":"breath-hold-left-breast-radiotherapy","kind":"protocol","name":"Deep inspiration breath-hold for left-sided breast radiotherapy","aka":["DIBH","deep inspiration breath hold","breath-hold radiotherapy","voluntary breath-hold","heart-sparing breast radiotherapy","active breathing coordinator","ABC breath-hold","gated breast radiotherapy"],"tldr":"For radiotherapy to the left breast or chest wall, you take a deep breath and hold it for about 20 to 30 seconds during each part of the treatment. Filling the lungs moves the heart away from the treated area, so it gets less radiation. You practise first, and the planning scan is done holding your breath. If breath-holding does not suit you, treatment while breathing normally is still safe.","summary":"NICE NG101 1.13.2 [2018] recommends a deep inspiratory breath-hold technique for people with left-sided breast cancer to reduce heart dose; the RCR UK consensus (2016) supported, unanimously, that every department have a breath-hold technique available and, very strongly, a mean heart dose under 2 Gy for more than 90% of left-sided patients not having internal mammary chain treatment. The rationale is dose: the Darby case-control study found major coronary events rose by 7.4% per gray of mean heart dose with no threshold.\n\nThe ESTRO-ACROP implementation guideline (2023, ungraded expert consensus) sets out the practice: coach the patient before the planning CT, aim for a comfortable rather than maximal breath-hold (about 20 to 30 seconds is achievable for more than 90% of breast patients), plan on a CT taken in breath-hold with the same monitoring equipment used on the treatment machine, verify both patient position and breath-hold level with imaging, ideally daily, and be able to re-image and re-plan if the breathing pattern changes. It does not recommend a routine extra free-breathing planning CT beyond the implementation stage, because of the added dose.\n\nVoluntary breath-hold without equipment was as reproducible and heart-sparing as a spirometry device (ABC) in the HeartSpare randomised crossover study, quicker and preferred by patients and radiographers; in larger-breasted women it gave lower heart and coronary artery doses than prone free-breathing (HeartSpare IB). Surface tracking with visual feedback is common; one small randomised trial of chest-surface versus abdominal-block feedback found no difference in accuracy.","asOf":"2026-11-11","links":[],"tags":[],"related":["breast-radiotherapy-positioning-and-setup"],"cancers":["breast-cancer"],"sections":[],"technologies":["respiratory-motion-management","surface-guided-radiotherapy","in-room-imaging-systems","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["deep-inspiration-breath-hold","cardiotoxicity","radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"You hold a deep breath for about half a minute while the machine is on. This moves your heart away from the radiation. You practise first and the team watches your breathing on a screen.","domain":"radiotherapy","setting":{"who":["radiographer","doctor","patient-or-carer"],"where":["radiotherapy-department"]},"population":"Adults having radiotherapy to the left breast or chest wall, with or without the regional lymph nodes, after surgery for early or locally advanced breast cancer. NICE found no evidence for right-sided breast cancer and made no recommendation for it; the RCR consensus adds patients having internal mammary chain radiotherapy on either side. Breath-hold for lung, lymphoma and upper abdominal tumours follows the same guideline but with different selection and imaging rules, and is not covered here.","trigger":"A decision to give radiotherapy to the left breast or chest wall, before the planning CT is booked.","steps":[{"action":"Offer a breath-hold technique to everyone having radiotherapy to the left breast or chest wall","why":"Holding a deep breath moves the heart away from the treated area and lowers the heart dose, and heart damage from radiotherapy rises with every unit of dose it receives.","source":"nice-ng101","quote":"Use a deep inspiratory breath-hold radiotherapy technique for people with left-sided breast cancer to reduce the dose to the heart.","grade":"[2018]"},{"action":"Coach the patient in the breath-hold before the planning CT, show them the equipment and agree how staff will talk to them during it","why":"People who have practised hold their breath more steadily, and steady breath-holds make the planning scan and every treatment line up.","source":"estro-acrop-breath-hold-2023","quote":"It is advisable to train patients in the BH procedure before computed tomography (CT), to familiarise them with the equipment and to inform them how the staff will communicate during the procedure.","grade":"Expert consensus (not graded)"},{"action":"Give written or video material the patient can keep to practise holding their breath at home","why":"Practice at home makes the planning appointment shorter and the breath-hold more even.","source":"estro-acrop-breath-hold-2023","quote":"Information presented as flyers, videos or slide-presentations may be useful material that the patient can keep and use to practice BH at home if necessary","grade":"Expert consensus (not graded)"},{"action":"Aim for a comfortable, natural deep breath held for about 20 to 30 seconds, not the deepest breath possible","why":"Most people can hold a breath this long, and a breath that is too deep is hard to repeat the same way every day.","source":"estro-acrop-breath-hold-2023","quote":"Most patients are able to hold their breath for 25–30 seconds: reports suggest that > 90% of breast cancer patients can achieve DIBH","grade":"Expert consensus (not graded)"},{"action":"Tell the patient that treatment while breathing normally is still safe if breath-holding does not suit them","why":"Language, distress or difficulty following instructions can make breath-hold the wrong choice, and no one should feel they have failed.","source":"estro-acrop-breath-hold-2023","quote":"The staff should reassure the patient that free-breathing (FB) is a safe option for treatment as well.","grade":"Expert consensus (not graded)"},{"action":"Take the planning CT in breath-hold, after setting up with reference marks made while breathing freely","why":"The plan must be made on the body in the same shape it will be in during treatment.","source":"estro-acrop-breath-hold-2023","quote":"The planning CT should be performed in DIBH and additional DIBH skin marks (non-permanent) can be added as needed.","grade":"Expert consensus (not graded)"},{"action":"Use the same breath-hold monitoring system and breath-hold level for every planning scan and every treatment","why":"Changing the equipment or the depth of breath between planning and treatment would put the heart and the breast in different places.","source":"estro-acrop-breath-hold-2023","quote":"To maximise reproducibility and reduce the risk of introducing a systematic error, all relevant imaging for treatment planning should be performed in BH, and at the same BH level as used throughout the treatment course.","grade":"Expert consensus (not graded)"},{"action":"At treatment, verify on images both the patient's position and the breath-hold level","why":"The monitor watches the skin or the airflow, not the heart or the breast; images show that the inside of the chest is where the plan expects it.","source":"estro-acrop-breath-hold-2023","quote":"For treatment delivery, image verification must encompass patient position (similar to treatments in FB) and verification of the BH level.","grade":"Expert consensus (not graded)"},{"action":"Image daily where possible, and re-image and re-plan if the breathing pattern seems to have changed","why":"A breath-hold can drift over a course of treatment; daily checks catch it before it moves dose onto the heart.","source":"estro-acrop-breath-hold-2023","quote":"Daily imaging for the verification of the position of the target in BH as well as verification of the BH level (if necessary to ensure consistency in OAR sparing).","grade":"Expert consensus (not graded)"},{"action":"Check each plan against a mean heart dose target, such as under 2 Gy where the internal mammary nodes are not treated","why":"A target makes it clear when breath-hold, or another heart-sparing method, is needed for a particular patient.","source":"rcr-breast-consensus-2016","quote":"In left-breast-affected patients undergoing radiotherapy not including the IMC, >90% of patients should be treated to a mean heart dose of <2 Gray (Gy).","grade":"Very strongly supported (90 to 99% of centres)"}],"bestInClass":{"statement":"A breath-hold technique for every person having left breast or chest wall radiotherapy (NICE NG101 1.13.2 [2018]; RCR 2016, unanimous that every department have one), with coaching before the planning CT, a comfortable breath-hold of about 20 to 30 seconds, planning and treatment with the same monitoring system at the same breath-hold level, and image verification of position and breath-hold level, daily where feasible (ESTRO-ACROP 2023, expert consensus). The guidelines agree on the technique; they differ in scope. NICE limits its recommendation to left-sided cancer, having found no evidence for right-sided; the RCR also asks for breath-hold to be available for internal mammary chain radiotherapy, and recommends it particularly for lower-half left breast tumours. No guideline read prefers one monitoring system over another; voluntary breath-hold without equipment was equivalent to a spirometry device in a randomised crossover study and quicker to deliver.","sources":["nice-ng101","rcr-breast-consensus-2016","estro-acrop-breath-hold-2023","heartspare-2013"]},"variants":[{"name":"Voluntary breath-hold without a device","differs":"The patient holds their breath to a level checked against skin marks, a laser or surface imaging, with no spirometer or valve.","evidence":"HeartSpare (23 patients, randomised crossover): voluntary DIBH and the Active Breathing Coordinator were comparable in positional reproducibility and normal-tissue sparing; voluntary was preferred by patients and radiographers, took less time and is cheaper. ESTRO-ACROP 2023 says voluntary approaches have been shown suitable for 3D-CRT breast treatments.","sources":["heartspare-2013","estro-acrop-breath-hold-2023"]},{"name":"Spirometry-controlled breath-hold (Active Breathing Coordinator)","differs":"The patient breathes through a mouthpiece with a nose clip; a valve holds the breath at a set lung volume and can interlock with the beam.","evidence":"Comparable heart sparing and reproducibility to voluntary breath-hold in HeartSpare, with longer set-up times and lower patient preference. No trial showing a clinical advantage was found.","sources":["heartspare-2013"]},{"name":"Surface tracking with visual feedback to the patient","differs":"An optical surface system or a marker block tracks the chest or abdomen, and the patient watches their own breath-hold on a screen or in goggles.","evidence":"BRAVEHeart (26 analysable patients, randomised): no difference in treatment accuracy, satisfaction or appointment length between chest-surface and abdominal-block feedback, though the chest surface correlated better with the chest wall (median 0.69 against 0.17). ESTRO-ACROP 2023 notes that visual coaching can decrease breath-hold to breath-hold variability in breast cancer patients.","sources":["braveheart-2024","estro-acrop-breath-hold-2023"]},{"name":"Prone free-breathing instead of supine breath-hold","differs":"The patient lies face down so the breast falls away from the chest wall, without holding their breath; used in some centres for larger breasts.","evidence":"HeartSpare stage IB (34 larger-breasted women, randomised crossover): supine voluntary breath-hold gave lower mean heart and coronary artery doses and better positional reproducibility than prone free-breathing. ESTRO-ACROP 2023 (positioning) says prone can be considered for larger breasts or where more lung sparing is needed, if equipment and expertise are available.","sources":["heartspare-ib-2015","estro-acrop-breast-positioning-2023"]},{"name":"An extra free-breathing planning CT alongside the breath-hold CT","differs":"A second planning scan is taken while breathing normally, to compare plans or keep a back-up plan for days the patient cannot hold their breath.","evidence":"ESTRO-ACROP 2023 accepts it while a department is learning the technique but does not recommend it for routine practice beyond implementation, because of the additional radiation; it notes the benefits are limited.","sources":["estro-acrop-breath-hold-2023"]}],"grades":[{"claim":"Use a deep inspiratory breath-hold technique for people with left-sided breast cancer","grade":"[2018] (NICE does not grade)","source":"nice-ng101"},{"claim":"All UK radiotherapy departments should have a breath-hold technique available","grade":"Unanimous support","source":"rcr-breast-consensus-2016","quote":"All UK radiotherapy departments should have a breath-hold technique available."},{"claim":"Breath-hold techniques recommended for those with lower-half left breast tumours","grade":"Consensus statement (no vote shown for this sentence)","source":"rcr-breast-consensus-2016","quote":"Breath-hold techniques are recommended for those with lower-half left breast tumours."},{"claim":"More than 90% of left-sided patients without internal mammary chain treatment to a mean heart dose under 2 Gy","grade":"Very strongly supported","source":"rcr-breast-consensus-2016"},{"claim":"Every centre should have a breath-hold technique for internal mammary chain radiotherapy","grade":"Consensus statement","source":"rcr-breast-consensus-2016","quote":"Every centre should have a breath-hold technique available for patients undergoing IMC radiotherapy."},{"claim":"An additional free-breathing planning CT adds dose for limited benefit","grade":"Expert consensus (not graded)","source":"estro-acrop-breath-hold-2023","quote":"However, the benefits of the acquisition of an additional FB CT scan are limited and add an increased imaging dose."},{"claim":"Rates of major coronary events rise with mean heart dose, by 7.4% per gray","grade":"Population-based case-control study","source":"darby-2013","quote":"Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold."}],"sources":[{"key":"estro-acrop-breath-hold-2023","label":"ESTRO-ACROP guideline: Recommendations on implementation of breath-hold techniques in radiotherapy","publisher":"ESTRO (Radiotherapy and Oncology; Aznar et al.)","year":2023,"url":"https://doi.org/10.1016/j.radonc.2023.109734","doi":"10.1016/j.radonc.2023.109734","gradingScheme":"Not graded: the authors combine published reports with common empirical experience (consensus of experts) and give take-home messages and an ideal implementation list.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng101","label":"Early and locally advanced breast cancer: diagnosis and management (NG101), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or updated.","read":"full-text","accessed":"2026-11-11"},{"key":"rcr-breast-consensus-2016","label":"Postoperative radiotherapy for breast cancer: UK consensus statements","publisher":"The Royal College of Radiologists","year":2016,"url":"https://www.rcr.ac.uk/media/uvzf4ttn/rcr-publications_postoperative-radiotherapy-for-breast-cancer-uk-consensus-statements_november-2016.pdf","gradingScheme":"Share of 48 centres voting for a statement: unanimous 100%, very strongly supported 90 to 99%, strongly supported 70 to 89%, majority 60 to 69%; 70% or more was consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"estro-acrop-breast-positioning-2023","label":"ESTRO-ACROP guideline for positioning, immobilisation and setup verification for local and loco-regional photon breast cancer irradiation","publisher":"ESTRO (Technical Innovations and Patient Support in Radiation Oncology; Mast et al.)","year":2023,"url":"https://doi.org/10.1016/j.tipsro.2023.100219","doi":"10.1016/j.tipsro.2023.100219","read":"full-text","accessed":"2026-11-11"},{"key":"heartspare-2013","label":"The UK HeartSpare Study: randomised evaluation of voluntary deep-inspiratory breath-hold in women undergoing breast radiotherapy","publisher":"Radiotherapy and Oncology (Bartlett et al.)","year":2013,"url":"https://doi.org/10.1016/j.radonc.2013.04.021","doi":"10.1016/j.radonc.2013.04.021","read":"abstract","accessed":"2026-11-11"},{"key":"heartspare-ib-2015","label":"The UK HeartSpare Study (Stage IB): randomised comparison of a voluntary breath-hold technique and prone radiotherapy after breast conserving surgery","publisher":"Radiotherapy and Oncology (Bartlett et al.)","year":2015,"url":"https://doi.org/10.1016/j.radonc.2014.11.018","doi":"10.1016/j.radonc.2014.11.018","read":"abstract","accessed":"2026-11-11"},{"key":"braveheart-2024","label":"Prospective randomized trial comparing 2 devices for deep inspiration breath hold management in breast radiation therapy: results of the BRAVEHeart trial","publisher":"Advances in Radiation Oncology (Byrne et al.)","year":2024,"url":"https://doi.org/10.1016/j.adro.2024.101572","doi":"10.1016/j.adro.2024.101572","read":"abstract","accessed":"2026-11-11"},{"key":"darby-2013","label":"Risk of ischemic heart disease in women after radiotherapy for breast cancer","publisher":"New England Journal of Medicine (Darby et al.)","year":2013,"url":"https://doi.org/10.1056/NEJMoa1209825","doi":"10.1056/NEJMoa1209825","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-breath-hold-left-breast-routine","idea-pu-breath-hold-visual-feedback","idea-pu-breath-hold-coaching-before-planning"],"gaps":["The ESTRO-ACROP breath-hold guideline (2023) is expert consensus and grades none of its recommendations; the practical steps here (coaching, breath-hold duration, daily imaging) rest on it and on small studies rather than on randomised trials of the steps themselves.","No randomised trial has shown that breath-hold reduces heart attacks or heart deaths; the benefit is inferred from lower heart dose combined with the dose-response relationship found by Darby et al. (2013), which was read as an abstract.","No guideline read sets a single rule for which patients gain enough to need breath-hold; the RCR uses a mean heart dose target and recommends it particularly for lower-half left breast tumours, NICE for all left-sided cancers.","Right-sided breast cancer: NICE found no evidence and made no recommendation; centres that use breath-hold for right-sided nodal treatment do so to spare the lung and liver, which was not examined here.","The ASTRO whole-breast radiotherapy guideline (2018) and its heart-sparing recommendations were not read; Elsevier's practicalradonc.org pages were not tried with a script after the Radiotherapy and Oncology PDF returned an HTML page.","The HeartSpare, HeartSpare IB and BRAVEHeart trials were read as abstracts only; all three are small (23 to 34 patients).","How often breath-hold is actually offered is not measured here; the guideline cites the POP-ART survey as showing large variation and under-use, which was not read."]},{"id":"dental-assessment-before-bone-modifying-agents","kind":"protocol","name":"Dental assessment before bone-modifying agents and jaw osteonecrosis prevention","aka":["MRONJ prevention","medication-related osteonecrosis of the jaw","dental check before zoledronic acid","dental check before denosumab","osteonecrosis of the jaw prevention"],"tldr":"Medicines that strengthen bone in cancer, such as zoledronic acid and denosumab, can rarely cause a patch of jawbone to break down, usually after a tooth is taken out. Before you start, see a dentist so any problem teeth can be treated first, keep your mouth very clean, and tell your dentist about the medicine. Report any jaw pain, loose teeth or exposed bone in the mouth.","summary":"MRONJ is exposed bone, or bone that can be probed through a fistula, in the jaw for more than 8 weeks in someone who has had a bone-modifying agent (BMA) or angiogenic inhibitor, with no radiotherapy or metastasis to the jaw (MASCC/ISOO/ASCO 2019). In cancer the doses are much higher than in osteoporosis (denosumab 120 mg monthly against 60 mg every 6 months), so the risk is greater: the Korean 2025 statement cites an incidence with zoledronate of 1.6 to 4 per cent in the first 2 years, rising after that, and finds that pretreatment dental care cut MRONJ by 77.3 per cent in one meta-analysis of people on high-dose bisphosphonates.\n\nMASCC/ISOO/ASCO recommend a comprehensive dental assessment when a BMA is started, discussion of modifiable risk factors, and avoiding elective dentoalveolar surgery during treatment; whether to stop the BMA before necessary surgery is uncertain. The Korean statement makes dental evaluation mandatory before high-dose therapy for cancer, ideally before it begins, with extraction of teeth that cannot be saved, treatment of gum and root infections, adjustment of ill-fitting dentures and education on oral hygiene and warning signs. NICE NG101 asks that the risk of jaw osteonecrosis be discussed before adjuvant bisphosphonates in breast cancer. Established MRONJ is staged by an experienced clinician and treated conservatively first (MASCC/ISOO/ASCO), whereas the Korean statement favours earlier surgery.","asOf":"2026-11-11","links":[],"tags":["protocol","bone-health","oral-care","supportive-care"],"related":["multiple-myeloma"],"cancers":[],"sections":["supportive-care"],"technologies":["bone-modifying-agents"],"targets":[],"drugs":["zoledronic-acid","denosumab"],"companies":[],"institutions":["mascc","asco","nice"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some bone medicines can rarely damage the jaw. See a dentist before you start. Keep your teeth clean. Tell your team about jaw pain or loose teeth.","domain":"supportive-care","setting":{"who":["doctor","nurse","patient-or-carer","multidisciplinary-team"],"where":["outpatient-clinic","community"]},"population":"Adults with cancer starting a bone-modifying agent (zoledronic acid or other bisphosphonates, or denosumab) for bone metastases, myeloma or treatment-induced bone loss, or an angiogenic inhibitor. Risks and some recommendations differ between the high doses used for bone metastases and the lower doses used to protect bone; the sources say which.","trigger":"A bone-modifying agent is planned.","steps":[{"action":"Before the first dose, arrange a comprehensive dental assessment and complete any needed dental treatment","why":"Most jaw osteonecrosis follows a tooth extraction or an infection; dealing with problem teeth first lowers that risk.","source":"mascc-isoo-asco-2019","quote":"In patients who initiate a BMA, preventive care includes comprehensive dental assessments, discussion of modifiable risk factors, and avoidance of elective dentoalveolar surgery (ie, surgery that involves the teeth or contiguous alveolar bone) during BMA treatment."},{"action":"For high-dose treatment of bone metastases or myeloma, treat the dental check as mandatory and complete it before treatment begins where possible","why":"The doses used in cancer carry a far higher risk than those used for osteoporosis.","source":"korean-2025","quote":"For patients scheduled to receive high-dose antiresorptives for oncologic indications, this dental evaluation is considered mandatory and should be completed ideally before therapy begins."},{"action":"At the dental visit, remove teeth that cannot be saved, treat gum and root infections, and adjust ill-fitting dentures","why":"Each of these is a way bacteria or pressure can reach the bone and start osteonecrosis.","source":"korean-2025","quote":"Extraction of non-restorable teeth or teeth with a poor prognosis"},{"action":"Discuss the risk and the modifiable risk factors with the person before starting","why":"Smoking, poor oral hygiene, steroids and other drugs add to the risk, and some can be changed.","source":"nice-ng101","quote":"Discuss the benefits and risks of bisphosphonate treatment with women, particularly the risk of osteonecrosis of the jaw, atypical femoral fractures and osteonecrosis of the external auditory canal."},{"action":"Teach the person to keep the mouth very clean, to tell every dentist about the medicine, and to report jaw pain, loose teeth, numbness or exposed bone","why":"Early signs found quickly are easier to treat, and the dentist can plan care around the medicine.","source":"korean-2025","quote":"Patient education on the importance of maintaining excellent oral hygiene and the signs and symptoms of MRONJ"},{"action":"During treatment, avoid elective tooth extractions, implants and other surgery on the jawbone","why":"Surgery on the jaw is the most common trigger while the medicine is in use.","source":"mascc-isoo-asco-2019","quote":"In patients who initiate a BMA, preventive care includes comprehensive dental assessments, discussion of modifiable risk factors, and avoidance of elective dentoalveolar surgery (ie, surgery that involves the teeth or contiguous alveolar bone) during BMA treatment."},{"action":"If jaw surgery becomes necessary, decide with the oncologist and dentist whether to pause the medicine; the evidence does not settle it","why":"Pausing may help the jaw heal but may raise the risk of fractures or bone problems from the cancer.","source":"mascc-isoo-asco-2019","quote":"It remains uncertain whether BMAs should be discontinued before dentoalveolar surgery."},{"action":"If osteonecrosis develops, have it staged by an experienced clinician and start with conservative treatment","why":"Conservative care, such as antimicrobial mouth rinses, comes first; surgery is for cases that do not settle.","source":"mascc-isoo-asco-2019","quote":"Staging of MRONJ should be performed by a clinician with experience in the management of MRONJ. Conservative measures comprise the initial approach to MRONJ treatment."}],"bestInClass":{"statement":"The MASCC/ISOO/ASCO guideline (2019) is the only oncology-specific international guideline and was read only as an abstract: dental assessment when a bone-modifying agent starts, attention to modifiable risk factors, no elective dentoalveolar surgery during treatment, uncertainty about pausing the drug before necessary surgery, staging by an experienced clinician and conservative treatment first. The Korean 2025 position statement, read in full, agrees on prevention and goes further: it makes the dental check mandatory before high-dose cancer treatment, sets drug-specific pauses before dental surgery, and favours early surgery for established MRONJ. It reports that the AAOMS 2022 position paper deliberately removed fixed drug holidays for lack of evidence. On pausing and on surgery, the sources disagree, and the oncology guideline leaves it open.","sources":["mascc-isoo-asco-2019","korean-2025","nice-ng101"]},"variants":[{"name":"Fixed drug holidays before dental surgery (Korean 2025)","differs":"Sets pauses before invasive dental procedures: 2 months for oral bisphosphonates in long-term users, 6 to 12 months for intravenous zoledronate, and surgery 3 to 4 months after the last denosumab injection, with 6 to 8 weeks of healing afterwards; the denosumab timing is built around the 6-monthly osteoporosis dose.","evidence":"Expert consensus from literature review and three rounds of surveys; the statement itself calls drug holidays one of the most controversial issues and notes that AAOMS (2022) offered no fixed holidays. MASCC/ISOO/ASCO say it is uncertain whether to stop the drug at all.","sources":["korean-2025","mascc-isoo-asco-2019"]},{"name":"Early surgery for established MRONJ (Korean 2025)","differs":"Advocates early and active surgical treatment at all stages of MRONJ, where MASCC/ISOO/ASCO start with conservative measures.","evidence":"The Korean statement cites better long-term outcomes with surgery than with conservative care; MASCC/ISOO/ASCO's position rests on its 2019 systematic review, which found only 10 randomised trials among 132 publications.","sources":["korean-2025","mascc-isoo-asco-2019"]}],"grades":[{"claim":"Pretreatment dental evaluation and preventive care in cancer patients on high-dose bisphosphonates","grade":"meta-analysis cited by the Korean statement: 77.3 per cent fewer cases","source":"korean-2025","quote":"One meta-analysis reported that pre-treatment dental evaluation and preventive care reduced MRONJ incidence by 77.3% in cancer patients receiving high-dose BPs"}],"sources":[{"key":"mascc-isoo-asco-2019","label":"Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline","publisher":"MASCC, ISOO and ASCO, Journal of Clinical Oncology","year":2019,"url":"https://europepmc.org/abstract/MED/31329513","doi":"10.1200/JCO.19.01186","read":"abstract","accessed":"2026-11-11"},{"key":"korean-2025","label":"Medication-Related Osteonecrosis of the Jaw: An Evidence-Based 2025 Position Statement from a Korean Multidisciplinary Task Force","publisher":"Five Korean societies, Endocrinology and Metabolism","year":2025,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12765892/","doi":"10.3803/EnM.2025.2712","gradingScheme":"Position statement built on literature review and three rounds of expert surveys; recommendations are not graded individually.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng101","label":"Early and locally advanced breast cancer: diagnosis and management (NG101), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations. Published July 2018, last updated April 2025.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The MASCC/ISOO/ASCO guideline was read only as an abstract, so its grades, its consensus levels and its advice on timing of the dental visit relative to the first dose are not given here.","The AAOMS 2022 position paper could not be read; its position is given only as the Korean statement reports it.","No guideline read settles whether to pause a bone-modifying agent before necessary dental surgery in people with bone metastases, where stopping may itself cause harm.","The Korean incidence figures and drug holiday table mix osteoporosis and cancer doses; the denosumab timing in particular assumes the 6-monthly osteoporosis dose, not the monthly cancer dose.","No source read gives how often to repeat dental checks during long-term treatment."]},{"id":"head-and-neck-radiotherapy-dental-assessment-osteoradionecrosis","kind":"protocol","name":"Dental assessment before head and neck radiotherapy and osteoradionecrosis prevention","aka":["dental check before radiotherapy","pre-radiotherapy dental assessment","osteoradionecrosis prevention","ORN of the jaw","jaw bone damage after radiotherapy","tooth extraction before radiotherapy","dental extraction and radiotherapy"],"tldr":"Radiotherapy to the mouth and jaw lowers the jawbone's ability to heal for the rest of your life, so a dentist should check your teeth before treatment starts and take out any that are unlikely to last, giving the gums time to heal. Afterwards, careful dental care for life and telling your dentist about the radiotherapy before any extraction help prevent bone damage called osteoradionecrosis.","summary":"The current guideline is ISOO-MASCC-ASCO 2024 (Peterson et al.), which could be read only as an abstract: it rated the prevention best practices and surgical management as evidence-based with strong evidence, relied on informal consensus elsewhere, made no recommendation on leukocyte- and platelet-rich fibrin or photobiomodulation for prevention, and judged hyperbaric oxygen for prevention or management largely unjustified. NCI PDQ (2024) sets out the pre-treatment dental work for high-dose head and neck radiotherapy: decide which teeth need extracting (advanced caries near the pulp, moderate or severe periodontal disease, periapical lesions symptomatic within 90 days, traumatising appliances), evaluate as early as possible so extraction sites can heal, maintain hygiene, prescribe jaw exercises against trismus and monitor for osteoradionecrosis. MASCC/ISOO 2020 gives expert opinion that dental evaluation and treatment before cancer therapy are desirable. On timing, a 2026 meta-analysis of eight retrospective cohorts found no overall link between the extraction-to-radiotherapy interval and osteoradionecrosis but higher risk in Western populations starting within 7 or 14 days; a 2022 meta-analysis in IMRT found extraction before radiotherapy has not been proven to reduce osteoradionecrosis compared with after, to be weighed against delay. For established osteoradionecrosis NICE NG36 says consider surgery to remove necrotic bone with soft tissue cover, and hyperbaric oxygen or medical management only within a trial.","asOf":"2026-11-11","links":[],"tags":[],"related":["head-and-neck-radiotherapy-oral-mucositis"],"cancers":["head-and-neck","oral-cavity-cancer","oropharyngeal-cancer"],"sections":[],"technologies":["hyperbaric-oxygen-radiation-injury","dry-mouth-teeth-after-head-neck-radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"See a dentist before mouth or throat radiotherapy. Bad teeth may need to come out first. After treatment, keep your teeth very clean, see your dentist regularly, and always tell any dentist you had radiotherapy.","domain":"radiotherapy","setting":{"who":["doctor","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","radiotherapy-department","community"]},"population":"Adults due to have, or who have had, radiotherapy that includes the jaws for head and neck cancer. The NICE guideline applies from age 16. Children's dental care (developing teeth) and medication-related osteonecrosis from bone-modifying drugs are separate and not covered.","trigger":"Radiotherapy to the head and neck has been decided on; the dental assessment should happen as soon as possible after that decision, and the protocol continues for life.","steps":[{"action":"Book a dental assessment as early as possible after radiotherapy is decided on","why":"Any extractions need time to heal before radiotherapy starts, and treatment should not be delayed waiting for dental work.","source":"nci-pdq-oral-2024","quote":"A dental evaluation is scheduled as early as possible to allow sufficient time to complete any necessary treatment and for tissues to heal after dental extractions and professional periodontal care.","grade":"Not graded (PDQ summary)"},{"action":"Decide which teeth to extract before treatment: advanced decay near the nerve, moderate or severe gum disease, root-tip infection symptomatic in the past 90 days, and appliances that rub the mouth","why":"Teeth like these are likely to need extraction later, and extraction from irradiated bone is the main trigger for osteoradionecrosis.","source":"nci-pdq-oral-2024","quote":"Determine need for medically necessary dental extractions and potential change in occlusal vertical dimension, based on the following:","grade":"Not graded (PDQ summary)"},{"action":"Treat dental disease before cancer therapy where the dentist judges it necessary","why":"Infection from teeth can spread locally and into the blood during treatment.","source":"mascc-isoo-2020","quote":"An expert opinion complements this guideline: Although there was insufficient evidence to support the use of professional oral care for OM prevention, the panel is of the opinion that dental evaluation and treatment as indicated before cancer therapy are desirable to reduce risk for local and systemic infections from odontogenic sources.","grade":"III (expert opinion)"},{"action":"Leave time for extraction sites to heal before the first fraction where the cancer allows, weighing the gain against any delay to treatment","why":"In Western cohorts, starting within one or two weeks of an extraction went with more osteoradionecrosis; overall the evidence is mixed and delay to cancer treatment carries its own risk.","source":"liu-timing-2026","quote":"In Western populations, patients initiating RT within < 7 days or < 14 days after dental extraction demonstrated significantly elevated ORN risk (OR = 3.07, 95%CI: 1.52-6.21 and OR = 2.01, 95%CI:1.10-3.68, respectively).","grade":"Meta-analysis of eight retrospective cohorts (Newcastle-Ottawa quality assessed)"},{"action":"Prescribe jaw opening and closing exercises, and keep up oral hygiene through and after treatment","why":"Exercises reduce jaw stiffness (trismus); a clean mouth lowers the risk of infection and decay in teeth left dry by radiotherapy.","source":"nci-pdq-oral-2024","quote":"Prescribe jaw opening and closing exercises to reduce risk of trismus","grade":"Not graded (PDQ summary)"},{"action":"Monitor for life for osteoradionecrosis and for new or recurrent cancer in the mouth, with regular dental review","why":"Bone damage can appear years after radiotherapy, often after an extraction or an injury, and early signs (exposed bone, pain, swelling) are easier to treat.","source":"nci-pdq-oral-2024","quote":"Monitor for risk of osteoradionecrosis, recurrent or new oral mucosal malignancy","grade":"Not graded (PDQ summary)"},{"action":"For established osteoradionecrosis, refer to a specialist team and consider surgery to remove dead bone with healthy tissue cover","why":"Dead bone does not heal on its own; removing it and covering the area with tissue that has a good blood supply is the treatment with the most support.","source":"nice-ng36","quote":"Consider surgery to remove necrotic bone and to establish soft tissue coverage in people with osteoradionecrosis.","grade":"[2016]"},{"action":"Do not use hyperbaric oxygen routinely to prevent or treat osteoradionecrosis; NICE limits it, and medical treatment, to clinical trials","why":"Trials have not shown a clear benefit, and it is time-consuming and expensive.","source":"isoo-mascc-asco-2024","quote":"The use of hyperbaric oxygen in prevention and management of ORN remains largely unjustified, with limited evidence to support its practice.","grade":"As stated in the abstract (individual grades not read)"}],"bestInClass":{"statement":"ISOO-MASCC-ASCO 2024 is the current international guideline; its abstract says the prevention best practices and surgical management are evidence-based with strong evidence, hyperbaric oxygen is largely unjustified, and no recommendation was possible for platelet-rich fibrin or photobiomodulation. Its individual recommendations could not be read. From the sources that could be read: an early dental assessment, extraction of teeth with a poor outlook before treatment with time to heal (NCI PDQ 2024; MASCC/ISOO 2020 expert opinion), jaw exercises and lifelong monitoring, and surgery for established osteoradionecrosis (NICE NG36 1.10.1), with hyperbaric oxygen or medical management only in trials (NICE NG36 1.10.2). How long to wait between extraction and radiotherapy is not settled: a 2026 meta-analysis found no overall effect but higher risk with under 7 or 14 days in Western cohorts, and a 2022 meta-analysis in IMRT found extraction before radiotherapy not proven better than after.","sources":["isoo-mascc-asco-2024","nci-pdq-oral-2024","mascc-isoo-2020","nice-ng36","liu-timing-2026","balermpas-imrt-2022"]},"variants":[{"name":"Fewer extractions before IMRT","differs":"Extracts only teeth that are clearly unsalvageable before modern intensity-modulated radiotherapy, accepting later extraction if needed, to avoid delaying treatment.","evidence":"Balermpas 2022 (seven studies, 875 patients, abstract read): \"Tooth extraction before IMRT is more common than after IMRT, but dental extractions before compared to extractions after IMRT have not been proven to reduce the incidence of ORN. Extractions of teeth before IMRT have to be balanced with any potential delay in initiating cancer therapy.\"","sources":["balermpas-imrt-2022"]},{"name":"Hyperbaric oxygen before extraction in irradiated bone","differs":"Gives a course of hyperbaric oxygen before and after a tooth extraction in a previously irradiated jaw.","evidence":"ISOO-MASCC-ASCO 2024 calls hyperbaric oxygen for prevention and management largely unjustified on limited evidence; NICE NG36 limits it to trials for treatment.","sources":["isoo-mascc-asco-2024","nice-ng36"]}],"grades":[{"claim":"Prevention best practices and surgical management of osteoradionecrosis are evidence-based with strong evidence","grade":"Evidence-based, strong evidence (as summarised in the abstract)","source":"isoo-mascc-asco-2024","quote":"Recommendations that were deemed evidence-based with strong evidence by the Expert Panel were those pertaining to best practices in prevention of ORN and surgical management."},{"claim":"No recommendation on leukocyte- and platelet-rich fibrin or photobiomodulation to prevent osteoradionecrosis","grade":"No recommendation possible","source":"isoo-mascc-asco-2024","quote":"No recommendation was possible for the utilization of leukocyte- and platelet-rich fibrin or photobiomodulation for prevention of ORN."},{"claim":"Hyperbaric oxygen or medical management for osteoradionecrosis only within a clinical trial","grade":"[2016]","source":"nice-ng36","quote":"Only consider hyperbaric oxygen therapy or medical management for treating osteoradionecrosis as part of a clinical trial."},{"claim":"Dental evaluation and treatment before cancer therapy are desirable","grade":"III (expert opinion)","source":"mascc-isoo-2020"},{"claim":"No overall association between extraction-to-radiotherapy interval and osteoradionecrosis","grade":"Meta-analysis of eight retrospective cohorts","source":"liu-timing-2026","quote":"No significant association was observed between the timing of pre-RT dental extraction and ORN risk in the overall population (OR = 0.99, 95%CI: 0.67-1.47)"}],"sources":[{"key":"isoo-mascc-asco-2024","label":"Prevention and Management of Osteoradionecrosis in Patients With Head and Neck Cancer Treated With Radiation Therapy: ISOO-MASCC-ASCO Guideline","publisher":"ISOO, MASCC and ASCO (Journal of Clinical Oncology; Peterson et al.)","year":2024,"url":"https://doi.org/10.1200/JCO.23.02750","doi":"10.1200/JCO.23.02750","gradingScheme":"ASCO guideline methodology: evidence quality and recommendation strength per recommendation, with informal consensus where evidence is limited (individual grades not read).","read":"abstract","accessed":"2026-11-11"},{"key":"nci-pdq-oral-2024","label":"Oral Complications (PDQ), Health Professional Version","publisher":"US National Cancer Institute","year":2024,"url":"https://www.cancer.gov/about-cancer/treatment/side-effects/mouth-throat/oral-complications-hp-pdq","gradingScheme":"PDQ summaries cite levels of evidence for individual studies in places; the table entries quoted here are ungraded.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-isoo-2020","label":"MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy","publisher":"MASCC and ISOO (Cancer; Elad et al.)","year":2020,"url":"https://doi.org/10.1002/cncr.33100","doi":"10.1002/cncr.33100","gradingScheme":"Level of evidence I to V; recommendation, suggestion, no guideline possible, or expert opinion.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng36","label":"Cancer of the upper aerodigestive tract: assessment and management in people aged 16 and over (NG36), recommendations 1.10","publisher":"NICE","year":2016,"url":"https://www.nice.org.uk/guidance/ng36/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written. 'Consider' marks a weaker recommendation than 'offer'.","read":"full-text","accessed":"2026-11-11"},{"key":"liu-timing-2026","label":"Timing for Radiotherapy Initiation After Dental Extraction and Risk of Osteoradionecrosis in Head and Neck Cancer Patients: A Systematic Review and Meta-Analysis","publisher":"World Journal of Otorhinolaryngology - Head and Neck Surgery (Liu et al.)","year":2026,"url":"https://doi.org/10.1002/wjo2.70097","doi":"10.1002/wjo2.70097","read":"abstract","accessed":"2026-11-11"},{"key":"balermpas-imrt-2022","label":"Dental extraction, intensity-modulated radiotherapy of head and neck cancer, and osteoradionecrosis: a systematic review and meta-analysis","publisher":"Strahlentherapie und Onkologie (Balermpas et al.)","year":2022,"url":"https://doi.org/10.1007/s00066-021-01896-w","doi":"10.1007/s00066-021-01896-w","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-dental-extraction-healing-interval"],"gaps":["The ISOO-MASCC-ASCO 2024 guideline, the current international standard, could be read only as an abstract (the publisher and ASCO pages refused a script). Its individual recommendations, including any on fluoride trays, the healing interval before radiotherapy, antibiotics around extraction, pentoxifylline and tocopherol, and dental implants in irradiated bone, are not reported here.","Fluoride trays or high-fluoride toothpaste after radiotherapy are common practice; no source read here states a graded recommendation for them.","The interval between extraction and the start of radiotherapy is not settled: the meta-analyses read (abstracts only) are of retrospective cohorts and disagree by population.","The UK guideline on the oral management of oncology patients (Royal College of Surgeons) could not be found at a readable address.","NICE NG36 dates from 2016 (last updated 2018)."]},{"id":"diagnostic-bronchoscopy-and-ebus-preparation","kind":"protocol","name":"Diagnostic flexible bronchoscopy and EBUS: preparation, sedation and aftercare","aka":["bronchoscopy","flexible bronchoscopy","EBUS","EBUS-TBNA","endobronchial ultrasound","camera test into the lungs","bronchoscopy sedation","bronchoscopy fasting","transbronchial biopsy"],"tldr":"A bronchoscopy passes a thin flexible camera into the airways to look and take samples; EBUS adds an ultrasound probe to sample lymph nodes in the chest, often to diagnose or stage lung cancer. You usually stop eating 4 hours before and clear fluids 2 hours before, have a numbing spray and usually sedation, and must not drive for 24 hours. Tell the team about blood thinners.","summary":"BTS 2013 (graded A to D, with good practice points) remains the most recent national guideline for diagnostic flexible bronchoscopy in the UK. Before: verbal and written information (Grade C); a staging chest CT before bronchoscopy for suspected lung cancer (Grade D); no food for 4 hours and clear fluids until 2 hours (Grade D); coagulation tests only when there are clinical risk factors (Grade D); clopidogrel stopped 7 days before endobronchial or transbronchial biopsy while low-dose aspirin continues (Grade C), anticoagulants per published guidance; asthma and COPD optimised; ideally a 4-week wait after myocardial infarction. Anticholinergic premedication is not used (Grade A), and antibiotic prophylaxis is not warranted (Grade B).\n\nDuring: intravenous sedation is offered unless contraindicated (Grade B), titrated so verbal contact is possible at all times, with midazolam the preferred drug (Grade B), no more than 5 mg drawn up initially under 70 years and 2 mg over 70, and only 1 mg/ml midazolam stocked; a short-acting opioid such as fentanyl may be added, given first (Grade B for combination). Topical lidocaine (Grade A), at the lowest effective dose with the total recorded. Continuous pulse oximetry (Grade C), oxygen for significant prolonged desaturation (Grade D), intravenous access until discharge, and a safety checklist for every procedure (BTS Quality Standard 2b).\n\nAfter: written information on post-bronchoscopy fever (Grade C) and, after transbronchial biopsy, on delayed complications such as pneumothorax (Grade D), with a chest X-ray if symptoms suggest one; no driving, legal documents or machinery for 24 hours after sedation. For EBUS, BTS quality standards set a staging sensitivity of at least 88% and complications below 1%.","asOf":"2026-11-11","links":[],"tags":[],"related":["anticoagulants-and-antiplatelets-before-endoscopy"],"cancers":["lung-cancer"],"sections":[],"technologies":["robotic-bronchoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bronchoscopy","ebus-tbna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A thin camera goes into your lungs to take samples. Do not eat for 4 hours before. You can drink water until 2 hours before. You get a numbing spray and usually medicine to make you sleepy. Do not drive for a day afterwards. Tell the team if you take blood thinners. Get help if you are short of breath or cough up a lot of blood.","domain":"screening-diagnostics","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","ward"]},"population":"Adults having a diagnostic flexible bronchoscopy, with or without endobronchial or transbronchial biopsy, and EBUS-TBNA, usually as a day case under conscious sedation. Intensive care bronchoscopy, rigid and therapeutic bronchoscopy, children, and general anaesthesia for robotic or navigational bronchoscopy are outside scope.","trigger":"A bronchoscopy or EBUS is booked, for example to diagnose or stage suspected lung cancer.","steps":[{"action":"Give spoken and written information about why the test is done, what happens and possible complications","why":"People who know what to expect tolerate the test better.","source":"bts-2013","quote":"Verbal and written patient information explaining indications and what to expect during the procedure, and potential complications should be provided to improve patient tolerance.","grade":"Grade C"},{"action":"Make sure a staging chest CT has been done before bronchoscopy for suspected lung cancer","why":"The scan shows where to sample and whether an EBUS of chest lymph nodes is needed at the same visit.","source":"bts-2013","quote":"A chest CT scan should be performed prior to a diagnostic bronchoscopy in patients with suspected lung cancer.","grade":"Grade D"},{"action":"Ask the person to have no food for 4 hours and clear fluids only until 2 hours before","why":"An empty stomach reduces the risk of vomiting into the lungs under sedation, without the harm of a long fast.","source":"bts-2013","quote":"It is sufficient for patients to have no food by mouth for 4 h and to allow clear fluids by mouth up to 2 h before bronchoscopy.","grade":"Grade D"},{"action":"Check clotting, platelets and haemoglobin only when there are clinical risk factors for abnormal clotting","why":"Routine blood tests in people without risk factors do not change what happens.","source":"bts-2013","quote":"Perform coagulation studies, platelet count and haemoglobin concentration when there are clinical risk factors for abnormal coagulation.","grade":"Grade D"},{"action":"If biopsies are planned, stop clopidogrel 7 days before; low-dose aspirin alone can continue; plan anticoagulants by published guidance","why":"Clopidogrel raises bleeding after biopsy of the airway; aspirin on its own adds little.","source":"bts-2013","quote":"Discontinue clopidogrel 7 days prior to consideration of EBB and TBLB. Low-dose aspirin alone can be continued.","grade":"Grade C"},{"action":"Do not give routine antibiotics or anticholinergic premedication","why":"Neither prevents complications, and anticholinergics may upset heart rate and blood pressure.","source":"bts-2013","quote":"Antibiotic prophylaxis is not warranted before bronchoscopy for the prevention of endocarditis, fever or pneumonia.","grade":"Grade B"},{"action":"Offer intravenous sedation unless there is a reason not to, and respect a preference to go without","why":"Sedation makes the test easier for most people; some prefer to stay fully awake and manage well.","source":"bts-2013","quote":"Intravenous sedation should be offered to patients undergoing bronchoscopy, provided there are no contraindications.","grade":"Grade B"},{"action":"Use midazolam titrated so the person can always talk; draw up no more than 5 mg at first (2 mg over 70) and stock only 1 mg/ml strength","why":"Small, measured doses avoid accidental oversedation, which has caused deaths.","source":"bts-2013","quote":"Intravenous midazolam is the preferred drug for sedation, having a rapid onset of action, being titratable to provide the required depth of sedation, and being reversible.","grade":"Grade B"},{"action":"Spray the throat and airways with lidocaine at the lowest dose that controls coughing, and record the total given","why":"Numbing the airway stops coughing; too much lidocaine can be toxic.","source":"bts-2013","quote":"Lidocaine should be used for topical anaesthesia during bronchoscopy, unless contraindicated.","grade":"Grade A"},{"action":"Monitor oxygen saturation continuously, record heart rate, breathing rate and blood pressure before, during and after, and keep intravenous access until discharge","why":"Oxygen levels often dip during the test and sedation can slow breathing, so problems are caught early.","source":"bts-2013","quote":"Patients should be monitored by continuous pulse oximetry during bronchoscopy.","grade":"Grade C"},{"action":"Apply the unit's safety checklist for every procedure","why":"A checklist catches the wrong patient, missing consent or a missed allergy before the test starts.","source":"bts-qs-2014","quote":"All units have a clearly defined safety checklist which is applied for each procedure.","grade":"Quality statement (ungraded)"},{"action":"Give written advice about fever after bronchoscopy and, after a lung biopsy, about delayed complications such as a collapsed lung; X-ray if symptoms suggest it","why":"A short fever is common and settles; breathlessness or chest pain after a biopsy can mean air has leaked and needs checking.","source":"bts-2013","quote":"Patients should be advised of the potential for delayed complications following TBLB and provided with written information regarding likely symptoms and action required.","grade":"Grade D"},{"action":"After sedation, advise no driving, no legal documents and no machinery for 24 hours","why":"Sedatives slow reactions and judgement for longer than people feel.","source":"bts-2013","quote":"Patients who had sedation should be advised not to drive, sign legally binding documents or operate machinery for 24 h after the procedure.","grade":"Good practice point"}],"bestInClass":{"statement":"BTS 2013, the most recent national guideline read: information beforehand (Grade C), staging CT first in suspected lung cancer (Grade D), 4 hours without food and clear fluids to 2 hours (Grade D), clopidogrel stopped 7 days before biopsy with aspirin continued (Grade C), no antibiotic (Grade B) or anticholinergic (Grade A) premedication, offered intravenous sedation (Grade B) with titrated low-strength midazolam (Grade B) and topical lidocaine (Grade A), continuous oximetry (Grade C), written aftercare advice and 24 hours without driving after sedation. BTS quality standards (2014) add a safety checklist for each procedure and, for EBUS, staging sensitivity of at least 88% with complications below 1%. The 2013 guideline is now old: its anticoagulant appendix predates current endoscopy guidance on direct oral anticoagulants, and propofol and general anaesthesia are increasingly used for EBUS and robotic bronchoscopy, which newer German (2026) and United States anaesthesia (2026) statements address but could not be read here.","sources":["bts-2013","bts-qs-2014"]},"variants":[{"name":"Unsedated bronchoscopy","differs":"Topical anaesthesia only, without intravenous sedation.","evidence":"BTS: some patients tolerate unsedated bronchoscopy well and their preference should be sought (Grade B).","sources":["bts-2013"]},{"name":"Propofol or general anaesthesia (advanced bronchoscopy, EBUS, robotic bronchoscopy)","differs":"Deeper sedation or general anaesthesia given by an anaesthetist instead of midazolam with an opioid.","evidence":"BTS 2013: propofol has similar efficacy to midazolam but should be given only by practitioners trained in it, such as anaesthetists, because of its narrow therapeutic window (Grade B). A 2026 multisociety United States consensus on anaesthesia for advanced diagnostic bronchoscopy exists but had no abstract available.","sources":["bts-2013","anesthesia-consensus-2026"]},{"name":"German Respiratory Society S2k guideline (2026)","differs":"Covers indications, preparation, execution, hygiene and aftercare for Germany, Austria and Switzerland.","evidence":"Only the abstract, which states scope and not recommendations, was reachable.","sources":["dgp-s2k-2026"]}],"grades":[{"claim":"Anticholinergic premedication not routinely used","grade":"Grade A","source":"bts-2013","quote":"Anticholinergics (glycopyrrolate or atropine) should not routinely be used prior to bronchoscopy due to a lack of clinical benefit and a possible increased risk of haemodynamic changes."},{"claim":"Oxygen when desaturation is significant and prolonged","grade":"Grade D","source":"bts-2013","quote":"Oxygen supplementation should be used when desaturation is significant (pulse oximeter oxygen saturation (SpO2)>4% change, or SpO2<90%) and prolonged (>1 min) to reduce the risk of hypoxaemia-related complications."},{"claim":"Limit midazolam drawn up before the procedure","grade":"Grade D","source":"bts-2013","quote":"No more than 5 mg midazolam should be initially drawn up into any syringe prior to bronchoscopy for patients under the age of 70 (2 mg midazolam for patients over 70) to prevent potential inadvertent oversedation associated with the practice of routinely drawing up 10 mg midazolam."},{"claim":"Combination opioid and midazolam sedation","grade":"Grade B","source":"bts-2013","quote":"Combination opioid and midazolam sedation should be considered in patients to improve bronchoscopic tolerance."},{"claim":"Written information on post-bronchoscopy fever","grade":"Grade C","source":"bts-2013","quote":"Patients should receive written information regarding post-bronchoscopy fever (PBF) and appropriate management advice."},{"claim":"Delay bronchoscopy for 4 weeks after a heart attack where possible","grade":"Grade D","source":"bts-2013","quote":"FB should ideally be delayed for 4 weeks after MI."},{"claim":"EBUS-TBNA complications recorded and below 1%","grade":"Quality statement (ungraded)","source":"bts-qs-2014","quote":"EBUS-TBNA Complication rates be recorded and audited to be <1%"}],"sources":[{"key":"bts-2013","label":"British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults (accredited by NICE)","publisher":"British Thoracic Society (Du Rand et al., Thorax 2013;68 Suppl 1)","year":2013,"url":"https://www.brit-thoracic.org.uk/document-library/guidelines/bronchoscopy/bts-guideline-for-diagnostic-flexible-bronchoscopy-in-adults/","doi":"10.1136/thoraxjnl-2013-203618","gradingScheme":"SIGN-based: evidence levels 1++ to 4; recommendations Grade A to D, and good practice points (√) for best practice without evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"bts-qs-2014","label":"BTS Quality Standards for Flexible Bronchoscopy (December 2014)","publisher":"British Thoracic Society","year":2014,"url":"https://www.brit-thoracic.org.uk/document-library/quality-standards/flexible-bronchoscopy/bts-quality-standards-for-flexible-bronchoscopy/","gradingScheme":"Quality statements with measures; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"dgp-s2k-2026","label":"Safety of diagnostic flexible bronchoscopy in adults: S2k guideline of the German Respiratory Society","publisher":"German Respiratory Society (Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin), Pneumologie","year":2026,"url":"https://doi.org/10.1055/a-2669-9409","doi":"10.1055/a-2669-9409","read":"abstract","accessed":"2026-11-11"},{"key":"anesthesia-consensus-2026","label":"Expert Consensus Statement on Anesthesia Care for Advanced Diagnostic Bronchoscopy (Society for Airway Management, Society for Head and Neck Anesthesia, Society for Ambulatory Anesthesia, American Association for Bronchology and Interventional Pulmonology)","publisher":"Anesthesia & Analgesia","year":2026,"url":"https://doi.org/10.1213/ane.0000000000008366","doi":"10.1213/ane.0000000000008366","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The BTS diagnostic bronchoscopy guideline dates from 2013 and is no longer listed on the BTS guidelines page, though the BTS document library still serves it; no newer UK guideline was found. Its anticoagulant appendix predates current guidance on direct oral anticoagulants (see the endoscopy anticoagulant protocol).","The German S2k guideline (2026) was read as an abstract only, and the 2026 United States anaesthesia consensus and the 2015 ESGE/ERS/ESTS endosonography guideline had no abstract available; their recommendations are not on this page.","EBUS-specific preparation (sedation depth, number of needle passes, rapid on-site evaluation) is drawn here only from the BTS quality standards; the BTS 2011 advanced bronchoscopy guideline was downloaded but not read for this page.","The fasting interval of 4 hours for food is a Grade D recommendation, shorter than many units' local policies of 6 hours; no source read compared them."]},{"id":"treatment-induced-diarrhoea-grading-and-management","kind":"protocol","name":"Diarrhoea from chemotherapy, targeted therapy and radiotherapy: grading, loperamide, octreotide and when to admit","aka":["chemotherapy-induced diarrhoea","CID","cancer treatment-induced diarrhea","loperamide for chemotherapy diarrhoea","octreotide for chemotherapy diarrhoea","complicated diarrhoea"],"tldr":"Treatment diarrhoea can turn dangerous quickly, especially with a low blood count. Drink plenty and start loperamide at the first loose stool if your team has told you to. Call the 24-hour line at once if it does not settle within a day, if there are seven or more stools a day, or with fever, blood, vomiting or dizziness. If cancer tablets are the cause and loperamide fails, stop them and ring.","summary":"The usual approach, as written by eviQ (Cancer Institute NSW) and NCI PDQ, follows the 2004 expert panel (Benson et al.): grade the diarrhoea with CTCAE, look for complicating features, and split uncomplicated from complicated diarrhoea. Uncomplicated grade 1 or 2 diarrhoea is managed at home with clear fluids, dietary changes and standard-dose loperamide (4 mg, then 2 mg every 4 hours or after each loose stool until 12 hours free of diarrhoea), increased to 2 mg every 2 hours if it persists beyond 24 hours. Grade 3 or 4 diarrhoea, or grade 1 or 2 with cramping, fever, sepsis, neutropenia, bleeding, nausea or vomiting, dehydration or falling performance status, or diarrhoea lasting beyond 48 hours on loperamide, is complicated: it usually needs admission, stool cultures, intravenous fluids, antibiotics and subcutaneous octreotide (100 to 150 micrograms three times daily, escalated to 500 micrograms). MASCC/ISOO recommend octreotide of at least 100 micrograms twice daily when loperamide fails after chemotherapy associated with transplant (level II), and suggest Lactobacillus probiotics to prevent diarrhoea from pelvic radiotherapy (level III). Anticancer treatment is interrupted and the dose modified by the regimen's own rules. Irinotecan, sacituzumab govitecan and neratinib have their own protocols; checkpoint inhibitor diarrhoea is immune colitis and is excluded. The latest ESMO guideline (2018) could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","diarrhoea","supportive-care"],"related":["irinotecan-early-cholinergic-syndrome-and-late-diarrhoea","neratinib-diarrhoea-prophylaxis-and-dose-escalation","octreotide-lanreotide","febrile-neutropenia-first-hour"],"cancers":[],"sections":["supportive-care"],"technologies":["probiotics-treatment-diarrhoea","bowel-after-pelvic-radiotherapy"],"targets":[],"drugs":["fluorouracil","capecitabine","irinotecan","sacituzumab-govitecan","idelalisib","pertuzumab","panitumumab","cetuximab","sorafenib"],"companies":[],"institutions":["nci","mascc","esmo"],"pathways":[],"terms":["ctcae-grading","immune-colitis","febrile-neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer treatment can cause runny poo. Drink lots and take the medicine your team gave you. Call them fast if it does not stop or you feel ill or hot.","domain":"symptom-management","setting":{"who":["nurse","doctor","pharmacist","patient-or-carer"],"where":["home","telephone-triage","chemotherapy-day-unit","acute-oncology-service","ward"]},"population":"Adults with diarrhoea caused by chemotherapy, targeted therapy or radiotherapy. Excludes diarrhoea from PD-1, PD-L1 or CTLA-4 checkpoint inhibitors, which is managed as immune-related colitis, and gastrointestinal graft-versus-host disease. Irinotecan and sacituzumab govitecan (early cholinergic and late diarrhoea) and neratinib (prophylaxis) have their own protocols. Children are not covered by the sources read.","trigger":"A person on cancer treatment reports more stools than usual, looser stools or a rise in stoma output.","steps":[{"action":"Before treatment starts, tell the person how likely diarrhoea is, when to start loperamide, how much to drink, and when to call","why":"Diarrhoea from treatment can become dangerous within a day or two; people who know what to do and when to ring act sooner.","source":"eviq-779","quote":"Educate patient about: the likelihood of experiencing diarrhoea prior to commencement of treatment"},{"action":"Grade the diarrhoea with CTCAE (stools per day above baseline, stoma output, effect on daily life) and ask about cramps, fever, blood, vomiting, dizziness and fluid intake","why":"The grade and any warning signs decide whether it can be managed at home or needs hospital care.","source":"eviq-779","quote":"The severity of treatment induced diarrhoea should be evaluated as per the CTCAE grading table below."},{"action":"Ask whether the person is on a checkpoint inhibitor; if so, manage as immune-related colitis instead and do not start antidiarrhoeals by this protocol","why":"Diarrhoea from immunotherapy can be inflammation of the bowel that needs steroids; slowing the bowel can hide it.","source":"eviq-779","quote":"If immune colitis is suspected antidiarrhoeal agents are contraindicated and management of this and any diarrhoea as a result of these agents should be according to the Management of immune related adverse events (irAEs) document."},{"action":"Manage uncomplicated grade 1 or 2 diarrhoea at home; arrange admission for grade 3 or 4, or for grade 1 or 2 with cramping, fever, sepsis, neutropenia, bleeding, nausea or vomiting, dehydration or falling performance status","why":"Diarrhoea with these features can lead to dehydration, kidney damage and infection, and needs drips, tests and closer watching.","source":"eviq-779","quote":"Uncomplicated patients presenting with grade 1-2 diarrhoea may be managed conservatively in the outpatient setting. However, patients with grade 3-4 diarrhoea or grade 1-2 diarrhoea plus one or more additional symptoms of cramping, fever, sepsis, neutropenia, frank bleeding, nausea or vomiting, dehydration or declining performance status, will often require hospital admission."},{"action":"Advise 8 to 10 large glasses of clear fluid a day, small bland meals, and a record of the number and consistency of stools","why":"Replacing lost fluid prevents dehydration, and a stool record shows the team whether things are improving.","source":"eviq-779","quote":"oral rehydration, approximately 8 to 10 large glasses of clear liquids per day (e.g. water, sports drinks, clear juices or broth)"},{"action":"Start loperamide 4 mg at the first loose stool, then 2 mg every 4 hours or after each unformed stool, until 12 hours free of diarrhoea","why":"Loperamide slows the bowel and controls most treatment-related diarrhoea when it is started early.","source":"eviq-779","quote":"4 mg at the first onset of diarrhoea followed by 2 mg every 4 hours or after every unformed stool and continued until diarrhoea free for 12 hrs."},{"action":"If diarrhoea lasts beyond 24 hours, increase loperamide to 2 mg every 2 hours; if it lasts beyond 48 hours, treat it as complicated","why":"Diarrhoea that does not respond to standard loperamide is more likely to become severe and needs a different approach.","source":"eviq-779","quote":"If diarrhoea persists beyond 24 hours, the dose of loperamide should be increased to 2 mg every 2 hours. If diarrhoea persists beyond 48 hours, the patient’s symptoms should be considered complicated and managed as grade 3-4 diarrhoea."},{"action":"For complicated diarrhoea, send stool for culture and C. difficile, check blood count and electrolytes, and give intravenous fluids and antibiotics as needed","why":"Infection and dehydration must be found and treated quickly, particularly when the blood count is low.","source":"eviq-779","quote":"Treatment may include aggressive intravenous rehydration, antidiarrhoeal medications, antibiotics, octreotide (for chemotherapy and targeted therapy induced diarrhoea, unresponsive to high dose loperamide) and a diagnostic work up. Stool should be sent for culture in these patients and electrolytes closely monitored."},{"action":"When high-dose loperamide fails, give octreotide 100 to 150 micrograms subcutaneously three times daily and escalate quickly up to 500 micrograms three times daily","why":"Octreotide reduces the fluid the bowel pours out and controls most diarrhoea that loperamide does not.","source":"eviq-779","quote":"The recommended starting dose is 100 to 150 micrograms three times daily given subcutaneously (alternatively can give 25-50 micrograms/hour via intravenous infusion), with the dose rapidly escalated to 500 micrograms three times a day subcutaneously/intravenously.","grade":"MASCC/ISOO level II (transplant-associated chemotherapy)"},{"action":"Interrupt the anticancer treatment until the diarrhoea has resolved and follow the regimen's protocol for dose changes","why":"Continuing the drug that causes the diarrhoea makes it worse; a lower dose can allow treatment to continue safely.","source":"eviq-779","quote":"Treatment with anti-cancer agents may need to be interrupted until symptoms have resolved and dose modification may be considered."},{"action":"Tell anyone taking cancer tablets to stop them and call the team if diarrhoea does not settle with loperamide","why":"With tablets at home, nobody else will stop the drug; carrying on can turn mild diarrhoea into a dangerous one.","source":"eviq-779","quote":"Patients taking oral anti-cancer therapy must be informed that if they develop diarrhoea which does not settle with loperamide, then they must STOP taking oral anti-cancer therapy and contact their treating team."},{"action":"For loose stools that persist through treatment, consider bile acid malabsorption and a gastroenterology referral","why":"Some long-lasting diarrhoea after pelvic radiotherapy, bowel or pancreatic surgery or some drugs is caused by bile acids and has its own treatment.","source":"eviq-779","quote":"For patients who have chronic loose stools that persist throughout treatment, bile acid malabsorption may be the cause"}],"bestInClass":{"statement":"No current guideline could be read in full that is newer than the 2004 expert panel on which the common approach rests: the 2018 ESMO guideline refused a script. The best-supported practice in the sources read is the eviQ version of that approach (also described by NCI PDQ, 2025): CTCAE grading with a check for complicating features, home management of uncomplicated grade 1 or 2 diarrhoea with fluids and standard-dose loperamide, escalation to high-dose loperamide at 24 hours, and admission with stool tests, intravenous fluids, antibiotics and octreotide for complicated diarrhoea. MASCC/ISOO give the only graded recommendation read, for octreotide after loperamide fails in transplant-associated chemotherapy (level II, 2014, unchanged in 2020). The sources differ on octreotide: eviQ reserves it for loperamide failure, while the 2004 panel, as PDQ reports it, would use high-dose octreotide first for grade 3 or 4 diarrhoea.","sources":["eviq-779","pdq-gi-2025","mascc-isoo-2014","mascc-isoo-2020","benson-2004","esmo-2018"]},"variants":[{"name":"High-dose loperamide from the first day, then octreotide (2004 expert panel, as reported by NCI PDQ)","differs":"Uses loperamide 2 mg every 2 hours from the first day of low-grade diarrhoea, followed by octreotide 100 to 150 micrograms every 8 hours, and octreotide 500 to 1500 micrograms every 8 hours as first-line treatment for grade 3 or 4 diarrhoea; suggests severe radiotherapy diarrhoea may be cared for in an outpatient unit or with intensive home nursing rather than in hospital.","evidence":"Expert panel consensus. PDQ notes that the optimal octreotide dose has not been established and that, in a prospective study of 32 people with diarrhoea refractory to loperamide, octreotide 100 micrograms three times a day resolved it in 30.","sources":["pdq-gi-2025","benson-2004"]},{"name":"Lactobacillus probiotics to prevent diarrhoea during pelvic radiotherapy (MASCC/ISOO)","differs":"Adds a probiotic containing Lactobacillus during pelvic radiotherapy or chemoradiotherapy to prevent diarrhoea.","evidence":"MASCC/ISOO suggestion at level III (2020, maintained from 2014). eviQ limits it to pelvic cancers and advises avoiding it in people who are or may become neutropenic, because of the risk of infection.","sources":["mascc-isoo-2020","eviq-779"]},{"name":"Diphenoxylate with atropine as an alternative to loperamide","differs":"Two tablets three or four times a day until 12 hours free of diarrhoea, instead of loperamide.","evidence":"eviQ lists it as an alternative but says loperamide appears more effective and is the agent guidelines recommend.","sources":["eviq-779"]}],"grades":[{"claim":"Octreotide of at least 100 micrograms subcutaneously twice daily for diarrhoea after standard- or high-dose chemotherapy associated with transplant, when loperamide is ineffective","grade":"Recommendation, level of evidence II","source":"mascc-isoo-2014","quote":"The panel recommends that octreotide, at a dose of ≥100 μg subcutaneously twice daily, be used to treat diarrhea induced by standard‐ or high‐dose chemotherapy associated with HSCT, if loperamide is ineffective (II)."},{"claim":"Lactobacillus probiotics may help prevent diarrhoea from pelvic radiotherapy or chemoradiotherapy","grade":"Suggestion, level of evidence III","source":"mascc-isoo-2020","quote":"The panel suggests that probiotics containing Lactobacillus spp. may be beneficial for the prevention of RT‐induced or RT‐CT–induced diarrhea in patients with pelvic malignancy."},{"claim":"Loperamide may be less effective in grade 3 or 4 diarrhoea","grade":"PDQ level of evidence I","source":"pdq-gi-2025","quote":"Regardless of the dose, however, loperamide may be less effective in patients with grade 3 or 4 diarrhea."}],"sources":[{"key":"eviq-779","label":"Treatment induced diarrhoea (ID 779, version 5)","publisher":"eviQ, Cancer Institute NSW","year":2022,"url":"https://www.eviq.org.au/p/779","gradingScheme":"Evidence-based summary endorsed by eviQ reference committees; recommendations are not graded. Last reviewed November 2020, updated May 2022, review due December 2022 and not yet repeated.","read":"full-text","accessed":"2026-11-11"},{"key":"pdq-gi-2025","label":"Gastrointestinal Complications (PDQ), Health Professional Version: Diarrhea","publisher":"National Cancer Institute","year":2025,"url":"https://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq","gradingScheme":"PDQ levels of evidence (I = randomised controlled trials, through to IV = expert opinion), attached to statements rather than recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-isoo-2014","label":"MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy","publisher":"MASCC/ISOO, Cancer","year":2014,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4164022/","doi":"10.1002/cncr.28592","gradingScheme":"MASCC/ISOO: recommendation (strong evidence) or suggestion (weaker evidence), with level of evidence I to V in brackets.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-isoo-2020","label":"MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy (2020 update)","publisher":"MASCC/ISOO, Cancer","year":2020,"url":"https://doi.org/10.1002/cncr.33100","doi":"10.1002/cncr.33100","gradingScheme":"MASCC/ISOO: recommendation or suggestion, with level of evidence I to V.","read":"full-text","accessed":"2026-11-11"},{"key":"benson-2004","label":"Recommended guidelines for the treatment of cancer treatment-induced diarrhea","publisher":"Journal of Clinical Oncology","year":2004,"url":"https://europepmc.org/abstract/MED/15254061","doi":"10.1200/JCO.2004.04.132","gradingScheme":"Expert panel consensus; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2018","label":"Diarrhoea in adult cancer patients: ESMO Clinical Practice Guidelines","publisher":"ESMO, Annals of Oncology","year":2018,"url":"https://doi.org/10.1093/annonc/mdy145","doi":"10.1093/annonc/mdy145","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 2018 ESMO guideline on diarrhoea, the latest ESMO edition, could not be read: Europe PMC holds no abstract and the publisher refused a script. Its grades and any differences from eviQ are not shown here.","The 2004 expert panel was read only as an abstract; its algorithm is reported here through NCI PDQ and eviQ.","NCCN and ASCO guidance on treatment-induced diarrhoea was not read; no ASCO guideline on the subject newer than 2004 was found.","The eviQ page is past its own review date (due December 2022); eviQ says it is reviewing high-priority documents first in 2026.","The optimal octreotide dose is not established: eviQ, PDQ and MASCC/ISOO give different starting doses (100 micrograms twice daily to 150 micrograms three times daily), and PDQ reports up to 1500 micrograms every 8 hours for severe diarrhoea.","Which antibiotics to give for complicated diarrhoea, and when, is not specified in the sources read; local febrile neutropenia and antimicrobial policies apply.","Dose modification rules for each anticancer drug come from each regimen's protocol and product information, not from these sources.","The sources read do not cover children."]},{"id":"diet-alcohol-and-weight-during-cancer-treatment","kind":"protocol","name":"Diet, alcohol and weight during cancer treatment","aka":["eating during chemotherapy","nutrition during cancer treatment","alcohol during chemotherapy","neutropenic diet","food safety during cancer treatment","supplements during cancer treatment"],"tldr":"During treatment the aim is to eat enough, especially protein, and keep weight steady; this is not the time to cut calories unless the team advises it. Handle food safely, but a strict 'neutropenic diet' is not recommended. Ask about alcohol, which may need limiting when platelets are low, and about foods that interact with your tablets. Regular exercise is recommended.","summary":"ESPEN's practical guideline (2021) recommends checking intake, weight change and BMI regularly from diagnosis (strong, very low evidence), no diets that restrict energy in people who are malnourished or at risk (strong, low), vitamins and minerals at about the recommended daily allowance and no high-dose micronutrients without a deficiency (strong, low), and for survivors a healthy weight, physical activity and a diet low in saturated fat, red meat and alcohol (strong, low). It finds insufficient data for a low-bacterial diet more than 30 days after allogeneic transplant. ASCO (2022) recommends regular aerobic and resistance exercise during curative treatment, recommends against neutropenic diets to prevent infection, and finds evidence for other diets and for weight loss during treatment very limited. NCI's Eating Hints (2022) gives practical food safety (clean hands, separate boards, thorough cooking, pasteurised products) and a longer list of foods to avoid when treatment raises infection risk, which goes further than the trials support. Alcohol advice is about specific risks: NCI says to limit or avoid it if platelets are low, and Macmillan to avoid it with diarrhoea. ACS (2025) says some oral drugs interact with food.","asOf":"2026-11-11","links":[],"tags":[],"related":["bleeding-precautions-when-platelets-are-low","food-safety-and-neutropenic-diet"],"cancers":[],"sections":["nutrition-lifestyle"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Try to eat enough, with plenty of protein, and keep your weight steady. Ask a dietitian if eating is hard. Tell your team about any vitamins or supplements. Wash hands and food and cook meat and eggs well, but you do not need a special restricted diet. Ask before drinking alcohol. Keep active if you can.","domain":"nutrition","setting":{"who":["patient-or-carer","doctor","nurse"],"where":["home","outpatient-clinic"]},"population":"Adults during active cancer treatment, and survivors after it. People who are malnourished, losing weight, or having treatment to the head, neck or digestive tract need individual advice from a dietitian; people after an allogeneic stem cell transplant follow their transplant team's food rules.","trigger":"Starting cancer treatment, or weight loss, poor appetite or questions about diet during treatment.","steps":[{"action":"Have intake, weight change and BMI checked from diagnosis and regularly during treatment, and ask for a dietitian if eating is difficult or weight is falling","why":"Weight and muscle loss are common and harder to reverse once advanced; early checks find them in time.","source":"espen-2021","quote":"To detect nutritional disturbances at an early stage, we recommend to regularly evaluate nutritional intake, weight change, and body mass index (BMI), beginning with cancer diagnosis and repeated depending on the stability of the clinical situation.","grade":"Recommendation B1-1: strength of recommendation strong, level of evidence very low, strong consensus"},{"action":"Eat enough, with extra protein and calories if needed, and do not start a diet that cuts calories while malnourished or at risk of it","why":"Treatment is easier to get through and complete when strength and weight are kept up.","source":"espen-2021","quote":"We recommend not to use dietary provisions that restrict energy intake in patients with or at risk of malnutrition.","grade":"Recommendation B3-2: strength of recommendation strong, level of evidence low, strong consensus"},{"action":"Tell the team about every vitamin, mineral, herb or supplement, and do not take high doses unless a deficiency has been found","why":"Some supplements change how cancer treatment works, and high doses have not been shown to help.","source":"nci-eating-hints","quote":"Tell your doctor, nurse, or dietitian about any vitamin, mineral, dietary supplements, or herbs you are already taking or plan to take.","grade":"Not graded (patient booklet); ESPEN B2-4 on high-dose micronutrients: strong, low evidence"},{"action":"Handle food safely: wash hands, knives and surfaces, keep raw meat separate, cook meat and eggs thoroughly, and use pasteurised juice and milk","why":"Some treatments make food poisoning more likely and more serious.","source":"nci-eating-hints","quote":"Wash your hands, knives, and countertops before and after you prepare food.","grade":"Not graded (patient booklet)"},{"action":"Do not follow a strict neutropenic diet to prevent infection unless your transplant or haematology team has a specific reason","why":"Trials found that restricted neutropenic diets do not reduce infections, and they make eating harder.","source":"asco-diet-2022","quote":"Neutropenic diets are not recommended to prevent infection in patients with cancer during active treatment.","grade":"ASCO guideline recommendation (strength not shown in the abstract)"},{"action":"Ask the team before drinking alcohol; limit or avoid it if platelets are low or there is diarrhoea","why":"Alcohol adds to bleeding risk when platelets are low and can make diarrhoea and dehydration worse.","source":"nci-bleeding-page","quote":"You may also be advised to limit or avoid alcohol if your platelet count is low.","grade":"Not graded (patient information)"},{"action":"If taking anticancer tablets, ask which foods and drinks to avoid and whether to take them with or without food","why":"Some foods change how much of an oral drug is absorbed, making it weaker or more toxic.","source":"acs-oral-chemo","quote":"Sometimes there are food and drug interactions that can change how well the chemo works, making it less effective or causing additional side effects.","grade":"Not graded (patient information)"},{"action":"Keep active: regular aerobic and resistance exercise is recommended during treatment given with the aim of cure","why":"Exercise during treatment improves fitness, strength and fatigue.","source":"asco-diet-2022","quote":"Oncology providers should recommend regular aerobic and resistance exercise during active treatment with curative intent and may recommend preoperative exercise for patients undergoing surgery for lung cancer.","grade":"ASCO guideline recommendation (strength not shown in the abstract)"}],"bestInClass":{"statement":"ESPEN's practical guideline (2021) and ASCO's exercise, diet and weight guideline (2022) are the current graded standards. They agree on screening intake and weight from diagnosis, avoiding calorie restriction in people who are malnourished or at risk, not using high-dose supplements without a deficiency, and exercise during treatment. ASCO recommends against neutropenic diets to prevent infection; ESPEN finds insufficient data for a low-bacterial diet after allogeneic transplant. Both say evidence for specific diets and for intentional weight loss during treatment is limited. After treatment, ESPEN recommends a healthy weight and a diet low in saturated fat, red meat and alcohol (strong, low evidence). Alcohol during treatment has no graded recommendation; patient guidance ties it to specific risks (low platelets, diarrhoea).","sources":["espen-2021","asco-diet-2022"]},"variants":[{"name":"Restricted food list when infection risk is high (NCI Eating Hints)","differs":"Beyond safe handling, advises avoiding produce that is hard to scrub such as berries and grapes, raw nuts, bulk bins, buffets and salad bars, mouldy cheeses, and leftover rice.","evidence":"Patient booklet, not graded. It goes further than ASCO 2022, which found that neutropenic diets did not decrease the risk of infection and recommends against them.","sources":["nci-eating-hints","asco-diet-2022"]},{"name":"Low-bacterial diet after allogeneic stem cell transplant","differs":"Some transplant units keep food restrictions for weeks after an allogeneic transplant.","evidence":"ESPEN 2021 recommendation C4-3: insufficient consistent clinical data to recommend a low-bacterial diet more than 30 days after allogeneic transplant (strength of recommendation none, low evidence); it cites a Cochrane review finding no evidence that low-bacterial diets prevent infection during neutropenia.","sources":["espen-2021"]},{"name":"Survivorship diet and weight (ESPEN, ACS)","differs":"After treatment, aims for a healthy weight (BMI 18.5 to 25), physical activity, and a diet based on vegetables, fruits and whole grains, low in saturated fat, red meat and alcohol.","evidence":"ESPEN 2021 recommendation C5-2, strong, low evidence; the ACS 2022 survivor guideline covers the same ground (abstract read; its recommendations were not).","sources":["espen-2021","acs-survivors-2022"]}],"grades":[{"claim":"Regular screening of intake, weight change and BMI from diagnosis","grade":"B1-1: strong, very low evidence, strong consensus","source":"espen-2021"},{"claim":"No energy-restricting diets in people malnourished or at risk","grade":"B3-2: strong, low evidence, strong consensus","source":"espen-2021"},{"claim":"Vitamins and minerals at about the recommended daily allowance; no high-dose micronutrients without a deficiency","grade":"B2-4: strong, low evidence, strong consensus","source":"espen-2021"},{"claim":"Low-bacterial diet more than 30 days after allogeneic transplant","grade":"C4-3: strength of recommendation none, low evidence, strong consensus","source":"espen-2021"},{"claim":"Survivors keep a healthy weight, stay active and eat a diet low in saturated fat, red meat and alcohol","grade":"C5-2: strong, low evidence, strong consensus","source":"espen-2021"},{"claim":"Neutropenic diets did not decrease infection risk","grade":"Finding of the ASCO 2022 systematic review","source":"asco-diet-2022","quote":"Neutropenic diets did not decrease risk of infection during cancer treatment."},{"claim":"Evidence for other diets and weight loss during treatment","grade":"Very limited (ASCO 2022)","source":"asco-diet-2022","quote":"Evidence for other dietary and weight loss interventions during cancer treatment was very limited."}],"sources":[{"key":"espen-2021","label":"ESPEN practical guideline: Clinical Nutrition in cancer","publisher":"ESPEN (Clinical Nutrition)","year":2021,"url":"https://www.espen.org/files/ESPEN-Guidelines/ESPEN-practical-guideline-clinical-nutrition-in-cancer.pdf","doi":"10.1016/j.clnu.2021.02.005","gradingScheme":"Each recommendation carries a strength (strong, weak or none), a level of evidence (high to very low) and the degree of consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-diet-2022","label":"Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline","publisher":"ASCO (Journal of Clinical Oncology)","year":2022,"url":"https://doi.org/10.1200/JCO.22.00687","doi":"10.1200/JCO.22.00687","gradingScheme":"ASCO evidence quality and recommendation strength; not shown in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"acs-survivors-2022","label":"American Cancer Society nutrition and physical activity guideline for cancer survivors","publisher":"American Cancer Society (CA: A Cancer Journal for Clinicians)","year":2022,"url":"https://doi.org/10.3322/caac.21719","doi":"10.3322/caac.21719","gradingScheme":"Not shown in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"nci-eating-hints","label":"Eating Hints: Before, During, and After Cancer Treatment","publisher":"National Cancer Institute (US)","year":2022,"url":"https://www.cancer.gov/publications/patient-education/eatinghints.pdf","gradingScheme":"Patient booklet; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nci-bleeding-page","label":"Bleeding and Bruising (Thrombocytopenia) and Cancer Treatment","publisher":"National Cancer Institute (US)","year":2022,"url":"https://www.cancer.gov/about-cancer/treatment/side-effects/bleeding-bruising","gradingScheme":"Patient information page; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"acs-oral-chemo","label":"Getting Oral Chemotherapy","publisher":"American Cancer Society (with ASCO medical review)","year":2025,"url":"https://www.cancer.org/cancer/treatment-types/chemotherapy/oral-chemotherapy.html","gradingScheme":"Patient information page; not graded. Last revised 15 May 2025.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-chemo-side-effects","label":"Side effects of chemotherapy","publisher":"Macmillan Cancer Support","year":2018,"url":"https://www.macmillan.org.uk/cancer-information-and-support/treatment/types-of-treatment/chemotherapy/side-effects-of-chemotherapy","gradingScheme":"Patient information page; not graded. Reviewed September 2018, page marked as under review.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ASCO 2022 guideline and the ACS 2022 survivor guideline were read as abstracts; their recommendation strengths and the ACS recommendations themselves were not read.","No graded recommendation on alcohol during active treatment was found; the advice read is tied to specific risks (low platelets, diarrhoea), and ESPEN's alcohol recommendation is for survivors.","Which foods interact with which oral anticancer drugs is in each drug's label and was not compiled here.","Evidence for any specific diet, and for intentional weight loss during treatment, is very limited (ASCO 2022).","The ESPEN guideline text extracts its grade separators as a stray letter, so grades are restated in plain words rather than quoted.","Macmillan's chemotherapy side effects page, the source for avoiding alcohol with diarrhoea, was last reviewed in 2018 and is marked as under review."]},{"id":"distress-screening-and-referral","kind":"protocol","name":"Distress screening with the distress thermometer, and referral by need","aka":["distress thermometer","NCCN distress thermometer and problem list","screening for distress","sixth vital sign","psychosocial screening","holistic needs assessment","stepped care for anxiety and depression"],"tldr":"Many people with cancer feel worried, low or overwhelmed, and money, work or caring for others add to it. Clinics often ask you to mark a scale from 0 to 10 for your distress in the past week and tick a list of problems. A score of 4 or more is a signal for the team to talk it through and offer help, such as a psychologist, social worker or chaplain. Screening only helps when someone acts on it.","summary":"NCCN's standard is that distress should be recognised, monitored, documented and treated promptly at all stages of disease and in all settings, with screening at the first visit, at appropriate intervals and whenever the clinical picture changes (Version 3.2019, the latest full text that could be read; the Version 1.2026 tool page still pairs the 0 to 10 thermometer with a problem list). The tool is a single 0 to 10 distress thermometer for the past week with a problem list of physical, emotional, social, practical and spiritual concerns. In NCCN 2019 a score of 4 or more triggers a further assessment and referral by the problem found (mental health, social work or chaplaincy); a score below 4 is handled by the oncology team as expected distress. The cut-off is a convention with known limits: NCCN itself cites a study in which a cut-off of 4 gave 95 per cent sensitivity and only 45 per cent specificity shortly after a breast cancer diagnosis.\n\nASCO (2014, adapting the pan-Canadian guideline) recommends that every patient be evaluated for symptoms of depression and anxiety at periodic times across the course of care using validated measures. ASCO's 2023 update sets out stepped care: education about depression and anxiety for everyone; for moderate symptoms, cognitive behavioural therapy, behavioural activation, mindfulness-based stress reduction, structured physical activity or psychosocial interventions; for severe symptoms, psychological therapy; and medicines where first-line care is unavailable, preferred, previously effective or has not worked.\n\nThe evidence that screening helps is conditional. In a randomised trial in 1,134 new patients, full screening with a problem checklist and triage lowered distress at three months against the thermometer alone, and the best predictor of improvement was receiving a referral; NCCN also records a randomised trial with no difference at 12 months, and concludes that screening is not enough without follow-up referral and treatment. In England the equivalent is the holistic needs assessment within personalised care and support planning (Macmillan and NHS); NICE's 2004 supportive and palliative care service guidance is retired.","asOf":"2026-11-11","links":[],"tags":["protocol","supportive-care","psychosocial"],"related":["rejuv-access-survivorship-care-uk"],"cancers":[],"sections":["supportive-care"],"technologies":["psycho-oncology","rejuv-mind-distress-screening","rejuv-mind-anxiety-after-cancer","rejuv-mind-depression-after-cancer","mindfulness-based-interventions","cbt-fatigue-distress"],"targets":[],"drugs":[],"companies":[],"institutions":["asco","nice","macmillan-cancer-support","ipos"],"pathways":[],"terms":["quality-of-life"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your team may ask how upset or worried you feel, from 0 to 10. If the number is 4 or more, they should talk with you and offer help.","domain":"supportive-care","setting":{"who":["nurse","doctor","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","ward"]},"population":"Adults with cancer at any stage, from diagnosis through treatment, survivorship and advanced disease. The NCCN guideline and the ASCO guidelines read are for adults; children and adolescents have separate psychosocial standards not covered here. Thoughts of suicide are among the problems NCCN lists; how urgently they are assessed is set by the local team's emergency pathway, which no source read here spells out.","trigger":"The first oncology visit, then at set intervals and at every change in disease or treatment: the end of treatment, recurrence, progression, or a serious complication.","steps":[{"action":"Screen every patient for distress at the first visit, then at regular intervals and at each change in disease status","why":"Distress is common and often missed in a busy clinic; asking at set moments catches it when it changes.","source":"nccn-2019","quote":"At a minimum, patients should be screened to ascertain their level of distress at the initial visit, at appropriate intervals, and as clinically indicated, especially with changes in disease status (eg, remission, recurrence, or progression; treatment-related complications).","grade":"category 2A"},{"action":"Ask the person to rate their distress over the past week on the 0 to 10 thermometer and to mark their concerns on the problem list","why":"One number shows how much distress there is; the problem list shows what it is about, which decides who can help.","source":"nccn-dt-2026","quote":"Instructions: Please circle the number (0–10) that best describes how much distress you have been experiencing in the past week, including today.","grade":"category 2A"},{"action":"Use validated, published measures for anxiety and depression when screening or assessing further","why":"A validated questionnaire is more reliable than a general impression, and allows a change to be measured over time.","source":"asco-2014","quote":"It is recommended that all patients with cancer be evaluated for symptoms of depression and anxiety at periodic times across the trajectory of care. Assessment should be performed using validated, published measures and procedures."},{"action":"For a score below 4, manage the concerns within the oncology team as part of usual supportive care","why":"Some distress is expected after a cancer diagnosis; the treating team can often address it directly.","source":"nccn-2019","quote":"Mild distress (DT score <4) is routinely managed by the primary oncology team and represents what the panel terms “expected distress” symptoms.","grade":"category 2A"},{"action":"For a score of 4 or more, go through the problem list with the person and refer to the right service: mental health, social work or chaplaincy","why":"A higher score needs a conversation and the right professional, matched to the problem behind it.","source":"nccn-2019","quote":"If the patient’s distress level is ≥4, a member of the oncology team looks at the Problem List (discussed in the next section) to identify key issues of concern and asks further questions to determine the best resources (psychiatry, psychology, social work, or chaplaincy professionals) to address the patient’s concerns.","grade":"category 2A"},{"action":"Offer every patient information about depression and anxiety, and match further help to how severe the symptoms are (stepped care)","why":"Most people need information and support; those with more severe symptoms need more intensive help.","source":"asco-2023","quote":"It is recommended to use a stepped-care model, that is, provide the most effective and least resource-intensive intervention based on symptom severity. All oncology patients should be offered education regarding depression and anxiety."},{"action":"For moderate or severe depression or anxiety, offer a psychological therapy first, and consider medicines where that is unavailable, preferred or has not worked","why":"Psychological therapies improved depression and anxiety in the trials reviewed; the evidence for medicines in people with cancer was less consistent.","source":"asco-2023","quote":"For patients with severe symptoms of depression or anxiety, clinicians should offer cognitive therapy, BA, CBT, MBSR, or interpersonal therapy. Treating clinicians may offer a pharmacologic regimen for depression or anxiety for patients who do not have access to first-line treatment, prefer pharmacotherapy, have previously responded well to pharmacotherapy, or have not improved following first-line psychological or behavioral management."},{"action":"Make sure every positive screen leads to a referral and a follow-up, not only a score in the notes","why":"Trials of screening without follow-up care found little benefit; those that linked screening to referral or treatment did better.","source":"nccn-2019","quote":"Overall, results of these studies show that screening, although a critical component of psychosocial care, is not sufficient to impact patient outcomes without adequate follow-up referrals and treatment."}],"bestInClass":{"statement":"Screen at the first visit, at set intervals and at every change in disease, with the NCCN distress thermometer and problem list or another validated measure, and act on what is found: a score of 4 or more (NCCN) leads to assessment and referral by problem, and anxiety and depression are treated by stepped care (ASCO 2023), psychological therapies first. NCCN (2019 full text, 2026 tool) and ASCO (2014, 2023) agree on routine screening with validated tools; they differ in emphasis, NCCN on general distress across practical, social and spiritual problems, ASCO on anxiety and depression specifically. The randomised evidence supports screening only when it is coupled to triage and referral. The full NCCN 2026 text and the full ASCO 2023 text could not be read, so their grades are not given here.","sources":["nccn-2019","nccn-dt-2026","nccn-insights-2026","asco-2014","asco-2023","carlson-2010"]},"variants":[{"name":"Holistic needs assessment within personalised care and support planning (England)","differs":"A structured assessment of physical, practical, emotional and social concerns, on paper or electronically, leading to a personalised care and support plan agreed through a series of conversations, rather than a single distress score. Macmillan's page does not say at which points it should be repeated.","evidence":"Described by Macmillan Cancer Support as part of the NHS personalised care model; no trial of it was read. NICE's 2004 service guidance on supportive and palliative care, which set out a four-level model of psychological support, is retired and NICE says the health system is not expected to follow it.","sources":["macmillan-pcsp","nice-csg4"]},{"name":"Full screening with personalised triage (Calgary trial)","differs":"Adds a problem checklist, an anxiety and depression screen, a personalised report on the medical file and an optional telephone triage with referral, rather than the thermometer alone.","evidence":"Randomised trial of 1,134 new patients with breast or lung cancer: in lung cancer, 20 per cent fewer patients in the triage arm still had high distress at three months; in breast cancer, full screening and triage both lowered distress against the thermometer alone. Receiving a referral was the best predictor of improvement. Read as an abstract.","sources":["carlson-2010"]},{"name":"A higher thermometer cut-off","differs":"Uses a cut-off above 4 to reduce false positives, for example 7 in women shortly after a breast cancer diagnosis.","evidence":"NCCN 2019 cites a study of 181 Dutch women in which a cut-off of 4 gave 95 per cent sensitivity and 45 per cent specificity, and a cut-off of 7 gave 73 and 84 per cent. NCCN kept 4 as its trigger.","sources":["nccn-2019"]}],"grades":[{"claim":"NCCN recommendations on distress management","grade":"category 2A unless otherwise noted","source":"nccn-2019","quote":"All recommendations are category 2A unless otherwise noted."},{"claim":"A cut-off of 4 is sensitive but not specific shortly after a breast cancer diagnosis","grade":"single diagnostic accuracy study, as cited by NCCN","source":"nccn-2019","quote":"However, an analysis including 181 Dutch women who completed the DT within 1 month after breast cancer diagnosis showed that sensitivity was 95% and specificity was only 45% when the recommended cut-off score of 4 was used."}],"sources":[{"key":"nccn-dt-2026","label":"NCCN Distress Thermometer and Problem List (NCCN Guidelines Distress Management, Version 1.2026, DIS-A)","publisher":"National Comprehensive Cancer Network","year":2026,"url":"https://www.nccn.org/docs/default-source/patient-resources/nccn_distress_thermometer.pdf","gradingScheme":"NCCN categories of evidence and consensus: category 1 (high-level evidence, uniform consensus), 2A (lower-level evidence, uniform consensus), 2B, 3.","read":"full-text","accessed":"2026-11-11"},{"key":"nccn-insights-2026","label":"NCCN Guidelines Insights: Distress Management, Version 1.2026","publisher":"Journal of the National Comprehensive Cancer Network","year":2026,"url":"https://europepmc.org/abstract/MED/41956112","doi":"10.6004/jnccn.2026.0018","read":"abstract","accessed":"2026-11-11"},{"key":"nccn-2019","label":"Distress Management, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology","publisher":"Journal of the National Comprehensive Cancer Network","year":2019,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6907687/","doi":"10.6004/jnccn.2019.0048","gradingScheme":"NCCN categories of evidence and consensus: category 1 (high-level evidence, uniform consensus), 2A (lower-level evidence, uniform consensus), 2B, 3.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2023","label":"Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2023,"url":"https://europepmc.org/abstract/MED/37075262","doi":"10.1200/JCO.23.00293","read":"abstract","accessed":"2026-11-11"},{"key":"asco-2014","label":"Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation","publisher":"ASCO, Journal of Clinical Oncology","year":2014,"url":"https://europepmc.org/abstract/MED/24733793","doi":"10.1200/JCO.2013.52.4611","read":"abstract","accessed":"2026-11-11"},{"key":"carlson-2010","label":"Screening for distress in lung and breast cancer outpatients: a randomized controlled trial","publisher":"Journal of Clinical Oncology","year":2010,"url":"https://europepmc.org/abstract/MED/20940193","doi":"10.1200/JCO.2009.27.3698","read":"abstract","accessed":"2026-11-11"},{"key":"macmillan-pcsp","label":"Personalised care and support planning (holistic needs assessment, treatment summary, cancer care review)","publisher":"Macmillan Cancer Support","year":2026,"url":"https://www.macmillan.org.uk/healthcare-professionals/innovation-in-cancer-care/personalised-care","read":"public-summary","accessed":"2026-11-11"},{"key":"nice-csg4","label":"Improving supportive and palliative care for adults with cancer (CSG4), retired","publisher":"NICE","year":2004,"url":"https://www.nice.org.uk/guidance/csg4","gradingScheme":"NICE does not grade recommendations; this service guideline is retired.","read":"public-summary","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The full NCCN Distress Management guideline, Version 1.2026, was not read: the journal summary is paywalled and NCCN does not allow its text to be reproduced. The cut-off, referral pathway and standards quoted are from Version 3.2019, the latest full text available, and may have changed in wording.","The ASCO 2023 update and the ASCO 2014 adaptation were read only as abstracts, so their grades, the named screening tools and the time points are not given here.","The pan-Canadian guideline that ASCO adapted, and the International Psycho-Oncology Society's quality standard, were not read.","NCCN cites one randomised trial of the thermometer and problem list that found no difference in distress at 12 months, and another that found benefit with triage; the size of the benefit of screening alone is not settled.","No source read sets a single best interval for repeat screening; NCCN says every visit ideally, and at minimum at set intervals and at changes.","Screening for children, adolescents and young adults, and for people with cognitive impairment or limited literacy, is not covered by the sources read."]},{"id":"dose-banding-of-anticancer-drugs","kind":"protocol","name":"Dose banding of anticancer drugs","aka":["dose banding","banded doses","standard dose bands","chemotherapy dose rounding","national dose banding tables","pre-made chemotherapy doses"],"tldr":"Dose banding means your calculated dose is rounded to the nearest of a set of standard doses, so the pharmacy can make doses in advance. The difference from your exact dose is kept small, and studies show it gives about the same amount of drug in your blood as an individually calculated dose.","summary":"In dose banding the individually calculated dose (by body surface area, weight or AUC) is rounded to a predefined standard dose for a range of calculated doses, so that doses can be prepared in advance, waiting times cut, waste reduced and products quality-controlled before use. BOPA (2025) asks that adult anticancer doses be banded where bands exist, to the NHS England (England, Wales and Northern Ireland) or SOPPG (Scotland) national tables, and notes banding is not usually used in children; for carboplatin, a changed creatinine or weight leads to a new calculated dose, from which the new band is chosen, never a percentage change from the old banded dose.\n\nThe pharmacokinetic case comes from Chatelut (2012): using clearance data from 1,012 adults and six drugs, banding into three BSA bands changed individual doses by minus 14% to plus 22% but gave a spread of drug exposure very similar to BSA dosing, with no significant loss of precision except for paclitaxel (32.0% against 30.7%), while flat dosing was less precise for four of the six drugs. A hospital that allowed a maximum deviation of 10% found more prepared doses could be reissued and less waste for all agents studied except carboplatin. The NHS England tables and principles, which set UK limits, could not be read.","asOf":"2026-11-11","links":[],"tags":[],"related":["body-size-based-dose-calculation","carboplatin-dose-calculation","sact-prescribing-and-pharmacy-verification","body-surface-area-dosing"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your dose may be rounded to a standard amount so it can be made ready sooner. The change is small and does not make the treatment weaker.","domain":"pharmacy","setting":{"who":["pharmacist","pharmacy-technician","doctor"],"where":["aseptic-unit","outpatient-clinic"]},"population":"Adults prescribed parenteral anticancer drugs for which national or local dose bands exist. Not usually used in children (BOPA).","trigger":"A dose has been calculated for a drug with defined bands.","steps":[{"action":"Calculate the individual dose first, then band adult doses to the national tables where bands exist","why":"Standard doses can be prepared ahead and checked in advance, shortening waits without losing accuracy.","source":"bopa-2025","quote":"Note: SACT for adult patients should be dose banded where bands are available."},{"action":"Do not band doses for children unless a paediatric protocol says so","why":"Children's doses and volumes must match their age and size more closely.","source":"bopa-2025","quote":"Dose banding not usually used in children."},{"action":"When weight or kidney function changes, recalculate the dose from the new values and choose the band from the new calculated dose","why":"Comparing against an already rounded dose can hide or exaggerate a real change.","source":"bopa-2025","quote":"Warning: it is NOT appropriate to use the previous banded dose to work out a percentage dose change threshold as this risks under or overestimating the actual carboplatin dose when banding."},{"action":"Use bands that keep each patient's exposure close to that of individual dosing","why":"Within sensible bands, the difference in drug levels between people is about the same as with exact body-size dosing.","source":"chatelut-2012","quote":"For the studied drugs, implementation of dose banding should be considered as it entails no significant increase in interindividual plasma exposure."}],"bestInClass":{"statement":"Band adult doses to national tables where they exist, starting from an individually calculated dose, and not usually in children (BOPA 2025); recalculate from new values rather than from the old band. The pharmacokinetic basis is Chatelut 2012 (no significant loss of precision against BSA dosing for five of six drugs). The UK national tables and their deviation limits could not be read, so no limit is stated; one hospital used a maximum deviation of 10%.","sources":["bopa-2025","chatelut-2012","samani-2022"]},"variants":[{"name":"Local bands with a maximum deviation of 10%","differs":"A hospital sets its own bands for paclitaxel, carboplatin, docetaxel, gemcitabine, irinotecan and oxaliplatin, allowing up to 10% deviation from the prescribed dose, built into electronic prescribing.","evidence":"In one hospital, reissuing of prepared doses rose for all agents except carboplatin (oxaliplatin from 3.7% to 27.8%) and waste fell, saving about 5,200 euros a year (van Huet 2025).","sources":["van-huet-2025"]}],"grades":[],"sources":[{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"chatelut-2012","label":"Dose banding as an alternative to body surface area-based dosing of chemotherapeutic agents","publisher":"British Journal of Cancer (Chatelut et al.)","year":2012,"url":"https://doi.org/10.1038/bjc.2012.357","doi":"10.1038/bjc.2012.357","read":"full-text","accessed":"2026-11-11"},{"key":"samani-2022","label":"Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers","publisher":"ESMO Open (Samani et al.)","year":2022,"url":"https://doi.org/10.1016/j.esmoop.2022.100401","doi":"10.1016/j.esmoop.2022.100401","read":"full-text","accessed":"2026-11-11"},{"key":"van-huet-2025","label":"Optimizing chemotherapy practices: The impact of dose banding on reissuing and waste reduction","publisher":"Journal of Oncology Pharmacy Practice (van Huet et al.)","year":2025,"url":"https://doi.org/10.1177/10781552251370560","doi":"10.1177/10781552251370560","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The NHS England national dose banding tables and principles, which set UK bands and the permitted deviation, returned a bot challenge and could not be read; the Scottish SOPPG tables were not read either.","No clinical outcome study compares banded with individually calculated doses; the evidence is pharmacokinetic simulation (Chatelut 2012) and operational (waste and reissuing).","Which drugs are suitable depends on the stability of the prepared product, which is not covered here."]},{"id":"dpyd-testing-before-fluoropyrimidines","kind":"protocol","name":"DPD deficiency testing before fluorouracil, capecitabine or tegafur, and dosing by the result","aka":["DPYD test","DPD test","DPYD genotyping before chemotherapy","uracil test before capecitabine","DPD deficiency screening","fluoropyrimidine pharmacogenetic testing","DPYD activity score dosing"],"tldr":"Before your first dose of fluorouracil (5-FU) given into a vein, capecitabine tablets or tegafur, you should have a blood test for DPD deficiency. A few people break these drugs down very slowly, and a normal dose can make them seriously ill. If the test finds this, the dose is lowered or a different drug is chosen. A normal result does not rule out side effects, so still report them quickly.","summary":"Fluoropyrimidines are cleared by dihydropyrimidine dehydrogenase (DPD). The EU review of 2020 recommends phenotype and/or genotype testing before systemic fluorouracil, capecitabine or tegafur, contraindicates them in known complete deficiency and advises a reduced starting dose in partial deficiency; the MHRA adopted the same advice for the UK in October 2020 ('test all patients'). Since October 2025 the US capecitabine label also tells prescribers to test for DPYD variants before starting unless treatment is urgent, while noting no FDA-authorised test exists.\n\nThere are two ways to test. Genotyping reads the four DPYD variants named in the EU product information (c.1905+1G>A, c.1679T>G, c.2846A>T, c.1236G>A/HapB3), which are considered virtually absent in people of African or Asian ancestry. Phenotyping measures plasma uracil: the EU product information treats 16 to under 150 ng/mL as indicative of partial and 150 ng/mL or more as indicative of complete deficiency, to be read with caution when kidney function is impaired.\n\nDosing by genotype uses an activity score. CPIC (2017 update) recommends a 50% reduction at activity score 1 (strong) and 25 to 50% at 1.5 (moderate), avoiding fluorouracil and its prodrugs at 0 or 0.5, with the dose raised in later cycles if the first two are tolerated. DPWG (2020) recommends 50% at both 1 and 1.5 and avoiding tegafur below 2, and calls testing 'essential'. Every source says severe toxicity can still occur with a normal result, most often in the first cycle or after a dose increase.","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["dpyd-genotyping","oncology-pharmacogenomics","fluorouracil-pharmacokinetic-dosing"],"targets":["dpyd"],"drugs":["fluorouracil","capecitabine","tegafur-gimeracil-oteracil","uridine-triacetate"],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacogenomics-term","dose-modification","neutropenia","mucositis","chemotherapy-side-effects-colorectal","chemotherapy-side-effects-pancreatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-henricks-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"simple":"Some people's bodies cannot clear 5-FU or capecitabine properly. A blood test before the first dose finds most of them, so the dose can be made safe. Ask your team whether you have had it.","domain":"chemotherapy-administration","setting":{"who":["doctor","pharmacist","nurse"],"where":["outpatient-clinic","chemotherapy-day-unit"]},"population":"Adults about to start systemic fluorouracil (intravenous), capecitabine or tegafur (as in S-1) for any cancer. Not topical fluorouracil, for which the EU and UK regulators say testing is not required because so little is absorbed. Flucytosine, an antifungal, is covered by the same EU review with different advice and is out of scope. CPIC states that data in children are extremely scarce.","trigger":"A fluoropyrimidine-containing regimen is planned for the first time.","steps":[{"action":"Before the first dose, send a DPD deficiency test for every patient due to start intravenous fluorouracil, capecitabine or tegafur","why":"In people of European ancestry, up to half of one per cent lack the enzyme completely and three to nine per cent have a partial lack (MHRA figures); at a normal dose they can have severe or fatal side effects.","source":"mhra-dsu-2020","quote":"test all patients for DPD deficiency before initiation of treatment with these products"},{"action":"Ask the patient whether they or anyone in their family has been found to have DPD deficiency","why":"A known family history can identify a risk the standard test misses, and the result already known in a relative can speed the decision.","source":"mhra-dsu-2020","quote":"ask patients whether they or their family members have history of complete or partial DPD deficiency"},{"action":"Test by genotype (the four DPYD variants), by measuring blood uracil, or both, following local guidance","why":"The EU recommends testing without fixing the method: genotyping reads inherited variants, while a uracil level measures how well the enzyme is working.","source":"xeloda-smpc","quote":"Phenotype and/or genotype testing prior to the initiation of treatment with Xeloda is recommended despite uncertainties regarding optimal pre-treatment testing methodologies."},{"action":"Read a uracil result against the EU thresholds, with caution if kidney function is reduced","why":"A high uracil level suggests the enzyme is not working, but poor kidney function can also raise it and give a false alarm.","source":"xeloda-smpc","quote":"Despite uncertainties on uracil thresholds defining complete and partial DPD deficiency, a blood uracil level ≥ 16 ng/mL and < 150 ng/mL should be considered indicative of partial DPD deficiency and associated with an increased risk for fluoropyrimidine toxicity."},{"action":"Do not give fluorouracil, capecitabine or tegafur to anyone with known complete DPD deficiency","why":"Without the enzyme the drug builds up to dangerous levels; no dose has been shown to be safe.","source":"ema-2020","quote":"Treatment with fluorouracil, capecitabine or tegafur-containing medicines is contraindicated in patients with known complete DPD deficiency."},{"action":"For a heterozygous carrier, reduce the starting dose by activity score: by 50% at a score of 1, by 25 to 50% at a score of 1.5","why":"A lower first dose brings the risk of severe side effects in carriers close to that of non-carriers.","source":"cpic-2017","quote":"Activity score 1: Reduce dose by 50% Activity score 1.5: Reduce dose by 25% to 50%","grade":"Activity score 1: Strong Activity score 1.5: Moderate"},{"action":"Raise the dose in later cycles if the first two cycles are well tolerated, and lower it if not","why":"Some carriers tolerate a full dose, and staying on a reduced dose without need may make the treatment less effective.","source":"cpic-2017","quote":"Given that some patients carrying decreased or no function variants tolerate normal doses of 5-fluorouracil, to maintain effectiveness, doses should be increased in subsequent cycles in patients experiencing no or clinically tolerable toxicity in the first two chemotherapy cycles or with subtherapeutic plasma concentrations."},{"action":"Watch every patient closely in the first cycle and after any dose increase, whatever the test showed","why":"Most severe reactions from DPD deficiency appear in the first cycle, and the test does not find every person at risk.","source":"mhra-dsu-2020","quote":"monitor all patients for toxicity particularly during the first cycle of treatment or after a dose increase"},{"action":"Tell the patient that a normal result does not rule out severe side effects, and give them the patient information leaflet","why":"Severe diarrhoea, mouth sores, fever or infection still need same-day contact with the team.","source":"mhra-dsu-2020","quote":"advise patients that despite negative test results for DPD deficiency, severe toxicity may still occur and ensure they have a copy of the patient information leaflet"},{"action":"For an overdose, give uridine triacetate within 96 hours","why":"Uridine triacetate is an antidote that limits the damage fluorouracil does when there is too much of it.","source":"fda-xeloda-2025","quote":"Administer uridine triacetate within 96 hours for management of XELODA overdose."}],"bestInClass":{"statement":"Test before the first systemic dose, act on the result, and keep watching. Europe and the UK test every patient (EMA 2020, MHRA 2020), by genotype, uracil level or both; the US label has since October 2025 told prescribers to genotype before capecitabine unless treatment is urgent. Avoid fluoropyrimidines in complete deficiency. For partial deficiency by genotype, the two pharmacogenetic guidelines differ at activity score 1.5: CPIC (2017) allows a 25 to 50% reduction (moderate) and DPWG (2020) recommends 50%; both reduce by 50% at activity score 1 (CPIC strong). CPIC adds titration upwards after two tolerated cycles. DPWG alone recommends phenotyping where the genotype cannot give a score, and avoiding tegafur in any carrier. A normal result does not remove the need to monitor the first cycle.","sources":["ema-2020","mhra-dsu-2020","xeloda-smpc","fda-xeloda-2025","cpic-2017","dpwg-2020"]},"variants":[{"name":"Uracil phenotyping instead of, or as well as, genotyping","differs":"Measures plasma uracil before treatment rather than reading DPYD variants; France is the country best known for it, and the EU product information gives the thresholds (16 to under 150 ng/mL partial, 150 ng/mL or more complete deficiency).","evidence":"The EU review accepted both methods because the best one is uncertain. A uracil test can find deficiency from causes other than the four common variants, but kidney impairment raises uracil and can mislead. DPWG recommends phenotyping where a genotype cannot be scored, and for any homozygous carrier.","sources":["xeloda-smpc","mhra-dsu-2020","dpwg-2020"]},{"name":"DPWG dosing: 50% at activity scores 1 and 1.5, and no tegafur in carriers","differs":"The Dutch guideline starts every heterozygous carrier at half dose of fluorouracil or capecitabine, recommends avoiding tegafur at any activity score below 2, and avoids systemic and cutaneous fluorouracil at a score of 0.","evidence":"The DPWG text compares itself with CPIC: CPIC allows 25 to 50% at a score of 1.5 on the basis of small capecitabine studies and makes no tegafur recommendation because evidence is too limited.","sources":["dpwg-2020","cpic-2017"]},{"name":"United States: genotype before capecitabine unless treatment is urgent","differs":"The US label (boxed warning and section 2.1, revised 10/2025) tells prescribers to test for DPYD variants before capecitabine unless immediate treatment is necessary, says no FDA-authorised test is available, and gives no dose for partial deficiency beyond individualising it.","evidence":"Regulatory labelling, not a graded guideline. The label notes that available tests vary in which variants they detect.","sources":["fda-xeloda-2025"]},{"name":"Wider genotyping panels","differs":"Laboratories test a defined minimum set of DPYD variants (tier 1) and an extended list (tier 2) rather than only the four variants named in the EU product information.","evidence":"A 2024 joint consensus of AMP, ACMG, CPIC, CAP, DPWG and others sets out the tiers for laboratory assays; only its abstract was read, and it states its recommendations are a reference guide, not prescriptive.","sources":["amp-2024"]},{"name":"Measuring the fluorouracil blood level during a continuous infusion","differs":"Adjusts the dose of an infusional fluorouracil regimen by the measured blood level rather than by body surface area alone.","evidence":"The EU review says it may improve clinical outcomes as a complement to pre-treatment testing; the MHRA gives the target area under the curve as 20 to 30 mg x h/L.","sources":["ema-2020","mhra-dsu-2020"]}],"grades":[{"claim":"Phenotype and/or genotype testing before fluoropyrimidines","grade":"Regulatory recommendation (not graded)","source":"ema-2020","quote":"Phenotype and/or genotype testing is therefore recommended before starting treatment with fluoropyrimidines."},{"claim":"Test for DPYD variants before capecitabine unless immediate treatment is necessary (US label)","grade":"Boxed warning (10/2025)","source":"fda-xeloda-2025","quote":"Prior to initiating XELODA, test patients for genetic variants of the DPYD gene unless immediate treatment is necessary."},{"claim":"Normal metabolisers: label dose","grade":"Strong","source":"cpic-2017","quote":"Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration."},{"claim":"Activity score 1: reduce the starting dose by 50%; 1.5: by 25 to 50%","grade":"Activity score 1: Strong Activity score 1.5: Moderate","source":"cpic-2017"},{"claim":"Activity score 0: avoid fluorouracil and its prodrugs","grade":"Strong","source":"cpic-2017","quote":"Activity score 0: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens."},{"claim":"Tegafur: no CPIC recommendation","grade":"no recommendation","source":"cpic-2017","quote":"As such, tegafur is rated as a CPIC “no recommendation” (see Supplement for definition)."},{"claim":"DPYD genotyping before fluoropyrimidines","grade":"Clinical implication score: essential","source":"dpwg-2020","quote":"This score dictates that DPYD genotyping prior to treatment must be performed for all patients initially being prescribed therapy with 5-FU, capecitabine or tegafur with DPD inhibitors, to optimize the initial dose and to prevent potentially fatal toxicity."}],"sources":[{"key":"ema-2020","label":"EMA recommendations on DPD testing prior to treatment with fluorouracil, capecitabine, tegafur and flucytosine (EMA/229267/2020)","publisher":"European Medicines Agency","year":2020,"url":"https://www.ema.europa.eu/en/news/ema-recommendations-dpd-testing-prior-treatment-fluorouracil-capecitabine-tegafur-and-flucytosine","gradingScheme":"A regulatory recommendation; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"mhra-dsu-2020","label":"5-fluorouracil (intravenous), capecitabine, tegafur: DPD testing recommended before initiation to identify patients at increased risk of severe and fatal toxicity (Drug Safety Update volume 14, issue 3)","publisher":"Medicines and Healthcare products Regulatory Agency (UK)","year":2020,"url":"https://www.gov.uk/drug-safety-update/5-fluorouracil-intravenous-capecitabine-tegafur-dpd-testing-recommended-before-initiation-to-identify-patients-at-increased-risk-of-severe-and-fatal-toxicity","gradingScheme":"Regulatory advice to healthcare professionals; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"xeloda-smpc","label":"Xeloda (capecitabine): summary of product characteristics, section 4.4","publisher":"European Medicines Agency (EPAR product information)","year":2026,"url":"https://www.ema.europa.eu/en/documents/product-information/xeloda-epar-product-information_en.pdf","gradingScheme":"Product information; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"fda-xeloda-2025","label":"XELODA (capecitabine) prescribing information, boxed warning and sections 2.1 and 5.1 revised 10/2025","publisher":"US Food and Drug Administration label (DailyMed)","year":2025,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e702d84d-7162-4751-bf37-d724cc7e45a5","gradingScheme":"Product labelling; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"cpic-2017","label":"Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update","publisher":"CPIC (Clinical Pharmacology & Therapeutics, Amstutz et al.)","year":2018,"url":"https://doi.org/10.1002/cpt.911","doi":"10.1002/cpt.911","gradingScheme":"Strength of each dosing recommendation printed as Strong or Moderate, or 'no recommendation' where evidence is too limited; the scheme is defined in the guideline's supplement, which was not read.","read":"full-text","accessed":"2026-11-11"},{"key":"dpwg-2020","label":"Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines","publisher":"DPWG, Royal Dutch Pharmacists Association (European Journal of Human Genetics, Lunenburg et al.)","year":2020,"url":"https://doi.org/10.1038/s41431-019-0540-0","doi":"10.1038/s41431-019-0540-0","gradingScheme":"A clinical implication score for testing before treatment: essential, beneficial, potentially beneficial or not required.","read":"full-text","accessed":"2026-11-11"},{"key":"amp-2024","label":"DPYD Genotyping Recommendations: A Joint Consensus Recommendation of AMP, ACMG, CPIC, CAP, DPWG, ESPT, PharmGKB and PharmVar","publisher":"Association for Molecular Pathology and partners (Journal of Molecular Diagnostics, Pratt et al.)","year":2024,"url":"https://doi.org/10.1016/j.jmoldx.2024.05.015","doi":"10.1016/j.jmoldx.2024.05.015","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-tr1-pre-emptive-pharmacogenomic-testing"],"gaps":["The four variants in the EU product information are, in its words, considered virtually absent in people of African or Asian ancestry, so a negative four-variant genotype says less for them; which wider panel to use is set out in the 2024 AMP consensus, of which only the abstract was read.","The guidelines disagree on the reduction at activity score 1.5 (CPIC 25 to 50%, DPWG 50%), and CPIC notes the 25% figure comes from small capecitabine studies with no data for infusional fluorouracil.","The CPIC guideline read is the 2017 update. Its website now redirects to ClinPGx, which serves no text to a script, so a newer CPIC revision could not be ruled out; none was found in Europe PMC.","The CPIC supplement defining its recommendation strengths was not read; grades are quoted as printed in the main table.","No ESMO or NCCN recommendation on DPD testing was read. ASCO and NCCN positions are not stated here.","Uracil thresholds are described by the EU product information itself as uncertain, and the turnaround time of testing, which can delay a first cycle, is not addressed by any source read.","In the US label, no dose is given for partial deficiency and no FDA-authorised DPYD test exists."]},{"id":"driving-flying-and-travel-during-cancer-treatment","kind":"protocol","name":"Driving, flying and travel during cancer treatment","aka":["driving and cancer","DVLA and cancer","flying with cancer","travel insurance and cancer","travel vaccinations during chemotherapy","taking cancer medicines abroad"],"tldr":"In Great Britain most people with cancer need not tell the DVLA, unless the cancer affects the brain or nerves, a doctor says they may be unfit to drive, or medicines affect driving. Before travelling abroad, ask the cancer team whether it is safe, avoid live vaccines unless the team agrees, carry medicines and a doctor's letter in hand luggage, and declare the cancer to the travel insurer.","summary":"The UK driving rules are law, not clinical guidance. The DVLA requires a car or motorcycle driver with cancer to tell it only if they develop problems with the brain or nervous system, a doctor says they might not be fit to drive, they are restricted to certain or adapted vehicles, or medication side effects could affect driving; bus, coach and lorry drivers must tell it if the condition will affect driving. Failing to declare a condition that affects driving carries a fine of up to £1,000. Under the drug-driving law in England, Scotland and Wales, prescribed opioids and benzodiazepines may be taken while driving only if they were prescribed, taken as advised, and are not impairing. Macmillan's travel guidance (2023, under review) says to ask the cancer team before flying, names reasons people may be advised not to fly (low platelets, raised pressure from a brain tumour, recent brain, chest, bowel or eye surgery), notes the clot risk of long flights, says live vaccines must not be given during or recently after chemotherapy or radiotherapy and some targeted or immunotherapy drugs, advises seeing a travel health professional at least 8 weeks before travel, carrying medicines and a doctor's letter in hand luggage in original packaging, and always declaring pre-existing conditions to the insurer. None of this is graded, and the CDC Yellow Book chapter on immunocompromised travellers could not be read.","asOf":"2026-11-11","links":[],"tags":[],"related":["sun-protection-during-and-after-cancer-treatment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Ask your team before you drive, fly or travel abroad. Do not drive if you feel sleepy from treatment or medicines. Tell the DVLA if your doctor says your cancer or treatment affects your driving. Do not have live vaccines during treatment unless your team says it is safe. Keep your medicines and a letter from your doctor in your hand luggage, and tell your travel insurer about your cancer.","domain":"supportive-care","setting":{"who":["patient-or-carer","doctor","nurse","pharmacist"],"where":["home","outpatient-clinic"]},"population":"Adults with cancer, during or after treatment, who drive or plan to travel. The driving rules are those of Great Britain (DVLA) and, for drug-driving, England, Scotland and Wales; other countries have their own rules. People who have had a stem cell transplant, leukaemia, or thymus cancer or thymectomy have specific vaccine restrictions named below.","trigger":"A person with cancer wants to drive, or plans a flight or a trip abroad.","steps":[{"action":"Ask the cancer team whether the cancer or the treatment affects driving, and tell the DVLA if it does","why":"A driver must declare a condition that affects driving, and not doing so can bring a fine or prosecution after an accident.","source":"dvla-cancer-driving","quote":"You must tell DVLA if your condition will affect your driving.","grade":"Legal requirement (Great Britain)"},{"action":"Do not drive if a treatment or medicine makes you sleepy, and ask the doctor or pharmacist before driving on opioids or benzodiazepines","why":"Driving while impaired by a prescribed medicine is an offence, even when the medicine was correctly prescribed.","source":"gov-drug-driving","quote":"It’s illegal in England, Scotland and Wales to drive with legal drugs in your body if it impairs your driving.","grade":"Legal requirement (England, Scotland and Wales)"},{"action":"Ask the cancer doctor or specialist nurse before booking a flight","why":"Low platelets, raised pressure in the brain and recent surgery to the brain, chest, bowel or eye can make flying unsafe.","source":"macmillan-flying","quote":"Always get advice from your cancer doctor or specialist nurse if you are thinking of flying anywhere.","grade":"Not graded (patient information)"},{"action":"On long journeys, ask the team about your clot risk and how to reduce it","why":"Sitting still for a long time and cancer treatment both raise the risk of a blood clot.","source":"macmillan-flying","quote":"Flying can increase the risk of developing a blood clot.","grade":"Not graded (patient information)"},{"action":"See a travel health professional at least 8 weeks before travel, and do not have live vaccines during or soon after chemotherapy, radiotherapy, some targeted or immunotherapy drugs, high-dose steroids or a transplant unless the cancer doctor says it is safe","why":"A live vaccine can cause a serious infection when the immune system is weak, and some vaccines need several doses over weeks.","source":"macmillan-vaccinations","quote":"If you have a weakened immune system, live vaccines may cause a serious or life-threatening infection.","grade":"Not graded (patient information, drawing on the UK Green Book)"},{"action":"Carry medicines in their original packaging in hand luggage, with a doctor's letter and a list of medicines by generic name, and enough supply for delays; check controlled-drug rules for opioids","why":"Customs and security may check medicines, some countries restrict them, and luggage can be lost.","source":"macmillan-medication-abroad","quote":"For security and customs checks, it is best to carry all medicines and letters from your doctor or other paperwork in your hand luggage.","grade":"Not graded (patient information)"},{"action":"Declare the cancer and any other conditions to the travel insurer, and tell them of changes before travel","why":"An insurer can refuse any claim, even an unrelated one, if a condition was not declared.","source":"macmillan-travel-insurance","quote":"You should always tell your insurer about pre-existing medical conditions.","grade":"Not graded (patient information)"},{"action":"If treatment raises the risk of infection, ask the team for advice before the trip and take care with food, water and hand washing abroad","why":"Infections from food and water can be more serious when the immune system is weak.","source":"macmillan-holiday","quote":"If you are at risk of infection because of cancer treatment , you need to be extra careful about what you eat and drink.","grade":"Not graded (patient information)"}],"bestInClass":{"statement":"Driving is governed by law rather than clinical guidance: in Great Britain the DVLA's cancer rules and the drug-driving law are the standard, and a driver follows them. For travel, no graded guideline was read; the best available version is the convergent UK patient guidance from Macmillan (2023): clearance from the cancer team before flying, no live vaccines during or soon after immunosuppressive treatment unless the cancer doctor agrees, a travel health appointment at least 8 weeks ahead, medicines in original packaging in hand luggage with a doctor's letter, and full declaration to the travel insurer.","sources":["dvla-cancer-driving","gov-drug-driving","macmillan-flying","macmillan-vaccinations","macmillan-medication-abroad","macmillan-travel-insurance"]},"variants":[{"name":"Lifelong caution on live vaccines after leukaemia or HIV-related cancer, and no yellow fever vaccine after thymus cancer or thymectomy (Macmillan)","differs":"Some people have to avoid live vaccines for life, and yellow fever vaccine is never given after thymus cancer or removal of the thymus.","evidence":"Patient information drawing on the UK Green Book, not graded.","sources":["macmillan-vaccinations"]},{"name":"Bus, coach and lorry licences","differs":"Drivers with these licences must tell the DVLA if the condition will affect driving, using form C1V rather than C1.","evidence":"Legal requirement (DVLA).","sources":["dvla-cancer-driving"]},{"name":"Advice not to drive when sleepy (Macmillan)","differs":"Puts the rule simply: if sleepy from chemotherapy or sleep problems, do not drive or operate machinery.","evidence":"Patient information, not graded: 'If you feel sleepy, do not drive or operate machinery.'","sources":["macmillan-chemo-side-effects"]}],"grades":[{"claim":"When a car or motorcycle driver with cancer must tell the DVLA","grade":"Legal requirement (Great Britain)","source":"dvla-cancer-driving","quote":"You do not need to tell DVLA if you have cancer, unless:"},{"claim":"Penalty for not declaring a condition that affects driving","grade":"Legal requirement (Great Britain)","source":"dvla-cancer-driving","quote":"You can be fined up to £1,000 if you do not tell DVLA about a medical condition that affects your driving."},{"claim":"Prescribed opioids and benzodiazepines may be taken when driving only if prescribed, taken as advised and not impairing","grade":"Legal requirement (England, Scotland and Wales)","source":"gov-drug-driving","quote":"you’ve been prescribed them and followed advice on how to take them by a healthcare professional"},{"claim":"Travel advice","grade":"Not graded: patient information pages without a grading scheme","source":"macmillan-flying"}],"sources":[{"key":"dvla-cancer-driving","label":"Cancer and driving","publisher":"GOV.UK (Driver and Vehicle Licensing Agency)","year":2026,"url":"https://www.gov.uk/cancer-and-driving","gradingScheme":"Legal requirements; not a graded guideline. Undated page, read as current on the access date.","read":"full-text","accessed":"2026-11-11"},{"key":"gov-drug-driving","label":"Drugs and driving: the law","publisher":"GOV.UK","year":2026,"url":"https://www.gov.uk/drug-driving-law","gradingScheme":"Legal requirements; not a graded guideline. Undated page, read as current on the access date.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-flying","label":"Can you fly with cancer?","publisher":"Macmillan Cancer Support","year":2023,"url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/travel/cancer-and-flying","gradingScheme":"Patient information page; not graded. Reviewed 1 March 2023, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-vaccinations","label":"Cancer and travel vaccinations","publisher":"Macmillan Cancer Support","year":2023,"url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/travel/getting-vaccinations","gradingScheme":"Patient information page; not graded. Reviewed 1 March 2023, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-medication-abroad","label":"Taking medication abroad","publisher":"Macmillan Cancer Support","year":2023,"url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/travel/taking-medication-abroad","gradingScheme":"Patient information page; not graded. Reviewed 1 March 2023, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-travel-insurance","label":"Cancer and buying travel insurance","publisher":"Macmillan Cancer Support","year":2023,"url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/travel/buying-travel-insurance","gradingScheme":"Patient information page; not graded. Reviewed 1 March 2023, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-holiday","label":"Taking care on holiday (travel and cancer)","publisher":"Macmillan Cancer Support","year":2023,"url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/travel/taking-care-on-holiday","gradingScheme":"Patient information page; not graded. Reviewed 1 March 2023, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-chemo-side-effects","label":"Side effects of chemotherapy","publisher":"Macmillan Cancer Support","year":2018,"url":"https://www.macmillan.org.uk/cancer-information-and-support/treatment/types-of-treatment/chemotherapy/side-effects-of-chemotherapy","gradingScheme":"Patient information page; not graded. Reviewed September 2018, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"cdc-yellow-book-immunocompromised","label":"CDC Yellow Book: immunocompromised travelers","publisher":"CDC","year":2026,"url":"https://www.cdc.gov/yellow-book/hcp/travelers-with-additional-considerations/immunocompromised-travelers.html","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The driving rules read are those of Great Britain; Northern Ireland and other countries have their own licensing rules, which were not read.","The DVLA's medical standards for professionals (Assessing fitness to drive), which set specific rules for brain tumours and other cancers affecting the nervous system, were not read.","The CDC Yellow Book chapter on immunocompromised travellers returned HTTP 403 and could not be read; the UK Green Book itself was not read, only Macmillan's account of it.","How long to wait after chemotherapy or other treatment before a live vaccine is safe varies by treatment and is not given in the sources read; the cancer doctor decides.","No source read gives a graded recommendation on preventing clots during travel for people with cancer.","All Macmillan travel pages were last reviewed in March 2023 and are marked as under review."]},{"id":"anticancer-drug-interaction-review","kind":"protocol","name":"Drug, herbal and food interaction review for anticancer treatment","aka":["drug interaction check before chemotherapy","DDI review","drug-drug interactions with anticancer drugs","herb-drug interactions","supplement interactions with chemotherapy","grapefruit and cancer drugs","CYP3A4 interactions","proton pump inhibitors and TKIs","St John's wort and chemotherapy"],"tldr":"Some everyday medicines, herbal remedies, supplements and even foods such as grapefruit can make cancer drugs stronger and more toxic or weaker and less effective. Before treatment starts, and whenever anything changes, the team should check everything you take. Tell them about every tablet, remedy, vitamin and supplement, even ones you buy yourself.","summary":"Interactions with anticancer drugs are common and change both efficacy and toxicity. ASCO-ONS (2024) requires a medication list that includes over-the-counter medicines, herbal products and supplements, updated at every encounter and reviewed by a licensed practitioner when it changes, and pre-treatment education on interactions with prescribed drugs, integrative therapies, over-the-counter drugs and foods. It notes that patients may not mention herbal products or vitamins because they do not regard them as medicines, so staff must ask. BOPA (2025) makes the interaction check part of the pharmacist's verification at cycle 1 and for any new medicine at later cycles.\n\nThe interactions that matter most are pharmacokinetic: strong CYP3A inhibitors and inducers with oral targeted drugs (the ibrutinib label requires dose changes with inhibitors, avoidance of strong inducers, and no grapefruit or Seville oranges), and acid suppressants that cut absorption of pH-dependent kinase inhibitors (erlotinib: avoid proton pump inhibitors if possible, separate H2 blockers and antacids). St John's wort, a strong inducer, lowers levels of irinotecan's active metabolite and of imatinib. A Dutch multidisciplinary group graded 290 potential interactions: 94 clinically relevant with an advised intervention, 110 not relevant, and 86 with too little evidence; it argues for building such rules into electronic prescribing. In 202 older adults on anticancer treatment, 12% used herbs and 4% had a potentially relevant herb-drug interaction, half judged clinically relevant (red yeast rice, red coneflower, turmeric, cannabis). One widely named checker, Cancer Drug Interactions (Radboud UMC and University of Liverpool), has been closed since 2023, with an archive last updated in 2022.","asOf":"2026-11-11","links":[],"tags":[],"related":["medicines-reconciliation-in-cancer-care","oral-anticancer-medicines-at-home","sact-prescribing-and-pharmacy-verification"],"cancers":[],"sections":[],"technologies":["st-johns-wort-interaction","dietary-supplements-treatment-interactions","traditional-chinese-herbal-medicine"],"targets":[],"drugs":["ibrutinib","erlotinib","irinotecan","imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Tell your cancer team about every medicine, vitamin, herbal remedy and supplement you take, and ask before starting anything new, because some can stop cancer drugs working or make them harmful.","domain":"pharmacy","setting":{"who":["pharmacist","doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","ward","home","community"]},"population":"Adults and children starting or receiving any systemic anticancer treatment, oral or intravenous, and especially oral targeted therapies, which carry most of the pharmacokinetic interactions.","trigger":"A new anticancer regimen is planned; any other medicine, supplement or herbal product is started, stopped or changed; or the person is admitted, transferred or discharged.","steps":[{"action":"Keep one medication list that includes prescribed and over-the-counter medicines, herbal products and supplements, update it at every visit and have a licensed practitioner review it when anything changes","why":"An interaction can only be found if every product the person takes is on the list.","source":"asco-ons-2024","quote":"The patient's medication list inclusive of prescribed and over-the-counter medications, herbal products, and supplements is updated and documented in the medical record at every encounter and reviewed by a licensed practitioner when a change occurs"},{"action":"Ask directly about herbal products, vitamins and supplements, because people often do not count them as medicines","why":"Many people do not mention remedies they buy themselves unless asked.","source":"asco-ons-2024","quote":"Some patients, at times, may not disclose their use of herbal product, supplements, and vitamins during interviews because they may not regard these as medications. Pharmacists and providers must proactively inquire and document herbal product and complementary medications use within the medication list."},{"action":"Before the first cycle, check every planned anticancer and supportive medicine against all the person's other medicines for interactions, contraindications and duplication","why":"This is the point where a regimen can still be changed or another medicine swapped before harm is done.","source":"bopa-2025","quote":"Check for potential interactions, contra-indications and duplication between all planned SACT & supportive medication and patient’s concurrent medication."},{"action":"At each later cycle, check any medicine started since the last cycle","why":"New prescriptions from other doctors, such as antibiotics, antifungals or antacids, are a common source of new interactions.","source":"bopa-2025","quote":"Check patient allergy status, interactions or contraindications against any new medicines prescribed since last cycle (when information accessible)."},{"action":"For oral targeted drugs metabolised by CYP3A, change the dose or avoid strong inhibitors and inducers as the label directs, and tell the person to avoid grapefruit and Seville oranges where the label says so","why":"Inhibitors raise blood levels and toxicity; inducers lower them and can make treatment fail.","source":"ibrutinib-label","quote":"Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain strong or moderate inhibitors of CYP3A."},{"action":"For kinase inhibitors that need stomach acid to be absorbed, avoid proton pump inhibitors where possible and time H2 blockers and antacids as the label directs","why":"Lowering stomach acid can stop the cancer drug being absorbed, so less of it reaches the cancer.","source":"erlotinib-label","quote":"For proton pump inhibitors, avoid concomitant use if possible. For H-2 receptor antagonists and antacids, modify the dosing schedule"},{"action":"Teach the person and their carers which medicines, remedies and foods interact with their treatment before it starts","why":"Most new medicines and supplements are started between clinic visits, often without the cancer team knowing.","source":"asco-ons-2024","quote":"Planned duration of treatment, schedule of treatment administration, plan for missed doses, drug names and supportive medications, and drug interactions with prescribed drugs, integrative therapies, over the counter drugs, and foods"},{"action":"Use a graded, maintained interaction reference, ideally built into electronic prescribing, rather than a general checker alone","why":"General checkers flag many interactions that do not matter and can miss ones that do; graded rules say which need action.","source":"van-leeuwen-2022","quote":"Integration of DDI guidelines into the national electronic prescribing system is essential to achieve optimal efficacy and minimal toxicity in patients receiving anticancer therapy."}],"bestInClass":{"statement":"A complete medication list including over-the-counter, herbal and supplement products, updated every visit and reviewed when it changes (ASCO-ONS 2024), with herbal use asked about directly; a pharmacist interaction check before cycle 1 and for each new medicine (BOPA 2025); label-directed management of CYP3A and acid-suppressant interactions; and patient education on interactions before treatment. No international guideline grades these steps; the only graded interaction-by-interaction guidance found is the Dutch multidisciplinary set (2022), read as an abstract.","sources":["asco-ons-2024","bopa-2025","van-leeuwen-2022","ibrutinib-label","erlotinib-label"]},"variants":[{"name":"Pharmacist-led reconciliation before early-phase trials","differs":"A pharmacist reconciles medicines against the trial protocol's prohibited and monitored lists before enrolment.","evidence":"In 501 trial patients at one French centre, reconciliation found 346 interactions, 158 with prohibited medicines, more than half of them herbal, and 51% of prohibited or monitored drugs had been missed by oncologists (Malifarge 2024).","sources":["malifarge-2024"]},{"name":"Screening for specific herbs known to interact","differs":"Uses a questionnaire on a set list of commonly used herbs with known interactions, then has two pharmacists judge each hit.","evidence":"In 202 adults aged 65 or over, herb use was 12% and potentially relevant herb-drug interactions 4%, half clinically relevant (Brokaar 2025).","sources":["brokaar-2025"]}],"grades":[],"sources":[{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and ONS (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded; developed from a systematic review (2015 to 2023), expert panel consensus and public comment.","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"van-leeuwen-2022","label":"Evidence- and consensus-based guidelines for drug-drug interactions with anticancer drugs; A practical and universal tool for management","publisher":"Seminars in Oncology (van Leeuwen et al., Dutch Multidisciplinary Expert group)","year":2022,"url":"https://doi.org/10.1053/j.seminoncol.2022.03.002","doi":"10.1053/j.seminoncol.2022.03.002","read":"abstract","accessed":"2026-11-11"},{"key":"ibrutinib-label","label":"Imbruvica (ibrutinib), US prescribing information","publisher":"US National Library of Medicine, DailyMed","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=0dfd0279-ff17-4ea9-89be-9803c71bab44","read":"full-text","accessed":"2026-11-11"},{"key":"erlotinib-label","label":"Erlotinib tablets, US prescribing information (Camber)","publisher":"US National Library of Medicine, DailyMed","year":2024,"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a3b2d622-b4d5-4819-862b-f8fd3adcec6f","read":"full-text","accessed":"2026-11-11"},{"key":"brokaar-2025","label":"The prevalence of clinically relevant herb-drug interactions between herbal products and anti-cancer therapy in older adults with cancer","publisher":"Exploratory Research in Clinical and Social Pharmacy (Brokaar et al.)","year":2025,"url":"https://doi.org/10.1016/j.rcsop.2025.100585","doi":"10.1016/j.rcsop.2025.100585","read":"abstract","accessed":"2026-11-11"},{"key":"malifarge-2024","label":"Impact of Medication Reconciliation in Oncology Early Phase Studies: A Drug-Drug Interaction Retrospective Study","publisher":"JCO Oncology Practice (Malifarge et al.)","year":2024,"url":"https://doi.org/10.1200/OP.22.00281","doi":"10.1200/OP.22.00281","read":"abstract","accessed":"2026-11-11"},{"key":"cancer-drug-interactions-site","label":"Cancer Drug Interactions (archived interaction checker)","publisher":"Radboud UMC and University of Liverpool","year":2023,"url":"https://cancer-druginteractions.org/","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No national or international guideline grades interaction review for anticancer drugs; ASCO-ONS and BOPA set standards without grades, and the graded Dutch guideline was read only as an abstract.","The Cancer Drug Interactions checker that BOPA 2025 names went offline in September 2023, and its archive (last updated June 2022) was due to close on 31 January 2025. No free, maintained, oncology-specific checker of the same scope was found; Stockley's, which BOPA also names, is a subscription product and was not read.","Evidence on most herb-drug interactions comes from small pharmacokinetic studies and case reports; for many popular supplements there is no evidence either way.","The St John's wort figures in the summary come from the OnCo record st-johns-wort-interaction and its cited study, not from a source read for this protocol."]},{"id":"egfr-inhibitor-rash-prophylaxis","kind":"protocol","name":"EGFR inhibitor rash: pre-emptive skin care, antibiotics and dose changes","aka":["EGFR inhibitor rash prophylaxis","acneiform rash","papulopustular rash","pre-emptive doxycycline","pre-emptive skin treatment","cetuximab rash","panitumumab rash","amivantamab skin care","COCOON regimen","STEPP regimen"],"tldr":"Drugs that block EGFR, such as cetuximab, panitumumab, amivantamab and EGFR tablets for lung cancer, very often cause an acne-like rash. Starting skin care on day one makes a bad rash much less likely: doxycycline or minocycline for the first weeks, moisturiser, sunscreen, and sometimes a mild steroid cream. Tell your team early if it spreads or hurts: a pause or lower dose may help.","summary":"The MASCC Skin Toxicity Study Group (2011) recommends pre-emptive management for EGFR inhibitor rash because it is frequent and appears in the first 2 to 4 weeks: hydrocortisone 1 per cent with moisturiser and sunscreen twice daily, plus doxycycline 100 mg twice daily (or minocycline 100 mg daily) for the first 6 weeks, based on the randomised STEPP trial. In STEPP (panitumumab, 95 people), protocol-specified grade 2 or worse skin toxicity in 6 weeks fell from 62 to 29 per cent; J-STEPP repeated the result in Japanese patients (62.5 to 21.3 per cent). A 2022 meta-analysis found oral antibiotics reduced grade 2 or worse rash by 40 per cent; topical antibiotics, vitamin K1 cream and sunscreen alone were not significant. For amivantamab, the 2026 US label now recommends the COCOON regimen at initiation: doxycycline or minocycline 100 mg twice daily for 12 weeks, then clindamycin 1 per cent lotion to the scalp for 9 months, a non-comedogenic moisturiser, daily 4 per cent chlorhexidine for hands and feet, and sun protection; in the COCOON trial (amivantamab with lazertinib, 201 people) it reduced grade 2 or worse dermatologic events by week 12 from 75 to 42 per cent. Doubts remain: in a post hoc analysis of the Valentino trial of first-line panitumumab, doxycycline prophylaxis did not significantly lower rash. Dose rules come from labels: panitumumab is withheld for 1 to 2 doses at grade 3 and restarted at 100, 80 then 60 per cent by occurrence. The ESMO 2021 guideline could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","skin-toxicity","egfr-inhibitor","supportive-care"],"related":[],"cancers":["colorectal","egfr-mutant-nsclc"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":["cetuximab","panitumumab","amivantamab","lazertinib","erlotinib","gefitinib","afatinib","osimertinib","hydrocortisone"],"companies":[],"institutions":[],"pathways":[],"terms":["rash-skin-toxicity","chemotherapy-side-effects-colorectal"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer drugs cause a spotty rash. Starting antibiotic tablets, moisturiser and sunscreen on day one helps. Tell your team if the rash gets bad.","domain":"symptom-management","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","home"]},"population":"Adults starting an EGFR-targeted drug: cetuximab or panitumumab (colorectal and head and neck cancer), amivantamab with or without lazertinib, and EGFR tyrosine kinase inhibitors (erlotinib, gefitinib, afatinib, osimertinib) in lung cancer. STEPP and J-STEPP were in metastatic colorectal cancer on panitumumab; COCOON in untreated EGFR-mutant lung cancer on amivantamab with lazertinib. Tetracyclines are not suitable in pregnancy or for some people with drug allergies; the sources read do not list contraindications in full.","trigger":"An EGFR-targeted drug is planned; prophylaxis starts on the first day of treatment.","steps":[{"action":"Start pre-emptive skin care on the first day of an EGFR inhibitor, rather than waiting for the rash","why":"The rash is very common and comes in the first weeks; treating early prevents most of the severe cases.","source":"mascc-2011","quote":"Based on the high frequency of rash in EGFRI-treated patients and the consistent presentation within the first 2–4 weeks of therapy, preventive/prophylactic management is recommended unless there are contraindications based on patient and/or health care provider factors [ 6 – 12 ].","grade":"Level II, grade A (systemic tetracycline)"},{"action":"Prescribe doxycycline 100 mg twice daily (or minocycline 100 mg daily) for the first 6 weeks, with hydrocortisone 1 per cent cream, a moisturiser and sunscreen twice daily","why":"The antibiotic is used for its anti-inflammatory effect on the skin, not for infection; with gentle skin care it halved moderate rash in the trial behind this advice.","source":"mascc-2011","quote":"Hydrocortisone 1% combined with moisturizer, sunscreen, and doxycycline 100 mg bid for the first 6 weeks is recommended based on randomized data.","grade":"Level II, grade A (tetracycline); Level II, grade C (topical hydrocortisone with moisturiser and sunscreen)"},{"action":"With amivantamab, follow the label regimen from day 1: doxycycline or minocycline 100 mg twice daily for 12 weeks, then clindamycin 1 per cent lotion on the scalp once daily for 9 months","why":"Amivantamab causes rash, scalp and nail problems over many months; a longer regimen covering the scalp reduced moderate skin problems in a randomised trial.","source":"rybrevant-label","quote":"Administer an oral antibiotic (doxycycline or minocycline, 100 mg orally twice daily) starting on Day 1 for the first 12 weeks of treatment.","grade":"US prescribing information"},{"action":"With amivantamab, add a non-comedogenic moisturiser on the face and body and a daily 4 per cent chlorhexidine wash for the hands and feet","why":"Moisturiser protects dry skin; the antiseptic wash aims to prevent infection around the nails (paronychia).","source":"rybrevant-label","quote":"Wash hands and feet with 4% chlorhexidine solution once daily.","grade":"US prescribing information"},{"action":"Advise sun protection during treatment and for 2 months after: sunscreen, hats and protective clothing, and limiting time in strong sun","why":"Sunlight makes the rash worse, and some of the tetracyclines make skin more sensitive to sun.","source":"vectibix-label","quote":"Advise patients to limit sun exposure (use sunscreen, wear hats) while receiving Vectibix and for 2 months after the last dose of Vectibix therapy","grade":"US prescribing information"},{"action":"If rash develops despite prophylaxis, treat with a medium- to high-potency topical steroid and continue or start the oral tetracycline","why":"The rash is inflammatory rather than true acne, so anti-inflammatory creams help; acne creams that dry the skin can make it worse.","source":"mascc-2011","quote":"Reactive use of medium- to high-potency topical corticosteroids is recommended based on studies showing in vitro release of inflammatory chemokines after EGFRI therapy.","grade":"Level IV, grade C"},{"action":"Panitumumab: at a first grade 3 skin reaction, withhold 1 to 2 doses and restart at the original dose once it is below grade 3; reduce to 80 then 60 per cent on later occurrences and stop on the fourth","why":"A pause lets the skin settle while keeping the treatment going; repeated severe rashes need a lower dose.","source":"vectibix-label","quote":"Upon first occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold 1 to 2 doses of Vectibix. If the reaction improves to < Grade 3, reinitiate Vectibix at the original dose.","grade":"US prescribing information"}],"bestInClass":{"statement":"Pre-emptive treatment from day 1 with an oral tetracycline, moisturiser, sunscreen and a mild topical steroid is the best-supported approach for EGFR antibodies, on the MASCC 2011 guideline (systemic tetracycline Level II, grade A) and two randomised trials (STEPP, J-STEPP), and oral antibiotics are the only preventive measure significant in the 2022 meta-analysis. For amivantamab the US label now builds the COCOON regimen into dosing, on the strength of a randomised trial. The evidence is not uniform: a post hoc analysis of first-line panitumumab in the Valentino trial found no significant reduction in rash with doxycycline. The ESMO 2021 dermatological toxicity guideline, the most recent international guideline, could not be read, and MASCC has not updated its 2011 guideline in any source found.","sources":["mascc-2011","stepp-2010","j-stepp-2015","egfr-ma-2022","rybrevant-label","cocoon-2025","valentino-2021","esmo-derm-2021"]},"variants":[{"name":"COCOON enhanced dermatologic management (amivantamab with lazertinib)","differs":"Twelve weeks of oral doxycycline or minocycline (rather than 6), then 9 months of clindamycin 1 per cent on the scalp, chlorhexidine 4 per cent on fingernails and toenails, and ceramide-based moisturiser at least daily.","evidence":"Randomised phase 2 trial of 201 people: grade 2 or worse dermatologic adverse events of interest by week 12 in 42 per cent against 75 per cent with standard care (odds ratio 0.24); patient-reported quality of life favoured the regimen. Now in the US amivantamab label.","sources":["cocoon-2025","rybrevant-label"]},{"name":"Reactive treatment only (first-line panitumumab, Valentino analysis)","differs":"Treating rash when it appears rather than with routine prophylaxis.","evidence":"Post hoc, non-randomised comparison within the Valentino trial (226 people): any-grade rash 81 per cent with doxycycline prophylaxis against 90 per cent without (P = 0.085), grade 3 or 4 rash 27 against 25 per cent; no difference in dose delays, reductions or survival.","sources":["valentino-2021"]}],"grades":[{"claim":"Pre-emptive skin treatment halved grade 2 or worse skin toxicity with panitumumab (STEPP)","grade":"randomised phase 2 open-label trial, n = 95","source":"stepp-2010","quote":"The incidence of protocol-specified >or= grade 2 skin toxicities during the 6-week skin treatment period was 29% and 62% for the pre-emptive and reactive groups, respectively."},{"claim":"The result was repeated in Japanese patients (J-STEPP)","grade":"randomised open-label trial, n = 95, P < 0.001","source":"j-stepp-2015","quote":"The primary end point was achieved (21.3 and 62.5% [risk ratio: 0.34; p < 0.001], for pre-emptive and reactive treatment, respectively)."},{"claim":"Oral antibiotics reduced grade 2 or worse acneiform rash by 40 per cent","grade":"systematic review and meta-analysis","source":"egfr-ma-2022","quote":"Oral antibiotics had the greatest efficacy in preventing grade 2 or higher acneiform eruptions with a relative risk reduction of 40% (RR = .6, 95% CI .46-.79, p < .01)."},{"claim":"The COCOON regimen reduced grade 2 or worse dermatologic events with amivantamab and lazertinib","grade":"randomised phase 2 trial, n = 201, p < 0.0001","source":"cocoon-2025","quote":"At a median follow-up of 7.1 months, COCOON DM demonstrated significant reduction in the primary end point versus SoC DM (42% versus 75%; OR, 0.24; 95% confidence interval, 0.13-0.45; p < 0.0001)."}],"sources":[{"key":"mascc-2011","label":"Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities","publisher":"MASCC Skin Toxicity Study Group, Supportive Care in Cancer","year":2011,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3128700/","doi":"10.1007/s00520-011-1197-6","gradingScheme":"Levels of evidence I (meta-analyses or high-powered randomised trials) to V (case reports); recommendation grades A (level I or consistent multiple studies) to D (little or no evidence).","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-derm-2021","label":"Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines","publisher":"ESMO, Annals of Oncology","year":2021,"url":"https://doi.org/10.1016/j.annonc.2020.11.005","doi":"10.1016/j.annonc.2020.11.005","read":"not-reachable","accessed":"2026-11-11"},{"key":"rybrevant-label","label":"RYBREVANT (amivantamab-vmjw) prescribing information","publisher":"Janssen Biotech, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1466c070-9f97-4fa4-a955-6a6b59981fb8","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"vectibix-label","label":"VECTIBIX (panitumumab) prescribing information, including boxed warning","publisher":"Amgen, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0fa4bca-f245-4d92-ae29-b0c630a315c2","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"stepp-2010","label":"Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer","publisher":"Journal of Clinical Oncology","year":2010,"url":"https://europepmc.org/abstract/MED/20142600","doi":"10.1200/JCO.2008.21.7828","read":"abstract","accessed":"2026-11-11"},{"key":"j-stepp-2015","label":"Randomized controlled trial on the skin toxicity of panitumumab in Japanese patients with metastatic colorectal cancer: HGCSG1001 study; J-STEPP","publisher":"Future Oncology","year":2015,"url":"https://europepmc.org/abstract/MED/25686117","doi":"10.2217/fon.14.251","read":"abstract","accessed":"2026-11-11"},{"key":"cocoon-2025","label":"Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial","publisher":"Journal of Thoracic Oncology","year":2025,"url":"https://europepmc.org/abstract/MED/40923969","doi":"10.1016/j.jtho.2025.07.117","read":"abstract","accessed":"2026-11-11"},{"key":"valentino-2021","label":"Systemic doxycycline for pre-emptive treatment of anti-EGFR-related skin toxicity in patients with metastatic colorectal cancer receiving first-line panitumumab-based therapy: a post hoc analysis of the Valentino study","publisher":"Supportive Care in Cancer","year":2021,"url":"https://europepmc.org/abstract/MED/33392769","doi":"10.1007/s00520-020-05972-2","read":"abstract","accessed":"2026-11-11"},{"key":"egfr-ma-2022","label":"Prevention and management of acneiform rash associated with EGFR inhibitor therapy: a systematic review and meta-analysis","publisher":"Asia-Pacific Journal of Clinical Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/35352492","doi":"10.1111/ajco.13740","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2021 dermatological toxicity guideline could not be read (no abstract in Europe PMC; the publisher refused a script), so its grades and any changes it made to the MASCC 2011 regimen are not given here.","MASCC's guideline is from 2011; no later MASCC edition was found. Its recommendations predate amivantamab and osimertinib.","The trials and the meta-analysis were read as abstracts only; tetracycline contraindications, side effects and interactions are not covered by the sources read.","Prophylaxis evidence is strongest for EGFR antibodies; for EGFR tyrosine kinase inhibitors such as osimertinib, which cause milder rash, no randomised trial of prophylaxis was read.","Dose rules for cetuximab and the EGFR tablets were not read here; each drug's own label sets them.","Paronychia (nail fold inflammation) and scalp problems, which last longer than the rash, are covered only in part: the MASCC guideline's paronychia recommendations rest on expert opinion."]},{"id":"survivorship-care-plan-and-treatment-summary","kind":"protocol","name":"End of treatment: treatment summary, survivorship care plan and handover to primary care","aka":["survivorship care plan","SCP","end of treatment summary","treatment summary","follow-up care plan","personalised care and support plan","cancer care review","Recovery Package"],"tldr":"When main treatment ends, you should get a written summary of the treatment you had, side effects to look out for, signs the cancer might be back, who to contact, and the follow-up planned. In England it goes to you and your GP. Trials found the written plan alone did not make people feel better; it works best with a real conversation about who looks after you next.","summary":"The Institute of Medicine's 2006 report recommended that every survivor receive a survivorship care plan: a treatment summary and a follow-up care plan, to improve communication with the patient and between the oncology team and primary care (as summarised in ASCO's 2014 statement, which also revised the template because plans were rarely completed). The NCI tells patients they should receive one when treatment ends. In England the same handover is part of personalised care and support planning: a holistic needs assessment and a personalised care and support plan; an end of treatment summary written by the hospital clinician and shared with the patient and GP, containing the treatment given, possible side effects, the signs and symptoms of recurrence and contact details; and a cancer care review in primary care, which the Quality and Outcomes Framework requires within 12 months of the end of acute treatment. ESMO's 2022 consensus names five components of survivorship care (physical effects, psychological effects, social, work and financial effects, surveillance for recurrence and second cancers, and prevention and health promotion) and leaves the care model to local circumstances.\n\nThe evidence on the written plan is consistently negative for patient-reported outcomes. In a randomised trial of 408 women after early breast cancer, a care plan reviewed with a nurse made no difference to distress or any patient-reported secondary outcome; its one gain was that more patients knew their GP was now responsible. A cluster randomised trial of automatically generated plans in endometrial cancer found more information received but no gain in satisfaction, and more symptoms and concern reported. A 2018 systematic review (13 randomised studies) and a 2020 meta-analysis (eight trials, 1,286 survivors) found no improvement in patient-reported outcomes, with more positive signals for information received and for care delivery when the plan comes with counselling. The defensible protocol is therefore the handover itself (the summary, the named responsible clinician, the needs assessment and the follow-up schedule) rather than the document as an end in itself.","asOf":"2026-11-11","links":[],"tags":["protocol","survivorship"],"related":["idea-acc-auto-generated-survivorship-plans","idea-acc-risk-stratified-follow-up","idea-acc-primary-care-shared-care-agreements","breast-cancer-follow-up-after-treatment","colorectal-cancer-follow-up-after-curative-treatment","distress-screening-and-referral"],"cancers":[],"sections":["supportive-care"],"technologies":["survivorship-care-plan","rejuv-access-survivorship-care-us","rejuv-access-survivorship-care-uk"],"targets":[],"drugs":[],"companies":[],"institutions":["nci","macmillan-cancer-support","asco","esmo"],"pathways":[],"terms":["late-effects","quality-of-life","rejuv-history-lost-in-transition","rejuv-history-ncsi-england"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"At the end of treatment, ask for a written summary of your treatment and your follow-up plan. Your family doctor should get a copy too.","domain":"survivorship","setting":{"who":["doctor","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","community"]},"population":"Adults completing primary treatment for cancer with curative intent, at the move from active treatment to follow-up. The trials read were in early breast cancer and endometrial cancer. People living with advanced cancer, and survivors of childhood cancer, have different follow-up arrangements not covered here.","trigger":"The end of initial treatment: the last surgery, chemotherapy or radiotherapy, or the start of long-term tablet treatment such as endocrine therapy.","steps":[{"action":"At the end of initial treatment, write a treatment summary and share it with the patient and their GP","why":"Your GP and other doctors need to know what treatment you had, sometimes years later, and you need a copy too.","source":"macmillan-pcsp","quote":"A Treatment Summary is a document produced by the hospital clinician at the end of initial treatment for cancer. It's designed to be shared with the patient and their GP."},{"action":"Include the treatment given, its possible side effects, the signs and symptoms of recurrence, and who to contact","why":"These are what you and your GP need in order to notice problems early and know where to turn.","source":"macmillan-pcsp","quote":"The End of Treatment Summary usually contains: an overview of any treatment the patient has received details of any potential side effects of treatment the signs and symptoms of cancer recurrence contact details to address any concerns."},{"action":"Give a follow-up care plan with the recommended follow-up, and cover emotional, social and financial needs as well as medical ones","why":"Knowing which tests and appointments to expect, and what help exists, makes the move out of active treatment less uncertain.","source":"nci-followup","quote":"A follow-up care plan is a summary of your treatment, along with recommendations for your cancer care after treatment ends. Your plan may also include suggestions to help meet other needs, such as emotional, social, or financial issues."},{"action":"Agree with the patient which doctor will be responsible for follow-up, and make sure the doctors share their notes","why":"Tests and decisions can fall between clinics; a named person and shared notes prevent that.","source":"nci-followup","quote":"Ask each doctor you see to share notes with your other doctors."},{"action":"Assess holistic needs and agree a personalised care and support plan","why":"Physical, practical, emotional and social problems after treatment are common and are easier to deal with when they are found early.","source":"macmillan-pcsp","quote":"A Personalised Care and Support Plan ensures people’s physical, practical, emotional and social needs are identified and addressed at the earliest opportunity."},{"action":"In England, offer a cancer care review in primary care within 12 months of the end of acute treatment","why":"A conversation with the GP or practice nurse brings the cancer experience into everyday care and points to local support.","source":"macmillan-pcsp","quote":"The Quality and Outcomes Framework (QOF) requires primary care professionals to carry out a CCR at the time of a patient's diagnosis (within 3 months) and after a patient has received acute treatment (within 12 months)."},{"action":"Plan survivorship care across physical and psychological effects, social, work and financial effects, surveillance, and health promotion","why":"Life after cancer treatment involves much more than checking for recurrence.","source":"esmo-2022","quote":"We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion."},{"action":"Do not rely on the written plan alone: pair it with a discharge conversation and make sure its recommendations are acted on","why":"In trials, handing over a document did not on its own make people feel better or less worried.","source":"jacobsen-2018","quote":"Findings are limited but more positive for proximal outcomes (eg, information received) and for care delivery, particularly when SCPs are accompanied by counseling to prepare survivors for future clinical encounters."}],"bestInClass":{"statement":"Every major body read still recommends a written handover at the end of treatment: a treatment summary and follow-up plan shared with the patient and primary care (NCI, ASCO 2014, the English personalised care model), within survivorship care that covers the five ESMO components. The trials disagree with the expectation behind it: randomised trials and two systematic reviews found that written plans do not improve distress, quality of life or satisfaction. The best-supported practice is to keep the summary for what it does do (move information and make responsibility clear) and put the effort into the needs assessment, the named responsible clinician and follow-through, not into the document. The full ESMO 2022 consensus and the full ASCO 2014 statement could not be read.","sources":["macmillan-pcsp","nci-followup","asco-2014","esmo-2022","grunfeld-2011","jacobsen-2018","hill-2020"]},"variants":[{"name":"Written survivorship care plan reviewed with a nurse, with transfer to primary care (Grunfeld trial)","differs":"A care plan reviewed in a 30-minute educational session with a nurse, and sent with a follow-up guideline to the GP, on top of a discharge visit.","evidence":"Randomised trial of 408 women after early breast cancer at nine centres: no difference in cancer-related distress at 12 months or in any patient-reported secondary outcome; more patients correctly named their GP as responsible for follow-up (98.7 against 89.1 per cent). Read as an abstract.","sources":["grunfeld-2011"]},{"name":"Automatically generated care plan from the hospital record (ROGY Care)","differs":"A patient-tailored plan generated by a button in the gynaecological oncology registration system, rather than written by hand.","evidence":"Cluster randomised trial in 12 Dutch hospitals with women newly diagnosed with endometrial cancer: more information received, no difference in satisfaction with information or care, and more symptoms, illness concern, emotional impact and GP contact reported in the care plan arm. Read as an abstract.","sources":["rogy-2015"]},{"name":"Holistic needs assessment, treatment summary and GP cancer care review (England)","differs":"Builds the handover from four parts (needs assessment and care plan, end of treatment summary, cancer care review in primary care, and health and well-being information) and ties the GP review to a contractual timing.","evidence":"Described by Macmillan Cancer Support as the NHS personalised care model, built on the earlier Recovery Package; no randomised trial of the package as a whole was read.","sources":["macmillan-pcsp"]}],"grades":[{"claim":"Survivorship care plans do not improve patient-reported outcomes","grade":"meta-analysis of eight randomised trials (1,286 survivors)","source":"hill-2020","quote":"SCPs appear feasible but do not improve survivors' patient-reported outcomes."},{"claim":"Randomised evidence on the effect of care plans on well-being is generally negative","grade":"systematic review of 13 randomised and 11 non-randomised studies","source":"jacobsen-2018","quote":"Existing research provides little evidence that SCPs improve health outcomes and health care delivery."},{"claim":"A care plan reviewed with a nurse did not reduce distress after breast cancer","grade":"single randomised trial, 408 women","source":"grunfeld-2011","quote":"There were no differences between groups on cancer-related distress or on any of the patient-reported secondary outcomes, and there were no differences when the two strata were analyzed separately."},{"claim":"ACS/ASCO breast survivorship recommendations mostly rest on consensus","grade":"expert consensus; most evidence not sufficient for a strong recommendation","source":"acs-asco-2016","quote":"Most of the evidence is not sufficient to warrant a strong evidence-based recommendation."}],"sources":[{"key":"macmillan-pcsp","label":"Personalised care and support planning (holistic needs assessment, end of treatment summary, cancer care review)","publisher":"Macmillan Cancer Support","year":2026,"url":"https://www.macmillan.org.uk/healthcare-professionals/innovation-in-cancer-care/personalised-care","read":"public-summary","accessed":"2026-11-11"},{"key":"nci-followup","label":"Follow-up care after cancer treatment","publisher":"National Cancer Institute","year":2026,"url":"https://www.cancer.gov/about-cancer/coping/survivorship/follow-up-care","read":"public-summary","accessed":"2026-11-11"},{"key":"asco-2014","label":"American Society of Clinical Oncology clinical expert statement on cancer survivorship care planning","publisher":"ASCO, Journal of Oncology Practice","year":2014,"url":"https://europepmc.org/abstract/MED/25316025","doi":"10.1200/JOP.2014.001321","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"ESMO Expert Consensus Statements on Cancer Survivorship: promoting high-quality survivorship care and research in Europe","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/35963481","doi":"10.1016/j.annonc.2022.07.1941","read":"abstract","accessed":"2026-11-11"},{"key":"acs-asco-2016","label":"American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline","publisher":"ACS and ASCO, Journal of Clinical Oncology","year":2016,"url":"https://europepmc.org/abstract/MED/26644543","doi":"10.1200/JCO.2015.64.3809","read":"abstract","accessed":"2026-11-11"},{"key":"grunfeld-2011","label":"Evaluating survivorship care plans: results of a randomized, clinical trial of patients with breast cancer","publisher":"Journal of Clinical Oncology","year":2011,"url":"https://europepmc.org/abstract/MED/22042959","doi":"10.1200/JCO.2011.36.8373","read":"abstract","accessed":"2026-11-11"},{"key":"rogy-2015","label":"Impact of an Automatically Generated Cancer Survivorship Care Plan on Patient-Reported Outcomes in Routine Clinical Practice: Longitudinal Outcomes of a Pragmatic, Cluster Randomized Trial","publisher":"Journal of Clinical Oncology","year":2015,"url":"https://europepmc.org/abstract/MED/26304900","doi":"10.1200/JCO.2014.60.3399","read":"abstract","accessed":"2026-11-11"},{"key":"scp-timing-2019","label":"A randomized trial of immediate versus delayed survivorship care plan receipt on patient satisfaction and knowledge of diagnosis and treatment","publisher":"Cancer","year":2019,"url":"https://europepmc.org/abstract/MED/30690714","doi":"10.1002/cncr.31875","read":"abstract","accessed":"2026-11-11"},{"key":"jacobsen-2018","label":"Systematic Review of the Impact of Cancer Survivorship Care Plans on Health Outcomes and Health Care Delivery","publisher":"Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/abstract/MED/29775389","doi":"10.1200/JCO.2018.77.7482","read":"abstract","accessed":"2026-11-11"},{"key":"hill-2020","label":"Survivorship Care Plans in Cancer: A Meta-Analysis and Systematic Review of Care Plan Outcomes","publisher":"The Oncologist","year":2020,"url":"https://europepmc.org/abstract/MED/32043786","doi":"10.1634/theoncologist.2019-0184","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 consensus and the ASCO 2014 statement were read only as abstracts, so the contents of the ASCO template and ESMO's detailed statements are not given here.","No graded guideline read was published after the randomised trials that found no benefit and explicitly re-weighed the care plan in their light.","NHS England's own personalised care pages did not return content to a script; the English model is described from Macmillan's page.","The evidence covers mainly breast and endometrial cancer; whether a written plan helps in cancers with heavier late effects (for example after chest radiotherapy or stem cell transplant) has not been tested in the trials read.","A 2019 trial found that a small gain in knowledge was seen in both arms and was probably due to repeating the questionnaire rather than to the plan; whether any form of the plan improves knowledge is not settled.","Survivors of childhood cancer have separate long-term follow-up guidance, not covered here."]},{"id":"enhanced-recovery-after-breast-reconstruction","kind":"protocol","name":"Enhanced recovery after breast reconstruction (ERAS pathway for implant and flap reconstruction)","aka":["ERAS breast reconstruction","enhanced recovery DIEP flap","fast-track breast reconstruction","perioperative care for breast reconstruction"],"tldr":"Enhanced recovery for breast reconstruction means good information beforehand, stopping smoking for a month, a short fast with a sugary drink two hours before, anti-sickness and pain medicines that spare opioids, keeping warm, eating within a day and getting up within a day, with close checks on a flap in the first three days.","summary":"The ERAS Society consensus review (2017; 18 items, GRADE) is the only specialty guideline found for breast reconstruction. Every recommendation is graded strong; evidence is high for opioid-sparing multimodal postoperative analgesia and conventional sutures, and moderate or low (often extrapolated from other surgery) for the rest: detailed counselling; one month without smoking or heavy alcohol and weight reduction to a BMI of 30 or less (high evidence for obesity); CT angiography if perforators need mapping; clear fluids to 2 hours and a maltodextrin drink 2 hours before (low evidence); VTE risk assessment and LMWH or heparin with mechanical methods for those at higher risk; chlorhexidine and IV antibiotics within 1 hour of incision; multimodal antiemetics; total intravenous anaesthesia; active warming above 36°C; avoiding over- and under-filling with balanced crystalloid, goal-directed therapy and vasopressors where needed; food within 24 hours; mobilisation within 24 hours; frequent flap monitoring in the first 72 hours; and physiotherapy and support after discharge. NICE NG180 offers an enhanced recovery programme for elective major surgery.","asOf":"2026-11-11","links":[],"tags":[],"related":["surgical-site-infection-prevention","vte-prophylaxis-after-cancer-surgery","routine-preoperative-tests"],"cancers":["breast-hr-positive","breast-her2-positive","tnbc"],"sections":[],"technologies":["eras-perioperative-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["breast-reconstruction","mastectomy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before breast reconstruction you will be helped to stop smoking and to understand the operation. You can drink clear fluids until two hours before. Afterwards you will be helped to eat and get out of bed within a day, and nurses will check a flap often for the first three days.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","home"]},"population":"Adults having breast reconstruction, with implants or with their own tissue (most often a DIEP flap), immediate or delayed. Many of the recommendations are extrapolated from other kinds of surgery, as the guideline says item by item.","trigger":"A decision to have breast reconstruction.","steps":[{"action":"Give detailed counselling about the reconstruction and the recovery before surgery","why":"Women who understand the choices and what to expect have less regret and recover better.","source":"eras-breast-recon-2017","quote":"Patients should receive detailed preoperative counseling.","grade":"Evidence level: Moderate. Recommendation grade: Strong (low harm)."},{"action":"Support one month without smoking or heavy drinking, and weight reduction to a BMI of 30 or less where that applies, before surgery","why":"Smoking, obesity and heavy drinking each raise the risk of flap loss, wound breakdown and infection.","source":"eras-breast-recon-2017","quote":"For daily smokers, 1 month of abstinence before surgery is beneficial. For patients who are obese, weight reduction to achieve a body mass index less than or equal to 30 kg/m 2 before surgery is beneficial. For alcohol abusers, 1 month of abstinence before surgery is beneficial.","grade":"Evidence level: Moderate for smoking; high for obesity; low for alcohol. Recommendation grade: Strong for all (high benefit, low harm)."},{"action":"If the blood vessels of a flap need mapping, use CT angiography","why":"Mapping the main vessel before a DIEP flap shortens the operation and reduces flap and donor-site problems.","source":"eras-breast-recon-2017","quote":"If preoperative perforator mapping is required, computed tomographic angiography is recommended.","grade":"Evidence level: Moderate. Recommendation grade: Strong."},{"action":"Keep the fast short: clear fluids until 2 hours before surgery, with a maltodextrin carbohydrate drink 2 hours before","why":"Clear drinks up to 2 hours before are safe, and a sugary drink reduces thirst, anxiety and the body's stress response.","source":"eras-breast-recon-2017","quote":"Preoperative fasting should be minimized and patients should be allowed to drink clear fluids up to 2 hours before surgery.","grade":"Fasting: Evidence level Moderate (based on extrapolated data), Recommendation grade Strong. Carbohydrate drink: Evidence level Low (based on extrapolated data), Recommendation grade Strong (low risk of harm) in the general patient population."},{"action":"Assess clot risk, and give LMWH or unfractionated heparin with mechanical methods to those at higher risk until they are walking or discharged","why":"Clots are more common after mastectomy with reconstruction than after mastectomy or lumpectomy alone.","source":"eras-breast-recon-2017","quote":"Patients should be assessed for venous thromboembolism risk. Unless contraindicated, and balanced by the risk of bleeding, patients at a higher risk should receive low-molecular-weight heparin or unfractionated heparin until they are ambulatory or discharged. Mechanical methods should be added.","grade":"Evidence level: Moderate. Recommendation grade: Strong."},{"action":"Prepare the skin with chlorhexidine and give IV antibiotics covering skin organisms within 1 hour of incision","why":"Infection is more common after mastectomy with an implant or flap than after other clean surgery.","source":"eras-breast-recon-2017","quote":"Chlorhexidine skin preparation and intravenous antibiotics covering common skin organisms should be given within 1 hour of incision.","grade":"Evidence level: Moderate (based on extrapolated data). Recommendation grade: Strong."},{"action":"Give multimodal anti-sickness medicines before and during surgery, and use total intravenous anaesthesia","why":"Combinations prevent more sickness than one drug, and intravenous anaesthesia causes less sickness than anaesthetic gases.","source":"eras-breast-recon-2017","quote":"Women should receive preoperative and intraoperative multimodal medications to mitigate postoperative nausea and vomiting.","grade":"Antiemetics: Evidence level Moderate, Recommendation grade Strong (high benefit, low harm). Total intravenous anaesthesia: Evidence level Moderate, Recommendation grade Strong."},{"action":"Warm the patient before and during surgery (forced air) and monitor temperature to keep it above 36°C","why":"Getting cold slows wound healing and triples the risk of wound infection.","source":"eras-breast-recon-2017","quote":"Temperature monitoring is required to ensure the patient’s body temperature is maintained above 36°C.","grade":"Evidence level: Moderate (based on extrapolated data). Recommendation grade: Strong."},{"action":"Avoid giving too much or too little fluid; use balanced crystalloid, goal-directed therapy, and vasopressors where needed","why":"Too much fluid harms a flap and the wound; too little risks a clot in the flap's vessels. Vasopressors do not harm free flaps.","source":"eras-breast-recon-2017","quote":"Overresuscitation or underresuscitation of fluids should be avoided, and water and electrolyte balance should be maintained. Goal-directed therapy is a useful method to achieve these goals. Balanced crystalloid solutions rather than saline is recommended. Vasopressors are recommended to support fluid management and do not negatively affect free flaps.","grade":"Evidence level: Moderate for all (based on extrapolated data). Recommendation grade: Strong."},{"action":"Use opioid-sparing multimodal pain relief after surgery (paracetamol with an NSAID, local anaesthetic blocks or infusions)","why":"Fewer opioids means less sickness and constipation and earlier walking.","source":"eras-breast-recon-2017","quote":"Multimodal postoperative pain management regimens are opioid-sparing and should be used.","grade":"Evidence level: High. Recommendation grade: Strong."},{"action":"Encourage drinking and eating as soon as possible, preferably within 24 hours, and getting up within the first 24 hours","why":"Early food helps wounds heal and early movement prevents clots, chest infection and muscle loss.","source":"eras-breast-recon-2017","quote":"Patients should be encouraged to take fluids and food orally as soon as possible, preferably within 24 hours after surgery.","grade":"Early feeding: Evidence level Moderate (based on extrapolated data), Recommendation grade Strong. Mobilisation: Evidence level Moderate (based on extrapolated data), Recommendation grade Strong (low risk)."},{"action":"Monitor a free flap frequently for the first 72 hours by clinical observation, with an implantable Doppler for a buried flap","why":"A clot in a flap's vessels happens in 2 to 5 in 100 flaps, mostly in the first three days, and early return to theatre saves the flap.","source":"eras-breast-recon-2017","quote":"Flap monitoring within the first 72 hours should occur frequently. Clinical evaluation is sufficient for monitoring, with implantable Doppler monitoring recommended in cases of buried flaps.","grade":"Evidence level: Moderate. Recommendation grade: Strong (low harm)."},{"action":"Arrange early physiotherapy, supervised exercise and support after discharge","why":"Early rehabilitation improves movement, pain and quality of life after breast surgery.","source":"eras-breast-recon-2017","quote":"Early physiotherapy, supervised exercise programs, and other supportive care initiatives should be instituted after discharge.","grade":"Evidence level: Moderate (based on extrapolated data). Recommendation grade: Strong (low harm)."}],"bestInClass":{"statement":"The ERAS Society consensus review (2017) is the only graded specialty guideline for breast reconstruction found, and all 18 of its recommendations are strong; only opioid-sparing analgesia and conventional sutures rest on high-quality evidence, and many items are extrapolated from other operations. NICE NG180 supports an enhanced recovery programme for elective major surgery and the same 2-hour clear-fluid fast.","sources":["eras-breast-recon-2017","nice-ng180"]},"variants":[{"name":"Antibiotics continued until drains come out","differs":"Continues antibiotics after surgery until the drains are removed.","evidence":"The ERAS review calls this common practice and cites a systematic review of observational studies in which more than 24 hours of antibiotics was associated with higher infection rates in reconstructions using acellular dermal matrix; it recommends antibiotics within 1 hour of incision and does not recommend continuing them.","sources":["eras-breast-recon-2017"]},{"name":"Regional anaesthesia instead of general anaesthesia","differs":"Uses regional anaesthesia as the main anaesthetic.","evidence":"The ERAS review reports that regional anaesthesia reduces opioid use but not pain, sickness, time to walking or hospital stay, and recommends general anaesthesia with total intravenous anaesthesia (moderate evidence, strong).","sources":["eras-breast-recon-2017"]}],"grades":[{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."},{"claim":"Maltodextrin drink 2 hours before surgery","grade":"Evidence level: Low (based on extrapolated data). Recommendation grade: Strong (low risk of harm) in the general patient population.","source":"eras-breast-recon-2017","quote":"Preoperative maltodextrin-based drinks should be given to patients 2 hours before surgery."},{"claim":"General anaesthesia with total intravenous anaesthesia","grade":"Evidence level : Moderate. Recommendation grade : Strong.","source":"eras-breast-recon-2017","quote":"General anesthesia with total intravenous anesthesia is recommended."},{"claim":"Conventional sutures for closure; debridement and negative-pressure therapy for complex wounds","grade":"Evidence level : High for sutures; moderate for negative-pressure wound therapy. Recommendation grade : Strong.","source":"eras-breast-recon-2017","quote":"For incisional closure, conventional sutures are recommended. Complex wounds following skin necrosis are treatable with débridement and negative-pressure wound therapy."},{"claim":"Mobilise within the first 24 hours","grade":"Evidence level : Moderate (based on extrapolated data). Recommendation grade : Strong (low risk).","source":"eras-breast-recon-2017","quote":"Patients should be mobilized within the first 24 hours after surgery."}],"sources":[{"key":"eras-breast-recon-2017","label":"Consensus Review of Optimal Perioperative Care in Breast Reconstruction: Enhanced Recovery after Surgery (ERAS) Society Recommendations","publisher":"ERAS Society (Plastic and Reconstructive Surgery)","year":2017,"url":"https://doi.org/10.1097/PRS.0000000000003242","doi":"10.1097/PRS.0000000000003242","gradingScheme":"GRADE evidence level (high, moderate, low) and recommendation grade (strong or weak), printed after each item; 'based on extrapolated data' marks evidence from other operations.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-shorter-fasting-before-surgery"],"gaps":["The guideline is from 2017 and rests on literature to about 2016; no update was found. Its authors note that most items rely on lower-level studies in reconstruction or on data extrapolated from other surgery.","The review's discussion of whether regional anaesthesia affects breast cancer recurrence predates the large randomised trial it was waiting for; that question is not covered here.","Drain management, antibiotic-coated or plain implants, mesh and acellular dermal matrix are not graded by the review and are not covered here.","Doses of antiemetics and analgesics and the details of a flap-monitoring schedule are local protocol matters; the review gives one reasonable schedule (hourly for 24 hours, two-hourly for the next 24, then every 3 to 4 hours) as an example, not a recommendation."]},{"id":"enhanced-recovery-after-colorectal-surgery","kind":"protocol","name":"Enhanced recovery after colorectal cancer surgery (ERAS pathway for bowel resection)","aka":["ERAS colorectal","ERAS bowel surgery","enhanced recovery colectomy","fast-track colorectal surgery","perioperative care for bowel cancer surgery"],"tldr":"Enhanced recovery is a package of care for bowel cancer surgery: getting fitter and better nourished beforehand, a sugary drink up to two hours before, antibiotic tablets with the bowel preparation, two anti-sickness drugs, no routine tubes or drains, the urinary catheter out the next day, and eating and walking from the day after the operation.","summary":"The current ERAS Society colorectal guideline (2025) could not be read: no abstract is indexed and the publisher refused a script. The most recent graded guideline that could be read in full is the 2024 Korean ERAS guideline for colorectal cancer (13 GRADE recommendations). Strong, high-quality: dexamethasone plus a 5-HT3 antagonist rather than either alone for nausea. Conditional for, high quality: oral antibiotics with mechanical bowel preparation. Conditional for, moderate: prehabilitation; preoperative oral nutritional supplements; carbohydrate loading up to 2 hours before; goal-directed fluid therapy in high-risk patients; TAP block; preoperative pharmacological thromboprophylaxis; urinary catheter out on day 1; early feeding and walking from day 1. Conditional against: routine intra-abdominal drain (moderate) and nasogastric tube (low). NICE NG180 offers an enhanced recovery programme to everyone having elective major surgery. On bowel preparation the bodies differ: WHO (2018) and the Korean guideline support oral antibiotics with mechanical preparation; NICE NG125 (recommendation from 2008) says not to use mechanical bowel preparation routinely to reduce infection; EUPEMEN does not recommend mechanical preparation alone.","asOf":"2026-11-11","links":[],"tags":[],"related":["surgical-site-infection-prevention","vte-prophylaxis-after-cancer-surgery","enhanced-recovery-after-liver-surgery","routine-preoperative-tests"],"cancers":["colorectal","rectal-cancer"],"sections":[],"technologies":["eras-perioperative-nutrition","prehabilitation"],"targets":[],"drugs":["dexamethasone","ondansetron"],"companies":[],"institutions":[],"pathways":[],"terms":["colectomy","total-mesorectal-excision","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before bowel cancer surgery you may be offered exercise and nutrition drinks. You can have a sugary drink up to two hours before. After the operation you will be helped to eat, drink and walk early, with fewer tubes, which speeds recovery.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","home"]},"population":"Adults having planned (elective) surgery for colon or rectal cancer, open or minimally invasive. Emergency surgery (obstruction, perforation) has its own ERAS guidance and is not covered. The Korean guideline was written for Korean practice and says where Korean evidence was thin.","trigger":"A decision to operate on the colon or rectum for cancer.","steps":[{"action":"Offer an enhanced recovery programme with preoperative, intraoperative and postoperative parts","why":"A coordinated package shortens recovery more than any single change on its own.","source":"nice-ng180","quote":"Use an enhanced recovery programme that includes preoperative, intraoperative and postoperative components.","grade":"Not graded (NICE NG180 1.2.2)"},{"action":"Offer prehabilitation (exercise, nutrition and psychological support) in the weeks before surgery","why":"Getting fitter before surgery helps the body cope with the operation.","source":"korea-eras-crc-2024","quote":"Prehabilitation is recommended for patients scheduled to undergo surgery for colorectal cancer.","grade":"Strength of the recommendation: Conditional for. Level of evidence: Moderate."},{"action":"Give oral nutritional supplements before surgery","why":"People with bowel cancer often lose weight and appetite, and poor nutrition raises the risk of complications.","source":"korea-eras-crc-2024","quote":"Preoperative nutritional support using oral nutritional supplements is recommended for patients scheduled for colorectal cancer surgery.","grade":"Strength of the recommendation: Conditional for. Level of evidence: Moderate."},{"action":"If bowel preparation is used, give oral antibiotics with it; do not use mechanical bowel preparation alone","why":"Antibiotic tablets taken with the bowel preparation roughly halved wound infections compared with preparation alone in the trials pooled.","source":"korea-eras-crc-2024","quote":"The use of oral antibiotics in conjunction with mechanical bowel preparation is recommended for patients scheduled for colorectal cancer surgery.","grade":"Strength of the recommendation: Conditional for. Level of evidence: High."},{"action":"Allow clear fluids until 2 hours before, and give a carbohydrate drink up to 2 hours before surgery","why":"A long fast leaves people thirsty and more resistant to insulin; a sugary drink shortly before is safe.","source":"korea-eras-crc-2024","quote":"Oral carbohydrate loading up to 2 hours before colorectal cancer surgery is recommended.","grade":"Strength of the recommendation: Conditional for. Level of evidence: Moderate."},{"action":"Start pharmacological thromboprophylaxis before surgery","why":"Bowel cancer surgery carries a real risk of blood clots in the legs and lungs.","source":"korea-eras-crc-2024","quote":"Preoperative pharmacologic thromboprophylaxis is recommended for patients scheduled for colorectal cancer surgery.","grade":"Strength of the recommendation: Conditional for. Level of evidence: Moderate."},{"action":"Prevent sickness with dexamethasone plus a 5-HT3 antagonist (such as ondansetron) rather than either drug alone","why":"Two drugs together prevent more sickness than one, and sickness delays eating and getting up.","source":"korea-eras-crc-2024","quote":"The use of dexamethasone in combination with a serotonin receptor antagonist rather than monotherapy is recommended for the prevention of postoperative nausea and vomiting in patients scheduled for colorectal cancer surgery.","grade":"Strength of the recommendation: Strong for. Level of evidence: High."},{"action":"Consider goal-directed fluid therapy during surgery for high-risk patients","why":"Matching fluid to measured need avoids both too much and too little fluid in people least able to cope with either.","source":"korea-eras-crc-2024","quote":"Goal-directed fluid therapy during surgery may be considered for high-risk patients undergoing colorectal cancer surgery.","grade":"Strength of the recommendation: Conditional for. Level of evidence: Moderate."},{"action":"Consider a transversus abdominis plane (TAP) block as part of pain relief","why":"A nerve block in the abdominal wall reduces pain and the need for opioids, which cause sickness and slow the bowel.","source":"korea-eras-crc-2024","quote":"Transverse abdominis plane block may be considered for pain control during surgery for colorectal cancer.","grade":"Strength of the recommendation: Conditional for. Level of evidence: Moderate."},{"action":"Do not place a routine intra-abdominal drain or nasogastric tube","why":"In the trials pooled, drains and stomach tubes did not prevent leaks or complications, and they add discomfort.","source":"korea-eras-crc-2024","quote":"It is suggested not to insert an intra-abdominal drain during surgery for colorectal cancer.","grade":"Drain: Conditional against, Moderate. Nasogastric tube: Conditional against, Low."},{"action":"Remove the urinary catheter the day after surgery","why":"An early catheter removal helps people walk sooner and go home sooner.","source":"korea-eras-crc-2024","quote":"It is recommended to remove urinary catheters the day after colorectal cancer surgery.","grade":"Strength of the recommendation: Conditional for. Level of evidence: Moderate."},{"action":"Start eating and drinking, and walking, from the day after surgery","why":"Early food and movement support recovery of the bowel and reduce chest problems and clots.","source":"korea-eras-crc-2024","quote":"Early feeding is recommended to start from the day after surgery for colorectal cancer.","grade":"Early feeding: Conditional for, Moderate. Early ambulation: Conditional for, Moderate."}],"bestInClass":{"statement":"The ERAS Society's 2025 colorectal guideline is the current specialty standard, but its recommendations could not be read for this page. Of what could be read, the 2024 Korean ERAS guideline gives the most recent graded recommendations, built on new meta-analyses of randomised trials: the strongest is two-drug nausea prophylaxis (strong, high); oral antibiotics with bowel preparation (conditional, high) agrees with WHO (conditional, moderate); and avoiding drains and nasogastric tubes, early catheter removal, early feeding and early walking are all supported. NICE NG180 supports an enhanced recovery programme and a 2-hour clear-fluid fast for all elective major surgery. Where they disagree is bowel preparation: NICE NG125 says not to use mechanical preparation routinely to reduce infection (a 2008 recommendation carried into the 2019 guideline) and is silent on oral antibiotics.","sources":["korea-eras-crc-2024","who-ssi-2018","nice-ng180","nice-ng125","eras-crc-2025"]},"variants":[{"name":"Thoracic epidural for open surgery and a catheter for 1 to 3 days (ERAS 2018)","differs":"Uses a thoracic epidural for open colorectal surgery and keeps the urinary catheter routinely for 1 to 3 days, rather than removing it on day 1.","evidence":"Listed as colorectal-specific recommendations of the 2018 ERAS guideline by a 2025 appraisal of all ERAS Society guidelines. The Korean guideline recommends catheter removal on day 1 (conditional, moderate) and a TAP block (conditional, moderate), and does not grade epidurals. Whether the 2025 ERAS edition kept these positions could not be read.","sources":["eras-overview-2025","korea-eras-crc-2024"]},{"name":"No routine bowel preparation (NICE)","differs":"Does not use mechanical bowel preparation routinely to reduce wound infection, and makes no recommendation on oral antibiotics.","evidence":"NICE NG125, a recommendation carried forward from 2008. WHO (2018) recommends against mechanical preparation alone (strong, moderate) and suggests oral antibiotics with it (conditional, moderate); the Korean guideline cites newer network meta-analyses for the combination.","sources":["nice-ng125","who-ssi-2018","korea-eras-crc-2024"]},{"name":"EUPEMEN European pathway","differs":"A low-residue diet for at least five days and two enemas the afternoon before left-sided operations; mechanical bowel preparation alone is not recommended except for a perioperative colonoscopy; immunonutrition preferred for the malnourished, 7 days before and 5 days after surgery.","evidence":"Consensus of a European multisociety network (2024) built on the literature; its recommendations are not graded item by item in the way GRADE guidelines are.","sources":["eupemen-2024"]}],"grades":[{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."},{"claim":"Clear fluids until 2 hours before the operation","grade":"Not graded (NICE NG180 1.4.1)","source":"nice-ng180","quote":"they may drink clear fluids until 2 hours before their operation"},{"claim":"Oral antibiotics with mechanical bowel preparation in elective colorectal surgery","grade":"Conditional Moderate","source":"who-ssi-2018","quote":"The panel suggests that preoperative oral antibiotics combined with mechanical bowel preparation should be used to reduce the risk of SSI in adult patients undergoing elective colorectal surgery."},{"claim":"No mechanical bowel preparation alone","grade":"Strong Moderate","source":"who-ssi-2018","quote":"The panel recommends that mechanical bowel preparation alone (without administration of oral antibiotics) should not be used for the purpose of reducing SSI in adult patients undergoing elective colorectal surgery."},{"claim":"No routine mechanical bowel preparation to reduce infection","grade":"Not graded (NICE NG125, recommendation dated 2008)","source":"nice-ng125","quote":"Do not use mechanical bowel preparation routinely to reduce the risk of surgical site infection. [2008]"},{"claim":"ERAS 2018: routine urinary catheter for 1 to 3 days (as listed by the 2025 appraisal)","grade":"Not stated in the appraisal","source":"eras-overview-2025","quote":"Routine transurethral catheterization is recommended for 1–3 days"},{"claim":"No routine nasogastric tube","grade":"Conditional against, Low","source":"korea-eras-crc-2024","quote":"It is suggested not to insert a nasogastric tube during surgery for colorectal cancer."},{"claim":"Early walking from the day after surgery","grade":"Conditional for, Moderate","source":"korea-eras-crc-2024","quote":"Early ambulation is recommended to commence on the day after surgery for colorectal cancer."}],"sources":[{"key":"eras-overview-2025","label":"Enhanced recovery after surgery: overarching themes of the ERAS Society Guidelines and Consensus Statements for Adult Specialty Surgery","publisher":"Perioperative Medicine","year":2025,"url":"https://doi.org/10.1186/s13741-025-00590-0","doi":"10.1186/s13741-025-00590-0","gradingScheme":"An appraisal; repeats the guidelines' own recommendations without new grades.","read":"full-text","accessed":"2026-11-11"},{"key":"eras-crc-2025","label":"Guidelines for perioperative care in elective colorectal surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations 2025","publisher":"ERAS Society (Surgery)","year":2025,"url":"https://doi.org/10.1016/j.surg.2025.109397","doi":"10.1016/j.surg.2025.109397","gradingScheme":"GRADE (per the 2018 edition's method); not read.","read":"not-reachable","accessed":"2026-11-11"},{"key":"korea-eras-crc-2024","label":"The 2024 Korean Enhanced Recovery After Surgery (ERAS) guidelines for colorectal cancer: a secondary publication","publisher":"Korean Society of Surgical Metabolism and Nutrition, ERAS Committee (Annals of Coloproctology)","year":2025,"url":"https://doi.org/10.3393/ac.2024.00836.0119","doi":"10.3393/ac.2024.00836.0119","gradingScheme":"GRADE: strength (strong or conditional, for or against) and level of evidence (high, moderate, low, very low), printed under each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"eupemen-2024","label":"The EUropean PErioperative MEdical Networking (EUPEMEN) project and recommendations for perioperative care in colorectal surgery","publisher":"EUPEMEN (International Journal of Surgery)","year":2024,"url":"https://doi.org/10.1097/JS9.0000000000001601","doi":"10.1097/JS9.0000000000001601","gradingScheme":"Narrative consensus; grades are quoted only where it repeats another guideline's.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng125","label":"Surgical site infections: prevention and treatment (NG125)","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng125/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the year in brackets is when the recommendation was last reviewed.","read":"full-text","accessed":"2026-11-11"},{"key":"who-ssi-2018","label":"Global guidelines for the prevention of surgical site infection, second edition","publisher":"World Health Organization","year":2018,"url":"https://iris.who.int/handle/10665/277399","gradingScheme":"GRADE: strength (strong or conditional) and quality of evidence (high, moderate, low, very low).","read":"full-text","accessed":"2026-11-11"},{"key":"eras-crc-2018","label":"Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations: 2018","publisher":"ERAS Society (World Journal of Surgery)","year":2019,"url":"https://doi.org/10.1007/s00268-018-4844-y","doi":"10.1007/s00268-018-4844-y","gradingScheme":"GRADE evidence level and recommendation grade per item; the abstract holds none.","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-shorter-fasting-before-surgery"],"gaps":["The ERAS Society 2025 colorectal guideline, the current specialty standard, could not be read: no abstract is indexed in Europe PMC or PubMed, and the journal refused a script. Its recommendations may differ from the Korean guideline's on any item here, and this page should be updated when it can be read.","The 2018 ERAS colorectal guideline could be read only as an abstract; the publisher and repository copies answered with a bot check.","The Korean guideline covers 13 questions; it does not address smoking and alcohol, anaemia, warming, antibiotic timing, epidural against other analgesia, or audit, which the ERAS liver guideline grades. Those items rest on other protocols here (surgical site infection prevention) or on sources not read.","Whether bowel preparation with oral antibiotics should be used for right-sided colon operations as well as rectal ones is where guidelines part; NICE's recommendation against routine preparation dates from 2008.","How long thromboprophylaxis should continue after discharge is covered by the VTE prophylaxis protocol, not here."]},{"id":"enhanced-recovery-after-cytoreductive-surgery-and-hipec","kind":"protocol","name":"Enhanced recovery after cytoreductive surgery with or without HIPEC","aka":["ERAS CRS HIPEC","ERAS cytoreductive surgery","enhanced recovery HIPEC","perioperative care for cytoreductive surgery","ERAS peritonectomy"],"tldr":"Enhanced recovery is a package of care for major surgery to remove cancer from the lining of the abdomen, sometimes with heated chemotherapy: stopping smoking and drinking, a nutrition check, treating anaemia, a short fast, four weeks of clot prevention, careful temperature and fluids in theatre, good pain relief, no routine nose tube, drinking from the day of surgery and getting up early.","summary":"The ERAS Society guideline for CRS with or without HIPEC (2020, two parts; 72 items graded by GRADE, consensus on 71 after a two-round Delphi of 24 experts, 37 strong recommendations, no consensus on preemptive fresh frozen plasma) is the only specialty guideline; only its abstracts could be read. Its item content is taken from the INDEPSO-ISPSM consensus (India, 2025), which reports it: preoperative counselling with smoking and heavy alcohol cessation; monitoring of intraperitoneal and core temperature, with active warming against hypothermia during CRS and against hyperthermia during HIPEC; at least two antiemetics; no prophylactic nasogastric drainage without risk factors for delayed gastric emptying; clear liquids on the day of surgery and solid food from day 1; preemptive enteral or parenteral nutrition for 7 days in selected patients; out of bed on the day of surgery with more than 2 hours of activity on day 2 and more than 6 hours after; urinary catheter out on the morning of day 3 when the bladder peritoneum was not stripped. The Indian consensus itself agreed on nutritional assessment, anaemia correction, fasting 6 to 8 hours for solids and 2 hours for liquids, carbohydrate loading, LMWH from 12 hours before surgery with pneumatic compression for 4 weeks, chlorhexidine-alcohol skin preparation, goal-directed fluids, and audit; it departed from ERAS by recommending drains for all patients and bowel preparation for left colonic or rectal resection. NICE NG180 (2020) offers enhanced recovery to everyone having elective major surgery.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","surgical-site-infection-prevention","enhanced-recovery-after-liver-surgery"],"cancers":["appendiceal","peritoneal-mesothelioma","ovarian","gastric"],"sections":[],"technologies":["hipec","hipec-pipac-devices","eras-perioperative-nutrition","prehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cytoreductive-surgery","hipec-procedure","colorectal-peritoneal-metastases","peritoneal-metastasis","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before the operation you will be asked to stop smoking and drinking, have your nutrition and blood count checked, and can drink clear fluids until two hours before. Afterwards you will be helped to drink and eat early and to get out of bed from the first day, and given injections against clots for four weeks.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","intensive-care","home"]},"population":"Adults having elective cytoreductive surgery with or without HIPEC for peritoneal surface malignancy (colorectal, appendiceal including pseudomyxoma peritonei, ovarian, gastric, peritoneal mesothelioma). The ERAS panel included general and gynaecological surgeons and anaesthetists.","trigger":"A decision to perform cytoreductive surgery, with or without HIPEC.","steps":[{"action":"Counsel before surgery and advise stopping smoking and heavy alcohol use","why":"Smoking and heavy drinking both raise the risk of complications after major surgery; stopping beforehand helps.","source":"indepso-2025","quote":"As per ERAS Society Recommendations, ( Hübner et al., 2020 ) patients should be offered preoperative counseling and advised for smoking cessation and abstinence from heavy alcohol consumption.","grade":"ERAS 2020 as reported by the consensus; grade not read"},{"action":"Assess nutrition as part of the preoperative assessment","why":"Malnutrition is common before this operation and raises the risk of complications.","source":"indepso-2025","quote":"Nutrition assessment should be a part of preoperative assessment","grade":"INDEPSO-ISPSM consensus (above 70% agreement)"},{"action":"Screen for anaemia at least four weeks before surgery so it can be treated","why":"Anaemia is common after chemotherapy and needs time to correct before a long operation with blood loss.","source":"indepso-2025","quote":"It should be screened for at least four weeks before surgery to provide adequate time for correction by medical therapy (vitamin supplementation or intravenous iron supplementation),","grade":"Consensus discussion; not a graded recommendation"},{"action":"Allow clear fluids until 2 hours before the operation, and consider a carbohydrate drink","why":"Long fasting leaves people thirsty and weaker; a sugary drink before abdominal surgery is safe.","source":"nice-ng180","quote":"Consider carbohydrate drinks before surgery for people having abdominal major or complex surgery .","grade":"Not graded (NICE NG180 1.4.2, 'consider')"},{"action":"Start low molecular weight heparin before surgery, use pneumatic compression, and continue prophylaxis for four weeks","why":"Without prevention the risk of blood clots after this operation is very high, and it lasts after discharge.","source":"indepso-2025","quote":"Thromboprophylaxis should be given 12 h preoperatively, with low-molecular-weight/equivalent heparin, and continued perioperatively with a pneumatic compression device till four weeks post-surgery.","grade":"INDEPSO-ISPSM consensus (above 70% agreement)"},{"action":"Prepare the skin with chlorhexidine in alcohol unless contraindicated","why":"The right skin antiseptic reduces wound infection.","source":"indepso-2025","quote":"Chlorhexidine-alcohol solution should be used for skin preparation unless contraindicated.","grade":"INDEPSO-ISPSM consensus (above 70% agreement)"},{"action":"Monitor intraperitoneal and core temperature continuously, warm actively during cytoreduction and prevent overheating during HIPEC","why":"People get cold during the long open phase and can overheat when heated chemotherapy is circulated; both cause complications.","source":"indepso-2025","quote":"Prevention of intraoperative hypothermia during the CRS phase and hyperthermia during the HIPEC phase by use of active warming devices should be indicated routinely.","grade":"ERAS 2020 as reported by the consensus; grade not read"},{"action":"Guide fluids by goal-directed monitoring (arterial line, cardiac output)","why":"Large fluid shifts happen during this surgery; measured fluid replacement avoids both too little and too much.","source":"indepso-2025","quote":"Goal-directed fluid management should be attempted using a combination of crystalloids and colloids. An arterial line/cardiac output monitoring may assist in achieving this goal.","grade":"INDEPSO-ISPSM strong consensus (above 90% agreement)"},{"action":"Give at least two anti-sickness drugs as prophylaxis","why":"Nausea is common after major abdominal surgery and the chemotherapy can add to it.","source":"indepso-2025","quote":"In CRS ± HIPEC candidates, a combination of atleast two antiemetic drugs (Ondansetron, Dexamethasone, Droperidol) should be indicated routinely to prevent PONV.","grade":"ERAS 2020 as reported by the consensus; grade not read"},{"action":"Use multimodal analgesia, including a thoracic epidural for 48 to 72 hours where suitable, and minimise opioids","why":"Good pain relief lets people breathe and move; an epidural also helps the bowel start working.","source":"indepso-2025","quote":"Thus, thoracic epidural analgesia (TEA: T5-11) containing local anesthetics and short-acting opiates for 48–72 h after CRS ± HIPEC is safe and recommended to prevent postoperative ileus.","grade":"Consensus discussion citing published studies; not a graded recommendation"},{"action":"Do not place a prophylactic nasogastric tube unless there are risk factors for delayed stomach emptying (resection of the lesser omentum)","why":"A nose tube slows the return of bowel function and is not needed for most people.","source":"indepso-2025","quote":"Prophylactic nasogastric drainage for CRS ± HIPEC, in the absence of risk factors for delayed gastric emptying (resection of lesser omentum), should not be done, as nasogastric decompression has been associated with undesired effects of delayed resumption of gastrointestinal motility.","grade":"ERAS 2020 as reported by the consensus; grade not read"},{"action":"Restart clear liquids on the day of surgery and solid food from day 1 where there are no risk factors for delayed emptying; consider planned tube or intravenous feeding for 7 days if intake is expected to be poor","why":"Early eating supports healing; some people, after very extensive surgery, will not manage enough by mouth.","source":"indepso-2025","quote":"Early oral intake resumption after CRS ± HIPEC, aiming for clear liquids on the day of surgery and solid food from postoperative day 1, without risk factors for delayed gastric emptying (resection of lesser omentum), is recommended.","grade":"ERAS 2020 as reported by the consensus; grade not read"},{"action":"Get the patient out of bed on the day of surgery, aiming for more than 2 hours of activity on day 2 and more than 6 hours a day after that","why":"Moving early reduces chest infections, clots and muscle loss, and helps the bowel recover.","source":"indepso-2025","quote":"Mobilization as early as the day of surgery (out of bed) with goals for more than two hours of physical exercises for postoperative day two and more than six hours after that should be performed routinely after CRS ± HIPEC to improve capacity to perform out-of-bed activities, facilitate resumption of gastrointestinal function and decrease postoperative complications.","grade":"ERAS 2020 as reported by the consensus; grade not read"},{"action":"Remove the urinary catheter on the morning of day 3 if the peritoneum over the bladder was not removed","why":"Catheters left in longer raise the risk of urine infection and slow getting up.","source":"indepso-2025","quote":"Removal of the urinary catheter as early as the morning of postoperative day three is recommended when peritonectomy over the bladder is not done.","grade":"ERAS 2020 as reported by the consensus; grade not read"},{"action":"Audit compliance with the pathway regularly","why":"Units that measure how often each element is delivered can improve it.","source":"indepso-2025","quote":"Regular audits for compliance with ERAS should be conducted as it is critical to ensure adherence to protocol.","grade":"INDEPSO-ISPSM consensus (above 70% agreement)"}],"bestInClass":{"statement":"The ERAS Society guideline for CRS with or without HIPEC (2020, Parts I and II) is the only specialty standard: 72 items graded by GRADE, 37 strong recommendations, consensus on all but preemptive fresh frozen plasma. Only its abstracts could be read, so its content is taken from the INDEPSO-ISPSM consensus (2025), which reports it and largely agrees. The two differ on drains (the Indian panel recommends them for all patients, which it says contradicts the ERAS guideline) and on mechanical bowel preparation (the Indian panel recommends it for left colonic and rectal resection). NICE NG180 (2020) supports an enhanced recovery programme and the 2-hour clear-fluid fast for all elective major surgery.","sources":["eras-crs-2020-part1","eras-crs-2020-part2","indepso-2025","nice-ng180"]},"variants":[{"name":"Routine intraperitoneal drains (INDEPSO-ISPSM, India)","differs":"Places intraperitoneal drains in every patient after CRS or HIPEC.","evidence":"Recommended by 79% of the Indian panel in round two; the consensus states this contradicts the ERAS guidelines, and it cites evidence that drains after elective surgery prolong stay and raise wound infection risk without earlier detection of collections.","sources":["indepso-2025"]},{"name":"Mechanical bowel preparation for left colonic or rectal resection (INDEPSO-ISPSM)","differs":"Gives bowel preparation when a left colonic or rectal resection is planned.","evidence":"Indian consensus (79.6% in round two); named by the consensus as a departure from the ERAS guideline. The underlying trials of oral antibiotic and mechanical preparation are mixed (MOBILE and MOBILE2, as reported by the consensus).","sources":["indepso-2025"]},{"name":"Incentive spirometry for all","differs":"Teaches every patient incentive spirometry before surgery.","evidence":"Indian consensus (87.5%); the consensus itself notes that the European Society of Anaesthesiology does not suggest preoperative incentive spirometry prevents pulmonary complications and that reviews disagree.","sources":["indepso-2025"]},{"name":"Empirical postoperative antibiotics for 72 hours","differs":"Continues antibiotics after surgery rather than giving prophylaxis only.","evidence":"Some groups do this, according to the Indian consensus; it states that additional postoperative doses are not required in clean contaminated surgery. The Indian panel left the antibiotic choice to each institution's policy.","sources":["indepso-2025"]}],"grades":[{"claim":"ERAS CRS/HIPEC guideline: consensus, strong recommendations and the one item without consensus","grade":"GRADE; two-round Delphi of 24 experts","source":"eras-crs-2020-part1","quote":"Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items, No consensus could be reached regarding the preemptive use of fresh frozen plasma."},{"claim":"Quality of evidence across the 72 items","grade":"GRADE quality of evidence","source":"eras-crs-2020-part2","quote":"Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively."},{"claim":"Where the Indian consensus departs from ERAS","grade":"INDEPSO-ISPSM modified Delphi (consensus above 70%)","source":"indepso-2025","quote":"Some of the panelists’ recommendations contradicted the standard ERAS guidelines, such as using intraperitoneal drains in all patients and mechanical bowel preparation for left-sided colonic or rectal resections."},{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."}],"sources":[{"key":"eras-crs-2020-part1","label":"Guidelines for Perioperative Care in Cytoreductive Surgery (CRS) with or without HIPEC: ERAS Society Recommendations, Part I: Preoperative and intraoperative management (Hübner et al.)","publisher":"ERAS Society (European Journal of Surgical Oncology)","year":2020,"url":"https://doi.org/10.1016/j.ejso.2020.07.041","doi":"10.1016/j.ejso.2020.07.041","gradingScheme":"GRADE quality of evidence (high, moderate, low, very low) and strength of recommendation, by two-round Delphi.","read":"abstract","accessed":"2026-11-11"},{"key":"eras-crs-2020-part2","label":"Guidelines for Perioperative Care in Cytoreductive Surgery (CRS) with or without HIPEC: ERAS Society Recommendations, Part II: Postoperative management and special considerations (Hübner et al.)","publisher":"ERAS Society (European Journal of Surgical Oncology)","year":2020,"url":"https://doi.org/10.1016/j.ejso.2020.08.006","doi":"10.1016/j.ejso.2020.08.006","gradingScheme":"GRADE quality of evidence (high, moderate, low, very low) and strength of recommendation, by two-round Delphi.","read":"abstract","accessed":"2026-11-11"},{"key":"indepso-2025","label":"INDEPSO-ISPSM consensus on peritoneal malignancies: enhanced recovery after surgery in cytoreductive surgery (CRS) with/without HIPEC","publisher":"INDEPSO and ISPSM (Gynecologic Oncology Reports)","year":2025,"url":"https://doi.org/10.1016/j.gore.2024.101662","doi":"10.1016/j.gore.2024.101662","gradingScheme":"Modified Delphi, two rounds, 48 voting surgeons: consensus above 70% of votes, strong consensus above 90%; no evidence grades.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-shorter-fasting-before-surgery"],"gaps":["The full texts of both parts of the ERAS Society CRS/HIPEC guideline (2020) could not be read: neither is open in PubMed Central, the publisher's text service needs a key, and the ERAS Society site refused a script. The grade of each item is not given here, and the item content is the Indian consensus authors' account of it.","Evidence specific to CRS and HIPEC is thin: 40% of the ERAS items rest on low-quality evidence, and the guideline calls for high-quality studies.","Whether fresh frozen plasma should be given preemptively did not reach consensus (ERAS 2020).","Drains and bowel preparation are handled differently by the ERAS and Indian panels; no trial settles either for CRS.","Anaesthetic doses, HIPEC drug regimens and temperature targets are in the guideline and local protocols and are not reproduced here."]},{"id":"enhanced-recovery-after-gastrectomy","kind":"protocol","name":"Enhanced recovery after gastrectomy (ERAS pathway for stomach cancer surgery)","aka":["ERAS gastrectomy","enhanced recovery gastric cancer surgery","fast-track gastrectomy","perioperative care for gastrectomy"],"tldr":"Enhanced recovery is a package of care that helps people recover from stomach surgery: a dietitian's assessment and feeding support for anyone undernourished, keyhole surgery for early cancers where suitable, no routine nose tube or drain, drinking and eating from the day after surgery and building up slowly, extra feeding support if eating stays low, and checking that every step happens.","summary":"The ERAS Society gastrectomy guideline (2014; 25 items, 8 procedure-specific, graded by GRADE) is the only ERAS gastrectomy edition. Its full text could not be read; its procedure-specific items and grades are quoted from the reproduction in Yamagata et al. (2019). Strong: no routine preoperative artificial nutrition, but optimise significantly malnourished patients with oral supplements or enteral nutrition (very low evidence); laparoscopy-assisted distal gastrectomy for early gastric cancer (high); no routine nasogastric or nasojejunal tube (high); avoid abdominal drains (high); individualised nutritional support for those clearly malnourished or unable to meet 60% of needs by day 6 (moderate); systematic audit (low). Weak: preoperative oral pharmaconutrition (insufficient evidence for gastrectomy), laparoscopy-assisted total gastrectomy, wound catheters and TAP block (no gastrectomy evidence), and drink and food at will from day 1 after total gastrectomy, increasing by tolerance (moderate). A 2025 meta-analysis of 27 randomised trials (3,274 patients) found ERAS shortened stay and sped bowel recovery without more complications or readmissions, with low to moderate certainty. NICE NG83 offers specialist dietetic support throughout radical treatment for oesophago-gastric cancer; NICE NG180 offers enhanced recovery for elective major surgery, clear fluids until 2 hours before, and suggests carbohydrate drinks for abdominal surgery. Japanese guidelines (2018) describe a slower model pathway.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","surgical-site-infection-prevention","enhanced-recovery-after-liver-surgery"],"cancers":["gastric"],"sections":[],"technologies":["eras-perioperative-nutrition","prehabilitation","enteral-parenteral-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gastrectomy","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before stomach surgery you will have your nutrition checked and get extra feeding if you need it. Afterwards you will usually not have a tube in your nose, and you can start drinking and eating from the next day, a little at a time.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","home"]},"population":"Adults having elective total or distal gastrectomy, open or laparoscopic, most often for gastric cancer. The ERAS items marked as procedure-specific apply to gastrectomy; the general ERAS elements (counselling, fasting, warming, clot prevention) are taken from the general sources. Oesophagectomy, including for junctional cancers resected through the chest, has its own ERAS guideline.","trigger":"A decision to remove all or part of the stomach.","steps":[{"action":"Assess nutrition and give tailored specialist dietetic support before, during and after treatment","why":"Stomach cancer often causes weight loss, and poor nutrition raises the risk of complications.","source":"nice-ng83","quote":"Offer nutritional assessment and tailored specialist dietetic support to people with oesophago‑gastric cancer before, during and after radical treatments.","grade":"Not graded (NICE NG83 1.6.1, 'offer')"},{"action":"Give oral supplements or tube feeding before surgery to anyone significantly malnourished, but not routine artificial nutrition to everyone","why":"Extra feeding helps those who are undernourished; for well-nourished people it adds nothing.","source":"yamagata-2019","quote":"Routine use of preoperative artificial nutrition is not warranted, but significantly malnourished patients should be optimized with oral supplements or enteral nutrition before surgery","grade":"Evidence level: Very low. Recommendation grade: Strong (ERAS 2014, as reproduced by Yamagata et al.)"},{"action":"Allow clear fluids until 2 hours before the operation, and consider a carbohydrate drink","why":"Long fasting leaves people thirsty and weaker; a sugary drink before abdominal surgery is safe.","source":"nice-ng180","quote":"Consider carbohydrate drinks before surgery for people having abdominal major or complex surgery .","grade":"Not graded (NICE NG180 1.4.2, 'consider')"},{"action":"Offer laparoscopy-assisted distal gastrectomy for early gastric cancer where suitable","why":"Keyhole surgery for early stomach cancer causes fewer complications and faster recovery, with the same cancer outcome as open surgery.","source":"yamagata-2019","quote":"Evidence supports LADG in early gastric cancer as it results in fewer complications, faster recovery and may be carried out to a standard that is oncologically equivalent to open surgery","grade":"Evidence level: High. Recommendation grade: Strong (ERAS 2014, as reproduced by Yamagata et al.)"},{"action":"Do not use nasogastric or nasojejunal tubes routinely","why":"A tube through the nose is uncomfortable and does not prevent leaks or vomiting after stomach surgery.","source":"yamagata-2019","quote":"Nasogastric tubes should not be used routinely","grade":"Evidence level: High. Recommendation grade: Strong (ERAS 2014, as reproduced by Yamagata et al.)"},{"action":"Avoid routine abdominal drains","why":"Drains bring their own complications and lengthen the hospital stay.","source":"yamagata-2019","quote":"Avoiding the use of abdominal drains may reduce drain‐related complications and shorten hospital stay after gastrectomy","grade":"Evidence level: High. Recommendation grade: Strong (ERAS 2014, as reproduced by Yamagata et al.)"},{"action":"After total gastrectomy, offer drink and food at will from the day after surgery, starting cautiously and increasing by tolerance","why":"Eating early is safe and helps recovery; without a stomach, small amounts often work best.","source":"yamagata-2019","quote":"Patients undergoing total gastrectomy should be offered drink and food at will from POD 1. They should be advised to begin cautiously and increase intake according to tolerance","grade":"Evidence level: Moderate. Recommendation grade: Weak (ERAS 2014, as reproduced by Yamagata et al.)"},{"action":"Give individualised nutritional support to anyone clearly malnourished or not meeting 60% of daily needs by day 6","why":"People who cannot eat enough after stomach surgery need extra feeding to heal.","source":"yamagata-2019","quote":"Patients clearly malnourished or those unable to meet 60% of daily requirements by POD 6 should be given individualized nutritional support","grade":"Evidence level: Moderate. Recommendation grade: Strong (ERAS 2014, as reproduced by Yamagata et al.)"},{"action":"Prioritise early oral feeding, early mobilisation and opioid-sparing multimodal pain relief, with anti-sickness prophylaxis","why":"These are the elements most strongly tied to faster recovery in the randomised trials.","source":"liu-2025","quote":"prioritizing early oral feeding, early mobilization, and opioid‑sparing multimodal analgesia as non‑negotiable drivers of recovery","grade":"Authors' recommendation from a meta-analysis (certainty of evidence generally low to moderate)"},{"action":"Audit compliance with each element systematically","why":"Units that measure how often each step is delivered improve compliance and results.","source":"yamagata-2019","quote":"Systematic audit improves compliance and clinical outcomes","grade":"Evidence level: Low. Recommendation grade: Strong (ERAS 2014, as reproduced by Yamagata et al.)"}],"bestInClass":{"statement":"The ERAS Society gastrectomy guideline (2014) remains the only specialty guideline and the current standard; read here through its abstract and a reproduction of its procedure-specific items with their grades. Its strongest items, on high-quality evidence, are laparoscopy-assisted distal gastrectomy for early cancer, no routine nasogastric tube and no routine abdominal drain. A 2025 meta-analysis of 27 randomised trials supports the pathway as a whole (shorter stay, faster bowel recovery, no excess complications or readmissions; low to moderate certainty). NICE NG83 and NG180 agree on dietetic support, enhanced recovery for major surgery and the 2-hour clear-fluid fast. Where practice differs most is in Japan, where the national guideline's model pathway starts food later and drains are still often placed after D2 surgery.","sources":["eras-gas-2014","yamagata-2019","liu-2025","nice-ng83","nice-ng180"]},"variants":[{"name":"Japanese model clinical pathway (Japanese Gastric Cancer Treatment Guidelines 2018)","differs":"Nasogastric tube out by day 1, drinks after day 1, solid food from day 2 to 4, and any drain out by day 5.","evidence":"As reported by Yamagata et al. (2019), who call it 'a bit slow from the viewpoint of ERAS'. A Japanese multicentre trial (2018) cited there found early oral feeding did not shorten stay and increased complications after distal gastrectomy, while it may shorten stay after total gastrectomy. The Japanese guideline itself was not read.","sources":["yamagata-2019"]},{"name":"Routine abdominal drain after D2 gastrectomy","differs":"Places a drain after gastrectomy, often to measure drain amylase for early detection of pancreatic fistula.","evidence":"Common in Japan, according to Yamagata et al.; ERAS 2014 recommends avoiding drains (high, strong), and there is no evidence that drain amylase monitoring improves short-term outcomes.","sources":["yamagata-2019","eras-gas-2014"]},{"name":"Preoperative immunonutrition (oral pharmaconutrition)","differs":"Gives arginine and omega-3 enriched drinks before surgery.","evidence":"ERAS 2014: benefit shown in major gastrointestinal surgery in general has not been reproduced in gastrectomy trials (moderate evidence, weak). Later meta-analyses cited by Yamagata et al. show effects on inflammation but no clear improvement in clinical outcomes.","sources":["yamagata-2019"]}],"grades":[{"claim":"ERAS gastrectomy guideline: 25 items graded by GRADE","grade":"GRADE: evidence high, moderate, low or very low; recommendation strong or weak","source":"eras-gas-2014","quote":"Results The available evidence has been summarized and recommendations are given for 25 items, eight of which contain procedure-specific evidence."},{"claim":"Laparoscopy-assisted total gastrectomy","grade":"Evidence level: Moderate. Recommendation grade: Weak","source":"yamagata-2019","quote":"There is some evidence supporting LATG owing to lower postoperative complications, shorter hospital stay and oncological safety. However, LATG is technically demanding"},{"claim":"TAP block for gastrectomy","grade":"Evidence level: Low. Recommendation grade: Weak","source":"yamagata-2019","quote":"Evidence is strong in support of TAP block in abdominal surgery, although the effect is evident only during the first 48 h after surgery and none of the evidence is from gastrectomies"},{"claim":"ERAS versus conventional care after gastrectomy","grade":"Meta-analysis of 27 randomised trials; certainty generally low to moderate","source":"liu-2025","quote":"ERAS significantly shortened length of stay and accelerated gastrointestinal recovery."},{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."}],"sources":[{"key":"eras-gas-2014","label":"Consensus guidelines for enhanced recovery after gastrectomy: Enhanced Recovery After Surgery (ERAS) Society recommendations (Mortensen et al.)","publisher":"ERAS Society (British Journal of Surgery)","year":2014,"url":"https://doi.org/10.1002/bjs.9582","doi":"10.1002/bjs.9582","gradingScheme":"GRADE: quality of evidence high, moderate, low or very low; recommendations strong or weak.","read":"abstract","accessed":"2026-11-11"},{"key":"yamagata-2019","label":"Current status of the 'enhanced recovery after surgery' program in gastric cancer surgery (Yamagata et al.)","publisher":"Annals of Gastroenterological Surgery","year":2019,"url":"https://doi.org/10.1002/ags3.12232","doi":"10.1002/ags3.12232","gradingScheme":"Review; Table 1 reproduces the ERAS 2014 procedure-specific items with their evidence level and recommendation grade (partially modified).","read":"full-text","accessed":"2026-11-11"},{"key":"liu-2025","label":"Enhanced recovery after gastrectomy: updated meta-analysis of 27 randomized trials (2018-2025) (Liu et al.)","publisher":"BMC Surgery","year":2025,"url":"https://doi.org/10.1186/s12893-025-03399-2","doi":"10.1186/s12893-025-03399-2","gradingScheme":"Systematic review and meta-analysis; certainty of evidence by GRADE.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng83","label":"Oesophago-gastric cancer: assessment and management in adults (NG83), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng83/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-shorter-fasting-before-surgery"],"gaps":["The full text of the ERAS Society gastrectomy guideline (2014) could not be read: it is not open in PubMed Central and the publisher returned a bot challenge. Its procedure-specific items and grades are quoted from a reproduction marked 'partially modified'; its 17 general items (counselling, fasting, warming, clot prevention and others) were not read and are covered here from NICE.","The guideline is 12 years old and predates most randomised trials of laparoscopic surgery for advanced gastric cancer and of robotic gastrectomy; no newer ERAS Society edition was found to November 2026.","When to start eating after distal as opposed to total gastrectomy is not settled; a Japanese multicentre trial found early feeding did not shorten stay after distal gastrectomy (as reported by Yamagata et al.).","The Japanese Gastric Cancer Treatment Guidelines were not read directly; the Japanese pathway is described from a review."]},{"id":"enhanced-recovery-after-gynaecological-cancer-surgery","kind":"protocol","name":"Enhanced recovery after gynaecological cancer surgery (ERAS pathway for gynaecologic oncology)","aka":["ERAS gynaecologic oncology","ERAS gynecologic oncology","enhanced recovery hysterectomy","enhanced recovery ovarian cancer surgery","perioperative care for gynaecological cancer"],"tldr":"After an operation for ovarian, womb or cervical cancer, enhanced recovery means eating a normal diet and getting up within a day, the drip and the urinary catheter out within a day, no routine drains, pain relief that relies less on opioids, and four weeks of blood clot injections after open surgery for cancer.","summary":"The ERAS Society has updated its gynecologic oncology guideline three times (2019, 2023 implementation update, 2026), but none of the updates is open and their abstracts state no recommendations. The latest edition whose recommendations could be read is the 2016 Part II on postoperative care (GRADE): compression stockings and intermittent pneumatic compression, and 28 days of extended prophylaxis after laparotomy for abdominal or pelvic cancer (high, strong); IV fluids stopped within 24 hours with balanced crystalloid (moderate, strong); a regular diet within 24 hours (high, strong); multimodal analgesia with regular paracetamol and an NSAID (high, strong); spinal anaesthesia with intrathecal morphine for open surgery (moderate, strong), with thoracic epidural an alternative (high, strong) and a TAP block where there is no neuraxial block (moderate, strong); no routine peritoneal drain, even after lymphadenectomy or bowel surgery (moderate, strong); urinary catheter out within 24 hours (low, strong); mobilisation within 24 hours (low, strong); laxatives and chewing gum to be considered (weak). NICE NG180 offers an enhanced recovery programme for all elective major surgery and allows clear fluids to 2 hours before.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","surgical-site-infection-prevention","routine-preoperative-tests","enhanced-recovery-after-colorectal-surgery"],"cancers":["ovarian","endometrial","cervical","vulvar"],"sections":[],"technologies":["eras-perioperative-nutrition","prehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hysterectomy","debulking","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After surgery for a gynaecological cancer you will be helped to eat, drink and get out of bed within a day. The drip and the catheter come out early. After open surgery you will usually have four weeks of injections to prevent blood clots.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["ward","theatre","home"]},"population":"Adults having planned surgery for gynaecological cancer (ovarian, endometrial, cervical), open or laparoscopic, including cytoreduction with bowel surgery and lymphadenectomy. Vulvar and vaginal surgery has its own ERAS guideline (2020), whose recommendations could not be read.","trigger":"A decision to operate for a gynaecological cancer.","steps":[{"action":"Offer an enhanced recovery programme for planned major surgery","why":"A coordinated package of care before, during and after the operation shortens recovery.","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery .","grade":"Not graded (NICE NG180 1.2.1)"},{"action":"Fit compression stockings and use intermittent pneumatic compression, and give 28 days of clot prevention after laparotomy for cancer","why":"The risk of a blood clot stays high for a month after open surgery for cancer, and extended injections more than halve it.","source":"eras-gyn-2016-postop","quote":"Patients should wear well-fitting compression stockings and have intermittent pneumatic compression. Extended prophylaxis (28 days) should be given to patients after laparotomy for abdominal or pelvic malignancies.","grade":"Evidence level: High. Recommendation grade: Strong."},{"action":"Stop intravenous fluids within 24 hours, using balanced crystalloid rather than saline","why":"Too much drip fluid causes swelling and slows the bowel; drinking replaces it.","source":"eras-gyn-2016-postop","quote":"Intravenous fluids should be terminated within 24 h after surgery. Balanced crystalloid solutions are preferred to 0.9% normal saline.","grade":"Evidence level: Moderate. Recommendation grade: Strong."},{"action":"Offer a regular diet within the first 24 hours after surgery","why":"Eating early is safe after gynaecological cancer surgery, including bowel surgery, and helps recovery.","source":"eras-gyn-2016-postop","quote":"A regular diet within the first 24 h after gynecologic/oncology surgery is recommended.","grade":"Evidence level: High. Recommendation grade: Strong."},{"action":"Use multimodal pain relief with regular paracetamol and an NSAID, oral opioids once eating, and IV patient-controlled analgesia only until the gut works","why":"Combining non-opioid painkillers reduces the opioid needed, and with it sickness and a slow bowel.","source":"eras-gyn-2016-postop","quote":"Acetaminophen and NSAIDs in combination should be administered regularly to all patients unless contraindication exists.","grade":"Evidence level: Use of multimodal analgesia: High. Combination of acetaminophen and NSAIDs: High. Recommendation grade: Strong."},{"action":"For open surgery, use spinal anaesthesia with intrathecal morphine or a thoracic epidural; without either, use a truncal block such as a TAP block","why":"These reduce pain and opioid use after an abdominal incision; an epidural can slow getting up and catheter removal.","source":"eras-gyn-2016-postop","quote":"Where patients have undergone general anesthesia without neuraxial blockade, a truncal block, such as TAP blocks, may reduce pain and opioid consumption for up to 24 h and should be employed.","grade":"Intrathecal morphine: Moderate. Thoracic epidural analgesia: High. TAP blocks: Moderate. Recommendation grade: Strong."},{"action":"Do not place a peritoneal drain routinely, even after lymph node removal or bowel surgery","why":"Drains did not prevent complications in the trials and can delay recovery.","source":"eras-gyn-2016-postop","quote":"Peritoneal drainage is not recommended routinely in gynecologic/oncology surgery including for patients undergoing lymphadenectomy or bowel surgery.","grade":"Evidence level: Moderate. Recommendation grade: Strong."},{"action":"Remove the urinary catheter early, preferably within 24 hours","why":"A catheter left in raises the risk of urine infection and keeps people in bed.","source":"eras-gyn-2016-postop","quote":"Urinary catheters should be used for postoperative bladder drainage for a short period preferably <24 h postoperatively.","grade":"Evidence level: Low. Recommendation grade: Strong."},{"action":"Encourage getting up within 24 hours of surgery","why":"Moving early reduces clots, chest infection and muscle loss.","source":"eras-gyn-2016-postop","quote":"Patients should be encouraged to mobilize within 24 h of surgery.","grade":"Evidence level: Low. Recommendation grade: Strong."},{"action":"Consider laxatives and chewing gum after surgery to help the bowel recover","why":"Both may shorten the time until the bowel starts working again.","source":"eras-gyn-2016-postop","quote":"The use of postoperative laxatives and chewing gum should be considered.","grade":"Evidence level: Laxatives: Low. Chewing gum: Moderate. Recommendation grade: Weak."},{"action":"Keep blood glucose below about 180 to 200 mg/dL (10 to 11 mmol/l), treating higher levels with insulin and regular checks","why":"High blood sugar after surgery raises the risk of infection and other complications.","source":"eras-gyn-2016-postop","quote":"Perioperative maintenance of blood glucose levels (<180–200 mg/dL) results in improved perioperative outcomes. Glucose levels above this range should be treated with insulin infusions and regular blood glucose monitoring to avoid the risk of hypoglycemia.","grade":"Evidence level: Treating hyperglycemia above 180–200 mg/dL: High. Recommendation grade: Strong."}],"bestInClass":{"statement":"The ERAS Society 2026 update is the current specialty standard, but no recommendation in it could be read. The latest readable recommendations, the 2016 postoperative guideline, are graded and most are strong: extended 28-day clot prevention after laparotomy for cancer, early diet and early stopping of IV fluids rest on high-quality evidence; no routine drains on moderate. NICE NG180 covers the general enhanced recovery programme and the 2-hour clear-fluid fast. Where ERAS 2016 is weakest is analgesia for major oncological and laparoscopic surgery (low evidence, weak).","sources":["eras-gyn-2026","eras-gyn-2016-postop","nice-ng180"]},"variants":[{"name":"Thoracic epidural for major gynaecological cancer surgery","differs":"Uses a thoracic epidural as the main analgesia after laparotomy for cancer.","evidence":"ERAS 2016 says it reduces pain but may not improve other outcomes, often needs IV opioids as well, and can worsen low blood pressure; IV patient-controlled analgesia is a suitable alternative (low evidence, weak).","sources":["eras-gyn-2016-postop"]},{"name":"Extended clot prevention after minimally invasive surgery","differs":"Gives 28 days of prophylaxis after laparoscopic surgery as well as open.","evidence":"ERAS 2016 says extended prophylaxis after minimally invasive surgery is likely not necessary without other high-risk features (raised BMI, previous VTE, coagulopathy, reduced mobility).","sources":["eras-gyn-2016-postop"]}],"grades":[{"claim":"Clear fluids until 2 hours before the operation","grade":"Not graded (NICE NG180 1.4.1)","source":"nice-ng180","quote":"they may drink clear fluids until 2 hours before their operation"},{"claim":"Spinal anaesthesia with intrathecal morphine for open surgery","grade":"Moderate Strong","source":"eras-gyn-2016-postop","quote":"Spinal anesthesia with intrathecal morphine is recommended"},{"claim":"Thoracic epidural for major oncological surgery","grade":"Evidence level: Low. Recommendation grade: Weak.","source":"eras-gyn-2016-postop","quote":"TEA may be considered but patients frequently require additional IV opioids in addition to TEA to achieve adequate analgesia"},{"claim":"Analgesia for laparoscopic surgery","grade":"Low Weak","source":"eras-gyn-2016-postop","quote":"Lack of evidence makes it difficult to recommend one analgesic intervention over another, however a multimodal approach should be employed"}],"sources":[{"key":"eras-gyn-2026","label":"Enhanced recovery after surgery (ERAS) society guidelines for gynecologic oncology: 2026 update","publisher":"ERAS Society (Gynecologic Oncology)","year":2026,"url":"https://doi.org/10.1016/j.ygyno.2026.05.022","doi":"10.1016/j.ygyno.2026.05.022","gradingScheme":"GRADE, per its abstract; the recommendations were not read.","read":"abstract","accessed":"2026-11-11"},{"key":"eras-gyn-2023","label":"Enhanced recovery after surgery (ERAS) society guidelines for gynecologic oncology: Addressing implementation challenges, 2023 update","publisher":"ERAS Society (Gynecologic Oncology)","year":2023,"url":"https://doi.org/10.1016/j.ygyno.2023.04.009","doi":"10.1016/j.ygyno.2023.04.009","gradingScheme":"GRADE, per its abstract; the recommendations were not read.","read":"abstract","accessed":"2026-11-11"},{"key":"eras-gyn-2019","label":"Guidelines for perioperative care in gynecologic/oncology: Enhanced Recovery After Surgery (ERAS) Society recommendations, 2019 update","publisher":"ERAS Society (International Journal of Gynecological Cancer)","year":2019,"url":"https://doi.org/10.1136/ijgc-2019-000356","doi":"10.1136/ijgc-2019-000356","gradingScheme":"GRADE, per its abstract; the recommendations were not read.","read":"abstract","accessed":"2026-11-11"},{"key":"eras-gyn-2016-postop","label":"Guidelines for postoperative care in gynecologic/oncology surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations, Part II","publisher":"ERAS Society (Gynecologic Oncology)","year":2016,"url":"https://doi.org/10.1016/j.ygyno.2015.12.019","doi":"10.1016/j.ygyno.2015.12.019","gradingScheme":"GRADE evidence level (high, moderate, low, very low) and recommendation grade (strong or weak), printed after each item and in its summary table.","read":"full-text","accessed":"2026-11-11"},{"key":"eras-vulvar-vaginal-2020","label":"Guidelines for vulvar and vaginal surgery: Enhanced Recovery After Surgery Society recommendations","publisher":"ERAS Society (American Journal of Obstetrics and Gynecology)","year":2020,"url":"https://doi.org/10.1016/j.ajog.2020.07.039","doi":"10.1016/j.ajog.2020.07.039","gradingScheme":"GRADE, per its abstract; the recommendations were not read.","read":"abstract","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-extended-clot-prevention-after-surgery"],"gaps":["The current ERAS gynecologic oncology guideline (2026) and the 2019 and 2023 updates could be read only as abstracts, which state no recommendations. Every graded step here is from the 2016 postoperative guideline and may have been revised since; this page should be updated when the 2026 text can be read.","The pre- and intra-operative items (counselling, prehabilitation, bowel preparation, carbohydrate loading, antibiotic and skin preparation, warming, nausea prophylaxis) are in the 2016 Part I and the later updates, none of which could be read. They are covered here only by NICE NG180 and by the surgical site infection and VTE protocols.","The vulvar and vaginal surgery guideline (2020) could be read only as an abstract.","The 2016 guideline gives glucose targets in mg/dL; the mmol/l figures in the step are a conversion, not the guideline's own."]},{"id":"enhanced-recovery-after-liver-surgery","kind":"protocol","name":"Enhanced recovery after liver surgery (ERAS pathway for hepatectomy)","aka":["ERAS liver","ERAS hepatectomy","enhanced recovery liver resection","fast-track liver surgery","perioperative care for liver resection"],"tldr":"Enhanced recovery is a package of care that helps people recover faster from liver surgery: preparation and stopping smoking and heavy drinking beforehand, a short fast with a sugary drink, keyhole surgery where possible, good pain relief that keeps you mobile, no routine tubes or drains, eating and getting out of bed on the day of surgery, and blood clot prevention.","summary":"The ERAS Society liver surgery recommendations (2022; 25 items, all with more than 80% agreement after three Delphi rounds) grade each element by GRADE. Strong recommendations with high-quality evidence: smoking cessation at least 4 weeks and alcohol cessation 4 to 8 weeks before surgery for heavy drinkers; nutritional assessment for all, with 7 to 14 days of enteral supplementation for the malnourished; continuous wound infiltration or TAP block as part of analgesia; no routine nasogastric tube; no routine drain after hepatectomy without biliary reconstruction; early oral intake with a normal diet; insulin to keep glucose below 8.3 mmol/l; PONV prophylaxis with at least two drugs; and low central venous pressure during transection with balanced crystalloid. Strong with moderate evidence: fasting 2 hours for clear fluids and 6 hours for solids, postoperative LMWH or heparin plus intermittent pneumatic compression, chlorhexidine-alcohol skin preparation, laparoscopic resection in trained teams, normothermia, early mobilisation from the day of surgery, and audit of compliance. Weaker: prehabilitation for high-risk patients 4 to 6 weeks before (weak, moderate evidence; content not established), carbohydrate loading (weak, low), preoperative methylprednisolone 500 mg (weak, moderate), antibiotic within 60 minutes before incision (weak, moderate), and immunonutrition (not recommended). NICE NG180 (2020) offers an enhanced recovery programme to everyone having elective major or complex surgery and allows clear fluids until 2 hours before.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","surgical-site-infection-prevention"],"cancers":["hcc","cholangiocarcinoma","intrahepatic-cholangiocarcinoma"],"sections":[],"technologies":["eras-perioperative-nutrition","prehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hepatectomy","liver-limited-metastatic-colorectal","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before liver surgery you will be helped to get fit, eat well and stop smoking or drinking. You can drink clear fluids until two hours before. After the operation you will be helped to eat, drink and get out of bed early, which speeds recovery.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","intensive-care","home"]},"population":"Adults having elective liver resection, open or laparoscopic, for any reason (most often hepatocellular carcinoma, cholangiocarcinoma or colorectal liver metastases). Liver transplantation has its own ERAS guideline (2022). Hepatectomy with biliary reconstruction is noted where the recommendations differ.","trigger":"A decision to operate on the liver.","steps":[{"action":"Give information and counselling about the operation before surgery, in writing or multimedia as well as spoken","why":"People who know what to expect take part in their own recovery, for example by eating and walking early.","source":"eras-liver-2022","quote":"Patients should receive preoperative information and counseling regarding the upcoming liver surgery. Brochures and multimedia supports might help to improve the verbal counseling.","grade":"Evidence level: Low. Grade of recommendation: Weak."},{"action":"Help people stop smoking at least 4 weeks before surgery, and heavy drinkers stop alcohol 4 to 8 weeks before","why":"Smoking and heavy drinking both raise the risk of complications, and stopping a few weeks ahead lowers it.","source":"eras-liver-2022","quote":"Preoperative smoking cessation should be counseled at least 4 weeks prior to hepatectomy. Alcohol cessation is recommended for heavy drinkers (>24 g/day for women or >36 g/day for men) 4–8 weeks before surgery.","grade":"Evidence level: Smoking: high, alcohol: high. Grade of recommendation: Smoking: strong, alcohol: strong."},{"action":"Assess nutrition before every liver operation and give 7 to 14 days of nutritional supplements to anyone malnourished","why":"Poorly nourished people have more complications, and a short period of feeding beforehand reduces them.","source":"eras-liver-2022","quote":"A nutritional assessment is necessary prior to all hepatic surgery. Malnourished patients (i.e., weight loss >10% or >5% over 3 months and reduced body mass index or a low fat-free mass index) should be optimized with enteral supplementation at least 7–14 days prior to surgery.","grade":"Evidence level : High. Grade of recommendation : Strong."},{"action":"Offer prehabilitation (exercise, diet, anxiety reduction) to high-risk patients, starting 4 to 6 weeks before surgery where the timing allows","why":"Getting fitter before surgery may help frail, older or malnourished people recover, though the best programme is not yet known.","source":"eras-liver-2022","quote":"Prehabilitation should be performed in high-risk patients (elderly, malnourished or overweight patients, smokers, or patients with psychological disorder) prior to liver surgery.","grade":"Evidence level: Moderate. Grade of recommendation: Weak."},{"action":"Allow clear fluids until 2 hours and food until 6 hours before anaesthesia, and consider a carbohydrate drink the evening before and 2 to 4 hours before","why":"Long fasting leaves people thirsty, dehydrated and more resistant to insulin; a sugary drink shortly before is safe.","source":"eras-liver-2022","quote":"Preoperative fasting of 2 h for liquids and 6 h for solids before anesthesia is safe and can be recommended.","grade":"Evidence level: Preoperative fasting: moderate, carbohydrate loading: low. Grade of recommendation: Preoperative fasting: strong, carbohydrate loading: weak."},{"action":"Avoid long-acting sedatives before surgery, especially in older people","why":"Long-acting sedatives slow waking and getting up after the operation.","source":"eras-liver-2022","quote":"Long-acting anxiolytic drugs should be avoided, particularly in the elderly.","grade":"Evidence level: Moderate. Grade of recommendation: Strong."},{"action":"Give antibiotic prophylaxis within 60 minutes before incision without continuing it afterwards, and prepare the skin with chlorhexidine in alcohol","why":"One well-timed dose and the right skin antiseptic reduce wound infection; longer courses add no benefit.","source":"eras-liver-2022","quote":"Antibiotic prophylaxis (such as cefazolin) within 60 min before surgical incision is recommended, with no benefit extending it into the postoperative period.","grade":"Evidence level: Antibiotics: moderate, skin preparation: moderate. Grade of recommendation: Antibiotics: weak, skin preparation: strong."},{"action":"Use a laparoscopic (keyhole) approach where the team is trained and it is clinically appropriate","why":"Keyhole liver surgery shortens the hospital stay and reduces complications.","source":"eras-liver-2022","quote":"In trained teams and when clinically appropriate, laparoscopic liver resection is recommended since it reduces postoperative length of stay and complication rates.","grade":"Evidence level : Moderate. Grade of recommendation : Strong."},{"action":"Keep central venous pressure low during liver transection, use balanced crystalloid for maintenance, and keep the patient warm","why":"Low venous pressure reduces bleeding from the cut liver; warmth reduces infection and bleeding.","source":"eras-liver-2022","quote":"Perioperative normothermia using multimodal temperature management (including circulating water garments or forced warm air) should be maintained during open and minimally invasive liver surgery.","grade":"Evidence level: Moderate. Grade of recommendation: Strong."},{"action":"Use multimodal analgesia, with wound catheter infiltration or a TAP block for open surgery, rather than relying on a thoracic epidural","why":"These give pain relief as good as an epidural with fewer problems with low blood pressure and getting up.","source":"eras-liver-2022","quote":"Continuous local anesthetic wound infiltration provides lower complication rates and overall equivalent analgesia to thoracic epidural analgesia.","grade":"Evidence level: High. Grade of recommendation: Strong."},{"action":"Do not place a routine nasogastric tube, or a routine abdominal drain after hepatectomy without biliary reconstruction","why":"Tubes and drains add discomfort and delay recovery without preventing complications.","source":"eras-liver-2022","quote":"The routine use of abdominal drain placement is not indicated for hepatectomy without biliary reconstruction.","grade":"Evidence level: High. Grade of recommendation: Strong."},{"action":"Give at least two anti-sickness drugs as prophylaxis","why":"Nausea after surgery is common and delays eating and walking.","source":"eras-liver-2022","quote":"Patients should receive postoperative nausea and vomiting prophylaxis with at least 2 antiemetic drugs such as dexamethasone and ondansetron.","grade":"Evidence level: High. Grade of recommendation: Strong."},{"action":"Start LMWH or heparin after the operation unless unsafe, with intermittent pneumatic compression","why":"Liver surgery carries a real clot risk, and prevention is safe for most people.","source":"eras-liver-2022","quote":"Low molecular weight heparin or unfragmented heparin reduces the risk of thromboembolic events and should be routinely started postoperatively unless exceptional circumstances make this unsafe.","grade":"Evidence level: Use of low molecular weight heparin or unfragmented heparin: moderate, use of intermittent pneumatic compression devices: moderate. Grade of recommendation: Use of low molecular weight heparin or unfragmented heparin: strong, use of intermittent pneumatic compression devices: strong."},{"action":"Restart eating and drinking a normal diet early, and keep blood glucose below 8.3 mmol/l with insulin if needed","why":"Early eating supports healing and recovery; high blood sugar raises the risk of complications.","source":"eras-liver-2022","quote":"Early oral intake with normal diet should be implemented after hepatectomy.","grade":"Evidence level: High. Grade of recommendation: Strong."},{"action":"Get the patient out of bed on the day of surgery and every day until discharge","why":"Moving early reduces chest infections, clots and muscle loss.","source":"eras-liver-2022","quote":"Early mobilization (out of bed) after liver surgery should be established from the operative day until hospital discharge.","grade":"Evidence level: Moderate. Grade of recommendation: Strong."},{"action":"Audit outcomes and compliance with each element and feed the results back to the team","why":"Units that measure how often each element is delivered improve their results.","source":"eras-liver-2022","quote":"Regular audit and feedback should be implemented and performed in liver surgery to monitor and improve postoperative outcomes and compliance to the ERAS program.","grade":"Evidence level: Moderate. Grade of recommendation: Strong."}],"bestInClass":{"statement":"The ERAS Society liver surgery recommendations (2022) are the current specialty standard and are graded element by element (listed in the summary); NICE NG180 (2020) supports an enhanced recovery programme for all elective major surgery and the 2-hour clear-fluid fast. The two agree on fasting; ERAS recommends carbohydrate loading (weak, low evidence) where NICE says consider carbohydrate drinks for abdominal major surgery. Thoracic epidural is not preferred: wound infiltration and TAP block give equivalent analgesia with fewer complications (high, strong).","sources":["eras-liver-2022","nice-ng180"]},"variants":[{"name":"Thoracic epidural for open liver surgery","differs":"Uses a thoracic epidural as the main analgesia after open hepatectomy.","evidence":"ERAS 2022 says it 'can provide excellent analgesia but has significant disadvantages' (low blood pressure, delayed mobility) and recommends multimodal analgesia (strong, high evidence for open surgery), with wound infiltration giving lower complication rates and equivalent analgesia.","sources":["eras-liver-2022"]},{"name":"Preoperative methylprednisolone","differs":"Gives a single 500 mg dose of methylprednisolone before liver resection.","evidence":"Recommended by ERAS 2022 with moderate evidence but a weak grade; no recommendation for people with diabetes.","sources":["eras-liver-2022"]},{"name":"Immunonutrition","differs":"Gives oral immune-enhancing formulas (arginine, omega-3 fatty acids, nucleotides) around surgery.","evidence":"Not recommended for liver surgery by ERAS 2022 because of a lack of evidence (low evidence, weak).","sources":["eras-liver-2022"]}],"grades":[{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."},{"claim":"Clear fluids until 2 hours before the operation","grade":"Not graded (NICE NG180 1.4.1)","source":"nice-ng180","quote":"they may drink clear fluids until 2 hours before their operation"},{"claim":"Carbohydrate drinks for abdominal major or complex surgery","grade":"Not graded (NICE NG180 1.4.2, 'consider')","source":"nice-ng180","quote":"Consider carbohydrate drinks before surgery for people having abdominal major or complex surgery ."},{"claim":"Immunonutrition not recommended in hepatic surgery","grade":"Evidence level : Low. Grade of recommendation : Weak.","source":"eras-liver-2022","quote":"Due to the lack of evidence, the use of immunonutrition in hepatic surgery is not recommended yet."},{"claim":"Low central venous pressure during transection, balanced crystalloid maintenance","grade":"Evidence level: High. Grade of recommendation: Strong.","source":"eras-liver-2022","quote":"Low central venous pressure (below 5 cm H 2 O) with close monitoring is recommended during hepatic transection."},{"claim":"No routine prophylactic nasogastric tube","grade":"Evidence level: High. Grade of recommendation: Strong.","source":"eras-liver-2022","quote":"Routine use of prophylactic nasogastric intubation is not recommended."},{"claim":"Insulin to keep glucose below 8.3 mmol/l","grade":"Evidence level: High. Grade of recommendation: Strong.","source":"eras-liver-2022","quote":"Insulin therapy for maintenance of normoglycemia (<8.3 mmol/l) is recommended."},{"claim":"Recommendations reached consensus","grade":"All 25 items above 80% agreement after 3 Delphi rounds","source":"eras-liver-2022","quote":"All of them obtained consensus (>80% agreement) after 3 Delphi rounds."}],"sources":[{"key":"eras-liver-2022","label":"Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations 2022","publisher":"ERAS Society (World Journal of Surgery)","year":2022,"url":"https://doi.org/10.1007/s00268-022-06732-5","doi":"10.1007/s00268-022-06732-5","gradingScheme":"GRADE evidence level (low, moderate, high) and grade of recommendation (weak or strong), printed after each item.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-shorter-fasting-before-surgery"],"gaps":["The recommendations rest on evidence published up to mid-2020; no newer ERAS liver guideline was found on the ERAS Society's list archived in October 2026.","The content and length of prehabilitation before liver surgery are not established (ERAS 2022).","Whether carbohydrate loading shortens hospital stay after liver surgery is not clear (ERAS 2022).","Drug doses for analgesia and antiemetics, and the details of low central venous pressure anaesthesia, are in the full guideline's tables and local protocols and are not reproduced here."]},{"id":"enhanced-recovery-after-lung-surgery","kind":"protocol","name":"Enhanced recovery after lung cancer surgery (ERAS pathway for lung resection)","aka":["ERAS thoracic","ERAS lung resection","enhanced recovery lobectomy","fast-track thoracic surgery","perioperative care for lung cancer surgery"],"tldr":"Enhanced recovery for lung cancer surgery means stopping smoking and getting fitter beforehand, keyhole surgery where possible, a short fast with a sugary drink, nerve blocks for pain, no routine stomach tube and an early catheter removal, drinking a few hours after the operation, getting up within a day, and physiotherapy.","summary":"The ERAS Society and ESTS guideline (2019; 45 items) is the specialty standard; only its abstract could be read, which lists key recommendations without grades: counselling, nutritional screening, smoking cessation, prehabilitation for high-risk patients, avoiding fasting, carbohydrate loading, no sedative premedication, VTE prophylaxis, warming, short-acting anaesthetics, regional anaesthesia, nausea control, opioid-sparing analgesia, euvolaemia, minimally invasive surgery, early chest drain removal, avoiding urinary catheters and early mobilisation. The graded detail here is from the Italian PACTS consensus (2020, USPSTF grades), read in full: VATS whenever possible (good, A); smoking cessation ideally 4 weeks before (fair, A); prehabilitation (poor, A); fasting 2 hours for clear fluids and 6 for solids (good, A) and carbohydrate loading (poor, A); no routine benzodiazepines (fair, B); temperature of at least 36 °C (good, A); balanced crystalloid (good, A) and near-zero fluid balance (fair, A); protective one-lung ventilation (fair, A); risk-based nausea prophylaxis (good, A); no routine nasogastric tube and early catheter removal (fair, A); locoregional analgesia with paravertebral block for VATS (good, A) and epidural for thoracotomy or high risk (fair, A); IV NSAIDs (good, A); no suction on drains without complications (good, D); oral intake 4 to 6 hours after surgery (fair, A); mobilisation within 24 hours and physiotherapy (fair, A).","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","surgical-site-infection-prevention","routine-preoperative-tests"],"cancers":["lung-cancer","nsclc"],"sections":[],"technologies":["eras-perioperative-nutrition","prehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lobectomy","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before lung surgery you will be helped to stop smoking and to get fitter. Keyhole surgery is used where it can be. Afterwards you can drink within hours, you will be helped out of bed within a day, and a physiotherapist will help your breathing.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","intensive-care"]},"population":"Adults having planned lung resection, mostly for lung cancer, by video-assisted thoracoscopic surgery (VATS) or thoracotomy. The PACTS consensus was written for Italian anaesthetic practice and covers thoracic surgery generally.","trigger":"A decision to operate on the lung.","steps":[{"action":"Support current smokers to stop, at least 2 to 3 weeks and ideally 4 weeks before surgery","why":"Smoking is a strong predictor of lung complications after the operation.","source":"pacts-2020-part1","quote":"Nonetheless, given that smoking status is a strong predictor of postoperative lung complications, we suggest smoking cessation at least 2-3 weeks before surgery (ideally 4 weeks before).","grade":"Level of evidence: Fair. Strength of recommendation: A."},{"action":"Offer exercise prehabilitation, ideally multimodal, before curative lung cancer surgery","why":"Getting fitter beforehand may reduce chest complications and the time in hospital.","source":"pacts-2020-part1","quote":"We recommend preoperative exercise rehabilitation (prehabilitation) in candidates for curative surgical intervention for lung cancer as it may reduce postoperative pulmonary complications.","grade":"Level of evidence: Poor. Strength of recommendation: A."},{"action":"Limit fasting to 2 hours for clear fluids and 6 hours for food, and give a carbohydrate drink up to 2 hours before","why":"A long fast causes thirst and stress without making anaesthesia safer; a sugary drink reduces discomfort and insulin resistance.","source":"pacts-2020-part1","quote":"We recommend limiting clear fluid and solid fasting up to 2 and 6 h, respectively, in patients undergoing lung surgery who are not at risk of delayed gastric emptying.","grade":"Fasting: Level of evidence Good, Strength A. Carbohydrate loading: Level of evidence Poor, Strength A."},{"action":"Avoid routine benzodiazepines before surgery, especially in older people","why":"Sedatives before the operation slow waking and getting up, particularly in older people.","source":"pacts-2020-part1","quote":"We suggest avoiding the routine use of benzodiazepines before thoracic surgery, especially in elderly people.","grade":"Level of evidence: Fair. Strength of recommendation: B."},{"action":"Use video-assisted thoracoscopic (keyhole) surgery whenever possible","why":"Keyhole lung surgery causes fewer complications, less pain and a shorter stay than open surgery.","source":"pacts-2020-part1","quote":"We recommend the video-assisted thoracoscopic approach for lung surgery whenever possible, because of the lower incidence of postoperative complications, shorter length of hospital stay, and lower levels of postoperative pain associated with this technique.","grade":"Level of evidence: Good. Strength of recommendation: A."},{"action":"Monitor temperature in operations over 30 minutes and keep core temperature at least 36 °C","why":"Getting cold during surgery raises the risk of infection, bleeding and heart problems.","source":"pacts-2020-part2","quote":"We recommend that intraoperative temperature be monitored using an appropriate system in all patients undergoing thoracic surgery lasting more than 30 min. A core temperature of at least 36 °C should be maintained.","grade":"Level of evidence: Good. Strength of recommendation: A."},{"action":"Use balanced crystalloid and aim for a near-zero fluid balance, with goal-directed therapy in high-risk patients","why":"Too much fluid after lung surgery can cause lung injury; too little can harm the kidneys.","source":"pacts-2020-part2","quote":"We recommend a near-zero, rather than restricted or permissive, fluid balance to patients undergoing thoracic surgery. In high-risk patients, a goal-directed approach to fluid therapy should be applied.","grade":"Near-zero balance: Level of evidence Fair, Strength A. Balanced crystalloid: Level of evidence Good, Strength A."},{"action":"Ventilate the lung gently during one-lung ventilation (low tidal volumes, recruitment, titrated PEEP, lowest oxygen needed)","why":"Protective ventilation reduces injury to the lung that is left.","source":"pacts-2020-part2","quote":"We recommend a protective ventilation approach during one-lung ventilation, based on the combination of low tidal volumes (≤ 6 mL/kg ideal body weight) with alveolar recruitment maneuvers, adequately titrated positive end-expiratory pressure (PEEP) and the lowest fraction of inspired oxygen (FiO2) to maintain satisfactory arterial oxygen saturation.","grade":"Level of evidence: Fair. Strength of recommendation: A."},{"action":"Assess the risk of sickness and give prophylaxis matched to it","why":"Sickness delays drinking, eating and getting up.","source":"pacts-2020-part2","quote":"We recommend evaluation of the risk of postoperative nausea and vomiting, and the use of appropriate prophylaxis according to the level of risk, in all patients undergoing lung surgery.","grade":"Level of evidence: Good. Strength of recommendation: A."},{"action":"Use regional anaesthesia as part of multimodal pain relief: a paravertebral block for VATS, a thoracic epidural for thoracotomy or high-risk patients, with IV NSAIDs and paracetamol","why":"Nerve blocks control pain while sparing opioids, which helps breathing, coughing and walking.","source":"pacts-2020-part2","quote":"We recommend thoracic paravertebral block for VATS, as part of a multimodal approach.","grade":"Paravertebral for VATS: Good, A. Epidural for thoracotomy or high risk: Fair, A. IV NSAIDs: Good, A."},{"action":"Do not place a routine nasogastric tube, and remove urinary catheters early, even with an epidural","why":"Tubes and catheters add discomfort and keep people in bed.","source":"pacts-2020-part2","quote":"We recommend the early removal of urinary catheters to promote mobilization in patients undergoing lung surgery, including those receiving thoracic epidural catheters.","grade":"Urinary catheter: Fair, A. Nasogastric tube: Fair, A."},{"action":"Do not use suction on the chest drain routinely when the lung has fully re-expanded and there are no complications","why":"Routine suction does not help an uncomplicated recovery and keeps the patient tied to the wall.","source":"pacts-2020-part2","quote":"The routine use of drainage with suction is not recommended in the absence of complications, provided there is full re-expansion of the residual parenchyma after lung resection.","grade":"Level of evidence: Good. Strength of recommendation: D."},{"action":"Start drinking 4 to 6 hours after surgery if there is no sickness, get up within 24 hours, and start physiotherapy","why":"Early drinking, movement and breathing exercises speed recovery and reduce chest complications.","source":"pacts-2020-part2","quote":"We recommend early mobilization of patients within the first 24 h after both minor and major thoracic surgery.","grade":"Oral intake 4 to 6 h: Fair, A. Mobilisation within 24 h: Fair, A. Physiotherapy: Fair, A."}],"bestInClass":{"statement":"The ERAS Society and ESTS guideline (2019) is the specialty standard; its abstract says most of its 45 recommendations are strong and lists the key elements, but the graded text could not be read. The PACTS consensus (2020) agrees with every element the ERAS abstract names and grades them: the strongest (good evidence, grade A) are VATS whenever possible, 2-hour and 6-hour fasting, warming, balanced crystalloid, risk-based nausea prophylaxis, paravertebral block for VATS and IV NSAIDs. NICE NG180 supports an enhanced recovery programme for elective major surgery.","sources":["eras-ests-lung-2019","pacts-2020-part1","pacts-2020-part2","nice-ng180"]},"variants":[{"name":"Chest drain removal at higher daily volumes (ERAS 2019)","differs":"Removes the chest drain even when the daily serous output is high, up to 450 ml in 24 hours.","evidence":"Listed as a lung-specific ERAS recommendation by a 2025 appraisal of all ERAS Society guidelines; PACTS suggests a lower threshold of 5 ml/kg a day or less (poor evidence, B). The grade in the ERAS guideline itself could not be read.","sources":["eras-overview-2025","pacts-2020-part2"]},{"name":"Thoracic epidural for all lung resections","differs":"Uses a thoracic epidural as standard analgesia, including for VATS.","evidence":"PACTS recommends epidural for thoracotomy, chest wall resection or high-risk patients (fair, A) and paravertebral block for VATS (good, A), with paravertebral in preference to epidural where coagulopathy is known or suspected (fair, A).","sources":["pacts-2020-part2"]},{"name":"Digital chest drainage systems","differs":"Uses a portable digital drainage system that measures air leak, rather than a conventional bottle.","evidence":"Suggested by PACTS to help early mobilisation (fair, B).","sources":["pacts-2020-part2"]},{"name":"Routine intensive care admission after lung resection","differs":"Admits every patient to intensive care after the operation.","evidence":"Not recommended by PACTS (poor evidence, D).","sources":["pacts-2020-part2"]}],"grades":[{"claim":"Key ERAS lung recommendations, and the grade of most of them","grade":"Not stated item by item in the abstract; 'the recommendation grade for most of the elements is strong'","source":"eras-ests-lung-2019","quote":"As the recommendation grade for most of the elements is strong, the use of a systematic perioperative care pathway has the potential to improve outcomes after surgery."},{"claim":"Carbohydrate loading up to 2 hours before lung surgery","grade":"Level of evidence: Poor. Strength of recommendation: A.","source":"pacts-2020-part1","quote":"We recommend preoperative carbohydrate loading with clear fluids up to 2 h prior to surgery for patients undergoing lung surgery, especially malnourished patients, in order to reduce perioperative discomfort and insulin resistance."},{"claim":"Balanced crystalloid rather than saline","grade":"Level of evidence: Good. Strength of recommendation: A.","source":"pacts-2020-part2","quote":"We recommend using balanced crystalloid solutions, rather than normal saline (NaCl 0.9%), as standard fluid of choice."},{"claim":"No routine nasogastric tube","grade":"Level of evidence: Fair. Strength of recommendation: A.","source":"pacts-2020-part2","quote":"We recommend avoiding the routine placement of a nasogastric tube, and early removal in patients in whom a nasogastric tube is used."},{"claim":"Thoracic epidural for thoracotomy or high-risk patients","grade":"Level of evidence: Fair. Strength of recommendation: A.","source":"pacts-2020-part2","quote":"We recommend the use of thoracic epidural analgesia in high-risk patients or in major surgical procedures where the parietal pleura (e.g., chest wall resection) is violated (i.e., thoracotomy, thoracosternotomy, chest wall resection)."},{"claim":"IV NSAIDs, with paracetamol","grade":"Level of evidence: Good. Strength of recommendation: A.","source":"pacts-2020-part2","quote":"We recommend the use of intravenous nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce peripheral sensitization to inflammation-induced pain in patients undergoing thoracic surgery."},{"claim":"Chest tubes removed at up to 450 ml a day of serous fluid (ERAS lung, as listed by the 2025 appraisal)","grade":"Not stated in the appraisal","source":"eras-overview-2025","quote":"Chest tubes should be removed even if the daily serous effusion is of high volume (up to 450 ml/24 h)"},{"claim":"Oral intake 4 to 6 hours after surgery","grade":"Level of evidence: Fair. Strength of recommendation: A.","source":"pacts-2020-part2","quote":"We recommend that, in adult patients undergoing thoracic surgery, oral intake, including clear liquids, can be initiated 4–6 h after surgery, in the absence of nausea and vomiting."},{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."}],"sources":[{"key":"eras-overview-2025","label":"Enhanced recovery after surgery: overarching themes of the ERAS Society Guidelines and Consensus Statements for Adult Specialty Surgery","publisher":"Perioperative Medicine","year":2025,"url":"https://doi.org/10.1186/s13741-025-00590-0","doi":"10.1186/s13741-025-00590-0","gradingScheme":"An appraisal; repeats the guidelines' own recommendations without new grades.","read":"full-text","accessed":"2026-11-11"},{"key":"eras-ests-lung-2019","label":"Guidelines for enhanced recovery after lung surgery: recommendations of the Enhanced Recovery After Surgery (ERAS) Society and the European Society of Thoracic Surgeons (ESTS)","publisher":"ERAS Society and ESTS (European Journal of Cardio-Thoracic Surgery)","year":2019,"url":"https://doi.org/10.1093/ejcts/ezy301","doi":"10.1093/ejcts/ezy301","gradingScheme":"Quality of evidence and recommendation grade per item, by the authors; the abstract gives no item grades.","read":"abstract","accessed":"2026-11-11"},{"key":"pacts-2020-part1","label":"Recommendations from the Italian intersociety consensus on Perioperative Anesthesia Care in Thoracic surgery (PACTS) part 1: preadmission and preoperative care","publisher":"PACTS group, Italian intersociety consensus (Perioperative Medicine)","year":2020,"url":"https://doi.org/10.1186/s13741-020-00168-y","doi":"10.1186/s13741-020-00168-y","gradingScheme":"USPSTF: level of evidence (good, fair, poor) and strength of recommendation (A, B, C, D, I), printed under each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"pacts-2020-part2","label":"Recommendations from the Italian intersociety consensus on Perioperative Anesthesia Care in Thoracic surgery (PACTS) part 2: intraoperative and postoperative care","publisher":"PACTS group, Italian intersociety consensus (Perioperative Medicine)","year":2020,"url":"https://doi.org/10.1186/s13741-020-00159-z","doi":"10.1186/s13741-020-00159-z","gradingScheme":"USPSTF: level of evidence (good, fair, poor) and strength of recommendation (A, B, C, D, I), printed under each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-shorter-fasting-before-surgery"],"gaps":["The ERAS Society and ESTS guideline (2019), the specialty standard, could be read only as an abstract; its grades for each of the 45 items, and any place it differs from PACTS, are not on this page.","PACTS is an Italian anaesthetic consensus graded on the USPSTF scheme; a grade A there is not the same as a 'strong' GRADE recommendation, and several grade A recommendations rest on poor evidence (prehabilitation, carbohydrate loading, locoregional anaesthesia in general).","When to remove the chest drain (PACTS suggests at 5 ml/kg a day or less of serous fluid, poor evidence, B) and the role of digital drainage are not settled.","Clot prevention after lung resection is in the VTE prophylaxis protocol; drug doses are local protocol matters."]},{"id":"enhanced-recovery-after-head-and-neck-free-flap-surgery","kind":"protocol","name":"Enhanced recovery after major head and neck cancer surgery with free flap reconstruction","aka":["ERAS head and neck","enhanced recovery free flap","perioperative care for head and neck cancer surgery","fast-track head and neck surgery"],"tldr":"Enhanced recovery after major head and neck cancer surgery means a short fast with a sugary drink, clot prevention, antibiotics, anti-sickness medicine, pain relief that spares opioids, careful fluids, frequent checks on the flap, getting up early, nutrition starting within a day of the operation, and a dietitian and speech and swallowing therapist from before surgery.","summary":"The ERAS Society consensus review (2017; 17 topic areas, GRADE) is the only specialty guideline; only its abstract could be read, which names the best-practice elements without grades: preoperative carbohydrate treatment and no prolonged fasting, pharmacological thromboprophylaxis, perioperative antibiotics for clean-contaminated procedures, corticosteroid and antiemetic medicines, short-acting anxiolytics, goal-directed fluids, opioid-sparing multimodal analgesia, frequent flap monitoring and early mobilisation. The nutrition part is graded in full by ASPEN (2026): screen everyone for malnutrition with a validated tool (very low or expert opinion, strong); comprehensive dietitian assessment for those at risk (very low, strong); protein 1.2 to 1.5 g/kg a day (very low, strong) and energy at least 30 kcal/kg a day (high, strong); dietitian input before and after surgery for as long as nutrition is at risk (very low, strong); postoperative nutrition within 24 hours (very low, weak); a speech pathologist before treatment likely to affect swallowing (moderate, strong); an interdisciplinary nutrition team (moderate, strong); the choice of gastrostomy or nasogastric tube made by the team (moderate, weak).","asOf":"2026-11-11","links":[],"tags":[],"related":["surgical-site-infection-prevention","vte-prophylaxis-after-cancer-surgery","oral-mucositis-prevention-and-oral-care","routine-preoperative-tests"],"cancers":["head-and-neck","oral-cavity-cancer"],"sections":[],"technologies":["eras-perioperative-nutrition","enteral-parenteral-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before and after head and neck cancer surgery, a dietitian and a speech and swallowing therapist will see you. You will not be kept hungry for long. After the operation feeding starts within a day, nurses check the reconstructed tissue often, and you will be helped to get up early.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","intensive-care"]},"population":"Adults having major surgery for head and neck cancer with free flap reconstruction (for example of the mouth, throat or larynx). The ASPEN nutrition recommendations cover adults with head and neck cancer having any treatment.","trigger":"A decision to operate with free flap reconstruction.","steps":[{"action":"Screen for malnutrition with a validated tool at first presentation, and repeat through treatment and recovery","why":"Many people with head and neck cancer cannot eat enough, and poor nutrition worsens healing and recovery.","source":"aspen-hn-2026","quote":"In adults with head and neck cancer, we recommend that all patients be screened for malnutrition using a validated tool at their first presentation to the healthcare facility and regularly throughout treatment and recovery to facilitate timely referral for nutrition intervention.","grade":"Certainty of evidence: Very low/expert opinion. Strength: Strong."},{"action":"Involve a dietitian before and after surgery, for as long as nutrition is at risk, with longer support after free flap reconstruction","why":"Extensive surgery and swallowing problems can affect eating for weeks.","source":"aspen-hn-2026","quote":"Patients undergoing certain surgical procedures, such as those with extensive surgical resections (eg, free flap reconstructions) or with dysphagia, may require dietetic support for a longer duration.","grade":"Quality of evidence: Very low/expert opinion. Strength: Strong."},{"action":"Arrange a speech and swallowing assessment before surgery likely to affect swallowing","why":"A baseline assessment and early education help plan rehabilitation and reduce swallowing problems.","source":"aspen-hn-2026","quote":"In adults with head and neck cancer receiving any treatment modality, we recommend consultation by a speech pathologist before treatment (surgery or radiotherapy with or without chemotherapy) for baseline assessment and education if the treatment is likely to affect swallowing function, or in the case of preexisting dysphagia.","grade":"Quality of evidence: Moderate. Strength: Strong."},{"action":"Apply the ERAS elements around the operation: a carbohydrate drink and no prolonged fasting, clot prevention, antibiotics, steroid and anti-sickness medicine, short-acting anxiolytics only, goal-directed fluids and opioid-sparing pain relief","why":"Together these reduce the body's stress response, sickness, pain and complications so that recovery is faster.","source":"eras-hn-2017","quote":"Among these elements are the provision of preoperative carbohydrate treatment, pharmacologic thromboprophylaxis, perioperative antibiotics in clean-contaminated procedures, corticosteroid and antiemetic medications, short acting anxiolytics, goal-directed fluid management, opioid-sparing multimodal analgesia, frequent flap monitoring, early mobilization, and the avoidance of preoperative fasting.","grade":"Graded by GRADE in the full text; grades not in the abstract read"},{"action":"Start nutrition (tube, oral or other) within 24 hours of surgery, increasing oral intake gradually with the surgical team, dietitian and speech therapist","why":"Early feeding helps meet the body's needs for healing; oral intake is built up only when swallowing is safe.","source":"aspen-hn-2026","quote":"In adults with head and neck cancer, we suggest early commencement (within 24 h) of postoperative nutrition intake (EN, oral, or otherwise) to meet estimated nutrition requirements.","grade":"Certainty of evidence: Very low. Strength: Weak."},{"action":"Aim for protein of 1.2 to 1.5 g/kg a day and energy of at least 30 kcal/kg a day","why":"These amounts meet the needs of most people with head and neck cancer and help keep muscle.","source":"aspen-hn-2026","quote":"In adults with head and neck cancer receiving any modality of treatment, we recommend an energy intake of at least 30 kcal/kg/day.","grade":"Energy: Certainty of evidence High, Strength Strong. Protein: Quality of evidence Very low/expert opinion, Strength Strong."},{"action":"Decide between a gastrostomy and a nasogastric tube as a team, by how long feeding is expected to last","why":"A gastrostomy suits feeding expected to last more than about 4 to 6 weeks; otherwise a nasal tube is usually enough.","source":"aspen-hn-2026","quote":"If EN is indicated, feeding via PEG/RIG may be more appropriate when anticipated for longer durations (commonly >4–6 weeks); otherwise, an NGT should be considered.","grade":"Quality of evidence: Moderate. Strength: Weak."},{"action":"Monitor the flap frequently and get the patient up early","why":"A clot in the flap's blood supply must be found quickly to save it, and moving early prevents chest infection and clots.","practice":"The ERAS abstract names frequent flap monitoring and early mobilisation among best practice (quoted in the step above); its schedule and grades are in the full text, which could not be read."}],"bestInClass":{"statement":"The ERAS Society consensus review (2017) is the only specialty guideline for this surgery, and its elements are listed in the abstract without grades. For nutrition, the ASPEN guideline (2026) is the most recent graded source and was read in full: its strongest recommendations rest on high-quality evidence for energy intake and moderate evidence for speech pathology before treatment and interdisciplinary care; most others are expert opinion graded strong. NICE NG180 supports an enhanced recovery programme for elective major surgery.","sources":["eras-hn-2017","aspen-hn-2026","nice-ng180"]},"variants":[{"name":"Arginine-enriched (immune-enhancing) nutrition","differs":"Gives arginine-supplemented feeds around surgery.","evidence":"ASPEN 2026 says it 'may be acceptable at the discretion of the interdisciplinary team', citing some evidence of fewer fistulas and shorter stays but limited evidence on survival (low certainty).","sources":["aspen-hn-2026"]}],"grades":[{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."},{"claim":"Protein intake 1.2 to 1.5 g/kg a day","grade":"Quality of Evidence: Very low/expert opinion. Strength: Strong.","source":"aspen-hn-2026","quote":"In adults with head and neck cancer receiving any modality of treatment, we recommend a protein intake of 1.2–1.5 g/kg/day, which would meet the needs of most patients with head and neck cancer."},{"claim":"Interdisciplinary nutrition management","grade":"Quality of evidence: Moderate. Strength: Strong.","source":"aspen-hn-2026","quote":"In adults with head and neck cancer, we recommend an interdisciplinary approach to nutrition management."},{"claim":"Arginine-supplemented nutrition","grade":"Certainty of evidence: Low","source":"aspen-hn-2026","quote":"Given the limited evidence on progression‐free and overall survival and some evidence of benefit for decreased fistula development and length of stay in adults with head and neck cancer, we suggest that using arginine‐supplemented nutrition may be acceptable at the discretion of the interdisciplinary team."},{"claim":"Scope of the ERAS head and neck review","grade":"GRADE, 17 topic areas","source":"eras-hn-2017","quote":"A total of 17 topic areas were identified for inclusion in the protocol for the perioperative care of patients undergoing major head and neck cancer surgery with free flap reconstruction."}],"sources":[{"key":"eras-hn-2017","label":"Optimal Perioperative Care in Major Head and Neck Cancer Surgery With Free Flap Reconstruction: A Consensus Review and Recommendations From the Enhanced Recovery After Surgery Society","publisher":"ERAS Society (JAMA Otolaryngology, Head and Neck Surgery)","year":2017,"url":"https://doi.org/10.1001/jamaoto.2016.2981","doi":"10.1001/jamaoto.2016.2981","gradingScheme":"GRADE, by consensus of the expert panel; item grades not in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"aspen-hn-2026","label":"Guidelines for nutrition in adults with head and neck cancer: The American Society for Parenteral and Enteral Nutrition","publisher":"ASPEN (Journal of Parenteral and Enteral Nutrition)","year":2026,"url":"https://doi.org/10.1002/jpen.70067","doi":"10.1002/jpen.70067","gradingScheme":"GRADE: certainty or quality of evidence (high, moderate, low, very low or expert opinion) and strength (strong or weak), printed under each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance"],"gaps":["The ERAS head and neck review (2017) could be read only as an abstract; the grade of each element, the flap-monitoring schedule, tracheostomy and airway care, and the antibiotic duration it recommends are not on this page.","The ERAS review searched literature to April 2015 and says the evidence is variable, with many recommendations drawn from other kinds of surgery; no update has been published.","Most of the ASPEN recommendations used here are expert opinion graded strong; only energy intake rests on high-certainty evidence.","Clot prevention, antibiotic choice and doses are local protocol matters and are covered in general by the VTE and surgical site infection protocols."]},{"id":"enhanced-recovery-after-oesophagectomy","kind":"protocol","name":"Enhanced recovery after oesophagectomy (ERAS pathway for oesophageal cancer surgery)","aka":["ERAS oesophagectomy","ERAS esophagectomy","enhanced recovery esophagectomy","fast-track oesophagectomy","perioperative care for oesophagectomy"],"tldr":"Enhanced recovery is a package of care that helps people recover from removal of the oesophagus: dietitian support, getting fitter beforehand, treating low iron, a short fast, keyhole surgery where the team is trained in it, an epidural for pain, early tube or mouth feeding, getting out of bed early, removing tubes once no longer needed, and four weeks of clot prevention.","summary":"The ERAS Society guideline for esophagectomy (2019; 39 items, each graded by GRADE) is the current specialty standard; its full text could not be read here, so its oesophagectomy-specific items are taken from the summary table in Halliday and Moorthy (Ann Surg Oncol 2022), which does not print grades. Items: nutrition assessment and treatment by individual risk with no routine immunonutrition; oral iron for iron-deficiency anaemia; multimodal prehabilitation; surgery 3 to 6 weeks after neoadjuvant chemotherapy or 6 to 10 weeks after neoadjuvant radiotherapy; no routine bowel preparation; solids until 6 hours (with caution in dysphagia) and clear fluids until 2 hours before; minimally invasive surgery where there is training and expertise; gastric conduit first line; nasogastric decompression of the conduit (unlike most ERAS pathways, which avoid routine nasogastric tubes); a single chest drain; balanced crystalloid; lung-protective ventilation; core temperature above 36 °C; level of postoperative care set by individual risk; thoracic epidural first line with paravertebral block as an alternative; early enteral feeding reaching full calories by day 3 to 6 by jejunostomy or nasojejunal tube; mobilisation from the day of surgery if feasible; chest drain removal below 200 ml a day without air or chyle leak; avoiding positive fluid balance; glucose below 10 mmol/l; and VTE prophylaxis for 4 weeks. Elements associated with a shorter stay in a meta-analysis cited there include immediate extubation, mobilisation by day 1, urinary catheter out by day 2 and oral fluids by day 1. NICE NG83 (2018) offers specialist dietetic support before, during and after radical treatment, and immediate enteral or parenteral nutrition after surgery.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","surgical-site-infection-prevention","enhanced-recovery-after-liver-surgery"],"cancers":["esophageal","oesophageal-adenocarcinoma","oesophageal-squamous-cell-carcinoma"],"sections":[],"technologies":["eras-perioperative-nutrition","prehabilitation","enteral-parenteral-nutrition"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oesophagectomy","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before the operation you will see a dietitian, be helped to get fitter and stop smoking, and can eat until six hours and drink clear fluids until two hours before. Afterwards you will be fed early, often through a small feeding tube, helped out of bed early, and given injections against clots for four weeks.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","intensive-care","home"]},"population":"Adults having elective oesophagectomy, open, hybrid or minimally invasive, most often for oesophageal or gastro-oesophageal junction cancer after neoadjuvant chemotherapy or chemoradiotherapy. The ERAS guideline is written for oesophageal resection; stomach-only operations have their own ERAS gastrectomy guideline.","trigger":"A decision to remove the oesophagus.","steps":[{"action":"Assess nutrition before surgery and give tailored specialist dietetic support before, during and after treatment","why":"Many people with oesophageal cancer have lost weight because swallowing is hard, and poor nutrition raises the risk of complications.","source":"nice-ng83","quote":"Offer nutritional assessment and tailored specialist dietetic support to people with oesophago‑gastric cancer before, during and after radical treatments.","grade":"Not graded (NICE NG83 1.6.1, 'offer')"},{"action":"Base nutritional treatment on individual risk, and do not give immunonutrition routinely","why":"Feeding support helps those at risk; special immune-boosting drinks have not been shown to help everyone.","source":"guide-oes-2022","quote":"Assessment and treatment based on individual risk; routine use of immunonutrition is not recommended"},{"action":"Treat iron-deficiency anaemia with oral iron before surgery","why":"Anaemia raises the chance of needing a blood transfusion and of complications.","source":"guide-oes-2022","quote":"Oral iron supplementation for iron-deficiency anaemia"},{"action":"Offer multimodal prehabilitation: an exercise programme, personalised nutritional support and psychological support","why":"Chemotherapy before surgery reduces fitness; getting fitter before the operation may help recovery.","source":"guide-oes-2022","quote":"Multimodal prehabilitation: exercise programme, personalised nutritional support, psychological support"},{"action":"Plan surgery 3 to 6 weeks after neoadjuvant chemotherapy, or 6 to 10 weeks after neoadjuvant radiotherapy","why":"This gives the body time to recover from treatment without letting the cancer grow back.","source":"guide-oes-2022","quote":"3–6 weeks after neoadjuvant chemotherapy or 6–10 weeks after neoadjuvant radiotherapy"},{"action":"Do not use routine bowel preparation; allow solid food until 6 hours and clear fluids until 2 hours before surgery, with caution if swallowing is difficult","why":"Long fasting leaves people thirsty and weaker; food can stay in a narrowed oesophagus, which is why dysphagia needs care.","source":"guide-oes-2022","quote":"Solid food allowed until 6 h prior to surgery (caution if any dysphagia); clear fluids until 2 h prior to surgery"},{"action":"Use minimally invasive surgery where the team has the training and expertise","why":"Keyhole and hybrid approaches can reduce lung complications in experienced hands; open, hybrid and minimally invasive approaches all have acceptable outcomes.","source":"guide-oes-2022","quote":"Recommended where there is appropriate training and expertise"},{"action":"Decompress the new stomach tube (conduit) with a nasogastric tube, and place a single chest drain rather than two","why":"After oesophagectomy the stomach is pulled up into the chest, and a nasogastric tube keeps it from swelling; one drain works as well as two and hurts less.","source":"guide-oes-2022","quote":"Single drain as effective as two and produces less discomfort"},{"action":"Keep core temperature above 36 °C during the operation","why":"Getting cold during surgery raises the risk of infection, bleeding and heart problems.","source":"guide-oes-2022","quote":"Maintain core temperature > 36 °C"},{"action":"Use a thoracic epidural as first-line pain relief, with a paravertebral block as the alternative","why":"Good pain relief lets people breathe deeply, cough and get up, which protects the lungs.","source":"guide-oes-2022","quote":"Thoracic epidural as first line; paravertebral blocks are an alternative"},{"action":"Start enteral or parenteral nutrition immediately after surgery","why":"After oesophagectomy eating by mouth takes time to build up, and early feeding supports healing.","source":"nice-ng83","quote":"Offer immediate enteral or parenteral nutrition after surgery to people who are having radical surgery for oesophageal and gastro-oesophageal junction cancers.","grade":"Not graded (NICE NG83 1.6.2, 'offer')"},{"action":"Feed into the gut early, by jejunostomy or nasojejunal tube, aiming for full calorie needs by day 3 to 6","why":"Feeding through the gut is safer than through a vein and helps the bowel recover.","source":"guide-oes-2022","quote":"Early enteral feeding; aim to achieve full calorie requirements by day 3–6; either jejunostomy or nasojejunal tube may be used"},{"action":"Mobilise from the day of surgery if feasible, with set daily increases in activity","why":"Moving early reduces chest infections, clots and muscle loss.","source":"guide-oes-2022","quote":"Early mobilisation with defined daily incremental increases in activity; start on day of surgery if feasible"},{"action":"Remove chest drains once they drain less than 200 ml a day with no air or chyle leak; avoid a positive fluid balance and keep blood glucose below 10 mmol/l","why":"Drains left in longer slow recovery; too much fluid strains the lungs and the join; high blood sugar raises infection risk.","source":"guide-oes-2022","quote":"Remove once draining < 200 ml/day and no evidence of air or chyle leak"},{"action":"Continue blood clot prevention for 4 weeks after surgery","why":"The risk of clots after major cancer surgery lasts for weeks after leaving hospital.","source":"guide-oes-2022","quote":"Continue for 4 weeks after surgery"},{"action":"Monitor compliance with each element in real time and audit outcomes continuously","why":"Compliance with oesophagectomy pathways varies widely, and units that measure it can improve it.","source":"guide-oes-2022","quote":"Real-time monitoring of compliance should be used to provide a continuous audit of implementation"}],"bestInClass":{"statement":"The ERAS Society esophagectomy guideline (2019) is the current specialty standard, graded item by item; it is read here through its abstract and an open summary of its oesophagectomy-specific items (Halliday and Moorthy 2022), so the grades are not reproduced. Two items differ from most ERAS pathways and are deliberate: nasogastric decompression of the gastric conduit is recommended, and thoracic epidural stays first line for analgesia. NICE NG83 (2018) agrees on nutrition: specialist dietetic support throughout and immediate enteral or parenteral feeding after surgery. NICE NG180 (2020) offers an enhanced recovery programme to everyone having elective major surgery and allows clear fluids until 2 hours before.","sources":["eras-oes-2019","guide-oes-2022","nice-ng83","nice-ng180"]},"variants":[{"name":"Route of early feeding: jejunostomy or nasojejunal tube","differs":"Some centres place a feeding jejunostomy at operation; others use a nasojejunal tube; some start oral intake early.","evidence":"The ERAS summary allows either tube, and there is insufficient evidence to recommend one route for postoperative enteral feeding (Halliday and Moorthy 2022).","sources":["guide-oes-2022"]},{"name":"Level of postoperative care","differs":"Some centres send every patient to intensive care or high dependency after oesophagectomy; others go straight to a surgical unit.","evidence":"The ERAS summary says the level of care should be personalised according to individual risk; the guide notes the two pathways involve different teams and practices.","sources":["guide-oes-2022"]},{"name":"Elements without enough evidence to recommend","differs":"Routine preoperative cardiopulmonary exercise testing, inspiratory muscle training and intraoperative pyloroplasty are used in some centres.","evidence":"There is insufficient evidence to recommend any of them (Halliday and Moorthy 2022, citing the ERAS guideline).","sources":["guide-oes-2022"]}],"grades":[{"claim":"The ERAS guideline graded 39 sections by GRADE","grade":"GRADE (individual grades not read)","source":"eras-oes-2019","quote":"Thirty-nine sections were ultimately produced and assessed for quality of evidence and recommendations."},{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."},{"claim":"Elements associated with a shorter hospital stay","grade":"Meta-analysis finding cited by the guide, not a graded recommendation","source":"guide-oes-2022","quote":"The presence of the following elements within the ERAS protocol is significantly associated with a reduction in length of stay after oesophagectomy: immediate extubation, mobilisation ≤ 1 day after surgery, removal of urinary catheter ≤ 2 days, commencing oral intake of fluid ≤ 1 day, enteral supplemental feeding ≤ 1 day, removal of epidural ≤ 4 days, and performing a contrast swallow ≤ 5 days."},{"claim":"Nasogastric decompression of the conduit","grade":"Not printed in the summary read","source":"guide-oes-2022","quote":"Nasogastric tube decompression is recommended"},{"claim":"Compliance with oesophagectomy ERAS pathways","grade":"Observational range cited by the guide","source":"guide-oes-2022","quote":"Compliance with ERAS protocols for oesophagectomy patients ranges from 56% to 78%, with up to 20% of patients having a major protocol deviation."}],"sources":[{"key":"eras-oes-2019","label":"Guidelines for Perioperative Care in Esophagectomy: Enhanced Recovery After Surgery (ERAS) Society Recommendations","publisher":"ERAS Society (World Journal of Surgery)","year":2019,"url":"https://doi.org/10.1007/s00268-018-4786-4","doi":"10.1007/s00268-018-4786-4","gradingScheme":"GRADE: quality of evidence and an overall recommendation for each of 39 sections (individual grades not read here).","read":"abstract","accessed":"2026-11-11"},{"key":"guide-oes-2022","label":"Guide to Enhanced Recovery for Cancer Patients Undergoing Surgery: ERAS and Oesophagectomy (Halliday and Moorthy)","publisher":"Annals of Surgical Oncology","year":2022,"url":"https://doi.org/10.1245/s10434-021-10384-5","doi":"10.1245/s10434-021-10384-5","gradingScheme":"Narrative review; its Table 1 summarises the ERAS 2019 oesophagectomy-specific recommendations without their grades.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng83","label":"Oesophago-gastric cancer: assessment and management in adults (NG83), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng83/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-shorter-fasting-before-surgery"],"gaps":["The full text of the ERAS Society esophagectomy guideline (2019) could not be read: it is not open in PubMed Central, and the publisher and the ERAS Society site refused a script. The grade of each item is therefore not given here; the items come from an open summary table, not the guideline's own words.","The ERAS guideline rests on evidence to about 2017. No newer ERAS Society oesophagectomy guideline was found in a Europe PMC search to November 2026, though prehabilitation and minimally invasive surgery evidence has grown since.","The best route for postoperative enteral feeding, and the value of routine cardiopulmonary exercise testing, inspiratory muscle training and pyloroplasty, are not settled (Halliday and Moorthy 2022).","Analgesic and anaesthetic doses and ventilator settings are in the guideline and local protocols and are not reproduced here."]},{"id":"enhanced-recovery-after-pancreatoduodenectomy","kind":"protocol","name":"Enhanced recovery after pancreatoduodenectomy (ERAS pathway for the Whipple operation)","aka":["ERAS Whipple","ERAS pancreatoduodenectomy","ERAS pancreaticoduodenectomy","enhanced recovery pancreatic surgery","fast-track Whipple"],"tldr":"Enhanced recovery is a package of care that helps people recover from the Whipple operation: going straight to surgery rather than having a bile duct stent first where safe, extra nutrition after much weight loss, enzyme capsules, keeping warm, good pain relief, antibiotics and clot prevention, the nose tube out at the end of the operation, removing the drain early when safe, and eating early.","summary":"The ERAS Society pancreatoduodenectomy recommendations (2019, published 2020; 27 items, GRADE, validated by a three-round Delphi) are the current specialty standard; only their abstract could be read. The abstract names the five items with the highest level of evidence: avoiding hypothermia, wound catheters as an alternative to epidural analgesia, antimicrobial prophylaxis, thromboprophylaxis, and preoperative nutritional intervention for severe weight loss (more than 15%). A narrative review (Longo et al. 2024) reports further ERAS items: preoperative biliary drainage is not routinely necessary, but is recommended for high bilirubin (above 15 mg/dl), neoadjuvant chemotherapy or recurrent cholangitis; a drain with early removal within 72 hours where drain amylase on day 1 is below 5000 U/l; the nasogastric tube removed in theatre; somatostatin analogues not routine. NICE NG85 (2018) offers resection rather than preoperative biliary drainage to fit patients with resectable cancer and jaundice, metal stents if drainage is needed, considers pancreatic enzyme replacement before and after resection, and offers early enteral rather than parenteral nutrition after pancreatoduodenectomy. A 2023 meta-analysis (3 randomised trials, 28 cohorts) found ERAS reduced stay, complications, delayed gastric emptying and cost without more readmissions, with better outcomes at higher compliance.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","surgical-site-infection-prevention","enhanced-recovery-after-liver-surgery"],"cancers":["pancreatic"],"sections":[],"technologies":["eras-perioperative-nutrition","prehabilitation","enteral-parenteral-nutrition","self-expanding-metal-stents"],"targets":[],"drugs":["pancrelipase"],"companies":[],"institutions":[],"pathways":[],"terms":["whipple","eating-after-whipple","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you are well enough, you will usually go straight to the operation rather than having a stent put in first. You may be given enzyme capsules to help digest food. After the operation you will be helped to eat early and get up, and tubes will come out as soon as it is safe.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","intensive-care","home"]},"population":"Adults having elective pancreatoduodenectomy (Whipple or pylorus-preserving), most often for pancreatic ductal adenocarcinoma, ampullary, distal bile duct or duodenal cancer, including after neoadjuvant chemotherapy. The ERAS guideline is written for pancreatoduodenectomy, not for other pancreatic resections.","trigger":"A decision to perform pancreatoduodenectomy.","steps":[{"action":"If the cancer is resectable and the person is fit, go to surgery rather than placing a biliary stent first, even with jaundice","why":"Draining the bile duct before surgery adds complications without improving survival, for people who can have the operation promptly.","source":"nice-ng85","quote":"Offer resectional surgery rather than preoperative biliary drainage to people who:","grade":"Not graded (NICE NG85 1.7.1, 'offer')"},{"action":"Where biliary drainage is needed before surgery (not yet fit, very high bilirubin, neoadjuvant chemotherapy, cholangitis), use an endoscopically placed self-expanding metal stent","why":"Some people need the jaundice relieved before surgery is safe.","source":"nice-ng85","quote":"If biliary drainage is needed in a person who has resectable pancreatic cancer and obstructive jaundice and is not yet fit enough for resectional surgery, offer endoscopically placed self‑expanding metal stents.","grade":"Not graded (NICE NG85 1.7.3, 'offer')"},{"action":"Give preoperative nutritional support to people with severe weight loss (more than 15%)","why":"Heavy weight loss is common in pancreatic cancer and raises the risk of complications; feeding beforehand helps.","source":"eras-pd-2019","quote":"The highest level of evidence was available for five items: avoiding hypothermia, use of wound catheters as an alternative to epidural analgesia, antimicrobial and thromboprophylaxis protocols and preoperative nutritional interventions for patients with severe weight loss (> 15%).","grade":"Highest level of evidence in the guideline (grade as printed not read)"},{"action":"Consider pancreatic enzyme replacement (enteric-coated pancreatin) before and after resection","why":"The pancreas makes the enzymes that digest food; after a Whipple, many people need capsules with meals to absorb fat and keep weight on.","source":"nice-ng85","quote":"Consider enteric-coated pancreatin before and after pancreatic cancer resection.","grade":"Not graded (NICE NG85 1.6.2, 'consider')"},{"action":"Allow clear fluids until 2 hours before surgery, and consider a carbohydrate drink","why":"Long fasting leaves people thirsty and weaker; a sugary drink before abdominal surgery is safe.","source":"nice-ng180","quote":"Consider carbohydrate drinks before surgery for people having abdominal major or complex surgery .","grade":"Not graded (NICE NG180 1.4.2, 'consider')"},{"action":"Keep the patient warm, and use antibiotic prophylaxis and thromboprophylaxis protocols","why":"Getting cold raises infection and bleeding risk; antibiotics and clot prevention are among the best-supported elements of the pathway.","source":"eras-pd-2019","quote":"The highest level of evidence was available for five items: avoiding hypothermia, use of wound catheters as an alternative to epidural analgesia, antimicrobial and thromboprophylaxis protocols and preoperative nutritional interventions for patients with severe weight loss (> 15%).","grade":"Highest level of evidence in the guideline (grade as printed not read)"},{"action":"Use multimodal pain relief, with either a thoracic epidural or wound catheters as the alternative to an epidural","why":"Good pain relief lets people breathe, cough and walk; wound catheters avoid some of the low blood pressure an epidural can cause.","source":"eras-pd-2019","quote":"The highest level of evidence was available for five items: avoiding hypothermia, use of wound catheters as an alternative to epidural analgesia, antimicrobial and thromboprophylaxis protocols and preoperative nutritional interventions for patients with severe weight loss (> 15%).","grade":"Highest level of evidence in the guideline (grade as printed not read)"},{"action":"Remove the nasogastric tube in theatre at the end of the operation rather than leaving it in routinely","why":"A nose tube is uncomfortable, and trials found no more complications without one.","source":"longo-2024","quote":"According to ERAS recommendations [ 2 ], the NGT should be removed in the operating room following surgery, and its routine use is not advised.","grade":"As reported by a narrative review; the guideline's grade was not read"},{"action":"Place a drain at operation and remove it early (within 72 hours) in people at low risk of a pancreatic leak, judged by drain amylase below 5000 U/l on day 1","why":"A leak from the pancreas join is the main danger after a Whipple; a drain detects it, and taking it out early when the risk is low avoids drain problems.","source":"longo-2024","quote":"According to ERAS recommendations [ 2 ], intraoperative drain placement with early removal (within 72 h) is advised for patients at low risk of POPF, identified by drainage amylase levels < 5000 U/L on post-operative day 1.","grade":"As reported by a narrative review; the guideline's grade was not read"},{"action":"Start eating or tube feeding early after surgery rather than feeding into a vein","why":"Feeding through the gut is safer than intravenous feeding and helps the bowel recover.","source":"nice-ng85","quote":"For people who have had pancreatoduodenectomy and who have a functioning gut, offer early enteral nutrition (including oral and tube feeding) rather than parenteral nutrition.","grade":"Not graded (NICE NG85 1.6.4, 'offer')"},{"action":"Measure compliance with the pathway and outcomes, and act on them","why":"Units that deliver more of the pathway have shorter stays and fewer complications.","source":"meta-pd-2023","quote":"Higher compliance is associated with better clinical outcomes, especially LOS and complications.","grade":"Systematic review and meta-analysis (3 randomised trials, 28 cohort studies)"}],"bestInClass":{"statement":"The ERAS Society pancreatoduodenectomy recommendations (2019, published 2020) are the current specialty standard, with the highest evidence for avoiding hypothermia, wound catheters as an alternative to epidural, antimicrobial and clot prophylaxis, and nutrition for severe weight loss; only the abstract could be read, so item grades are not given. NICE NG85 (2018) and the ERAS recommendations as reported by Longo et al. agree that preoperative biliary drainage should not be routine for people fit for prompt surgery; they differ in how they define the exceptions (NICE: not yet fit for surgery; ERAS as reported: bilirubin above 15 mg/dl, neoadjuvant chemotherapy or recurrent cholangitis). NICE adds pancreatic enzyme replacement before and after resection and early enteral rather than parenteral feeding.","sources":["eras-pd-2019","nice-ng85","longo-2024","meta-pd-2023"]},"variants":[{"name":"No drain after pancreatoduodenectomy","differs":"Omits the intraperitoneal drain altogether.","evidence":"Longo et al. (2024) report that recent literature does not give clear evidence for a no-drain approach in pancreatic surgery; ERAS, as they report it, advises a drain with early removal in low-risk patients.","sources":["longo-2024"]},{"name":"Prophylactic somatostatin analogues (octreotide, pasireotide)","differs":"Gives a somatostatin analogue around surgery to reduce pancreatic fistula.","evidence":"As reported by Longo et al., ERAS finds moderate evidence that these may reduce fistula severity but does not recommend routine use; NCCN, as they report it, does not recommend routine octreotide.","sources":["longo-2024"]},{"name":"Thoracic epidural as the default analgesia","differs":"Uses a thoracic epidural for every open pancreatoduodenectomy.","evidence":"The ERAS abstract places wound catheters among the highest-evidence items as an alternative to epidural; Longo et al. describe the epidural's benefits as reported by ERAS, and note that TAP block is not currently recommended in pancreatic surgery for lack of studies.","sources":["eras-pd-2019","longo-2024"]}],"grades":[{"claim":"27 ERAS items, GRADE, Delphi-validated","grade":"GRADE; consensus after three Delphi rounds","source":"eras-pd-2019","quote":"Consensus among experts was reached after three rounds."},{"claim":"Preoperative biliary drainage not always necessary, with stated exceptions","grade":"Reported as strong evidence by a narrative review","source":"longo-2024","quote":"According to ERAS recommendations [ 2 ], there is strong evidence that preoperative biliary drainage is not always necessary, as it appears to increase postoperative complications without offering survival benefits."},{"claim":"ERAS versus traditional care in pancreatoduodenectomy","grade":"Systematic review and meta-analysis","source":"meta-pd-2023","quote":"This review demonstrated that ERAS is safe and feasible in pancreaticoduodenectomy, improves clinical outcome such as LOS, complications, DGE and mortality rates, without changing readmissions and reoperations, while delivering significant cost savings."},{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."}],"sources":[{"key":"eras-pd-2019","label":"Guidelines for Perioperative Care for Pancreatoduodenectomy: Enhanced Recovery After Surgery (ERAS) Recommendations 2019 (Melloul et al.)","publisher":"ERAS Society (World Journal of Surgery)","year":2020,"url":"https://doi.org/10.1007/s00268-020-05462-w","doi":"10.1007/s00268-020-05462-w","gradingScheme":"GRADE level of evidence for each of 27 items; recommendations validated by a Delphi process (individual grades not read here).","read":"abstract","accessed":"2026-11-11"},{"key":"longo-2024","label":"Enhanced Recovery After Surgery (ERAS) in Pancreatic Surgery: The Surgeon's Point of View (Longo et al.)","publisher":"Journal of Clinical Medicine","year":2024,"url":"https://doi.org/10.3390/jcm13206205","doi":"10.3390/jcm13206205","gradingScheme":"Narrative review; reports ERAS recommendations in its own words without their grades.","read":"full-text","accessed":"2026-11-11"},{"key":"meta-pd-2023","label":"Costs and clinical benefits of enhanced recovery after surgery (ERAS) in pancreaticoduodenectomy: an updated systematic review and meta-analysis","publisher":"Journal of Cancer Research and Clinical Oncology","year":2023,"url":"https://doi.org/10.1007/s00432-022-04508-x","doi":"10.1007/s00432-022-04508-x","gradingScheme":"Systematic review and meta-analysis of studies 2000 to 2021; no recommendation grades.","read":"abstract","accessed":"2026-11-11"},{"key":"nice-ng85","label":"Pancreatic cancer in adults: diagnosis and management (NG85), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-shorter-fasting-before-surgery"],"gaps":["The full text of the ERAS Society pancreatoduodenectomy recommendations (2019) could not be read: it is not open in PubMed Central, and the publisher and the ERAS Society site refused a script. Item grades are therefore not given, and the drain, nasogastric tube, biliary drainage and somatostatin items are taken from a narrative review's report of them, not the guideline's words.","The evidence behind most items is from cohort studies; the meta-analysis found only 3 randomised trials of the pathway as a whole.","Whether to drain at all, and whether somatostatin analogues help, remain unsettled.","NICE NG85 notes that supplies of pancreatic enzyme replacement were disrupted from September 2024; availability varies.","Doses (enzymes, analgesia, thromboprophylaxis) are in the guidelines, product information and local protocols and are not reproduced here."]},{"id":"enhanced-recovery-after-radical-cystectomy","kind":"protocol","name":"Enhanced recovery after radical cystectomy (ERAS pathway for bladder removal)","aka":["ERAS cystectomy","enhanced recovery bladder cancer surgery","fast-track cystectomy","perioperative care for radical cystectomy"],"tldr":"Enhanced recovery after bladder removal means getting fitter beforehand, no bowel preparation and no long fast, pain relief that spares opioids, the stomach tube out at the end of the operation, and four weeks of blood clot injections, in a hospital that does at least 20 of these operations a year.","summary":"The EAU 2026 bladder cancer guideline gives four strong recommendations around cystectomy: do not offer preoperative bowel preparation; use 'fast track' measures to shorten bowel recovery; offer pharmacological VTE prophylaxis such as LMWH from the first day after surgery for at least four weeks; and do at least 20 cystectomies per hospital per year. Its text adds that there is no universal ERAS protocol for cystectomy, that prehabilitation may help but lacks randomised trials, and that ERAS reduced ileus from 22% to 7.3% at the cost of somewhat more pain. The ERAS Society guideline (2013) found evidence for only 7 of 22 items (no bowel preparation, early nasogastric tube removal, Doppler-guided fluids and multimodal ileus prevention); its 2025 surgeons' update by e-Delphi highly recommends medical optimisation and no bowel preparation, moderately recommends robotic cystectomy with intracorporeal diversion, and supports medical thromboprophylaxis, removing the nasogastric tube at the end of surgery, fluid restriction and opioid-sparing anaesthesia, with no consensus on epidurals and consensus against resection-site drains.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery","surgical-site-infection-prevention","routine-preoperative-tests","enhanced-recovery-after-colorectal-surgery"],"cancers":["urothelial","muscle-invasive-bladder-cancer"],"sections":[],"technologies":["eras-perioperative-nutrition","prehabilitation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cystectomy","prehabilitation-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before bladder removal you will not need a bowel clear-out or a long fast. Afterwards the stomach tube is taken out early, you will be helped to eat and move, and you will have injections for four weeks to prevent clots.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","home"]},"population":"Adults having radical cystectomy with urinary diversion (ileal conduit or neobladder) for bladder cancer, open or robotic.","trigger":"A decision to remove the bladder.","steps":[{"action":"Have cystectomy done in a hospital that performs at least 20 a year","why":"Concentrating these operations in fewer, busier centres has lowered deaths and repeat operations.","source":"eau-mibc-2026","quote":"Perform at least 20 radical cystectomies (RCs) per hospital/per year.","grade":"Strength rating: Strong"},{"action":"Offer prehabilitation (exercise, nutrition, stopping smoking) and optimise medical conditions before surgery","why":"Better fitness and health before the operation may reduce complications, though trials are missing.","source":"eau-mibc-2026","quote":"Similar to other tumour types, such as colorectal cancer, a multimodal prehabilitation programme (i.e. physiotherapy, nutritional intervention, cessation of smoking) may improve patient health status before surgery and reduce subsequent postoperative complications [367]. However, evidence is limited and RCTs are missing.","grade":"Not a graded recommendation (EAU text)"},{"action":"Do not give bowel preparation before cystectomy","why":"Bowel preparation did not improve outcomes and causes dehydration and discomfort.","source":"eau-mibc-2026","quote":"Do not offer preoperative bowel preparation.","grade":"Strength rating: Strong"},{"action":"Use fast-track (ERAS) measures to speed bowel recovery: no long fast, carbohydrate loading where used, opioid-sparing pain relief and early mobilisation","why":"In the study the guideline cites, ERAS cut bowel paralysis after surgery from 22% to 7.3%, though people reported a little more pain.","source":"eau-mibc-2026","quote":"Employ ‘fast track’ measurements to reduce the time to bowel recovery.","grade":"Strength rating: Strong"},{"action":"Remove the nasogastric tube at the end of surgery","why":"Early removal reduced complications, time to bowel recovery and hospital stay.","source":"eras-cystectomy-update-2025","quote":"Medical thromboprophylaxis should be administered and nasogastric tube should be removed at the end of surgery.","grade":"Recommended by e-Delphi consensus (abstract; item grades not read)"},{"action":"Restrict fluids around surgery and use opioid-sparing anaesthesia","why":"Too much fluid slows the bowel; fewer opioids mean less sickness and ileus.","source":"eras-cystectomy-update-2025","quote":"Perioperative fluid restriction as well as opioid-sparing anesthesia protocols should be implemented.","grade":"Recommended by e-Delphi consensus (abstract; item grades not read)"},{"action":"Give LMWH from the first day after surgery for at least four weeks","why":"Clots are common after cystectomy, especially after chemotherapy beforehand, and four weeks of injections lowered them.","source":"eau-mibc-2026","quote":"Offer pharmacological venous thromboembolism prophylaxis, such as low-molecular-weight heparin, to RC patients, starting the first day post-surgery for a period of at least four weeks.","grade":"Strength rating: Strong"}],"bestInClass":{"statement":"The EAU 2026 guideline is the most recent graded source and was read in full: no bowel preparation, fast-track measures, four weeks of LMWH and a minimum hospital volume are all strong recommendations. The ERAS Society's own cystectomy guideline is from 2013 and found evidence for few items; the 2025 surgeons' e-Delphi update agrees with EAU on bowel preparation and thromboprophylaxis and adds early nasogastric tube removal, fluid restriction and opioid-sparing anaesthesia. NICE NG180 supports an enhanced recovery programme for elective major surgery.","sources":["eau-mibc-2026","eras-cystectomy-update-2025","eras-cystectomy-2013","nice-ng180"]},"variants":[{"name":"Robot-assisted cystectomy with intracorporeal urinary diversion","differs":"Does the whole operation, including the urinary diversion, robotically inside the abdomen.","evidence":"Moderately recommended by the 2025 surgeons' e-Delphi, which says it can help apply other ERAS items such as early mobilisation; the EAU text reports a 2023 meta-analysis of eight RCTs comparing open and robotic cystectomy.","sources":["eras-cystectomy-update-2025","eau-mibc-2026"]},{"name":"Epidural analgesia and resection-site drains","differs":"Uses an epidural for pain relief and leaves a drain at the operation site.","evidence":"The 2025 e-Delphi reached no consensus on epidurals and a consensus against resection-site drainage.","sources":["eras-cystectomy-update-2025"]},{"name":"ERAS before cystectomy (Hong Kong)","differs":"Recommends that ERAS be considered before cystectomy, to reduce ileus and VTE.","evidence":"Consensus statement 6 of the Hong Kong urological societies (2025), citing retrospective studies.","sources":["hk-mibc-2025"]}],"grades":[{"claim":"Offer an enhanced recovery programme for elective major or complex surgery","grade":"Not graded (NICE NG180 1.2.1)","source":"nice-ng180","quote":"Offer an enhanced recovery programme to people having elective major or complex surgery ."},{"claim":"No universal ERAS protocol for cystectomy","grade":"Not a graded recommendation (EAU text)","source":"eau-mibc-2026","quote":"While there is no universal ERAS protocol for RC, preoperative recommendations include no bowel preparation or fasting, and may also include same-day admission, carbohydrate loading and a preoperative exercise programme."},{"claim":"Evidence base of the 2013 ERAS cystectomy guideline","grade":"GRADE; 7 of 22 items studied in cystectomy","source":"eras-cystectomy-2013","quote":"Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied."},{"claim":"Medical optimisation and no bowel preparation","grade":"'Highly recommended' (e-Delphi, abstract)","source":"eras-cystectomy-update-2025","quote":"Preoperative medical optimization and avoiding bowel preparation are highly recommended."},{"claim":"ERAS considered before cystectomy","grade":"Consensus statement (Hong Kong)","source":"hk-mibc-2025","quote":"Statement 6: Before undergoing RC, the Enhanced Recovery After Surgery (ERAS) approach should be considered to reduce the risks of post-operative ileus and venous thromboembolism."}],"sources":[{"key":"eau-mibc-2026","label":"EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer, 2026 edition","publisher":"European Association of Urology","year":2026,"url":"https://uroweb.org/guidelines/muscle-invasive-and-metastatic-bladder-cancer","gradingScheme":"Level of evidence (1a to 4) for summaries of evidence, and a strength rating (strong or weak) for each recommendation, printed beside it.","read":"full-text","accessed":"2026-11-11"},{"key":"eras-cystectomy-2013","label":"Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced Recovery After Surgery (ERAS) society recommendations","publisher":"ERAS Society (Clinical Nutrition)","year":2013,"url":"https://doi.org/10.1016/j.clnu.2013.09.014","doi":"10.1016/j.clnu.2013.09.014","gradingScheme":"GRADE, with consensus where cystectomy evidence was lacking; item grades not in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"eras-cystectomy-update-2025","label":"Enhanced Recovery After Surgery for patients undergoing radical cystectomy: Surgeons' perspectives and recommendations ten years after its implementation","publisher":"European Journal of Surgical Oncology","year":2025,"url":"https://doi.org/10.1016/j.ejso.2024.109543","doi":"10.1016/j.ejso.2024.109543","gradingScheme":"Level of evidence per item from a systematic review, then e-Delphi expert consensus; the abstract gives only the direction and strength in words.","read":"abstract","accessed":"2026-11-11"},{"key":"hk-mibc-2025","label":"Consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology on the management of muscle-invasive bladder cancer","publisher":"Hong Kong Urological Association and Hong Kong Society of Uro-Oncology (Frontiers in Oncology)","year":2025,"url":"https://doi.org/10.3389/fonc.2025.1564487","doi":"10.3389/fonc.2025.1564487","gradingScheme":"Consensus statements, not graded by evidence level.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng180","label":"Perioperative care in adults (NG180), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng180/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider') signals strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-enhanced-recovery-with-measured-compliance","idea-pu-extended-clot-prevention-after-surgery"],"gaps":["The ERAS Society cystectomy guideline (2013) and its 2025 surgeons' update could be read only as abstracts; the item-by-item levels of evidence are not on this page.","The ERAS Society guideline is more than ten years old and found cystectomy-specific evidence for only 7 of its 22 items; much of the pathway is extrapolated from colorectal surgery.","The EAU text says prehabilitation for cystectomy lacks randomised trials, and that people on ERAS reported more pain (VAS 3.1 against 1.1) while ileus fell.","Stoma care for an ileal conduit, and catheter and neobladder care at home, are not covered here."]},{"id":"exercise-during-and-after-cancer-treatment","kind":"protocol","name":"Exercise during and after cancer treatment: assessment, dose and referral","aka":["exercise prescription in cancer","physical activity after cancer","exercise oncology","structured exercise after colon cancer","CHALLENGE exercise programme","avoid inactivity"],"tldr":"Exercise is safe for most people during and after cancer treatment and helps with tiredness, fitness, strength and mood. The usual aim is to build up to about 30 minutes of moderate activity such as brisk walking three times a week, plus strength exercise twice a week, starting low. Some people should be checked first, for example with cancer in the bones, heart or lung disease, or nerve damage.","summary":"ASCO (2022) recommends that oncology providers recommend regular aerobic and resistance exercise during active treatment with curative intent, and says preoperative exercise may be recommended before lung cancer surgery. The ACSM roundtable (2019) concluded that exercise testing and training are generally safe, that every survivor should avoid inactivity, and that moderate aerobic training at least three times a week for at least 30 minutes, for 8 to 12 weeks, with or without resistance training twice a week, improves anxiety, depression, fatigue, physical function and quality of life. It adapts the NCCN triage: no further evaluation for people without comorbidities; a pre-exercise medical evaluation for neuropathy, musculoskeletal problems, poor bone health or lymphoedema; and evaluation, clearance and referral to trained staff for bone metastases, recent lung or abdominal surgery, an ostomy, cardiopulmonary disease, ataxia, extreme fatigue or severe malnutrition. COSA (2018) calls for referral to an accredited exercise physiologist or physiotherapist as best practice.\n\nThe CHALLENGE trial (2025) is the first phase 3 evidence of a survival effect: a three-year structured programme started after adjuvant chemotherapy for colon cancer lengthened disease-free survival (5-year 80.3 against 73.9 per cent, hazard ratio 0.72), with findings consistent with longer overall survival. The ESMO Express Update (2026) now says patients with resected stage III or high-risk stage II colon cancer should be told of this evidence and of their eligibility [I, A], and that participation can be recommended after shared decision-making [II, B; ESMO-MCBS A].","asOf":"2026-11-11","links":[],"tags":["protocol","exercise","survivorship","supportive-care"],"related":["cancer-related-fatigue-screening-and-management","lymphoedema-risk-reduction-surveillance-and-treatment"],"cancers":["colon-cancer"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["exercise-oncology","exercise-during-chemotherapy","structured-exercise-survivorship","exercise-prescription-after-cancer"],"targets":[],"drugs":[],"companies":[],"institutions":["asco","esmo"],"pathways":[],"terms":["cancer-related-fatigue","bone-metastases"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-challenge-exercise-nejm-2025"],"journals":[],"dependsOn":[],"notes":[],"simple":"Moving your body is good during and after cancer treatment. Start slowly. Ask your team if you need a check first.","domain":"survivorship","setting":{"who":["doctor","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","community","home"]},"population":"Adults during curative-intent treatment and after treatment (ASCO 2022; ACSM 2019; COSA 2018). The colon cancer recommendation applies to people with resected stage III or high-risk stage II colon cancer who have finished adjuvant chemotherapy (ESMO 2026, CHALLENGE). Evidence in advanced cancer is thinner: ASCO-SIO 2024 found it insufficient to recommend exercise for fatigue in advanced cancer or at the end of life. Children have their own ACSM consensus (2026), not read here.","trigger":"A cancer diagnosis; the start of treatment; the end of treatment; and at follow-up.","steps":[{"action":"Recommend regular aerobic and resistance exercise to everyone on curative-intent treatment, and tell every survivor to avoid inactivity","why":"Exercise during treatment improves fitness, strength and tiredness, and being inactive makes recovery slower.","source":"asco-2022","quote":"Oncology providers should recommend regular aerobic and resistance exercise during active treatment with curative intent and may recommend preoperative exercise for patients undergoing surgery for lung cancer."},{"action":"Triage before starting: no extra evaluation for people without comorbidities; a medical evaluation first for neuropathy, musculoskeletal problems, poor bone health or lymphoedema","why":"Most people can simply start; some side effects need the programme adjusting to avoid falls or injury.","source":"acsm-2019","quote":"No comorbidities No further pre-exercise medical evaluation * Follow general exercise recommendations Peripheral neuropathy, arthritis/musculoskeletal issues, poor bone health (e.g., osteopenia or osteoporosis), lymphedema Recommend pre-exercise medical evaluation * Modify general exercise recommendations based on assessments Consider referral to trained personnel"},{"action":"Require medical clearance and refer to trained staff before exercise for bone metastases, recent lung or abdominal surgery, an ostomy, heart or lung disease, ataxia, extreme fatigue, severe malnutrition or a worsening condition","why":"These carry a higher risk of harm during exercise, such as fracture or a heart problem, and need a supervised programme.","source":"acsm-2019","quote":"Lung or abdominal surgery, ostomy, cardiopulmonary disease, ataxia, extreme fatigue, severe nutritional deficiencies, worsening/changing physical condition (i.e., lymphedema exacerbation), bone metastases Pre-exercise medical evaluation * and clearance by physician prior to exercise Referral to trained personnel"},{"action":"Do not make a fitness test a condition of starting low-intensity walking, cycling, gradual resistance training or stretching","why":"Requiring tests first puts people off; most can start gentle exercise safely without them.","source":"acsm-2019","quote":"For this reason, no assessments are required to start low intensity aerobic training (i.e., walking or cycling), resistance training with gradual progression, or a flexibility program in most survivors."},{"action":"Prescribe moderate aerobic exercise at least three times a week for at least 30 minutes, for 8 to 12 weeks or more, with resistance training at least twice a week if possible","why":"This is the dose that most consistently improved tiredness, mood, physical function and quality of life in trials.","source":"acsm-2019","quote":"Based on the current literature, an effective exercise prescription that most consistently addresses health-related outcomes experienced due to a cancer diagnosis and cancer treatment includes moderate intensity aerobic training at least 3 times per week, for at least 30 minutes, for at least 8–12 weeks. The addition of resistance training to aerobic training, at least 2 times per week, using at least 2 sets of 8–15 repetitions at least 60% of one repetition maximum, appears to results in similar benefits"},{"action":"With bone metastases or bone loss, avoid high-impact loads, loaded or extreme bending of the spine and twisting movements","why":"Weakened bone can break under heavy or sudden loads.","source":"acsm-2019","quote":"Avoid contraindicated movements that place an excessively high load on fragile skeletal sites. These include the following: high-impact loads, hyperflexion or hyperextension of the trunk, flexion or extension of the trunk with added resistance, and dynamic twisting motion"},{"action":"Refer to an exercise professional with cancer experience (an accredited exercise physiologist or physiotherapist) where one is available","why":"A trained professional can tailor the programme to the person's treatment and side effects and keep it safe.","source":"cosa-2018","quote":"best practice cancer care to include referral to an accredited exercise physiologist or physiotherapist with experience in cancer care."},{"action":"After surgery and adjuvant chemotherapy for stage III or high-risk stage II colon cancer, tell the person about the survival evidence for a structured exercise programme and their eligibility, and agree whether to join one","why":"In a large randomised trial a coached three-year programme lowered the chance of the cancer coming back or of dying.","source":"esmo-colon-2026","quote":"Patients with resected stage III or high-risk stage II colon cancer should be informed of the available evidence suggesting survival benefits from a structured exercise programme [I, A].","grade":"[I, A]"}],"bestInClass":{"statement":"For everyone during curative treatment, ASCO 2022 (recommend aerobic and resistance exercise) and the ACSM 2019 roundtable (dose, triage, avoid inactivity) agree; COSA 2018 goes further in calling referral to an accredited exercise professional best practice. After colon cancer, ESMO's 2026 Express Update is the strongest graded recommendation read, resting on the CHALLENGE trial: inform eligible patients [I, A] and recommend a structured programme after shared decision-making [II, B; MCBS A]. No guideline read yet extends the survival claim to other cancers.","sources":["asco-2022","acsm-2019","cosa-2018","esmo-colon-2026","challenge-2025"]},"variants":[{"name":"CHALLENGE structured programme after colon cancer","differs":"Three years of behavioural support and supervised exercise, aiming for an increase of at least 10 MET-hours a week in recreational aerobic activity (about 150 minutes of moderate activity), starting soon after adjuvant chemotherapy.","evidence":"Phase 3 trial of 889 patients: disease-free survival hazard ratio 0.72 (95 per cent confidence interval 0.55 to 0.94); hazard ratio for death 0.63; musculoskeletal adverse events 18.5 against 11.5 per cent. ESMO 2026 notes adherence to supervised sessions fell from 79 per cent in months 1 to 6 to 44 per cent in months 13 to 36.","sources":["challenge-2025","esmo-colon-2026"]},{"name":"Preoperative exercise before lung cancer surgery","differs":"Exercise before an operation rather than during or after treatment.","evidence":"ASCO 2022: may be recommended, because it reduced postoperative length of stay and complications in patients with lung cancer.","sources":["asco-2022"]},{"name":"Older adults (over 65)","differs":"A consensus panel set 11 good-practice recommendations for older survivors on medical clearance, pre-exercise assessment, prescription, tolerance and safety, delivery and behavioural support, aiming to keep barriers low.","evidence":"Consensus (GRADE evidence-to-decision framework for good practice statements, 85 per cent agreement threshold), not graded evidence.","sources":["older-adults-2026"]}],"grades":[{"claim":"Participation in a structured exercise programme after colon cancer","grade":"[II, B; ESMO-MCBS v2.0 score: A]","source":"esmo-colon-2026","quote":"After discussion and joint decision making on exercise intensity and implementability, participation of eligible patients in a structured exercise programme can be recommended [II, B; ESMO-Magnitude of Clinical Benefit Scale (MCBS) v2.0 score: A]."},{"claim":"Exercise reduces fatigue during treatment","grade":"Moderate; Strong","source":"asco-sio-2024","quote":"1.1. Clinicians should recommend exercise (aerobic, resistance, or a combination) to reduce the severity of fatigue during cancer treatment."},{"claim":"Disease-free survival with structured exercise after colon cancer","grade":"phase 3 randomised trial, P = 0.02","source":"challenge-2025","quote":"At a median follow-up of 7.9 years, disease-free survival was significantly longer in the exercise group than in the health-education group (hazard ratio for disease recurrence, new primary cancer, or death, 0.72; 95% confidence interval [CI], 0.55 to 0.94; P = 0.02)."}],"sources":[{"key":"asco-2022","label":"Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/35576506","doi":"10.1200/JCO.22.00687","read":"abstract","accessed":"2026-11-11"},{"key":"acsm-2019","label":"Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable","publisher":"American College of Sports Medicine, Medicine and Science in Sports and Exercise","year":2019,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8576825/","doi":"10.1249/MSS.0000000000002116","gradingScheme":"Evidence rated as strong, moderate or insufficient for each outcome; prescriptions are not graded individually.","read":"full-text","accessed":"2026-11-11"},{"key":"cosa-2018","label":"Clinical Oncology Society of Australia position statement on exercise in cancer care","publisher":"COSA, Medical Journal of Australia","year":2018,"url":"https://europepmc.org/abstract/MED/29719196","doi":"10.5694/mja18.00199","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-colon-2026","label":"ESMO Clinical Practice Guideline Express Update on the adoption of physical exercise in patients with localised colon cancer","publisher":"ESMO, ESMO Open","year":2026,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12947638/","doi":"10.1016/j.esmoop.2025.106019","gradingScheme":"ESMO levels of evidence I to V and grades of recommendation A to E, with ESMO-MCBS v2.0 scores.","read":"full-text","accessed":"2026-11-11"},{"key":"challenge-2025","label":"Structured Exercise after Adjuvant Chemotherapy for Colon Cancer (CHALLENGE)","publisher":"New England Journal of Medicine","year":2025,"url":"https://europepmc.org/abstract/MED/40450658","doi":"10.1056/NEJMoa2502760","read":"abstract","accessed":"2026-11-11"},{"key":"asco-sio-2024","label":"Management of Fatigue in Adult Survivors of Cancer: ASCO-Society for Integrative Oncology Guideline Update","publisher":"ASCO and SIO, Journal of Clinical Oncology","year":2024,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12082589/","doi":"10.1200/JCO.24.00541","gradingScheme":"Evidence quality high to insufficient; recommendation strong or conditional.","read":"full-text","accessed":"2026-11-11"},{"key":"older-adults-2026","label":"Exercise recommendations for older adults living with and beyond cancer: a consensus statement","publisher":"Cancer","year":2026,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12778376/","doi":"10.1002/cncr.70252","gradingScheme":"Good practice statements; consensus at 85 per cent agreement.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-crc-exercise-as-a-funded-treatment","idea-bio2-prehabilitation-standard"],"gaps":["The ASCO 2022 guideline was read only as an abstract; its strength and evidence ratings, and its special considerations for advanced cancer, are not given here.","COSA 2018 was read only as an abstract; whether COSA has updated its statement since was not established.","The CHALLENGE result is for colon cancer after adjuvant chemotherapy; whether a structured programme improves survival after other cancers has not been shown in a phase 3 trial.","No UK national guideline on exercise in cancer was read; NICE has no dedicated guideline on it.","The ACSM 2026 consensus on exercise for children and adolescents with cancer was found but not read (title and abstract only in Europe PMC)."]},{"id":"eye-care-with-ocular-toxic-antibody-drug-conjugates","kind":"protocol","name":"Eye care with antibody-drug conjugates that harm the cornea: belantamab, mirvetuximab, tisotumab and enfortumab","aka":["ADC eye care","ADC ocular toxicity","Blenrep eye exams","Blenrep REMS","Elahere eye drops","Tivdak eye drops and cold packs","keratopathy with antibody-drug conjugates","corneal toxicity with ADCs"],"tldr":"Some antibody-drug conjugates damage the front surface of the eye (the cornea), causing dry, gritty or painful eyes and blurred vision. With belantamab, mirvetuximab and tisotumab, an eye specialist examines you before and during treatment, you use eye drops on a schedule, and no contact lenses. Report any change in your sight at once: the dose can be paused or lowered, and most problems improve.","summary":"Four antibody-drug conjugates have ocular warnings in their US labels. Belantamab mafodotin (BLENREP) has a boxed warning and is available only through a REMS: an eye care professional performs a slit lamp examination and best-corrected visual acuity (BCVA) at baseline (within 4 weeks before the first dose) and before every dose (within 10 days), patients use preservative-free artificial tears at least four times a day, and avoid contact lenses; doses are held and reduced by a grade built from corneal findings and loss of Snellen lines. In DREAMM-7, ocular toxicity occurred in 92 per cent and 83 per cent needed a dose modification for it. Mirvetuximab soravtansine (ELAHERE) has a boxed warning: examination with visual acuity and slit lamp before starting, every other cycle for the first 8 cycles and as indicated; corticosteroid eye drops six times daily from the day before each infusion to day 4, then four times daily on days 5 to 8; lubricating drops at least four times daily. Tisotumab vedotin (TIVDAK) has a boxed warning: examination before every cycle for the first nine cycles; a steroid drop before each infusion and three times daily for 72 hours after; a vasoconstrictor drop immediately before each infusion; cold packs over the eyes throughout the infusion; lubricating drops for the whole of treatment and 30 days after. Enfortumab vedotin (PADCEV) has no box: monitor, consider artificial tears for prophylaxis, and an eye examination if symptoms occur.\n\nWhere sources differ: the US BLENREP label permanently stops the drug after a recurrent grade 4 finding, while a 2025 Latin American expert panel (haematologists and ophthalmologists) held that no ocular event mandates permanent discontinuation and that dose decisions should give priority to myeloma control. The labels for mirvetuximab and tisotumab require steroid drops; the BLENREP label does not instruct them, and the panel leaves them to the ophthalmologist.","asOf":"2026-11-11","links":[],"tags":["protocol","ocular-toxicity","antibody-drug-conjugate","supportive-care"],"related":[],"cancers":["multiple-myeloma","myeloma-relapsed-refractory","platinum-resistant-ovarian-cancer","recurrent-metastatic-cervical-cancer","urothelial"],"sections":["adcs","supportive-care"],"technologies":["adc"],"targets":[],"drugs":["belantamab-mafodotin","mirvetuximab-soravtansine","tisotumab-vedotin","enfortumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["ocular-toxicity","adc-side-effects-breast"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer drugs can hurt the front of the eye. An eye doctor checks your eyes often. Use the eye drops you are given, do not wear contact lenses, and tell your team about any eye change.","domain":"supportive-care","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["chemotherapy-day-unit","outpatient-clinic","home"]},"population":"Adults receiving belantamab mafodotin (multiple myeloma), mirvetuximab soravtansine (folate receptor alpha positive platinum-resistant ovarian cancer), tisotumab vedotin (recurrent or metastatic cervical cancer) or enfortumab vedotin (urothelial cancer). The steps are each drug's US label; other countries' summaries of product characteristics may differ and were not read. Other ADCs with eye effects in their labels are not covered here.","trigger":"One of these drugs is planned, and before each dose while it continues.","steps":[{"action":"Belantamab: arrange an eye examination by an ophthalmologist or optometrist, with slit lamp and best-corrected visual acuity, within 4 weeks before the first dose and within 10 days before every later dose","why":"Corneal changes are found on examination before the person notices them, and they decide whether the next dose is given in full, reduced or held.","source":"blenrep-label","quote":"Perform baseline exam within 4 weeks prior to the first dose. Perform each follow-up exam within 10 days prior to the next planned dose.","grade":"US prescribing information (boxed warning)"},{"action":"Belantamab: prescribe only within the BLENREP REMS, and give the person the REMS Patient Guide","why":"In the US the drug can only be prescribed, dispensed and given by certified prescribers and settings, so that every person is counselled and monitored.","source":"blenrep-label","quote":"Prescribers must counsel patients receiving BLENREP on the risk of ocular toxicity, the need for monitoring via ophthalmic exams before each dose, and provide patients with the BLENREP REMS Patient Guide.","grade":"US prescribing information (REMS)"},{"action":"Belantamab: advise preservative-free artificial tears at least four times a day from the first infusion to the end of treatment, and no contact lenses","why":"Lubricating the eye eases dryness and grittiness; contact lenses can worsen damage to the corneal surface.","source":"blenrep-label","quote":"Counsel patients to use preservative‑free artificial tears at least 4 times a day starting with the first infusion and continuing until the end of treatment, and to avoid wearing contact lenses for the duration of therapy.","grade":"US prescribing information"},{"action":"Belantamab: for grade 2 or 3 findings, hold the drug until both the cornea and the visual acuity are back to grade 1 or less, then restart at a reduced dose; do not raise the dose again","why":"Holding the drug lets the cornea recover; most changes resolve, and a lower dose lowers the chance they return.","source":"blenrep-label","quote":"Withhold BLENREP until improvement in both corneal exam findings and change in BCVA to Grade 1 or less. Resume treatment at Reduced Dosage Level 1 as per Table 1 . If recurrent Grade 2 or 3 ocular toxicity is experienced, resume treatment at Reduced Dosage Level 2.","grade":"US prescribing information (Table 2)"},{"action":"Belantamab: warn the person to take care driving or operating machinery while their sight is affected","why":"Blurred vision can make driving and reading unsafe.","source":"blenrep-label","quote":"Changes in visual acuity may be associated with difficulty for driving and reading. Counsel patients to use caution when driving or operating machinery.","grade":"US prescribing information"},{"action":"Mirvetuximab: arrange an eye examination with visual acuity and slit lamp before starting, every other cycle for the first 8 cycles, and whenever symptoms appear","why":"Eye problems usually start in the first weeks; regular checks find them early.","source":"elahere-label","quote":"Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated.","grade":"US prescribing information (boxed warning)"},{"action":"Mirvetuximab: prescribe corticosteroid eye drops after a slit lamp examination, one drop in each eye six times a day from the day before each infusion to day 4, then four times a day on days 5 to 8","why":"Steroid drops given around each infusion are meant to reduce inflammation of the cornea; the label asks for a slit lamp check first because steroid drops can mask infection or raise eye pressure.","source":"elahere-label","quote":"Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle of ELAHERE","grade":"US prescribing information"},{"action":"Mirvetuximab: advise lubricating eye drops at least four times a day, at least 10 minutes after the steroid drops, and no contact lenses unless the team advises otherwise","why":"Lubricant drops ease dryness; leaving a gap stops them washing the steroid drop out.","source":"elahere-label","quote":"Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops","grade":"US prescribing information"},{"action":"Tisotumab: arrange an eye examination before every cycle for the first nine cycles, including visual acuity, slit lamp of the front of the eye and eye movement","why":"Conjunctivitis and corneal damage are common with this drug, and can lead to ulcers if missed.","source":"tivdak-label","quote":"Conduct an ophthalmic exam prior to initiation of TIVDAK, prior to every cycle for the first nine cycles, and as clinically indicated. The ophthalmic exam should include visual acuity, slit lamp exam of the anterior segment of the eye, and an assessment of normal eye movement.","grade":"US prescribing information (boxed warning)"},{"action":"Tisotumab: give a steroid drop in each eye before each infusion and three times a day for 72 hours after, and a vasoconstrictor drop in each eye immediately before the infusion","why":"The steroid calms inflammation; the vasoconstrictor narrows the small vessels of the eye surface so that less drug reaches it during the drip.","source":"tivdak-label","quote":"Instruct patients to administer one drop in each eye prior to each infusion and to continue to administer eye drops in each eye three times daily for 72 hours after each infusion.","grade":"US prescribing information"},{"action":"Tisotumab: put cold packs fully over the eyes after the vasoconstrictor drops and keep the eye area cold for the whole infusion","why":"Cooling also narrows the vessels, again reducing how much drug reaches the eye surface.","source":"tivdak-label","quote":"Apply cold packs fully over the eyes following administration of the vasoconstrictor eye drops. Change cold packs as needed throughout infusion to ensure eye area remains cold during the entire infusion","grade":"US prescribing information"},{"action":"Tisotumab: advise lubricating drops for the whole of treatment and for 30 days after the last dose, no contact lenses, and to bring all eye drops to each infusion","why":"Eye problems can appear after treatment stops; in the main trial some began more than 30 days after the last dose.","source":"tivdak-label","quote":"Topical lubricating eye drops: Instruct patients to administer for the duration of therapy and for 30 days after the last dose of TIVDAK.","grade":"US prescribing information"},{"action":"Tisotumab: stop the drug permanently for ulcerative keratitis, perforation or any conjunctival or corneal scarring","why":"These are signs of damage that could threaten sight if treatment continued.","source":"tivdak-label","quote":"Ulcerative keratitis or perforation","grade":"US prescribing information (Table 2)"},{"action":"Enfortumab: watch for eye symptoms, consider artificial tears to prevent dry eye, and refer for an eye examination if symptoms occur or persist","why":"Dry eye affects about a third of people on enfortumab; it is usually milder than with the other three drugs.","source":"padcev-label","quote":"Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve.","grade":"US prescribing information (warning, not boxed)"}],"bestInClass":{"statement":"For each drug, the current US prescribing information is the governing protocol: no international guideline on ADC eye care was found. All four share regular examination by an eye care professional, lubricating drops and avoiding contact lenses; they differ in the frequency of examination (every dose for belantamab; every other cycle for 8 cycles for mirvetuximab; every cycle for 9 cycles for tisotumab; on symptoms for enfortumab) and in prophylaxis (steroid drops for mirvetuximab and tisotumab, plus a vasoconstrictor and cold packs for tisotumab; lubricants alone for belantamab). On belantamab, the US label and the 2025 Latin American expert panel disagree on stopping: the label stops the drug after a recurrent grade 4 finding; the panel says no ocular event requires permanent discontinuation, and that dose decisions should give priority to myeloma control and be shared between haematologist and ophthalmologist.","sources":["blenrep-label","elahere-label","tivdak-label","padcev-label","belamaf-latam-2025"]},"variants":[{"name":"Latin American expert panel approach to belantamab eye events (2025)","differs":"Examination before each dose, or monthly, for the first 3 months and then as the ophthalmologist decides, rather than before every dose throughout; a simpler mild, moderate and severe grading by ophthalmologists in place of the trial grading scale; topical antibiotics and steroids at the ophthalmologist's discretion; and no ocular event that by itself mandates stopping treatment.","evidence":"Consensus of 13 haematologists, oncologists and ophthalmologists from Argentina, Brazil, Colombia and Mexico, built on discussion, the DREAMM trials and experience; recommendations are not graded. It is written for settings where the drug may be approved and specialist access is uneven.","sources":["belamaf-latam-2025"]}],"grades":[{"claim":"Belantamab: ocular toxicity in 92 per cent in DREAMM-7, grade 3 or 4 in 77 per cent","grade":"US prescribing information, trial data","source":"blenrep-label","quote":"In DREAMM-7, ocular toxicity occurred in 92% of patients, including Grade 3 or 4 in 77% of patients."},{"claim":"Mirvetuximab: ocular adverse reactions in 59 per cent of people with ovarian cancer","grade":"US prescribing information, pooled trial data","source":"elahere-label","quote":"Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE."},{"claim":"Tisotumab: ocular adverse reactions in 55 per cent of people with cervical cancer","grade":"US prescribing information, pooled trial data","source":"tivdak-label","quote":"Ocular adverse reactions occurred in 55% of patients with cervical cancer treated with TIVDAK across clinical trials."},{"claim":"Belantamab: no ocular event indicates permanent discontinuation (panel view, differs from the US label)","grade":"expert panel consensus, ungraded","source":"belamaf-latam-2025","quote":"No ocular events indicate permanent discontinuation of belantamab mafodotin treatment."}],"sources":[{"key":"blenrep-label","label":"BLENREP (belantamab mafodotin) prescribing information, including boxed warning and REMS","publisher":"GlaxoSmithKline, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aef7c34c-fef8-407c-99c0-a68aded53c60","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"elahere-label","label":"ELAHERE (mirvetuximab soravtansine) prescribing information, including boxed warning","publisher":"ImmunoGen, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00c424b5-6ccd-48ab-9e88-1986451120e2","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"tivdak-label","label":"TIVDAK (tisotumab vedotin) prescribing information, including boxed warning","publisher":"Seagen, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9fe3f32-4219-466e-acb9-3f609b4f4df1","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"padcev-label","label":"PADCEV (enfortumab vedotin) prescribing information","publisher":"Seagen, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b5631d3e-4604-4363-8f20-11dfc5a4a8ed","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"belamaf-latam-2025","label":"Practical Guidance on the Clinical Management of Ocular Adverse Events Associated with Belantamab Mafodotin for Patients with Relapsed/Refractory Multiple Myeloma: Latin American Expert Panel Recommendations","publisher":"Oncology and Therapy","year":2025,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12378815/","doi":"10.1007/s40487-025-00354-2","gradingScheme":"Expert panel of 13 specialists; recommendations by discussion, not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No ESMO, ASCO, NCCN or other society guideline on eye care with ADCs was found; every step rests on a US label or one regional expert panel.","The European and UK summaries of product characteristics for these drugs were not read; their examination schedules and dose rules may differ from the US labels.","The BLENREP label covers belantamab with bortezomib and dexamethasone; the Latin American panel also describes a schedule with pomalidomide and dexamethasone (DREAMM-8) that the US label read does not include.","Whether steroid drops help with belantamab is not settled in the sources read: the US label does not instruct them and the panel leaves them to the ophthalmologist.","The evidence that cold packs and vasoconstrictor drops reduce eye toxicity with tisotumab is not described in the label sections read; they were part of the trial programme.","Who should not receive these drugs because of existing eye disease is not settled: the panel says no one should be excluded on that basis alone and that people with conditions such as Sjogren's syndrome or severe dry eye need an individual benefit and risk assessment."]},{"id":"irae-ocular","kind":"protocol","name":"Eye side effects of checkpoint inhibitors: dry eye, uveitis and optic neuritis","aka":["checkpoint inhibitor uveitis","ocular irAEs","Eye-irAEs","immune-related uveitis","immune-related optic neuritis","immune-related dry eye disease","ophthalmic immune-related adverse events"],"tldr":"Immunotherapy can occasionally cause dry, gritty eyes or inflammation inside the eye (uveitis), and rarely of the nerve to the eye. Red or painful eyes, sensitivity to light, floaters, blurred or double vision, or drooping eyelids should be reported so an eye specialist can see you. Most is treated with eye drops and immunotherapy usually continues; sudden loss of vision is an emergency.","summary":"Dry eye (1 to 24% in prospective trials) and uveitis (under 1% to 6%) are the commonest ocular irAEs; optic neuritis, orbital inflammation, thyroid eye disease and eye-movement disorders from myasthenia or myositis also occur (SITC 2021). Most begin within 6 months of starting treatment. Infection and metastasis to the eye must be excluded, and steroids given before an eye examination can worsen an infection or mask the diagnosis.\n\nSITC 2021: ophthalmology input for diagnosis, grading and management; consider referral for grade 1 to 2 symptoms and refer immediately for grade 3 or more; MRI brain with pituitary views if there are ocular or bulbar symptoms; start steroids for eye symptoms only under an ophthalmologist unless needed for another irAE; artificial tears for symptoms.\n\nThe 2025 Eye-irAE consensus definitions add disease-specific treatment: anterior uveitis is treated with topical steroid with review every 1 to 2 weeks and the checkpoint inhibitor is not stopped; posterior and panuveitis step up to local injections, with holding the checkpoint inhibitor or oral steroids only if disease progresses; immune-related optic neuritis is treated by withholding the checkpoint inhibitor and giving IV methylprednisolone 1000 mg daily for 3 to 5 days once infection is excluded; dry eye is managed locally and the checkpoint inhibitor usually continues.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","ophthalmology"],"related":["irae-neurological","irae-thyroid","irae-hypophysitis-adrenal"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab","methylprednisolone"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can sometimes affect the eyes. Tell your team about red, painful or dry eyes, or blurred or double vision. Sudden loss of sight is an emergency.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","acute-oncology-service","telephone-triage","emergency-department"]},"population":"Adults receiving or who have received an immune checkpoint inhibitor who develop eye symptoms. People with a past history of uveitis, autoimmune eye disease or eye metastases need particular care. Children are not addressed by these sources.","trigger":"Red, painful, dry or gritty eyes, light sensitivity, floaters, blurred vision, loss of vision, double vision, or droopy or puffy eyelids during or after checkpoint inhibitor treatment.","steps":[{"action":"For grade 1 to 2 eye symptoms, consider referral to an ophthalmologist","why":"Even mild-looking symptoms can hide inflammation that threatens sight.","source":"sitc-2021","quote":"Eye symptoms of visual disturbance; red, painful, dry, or irritated eyes; double vision; droopy or puffy eyelids; and difficultly moving the eyes that are grade 1–2 in any patient undergoing immunotherapy should prompt the clinician to consider ophthalmological referral if available."},{"action":"For grade 3 or more eye symptoms, refer to an ophthalmologist immediately","why":"Severe inflammation can cause permanent loss of vision.","source":"sitc-2021","quote":"Eye symptoms of visual disturbance; red, painful, dry or irritated eyes; double vision; droopy or puffy eyelids; and difficultly moving the eyes that are grade ≥3 in any patient undergoing immunotherapy should prompt immediate ophthalmological referral."},{"action":"Do not start steroids for eye symptoms before an ophthalmologist has examined the eye, unless they are needed for another side effect","why":"Steroids can worsen an eye infection that looks the same, and can hide the signs the specialist needs.","source":"sitc-2021","quote":"Initiation of systemic or topical treatment with corticosteroids for eye symptoms should occur under the guidance of an ophthalmologist, unless systemic steroids are needed for non-ophthalmological issues."},{"action":"If there are eye-movement problems or other bulbar symptoms, obtain an MRI of the brain including the pituitary","why":"Double vision or droopy lids may come from myasthenia, myositis, hypophysitis or the brain rather than the eye.","source":"sitc-2021","quote":"If ocular or bulbar symptoms are present (eg, difficulty moving eyes), MRI of the brain (including pituitary cuts) should be conducted."},{"action":"For uveitis, test for syphilis, tuberculosis, Lyme disease where endemic, and sarcoidosis","why":"Infections and sarcoidosis cause the same inflammation and need different treatment.","source":"eye-irae-2025","quote":"For all uveitis anatomic locations, testing to rule out syphilis, tuberculosis, Lyme disease (in endemic areas) and sarcoidosis should be done."},{"action":"Treat anterior uveitis with steroid eye drops, reviewing every 1 to 2 weeks, and continue the checkpoint inhibitor","why":"Inflammation at the front of the eye can usually be controlled with drops alone.","source":"eye-irae-2025","quote":"For irAU, a topical ophthalmic corticosteroid is recommended with follow-up every 1–2 weeks until symptoms and signs resolve."},{"action":"For posterior uveitis or panuveitis that persists or worsens, step up to steroid injections in or around the eye, and consider holding the checkpoint inhibitor or giving oral steroids only if it still progresses","why":"Deeper inflammation can damage the retina, but local treatment often avoids stopping cancer treatment.","source":"eye-irae-2025","quote":"For irPanU, the recommended treatment would be to initiate a topical ophthalmic corticosteroid to treat the anterior segment inflammation with follow-up every 1–2 weeks. If findings persist or worsen on follow-up, then intraocular steroids may be considered. If disease progresses despite this, consider holding the ICI and/or initiating oral corticosteroids."},{"action":"For immune-related optic neuritis, withhold the checkpoint inhibitor and give IV methylprednisolone 1000 mg daily for 3 to 5 days once infection is excluded","why":"Inflammation of the optic nerve can cause rapid, lasting loss of sight.","source":"eye-irae-2025","quote":"Most cases of irON should be treated, including withholding of ICI and initiation of immunomodulation. Intravenous methylprednisolone (IVMP) at a dose of 1000 mg daily or equivalent should be initiated as soon as infectious causes are ruled out and can be continued for 3–5 days."},{"action":"Manage dry eye with local eye treatment and continue the checkpoint inhibitor in most cases; discuss a planned break only if the cornea is at risk","why":"Dry eye is usually managed with eye treatments alone.","source":"eye-irae-2025","quote":"If the irDED cannot be adequately controlled with local therapies and there is risk of permanent damage to the cornea, then a scheduled break in ICI may be discussed with the oncology team. For most cases, ICI may be continued."}],"bestInClass":{"statement":"SITC 2021 sets the frame: ophthalmology involvement, immediate referral at grade 3 or more, and no steroids for eye symptoms until an ophthalmologist has examined the eye. The 2025 Eye-irAE consensus definitions, written by uveitis specialists and neuro-ophthalmologists through a modified Delphi process, are the most recent and most specific source: they keep the checkpoint inhibitor going for anterior uveitis and most dry eye, treat locally first for deeper uveitis, and withhold the checkpoint inhibitor with IV methylprednisolone for optic neuritis. Neither source grades its recommendations, and there are no trials.","sources":["sitc-2021","eye-irae-2025"]},"variants":[{"name":"Grade-driven referral without disease-specific treatment (SITC 2021)","differs":"Refers by CTCAE grade and leaves treatment to the ophthalmologist, without saying when the checkpoint inhibitor may continue for a specific eye condition.","evidence":"Expert consensus; no level of evidence printed for the ophthalmological recommendations.","sources":["sitc-2021"]}],"grades":[{"claim":"Anterior uveitis: the checkpoint inhibitor should not be discontinued","grade":"consensus (modified Delphi), not graded","source":"eye-irae-2025","quote":"Consensus was reached that the ICI should not be discontinued and that irAU can generally be successfully controlled with topical therapy."},{"claim":"Immediate ophthalmology referral for grade 3 or more eye symptoms","grade":"not graded (expert consensus)","source":"sitc-2021"}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"eye-irae-2025","label":"Consensus disease definitions for ophthalmic immune-related adverse events of immune checkpoint inhibitors","publisher":"Journal for ImmunoTherapy of Cancer","year":2025,"url":"https://europepmc.org/article/PMC/PMC11979595","doi":"10.1136/jitc-2024-011049","gradingScheme":"Modified Delphi consensus using the RAND/UCLA Appropriateness Method, 29 panellists from 25 academic centres; definitions and treatment guidance, not graded recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline was read only as its abstract and its ocular table is not compared here.","The online supplemental tables of the 2025 Eye-irAE definitions, which the authors call the primary reference, were not read; the steps rest on the main text only.","The 2025 panel did not set visual acuity thresholds for severity, so what counts as vision-threatening remains a clinical judgement."]},{"id":"fdg-pet-ct-preparation","kind":"protocol","name":"FDG PET-CT scan preparation: fasting, blood glucose and diabetes","aka":["PET scan preparation","PET-CT prep","fasting before PET scan","blood sugar before PET","diabetes and PET scan","FDG PET fasting","insulin before PET scan"],"tldr":"A PET-CT scan uses a sugar-like tracer, so food, sugar, exercise and cold can all blur the pictures. Do not eat for at least 4 hours before (plain water is fine and helps), take your usual medicines, avoid hard exercise the day before, and keep warm. If you have diabetes, the unit will give you a plan for your tablets or insulin and will check your blood sugar when you arrive.","summary":"EANM 2015 (version 2.0, ungraded): nothing but plain water for at least 4 hours before the FDG injection; medication as prescribed; about 1 litre of water in the 2 hours before; no coffee, caffeinated or 'sugar-free' drinks; glucose-containing intravenous fluids and parenteral nutrition stopped at least 4 hours before; no strenuous exercise for at least 6 hours and preferably 24; warmth from 30 to 60 minutes before injection to limit brown fat uptake; seated or lying and silent during the uptake phase, especially in head and neck cancer; void before imaging. Blood glucose must be measured before FDG; in clinical studies scanning proceeds below 11 mmol/L (about 200 mg/dL) and is rescheduled at or above it, though hyperglycaemia in brittle diabetes is not an absolute contraindication. Insulin to lower glucose is given only if more than 4 hours will pass before FDG (rapid-acting, subcutaneous). Type 2 diabetes on tablets: late morning slot, tablets continued; insulin-treated diabetes: late morning after normal breakfast and insulin with FDG no sooner than 4 hours after rapid-acting insulin, or early morning; insulin pumps off for at least 4 hours. Uptake time 60 minutes (55 to 75), kept within 10 minutes on repeat scans for response assessment. Pregnancy needs a clinical decision; breastfeeding need not stop, with close contact limited for 12 hours. An Australian joint diabetes and nuclear medicine guideline (2026) gives diabetes-specific protocols; it was read as a summary abstract only.","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["fdg-pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before a PET scan: no food for 4 hours, only plain water, no coffee or sweets, no hard exercise, keep warm. Take your normal medicines. If you have diabetes, ask the scan team for a plan for your insulin or tablets.","domain":"screening-diagnostics","setting":{"who":["patient-or-carer","radiographer","nurse","doctor"],"where":["home","outpatient-clinic"]},"population":"Adults having FDG PET-CT for cancer diagnosis, staging or response assessment, including people with diabetes. Children follow the SNMMI/EANM paediatric oncology guideline (2021), which was not read here. Brain imaging, infection and inflammation, and other tracers (PSMA, DOTATATE, FES) have their own preparation and are not covered.","trigger":"An FDG PET-CT scan is booked.","steps":[{"action":"When booking, ask about diabetes, claustrophobia and possible pregnancy or breastfeeding","why":"Each changes how the scan is prepared or timed, and finding out early avoids a wasted visit.","source":"eanm-2015","quote":"A specific inquiry about claustrophobia at the time the patient is scheduled for the study may decrease the number of nondiagnostic studies and cancellations, and allow premedication planning.","grade":"ungraded"},{"action":"Eat or drink nothing but plain water for at least 4 hours before the tracer injection; take usual medicines","why":"Food raises blood sugar and insulin, which pull the tracer into muscle and away from the cancer.","source":"eanm-2015","quote":"Nondiabetic patients should not consume any food, simple carbohydrates or liquids other than plain (unflavoured) water for at least 4 h prior to the start of the FDG PET/CT study (i.e. with respect to the time of injection of FDG).","grade":"ungraded"},{"action":"Drink plenty of plain water beforehand, for example about a litre in the 2 hours before the injection, and avoid coffee and sugar-free drinks","why":"Water dilutes the tracer in the urine, giving clearer pictures and a lower radiation dose to the bladder.","source":"eanm-2015","quote":"Adequate prehydration is important to ensure a sufficiently low concentration of FDG in the urine (fewer artefacts) and for radiation safety reasons.","grade":"ungraded"},{"action":"Stop glucose-containing drips and parenteral nutrition at least 4 hours before the injection","why":"Glucose in a drip raises blood sugar just as food does.","source":"eanm-2015","quote":"Parenteral nutrition and intravenous fluids containing glucose should be discontinued at least 4 h before the time of FDG injection.","grade":"ungraded"},{"action":"Avoid strenuous exercise for at least 6 hours before the scan, and preferably for 24 hours","why":"Working muscles take up the tracer and can hide or mimic disease.","source":"eanm-2015","quote":"Patients must avoid strenuous exercise for at least 6 h before the FDG PET/CT study, and preferably for 24 h.","grade":"ungraded"},{"action":"Check blood glucose on arrival, before the tracer is given","why":"High sugar competes with the tracer and lowers the quality of the scan; low sugar is unsafe.","source":"eanm-2015","quote":"Blood glucose level must be measured prior to administering FDG.","grade":"ungraded"},{"action":"Scan if plasma glucose is below 11 mmol/L; at or above it, reschedule, unless the scan is needed despite poorly controlled diabetes, and record the value","why":"Very high sugar makes the scan less accurate, but an important scan should not be refused just for that.","source":"eanm-2015","quote":"If the plasma glucose level is higher than or equal to 11 mmol/L (about 200 mg/dL), the FDG PET/CT study should be rescheduled or the patient excluded depending on the patient’s circumstances and the trial being conducted.","grade":"ungraded"},{"action":"Do not give insulin to bring glucose down unless more than 4 hours will pass before the tracer injection, and then use rapid-acting insulin under the skin","why":"Insulin pushes the tracer into muscle, which spoils the scan if given too close to it.","source":"eanm-2015","quote":"Insulin should not be given to reduce glucose levels (this leads to greater muscle uptake of FDG) unless the interval between administration of insulin and administration of FDG is more than 4 h.","grade":"ungraded"},{"action":"For people on insulin, plan the slot with them: late morning after normal breakfast and insulin with the tracer at least 4 hours after rapid-acting insulin, or early morning; switch insulin pumps off for at least 4 hours","why":"Timing the scan around insulin keeps sugar steady without leaving insulin active at the injection.","source":"eanm-2015","quote":"FDG should be injected no sooner than 4 h after subcutaneous injection of rapid-acting insulin or 6 h after subcutaneous injection of short-acting insulin.","grade":"ungraded"},{"action":"For people on tablets for type 2 diabetes, book late morning and continue the tablets; stop metformin only if intravenous contrast will be given (see the contrast protocol)","why":"Tablets do not interfere with the scan in the way insulin does.","source":"eanm-2015","quote":"Patients continue to take oral medication to control their blood sugar.","grade":"ungraded"},{"action":"Keep the person warm from 30 to 60 minutes before the injection until the scan ends, and have them sit or lie quietly without talking during the uptake time","why":"Cold switches on brown fat and talking or chewing works muscles, both of which take up the tracer.","source":"eanm-2015","quote":"The patient should be kept warm starting 30 – 60 min before the injection of FDG and continuing throughout the subsequent uptake period and examination to minimise FDG accumulation in brown fat (especially relevant in winter or if the room is air-conditioned).","grade":"ungraded"},{"action":"Scan about 60 minutes after the injection (55 to 75), and keep the same uptake time, within 10 minutes, on repeat scans that compare response","why":"Tracer uptake keeps rising with time, so comparing scans fairly needs the same wait each time.","source":"eanm-2015","quote":"When repeating an FDG PET/CT study in the same patient, especially in the context of therapy response assessment, it is essential to apply the same uptake interval to within 10 min","grade":"ungraded"},{"action":"If breastfeeding, feed just before the injection and limit close contact for 12 hours; expressed milk can be given by bottle","why":"Little tracer passes into milk, but the mother's body gives off radiation for some hours.","source":"eanm-2015","quote":"The ICRP does not recommend interruption of breastfeeding after FDG administration since little FDG is excreted in the milk","grade":"ungraded"}],"bestInClass":{"statement":"EANM procedure guideline version 2.0 (2015), the current European adult oncology FDG guideline: at least 4 hours' fast with plain water encouraged, no strenuous exercise for at least 6 hours, warmth and quiet rest during uptake, blood glucose measured before injection with scanning below 11 mmol/L, no insulin within 4 hours of FDG, diabetes-specific timing of tablets, insulin and pumps, and a standard 60-minute uptake kept consistent across response scans. The guideline is ungraded consensus; no newer adult oncology FDG guideline from EANM or SNMMI was found.","sources":["eanm-2015"]},"variants":[{"name":"Diabetes-specific preparation protocols (Australia and New Zealand)","differs":"A joint guideline of the Australian Diabetes Society and the Australian and New Zealand Society of Nuclear Medicine sets preparation by diabetes type, covering fasting, oral glucose-lowering medicines, insulin regimens and insulin pumps.","evidence":"Described as developed from a literature review and refined by a multidisciplinary expert panel. Only the summary abstract was read, so its specific instructions (for example on SGLT2 inhibitors or GLP-1 receptor agonists) are not stated here.","sources":["ads-anzsnm-2026"]}],"grades":[{"claim":"Scan can proceed when plasma glucose is below 11 mmol/L (clinical studies)","grade":"ungraded","source":"eanm-2015","quote":"If the plasma glucose level is lower than 11 mmol/L (about 200 mg/dL), the FDG PET/CT study can be performed."},{"claim":"Hyperglycaemia in brittle or poorly controlled diabetes is not an absolute contraindication","grade":"ungraded","source":"eanm-2015","quote":"Therefore we recommend the same advice and suggest recording the blood glucose level and any other information that could be relevant for interpretation of the examination."},{"claim":"Standard uptake time of 60 minutes","grade":"ungraded","source":"eanm-2015","quote":"Note that consistency of SUV measurements (in-house and when compared to the literature) depends on strict observance of the uptake time, and therefore a 60 min interval is recommended with an acceptable range of 55 – 75 min"}],"sources":[{"key":"eanm-2015","label":"FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0","publisher":"European Association of Nuclear Medicine (Boellaard et al., European Journal of Nuclear Medicine and Molecular Imaging)","year":2015,"url":"https://doi.org/10.1007/s00259-014-2961-x","doi":"10.1007/s00259-014-2961-x","gradingScheme":"Procedure guideline; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ads-anzsnm-2026","label":"Joint Australian Diabetes Society/Australian and New Zealand Society of Nuclear Medicine procedure guideline for FDG PET/CT imaging in patients with type 1 and type 2 diabetes (summary and commentary)","publisher":"Internal Medicine Journal","year":2026,"url":"https://doi.org/10.1111/imj.70344","doi":"10.1111/imj.70344","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-sglt2-glp1-plan-before-pet"],"gaps":["The EANM guideline dates from 2015 and predates SGLT2 inhibitors and GLP-1 receptor agonists in wide use; it does not say how to handle them before FDG PET. The Australian and New Zealand diabetes guideline may, but only its summary abstract was read.","None of the recommendations read is graded; they are expert consensus.","The SNMMI/EANM paediatric oncology FDG guideline (2021) was not read, so preparation for children is not covered.","Sedation for claustrophobia and drugs to reduce brown fat uptake (diazepam, propranolol) are mentioned by EANM with conflicting results and are not recommended routinely."]},{"id":"fertility-preservation-before-cancer-treatment","kind":"protocol","name":"Fertility discussion and preservation before cancer treatment","aka":["oncofertility referral","egg freezing before chemotherapy","sperm banking before cancer treatment","embryo freezing before cancer treatment","ovarian tissue freezing","GnRH agonist ovarian protection during chemotherapy","goserelin to protect the ovaries"],"tldr":"Some cancer treatments can make it harder or impossible to have children later. Before treatment, your team should discuss this and, if you want, refer you quickly to a fertility specialist. Freezing sperm, eggs, embryos or ovarian tissue are the established options; an injection to rest the ovaries during chemotherapy can be added for some women with breast cancer but does not replace freezing.","summary":"Every person whose treatment may affect fertility should be told about the risk and the options before treatment, at the earliest opportunity where treatment is urgent (NICE NG257, 2026; ASCO 2025), and those who are interested or unsure referred promptly to a reproductive specialist (ASCO). NICE offers sperm cryopreservation, and oocyte or embryo cryopreservation, to people of reproductive age facing treatment likely to make them infertile, and ovarian tissue cryopreservation when oocyte or embryo storage is not feasible, for example before puberty; NHS-funded preservation is not bound by the usual eligibility criteria such as the lower age limit, and storage is reviewed at least every 5 years.\n\nESHRE (2020) recommends the GnRH antagonist protocol for ovarian stimulation for its speed and safety (strong), random-start stimulation as an option in urgent cycles (weak), and concurrent letrozole in oestrogen-sensitive cancers (good practice point). GnRH agonists during chemotherapy should be offered as an option for ovarian function protection in premenopausal women with breast cancer (ESHRE, strong), but not instead of cryopreservation (ESHRE; ASCO 2025: an adjunct only, in breast cancer). ASCO adds that testicular tissue freezing in prepubertal boys is experimental, that ovarian tissue cryopreservation is the only established method before puberty in girls, and that sperm collected soon after starting treatment may carry more genetic damage.","asOf":"2026-11-11","links":[],"tags":["protocol","fertility","survivorship","aya"],"related":["letrozole","rejuv-paed-fertility-female","rejuv-paed-fertility-male","rejuv-access-fertility-preservation"],"cancers":[],"sections":["supportive-care"],"technologies":["fertility-preservation"],"targets":[],"drugs":["goserelin","leuprolide"],"companies":[],"institutions":["nice","asco"],"pathways":[],"terms":["lymphoma-tx-fertility-preservation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer treatment can affect having children later. Ask about this before treatment starts. Sperm, eggs or embryos can be frozen and stored.","domain":"survivorship","setting":{"who":["doctor","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","acute-oncology-service"]},"population":"People of any sex facing cancer treatment that may impair fertility (chemotherapy, pelvic or total body radiotherapy, surgery to reproductive organs), including adolescents and, for some methods, children. NICE NG257 applies to NHS care in England. ESHRE's guideline is for women and transgender men; ASCO's covers adults and children of all sexes.","trigger":"A treatment plan is being made that may impair fertility, before the first treatment.","steps":[{"action":"Before treatment, tell the person about the risk to fertility and discuss preservation, as early as possible when treatment is urgent","why":"The window closes once treatment starts; a short conversation now keeps choices open.","source":"nice-ng257","quote":"Discuss fertility preservation as an option with people who are preparing for medical treatment, or who have a medical condition, that is likely to impair their fertility. For people who need urgent treatment, this discussion should take place at the earliest possible opportunity."},{"action":"Refer anyone interested or unsure to a reproductive specialist promptly","why":"Specialists can explain the options and start them quickly, often without delaying cancer treatment.","source":"asco-2025","quote":"Patients interested in or uncertain about FP should be referred to reproductive specialists."},{"action":"Offer sperm cryopreservation before treatment to people with male reproductive organs of reproductive age","why":"Sperm banking is quick, established and is best done before the first dose.","source":"nice-ng257","quote":"Offer sperm cryopreservation to men (and boys), and trans women and non-binary people with male reproductive organs who are of reproductive age, and who are preparing for medical treatment, or who have a medical condition, that is likely to make them infertile."},{"action":"Collect sperm before treatment where possible, because sperm collected soon after treatment starts may carry more genetic damage","why":"Chemotherapy can damage sperm made in the weeks after it starts.","source":"asco-2025","quote":"Males should be advised of potentially higher genetic damage risks in sperm collected soon after cancer-directed therapy initiation and completion."},{"action":"Offer oocyte or embryo cryopreservation to people with female reproductive organs of reproductive age","why":"Frozen eggs or embryos are the established ways to keep the chance of a pregnancy later.","source":"nice-ng257","quote":"Offer oocyte or embryo cryopreservation (as appropriate) to women (and girls), and trans men and non-binary people with female reproductive organs who are of reproductive age, and who are preparing for medical treatment, or who have a medical condition, that is likely to make them infertile."},{"action":"Use a GnRH antagonist stimulation protocol, starting at any point in the cycle if time is short","why":"ESHRE prefers this protocol because it is feasible when treatment is urgent, takes a short time and is safe.","source":"eshre-2020","quote":"For ovarian stimulation in women seeking FP for medical reasons, the GnRH antagonist protocol is recommended for its feasibility in urgent situations, short time and safety reasons","grade":"STRONG, very low quality evidence"},{"action":"In oestrogen-sensitive cancers, add letrozole during stimulation","why":"Letrozole keeps oestrogen levels lower while the ovaries are stimulated.","source":"eshre-2020","quote":"In ovarian stimulation for FP in oestrogen-sensitive diseases the concomitant use of anti-oestrogen therapy, such as letrozole, is probably recommended.","grade":"GPP (good practice point)"},{"action":"Consider ovarian tissue cryopreservation when egg or embryo freezing is not feasible, for example before puberty or when there is no time for stimulation","why":"Ovarian tissue can be removed and frozen without hormone stimulation, and later put back to try to restore fertility.","source":"nice-ng257","quote":"Consider ovarian tissue cryopreservation when oocyte or embryo cryopreservation is not feasible, for example, in girls before puberty."},{"action":"For premenopausal women with breast cancer having chemotherapy, offer a GnRH agonist during chemotherapy as an option to protect ovarian function, in addition to, not instead of, freezing","why":"Resting the ovaries during chemotherapy helps protect how they work, but the evidence that it keeps the chance of pregnancy is limited.","source":"eshre-2020","quote":"GnRH agonists during chemotherapy should be offered as an option for ovarian function protection in premenopausal breast cancer patients receiving chemotherapy; however, limited evidence exists on their protective effect on the ovarian reserve and the potential for future pregnancies","grade":"STRONG, high quality evidence"},{"action":"Offer psychological support and decision aids to people deciding about fertility preservation","why":"These decisions come at the same time as a cancer diagnosis and are hard to make quickly.","source":"eshre-2020","quote":"It is recommended to provide decision aids to patients who are considering FP","grade":"STRONG, low quality evidence"},{"action":"Review stored material at least every 5 years, and keep NHS-funded storage for those still at significant risk of infertility","why":"Storage depends on renewed consent and on whether the person still needs it.","source":"nice-ng257","quote":"Organise follow-ups at least every 5 years with people who have had their material preserved to determine whether or not there is a need to continue NHS-funded storage."}],"bestInClass":{"statement":"NICE NG257 (2026) and ASCO (2025) are the most recent and agree: discuss fertility before treatment, refer quickly, offer sperm, oocyte or embryo cryopreservation, and use ovarian tissue cryopreservation where egg or embryo storage is not feasible, including before puberty. ESHRE (2020) gives the most detail on how, with graded recommendations for the stimulation protocol and for each method. On GnRH agonists the three agree that they do not replace cryopreservation; ESHRE recommends offering them for ovarian protection in premenopausal women with breast cancer (strong, high quality evidence) and ASCO allows them as an adjunct in breast cancer, while ESHRE says the evidence for their effect on ovarian reserve and future pregnancy is limited. ASCO also allows GnRH agonists to stop periods in people who need urgent treatment for an oncological emergency, a different purpose. ESMO's 2020 guideline could not be read.","sources":["nice-ng257","asco-2025","eshre-2020","esmo-2020"]},"variants":[{"name":"GnRH agonist as an adjunct in breast cancer only (ASCO 2025)","differs":"Says GnRH agonists should not replace established methods and may be offered as an adjunct to females with breast cancer, and may be offered for menstrual suppression when urgent treatment is needed.","evidence":"ASCO 2025, read as an abstract; grades not seen. ESHRE grades its breast cancer recommendation strong on high-quality evidence.","sources":["asco-2025","eshre-2020"]},{"name":"Post-treatment fertility preservation (ASCO 2025)","differs":"Offers preservation after treatment to people who did not have it before, or did not store enough eggs or embryos.","evidence":"ASCO 2025, read as an abstract.","sources":["asco-2025"]},{"name":"In vitro maturation of oocytes","differs":"Collects immature eggs without full stimulation and matures them in the laboratory, where stimulation is not feasible.","evidence":"ASCO 2025 calls it an emerging method that may be offered; ESHRE (2020) says it requires specific expertise and that maturation after removal of ovarian tissue is experimental.","sources":["asco-2025","eshre-2020"]}],"grades":[{"claim":"GnRH antagonist protocol for ovarian stimulation for fertility preservation","grade":"STRONG, very low (⊕◯◯◯)","source":"eshre-2020"},{"claim":"Random-start ovarian stimulation in urgent cycles","grade":"WEAK, low (⊕⊕◯◯)","source":"eshre-2020","quote":"In urgent FP cycles, random-start ovarian stimulation is an option"},{"claim":"Oocyte cryopreservation as an established option","grade":"STRONG, low (⊕⊕◯◯)","source":"eshre-2020","quote":"Oocyte cryopreservation should be offered as an established option for FP"},{"claim":"Embryo cryopreservation as an established option","grade":"STRONG, low (⊕⊕◯◯)","source":"eshre-2020","quote":"Embryo cryopreservation is an established option for FP"},{"claim":"Ovarian tissue cryopreservation where oocyte or embryo storage is not feasible, or by preference, before moderate or high-risk treatment","grade":"STRONG, low (⊕⊕◯◯)","source":"eshre-2020","quote":"It is recommended to offer OTC in patients undergoing moderate/high-risk gonadotoxic treatment where oocyte/embryo cryopreservation is not feasible, or at patient preference"},{"claim":"GnRH agonists during chemotherapy for ovarian protection in premenopausal breast cancer","grade":"STRONG, high (⊕⊕⊕⊕)","source":"eshre-2020"},{"claim":"GnRH agonists not instead of cryopreservation in breast cancer","grade":"STRONG, moderate (⊕⊕⊕◯)","source":"eshre-2020","quote":"In women with breast cancer, GnRH agonists during chemotherapy should not be considered an option for FP instead of cryopreservation techniques"},{"claim":"GnRH agonists in cancers other than breast cancer","grade":"STRONG, very low (⊕◯◯◯)","source":"eshre-2020","quote":"In malignancies other than breast cancer, GnRH agonists should not be routinely offered as an option for ovarian function protection and FP without discussion of the uncertainty about its benefit"}],"sources":[{"key":"nice-ng257","label":"Fertility problems: assessment and treatment (NG257), fertility preservation for medical indications","publisher":"NICE","year":2026,"url":"https://www.nice.org.uk/guidance/ng257/chapter/Fertility-preservation-for-medical-indications","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'consider') and each is dated, for example [2026] or [2013, amended 2026]. Published 31 March 2026, replacing CG156.","read":"full-text","accessed":"2026-11-11"},{"key":"eshre-2020","label":"ESHRE guideline: female fertility preservation","publisher":"European Society of Human Reproduction and Embryology (ESHRE), Human Reproduction Open","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7666361/","doi":"10.1093/hropen/hoaa052","gradingScheme":"Each recommendation labelled STRONG or WEAK with evidence quality high ⊕⊕⊕⊕, moderate ⊕⊕⊕◯, low ⊕⊕◯◯ or very low ⊕◯◯◯; GPP for good practice points; research only for interventions to be used only in research.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2025","label":"Fertility Preservation in People With Cancer: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2025,"url":"https://europepmc.org/abstract/MED/40106739","doi":"10.1200/JCO-24-02782","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2020","label":"Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines","publisher":"ESMO, Annals of Oncology","year":2020,"url":"https://doi.org/10.1016/j.annonc.2020.09.006","doi":"10.1016/j.annonc.2020.09.006","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-acc-default-fertility-preservation-referral"],"gaps":["The ESMO 2020 guideline could not be read: Europe PMC holds no abstract and the publisher refused a script.","ASCO 2025 was read only as an abstract; its grades, its two errata and its detailed recommendations for children are not given here.","ESHRE's female guideline dates from 2020; NICE NG257 points to part D of ESHRE's 2025 ovarian stimulation guideline for fertility preservation, which was not read.","No source read gives live birth rates per stored egg, embryo or tissue graft; ESHRE asks that each centre give its own rates.","The evidence that GnRH agonists protect future pregnancy, as opposed to ovarian function, is limited (ESHRE); outside breast cancer ESHRE advises against offering them routinely without discussing the uncertainty about their benefit.","No source read gives the number of days ovarian stimulation takes, so the delay to cancer treatment is not stated here."]},{"id":"paediatric-fertility-preservation","kind":"protocol","name":"Fertility preservation for children and young people before cancer treatment","aka":["oncofertility in children","paediatric fertility preservation","sperm banking teenagers","ovarian tissue freezing children","testicular tissue cryopreservation","fertility counselling before chemotherapy"],"tldr":"Some cancer treatments can stop a child having children of their own later. Before treatment, the team should talk with the family about this risk and refer them to a fertility specialist if they want, or are unsure. Teenagers who have started puberty can bank sperm or eggs; for younger girls ovarian tissue can be frozen, and for younger boys testicular tissue freezing is still experimental.","summary":"Children's Oncology Group endorses the ASCO 2025 guideline update (166 studies, GRADE) for children. Discuss the possibility of infertility as early as possible before treatment (strong, moderate), offer an evaluation of reproductive risk that accounts for the gonadotoxicity of planned and possible future treatment (strong, moderate), and refer anyone interested or uncertain to reproductive specialists as soon as possible (strong, very low), with prompt access to a multidisciplinary fertility preservation team (good practice). Children and adolescents who have started puberty should be offered established methods with their assent and parental consent (strong, moderate): sperm banking for all pubertal and postpubertal males before treatment (strong, high), with testicular sperm extraction if no sample can be produced (strong, high), and embryo or oocyte cryopreservation in females (strong, high). For prepubertal patients the only options are ovarian tissue cryopreservation, an established method that needs no ovarian stimulation or delay (strong, moderate), and testicular tissue cryopreservation, which is experimental and for trials only (strong, very low). Hormonal suppression does not protect male fertility (strong, high); GnRH agonists must not replace established methods (conditional, moderate). Ovarian transposition may be offered before pelvic radiotherapy (strong, moderate). Revisit fertility at follow-up and when plans change (strong, low).","asOf":"2026-11-11","links":[],"tags":["protocol","paediatric","fertility"],"related":["oncofertility-consortium","goserelin","leuprolide"],"cancers":["childhood-cancers"],"sections":["supportive-care"],"technologies":["fertility-preservation","rejuv-paed-fertility-male","rejuv-paed-fertility-female"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["asco"],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer treatments affect whether a child can have babies later. The team should talk about this before treatment and offer ways to protect fertility, like freezing sperm, eggs or tissue.","domain":"paediatric","setting":{"who":["doctor","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward"]},"population":"Children, adolescents and young adults with cancer facing treatment that may affect fertility, as ASCO 2025 (adult and paediatric patients) and its COG endorsement scope it. Methods differ by pubertal stage. The PanCareLIFE and IGHG guidelines cover people diagnosed at 25 or younger.","trigger":"A child or young person is diagnosed with cancer and treatment is being planned.","steps":[{"action":"Talk about the possibility of infertility as soon as possible after diagnosis, before treatment starts","why":"Many options must be done before the first dose of treatment, so a late conversation can close them off.","source":"asco-fp-2025","quote":"FP approaches should be discussed before cancer-directed therapy.","grade":"Strong, Moderate quality evidence"},{"action":"Assess and explain the child's own risk, taking account of the planned treatment and any treatment that may follow","why":"Risk differs between treatments, and for many newer treatments it is not yet known, so the family needs to hear what applies to their child.","source":"asco-fp-2025","quote":"People with cancer should be evaluated for and counseled about reproductive risks at diagnosis and during survivorship.","grade":"Strong, Moderate quality evidence"},{"action":"Refer every family who is interested, or unsure, to a reproductive specialist straight away","why":"Uncertain families benefit from expert advice too, and delay can rule options out.","source":"asco-fp-2025","quote":"Patients interested in or uncertain about FP should be referred to reproductive specialists.","grade":"Strong, Very low quality evidence"},{"action":"Make sure the team can reach a multidisciplinary fertility preservation service quickly","why":"Fertility specialists, psychological support, social work, financial counselling and genetic counselling may all be needed within days.","source":"asco-fp-2025","quote":"Oncology teams should ensure prompt access to a multidisciplinary FP team.","grade":"Good practice statement"},{"action":"For a child who has started puberty, offer established methods with the child's assent and a parent's or guardian's consent","why":"A young person who has begun puberty can usually store sperm or eggs, and their own agreement matters alongside the parents'.","source":"asco-fp-2025","quote":"Established FP methods in children who have begun puberty should be offered with patient assent and parent/guardian consent.","grade":"Strong, Moderate quality evidence"},{"action":"Offer sperm banking to every pubertal and postpubertal boy before treatment, and testicular sperm extraction if he cannot produce a sample","why":"Frozen sperm is the most reliable way for a boy to keep the chance of biological children; even a small sample can be used later.","source":"asco-fp-2025","quote":"Sperm cryopreservation should be offered to males before cancer-directed treatment, with testicular sperm extraction if unable to provide semen samples.","grade":"Strong, High quality evidence"},{"action":"Collect sperm before treatment starts, and do not let poor counts or urgency stop banking","why":"Sperm collected soon after starting treatment may carry more genetic damage; modern IVF can use very few sperm.","source":"asco-fp-2025","quote":"Males should be advised of potentially higher genetic damage risks in sperm collected soon after cancer-directed therapy initiation and completion.","grade":"Strong, Low quality evidence"},{"action":"For a girl who has started puberty, offer embryo or egg freezing where there is time for ovarian stimulation","why":"Both are established methods; stimulation no longer has to wait for a particular day of the cycle.","source":"cog-fp-2025","grade":"Strong, High quality evidence"},{"action":"For a girl before puberty, or one who cannot delay treatment, offer ovarian tissue freezing","why":"It needs no hormone stimulation or delay and is the only established option before puberty.","source":"asco-fp-2025","quote":"The only established method for prepubertal females is OTC.","grade":"Strong, Moderate quality evidence"},{"action":"For a boy before puberty, offer testicular tissue freezing only within a clinical trial or approved research protocol","why":"The method is still investigational, so it is offered as research rather than as routine care.","source":"asco-fp-2025","quote":"Testicular tissue cryopreservation in prepubertal males is experimental and should be offered only in a clinical trial.","grade":"Strong, Very low quality evidence"},{"action":"Do not offer hormonal suppression to protect a boy's fertility, and do not use GnRH agonists in place of established methods in girls","why":"Hormone suppression is not effective for boys; in girls, ASCO allows GnRH agonists only as an addition, in breast cancer, and asks for trials elsewhere.","source":"asco-fp-2025","quote":"Gonadotropin-releasing hormone agonist (GnRHa) should not be used in place of established FP methods but may be offered as an adjunct to females with breast cancer.","grade":"Strong, High quality evidence (males); Conditional, Moderate quality evidence (GnRHa)"},{"action":"Where pelvic radiotherapy is planned, consider moving the ovaries out of the field (ovarian transposition) close to the time of radiotherapy","why":"Moving the ovaries can shield them from radiation, though scatter means it does not always work.","source":"cog-fp-2025","grade":"Strong, Moderate quality evidence"},{"action":"Revisit fertility at follow-up visits, when treatment plans change, and when pregnancy is being considered, and record each discussion","why":"A child's wishes change as they grow up, and options such as egg or embryo freezing remain possible after treatment for some.","source":"cog-fp-2025","grade":"Strong, Low quality evidence"}],"bestInClass":{"statement":"The ASCO 2025 guideline update, endorsed by the Children's Oncology Group in June 2025, is the current standard and replaces the 2018 version: early discussion and risk assessment before treatment, immediate referral for anyone interested or uncertain, established methods for pubertal children with their assent and parental consent, ovarian tissue cryopreservation as an established method for prepubertal girls, and testicular tissue cryopreservation for prepubertal boys only in trials. The PanCareLIFE and IGHG recommendations (2021) cover the same ground for patients diagnosed at 25 or younger with GRADE; they were read only as abstracts here, so where they differ from ASCO is not stated.","sources":["cog-fp-2025","asco-fp-2025","pancarelife-female-2021","pancarelife-male-2021"]},"variants":[{"name":"GnRH agonist for menstrual suppression in an oncology emergency","differs":"Gives a GnRH agonist when chemotherapy must start urgently, for its benefits such as suppressing periods, rather than as a fertility method.","evidence":"ASCO 2025, conditional recommendation, low quality evidence.","sources":["cog-fp-2025","asco-fp-2025"]}],"grades":[{"claim":"Discuss infertility as early as possible before treatment","grade":"Strong, Moderate quality evidence","source":"cog-fp-2025"},{"claim":"Refer interested or uncertain patients to reproductive specialists","grade":"Strong, Very low quality evidence","source":"cog-fp-2025"},{"claim":"Established methods for children who have begun puberty, with assent and consent","grade":"Strong, Moderate quality evidence","source":"cog-fp-2025"},{"claim":"Sperm cryopreservation before treatment","grade":"Strong, High quality evidence","source":"cog-fp-2025"},{"claim":"No hormonal suppression to preserve male fertility","grade":"Strong, High quality evidence","source":"cog-fp-2025"},{"claim":"Testicular tissue cryopreservation in prepubertal males only in trials","grade":"Strong, Very low quality evidence","source":"cog-fp-2025"},{"claim":"Ovarian tissue cryopreservation as an established method","grade":"Strong, Moderate quality evidence","source":"cog-fp-2025"},{"claim":"GnRH agonists not in place of established methods","grade":"Conditional, Moderate quality evidence","source":"cog-fp-2025"},{"claim":"Ovarian transposition before pelvic radiotherapy","grade":"Strong, Moderate quality evidence","source":"cog-fp-2025"}],"sources":[{"key":"cog-fp-2025","label":"Fertility Preservation in People with Cancer: ASCO Clinical Practice Guideline Update (COG endorsement, version date 27 August 2025)","publisher":"Children's Oncology Group","year":2025,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_Fertility_Guideline_Document_27AUG2025-new-logo.pdf","gradingScheme":"Reprints the source guideline's strength (strong or conditional) and quality of evidence (high, moderate, low, very low) for each recommendation; good practice statements are ungraded.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-fp-2025","label":"Fertility Preservation in People With Cancer: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2025,"url":"https://europepmc.org/abstract/MED/40106739","doi":"10.1200/JCO-24-02782","gradingScheme":"Strength strong or conditional, evidence quality high to very low, as reprinted by COG.","read":"abstract","accessed":"2026-11-11"},{"key":"pancarelife-female-2021","label":"Fertility preservation for female patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group","publisher":"PanCareLIFE and IGHG, The Lancet Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/33539753","doi":"10.1016/S1470-2045(20)30594-5","read":"abstract","accessed":"2026-11-11"},{"key":"pancarelife-male-2021","label":"Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group","publisher":"PanCareLIFE and IGHG, The Lancet Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/33539754","doi":"10.1016/S1470-2045(20)30582-9","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-acc-default-fertility-preservation-referral"],"gaps":["The PanCareLIFE and IGHG 2021 recommendations, the main paediatric-specific fertility guidelines, were read only as abstracts, which do not state the recommendations; their risk thresholds by treatment (for example by cumulative alkylating agent dose) are not given here.","The full text of ASCO 2025 is not open access; recommendations were read in its abstract and as reprinted by COG.","No source read here gives a treatment-by-treatment risk table for children; that assessment is left to the team.","Funding and access to fertility preservation for children vary by country and were not reviewed.","NICE CG156 and ESHRE guidance on fertility preservation were not read for this protocol."]},{"id":"fertility-protection-before-pelvic-radiotherapy","kind":"protocol","name":"Fertility protection before pelvic radiotherapy: ovarian transposition, egg, embryo and sperm freezing","aka":["ovarian transposition","oophoropexy","ovariopexy","fertility preservation before radiotherapy","sperm banking before radiotherapy","egg freezing before radiotherapy","ovarian tissue cryopreservation","oncofertility pelvic radiotherapy","premature ovarian insufficiency after radiotherapy"],"tldr":"Radiotherapy to the pelvis can stop the ovaries working and end fertility, and can damage sperm production. Before treatment starts, your team should talk with you about fertility and refer you quickly if you want to protect it: sperm, eggs or embryos can be frozen, and for some women a surgeon can move the ovaries up out of the radiation field.","summary":"Ovaries are very sensitive to radiation: in women under 40, under 2 Gy is estimated to destroy half the oocytes and 14 Gy may cause complete ovarian failure (review of Wallace et al.), far below pelvic doses for cervical, rectal or anal cancer. NICE NG257 (March 2026) says to discuss fertility preservation with everyone preparing for treatment likely to impair fertility, at the earliest opportunity if treatment is urgent; to offer sperm cryopreservation, and oocyte or embryo cryopreservation, to those of reproductive age; to consider ovarian tissue cryopreservation when those are not feasible; and not to apply the usual NHS fertility eligibility criteria. ASCO (2025) lists ovarian transposition among established methods for females, with embryo, oocyte and ovarian tissue cryopreservation.\n\nESHRE (2020) says women having pelvic radiotherapy without chemotherapy may be offered ovarian transposition to prevent premature ovarian insufficiency (WEAK, low certainty), that women with reduced ovarian reserve or at risk of ovarian metastases are not candidates (good practice point), and that transposition can be done at the same time as ovarian tissue cryopreservation. A 2026 review: transposition is for premenopausal women, generally 40 or younger, whose ovaries need not be removed; ovaries are moved at least 4 cm from the field or 1.5 cm above the iliac crest and marked with clips; reported success ranges from 15% to 100%, about 50% to 65% in cervical cancer after external beam radiotherapy, lower with chemotherapy; ovarian metastasis is rare (0.36% in cervical cancer). A 2022 meta-analysis of 1,160 women with cervical cancer found preserved ovarian function in 61% after external beam radiotherapy. Pregnancies after transposition and pelvic radiotherapy are few; a gestational carrier may be an option when the uterus has been affected by radiation (review).","asOf":"2026-11-11","links":[],"tags":[],"related":["radiotherapy-pregnancy-and-breastfeeding-enquiry","radiotherapy-consent"],"cancers":["cervical","rectal-cancer","anal","hodgkin-lymphoma"],"sections":[],"technologies":["fertility-preservation"],"targets":[],"drugs":[],"companies":[],"institutions":["asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Pelvic radiotherapy can affect having children later. Ask about it before treatment starts. Sperm, eggs or embryos can be stored. Some women can have their ovaries moved higher in the body, out of the way of the radiation.","domain":"radiotherapy","setting":{"who":["doctor","multidisciplinary-team","nurse","patient-or-carer"],"where":["outpatient-clinic","radiotherapy-department","theatre"]},"population":"People of reproductive age, and children, about to have radiotherapy to the pelvis or nearby (cervical, rectal, anal, bladder and other pelvic cancers, pelvic sarcoma, some lymphomas), whose fertility or ovarian function the treatment is likely to impair. Ovarian transposition applies to premenopausal women whose ovaries are normal and need not be removed. Prepubertal children are named only where the sources address them.","trigger":"A plan for radiotherapy that will include, or come close to, the ovaries, uterus or testes, made before treatment starts.","steps":[{"action":"Before treatment, discuss fertility and fertility preservation with everyone whose treatment is likely to impair fertility; if treatment is urgent, have this talk at the earliest possible opportunity","why":"Once radiotherapy starts, some options are lost; the conversation has to happen first.","source":"nice-ng257","quote":"Discuss fertility preservation as an option with people who are preparing for medical treatment, or who have a medical condition, that is likely to impair their fertility. For people who need urgent treatment, this discussion should take place at the earliest possible opportunity.","grade":"[2026]"},{"action":"Refer people interested in or unsure about fertility preservation to a reproductive specialist, with prompt access to a multidisciplinary fertility team","why":"Specialists can say quickly which options are realistic before treatment begins.","source":"asco-fp-2025","quote":"Patients interested in or uncertain about FP should be referred to reproductive specialists.","grade":"as printed in the abstract (full grade not read)"},{"action":"Offer sperm cryopreservation to men and boys of reproductive age before treatment likely to make them infertile","why":"Stored sperm keeps the option of biological children open even if production stops.","source":"nice-ng257","quote":"Offer sperm cryopreservation to men (and boys), and trans women and non-binary people with male reproductive organs who are of reproductive age, and who are preparing for medical treatment, or who have a medical condition, that is likely to make them infertile.","grade":"[2026]"},{"action":"Offer egg or embryo freezing, as appropriate, to women and girls of reproductive age before treatment likely to make them infertile","why":"Eggs or embryos frozen before radiotherapy are not exposed to it.","source":"nice-ng257","quote":"Offer oocyte or embryo cryopreservation (as appropriate) to women (and girls), and trans men and non-binary people with female reproductive organs who are of reproductive age, and who are preparing for medical treatment, or who have a medical condition, that is likely to make them infertile.","grade":"[2026]"},{"action":"Consider ovarian tissue freezing when egg or embryo freezing is not feasible, for example before puberty or when there is no time for stimulation","why":"Ovarian tissue can be removed quickly and stored without hormone treatment.","source":"nice-ng257","quote":"Consider ovarian tissue cryopreservation when oocyte or embryo cryopreservation is not feasible, for example, in girls before puberty.","grade":"[2026]"},{"action":"For premenopausal women having pelvic radiotherapy without chemotherapy, offer ovarian transposition to protect ovarian function","why":"Moving the ovaries out of the beam can keep them making hormones and avoid early menopause.","source":"eshre-2020","quote":"Where pelvic radiotherapy without chemotherapy is planned, women may be offered ovarian transposition with the aim to prevent POI (Gubbala et al., 2014; Hoekman et al., 2019).","grade":"WEAK ⊕⊕◯◯"},{"action":"Do not offer transposition to women with reduced ovarian reserve or at risk of ovarian metastases","why":"Moving ovaries that have few eggs left gains little, and moving ovaries that may hold cancer can spread it.","source":"eshre-2020","quote":"Women with reduced ovarian reserve and women at risk of having ovarian metastases are inappropriate candidates for ovarian transposition.","grade":"GPP"},{"action":"Consider combining transposition with ovarian tissue freezing in the same operation","why":"One operation can both protect the remaining ovary and store tissue as a back-up.","source":"eshre-2020","quote":"Ovarian transposition can be performed at the same time as OTC in patients who will receive pelvic irradiation.","grade":"GPP"},{"action":"Place the transposed ovaries at least 4 cm from the radiation field or 1.5 cm above the iliac crest","why":"The further the ovaries are from the field, the more likely they are to keep working.","source":"ot-review-2026","quote":"The location of transposed ovaries should be at least 4 cm from the radiation field or 1.5 cm above the iliac crest to avoid gonadotoxic radiation doses.","grade":"narrative review (no grade)"},{"action":"Mark the lower edge of each transposed ovary with radiopaque clips so the planning team can see and spare it","why":"The radiotherapy planners need to find the ovaries on the planning scan to keep dose off them.","source":"ot-review-2026","quote":"The inferior margin of the ovaries should be tagged with radiopaque surgical clips for future identification on CT imaging (Buonomo et al., 2021).","grade":"narrative review (no grade)"},{"action":"Tell the person that transposition does not always work, that chemotherapy lowers the chance, and that pregnancies after pelvic radiotherapy are few","why":"Realistic expectations matter: keeping the ovaries working is not the same as being able to carry a pregnancy after radiation to the uterus.","source":"ot-review-2026","quote":"Approximately 50–65% of patients with cervical cancer who undergo OT followed by external beam radiation therapy with or without brachytherapy maintain ovarian function; adjuvant chemotherapy further reduces ovarian function preservation.","grade":"narrative review (no grade)"},{"action":"For NHS-funded fertility preservation, do not apply the usual fertility treatment eligibility rules, including the lower age limit","why":"Preservation before cancer treatment is a different situation from treating infertility.","source":"nice-ng257","quote":"For NHS-funded fertility preservation, do not apply the eligibility criteria used for conventional fertility treatment, including the lower age limit.","grade":"[2013, amended 2026]"}],"bestInClass":{"statement":"Discuss fertility before treatment with everyone at risk and refer promptly (NICE NG257 2026; ASCO 2025); offer sperm, egg or embryo cryopreservation, and consider ovarian tissue cryopreservation when those are not feasible (NICE [2026]). For premenopausal women having pelvic radiotherapy, ovarian transposition is an established option (ASCO 2025) that ESHRE (2020) supports weakly and only without chemotherapy (WEAK, low certainty), excluding women with reduced ovarian reserve or a risk of ovarian metastases. Where done, the ovaries go at least 4 cm from the field or 1.5 cm above the iliac crest, marked with clips (2026 review). NICE NG257 does not mention ovarian transposition; the guidelines differ on whether chemotherapy alongside radiotherapy rules it out (ESHRE limits it to radiotherapy without chemotherapy; ASCO's abstract sets no such limit).","sources":["nice-ng257","asco-fp-2025","eshre-2020","ot-review-2026"]},"variants":[{"name":"Transposition alongside chemoradiotherapy","differs":"Many women with cervical, rectal or anal cancer have chemotherapy with their radiotherapy. ESHRE's recommendation covers radiotherapy without chemotherapy; the 2026 review reports transposition in these settings with lower success when chemotherapy is added.","evidence":"Observational series; ovarian function preserved in about 50% to 65% after external beam radiotherapy for cervical cancer, lower with adjuvant chemotherapy (review); 61% after external beam radiotherapy in a 2022 meta-analysis of 29 studies.","sources":["eshre-2020","ot-review-2026","ot-meta-2022"]},{"name":"Transposition in rectal and anal cancer","differs":"Higher baseline risk of ovarian metastasis than in cervical cancer (about 1% to 8%, around 5% in premenopausal women), so the 2026 review judges the risks may outweigh the benefits in locally advanced disease.","evidence":"Review of retrospective data; no ovarian metastases after transposition reported in this subgroup.","sources":["ot-review-2026"]},{"name":"Placing the ovaries behind the uterus (Hodgkin lymphoma)","differs":"Older technique for lymphoma fields in which the uterus shields the ovaries; most successful pregnancies after transposition and pelvic radiotherapy were in Hodgkin lymphoma with an inverted Y field and a lead shield to the uterus.","evidence":"Historical case series, cited in the 2026 review.","sources":["ot-review-2026"]},{"name":"Opportunistic salpingectomy at transposition","differs":"Removing the fallopian tubes at the same operation to lower the later risk of ovarian cancer, which the review says should be considered.","evidence":"Review citing data that salpingectomy can reduce ovarian cancer risk by up to 65%; not specific to transposition.","sources":["ot-review-2026"]}],"grades":[{"claim":"Ovarian transposition before pelvic radiotherapy without chemotherapy","grade":"WEAK ⊕⊕◯◯","source":"eshre-2020"},{"claim":"Not for women with reduced ovarian reserve or at risk of ovarian metastases","grade":"GPP","source":"eshre-2020"},{"claim":"Provide decision aids to patients considering fertility preservation","grade":"STRONG ⊕⊕◯◯","source":"eshre-2020","quote":"It is recommended to provide decision aids to patients who are considering FP (Peate et al., 2009; Anazodo et al., 2019; Wang et al., 2019)."},{"claim":"Ovarian transposition is an established fertility preservation method for females","grade":"as printed in the abstract (grade not read)","source":"asco-fp-2025","quote":"For females, established FP methods should be offered, including embryo, oocyte, and ovarian tissue cryopreservation (OTC), ovarian transposition, and conservative gynecologic surgery."},{"claim":"Offer sperm cryopreservation before treatment likely to cause infertility","grade":"[2026]","source":"nice-ng257"}],"sources":[{"key":"nice-ng257","label":"Fertility problems: assessment and treatment (NG257), section 1.53 Fertility preservation for medical indications (published 31 March 2026)","publisher":"NICE","year":2026,"url":"https://www.nice.org.uk/guidance/ng257/chapter/Fertility-preservation-for-medical-indications","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended ([2026], [2013, amended 2026]).","read":"full-text","accessed":"2026-11-11"},{"key":"eshre-2020","label":"ESHRE guideline: female fertility preservation","publisher":"European Society of Human Reproduction and Embryology (Human Reproduction Open)","year":2020,"url":"https://doi.org/10.1093/hropen/hoaa052","doi":"10.1093/hropen/hoaa052","gradingScheme":"GRADE: recommendations STRONG or WEAK with certainty of evidence from ⊕⊕⊕⊕ (high) to ⊕◯◯◯ (very low); GPP good practice point; RESEARCH ONLY.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-fp-2025","label":"Fertility Preservation in People With Cancer: ASCO Guideline Update","publisher":"American Society of Clinical Oncology (Journal of Clinical Oncology)","year":2025,"url":"https://doi.org/10.1200/JCO-24-02782","doi":"10.1200/JCO-24-02782","gradingScheme":"ASCO guideline methodology (evidence quality and recommendation strength; full text not read).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-fp-2020","label":"Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines","publisher":"European Society for Medical Oncology (Annals of Oncology)","year":2020,"url":"https://doi.org/10.1016/j.annonc.2020.09.006","doi":"10.1016/j.annonc.2020.09.006","read":"not-reachable","accessed":"2026-11-11"},{"key":"ot-review-2026","label":"The role of ovarian transposition prior to pelvic radiation: A review","publisher":"Lim et al., Gynecologic Oncology Reports","year":2026,"url":"https://doi.org/10.1016/j.gore.2026.102079","doi":"10.1016/j.gore.2026.102079","gradingScheme":"Narrative review; no grades.","read":"full-text","accessed":"2026-11-11"},{"key":"ot-meta-2022","label":"Outcomes of ovarian transposition in cervical cancer; an updated meta-analysis","publisher":"BMC Women's Health","year":2022,"url":"https://doi.org/10.1186/s12905-022-01887-8","doi":"10.1186/s12905-022-01887-8","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2020 fertility preservation guideline could not be read: Europe PMC holds no text for it.","The ASCO 2025 update was read as an abstract only, so its grades and its detail on ovarian transposition are not quoted.","NICE NG257 does not address ovarian transposition or gonadal shielding; no UK guideline found sets out when transposition should be offered.","Testicular shielding and minimising testicular dose during pelvic radiotherapy were not covered by any source read here.","The evidence for transposition is observational, with wide variation in technique, dose and outcome definitions; no randomised trial exists.","The 2022 meta-analysis reports some confidence intervals that do not fit their point estimates in the abstract; only its 61% figure after external beam radiotherapy is used here."]},{"id":"paediatric-fever-and-neutropenia","kind":"protocol","name":"Fever and neutropenia in children with cancer or after stem cell transplant","aka":["paediatric febrile neutropenia","pediatric fever and neutropenia","neutropenic fever in children","paediatric neutropenic sepsis","FN in children"],"tldr":"A child having cancer treatment who gets a fever, or seems unwell, needs to be seen in hospital straight away, using the team's number. There blood cultures are taken from every channel of the central line and one strong antibiotic is started through a drip. Children at low risk may finish at home or by mouth, and antibiotics can often stop after two days if cultures stay clear.","summary":"The International Pediatric Fever and Neutropenia Guideline Panel's 2023 update (79 randomised trials, GRADE) covers patients aged 0 to 18 receiving chemotherapy for cancer and recipients of haematopoietic cell transplant, and is endorsed by the Children's Oncology Group. Adopt a validated paediatric risk stratification rule (strong, low). Take blood cultures from all lumens of a central venous catheter at onset (strong, low); a peripheral culture alongside is conditional, because it adds 12% of bacteraemias but causes pain and contaminants. Urine where a clean-catch specimen is readily available (conditional); chest radiograph only with respiratory signs (strong, moderate).\n\nHigh-risk episodes get monotherapy with an antipseudomonal beta-lactam, a fourth-generation cephalosporin or a carbapenem (strong, high); a second anti-Gram-negative agent or a glycopeptide is reserved for instability, suspected resistance or high-resistance centres. A new good practice statement asks for therapy as soon as possible in the clinically unstable child, ideally much sooner than an hour after presentation; the panel could not agree a time target for well, low-risk children. Low-risk episodes may be managed as outpatients or with oral antibiotics where the infrastructure allows (conditional). Antibiotics stop at 48 hours with negative cultures once the child has been well and afebrile for 24 hours, with marrow recovery (strong) or, new in 2023, without it in low-risk FN (conditional). For fever lasting 96 hours or more in children at high risk of invasive fungal disease: CT chest (strong), consider abdominal ultrasound, do not use beta-D-glucan or fungal PCR, and start caspofungin or liposomal amphotericin B (strong, high) unless a pre-emptive approach is chosen. NICE CG151, for any age, recommends piperacillin with tazobactam alone first and names the modified Alexander rule for children under 18.","asOf":"2026-11-11","links":[],"tags":["protocol","paediatric","neutropenic-sepsis"],"related":["febrile-neutropenia-first-hour"],"cancers":["childhood-cancers","all-leukemia","aml"],"sections":["supportive-care"],"technologies":["allogeneic-hsct","implanted-ports"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["nice"],"pathways":[],"terms":["febrile-neutropenia","neutropenia","central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer treatment can leave a child with few white blood cells to fight germs. A fever during treatment is an emergency. Ring the cancer team's number and go to hospital. The child will have blood tests and an antibiotic quickly.","domain":"paediatric","setting":{"who":["patient-or-carer","nurse","doctor","emergency-team"],"where":["home","telephone-triage","emergency-department","ward","outpatient-clinic"]},"population":"Children and young people aged 0 to 18 receiving chemotherapy for cancer, and recipients of haematopoietic cell transplant, as the 2023 international guideline scopes it. Adults are covered by the adult first-hour protocol.","trigger":"A child having chemotherapy or after a stem cell transplant has a fever, or becomes unwell, while neutropenic or likely to be.","steps":[{"action":"Before treatment starts, give the family written and spoken information on infection during treatment and the 24-hour number to ring","why":"Most fevers start at home, so parents need to know what to look for and whom to call before it happens.","source":"nice-cg151","quote":"Provide patients having anticancer treatment and their carers with written and oral information, both before starting and throughout their anticancer treatment, on:"},{"action":"If the child is unstable, start the guideline's empiric antibiotic as soon as possible while other measures to stabilise them are taken","why":"A child with a serious infection and few white cells can get worse within hours, and early antibiotics are what improve survival.","source":"ipfn-2023","quote":"For febrile patients who are clinically unstable, initiate FN CPG-consistent empiric antibacterial therapy as soon as possible.","grade":"Good practice statement"},{"action":"Stratify the episode as high or low risk with a validated paediatric rule, and use it to decide the rest of the care","why":"Risk decides who needs intravenous antibiotics in hospital and who can be treated more lightly, at home or by mouth.","source":"ipfn-2023","quote":"Adopt a validated risk stratification strategy and incorporate it into routine clinical management","grade":"strong recommendation, low-quality evidence"},{"action":"Take blood cultures from every lumen of the central venous catheter at the onset of the fever","why":"Germs can sit in one channel of the line and not another; sampling all of them finds more infections.","source":"ipfn-2023","quote":"Obtain blood cultures at the onset of FN from all lumens of central venous catheters","grade":"strong recommendation, low-quality evidence"},{"action":"Consider a peripheral blood culture as well as the line cultures","why":"In the panel's review, 12% of true bloodstream infections were found only in the peripheral culture; it is conditional because it hurts and it is not known whether finding them changes the outcome.","source":"ipfn-2023","quote":"Consider obtaining peripheral blood cultures concurrent with central venous catheter cultures","grade":"conditional recommendation, moderate-quality evidence"},{"action":"Consider urinalysis and urine culture where a clean-catch, mid-stream sample is easy to get, without delaying the antibiotic","why":"Urine infections in these children often cause no symptoms; NICE asks for urinalysis in all children under 5.","source":"ipfn-2023","quote":"Consider urinalysis and urine culture in patients where a clean-catch, mid-stream specimen is readily available","grade":"conditional recommendation, low-quality evidence"},{"action":"Take a chest X-ray only if the child has breathing signs or symptoms","why":"Pneumonia is very rare without chest symptoms, and leaving out the X-ray in those children did no harm.","source":"ipfn-2023","quote":"Obtain chest radiography only in patients with respiratory signs or symptoms","grade":"strong recommendation, moderate-quality evidence"},{"action":"In high-risk fever and neutropenia, give one antipseudomonal beta-lactam, fourth-generation cephalosporin or carbapenem on its own, chosen by local resistance patterns","why":"Twelve trials found adding an aminoglycoside did not reduce treatment failure or deaths, so one drug is enough for most children.","source":"ipfn-2023","quote":"Use monotherapy with an antipseudomonal β-lactam, a fourth-generation cephalosporin or a carbapenem as empiric antibacterial therapy in pediatric high-risk FN","grade":"strong recommendation, high-quality evidence"},{"action":"Add a second anti-Gram-negative drug or a glycopeptide only for a child who is unstable, a suspected resistant infection, or a centre with high resistance","why":"Extra antibiotics add side effects and resistance without helping the stable child.","source":"ipfn-2023","quote":"Reserve addition of a second anti-Gram-negative agent or a glycopeptide for patients who are clinically unstable, when a resistant infection is suspected, or for centers with a high rate of resistant pathogens","grade":"strong recommendation, moderate-quality evidence"},{"action":"In low-risk fever and neutropenia, consider treatment at home or a step down to home, where careful monitoring and follow-up are in place","why":"Five trials found no difference in failure or death and almost four fewer days in hospital, provided the family can reach the team and come back quickly.","source":"ipfn-2023","quote":"Consider initial or step-down outpatient management if the infrastructure is in place to ensure careful monitoring and follow-up","grade":"conditional recommendation, moderate-quality evidence"},{"action":"Consider oral antibiotics for a low-risk child who can reliably take them by mouth","why":"Oral treatment worked as well as intravenous in the trials, but readmission was more common, so it is offered rather than required.","source":"ipfn-2023","quote":"Consider oral antibacterial therapy administration if the patient is able to tolerate this route of administration reliably","grade":"conditional recommendation, moderate-quality evidence"},{"action":"Do not broaden the antibiotics for persistent fever alone in a child who is clinically stable; escalate if the child becomes unstable","why":"Fever on its own often settles; changing drugs adds harm. Instability is the signal to widen cover.","source":"ipfn-2023","quote":"Do not broaden the initial empiric antibacterial regimen based solely on persistent fever in patients who are clinically stable","grade":"strong recommendation, low-quality evidence"},{"action":"Stop the antibiotics once the child has been well and without fever for 24 hours, the blood cultures are negative at 48 hours, and the marrow is recovering","why":"The risk of the fever coming back is very low at this point, and every extra day of antibiotics has costs.","source":"ipfn-2023","quote":"In both high-risk and low-risk FN patients who have been clinically well and afebrile for at least 24 hours, discontinue empiric antibacterial therapy if blood cultures remain negative at 48 hours if there is evidence of marrow recovery","grade":"strong recommendation, low-quality evidence"},{"action":"In low-risk episodes, consider stopping at 48 hours on the same terms even before the marrow recovers","why":"New in 2023: trials showed stopping was as safe as continuing in low-risk children, moving the point from 72 to 48 hours.","source":"ipfn-2023","quote":"In patients with low-risk FN who have been clinically well and afebrile for at least 24 hours, consider discontinuation of empiric antibacterial therapy if blood cultures remain negative at 48 hours despite no evidence of marrow recovery","grade":"conditional recommendation, moderate-quality evidence"},{"action":"If fever lasts 96 hours or more in a child at high risk of fungal infection, do a CT of the lungs","why":"The lungs are the commonest site of fungal infection, and CT shows the typical signs.","source":"ipfn-2023","quote":"Perform computed tomography (CT) of lungs","grade":"strong recommendation, low-quality evidence"},{"action":"Do not use beta-D-glucan or fungal PCR in blood to guide antifungal treatment at this point","why":"These tests gave wrong positive results too often (positive predictive values of 49% and 17%) to be useful.","source":"ipfn-2023","quote":"Do not use fungal polymerase chain reaction testing in blood","grade":"strong recommendation, moderate-quality evidence"},{"action":"For high-risk children with fever of 96 hours or more despite broad antibiotics, start caspofungin or liposomal amphotericin B, unless a pre-emptive approach is chosen","why":"These two worked equally well in trials, and liposomal amphotericin harms the kidneys less than the older form.","source":"ipfn-2023","quote":"In IFD high-risk patients with prolonged (≥ 96 hours) FN unresponsive to broad-spectrum antibacterial therapy, initiate caspofungin or liposomal amphotericin B for empiric antifungal therapy unless a pre-emptive antifungal therapy approach is chosen","grade":"strong recommendation, high-quality evidence"}],"bestInClass":{"statement":"The International Pediatric Fever and Neutropenia Guideline Panel's 2023 update, endorsed by the Children's Oncology Group in May 2023, is the only current guideline built on paediatric trials alone and is the standard to follow: validated risk stratification, cultures from every lumen, single-agent antipseudomonal therapy for high-risk episodes, outpatient or oral options for low-risk ones, and stopping at 48 hours once well and afebrile for 24 hours. On the first drug, NICE CG151 (written for any age) is narrower and names piperacillin with tazobactam alone, while the international panel allows any antipseudomonal beta-lactam, fourth-generation cephalosporin or carbapenem by local epidemiology; both advise against a routine aminoglycoside or glycopeptide. On timing, NICE says immediately with no clock, the international panel says as soon as possible for the unstable child (ideally well inside an hour) and could not agree a target for well, low-risk children, some preferring to wait for the neutrophil count. NICE asks for urinalysis in every child under 5; the panel makes urine conditional on an easy clean-catch sample.","sources":["ipfn-2023","cog-fn-2023","nice-cg151"]},"variants":[{"name":"Piperacillin with tazobactam as the single first antibiotic (NICE CG151, all ages)","differs":"Names one drug, piperacillin with tazobactam, as the first empiric antibiotic, asks for urinalysis in all children aged under 5, and names the modified Alexander rule as an example of a risk score for children under 18. NICE noted at publication that piperacillin with tazobactam had no UK marketing authorisation for children under 2.","evidence":"NICE does not grade recommendations; its evidence review for monotherapy is in the adult protocol. The international panel's broader choice rests on 12 paediatric trials of monotherapy against combination therapy.","sources":["nice-cg151","ipfn-2023"]},{"name":"Waiting for the neutrophil count in well, low-risk children","differs":"Some centres give the first antibiotic only once the count confirms neutropenia, in children who look well and are at low risk; others give it before the count. The international panel was split and made no statement, asking institutions to speed up the count.","evidence":"No graded recommendation either way; the panel names it as needing more research.","sources":["ipfn-2023"]},{"name":"Pre-emptive rather than empiric antifungal therapy","differs":"In non-transplant children at high risk of fungal infection who are not on mould-active prophylaxis, antifungal treatment for prolonged fever is held until tests or imaging suggest fungal infection, instead of being started on fever alone.","evidence":"Conditional recommendation, moderate-quality evidence, from one trial in which pre-emptive therapy shortened antifungal use (median 6 against 11 days) with no difference in fungal infection; it excluded transplant recipients and children on voriconazole or posaconazole.","sources":["ipfn-2023"]}],"grades":[{"claim":"Validated risk stratification in routine care","grade":"strong recommendation, low-quality evidence","source":"ipfn-2023"},{"claim":"Blood cultures from all lumens of a central venous catheter","grade":"strong recommendation, low-quality evidence","source":"ipfn-2023"},{"claim":"Monotherapy for high-risk fever and neutropenia","grade":"strong recommendation, high-quality evidence","source":"ipfn-2023"},{"claim":"Outpatient or step-down management in low-risk fever and neutropenia","grade":"conditional recommendation, moderate-quality evidence","source":"ipfn-2023"},{"claim":"Stopping antibiotics at 48 hours in low-risk fever and neutropenia without marrow recovery","grade":"conditional recommendation, moderate-quality evidence","source":"ipfn-2023"},{"claim":"Caspofungin or liposomal amphotericin B for prolonged fever in high-risk children","grade":"strong recommendation, high-quality evidence","source":"ipfn-2023"},{"claim":"Do not use beta-D-glucan to guide empiric antifungal management","grade":"strong recommendation, low-quality evidence","source":"ipfn-2023","quote":"Do not use β-D-glucan (strong recommendation, low-quality evidence)."},{"claim":"Antibiotics as soon as possible in the clinically unstable child","grade":"Good practice statement","source":"ipfn-2023"}],"sources":[{"key":"ipfn-2023","label":"Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update","publisher":"International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology","year":2023,"url":"https://europepmc.org/article/PMC/PMC10022858","doi":"10.1200/jco.22.02224","gradingScheme":"GRADE: recommendations strong or conditional, evidence high, moderate, low or very low, printed together after each recommendation; good practice statements are ungraded.","read":"full-text","accessed":"2026-11-11"},{"key":"cog-fn-2023","label":"Guideline for the Management of Fever and Neutropenia in Children with Cancer and/or Undergoing Hematopoietic Stem-Cell Transplantation (COG endorsement, version date 14 July 2023)","publisher":"Children's Oncology Group","year":2023,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_FN_Guideline_Document-14JULY2023-new-logo.pdf","gradingScheme":"Reprints the source guideline's GRADE strength and quality for each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-cg151","label":"Neutropenic sepsis: prevention and management in people with cancer (CG151), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg151/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'do not offer', 'consider').","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The guideline does not define the fever or neutrophil thresholds that start the pathway; those come from local or national protocols and differ between countries.","The guideline's Data Supplement, which lists the validated risk rules and trial details, was not read.","No time-to-antibiotic target is set for clinically well children; the panel was divided on whether to wait for the neutrophil count in low-risk children.","The safety of stopping antibiotics early in high-risk children with a respiratory virus is named by the panel as a knowledge gap.","It is uncertain whether a child already on mould-active prophylaxis who develops prolonged fever should switch antifungal or continue the same one.","NICE NG254 (suspected sepsis in under 16s) was not read for this protocol."]},{"id":"colorectal-cancer-follow-up-after-curative-treatment","kind":"protocol","name":"Follow-up after curative treatment for colorectal cancer","aka":["bowel cancer follow-up","colorectal cancer surveillance","CEA and CT surveillance after bowel cancer","colonoscopy after bowel cancer surgery"],"tldr":"After an operation to cure bowel cancer, you will usually have regular blood tests (CEA) and CT scans for the first 3 years, and a colonoscopy about a year after surgery. The aim is to find a return early enough to operate again. How often you are tested differs between countries, and the large trials found that testing more often does not, on average, help people live longer.","summary":"NICE NG151 offers follow-up for the first 3 years after potentially curative surgery for non-metastatic colorectal cancer, with serum carcinoembryonic antigen (CEA) and CT of the chest, abdomen and pelvis, and does not set a frequency. The American Cancer Society (2015) endorses the NCCN schedule for stages I to III: history and examination and CEA every 3 to 6 months for 2 years, then every 6 months to 5 years; CT every 12 months; colonoscopy at 1 year. ASCO (2013) gives CEA every 3 to 6 months for 5 years and CT annually for 3 years in most cases. Colonoscopy is at 1 year after surgery in all these sources; the next is after 3 more years (BSG/ACPGBI 2020, NCCN) or 5 years (ASCO). PET-CT is not a surveillance test.\n\nThe evidence for intensity is weak: the 2019 Cochrane review of 19 randomised trials (13,216 people) found that intensive follow-up made little or no difference to overall survival (hazard ratio 0.91, high-quality evidence), although it nearly doubled salvage surgery with curative intent. Surveillance is only for people fit for further surgery or treatment, and colonoscopic surveillance stops in general at about 75 or with a life expectancy under 10 years (BSG/ACPGBI). People who had sphincter-preserving surgery should be told about low anterior resection syndrome and how to get help (NICE).","asOf":"2026-11-11","links":[],"tags":["protocol","follow-up","survivorship"],"related":[],"cancers":["colorectal"],"sections":["supportive-care"],"technologies":["cea-surveillance-colorectal","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":["nice","asco"],"pathways":[],"terms":["low-anterior-resection-syndrome","colonoscopy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After bowel cancer surgery you have check-ups: blood tests, scans and a camera test of the bowel. These look for the cancer coming back. Tell your team about new symptoms between check-ups.","domain":"survivorship","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","community","telephone-triage"]},"population":"Adults who have had potentially curative treatment for non-metastatic colorectal cancer (stages I to III). Stage IV after resection of metastases with no evidence of disease has a more intensive schedule in the ACS and NCCN tables, mentioned as a variant. Hereditary syndromes such as Lynch syndrome have their own colonoscopy schedules and are not covered here.","trigger":"Curative surgery and any adjuvant treatment are complete.","steps":[{"action":"Decide with the person whether surveillance suits them, given their fitness for further surgery and their wishes","why":"Tests only help if finding a return would lead to treatment; someone who could not have further surgery or treatment gains nothing from them.","source":"acs-2015","quote":"Testing should only be performed in patients in whom the results will change treatment decisions."},{"action":"Offer follow-up for at least the first 3 years, with CEA blood tests and CT of the chest, abdomen and pelvis","why":"Most returns happen in the first few years, and finding them with CEA and liver imaging makes them more likely to be operable.","source":"nice-ng151","quote":"For people who have had potentially curative surgical treatment for non-metastatic colorectal cancer, offer follow-up for detection of local recurrence and distant metastases for the first 3 years. Follow-up should include serum carcinoembryonic antigen (CEA) and CT scan of the chest, abdomen and pelvis."},{"action":"See the person and check CEA every 3 to 6 months for the first 2 years, then every 6 months up to 5 years for T2 or larger tumours","why":"This is the frequency in the American schedules; people at higher risk of return are seen at the more frequent end.","source":"acs-2015","quote":"Recommendation 4: Carcinoembryonic antigen (CEA) testing should be conducted every 3–6 months for the first 2 years and every 6 months for years 3–5 for those with T2 or greater lesions. CEA is not recommended after 5 years.","grade":"2A"},{"action":"Do a CT of the chest, abdomen and pelvis every 12 months; for 3 years under ASCO, up to 5 years for higher-risk and stage III disease under NCCN","why":"Yearly scans find spread to the liver or lungs while it may still be removable.","source":"acs-2015","quote":"In contrast to the NCCN recommendations, ASCO recommends CT scans of the abdomen and chest annually for only 3 years for CRC survivors.","grade":"2A"},{"action":"Do a colonoscopy within a year of diagnosis or surgery, sooner if the whole bowel was not seen before the operation","why":"It finds polyps or a second cancer that were missed or have grown since, and clears the bowel.","source":"bsg-2020","quote":"We recommend that patients who have undergone a potentially curative CRC resection should have a clearance colonoscopy within a year of their diagnosis","grade":"GRADE of evidence: low; strength of recommendation: strong"},{"action":"After a clear colonoscopy, repeat it after 3 more years, then decide further surveillance by the findings","why":"Polyps take years to turn into cancer, so a clear colonoscopy buys time before the next.","source":"bsg-2020","quote":"We recommend that once a clearance colonoscopy has been performed in the postoperative period in patients who have had a CRC resection, their next surveillance should be performed after an interval of 3 years.","grade":"GRADE of evidence: low; strength of recommendation: strong"},{"action":"Do not use PET-CT or routine blood counts and liver tests for surveillance, and stop routine CEA and CT after 5 years","why":"They add cost and false alarms without finding treatable returns earlier.","source":"acs-2015","quote":"After five years, routine CEA monitoring is not recommended After five years, routine CT scans are not recommended Routine use of PET/CT is not recommended for any stage","grade":"2A"},{"action":"Stop colonoscopic surveillance in general at about 75 or when life expectancy is under 10 years","why":"A new polyp takes many years to become a cancer that causes harm, so late surveillance rarely helps.","source":"bsg-2020","quote":"surveillance should only be performed in people whose life-expectancy is greater than 10 years, and in general not in people older than about 75 years.","grade":"GRADE of evidence: low; strength of recommendation: weak"},{"action":"Before sphincter-preserving surgery, explain low anterior resection syndrome and tell the person to seek help from their GP if it happens","why":"Bowel urgency, frequency and leakage after rectal surgery are common and treatable, and may start after discharge.","source":"nice-ng151","quote":"Give information on low anterior resection syndrome (LARS) to people who will potentially have sphincter-preserving surgery."},{"action":"Give a written plan saying who does each test, and when, so the GP or nurse can follow it","why":"Follow-up is often shared between hospital and primary care, and missed tests happen when nobody knows whose job they are.","source":"asco-2013","quote":"A treatment plan from the specialist should have clear directions on appropriate follow-up by a nonspecialist."}],"bestInClass":{"statement":"All sources agree on surveillance with CEA and CT for the first years after curative treatment and a colonoscopy within a year; they differ on frequency and length. NICE NG151 (2020) sets 3 years with CEA and CT and no frequency; ASCO (2013) sets CEA every 3 to 6 months for 5 years, CT annually for 3 years, and colonoscopy at 1 year then every 5 years; the American Cancer Society (2015) endorses NCCN's longer schedule, with CT every 12 months up to 5 years for higher-risk stage I to III disease and colonoscopy at 1 and 3 years; BSG/ACPGBI (2020) set colonoscopy at 1 year and 3 years after that. The best-supported reading of the trials (Cochrane 2019, 19 randomised trials, high-quality evidence) is that intensive follow-up finds more returns that can be operated on but makes little or no difference to overall survival, which supports the shorter, lighter end of these schedules for most people. ESMO's 2020 colon and 2025 rectal guidelines could not be read.","sources":["nice-ng151","nice-ng151-rationale","acs-2015","asco-2013","bsg-2020","cochrane-2019","esmo-colon-2020","esmo-rectal-2025"]},"variants":[{"name":"NCCN schedule endorsed by the American Cancer Society","differs":"CT every 12 months for stages I to III in years 1 and 2 and up to 5 years for higher-risk and stage III disease; colonoscopy at 1 year, at 3 years and then every 5 years; proctoscopy every 6 months for rectal cancer; and, for stage IV with no evidence of disease, CT every 3 to 6 months in years 1 and 2.","evidence":"Level of evidence 2A for the whole table, as printed by the ACS; the ACS notes that ASCO does not recommend the 3-year colonoscopy.","sources":["acs-2015"]},{"name":"ASCO endorsement of Cancer Care Ontario (2013)","differs":"History, examination and CEA every 3 to 6 months for 5 years; CT of abdomen and chest annually for 3 years in most cases; colonoscopy 1 year after surgery and then every 5 years, guided by the previous one.","evidence":"An endorsement of a guideline built on the same trials; read as an abstract.","sources":["asco-2013"]},{"name":"Three years and no frequency (NICE NG151)","differs":"Sets the length (the first 3 years) and the tests (CEA and CT of chest, abdomen and pelvis) and leaves the frequency to local practice; leaves colonoscopic surveillance to the BSG and ACPGBI guidance.","evidence":"NICE's committee found that recurrence was more likely to be resectable with regular follow-up including CEA and liver imaging, and found no evidence to change its 2011 recommendation.","sources":["nice-ng151","nice-ng151-rationale"]},{"name":"Ultrasound-led follow-up, CEA only if raised before treatment (German S3 guideline)","differs":"Schedules history and examination and abdominal ultrasound at intervals, with CT at a single point and the choice between CT and ultrasound made individually; re-assesses CEA after curative treatment where it was raised before; colonoscopy within 6 months of surgery if the bowel was not fully examined before; length of follow-up, 3 or 5 years, decided individually.","evidence":"The 2025 English-language summary of the German S3 guideline cites the same Cochrane review and an earlier meta-analysis that did find a benefit of intensive follow-up. Its table of months lost its column positions in the text read, so the exact months for each test are not given here.","sources":["german-s3-2025"]}],"grades":[{"claim":"Surveillance colonoscopy on a risk-based schedule","grade":"2A","source":"acs-2015","quote":"Recommendation 2: CRC survivors should receive surveillance colonoscopy according to a schedule based on based on risk. Level of Evidence = 2A"},{"claim":"History and examination every 3 to 6 months for 2 years, every 6 months to 5 years, then annually","grade":"2A","source":"acs-2015","quote":"Recommendation 3: CRC survivors should receive a history and physical every 3–6 months in the first 2 years and every 6 months in years 3–5, and annually after 5 years."},{"claim":"CT of chest, abdomen and pelvis every 12 months for stages I to III, up to 5 years","grade":"2A","source":"acs-2015","quote":"Recommendation 5: Chest/abdominal/pelvic CT should be performed every 12 months (stages I-III) or every 3–6 months (stage IV, NED) for up to 5 years."},{"claim":"Clearance colonoscopy within a year of diagnosis after curative resection","grade":"GRADE of evidence low; strength strong","source":"bsg-2020"},{"claim":"Next colonoscopy 3 years after the clearance colonoscopy","grade":"GRADE of evidence low; strength strong","source":"bsg-2020"},{"claim":"Intensive follow-up and overall survival","grade":"high-quality evidence (GRADE): little or no difference","source":"cochrane-2019","quote":"Overall survival: we found intensive follow-up made little or no difference (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.80 to 1.04: I² = 18%; high-quality evidence)."},{"claim":"Intensive follow-up and salvage surgery with curative intent","grade":"high-quality evidence (GRADE): more frequent","source":"cochrane-2019","quote":"Salvage surgery with curative intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98, 95% CI 1.53 to 2.56; I² = 31%; high-quality evidence)."}],"sources":[{"key":"nice-ng151","label":"Colorectal cancer (NG151), recommendations","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'consider'). Published January 2020, last updated December 2021.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng151-rationale","label":"Colorectal cancer (NG151), rationale and impact","publisher":"NICE","year":2020,"url":"https://www.nice.org.uk/guidance/ng151/chapter/Rationale-and-impact","read":"full-text","accessed":"2026-11-11"},{"key":"acs-2015","label":"American Cancer Society Colorectal Cancer Survivorship Care Guidelines","publisher":"American Cancer Society, CA: A Cancer Journal for Clinicians","year":2015,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5385892/","doi":"10.3322/caac.21286","gradingScheme":"Each recommendation printed with a level of evidence on the scheme the ACS used (for example 2A); the surveillance table carries 2A as a whole.","read":"full-text","accessed":"2026-11-11"},{"key":"bsg-2020","label":"British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines","publisher":"BSG, ACPGBI and PHE, Gut","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6984062/","doi":"10.1136/gutjnl-2019-319858","gradingScheme":"GRADE: quality of evidence (high, moderate, low, very low) and strength of recommendation (strong or weak) printed after each statement; good practice recommendations where GRADE was inappropriate.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2013","label":"Follow-up care, surveillance protocol, and secondary prevention measures for survivors of colorectal cancer: ASCO clinical practice guideline endorsement","publisher":"ASCO, Journal of Clinical Oncology","year":2013,"url":"https://europepmc.org/abstract/MED/24220554","doi":"10.1200/JCO.2013.50.7442","read":"abstract","accessed":"2026-11-11"},{"key":"cochrane-2019","label":"Follow-up strategies for patients treated for non-metastatic colorectal cancer","publisher":"Cochrane Database of Systematic Reviews","year":2019,"url":"https://europepmc.org/abstract/MED/31483854","doi":"10.1002/14651858.CD002200.pub4","gradingScheme":"GRADE quality of evidence for each outcome (high, moderate, low, very low).","read":"abstract","accessed":"2026-11-11"},{"key":"german-s3-2025","label":"Clinical Practice Guideline: Colorectal Cancer: Diagnosis, Treatment, Prevention, and Long-Term Follow-Up Care","publisher":"Deutsches Ärzteblatt International (summary of the German S3 guideline)","year":2025,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12947252/","doi":"10.3238/arztebl.m2025.0196","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-colon-2020","label":"Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2020,"url":"https://doi.org/10.1016/j.annonc.2020.06.022","doi":"10.1016/j.annonc.2020.06.022","read":"not-reachable","accessed":"2026-11-11"},{"key":"esmo-rectal-2025","label":"Localised rectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2025,"url":"https://doi.org/10.1016/j.annonc.2025.05.528","doi":"10.1016/j.annonc.2025.05.528","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-acc-risk-stratified-follow-up"],"gaps":["ESMO's localised colon (2020) and localised rectal (2025) guidelines could not be read: Europe PMC holds no abstract for either and the publisher refused a script. Their schedules are not stated here.","NCCN's own guideline requires a login; its schedule is given here only as reproduced and endorsed in the American Cancer Society guideline of 2015, which may be older than the current NCCN version.","NICE sets no frequency for CEA or CT, and no source read compares, for example, 6-monthly with yearly CT in a trial.","The Cochrane review found harms of intensive follow-up and salvage treatment poorly reported, and that intensive follow-up probably makes little or no difference to quality of life, anxiety or depression.","No source read sets a CEA level that should trigger investigation."]},{"id":"breast-cancer-follow-up-after-treatment","kind":"protocol","name":"Follow-up after treatment for early breast cancer","aka":["breast cancer surveillance","breast cancer follow-up mammogram","follow-up after breast cancer surgery","breast cancer survivorship care"],"tldr":"After treatment for early breast cancer, the main test is a yearly mammogram, usually for 5 years and then through the national screening programme. Routine scans and blood tests are not recommended when you are well, because the evidence does not show they help. You should get a written plan saying who to contact and which symptoms to report.","summary":"NICE NG101 offers annual mammography for 5 years to everyone who has had or is being treated for breast cancer, including DCIS, and for women continued annually until they enter the national screening programme; no mammography of the soft tissues on the side of a mastectomy; and no routine ultrasound or MRI for surveillance. ASCO (2013) recommends history and physical examination every 3 to 6 months for the first 3 years, every 6 to 12 months in years 4 and 5, and annually after that, with the first post-treatment mammogram 1 year after the initial one and at least 6 months after radiotherapy. Both advise against routine blood tests, tumour markers and body imaging in people without symptoms; the ACS/ASCO survivorship guideline (2016) agrees.\n\nEvery person should have an agreed written care plan held by them and their GP, with named professionals, dates for review of adjuvant therapy, the surveillance mammography, symptoms to report and how to reach specialist care quickly (NICE). Primary care follow-up includes healthy lifestyle advice, monitoring for long-term effects of treatment, and support to keep taking endocrine therapy (ACS/ASCO). Bone density checks on aromatase inhibitors and lymphoedema care are covered by their own protocols.","asOf":"2026-11-11","links":[],"tags":["protocol","follow-up","survivorship"],"related":[],"cancers":["breast-cancer"],"sections":["supportive-care"],"technologies":["mammography","survivorship-care-plan"],"targets":[],"drugs":[],"companies":[],"institutions":["nice","asco"],"pathways":[],"terms":["dcis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After breast cancer treatment you have a mammogram every year. You do not need regular scans or blood tests if you feel well. Tell your team about any new lump or symptom.","domain":"survivorship","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","community"]},"population":"Adults who have completed primary treatment with curative intent for early or locally advanced breast cancer, or DCIS. The NHS screening programme rules in NG101 apply in England and Wales. People with metastatic breast cancer, and people at very high inherited risk who have their own MRI surveillance schedules, are not covered here.","trigger":"Primary treatment (surgery, with any chemotherapy and radiotherapy) is complete; endocrine therapy may continue.","steps":[{"action":"Give the person and their GP an agreed written care plan with named professionals, review dates, the mammogram schedule, symptoms to report and how to reach the specialist team","why":"Most returns are noticed by the person between appointments, so knowing what to look for and whom to call matters more than the visits themselves.","source":"nice-ng101","quote":"Ensure all people who have had treatment for breast cancer have an agreed, written care plan, recorded in their notes by a named healthcare professional (or professionals) from the multidisciplinary team. Give a copy to the person and to their GP."},{"action":"Offer a mammogram every year for 5 years, then for women continue yearly until they join the national breast screening programme","why":"Mammography finds a return in the treated breast or a new cancer in the other breast early.","source":"nice-ng101","quote":"Offer annual mammography for 5 years to all people who have had or are being treated for breast cancer, including DCIS."},{"action":"After breast-conserving surgery, time the first mammogram 1 year after the diagnostic one and at least 6 months after radiotherapy","why":"Changes from radiotherapy settle over months, and an early image is harder to read.","source":"asco-2013","quote":"For women who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy."},{"action":"Do not do mammography of the chest wall on the side of a mastectomy","why":"There is no breast tissue left to image there; changes are found by examination and symptoms.","source":"nice-ng101","quote":"Do not perform mammography of the ipsilateral soft tissues after mastectomy."},{"action":"Do not use ultrasound or MRI routinely for surveillance","why":"NICE found no reason to use them routinely for people at ordinary risk; they find more harmless changes that then need checking.","source":"nice-ng101","quote":"Do not routinely use ultrasound or MRI for post-treatment surveillance in people who have had treatment for invasive breast cancer or DCIS."},{"action":"Review history and examine every 3 to 6 months for 3 years, every 6 to 12 months in years 4 and 5, then yearly","why":"Regular review is a chance to check symptoms, side effects and whether endocrine therapy is being taken.","source":"asco-2013","quote":"Physical examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter."},{"action":"Do not order routine blood tests, tumour markers, bone scans, chest X-rays, CT or PET in someone who is well with a normal examination","why":"The evidence does not support these tests in people without symptoms, and a false alarm leads to more tests and worry.","source":"asco-2013","quote":"is not recommended for routine follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination."},{"action":"Advise a healthy weight, regular physical activity, and alcohol below 5 units a week","why":"These are linked with a lower risk of the cancer coming back.","source":"nice-ng101","quote":"Advise people who have had or are being treated for breast cancer that a healthy lifestyle is associated with a lower risk of recurrence, and that this should include:"},{"action":"In primary care, watch for long-term effects of treatment and support the person to keep taking endocrine therapy","why":"Long-term side effects affect daily life, and stopping endocrine therapy early loses part of its benefit.","source":"acs-asco-2016","quote":"Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy."}],"bestInClass":{"statement":"NICE NG101 (last updated 2025) and ASCO (2013, reaffirmed by ACS/ASCO in 2016) agree on the core: yearly mammography, clinical review, a written plan, and no routine blood tests, tumour markers or body imaging in people without symptoms. They differ in detail: NICE sets mammography yearly for 5 years and then hands over to the screening programme, and advises against routine ultrasound or MRI; ASCO sets a schedule of clinical examinations (every 3 to 6 months for 3 years, 6 to 12 months to year 5, then yearly) that NICE does not specify. The ESMO 2024 early breast cancer guideline could not be read.","sources":["nice-ng101","asco-2013","acs-asco-2016","esmo-2024"]},"variants":[{"name":"Scheduled clinical examinations (ASCO)","differs":"Sets a frequency for history and examination for life (every 3 to 6 months for 3 years, every 6 to 12 months for years 4 and 5, then yearly), where NICE sets no visit schedule and relies on the written plan and open access to the specialist team.","evidence":"ASCO's 2013 update found no new evidence that warranted changing its 2006 recommendations; ACS/ASCO (2016) say most evidence is not sufficient for a strong evidence-based recommendation. Read as abstracts.","sources":["asco-2013","acs-asco-2016"]},{"name":"Mammography handed to the screening programme after 5 years (NICE)","differs":"After 5 years of yearly mammography, women continue yearly until they enter the NHS Breast Screening Programme in England or Breast Test Wales, after which screening follows the programme's own interval.","evidence":"NICE recommendation [2009, amended 2023]; NICE does not grade recommendations.","sources":["nice-ng101"]}],"grades":[{"claim":"Annual mammography for 5 years after breast cancer, including DCIS","grade":"not graded (NICE); dated [2009, amended 2023]","source":"nice-ng101"},{"claim":"No routine ultrasound or MRI surveillance","grade":"not graded (NICE); dated [2009, amended 2023]","source":"nice-ng101"},{"claim":"Most survivorship recommendations","grade":"evidence not sufficient for a strong evidence-based recommendation (ACS/ASCO's own statement)","source":"acs-asco-2016","quote":"Most of the evidence is not sufficient to warrant a strong evidence-based recommendation."}],"sources":[{"key":"nice-ng101","label":"Early and locally advanced breast cancer: diagnosis and management (NG101), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'consider', 'do not') and each is dated, for example [2009, amended 2023]. Published July 2018, last updated April 2025.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2013","label":"Breast cancer follow-up and management after primary treatment: ASCO clinical practice guideline update","publisher":"ASCO, Journal of Clinical Oncology","year":2013,"url":"https://europepmc.org/abstract/MED/23129741","doi":"10.1200/JCO.2012.45.9859","read":"abstract","accessed":"2026-11-11"},{"key":"acs-asco-2016","label":"American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline","publisher":"American Cancer Society and ASCO, Journal of Clinical Oncology","year":2016,"url":"https://europepmc.org/abstract/MED/26644543","doi":"10.1200/JCO.2015.64.3809","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2024","label":"Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2024,"url":"https://doi.org/10.1016/j.annonc.2023.11.016","doi":"10.1016/j.annonc.2023.11.016","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-acc-risk-stratified-follow-up"],"gaps":["The ESMO 2024 early breast cancer guideline could not be read: Europe PMC holds no abstract and the publisher refused a script. Its follow-up schedule is not stated here.","ASCO's follow-up guideline dates from 2013 and reaffirms 2006 recommendations; no later ASCO follow-up guideline was found in Europe PMC.","The ACS/ASCO 2016 survivorship guideline was read only as an abstract, so its detailed recommendations on late effects are not given here.","No source read says how long yearly mammography should continue for men with breast cancer or for people outside a national screening programme after 5 years.","Women at high inherited risk (for example BRCA carriers) follow separate MRI surveillance schedules not covered here."]},{"id":"food-safety-and-neutropenic-diet","kind":"protocol","name":"Food safety during cancer treatment and the evidence against neutropenic diets","aka":["neutropenic diet","low-microbial diet","low-bacterial diet","clean diet","food restrictions during chemotherapy","food safety neutropenia","protective diet"],"tldr":"Strict lists of banned foods (the 'neutropenic diet') do not prevent infections in trials, in children or adults, and they make eating harder. What matters is ordinary food safety: clean hands and surfaces, raw meat kept apart, fruit and vegetables washed, meat and eggs cooked through, and no unpasteurised milk or cheese, mouldy food or unsafe water. Transplant teams may differ.","summary":"The 2025 POGO guideline, endorsed by the Children's Oncology Group, reviewed 8 randomised trials and suggests that food restrictions not be routinely used to prevent infection in children with cancer (conditional, moderate quality) or after autologous or allogeneic HCT (conditional, low quality), with a good practice statement to follow safe food handling, storing, preparation and consumption as set by applicable health authorities. ASCO (2022) does not recommend neutropenic diets to prevent infection in adults during active treatment. Meta-analysis of 6 randomised trials (Ma 2022) found no reduction in infection (risk ratio 1.13, 95% CI 0.97 to 1.31) or mortality, and a 2025 systematic review of 5 trials in adults having high-dose therapy found no benefit and a tendency to worse nutritional status. One older trial in 153 adults with AML or high-risk MDS found fewer bloodstream infections with restrictions; the POGO panel judged it indirect for children.\n\nThe older CDC/IDSA/ASBMT HCT guideline (2009) still recommends a low-microbial diet before engraftment (CIII, noting evidence is lacking) and a food-safety diet after it until immunosuppression stops; its safe handling advice (separate raw meat, wash produce, cook meat to a measured internal temperature, refrigerate leftovers within 2 hours) is what most food safety teaching uses. The items safe handling advice agrees on everywhere are unpasteurised milk and cheese, undercooked eggs and meat, mouldy food and possibly contaminated water.","asOf":"2026-11-11","links":[],"tags":["protocol","neutropenic-diet","food-safety","paediatric"],"related":["diet-alcohol-and-weight-during-cancer-treatment","neutropenic-precautions-and-daily-life"],"cancers":["childhood-cancers","aml","all-leukemia"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["asco"],"pathways":[],"terms":["neutropenia","febrile-neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"You do not need to give up fresh fruit and vegetables during cancer treatment. Wash them well. Cook meat and eggs fully. Avoid unpasteurised milk and cheese. Keep the kitchen clean. Ask your team if you have had a transplant.","domain":"infection-prevention","setting":{"who":["patient-or-carer","nurse","doctor","multidisciplinary-team"],"where":["home","ward","outpatient-clinic"]},"population":"Adults and children having chemotherapy, including during neutropenia, and recipients of autologous or allogeneic haematopoietic cell transplant. The POGO guideline covers ages 1 to 18; ASCO covers adults in active treatment. Transplant centres may keep stricter rules (variants).","trigger":"Cancer treatment that can lower the neutrophil count is planned, or a person or family asks what they can safely eat.","steps":[{"action":"Before treatment starts, teach the patient and whoever cooks for them safe food handling","why":"Food poisoning germs such as Salmonella and Campylobacter can cause severe infection when white cells are low; the teaching works best before the first course.","source":"hct-2009","quote":"This review and education should be done before the conditioning regimen (ie, chemotherapy and radiation) begins (BIII).","grade":"BIII"},{"action":"Follow the food safety advice of the local or national health authority for handling, storing, preparing and eating food","why":"This is the measure every guideline agrees on; local advice fits local foods and water.","source":"pogo-2025","quote":"Follow practices for safe food handling, storing, preparation and consumption outlined by applicable health authorities.","grade":"Good practice statement"},{"action":"Do not put children with cancer on a routine restrictive neutropenic diet","why":"Six trials in people having chemotherapy showed no consistent drop in infections, and restrictions can harm eating, nutrition and quality of life.","source":"pogo-2025","quote":"We suggest that food restrictions not be routinely used for the prevention of infections in paediatric patients with cancer (conditional recommendation, moderate quality evidence)","grade":"conditional recommendation, moderate quality evidence"},{"action":"Do not routinely restrict food for children after autologous or allogeneic stem cell transplant","why":"Two transplant trials found no benefit, though there are no trials in children after transplant.","source":"pogo-2025","quote":"We suggest that food restrictions not be routinely used for the prevention of infections in paediatric autologous HCT and allogeneic HCT recipients (conditional recommendation, low quality evidence)","grade":"conditional recommendation, low quality evidence"},{"action":"Do not recommend a neutropenic diet to adults during active cancer treatment","why":"ASCO's review found neutropenic diets did not lower the risk of infection.","source":"asco-2022","quote":"Neutropenic diets are not recommended to prevent infection in patients with cancer during active treatment."},{"action":"Keep raw meat, poultry, fish and seafood on separate boards and surfaces, and wash hands, boards and knives in warm soapy water after handling them","why":"Raw meat is the commonest source of the germs that cause food poisoning; keeping it apart stops them reaching food that will not be cooked.","source":"hct-2009","quote":"Persons preparing food should always use separate cutting boards or wash the board(s) with warm water and soap between cutting different food items (AIII).","grade":"AIII"},{"action":"Wash all fresh fruit and vegetables well under running water before eating","why":"Washing removes most of the soil and germs on produce, so fresh fruit and vegetables can stay in the diet.","source":"hct-2009","quote":"All fresh produce should be washed thoroughly under running water before serving (AIII)","grade":"AIII"},{"action":"Cook meat right through, checking the inside temperature with a food thermometer","why":"Colour is not a reliable guide; the temperature inside the meat is what shows germs have been killed.","source":"hct-2009","quote":"Persons cooking food for HCT recipients should follow established guidelines for monitoring internal cooking temperatures for meats, which is the only method for determining if meat has been adequately cooked (AII).","grade":"AII"},{"action":"Refrigerate leftovers within 2 hours of cooking and reheat them until steaming hot throughout","why":"Germs multiply in food left at room temperature; prompt cooling and thorough reheating stop them.","source":"hct-2009","quote":"refrigerate leftovers within 2 hours of cooking (AII)","grade":"AII"},{"action":"Avoid unpasteurised milk and cheese, undercooked eggs and meat, food with mould, and drinking water that may be contaminated","why":"These are the foods that food safety guidance treats as risky everywhere; other foods, such as sushi, depend on local context.","source":"pogo-2025","quote":"For some food items, safe food handling guidance should be consistent across jurisdictions, such as avoidance of unpasteurised milks and cheeses, undercooked eggs and meats, food with visible or introduced mould, and potentially contaminated drinking water."}],"bestInClass":{"statement":"Teach and follow ordinary food safety, and do not impose a restrictive neutropenic diet. For children with cancer and after transplant this is the POGO 2025 guideline endorsed by the Children's Oncology Group (conditional recommendations against routine food restrictions, moderate and low quality evidence, plus a good practice statement on food safety); for adults in active treatment it is ASCO 2022 (neutropenic diets not recommended). The older CDC/IDSA/ASBMT HCT guideline (2009) differs: it recommends a low-microbial diet before engraftment, while grading that CIII and saying evidence for its efficacy is lacking, and a food-safety diet after engraftment until immunosuppression ends. A randomised trial after HSCT in 222 adults (Stella 2023) found an unrestricted diet non-inferior to a protective diet, with higher patient satisfaction.","sources":["pogo-2025","cog-food-2025","asco-2022","hct-2009","stella-2023","ma-2022"]},"variants":[{"name":"Low-microbial diet before engraftment, then a food-safety diet (CDC/IDSA/ASBMT HCT guideline, 2009)","differs":"Restricts the diet of transplant recipients before engraftment, then keeps a list of foods to avoid (raw sprouts, fresh salsa, berries, unroasted raw nuts, soft and mould-ripened cheeses, raw honey and others) for 3 months after autologous transplant and, after allogeneic transplant, until all immunosuppression stops and live vaccines can be given.","evidence":"The low-microbial diet is graded CIII, with the guideline stating that evidence for its efficacy is lacking; many of the individual food bans are graded EII. Later trials and the 2025 POGO guideline do not support routine restrictions.","sources":["hct-2009","pogo-2025"]},{"name":"Transplant centres that keep a protective diet","differs":"Many centres still use a neutropenic or low-bacterial diet as standard after HSCT; the 2025 Nutrients review cites a European survey of 2015 and 2016 in which over 90% of centres in 23 countries did so.","evidence":"Five randomised trials in 510 adults on high-dose therapy found no advantage on any endpoint and a tendency to worse nutritional status (Nutrients 2025); the Stella 2023 trial found an unrestricted diet non-inferior after HSCT.","sources":["nutrients-2025","stella-2023"]},{"name":"Restrictions during AML induction in older adults","differs":"Some leukaemia units restrict uncooked foods during induction chemotherapy for acute myeloid leukaemia.","evidence":"One randomised trial of 153 patients (median age 64) with AML or high-risk MDS reported fewer bloodstream infections with food restriction (14% against 29%); the POGO panel judged it indirect for children, and the pooled trials show no overall benefit.","sources":["pogo-2025"]}],"grades":[{"claim":"No routine food restrictions in children with cancer","grade":"conditional recommendation, moderate quality evidence","source":"pogo-2025"},{"claim":"No routine food restrictions in children after autologous or allogeneic HCT","grade":"conditional recommendation, low quality evidence","source":"pogo-2025"},{"claim":"Follow local health authority food safety practices","grade":"Good practice statement","source":"pogo-2025"},{"claim":"Low-microbial diet for HCT recipients before engraftment","grade":"CIII","source":"hct-2009","quote":"A low-microbial diet is recommended for HCT recipients prior to engraftment 771, 772, although evidence for its efficacy to prevent infection is lacking (CIII)"},{"claim":"Review general food safety practices before transplant","grade":"AIII","source":"hct-2009"},{"claim":"Pooled infection risk with a neutropenic diet across 6 randomised trials","grade":"risk ratio 1.13, 95% CI 0.97 to 1.31 (meta-analysis, not a guideline grade)","source":"ma-2022","quote":"The meta-analysis found that patients in the study group had similar results for the incidence of infection compared with the patients in the control group (risk ratio, 1.13; 95% CI, 0.97 to 1.31; P = 0.11)."}],"sources":[{"key":"pogo-2025","label":"Use of food restrictions to prevent infections in paediatric patients with cancer and haematopoietic cell transplantation recipients: a systematic review and clinical practice guideline","publisher":"Pediatric Oncology Group of Ontario (POGO), eClinicalMedicine","year":2025,"url":"https://europepmc.org/article/PMC/PMC11872571","doi":"10.1016/j.eclinm.2025.103093","gradingScheme":"GRADE: strong or conditional recommendations, evidence high, moderate, low or very low; good practice statements ungraded.","read":"full-text","accessed":"2026-11-11"},{"key":"cog-food-2025","label":"Food restrictions to prevent infection in paediatric patients with cancer and HCT recipients (COG endorsement, version date 23 July 2025)","publisher":"Children's Oncology Group","year":2025,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_Food_Restrictions_Document_23JULY2025-new-logo.pdf","gradingScheme":"Reprints the source guideline's GRADE strength and quality.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2022","label":"Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2022,"url":"https://europepmc.org/article/MED/35576506","doi":"10.1200/jco.22.00687","read":"abstract","accessed":"2026-11-11"},{"key":"hct-2009","label":"Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective","publisher":"CDC, IDSA, ASBMT and international partners (Biology of Blood and Marrow Transplantation)","year":2009,"url":"https://europepmc.org/article/PMC/PMC3103296","doi":"10.1016/j.bbmt.2009.06.019","gradingScheme":"Strength A (always offer) to E (never offer); quality of evidence I (at least one randomised trial), II (non-randomised, cohort or case-control studies), III (expert opinion or descriptive studies); printed together, for example BIII.","read":"full-text","accessed":"2026-11-11"},{"key":"ma-2022","label":"Neutropenic Diet Cannot Reduce the Risk of Infection and Mortality in Oncology Patients With Neutropenia","publisher":"Frontiers in Oncology","year":2022,"url":"https://europepmc.org/article/PMC/PMC8959862","doi":"10.3389/fonc.2022.836371","read":"full-text","accessed":"2026-11-11"},{"key":"nutrients-2025","label":"A Neutropenic Diet in Haemato-Oncological Patients Receiving High-Dose Therapy and Hematopoietic Stem Cell Transplantation: A Systematic Review","publisher":"Nutrients","year":2025,"url":"https://europepmc.org/article/PMC/PMC11901642","doi":"10.3390/nu17050768","read":"full-text","accessed":"2026-11-11"},{"key":"stella-2023","label":"Nonrestrictive diet does not increase infections during post-HSCT neutropenia: data from a multicenter randomized trial","publisher":"Blood Advances","year":2023,"url":"https://europepmc.org/article/MED/37450382","doi":"10.1182/bloodadvances.2023010348","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ASCO 2022 guideline was read as an abstract only, so its grade for the neutropenic diet recommendation is not given here.","There is no agreed definition of a neutropenic diet, so the trials tested different restrictions; the POGO panel names cured meats, nuts, seeds, teas and chutneys as items with few data.","No randomised trial has tested food restrictions in children after stem cell transplant.","The CDC/IDSA/ASBMT HCT guideline dates from 2009 and no later edition was found; its transplant food lists have not been revised against the trials since.","UK national guidance on food during neutropenia (for example from the British Dietetic Association) was not found at a public address and is not cited."]},{"id":"g-csf-prophylaxis-by-febrile-neutropenia-risk","kind":"protocol","name":"G-CSF prophylaxis by febrile neutropenia risk","aka":["primary G-CSF prophylaxis","secondary G-CSF prophylaxis","pegfilgrastim after chemotherapy","filgrastim injections","white cell growth factor injections"],"tldr":"Some chemotherapy lowers the white cells that fight infection so much that a fever becomes dangerous. If your treatment carries a high risk of this, or you had an infection with low white cells on an earlier cycle, you may be given injections of a growth factor (G-CSF) after each cycle to help your white cells recover faster.","summary":"Primary prophylaxis with G-CSF is warranted when the regimen's risk of febrile neutropenia is about 20 per cent or higher and no equally effective and safe regimen without it exists (ASCO 2015; EORTC 2010 likewise for regimens at high risk, 20 per cent or more). For regimens with a risk of 10 to 20 per cent, patient factors such as age 65 or over decide (EORTC), and ASCO recommends prophylaxis for those at high risk from age, medical history, disease and the myelotoxicity of the regimen. After an episode of febrile neutropenia, G-CSF should be given in later cycles (secondary prophylaxis, EORTC). G-CSF is also used where it is part of a dose-dense or dose-intense regimen with proven benefit, or to keep dose intensity where cutting the dose worsens the outlook.\n\nNICE CG151 frames the same rule from the other side: do not routinely offer G-CSF to prevent neutropenic sepsis unless it is an integral part of the regimen or needed to maintain dose intensity. Filgrastim (including biosimilars), lenograstim and pegfilgrastim are all effective (EORTC); pegfilgrastim is given once per cycle, which may avoid the short courses of daily injections seen in audits. ASCO advises dose-dense regimens needing G-CSF only in trials or where efficacy data are convincing. The AGIHO 2026 update confirms most of its 2014 recommendations and adds guidance for immunotherapy settings.","asOf":"2026-11-11","links":[],"tags":["protocol","neutropenia","supportive-care"],"related":["febrile-neutropenia-first-hour"],"cancers":[],"sections":["supportive-care"],"technologies":["g-csf-growth-factors"],"targets":[],"drugs":["filgrastim","pegfilgrastim","lenograstim"],"companies":[],"institutions":["nice","asco"],"pathways":[],"terms":["febrile-neutropenia","neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some chemotherapy lowers the cells that fight germs. A small injection after treatment can help these cells come back faster. It is given to people at high risk.","domain":"supportive-care","setting":{"who":["doctor","pharmacist","nurse","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","home"]},"population":"Adults having chemotherapy for solid tumours or lymphoproliferative cancers. Acute myeloid leukaemia, myelodysplastic syndromes, stem cell mobilisation and children are outside the scope of the guidelines read (ASCO 2015 did not address AML or MDS).","trigger":"A chemotherapy regimen is planned, and again before each cycle.","steps":[{"action":"Before the first cycle, estimate the regimen's risk of febrile neutropenia: high (20 per cent or more), intermediate (10 to 20 per cent) or low","why":"The regimen's own risk is the starting point for deciding whether G-CSF is needed.","source":"eortc-2010","quote":"We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN."},{"action":"Add the person's own risk factors, such as age 65 or over and the neutrophil count, and reassess before every cycle","why":"The same regimen is riskier in an older or frailer person, and risk changes from cycle to cycle.","source":"eortc-2010","quote":"We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy."},{"action":"Give G-CSF from the first cycle when the overall risk is about 20 per cent or more and no equally effective regimen without it is available","why":"ASCO and EORTC set this as the level of risk at which preventing infection is worth the injections.","source":"asco-2015","quote":"Prophylactic use of CSFs to reduce the risk of febrile neutropenia is warranted when the risk of febrile neutropenia is approximately 20% or higher and no other equally effective and safe regimen that does not require CSFs is available."},{"action":"For an intermediate-risk regimen, give G-CSF when the person's risk factors raise the overall risk","why":"A 10 to 20 per cent regimen becomes high risk in, for example, an older person or someone with other illnesses.","source":"eortc-2010","quote":"When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN."},{"action":"After an episode of febrile neutropenia, give G-CSF in the following cycles","why":"A person who has had one episode is likely to have another on the same treatment, and it avoids cutting or delaying the dose.","source":"eortc-2010","quote":"It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles."},{"action":"Do not give G-CSF routinely to everyone on chemotherapy; give it where it is part of the regimen or needed to keep the dose","why":"For most regimens the risk is too low for routine injections to help.","source":"nice-cg151","quote":"Do not routinely offer G-CSF for the prevention of neutropenic sepsis in adults receiving chemotherapy unless they are receiving G-CSF as an integral part of the chemotherapy regimen or in order to maintain dose intensity."},{"action":"Choose filgrastim (or a biosimilar), lenograstim or pegfilgrastim; give the full course","why":"All work; pegfilgrastim is one injection a cycle, which avoids courses of daily injections being stopped too early.","source":"eortc-2010","quote":"Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated."},{"action":"Use dose-dense regimens that depend on G-CSF only where they have proven benefit or in a trial","why":"Giving chemotherapy closer together is only worth its toxicity where it improves survival.","source":"asco-2015","quote":"Dose-dense regimens that require CSFs should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data."}],"bestInClass":{"statement":"ASCO (2015) and EORTC (2010) agree on the threshold: primary prophylaxis when the risk of febrile neutropenia is about 20 per cent or more, with patient factors deciding for regimens at 10 to 20 per cent, and secondary prophylaxis after an episode. NICE CG151 states the rule negatively (no routine G-CSF unless integral to the regimen or to maintain dose intensity) and recommends fluoroquinolone prophylaxis instead for adults expected to have severe neutropenia. The AGIHO 2026 update is the most recent guideline and says it confirms most of its 2014 recommendations; its grades were not read. All the international sources read in full or abstract are 2010 to 2015 apart from AGIHO, and NCCN's current version could not be read.","sources":["asco-2015","eortc-2010","nice-cg151","agiho-2026","nccn-2022"]},"variants":[{"name":"Antibiotic prophylaxis rather than G-CSF (NICE CG151)","differs":"NICE offers a fluoroquinolone during the expected period of neutropenia to adults with acute leukaemias, stem cell transplants or solid tumours in whom a neutrophil count of 0.5 × 10⁹ per litre or lower is expected from chemotherapy, points to the MHRA January 2024 advice on fluoroquinolone risks, and does not offer G-CSF routinely.","evidence":"NICE recommendations are not graded; the G-CSF recommendation dates from 2012.","sources":["nice-cg151"]},{"name":"G-CSF guidance for immunotherapy settings (AGIHO 2026)","differs":"Adds recommendations on G-CSF in immunotherapy settings and new G-CSF formulations, alongside the 2014 recommendations it confirms.","evidence":"Levels of evidence and strengths of recommendation set by ESCMID criteria after a literature search to December 2024; read as an abstract only, so the recommendations themselves are not given here.","sources":["agiho-2026"]}],"grades":[],"sources":[{"key":"nice-cg151","label":"Neutropenic sepsis: prevention and management in people with cancer (CG151), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg151/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'do not routinely offer').","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2015","label":"Recommendations for the Use of WBC Growth Factors: ASCO Clinical Practice Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2015,"url":"https://europepmc.org/abstract/MED/26169616","doi":"10.1200/JCO.2015.62.3488","read":"abstract","accessed":"2026-11-11"},{"key":"eortc-2010","label":"2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours","publisher":"EORTC, European Journal of Cancer","year":2011,"url":"https://europepmc.org/abstract/MED/21095116","doi":"10.1016/j.ejca.2010.10.013","read":"abstract","accessed":"2026-11-11"},{"key":"agiho-2026","label":"Evidence-based AGIHO guideline update on prophylaxis of infectious complications with granulocyte-stimulating factors (G-CSF) for the treatment of adult patients with cancer","publisher":"AGIHO of the German Society of Hematology and Medical Oncology (DGHO), European Journal of Cancer","year":2026,"url":"https://europepmc.org/abstract/MED/41570611","doi":"10.1016/j.ejca.2026.116244","gradingScheme":"ESCMID criteria for level of evidence and strength of recommendation (not read).","read":"abstract","accessed":"2026-11-11"},{"key":"nccn-2022","label":"NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2022","publisher":"NCCN, Journal of the National Comprehensive Cancer Network","year":2022,"url":"https://europepmc.org/abstract/MED/35545171","doi":"10.6004/jnccn.2022.0026","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["Every source except NICE was read only as an abstract, so their grades, their lists of high-risk regimens and their advice on timing (for example how soon after chemotherapy to start) are not given here.","The AGIHO 2026 update is the most recent guideline found; its individual recommendations and grades were not in the abstract.","NCCN's current Hematopoietic Growth Factors guideline requires a login and its 2022 Insights paper returned 403; ESMO's 2016 febrile neutropenia guideline could not be read.","No source read gives a list of which regimens fall above 20 per cent; EORTC 2010 publishes one, which was not read.","The sources read do not cover G-CSF with immunotherapy combinations, where AGIHO 2026 says it adds guidance."]},{"id":"gadolinium-contrast-kidney-impairment","kind":"protocol","name":"Gadolinium contrast for MRI in kidney impairment: NSF risk by agent group","aka":["gadolinium and kidneys","MRI contrast and kidney disease","nephrogenic systemic fibrosis","NSF","GBCA","GBCM","gadolinium-based contrast agent","eGFR before MRI","MRI dye kidneys","gadolinium dialysis"],"tldr":"Many MRI scans for cancer use a dye containing gadolinium. Older types could cause a rare, serious scarring disease (nephrogenic systemic fibrosis) in people with very weak kidneys. The types used for most scans today carry a very low risk, so an important scan should not be refused because of the kidneys. Tell the team if you have kidney disease, are on dialysis, or are pregnant or breastfeeding.","summary":"NSF occurs almost only in people with acute kidney injury or an eGFR below 30 ml/min/1.73 m², above all below 15 or on dialysis, and was linked mainly to linear agents: gadodiamide caused most cases, with an estimated incidence of 3 to 18% in severe kidney failure (ESUR 2026). The groupings differ by body. ESUR puts the macrocyclic agents (gadobutrol, gadoterate, gadoteridol, gadopiclenol) at lowest risk, the linear liver-specific agents gadobenate and gadoxetate at intermediate risk and approved in Europe for liver imaging only, and gadodiamide, gadopentetate and gadoversetamide at highest risk, now suspended or withdrawn for intravenous use in Europe. ACR/NKF (2021) put gadobenate with the macrocyclic agents in group II (very low risk: no NSF in 4,931 administrations at eGFR below 30; upper 95% bound 0.07%), gadoxetate in group III (limited data, no unconfounded cases) and the old linear agents in group I.\n\nFor lowest-risk or group II agents a kidney blood test beforehand is not mandatory (ESUR) or optional (ACR/NKF); ACR/NKF require it for group III. A clinically indicated scan is never denied (ESUR) and group II contrast is not withheld if harm would follow (ACR/NKF). Use the smallest diagnostic dose and record the agent and dose. No drug prophylaxis prevents NSF. Dialysis is not started or changed for group II or III agents (ACR/NKF); ESUR needs no immediate dialysis after macrocyclic agents but does after linear agents in haemodialysis patients, repeated on the next two days. ESUR suggests waiting between elective gadolinium MRIs: 7 days optimally (60 hours minimum) when eGFR is below 30, 48 hours (16 minimum) at 30 to 60. Gadolinium is not a meaningful kidney toxin at approved doses, so metformin needs no change. In pregnancy the smallest dose of a macrocyclic agent may be given when there is a very strong indication; breastfeeding continues normally after macrocyclic agents; ESUR advises no gadolinium in a pregnant or breastfeeding woman with kidney impairment. Gadolinium is retained in brain and body after repeated doses, most after linear agents, with no confirmed neurological symptoms.","asOf":"2026-11-11","links":[],"tags":[],"related":["iodinated-contrast-kidney-and-metformin","contrast-reaction-history-and-premedication","mri-safety-screening-implants"],"cancers":[],"sections":[],"technologies":["gadolinium-based-contrast-agents","mri"],"targets":[],"drugs":["gadobutrol","gadoterate-meglumine","gadoteridol","gadopiclenol","gadobenate-dimeglumine","gadoxetate-disodium","gadodiamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"MRI scans often use a dye called gadolinium. Old types could harm people with very weak kidneys. Today's types are much safer. Tell the team if you have kidney problems or have dialysis. You do not usually need extra dialysis after the scan. You can keep breastfeeding.","domain":"screening-diagnostics","setting":{"who":["radiographer","doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","ward","emergency-department"]},"population":"Adults and children having intravenous gadolinium-based contrast for MRI, with attention to people with acute kidney injury, an eGFR below 30 ml/min/1.73 m², or on dialysis, and to pregnant and breastfeeding women. Allergy to contrast is a separate protocol; iodinated contrast for CT is in its own protocol.","trigger":"A contrast-enhanced MRI is requested.","steps":[{"action":"Do not refuse a clinically well-indicated contrast MRI because of kidney function","why":"With today's agents the risk to the kidneys and skin is very low, and a missed diagnosis can be the bigger harm.","source":"esur-2026","quote":"Never deny a patient a clinically well-indicated enhanced MR-examination."},{"action":"Choose a lowest-risk agent (macrocyclic in Europe; ACR group II in the United States) for anyone with eGFR below 30, acute kidney injury or dialysis, keeping the liver-specific agents for liver imaging","why":"The NSF cases came almost all from older linear agents; the newer, more stable agents have very few or none.","source":"acr-nkf-2021","quote":"The risk of NSF is very low for a standard dose (0.1 mmol/kg) of group II GBCM, even in patients with eGFR <30 mL/min per 1.73 m 2 or AKI.","grade":"Consensus statement (ungraded)"},{"action":"For a lowest-risk or group II agent, a kidney blood test beforehand is not required; check kidney function first for a group III (gadoxetate) agent","why":"A routine blood test adds delay without changing what happens when the agent is very low risk.","source":"acr-nkf-2021","quote":"Kidney function screening is optional for group II GBCM but is necessary for group III GBCM.","grade":"Consensus statement (ungraded)"},{"action":"Use the smallest dose that gives a diagnostic result and record the agent's name and dose in the notes","why":"Risk rises with dose, and a record lets later teams know exactly what was given.","source":"esur-2026","quote":"Always record the name and dose of the contrast agent used in the patient records."},{"action":"Tell a person with acute kidney injury or stage 4 or 5 kidney disease about the small risk of NSF, why contrast is needed and the alternatives","why":"They are the people in whom the risk is real, even if small, and the choice is shared.","source":"acr-nkf-2021","quote":"Although written documentation of informed consent is not required before administration of group II or group III GBCM, patients with known AKI or known stage 4 or 5 CKD should be informed of the potential risk of NSF associated with GBCM administration, the reason GBCM administration is indicated, and whether there are viable alternative diagnostic strategies.","grade":"Consensus statement (ungraded)"},{"action":"Do not give any drug or extra dialysis to prevent NSF; do not start or change dialysis because of a group II or III agent","why":"No preventive treatment has been shown to work, and starting dialysis has its own risks.","source":"acr-nkf-2021","quote":"Dialysis should not be initiated or altered based on group II or group III GBCM administration.","grade":"Consensus statement (ungraded)"},{"action":"In a person on haemodialysis given a linear agent (for example a liver-specific agent), arrange dialysis straight after and on the next two days; after a macrocyclic agent no immediate session is needed","why":"Linear agents release gadolinium more easily, and dialysis is the only way to clear them when the kidneys do not.","source":"esur-2026","quote":"An immediate dialysis session is not needed after macrocyclic gadolinium-based contrast agents but is indicated after linear agents (e.g., liver-specific agents) and needs to be repeated on the following two days."},{"action":"If eGFR is below 30, space elective contrast MRIs: ideally 7 days apart and at least 60 hours, unless the situation is urgent","why":"Weak kidneys take days to clear the dye, and a second dose before the first has gone adds to the body's load.","source":"esur-2026","quote":"In emergency or life-threatening situations, employ less waiting time between contrast- enhanced MRI with successive gadolinium-based contrast agent administrations."},{"action":"Do not stop metformin for a gadolinium scan","why":"Gadolinium at approved doses does not injure the kidneys in a way that makes metformin dangerous.","source":"esur-2026","quote":"No special precautions are necessary when diabetic patients on metformin are given gadolinium-based contrast agents as the risk of CA-AKI is extremely low and lactic acidosis has never been reported in this scenario."},{"action":"In pregnancy give gadolinium only for a very strong indication, as the smallest dose of a macrocyclic agent; do not give it to a pregnant or breastfeeding woman with kidney impairment","why":"The dye crosses to the baby, so it is kept for scans that are truly needed; with weak kidneys the mother clears it slowly.","source":"esur-2026","quote":"When there is a very strong indication for enhanced MRI, the smallest possible dose of a macrocyclic gadolinium contrast agent may be given to the pregnant female."},{"action":"Tell breastfeeding mothers they can carry on normally after a macrocyclic agent","why":"Only a tiny amount reaches breast milk and less still is absorbed by the baby.","source":"esur-2026","quote":"Breast feeding may be continued normally when macrocyclic gadolinium-based contrast agents are given to the mother."}],"bestInClass":{"statement":"Use a lowest-risk agent (ESUR: macrocyclic; ACR/NKF: group II) at the smallest diagnostic dose, never deny or delay an indicated contrast MRI on kidney grounds, do not require an eGFR beforehand for these agents (ESUR 2026: not mandatory; ACR/NKF 2021: optional), and do not give prophylaxis or alter dialysis. The two bodies disagree on two points. Gadobenate (MultiHance) is a lowest-risk group II agent for ACR/NKF but an intermediate-risk linear agent in ESUR, approved in Europe for liver imaging only. In haemodialysis patients ESUR still arranges dialysis after linear agents, on three consecutive days, while ACR/NKF say dialysis should not be started or changed for group II or III agents. Neither body grades its statements.","sources":["esur-2026","acr-nkf-2021"]},"variants":[{"name":"Kidney blood test for every contrast MRI","differs":"Some departments still require an eGFR before any gadolinium.","evidence":"ESUR 2026 states testing is not mandatory for lowest-risk agents; ACR/NKF make it optional for group II and necessary for group III. Earlier guidance (ACR 2018, KDIGO 2013) is compared in ACR/NKF table 3.","sources":["esur-2026","acr-nkf-2021"]},{"name":"Dialysis after gadolinium in people already on dialysis (KDIGO and the earlier ACR position)","differs":"KDIGO (2013), as summarised by ACR/NKF, performs dialysis immediately after gadolinium and possibly again at 24 hours; the 2018 ACR manual gave gadolinium as soon as possible before a scheduled dialysis session. ACR/NKF 2021 say not to start or alter dialysis for group II or III agents; ESUR keeps dialysis after linear agents only.","evidence":"ACR/NKF: no evidence that dialysis prevents NSF; ESUR agrees that haemodialysis has not been shown to protect against NSF.","sources":["acr-nkf-2021","esur-2026"]},{"name":"Avoiding gadolinium below eGFR 15 (KDIGO 2013 as summarised by ACR/NKF)","differs":"Avoid gadolinium if eGFR is below 15 unless there is no alternative, and treat macrocyclic versus linear structure as the dividing line rather than ACR groups.","evidence":"Stated in ACR/NKF table 3 as the historical KDIGO position; KDIGO was not read directly.","sources":["acr-nkf-2021"]}],"grades":[{"claim":"Group II contrast is not withheld or delayed if harm would result","grade":"Consensus statement (ungraded)","source":"acr-nkf-2021","quote":"Group II GBCM should not be withheld or delayed if harm would result from not proceeding with an indicated contrast-enhanced MRI."},{"claim":"No prophylaxis for NSF","grade":"Consensus statement (ungraded)","source":"acr-nkf-2021","quote":"Prophylaxis is not indicated for the prevention of NSF."},{"claim":"Recommendations unchanged for chemotherapy, nephrotoxic drugs or same-day contrast CT","grade":"Consensus statement (ungraded)","source":"acr-nkf-2021","quote":"The above recommendations should not be altered in patients receiving nephrotoxic medications, chemotherapy, or contrast-enhanced CT."},{"claim":"Kidney test not mandatory for lowest-risk agents","grade":"ungraded (handbook)","source":"esur-2026","quote":"Laboratory testing of renal function (eGFR) prior to contrast agent use is not mandatory."},{"claim":"No gadolinium in a pregnant or breastfeeding woman with kidney impairment","grade":"ungraded (handbook)","source":"esur-2026","quote":"Do not administer gadolinium-based contrast agents."}],"sources":[{"key":"esur-2026","label":"Contrast Media Safety Committee Guidelines 2026 (successor to ESUR Guidelines on Contrast Agents 10.0)","publisher":"European Society of Urogenital Radiology (ESUR) Contrast Media Safety Committee","year":2026,"url":"https://www.esur.org/wp-content/uploads/2026/10/Guidelines-2026.pdf","gradingScheme":"The handbook prints no grades.","read":"full-text","accessed":"2026-11-11"},{"key":"acr-nkf-2021","label":"Use of Intravenous Gadolinium-Based Contrast Media in Patients With Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation","publisher":"American College of Radiology and National Kidney Foundation (Weinreb et al., Kidney Medicine; also published in Radiology, 10.1148/radiol.2020202903)","year":2021,"url":"https://doi.org/10.1016/j.xkme.2020.10.001","doi":"10.1016/j.xkme.2020.10.001","gradingScheme":"Consensus statements without formal grades.","read":"full-text","accessed":"2026-11-11"},{"key":"acr-manual-contrast","label":"ACR Manual on Contrast Media","publisher":"American College of Radiology","year":2024,"url":"https://www.acr.org/Clinical-Resources/Contrast-Manual","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-pu-no-fasting-before-contrast"],"gaps":["The ACR Manual on Contrast Media could not be read; ACR's current grouping is taken from the 2021 ACR/NKF paper, which predates gadopiclenol and so does not place it. ESUR 2026 places gadopiclenol at lowest risk.","The dose-related risk of NSF for group II and III agents is unknown (ACR/NKF), and the absolute risk below eGFR 15 or on dialysis rests on observational cohorts with small numbers of exposed patients.","The clinical significance of gadolinium retained in the brain and body after repeated doses is not known (ESUR 2026); all studies have been retrospective. This matters for people with cancer having many surveillance MRIs, and no source read sets a cumulative limit.","Neither source grades its recommendations.","KDIGO's 2013 position is shown only as ACR/NKF summarise it; KDIGO was not read."]},{"id":"geriatric-assessment-before-systemic-cancer-therapy","kind":"protocol","name":"Geriatric assessment before systemic cancer therapy in older adults","aka":["geriatric assessment in oncology","GA-guided management","Practical Geriatric Assessment","G8 screening","CARG chemotherapy toxicity score","assessment of older people before chemotherapy"],"tldr":"If you are 65 or over and about to start chemotherapy, targeted therapy or immunotherapy, your team should check more than the cancer: how well you move and manage day to day, memory, mood, other illnesses, medicines, nutrition and who supports you. The results help choose a treatment you can tolerate and find problems that can be fixed, such as falls, poor nutrition or too many tablets.","summary":"ASCO (2023) recommends that every person with cancer aged 65 or over with impairments found on geriatric assessment (GA) has GA-guided management in their care plan, using the results both to inform the treatment decision and to address the impairments through interventions, counselling and referrals; this includes chemotherapy, targeted therapy and immunotherapy (evidence based, high quality, strong). The GA should cover physical and cognitive function, emotional health, comorbidities, polypharmacy, nutrition and social support (high, strong); the Practical Geriatric Assessment is one option (informal consensus, weak).\n\nLife expectancy is estimated with a validated tool such as the Lee or Schonberg index from ePrognosis (strong that it predicts mortality; weak that it improves decisions). A G8 screen of 14 or below prompts a full assessment, and the CARG toxicity tool scores the risk of serious chemotherapy toxicity (0 to 5 low, 6 to 9 intermediate, 10 to 23 high); at intermediate or high risk, ASCO's table suggests the full assessment and considering treatment modifications. Clinicians should share GA results with patients and caregivers, and implement targeted interventions for problems outside the cancer (informal consensus, moderate).","asOf":"2026-11-11","links":[],"tags":["protocol","geriatric-oncology","supportive-care"],"related":["idea-moon-geriatric-assessment-default","idea-tr1-geriatric-dose-finding-cohorts"],"cancers":[],"sections":["supportive-care"],"technologies":["geriatric-assessment","g8-geriatric-screening"],"targets":[],"drugs":[],"companies":[],"institutions":["asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before cancer treatment, older people should have a full check of health, memory, mood, medicines, food and support. This helps pick safer treatment.","domain":"supportive-care","setting":{"who":["doctor","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic"]},"population":"Adults aged 65 and over with cancer who are being considered for or receiving systemic therapy (chemotherapy, targeted therapy or immunotherapy). Assessment before surgery or radiotherapy alone is outside ASCO's 2023 scope.","trigger":"A person aged 65 or over is being considered for systemic cancer therapy.","steps":[{"action":"Assess everyone aged 65 or over before systemic treatment, and build geriatric assessment-guided management into the care plan when impairments are found","why":"Trials showed that acting on the assessment reduces serious side effects, and problems such as falls or poor nutrition are often missed otherwise.","source":"asco-2023","quote":"All patients with cancer aged 65 and over with geriatric assessment (GA)-identified impairments should have GA-guided management (GAM) included in their care plan.","grade":"evidence based; evidence quality high; strength strong"},{"action":"Cover physical function, cognition, emotional health, other illnesses, medicines, nutrition and social support","why":"These are the areas linked with how older people fare on cancer treatment.","source":"asco-2023","quote":"A GA should include high priority aging-related domains known to be associated with outcomes in older patients with cancer to include assessment of physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support.","grade":"evidence based; evidence quality high; strength strong"},{"action":"Use a short screen such as the G8 where a full assessment cannot be done for everyone, and do the full assessment when it is 14 or below","why":"A quick screen finds the people who most need the full assessment.","source":"asco-2023","quote":"Score: 0–14 recommend completing a full geriatric assessment evaluation"},{"action":"Estimate the risk of serious chemotherapy toxicity with the CARG tool, and at intermediate or high risk consider changing the treatment plan","why":"The score combines age, the cancer, the treatment, blood tests and the assessment to predict harm before it happens.","source":"asco-2023","quote":"For Intermediate and High Risk patients, consider administering the full PGA and implement the recommendations noted above based on the patient-reported results"},{"action":"Estimate life expectancy apart from the cancer with a validated index such as the Lee or Schonberg index","why":"Other illnesses may shape someone's future more than the cancer, which matters for treatments whose benefit comes years later.","source":"asco-2023","quote":"Based on the best clinical opinion of the Expert Panel, clinicians should use one of the validated tools listed at ePrognosis ( https://eprognosis.ucsf.edu/ ) to estimate life expectancy (LE) greater than or equal to 4 years.","grade":"informal consensus; strong that it predicts mortality, weak that it improves outcomes or decisions"},{"action":"Use the results to choose the treatment with the person and their carer, and act on problems outside the cancer, such as falls, poor nutrition or too many medicines","why":"The point of the assessment is what is done with it: a safer plan and fixes for problems that can be fixed.","source":"asco-2023","quote":"In addition, clinicians should implement targeted, GA-guided interventions to manage nononcologic problems.","grade":"informal consensus; evidence quality moderate; strength moderate"}],"bestInClass":{"statement":"ASCO's 2023 update, read in full, is the most recent guideline and the only one read: geriatric assessment-guided management for everyone aged 65 or over with impairments, extended from chemotherapy to all systemic therapy, on high-quality evidence with a strong recommendation; a GA covering function, cognition, mood, comorbidity, medicines, nutrition and social support; and the Practical Geriatric Assessment as one practical tool. The SIOG and ESMO positions on geriatric assessment were not read, so differences between societies are not stated here.","sources":["asco-2023"]},"variants":[{"name":"Screen first, full assessment for those who screen positive (G8)","differs":"Uses the 8-item G8 screen (food intake, weight loss, mobility, neuropsychological problems, BMI, prescription drugs, self-rated health and age), with a full GA for scores of 14 or below, rather than a full GA for everyone; the VES-13 is listed as an alternative screen.","evidence":"Listed in ASCO's 2023 table of assessment tools; the GERICO trial cited there enrolled vulnerable patients by G8 of 14 or below.","sources":["asco-2023"]},{"name":"CRASH instead of CARG for toxicity risk","differs":"Uses the Chemotherapy Risk Assessment Scale for High-Age Patients to estimate chemotherapy toxicity risk.","evidence":"ASCO's 2023 table lists CRASH as an alternative tool.","sources":["asco-2023"]}],"grades":[{"claim":"The Practical Geriatric Assessment as one option","grade":"informal consensus; evidence quality moderate; strength weak","source":"asco-2023","quote":"The Panel recommends the Practical Geriatric Assessment (PGA) as one option for this purpose."}],"sources":[{"key":"asco-2023","label":"Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2023,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12803700/","doi":"10.1200/JCO.23.00933","gradingScheme":"Each recommendation printed with type (evidence based or informal consensus), evidence quality (high, moderate, low, insufficient) and strength (strong, moderate, weak).","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-acc-geriatric-assessment-by-default","idea-acc-electronic-frailty-index-oncology"],"gaps":["Only ASCO was read. The SIOG recommendations and ESMO's position on geriatric assessment were not read, and NICE has no cancer-specific geriatric assessment guidance.","The text read is the author manuscript in PubMed Central; a 2025 erratum to the guideline exists and was not read.","ASCO does not say who should carry out the assessment or how long it should take; the Practical Geriatric Assessment is offered as one option.","The CARG table's suggested treatment modifications for intermediate and high risk are not reproduced here."]},{"id":"allo-hct-gvhd-prophylaxis","kind":"protocol","name":"GVHD prophylaxis after allogeneic stem cell transplant: choosing the regimen","aka":["GvHD prophylaxis regimen","post-transplant cyclophosphamide","PTCy","ATG prophylaxis","calcineurin inhibitor and methotrexate","tacrolimus and mycophenolate"],"tldr":"After a donor transplant, everyone takes medicines to stop the donor's immune cells attacking their body (graft-versus-host disease). The combination depends on the donor, the pre-transplant treatment and whether the cells came from blood or marrow. Newer combinations reduce graft-versus-host disease; in the main trial they did not lengthen life, and each has its own side effects.","summary":"EBMT 2024 (GRADE, ten PICO questions, 22 experts and a methodologist; abstract read): rabbit anti-T-cell globulin (ATG) or post-transplantation cyclophosphamide (PTCy) is standard prophylaxis in peripheral blood stem cell transplants from unrelated donors; ruxolitinib is the new standard for steroid-refractory acute and chronic GVHD; belumosudil is added for steroid-refractory chronic GVHD. The panel states its recommendations favour European practice.\n\nBMT CTN 1703 (phase III, 431 adults, reduced-intensity conditioning, matched related or matched or 7/8 unrelated donors): PTCy-tacrolimus-mycophenolate mofetil gave more GVHD-free, relapse-free survival at one year than tacrolimus-methotrexate (52.7% against 34.9%; HR 0.64), with no substantial difference in overall or disease-free survival, relapse, transplant-related death or engraftment.\n\nABHH/SBTMO 2026 (GRADE systematic review, 11 PICO questions, 54 studies): calcineurin inhibitor plus methotrexate reduces acute GVHD (very low quality); calcineurin inhibitor plus mycophenolate can be preferred after myeloablative conditioning for less mucositis and toxicity; adding rATG is recommended; calcineurin inhibitor plus mycophenolate after reduced-intensity conditioning; high-dose PTCy (50 mg/kg days +3 and +4) with a calcineurin inhibitor with or without mycophenolate for haploidentical donors, and with reduced chronic GVHD in matched donors (RCTs) at the cost of more haemorrhagic cystitis (cohorts); PTCy with ATG raises EBV reactivation; abatacept added to calcineurin inhibitor and methotrexate lowers grade III to IV acute GVHD (very low quality).","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","transplant","gvhd"],"related":["gvhd-ruxolitinib-steroid-refractory"],"cancers":[],"sections":[],"technologies":["allogeneic-hsct","gvhd-prophylaxis"],"targets":[],"drugs":["cyclophosphamide","methotrexate","sirolimus"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","conditioning-regimen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After a donor transplant you take medicines to stop the donor cells attacking your body. Your team chooses the combination that suits your donor and treatment.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","pharmacist","multidisciplinary-team"],"where":["ward"]},"population":"Adults receiving an allogeneic haematopoietic cell transplant for a haematological cancer. EBMT 2024 and ABHH/SBTMO 2026 address adults; paediatric practice is not covered by the sources read.","trigger":"Planning an allogeneic transplant, once donor type, conditioning intensity and graft source are known.","steps":[{"action":"Choose the prophylaxis regimen by donor type, conditioning intensity and graft source","why":"The best-tested combination differs between a sibling, an unrelated or a half-matched donor, and between blood and marrow grafts.","source":"abhh-sbtmo-2026","quote":"The choice of GvHD prophylaxis should therefore be guided by donor type (matched sibling, matched unrelated, or haploidentical), conditioning regimen (myeloablative versus non-myeloablative/reduced intensity), and graft source (peripheral blood or bone marrow)."},{"action":"For a peripheral blood transplant from an unrelated donor, include antithymocyte globulin or post-transplant cyclophosphamide","why":"Both reduce graft-versus-host disease in this setting and are the European standard.","source":"ebmt-gvhd-2024","quote":"(2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors"},{"action":"After reduced-intensity conditioning from a matched donor, consider post-transplant cyclophosphamide with tacrolimus and mycophenolate rather than tacrolimus and methotrexate","why":"In a randomised trial it gave more people a year free of severe GVHD and relapse, though survival was similar.","source":"bmt-ctn-1703","quote":"Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate."},{"action":"For a haploidentical donor, give high-dose post-transplant cyclophosphamide (50 mg/kg on days +3 and +4) with a calcineurin inhibitor, with or without mycophenolate","why":"Compared with the sirolimus-based version, it caused less bladder bleeding and liver blockage, with the same GVHD control.","source":"abhh-sbtmo-2026","quote":"In patients undergoing haploidentical allo-HCT for malignant diseases, using either myeloablative or non-myeloablative conditioning and bone marrow or peripheral blood grafts, a regimen with high-dose PTCy plus CNI with or without MMF, compared with high-dose PTCy plus sirolimus and MMF, reduces hemorrhagic cystitis and sinusoidal obstructive syndrome risks, despite showing no significant differences in the risk of Grade II–IV or III–IV aGvHD, cGvHD, NRM, OS, or EFS."},{"action":"After myeloablative conditioning from a matched donor, a calcineurin inhibitor with mycophenolate may be preferred to one with methotrexate","why":"GVHD control is similar, with less mouth ulceration and less kidney and lung toxicity.","source":"abhh-sbtmo-2026","quote":"However, the combination with MMF can be recommended due to lower toxicity (nephrotoxicity and respiratory failure), particularly with tacrolimus and the lower incidence of mucositis (regardless of cyclosporine and tacrolimus), when compared to the combination with methotrexate.","grade":"Quality of evidence: very low to moderate"},{"action":"Consider adding rabbit antithymocyte globulin to standard prophylaxis for matched sibling or unrelated peripheral blood transplants","why":"It reduced acute GVHD in pooled studies without a clear survival change.","source":"abhh-sbtmo-2026","quote":"In patients undergoing allo-HCT, the use of rATG in combination with standard GvHD prophylaxis is recommended over standard prophylaxis alone.","grade":"Quality of evidence: very low to moderate"},{"action":"When post-transplant cyclophosphamide is combined with antithymocyte globulin, monitor for EBV reactivation","why":"The combination reduces GVHD but, in pooled studies, raised the risk of the Epstein-Barr virus reactivating.","source":"abhh-sbtmo-2026","quote":"In patients undergoing allo-HCT with haploidentical, related or unrelated matched donors or unrelated mismatched donors, the regimen combining high-dose PTCy plus ATG is associated with reduced risks of Grade II-IV aGvHD, and cGvHD, as well an increased risk of EBV reactivation when compared with other regimens lacking this combination."}],"bestInClass":{"statement":"EBMT 2024 is the current European standard (GRADE, ten PICO questions) and makes ATG or PTCy standard for unrelated-donor peripheral blood transplants; only its abstract could be read. BMT CTN 1703 is the one phase III trial read: PTCy-tacrolimus-mycophenolate improved GVHD-free, relapse-free survival over tacrolimus-methotrexate after reduced-intensity conditioning, without a survival difference. ABHH/SBTMO 2026 is the most recent full GRADE systematic review read; it reaches compatible conclusions but rates most evidence very low to moderate, mostly from observational studies, and is written with low- and middle-income settings in mind. None of the sources read names one regimen as best for every transplant: all tie the choice to donor, conditioning and graft source.","sources":["ebmt-gvhd-2024","bmt-ctn-1703","abhh-sbtmo-2026"]},"variants":[{"name":"Abatacept with a calcineurin inhibitor and methotrexate (ABHH/SBTMO 2026)","differs":"Adds abatacept to calcineurin inhibitor and methotrexate for matched or mismatched unrelated donors.","evidence":"Randomised trials pooled by ABHH: 28% lower risk of grade III to IV acute GVHD at three months and 12% lower relapse at 24 months, no difference in chronic GVHD or survival. Quality of evidence: very low.","sources":["abhh-sbtmo-2026"]},{"name":"Triple prophylaxis with sirolimus after reduced-intensity conditioning (ABHH/SBTMO 2026)","differs":"Ciclosporin, mycophenolate and sirolimus for related or unrelated matched or mismatched donors.","evidence":"Lower grade II to IV acute GVHD and better two-year survival; quality of evidence very low to low.","sources":["abhh-sbtmo-2026"]},{"name":"Tacrolimus with sirolimus after myeloablative conditioning (ABHH/SBTMO 2026)","differs":"Replaces methotrexate with sirolimus alongside tacrolimus.","evidence":"Three pooled randomised trials showed no greater benefit than calcineurin inhibitor plus methotrexate for acute or chronic GVHD or mortality.","sources":["abhh-sbtmo-2026"]}],"grades":[{"claim":"CNI plus mycophenolate after myeloablative matched-donor transplant","grade":"Quality of evidence: varied between very low and moderate","source":"abhh-sbtmo-2026","quote":"Quality of Evidence: varied between very low and moderate, depending on the analyzed outcome."},{"claim":"Adding rATG to standard prophylaxis","grade":"Quality of evidence: ranged from very low to moderate","source":"abhh-sbtmo-2026","quote":"Quality of Evidence: ranged from very low to moderate, depending on the outcome assessed."},{"claim":"Abatacept plus CNI and methotrexate","grade":"Quality of evidence: very low","source":"abhh-sbtmo-2026"},{"claim":"ATG or PTCy standard for unrelated-donor PBSC transplants","grade":"GRADE (strength not stated in the abstract)","source":"ebmt-gvhd-2024"}],"sources":[{"key":"ebmt-gvhd-2024","label":"Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation (2024)","publisher":"EBMT, The Lancet Haematology","year":2024,"url":"https://europepmc.org/abstract/MED/38184001","doi":"10.1016/S2352-3026(23)00342-3","gradingScheme":"GRADE applied to ten PICO questions, with recommendation strength voted in two consensus meetings; the abstract does not give the strength of each recommendation.","read":"abstract","accessed":"2026-11-11"},{"key":"bmt-ctn-1703","label":"Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis (BMT CTN 1703, NCT03959241)","publisher":"New England Journal of Medicine","year":2023,"url":"https://europepmc.org/abstract/MED/37342922","doi":"10.1056/NEJMoa2215943","gradingScheme":"Randomised phase III trial; not a graded recommendation.","read":"abstract","accessed":"2026-11-11"},{"key":"abhh-sbtmo-2026","label":"Prophylaxis of graft-versus-host-disease: systematic evidence-based recommendations of the Brazilian Association of Hematology, Hemotherapy and Cell Therapy (ABHH) and the Brazilian Society of Cellular Therapy and Bone Marrow Transplantation (SBTMO)","publisher":"ABHH and SBTMO, Hematology, Transfusion and Cell Therapy","year":2026,"url":"https://europepmc.org/article/PMC/PMC13382006","doi":"10.1016/j.htct.2026.106494","gradingScheme":"GRADE: quality of evidence printed per outcome and per recommendation as very low, low, moderate or high; recommendations are worded as 'recommended' or 'can be recommended' without a separate strength.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The EBMT 2024 recommendations could be read only as their abstract: the strength of each recommendation, the doses, and the advice for matched sibling and haploidentical donors are not stated here.","BMT CTN 1703 was read only as its abstract; its toxicity and infection data are not given.","ABHH/SBTMO 2026 is internally inconsistent on antithymocyte globulin: the evidence synthesis finds the chronic GVHD reduction significant only in the high-dose subgroup, while the summary section says the low-dose subgroup. The supplementary forest plots that would settle it were not read.","No ASTCT, NCCN or NICE guidance on GVHD prophylaxis was read; US and UK practice may differ from the European and Brazilian recommendations.","Paediatric prophylaxis is not covered by the sources read."]},{"id":"hand-hygiene-in-cancer-care","kind":"protocol","name":"Hand hygiene in cancer care: staff, patients, families and visitors","aka":["WHO five moments for hand hygiene","hand washing during chemotherapy","alcohol hand rub","hand decontamination","bare below the elbows","clean hands"],"tldr":"Clean hands are the single most important way to stop infections spreading to someone whose immunity is low. Staff clean their hands at five set moments around every patient, usually with alcohol rub, and with soap and water when hands are dirty or when there is diarrhoea such as C. difficile. Patients, families and visitors should clean their hands too, and ask staff to if they have not.","summary":"The WHO 2009 guideline (CDC/HICPAC categories) is the international standard, and NICE CG139 the UK one for community care. Alcohol-based handrub is the preferred means of routine hand antisepsis when hands are not visibly soiled (WHO IA; NICE 'preferably with a handrub'); wash with soap and water when hands are visibly dirty or soiled with body fluids (IB), after the toilet (II), and when spore-forming organisms such as Clostridioides difficile are suspected or proven (IB). WHO's five moments: before touching a patient, before a clean or aseptic procedure (including handling an invasive device such as a central line, whether or not gloves are worn, IB), after body fluid exposure risk (IA), after touching a patient (IB) and after touching the patient's surroundings (IB); also after removing gloves. Gloves do not replace hand hygiene (IB). Handrub takes 20 to 30 seconds and handwashing 40 to 60 seconds (WHO); NICE asks for vigorous rubbing for at least 10 to 15 seconds when washing. Staff do not wear artificial nails with direct patient contact (WHO IA) and are bare below the elbows (NICE). Programmes should be multimodal with monitoring and feedback (IA). For families, the Dutch paediatric oncology guideline makes hand hygiene by patients, carers and staff a strong good practice statement; NICE asks that patients and carers are taught hand decontamination before discharge; the HCT guideline asks all visitors to clean hands before and after visits.","asOf":"2026-11-11","links":[],"tags":["protocol","hand-hygiene"],"related":["central-line-maintenance-bundle","neutropenic-precautions-and-daily-life","paediatric-clostridioides-difficile"],"cancers":["childhood-cancers"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["who","nice"],"pathways":[],"terms":["neutropenia","central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Wash or rub your hands often, and ask everyone who touches you or your child to do the same. Use soap and water if hands look dirty or someone has diarrhoea.","domain":"infection-prevention","setting":{"who":["nurse","doctor","patient-or-carer","multidisciplinary-team"],"where":["ward","chemotherapy-day-unit","outpatient-clinic","home","community"]},"population":"Everyone who has contact with a person having cancer treatment: health-care workers in any setting (WHO, NICE), and patients, families and visitors at home and in hospital, including children with cancer (Dutch guideline) and transplant recipients (HCT guideline).","steps":[{"action":"Use alcohol-based handrub as the usual way to clean hands when they are not visibly dirty","why":"Alcohol rub kills more germs, faster, than soap and water, and is quicker to use at the bedside.","source":"who-2009","quote":"Use an alcohol-based handrub as the preferred means for routine hand antisepsis in all other clinical situations described in items D(a) to D(f) listed below, if hands are not visibly soiled (IA).","grade":"IA"},{"action":"Wash with soap and water when hands are visibly dirty or soiled with body fluids, and after using the toilet","why":"Alcohol does not cut through dirt or body fluids; washing removes them.","source":"who-2009","quote":"Wash hands with soap and water when visibly dirty or visibly soiled with blood or other body fluids (IB) or after using the toilet (II).","grade":"IB (soiled); II (after the toilet)"},{"action":"Use soap and water, not alcohol rub, when C. difficile or another spore-forming germ is suspected or confirmed, or there is infectious diarrhoea","why":"Alcohol does not kill the spores of C. difficile; washing removes them from the hands.","source":"who-2009","quote":"If exposure to potential spore-forming pathogens is strongly suspected or proven, including outbreaks of Clostridium difficile, hand washing with soap and water is the preferred means (IB).","grade":"IB"},{"action":"Clean hands before and after touching the patient","why":"This stops germs passing from staff to patient, and from one patient to the next.","source":"who-2009","quote":"before and after touching the patient (IB);","grade":"IB"},{"action":"Clean hands immediately before any clean or aseptic task, such as opening a line, giving an injection or a lumbar puncture, and before putting on gloves","why":"Most line and procedure infections come from the patient's own skin germs or the last surface touched; gloves alone may not prevent contamination.","source":"who-2009","quote":"For some tasks on clean sites (lumbar puncture, surgical procedures, tracheal suctioning, etc.), the use of gloves is standard procedure. In this case, hand hygiene is required before donning gloves because gloves alone may not entirely prevent contamination"},{"action":"Clean hands after any contact with body fluids, mucous membranes, broken skin or wound dressings","why":"Hands can pick up germs from body fluids even without visible soiling, and carry them to a clean body site or to the next surface.","source":"who-2009","quote":"after contact with body fluids or excretions, mucous membranes, non-intact skin, or wound dressings (IA);","grade":"IA"},{"action":"Clean hands after touching anything in the patient's immediate surroundings, including equipment, and after taking off gloves","why":"Bed rails, pumps and tables near the patient carry their germs; gloves can have tiny holes and hands are contaminated when they come off.","source":"nice-cg139","quote":"immediately after any other activity or contact with a patient's surroundings that could potentially result in hands becoming contaminated"},{"action":"Do not treat gloves as a substitute for hand hygiene","why":"Gloves reduce but do not stop contamination of the hands.","source":"who-2009","quote":"The use of gloves does not replace the need for hand hygiene by either handrubbing or handwashing (IB).","grade":"IB"},{"action":"Rub until the hands are dry, covering every surface: about 20 to 30 seconds with handrub, 40 to 60 seconds for a full handwash","why":"Missed areas, such as fingertips and thumbs, and wet hands are where germs survive.","source":"who-2009","quote":"Apply a palmful of alcohol-based handrub and cover all surfaces of the hands. Rub hands until dry (IB).","grade":"IB"},{"action":"For staff, be bare below the elbows: no false nails, nail polish, wristwatch or stoned rings, with nails short and cuts covered","why":"Nails, jewellery and sleeves stop the hands and wrists being cleaned properly and harbour germs.","source":"nice-cg139","quote":"being bare below the elbow when delivering direct patient care (for the purposes of this guideline, bare below the elbow means: not wearing false nails, nail polish, a wristwatch or stoned rings; wearing short-sleeved garments or being able to roll or push up sleeves)"},{"action":"Teach patients and carers how and when to clean their hands before they go home","why":"Most cancer treatment is given as an outpatient, so families do much of the care, including line care, at home.","source":"nice-cg139","quote":"Patients and carers should be educated about and trained in techniques of hand decontamination, insertion of intermittent catheters where applicable, and catheter management before discharge from hospital."},{"action":"Ask every visitor to clean their hands before and after the visit","why":"Visitors can bring germs that are harmless to them and serious to someone with low immunity.","source":"hct-2009","quote":"All visitors should perform hand hygiene before and after visits."},{"action":"Run hand hygiene as a multimodal programme, with monitoring of staff adherence and feedback","why":"Products alone do not change behaviour; education, leadership, reminders and feedback do.","source":"who-2009","quote":"Monitor HCWs’ adherence to recommended hand hygiene practices and provide them with performance feedback (IA).","grade":"IA"}],"bestInClass":{"statement":"The WHO 2009 guideline, with its five moments, alcohol handrub as the default (IA) and soap and water for visible soiling (IB) or spore-forming organisms such as C. difficile (IB), is the international standard and is reflected in NICE CG139 for the UK. The two differ only in detail: WHO grades each recommendation with CDC/HICPAC categories and gives 20 to 30 seconds for handrub and 40 to 60 seconds for handwashing; NICE does not grade, describes five equivalent circumstances, asks for at least 10 to 15 seconds of vigorous rubbing when washing, and adds bare below the elbows. For families of children with cancer, the Dutch guideline (2024, endorsed by the Children's Oncology Group) makes hand hygiene by patients, carers and staff the one strong good practice statement among its daily-life recommendations.","sources":["who-2009","nice-cg139","dcog-2024","hct-2009"]},"variants":[{"name":"Handwashing time (NICE CG139)","differs":"Asks that hands be rubbed together vigorously for a minimum of 10 to 15 seconds during a handwash, against WHO's 40 to 60 seconds for the whole handwashing procedure.","evidence":"NICE does not grade; the wording dates from 2003. WHO gives its durations in the technique figures rather than as graded recommendations.","sources":["nice-cg139","who-2009"]},{"name":"Patients asking staff to clean their hands","differs":"Some hospitals invite patients and families to remind staff to clean their hands. WHO asks governments to encourage partnerships between patients, families and health-care workers to promote hand hygiene.","evidence":"WHO Category II.","sources":["who-2009"]}],"grades":[{"claim":"Alcohol-based handrub preferred for routine hand antisepsis","grade":"IA","source":"who-2009"},{"claim":"Hand hygiene before handling an invasive device, with or without gloves","grade":"IB","source":"who-2009","quote":"before handling an invasive device for patient care, regardless of whether or not gloves are used (IB);"},{"claim":"No artificial fingernails or extenders with direct patient contact","grade":"IA","source":"who-2009","quote":"Do not wear artificial fingernails or extenders when having direct contact with patients (IA)."},{"claim":"Multimodal hand hygiene promotion with education and senior support","grade":"IA","source":"who-2009"},{"claim":"Hand hygiene by patients, caregivers and medical personnel (children with cancer)","grade":"STRONG recommendation, GOOD PRACTICE STATEMENT","source":"dcog-2024","quote":"Proper hand hygiene should be performed by patients, caregivers, and medical personnel (STRONG recommendation, GOOD PRACTICE STATEMENT)."},{"claim":"Health-care workers and others in contact with HCT recipients follow hand hygiene","grade":"AIII","source":"hct-2009"}],"sources":[{"key":"who-2009","label":"WHO Guidelines on Hand Hygiene in Health Care: First Global Patient Safety Challenge, Clean Care is Safer Care","publisher":"World Health Organization","year":2009,"url":"https://www.who.int/publications/i/item/9789241597906","gradingScheme":"CDC/HICPAC categories as adapted by WHO: IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and a strong theoretical rationale), IC (required by regulation or standard), II (suggested).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-cg139","label":"Healthcare-associated infections: prevention and control in primary and community care (CG139), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg139/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended.","read":"full-text","accessed":"2026-11-11"},{"key":"dcog-2024","label":"Less restrictions in daily life: a clinical practice guideline for children with cancer","publisher":"Dutch Children's Oncology Group (DCOG), Supportive Care in Cancer","year":2024,"url":"https://europepmc.org/article/PMC/PMC11162397","doi":"10.1007/s00520-024-08537-9","gradingScheme":"GRADE: STRONG or WEAK with quality of evidence, EXPERT opinion, or GOOD PRACTICE STATEMENT.","read":"full-text","accessed":"2026-11-11"},{"key":"hct-2009","label":"Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective","publisher":"CDC, IDSA, ASBMT and international partners (Biology of Blood and Marrow Transplantation)","year":2009,"url":"https://europepmc.org/article/PMC/PMC3103296","doi":"10.1016/j.bbmt.2009.06.019","gradingScheme":"Strength A to E with quality I to III, printed together, for example AIII.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No guideline read is specific to hand hygiene in cancer care; the measures are general ones applied to people with low immunity.","The WHO guideline dates from 2009 and its evidence base has not been re-graded since; WHO's later hand hygiene materials were not read.","CDC's patient page on preventing infection during cancer treatment was not read, so its advice to patients is not reflected here.","There is no graded recommendation on how often patients and families should clean their hands at home; the paediatric guideline's statement is a good practice statement."]},{"id":"hand-foot-syndrome-prevention-and-dose-modification","kind":"protocol","name":"Hand-foot syndrome and hand-foot skin reaction: prevention, skin care and dose changes","aka":["hand-foot syndrome","HFS","palmar-plantar erythrodysesthesia","PPE","PPES","hand-foot skin reaction","HFSR","capecitabine hand-foot syndrome","urea cream for hand-foot","topical diclofenac for hand-foot syndrome"],"tldr":"Capecitabine, liposomal doxorubicin and tablets such as sorafenib and regorafenib can make the palms and soles red, sore, peeling or blistered. From the start, avoid rubbing, heat and long soaks, wear well-fitting shoes and moisturise daily; with sorafenib, a 10 per cent urea cream from day one helps. If hands or feet become painful or limit what you do, stop capecitabine and call your team.","summary":"Hand-foot syndrome (HFS) from capecitabine and pegylated liposomal doxorubicin, and hand-foot skin reaction (HFSR) from multikinase inhibitors, are managed by prevention, inspection at every cycle, and dose modification by CTCAE grade. Labels set the dose rules: capecitabine is withheld for grade 2 or worse until grade 0 to 1 and restarted at 100, 75 or 50 per cent of the current dose by occurrence (grade 2) or at 75 or 50 per cent (grade 3), and patients are told to stop the tablets themselves at grade 2; liposomal doxorubicin is delayed up to 2 weeks for grade 2 or worse and reduced by 25 per cent after grade 3; regorafenib is reduced to 120 mg at the first grade 2 HFSR and to 80 mg if it recurs, and interrupted for at least 7 days at grade 3.\n\nFor prevention, general measures (avoiding friction, heat and water exposure, fitted gloves and footwear, regular emollients) are universal advice without randomised proof. 10 per cent urea cream three times daily from day 1 of sorafenib lowered any-grade HFSR (56.0 against 73.6 per cent) and grade 2 or worse HFSR (20.7 against 29.2 per cent) in an open trial of 871 people; a blinded trial of 20 per cent urea was not significant on its primary measure. With capecitabine, oral celecoxib reduces grade 2 or worse HFS in network meta-analyses but carries cardiovascular and gastrointestinal risk; topical diclofenac gel reduced grade 2 to 3 HFS from 15.0 to 3.8 per cent in the D-TORCH trial and leads the 2026 network meta-analysis, but a 2026 real-world study found no benefit and a Japanese phase 3 trial is under way. Pyridoxine does not work. The ESMO 2021 guideline could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","hand-foot-syndrome","skin-toxicity","supportive-care"],"related":["celecoxib"],"cancers":[],"sections":["supportive-care"],"technologies":["vitamin-b6-pyridoxine"],"targets":[],"drugs":["capecitabine","capox","pegylated-liposomal-doxorubicin","sorafenib","regorafenib","cabozantinib","lenvatinib","sunitinib","tegafur-gimeracil-oteracil"],"companies":[],"institutions":[],"pathways":[],"terms":["hand-foot-syndrome"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer medicines make hands and feet sore. Keep them cool and moisturised. If they hurt or blister, stop the tablets and call your team.","domain":"symptom-management","setting":{"who":["nurse","doctor","pharmacist","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","home"]},"population":"Adults taking capecitabine (alone or in combination) or receiving pegylated liposomal doxorubicin, and adults taking multikinase inhibitors that cause hand-foot skin reaction (regorafenib, sorafenib, cabozantinib, lenvatinib, sunitinib and others). The urea cream trials were in advanced hepatocellular carcinoma on sorafenib; the diclofenac trial in breast and gastrointestinal cancers on capecitabine. Dose rules differ by drug and come from each drug's own label.","trigger":"A drug that causes hand-foot syndrome or skin reaction is started, and at every cycle or review while it continues.","steps":[{"action":"Before treatment starts, teach hand and foot care: avoid rubbing, pressure and long exposure to hot water, wear well-fitted (not tight) gloves and footwear, and moisturise hands and feet every day","why":"Pressure, friction and heat bring the reaction on where the skin is under most stress; moisturising keeps the skin supple. These measures are safe, though no trial has proved them on their own.","source":"jp-review-2025","quote":"Preventive measures (grade 0) include avoiding mechanical or chemical stress, limiting water exposure, wearing appropriately fitted gloves, regular use of emollients, and patient education.","grade":"expert review; no randomised trial of these measures alone"},{"action":"Look at the palms and soles and ask about pain or difficulty with daily activities before every cycle","why":"The reaction is often under-reported; seeing it early allows a short break before it becomes severe.","source":"s1-esmo-open-2023","quote":"As its incidence may be underestimated, the panel recommended that providers carry out visual inspections of the palms of the hands and soles of the feet in addition to taking history on HFS-related symptoms prior to each cycle.","grade":"international expert panel recommendation, ungraded"},{"action":"With sorafenib, offer 10 per cent urea cream on the hands and feet three times a day from the first day of treatment","why":"Urea softens the thickened skin where the reaction starts; in a large trial it lowered the chance of a reaction and delayed it.","source":"ren-2015","quote":"UBC prophylaxis in patients with advanced HCC starting sorafenib reduced HFSR rates, extended the time to first occurrence of HFSR, and improved patient quality of life compared with BSC.","grade":"randomised open-label trial, n = 871"},{"action":"With capecitabine, consider topical diclofenac gel on the palms, explaining that the evidence is mixed","why":"An anti-inflammatory gel blocks a step in the inflammation behind the reaction; one randomised trial found it prevented most moderate cases, but a later study in routine care did not.","source":"d-torch-2024","quote":"Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003).","grade":"single-site randomised double-blind trial, n = 264"},{"action":"Do not give pyridoxine (vitamin B6) to prevent hand-foot syndrome","why":"Several trials found that it does not prevent the reaction.","source":"jp-review-2025","quote":"Pyridoxine Most RCTs on pyridoxine showed negative results, and multiple systematic reviews and meta-analyses have shown insufficient efficacy [ 59 , 60 ].","grade":"systematic reviews and meta-analyses"},{"action":"Capecitabine: tell the person to stop the tablets and call the team if the reaction reaches grade 2 (painful, or limiting daily activities)","why":"Stopping at once lets the skin recover quickly; continuing makes it worse and can lead to a longer break.","source":"xeloda-label","quote":"Instruct patients experiencing grade 2 palmar-plantar erythrodysesthesia syndrome or greater to stop taking XELODA immediately and to contact their healthcare provider.","grade":"US prescribing information"},{"action":"Capecitabine: withhold until grade 0 to 1, then restart at the same or a lower dose by grade and occurrence (grade 2: 100, 75, then 50 per cent; grade 3: 75, then 50 per cent); do not replace missed doses","why":"Lowering the dose after a reaction makes a repeat less likely while keeping the treatment going.","source":"xeloda-label","quote":"Withhold XELODA and then resume at same or reduced dose or permanently discontinue based on severity and occurrence","grade":"US prescribing information (Table 1)"},{"action":"Liposomal doxorubicin: delay the next dose for a first grade 2 or worse reaction, for up to 2 weeks, and reduce by 25 per cent after a grade 3 reaction","why":"The reaction usually appears after two or three cycles and settles with a delay; a lower dose makes it less likely to return.","source":"doxil-label","quote":"Delay DOXIL liposomal infusion for the first episode of Grade 2 or greater HFS","grade":"US prescribing information"},{"action":"Regorafenib: reduce to 120 mg at the first grade 2 skin reaction and to 80 mg if it recurs; interrupt for at least 7 days for grade 3","why":"The reaction is most common in the first cycle; stepping the dose down lets most people continue.","source":"stivarga-label","quote":"Grade 2 hand-foot skin reaction (HFSR) [palmar-plantar erythrodysesthesia syndrome (PPES)] that is recurrent or does not improve within 7 days despite dose reduction; interrupt therapy for a minimum of 7 days for Grade 3 HFSR","grade":"US prescribing information"},{"action":"For established reactions, use moisturisers and 10 per cent urea cream for thickened skin, and a potent topical steroid for painful inflamed areas, stepping down once better","why":"Steroid creams calm the inflammation and urea softens the hard skin; Western guidelines recommend them, though no trial has tested them for this.","source":"jp-review-2025","quote":"Various guidelines recommend high potent topical steroid therapy for grade ≥ 2 HFS/HFSR [ 13 , 14 ], and such is used in clinical practice, although no RCTs have been conducted.","grade":"guideline recommendation cited by the review; no randomised trials"},{"action":"In metastatic colorectal cancer, if capecitabine or infusional fluorouracil hand-foot syndrome causes pain or limits function, consider switching to S-1 once it has settled to grade 1 or less","why":"S-1 is a different fluoropyrimidine tablet that causes much less hand-foot syndrome, so treatment can continue at full strength.","source":"s1-esmo-open-2023","quote":"In patients who experience pain and/or functional impairment due to HFS during treatment with capecitabine or infusional 5-FU, a switch to S-1 is recommended without prior dose reduction of capecitabine/5-FU.","grade":"international expert panel recommendation, ungraded"}],"bestInClass":{"statement":"Dose modification by grade, from each drug's label, is the core of management, with inspection of hands and feet at every cycle and early self-stopping of capecitabine at grade 2. For prevention, the strongest single result is 10 per cent urea cream from day 1 of sorafenib (large open trial; a blinded trial of 20 per cent urea was not significant on its main measure). For capecitabine, two network meta-analyses agree that oral celecoxib reduces moderate to severe HFS but its cardiovascular and gastrointestinal risks limit routine use; topical diclofenac had the strongest effect in the 2026 network meta-analysis and in one randomised trial, but a 2026 real-world study found no benefit and a confirmatory phase 3 trial (J-DIRECT) is under way, so it is reasonable to offer but not yet established. Urea cream beat an antioxidant ointment for capecitabine in one trial. Pyridoxine does not work. The ESMO 2021 dermatological toxicity guideline, which is the main international guideline, could not be read.","sources":["xeloda-label","doxil-label","stivarga-label","ren-2015","lee-2020","nma-2022","nma-2026","d-torch-2024","diclo-hfs-2026","mapisal-2015","jp-review-2025","esmo-derm-2021"]},"variants":[{"name":"Oral celecoxib with capecitabine","differs":"Celecoxib 200 mg twice daily alongside capecitabine to prevent HFS.","evidence":"The 2022 network meta-analysis (15 trials, 2715 patients) found only celecoxib significantly prevented grade 2 or worse HFS (odds ratio 0.29); the 2026 network meta-analysis also found a reduction (risk ratio 0.46). The Japanese review advises limiting it because of cardiovascular and gastrointestinal risk with long-term use.","sources":["nma-2022","nma-2026","jp-review-2025"]},{"name":"Topical diclofenac in routine care (DICLO-HFS, Turkey)","differs":"1 per cent diclofenac gel twice daily from the start of capecitabine as routine practice, compared with active monitoring, in two centres.","evidence":"Prospective observational study of 151 people: grade 2 or worse HFS 16.9 per cent with diclofenac against 13.8 per cent with monitoring (not significant); the authors concluded the findings do not support routine diclofenac prophylaxis. Not randomised.","sources":["diclo-hfs-2026"]},{"name":"Urea cream rather than an antioxidant ointment with capecitabine","differs":"10 per cent urea cream as the preventive cream for capecitabine, compared with Mapisal, an antioxidant ointment.","evidence":"Randomised phase 3 trial of 152 evaluable people: any-grade HFS in 6 weeks 22.4 per cent with urea against 39.5 per cent with the ointment. There was no untreated control group.","sources":["mapisal-2015"]},{"name":"Asian practice (Japanese pharmacist-led review)","differs":"Topical steroids are not used for grade 1 HFS, and lidocaine patches and antiseptic solutions are not used for grade 3, unlike Western guidance; urea cream used with caution because of irritation.","evidence":"Narrative review of 53 articles by a Japanese pharmacist-led group; based on differences in skin type and lack of Asian safety data rather than trials.","sources":["jp-review-2025"]}],"grades":[{"claim":"Urea cream 10 per cent reduced grade 2 or worse HFSR with sorafenib","grade":"randomised open-label trial, P = .004","source":"ren-2015","quote":"as was the incidence of grade ≥ 2 HFSR (20.7% v 29.2%, respectively; OR, 0.635; 95% CI, 0.466 to 0.866; P = .004)."},{"claim":"Urea cream 20 per cent did not significantly reduce cumulative HFSR in a blinded trial with sorafenib","grade":"randomised double-blind trial, not significant on cumulative incidence","source":"lee-2020","quote":"The urea cream group showed a trend towards a lower cumulative incidence of any-grade HFSR (log-rank, P = 0.247) and severe HFSR of grade II or higher (log-rank, P = 0.394) without statistical significance."},{"claim":"Topical diclofenac and celecoxib reduced moderate to severe HFS in the 2026 network meta-analysis","grade":"network meta-analysis of 13 RCTs, 1983 patients","source":"nma-2026","quote":"Both topical diclofenac (RR 0.26, 95% CI 0.10 to 0.66) and celecoxib (RR 0.46, 95% CI 0.26 to 0.84) significantly reduced the risk of moderate to severe HFS compared with placebo."},{"claim":"Only celecoxib prevented moderate to severe HFS in the 2022 network meta-analysis","grade":"Bayesian network meta-analysis of 15 RCTs, 2715 patients","source":"nma-2022","quote":"The analysis showed only celecoxib could significantly prevent the incidence of moderate to severe HFS (grade ≥2) (OR 0.29, 95% CrI 0.13 to 0.68)."},{"claim":"Topical diclofenac did not reduce grade 2 or worse HFS in routine care","grade":"prospective observational study, n = 151, not significant","source":"diclo-hfs-2026","quote":"In this prospective real-world study, prophylactic topical diclofenac did not reduce clinically significant capecitabine-induced HFS or delay its onset compared with active monitoring."}],"sources":[{"key":"esmo-derm-2021","label":"Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines","publisher":"ESMO, Annals of Oncology","year":2021,"url":"https://doi.org/10.1016/j.annonc.2020.11.005","doi":"10.1016/j.annonc.2020.11.005","read":"not-reachable","accessed":"2026-11-11"},{"key":"jp-review-2025","label":"Chemotherapy-related hand-foot syndrome and hand-foot skin reaction: a review of management and possible approaches for Asian patients by the Japanese pharmacist-led oncodermatology study team","publisher":"International Journal of Clinical Oncology","year":2025,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12644181/","doi":"10.1007/s10147-025-02895-y","gradingScheme":"Narrative review of 53 articles; recommendations not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"s1-esmo-open-2023","label":"Fluoropyrimidine-induced hand-foot syndrome and cardiotoxicity: recommendations for the use of the oral fluoropyrimidine S-1 in metastatic colorectal cancer","publisher":"ESMO Open","year":2023,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10163153/","doi":"10.1016/j.esmoop.2023.101199","gradingScheme":"International expert group recommendations from published data; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"xeloda-label","label":"XELODA (capecitabine) prescribing information","publisher":"H2-Pharma, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e702d84d-7162-4751-bf37-d724cc7e45a5","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"doxil-label","label":"DOXIL (doxorubicin hydrochloride liposome injection) prescribing information","publisher":"Baxter, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1c153e9e-4cf2-4ac7-9cf9-16f9b48d7dce","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"stivarga-label","label":"STIVARGA (regorafenib) prescribing information","publisher":"Bayer, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=824f19c9-0546-4a8a-8d8f-c4055c04f7c7","gradingScheme":"US prescribing information: regulatory labelling, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ren-2015","label":"Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma","publisher":"Journal of Clinical Oncology","year":2015,"url":"https://europepmc.org/abstract/MED/25667293","doi":"10.1200/JCO.2013.52.9651","read":"abstract","accessed":"2026-11-11"},{"key":"lee-2020","label":"Effect of urea cream on sorafenib-associated hand-foot skin reaction in patients with hepatocellular carcinoma: a multicenter, randomised, double-blind controlled study","publisher":"European Journal of Cancer","year":2020,"url":"https://europepmc.org/abstract/MED/33039810","doi":"10.1016/j.ejca.2020.09.012","read":"abstract","accessed":"2026-11-11"},{"key":"mapisal-2015","label":"Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group","publisher":"Journal of Clinical Oncology","year":2015,"url":"https://europepmc.org/abstract/MED/26124485","doi":"10.1200/JCO.2014.60.4587","read":"abstract","accessed":"2026-11-11"},{"key":"d-torch-2024","label":"Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial","publisher":"Journal of Clinical Oncology","year":2024,"url":"https://europepmc.org/abstract/MED/38412399","doi":"10.1200/JCO.23.01730","read":"abstract","accessed":"2026-11-11"},{"key":"diclo-hfs-2026","label":"Topical Diclofenac for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Prospective Real-World Study","publisher":"JCO Global Oncology","year":2026,"url":"https://europepmc.org/abstract/MED/42623594","doi":"10.1200/GO-26-00151","read":"abstract","accessed":"2026-11-11"},{"key":"nma-2022","label":"Chemotherapy-induced hand foot syndrome: comparative efficacy and safety of pharmacological prophylaxis: systematic review and Bayesian network meta-analysis","publisher":"BMJ Supportive & Palliative Care","year":2022,"url":"https://europepmc.org/abstract/MED/36564149","doi":"10.1136/spcare-2022-004011","read":"abstract","accessed":"2026-11-11"},{"key":"nma-2026","label":"Hand-foot syndrome prevention: pharmacological interventions: systematic review and network meta-analysis","publisher":"BMJ Supportive & Palliative Care","year":2026,"url":"https://europepmc.org/abstract/MED/41207711","doi":"10.1136/spcare-2025-005639","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-topical-diclofenac-during-capecitabine"],"gaps":["The ESMO 2021 dermatological toxicity guideline could not be read (no abstract in Europe PMC; the publisher refused a script), so its grades and its preventive recommendations are not given here. No MASCC guideline specific to hand-foot syndrome was found.","The trials, network meta-analyses and the D-TORCH and DICLO-HFS studies were read as abstracts only.","Whether topical diclofenac works on the soles is unknown: D-TORCH applied it to the palms only. The Japanese phase 3 trial J-DIRECT, testing a cream on palms and soles, had not reported in what was read.","General measures (avoiding friction and heat, emollients) are universal advice with no randomised trial behind them on their own.","Dose rules for multikinase inhibitors other than regorafenib (sorafenib, cabozantinib, lenvatinib, sunitinib) were not read here; each drug's own label sets them.","The Western guideline recommendations on topical steroids are known here only as the Japanese review reports them."]},{"id":"hdr-brachytherapy-room-safety-and-stuck-source-emergency","kind":"protocol","name":"HDR brachytherapy: treatment-room safety and the stuck-source emergency","aka":["HDR source emergency","stuck source procedure","source fails to retract","afterloader emergency procedure","remote afterloader safety","HDR brachytherapy safety checks","PDR brachytherapy safety","emergency container brachytherapy","afterloader daily checks"],"tldr":"In high-dose-rate brachytherapy a machine pushes a tiny, very radioactive source along tubes into the treatment area for a few minutes, then pulls it back into a shielded safe. You are alone in the room while it runs, but staff watch and talk to you throughout. The machine is checked every treatment day, and the team practises for the rare case the source does not go back.","summary":"An HDR or pulsed-dose-rate afterloader is checked before the first treatment of each day (IAEA SSG-46 para 5.134; US 10 CFR 35.643(a)(1)): door interlocks, source-exposed lights, viewing and intercom, emergency equipment, radiation monitors, timer, clock and decayed source activity; any failure locks the console off until it is fixed (35.643(d), (e)). During delivery no one but the patient is in the room (SSG-46 5.107), the patient is watched continuously (35.615(d)), opening the door retracts the source (35.615(b)), and anyone entering confirms with a monitor that radiation has returned to background (35.615(c)). HDR rooms carry permanently installed area monitors (SSG-46 5.155).\n\nAn emergency container large enough for the whole applicator, and a kit of long-handled forceps and clamps, sits close to the patient (SSG-46 5.135, 5.316; 35.615(g)). The manufacturer's one-page emergency procedure is posted at the console with the names and numbers of the responsible physician, physicist and radiation protection officer (35.610(a)(4), (b), (c)). If the source fails to return, the sequence escalates step by step: console retract, entry with a survey meter, retract at the unit, hand crank, survey, removal of the applicator into the emergency container, survey of patient and container, removal of the patient, notification (SSG-46 5.136). Because the response must happen within minutes, IAEA asks for a radiation oncologist, a medical physicist and a radiation therapy technologist to be immediately available during every HDR application (5.317); the US rule requires the authorised user and the authorised medical physicist to be physically present at the start of every HDR treatment, and a physicist with a trained physician throughout (35.615(f)(2)). Staff drill the procedure initially and at least yearly (35.610(e)). Afterwards the engineer inspects the unit, the physicist estimates the patient's dose and the radiation protection officer the staff doses, and the event is reported to the regulator where required and to a learning system such as SAFRON or ROSEIS (SSG-46 5.319).\n\nThe accident these rules answer is real: in a case recorded by the IAEA, staff disregarded an area monitor alarm because the console read 'safe', the source had broken off inside a catheter, the patient went home with it for almost four days and died, and 94 other people were exposed (SRS-17, event 84).","asOf":"2026-11-11","links":[],"tags":[],"related":["radiotherapy-patient-identification-and-time-out"],"cancers":["cervical"],"sections":[],"technologies":["hdr-brachytherapy","brachytherapy-afterloaders","brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":["iaea"],"pathways":[],"terms":["brachytherapy-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"During this treatment you are alone in the room, but the team can see and hear you all the time. If you feel unwell, say so: they can stop the machine at once. The machine is checked every day before anyone is treated.","domain":"radiotherapy","setting":{"who":["radiographer","doctor","multidisciplinary-team"],"where":["radiotherapy-department","theatre"]},"population":"Adults and children having high-dose-rate or pulsed-dose-rate brachytherapy from a remote afterloader (cervical, endometrial, prostate, oesophageal, bronchial, breast, skin and other sites), and the staff who deliver it. Low-dose-rate permanent seed implants are a separate protocol; manual brachytherapy and the planning of the dose are not covered.","trigger":"A treatment day with a remote afterloader begins, or an afterloader signals that the source has not returned to its safe.","steps":[{"action":"Before the first patient of the day, run the afterloader's routine checks","why":"The checks find a faulty door switch, light, monitor or timer before anyone is treated.","source":"iaea-ssg46","quote":"The HDR/PDR afterloader should undergo routine quality assurance tests at the beginning of each treatment day"},{"action":"Check at least the door interlocks, source-exposed lights, viewing and intercom, emergency equipment, radiation monitors, timer, clock and decayed source activity; if any fails, lock the console off and do not treat","why":"Each of these is a safety barrier; treating with one broken removes a layer of protection.","source":"nrc-10cfr35-643","quote":"If the results of the checks required in paragraph (d) of this section indicate the malfunction of any system, a licensee shall lock the control console in the off position and not use the unit except as may be necessary to repair, replace, or check the malfunctioning system."},{"action":"Put the emergency container and the emergency kit (long-handled forceps, clamps) in the room, next to the patient, and make sure the container can take the whole applicator","why":"If the source sticks, the applicator with the source inside is pulled out and put straight into the shielded container.","source":"iaea-ssg46","quote":"The emergency container should be placed close to the patient and should be sufficiently large that it can accept the entire applicator assembly containing the source removed from the patient."},{"action":"Keep the written emergency procedure, with the names and telephone numbers of the responsible physician, physicist and radiation safety officer, at the console","why":"In an emergency there is no time to look for instructions or phone numbers.","source":"nrc-10cfr35-610","quote":"A copy of the procedures required by paragraph (a)(4) of this section must be physically located at the unit console."},{"action":"Check the patient, the prescription and the treatment plan against each other independently before the source is driven out","why":"In a recorded case the physicist picked up the wrong patient's chart at the console and the wrong programme was run.","source":"iaea-srs17","quote":"Insufficient safety provisions (defence in depth): There was no independent check of the information used for the treatment."},{"action":"Make sure the trained staff are there: for HDR, the radiation oncologist and the physicist present when treatment starts, and a physicist with a trained physician throughout (US rule); a radiation oncologist, physicist and radiation therapy technologist immediately available during every application (IAEA)","why":"If the source sticks, the response has to happen within minutes, by people trained to do it.","source":"iaea-ssg46","quote":"In HDR applications, the short response time (minutes) required for contingency actions imposes the need for the immediate availability of a radiological medical practitioner, a medical physicist and a medical radiation technologist during all applications."},{"action":"During delivery, let no one but the patient stay in the room, and watch and listen to the patient throughout on camera and intercom","why":"Staff are protected by the shielded walls, and the patient is never out of sight or earshot.","source":"iaea-ssg46","quote":"For external beam radiotherapy, HDR and PDR brachytherapy, no one should be in the treatment room during the delivery of treatment, except the patient being treated."},{"action":"On entering the room after treatment, confirm with a radiation monitor that levels are back to background, and treat any monitor alarm as real until proved otherwise, even if the console says the source is safe","why":"In a fatal accident the console read 'safe' while the source had broken off inside the patient; the alarm was right and was ignored.","source":"iaea-srs17","quote":"Staff ignored a monitor alarm and assumed that a 'safe' indication on the console was correct (previous false alarms of the external monitor contributed to this assumption)."},{"action":"If the source does not return, follow the posted sequence and move to the next step only if the last one failed: emergency retract at the console; enter with a survey meter; retract at the unit; crank the source back by hand; survey; remove the applicator into the emergency container; survey the patient and the container; take the patient out of the room","why":"Each step is quicker and safer than the next, and each survey shows whether the source is back in its safe.","source":"iaea-ssg46","quote":"Manufacturers provide suggested emergency procedures to be implemented if the source fails to return to the safe."},{"action":"After the event, have the engineer inspect the unit, the physicist estimate the patient's dose and clear the unit for reuse, and the radiation protection officer estimate staff doses; record everything, notify the regulator where required and report to a learning system","why":"The patient needs to know what dose they received, and other departments learn from the event.","source":"iaea-ssg46","quote":"The medical physicist should make an assessment of the patient doses arising from the incident, and should check the machine for re-use after the engineer has completed the inspection and any associated maintenance."},{"action":"Drill the emergency procedure with every operator, physicist and physician when they start and at least once a year","why":"A procedure used once in years is only reliable if it has been practised.","source":"nrc-10cfr35-610","quote":"A licensee shall ensure that operators, authorized medical physicists, and authorized users participate in drills of the emergency procedures, initially and at least annually."}],"bestInClass":{"statement":"A daily pre-treatment check of the afterloader and its room (IAEA SSG-46 5.134; 10 CFR 35.643), an emergency container and kit beside the patient (SSG-46 5.135; 35.615(g)), the manufacturer's escalating stuck-source procedure posted at the console (SSG-46 5.136; 35.610), continuous observation with no one else in the room, a monitor check on every entry, and annual drills (35.610(e); SSG-46 5.316). The two frameworks differ on staffing: IAEA asks for a radiation oncologist, a physicist and a radiation therapy technologist immediately available during all HDR applications; the US rule requires the authorised user and physicist to be physically present when each HDR treatment starts and a physicist with a trained physician to be present throughout. Neither grades its requirements: one is a safety standard and the other regulation, and the evidence behind both is the record of accidents.","sources":["iaea-ssg46","nrc-10cfr35-610","nrc-10cfr35-615","nrc-10cfr35-643","iaea-srs17"]},"variants":[{"name":"US regulation: physician and physicist physically present","differs":"10 CFR 35.615(f)(2) requires an authorised user and an authorised medical physicist to be physically present during the initiation of every HDR treatment, and a physicist plus an authorised user or trained physician to be physically present during its continuation. Medium and pulsed-dose-rate units need the physicist and a trained physician present at initiation and immediately available during continuation. The IAEA guide asks for immediate availability rather than physical presence.","evidence":"Regulation, not graded. Its rationale, the minutes available to act, is the one SSG-46 gives.","sources":["nrc-10cfr35-615","iaea-ssg46"]},{"name":"Manufacturer's unit-specific emergency card","differs":"Each afterloader's maker supplies its own single-page emergency sequence, which is what is posted at the console. IAEA gives the general order of steps; the unit's own card governs the details, such as where the emergency retract button and hand crank are.","evidence":"SSG-46 says these procedures are specific to the unit and assume the applicator is intact.","sources":["iaea-ssg46"]},{"name":"AAPM Task Group 59 (US professional report, 1998)","differs":"Sets out HDR procedures for staffing and training, treatment-specific quality assurance and emergency procedures, with an extensive quality assurance checklist. Only its abstract was read here.","evidence":"A professional consensus report; its content was not read beyond the abstract and no step rests on it.","sources":["aapm-tg59"]}],"grades":[{"claim":"Daily quality assurance tests of the HDR or PDR afterloader","grade":"Safety Guide recommendation (ungraded)","source":"iaea-ssg46"},{"claim":"Spot checks before the first HDR use each day, covering interlocks, lights, intercom, emergency equipment, monitors, timer, clock and source activity","grade":"Regulatory requirement (ungraded)","source":"nrc-10cfr35-643","quote":"Before the first use of a high dose-rate, medium dose-rate, or pulsed dose-rate remote afterloader unit on a given day;"},{"claim":"Emergency response equipment near each treatment room for a source left unshielded or lodged in the patient","grade":"Regulatory requirement (ungraded)","source":"nrc-10cfr35-615","quote":"A licensee shall have applicable emergency response equipment available near each treatment room to respond to a source—"},{"claim":"Anyone entering the room confirms with a monitor that radiation has returned to ambient levels","grade":"Regulatory requirement (ungraded)","source":"nrc-10cfr35-615","quote":"A licensee shall require any individual entering the treatment room to assure, through the use of appropriate radiation monitors, that radiation levels have returned to ambient levels."},{"claim":"Staff trained on the stuck-source procedure and taking part in drills","grade":"Safety Guide recommendation (ungraded)","source":"iaea-ssg46","quote":"Staff should be trained on how to apply such a procedure and should regularly participate in drills and exercises."}],"sources":[{"key":"iaea-ssg46","label":"Radiation Protection and Safety in Medical Uses of Ionizing Radiation, Specific Safety Guide No. SSG-46","publisher":"International Atomic Energy Agency, jointly sponsored by PAHO and WHO","year":2018,"url":"https://www-pub.iaea.org/MTCD/Publications/PDF/PUB1775_web.pdf","gradingScheme":"An IAEA Safety Guide: recommendations ('should') on how to meet the Safety Requirements (GSR Part 3); not graded by evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"nrc-10cfr35-610","label":"10 CFR 35.610 Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2018,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-H/section-35.610","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nrc-10cfr35-615","label":"10 CFR 35.615 Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2002,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-H/section-35.615","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nrc-10cfr35-643","label":"10 CFR 35.643 Periodic spot-checks for remote afterloader units","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2002,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-H/section-35.643","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"iaea-srs17","label":"Lessons Learned from Accidental Exposures in Radiotherapy, Safety Reports Series No. 17 (section 2.10, high dose rate brachytherapy)","publisher":"International Atomic Energy Agency","year":2000,"url":"https://www-pub.iaea.org/MTCD/Publications/PDF/Pub1084_web.pdf","gradingScheme":"A collection of reported accidents with their causes and remedies; no recommendations are graded.","read":"full-text","accessed":"2026-11-11"},{"key":"aapm-tg59","label":"High dose-rate brachytherapy treatment delivery: report of the AAPM Radiation Therapy Committee Task Group No. 59","publisher":"American Association of Physicists in Medicine (Kubo et al., Medical Physics)","year":1998,"url":"https://doi.org/10.1118/1.598232","doi":"10.1118/1.598232","gradingScheme":"Professional task group report; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"acr-abs-hdr","label":"ACR-ABS Practice Parameter for the Performance of High-Dose-Rate Brachytherapy","publisher":"American College of Radiology and American Brachytherapy Society","year":2020,"url":"https://www.acr.org/-/media/ACR/Files/Practice-Parameters/HDR-Brachy.pdf","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No source read grades these steps by evidence. They are a safety standard (IAEA), regulation (NRC) and lessons from accidents (IAEA SRS-17); there are no trials of emergency procedures, and stuck-source events are too rare to compare approaches.","The AAPM TG-59 report was read only as its abstract, and the ACR-ABS HDR practice parameter could not be read (the ACR address served a JavaScript shell to a script). Their checklists are not reproduced here.","UK requirements (the Ionising Radiations Regulations 2017 and their approved code of practice, and IPEM guidance on afterloader quality control) were not read, so the UK position on staffing during HDR delivery is not stated.","The year given for 10 CFR 35.610 is that of its latest amendment printed in the section (83 FR 33110, July 2018); 35.615 and 35.643 print no amendment history in the text read, and the year given for them is that of the 2002 rule (67 FR 20370) which 35.610 cites as its origin.","SRS-17 dates from 2000; newer accident reports (ROSEIS, SAFRON, RO-ILS) were not searched."]},{"id":"paediatric-cisplatin-hearing-protection","kind":"protocol","name":"Hearing protection for children receiving cisplatin","aka":["cisplatin ototoxicity prevention in children","sodium thiosulfate otoprotection","Pedmark","Pedmarqsi","cisplatin hearing loss children","ototoxicity surveillance"],"tldr":"Cisplatin can permanently damage a child's hearing. For many children whose cancer has not spread, a drug called sodium thiosulfate, given as a short drip six hours after each dose of cisplatin, roughly halves the chance of hearing loss. Hearing is tested during treatment and for years after, and any loss is referred to a hearing specialist.","summary":"The international guideline (Freyer et al., 2020, GRADE, endorsed by the Children's Oncology Group in August 2020) covers children and adolescents aged 0 to 18 receiving cisplatin. Sodium thiosulfate: use it in non-metastatic hepatoblastoma (strong, high quality, from SIOPEL 6, where any hearing loss fell from 63% to 33% with no loss of survival); consider it in other non-metastatic cancers (weak, low); and do not use it routinely in metastatic cancers (weak, low), because in the post-hoc metastatic subgroup of ACCL0431 3-year overall survival was 45% with it against 84% without, an estimate the panel judged open to bias and asked to be discussed with families. Do not use amifostine (strong, high), sodium diethyldithiocarbamate (strong, low) or intratympanic therapy (strong, low), and do not change the cisplatin infusion length to protect hearing (strong, low), except that sodium thiosulfate needs cisplatin infusions of 6 hours or less.\n\nThe US label for PEDMARK limits it to children aged 1 month or older with localised, non-metastatic solid tumours, gives it over 15 minutes starting 6 hours after each cisplatin infusion and at least 10 hours before the next, doses by weight-based surface area, and says not to start it with a serum sodium above 145 mmol/L. The IGHG recommends hearing surveillance from the end of treatment at the latest: yearly under 6 years, every other year from 6 to 12, and every 5 years over 12, with pure-tone audiometry at 1000 to 8000 Hz from age 6 and a referral for any loss of more than 15 dB.","asOf":"2026-11-11","links":[],"tags":["protocol","paediatric","ototoxicity"],"related":["idea-moon-hearing-protection-cisplatin"],"cancers":["childhood-cancers","hepatoblastoma","medulloblastoma","osteosarcoma","neuroblastoma","paediatric-germ-cell-tumours"],"sections":["supportive-care"],"technologies":["hearing-after-platinum-chemotherapy","rejuv-paed-hearing"],"targets":[],"drugs":["sodium-thiosulfate","cisplatin","amifostine"],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":["late-effects"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"One cancer medicine, cisplatin, can hurt hearing. Another medicine, given six hours later, can protect it for many children. Their hearing is checked during and after treatment.","domain":"paediatric","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer","multidisciplinary-team"],"where":["ward","chemotherapy-day-unit","outpatient-clinic"]},"population":"Children and adolescents aged 0 to 18 receiving cisplatin for cancer (the guideline notes it may also apply to older adolescents and young adults); the drug label excludes babies under 1 month and children with metastatic cancer. Surveillance recommendations cover childhood, adolescent and young adult survivors treated with cisplatin or with head or brain radiotherapy of 30 Gy or more. Adults are not covered.","trigger":"A child or adolescent is due to start a cisplatin-containing regimen.","steps":[{"action":"Plan hearing tests during treatment for every child receiving cisplatin","why":"Hearing loss from cisplatin often starts in the high pitches a child does not notice, so it has to be measured.","source":"ighg-2019","quote":"Surveillance is usually mandatory for at-risk patients during treatment."},{"action":"In non-metastatic hepatoblastoma, give sodium thiosulfate with each cisplatin dose","why":"In the SIOPEL 6 trial hearing loss fell from 63% to 33% of children, and survival was not reduced.","source":"freyer-2020","quote":"Use sodium thiosulfate for the prevention of cisplatin-induced ototoxicity in children and adolescents with non-metastatic hepatoblastoma","grade":"Strong, high quality"},{"action":"In other non-metastatic cancers, consider sodium thiosulfate and discuss it with the family","why":"Hearing protection should not depend on the type of cancer, but the survival evidence outside hepatoblastoma is less certain.","source":"freyer-2020","quote":"Consider sodium thiosulfate for the prevention of cisplatin-induced ototoxicity in children and adolescents with non-metastatic cancers other than hepatoblastoma","grade":"Weak, low quality"},{"action":"In metastatic cancers, do not give sodium thiosulfate routinely, but discuss it as an option","why":"In one trial, children with metastatic disease who had it survived less often; that finding may be due to chance or bias, so the family's values matter.","source":"freyer-2020","quote":"We suggest sodium thiosulfate not be used routinely for the prevention of cisplatin-induced ototoxicity for children and adolescents with metastatic cancers","grade":"Weak, low quality"},{"action":"Do not give sodium thiosulfate to a baby under 1 month old","why":"Babies this young control their blood sodium less well, and the drug raises the risk of sodium going too high.","source":"pedmark-label","quote":"PEDMARK is not indicated and not recommended for use in pediatric patients younger than 1 month of age."},{"action":"Where sodium thiosulfate is planned, keep each cisplatin infusion to 6 hours or less","why":"Both trials used cisplatin infusions of 6 hours or less; after a longer infusion the damage may already be done.","source":"freyer-2020","quote":"However, if sodium thiosulfate is to be introduced as an otoprotectant, then the cisplatin infusion will need to be 6 h or less, as was required in the SIOPEL 6 and ACCL0431 trials."},{"action":"Check sodium and potassium first, and do not start sodium thiosulfate if the sodium is above 145 mmol/L","why":"The drug can push sodium too high and potassium too low.","source":"pedmark-label","quote":"Do not initiate PEDMARK infusions in patients with baseline serum sodium greater than 145 mmol/L"},{"action":"Give sodium thiosulfate over 15 minutes, starting 6 hours after each cisplatin infusion ends","why":"This is the timing both trials used and the label sets; the guideline says that if sodium thiosulfate is used it should be given the same way.","source":"pedmark-label","quote":"Administer PEDMARK as an intravenous infusion over 15 minutes starting 6 hours after completion of cisplatin infusion."},{"action":"On multi-day cisplatin, give it at least 10 hours before the next cisplatin dose, and skip it if that gap cannot be kept","why":"The gap stops the protector being in the blood when the next dose of cisplatin is given.","source":"pedmark-label","quote":"Do not administer PEDMARK if the next cisplatin infusion is scheduled to begin in less than 10 hours"},{"action":"Do not use amifostine to protect hearing","why":"Five trials, two of them in children, showed no benefit, and it causes low calcium, sickness and low blood pressure.","source":"freyer-2020","quote":"Do not use amifostine for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer","grade":"Strong, high quality"},{"action":"Do not use sodium diethyldithiocarbamate or intratympanic (ear-drum) injections to protect hearing","why":"Neither showed a benefit that mattered, both have harms or practical problems, and the ear injections are hard to repeat in children.","source":"freyer-2020","quote":"Do not use intratympanic middle ear therapy for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer","grade":"Strong, low quality"},{"action":"Do not lengthen or shorten the cisplatin infusion just to protect hearing","why":"The two trials that tested infusion length did not show it changes hearing loss.","source":"freyer-2020","quote":"Do not alter cisplatin infusion duration, as a means in itself, to reduce ototoxicity in children and adolescents with cancer","grade":"Strong, low quality"},{"action":"After treatment, test hearing from the end of treatment at the latest: yearly under 6, every other year from 6 to 12, every 5 years over 12","why":"Hearing loss can appear or worsen years later, and young children are still learning to speak.","source":"ighg-2019","quote":"consensus among the guideline panel was that surveillance in survivors should start no later than the end of treatment and should be done annually for children younger than 6 years of age, every other year for children 6–12 years of age, and every 5 years for adolescents and young adults older than 12 years","grade":"strong (level A and B evidence for cisplatin)"},{"action":"Use pure-tone audiometry at 1000 to 8000 Hz from age 6; under 6, refer to an audiologist for an age-appropriate assessment","why":"Pure-tone tests are the standard measure once a child can do them; younger children need a specialist's methods.","source":"ighg-2019","quote":"The guideline panel recommends that pure-tone audiometry at 1000–8000 Hz is the gold standard for routine surveillance of CAYA cancer survivors aged 6 years or older to avoid over-testing","grade":"strong recommendations"},{"action":"Refer any child with symptoms of hearing loss or tinnitus, or a loss of more than 15 dB, to an audiologist or ear, nose and throat service","why":"Hearing aids, remote microphones and support at school reduce the effect on speech and learning.","source":"ighg-2019","quote":"The guideline panel strongly recommends (based on expert opinion) that referral to an audiologist, auditory clinic, or ear, nose, and throat physician as appropriate for any survivor who has symptoms suggesting hearing loss, atypical audiological test results showing a loss of more than 15 dB at 1000–8000 Hz, or both.","grade":"strong (expert opinion)"}],"bestInClass":{"statement":"The 2020 international guideline (Freyer et al.), endorsed by the Children's Oncology Group, is the only guideline on preventing cisplatin hearing loss in children and has not been replaced: sodium thiosulfate for non-metastatic hepatoblastoma (strong), considered for other non-metastatic cancers (weak), not routinely in metastatic cancers (weak), and no amifostine, sodium diethyldithiocarbamate, intratympanic therapy or change of infusion length. The US label for PEDMARK sets the practical limits the guideline leaves open: age 1 month or older, localised non-metastatic solid tumours, cisplatin infusions of 1 to 6 hours, a 15-minute infusion 6 hours after cisplatin and at least 10 hours before the next dose. The two trials used different doses (20 g/m2 in SIOPEL 6, 16 g/m2 in ACCL0431); the guideline accepts either, and the label doses by weight band. Surveillance follows the IGHG and PanCare recommendations, which say the use of an otoprotectant does not change the surveillance schedule.","sources":["freyer-2020","cog-ototox-2020","pedmark-label","ighg-2019"]},"variants":[{"name":"Sodium thiosulfate offered in metastatic disease after discussion","differs":"Some families and teams choose sodium thiosulfate for a child with metastatic cancer, for example where the child is blind and hearing is the main sense, after the survival uncertainty is explained.","evidence":"The guideline's weak recommendation against routine use was made weak at the patient representatives' request so that it could be discussed; the panel names a child with blindness as a case where benefit probably outweighs risk. The US label does not cover metastatic cancer.","sources":["freyer-2020","pedmark-label"]}],"grades":[{"claim":"Sodium thiosulfate in non-metastatic hepatoblastoma","grade":"Strong, high quality","source":"freyer-2020"},{"claim":"Sodium thiosulfate considered in other non-metastatic cancers","grade":"Weak, low quality","source":"freyer-2020"},{"claim":"Sodium thiosulfate not routinely in metastatic cancers","grade":"Weak, low quality","source":"freyer-2020"},{"claim":"No amifostine","grade":"Strong, high quality","source":"freyer-2020"},{"claim":"No sodium diethyldithiocarbamate","grade":"Strong, low quality","source":"freyer-2020","quote":"Do not use sodium diethyldithiocarbamate for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer"},{"claim":"No intratympanic therapy","grade":"Strong, low quality","source":"freyer-2020"},{"claim":"Do not alter cisplatin infusion duration to protect hearing","grade":"Strong, low quality","source":"freyer-2020"},{"claim":"Hearing surveillance after cisplatin, from the end of treatment","grade":"strong (level A and B evidence)","source":"ighg-2019"}],"sources":[{"key":"freyer-2020","label":"Prevention of cisplatin-induced ototoxicity in children and adolescents with cancer: a clinical practice guideline","publisher":"International panel (Pediatric Oncology Group of Ontario), The Lancet Child & Adolescent Health","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7521149/","doi":"10.1016/S2352-4642(19)30336-0","gradingScheme":"GRADE: recommendation strong or weak, evidence high, moderate, low or very low quality, printed in the guideline's summary table.","read":"full-text","accessed":"2026-11-11"},{"key":"cog-ototox-2020","label":"Prevention of Cisplatin-induced Ototoxicity in Children and Adolescents with Cancer (COG endorsement, version date 27 August 2020)","publisher":"Children's Oncology Group","year":2020,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_Cisplatin_Ototox_Guideline_Document_27AUG2020-new-logo.pdf","gradingScheme":"Reprints the source guideline's GRADE strength and quality for each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"ighg-2019","label":"Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium","publisher":"IGHG and PanCare, The Lancet Oncology","year":2019,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7549756/","doi":"10.1016/S1470-2045(18)30858-1","gradingScheme":"Evidence levels A (high) to C (low) by Cochrane Childhood Cancer and IGHG criteria, with recommendations strong or weak, or expert opinion where no evidence exists.","read":"full-text","accessed":"2026-11-11"},{"key":"pedmark-label","label":"PEDMARK (sodium thiosulfate injection) prescribing information, SPL version 7","publisher":"Fennec Pharmaceuticals, via DailyMed (US National Library of Medicine)","year":2025,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f98c7076-2a7b-4fd7-ab90-eed5e9137bae","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The European label for sodium thiosulfate (Pedmarqsi) was not read; its age limits and dosing may differ from the US label quoted here.","The guideline does not set a baseline or during-treatment hearing test schedule; the IGHG schedule quoted is for survivors after treatment, and timing of tests during treatment follows local protocols.","Whether sodium thiosulfate is safe in children with metastatic cancer is not settled; the only data are a post-hoc subgroup of one trial, and the panel asks for more research.","The best dose of sodium thiosulfate is not known; the two trials used 20 g/m2 and 16 g/m2.","No guideline read here says how to protect hearing in a child who already has hearing loss and needs more cisplatin.","The guideline was written for high-income countries and set a 5-year review; no update had been published by November 2026."]},{"id":"cardio-oncology-risk-assessment-and-cardiac-surveillance","kind":"protocol","name":"Heart risk assessment and monitoring before, during and after heart-toxic cancer treatment","aka":["cardio-oncology baseline assessment","echocardiogram during trastuzumab","anthracycline cardiotoxicity monitoring","HFA-ICOS risk score","cancer therapy-related cardiac dysfunction","cardiac monitoring in cancer survivors"],"tldr":"Some cancer treatments, such as anthracyclines (doxorubicin, epirubicin) and trastuzumab, can weaken the heart. Before they start, your team should check your heart risk, usually with blood pressure, blood tests, an ECG and a heart scan, repeated during treatment; a fall in heart function does not always mean stopping. Afterwards, tell any doctor about new breathlessness, swelling or chest pain.","summary":"Before treatment with anthracyclines, HER2-targeted therapy, VEGF inhibitors, some kinase inhibitors for CML, proteasome inhibitors and immunomodulatory drugs, RAF and MEK inhibitors or androgen deprivation therapy, the HFA-ICOS proformas (2020) stratify cardiovascular risk as low, medium, high or very high from history, blood pressure, glycated haemoglobin, kidney function, ECG, cardiac biomarkers (troponin and natriuretic peptides, where available) and echocardiography. Risk stratification should be prompt and should not delay treatment unless risk is high or very high or there is pre-existing cardiovascular disease; withholding effective treatment in those groups is a multidisciplinary decision with a cardiologist. HFA-ICOS also recommend a baseline echocardiogram, ECG, troponin and natriuretic peptide for everyone starting immune checkpoint inhibitors or CAR-T therapy.\n\nBSE and BCOS (2021) set a comprehensive baseline echocardiogram including LVEF, global longitudinal strain (GLS) and right ventricular function, and define cancer therapy-related cardiac dysfunction (CTRCD) as an LVEF fall of more than 10 percentage points to below 50 per cent; IC-OS (2022) grades asymptomatic CTRCD as mild (LVEF 50 per cent or more with a new relative GLS fall over 15 per cent and/or a rise in biomarkers), moderate or severe (LVEF below 40 per cent). How often to repeat the echocardiogram differs widely between guidelines (from every 3 months on trastuzumab to undefined), with no strong evidence that any schedule improves outcomes; risk-based schedules such as those of HFA-EACVI (2020) repeat it more often at higher risk. Asymptomatic falls to 40 to 49 per cent may allow HER2 therapy to continue with cardio-oncology support. In survivors, ASCO (2017) asks for a low threshold for cardiac evaluation after any potentially cardiotoxic therapy, and imaging surveillance for certain higher-risk survivors.","asOf":"2026-11-11","links":[],"tags":["protocol","cardio-oncology","survivorship"],"related":["paper-lyon-eur-heart-j","idea-acc-risk-stratified-cardio-oncology-pathway"],"cancers":[],"sections":["supportive-care"],"technologies":["cardio-oncology","strain-echocardiography-gls"],"targets":[],"drugs":["doxorubicin","epirubicin","trastuzumab","pertuzumab"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["cardiotoxicity","trastuzumab-cardiotoxicity","anthracycline"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer medicines can affect the heart. Your team checks your heart before and during treatment. Tell them if you get breathless or your ankles swell.","domain":"survivorship","setting":{"who":["doctor","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","community"]},"population":"Adults with cancer about to receive, receiving or having completed potentially cardiotoxic treatment, above all anthracyclines and HER2-targeted therapy; the risk proformas also cover VEGF inhibitors, BCR-ABL kinase inhibitors, myeloma therapies, RAF and MEK inhibitors and androgen deprivation therapy. Children and survivors of childhood cancer have separate surveillance guidelines and are not covered here. Myocarditis from immune checkpoint inhibitors is covered only as a baseline step.","trigger":"A potentially cardiotoxic cancer treatment is planned; during it; and after it has ended.","steps":[{"action":"Before a heart-toxic treatment, talk with the person about the risk to the heart if that risk is significant","why":"Knowing the risk lets people report symptoms early and take part in decisions about monitoring.","source":"asco-2017","quote":"It is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy."},{"action":"Stratify baseline cardiovascular risk with the HFA-ICOS proforma for the treatment class, using history, blood pressure, ECG, HbA1c, kidney function, cardiac biomarkers where available and an echocardiogram","why":"A structured score finds the people who need a cardiologist before treatment and closer monitoring during it.","source":"hfa-icos-2020","quote":"Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies."},{"action":"Do not delay cancer treatment for the assessment unless risk is high or very high or there is heart disease already","why":"For most people the cancer is the greater threat; only those at highest heart risk need a cardiology decision first.","source":"hfa-icos-2020","quote":"Baseline CV risk stratification should be completed promptly and should not delay starting cancer treatment (unless high or very high risk or pre-existing CVD is present)."},{"action":"Withhold an effective but heart-toxic treatment only after a joint decision between the oncologist or haematologist and a cardiologist","why":"Stopping a treatment that controls the cancer has its own cost, and the balance needs both specialists.","source":"hfa-icos-2020","quote":"Decisions to withhold effective but potentially cardiotoxic cancer treatments in cancer patients at high or very high risk of CVD should only be made after multidisciplinary team discussion between the treating oncologist/haematologist and cardiologist"},{"action":"Before immune checkpoint inhibitors or CAR-T therapy, record a baseline echocardiogram, ECG, troponin and natriuretic peptide","why":"Heart inflammation from these treatments is rare but serious, and a baseline makes a later change easy to see.","source":"hfa-icos-2020","quote":"we recommend all patients scheduled to receive ICI or CAR-T therapy have a baseline echocardiogram, electrocardiogram (ECG) and measurement of cardiac troponin and a natriuretic peptide, which serve as a baseline reference if new cardiac complications develop."},{"action":"Before anthracyclines or HER2 therapy, do a comprehensive baseline echocardiogram including LVEF, global longitudinal strain and right ventricular function","why":"Later scans are compared with this one, so it must measure the same things the same way.","source":"bse-bcos-2021","quote":"All patients should undergo a comprehensive baseline echocardiogram to include the BSE minimum transthoracic dataset ( 3 ) with additional cardio-oncology measurements ( Table 1 )."},{"action":"Repeat the echocardiogram during treatment on a schedule set by the person's risk and the treatment","why":"Guidelines differ on how often, and no schedule has been shown to improve outcomes, so higher-risk people are scanned more often.","source":"bse-bcos-2021","quote":"Furthermore, there is no strong evidence to support a specific schedule of screening or any evidence that it improves outcomes for screened patients ( 22 )."},{"action":"Call it cancer therapy-related cardiac dysfunction when LVEF falls by more than 10 percentage points to below 50 per cent, and refer to cardio-oncology","why":"A shared definition lets oncology and cardiology act on the same finding.","source":"bse-bcos-2021","quote":"We define CTRCD as a decrease in LVEF by > 10% (10 absolute percentage points) to a value < 50%."},{"action":"Grade asymptomatic dysfunction by severity, treating a fall in LVEF below 40 per cent as severe","why":"Severity guides whether treatment can continue with heart medicines or needs to pause.","source":"ic-os-2022","quote":"A reduction in LVEF to <40% indicates severe asymptomatic CTRCD, with recent data suggesting an association with poor prognosis in multiple cancers and treatment regimens."},{"action":"With an asymptomatic fall in LVEF to 40 to 49 per cent on HER2 therapy, consider continuing treatment with cardio-oncology support rather than stopping","why":"Growing evidence shows many people in this range can finish their cancer treatment safely with heart medicines and closer monitoring.","source":"bse-bcos-2021","quote":"However, there are increasing data to suggest that patients with asymptomatic reductions in LVEF to 40 to 49%, with guidance from a cardio-oncology team and personalized monitoring and treatment, can safely complete their cancer treatment without a significant increase in cardiac events ( 24 , 25 )."},{"action":"After treatment, keep a low threshold for heart tests in any survivor who had potentially cardiotoxic therapy, and offer imaging surveillance to higher-risk survivors","why":"Heart damage can appear years later, and treating it early can stop or reverse it.","source":"asco-2017","quote":"Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy."}],"bestInClass":{"statement":"The 2022 ESC cardio-oncology guideline, developed with EHA, ESTRO and IC-OS, is the current comprehensive guideline, and it could not be read here. The sources read agree on the shape of care: structured baseline risk assessment (HFA-ICOS 2020), a comprehensive baseline echocardiogram with LVEF and GLS (BSE/BCOS 2021), a shared definition of cardiac dysfunction (IC-OS 2022 grades it mild, moderate or severe; BSE/BCOS use an LVEF fall of more than 10 points to below 50 per cent), and a low threshold for evaluating survivors (ASCO 2017). They disagree on how often to scan during treatment: from every 3 months on trastuzumab (FDA, ESMO 2020) to risk-based schedules (HFA-EACVI 2020) to a frequency left to the clinician (ASCO 2017), with no strong evidence for any schedule.","sources":["hfa-icos-2020","ic-os-2022","bse-bcos-2021","asco-2017","esc-2022"]},"variants":[{"name":"Risk-based echocardiography schedules (HFA-EACVI 2020, as tabulated by BSE/BCOS)","differs":"For anthracyclines, scans after a cumulative 240 mg/m² of doxorubicin or equivalent at low risk, at half of planned treatment as well at medium risk, and every two cycles at high risk; for adjuvant HER2 therapy, every four cycles (12 weeks) at low risk, every three cycles at medium risk and every two cycles at high risk, reducing if stable at 4 months.","evidence":"Expert consensus; BSE/BCOS note wide variation between guidelines and no strong evidence for any schedule. The HFA-EACVI paper itself was not read.","sources":["bse-bcos-2021"]},{"name":"Every 3 months on HER2 therapy (FDA labelling and ESMO 2020, as tabulated by BSE/BCOS)","differs":"A fixed 3-monthly echocardiogram throughout HER2-targeted therapy, regardless of baseline risk; ESMO 2020 scans after 250 mg/m² of doxorubicin or equivalent and then after each further 100 mg/m².","evidence":"BSE/BCOS call the 3-monthly frequency controversial with limited compliance. The ESMO paper was not read.","sources":["bse-bcos-2021"]},{"name":"Frequency left to the clinician (ASCO 2017)","differs":"Leaves the frequency of surveillance to the treating team, with routine imaging offered to those at increased risk.","evidence":"ASCO survivors guideline; read as an abstract and as tabulated by BSE/BCOS.","sources":["asco-2017","bse-bcos-2021"]}],"grades":[{"claim":"Moderate asymptomatic CTRCD","grade":"IC-OS consensus definition","source":"ic-os-2022","quote":"Moderate asymptomatic CTRCD requires (i) a fall in LVEF into a clearly abnormal range (40–49%) with a change in LVEF beyond the described variability of the most commonly used Echo-based 2D LVEF measurements (i.e. by >10 percentage points), or (ii) a smaller change in LVEF but with a concomitant significant fall in GLS and/or new rise in cardiac biomarkers."},{"claim":"Mild asymptomatic CTRCD","grade":"IC-OS consensus definition","source":"ic-os-2022","quote":"Mild asymptomatic CTRCD is defined as preserved LVEF (i.e. LVEF ≥ 50%) with >15% reduction in GLS relative to baseline and/or new rise in troponin or NPs."}],"sources":[{"key":"hfa-icos-2020","label":"Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society","publisher":"HFA of the ESC and IC-OS, European Journal of Heart Failure","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8019326/","doi":"10.1002/ejhf.1920","gradingScheme":"Position statement; each risk factor in the proformas carries a level of evidence on the standard definitions used in cardiology and oncology guidelines.","read":"full-text","accessed":"2026-11-11"},{"key":"ic-os-2022","label":"Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement","publisher":"IC-OS, European Heart Journal","year":2022,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8803367/","doi":"10.1093/eurheartj/ehab674","gradingScheme":"Consensus definitions; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"bse-bcos-2021","label":"British Society for Echocardiography and British Cardio-Oncology Society guideline for transthoracic echocardiographic assessment of adult cancer patients receiving anthracyclines and/or trastuzumab","publisher":"BSE and BCOS, Echo Research and Practice","year":2021,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8052569/","doi":"10.1530/ERP-21-0001","gradingScheme":"Society guideline; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2017","label":"Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: ASCO Clinical Practice Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2017,"url":"https://europepmc.org/abstract/MED/27918725","doi":"10.1200/JCO.2016.70.5400","read":"abstract","accessed":"2026-11-11"},{"key":"esc-2022","label":"2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)","publisher":"ESC, European Heart Journal","year":2022,"url":"https://doi.org/10.1093/eurheartj/ehac244","doi":"10.1093/eurheartj/ehac244","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 2022 ESC cardio-oncology guideline could not be read: it is not in PubMed Central, the publisher returned 403 and the ESC page offered only a slide set made of images. Its class and level of each recommendation, its surveillance schedules and its advice on cardioprotection (for example dexrazoxane, liposomal anthracyclines, ACE inhibitors or beta-blockers) are not given here.","ASCO 2017 was read only as an abstract; which survivors it counts as higher risk, and its imaging intervals, are not given here.","No source read sets a surveillance schedule for survivors years after anthracyclines or chest radiotherapy; ASCO leaves frequency to the clinician.","Monitoring for immune checkpoint inhibitor myocarditis, VEGF inhibitor hypertension and arrhythmias with BTK inhibitors is beyond the baseline step given here.","The ESMO 2020 cardio-oncology consensus and the HFA-EACVI 2020 imaging statement are described only as BSE/BCOS tabulate them."]},{"id":"hepatic-dose-adjustment-of-anticancer-drugs","kind":"protocol","name":"Hepatic dose adjustment of anticancer drugs in reduced liver function","aka":["liver impairment chemotherapy dosing","hepatic impairment dose reduction","Child-Pugh dosing","NCI Organ Dysfunction Working Group criteria","NCI ODWG","chemotherapy and raised bilirubin","liver metastases dose adjustment"],"tldr":"Many cancer drugs are broken down by the liver, so if your liver is not working well the dose may need lowering or a different drug may be safer. Your liver blood tests are checked before each cycle, and the team follows the drug's own instructions, which grade liver function in one of two ways that do not always agree.","summary":"No international consensus covers anticancer dosing in liver impairment; the dose comes from each drug's label, set from dedicated pharmacokinetic studies. Labels use one of two scales. Child-Pugh scores encephalopathy, ascites, bilirubin, albumin and prothrombin time or INR into mild (A, 5 to 6), moderate (B, 7 to 9) and severe (C, 10 to 15); the NCI Organ Dysfunction Working Group criteria use only total bilirubin and AST, in groups A (normal) to D (severe). The FDA's September 2026 draft guidance, which replaces the 2003 guidance, recommends Child-Pugh for cirrhosis, allows NCI criteria in cancer studies except hepatobiliary cancers, warns that a Child-Pugh score taken during or just after an acute event can overstate impairment, and notes non-liver causes of a raised bilirubin or INR (Gilbert's syndrome, vitamin K deficiency, anticoagulants).\n\nThe two scales disagree: across five drugs, 64.9%, 73.7% and 61.5% of people with mild, moderate and severe impairment by Child-Pugh were at least one category less impaired by NCI criteria (Elmeliegy 2021), so the clinician should apply the scale the label used. People with moderate or severe impairment are usually excluded from cancer trials, so labels often rest on studies in people without cancer and on modelling (Yang 2022). In practice, BOPA (2025) asks the pharmacist to check liver function and modify doses as the drug or regimen literature directs at each cycle. A worked example: ibrutinib for B-cell cancers is 140 mg daily in Child-Pugh A, 70 mg in Child-Pugh B, and avoided in Child-Pugh C.","asOf":"2026-11-11","links":[],"tags":[],"related":["child-pugh","renal-dose-adjustment-of-anticancer-drugs","sact-prescribing-and-pharmacy-verification"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your liver blood tests are checked before each treatment. If your liver is struggling, some drugs are given at a lower dose or swapped.","domain":"pharmacy","setting":{"who":["doctor","pharmacist"],"where":["outpatient-clinic","ward","aseptic-unit"]},"population":"Adults with cancer prescribed systemic anticancer drugs who have abnormal liver tests, liver metastases, cirrhosis or a primary liver or biliary cancer. Children are not covered.","trigger":"A new regimen is planned, or bilirubin, transaminases, albumin or INR are abnormal before a cycle.","steps":[{"action":"Check liver function before every cycle and modify doses as the drug's or regimen's literature directs","why":"Liver function can change quickly with liver metastases or drug toxicity, and some drugs build up dangerously when it falls.","source":"bopa-2025","quote":"Check hepatic function and ensure drug doses are modified accordingly where appropriate as per drug/regimen literature."},{"action":"Find out which scale the drug's label uses for liver impairment, Child-Pugh or NCI criteria, and grade the person on that scale","why":"The two scales often put the same person in different categories, so using the wrong one can give the wrong dose.","source":"elmeliegy-2021","quote":"NCIc tended to classify subjects as less impaired versus Child‐Pugh (64.9%, 73.7%, and 61.5% of subjects with mild, moderate, and severe HI, respectively, via Child‐Pugh were classified as at least 1 category less impaired via NCIc)."},{"action":"Use Child-Pugh for people with cirrhosis and for liver and biliary cancers; NCI criteria are an option in other cancers","why":"In cirrhosis and liver cancers, Child-Pugh captures how well the liver works better than two blood tests can.","source":"fda-hepatic-2026","quote":"FDA recommends using the Child-Pugh (CP) classification to categorize the degree of HI in subjects with cirrhosis due to chronic liver disease. In subjects with cancer, sponsors can use the National Cancer Institute (NCI) Organ Dysfunction Working Group criteria (NCI Criteria) to categorize the degree of HI, except for subjects with hepatobiliary cancers."},{"action":"Do not score Child-Pugh during or just after an acute event such as bleeding, infection, surgery or transfusion","why":"The score can be temporarily worse than the liver's usual ability to clear drugs.","source":"fda-hepatic-2026","quote":"Further, determining a CP score during or shortly after an acute event (e.g., alcohol recidivism, gastrointestinal bleed, surgery, transfusions, infections, flare of underlying liver disease) is not recommended because it may produce a higher score that may not reflect baseline drug metabolic capacity."},{"action":"Rule out non-liver causes of an abnormal result, such as Gilbert's syndrome for bilirubin or anticoagulants for INR","why":"A raised number that does not come from the liver should not cut a dose.","source":"fda-hepatic-2026","quote":"For example, Vitamin K deficiency or anti-coagulant drugs may increase INR, Gilbert’s syndrome may increase total bilirubin via unconjugated bilirubin, and intravenous fluid administration may dilute serum albumin."},{"action":"Apply the label's recommendation for the person's category: a reduced dose, closer monitoring, or avoiding the drug","why":"The label holds the only measured data on how the drug behaves when the liver is impaired.","source":"ibrutinib-label","quote":"The recommended dosage is 140 mg daily for patients with mild hepatic impairment (Child-Pugh class A). The recommended dosage is 70 mg daily for patients with moderate hepatic impairment (Child-Pugh class B). Avoid the use of IMBRUVICA in patients with severe hepatic impairment (Child-Pugh class C)"},{"action":"Where the label has no data for moderate or severe impairment, weigh the treatment goal and alternatives with the team and monitor closely","why":"People with significant liver impairment are usually left out of cancer trials, so dosing is often uncertain.","source":"yang-2022","quote":"Patients with cancer and advanced hepatic impairment (HI) (i.e., moderate and severe impairment) are often excluded from first‐in‐patient, phase II, and phase III studies."}],"bestInClass":{"statement":"There is no graded or consensus guideline for anticancer dosing in liver impairment; the best-supported practice is to check liver function every cycle (BOPA 2025), grade it on the scale the drug's label used (Child-Pugh in cirrhosis and hepatobiliary cancers, NCI criteria allowed in other cancers, per the FDA's 2026 draft guidance), exclude acute events and non-hepatic causes, and follow the label's dose, monitoring or avoidance advice. Because the scales disagree in most people with impairment (Elmeliegy 2021) and labels rest on limited data, decisions for moderate or severe impairment are individual. The Krens recommendations, which UK pharmacists use, could not be read.","sources":["bopa-2025","fda-hepatic-2026","elmeliegy-2021","yang-2022","ibrutinib-label"]},"variants":[{"name":"Reference tables of hepatic dose recommendations (Krens et al.)","differs":"Uses a published table of dose recommendations for anticancer drugs by degree of liver impairment rather than each label alone.","evidence":"Named by BOPA 2025 as a reference; could not be read, so its recommendations and method are not described.","sources":["krens-2023","bopa-2025"]}],"grades":[],"sources":[{"key":"fda-hepatic-2026","label":"Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosage (draft guidance for industry)","publisher":"US Food and Drug Administration (CDER)","year":2026,"url":"https://www.fda.gov/media/71311/download","gradingScheme":"Draft guidance, nonbinding and not for implementation; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"elmeliegy-2021","label":"Discordance Between Child-Pugh and National Cancer Institute Classifications for Hepatic Dysfunction: Implications on Dosing Recommendations for Oncology Compounds","publisher":"Journal of Clinical Pharmacology (Elmeliegy et al.)","year":2021,"url":"https://doi.org/10.1002/jcph.1702","doi":"10.1002/jcph.1702","read":"full-text","accessed":"2026-11-11"},{"key":"yang-2022","label":"Analysis of US Food and Drug Administration Oncology Approvals on the Characterization of Hepatic Impairment Effect and Dosing Recommendations","publisher":"Clinical Pharmacology and Therapeutics (Yang et al.)","year":2022,"url":"https://doi.org/10.1002/cpt.2505","doi":"10.1002/cpt.2505","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ibrutinib-label","label":"Imbruvica (ibrutinib), US prescribing information","publisher":"US National Library of Medicine, DailyMed","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=0dfd0279-ff17-4ea9-89be-9803c71bab44","read":"full-text","accessed":"2026-11-11"},{"key":"krens-2023","label":"Dose recommendations for anticancer drugs in patients with renal or hepatic impairment: an update","publisher":"The Lancet Oncology (Krens et al.)","year":2023,"url":"https://doi.org/10.1016/S1470-2045(23)00216-4","doi":"10.1016/S1470-2045(23)00216-4","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No international consensus or graded guideline on anticancer dosing in liver impairment was found, and the most-used reference tables (Krens et al., Lancet Oncology 2019 and 2023) could not be read.","The FDA guidance is a September 2026 draft for drug developers, not a clinical guideline; how labels and practice will follow it is not yet known.","How to dose when liver tests are abnormal because of liver metastases rather than cirrhosis, and how quickly to re-escalate when they improve, is not settled by the sources read."]},{"id":"hepatitis-b-screening-and-reactivation-prophylaxis","kind":"protocol","name":"Hepatitis B testing before cancer treatment and prevention of reactivation","aka":["HBV screening before chemotherapy","hepatitis B reactivation prophylaxis","HBV reactivation","anti-HBc positive before rituximab","entecavir prophylaxis"],"tldr":"Hepatitis B can sleep in the liver for years and wake up when cancer treatment weakens the immune system, sometimes damaging the liver badly. A blood test before treatment finds people at risk. Those who have it, or have had it and get high-risk treatment such as rituximab or a stem cell transplant, take an antiviral tablet during and for at least a year after treatment, or are checked closely.","summary":"ASCO's 2020 Provisional Clinical Opinion moved from risk-based to universal testing: everyone anticipating systemic anticancer therapy has HBsAg, anti-HBc (total Ig or IgG) and anti-HBs before or at the start of treatment, without delaying it (strong). Chronic HBV (HBsAg-positive) on any systemic anticancer therapy gets antiviral prophylaxis for the whole of treatment and at least 12 months after, with ALT and HBV DNA at baseline and every 6 months, monthly ALT for 3 months after stopping antivirals, and a clinician experienced in HBV (strong). Past HBV (HBsAg-negative, anti-HBc-positive) with anti-CD20 antibodies or stem cell transplant gets prophylaxis from the start and for at least 12 months after (strong), or, where follow-up can be relied on, HBsAg and HBV DNA every 3 months with antivirals at the first sign of reactivation (HBsAg appears or HBV DNA above 1,000 IU/mL). Past HBV with other regimens is monitored with HBsAg and ALT every 3 months. Hormonal therapy alone follows non-cancer HBV guidance (moderate).\n\nAPASL 2021 stratifies by the risk of the immunosuppressive therapy and by liver fibrosis, prefers entecavir, tenofovir or TAF (evidence I, recommendation 1), and considers stopping nucleos(t)ide analogues 6 months after immunosuppression ends in selected patients, where ASCO says at least 12 months. Anti-HBc can be falsely positive after intravenous immunoglobulin, so testing before IVIG is simpler to read.","asOf":"2026-11-11","links":[],"tags":["protocol","hepatitis-b","infection-prevention"],"related":["lymphoma-tx-hepatitis-b-reactivation"],"cancers":["non-hodgkin-lymphoma","dlbcl","cll"],"sections":["supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant"],"targets":[],"drugs":["rituximab","obinutuzumab"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["hbv-hcv","lymphoma-tx-hepatitis-b-reactivation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before cancer treatment, you should have a blood test for hepatitis B. If it shows the virus now or in the past, you may need a daily tablet to keep it asleep. Your treatment does not need to wait for the result.","domain":"infection-prevention","setting":{"who":["doctor","nurse","pharmacist"],"where":["outpatient-clinic","chemotherapy-day-unit"]},"population":"Adults with cancer about to start systemic anticancer therapy (chemotherapy, targeted therapy, immunotherapy, anti-CD20 antibodies, stem cell transplant), as ASCO scopes it. APASL covers anyone starting immunosuppressive therapy. Children are not addressed by ASCO; APASL's guideline names no paediatric doses.","trigger":"Systemic anticancer therapy is being planned.","steps":[{"action":"Test everyone due to start systemic anticancer therapy for hepatitis B with HBsAg, anti-HBc (total or IgG) and anti-HBs, before or at the start of treatment","why":"Asking about risk factors misses many carriers; testing everyone finds all the people whose virus could reactivate.","source":"asco-pco-2020","quote":"All patients with cancer anticipating systemic anticancer therapy should be tested for hepatitis B virus (HBV) by three tests--hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to, or at the beginning of, systemic anticancer therapy.","grade":"Strength of recommendation: strong"},{"action":"Do not hold back cancer treatment while waiting for the results","why":"The cancer is the more urgent problem, and prophylaxis can start alongside treatment.","source":"asco-pco-2020","quote":"Anticancer therapy should not be delayed for the results of these screening tests."},{"action":"Order anti-HBc as total Ig or IgG, not IgM, and read it with caution after intravenous immunoglobulin","why":"IgM is a test for a new infection; immunoglobulin infusions can carry anti-HBc and give a false positive.","source":"asco-pco-2020","quote":"anti-HBc testing after IVIG should be interpreted with caution."},{"action":"For chronic hepatitis B (HBsAg positive), give antiviral prophylaxis throughout any systemic anticancer therapy and for at least 12 months after it ends","why":"Without it the virus can flare during or after treatment and damage the liver.","source":"asco-pco-2020","quote":"Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy for the duration of anticancer therapy, as well as for at least 12 months after receipt of the last anticancer therapy.","grade":"Strength of recommendation: strong"},{"action":"Choose an antiviral with a high barrier to resistance: entecavir, tenofovir disoproxil or tenofovir alafenamide","why":"Older drugs such as lamivudine let resistant virus emerge during long courses.","source":"apasl-2021","quote":"4.3 Preferred NUCs include entecavir, tenofovir and TAF","grade":"evidence I, recommendation 1"},{"action":"Check ALT and HBV DNA at baseline and every 6 months on antivirals, then ALT at least monthly for 3 months after the antiviral stops","why":"Hepatitis can flare when the antiviral is withdrawn, so the months after stopping need closer checks.","source":"asco-pco-2020","quote":"As such, ALT levels should be monitored frequently, at least monthly for the first 3 months after the cessation of antiviral therapy and every 3 months thereafter."},{"action":"Share the care of anyone with chronic hepatitis B with a clinician experienced in managing it","why":"They decide how long antivirals continue and check for cirrhosis and liver cancer.","source":"asco-pco-2020","quote":"Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy."},{"action":"For past hepatitis B (HBsAg negative, anti-HBc positive) with an anti-CD20 antibody or a stem cell transplant, start prophylaxis with the cancer treatment and continue it for at least 12 months after","why":"These treatments carry the highest risk of waking a resolved infection.","source":"asco-pco-2020","quote":"Patients with past HBV receiving anticancer therapies associated with an established high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should be started on antiviral prophylaxis at the beginning of anticancer therapy and continued on antiviral therapy for at least 12 months after the cessation of anticancer therapy.","grade":"Strength of recommendation: strong"},{"action":"For past hepatitis B with other regimens, check HBsAg and ALT every 3 months during treatment and start an antiviral only if HBsAg returns or HBV DNA exceeds 1,000 IU/mL with a flare","why":"The reactivation risk with most other cancer drugs is unclear and probably low, so watching is enough.","source":"asco-pco-2020","quote":"Patients with past HBV undergoing anticancer therapies that are not clearly associated with a high risk of HBV reactivation (eg, regimens that do not include anti-CD20 monoclonal antibodies or stem-cell transplantation) should be followed carefully during cancer treatment, with HBsAg and ALT testing every 3 months (with subsequent HBV DNA testing if a hepatitis flare develops), with initiation of antiviral therapy only if HBsAg becomes positive or HBV DNA exceeds 1,000 IU/mL in the setting of a hepatitis flare.","grade":"Strength of recommendation: strong"},{"action":"For hormonal therapy alone, follow the usual hepatitis B guidance rather than a cancer-specific plan, and reassess if treatment changes","why":"Hormone treatment on its own is unlikely to reactivate the virus.","source":"asco-pco-2020","quote":"Hormonal therapy without systemic anticancer therapy is unlikely to increase the risk of HBV reactivation in patients with chronic or past HBV.","grade":"Strength of recommendation: moderate"}],"bestInClass":{"statement":"Test everyone before systemic anticancer therapy with HBsAg, anti-HBc and anti-HBs, without delaying treatment (ASCO 2020, strong; APASL 2021 also screens all patients planned for immunosuppressive therapy, evidence II-2, recommendation 1). Give a high-barrier antiviral (entecavir, tenofovir or TAF) to everyone with chronic hepatitis B on systemic therapy and to people with past infection on anti-CD20 antibodies or stem cell transplant. Where they differ: ASCO continues prophylaxis for at least 12 months after the last anticancer treatment, while APASL considers stopping 6 months after immunosuppression ends for HBsAg-positive patients without advanced fibrosis or with low HBV DNA, and for those who remain HBsAg negative; APASL also asks for a hepatologist's fibrosis assessment in every positive patient and treats anyone with advanced fibrosis or cirrhosis whatever the drug risk. ASCO allows close monitoring every 3 months in place of prophylaxis for past infection on high-risk therapy where follow-up is reliable.","sources":["asco-pco-2020","apasl-2021"]},"variants":[{"name":"Risk stratified by drug and liver fibrosis (APASL 2021)","differs":"Grades each immunosuppressive therapy as high, moderate or low risk, gives pre-emptive antivirals to all HBsAg-positive or anti-HBc-positive patients in the high-risk group and to those with advanced fibrosis or cirrhosis in the others, monitors liver tests every 12 weeks in the rest, and considers stopping antivirals 6 months after immunosuppression ends.","evidence":"Graded on a modified GRADE scale; pre-emptive antivirals in the high-risk group are evidence I, recommendation 1; stopping at 6 months is evidence II-2, recommendation 1.","sources":["apasl-2021"]},{"name":"Monitoring instead of prophylaxis for past infection on high-risk therapy (ASCO alternative)","differs":"HBsAg and HBV DNA every 3 months during and up to 12 months after treatment, with antivirals started immediately if HBsAg appears or HBV DNA exceeds 1,000 IU/mL.","evidence":"Offered by ASCO only where patients and clinicians can keep to frequent, consistent follow-up; part of a strong, informal-consensus recommendation.","sources":["asco-pco-2020"]},{"name":"Risk-based testing (earlier ASCO opinions, and some national guidance)","differs":"Tests only people with risk factors for hepatitis B or those due to receive anti-CD20 antibodies or a stem cell transplant.","evidence":"ASCO replaced this with universal testing in 2020 on the basis of large prospective cohorts in which risk-factor questions missed infected patients; no randomised trial compares the two, and ASCO calls one unethical. Cost-effectiveness of universal testing in solid tumours is inconsistent across six analyses.","sources":["asco-pco-2020"]}],"grades":[{"claim":"Universal three-test HBV screening before systemic anticancer therapy","grade":"Type: evidence-based; benefits outweigh harms; Strength of recommendation: strong","source":"asco-pco-2020"},{"claim":"Antiviral prophylaxis for chronic HBV throughout and 12 months after anticancer therapy","grade":"Type of recommendation: informal consensus, benefits outweigh harms; Strength of recommendation: strong","source":"asco-pco-2020"},{"claim":"Hormonal therapy alone follows non-cancer HBV guidance","grade":"Type: informal consensus; benefits outweigh harms; Strength of recommendation: moderate","source":"asco-pco-2020"},{"claim":"Screen all patients planned to receive immunosuppressive therapy","grade":"evidence II-2, recommendation 1","source":"apasl-2021","quote":"All patients planned to receive immunosuppressive therapy should be screened."},{"claim":"Pre-emptive nucleos(t)ide analogues for all HBsAg-positive or anti-HBc-positive patients in the high-risk group","grade":"evidence I, recommendation 1","source":"apasl-2021"}],"sources":[{"key":"asco-pco-2020","label":"Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update","publisher":"ASCO, Journal of Clinical Oncology","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11828660/","doi":"10.1200/JCO.20.01757","gradingScheme":"ASCO prints the type of recommendation (evidence-based or informal consensus), the balance of benefits and harms, and the strength (strong, moderate, weak) after each recommendation.","read":"full-text","accessed":"2026-11-11"},{"key":"apasl-2021","label":"APASL clinical practice guideline on hepatitis B reactivation related to the use of immunosuppressive therapy","publisher":"Asian Pacific Association for the Study of the Liver, Hepatology International","year":2021,"url":"https://europepmc.org/article/PMC/PMC8382940","doi":"10.1007/s12072-021-10239-x","gradingScheme":"Evidence I (randomised trials), II-1, II-2, II-3 or III (expert opinion); recommendation 1 (strong) or 2 (weaker), printed as [Grading: evidence, recommendation].","read":"full-text","accessed":"2026-11-11"},{"key":"easl-2025","label":"EASL Clinical Practice Guidelines on the management of hepatitis B virus infection","publisher":"European Association for the Study of the Liver, Journal of Hepatology","year":2025,"url":"https://doi.org/10.1016/j.jhep.2025.03.018","doi":"10.1016/j.jhep.2025.03.018","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-hepatitis-b-testing-before-systemic-treatment"],"gaps":["The EASL 2025 guideline, which has a section on reactivation prophylaxis, could not be read in full: the publisher's page returned a bot challenge to a script. Its durations and risk categories are not stated here.","ASCO found no randomised trial of universal against risk-based testing, and the reactivation risk of most anticancer drugs other than anti-CD20 antibodies and stem cell transplant is not known.","ASCO (at least 12 months) and APASL (consider stopping at 6 months in selected patients) disagree on how long prophylaxis continues after treatment.","Neither guideline read here gives paediatric doses; ASCO's table summarises an Indian National Association for Study of the Liver guideline that uses entecavir for children over 2, and entecavir or tenofovir disoproxil over 12.","No current UK national guideline on hepatitis B screening before chemotherapy was found and read for this protocol."]},{"id":"hot-flushes-on-endocrine-therapy-non-hormonal-options","kind":"protocol","name":"Hot flushes on breast cancer endocrine therapy and prostate cancer hormone therapy: non-hormonal options","aka":["hot flashes on tamoxifen","hot flushes on aromatase inhibitors","vasomotor symptoms on endocrine therapy","hot flushes on androgen deprivation therapy","night sweats on hormone therapy","elinzanetant for hot flushes","fezolinetant after breast cancer"],"tldr":"Hormone treatments for breast and prostate cancer often cause hot flushes, sometimes for years. After breast cancer, hormone replacement therapy is usually ruled out. Options include cognitive behavioural therapy, hypnosis, venlafaxine, some SSRIs (not with tamoxifen), gabapentin and, in a large trial, elinzanetant. For men, NICE suggests medroxyprogesterone first. Herbal remedies are not advised.","summary":"Breast cancer. NICE NG101 asks teams to tell women about early menopause and menopausal symptoms, not to offer HRT routinely after breast cancer (it is contraindicated and off-label; in exceptional circumstances, after discussion of the risks, for severe symptoms), to consider SSRIs for hot flushes but not with tamoxifen, and not to offer soy, red clover, black cohosh, vitamin E or magnetic devices. NICE NG23 (2024) adds menopause-specific cognitive behavioural therapy for vasomotor symptoms where HRT is contraindicated or not wanted. CCO (2016) lists paroxetine, venlafaxine, gabapentin and clonidine as alternatives to hormone therapy and warns against paroxetine and fluoxetine with tamoxifen because they inhibit CYP2D6; ASCO (2018) recommends cognitive behavioural therapy, slow breathing, hypnosis, venlafaxine and gabapentin for women and men. NAMS (2023) grades CBT, clinical hypnosis, SSRIs and SNRIs, gabapentin and fezolinetant as Level I, oxybutynin Levels I to II, and does not recommend paced respiration, cooling techniques, acupuncture, supplements or clonidine.\n\nThe neurokinin antagonists. In OASIS-4 (474 women on endocrine therapy for HR-positive breast cancer or its prevention), elinzanetant 120 mg reduced moderate to severe hot flushes by 3.4 more episodes a day than placebo at 12 weeks. The US label (August 2026) is for vasomotor symptoms due to menopause, requires liver tests before starting and at three months, and restricts use with CYP3A4 inhibitors and inducers. Fezolinetant is recommended by NICE (TA1143, 2026) when HRT is unsuitable, but people having treatment for breast cancer or other oestrogen-dependent cancers are outside its marketing authorisation, and after treatment its use should rest on an individual risk assessment. ACP (2026, general menopause) places the neurokinin antagonists third line.\n\nProstate cancer. NICE NG131 offers medroxyprogesterone 20 mg a day for 10 weeks for troublesome hot flushes from long-term androgen suppression, then cyproterone acetate if that fails, and tells men there is no good-quality evidence for complementary therapies. CCO lists venlafaxine, medroxyprogesterone, cyproterone or gabapentin, and says acupuncture might be a suitable alternative.","asOf":"2026-11-11","links":[],"tags":["protocol","symptom-management","hot-flushes"],"related":["bone-health-on-hormone-therapy","sexual-health-assessment-and-interventions","black-cohosh"],"cancers":["breast-hr-positive","prostate"],"sections":["supportive-care"],"technologies":["endocrine-therapy","androgen-deprivation","menopause-after-cancer-treatment","acupuncture-hot-flushes","hypnosis-cancer-care"],"targets":[],"drugs":["elinzanetant","tamoxifen","letrozole","anastrozole","exemestane","goserelin","leuprolide","megestrol-progestins"],"companies":[],"institutions":["nice","asco","ontario-health-cancer-care-ontario"],"pathways":[],"terms":["hot-flushes-on-hormone-therapy","aromatase-inhibitor","adt","menopause-after-chemotherapy-breast"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Hormone treatment for cancer can cause hot flushes. Talking therapy and some medicines help. Ask your team before taking herbal remedies.","domain":"symptom-management","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","community"]},"population":"Adults with hot flushes or night sweats caused by endocrine therapy for breast cancer (tamoxifen, aromatase inhibitors, ovarian suppression) or by androgen deprivation for prostate cancer. NG23 and the ACP and NAMS statements are written for menopause in general; their use here is noted where it applies. Women with non-hormone-sensitive cancers who have an early menopause from treatment are a different group: CCO advises considering hormone therapy until about 51.","trigger":"Starting endocrine therapy or androgen deprivation, and whenever troublesome hot flushes or night sweats are reported.","steps":[{"action":"Before and during treatment, tell women about the possibility of early menopause and menopausal symptoms","why":"Knowing what to expect, and that help exists, makes it easier to cope and to stay on treatment.","source":"nice-ng101","quote":"Offer women information and counselling about the possibility of early menopause and menopausal symptoms associated with breast cancer treatment."},{"action":"Do not routinely offer HRT after breast cancer; consider it only in exceptional circumstances for severe symptoms, after discussing the risks","why":"Hormone replacement could feed a hormone-sensitive cancer; it is contraindicated after breast cancer.","source":"nice-ng101","quote":"Do not routinely offer HRT (including oestrogen/progestogen combination) to women with menopausal symptoms and a history of breast cancer."},{"action":"Offer menopause-specific cognitive behavioural therapy for hot flushes when HRT is ruled out or not wanted","why":"These have good evidence, no drug interactions and no effect on the cancer treatment.","source":"nice-ng23","quote":"Consider menopause-specific cognitive behavioural therapy (CBT) as an option for vasomotor symptoms associated with menopause: in addition to HRT or for people for whom HRT is contraindicated or for those who prefer not to take HRT."},{"action":"Where medicine is wanted, consider venlafaxine, an SSRI or gabapentin; with tamoxifen, avoid paroxetine and fluoxetine","why":"These reduce hot flushes; paroxetine and fluoxetine can block the enzyme that turns tamoxifen into its active form.","source":"cco-2017","quote":"Women with breast cancer taking tamoxifen should not be offered paroxetine or fluoxetine because those agents inhibit CYP2D6 activity, which transforms tamoxifen into its active metabolites."},{"action":"Consider elinzanetant for moderate to severe hot flushes on endocrine therapy, with liver blood tests before starting and three months after","why":"In a large trial it cut hot flushes in women on endocrine therapy; the label asks for liver monitoring.","source":"oasis4-2025","quote":"Elinzanetant led to a significantly lower frequency of vasomotor symptoms associated with endocrine therapy than placebo."},{"action":"Do not use fezolinetant during breast cancer treatment; after treatment, decide on an individual risk assessment","why":"People having treatment for oestrogen-dependent cancers are outside the drug's licence in the UK.","source":"nice-ta1143","quote":"For people who have had breast cancer or other oestrogen-dependent cancers and are no longer having treatment, any decision to use fezolinetant should be based on an individual risk assessment."},{"action":"Advise against soy, red clover, black cohosh, vitamin E and magnetic devices for hot flushes after breast cancer","why":"They have not been shown to work, and some may interact with cancer treatment.","source":"nice-ng101","quote":"Do not offer soy (isoflavone), red clover, black cohosh, vitamin E or magnetic devices to treat vasomotor symptoms in women with breast cancer."},{"action":"For men with troublesome hot flushes on long-term androgen deprivation, offer medroxyprogesterone 20 mg a day for 10 weeks and review","why":"It is the first-line medicine NICE recommends for hot flushes from prostate cancer hormone therapy.","source":"nice-ng131","quote":"Offer medroxyprogesterone (20 mg per day), initially for 10 weeks, to manage troublesome hot flushes caused by long-term androgen suppression. Evaluate the effect at the end of the treatment period."},{"action":"If that fails or is not tolerated, consider cyproterone acetate; tell men there is no good-quality evidence for complementary therapies","why":"A second hormonal option exists; complementary treatments have not been shown to help.","source":"nice-ng131","quote":"Consider cyproterone acetate (50 mg twice a day for 4 weeks) to treat troublesome hot flushes if medroxyprogesterone is not effective or not tolerated."}],"bestInClass":{"statement":"For women on breast cancer endocrine therapy: information, no routine HRT, CBT (NICE NG23; NAMS Level I; ASCO 2018), then non-hormonal medicines such as venlafaxine, gabapentin or an SSRI that does not interact with tamoxifen (NICE NG101; CCO; ASCO), and now elinzanetant, the only neurokinin antagonist with a phase 3 trial in this population (OASIS-4); fezolinetant is outside its UK licence during treatment for oestrogen-dependent cancer. For men on androgen deprivation: medroxyprogesterone first, then cyproterone (NICE NG131), with venlafaxine and gabapentin as non-hormonal alternatives (CCO; ASCO). The guidelines disagree on breathing and acupuncture: ASCO recommends slow breathing and CCO calls acupuncture a possible alternative for men, while NAMS does not recommend paced respiration or acupuncture and NICE tells men there is no good-quality evidence for complementary therapies.","sources":["nice-ng101","nice-ng23","nice-ng131","nice-ta1143","cco-2017","asco-2018","nams-2023","oasis4-2025","lynkuet-label-2026"]},"variants":[{"name":"NAMS 2023 nonhormone therapy position statement (general menopause)","differs":"Grades options by level: recommends CBT, clinical hypnosis, SSRIs and SNRIs, gabapentin and fezolinetant (Level I), oxybutynin (Levels I to II), weight loss and stellate ganglion block (Levels II to III); does not recommend paced respiration, cooling, trigger avoidance, exercise, yoga, acupuncture, supplements, clonidine or pregabalin.","evidence":"Position statement from a literature review by an advisory panel; read as an abstract. It names oestrogen-dependent cancers as a reason a woman may not be a candidate for hormone therapy.","sources":["nams-2023"]},{"name":"ACP 2026 guideline (general menopause)","differs":"Puts oestrogen first for women without contraindications, SNRIs (desvenlafaxine or venlafaxine) second, and SSRIs, gabapentin or the neurokinin antagonists elinzanetant or fezolinetant third.","evidence":"GRADE-based; SNRIs conditional with moderate-certainty evidence; neurokinin antagonists conditional with moderate-certainty evidence. Not written for people with cancer. Read as an abstract.","sources":["acp-2026"]},{"name":"Acupuncture for men's hot flushes on androgen deprivation (CCO)","differs":"Uses acupuncture instead of medicine.","evidence":"CCO says acupuncture might be a suitable alternative, on eleven publications of low quality; NICE NG131 says there is no good-quality evidence for complementary therapies, and NAMS (for women) does not recommend acupuncture.","sources":["cco-2017","nice-ng131","nams-2023"]},{"name":"Hormone therapy until average menopause age after non-hormone-sensitive cancers (CCO)","differs":"For premenopausal women whose cancer is not hormone-sensitive and who develop hot flushes from treatment, hormone therapy until about 51 rather than non-hormonal options.","evidence":"CCO expert panel, resting mainly on high-quality guidelines for the general population; it states that hormone-sensitive breast cancer is a contraindication to systemic hormone therapy.","sources":["cco-2017"]}],"grades":[{"claim":"Elinzanetant reduced hot flush frequency at 12 weeks in OASIS-4","grade":"phase 3 randomised trial, P<0.001","source":"oasis4-2025","quote":"At week 12, the mean change was -7.8 episodes (95% CI, -8.5 to -7.1) among those receiving elinzanetant and -4.2 episodes (95% CI, -5.2 to -3.2) among those receiving placebo (least-squares mean difference, -3.4 episodes; 95% CI, -4.2 to -2.5; P<0.001)."},{"claim":"Neurokinin antagonists as third-line treatment in general menopause","grade":"conditional recommendation; moderate-certainty evidence (ACP)","source":"acp-2026","quote":"or neurokinin receptor antagonists, either elinzanetant or fezolinetant (moderate-certainty evidence)."},{"claim":"Medicines for men's hot flushes","grade":"eleven publications of low quality (CCO)","source":"cco-2017","quote":"The evidence base for these recommendations consists of eleven publications of low quality"},{"claim":"NICE breast cancer recommendations on menopausal symptoms","grade":"NICE does not grade recommendations","source":"nice-ng101","quote":"Consider selective serotonin reuptake inhibitor (SSRI) antidepressants for women with breast cancer for relieving menopausal symptoms, particularly hot flushes, but not for those taking tamoxifen."}],"sources":[{"key":"nice-ng101","label":"Early and locally advanced breast cancer: diagnosis and management (NG101), recommendations 1.14.20 to 1.14.25","publisher":"NICE","year":2025,"url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider', 'do not offer') signals the strength.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng23","label":"Menopause: identification and management (NG23), recommendation 1.5.2","publisher":"NICE","year":2026,"url":"https://www.nice.org.uk/guidance/ng23/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider', 'do not offer') signals the strength.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng131","label":"Prostate cancer: diagnosis and management (NG131), recommendations 1.4.3 to 1.4.5","publisher":"NICE","year":2021,"url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider', 'do not offer') signals the strength.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ta1143","label":"Fezolinetant for treating moderate to severe vasomotor symptoms associated with menopause (TA1143)","publisher":"NICE","year":2026,"url":"https://www.nice.org.uk/guidance/ta1143","read":"full-text","accessed":"2026-11-11"},{"key":"cco-2017","label":"Interventions to address sexual problems in people with cancer (Cancer Care Ontario guideline), vasomotor symptom recommendations","publisher":"Cancer Care Ontario, Current Oncology","year":2017,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5486385/","doi":"10.3747/co.24.3583","gradingScheme":"Recommendations are not graded; each states the number and quality of the publications behind it.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2018","label":"Interventions to Address Sexual Problems in People With Cancer: ASCO Clinical Practice Guideline Adaptation of Cancer Care Ontario Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/abstract/MED/29227723","doi":"10.1200/JCO.2017.75.8995","read":"abstract","accessed":"2026-11-11"},{"key":"nams-2023","label":"The 2023 nonhormone therapy position statement of The North American Menopause Society","publisher":"The North American Menopause Society, Menopause","year":2023,"url":"https://europepmc.org/abstract/MED/37252752","doi":"10.1097/GME.0000000000002200","gradingScheme":"Level I (good and consistent scientific evidence), Level II (limited or inconsistent), Level III (consensus and expert opinion).","read":"abstract","accessed":"2026-11-11"},{"key":"acp-2026","label":"Pharmacologic Treatments for Females With Menopausal Vasomotor Symptoms: A Clinical Guideline From the American College of Physicians","publisher":"American College of Physicians, Annals of Internal Medicine","year":2026,"url":"https://europepmc.org/abstract/MED/42832802","doi":"10.7326/ANNALS-26-01205","gradingScheme":"GRADE: strong or conditional recommendation; high, moderate or low certainty of evidence.","read":"abstract","accessed":"2026-11-11"},{"key":"oasis4-2025","label":"Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer (OASIS-4)","publisher":"New England Journal of Medicine","year":2025,"url":"https://europepmc.org/abstract/MED/40454634","doi":"10.1056/NEJMoa2415566","read":"abstract","accessed":"2026-11-11"},{"key":"nk-review-2026","label":"Neurokinin pathway antagonists for vasomotor symptoms in women with breast cancer: focus on elinzanetant and fezolinetant","publisher":"The Breast","year":2026,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13213637/","doi":"10.1016/j.breast.2026.104812","read":"full-text","accessed":"2026-11-11"},{"key":"lynkuet-label-2026","label":"LYNKUET (elinzanetant) capsules, US prescribing information (DailyMed, version of 4 August 2026)","publisher":"Bayer HealthCare Pharmaceuticals, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f42884ff-7dff-419c-8a0c-affe2ed73818","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The regulatory status of elinzanetant specifically for hot flushes caused by endocrine therapy is not settled by the sources read: the US label read (August 2026) is indicated for vasomotor symptoms due to menopause and does not mention breast cancer, while a 2026 review lists its status in breast cancer as approved without saying by which agency or for which wording. The EMA product page refused a script.","Elinzanetant and fezolinetant have not been compared head to head with venlafaxine, gabapentin or CBT in people with cancer; NICE notes that fezolinetant has not been compared directly with non-hormonal treatments.","Fezolinetant trials in women on endocrine therapy (HIGHLIGHT, FLASH-Breast and VENT, listed in the 2026 review) had not reported.","The NAMS 2023 statement and the ACP 2026 guideline were read only as abstracts, and both are written for menopause in general, not for people with cancer.","The SIO guideline on integrative therapies during and after breast cancer, endorsed by ASCO in 2018, was read only as an abstract, which does not mention hot flushes.","Which SSRIs or SNRIs are safest with tamoxifen beyond paroxetine and fluoxetine, and the effect of neurokinin antagonists with CDK4/6 inhibitors, are raised in the 2026 review but not settled by a guideline read.","NICE NG131's hot flush recommendations date from 2014; no later NICE review of non-hormonal options for men was found."]},{"id":"hypercalcaemia-of-malignancy-management","kind":"protocol","name":"Hypercalcaemia of malignancy: assessment, intravenous fluids, bisphosphonate or denosumab","aka":["malignant hypercalcaemia","hypercalcemia of malignancy treatment","HCM","high calcium in cancer","cancer-related hypercalcaemia"],"tldr":"Some cancers raise the calcium level in the blood. It causes thirst, passing a lot of urine, constipation, sickness, tiredness and confusion, and can be dangerous. A blood test confirms it. Treatment is a drip of fluid, then a medicine that stops calcium leaving the bones (a bisphosphonate such as zoledronic acid, or denosumab), alongside treatment of the cancer itself.","summary":"Society for Endocrinology 2016: measure calcium adjusted for albumin. Under 3.0 mmol/L is often asymptomatic; 3.0 to 3.5 usually needs prompt treatment; over 3.5 needs urgent correction for the risk of dysrhythmia and coma. Check phosphate, PTH, urea and electrolytes and an ECG for a short QT; high calcium with a low PTH points to malignancy. Review drugs and supplements. Rehydrate with intravenous 0.9% saline, 4 to 6 L over 24 hours, watching for fluid overload in the elderly or with renal impairment; loop diuretics do not lower calcium and are only for overload. Then an intravenous bisphosphonate: zoledronic acid 4 mg over 15 minutes, pamidronate 30 to 90 mg or ibandronic acid 2 to 4 mg, more slowly and at reduced dose in renal impairment; the calcium nadir comes at 2 to 4 days. Prednisolone 40 mg daily for lymphoma and other calcitriol-driven causes. Denosumab, calcitonin and calcimimetics under specialist supervision.\n\nEndocrine Society 2023 (GRADE): treat with denosumab or an intravenous bisphosphonate (strong recommendation); suggests denosumab rather than an intravenous bisphosphonate, calcitonin with a bisphosphonate or denosumab for severe hypercalcaemia, denosumab for refractory or recurrent cases despite bisphosphonate, an antiresorptive added to glucocorticoids for calcitriol-driven tumours, and a calcimimetic or antiresorptive for parathyroid carcinoma (all conditional, low certainty). Treating the cancer is what controls hypercalcaemia and prevents recurrence.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency","metabolic"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["zoledronic-acid","pamidronate","ibandronic-acid","denosumab","cinacalcet"],"companies":[],"institutions":[],"pathways":[],"terms":["bone-metastases"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer can make your blood calcium too high. You may feel very thirsty, sick, constipated or muddled. Tell your cancer team. A drip and a bone medicine bring it down.","domain":"emergencies","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["acute-oncology-service","emergency-department","ward","telephone-triage"]},"population":"Adults with cancer and a raised adjusted calcium. Lymphoma and other tumours that raise calcitriol, and parathyroid carcinoma, have steps of their own. Children, and hypercalcaemia from primary hyperparathyroidism alone, are not covered.","trigger":"Thirst, polyuria, nausea, constipation, confusion or drowsiness in a person with cancer, or a raised adjusted calcium on a routine blood test.","steps":[{"action":"Think of hypercalcaemia in anyone with cancer who has thirst, passes a lot of urine, is constipated, nauseated, low in mood or confused","why":"The symptoms are vague and easily put down to the cancer or its treatment.","source":"sfe-2016","quote":"Polyuria and thirst Anorexia, nausea and constipation Mood disturbance, cognitive dysfunction, confusion and coma"},{"action":"Measure calcium adjusted for albumin, with phosphate, PTH, urea and electrolytes","why":"Low albumin, common in cancer, hides a high free calcium; a low PTH with high calcium points to the cancer as the cause.","source":"sfe-2016","quote":"Serum calcium is bound to albumin, and measurements should be adjusted for serum albumin."},{"action":"Treat an adjusted calcium above 3.5 mmol/L as urgent","why":"At that level the risk of heart rhythm problems and coma is high.","source":"sfe-2016","quote":">3.5 mmol/L: requires urgent correction due to the risk of dysrhythmia and coma"},{"action":"Record an ECG and look for a short QT interval or conduction problems","why":"High calcium affects the heart's electrical activity.","source":"sfe-2016","quote":"Look for shortened QT interval or other conduction abnormalities"},{"action":"Review all medicines, including supplements and over-the-counter products, and stop those that raise calcium","why":"Thiazides, lithium, calcium and vitamin D supplements can add to the problem.","source":"sfe-2016","quote":"Drugs including supplements and over-the-counter preparations"},{"action":"Rehydrate with intravenous 0.9% saline, 4 to 6 litres over 24 hours, watching for fluid overload in older people or with kidney impairment","why":"High calcium makes the kidneys lose water, and dehydration in turn stops them clearing calcium.","source":"sfe-2016","quote":"Intravenous 0.9% saline 4–6 L in 24 h Monitor for fluid overload if renal impairment or elderly"},{"action":"Do not use loop diuretics to lower calcium; use them only for fluid overload","why":"They do not reduce calcium and can worsen dehydration.","source":"sfe-2016","quote":"Loop diuretics rarely used and only if fluid overload develops; not effective for reducing serum calcium"},{"action":"Give an antiresorptive drug: denosumab or an intravenous bisphosphonate","why":"These stop bone releasing calcium; the Endocrine Society makes this its one strong recommendation.","source":"es-2023","quote":"The panel recommends (strong recommendation) in adults with HCM treatment with denosumab (Dmab) or an intravenous (IV) bisphosphonate (BP).","grade":"strong recommendation"},{"action":"If using a bisphosphonate, give zoledronic acid 4 mg over 15 minutes (or pamidronate or ibandronic acid), more slowly and at a lower dose if the kidneys are impaired","why":"Bisphosphonates are cleared by the kidneys and can damage them if given too fast.","source":"sfe-2016","quote":"Give more slowly and consider dose reduction in renal impairment"},{"action":"For severe hypercalcaemia, consider calcitonin with the bisphosphonate or denosumab as initial treatment","why":"Calcitonin works within hours, while bisphosphonates and denosumab take days.","source":"es-2023","quote":"The panel suggests (conditional recommendation) (1) in adults with HCM, the use of Dmab rather than an IV BP; (2) in adults with severe HCM, a combination of calcitonin and an IV BP or Dmab therapy as initial treatment; and (3) in adults with refractory/recurrent HCM despite treatment with BP, the use of Dmab.","grade":"conditional recommendation, low certainty of evidence"},{"action":"In lymphoma and other causes driven by calcitriol, use a glucocorticoid such as prednisolone 40 mg daily, adding a bisphosphonate or denosumab if calcium stays high","why":"Steroids switch off the excess vitamin D production these tumours cause.","source":"sfe-2016","quote":"Glucocorticoids (inhibit 1,25OHD production) In lymphoma, other granulomatous diseases or 25OHD poisoning Prednisolone 40 mg daily"},{"action":"Recheck calcium over the following days, expecting the lowest level at 2 to 4 days, and watch for low calcium","why":"Overshoot is possible, especially with vitamin D deficiency or a suppressed PTH.","source":"sfe-2016","quote":"Monitor serum calcium response: will reach nadir at 2–4 days Can cause hypocalcaemia if vitamin D deficiency or suppressed PTH"},{"action":"Plan treatment of the underlying cancer","why":"Lowering calcium buys time; treating the cancer is what keeps it down.","source":"es-2023","quote":"Treatment of the primary malignancy is instrumental for controlling hypercalcemia and preventing its recurrence."}],"bestInClass":{"statement":"Both sources start with assessment and intravenous saline and then an antiresorptive. They differ on which one: the Endocrine Society 2023 recommends denosumab or an intravenous bisphosphonate (strong) and suggests denosumab rather than a bisphosphonate (conditional, low certainty), while the Society for Endocrinology 2016 emergency guidance gives an intravenous bisphosphonate first and keeps denosumab, calcitonin and calcimimetics for specialists when the response is poor. The Endocrine Society also suggests calcitonin with the antiresorptive for severe hypercalcaemia. Saline volumes, the bisphosphonate doses and the warning against loop diuretics come from the Society for Endocrinology; the Endocrine Society's full text, which may give its own, could not be read.","sources":["es-2023","sfe-2016"]},"variants":[{"name":"Denosumab first (Endocrine Society 2023)","differs":"Suggests denosumab rather than an intravenous bisphosphonate for hypercalcaemia of malignancy, and denosumab for cases refractory or recurrent despite a bisphosphonate.","evidence":"Conditional recommendation, low certainty (GRADE).","sources":["es-2023"]},{"name":"Bisphosphonate first, denosumab under specialist care (Society for Endocrinology 2016)","differs":"Uses zoledronic acid, pamidronate or ibandronic acid after saline, and lists denosumab, calcitonin and calcimimetics as second-line treatments under specialist supervision.","evidence":"Expert emergency guidance, not graded.","sources":["sfe-2016"]},{"name":"Parathyroid carcinoma","differs":"Treats hypercalcaemia from parathyroid carcinoma with either a calcimimetic or an antiresorptive.","evidence":"Conditional recommendation, low certainty (Endocrine Society 2023).","sources":["es-2023"]}],"grades":[{"claim":"Treat with denosumab or an intravenous bisphosphonate","grade":"strong recommendation","source":"es-2023"},{"claim":"Denosumab rather than an intravenous bisphosphonate","grade":"conditional, low certainty","source":"es-2023"},{"claim":"Calcitonin with a bisphosphonate or denosumab for severe hypercalcaemia","grade":"conditional, low certainty","source":"es-2023"},{"claim":"Denosumab for hypercalcaemia refractory or recurrent despite a bisphosphonate","grade":"conditional, low certainty","source":"es-2023"},{"claim":"Add an antiresorptive to glucocorticoids for calcitriol-driven tumours with persistent severe hypercalcaemia","grade":"conditional, low certainty","source":"es-2023","quote":"The panel suggests (conditional recommendation) the addition of an IV BP or Dmab in adult patients with hypercalcemia due to tumors associated with high calcitriol levels who are already receiving glucocorticoid therapy but continue to have severe or symptomatic HCM."}],"sources":[{"key":"es-2023","label":"Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline","publisher":"Endocrine Society, Journal of Clinical Endocrinology and Metabolism","year":2023,"url":"https://europepmc.org/abstract/MED/36545746","doi":"10.1210/clinem/dgac621","gradingScheme":"GRADE: 'recommends' is a strong and 'suggests' a conditional recommendation, with certainty of evidence rated high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"sfe-2016","label":"Society for Endocrinology Endocrine Emergency Guidance: emergency management of acute hypercalcaemia in adult patients","publisher":"Society for Endocrinology, Endocrine Connections","year":2016,"url":"https://europepmc.org/article/PMC/PMC5314807","doi":"10.1530/EC-16-0055","gradingScheme":"Expert emergency guidance; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The Endocrine Society 2023 guideline was read only as its abstract; its full text, with doses, fluid advice and the evidence tables, returned 403 to a script.","No UK national (NICE) guideline on hypercalcaemia of malignancy was found; UK acute oncology services use local and regional policies that were not read.","The Endocrine Society rates the evidence comparing denosumab with bisphosphonates as low certainty; no head-to-head randomised trial in hypercalcaemia of malignancy was read here.","Calcitonin is not in the corpus as a drug record and is named here without a link."]},{"id":"hyperleukocytosis-leukostasis","kind":"protocol","name":"Hyperleukocytosis and leukostasis in acute leukaemia: supportive care, cytoreduction and leukapheresis","aka":["leukostasis","hyperleukocytosis","white cell count over 100","leukapheresis for AML","leukoreduction"],"tldr":"In some leukaemias the white cell count is so high that the blood thickens and blocks small vessels in the lungs, brain and kidneys. This leukostasis is an emergency. The cells are brought down quickly with hydroxyurea and then chemotherapy; sometimes a machine filters them out. Blood transfusions are avoided unless really needed, because they thicken the blood further.","summary":"Hyperleukocytosis is a white cell count above 100,000/µL from leukaemic proliferation; leukostasis is end-organ injury from it, which can occur at lower counts and is commoner in AML than ALL because myeloid blasts are larger (ATS Scholar 2025). The lungs, kidneys and brain are most affected; intracranial haemorrhage is the most feared complication. Tumour lysis syndrome (up to 10%) and DIC (30 to 40%) accompany it. Diagnosis is usually presumptive. There should be a low threshold for intensive care.\n\nSupportive care: fluids with close fluid-balance monitoring, electrolytes and uric acid at least every 6 hours, allopurinol or rasburicase, red cell transfusion only for symptomatic anaemia because it raises viscosity, and prompt platelets, plasma and fibrinogen for DIC. Cytoreduction: hydroxyurea before induction chemotherapy; all-trans retinoic acid at once if acute promyelocytic leukaemia is suspected. Leukapheresis can be considered but is institution-specific; a 2026 meta-analysis of 13 retrospective studies (1406 patients in the main analysis) found no clear reduction in 30-day mortality (OR 0.94, 95% CI 0.65 to 1.34; very low certainty). Red cell exchange is reported as an alternative for rapid leukoreduction (Blood 2024). ASFA's tenth edition (2026) categorises leukocytapheresis, but its category could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency","haematology"],"related":["tumour-lysis-syndrome-prevention-and-treatment"],"cancers":["aml","all-leukemia","leukaemia"],"sections":[],"technologies":[],"targets":[],"drugs":["hydroxyurea","tretinoin-atra","allopurinol","rasburicase","cytarabine"],"companies":[],"institutions":[],"pathways":[],"terms":["apheresis","tumor-lysis-syndrome"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A very high white cell count in leukaemia can block small blood vessels. Breathlessness, confusion or a bad headache need urgent hospital care.","domain":"emergencies","setting":{"who":["doctor","nurse","multidisciplinary-team"],"where":["emergency-department","ward","intensive-care"]},"population":"Adults with acute leukaemia, above all acute myeloid leukaemia, and a very high white cell count, with or without signs of organ injury. Chronic leukaemias and children are mentioned by the sources but not covered here.","trigger":"A white cell count above 100,000/µL in suspected or known acute leukaemia, or breathlessness, low oxygen, confusion, headache, visual change or kidney injury with a high blast count.","steps":[{"action":"Treat leukostasis as an emergency, with a low threshold for intensive care","why":"People can deteriorate quickly, with breathing failure or bleeding in the brain.","source":"ats-2025","quote":"These patients may experience rapid decompensation, and there should be a low threshold to admit them to an intensive care unit (Figure 1)."},{"action":"Do not wait for a count above 100,000/µL: suspect leukostasis from organ symptoms in a person with a high blast count","why":"Organ damage can happen at lower counts, and the diagnosis is usually made on clinical grounds.","source":"ats-2025","quote":"Leukostasis is a clinical emergency characterized by end-organ injury from malignant hyperleukocytosis but can also occur at WBC counts <100,000/μl (2)."},{"action":"Give intravenous fluids while watching fluid balance closely","why":"Fluids dilute the blood and protect the kidneys, but too much can worsen breathing.","source":"ats-2025","quote":"Although vigorous fluid administration can reduce WBC concentration and blood viscosity and mitigate consequences of TLS, it has a potential to cause volume overload and exacerbate respiratory impairment, so close monitoring of fluid balance is important."},{"action":"Check electrolytes and uric acid at least every 6 hours, and give allopurinol or rasburicase","why":"Leukaemia cells breaking down release potassium, phosphate and uric acid that can damage the kidneys and heart.","source":"ats-2025","quote":"Given the high risk of TLS, frequent electrolyte and uric acid monitoring (at least every 6 h) is needed."},{"action":"Avoid red cell transfusion unless anaemia is causing symptoms","why":"Adding red cells makes thick blood thicker and can worsen the blockage.","source":"ats-2025","quote":"Blood transfusions should be avoided unless the patient has symptomatic anemia because increased blood viscosity can worsen leukostasis."},{"action":"If DIC is suspected, give platelets, fresh frozen plasma and fibrinogen promptly","why":"Clotting failure is common and, with leukostasis, raises the risk of bleeding in the brain.","source":"ats-2025","quote":"DIC is common, and treatment with platelets, fresh frozen plasma, and fibrinogen should be promptly initiated if this is suspected."},{"action":"Lower the count with hydroxyurea before induction chemotherapy, and start all-trans retinoic acid at once if acute promyelocytic leukaemia is suspected","why":"Bringing the count down quickly relieves the blockage; promyelocytic leukaemia needs its own urgent treatment.","source":"ats-2025","quote":"If acute promyelocytic leukemia is suspected, all-trans retinoic acid should be initiated immediately to induce differentiation (1)."},{"action":"Consider leukapheresis case by case, weighing procedural risks, especially in promyelocytic leukaemia","why":"Filtering the white cells out works quickly, but it has not been shown to save lives and practice differs between hospitals.","source":"ats-2025","quote":"Additionally, the beneficial effect on early clinical outcomes with leukapheresis has not been definitively demonstrated (2)."}],"bestInClass":{"statement":"No graded guideline on hyperleukocytosis could be read for this page. The sources read agree on supportive care (fluids with care, tumour lysis prophylaxis, avoiding unnecessary red cell transfusion, correcting DIC) and on rapid cytoreduction with hydroxyurea and then induction chemotherapy, with ATRA at once for suspected promyelocytic leukaemia. They disagree, or are uncertain, about leukapheresis: the ATS Scholar article and the Journal of Hospital Medicine review describe it as optional and institution-dependent, and the 2026 meta-analysis of 13 retrospective studies found no clear effect on 30-day mortality, at very low certainty. ASFA (2026) gives the formal apheresis category but could not be read.","sources":["ats-2025","jhm-2026","leukapheresis-ma-2026","asfa-2026"]},"variants":[{"name":"Routine leukapheresis for hyperleukocytosis","differs":"Removes leukaemic cells by apheresis as soon as the count is very high or leukostasis is suspected, alongside cytoreduction.","evidence":"2026 meta-analysis: 13 retrospective comparative studies; 30-day mortality OR 0.94 (95% CI 0.65 to 1.34), most studies at serious risk of bias, certainty very low, with confounding by indication.","sources":["leukapheresis-ma-2026"]},{"name":"Red cell exchange instead of leukapheresis","differs":"Uses red cell exchange to remove white cells, which can also correct severe anaemia without raising viscosity.","evidence":"Blood 2024: similar leukoreduction to standard therapeutic leukoreduction, possibly better in severe anaemia, monocytic leukaemias or when rapid treatment is needed. Read as an abstract only.","sources":["rce-2024"]},{"name":"Cytarabine as an early cytoreductive agent","differs":"Uses cytarabine as well as hydroxyurea to bring the count down until definitive treatment starts.","evidence":"Named in the Journal of Hospital Medicine 2026 review abstract; no comparative data read.","sources":["jhm-2026"]}],"grades":[{"claim":"Leukapheresis and 30-day mortality in AML with hyperleukocytosis","grade":"GRADE: very low certainty","source":"leukapheresis-ma-2026","quote":"Most studies were at serious risk of bias, and certainty of evidence was very low."}],"sources":[{"key":"ats-2025","label":"Management of Leukostasis in Acute Myeloid Leukemia","publisher":"ATS Scholar (American Thoracic Society)","year":2025,"url":"https://europepmc.org/article/PMC/PMC12712836","doi":"10.34197/ats-scholar.2025-0039OT","gradingScheme":"A short teaching article; not a graded guideline.","read":"full-text","accessed":"2026-11-11"},{"key":"jhm-2026","label":"Approach to hyperleukocytosis and leukostasis-inpatient management strategies","publisher":"Journal of Hospital Medicine","year":2026,"url":"https://europepmc.org/abstract/MED/41058090","doi":"10.1002/jhm.70199","read":"abstract","accessed":"2026-11-11"},{"key":"leukapheresis-ma-2026","label":"Leukapheresis versus no leukapheresis for hyperleukocytosis in acute myeloid leukemia: an updated systematic review and meta-analysis of early mortality","publisher":"Expert Review of Hematology","year":2026,"url":"https://europepmc.org/abstract/MED/42185077","doi":"10.1080/17474086.2026.2680138","gradingScheme":"GRADE certainty of evidence; ROBINS-I risk of bias.","read":"abstract","accessed":"2026-11-11"},{"key":"rce-2024","label":"Red cell exchange for rapid leukoreduction in adults with hyperleukocytosis and leukostasis","publisher":"Blood","year":2024,"url":"https://europepmc.org/abstract/MED/38052031","doi":"10.1182/blood.2023021895","read":"abstract","accessed":"2026-11-11"},{"key":"asfa-2026","label":"Guidelines on the Use of Therapeutic Apheresis in Clinical Practice: Evidence-Based Approach From the Writing Committee of the American Society for Apheresis, The Tenth Special Issue","publisher":"American Society for Apheresis, Journal of Clinical Apheresis","year":2026,"url":"https://europepmc.org/abstract/MED/42747330","doi":"10.1002/jca.70141","gradingScheme":"Each indication carries an ASFA category and a grade; the abstract read describes 183 graded and categorised indications but gives none of them.","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No graded guideline on hyperleukocytosis or leukostasis was read. The ASFA tenth edition (2026) categorises leukocytapheresis, but only its abstract could be read; the ELN 2022 AML and 2019 APL recommendations were not read in full.","The steps rest mainly on a short teaching article (ATS Scholar 2025) that cites reviews; they describe common practice rather than graded recommendations.","The white cell count at which to start cytoreduction or apheresis, and the hydroxyurea dose, are not set by any source read here.","Leukapheresis has never been tested in a randomised trial; the meta-analysis is of retrospective studies with confounding by indication.","Leukostasis in chronic leukaemias and in children is not covered."]},{"id":"hyponatraemia-siadh","kind":"protocol","name":"Hyponatraemia and SIADH in cancer: emergency hypertonic saline, safe correction and treating the cause","aka":["low sodium in cancer","SIADH","SIAD","syndrome of inappropriate antidiuretic hormone","paraneoplastic hyponatraemia","hypertonic saline bolus"],"tldr":"Low sodium in the blood is common in cancer, especially small-cell lung cancer, and can also come from some cancer drugs, sickness or diarrhoea. Vomiting, confusion, drowsiness or a fit with low sodium is an emergency: hospital teams give a strong salt drip in small doses and check often, because raising sodium too fast can damage the brain. Then the cause is treated.","summary":"Treatment follows symptoms, not the number (Society for Endocrinology 2016): severe symptoms (vomiting, seizures, reduced consciousness, cardiorespiratory arrest) need immediate hypertonic saline whatever the cause, supervised by a senior clinician, aiming for a 5 mmol/L rise in the first hour; if limits of 10 mmol/L in 24 hours or 18 mmol/L in 48 hours are exceeded, hypertonic fluid stops and an experienced clinician considers hypotonic fluid, with or without an antidiuretic such as desmopressin, to re-lower. After the emergency, urine osmolality and urine sodium define the cause.\n\nThe Korean Society of Nephrology 2022 guideline suggests rapid intermittent boluses rather than slow continuous infusion (B, low), based on the SALSA trial (178 patients: overcorrection 17.2% against 24.2%, not significant; re-lowering treatment needed less often with boluses, 41.4% against 57.1%), and tabulates the European bolus regimen of 150 mL over 20 minutes repeated two to three times for severe symptoms; it notes the European guideline graded bolus therapy 1D. It sets a stricter limit of 8 mmol/L a day for people at high risk of osmotic demyelination. For SIAD it names fluid restriction as standard, with oral salt plus a loop diuretic, or a vaptan, second line; it suggests vaptans for moderate to severe hyponatraemia (B, low) where the European guideline recommends against them in people without moderately severe or severe symptoms. In people with brain disease, including brain tumours, it warns against fluid restriction because of volume depletion.\n\nIn cancer, SIADH is the usual cause, most often with small-cell lung cancer, from ectopic vasopressin or from anticancer and palliative drugs; vomiting and diarrhoea cause hypovolaemic hyponatraemia (The Oncologist 2012). A 2026 scoping review of 86 SCLC patients on tolvaptan reported an initial response in all cases and overcorrection in five.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency","electrolytes"],"related":["irae-hypophysitis-adrenal"],"cancers":["sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Low sodium can make you confused, sick or drowsy. It can be caused by the cancer or its treatment. If this happens, ring your cancer team the same day.","domain":"emergencies","setting":{"who":["doctor","nurse","pharmacist","emergency-team"],"where":["emergency-department","acute-oncology-service","ward","intensive-care"]},"population":"Adults with cancer who have a serum sodium below 135 mmol/L, with or without symptoms. The Society for Endocrinology guidance covers adults with severe or moderately severe symptoms; the Korean guideline also covers chronic and mild hyponatraemia and makes a separate recommendation for children's maintenance fluids, not covered here.","trigger":"A low sodium on a blood test, or vomiting, confusion, drowsiness or a seizure in a person with cancer, particularly small-cell lung cancer, or someone taking anticancer or palliative drugs that can cause SIADH.","steps":[{"action":"Judge urgency by symptoms and signs, not by the sodium level alone","why":"A very low sodium can cause no symptoms, while a moderate one can cause fits if it fell quickly.","source":"sfe-2016","quote":"Severity of clinical presentation may not match the degree of hyponatraemia: profound hyponatraemia may be symptom-free, while some patients with moderate biochemistry may have significant neurological symptoms and signs."},{"action":"For severe symptoms (vomiting, seizures, reduced consciousness, cardiorespiratory arrest), give hypertonic saline immediately, whatever the cause","why":"Swelling of the brain from low sodium can kill; the cause can be found afterwards.","source":"sfe-2016","quote":"Patients with severe symptoms require immediate treatment with hypertonic saline, irrespective of the cause of the hyponatraemia."},{"action":"Have a senior, experienced clinician decide on and supervise hypertonic saline, aiming for a 5 mmol/L rise in the first hour","why":"Raising sodium a little quickly relieves brain swelling; raising it too far is dangerous.","source":"sfe-2016","quote":"The aim is to achieve a 5 mmol/L rise in serum Na+ within the first hour, reducing immediate danger from cerebral oedema while minimising the risk of over-rapid correction and osmotic demyelination."},{"action":"Give hypertonic saline as repeated small boluses rather than a slow continuous infusion","why":"In a randomised trial boluses reached the first-hour target more often and needed fewer corrections afterwards, with no more overcorrection.","source":"ksn-2022","quote":"We suggest RIB administration of hypertonic saline in patients with symptomatic severe hypotonic hyponatremia (B, low).","grade":"B, low"},{"action":"Check sodium 1 hour after the first dose of hypertonic saline, then every 6 hours, and reassess once symptoms improve or sodium has risen by 5 to 9 mmol/L","why":"Sodium can rise faster than planned, especially once the body starts passing more urine.","source":"ksn-2022","quote":"We suggest checking SNa concentration 1 hour after first hypertonic saline administration, then re-checking SNa concentration every 6 hours to adjust the administration interval or infusion rate of hypertonic saline [1]."},{"action":"Stop hypertonic fluid if sodium rises by more than 10 mmol/L in 24 hours or 18 mmol/L in 48 hours, and get expert advice on re-lowering with hypotonic fluid with or without desmopressin","why":"Correcting too fast can cause osmotic demyelination, a permanent brain injury.","source":"sfe-2016","quote":"If the limit of 10 mmol/L in the first 24 h or 18 mmol/L in the first 48 h of treatment is exceeded, hypertonic fluid should be stopped."},{"action":"Use a stricter limit of 8 mmol/L a day for people at high risk: sodium of 105 mmol/L or less, low potassium, alcohol misuse, malnutrition or advanced liver disease","why":"These people are more likely to be harmed by fast correction, and malnutrition is common in advanced cancer.","source":"ksn-2022","quote":"SNa concentration should not be corrected by ≥ 10 mmol/L per day, with a more stringent limit of > 8 mmol/L per day for patients at high risk of ODS (SNa concentration ≤ 105 mmol/L, hypokalemia, alcoholism, malnutrition, and advanced liver disease) [2]."},{"action":"Once the emergency is controlled, measure urine osmolality and urine sodium, and review the drug history, to find the cause","why":"Treatment differs by cause: the wrong treatment, such as fluid restriction when someone is dry, can make sodium fall further.","source":"sfe-2016","quote":"Measurement of urine osmolality and urine Na+ concentration are central to defining the aetiology of hyponatraemia."},{"action":"In a person with cancer, think first of SIADH (from small-cell lung cancer above all, or from anticancer and palliative drugs), and of fluid loss from vomiting and diarrhoea","why":"These are the usual causes in cancer and need opposite treatments.","source":"castillo-2012","quote":"Hyponatremia in the cancer patient is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH), which develops more frequently with SCLC than with other malignancies."},{"action":"For SIADH without severe symptoms, restrict free water first; second line is oral salt with a loop diuretic, or a vaptan such as tolvaptan, with close sodium checks","why":"Fluid restriction lets the kidneys correct sodium slowly; tablets are added if it is not enough.","source":"ksn-2022","quote":"In patients with SIAD, the standard treatment is the restriction of free water because of water retention [32]."},{"action":"In people with a brain tumour or brain metastases, avoid fluid restriction and individualise treatment","why":"Low sodium with brain disease can come from salt loss or low cortisol as well as SIADH, and becoming dry can harm the brain.","source":"ksn-2022","quote":"Therefore, in the case of hyponatremia accompanying these cerebral diseases, clinicians should avoid volume depletion through water restriction [63]."}],"bestInClass":{"statement":"For the emergency, the guidelines read agree: severe symptoms mean immediate hypertonic saline, a first-hour rise of about 5 mmol/L, and limits of 10 mmol/L in 24 hours and 18 mmol/L in 48 hours (Society for Endocrinology 2016, drawing on the 2014 European and 2013 American guidelines). How to give it has trial evidence since 2014: the SALSA randomised trial found boluses no more likely to overcorrect than continuous infusion and less likely to need re-lowering, and the Korean 2022 guideline therefore suggests boluses (B, low). Where they disagree is chronic SIADH: the Korean guideline suggests a vaptan for moderate to severe hyponatraemia (B, low), while it reports that the European 2014 guideline recommends against vaptans in SIAD without moderately severe or severe symptoms. None of these is cancer-specific; the oncology-specific source read (The Oncologist 2012) is a review. The 2014 European guideline itself could not be read in full.","sources":["sfe-2016","ksn-2022","salsa-2021","ese-2014","castillo-2012"]},"variants":[{"name":"Slow continuous infusion of hypertonic saline","differs":"Gives hypertonic saline as a continuous infusion (for example 0.5 to 2 mL/kg/hour, the 2013 American regimen for moderate symptoms, as tabulated by KSN 2022) rather than boluses.","evidence":"SALSA, 178 patients: no difference in overcorrection (24.2% with infusion against 17.2% with boluses, P = .26) but more re-lowering treatment with infusion (57.1% against 41.4%, P = .04).","sources":["salsa-2021","ksn-2022"]},{"name":"Vaptans (tolvaptan) for SIADH in small-cell lung cancer","differs":"Uses an oral vasopressin receptor antagonist when fluid restriction fails or is not possible, often during chemotherapy when fluids are needed.","evidence":"KSN 2022 suggests vaptans in SIAD with moderate to severe hyponatraemia (B, low; 12 trials, no survival benefit); a 2026 scoping review of 86 SCLC patients reported a response in all and overcorrection in five, and secondary failure that can signal tumour progression.","sources":["ksn-2022","tolvaptan-sclc-2026"]}],"grades":[{"claim":"Rapid intermittent bolus of hypertonic saline for symptomatic severe hyponatraemia","grade":"B, low","source":"ksn-2022"},{"claim":"Vaptans in SIAD with moderate to severe hyponatraemia","grade":"B, low","source":"ksn-2022","quote":"We suggest treatment with vaptans in syndrome of inappropriate antidiuresis (SIAD) patients with moderate to severe hyponatremia (B, low)."},{"claim":"Desmopressin applied individually to prevent or treat overcorrection","grade":"B, very low","source":"ksn-2022","quote":"We suggest that desmopressin should be applied individually according to risk factors affecting overcorrection, hypertonic saline therapeutic regimen, and whether to administer dextrose solution during overcorrection in patients with hyponatremia (B, very low)."},{"claim":"Individualised treatment of hyponatraemia with brain disease","grade":"E (expert consensus)","source":"ksn-2022","quote":"We consider it reasonable that treatment with hypertonic or isotonic saline infusion, oral sodium chloride, or fludrocortisone for the correction of hypo-osmolar hyponatremia should be individualized among patients with cerebral diseases (E)."},{"claim":"Hypertonic saline in small fixed boluses (as the European 2014 guideline grades it, reported by KSN 2022)","grade":"1D (European); expert opinion (American)","source":"ksn-2022","quote":"Although the American (2013) and European (2014) guidelines recommend administering hypertonic saline in small, fixed boluses (recommendation grade: expert opinion in the American guidelines, 1D in the European guidelines), they were not based on high-quality RCT evidence [1,2,17]."}],"sources":[{"key":"sfe-2016","label":"Society for Endocrinology Endocrine Emergency Guidance: Emergency management of severe symptomatic hyponatraemia in adult patients","publisher":"Society for Endocrinology, Endocrine Connections","year":2016,"url":"https://europepmc.org/article/PMC/PMC5314809","doi":"10.1530/EC-16-0058","gradingScheme":"Emergency guidance from the Society for Endocrinology Clinical Committee; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ksn-2022","label":"Korean Society of Nephrology 2022 recommendations on controversial issues in diagnosis and management of hyponatremia","publisher":"Korean Society of Nephrology, Korean Journal of Internal Medicine","year":2022,"url":"https://europepmc.org/article/PMC/PMC9666265","doi":"10.3904/kjim.2022.174","gradingScheme":"Strength A (strong), B (conditional), C (against), I (inconclusive) or E (expert consensus), with quality of evidence high, moderate, low or very low, printed as '(B, low)'.","read":"full-text","accessed":"2026-11-11"},{"key":"ese-2014","label":"Clinical practice guideline on diagnosis and treatment of hyponatraemia (ESE, ESICM and ERBP/ERA-EDTA)","publisher":"European Society of Endocrinology, European Journal of Endocrinology","year":2014,"url":"https://europepmc.org/abstract/MED/24569125","doi":"10.1530/EJE-13-1020","gradingScheme":"Grades are printed as a number and a letter (for example 1D), as KSN 2022 reports them; the abstract read gives no recommendations and no grading key.","read":"abstract","accessed":"2026-11-11"},{"key":"salsa-2021","label":"Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial","publisher":"JAMA Internal Medicine","year":2021,"url":"https://europepmc.org/abstract/MED/33104189","doi":"10.1001/jamainternmed.2020.5519","read":"abstract","accessed":"2026-11-11"},{"key":"castillo-2012","label":"Diagnosis and management of hyponatremia in cancer patients","publisher":"The Oncologist","year":2012,"url":"https://europepmc.org/abstract/MED/22618570","doi":"10.1634/theoncologist.2011-0400","read":"abstract","accessed":"2026-11-11"},{"key":"tolvaptan-sclc-2026","label":"Tolvaptan for paraneoplastic SIADH in small cell lung cancer: a scoping review","publisher":"Cancer Treatment and Research Communications","year":2026,"url":"https://doi.org/10.1016/j.ctarc.2026.101233","doi":"10.1016/j.ctarc.2026.101233","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 2014 European guideline (ESE, ESICM, ERBP) could not be read in full: its publisher refused a script and the Springer copy returned a bot check. Its recommendations appear here only as the Korean 2022 guideline reports them.","The Society for Endocrinology bolus regimen is in figures that are images; the dose of hypertonic saline it recommends was not read as text. The European regimen (150 mL over 20 minutes, two to three times) is given as tabulated by KSN 2022.","No cancer-specific guideline on hyponatraemia was found; the oncology sources read are a 2012 review and a 2026 scoping review, both as abstracts. The Italian SIE, SIN and AIOM consensus (2018) was not read.","Hyponatraemia from adrenal insufficiency after checkpoint inhibitors is not covered here; see the protocol on hypophysitis and adrenal insufficiency.","NICE has no guideline on hyponatraemia; its Clinical Knowledge Summary refused a script."]},{"id":"icans-grading-and-management","kind":"protocol","name":"ICANS after CAR T-cell therapy: ICE score, ASTCT grading, steroids and seizure management","aka":["ICANS management","immune effector cell-associated neurotoxicity syndrome","ICE score","CAR-T neurotoxicity","CAPD score for children"],"tldr":"In the weeks after CAR T-cell therapy, some people become confused, struggle to find words or write, become very sleepy, or rarely have seizures. This is ICANS. Nurses check a short test of orientation, naming, writing and counting (the ICE score). Steroids such as dexamethasone treat it, and most people recover. A carer who notices confusion or odd speech should call the centre at once.","summary":"ICANS is graded by ASTCT 2019 with the 10-point ICE score (orientation 4, naming 3, following commands 1, writing 1, attention 1): 7 to 9 is grade 1, 3 to 6 grade 2, 0 to 2 grade 3, and 0 because the patient cannot be roused grade 4. The overall grade is the worst of the ICE score, level of consciousness, seizures, motor weakness and raised intracranial pressure or cerebral oedema. Children under 12 are assessed with the Cornell Assessment of Pediatric Delirium (CAPD), where 9 or more counts as grade 3. Headache alone is not a marker; expressive aphasia is the most specific early sign.\n\nSITC 2020: baseline ICE (or CAPD) before infusion; ICE twice daily in the first week after axicabtagene ciloleucel. Work-up with CRP, blood count, metabolic panel, fibrinogen and PT/INR, and consider head CT, EEG and MRI, without delaying treatment. Steroids for grade 3 or 4 (LE: 4) and for grade 2 after CD28-costimulated products such as axicabtagene ciloleucel and brexucabtagene autoleucel (LE: 3); consider them for grade 2 after 4-1BB products such as tisagenlecleucel. Give at least 2 doses and taper fast on improvement (LE: 3). With low-grade CRS and ICANS together, treat the ICANS first with steroids, since tocilizumab may worsen neurotoxicity (LE: 5). Levetiracetam for seizures (LE: 4); prophylaxis only for high-risk patients (LE: 4), and EBMT/JACIE 2019 does not recommend it routinely. Suspected cerebral oedema goes to intensive care at once. Dexamethasone 0.5 mg/kg, at most 10 mg a dose, and methylprednisolone 2 mg/kg/day are the commonly used steroids (SITC).","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t","acute-oncology"],"related":["crs-grading-and-management"],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["dexamethasone","tocilizumab","axicabtagene-ciloleucel","tisagenlecleucel","lisocabtagene-maraleucel","brexucabtagene-autoleucel","idecabtagene-vicleucel","ciltacabtagene-autoleucel","obecabtagene-autoleucel"],"companies":[],"institutions":["sitc"],"pathways":[],"terms":["icans","lymphoma-tx-crs-icans"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"CAR T-cell therapy can sometimes cause confusion or trouble speaking. Nurses do a quick word and writing test every day to catch it early. Steroids usually help. Tell the team at once if the person seems muddled.","domain":"cell-therapy-toxicity","setting":{"who":["nurse","doctor","patient-or-carer","multidisciplinary-team"],"where":["ward","intensive-care","outpatient-clinic","home"]},"population":"Adults and children treated with CAR T-cell therapy or another immune effector cell therapy (ASTCT applies the definition to any therapy that engages T cells, including bispecific antibodies). Children under 12 are graded with the CAPD rather than the ICE score.","trigger":"Any change in speech, writing, attention, alertness or behaviour, a tremor, a seizure or a falling ICE score after immune effector cell infusion.","steps":[{"action":"Record a baseline ICE score (CAPD in children under 12) before infusion","why":"The score is only meaningful against the person's own starting point.","source":"sitc-iec-2020","quote":"All patients should receive baseline neurological evaluations, including ICE scores (for adults) or CAPD scores (for children<12 years) prior to CAR T cell therapy","grade":"LE: 4"},{"action":"Score ICE regularly after infusion, at least twice daily in the first week after axicabtagene ciloleucel","why":"Neurotoxicity can start subtly and worsen within hours; frequent checks catch it early.","source":"sitc-iec-2020","quote":"Patients treated with axicabtagene ciloleucel should be assessed for ICANS twice daily during the first week after infusion.","grade":"LE: 3"},{"action":"Grade ICANS with the ASTCT scale, using the ICE score and the worst of consciousness, seizures, motor findings and signs of raised pressure","why":"The grade decides treatment, and the ICE score alone can miss seizures or brain swelling.","source":"astct-2019","quote":"Score 10: No impairment Score 7–9: Grade 1 ICANS Score 3–6: Grade 2 ICANS Score 0–2: Grade 3 ICANS Score 0 due to patient unarousable and unable to perform ICE assessment: Grade 4 ICANS"},{"action":"In children under 12, use the Cornell Assessment of Pediatric Delirium; a score of 9 or more counts as grade 3","why":"Young children cannot do the ICE tasks.","source":"astct-2019","quote":"A CAPD score of ≥9 is suggestive of delirium and should be considered as grade 3 ICANS."},{"action":"Watch especially for word-finding difficulty; do not treat headache alone as ICANS","why":"Expressive aphasia is the most specific early sign, while headache is common for other reasons.","source":"astct-2019","quote":"Thus, headache alone is not a useful marker of ICANS. Expressive aphasia, on the other hand, appears to be a very specific symptom of ICANS."},{"action":"Work up with CRP, full blood count, metabolic panel, fibrinogen and PT/INR, consider a head CT, and consider EEG and brain MRI","why":"These look for bleeding, seizures, swelling and other causes of confusion.","source":"sitc-iec-2020","quote":"For patients who develop ICANS, the work-up should include CRP, CBC, CMP, fibrinogen, prothrombin time test, and international normalized ratio (PT/INR). A head CT should also be considered.","grade":"LE: 4"},{"action":"Do not delay treatment while waiting for imaging","why":"Mental status changes define ICANS; scans may be normal early on.","source":"sitc-iec-2020","quote":"Brain CT or MRI may be used to evaluate cerebral edema in cases of grade 3 ICANS in adults, but the initiation of ICANS management should not be delayed for confirmation of neurological symptoms with imaging findings","grade":"LE: 4"},{"action":"Give corticosteroids for grade 3 or 4 ICANS, and for grade 2 after CD28-costimulated products; consider them for grade 2 after 4-1BB products","why":"Steroids shorten and soften neurotoxicity; products with CD28 domains cause more of it.","source":"sitc-iec-2020","quote":"Steroids are recommended for grade 3 or grade 4 ICANS","grade":"LE: 4 (grade 3 to 4); LE: 3 (grade 2 after CD28 products)"},{"action":"When ICANS occurs with low-grade CRS, treat the ICANS first with steroids rather than tocilizumab","why":"Tocilizumab does not cross into the brain well and may make neurotoxicity worse.","source":"sitc-iec-2020","quote":"Because of the possibility that tocilizumab may worsen neurotoxicity, the management of neurotoxicity may take precedence over the management of low-grade CRS","grade":"LE: 5"},{"action":"Give at least two doses of steroid, then taper quickly once there is improvement","why":"A short course limits the effect of steroids on the CAR T cells.","source":"sitc-iec-2020","quote":"If steroids are used in the management of ICANS, at least 2 doses should be given and a fast taper should be used once there is improvement","grade":"LE: 3"},{"action":"Treat seizures with levetiracetam; give it as prophylaxis only to patients at high risk of neurotoxicity","why":"There is not enough evidence to give anti-seizure medicine to everyone.","source":"sitc-iec-2020","quote":"To manage seizures in patients treated with CAR T cell therapies, levetiracetam is recommended","grade":"LE: 4"},{"action":"If cerebral oedema is suspected, move the patient to intensive care immediately for imaging and treatment of raised intracranial pressure","why":"Brain swelling after CAR T cells is rare but can be fatal within hours.","source":"sitc-iec-2020","quote":"If cerebral edema is suspected based on clinical signs and symptoms, patients should be immediately referred to intensive care where rapid imaging and management of intracranial hypertension should be performed","grade":"LE: 4"},{"action":"Advise patients not to drive until any neurological symptoms have resolved and for the period their product label or centre sets (8 weeks in EBMT/JACIE 2019, two weeks on US labels since 2025)","why":"Neurotoxicity can come and go after discharge.","source":"ebmt-2019","quote":"Patients are advised not to drive for 8 weeks after the infusion and only after resolution of any neurological symptoms."}],"bestInClass":{"statement":"Grade with the ASTCT 2019 ICE score and multi-domain scale in adults and the CAPD in children under 12; ASTCT updated its grading in 2026 and the changes could not be read. For treatment, SITC 2020 is the most detailed graded guideline read: steroids for grade 3 to 4 (LE: 4) and for grade 2 after CD28-costimulated products (LE: 3), steroids before tocilizumab when ICANS accompanies low-grade CRS (LE: 5), at least two doses with a fast taper (LE: 3), levetiracetam for seizures (LE: 4) and intensive care for suspected cerebral oedema (LE: 4). ASCO 2021 (abstract) agrees that moderate to severe ICANS is managed with corticosteroids and supportive care. On seizure prophylaxis the sources differ: SITC allows levetiracetam prophylaxis for high-risk patients, EBMT/JACIE 2019 does not recommend it routinely except with a history of seizures or CNS disease.","sources":["astct-2019","astct-2026","sitc-iec-2020","asco-cart-2021","ebmt-2019"]},"variants":[{"name":"No routine seizure prophylaxis (EBMT/JACIE 2019)","differs":"Does not recommend anti-epileptic prophylaxis such as levetiracetam routinely, except for patients with a history of seizures or central nervous system disease.","evidence":"Expert best practice recommendation, not graded.","sources":["ebmt-2019"]},{"name":"Prophylactic levetiracetam for high-risk patients (SITC 2020)","differs":"Finds the evidence insufficient for everyone but allows prophylactic levetiracetam for patients judged high risk from their history, disease or product.","evidence":"LE: 4.","sources":["sitc-iec-2020"]},{"name":"Two weeks near a healthcare facility and no driving for two weeks (US labels since June 2025)","differs":"For BCMA- and CD19-directed autologous CAR T-cell products, the FDA ended the risk-management programme in June 2025 and revised the US labels to monitor for at least two weeks (daily for at least one), to stay near a healthcare facility for at least two weeks and to avoid driving for two weeks, against 4 weeks near the centre and 8 weeks without driving in EBMT/JACIE 2019.","evidence":"Regulatory decision based on the stability of adverse event reports and clinical experience; not a trial comparison.","sources":["fda-rems-2025","ebmt-2019"]}],"grades":[{"claim":"Baseline ICE or CAPD before CAR T-cell therapy","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"ICANS assessment twice daily in the first week after axicabtagene ciloleucel","grade":"LE: 3","source":"sitc-iec-2020"},{"claim":"Steroids for grade 2 ICANS after CD28-costimulated products","grade":"LE: 3","source":"sitc-iec-2020","quote":"For patients with grade 2 ICANS after being treated with CD28 costimulated CAR T cell products such as axicabtagene ciloleucel and brexucabtagen autoleucel, steroids should be used to mitigate the duration and severity of ICANS"},{"claim":"Steroids for grade 3 or 4 ICANS","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Neurotoxicity takes precedence over low-grade CRS","grade":"LE: 5","source":"sitc-iec-2020"},{"claim":"Prophylactic levetiracetam may be considered in high-risk patients","grade":"LE: 4","source":"sitc-iec-2020","quote":"However, in patients deemed to be at high-risk of developing neurotoxicity based on history, disease characteristics, or the product being administered, prophylactic levetiracetam may be considered"},{"claim":"Moderate to severe ICANS managed with corticosteroids and supportive care","grade":"expert consensus","source":"asco-cart-2021","quote":"On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell-associated neurotoxicity syndrome should be managed with corticosteroids and supportive care."}],"sources":[{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"astct-2019","label":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","publisher":"American Society for Transplantation and Cellular Therapy, Biology of Blood and Marrow Transplantation","year":2019,"url":"https://europepmc.org/article/PMC/PMC12180426","doi":"10.1016/j.bbmt.2018.12.758","gradingScheme":"A consensus grading system (grades 1 to 4), not a set of graded recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"astct-2026","label":"ASTCT Consensus Grading for Toxicities after Immune Effector Cell Therapy","publisher":"American Society for Transplantation and Cellular Therapy, Transplantation and Cellular Therapy","year":2026,"url":"https://europepmc.org/abstract/MED/42711241","doi":"10.1016/j.jtct.2026.05.020","gradingScheme":"Consensus definitions and grading criteria; the abstract gives no grades.","read":"abstract","accessed":"2026-11-11"},{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-eha-2022","label":"Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)","publisher":"EBMT, JACIE and EHA, Annals of Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/34923107","doi":"10.1016/j.annonc.2021.12.003","read":"abstract","accessed":"2026-11-11"},{"key":"asco-cart-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724386","doi":"10.1200/JCO.21.01992","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus.","read":"abstract","accessed":"2026-11-11"},{"key":"fda-rems-2025","label":"FDA Eliminates Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies (FDA Safety Communication, 26 June 2025)","publisher":"US Food and Drug Administration","year":2025,"url":"https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-eliminates-risk-evaluation-and-mitigation-strategies-rems-autologous-chimeric-antigen-receptor","gradingScheme":"A regulatory safety communication; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ASTCT 2026 update of the consensus grading for CRS, ICANS and IEC-HS was read only as its abstract, which says the panel considered updating the 2019 criteria but does not say what changed. The 2019 grading is used here; check the 2026 paper before relying on a grade boundary.","The EBMT/JACIE/EHA 2022 recommendations (the current European edition) and the ASCO 2021 CAR T-cell guideline were read only as abstracts; the 2019 EBMT/JACIE edition was read in full and is cited where the steps rest on EBMT.","Anakinra for steroid-refractory ICANS is discussed in the literature but SITC names it as a third-line agent for CRS, not ICANS; no guideline read here grades it for ICANS.","European product information (SmPC) driving and proximity advice was not read for this page; the US position is from the FDA communication, not from the labels themselves.","No randomised trial read here tests steroid dose or timing for ICANS."]},{"id":"iec-hs-management","kind":"protocol","name":"IEC-HS after CAR T-cell therapy: recognition and stepwise treatment","aka":["IEC-HS","immune effector cell-associated HLH-like syndrome","carHLH","HLH/MAS after CAR T","macrophage activation syndrome after CAR T","MAS-L"],"tldr":"Rarely after CAR T-cell therapy the immune system stays switched on after cytokine release syndrome has settled, and starts damaging the blood, liver and clotting (IEC-HS). It shows as very high ferritin, falling blood counts, low clotting proteins and liver test changes. It is treated with anakinra and steroids, adding other drugs if it worsens, while infection and relapse are ruled out.","summary":"ASTCT 2023 named and defined IEC-HS: a hyperinflammatory syndrome with features of macrophage activation or HLH, attributable to immune effector cell therapy, with new or worsening cytopenias, hyperferritinaemia, coagulopathy with hypofibrinogenaemia and/or transaminitis. It usually follows CRS and appears as CRS resolves; it is a diagnosis of exclusion, and a substantially raised (more than twice the upper limit or baseline) or rapidly rising ferritin is a prerequisite. Fever is deliberately not a criterion, to keep it distinct from CRS. Grading (Table 2) follows CTCAE 'immune system disorder, other', grade 1 to 5.\n\nTreatment (expert opinion, Figure 3 and Table 3): start before life-threatening complications with anakinra (adults 100 to 200 mg subcutaneous or intravenous every 6 to 12 hours) with or without corticosteroids (adults dexamethasone 10 to 40 mg daily), allowing about 48 hours to judge effect before adding agents; ruxolitinib second line, dose-reduced with azoles or renal impairment; for refractory life-threatening disease, etoposide 50 to 100 mg/m2 once (not HLH-94 induction doses), or emapalumab where IFN-gamma is high (debated). Tocilizumab is discouraged for IEC-HS without CRS. Supportive: daily blood count, PT/PTT and fibrinogen, daily renal and liver tests, fibrinogen replacement, transfusion, cautious G-CSF, infectious disease input and prophylaxis matched to the immunosuppression. SITC 2020 (LE: 4): cryoprecipitate for delayed hypofibrinogenaemia, anakinra and steroids for late tocilizumab-refractory HLH/MAS-like toxicity, etoposide only as a last resort.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t","acute-oncology"],"related":["crs-grading-and-management","icans-grading-and-management","car-t-infection-prevention"],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["dexamethasone","methylprednisolone","ruxolitinib","etoposide","emapalumab"],"companies":[],"institutions":["sitc"],"pathways":[],"terms":["crs","cytopenias"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After CAR T-cell therapy a rare, serious inflammation can follow the early fever. It is found on blood tests and treated in hospital with medicines that calm the immune system.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","nurse","pharmacist","multidisciplinary-team"],"where":["ward","intensive-care"]},"population":"Adults and children after CAR T-cell therapy (CD19, CD22 or BCMA directed), usually as cytokine release syndrome is resolving. The ASTCT panel notes similar toxicity after bispecific T-cell engagers, but its framework was built on CAR T-cell experience. Paediatric starting doses differ (ASTCT Table 3).","trigger":"Rising ferritin with new or worsening cytopenias, falling fibrinogen or rising liver enzymes after CAR T-cell infusion, typically as CRS settles.","steps":[{"action":"Suspect IEC-HS when, after CAR T-cell therapy, ferritin rises with new or worsening cytopenias, low fibrinogen or raised liver enzymes","why":"This is a different illness from the early fever and needs different treatment.","source":"astct-iechs-2023","quote":"We ultimately define IEC-HS as the development of a pathological and biochemical hyperinflammatory syndrome that 1) manifests with features of macrophage activation/HLH, 2) is attributable to IEC therapy, and 3) is associated with progression or new onset of cytopenias, hyperferritinemia, coagulopathy with hypofibrinogenemia and/or transaminitis."},{"action":"Distinguish it from severe or returning CRS, which is managed differently","why":"IEC-HS usually starts as the first inflammation is settling; calling severe CRS by this name would change treatment wrongly.","source":"astct-iechs-2023","quote":"Hence, it is imperative to distinguish suspected IEC-HS from CRS recurrence or a prolonged severe CRS, to pursue treatment options and monitoring accordingly."},{"action":"Require a substantially raised or rapidly rising ferritin; with a normal ferritin, look for another cause","why":"A normal ferritin makes this syndrome very unlikely.","source":"astct-iechs-2023","quote":"Nonetheless, given the high negative predictive value of a normal ferritin, substantial elevations in ferritin are a prerequisite to a diagnosis of IEC-HS and normal ferritin values with ongoing inflammation should prompt considerations of alternative etiologies."},{"action":"Rule out infection and progressing cancer quickly: blood, urine and sputum cultures, viral and fungal testing, and marrow or PET-CT as needed","why":"Infection and relapse can look the same and need quite different treatment.","source":"astct-iechs-2023","quote":"Expediency should be given to excluding the most common and dangerous concurrent diagnoses, including infection and/or progressive malignancy."},{"action":"Check the full blood count, clotting times and fibrinogen every day, and kidney and liver function often","why":"Patients can deteriorate quickly, and bleeding risk rises as fibrinogen falls.","source":"astct-iechs-2023","quote":"Daily monitoring of complete blood cell count with differential, coagulation parameters (PT/PTT) and fibrinogen are recommended for patients with IEC-HS."},{"action":"Replace fibrinogen (cryoprecipitate) when it falls","why":"Low fibrinogen out of proportion to other clotting tests is a hallmark and causes delayed, severe bleeding.","source":"sitc-iec-2020","quote":"Delayed coagulopathy may possibly be one hallmark of delayed onset HLH/MAS-like toxicity, typically hypofibrinogenemia disproportionately worse than changes in PT/PTT, which requires close follow-up and replacement with cryoprecipitate","grade":"LE: 4"},{"action":"Start anakinra, with or without corticosteroids, before life-threatening complications, and allow about 48 hours to judge the effect before adding another drug","why":"Early treatment may stop it progressing; piling on drugs too fast adds infection risk.","source":"astct-iechs-2023","quote":"Therapy should generally be initiated with corticosteroids +/− anakinra prior to development of life-threatening complications and, if possible, a time interval to evaluate for efficacy (e.g., 48 hours) should elapse before additional agents are added to avoid cumulative toxicity of multiple immunosuppressive agents."},{"action":"Do not give tocilizumab for IEC-HS without CRS features","why":"There is no evidence it works in HLH-like illness, and most patients have already had it for CRS.","source":"astct-iechs-2023","quote":"Additionally, despite established efficacy in CRS, use of tocilizumab or other IL-6 blocking agents (e.g., siltuximab) for IEC-HS, without CRS manifestations, was specifically discouraged due to lack of evidence for efficacy in any HLH-related context, and since most patients will have already received tocilizumab prior to the onset of IEC-HS."},{"action":"If it worsens despite anakinra and steroids, add ruxolitinib, reducing the dose with kidney impairment or azole antifungals","why":"Ruxolitinib blocks several inflammatory signals at once; its levels rise with poor kidney function and some antifungals.","source":"astct-iechs-2023","quote":"As ruxolitinib levels increase with renal dysfunction and with concurrent CYP3A4 inhibitors, including antifungal agents (i.e., azoles), appropriate dose reductions must be made."},{"action":"Keep etoposide as a last resort for late, tocilizumab-refractory disease","why":"Etoposide kills activated T cells, including the CAR T cells, so it is kept for when the patient's life takes priority.","source":"sitc-iec-2020","quote":"Etoposide should only be administered to patients experiencing late-onset, tocilizumab-refractory HLH/MAS-like symptoms after CAR T cell therapy as a last resort","grade":"LE: 4"},{"action":"Involve infectious disease specialists and match antimicrobial prophylaxis to the immunosuppression given","why":"Each added immunosuppressant raises the risk of fungal, viral and Pneumocystis infection.","source":"astct-iechs-2023","quote":"As the risk of infection in patients with IEC-HS incrementally increases with additive use of immunosuppression, infectious disease consultation is strongly encouraged—particularly with clinical deterioration."},{"action":"Once the clinical picture and blood tests have stabilised, taper treatment gradually while watching for a flare","why":"Long immunosuppression causes infections, but stopping too fast can let the syndrome return.","source":"astct-iechs-2023","quote":"Nonetheless, given the deleterious impact of immunosuppression, including risk of infection—when clinical and laboratory parameters have stabilized, gradually tapering therapy is encouraged while monitoring for recrudescence of symptoms."}],"bestInClass":{"statement":"The ASTCT 2023 consensus is the only document that defines, grades and sets out treatment for IEC-HS as a named syndrome, and is the best available source; its treatment advice is expert opinion, stated by the panel as not evidence-based. SITC 2020, written before the term existed, agrees on the shape: cryoprecipitate for disproportionate hypofibrinogenaemia, anakinra and steroids for late tocilizumab-refractory HLH/MAS-like toxicity, and etoposide only as a last resort (all LE: 4). The two differ in emphasis on etoposide: SITC limits it to a last resort; ASTCT also places it after first- and second-line therapy but gives a moderate single dose (50 to 100 mg/m2, possibly weekly) and advises against HLH-94 induction dosing. EBMT/JACIE 2019 says only that delayed macrophage activation syndrome is managed with standard approaches. The ASTCT 2026 update to the consensus grading, which includes IEC-HS, was read only as its abstract.","sources":["astct-iechs-2023","sitc-iec-2020","ebmt-2019","astct-2026"]},"variants":[{"name":"Emapalumab where interferon-gamma is high (ASTCT 2023)","differs":"Considers the anti-interferon-gamma antibody emapalumab for life-threatening IEC-HS, especially with documented IFN-gamma elevation, at the package-insert dose.","evidence":"Evidence is from a small paediatric primary HLH cohort; the panel calls adult use extrapolative and notes cost and urgent procurement may be prohibitive. No consensus was reached.","sources":["astct-iechs-2023"]},{"name":"Switching off the CAR T cells with a safety switch (ASTCT 2023)","differs":"For constructs carrying a targetable safety switch (for example truncated EGFR, targeted by cetuximab), turning the CAR T cells off is considered before etoposide in rapidly progressive disease.","evidence":"Expert opinion; applies only to constructs that carry such a switch, which commercial products in the sources do not describe.","sources":["astct-iechs-2023"]},{"name":"Anakinra and steroids as third-line CRS agents (SITC 2020)","differs":"Frames late HLH/MAS-like toxicity within the CRS algorithm, considering third-line CRS agents such as anakinra and steroids, rather than as a separate syndrome with its own grading.","evidence":"LE: 4.","sources":["sitc-iec-2020"]},{"name":"Standard approaches for delayed macrophage activation syndrome (EBMT/JACIE 2019)","differs":"States that delayed macrophage activation syndrome and CRS are managed with standard approaches, without a specific algorithm.","evidence":"Ungraded best practice recommendation.","sources":["ebmt-2019"]}],"grades":[{"claim":"Treatment recommendations for IEC-HS","grade":"expert opinion, not evidence-based","source":"astct-iechs-2023","quote":"Due to lack of prospective clinical trials for IEC-HS and limited literature on treatment approaches for HLH-like manifestations following CAR T cells—the following treatment recommendations are derived from expert opinion, rely on available evidence from CRS/IEC-HS cohorts and previous evidence with treatment of pHLH and sHLH, and warrant prospective studies."},{"claim":"Cryoprecipitate for delayed hypofibrinogenaemia","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Anakinra and steroids for late, tocilizumab-refractory HLH/MAS-like pathology","grade":"LE: 4","source":"sitc-iec-2020","quote":"For treatment of late-onset, HLH/MAS-like pathology, which may be tocilzumab-refractory, third-line CRS agents such as anakinra and steroids may be considered (LE: 4)."},{"claim":"Etoposide only as a last resort","grade":"LE: 4","source":"sitc-iec-2020"}],"sources":[{"key":"astct-iechs-2023","label":"Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (ASTCT consensus, Hines et al.)","publisher":"American Society for Transplantation and Cellular Therapy, Transplantation and Cellular Therapy","year":2023,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10330221/","doi":"10.1016/j.jtct.2023.03.006","gradingScheme":"Expert consensus of a 30-member ASTCT panel; treatment recommendations are stated to be derived from expert opinion and not evidence-based. Grading of IEC-HS severity follows CTCAE 'immune system disorder, other' (grades 1 to 5).","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"astct-2026","label":"ASTCT Consensus Grading for Toxicities after Immune Effector Cell Therapy","publisher":"American Society for Transplantation and Cellular Therapy, Transplantation and Cellular Therapy","year":2026,"url":"https://europepmc.org/abstract/MED/42711241","doi":"10.1016/j.jtct.2026.05.020","gradingScheme":"Consensus definitions and grading criteria; the abstract gives no grades.","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ASTCT 2026 updated consensus grading, which reconsidered the IEC-HS criteria, was read only as its abstract; whether the definition or grade boundaries above changed is not known here.","No prospective trial of any IEC-HS treatment exists in the sources read; every treatment step is expert opinion or LE: 4.","The ASTCT panel reached no consensus on etoposide, emapalumab or other salvage agents, and on how fast to taper; the role of pre-emptive treatment is unknown.","The ASTCT diagnostic table (Table 1) and Figure 3 drawing were read as text and legend only; the figure image itself was not read.","Whether the same framework applies after bispecific T-cell engagers is named as future research by the ASTCT panel."]},{"id":"image-guided-core-biopsy-preparation-and-aftercare","kind":"protocol","name":"Image-guided core needle biopsy of the breast and liver: preparation and aftercare","aka":["core biopsy","core needle biopsy","needle biopsy","ultrasound-guided biopsy","breast biopsy","liver biopsy","percutaneous liver biopsy","vacuum-assisted biopsy","biopsy aftercare","biopsy marker clip"],"tldr":"A core biopsy uses a hollow needle, guided by ultrasound or a scan, to take thin strips of tissue so a pathologist can say what an abnormality is. Breast biopsies are done under local anaesthetic in clinic, sometimes leaving a tiny marker. Liver biopsies need a plan for blood thinners and a few hours of observation; call the hospital for fever, breathlessness, heavy bleeding or bad pain.","summary":"Breast. The NHS Breast Screening Programme assesses significant abnormalities by core or vacuum-assisted biopsy, with ultrasound as the guidance of choice, a permanent image of the needle in the lesion, a marker clip where the lesion may be hard to find again or there are several, and review of every needle biopsy at the multidisciplinary meeting. Fine needle aspiration may be added to, not substituted for, core biopsy. Every woman with a non-operative diagnosis of invasive cancer has axillary ultrasound, with core biopsy of the most suspicious abnormal node preferred to fine needle aspiration where safe (NHSBSP 2026). B3 lesions of uncertain malignant potential are managed by the MDT, usually by vacuum-assisted excision.\n\nLiver (BSG, RCR and RCPath 2020, GRADE). Give risk information in advance, verbally and in writing, in the form \"of 1000 people like you\" (Strong, high quality). Use image guidance for focal lesions (Strong). Bleeding occurs in up to 10%, major bleeding in under 2%, and death in fewer than 1 in 1000. Anticoagulants and antiplatelets are stopped by table 2: warfarin 5 days with an INR check, direct oral anticoagulants 2 days (longer for dabigatran with impaired kidney function), clopidogrel, prasugrel or ticagrelor 7 days, and aspirin 3 to 7 days for elective biopsies, considered against why it is taken (Moderate). An INR of 1.5 to 2.0 is not a contraindication to a targeted biopsy in stable liver disease, fresh frozen plasma is not used to correct an INR of 2.0 or less (Strong), and a platelet count below 50 x 10^9/L calls for a transvenous route where possible (Strong). Observe for at least 3 hours with pulse and blood pressure (Strong, weak evidence). People with a strong suspicion of malignancy are not biopsied as a day case, because they may bleed more. At discharge: rest the remainder of the day, no driving that day, no strenuous activity for 48 hours, and call the hospital for chills, fever, breathlessness, bright red bleeding, severe chest, shoulder or abdominal pain, blood in the stool or a swelling abdomen.","asOf":"2026-11-11","links":[],"tags":[],"related":["anticoagulants-and-antiplatelets-before-endoscopy"],"cancers":["breast-cancer","hcc"],"sections":[],"technologies":["vacuum-assisted-breast-biopsy","ultrasound","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["core-needle-biopsy","biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A needle takes a small piece of tissue to find out what a lump or patch is. A scan guides the needle. You will have a numbing injection. Tell the team if you take blood thinners. After a liver biopsy you stay a few hours to be checked. Call the hospital if you get a fever, bad pain, bleeding or trouble breathing.","domain":"screening-diagnostics","setting":{"who":["doctor","nurse","radiographer","patient-or-carer"],"where":["outpatient-clinic","ward","home"]},"population":"Adults having an ultrasound- or CT-guided percutaneous core needle biopsy of a breast or axillary abnormality (including in breast screening assessment) or of a focal liver lesion. Non-lesional liver biopsy for liver disease, transjugular biopsy and children are outside scope except where the liver guideline's thresholds send someone to a transvenous route. Lung biopsy is not covered (see gaps).","trigger":"Imaging shows an abnormality that needs a tissue diagnosis, and a core biopsy is planned.","steps":[{"action":"Give information about the risks and benefits in advance, spoken and written, in a language the person understands","why":"People decide better, and worry less, when they have read about the procedure before the day.","source":"bsg-liver-2020","quote":"Patients should be given information about the risks and benefits of the procedure, in advance of the procedure where possible","grade":"Strength of recommendation STRONG; quality of evidence HIGH"},{"action":"Describe risks as numbers out of 1000 people like the patient","why":"A number out of a thousand is easier to picture than a percentage or a word like rare.","source":"bsg-liver-2020","quote":"Information on risks should be readily understood and the following is recommended ‘of 1000 people like you having a liver biopsy, X will develop (complication)’","grade":"Strength of recommendation MODERATE; evidence WEAK"},{"action":"Before a liver biopsy, plan each blood thinner by the guideline's table: warfarin stopped 5 days before with an INR check, a direct oral anticoagulant 2 days before (longer for dabigatran with weak kidneys)","why":"Blood thinners raise the chance of bleeding inside the liver, but stopping them has its own risks, so each is timed.","source":"bsg-liver-2020","quote":"Direct oral anticoagulant drugs should be stopped for 2 days prior to the day of the biopsy or longer if taking dabigatran, depending on the renal function.","grade":"Strength of recommendation STRONG; evidence WEAK (table 2)"},{"action":"Where time allows, consider stopping aspirin 3 days before a percutaneous liver biopsy, weighing why it is taken and how urgent the biopsy is","why":"Aspirin adds a little to bleeding risk; for someone with a heart stent stopping it can be more dangerous, so a senior decision is needed.","source":"bsg-liver-2020","quote":"We recommend that, where time allows, stopping aspirin 3 days prior to percutaneous biopsy should be considered, but the decision will depend on the indications for aspirin and the urgency of the biopsy","grade":"Strength of recommendation MODERATE; evidence WEAK"},{"action":"Do not give fresh frozen plasma to correct an INR of 2.0 or less; if the platelet count is below 50, use a transvenous route where possible","why":"Plasma has not been shown to reduce bleeding, and when platelets are very low a route through a vein in the neck avoids puncturing the liver surface.","source":"bsg-liver-2020","quote":"Where the platelet count is <50 x 10 9 /L, a transvenous approach is recommended, where possible","grade":"Strength of recommendation STRONG; evidence MODERATE"},{"action":"Use image guidance (ultrasound or CT) to target a focal liver lesion","why":"Seeing the needle reach the abnormality makes the sample more useful and avoids blood vessels.","source":"bsg-liver-2020","quote":"Image-guided liver biopsies should be used for targeting focal lesions or in patients with altered liver anatomy (such as split liver graft or prior liver resection)","grade":"Strength of recommendation STRONG; quality of evidence WEAK"},{"action":"For a breast abnormality, take core or vacuum-assisted biopsies under ultrasound guidance where possible and keep an image of the needle in the lesion","why":"A core of tissue tells the team whether a lump is cancer, what type, and how fast-growing; the image proves the right spot was sampled.","source":"nhsbsp-assessment-2026","quote":"Ultrasound is the technique of choice for guided needle sampling. A permanent record of images showing the biopsy needle in the target lesion should be made.","grade":"NHSBSP guidance (ungraded)"},{"action":"Place a marker clip when the area may be hard to find again, when there are several lesions, or when the biopsy might remove the abnormality","why":"The tiny metal marker lets the surgeon or radiologist find exactly the same spot later.","source":"nhsbsp-assessment-2026","quote":"Marker placing is particularly important to facilitate treatment planning/surgical localisation when there are multiple lesions or when there is any risk that the area of concern could be removed or rendered difficult to see by the biopsy.","grade":"NHSBSP guidance (ungraded)"},{"action":"If invasive breast cancer is diagnosed on a needle biopsy, scan the armpit on the same side and biopsy the most suspicious abnormal node","why":"Knowing whether the lymph nodes are involved changes the operation and treatment plan.","source":"nhsbsp-assessment-2026","quote":"All patients with a non-operative diagnosis of invasive breast cancer should have ipsilateral axillary ultrasound performed, preferably at the time of initial assessment.","grade":"NHSBSP guidance (ungraded)"},{"action":"Review every needle biopsy result at the multidisciplinary meeting before deciding what happens next","why":"The radiologist, pathologist and surgeon check together that the result matches the scan before anyone acts on it.","source":"nhsbsp-assessment-2026","quote":"All needle biopsies carried out as part of screening assessment must be reviewed at the multi-disciplinary meeting (MDM), where further management of each case should be agreed and documented.","grade":"NHSBSP guidance (ungraded)"},{"action":"After a liver biopsy, observe for at least 3 hours with regular pulse and blood pressure","why":"Bleeding after a liver biopsy usually shows itself in the first few hours, while the person is still in hospital.","source":"bsg-liver-2020","quote":"Patients should be monitored for at least 3 hours after liver biopsy with regular clinical observations and measurement of blood pressure and pulse","grade":"Strength of recommendation STRONG; evidence WEAK"},{"action":"Do not do a liver biopsy as a day case when cancer is strongly suspected","why":"Liver tumours can bleed more after a needle biopsy, so an overnight stay may be safer.","source":"bsg-liver-2020","quote":"Patients with a strong suspicion of malignancy should not be biopsied as a day case because such patients may have a higher risk of haemorrhage than patients without cancer.","grade":"Text statement (no separate grade)"},{"action":"At discharge, advise rest for the rest of the day, no driving that day, no strenuous activity for 48 hours, and give a number to call for fever, breathlessness, bleeding or severe pain","why":"These are the signs of the uncommon complications, bleeding, a leak or infection, that need treatment quickly.","source":"bsg-liver-2020","quote":"If a patient experiences any symptoms such as chills, high fever, difficulty breathing, excessive bright red bleeding from the biopsy site, severe chest, shoulder or abdominal pain, passing blood in the stool or increasing abdominal swelling, then they are instructed to call the hospital.","grade":"Text statement (no separate grade)"}],"bestInClass":{"statement":"For liver core biopsy, the BSG, RCR and RCPath 2020 guideline is the most complete graded standard: advance written risk information in numbers out of 1000 (Strong), image guidance for focal lesions (Strong), a drug-by-drug plan for anticoagulants and antiplatelets (Strong, weak evidence), no fresh frozen plasma for an INR of 2.0 or less (Strong), a transvenous route when platelets are below 50 x 10^9/L (Strong), at least 3 hours of observation (Strong, weak evidence), no day-case biopsy when cancer is strongly suspected, and clear discharge advice. For breast core biopsy, the NHS Breast Screening Programme assessment guidance (updated January 2026) sets the standard in England: ultrasound-guided core or vacuum-assisted biopsy, a marker clip where needed, axillary ultrasound in invasive cancer and multidisciplinary review of every result. It does not address blood thinners or aftercare, which are left to local policy.","sources":["bsg-liver-2020","nhsbsp-assessment-2026"]},"variants":[{"name":"Fine needle aspiration cytology instead of core biopsy (breast)","differs":"A thinner needle draws out cells rather than a strip of tissue.","evidence":"NHSBSP allows it in addition to core biopsy where high quality cytology with immediate reporting is available, and alone only in exceptional cases where core biopsy is not possible, because core biopsy gives invasive status, subtype, grade and receptor status.","sources":["nhsbsp-assessment-2026"]},{"name":"Shorter observation after liver biopsy","differs":"Some units observe for 1 hour rather than 3.","evidence":"BSG notes one recent study suggesting 1 hour is enough to recognise all major complications, but recommends at least 3 hours for low-risk patients and up to 8 hours otherwise.","sources":["bsg-liver-2020"]},{"name":"Continuing aspirin for urgent liver biopsy","differs":"Aspirin is continued rather than paused.","evidence":"BSG table 2: for urgent biopsies aspirin can be continued at the clinician's discretion; empirical experience in post-transplant biopsies suggests pausing may not be necessary.","sources":["bsg-liver-2020"]}],"grades":[{"claim":"Advance risk information, verbal and written","grade":"Strength of recommendation STRONG; quality of evidence HIGH","source":"bsg-liver-2020"},{"claim":"Image guidance for focal liver lesions","grade":"Strength of recommendation STRONG; quality of evidence WEAK","source":"bsg-liver-2020"},{"claim":"No fresh frozen plasma to correct an INR of 2.0 or less","grade":"Strength of recommendation STRONG; evidence MODERATE","source":"bsg-liver-2020","quote":"We recommend FFP should not be used to correct an INR ≤2.0 prior to liver biopsy"},{"claim":"Consider stopping aspirin 3 days before percutaneous biopsy where time allows","grade":"Strength of recommendation MODERATE; evidence WEAK","source":"bsg-liver-2020"},{"claim":"Monitor at least 3 hours after liver biopsy","grade":"Strength of recommendation STRONG; evidence WEAK","source":"bsg-liver-2020"},{"claim":"Day-case liver biopsy is safe when there are no increased risk factors and the person can get help after leaving","grade":"Strength of recommendation STRONG; evidence WEAK","source":"bsg-liver-2020","quote":"Liver biopsy may be safely done as a day case procedure if there are no increased risk factors and the patient can be looked after when they have left hospital, can seek appropriate advice and access appropriate medical help if needed"},{"claim":"Risk of bleeding and death after percutaneous liver biopsy","grade":"Summary statement (ungraded)","source":"bsg-liver-2020","quote":"Bleeding occurs in up to 10% with major bleeding occurring in less than 2%."}],"sources":[{"key":"bsg-liver-2020","label":"Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology","publisher":"British Society of Gastroenterology, Royal College of Radiologists and Royal College of Pathologists (Neuberger et al., Gut)","year":2020,"url":"https://doi.org/10.1136/gutjnl-2020-321299","doi":"10.1136/gutjnl-2020-321299","gradingScheme":"GRADE: each recommendation printed with a strength (STRONG, MODERATE, LOW) and a quality of evidence (HIGH, MODERATE, WEAK).","read":"full-text","accessed":"2026-11-11"},{"key":"nhsbsp-assessment-2026","label":"Clinical guidance for breast cancer screening assessment (updated 22 January 2026)","publisher":"NHS England, NHS Breast Screening Programme (gov.uk)","year":2026,"url":"https://www.gov.uk/government/publications/breast-screening-clinical-guidelines-for-screening-management/clinical-guidance-for-breast-cancer-screening-assessment","gradingScheme":"Programme guidance; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"bts-lung-biopsy-2003","label":"Guidelines for radiologically guided lung biopsy","publisher":"British Thoracic Society (Manhire et al., Thorax)","year":2003,"url":"https://doi.org/10.1136/thorax.58.11.920","doi":"10.1136/thorax.58.11.920","read":"not-reachable","accessed":"2026-11-11"},{"key":"sir-2019","label":"Society of Interventional Radiology Consensus Guidelines for the Periprocedural Management of Thrombotic and Bleeding Risk in Patients Undergoing Percutaneous Image-Guided Interventions, Part II: Recommendations","publisher":"Society of Interventional Radiology (Journal of Vascular and Interventional Radiology)","year":2019,"url":"https://doi.org/10.1016/j.jvir.2019.04.017","doi":"10.1016/j.jvir.2019.04.017","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["Lung core biopsy is not covered. The British Thoracic Society guideline (2003) could not be read: PubMed Central serves its text as a scanned PDF behind a bot check, the publisher returned 429 and Europe PMC returned 403. No more recent open guideline on CT-guided lung biopsy was found in Europe PMC; pneumothorax monitoring, chest X-ray timing and air travel after lung biopsy are therefore not on this page.","The SIR 2019 consensus on bleeding risk in image-guided procedures, which classifies breast and liver biopsy by bleeding risk and sets drug intervals used in North America, is paywalled and has no abstract in Europe PMC; it was not read.","The NHS Breast Screening Programme guidance does not address blood thinners, bruising or aftercare after breast biopsy; those come from local policies, none of which was read.","BSG's 48-hour restriction on strenuous activity rests, in its own words, on weak evidence.","Needle-tract seeding of cancer after biopsy of a liver tumour is not addressed in the passages read."]},{"id":"head-and-neck-radiotherapy-immobilisation-mask","kind":"protocol","name":"Immobilisation mask for head and neck and brain radiotherapy, including mask anxiety","aka":["radiotherapy mask","thermoplastic mask","shell","head and neck mask","mask anxiety","claustrophobia during radiotherapy","mould room","open-face mask","five-point mask"],"tldr":"For radiotherapy to the head or neck you wear a close-fitting plastic mesh mask, moulded to your face while it is warm and clipped to the table, so you are in exactly the same place every day. About a quarter of people feel anxious in the mask. Tell the team early: they can explain each step, give breaks, let you play music, and in some departments use a mask with the face left open.","summary":"The ESTRO ACROP guideline (2017) sets out the radiation therapist's procedure: a full explanation beforehand, including the mask's temperature and how to signal for help; removal of dentures, hearing aids and piercings in the field; a straight, comfortable and reproducible position with every device indexed to the couch; any mouth bite or stent in place before moulding; a mask of three or more fixation points (five points when the low neck is treated, or a shoulder retractor with a three-point mask); a check of the material's temperature before it touches the skin; moulding within one to two minutes and hardening for five to fifteen; reassurance during hardening; removal and refitting before the CT scan; and labelling of the mask. It advises against cutting out the mask except for a bite block or tracheostomy.\n\nMask anxiety affected 26% of 100 consecutive patients in one Australian cohort and 27.3% of 410 in a validation study of a four-item screen (R-MAQ); in a prospective cohort it fell during treatment in 72% of those affected. Both Australian studies recommend routine screening, which no guideline yet requires. One randomised trial (216 patients, India, 2025) found music with guided relaxation in the first five sessions lowered mask anxiety. The OPEN phase 3 trial (230 non-claustrophobic patients, 2026) found open-face masks with surface-guided radiotherapy as accurate as a closed five-point mask and better tolerated, which departs from the ESTRO advice against cutting the mask; claustrophobic patients were excluded.","asOf":"2026-11-11","links":[],"tags":[],"related":["radiotherapy-patient-identification-and-time-out","head-and-neck-radiotherapy-oral-mucositis","head-and-neck-radiotherapy-dental-assessment-osteoradionecrosis"],"cancers":["head-and-neck"],"sections":[],"technologies":["surface-guided-radiotherapy","patient-positioning-surface-guidance-systems","imrt-igrt","music-therapy-cancer","relaxation-guided-imagery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A warm plastic mesh is shaped over your face and goes hard as it cools. It holds your head still during treatment. You can still breathe and signal to the team. If it makes you anxious, say so: there are ways to help.","domain":"radiotherapy","setting":{"who":["radiographer","patient-or-carer"],"where":["radiotherapy-department"]},"population":"Adults having external beam radiotherapy to the head and neck, or to the brain, with a thermoplastic mask. The procedure steps are written for head and neck cancer; brain radiotherapy uses the same masks without the shoulder section. Children usually need play specialist preparation or anaesthesia, which the sources read do not address. Stereotactic radiosurgery frames are covered in the stereotactic protocol.","trigger":"The mould-room or planning CT appointment at which the mask is made, and every treatment session after it.","steps":[{"action":"Before making the mask, give the patient a full explanation of the procedure","why":"Knowing what will happen, and what it will feel like, makes the appointment less frightening.","source":"estro-acrop-hn-2017","quote":"A full and detailed explanation of the procedure should be given to the patient by an RTT.","grade":"Guideline (ungraded)"},{"action":"Explain that the mask will feel warm, stress keeping still and breathing normally, and agree how the patient will signal if they are in difficulty","why":"Being able to stop things at any moment gives back a sense of control.","source":"estro-acrop-hn-2017","quote":"Other aspects related to both the safety and efficacy of the procedure should be discussed with the patient including the likely mask temperature, and how the patient can alert the RTTs if they are having difficulty during the procedure.","grade":"Guideline (ungraded)"},{"action":"Ask about anxiety in the mask early, using a screening question or tool, and plan support for those who screen positive","why":"About one person in four finds the mask distressing, and staff do not always notice.","source":"nixon-2019","quote":"Due to its high prevalence and variable patterns over time, it is recommended that routine screening for mask anxiety be implemented as standard care throughout the course of RT for HNC.","grade":"Recommendation of a prospective cohort study (35 patients); not a guideline"},{"action":"Remove dentures, hearing aids, earrings and piercings in the treated area before moulding","why":"Anything worn when the mask is made must be the same every day, and metal can disturb the scan and the dose.","source":"estro-acrop-hn-2017","quote":"Any dentures, hearing aids, toupees, earrings and all kinds of piercings in the treated area including tongue piercings must also be removed.","grade":"Guideline (ungraded)"},{"action":"Position the patient straight and comfortably, with the neck rest and every support indexed to the couch, and any mouth bite or stent in place before the mask is made","why":"The mask can only hold a position that can be repeated exactly each day.","source":"estro-acrop-hn-2017","quote":"All immobilisation devices must be indexed and fixed to the couch, to minimise rotational and translational errors.","grade":"Guideline (ungraded)"},{"action":"Choose a mask with three or more fixation points, a five-point mask when the low neck is treated, or a shoulder retractor with a three-point mask","why":"The lower neck and shoulders move unless they are held too.","source":"estro-acrop-hn-2017","quote":"If treating the low neck, a 5-point mask is recommended. If a 3-point mask is used, a device to maintain shoulder position, such as a retractor, is mandatory.","grade":"Guideline (ungraded)"},{"action":"Keep the airway clear, enlarging the nose and mouth openings if needed and leaving a gap over a tracheostomy","why":"The patient must be able to breathe freely throughout.","source":"estro-acrop-hn-2017","quote":"It may be necessary to cover the hair with cotton-type material and to ensure that the patient’s airway is not compromised during the procedure.","grade":"Guideline (ungraded)"},{"action":"Check the temperature of the softened material before it touches the skin","why":"The plastic is softened in hot water or an oven and could burn if applied too hot.","source":"estro-acrop-hn-2017","quote":"The temperature of the material must be checked before placing on the patient’s skin to avoid burns.","grade":"Guideline (ungraded)"},{"action":"Support and reassure the patient while the mask hardens, encouraging slow abdominal breathing","why":"The mask takes several minutes to set, and calm breathing helps people relax.","source":"estro-acrop-hn-2017","quote":"The patient should be supported and reassured by the RTTs during this time period. Motivating and supporting patients to use abdominal breathing will help them to relax during the whole procedure.","grade":"Guideline (ungraded)"},{"action":"Remove and refit the mask before the planning CT to check the fit, giving the patient a short break","why":"A mask that fits at the scan will fit at treatment, and the break helps.","source":"estro-acrop-hn-2017","quote":"It is recommended that the mask be removed and refitted prior to commencement of CT scanning to ensure that the fit is correct and that the immobilisation provided by the mask is adequate.","grade":"Guideline (ungraded)"},{"action":"Label the mask with the patient's name and the neck rest and wedges used, and record the position in the chart","why":"Each mask belongs to one person and must be used with the same supports every day.","source":"estro-acrop-hn-2017","quote":"For safety reasons, the patient name, type of neck rest and wedges used should always be documented on the patient mask, preferably using a method that can identify the mask in the oncology information system.","grade":"Guideline (ungraded)"},{"action":"For people with mask anxiety, offer music and guided relaxation during the first sessions, alongside the team's explanation and breaks","why":"In one randomised trial, music with guided relaxation lowered anxiety in the mask within five sessions.","source":"music-rct-2025","quote":"At the end of five RT sessions, the intervention group showed a statistically significant reduction in mask anxiety scores [median (IQR): 2 (2)] compared to the control group [median (IQR): 6 (1)], with p < 0.001.","grade":"Single randomised trial (216 patients)"}],"bestInClass":{"statement":"Make the mask by the ESTRO ACROP procedure (2017): explanation and an agreed signal, a straight reproducible position with every device indexed, any bite block in place first, three or more fixation points and five for the low neck, a temperature check before the material touches the skin, reassurance while it sets, and a refit before the CT. Screen for mask anxiety early (recommended by the Australian cohort studies and supported by a validated four-item screen, R-MAQ, though no guideline yet requires it) and offer support, including music with guided relaxation (one randomised trial). Where surface-guided radiotherapy is available, an open-face mask is as accurate as a closed five-point mask and better tolerated (OPEN phase 3 randomised trial, 2026); this departs from ESTRO's 2017 advice against cutting out the mask, written before such trials existed.","sources":["estro-acrop-hn-2017","nixon-2018","nixon-2019","rmaq-2025","music-rct-2025","open-rct-2026"]},"variants":[{"name":"Open-face mask with surface-guided radiotherapy","differs":"The mask leaves the eyes, nose and mouth uncovered and a surface camera tracks the exposed face, neck and upper chest from set-up through treatment. ESTRO ACROP (2017) advises against cutting out the mask except for a bite block or tracheostomy.","evidence":"OPEN phase 3 trial: 230 non-claustrophobic patients randomised to a closed five-point mask or an open three- or five-point mask with surface guidance; set-up accuracy equivalent (larger longitudinal shifts with the closed mask, P < 0.001) and tolerability, experience and distress better with both open masks (p < 0.01). An earlier open-face mask study treated five claustrophobic patients who could only tolerate the open mask.","sources":["open-rct-2026","open-methods-2026","li-2013","estro-acrop-hn-2017"]},{"name":"Routine screening with a validated tool (R-MAQ)","differs":"A four-item questionnaire given before planning identifies people at risk of an anxious response to the mask, rather than relying on staff noticing or a single distress question.","evidence":"Validation in 410 patients: area under the ROC curve 0.78, with 27.3% showing an anxious response at planning; comparable or better than a general claustrophobia questionnaire. No trial yet shows that screening changes outcomes.","sources":["rmaq-2025"]}],"grades":[{"claim":"A quarter of patients report mask anxiety","grade":"Mixed-methods cohort (100 patients)","source":"nixon-2018","quote":"In phase one, 26% of participants self‐identified as being anxious about the use of a thermoplastic mask."},{"claim":"Mask anxiety usually eases during treatment","grade":"Prospective cohort (35 patients)","source":"nixon-2019","quote":"In 72% of participants, the level of initial distress was found to reduce over time."},{"claim":"Open masks with surface guidance give equivalent accuracy and a better experience","grade":"Phase 3 randomised trial (230 patients)","source":"open-rct-2026","quote":"At treatment completion patient experience metrics, including tolerability, overall experience and distress, were significantly more favourable for both open-mask cohorts compared to closed masks (p < 0.01)."},{"claim":"A brief screen predicts an anxious response at planning","grade":"Validation study (410 patients)","source":"rmaq-2025","quote":"Of the 410 participants (mean age 62), 27.3% presented an anxious response to the immobilization mask during planning exams."}],"sources":[{"key":"estro-acrop-hn-2017","label":"ESTRO ACROP guidelines for positioning, immobilisation and position verification of head and neck patients for radiation therapists","publisher":"ESTRO ACROP (Leech et al., Technical Innovations and Patient Support in Radiation Oncology)","year":2017,"url":"https://doi.org/10.1016/j.tipsro.2016.12.001","doi":"10.1016/j.tipsro.2016.12.001","gradingScheme":"Guidance based on a literature review, a European survey and committee experience; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nixon-2018","label":"Exploring the prevalence and experience of mask anxiety for the person with head and neck cancer undergoing radiotherapy","publisher":"Journal of Medical Radiation Sciences (Nixon et al.)","year":2018,"url":"https://doi.org/10.1002/jmrs.308","doi":"10.1002/jmrs.308","read":"full-text","accessed":"2026-11-11"},{"key":"nixon-2019","label":"A prospective examination of mask anxiety during radiotherapy for head and neck cancer and patient perceptions of management strategies","publisher":"Journal of Medical Radiation Sciences (Nixon et al.)","year":2019,"url":"https://doi.org/10.1002/jmrs.346","doi":"10.1002/jmrs.346","read":"full-text","accessed":"2026-11-11"},{"key":"rmaq-2025","label":"Development and Validation of a Rapid Screening Measure for Mask Anxiety in Head and Neck Cancer Patients Undergoing Radiotherapy","publisher":"Psycho-Oncology","year":2025,"url":"https://doi.org/10.1002/pon.70369","doi":"10.1002/pon.70369","read":"full-text","accessed":"2026-11-11"},{"key":"music-rct-2025","label":"Effect of music therapy and relaxation visualization intervention on mask anxiety in head and neck cancer patients undergoing radiotherapy: a randomized controlled trial","publisher":"Supportive Care in Cancer","year":2025,"url":"https://doi.org/10.1007/s00520-025-09901-z","doi":"10.1007/s00520-025-09901-z","read":"abstract","accessed":"2026-11-11"},{"key":"open-rct-2026","label":"OPEN: optimising patient experience in head and neck radiotherapy, a phase 3 randomised control trial comparing open versus closed face masks","publisher":"Radiotherapy and Oncology (Nicholson et al.)","year":2026,"url":"https://doi.org/10.1016/j.radonc.2026.111779","doi":"10.1016/j.radonc.2026.111779","read":"abstract","accessed":"2026-11-11"},{"key":"open-methods-2026","label":"Surface-guided radiotherapy setup using an open-face mask for head and neck cancer; the OPEN trial approach","publisher":"MethodsX","year":2026,"url":"https://doi.org/10.1016/j.mex.2026.104186","doi":"10.1016/j.mex.2026.104186","read":"full-text","accessed":"2026-11-11"},{"key":"li-2013","label":"Migration from full-head mask to \"open-face\" mask for immobilization of patients with head and neck cancer","publisher":"Journal of Applied Clinical Medical Physics (Li et al.)","year":2013,"url":"https://doi.org/10.1120/jacmp.v14i5.4400","doi":"10.1120/jacmp.v14i5.4400","read":"full-text","accessed":"2026-11-11"},{"key":"nci-rt-and-you","label":"Radiation Therapy and You: Support for People With Cancer (April 2021)","publisher":"US National Cancer Institute","year":2021,"url":"https://www.cancer.gov/publications/patient-education/radiation-therapy-and-you","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-open-face-masks","idea-pu-mask-anxiety-screening"],"gaps":["No society guideline on preventing or managing mask anxiety was found. The screening recommendation comes from the authors of two Australian cohort studies, and the only randomised trial of a calming intervention found is a single-centre trial from India read as an abstract.","The ESTRO ACROP guideline dates from 2017 and grades nothing; it predates the open-mask trials and advises against cutting out the mask.","The OPEN trial excluded claustrophobic patients, so whether open masks let people who cannot tolerate a closed mask complete treatment is not tested in it; it was read as an abstract.","Medication for mask anxiety (for example a short-acting anxiolytic before sessions) is reported by patients in the cohort studies, but no source read gives a recommendation on it.","Preparation of children (play, desensitisation, anaesthesia) was not examined."]},{"id":"irae-hepatitis","kind":"protocol","name":"Immune-mediated hepatitis from checkpoint inhibitors, by grade","aka":["checkpoint inhibitor hepatitis","ICI hepatotoxicity","immune-related hepatitis","IMH","immunotherapy liver inflammation"],"tldr":"Immunotherapy can inflame the liver, usually without symptoms, so liver blood tests are checked before every dose. If the tests rise, immunotherapy is paused and steroids are given; severe cases mean stopping immunotherapy. Yellow skin or eyes, dark urine or pale stools need a call to your cancer team the same day.","summary":"Hepatitis (raised ALT or AST) occurs in about 5% on PD-(L)1 or CTLA-4 inhibitors alone and 19% on combinations (9% grade 3 or more), typically 1 to 15 weeks after starting (SITC 2021); AASLD 2023 gives 1 to 15% across trials and observational studies, mostly asymptomatic in the first 6 to 12 weeks. Only about 30% of demonstrable liver injury in advanced cancer is drug-induced, so metastases, sepsis and other causes are excluded with imaging (AASLD).\n\nSITC 2021: liver tests before every infusion. From grade 2, a workup including clotting, bilirubin, iron studies, an autoimmune hepatitis panel and viral hepatitis serology; imaging for grade 3 or more if there is liver disease or suspected metastases. Recheck weekly for grades 1 to 2, every 1 to 2 days for grade 3 or more. Grade 2: prednisone 0.5 to 1 mg/kg/day; grades 3 to 4: methylprednisolone 1 to 2 mg/kg/day; taper over 4 to 6 weeks once tests are grade 1 or less (LE: 1). No improvement in 10 to 14 days, or relapse on taper: mycophenolate mofetil (LE: 4). Never infliximab (LE: 1).\n\nAASLD 2023 agrees on grade 2 (withhold and consider prednisone 0.5 to 1.0 mg/kg/day), and for grade 3 or more permanently discontinues the checkpoint inhibitor, with intravenous steroids at 1 to 1.5 mg/kg/day and admission for jaundice, keeping liver biopsy for persistent grade 3 injury or jaundice despite steroids. ESMO 2022 could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","acute-oncology"],"related":["irae-colitis","irae-pneumonitis"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab","prednisone","methylprednisolone"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can sometimes inflame the liver. Your blood tests check for this before each dose. If you notice yellow skin or eyes, ring your cancer helpline.","domain":"immunotherapy-toxicity","setting":{"who":["nurse","doctor","pharmacist","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","acute-oncology-service","ward"]},"population":"Adults treated with an immune checkpoint inhibitor, alone or combined with another, whose liver tests rise or who develop jaundice. People with liver metastases or chronic liver disease need the alternative causes excluded with particular care. Children are not addressed.","trigger":"A rise in ALT, AST or bilirubin on the pre-dose blood test, or symptoms such as jaundice, dark urine or right upper abdominal pain, during or after checkpoint inhibitor treatment.","steps":[{"action":"Check liver tests before every checkpoint inhibitor infusion","why":"Immune hepatitis is usually silent and is found on the blood test.","source":"sitc-2021","quote":"Liver biochemical tests (aka liver function tests (LFTs)) should be checked prior to each ICI infusion."},{"action":"From grade 2, send clotting, bilirubin, alkaline phosphatase, iron studies, an autoimmune hepatitis panel and a viral hepatitis panel","why":"These separate immune hepatitis from viral hepatitis, other autoimmune liver disease and iron overload.","source":"sitc-2021","quote":"Diagnostic workup for grade ≥2 liver toxicity should include ALT, AST, alkaline phosphatase, prothrombin time/international normalized ratio (PT/INR) serum bilirubin, iron studies, autoimmune hepatitis panel (antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), antimitochondrial antibody (AMA), peripheral ANCA (p-ANCA), and antismooth muscle antibody (ASMA)), and viral hepatitis panel."},{"action":"Image the liver to look for metastases, sepsis and other causes","why":"In people with advanced cancer, most liver test rises are not caused by the drug.","source":"aasld-2023","quote":"Recent studies suggest that bona fide DILI is only responsible for 30% of cases of demonstrable liver injury in patients with advanced cancer, whereas hepatic metastases, sepsis, and other causes of liver disease account for the remainder, emphasizing the importance of contrast‐enhanced CT and MR scanning in evaluation of these patients."},{"action":"Recheck liver tests weekly for grades 1 to 2 and every 1 to 2 days for grade 3 or more","why":"Severe hepatitis can progress within days.","source":"sitc-2021","quote":"LFTs should be rechecked weekly for patients experiencing grade 1–2 liver toxicities, and should be rechecked every 1–2 days for patients with liver toxicities of grade ≥3."},{"action":"For grade 1, continue treatment with more frequent tests; for grade 2, withhold the checkpoint inhibitor","why":"Mild rises often settle without stopping; a moderate rise needs a pause.","source":"aasld-2023","quote":"For patients with grade 1 liver injury (ALT > 1–3× ULN and/or total bilirubin > 1–1.5× ULN), continued therapy with more frequent laboratory monitoring is advisable."},{"action":"Give prednisone 0.5 to 1 mg/kg/day for grade 2 and methylprednisolone 1 to 2 mg/kg/day for grades 3 and 4","why":"Steroids calm the immune attack on the liver; the dose rises with severity.","source":"sitc-2021","quote":"Grade 2 liver toxicity should be treated initially with prednisone 0.5–1 mg/kg/day (or equivalent), and grades 3 and 4 should be treated initially with methylprednisolone 1–2 mg/kg/day (or equivalent)."},{"action":"Taper steroids over 4 to 6 weeks once the liver tests are back to grade 1 or less","why":"A fast taper risks rebound hepatitis.","source":"sitc-2021","quote":"Corticosteroids should be tapered over a period of 4–6 weeks after LFTs revert to grade ≤1","grade":"LE: 1"},{"action":"If tests have not improved to grade 1 within 10 to 14 days of steroids, or hepatitis returns on the taper, add mycophenolate mofetil","why":"Steroid-refractory hepatitis needs a second immunosuppressant.","source":"sitc-2021","quote":"If ALT or AST results do not improve to grade ≤1 within 10–14 days of corticosteroid initiation, or if liver toxicity recurs after steroid taper, mycophenolate mofetil (1–2 g divided two times per day) may be given","grade":"LE: 4"},{"action":"Do not use infliximab for immune hepatitis","why":"Infliximab can itself damage the liver.","source":"sitc-2021","quote":"Infliximab should not be used in patients with liver toxicity, given the risk for hepatotoxicity","grade":"LE: 1"},{"action":"Keep a liver biopsy for grade 3 injury or jaundice that persists despite steroids","why":"Biopsy rarely changes early management but helps when steroids are failing.","source":"aasld-2023","quote":"Liver biopsy typically demonstrates lobular or periportal hepatitis and is generally not recommended unless patients have persistent grade 3 hepatotoxicity or jaundice despite corticosteroids."},{"action":"After immunosuppression is tapered, keep checking liver tests every 2 to 4 weeks","why":"Hepatitis can rebound after steroids stop.","source":"aasld-2023","quote":"After tapering of immunosuppression, the liver tests should continue to be monitored every 2–4 weeks because of the risk of rebound hepatitis."}],"bestInClass":{"statement":"SITC 2021 and AASLD 2023 agree on the frame: liver tests before every dose, exclusion of metastases, infection and viral hepatitis, prednisone 0.5 to 1 mg/kg/day for grade 2, and mycophenolate mofetil when steroids fail. They differ for grade 3 or more: SITC gives methylprednisolone 1 to 2 mg/kg/day and does not state discontinuation in its hepatitis section; AASLD permanently discontinues the checkpoint inhibitor and considers intravenous steroids at 1 to 1.5 mg/kg/day with admission for jaundice. SITC grades the 4 to 6 week taper LE: 1 and the warning against infliximab LE: 1; AASLD's guidance is expert consensus. ASCO 2021 permanently stops checkpoint inhibitors after most grade 4 toxicities; its hepatitis table and ESMO 2022 were not read.","sources":["sitc-2021","aasld-2023","asco-2021","esmo-2022"]},"variants":[{"name":"Permanent discontinuation from grade 3 (AASLD 2023)","differs":"For ALT 5 to 20 times the upper limit and/or bilirubin 3 to 10 times, or symptomatic liver dysfunction, permanently discontinues the checkpoint inhibitor and considers intravenous steroids at 1 to 1.5 mg/kg/day with hospital admission for jaundice; names azathioprine as well as mycophenolate for steroid-refractory disease.","evidence":"Expert-panel practice guidance commissioned instead of a guideline because randomised trials are lacking.","sources":["aasld-2023"]},{"name":"Tacrolimus or antithymocyte globulin for refractory hepatitis (SITC 2021)","differs":"Lists tacrolimus and antithymocyte globulin as other agents to consider, and a liver biopsy if mycophenolate fails to bring tests to grade 1 within 10 to 14 days.","evidence":"Not graded (expert consensus), based on use in autoimmune hepatitis.","sources":["sitc-2021"]}],"grades":[{"claim":"Steroid taper over 4 to 6 weeks after liver tests return to grade 1 or less","grade":"LE: 1","source":"sitc-2021"},{"claim":"Mycophenolate mofetil for steroid-refractory or recurrent hepatitis","grade":"LE: 4","source":"sitc-2021"},{"claim":"No infliximab in liver toxicity","grade":"LE: 1","source":"sitc-2021"},{"claim":"Grade 3 or more: permanently discontinue the checkpoint inhibitor","grade":"expert opinion (practice guidance)","source":"aasld-2023","quote":"For patients with grade 3 or higher hepatotoxicity (ALT 5–20× ULN and/or bilirubin 3–10× ULN or symptomatic liver dysfunction), the ICI should be permanently discontinued, and i.v. steroids at a dose of 1–1.5 mg/kg per day along with hospitalization for patients with jaundice should be considered."},{"claim":"General rule: permanent discontinuation after grade 4","grade":"expert consensus","source":"asco-2021"}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"aasld-2023","label":"AASLD practice guidance on drug, herbal, and dietary supplement induced liver injury","publisher":"American Association for the Study of Liver Diseases, Hepatology","year":2023,"url":"https://europepmc.org/article/PMC/PMC9936988","doi":"10.1002/hep.32689","gradingScheme":"Practice guidance developed by consensus of an expert panel after review of the literature; guidance statements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline update was read only as its abstract, which gives the general rules (continue for grade 1, hold for most grade 2, high-dose steroids for grade 3, taper over at least 4 to 6 weeks, stop for grade 4) but not its organ-by-organ tables.","SITC's hepatitis section does not say whether to stop the checkpoint inhibitor permanently after grade 3 hepatitis; AASLD does, and the ASCO hepatitis table was not read, so the guidelines' positions on re-challenge after grade 3 hepatitis are not compared here.","No randomised trial of second-line treatment for steroid-refractory immune hepatitis was found among the sources read."]},{"id":"irae-colitis","kind":"protocol","name":"Immune-related diarrhoea and colitis from checkpoint inhibitors, by grade","aka":["checkpoint inhibitor colitis","immune checkpoint inhibitor diarrhoea","immune-mediated colitis","ICI colitis management","immunotherapy colitis"],"tldr":"Immunotherapy drugs such as pembrolizumab, nivolumab and ipilimumab can make the immune system attack the bowel, causing diarrhoea, tummy pain or blood in the stool. Ring your cancer team's 24-hour line as soon as diarrhoea starts. Mild cases are watched; anything more is treated with steroids, and if steroids do not work within a few days, with a drip such as infliximab.","summary":"Diarrhoea is reported in about 44% of patients on combined CTLA-4 and PD-(L)1 blockade (10% grade 3 or more), 36% on CTLA-4 inhibitors and 11% on PD-(L)1 inhibitors; colitis in 16%, 8% and 1% respectively (SITC 2021). Median onset is 5 to 10 weeks.\n\nSITC 2021: work up grade 1 with full blood count, metabolic panel and faecal lactoferrin, and continue the checkpoint inhibitor with monitoring. From grade 2, add faecal calprotectin and stool infection tests (C. difficile, CMV), hold the drug and start prednisone 1 mg/kg/day; grades 3 and 4 take 1 to 2 mg/kg/day, grade 4 intravenously. Sigmoidoscopy or colonoscopy with biopsy for grade 3 or more, or grade 2 lasting 5 days or more; CT for suspected perforation or toxic megacolon. Steroids are tapered within 4 weeks once symptoms reach grade 1 or less. No response in 3 to 5 days, recurrence on taper or severe ulceration at endoscopy: infliximab 5 mg/kg at 0, 2 and 6 weeks, switching to vedolizumab 300 mg on the same schedule if symptoms persist after the second infliximab dose. Screen for hepatitis B, HIV and tuberculosis first without delaying the dose. Re-challenge once symptoms are grade 1 or less on under 10 mg prednisone a day, after repeat endoscopy.\n\nASCO 2021 sets the general frame (continue for grade 1, hold for grade 2, high-dose steroids for grade 3, permanently stop for most grade 4) and tapers over at least 4 to 6 weeks, longer than SITC's 4 weeks for colitis. ESMO 2022 could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","acute-oncology"],"related":["idea-bio2-steroid-sparing-irae"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","dostarlimab","tremelimumab","avelumab","prednisone"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["immune-colitis","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can cause the bowel to become inflamed. If you get diarrhoea, ring your cancer helpline straight away. Steroid tablets or a drip usually settle it, and many people can restart immunotherapy afterwards.","domain":"immunotherapy-toxicity","setting":{"who":["patient-or-carer","nurse","doctor","pharmacist"],"where":["telephone-triage","acute-oncology-service","outpatient-clinic","emergency-department","ward"]},"population":"Adults treated with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1 or anti-CTLA-4, alone or combined) who develop diarrhoea or symptoms of colitis. Combination CTLA-4 and PD-(L)1 treatment carries the highest risk. People with pre-existing inflammatory bowel disease, and children, are not addressed separately here.","trigger":"A person on or after checkpoint inhibitor treatment reports looser or more frequent stools, abdominal pain, or blood or mucus in the stool.","steps":[{"action":"Before the first dose, teach the patient and carer which symptoms to report and whom to call","why":"Colitis usually starts at home weeks into treatment; early reporting is what keeps a mild case from becoming a severe one.","source":"sitc-2021","quote":"Patients should receive dedicated education on irAEs by a medical professional and may receive additional materials such as informational booklets or reference cards."},{"action":"For grade 1 diarrhoea, check full blood count, a metabolic panel and faecal lactoferrin, and continue the checkpoint inhibitor with close monitoring","why":"Mild diarrhoea often settles, and stopping an effective cancer drug has its own cost; the tests give a baseline if it worsens.","source":"sitc-2021","quote":"Diagnostic workup for grade 1 diarrhea or colitis symptoms should include CBC, CMP, and fecal lactoferrin."},{"action":"From grade 2, add faecal calprotectin and stool tests for infection, including C. difficile and CMV","why":"Infection causes the same symptoms and needs different treatment; ruling it out matters before and alongside immune suppression.","source":"sitc-2021","quote":"Additional workup should be performed for patients with diarrhea or colitis symptoms of grade ≥2, and these additional tests should include fecal calprotectin, and stool infectious analysis (stool ova and parasite, C. difficile and cytomegalovirus (CMV) testing via polymerase chain reaction (PCR) if available or if high index of suspicion is present, among other infectious studies (eg, COVID-19))."},{"action":"Do not wait for every test before starting treatment","why":"The search for another cause runs alongside treatment, not ahead of it.","source":"sitc-2021","quote":"Diagnostic evaluation for all irAEs should attempt to rule out other possible etiologies (eg, diarrhea/colitis associated with Clostridium difficile infection), but treatment for irAEs should be initiated as is deemed clinically appropriate."},{"action":"Arrange an abdominal CT if there are signs of perforation or toxic megacolon","why":"These complications need a surgeon as well as steroids, and endoscopy may be unsafe.","source":"sitc-2021","quote":"Abdominal CT scan should be obtained in patients with signs and symptoms of colitis complications, such as bowel perforation or toxic megacolon."},{"action":"Arrange flexible sigmoidoscopy or colonoscopy with biopsy for grade 3 or more, or for grade 2 lasting 5 days or longer","why":"Seeing and sampling the bowel confirms the diagnosis and shows ulceration, which changes treatment.","source":"sitc-2021","quote":"Flexible sigmoidoscopy and/or colonoscopy with biopsy should be performed for patients with diarrhea or colitis symptoms of grade ≥3 or with persistent (≥5 days) diarrhea or colitis symptoms of grade 2","grade":"LE: 4"},{"action":"For grade 2, hold the checkpoint inhibitor and start steroids","why":"Holding the drug and calming the immune reaction early prevents progression.","source":"sitc-2021","quote":"Corticosteroids should be started in patients experiencing diarrhea or colitis symptoms of grade ≥2."},{"action":"Give prednisone 1 mg/kg/day (or equivalent) for grade 2 and 1 to 2 mg/kg/day for grades 3 and 4, intravenously for grade 4","why":"The dose matches the severity; the sickest patients may not absorb tablets.","source":"sitc-2021","quote":"The initial dose of prednisone should be 1 mg/kg/day (or equivalent) for grade 2 diarrhea or colitis and 1–2 mg/kg/day for grades 3 and 4. Grade 4 diarrhea or colitis should initially be treated with IV corticosteroids."},{"action":"When starting steroids, warn about high blood sugar, mood change, poor sleep, gastritis, weight gain and infections such as Pneumocystis pneumonia","why":"High-dose steroids have their own side effects, and some need prevention or monitoring.","source":"sitc-2021","quote":"When beginning corticosteroid therapy, patients should be specifically counseled about potential toxicities, including hyperglycemia, mood disturbances, insomnia, gastritis, weight gain, and opportunistic infections (eg, Pneumocystis pneumonia)","grade":"LE: 1"},{"action":"Taper the steroids once symptoms are grade 1 or less","why":"Stopping too fast risks a flare; SITC tapers colitis within 4 weeks of improvement, ASCO over at least 4 to 6 weeks (see variants).","source":"sitc-2021","quote":"Corticosteroids should be tapered within 4 weeks after improvement of diarrhea or colitis symptoms to grade ≤1","grade":"LE: 1"},{"action":"Test for hepatitis B, HIV and tuberculosis before infliximab or vedolizumab, but do not hold the dose for the results","why":"These drugs can reactivate hidden infections, yet the colitis cannot wait for the laboratory.","source":"sitc-2021","quote":"Prior to administration of infliximab or vedolizumab, patients should be tested for HBV, HIV, and TB. Administration of infliximab or vedolizumab should not be delayed if test results are pending."},{"action":"If there is no response to steroids within 3 to 5 days, a relapse on taper, or severe ulceration at endoscopy, give infliximab 5 mg/kg at 0, 2 and 6 weeks","why":"Colitis that does not settle on steroids is steroid-refractory, and a biologic works faster than more steroid.","source":"sitc-2021","quote":"If diarrhea or colitis symptoms do not respond to corticosteroid therapy within 3–5 days, if diarrhea or colitis symptoms recur after tapering corticosteroids, or if there is severe ulcerative presentation on colonoscopy, 3 doses of infliximab (5 mg/kg) should be administered at 0, 2, and 6 weeks","grade":"LE: 1"},{"action":"If symptoms persist after the second infliximab dose, give vedolizumab 300 mg at 0, 2 and 6 weeks instead of the third","why":"Vedolizumab acts only on the gut, and SITC uses it as the next step when infliximab is not working.","source":"sitc-2021","quote":"If diarrhea or colitis symptoms persist after the second dose of infliximab treatment, the third dose should be held and 3 doses of vedolizumab (300 mg) should be administered at 0, 2, and 6 weeks","grade":"LE: 1"},{"action":"If grade 3 or more does not improve on immune suppression, repeat the endoscopy with C. difficile and CMV testing","why":"A new infection on steroids is a common reason for failure.","source":"sitc-2021","quote":"If no clinical improvement is observed following immunosuppressive therapy in patients with grade ≥3 diarrhea or colitis, a repeat endoscopy with infectious workup ( C. difficile and CMV) should be performed."},{"action":"Consider restarting the checkpoint inhibitor once symptoms are grade 1 or less on under 10 mg prednisone a day, after a repeat endoscopy, and watch for recurrence","why":"Many patients can safely restart; in one retrospective study about a third had colitis again.","source":"sitc-2021","quote":"These patients may be re-challenged with ICIs if their symptoms are stable (grade ≤1 or baseline) with <10 mg/day of prednisone (or equivalent)","grade":"LE: 4"}],"bestInClass":{"statement":"The most detailed current recommendations that could be read are SITC 2021, graded by Oxford level: steroids from grade 2 (prednisone 1 mg/kg/day for grade 2, 1 to 2 mg/kg/day for grades 3 and 4, intravenous for grade 4), endoscopy with biopsy for grade 3 or persistent grade 2, infliximab after 3 to 5 days without response, then vedolizumab, and a steroid taper within 4 weeks of improvement. ASCO 2021 agrees on the frame (continue at grade 1, hold at grade 2, high-dose steroids at grade 3) but tapers over at least 4 to 6 weeks and generally stops checkpoint inhibitors permanently after grade 4, where SITC allows a hold rather than discontinuation for grade 3 or more. ESMO 2022, the European guideline, could not be read and is not compared here.","sources":["sitc-2021","asco-2021","esmo-2022"]},"variants":[{"name":"Longer steroid taper and permanent stop after grade 4 (ASCO 2021)","differs":"Tapers corticosteroids over at least 4 to 6 weeks for irAEs in general, and recommends permanent discontinuation of checkpoint inhibitors after most grade 4 toxicities.","evidence":"Expert consensus (informal consensus process); the abstract was read, not the colitis table.","sources":["asco-2021"]},{"name":"Hold rather than stop after grade 3 or 4 colitis (SITC 2021)","differs":"Allows checkpoint inhibitors to be withheld rather than discontinued for grade 3 or more diarrhoea or colitis, with re-challenge when stable at grade 1 or less on under 10 mg prednisone a day.","evidence":"LE: 4 (case series level).","sources":["sitc-2021"]},{"name":"Early biologic, within 10 days of onset","differs":"Gives infliximab or vedolizumab early rather than after steroids fail. SITC reports emerging evidence that early use (under 10 days from symptom onset) may be associated with fewer hospitalisations, fewer taper failures, shorter steroid courses and shorter symptoms, but does not recommend it as first line.","evidence":"Observational evidence cited by SITC; no head-to-head trial of infliximab against vedolizumab.","sources":["sitc-2021"]}],"grades":[{"claim":"Endoscopy with biopsy for grade 3 or more, or grade 2 for 5 days or more","grade":"LE: 4","source":"sitc-2021"},{"claim":"Steroid taper within 4 weeks after improvement to grade 1 or less","grade":"LE: 1","source":"sitc-2021","quote":"Corticosteroids should be tapered within 4 weeks after improvement of diarrhea or colitis symptoms to grade ≤1"},{"claim":"Infliximab 5 mg/kg at 0, 2 and 6 weeks for steroid-refractory or recurrent colitis","grade":"LE: 1","source":"sitc-2021"},{"claim":"Vedolizumab 300 mg at 0, 2 and 6 weeks if symptoms persist after two infliximab doses","grade":"LE: 1","source":"sitc-2021"},{"claim":"Re-challenge when grade 1 or less on under 10 mg prednisone a day","grade":"LE: 4","source":"sitc-2021"},{"claim":"Grade 1: continue with close monitoring; grade 3: suspend and start high-dose corticosteroids","grade":"expert consensus","source":"asco-2021","quote":"Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids."},{"claim":"Corticosteroid taper over at least 4 to 6 weeks","grade":"expert consensus","source":"asco-2021","quote":"Corticosteroids should be tapered over the course of at least 4-6 weeks."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline update was read only as its abstract, which gives the general rules (continue for grade 1, hold for most grade 2, high-dose steroids for grade 3, taper over at least 4 to 6 weeks, stop for grade 4) but not its organ-by-organ tables.","The NCCN guideline on management of immunotherapy-related toxicities was not read; NCCN's full guidelines need an account.","No randomised trial read here compares infliximab with vedolizumab, or early biologic with steroids first, for checkpoint inhibitor colitis.","How to manage people who start a checkpoint inhibitor with existing inflammatory bowel disease is mentioned by SITC (flares in a substantial minority) but not set out as steps here."]},{"id":"irae-myocarditis","kind":"protocol","name":"Immune-related myocarditis from checkpoint inhibitors","aka":["checkpoint inhibitor myocarditis","ICI myocarditis","immune checkpoint inhibitor-associated myocarditis","immunotherapy heart inflammation","myocarditis-myositis-myasthenia overlap"],"tldr":"Rarely, immunotherapy inflames the heart muscle. It usually starts in the first three months and can be fatal, so new chest pain, breathlessness, palpitations, fainting, or new muscle weakness, drooping eyelids or double vision need urgent assessment. It is treated in hospital with very high-dose steroids straight away.","summary":"Uncommon (about 1% in an eight-centre registry) but with high mortality: 50% of patients with myocarditis died in one retrospective series, and it clusters with myositis and myasthenia gravis, so suspicion of one should prompt a search for all three (SITC 2021). Median onset 34 days after starting. Troponin is raised in 94% and the ECG abnormal in 89%, while ejection fraction is normal in about half.\n\nSITC 2021: consider myocarditis in anyone with new cardiac symptoms, arrhythmia, heart block or a raised troponin who has had a checkpoint inhibitor in the past 12 weeks; admit, involve cardiology, and obtain ECG, troponin and cardiac MRI (with or without endomyocardial biopsy), plus the shared myositis and myasthenia panel. Give methylprednisolone 1000 mg IV daily for 3 to 5 days as soon as the diagnosis is likely, until troponin normalises, then a 4 to 6 week prednisone taper; seriously consider permanent discontinuation. If there is no response within 24 hours add antithymocyte globulin, mycophenolate mofetil, abatacept or alemtuzumab (LE: 4); avoid infliximab (LE: 4). Manage in a coronary care unit with temporary pacing available. A retrospective study found steroids within 24 hours of admission were followed by fewer major cardiac events than later steroids.\n\nASCO 2021 makes cardiac toxicity one of the exceptions to continuing treatment for grade 1 toxicity. The ESC 2022 and ESC 2025 guidelines could not be read here.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","acute-oncology","cardio-oncology"],"related":["irae-neurological","checkpoint-inhibitor-baseline-and-monitoring","irae-rheumatological"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","cardiac-biomarker-monitoring"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab","methylprednisolone","alemtuzumab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["myocarditis","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021","paper-lyon-eur-heart-j"],"journals":[],"dependsOn":[],"notes":[],"simple":"Very rarely, immunotherapy can inflame the heart. Chest pain, breathlessness, a racing or irregular heartbeat, fainting, or new weakness or double vision need urgent help.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","emergency-team","patient-or-carer","multidisciplinary-team"],"where":["emergency-department","acute-oncology-service","telephone-triage","ward","intensive-care"]},"population":"Adults who have received an immune checkpoint inhibitor, alone or in combination, usually within the previous 12 weeks; the risk is higher with combined PD-1 and CTLA-4 blockade. Children are not addressed by these sources.","trigger":"New chest pain, breathlessness, palpitations, syncope, arrhythmia, heart block or an unexplained raised troponin; or new myositis or myasthenia-like symptoms, which call for a cardiac work-up as well.","steps":[{"action":"Suspect myocarditis in anyone with new cardiac symptoms, arrhythmia, heart block or a raised troponin after a checkpoint inhibitor in the past 12 weeks; admit and involve cardiology","why":"Myocarditis can deteriorate within hours and is often fatal if missed.","source":"sitc-2021","quote":"A diagnosis of ICI-induced myocarditis should be considered in any patient developing new cardiac symptoms, new cardiac arrhythmias, new heart blocks, or cardiac lab findings (eg, asymptomatic troponin elevation) who has received an ICI therapy in the past 12 weeks. Suspicion of ICI-induced myocarditis should trigger hospital admittance and consultation with a cardiologist."},{"action":"Obtain an ECG, serum troponin and cardiac MRI, with right heart catheterisation and myocardial biopsy where needed","why":"Troponin and ECG are abnormal in most cases; MRI or biopsy confirms the diagnosis.","source":"sitc-2021","quote":"Patients with suspected ICI-induced myocarditis should undergo cardiac MRI if available (with or without right heart catheterization and myocardial biopsy), EKG, and testing for serum troponin levels."},{"action":"Look for myositis and myasthenia gravis at the same time, with CK, ESR, CRP, myasthenia antibodies, aldolase, nerve conduction studies and EMG","why":"The three conditions often occur together, and each raises the danger of the others.","source":"sitc-2021","quote":"Should have testing including erythrocyte sedimentation rate (ESR), C reactive protein (CRP), creatine kinase (CK), antibody tests (acetylcholine, muscle-specific kinase (MusK), striational), aldolase, troponin, EKG, nerve conduction, and electromyography (EMG)."},{"action":"Give methylprednisolone 1000 mg IV daily for 3 to 5 days as soon as the diagnosis is likely, until troponin normalises, then taper prednisone over 4 to 6 weeks","why":"Early high-dose steroids were followed by fewer serious heart events than delayed treatment.","source":"sitc-2021","quote":"Patients with suspected ICI-induced myocarditis should receive high-dose corticosteroids (1000 mg methylprednisolone IV or equivalent daily for 3–5 days, until troponin normalizes) as soon as possible once the diagnosis is considered likely, followed by 4–6 weeks 1–2 mg/kg prednisone taper."},{"action":"Seriously consider stopping the checkpoint inhibitor permanently","why":"Restarting risks a recurrence of a condition with high mortality.","source":"sitc-2021","quote":"Permanent discontinuation of ICI therapy should be seriously considered."},{"action":"If there is no response to steroids within 24 hours, add antithymocyte globulin, mycophenolate mofetil, abatacept or alemtuzumab","why":"Steroid-resistant myocarditis needs a second immunosuppressant quickly.","source":"sitc-2021","quote":"If signs or symptoms do not respond to corticosteroid therapy within 24 hours, additional therapies such as ATG, mycophenolate mofetil, abatacept, or alemtuzumab should be considered as additional treatment","grade":"LE: 4"},{"action":"Avoid infliximab for steroid-refractory myocarditis","why":"In one study infliximab was linked to a higher risk of cardiovascular death.","source":"sitc-2021","quote":"Caution is advised against the use infliximab for steroid-refractory myocarditis","grade":"LE: 4"},{"action":"Manage in a coronary care unit with temporary pacing quickly available","why":"Heart block and dangerous rhythms can appear suddenly.","source":"sitc-2021","quote":"Management of cardiac irAEs should take place in a coronary care unit, with temporary pacemaker support available for rapid access if indicated."},{"action":"Assess breathing function frequently","why":"Overlapping myositis or myasthenia can weaken the breathing muscles.","source":"sitc-2021","quote":"Should receive frequent pulmonary assessment in addition to typical irAE treatment (ie, corticosteroids)."}],"bestInClass":{"statement":"Of the guidelines that could be read, SITC 2021 is the only one with a myocarditis protocol: admission, cardiology, ECG, troponin and cardiac MRI; methylprednisolone 1000 mg daily for 3 to 5 days as early as possible; serious consideration of permanent discontinuation; second-line antithymocyte globulin, mycophenolate, abatacept or alemtuzumab within 24 hours if there is no response (LE: 4), and caution against infliximab (LE: 4). Every recommendation rests on retrospective series and case reports; there are no randomised trials. ASCO 2021 (abstract) agrees that cardiac toxicity is not one where treatment continues at grade 1. The 2022 ESC cardio-oncology guideline, the 2025 ESC myocarditis guideline and ESMO 2022 could not be read, so whether they differ on dose, timing or the second-line agent is not stated here.","sources":["sitc-2021","asco-2021","esc-2022-cardio-oncology","esc-2025-myocarditis","esmo-2022"]},"variants":[{"name":"Baseline ECG and troponin for patients at higher risk (SITC 2021)","differs":"Considers a baseline ECG for patients at higher risk of myocarditis (cardiac disease, diabetes, combined PD-(L)1 and CTLA-4 blockade) and a baseline troponin, so that later results can be compared; SITC notes there is no evidence that troponin screening in patients without symptoms improves outcome.","evidence":"Expert consensus; no level of evidence printed.","sources":["sitc-2021"]}],"grades":[{"claim":"Second-line antithymocyte globulin, mycophenolate mofetil, abatacept or alemtuzumab if no response in 24 hours","grade":"LE: 4","source":"sitc-2021"},{"claim":"Caution against infliximab in steroid-refractory myocarditis","grade":"LE: 4","source":"sitc-2021"},{"claim":"Methylprednisolone 1000 mg daily for 3 to 5 days, and admission with cardiology","grade":"not graded (expert consensus)","source":"sitc-2021"},{"claim":"Cardiac toxicity is an exception to continuing treatment at grade 1","grade":"expert consensus","source":"asco-2021","quote":"in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, except for some neurologic, hematologic, and cardiac toxicities."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esc-2022-cardio-oncology","label":"2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)","publisher":"European Society of Cardiology, European Heart Journal","year":2022,"url":"https://doi.org/10.1093/eurheartj/ehac244","doi":"10.1093/eurheartj/ehac244","read":"not-reachable","accessed":"2026-11-11"},{"key":"esc-2025-myocarditis","label":"2025 ESC Guidelines for the management of myocarditis and pericarditis","publisher":"European Society of Cardiology, European Heart Journal","year":2025,"url":"https://doi.org/10.1093/eurheartj/ehaf192","doi":"10.1093/eurheartj/ehaf192","read":"not-reachable","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The 2022 ESC cardio-oncology guideline (the European cardiology standard for checkpoint inhibitor myocarditis) and the 2025 ESC guideline on myocarditis and pericarditis could not be read: the publisher returned 403 to a script and Europe PMC holds neither abstract nor full text. Their diagnostic criteria, steroid regimen and second-line choices are not compared here.","The ASCO 2021 guideline was read only as its abstract and its cardiac table is not compared here.","No randomised trial of any treatment for checkpoint inhibitor myocarditis was found among the sources read; the evidence for early steroids is one retrospective study of 126 patients, and the second-line agents rest on case series (LE: 4).","Whether routine troponin screening during treatment changes outcomes is unknown; SITC says there is no evidence that it does in patients without symptoms."]},{"id":"irae-pneumonitis","kind":"protocol","name":"Immune-related pneumonitis from checkpoint inhibitors, by grade","aka":["checkpoint inhibitor pneumonitis","CIP","immune checkpoint inhibitor lung inflammation","ICI pneumonitis management","immunotherapy pneumonitis"],"tldr":"Immunotherapy can inflame the lungs. A new cough, breathlessness or chest pain during or after immunotherapy should be reported to your cancer team the same day. A CT scan of the chest confirms it, and steroids are the main treatment; severe cases need hospital and steroids through a drip.","summary":"Pneumonitis occurs in about 4% of people on PD-(L)1 inhibitors (1% grade 3 or more), 1% on anti-CTLA-4 and 7% on combinations in trials, with higher rates in single-centre practice (19% in one series) and in lung and kidney cancer, smokers, people with asthma or prior chest radiotherapy (SITC 2021). Median onset is about 3 months.\n\nSITC 2021: high-resolution CT of the chest for suspected pneumonitis, with pulmonary function tests (spirometry and DLCO) if the CT is negative. Grade 2: prednisone 1 to 2 mg/kg/day, tapered over 4 to 6 weeks. Grade 3 or more: intravenous methylprednisolone 1 to 2 mg/kg/day, tapered over 4 to 6 weeks. If high-dose steroids do not help within 72 hours, or the illness is life-threatening, the options, in no order, are mycophenolate mofetil, high-dose IVIG, infliximab, cyclophosphamide or tocilizumab, each on low-level evidence. After grade 2, re-challenge may follow complete resolution, with closer follow-up; recurrence was 25% in a small series.\n\nASCO 2021 gives the general frame: hold for grade 2, high-dose steroids for grade 3, taper over at least 4 to 6 weeks, permanently stop for grade 4. The Chinese 2022 consensus grades by symptoms and the share of lung involved on CT, monitors grade 1, treats grades 2 to 3 with prednisolone-equivalent 1 to 2 mg/kg/day, assesses response at 48 to 72 hours and keeps steroid courses to 6 to 8 weeks, not over 12. ESMO 2022 could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","acute-oncology"],"related":["irae-colitis","idea-bio2-steroid-sparing-irae"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","dostarlimab","tremelimumab","avelumab","prednisone","cyclophosphamide","tocilizumab","methylprednisolone"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["pneumonitis","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can sometimes inflame the lungs. If you become breathless or start coughing, ring your cancer helpline. Steroids usually help.","domain":"immunotherapy-toxicity","setting":{"who":["patient-or-carer","nurse","doctor","pharmacist"],"where":["telephone-triage","acute-oncology-service","outpatient-clinic","emergency-department","ward","intensive-care"]},"population":"Adults treated with an immune checkpoint inhibitor, alone or combined, who develop new or worsening breathlessness, cough, chest pain, fever or low oxygen, or new changes on a chest scan. Radiation pneumonitis and infection are differential diagnoses, not covered here. Children are not addressed.","trigger":"New or worsening cough, breathlessness, chest pain or falling oxygen saturation during or after checkpoint inhibitor treatment, or new lung changes on a routine scan.","steps":[{"action":"Before starting, refer people with existing autoimmune interstitial lung disease to a lung specialist for lung function tests and risk assessment","why":"Existing lung scarring raises the risk of pneumonitis, so a baseline helps both the decision to treat and later comparison.","source":"sitc-2021","quote":"Patients with pre-existing autoimmune ILD should be referred to a specialist where possible before initiation of ICI therapy for the consideration of pulmonary function tests (PFTs) and risk assessment","grade":"LE: 3"},{"action":"Teach the patient that a new cough, breathlessness or chest pain must be reported promptly","why":"Pneumonitis can worsen quickly, so it needs prompt assessment.","source":"sitc-2021","quote":"Patients should receive dedicated education on irAEs by a medical professional and may receive additional materials such as informational booklets or reference cards."},{"action":"Arrange a high-resolution CT of the chest for suspected pneumonitis; if it is normal, consider lung function tests including spirometry and DLCO","why":"CT shows the inflammation; lung function tests can find a deficit that the scan misses.","source":"sitc-2021","quote":"Patients with suspected pneumonitis should be examined via high-resolution CT of the chest. If the CT scan is negative, PFTs should be considered to identify a potential functional deficit","grade":"LE: 4"},{"action":"Look for infection and other causes alongside, without delaying treatment","why":"Infection, clots, heart failure, radiation pneumonitis and the cancer itself can all look like pneumonitis.","source":"sitc-2021","quote":"Diagnostic evaluation for all irAEs should attempt to rule out other possible etiologies (eg, diarrhea/colitis associated with Clostridium difficile infection), but treatment for irAEs should be initiated as is deemed clinically appropriate."},{"action":"For grade 1, keep monitoring; for grade 2, hold the checkpoint inhibitor","why":"Under the general rules, grade 1 can continue with close follow-up and grade 2 needs a pause and treatment.","source":"sitc-2021","quote":"Unless otherwise specified, patients experiencing grade 2 irAEs should have ICI therapy temporarily withheld and be treated with corticosteroids depending on the toxicity in question."},{"action":"For grade 2, give prednisone 1 to 2 mg/kg/day (or equivalent) and taper over 4 to 6 weeks; for grade 3 or more, give intravenous methylprednisolone 1 to 2 mg/kg/day and taper over 4 to 6 weeks","why":"Steroids settle the inflammation in most people; the slower taper reduces relapse.","source":"sitc-2021","quote":"Patients experiencing grade 2 pneumonitis should receive 1–2 mg/kg/day prednisone (or equivalent), tapering over 4–6 weeks. For pneumonitis of grade ≥3, patients should receive 1–2 mg/kg/day methylprednisolone IV or equivalent, tapering over 4–6 weeks","grade":"LE: 3"},{"action":"Counsel about steroid side effects, including Pneumocystis pneumonia","why":"Long courses of high-dose steroids raise the risk of infection, high blood sugar and mood change.","source":"sitc-2021","quote":"When beginning corticosteroid therapy, patients should be specifically counseled about potential toxicities, including hyperglycemia, mood disturbances, insomnia, gastritis, weight gain, and opportunistic infections (eg, Pneumocystis pneumonia)","grade":"LE: 1"},{"action":"For grade 3, suspend the checkpoint inhibitor; after grade 4, stop it permanently","why":"Life-threatening pneumonitis generally rules out further checkpoint inhibitor treatment under ASCO's general rules.","source":"asco-2021","quote":"In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, except for endocrinopathies that have been controlled by hormone replacement.","grade":"expert consensus"},{"action":"If there is no improvement within 72 hours of high-dose steroids, or the illness is life-threatening, add a second immunosuppressant with a lung specialist","why":"Steroid-refractory pneumonitis has a high death rate; SITC lists mycophenolate mofetil, high-dose IVIG, infliximab, cyclophosphamide or tocilizumab in no particular order.","source":"sitc-2021","quote":"If high-dose corticosteroid therapy does not improve pneumonitis symptoms within 72 hours (or if symptoms are life-threatening), options include (in no particular order) mycophenolate mofetil (1–1.5 g two times per day, tapering in consultation with a pulmonary specialist","grade":"LE: 3 (mycophenolate), LE: 4 (IVIG, infliximab, tocilizumab)"},{"action":"After grade 2 pneumonitis, consider re-challenge only once symptoms have fully resolved, with more frequent review afterwards","why":"Pneumonitis can come back, with or without re-challenge.","source":"sitc-2021","quote":"If patients have experienced grade 2 pneumonitis, they may be re-challenged with ICIs upon complete resolution of symptoms. These patients should be monitored through more frequent consultations with their physician","grade":"LE: 4"}],"bestInClass":{"statement":"SITC 2021 is the most detailed guideline that could be read: high-resolution chest CT, prednisone 1 to 2 mg/kg/day for grade 2 and intravenous methylprednisolone 1 to 2 mg/kg/day for grade 3 or more, each tapered over 4 to 6 weeks (LE: 3), a second immunosuppressant after 72 hours without response, and re-challenge after grade 2 only when symptoms have fully resolved. ASCO 2021 agrees on the frame and on a taper of at least 4 to 6 weeks, and permanently stops checkpoint inhibitors after grade 4. The Chinese 2022 consensus adds CT extent to the grade, a 48 to 72 hour response check and a 6 to 8 week, at most 12 week, steroid course. ESMO 2022 was not read. All the second-line drugs rest on case series or small cohorts; none has been compared in a randomised trial that could be read.","sources":["sitc-2021","asco-2021","cn-cip-2022","esmo-2022"]},"variants":[{"name":"Grading by CT extent and a fixed steroid course (Chinese expert consensus, 2022)","differs":"Grades pneumonitis by symptoms together with the share of lung involved on CT (under 25%, 25 to 50%, over 50%), recommends prednisolone-equivalent 1 to 2 mg/kg/day for grades 2 to 3 and intravenous steroids for more severe or acute cases, checks response at 48 to 72 hours and limits the course to 6 to 8 weeks, not more than 12. It judges Pneumocystis prophylaxis generally unnecessary except for 20 mg a day for more than 6 weeks.","evidence":"Expert consensus, not graded.","sources":["cn-cip-2022"]},{"name":"Permanent stop after grade 4 (ASCO 2021)","differs":"States permanent discontinuation for grade 4 toxicities in general; SITC allows re-challenge only after grade 2 pneumonitis.","evidence":"Expert consensus.","sources":["asco-2021"]}],"grades":[{"claim":"Grade 2: prednisone 1 to 2 mg/kg/day; grade 3 or more: intravenous methylprednisolone 1 to 2 mg/kg/day; taper over 4 to 6 weeks","grade":"LE: 3","source":"sitc-2021"},{"claim":"High-resolution chest CT for suspected pneumonitis; lung function tests if CT is negative","grade":"LE: 4","source":"sitc-2021"},{"claim":"Mycophenolate mofetil for steroid-refractory pneumonitis","grade":"LE: 3","source":"sitc-2021"},{"claim":"High-dose IVIG, infliximab or tocilizumab for steroid-refractory pneumonitis","grade":"LE: 4","source":"sitc-2021"},{"claim":"Re-challenge after grade 2 once symptoms have completely resolved","grade":"LE: 4","source":"sitc-2021"},{"claim":"Steroid taper over at least 4 to 6 weeks; permanent discontinuation after grade 4","grade":"expert consensus","source":"asco-2021","quote":"Corticosteroids should be tapered over the course of at least 4-6 weeks."},{"claim":"Response to steroids assessed within 48 to 72 hours","grade":"expert consensus (not graded)","source":"cn-cip-2022","quote":"For CIP, clinical improvements should be assessed within 48 to 72 hours of GCS treatment."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"},{"key":"cn-cip-2022","label":"Chinese expert consensus on the multidisciplinary management of pneumonitis associated with immune checkpoint inhibitor","publisher":"Thoracic Cancer (Chinese expert panel)","year":2022,"url":"https://europepmc.org/article/PMC/PMC9715776","doi":"10.1111/1759-7714.14693","gradingScheme":"Nine consensus statements; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline update was read only as its abstract, which gives the general rules (continue for grade 1, hold for most grade 2, high-dose steroids for grade 3, taper over at least 4 to 6 weeks, stop for grade 4) but not its organ-by-organ tables.","A 2025 Chinese expert consensus on the diagnosis and management of checkpoint inhibitor pneumonitis (doi 10.3760/cma.j.cn112147-20241121-00694) is listed in Europe PMC without open full text; it was not read.","SITC names an ECOG-ACRIN trial comparing IVIG with infliximab for steroid-refractory pneumonitis; its result was not looked for here, and no randomised evidence on second-line treatment was read.","Guidelines differ on whether steroid courses for pneumonitis need Pneumocystis prophylaxis; SITC asks for counselling, the Chinese consensus limits prophylaxis to 20 mg a day for more than 6 weeks, and the ASCO and ESMO positions were not read."]},{"id":"irae-skin","kind":"protocol","name":"Immune-related skin reactions from checkpoint inhibitors, including blistering and severe erosive rashes","aka":["checkpoint inhibitor rash","immunotherapy skin toxicity","ICI bullous pemphigoid","ICI SJS/TEN","dermatologic irAE","D-irAE"],"tldr":"Rash and itching are among the commonest and earliest side effects of immunotherapy, usually a few weeks in, and most are mild. Blisters, peeling skin, sore skin, or sores in the mouth, eyes or genitals are different: they can be serious and need the cancer team the same day.","summary":"Rash occurs in 23% on anti-CTLA-4 (1% grade 3 or more), 10% on anti-PD-(L)1 and 41% on combinations (5% grade 3 or more), on average 3 to 4 weeks after starting (SITC 2021). Rare severe forms include bullous pemphigoid (about 1% on anti-PD-(L)1), pemphigus, lichenoid eruptions and SJS/TEN, which has mucosal involvement and can arise suddenly or evolve from a lichenoid rash that fails treatment.\n\nSITC 2021: for itch without rash, high-potency topical steroids and GABA agonists may be considered (LE: 4). Work up rash with blood count, metabolic panel, percentage of body surface affected, special features (blisters, mucosal involvement) and allergy history; consider dermatology referral, and for grade 3 or more refer and consider biopsy. Blisters or mucosal involvement trigger biopsy with direct immunofluorescence and serology for pemphigus and pemphigoid. Interrupt the checkpoint inhibitor until resolution or significant improvement. Refer to dermatology if topical or oral steroids fail, the rash is grade 3 or more, or intolerable. For rashes that recur on taper, a steroid-sparing drug matched to the diagnosis: rituximab for pemphigus (LE: 1) or bullous pemphigoid (LE: 4), dupilumab for eczema (LE: 1), infliximab for lichenoid rash, omalizumab for urticaria or itch (LE: 1). Re-challenge after grade 3 rash is possible. A rash not responding to immunosuppression may be infected.\n\nThe 2024 D-irAE consensus separates ICI-erosive mucocutaneous disease, including an SJS/TEN-like acute form, from classic SJS/TEN and says it usually means at least holding and often permanently stopping the checkpoint inhibitor. ESMO 2022 could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","dermatology"],"related":["irae-colitis","checkpoint-inhibitor-baseline-and-monitoring"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab","rituximab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy often causes an itchy rash, which creams usually settle. Blisters, painful or peeling skin, or mouth sores need a same-day call to your cancer team.","domain":"immunotherapy-toxicity","setting":{"who":["patient-or-carer","nurse","doctor","pharmacist"],"where":["telephone-triage","outpatient-clinic","acute-oncology-service","ward"]},"population":"Adults treated with an immune checkpoint inhibitor who develop itch, rash, blistering or mucosal sores. Rashes from other drugs given at the same time (for example antibiotics or chemotherapy) are a differential diagnosis. Children are not addressed.","trigger":"New itch or rash during or after checkpoint inhibitor treatment, and urgently any blistering, skin pain, peeling or sores in the mouth, eyes or genitals.","steps":[{"action":"For itch without a rash, consider a high-potency topical steroid and a GABA agonist","why":"Itch alone often responds to treatment on the skin and a nerve-calming tablet.","source":"sitc-2021","quote":"For patients with pruritus without rash, treatment with high-potency topical corticosteroids and GABA agonists may be considered","grade":"LE: 4"},{"action":"For a rash, check blood count and metabolic panel, estimate the body surface area involved, look for blisters or mucosal involvement, and ask about allergy","why":"Body surface area sets the grade, and blisters or mucosal sores point to rarer, more serious diagnoses.","source":"sitc-2021","quote":"Workup for patients with potential ICI-related rash (grade <3) should include CBC with differential, CMP, assessment of the percentage body surface area involved by the rash, assessment of special features (eg, bullous formation, mucosal involvement), and patient history of allergy or atopy."},{"action":"For grade 3 or more, refer to a dermatologist and consider a skin biopsy","why":"Severe rashes need a firm diagnosis to choose the right treatment.","source":"sitc-2021","quote":"Workup for patients with potential ICI-related rash (grade ≥3) should also include referral to a dermatologist and possible skin biopsy."},{"action":"If there are blisters or mucosal sores, suspect pemphigoid, pemphigus, lichenoid rash or SJS/TEN and arrange biopsy with immunofluorescence and antibody tests","why":"These conditions look alike but are treated differently, and SJS/TEN can be life-threatening.","source":"sitc-2021","quote":"Rash with blisters, mucosal involvement, or bullous formation should trigger suspicion of lichenoid rash, pemphigus, pemphigoid, or SJS/TEN and follow-up testing, including skin biopsy with direct immunofluorescence studies and serum antibodies to desmogleins 1 and 3, bullous pemphigoid antigens 1 and 2, and indirect immunofluorescence studies in salt-split skin."},{"action":"Interrupt the checkpoint inhibitor until the rash has resolved or improved significantly","why":"Pausing the drug lets the skin settle; for most rashes it can be restarted.","source":"sitc-2021","quote":"ICI therapy should be interrupted until resolution or significant improvement of symptoms."},{"action":"Ask for a dermatology opinion if the rash does not respond to topical or oral steroids, is grade 3 or more, or is intolerable","why":"Specialist diagnosis opens up targeted treatments and avoids long courses of steroids.","source":"sitc-2021","quote":"If ICI-related rash does not respond to topical or oral corticosteroids, is grade ≥3, or is intolerable, a dermatological consultation is recommended."},{"action":"If a grade 2 or higher rash comes back as steroids are tapered, use a steroid-sparing drug matched to the diagnosis","why":"Rituximab for pemphigus or pemphigoid, dupilumab for eczema, infliximab for lichenoid rash and omalizumab for urticaria or itch avoid repeated steroid courses.","source":"sitc-2021","quote":"Grade ≥2 dermatological events (rash, pruritus) may recur after steroid taper. Therefore, a dermatological consultation or use of a steroid-sparing agent is recommended (rituximab for pemphigus","grade":"LE: 1 (rituximab for pemphigus, dupilumab, omalizumab); LE: 4 (rituximab for pemphigoid)"},{"action":"If a rash does not respond to immune suppression, take cultures for infection","why":"Steroid-treated skin can become infected, which looks like a worsening rash.","source":"sitc-2021","quote":"Rash that does not respond to immunosuppressive therapy should underscore the possibility of an infection and corresponding cultures should be obtained."},{"action":"Treat erosive mucocutaneous disease, including the SJS/TEN-like form, as an emergency that usually means holding and often permanently stopping the checkpoint inhibitor","why":"Skin pain, erosions and a positive Nikolsky sign coming on within two weeks signal a severe reaction that usually needs systemic immune suppression.","source":"dirae-2024","quote":"This presentation, given its severity, usually necessitates at least holding of the ICI, and often permanent discontinuation of ICI therapy."},{"action":"After a grade 3 rash that has settled, consider re-challenge","why":"Most skin reactions do not rule out further immunotherapy.","source":"sitc-2021","quote":"Patients who have experienced grade 3 ICI-related rash may be re-challenged with ICIs."}],"bestInClass":{"statement":"SITC 2021 is the most detailed guideline read: assess body surface area and special features, interrupt the checkpoint inhibitor until improvement, refer to dermatology for grade 3 or more or for treatment failure, biopsy blistering or mucosal rashes, and use steroid-sparing drugs matched to the diagnosis when rashes recur on taper (rituximab for pemphigus, LE: 1; dupilumab for eczema, LE: 1; omalizumab for urticaria or itch, LE: 1). The 2024 D-irAE consensus adds diagnostic definitions, separating ICI-erosive mucocutaneous disease, with an acute SJS/TEN-like subtype and an indolent erosive lichen planus-like subtype, and states that it usually means holding and often permanently stopping the checkpoint inhibitor. ASCO 2021's general frame applies (continue at grade 1, hold at grade 2, high-dose steroids and suspension at grade 3, permanent stop at grade 4); its skin table and ESMO 2022 were not read.","sources":["sitc-2021","dirae-2024","asco-2021","esmo-2022"]},"variants":[{"name":"Consensus disease definitions for skin irAEs (D-irAE, 2024)","differs":"Defines specific dermatologic irAEs by expert panel adjudication, including ICI-erosive mucocutaneous disease with an acute SJS/TEN-like subtype (onset over at most 2 weeks without a preceding rash, erosive plaques, positive Nikolsky sign) and an indolent erosive lichen planus-like subtype.","evidence":"Consensus definitions for diagnosis and research, not treatment recommendations.","sources":["dirae-2024"]}],"grades":[{"claim":"High-potency topical steroids and GABA agonists for itch without rash","grade":"LE: 4","source":"sitc-2021"},{"claim":"Rituximab for pemphigus","grade":"LE: 1","source":"sitc-2021"},{"claim":"Rituximab for bullous pemphigoid","grade":"LE: 4","source":"sitc-2021"},{"claim":"Dupilumab for eczema; omalizumab for urticaria or itch","grade":"LE: 1","source":"sitc-2021"},{"claim":"General rule: grade 3 toxicities warrant suspension and high-dose corticosteroids","grade":"expert consensus","source":"asco-2021","quote":"Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"dirae-2024","label":"Defining D-irAEs: consensus-based disease definitions for the diagnosis of dermatologic adverse events from immune checkpoint inhibitor therapy","publisher":"Journal for ImmunoTherapy of Cancer (international expert panel)","year":2024,"url":"https://europepmc.org/article/PMC/PMC11015215","doi":"10.1136/jitc-2023-007675","gradingScheme":"Expert panel adjudication with median scores (1 to 9) for each element of a definition; definitions, not graded recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline update was read only as its abstract, which gives the general rules (continue for grade 1, hold for most grade 2, high-dose steroids for grade 3, taper over at least 4 to 6 weeks, stop for grade 4) but not its organ-by-organ tables.","SITC gives no steroid doses specific to severe skin reactions, and none of the sources read sets out burns-unit or intensive care management of SJS/TEN; those steps are not written here.","The 2024 Chinese expert consensus on checkpoint inhibitor skin reactions is listed in Europe PMC without open full text and was not read."]},{"id":"irae-diabetes","kind":"protocol","name":"Immune-related type 1 diabetes and diabetic ketoacidosis from checkpoint inhibitors","aka":["checkpoint inhibitor diabetes","ICI-induced diabetes","ir-T1DM","CPI-DM","CIADM","immunotherapy diabetes","checkpoint inhibitor DKA"],"tldr":"Rarely, immunotherapy destroys the cells that make insulin. Blood sugar can rise within days and become dangerous (diabetic ketoacidosis). Thirst, passing a lot of urine, being sick or feeling drowsy need urgent help. It is treated with insulin, which is almost always lifelong, and not with steroids.","summary":"Rare (about 1%; 0.2 to 1.4% in the SITC 2025 definitions) but frequently serious: diabetic ketoacidosis is present at diagnosis in up to 70% (ESE 2022). Most cases follow PD-1 or PD-L1 inhibitors (76% and 8% in the series ESE cites, against 4% for CTLA-4 inhibitors); onset ranges from soon after the first dose to a year later (median 2 to 4.8 months). Autoantibodies (mostly GAD65) are found in 40 to 53%. SGLT2 inhibitors add to the risk of ketoacidosis (ESE).\n\nGlucose is checked before every infusion and HbA1c at the start (SITC 2025 definitions). New or worsening hyperglycaemia above 11.1 mmol/L (200 mg/dL), especially without diabetes or new steroids, raises suspicion; urine ketones and blood pH screen for ketoacidosis. Ketoacidosis is treated in hospital with intravenous insulin and fluids under the usual protocols, and the checkpoint inhibitor is held until it resolves. Insulin is started urgently once the diagnosis is suspected; high-dose steroids do not help (ESE, +000). C-peptide and islet autoantibodies support the diagnosis but a normal C-peptide early on does not exclude it. Treatment is a multiple-injection insulin regimen with endocrinology referral and education; recovery is rare.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","endocrine","acute-oncology"],"related":["irae-thyroid","irae-hypophysitis-adrenal","checkpoint-inhibitor-baseline-and-monitoring"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","atezolizumab","durvalumab","cemiplimab","avelumab","dostarlimab","ipilimumab","tremelimumab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["immune-endocrinopathy","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Very rarely, immunotherapy causes diabetes that needs insulin. If you are very thirsty, passing a lot of urine or being sick, contact your cancer helpline straight away.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","emergency-team","patient-or-carer","pharmacist"],"where":["chemotherapy-day-unit","outpatient-clinic","emergency-department","acute-oncology-service","telephone-triage","ward"]},"population":"Adults receiving or who have received an immune checkpoint inhibitor, most often a PD-1 or PD-L1 inhibitor. People with pre-existing type 2 diabetes can also develop it. Children are not addressed by these sources.","trigger":"Raised blood glucose on a pre-infusion test, or thirst, passing large amounts of urine, weight loss, vomiting, abdominal pain or drowsiness during or after checkpoint inhibitor treatment.","steps":[{"action":"Check glucose before every infusion and HbA1c when the checkpoint inhibitor is started","why":"This diabetes comes on quickly, so a routine glucose test is the earliest warning.","source":"sitc-2025-endocrine","quote":"To enable prompt identification of ir-T1DM, ICI-treated patients should undergo routine metabolic panels including glucose measurement prior to each infusion, as well as glycated hemoglobin at ICI initiation."},{"action":"Suspect immune diabetes in anyone with new or worsening glucose above 11.1 mmol/L (200 mg/dL), especially without diabetes or new steroids","why":"Steroids and type 2 diabetes are common causes of high sugar; a sudden rise without them points to the immunotherapy.","source":"sitc-2025-endocrine","quote":"ir-T1DM should be suspected in any patient with emergent or worsening hyperglycemia (>200 mg/dL or 11.1 mmol/L) following ICI treatment, especially in those with no history of diabetes and no new prescription of glucocorticoids, and in those with previously well-controlled T2DM."},{"action":"Test urine ketones and blood pH in anyone with high glucose","why":"Ketoacidosis is common at diagnosis and can be found before it becomes life-threatening.","source":"ese-2022","quote":"When hyperglycemia is present, urine ketone testing and blood pH measurement are recommended for early diagnosis of diabetic ketoacidosis (DKA)."},{"action":"Admit for severe hyperglycaemia or ketoacidosis, and hold the checkpoint inhibitor until ketoacidosis has resolved","why":"Ketoacidosis needs hospital treatment, and the next dose can wait until it is under control.","source":"sitc-2021","quote":"If patients experience severe hyperglycemia or DKA on ICIs, they should be hospitalized."},{"action":"Treat ketoacidosis with intravenous insulin and fluid resuscitation under the hospital's standard guideline","why":"Immune diabetes causes a profound lack of insulin, so it is treated like any severe ketoacidosis.","source":"ese-2022","quote":"We recommend that patients presenting with DKA should be managed with i.v. insulin and fluid resuscitation according to current guidelines","grade":"good clinical practice"},{"action":"Start insulin urgently once immune diabetes is suspected, even if the cause of the high sugar is not yet certain","why":"Waiting for proof risks a hyperglycaemic crisis; the diagnosis can be revisited once the patient is stable.","source":"sitc-2025-endocrine","quote":"Once ir-T1DM is suspected, or if the etiology of hyperglycemia is unclear, the patient should be considered for urgent insulin initiation, to minimize the risk of hyperglycemic crisis."},{"action":"Do not give high-dose steroids to treat the diabetes","why":"Steroids do not rescue the insulin-making cells and push blood sugar higher.","source":"ese-2022","quote":"We recommend against the use of high-dose glucocorticoids for treatment of ICI-induced DM","grade":"+000"},{"action":"Send HbA1c, C-peptide and islet autoantibodies, and counsel on diet, glucose monitoring and insulin","why":"These tests support the diagnosis, and the patient needs the skills to manage insulin from the start.","source":"sitc-2021","quote":"Patients with new-onset diabetes (type I) should be tested for hemoglobin A1c, C-peptide, autoantibodies and counseled on diabetes management, including diet and lifestyle changes, glucose monitoring, and insulin treatment."},{"action":"Do not let a detectable C-peptide early on rule the diagnosis out; repeat glucose and C-peptide within a month","why":"Insulin production can fall quickly over the first weeks.","source":"sitc-2025-endocrine","quote":"A detectable C-peptide should not be regarded as a reassuring result to exclude the diagnosis of ir-T1DM, as C-peptide level can decline rapidly in ir-T1DM."},{"action":"Continue with subcutaneous insulin, usually a multiple-injection regimen, with targets set for the person's age and prognosis","why":"The insulin-making cells rarely recover, so insulin is almost always lifelong.","source":"ese-2022","quote":"We recommend treating ICI-induced persistent DM due to islet destruction with s.c. insulin","grade":"++00"},{"action":"Refer promptly to an endocrinologist experienced in type 1 diabetes","why":"Insulin-deficient diabetes needs close glucose monitoring and dose adjustment.","source":"sitc-2025-endocrine","quote":"Patients with suspected or confirmed ir-T1DM should therefore be referred promptly to an endocrinologist with expertise in T1DM management."}],"bestInClass":{"statement":"SITC 2021, ESE 2022 and the SITC 2025 endocrine definitions agree: screen glucose routinely, look for ketoacidosis when glucose is high, treat ketoacidosis in hospital with intravenous insulin and fluids, start insulin early, and do not use high-dose steroids. ESE is the only one to grade its recommendations (GRADE): subcutaneous insulin for persistent diabetes ++00, no high-dose glucocorticoids +000. SITC 2021 holds the checkpoint inhibitor until ketoacidosis resolves; ESE treats a controlled endocrinopathy as no reason to stop. None of the sources read sets a glucose threshold for holding treatment other than ketoacidosis.","sources":["ese-2022","sitc-2021","sitc-2025-endocrine"]},"variants":[{"name":"Hold only until ketoacidosis resolves (SITC 2021)","differs":"Evaluates every patient with hyperglycaemia for ketoacidosis and holds the checkpoint inhibitor until it is resolved, rather than holding for diabetes as such.","evidence":"Expert consensus; no level of evidence printed.","sources":["sitc-2021"]}],"grades":[{"claim":"Intravenous insulin and fluids for ketoacidosis","grade":"good clinical practice","source":"ese-2022"},{"claim":"No high-dose glucocorticoids for checkpoint inhibitor diabetes","grade":"+000","source":"ese-2022"},{"claim":"Subcutaneous insulin for persistent diabetes","grade":"++00","source":"ese-2022"},{"claim":"Regular training on managing the condition, including diet and physical activity","grade":"Good clinical practice","source":"ese-2022","quote":"We recommend that patients with DM are provided with appropriate and regular training on managing their condition and treatment, including diet and physical activity"}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"ese-2022","label":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline","publisher":"European Society of Endocrinology, European Journal of Endocrinology","year":2022,"url":"https://europepmc.org/article/PMC/PMC9641795","doi":"10.1530/EJE-22-0689","gradingScheme":"GRADE: quality of evidence printed as +000 (very low), ++00 (low), +++0 (moderate) or ++++ (strong); 'recommend' is a strong and 'suggest' a weak recommendation; recommendations not formally graded are marked good clinical practice.","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-2025-endocrine","label":"Consensus-based disease definitions for endocrine immune-related adverse events of immune checkpoint inhibitors","publisher":"Journal for ImmunoTherapy of Cancer","year":2025,"url":"https://europepmc.org/article/PMC/PMC12530408","doi":"10.1136/jitc-2025-011865","gradingScheme":"RAND/UCLA Appropriateness Method (modified Delphi) consensus of a multidisciplinary panel; statements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline was read only as its abstract, which does not give its diabetes recommendations.","No source read says whether, or when, to restart the checkpoint inhibitor after ketoacidosis has been treated; ESE's general position is that a controlled endocrinopathy does not stop treatment.","The evidence is small: ESE's systematic review found two studies with 29 patients in total, with insulin withdrawal reported in one."]},{"id":"implanted-port-access-and-care","kind":"protocol","name":"Implanted port access, flushing and care in adults having cancer treatment","aka":["port access","accessing a portacath","port-a-cath care","Huber needle access","port flush","port de-access","TIVAD care","totally implantable venous access device care","chemo port care"],"tldr":"A port is a small disc under the skin of the chest or arm that lets nurses give treatment and take blood through a special needle. Each time it is used the nurse should clean their hands and your skin, check that blood comes back before giving treatment and flush it with salt water, and between courses it is usually flushed about every four weeks.","summary":"Port care rests on general central line infection prevention rather than port-specific trials. Hand hygiene before and after accessing (CDC/HICPAC Category IB) and aseptic technique (CDC IB; NICE CG139 names ANTT as one framework) come first. Skin and hub antisepsis is chlorhexidine in alcohol: CDC IA (>0.5% with alcohol, during dressing changes), epic3 IVAD23 Class A (2% chlorhexidine in 70% isopropyl alcohol, allowed to air dry), ESMO [I, A]. Hubs and connectors are scrubbed before each access (CDC IA, SHEA moderate quality, epic3 IVAD30 Class D/GPP for at least 15 seconds). Drying times beyond 'allow to dry' come from manufacturers and local policy.\n\nAccess is with a non-coring needle under aseptic technique, and blood return is confirmed before treatment; no guideline read grades either step, and the INS standards, which do address port access, could not be read. The site of an accessed port is covered with a sterile transparent dressing changed every 7 days or sooner if lifted or damp (NICE 1.4.3.4; CDC Category II for implanted sites). Needle change intervals are not stated in the national guidelines read; UK local policy changes the needle weekly.\n\nFlush with 0.9% saline after every infusion or sample (ESMO [II, B]; epic3 IVAD34 Class A for frequently accessed lumens). On the lock, the evidence favours saline: the Cochrane review (2022, 12 RCTs, 2422 adults) found low-certainty evidence of fewer occlusions with heparin (RR 0.70, 95% CI 0.51 to 0.95) and was uncertain of any benefit; in ports specifically, a randomised trial of 802 patients found saline non-inferior to heparin 300 U/3 ml. NICE keeps heparin where the port maker recommends it (1.4.4.7, 2003). For ports not in use ESMO recommends a four-weekly flush [III, C]; a 2025 meta-analysis of 11 mostly observational studies tended to support three months, with caution.\n\nNo national or international guideline read recommends a mask for the clinician or the patient, or the patient turning their head away, at port access or dressing change; masks in these guidelines are for line insertion or splash risk. Some local policies require both (variants).","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["implanted-ports","infusion-devices-vascular-access","huber-needles-port-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access","febrile-neutropenia","vte","extravasation-infusion-reaction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A port is a little device under your skin for treatment and blood tests. The nurse cleans their hands and your skin, puts a special needle in, checks it works and rinses it with salt water. Tell your team if the skin over it goes red, sore or swollen, or if you get a fever.","domain":"vascular-access","setting":{"who":["nurse","patient-or-carer"],"where":["chemotherapy-day-unit","ward","outpatient-clinic","home","community"]},"population":"Adults with an implanted port (totally implantable venous access device) having cancer treatment, in any cancer. The general guidelines cited cover all central venous catheters in adults (SHEA states its recommendations are not stratified by catheter type); children, power injection through the port, and ports placed for dialysis or parenteral nutrition alone follow their own protocols and are not covered here.","trigger":"A port is to be used for treatment or blood sampling, or is due its routine flush while not in use.","steps":[{"action":"Look at and feel the skin over the port before you start, and do not use the port if there are signs of infection","why":"Redness, swelling, pain or discharge over the port can mean the pocket is infected, and pushing a needle through it can carry germs into the blood.","source":"cdc-hicpac-2011","quote":"Monitor the catheter sites visually when changing the dressing or by palpation through an intact dressing on a regular basis, depending on the clinical situation of the individual patient.","grade":"Category IB"},{"action":"Clean your hands before and after touching the port, the needle or the dressing","why":"Hands are the commonest route by which germs reach a line.","source":"cdc-hicpac-2011","quote":"Hand hygiene should be performed before and after palpating catheter insertion sites as well as before and after inserting, replacing, accessing, repairing, or dressing an intravascular catheter.","grade":"Category IB"},{"action":"Use aseptic technique throughout, such as Aseptic Non Touch Technique, with sterile gloves for the needle insertion","why":"The port's catheter ends in a large vein near the heart, so anything that touches the needle or hub must stay sterile.","source":"nice-cg139","quote":"An aseptic technique must be used for vascular access device catheter site care and when accessing the system","grade":"[new 2012]"},{"action":"Clean the skin over the port with 2% chlorhexidine in 70% alcohol and let it dry completely before the needle goes in","why":"Chlorhexidine with alcohol kills skin bacteria best, and it only works fully once it has dried; drying also stops it being carried into the skin by the needle.","source":"epic3","quote":"Use a single-use application of 2% chlorhexidine gluconate in 70% isopropyl alcohol (or povidone iodine in alcohol for patients with sensitivity to chlorhexidine) to clean the central catheter insertion site during dressing changes, and allow to air dry.","grade":"Class A"},{"action":"Put a non-coring (Huber type) needle through the centre of the septum, at right angles, until it meets the back of the port","why":"An ordinary needle cuts a core out of the port's silicone membrane and can make it leak; a non-coring needle parts it so it reseals.","practice":"No national guideline that could be read grades or states the needle type, because each assumes it: ESMO names 'huber needle dislodge' among causes of occlusion, and the port manufacturers' instructions and every local policy read (NHS Borders, Shared Health Manitoba) specify a non-coring needle. The INS standards, which address it, could not be read."},{"action":"Draw back to check for blood return before giving any treatment, and do not give vesicant treatment if there is none","why":"Blood coming back shows the needle is in the port and the catheter is open; without it a drug may be going into the tissue instead of the vein.","practice":"No guideline read grades this step, though all assume it: ESMO lists catheter dysfunction and failure of aspiration among signs of occlusion and infection, and the port trial of Goossens 2013 counted 'easy injection, impossible aspiration' as its primary outcome. NHS Borders states it as a rule (see variants)."},{"action":"Scrub the needleless connector or hub with an antiseptic each time before it is used, and access it only with sterile devices","why":"The connector is touched many times during a course of treatment and is a main route for germs into an accessed port.","source":"cdc-hicpac-2011","quote":"Minimize contamination risk by scrubbing the access port with an appropriate antiseptic (chlorhexidine, povidone iodine, an iodophor, or 70% alcohol) and accessing the port only with sterile devices","grade":"Category IA"},{"action":"Flush with 0.9% saline after every infusion and every blood sample","why":"Flushing clears blood and drug from the catheter so it does not clot or let incompatible drugs mix.","source":"esmo-2015","quote":"Routine flushing with saline, after the completion of any infusion or blood sampling, is recommended","grade":"[II, B]"},{"action":"While the needle stays in, cover it with a sterile transparent dressing and change it every 7 days, or sooner if it lifts, gets wet or soiled","why":"A sealed clear dressing keeps germs out and lets the site be checked without removing it.","source":"nice-cg139","quote":"Change the transparent semipermeable membrane dressing covering a central venous access device insertion site every 7 days, or sooner if the dressing is no longer intact or moisture collects under it.","grade":"[2012]"},{"action":"Keep an accessed port out of baths and swimming pools; showering is allowed with the dressing protected","why":"Soaking the needle site lets water and germs under the dressing.","source":"cdc-hicpac-2011","quote":"Do not submerge the catheter or catheter site in water.","grade":"Category IB"},{"action":"Lock the port with 0.9% saline before removing the needle, using heparin only where the port maker's instructions or local policy require it","why":"Trials in adults have not shown clearly that heparin keeps ports open better than saline, and heparin can rarely cause bleeding or a drop in platelets.","source":"nice-cg139","quote":"Preferably, a sterile 0.9 percent sodium chloride injection should be used to flush and lock catheter lumens.","grade":"[2003]"},{"action":"To remove the needle, clean the hub, flush and lock, steady the port with one hand and withdraw the needle, then press on the site with sterile gauze","why":"Steadying the port stops the needle springing back and causing a needlestick injury; pressure stops bleeding.","source":"nice-cg139","quote":"Decontaminate the injection port or vascular access device catheter hub before and after accessing the system using chlorhexidine gluconate in 70% alcohol.","grade":"[new 2012]"},{"action":"When the port is not in use between courses, flush it every four weeks","why":"A regular flush keeps the catheter from blocking; some centres now leave longer gaps (see variants).","source":"esmo-2015","quote":"To maintain patency of subcutaneous ports that are not in active use, a four weekly flush is recommended","grade":"[III, C]"},{"action":"Teach the patient and carer what to watch for and ask them to report any change at the port or any new discomfort","why":"Most problems start between visits, and the person living with the port is the first to see them.","source":"cdc-hicpac-2011","quote":"Encourage patients to report any changes in their catheter site or any new discomfort to their provider.","grade":"Category II"},{"action":"Treat fever, chills, low blood pressure, or redness, pain, swelling or discharge over the port as a possible line infection: take paired blood cultures from the port and a vein and start treatment","why":"Infection of the port or bloodstream needs blood cultures before antibiotics and can need the port removed; in someone with low white cells it is an emergency.","source":"esmo-2015","quote":"If CRBSI is suspected, collect paired blood (acquiring the same volume of blood) from the catheter and from a peripheral vein","grade":"[II, A]"},{"action":"If the port will not flush or will not give blood back, or the arm, neck or face swells, stop and get it assessed, with an ultrasound scan if a clot is suspected","why":"A blocked port or a clot around the catheter needs to be found and treated rather than forced.","source":"esmo-2015","quote":"Doppler ultrasound should be carried out if thrombosis is suspected","grade":"[III, A]"}],"bestInClass":{"statement":"Hand hygiene, aseptic technique, chlorhexidine in alcohol on the skin and hub allowed to dry, a non-coring needle, a check for blood return, a 0.9% saline flush after every use, a transparent dressing changed every 7 days while accessed, and a four-weekly flush when the port is not in use (ESMO 2015 [III, C]). On the lock, the guidelines differ. ESMO 2015 and epic3 (Class A for frequently accessed lumens) favour saline, supported by a port-specific randomised trial (Goossens 2013, saline non-inferior to heparin in 802 patients) and a Cochrane review (2022) that could not show heparin is better; NICE CG139 (2003 wording) keeps heparin where the port manufacturer recommends it, and ESMO says that if heparin is used it should be more than 500 units. Masks for the clinician or patient, and the patient turning their head away, are not part of any national or international guideline read; they are local practice.","sources":["esmo-2015","cdc-hicpac-2011","epic3","nice-cg139","cochrane-heparin-saline-2022","goossens-2013"]},"variants":[{"name":"Heparin lock","differs":"Locks the port with heparinised saline (often 100 units/ml) after the saline flush, instead of saline alone. NHS Borders locks with 4 ml of 100 units/ml when the port is not in use; the Manitoba procedure locks with 3 or 6 ml of 100 units/ml depending on port size.","evidence":"Cochrane 2022 (12 RCTs, 2422 adults, two oncology studies): low-certainty evidence that heparin may give fewer occlusions (RR 0.70, 95% CI 0.51 to 0.95), no clear difference in patency duration, bloodstream infection or bleeding, and too few patients to detect heparin-induced thrombocytopenia. Goossens 2013 (802 port patients): saline lock non-inferior to heparin 300 U/3 ml. NICE keeps heparin where the manufacturer recommends it.","sources":["cochrane-heparin-saline-2022","goossens-2013","nice-cg139","nhs-borders-tivad-2020","manitoba-p02-2"]},{"name":"Longer flushing interval between courses","differs":"Flushes a port that is not in use every two to three months, or longer, rather than every four weeks.","evidence":"ESMO notes reports of every 8 weeks or every 3 to 4 months and calls for prospective study. A 2025 meta-analysis of 11 studies (4924 participants, mostly observational) tended to support three-monthly flushing with no expected rise in occlusion or overall complications, to be read with caution; one analysis showed more occlusion at two to three months (RR 1.50) that did not survive sensitivity analysis. A single-centre retrospective study in 617 people with breast cancer found no difference in complications with intervals of 91 to 120 days.","sources":["esmo-2015","liu-flush-interval-2025","wang-breast-flush-2022"]},{"name":"Masks for clinician and patient, and the patient's head turned away","differs":"The clinician wears a procedure mask, a mask is placed on the patient and anyone staying nearby, and the patient lies flat with their head turned away from the port during access. Shared Health Manitoba P02.2 states: \"Put a procedure mask on. Place a mask on the patient, as well as any other individuals who will remain in the vicinity.\" and \"Have the patient lay supine, and turn their head away from the port.\" The procedure applies to all ages, has a sterile field and drape, and is written for paramedic practitioners.","evidence":"No national or international guideline read recommends it (ESMO 2015, CDC/HICPAC 2011, SHEA 2022, epic3, NICE CG139). Those guidelines specify masks only as part of maximal sterile barrier precautions for inserting a central line, or where blood or body fluid may splash (epic3 SP29, Class D/GPP H&S). The rationale is to keep droplets from the mouth and nose off the sterile field; no trial of it at port access was found.","sources":["manitoba-p02-2","cdc-hicpac-2011","shea-clabsi-2022","epic3"]},{"name":"Weekly needle change with a new puncture site, and a minimum skin drying time","differs":"NHS Borders changes the needle weekly if the port is in constant use, using a different puncture site, and lets chlorhexidine dry for at least a minute; it also makes blood return a rule before any intravenous therapy.","evidence":"Local policy (issue 2, August 2020; its review date of July 2023 has passed). The national guidelines read give no needle change interval and no drying time beyond 'allow to dry'.","sources":["nhs-borders-tivad-2020"]}],"grades":[{"claim":"Hand hygiene before and after accessing or dressing an intravascular catheter","grade":"Category IB","source":"cdc-hicpac-2011"},{"claim":"Chlorhexidine above 0.5% with alcohol for skin preparation during dressing changes","grade":"Category IA","source":"cdc-hicpac-2011","quote":"Prepare clean skin with a >0.5% chlorhexidine preparation with alcohol before central venous catheter and peripheral arterial catheter insertion and during dressing changes."},{"claim":"2% chlorhexidine in 70% isopropyl alcohol at the central catheter site during dressing changes, allowed to air dry","grade":"Class A","source":"epic3"},{"claim":"Chlorhexidine above 0.5% with alcohol for antisepsis, as a main strategy against catheter infection","grade":"[I, A]","source":"esmo-2015","quote":"Use of >0.5% chlorhexidine skin preparation with alcohol for antisepsis [I, A]"},{"claim":"Scrub the access port with an antiseptic and access it only with sterile devices","grade":"Category IA","source":"cdc-hicpac-2011"},{"claim":"Disinfect hubs, needleless connectors and injection ports before access","grade":"Quality of Evidence: MODERATE","source":"shea-clabsi-2022","quote":"Disinfect catheter hubs, needleless connectors, and injection ports before accessing the catheter (Quality of Evidence: MODERATE)"},{"claim":"Decontaminate the access port or hub with 2% chlorhexidine in 70% alcohol for at least 15 seconds and let it dry","grade":"Class D/GPP","source":"epic3","quote":"The hub should be cleaned for a minimum of 15 s and allowed to dry before accessing the system."},{"claim":"Saline flush after every infusion or blood sample","grade":"[II, B]","source":"esmo-2015"},{"claim":"Sterile normal saline to flush and lock lumens accessed frequently","grade":"Class A","source":"epic3","quote":"Use sterile normal saline for injection to flush and lock catheter lumens that are accessed frequently."},{"claim":"Heparin versus saline flushing made no difference to thrombosis rates","grade":"[I, C]","source":"esmo-2015","quote":"However, when compared with 0.9% normal saline flushing, no differences in thrombosis rates were found [I, C]"},{"claim":"Heparin lock may reduce occlusion compared with saline (RR 0.70, 95% CI 0.51 to 0.95)","grade":"low-certainty evidence","source":"cochrane-heparin-saline-2022"},{"claim":"Four-weekly flush for ports not in active use","grade":"[III, C]","source":"esmo-2015"},{"claim":"Replace transparent dressings on implanted CVC sites no more than once a week, unless soiled or loose, until the site has healed","grade":"Category II","source":"cdc-hicpac-2011","quote":"Replace transparent dressings used on tunneled or implanted CVC sites no more than once per week (unless the dressing is soiled or loose), until the insertion site has healed."},{"claim":"Paired blood cultures from the catheter and a peripheral vein when line infection is suspected","grade":"[II, A]","source":"esmo-2015"},{"claim":"Remove the line for, among others, port abscess, tunnel infection or severe sepsis","grade":"[II, A]","source":"esmo-2015","quote":"Indications to remove the CVC are: severe sepsis, suppurative (septic) thrombophlebitis, endocarditis, tunnel infection, port abscess"},{"claim":"Masks and eye protection where blood or body fluid may splash into the face and eyes (the only epic3 mask recommendation relevant to line care)","grade":"Class D/GPP H&S","source":"epic3","quote":"Fluid-repellent surgical face masks and eye protection must be worn where there is a risk of blood or body fluids splashing into the face and eyes."},{"claim":"Maximal sterile barrier precautions, including a mask, for inserting central lines, PICCs or a guidewire exchange (not for accessing a port)","grade":"Category IB","source":"cdc-hicpac-2011","quote":"Use maximal sterile barrier precautions, including the use of a cap, mask, sterile gown, sterile gloves, and a sterile full body drape, for the insertion of CVCs, PICCs, or guidewire exchange"}],"sources":[{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I (large good-quality RCT or meta-analysis) to V (no control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system; ungraded statements are standard practice in the experts' view.","read":"full-text","accessed":"2026-11-11"},{"key":"cdc-hicpac-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue (insufficient evidence or no consensus).","read":"full-text","accessed":"2026-11-11"},{"key":"shea-clabsi-2022","label":"Strategies to prevent central line-associated bloodstream infections in acute-care hospitals: 2022 Update","publisher":"SHEA, IDSA, APIC (Infection Control and Hospital Epidemiology)","year":2022,"url":"https://doi.org/10.1017/ice.2022.87","doi":"10.1017/ice.2022.87","gradingScheme":"Quality of evidence HIGH, MODERATE or LOW, with each recommendation classed as an essential practice, an additional approach or an unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"epic3","label":"epic3: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England","publisher":"Journal of Hospital Infection (Loveday et al., commissioned by the Department of Health)","year":2014,"url":"https://doi.org/10.1016/S0195-6701(13)60012-2","doi":"10.1016/S0195-6701(13)60012-2","gradingScheme":"SIGN-style classes A (1++ or consistent 1+ evidence) to D (level 3 or 4 evidence), GPP (good practice point from the guideline group's experience), H&S (health and safety legislation).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-cg139","label":"Healthcare-associated infections: prevention and control in primary and community care (CG139), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg139/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended ([2003], [2012], [new 2012]).","read":"full-text","accessed":"2026-11-11"},{"key":"cochrane-heparin-saline-2022","label":"Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults","publisher":"Cochrane Database of Systematic Reviews","year":2022,"url":"https://doi.org/10.1002/14651858.CD008462.pub4","doi":"10.1002/14651858.CD008462.pub4","gradingScheme":"GRADE certainty of evidence: high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"goossens-2013","label":"Comparing normal saline versus diluted heparin to lock non-valved totally implantable venous access devices in cancer patients: a randomised, non-inferiority, open trial","publisher":"Annals of Oncology (Goossens et al.)","year":2013,"url":"https://doi.org/10.1093/annonc/mdt114","doi":"10.1093/annonc/mdt114","read":"abstract","accessed":"2026-11-11"},{"key":"liu-flush-interval-2025","label":"Is it feasible to prolong the flushing interval for totally implantable venous access devices (TIVADs)? A systematic review and meta-analysis","publisher":"International Journal of Clinical Oncology (Liu et al.)","year":2025,"url":"https://doi.org/10.1007/s10147-024-02665-2","doi":"10.1007/s10147-024-02665-2","read":"abstract","accessed":"2026-11-11"},{"key":"wang-breast-flush-2022","label":"Safety and feasibility assessment of extending the flushing interval in totally implantable venous access port flushing during the non-treatment stage for patients with breast cancer","publisher":"Frontiers in Oncology (Wang et al.)","year":2022,"url":"https://doi.org/10.3389/fonc.2022.1021488","doi":"10.3389/fonc.2022.1021488","read":"abstract","accessed":"2026-11-11"},{"key":"ins-2024","label":"Infusion Therapy Standards of Practice, 9th Edition","publisher":"Infusion Nurses Society (Journal of Infusion Nursing)","year":2024,"url":"https://doi.org/10.1097/NAN.0000000000000532","doi":"10.1097/NAN.0000000000000532","read":"not-reachable","accessed":"2026-11-11"},{"key":"nhs-borders-tivad-2020","label":"Totally Implanted Venous Access Devices (TIVAD) or PortaCath Protocol, issue 2","publisher":"NHS Borders","year":2020,"url":"https://rightdecisions.scot.nhs.uk/media/1806/protocol-for-tivad-port-2020_1.pdf","read":"full-text","accessed":"2026-11-11"},{"key":"manitoba-p02-2","label":"P02.2: Medication and fluid administration by subcutaneous port (clinical procedure, version 2025-05-20)","publisher":"Shared Health Manitoba","year":2025,"url":"https://healthproviders.sharedhealthmb.ca/download/924/p-standard-clinical-procedures/42744/p02-2-medication-fluid-administration-by-subcutaneous-port.pdf","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-masks-and-head-turn-at-port-access-infection-study"],"gaps":["No national or international guideline read (ESMO 2015, CDC/HICPAC 2011, SHEA 2022, epic3 2014, NICE CG139) recommends a mask on the clinician or the patient, or the patient turning their head away, when a port is accessed, flushed or dressed. Their mask recommendations cover central line insertion (maximal sterile barrier precautions) and splash risk only. A public provincial procedure (Shared Health Manitoba P02.2) requires both; whether the INS standards address it could not be checked.","The INS Infusion Therapy Standards of Practice, 9th edition (2024), the most detailed standard on port access, needle change and flushing, could not be read: the journal served no standards text to a script and no open copy was found. Nothing here rests on it.","No current edition of the RCN Standards for Infusion Therapy could be found to read, and the ONS Access Device Standards of Practice is a priced book; neither is cited.","The needle change interval for a port left accessed is not stated in any national guideline read. Weekly change is common local practice (NHS Borders).","Skin drying time: the guidelines say only to let the antiseptic dry, or to follow the manufacturer. The one-minute and 30-second figures in local policies are local.","The heparin versus saline evidence is low to very low certainty across all central venous catheters, with only two oncology studies in the Cochrane review; the Cochrane full text, the Goossens trial and the flushing-interval studies were read as abstracts only.","The ESMO guideline dates from 2015 and the CDC guideline from 2011 (updated 2017); no newer ESMO guideline on venous access was found."]},{"id":"indwelling-pleural-catheter-drainage-at-home","kind":"protocol","name":"Indwelling pleural catheter: draining fluid from the chest at home","aka":["IPC drainage","PleurX drainage at home","Rocket IPC drainage","tunnelled pleural catheter care","home drainage of a malignant pleural effusion","draining a pleural catheter"],"tldr":"An indwelling pleural catheter is a thin tube left in the chest so that fluid caused by cancer can be drained at home, by a nurse, a relative or yourself, using vacuum bottles. Drain as often as your breathing needs, or daily if the aim is for the fluid to stop; slow or stop if it hurts; and call the team for fever, redness, a damaged tube, or worse breathlessness when nothing drains.","summary":"The BTS pleural guideline (2023) offers people with a malignant pleural effusion and no known non-expandable lung a choice of IPC or pleurodesis first line (conditional), and favours an IPC where more than a quarter of the lung will not re-expand. After insertion every patient should be referred to the community nursing team, and patients and relatives supported to drain and keep a drainage diary (good practice points). Drainage uses the manufacturer's vacuum bottles and procedure; the usual starting frequency is three times a week. Daily drainage raises the rate of spontaneous pleurodesis and shortens time to catheter removal (ASAP: 47% vs 24% with every-other-day drainage; AMPLE-2: 44.2% vs 15.9% at 6 months against symptom-guided drainage) without improving breathlessness, so BTS recommends daily drainage only where removal is a priority (conditional) and tells patients they do not need daily drainage to control breathlessness (strong, by consensus). About 500 mL is usually drained at a time, up to 1500 mL, slowed or stopped for pain or cough. Infection (pleural infection 3.2% to 5%) usually responds to antibiotics without removing the catheter (ATS/STS/STR, weak). Removal is considered after less than 50 mL on three consecutive drainages with no reaccumulation on imaging. Talc instilled through the IPC doubles pleurodesis at 35 days (43% vs 23%, IPC-PLUS) and BTS offers it where removal matters (conditional, by consensus).","asOf":"2026-11-11","links":[],"tags":[],"related":["care-in-the-last-days-of-life","malignant-ascites-drainage"],"cancers":["lung-cancer","breast-cancer","mesothelioma","pleural-mesothelioma"],"sections":[],"technologies":["indwelling-pleural-catheters"],"targets":[],"drugs":["talc-sclerosant"],"companies":[],"institutions":[],"pathways":[],"terms":["malignant-pleural-effusion","pleurodesis","pleural-effusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"The tube stays in your chest. A nurse, a family member or you attach a vacuum bottle to drain the fluid when you are breathless. Stop if it hurts. Call your team if you get a fever, the skin goes red, the tube is damaged, or you get more breathless and nothing comes out.","domain":"palliative","setting":{"who":["nurse","patient-or-carer","doctor"],"where":["home","community","outpatient-clinic"]},"population":"Adults with a malignant pleural effusion who have had a tunnelled indwelling pleural catheter (PleurX, Rocket and others) inserted, whether the lung re-expands or not. IPCs for non-malignant (transudative) effusions are not covered: BTS does not in general endorse them. Children are not covered by these sources.","trigger":"Discharge home after insertion of an indwelling pleural catheter.","steps":[{"action":"Before insertion, offer people without known non-expandable lung a choice between an IPC and pleurodesis, and talk through what living with a tube means","why":"Both work for breathlessness; the catheter avoids a hospital stay but stays in the body, which matters to some people.","source":"bts-2023","quote":"Patients without known non-expandable lung should be offered a choice of indwelling pleural catheter (IPC) or pleurodesis as first-line intervention in the management of MPE.","grade":"Conditional"},{"action":"On discharge, refer every patient with a new IPC to the community nursing team for an early check of the wound, symptoms and drainage, and removal of sutures","why":"Someone needs to check the wound and help with the first drainages at home.","source":"bts-2023","quote":"All patients who have had an IPC inserted should be referred to the community nursing team on discharge for an early assessment of the wound site, symptom control, support with IPC drainage and removal of sutures.","grade":"Good practice point (ungraded)"},{"action":"Teach the patient and relatives to drain the catheter and keep a drainage diary if they feel able to","why":"Draining at home without waiting for a nurse gives people more independence, and the diary shows when fluid is slowing down.","source":"bts-2023","quote":"Patients and their relatives should be supported to perform community drainage and complete a drainage diary if they feel able to do so, to promote independence and self-management.","grade":"Good practice point (ungraded)"},{"action":"Drain with the manufacturer's vacuum bottles and follow the procedure in the drainage pack","why":"Each catheter system has its own valve and bottle, and the pack's instructions keep the procedure clean and air-tight.","source":"bts-procedures-2023","quote":"All manufacturers' drainage packs contain comprehensive procedure guidelines which should be adhered to.","grade":"Clinical practice point (ungraded)"},{"action":"Agree how often to drain: as breathlessness requires, or daily if the lung re-expands and the aim is for the fluid to stop so the catheter can come out","why":"Draining every day makes the lung lining stick together sooner, but it does not make breathing better than draining when needed.","source":"bts-procedures-2023","quote":"Drainage frequency should be guided by patient symptoms, unless aiming for pleurodesis in those with expansile lungs, in which case IPC drainage should be as frequent as possible (daily) as tolerated by the patient.","grade":"Clinical statement (ungraded); see grades for the BTS guideline recommendation"},{"action":"Drain about 500 mL at a time, no more than 1500 mL, and slow or stop if there is chest pain or a persistent cough","why":"Pain towards the end of drainage often means the lung cannot expand to fill the space, and pulling harder does harm.","source":"bts-procedures-2023","quote":"Usually around 500 mL are drained, but up to 1500 mL pleural fluid may be drained","grade":"Grade C (the 1500 mL ceiling, as cited by the statement); the statement calls the figure arbitrary"},{"action":"Keep the exit site clean and dry; shower once the dressing allows, and bath or swim only after both sutures are out, changing a wet dressing promptly","why":"The main long-term risk is infection getting in along the tube.","source":"bts-procedures-2023","quote":"After both sutures are removed, patients can have a bath and swim, although care should be taken to keep the IPC site clean and dry, such as with a waterproof dressing and prompt changing of the dressing should it get wet.","grade":"Clinical statement (ungraded)"},{"action":"Tell the patient to call the team for increasing chest pain, fever, redness around the catheter or if it seems to have moved","why":"These can be signs of infection or a displaced tube, which are treatable if caught early.","source":"bts-leaflet-2023","quote":"Contact your doctor if you have increasing chest pain, fever or any redness around the IPC, or if you are concerned the IPC has become dislodged.","grade":"Patient information (ungraded)"},{"action":"Start antibiotics if catheter infection is suspected, refer promptly to the respiratory team if pleural infection is suspected, and do not routinely remove the catheter","why":"Most catheter infections clear with antibiotics and the catheter can stay.","source":"bts-procedures-2023","quote":"Antibiotic therapy should be commenced if IPC-related infection is suspected.","grade":"Clinical practice point (ungraded); ATS/STS/STR 2018: weak recommendation to treat with antibiotics and not remove the catheter"},{"action":"Seek hospital advice if nothing drains and the patient is more breathless","why":"The tube may be blocked or the fluid may have split into pockets, which the team can treat.","source":"bts-procedures-2023","quote":"Secondary care advice should be sought in the event drainage stops in the presence of worsening breathlessness.","grade":"Clinical practice point (ungraded)"},{"action":"If the catheter or valve is damaged, clamp it; if it falls out, close the site with adhesive strips and an occlusive dressing and call the respiratory team","why":"An open catheter lets air into the chest and fluid out.","source":"bts-procedures-2023","quote":"In the rare event of damage to the catheter or its valve the catheter should be clamped to avoid air entry to the pleural cavity or leakage of pleural fluid.","grade":"Appendix 9 troubleshooting (ungraded)"},{"action":"When less than 50 mL drains on three drainages in a row, contact the respiratory team to consider removing the catheter","why":"The lining may have sealed itself, and the tube can then come out as a day case.","source":"bts-procedures-2023","quote":"If the catheter drains less than 50 mL on three consecutive occasions the respiratory team should be contacted for consideration of catheter removal.","grade":"Clinical practice point (ungraded)"},{"action":"Dispose of the fluid and bottle as local clinical waste rules say; check the rules if the patient is having chemotherapy","why":"Body fluids during some cancer drugs can carry drug residues, so some areas collect them as clinical waste.","source":"bts-procedures-2023","quote":"If the patient is not receiving chemotherapy/immunotherapy the drainage fluid can be disposed of down the toilet and the bottle with the household rubbish.","grade":"Appendix 9 (ungraded)"}],"bestInClass":{"statement":"The BTS guideline for pleural disease (2023) with the BTS clinical statement on pleural procedures (2023) is the most detailed current standard for home IPC care, and agrees with the ATS/STS/STR guideline (2018) that an IPC and pleurodesis are both reasonable first choices, that an IPC is preferred when the lung will not re-expand, and that catheter infections are treated with antibiotics without removing the catheter. The one real choice is drainage frequency: two randomised trials show that daily drainage roughly doubles spontaneous pleurodesis without improving breathlessness, so BTS ties daily drainage to the patient's own priority (removal of the catheter) and says plainly that it is not needed for symptom control.","sources":["bts-2023","bts-procedures-2023","ats-2018","asap-2017","ample2-2018"]},"variants":[{"name":"Daily (aggressive) drainage","differs":"Drains every day from the start, aiming for the pleura to seal and the catheter to come out.","evidence":"ASAP: autopleurodesis 47% vs 24% with every-other-day drainage, median 54 vs 90 days, no difference in adverse events or quality of life. AMPLE-2: spontaneous pleurodesis 44.2% vs 15.9% at 6 months against symptom-guided drainage, no difference in breathlessness, better EQ-5D. BTS: conditional recommendation where removal is a priority.","sources":["asap-2017","ample2-2018","bts-2023"]},{"name":"Symptom-guided drainage","differs":"Drains only when breathlessness returns.","evidence":"Breathlessness was no worse than with daily drainage in AMPLE-2; fewer drainages and lower cost. BTS: patients should be told they do not need daily drainage to control symptoms (strong, by consensus).","sources":["ample2-2018","bts-2023"]},{"name":"Three times a week (usual UK starting regime) or every other day (ASAP comparator)","differs":"A fixed regular schedule between the two.","evidence":"BTS clinical statement calls three times a week the usual starting frequency; every-other-day was the standard arm in ASAP and gave less pleurodesis than daily drainage.","sources":["bts-procedures-2023","asap-2017"]},{"name":"Talc through the IPC","differs":"Instils 4 g of talc slurry through the catheter as an outpatient once it is clear the lung re-expands.","evidence":"IPC-PLUS: pleurodesis at day 35 in 43% with talc vs 23% with placebo, no excess adverse events. BTS 2023: offer where pleurodesis and removal matter to the patient or clinician (conditional, by consensus).","sources":["ipc-plus-2018","bts-2023"]},{"name":"Flutter bag or underwater seal instead of a vacuum bottle","differs":"Some NHS trusts use flutter bags for community patients who find vacuum drainage uncomfortable; underwater seal drains are used for inpatients to save cost or to drain an infected effusion.","evidence":"Named by the BTS clinical statement (appendix 9) as local practice (Torbay and South Devon NHS Foundation Trust); the licensed method is the manufacturer's vacuum bottle. No comparative evidence was found.","sources":["bts-procedures-2023"]}],"grades":[{"claim":"Daily drainage where IPC removal is a priority","grade":"Conditional","source":"bts-2023","quote":"Where IPC removal is a priority, daily IPC drainages are recommended to offer increased rates of pleurodesis when compared with less frequent drainages of symptom-guided or alternate drainage regimes."},{"claim":"Daily drainage is not needed to control breathlessness","grade":"Strong (by consensus)","source":"bts-2023","quote":"Patients should be advised that they do not require daily drainage to control symptoms of breathlessness and chest pain if they wish to opt for a less intensive regime."},{"claim":"Talc via the IPC where pleurodesis matters","grade":"Conditional (by consensus)","source":"bts-2023","quote":"Instillation of talc via an IPC should be offered to patients with expandable lung where the clinician or patient deems achieving pleurodesis and IPC removal to be important."},{"claim":"IPC rather than talc when more than 25% of the lung does not re-expand","grade":"Good practice point (ungraded)","source":"bts-2023","quote":"In patients with radiologically significant (>25%) non-expandable lung requiring intervention for a symptomatic MPE, current evidence suggests the use of an IPC rather than talc pleurodesis."},{"claim":"IPC or pleurodesis for expandable lung; IPC for non-expandable lung; antibiotics without removal for IPC infection","grade":"Weak recommendations (GRADE)","source":"ats-2018","quote":"treating IPC-associated infections with antibiotics and not removing the catheter"},{"claim":"Consider removal after three low drainages and no reaccumulation","grade":"Clinical statement (ungraded)","source":"bts-procedures-2023","quote":"Consider removal of IPCs when <50 mL are drained on three consecutive occasions and there is an absence of symptoms of fluid reaccumulation and no substantial residual pleural effusion on imaging."},{"claim":"Infection rate and response to antibiotics","grade":"Complications table (observational studies)","source":"bts-procedures-2023","quote":"IPC related pleural infections carry a 0.29% mortality rate, but the majority (94%) respond to antibiotics treatment."}],"sources":[{"key":"bts-2023","label":"British Thoracic Society Guideline for pleural disease (Roberts et al., Thorax 2023)","publisher":"British Thoracic Society","year":2023,"url":"https://www.brit-thoracic.org.uk/clinical-resources/guidelines/pleural-disease/","doi":"10.1136/thorax-2022-219784","gradingScheme":"GRADE-based recommendations, Strong or Conditional, marked 'by consensus' where evidence was lacking; good practice points are ungraded.","read":"full-text","accessed":"2026-11-11"},{"key":"bts-procedures-2023","label":"British Thoracic Society Clinical Statement on pleural procedures (Asciak et al., Thorax 2023), with online appendices 1-4 and 9","publisher":"British Thoracic Society","year":2023,"url":"https://www.brit-thoracic.org.uk/clinical-resources/clinical-statements/pleural-procedures/","doi":"10.1136/thorax-2022-219371","gradingScheme":"A clinical statement: clinical practice points are not graded; cited guideline grades are quoted where the statement gives them.","read":"full-text","accessed":"2026-11-11"},{"key":"bts-leaflet-2023","label":"Sample patient information leaflet: indwelling pleural catheter (BTS clinical statement on pleural procedures, online appendix 13)","publisher":"British Thoracic Society","year":2023,"url":"https://www.brit-thoracic.org.uk/document-library/clinical-statements/pleural-procedures/online-appendix-13-pleural-procedures-ipc-patient-information-leaflet/","gradingScheme":"Patient information; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ats-2018","label":"Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline (Feller-Kopman et al., Am J Respir Crit Care Med 2018)","publisher":"American Thoracic Society, Society of Thoracic Surgeons, Society of Thoracic Radiology","year":2018,"url":"https://doi.org/10.1164/rccm.201807-1415ST","doi":"10.1164/rccm.201807-1415st","gradingScheme":"GRADE: strong or weak (conditional) recommendations.","read":"abstract","accessed":"2026-11-11"},{"key":"asap-2017","label":"Randomized Trial of Pleural Fluid Drainage Frequency in Patients with Malignant Pleural Effusions: the ASAP Trial (Wahidi et al., Am J Respir Crit Care Med 2017)","publisher":"American Thoracic Society","year":2017,"url":"https://doi.org/10.1164/rccm.201607-1404OC","doi":"10.1164/rccm.201607-1404oc","gradingScheme":"Randomised controlled trial; no grade.","read":"abstract","accessed":"2026-11-11"},{"key":"ample2-2018","label":"Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial (Muruganandan et al., Lancet Respir Med 2018)","publisher":"The Lancet Respiratory Medicine","year":2018,"url":"https://doi.org/10.1016/S2213-2600(18)30288-1","doi":"10.1016/s2213-2600(18)30288-1","gradingScheme":"Randomised controlled trial; no grade.","read":"abstract","accessed":"2026-11-11"},{"key":"ipc-plus-2018","label":"Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion: IPC-PLUS (Bhatnagar et al., N Engl J Med 2018)","publisher":"New England Journal of Medicine","year":2018,"url":"https://doi.org/10.1056/NEJMoa1716883","doi":"10.1056/nejmoa1716883","gradingScheme":"Randomised controlled trial; no grade.","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-daily-pleural-catheter-drainage-offered"],"gaps":["The step-by-step drainage instructions in the BTS clinical statement (appendix 9, boxes 2 and 3) are images and were not read; the manufacturers' instructions in each pack were not read either.","The full texts of the ATS/STS/STR guideline, AMPLE-2, ASAP and IPC-PLUS are paywalled; only their abstracts were read.","The 1500 mL ceiling per drainage is, in the BTS statement's own word, arbitrary; no trial has compared drainage volumes.","The BTS sample leaflet tells patients infection affects 'about 1 in 50 people', while the same statement's complications table gives pleural infection at 3.2% to 5% and cellulitis at 1.6% to 2.5%; the leaflet figure appears to understate the risk.","No trial has tested dressing type, dressing change frequency or the cleaning steps of home drainage; these rest on the manufacturers' procedures.","Whether daily drainage is worth its cost and burden for people with a short prognosis, who may not live to have the catheter removed, is left to patient choice."]},{"id":"car-t-infection-prevention","kind":"protocol","name":"Infection screening, prophylaxis and immunoglobulin replacement around CAR T-cell therapy","aka":["CAR-T antimicrobial prophylaxis","CAR T infection prevention","IVIG after CAR T","hypogammaglobulinaemia after CAR T","PJP prophylaxis CAR T"],"tldr":"Infections are the commonest serious problem in the months after CAR T-cell therapy. You are first tested for hepatitis B, HIV and other viruses. Afterwards most centres give tablets against shingles, cold sores and a type of pneumonia for at least six months, check antibody levels, and may give antibody infusions if they are low and infections recur. Any fever needs a call to the team at once.","summary":"ASTCT 2024: screen before lymphodepletion with HIV antibody, hepatitis B (HBsAg, anti-HBc, anti-HBs), hepatitis C antibody, CMV IgG and HTLV-1, syphilis by risk, and baseline HBV DNA if HBsAg is positive; delay for symptomatic lower respiratory infection. Prophylaxis: acyclovir or valacyclovir from lymphodepletion until at least 6 months after infusion (shorter in children); trimethoprim-sulfamethoxazole for Pneumocystis from count recovery (by day 30) until at least 6 months, after a study in which 2 of 40 patients developed severe PJP when prophylaxis stopped at 3 months; entecavir for at-risk hepatitis B until at least 12 months; fluconazole through neutropenia where antifungal prophylaxis is universal, and mould-active azoles for higher risk; fluoroquinolone prophylaxis is controversial and may be replaced by monitoring with prompt antibiotics. Any fever after infusion needs an infection work-up and broad-spectrum antibiotics, since CRS treatment can mask infection.\n\nImmunoglobulin: measure IgG before and in the first 3 months; consider IVIG for IgG of 400 mg/dL or less with severe or recurrent bacterial infections, and when IgG is under 200 mg/dL (ASTCT). SITC 2020 measures B cells and immunoglobulins monthly and considers replacement for high-risk adults and for children with IgG under 400 mg/dL; EBMT/JACIE 2019 keeps IgG at 500 mg/dL or more in children with B-cell aplasia and recommends tenofovir, not entecavir, for a history of hepatitis B.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t","infection"],"related":["crs-grading-and-management","icans-grading-and-management","bispecific-step-up-dosing"],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["human-normal-immunoglobulin","axicabtagene-ciloleucel","tisagenlecleucel","lisocabtagene-maraleucel","brexucabtagene-autoleucel","idecabtagene-vicleucel","ciltacabtagene-autoleucel","obecabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-immunoglobulin-replacement","hbv-hcv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After CAR T-cell therapy your immune system is weak for months. You will take tablets to prevent some infections and have regular blood tests. Ring the team at once if you get a fever.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["ward","outpatient-clinic","home"]},"population":"Adults, adolescents and children receiving CD19- or BCMA-directed CAR T cells for haematological cancers. Doses and durations differ in children (ASTCT). People receiving bispecific antibodies have separate consensus advice (see the step-up dosing protocol).","trigger":"Planning CAR T-cell therapy, and the months after infusion.","steps":[{"action":"Before lymphodepletion, screen for HIV, hepatitis B (HBsAg, anti-HBc, anti-HBs), hepatitis C and CMV, with HBV DNA if HBsAg is positive","why":"Hidden infections can flare when the immune system is suppressed; knowing about them allows prevention.","source":"astct-inf-2024","quote":"Laboratory screening should include HIV antibodies (preferably fourth-generation antigen/antibody combination), hepatitis B virus surface antibody (anti-HBs) and antigen (HBsAg), HBV core Ab (anti-HBc), hepatitis C virus antibody (anti-HCV) with reflex nucleic acid testing if positive; Treponema pallidum testing based on risk factors (screening per institutional guidelines with treponemal or nontreponemal testing)."},{"action":"Prevent herpes simplex and shingles with acyclovir or valacyclovir from lymphodepletion until at least 6 months after infusion","why":"Without prophylaxis, up to half of patients developed herpes virus infections, mostly shingles, in one series.","source":"astct-inf-2024","quote":"Antiviral HSV and VZV should be prevented with acyclovir or valacyclovir from the start of lymphodepletion therapy until at least 6 mo postinfusion."},{"action":"Give trimethoprim-sulfamethoxazole against Pneumocystis from count recovery until at least 6 months after infusion","why":"Pneumocystis pneumonia after CAR T cells can be severe; stopping prophylaxis at 3 months was followed by cases needing ventilation.","source":"astct-inf-2024","quote":"Prophylaxis against Pneumocystis jirovecii (PJP) with trimethoprim-sulfamethoxazole (TMP/SMX) is recommended to start post-CAR T cell infusion until at least 6 mo."},{"action":"Give antiviral prophylaxis to people with a history of hepatitis B","why":"Hepatitis B can reactivate with severe liver damage; ASTCT names entecavir until at least 12 months, EBMT/JACIE tenofovir.","source":"ebmt-2019","quote":"For patients with a history of hepatitis B infection, prophylaxis with tenofovir is recommended."},{"action":"Where antifungal prophylaxis is used, give fluconazole through neutropenia, and consider a mould-active azole for those at higher risk","why":"Fungal infections are uncommon overall but more likely with prolonged neutropenia, severe CRS or high-dose steroids.","source":"astct-inf-2024","quote":"For centers that practice universal antifungal prophylaxis, fluconazole can begin with lymphodepletion to cover the neutropenic period until neutrophil recovery."},{"action":"Decide locally between fluoroquinolone prophylaxis during neutropenia and close monitoring with prompt intravenous antibiotics","why":"Routine antibacterial prophylaxis is controversial, and none of the paediatric studies used it.","source":"astct-inf-2024","quote":"Routine prophylaxis with fluoroquinolones (alternatively 3rd generation oral cephalosporins) remains controversial"},{"action":"Investigate every fever after infusion for infection and start broad-spectrum antibiotics promptly","why":"CRS treatment with tocilizumab or steroids can hide the signs of infection.","source":"astct-inf-2024","quote":"Fevers after CAR T-cell infusion should warrant prompt infectious workup and initiation of broad-spectrum antibiotics."},{"action":"Measure IgG before CAR T cells and during the first 3 months, and keep checking B cells and immunoglobulins afterwards","why":"CD19 and BCMA CAR T cells remove antibody-making cells, which can leave people unable to fight bacterial infections for months or years.","source":"sitc-iec-2020","quote":"Following CAR T cell therapy, B cell counts and serum immunoglobulins should be measured monthly","grade":"LE: 4"},{"action":"Consider immunoglobulin replacement when IgG is 400 mg/dL or less with severe or recurrent bacterial infections, or below 200 mg/dL","why":"Replacement prevents infections in people who cannot make their own antibodies; there are no randomised trials after CAR T cells.","source":"astct-inf-2024","quote":"IVIG can also be considered when IgG < 200 mg/dL, particularly when associated with extremely low IgA levels, irrespective of the time from CAR T-cell infusion and the incidence and severity of infections"},{"action":"In children with B-cell aplasia, give immunoglobulin replacement to keep IgG at or above the institutional threshold","why":"Replacement after CAR T cells has been standard in paediatric centres; EBMT notes there is no consensus on routine replacement in adults, who can keep long-lived plasma cells that go on making antibody.","source":"ebmt-2019","quote":"Children with B-cell aplasia should receive immunoglobulin replacement to maintain IgG levels according to institutional guidelines for IgG substitution (i.e. ≥500mg/dL)."}],"bestInClass":{"statement":"ASTCT 2024, the most recent and most specific source read, sets antiviral prophylaxis for herpes viruses and Pneumocystis prophylaxis each for at least 6 months, hepatitis B prophylaxis for at least 12 months where needed, risk-adapted antifungal prophylaxis, and leaves routine antibacterial prophylaxis to local choice. On immunoglobulin replacement the sources differ in threshold: ASTCT considers IVIG at IgG of 400 mg/dL or less with severe or recurrent bacterial infection or below 200 mg/dL in anyone, SITC 2020 for high-risk adults and children under 400 mg/dL (LE: 4), and EBMT/JACIE 2019 keeps children at 500 mg/dL or more. On hepatitis B, ASTCT names entecavir and EBMT/JACIE tenofovir. ASTCT says the evidence is mostly retrospective and extrapolated from transplantation.","sources":["astct-inf-2024","sitc-iec-2020","ebmt-2019"]},"variants":[{"name":"Tenofovir for hepatitis B (EBMT/JACIE 2019)","differs":"Recommends tenofovir prophylaxis for a history of hepatitis B, where ASTCT 2024 names entecavir 0.5 mg daily from lymphodepletion until at least 12 months.","evidence":"Expert recommendations in both; no comparison.","sources":["ebmt-2019","astct-inf-2024"]},{"name":"Immunoglobulin for high-risk adults and for children under 400 mg/dL (SITC 2020)","differs":"Considers immunoglobulin supplementation for adults judged at high risk or with recurrent infections and for children with IgG under 400 mg/dL; home subcutaneous immunoglobulin for long-term B-cell aplasia.","evidence":"LE: 4.","sources":["sitc-iec-2020"]},{"name":"Shorter antiviral prophylaxis in children (ASTCT 2024)","differs":"Reports that children usually receive shorter antiviral prophylaxis, often 3 months (range 1 to 6 in studies), and that antibacterial prophylaxis is not universally recommended in children, adolescents and young adults.","evidence":"Expert panel best practice considerations.","sources":["astct-inf-2024"]}],"grades":[{"claim":"B-cell counts and immunoglobulins measured monthly after CAR T cells","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Immunoglobulin for high-risk adults and children with IgG under 400 mg/dL","grade":"LE: 4","source":"sitc-iec-2020","quote":"For adult patients deemed to be at high risk of infections or with recurrent infections and for children with serum IgG levels less than 400 mg/dL, immunoglobulin supplementation should be considered"},{"claim":"Antiviral and Pneumocystis prophylaxis for at least 6 months","grade":"best practice consideration (expert panel; not graded)","source":"astct-inf-2024"}],"sources":[{"key":"astct-inf-2024","label":"Best Practice Considerations by The American Society of Transplant and Cellular Therapy: Infection Prevention and Management After Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies","publisher":"ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy","year":2024,"url":"https://europepmc.org/article/PMC/PMC12826105","doi":"10.1016/j.jtct.2024.07.018","gradingScheme":"Expert panel best practice considerations synthesising mostly retrospective evidence; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["A 2026 Australian consensus statement on preventing infections after CD19 CAR T cells for lymphoma (Internal Medicine Journal) and the 2021 French (SFGM-TC) recommendations are listed in Europe PMC without open full text and were not read.","Vaccination after CAR T cells is discussed by ASTCT at length but was not set out as steps here; EBMT/JACIE 2019 made no specific recommendation.","There are no randomised trials of immunoglobulin replacement or of any antimicrobial prophylaxis after CAR T cells (ASTCT)."]},{"id":"infusion-reaction-management","kind":"protocol","name":"Infusion and hypersensitivity reactions during anticancer treatment: recognition, emergency treatment and rechallenge","aka":["infusion reaction","infusion-related reaction","hypersensitivity reaction to chemotherapy","anaphylaxis in the chemotherapy unit","chemotherapy allergic reaction","taxane reaction","platinum allergy","rituximab infusion reaction","rechallenge after infusion reaction"],"tldr":"Some cancer drugs can cause a reaction while they go in: flushing, itching, a rash, chills, tightness in the chest or throat, or feeling faint. Tell the nurse at once. They will stop the drip and check you; most reactions are mild and settle, and many people can then carry on more slowly. A severe allergic reaction (anaphylaxis) is treated at once with an adrenaline injection into the thigh.","summary":"ESMO (2017) is the only oncology guideline read; it is mostly graded [V, C] (expert opinion), because reactions are unpredictable and hard to study in trials. Preparation: ask about allergy and atopy, check oral premedication was taken, have the protocol and resuscitation equipment at hand (ESMO [V, C]; ASCO-ONS 2024 standard 3.12.7). Early odd sensations or an urge to pass urine or stool can precede a reaction and warrant blood pressure and pulse.\n\nManagement: stop the drug, keep the line, assess airway, breathing, circulation and consciousness, call for help, oxygen if needed. Anaphylaxis is treated with intramuscular adrenaline into the anterolateral thigh: ESMO gives 0.01 mg/kg up to 0.5 mL of 1 mg/mL [IV, B], repeatable every 5 to 15 minutes [V, C]; Resuscitation Council UK (2021) gives 500 micrograms for adults and repeats after 5 minutes if problems persist, with IV fluids early for shock. The two differ on adjuncts: ESMO recommends H1 plus H2 antihistamines [I, B] and allows corticosteroids against biphasic reactions [V, D]; RCUK calls antihistamines third-line, for skin symptoms after stabilisation, and no longer advises corticosteroids routinely (very low-certainty evidence). RCUK keeps the patient supine and warns against sudden sitting or standing.\n\nCytokine-release type reactions to antibodies (rituximab, for example) are managed by stopping, symptomatic treatment and restarting at half the rate [IV, B]. Document with a CTCAE grade [V, B]. Rechallenge with a slower rate and more premedication usually succeeds [V, C], but ESMO advises against rechallenge after grade 3 or higher or true anaphylaxis [V, B]; desensitisation in experienced centres is the alternative. RCUK refers everyone with anaphylaxis to an allergy clinic and measures tryptase when the diagnosis is uncertain.","asOf":"2026-11-11","links":[],"tags":[],"related":["sact-administration-checks-at-the-chair","premedication-before-reaction-prone-anticancer-drugs"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["paclitaxel","docetaxel","carboplatin","oxaliplatin","etoposide","asparaginase","pegylated-liposomal-doxorubicin","rituximab","cetuximab","trastuzumab","daratumumab"],"companies":[],"institutions":[],"pathways":[],"terms":["extravasation-infusion-reaction","crs"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you feel strange, itchy, flushed, short of breath or faint during your drip, say so at once. The nurse will stop it and help you. It is common and is treated quickly.","domain":"chemotherapy-administration","setting":{"who":["nurse","doctor","pharmacist"],"where":["chemotherapy-day-unit","ward","home"]},"population":"Adults receiving intravenous anticancer drugs, chemotherapy or antibodies. ESMO's adrenaline dose is weight-based; the RCUK guideline covers adults and children with separate doses. Cytokine release syndrome after CAR-T cells or bispecific antibodies has its own grading and treatment and is not covered here.","trigger":"During or soon after an infusion, the patient develops flushing, itch, rash, chills, fever, chest or back pain, breathlessness, wheeze, throat tightness, dizziness, low blood pressure, or says they feel odd.","steps":[{"action":"Before giving any drug, ask about past reactions, allergies, atopy and current medicines","why":"A history of allergy, asthma or heart disease, or medicines such as beta-blockers, changes the risk and how a reaction is treated.","source":"esmo-2017","quote":"Before the administration of any drug, the patient should be asked about medical history, previous allergic disorders, atopic status and concomitant treatments","grade":"[V, C]"},{"action":"If premedication was to be taken by mouth, check the patient actually took it","why":"A missed steroid dose before a taxane, for example, raises the chance of a reaction.","source":"esmo-2017","quote":"If premedications are to be taken orally, oncology nurses should check that the patient has actually taken them","grade":"[V, C]"},{"action":"Keep the reaction protocol, the drugs and the resuscitation equipment within reach before starting","why":"Anaphylaxis needs treatment within minutes; there is no time to fetch things.","source":"esmo-2017","quote":"An updated protocol for the management of IRs should be at hand as well as the medical equipment needed for resuscitation","grade":"[V, C]"},{"action":"Take it seriously when a patient says they feel odd, or suddenly needs to pass urine or open their bowels, and check blood pressure and pulse","why":"These feelings can come just before a reaction becomes obvious.","source":"esmo-2017","quote":"Those symptoms should be taken seriously and the patient should be evaluated by measuring blood pressure and pulse rate","grade":"[V, C]"},{"action":"Stop the infusion at once, keep the intravenous line in, and call for help","why":"Stopping the drug limits the dose that causes the reaction, and the line is needed for fluids and drugs.","source":"esmo-2017","quote":"Stop the administration of medication","grade":"[V, C]"},{"action":"Assess airway, breathing, circulation and consciousness; keep the patient lying flat, or sitting if breathing is easier, and do not let them stand or sit up suddenly","why":"In anaphylaxis, sitting or standing up suddenly can make blood pressure collapse.","source":"rcuk-2021","quote":"Changes in posture from supine to standing or sitting upright have been associated with cardiovascular collapse and death during anaphylaxis."},{"action":"If it is anaphylaxis, give adrenaline into the muscle of the outer thigh (adult 500 micrograms, 0.5 mL of 1 mg/mL), and repeat after 5 minutes if breathing or circulation problems persist","why":"Adrenaline is the only drug that reverses the airway swelling, wheeze and collapse of anaphylaxis; delay is the main avoidable cause of death.","source":"rcuk-2021","quote":"Repeat IM adrenaline after 5 minutes if Airway/Breathing/Circulation problems persist."},{"action":"Give intravenous fluid early if blood pressure is low or there is shock","why":"Anaphylaxis makes blood vessels leak, so the circulation needs filling quickly.","source":"rcuk-2021","quote":"IV fluids are recommended for refractory anaphylaxis, and must be given early if hypotension or shock is present."},{"action":"Do not let antihistamines or steroids delay adrenaline; once the patient is stable, a non-sedating antihistamine can treat itch and hives","why":"Antihistamines help the skin but do nothing for the life-threatening part of the reaction.","source":"rcuk-2021","quote":"Antihistamines are considered a third-line intervention and should not be used to treat Airway/Breathing/Circulation problems during initial emergency treatment."},{"action":"For a cytokine-release type reaction to an antibody, stop briefly, treat the symptoms, then restart at half the rate and increase as tolerated","why":"These reactions, common with the first dose of drugs such as rituximab, usually settle and become milder with later doses.","source":"esmo-2017","quote":"After resolution of symptoms, the infusion can be restarted at half the rate and titrated to tolerance","grade":"[IV, B]"},{"action":"If the diagnosis of anaphylaxis is uncertain, take blood for mast cell tryptase","why":"A raised tryptase supports the diagnosis, which matters for deciding whether the drug can ever be given again.","source":"rcuk-2021","quote":"Mast cell tryptase should be measured in all patients with suspected anaphylaxis where the diagnosis is uncertain."},{"action":"After a severe reaction, observe closely; ESMO advises 24 hours","why":"Symptoms can come back hours later.","source":"esmo-2017","quote":"After a severe reaction, close observation for 24 h is recommended","grade":"[V, C]"},{"action":"Record the reaction with its CTCAE grade, the pre-infusion assessment and what was given","why":"The grade and the record decide whether, and how, the drug is given next time.","source":"esmo-2017","quote":"Accurate documentation of the IR episode is critical, and should include pre-infusion assessments, an appropriate description and grading of the IR (according to accepted classifications such as CTCAE) and how it was managed","grade":"[V, B]"},{"action":"Do not rechallenge after a grade 3 or higher reaction or true anaphylaxis; after milder reactions, restart slower with extra premedication","why":"After a mild reaction most people can continue safely; after anaphylaxis the next dose could be fatal unless given by a specialist desensitisation.","source":"esmo-2017","quote":"However, rechallenge in IRs with CTCAE severity grade 3 or higher or in true anaphylaxis should not be attempted","grade":"[V, B]"},{"action":"Refer anyone who had anaphylaxis to an allergy clinic","why":"Specialist testing can confirm which drug caused it and whether a desensitisation or an alternative is possible.","source":"rcuk-2021","quote":"All patients should be referred to a specialist clinic for allergy assessment."}],"bestInClass":{"statement":"Prepare (history, premedication taken, protocol and equipment at hand), stop the drug at the first sign, assess ABC, and give intramuscular adrenaline promptly for anaphylaxis, repeated after 5 minutes if needed (RCUK 2021; ESMO 2017 [IV, B]), with early IV fluids for shock and the patient kept flat. The guidelines disagree on adjuncts: ESMO 2017 recommends combined H1 and H2 antihistamines [I, B] and allows corticosteroids against biphasic reactions [V, D], while RCUK 2021, developed later with GRADE methods, makes antihistamines third-line for skin symptoms after stabilisation and no longer advises corticosteroids routinely. Restart antibody cytokine-release reactions at half rate [IV, B]; grade and document [V, B]; no rechallenge after grade 3 or more or anaphylaxis except by desensitisation [V, B].","sources":["esmo-2017","rcuk-2021","asco-ons-2024"]},"variants":[{"name":"ESMO adjuncts: H1 plus H2 antihistamine and corticosteroids","differs":"Gives an H1 antihistamine (diphenhydramine) with an H2 antagonist intravenously, and corticosteroids at the equivalent of 1 to 2 mg/kg of methylprednisolone every 6 hours, as part of reaction treatment.","evidence":"ESMO grades the combined antihistamines [I, B] and says corticosteroids are effective in preventing biphasic reactions but not critical [V, D]. RCUK (2021) found little evidence that corticosteroids prevent biphasic reactions, notes data linking early steroids to more intensive care admission, and no longer advises them routinely, on very low-certainty evidence. ESMO names ranitidine as the H2 antagonist; it has since been withdrawn in several countries.","sources":["esmo-2017","rcuk-2021"]},{"name":"Desensitisation instead of stopping the drug for good","differs":"After a reaction to a drug that is still the best treatment (a platinum, a taxane or an antibody), it is given again starting from a small diluted dose with a long infusion and stepwise increases, in an experienced centre, for every course.","evidence":"ESMO notes desensitisation has been used with varying success, gives tolerance only while exposure continues, and has no standard protocol. The EAACI position paper (2022) covers skin tests, drug provocation and desensitisation for chemotherapy reactions; only its abstract was read.","sources":["esmo-2017","eaaci-2022"]},{"name":"Skin testing before re-exposure to carboplatin","differs":"Uses a skin test to judge the risk of a severe reaction before carboplatin is given again.","evidence":"ESMO says a negative skin test seems to predict, with reasonable reliability, the absence of a severe reaction at the next infusion; EAACI's recommendations on skin tests could not be read beyond the abstract.","sources":["esmo-2017","eaaci-2022"]}],"grades":[{"claim":"IM adrenaline 0.01 mg/kg (1 mg/mL, maximum 0.5 mL) into the lateral thigh for anaphylaxis","grade":"[IV, B]","source":"esmo-2017","quote":"When a patient fulfils any of the three criteria of anaphylaxis (see Table 2 ), epinephrine (adrenaline) must be delivered immediately at a dose of 0.01 mg/kg (1 mg/mL dilution, to a maximum total dose of 0.5 mL) intramuscularly into the lateral thigh muscle"},{"claim":"Adrenaline may be repeated every 5 to 15 minutes","grade":"[V, C]","source":"esmo-2017"},{"claim":"Combined H1 and H2 antagonists are superior to either alone","grade":"[I, B]","source":"esmo-2017","quote":"Antihistamines: the combined use of H1 and H2 antagonists is superior to the use of H1 (diphenhydramine) or H2 antagonists (ranitidine, cimetidine) alone"},{"claim":"Corticosteroids prevent biphasic reactions but are not critical","grade":"[V, D]","source":"esmo-2017","quote":"Corticosteroids are effective in preventing biphasic reactions, but are not critical in the management of anaphylaxis"},{"claim":"Corticosteroids no longer advised for routine emergency treatment of anaphylaxis","grade":"very low-certainty evidence (GRADE)","source":"rcuk-2021","quote":"Corticosteroids (e.g. hydrocortisone) are no longer advised for the routine emergency treatment of anaphylaxis."},{"claim":"Restart at half the rate after a cytokine-release type reaction resolves","grade":"[IV, B]","source":"esmo-2017"},{"claim":"No rechallenge after CTCAE grade 3 or higher or true anaphylaxis","grade":"[V, B]","source":"esmo-2017"},{"claim":"Rechallenge after milder reactions with a slower rate and more premedication","grade":"[V, C]","source":"esmo-2017","quote":"After all symptoms have resolved, rechallenge with a reduced infusion rate and additional premedication (such as corticosteroids and antihistamines) is usually successful"},{"claim":"Hypersensitivity order sets and medications accessible in time","grade":"Standard (not graded)","source":"asco-ons-2024","quote":"Hypersensitivity order sets and medications are accessible within the appropriate timeframe for optimal treatment"}],"sources":[{"key":"esmo-2017","label":"Management of infusion reactions to systemic anticancer therapy: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology, Roselló et al.)","year":2017,"url":"https://doi.org/10.1093/annonc/mdx216","doi":"10.1093/annonc/mdx216","gradingScheme":"[level, grade]: levels I (large randomised trial or meta-analysis) to V (studies without control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"},{"key":"rcuk-2021","label":"Emergency treatment of anaphylaxis: guidelines for healthcare providers (May 2021)","publisher":"Resuscitation Council UK","year":2021,"url":"https://www.resus.org.uk/sites/default/files/2021-05/Emergency%20Treatment%20of%20Anaphylaxis%20May%202021_0.pdf","gradingScheme":"Developed with GRADE Evidence to Decision frameworks (GRADE-ADOLOPMENT); certainty of evidence high, moderate, low or very low.","read":"full-text","accessed":"2026-11-11"},{"key":"eaaci-2022","label":"Hypersensitivity reactions to chemotherapy: an EAACI Position Paper","publisher":"European Academy of Allergy and Clinical Immunology (Allergy)","year":2022,"url":"https://doi.org/10.1111/all.15113","doi":"10.1111/all.15113","read":"abstract","accessed":"2026-11-11"},{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and the Oncology Nursing Society (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO guideline dates from 2017 and most of its recommendations are expert opinion ([V, C]); no newer ESMO guideline on infusion reactions was found. Some drugs it names have changed since (ranitidine withdrawn in several countries).","ESMO and RCUK disagree on antihistamines and corticosteroids; RCUK is newer and GRADE-based but general rather than oncology-specific.","The EAACI position paper on chemotherapy hypersensitivity (2022), the most detailed source on skin testing and desensitisation, was read as an abstract only. The World Allergy Organization guidance (2020) was not read.","No national nursing standard for reaction management in the chemotherapy unit (ONS, UKONS) could be read.","ESMO advises 24 hours of observation after a severe reaction; RCUK sets risk-stratified observation times (from 2 hours to at least 12 hours) for anaphylaxis in general. Neither addresses the day unit specifically."]},{"id":"insomnia-in-adults-with-cancer","kind":"protocol","name":"Insomnia in adults with cancer: screening, assessment and CBT-I first","aka":["insomnia during cancer treatment","sleep problems after cancer","CBT-I","cognitive behavioural therapy for insomnia","digital CBT-I","sleeping tablets in cancer","melatonin for sleep in cancer"],"tldr":"Trouble sleeping is very common during and after cancer treatment, and it often lasts. Your team should ask about your sleep at every stage. The treatment with the best evidence is cognitive behavioural therapy for insomnia (CBT-I), face to face or online. Sleeping tablets can help for a short time but are not recommended for long-term use; exercise can help too.","summary":"ESMO (2023) recommends that every patient with cancer be screened and assessed for insomnia regularly, from diagnosis through treatment and survivorship [I, A]; that people who screen positive have their severity measured with a validated tool, with the Insomnia Severity Index recommended [II, B]; and that a clinical interview is needed for a detailed evaluation [I, A]. CBT-I is the standard of care for insomnia in cancer survivors [I, A]. Where face-to-face CBT-I cannot be had, electronic CBT-I should be offered [II, A]; brief behavioural therapy should be considered during active treatment [II, B]; and mindfulness-based therapy is an alternative when CBT-I is not available or is preferred [II, B]. Exercise tailored to the person should be offered alone or alongside [II, B].\n\nHypnotics are an option, but their limited evidence of benefit does not outweigh the harms of long-term use [II, C]; short-term use of up to two weeks is not ruled out. Melatonin should be considered when circadian disruption is thought to maintain the insomnia and non-drug options are limited [II, B]; ESMO notes studies used 2 to 20 mg and that there is no dosing recommendation. Bright light therapy has insufficient evidence [II, C]. MASCC (2023) found no high-quality evidence to recommend cannabis for insomnia or other psychological symptoms in cancer.","asOf":"2026-11-11","links":[],"tags":["protocol","supportive-care","sleep"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["cbt-insomnia-cancer","rejuv-mind-sleep-after-cancer","rejuv-mind-sleeping-tablets-after-cancer","sleep-circadian-interventions","mindfulness-based-interventions","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":["quality-of-life","cancer-related-fatigue"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you cannot sleep, tell your team. A short course called CBT-I helps most. Sleeping pills are only for a short time.","domain":"symptom-management","setting":{"who":["nurse","doctor","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","home","community"]},"population":"Adults with cancer, during any phase of treatment and in survivorship. ESMO's strongest treatment recommendation (CBT-I as standard of care) is made for cancer survivors; for people in active treatment it recommends considering the briefer behavioural version. Children and adolescents are not covered.","trigger":"At diagnosis, before primary treatment, and regularly during treatment and survivorship; or whenever a person reports poor sleep.","steps":[{"action":"Screen every patient for insomnia regularly, from diagnosis and before treatment through to survivorship","why":"Sleep problems are common, often start with the diagnosis and treatment, and can last for years if nobody asks.","source":"esmo-2023","quote":"All patients with cancer should be regularly screened and assessed for insomnia during all phases of their treatment (e.g. after diagnosis and prior to surgery or any other primary treatment) and during the survivorship trajectory [I, A]","grade":"[I, A]"},{"action":"For a positive screen, measure severity with a validated tool such as the Insomnia Severity Index, and repeat it over time","why":"A score shows how severe the problem is and whether treatment is working.","source":"esmo-2023","quote":"The ISI is recommended for assessment of insomnia severity in patients with cancer [II, B]","grade":"[II, B]"},{"action":"Assess in a clinical interview, including the factors that keep the insomnia going such as pain, low mood, anxiety and fatigue","why":"Insomnia is tangled up with pain, worry, depression and tiredness, and each makes the others worse; the interview finds what to treat.","source":"esmo-2023","quote":"A clinical interview is needed for a detailed insomnia evaluation [I, A]","grade":"[I, A]"},{"action":"Offer cognitive behavioural therapy for insomnia (CBT-I) as the first treatment","why":"CBT-I, which retrains sleep habits and the worries that keep people awake, has the strongest evidence and lasting effects without the risks of tablets.","source":"esmo-2023","quote":"CBT-I is recommended as the standard of care for treating insomnia in cancer survivors [I, A]","grade":"[I, A]"},{"action":"Where face-to-face CBT-I is not available, offer electronic CBT-I; during active treatment, consider brief behavioural therapy","why":"Online programmes worked about as well in trials, and a shorter version is easier to manage while having treatment.","source":"esmo-2023","quote":"eCBT-I should be offered to cancer survivors with insomnia when face-to-face CBT-I is not available due to cost, lack of trained therapists, or physical or geographical constraints [II, A]","grade":"[II, A]"},{"action":"Offer exercise suited to the person's abilities, alone or alongside other treatment","why":"Exercise improves sleep and has wider benefits after cancer.","source":"esmo-2023","quote":"While currently available evidence is moderate, the general benefits of physical exercise suggest that exercise tailored to the patient’s abilities and needs should be offered as a stand-alone or supplementary intervention for insomnia in patients with cancer and cancer survivors [II, B]","grade":"[II, B]"},{"action":"Use sleeping tablets only for short periods; do not rely on them long term","why":"The evidence that they help is limited, and long-term use brings side effects and risks.","source":"esmo-2023","quote":"Hypnotics are an option for treating insomnia in patients with cancer and cancer survivors; however, the limited evidence for efficacy does not outweigh the side-effects and risks of AEs associated with long-term use [II, C]. This recommendation does not preclude short-term use (≤2 weeks).","grade":"[II, C]"},{"action":"Consider melatonin when disrupted body-clock rhythms seem to keep the insomnia going and non-drug options are limited","why":"Melatonin may help when the body clock is out of step, and it has few side effects.","source":"esmo-2023","quote":"Melatonin should be considered in patients with cancer and cancer survivors when circadian rhythm disruption is believed to be an important factor in maintaining the insomnia and when suitable nonpharmacological options are limited [II, B]","grade":"[II, B]"}],"bestInClass":{"statement":"ESMO 2023 is the latest specialist guideline found and was read in full: screen everyone regularly, assess with the Insomnia Severity Index and a clinical interview, and treat with CBT-I first [I, A], electronic CBT-I where face-to-face therapy is unavailable [II, A], brief behavioural therapy during active treatment [II, B], mindfulness-based therapy as an alternative [II, B] and exercise alongside [II, B]. Hypnotics are for short-term use only [II, C]. ESMO notes that the American College of Physicians, the European Sleep Research Society and the American Academy of Sleep Medicine also recommend CBT-I as standard care for insomnia in general. MASCC (2023) does not recommend cannabis for insomnia in cancer.","sources":["esmo-2023","mascc-cannabis-2023"]},"variants":[{"name":"Brief behavioural therapy for insomnia (BBT-I) during active treatment","differs":"A shorter behavioural programme, with less burden on the patient, in place of full CBT-I while treatment is ongoing.","evidence":"Recommended by ESMO for patients in active treatment [II, B].","sources":["esmo-2023"]},{"name":"Mindfulness-based therapy","differs":"Mindfulness training instead of CBT-I.","evidence":"ESMO: to be offered when CBT-I is not available or the survivor prefers it [II, B]; in the meta-analysis ESMO cites it was better than attention-control conditions such as sleep hygiene education.","sources":["esmo-2023"]},{"name":"Sleep hygiene advice alone","differs":"Advice on caffeine, alcohol, screens and the bedroom, without the other parts of CBT-I.","evidence":"ESMO describes sleep hygiene education as one component of CBT-I, and cites mindfulness-based therapy outperforming sleep hygiene education as an attention-control condition; it is not recommended as a stand-alone treatment in any source read.","sources":["esmo-2023"]},{"name":"Cannabis for sleep","differs":"Cannabis or cannabinoids used for insomnia.","evidence":"MASCC (2023): of 15 randomised trials, none assessed psychological symptoms as the primary outcome; no high-quality evidence to recommend it.","sources":["mascc-cannabis-2023"]}],"grades":[{"claim":"Bright light therapy for insomnia","grade":"[II, C]","source":"esmo-2023","quote":"There is currently insufficient evidence to support the use of bright light therapy in treating insomnia in patients with cancer and cancer survivors [II, C]"},{"claim":"Mindfulness-based therapy as an alternative to CBT-I","grade":"[II, B]","source":"esmo-2023","quote":"MBT should be offered to cancer survivors with insomnia when CBT-I is not available or when MBT is preferable to survivors [II, B]"},{"claim":"Brief behavioural therapy during active treatment","grade":"[II, B]","source":"esmo-2023","quote":"BBT-I, which reduces the patient burden of the intervention, should be considered for patients in active treatment for cancer who are experiencing insomnia [II, B]"},{"claim":"Cannabis for psychological symptoms including insomnia","grade":"no high-quality evidence (MASCC)","source":"mascc-cannabis-2023","quote":"There is no high-quality evidence to recommend the use of cannabis as an intervention for psychological symptoms in patients with cancer until more high-quality research demonstrates benefit."}],"sources":[{"key":"esmo-2023","label":"Insomnia in adult patients with cancer: ESMO Clinical Practice Guideline","publisher":"ESMO, ESMO Open","year":2023,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10774975/","doi":"10.1016/j.esmoop.2023.102047","gradingScheme":"ESMO levels of evidence (Roman numerals) and grades of recommendation (letters), as set out in the guideline's Supplementary Table S5, which was not read.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-cannabis-2023","label":"Multinational Association of Supportive Care in Cancer (MASCC) guidelines: cannabis for psychological symptoms including insomnia, anxiety, and depression","publisher":"MASCC, Supportive Care in Cancer","year":2023,"url":"https://europepmc.org/abstract/MED/36809575","doi":"10.1007/s00520-023-07628-3","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["ESMO's grading table is in Supplementary Table S5, which was not read; grades are quoted as printed in the recommendations.","ESMO makes its strongest CBT-I recommendation for survivors; the evidence for full CBT-I during active treatment, and for sleep restriction in people who are very tired or at risk of falls or seizures, is not settled in the text read.","ESMO gives no melatonin dose; studies used 2 to 20 mg.","Access to CBT-I is limited in many health systems; how many patients with cancer are offered it has not been measured in any source read.","No ASCO or NCCN insomnia guideline was read; NCCN's survivorship guideline covers sleep but its text cannot be reproduced."]},{"id":"intrathecal-chemotherapy-and-vinca-alkaloid-safety","kind":"protocol","name":"Intrathecal chemotherapy safety and vinca alkaloids given only by minibag","aka":["intrathecal chemotherapy safety","ITC register","vincristine minibag","wrong-route vincristine","never event vincristine","spinal chemotherapy checks","HSC 2008/001","NPSA RRR004","ISMP best practice 1"],"tldr":"Some treatments are injected into the fluid around the spine (intrathecal chemotherapy). Vincristine and related drugs, given into a vein, are fatal if injected there by mistake. Hospitals prevent this by keeping spinal chemotherapy separate in time and place, using only trained and registered staff, double checking with you, and giving vincristine from a small drip bag rather than a syringe.","summary":"Vinca alkaloids (vincristine, vinblastine, vindesine, vinorelbine) cause paralysis and almost always death if injected intrathecally; HSC 2008/001 cites 55 such incidents worldwide. The safeguards are of two kinds. First, intrathecal chemotherapy is separated: ASCO-ONS (2024, standard 3.13) requires it to be prepared separately, uniquely labelled, stored and delivered apart from other chemotherapy, and given immediately after a time out with a two-practitioner double check. England's HSC 2008/001 goes further: a register of trained and authorised staff for every task (prescribing, dispensing, issuing, checking, administering), issue only after written confirmation that the day's intravenous chemotherapy has been given (paediatric exceptions), a separate room with walls and a door used for nothing else in that session, a check by a second registered person and the patient if they wish, and normal working hours.\n\nSecond, intravenous vinca alkaloids are given only by infusion from a minibag, never a syringe. ISMP Best Practice 1 applies this in every setting, and ISMP does not accept large-volume syringes as an alternative; ASCO-ONS requires it where intrathecal chemotherapy is given; the NPSA alert of 2008 applied it to adult and adolescent units and not to paediatric units. Extravasation was similarly rare with syringes and minibags (0.03% and 0.04% in an Australian study cited by ISMP).","asOf":"2026-11-11","links":[],"tags":[],"related":["sact-administration-checks-at-the-chair","sact-prescribing-and-pharmacy-verification"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["vincristine","vinblastine","vinorelbine","vindesine","methotrexate","cytarabine"],"companies":[],"institutions":[],"pathways":[],"terms":["intrathecal-therapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Spinal chemotherapy is given in a separate room, at a separate time, by specially trained staff, with extra checks you can join in. Vincristine is put up as a small drip bag so it cannot be mistaken for a spinal injection.","domain":"chemotherapy-administration","setting":{"who":["doctor","nurse","pharmacist","pharmacy-technician"],"where":["ward","chemotherapy-day-unit","aseptic-unit","theatre"]},"population":"Adults and children receiving intrathecal or intraventricular chemotherapy (methotrexate, cytarabine, hydrocortisone, for example in acute lymphoblastic leukaemia and CNS lymphoma), and everyone receiving an intravenous vinca alkaloid. Paediatric practice on minibags differs between sources (see variants).","trigger":"Intrathecal or intraventricular chemotherapy is planned, or an intravenous vinca alkaloid is prescribed.","steps":[{"action":"Keep a register of staff trained and authorised to prescribe, dispense, issue, check or give intrathecal chemotherapy, and let only them do it","why":"Most fatal errors happened when someone unfamiliar with the process gave the injection.","source":"hsc-2008","quote":"A register should be established and maintained which lists designated personnel who have been trained and authorised to prescribe, dispense, issue, check or administer intrathecal chemotherapy"},{"action":"Prepare intrathecal drugs separately, label them uniquely, and store and deliver them apart from all other chemotherapy","why":"Physical separation stops an intravenous syringe being picked up by mistake.","source":"asco-ons-2024","quote":"Labeled immediately after preparation with a uniquely identifiable label for intrathecal or intraventricular medication"},{"action":"Issue intrathecal drugs only after written confirmation that the patient's intravenous chemotherapy for that day has already been given","why":"If the intravenous drugs are already in the patient, there is nothing left to mix up.","source":"hsc-2008","quote":"Intrathecal chemotherapy drugs should be issued at a different time from drugs for intravenous chemotherapy. Intravenous chemotherapy drugs should be issued first."},{"action":"Give intrathecal chemotherapy in a separate room, with walls and a door, where no other chemotherapy is given or stored during that session","why":"A curtained bay next to an intravenous chemotherapy chair is where mix-ups happen.","source":"hsc-2008","quote":"This area should be a separate room (ie. with walls and a door). A curtained off area with a sign is not a suitable alternative."},{"action":"Immediately before the injection, hold a time out and a double check by a second registered person, involving the patient if they wish","why":"A second trained person, and the patient, checking drug, dose and route catch the wrong syringe.","source":"hsc-2008","quote":"These checks should include a member of staff (not the member of staff who will be administering the ITC on that occasion) appropriately trained, deemed competent and on the register to carry out this check, the patient and, if appropriate, a relative or guardian."},{"action":"Record the checks","why":"The record shows each check happened and by whom.","source":"hsc-2008","quote":"The checks made should be recorded."},{"action":"Give intravenous vincristine and other vinca alkaloids only from a minibag of compatible fluid, never from a syringe","why":"A minibag cannot be connected to a spinal needle, so the fatal wrong-route error becomes impossible.","source":"ismp-2026","quote":"BEST PRACTICE 1: Dispense vinCRIStine and other vinca alkaloids in a minibag of a compatible solution and not in a syringe."},{"action":"Do not use a large-volume syringe as a substitute for a minibag","why":"Wrong-route errors have still happened with diluted doses in syringes.","source":"ismp-2026","quote":"ISMP does not recommend the use of large volume syringes as an acceptable alternative to the minibag."},{"action":"Where intrathecal chemotherapy is given, make the minibag rule a written policy","why":"The two procedures meet in the same units, so the rule must be part of the intrathecal policy.","source":"asco-ons-2024","quote":"The health care organization that administers antineoplastic therapy directly into the cerebral spinal fluid has policy that specifies that intravenous vinca alkaloids are administered only by infusion, for example, mini bags"}],"bestInClass":{"statement":"Separate intrathecal chemotherapy in time, place and people: a register of authorised staff, separate preparation and labelling, issue only after the day's intravenous chemotherapy, a dedicated room, and a recorded double check with the patient (HSC 2008/001; ASCO-ONS 2024 standard 3.13), and give every intravenous vinca alkaloid from a minibag, never a syringe (ISMP Best Practice 1, all settings). The sources differ on scope: ISMP applies minibags wherever vincristine is given, ASCO-ONS requires the policy where intrathecal chemotherapy is given, and the NPSA alert of 2008 applied it to adult and adolescent units but not paediatric units. None of these standards is graded.","sources":["hsc-2008","asco-ons-2024","ismp-2026","npsa-rrr004"]},"variants":[{"name":"Syringes for vincristine in paediatric units","differs":"Paediatric units give vincristine by syringe, relying on intrathecal separation and checks rather than minibags.","evidence":"The NPSA alert (2008) states it does not apply to children and teenagers treated in a paediatric unit, where minibags were not being recommended. ISMP (2026) applies Best Practice 1 in every setting, and its FAQ describes back-flushing a minibag line for adults and children to limit drug left in tubing.","sources":["npsa-rrr004","ismp-2026"]}],"grades":[{"claim":"Intrathecal drugs administered immediately after a time out and two-practitioner double check","grade":"Standard (not graded)","source":"asco-ons-2024","quote":"Administered immediately after a time out, double check procedure that involves two licensed practitioners or other licensed clinicians approved by the health care organization to prepare or administer antineoplastic therapy"},{"claim":"Vinca alkaloids by minibag, not syringe, in every patient care setting","grade":"ISMP Targeted Medication Safety Best Practice (not graded)","source":"ismp-2026","quote":"For example, the Best Practice 1 related to vinCRIStine should be implemented in whatever patient care setting this treatment is provided."},{"claim":"Minibag alert applies to adult and adolescent units only","grade":"NPSA rapid response report (not graded)","source":"npsa-rrr004","quote":"It does not apply to children and teenagers being treated in a paediatric unit where minibags are not being recommended to administer vinca alkaloids."}],"sources":[{"key":"hsc-2008","label":"HSC 2008/001: Updated national guidance on the safe administration of intrathecal chemotherapy","publisher":"Department of Health (England)","year":2008,"url":"http://www.dh.gov.uk/en/Publicationsandstatistics/Lettersandcirculars/Healthservicecirculars/DH_086870","gradingScheme":"Health service circular; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"npsa-rrr004","label":"NPSA/2008/RRR004: Using vinca alkaloid minibags (adult/adolescent units)","publisher":"National Patient Safety Agency (England)","year":2008,"url":"http://www.nrls.npsa.nhs.uk/resources/?entryid45=59890","gradingScheme":"Rapid response report; not graded.","read":"public-summary","accessed":"2026-11-11"},{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and the Oncology Nursing Society (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ismp-2026","label":"ISMP Targeted Medication Safety Best Practices for Hospitals: Frequently Asked Questions","publisher":"Institute for Safe Medication Practices (ECRI)","year":2026,"url":"https://online.ecri.org/hubfs/ISMP/Resources/ISMP_TargetedMedicationSafetyBestPractices_Hospitals_FAQ.pdf","gradingScheme":"Consensus best practices; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["HSC 2008/001 is from 2008 and its review date (August 2011) has long passed; no replacement was found, and BOPA's 2025 standards still cite it.","The NPSA alert itself (PDF) was not read; only its summary page. Later NHS alerts on non-Luer (spinal-specific) connectors, which HSC 2008/001 anticipates, were not read.","The current ISMP Best Practices document itself was not read, only its FAQ, which quotes Best Practice 1 verbatim.","No source read gives outcome data for the register or room separation; the safeguards rest on analysis of past fatal errors."]},{"id":"iodinated-contrast-kidney-and-metformin","kind":"protocol","name":"Iodinated contrast for CT: kidney function checks, kidney protection and metformin","aka":["contrast nephropathy prevention","contrast-induced nephropathy","contrast-associated acute kidney injury","CA-AKI","PC-AKI","CT contrast and kidneys","eGFR before CT","metformin and contrast","IV hydration before CT"],"tldr":"Many cancer scans use a dye containing iodine. If your kidneys work normally the dye is very unlikely to harm them, and you do not need to stop eating or drinking beforehand. If your kidneys are known to be weak, the team checks a recent blood test, may give you fluid through a drip around the scan, and may ask you to pause metformin for two days.","summary":"Risk is judged from the estimated glomerular filtration rate (eGFR). For intravenous contrast the threshold for extra care is an eGFR below 30 ml/min/1.73 m², or acute kidney injury (ESUR 2026, ACR/NKF 2020, NICE NG148 2024); intra-arterial injection with first-pass renal exposure lowers the ESUR threshold to 45. ESUR measures eGFR within 7 days for inpatients or the acutely ill and within 3 months otherwise; NICE uses an eGFR from the past 6 months, or screening questions when there is none, and proceeds without a blood test if the answers are negative and the person is stable. Emergency imaging is not delayed for kidney function (NICE 1.1.7 [2024]; ACR/NKF).\n\nPrevention in at-risk patients is intravenous volume expansion with 0.9% saline or isotonic bicarbonate, which ESUR finds equally effective (Level of evidence A) and recommends for at-risk patients (Level B). ESUR gives regimens (saline 1 ml/kg/h for 3 to 4 hours before and 4 to 6 hours after, or bicarbonate 3 ml/kg/h for 1 hour before; Level D) and does not accept oral fluids alone (Level D); NICE encourages oral hydration for those at increased risk and considers IV fluids for inpatients at particularly high risk. ACR/NKF prefer saline. N-acetylcysteine, statins, vitamin C and prophylactic dialysis are not recommended (ESUR Level A or B). Use low- or iso-osmolar contrast at the lowest diagnostic dose and recheck eGFR at 48 hours in at-risk patients.\n\nThe guidelines differ on ACE inhibitors and angiotensin receptor blockers: ESUR says they need not be stopped (Level B); NICE says consider stopping them temporarily when eGFR is below 30 [2013, amended 2024]. ESUR found insufficient evidence to withhold nephrotoxic chemotherapy before contrast (Level C). Metformin continues unless eGFR is below 30, there is acute kidney injury, or the injection is intra-arterial with first-pass renal exposure; then it stops at the time of contrast and restarts after an eGFR check at 48 hours (ESUR Level D; ACR/NKF agrees at eGFR below 30). People with myeloma and normal kidney function are not at higher risk if well hydrated; Bence Jones testing beforehand is not recommended (ESUR 2026). Fasting before low- or iso-osmolar contrast is not recommended (ESUR 2026).","asOf":"2026-11-11","links":[],"tags":[],"related":["contrast-reaction-history-and-premedication"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["iodinated-contrast-media","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"CT scans often use a dye. Tell the team if you have kidney problems or take metformin for diabetes. Most people need nothing special. If your kidneys are weak you may get a drip of fluid and a blood test afterwards. An urgent scan should not be delayed for a blood test.","domain":"screening-diagnostics","setting":{"who":["radiographer","doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","ward","emergency-department"]},"population":"Adults having intravenous iodine-based contrast for CT or other X-ray imaging, including people with cancer, kidney disease, myeloma or diabetes treated with metformin. Intra-arterial injection with first-pass renal exposure (left heart, suprarenal aorta, renal arteries) has a lower threshold and is noted, not detailed. Children (eGFR by the revised Schwartz formula in ESUR), people on dialysis (discussed with the kidney team) and gadolinium contrast for MRI are named where the sources address them; allergy to contrast is a separate protocol.","trigger":"A CT or other examination with intravascular iodine-based contrast is requested.","steps":[{"action":"When requesting a non-urgent contrast CT, find out whether the person has kidney disease","why":"Weak kidneys are the main thing that raises the small risk of kidney injury after contrast.","source":"nice-ng148","quote":"Before requesting a non-urgent iodine-based contrast media CT scan, assess whether the person has pre-existing kidney disease.","grade":"[2024]"},{"action":"Use a recent eGFR if there is one; if not, ask the screening questions about kidney disease, kidney specialists and acute illness, and test eGFR only if an answer is yes","why":"Most people do not need a fresh blood test; the questions find those who do.","source":"nice-ng148","quote":"If available, use an eGFR measurement from the past 6 months to support decision making about the use of iodine-based contrast media. If the person has been acutely unwell or clinically unstable since their last eGFR test, consider using a more recent eGFR.","grade":"[2024]"},{"action":"Do not delay contrast in an emergency to wait for a kidney test","why":"When a scan is urgent, missing a diagnosis is a bigger danger than the small risk to the kidneys.","source":"nice-ng148","quote":"Do not delay the use of iodine-based contrast media in an emergency if the risk of delaying the contrast media is likely to be clinically significant.","grade":"[2024]"},{"action":"Talk through the benefits and risks of the contrast scan with the person, and consider imaging without iodine contrast if they are at risk","why":"For someone with weak kidneys there may be another way to get the answer, and the choice is theirs to share.","source":"nice-ng148","quote":"Discuss the benefits and risks of tests or treatments that use iodine-based contrast media with the person, and their family members and carers if appropriate.","grade":"[2024]"},{"action":"For an at-risk person (eGFR below 30 for intravenous contrast, or acute kidney injury), give intravenous fluid around the scan: 0.9% saline or isotonic sodium bicarbonate","why":"Fluid through a drip before and after the scan is the one measure shown to lower the risk.","source":"esur-2018-pcaki","quote":"Preventive hydration should be used to reduce the incidence of PC-AKI in at-risk patients.","grade":"Level of evidence B"},{"action":"Use either saline 1 ml/kg/h for 3 to 4 hours before and 4 to 6 hours after the contrast, or bicarbonate 1.4% 3 ml/kg/h for 1 hour before; let the referring doctor tailor fluids in severe heart failure or end-stage kidney failure","why":"Both fluids work about equally well; too much fluid can be dangerous for a weak heart.","source":"esur-2018-pcaki","quote":"Intravenous saline and bicarbonate protocols have similar efficacy for hydration.","grade":"Level of evidence A"},{"action":"Do not rely on drinks alone to protect at-risk kidneys, though drinking freely is encouraged","why":"Drinking is sensible but has not been shown to be enough on its own for people at real risk.","source":"esur-2018-pcaki","quote":"Oral hydration as the sole means of prevention is not recommended.","grade":"Level of evidence D"},{"action":"Do not give N-acetylcysteine, statins, vitamin C or dialysis to prevent kidney injury from contrast","why":"None of them has been shown to protect the kidneys consistently.","source":"esur-2026","quote":"No pharmacological prophylaxis (with statins, renal vasodilators, receptor antagonists of endogenous vasoactive mediators or cytoprotective drugs, etc.) has been shown to offer consistent protection against CA-AKI."},{"action":"Use a low- or iso-osmolar contrast agent at the lowest dose that gives a diagnostic scan","why":"Less contrast, and contrast closer to the body's own concentration, means less strain on the kidneys.","source":"esur-2026","quote":"Use the lowest dose of contrast medium consistent with a diagnostic result."},{"action":"Do not hold back chemotherapy or other nephrotoxic drugs routinely because of the scan; minimise nephrotoxic drugs in people with chronic kidney disease","why":"There is not enough evidence that stopping them for a scan helps, and stopping cancer treatment has its own cost.","source":"esur-2018-pcaki","quote":"There is insufficient evidence to recommend withholding nephrotoxic drugs such as NSAIDs, antimicrobial agents or chemotherapeutic agents before CM administration.","grade":"Level of evidence C"},{"action":"If the person takes metformin and has an eGFR below 30, acute kidney injury, or intra-arterial contrast with first-pass renal exposure, stop metformin at the time of contrast and restart it after an eGFR check within 48 hours; otherwise carry on as normal","why":"Metformin does not harm the kidneys, but if the kidneys are injured it can build up and cause a rare dangerous acid build-up in the blood.","source":"esur-2026","quote":"Stop taking metformin from the time of contrast medium administration. Measure eGFR within 48 hours and restart metformin if renal function has not changed significantly."},{"action":"In myeloma, check kidney function and calcium, make sure the person is well hydrated, and do not test for Bence Jones protein just because of the scan","why":"Myeloma often affects the kidneys and raises calcium, but with normal kidneys and good hydration the risk is not higher.","source":"esur-2026","quote":"Multiple myeloma patients with normal renal function are not at increased risk of CA-AKI if they are well hydrated and low- or iso-osmolar iodine-based contrast media are used."},{"action":"For people on dialysis or with a kidney transplant, discuss the scan with the kidney team, without delaying emergency imaging; extra dialysis to clear iodine contrast is not needed","why":"Their kidney care is specialised, but dialysis timing does not need to be changed for the dye.","source":"nice-ng148","quote":"Discuss the person's care with a nephrology team before offering iodine-based contrast media to adults on renal replacement therapy, including people with a renal transplant, but do not delay emergency imaging for this.","grade":"[2019]"},{"action":"Do not ask people to fast before a scan with modern low- or iso-osmolar contrast","why":"Fasting dates from older dyes that made people sick; it is not needed now and can leave people dehydrated.","source":"esur-2026","quote":"Fasting is not recommended before administration of low- or iso-osmolar non-ionic iodine-based contrast media, gadolinium-based agents or ultrasound contrast agents."},{"action":"In at-risk patients, recheck eGFR 48 hours after the contrast, and follow up for at least 30 days if kidney injury is found","why":"Kidney injury from contrast shows up in blood tests over two to three days and needs following until it settles.","source":"esur-2026","quote":"Determine eGFR 48 hours after contrast medium administration."}],"bestInClass":{"statement":"Judge risk from eGFR, with extra care for intravenous contrast only when eGFR is below 30 ml/min/1.73 m² or there is acute kidney injury (ESUR 2026, ACR/NKF 2020, NICE NG148 2024 all draw the line at 30); never delay emergency imaging for a kidney result (NICE [2024]; ACR/NKF: contrast for a life-threatening diagnosis should not be withheld on kidney function). For those at risk, intravenous 0.9% saline or isotonic bicarbonate around the scan (ESUR Level A for equivalence, Level B for use; ACR/NKF prefer saline; NICE considers it for inpatients at particularly high risk), no drug prophylaxis, the lowest diagnostic dose of low- or iso-osmolar contrast, and an eGFR at 48 hours. Metformin is stopped only below eGFR 30, in acute kidney injury or with first-pass intra-arterial contrast (ESUR Level D; ACR/NKF agree at eGFR below 30). The guidelines differ on when an eGFR must have been taken (ESUR: 7 days for inpatients or the acutely ill, 3 months otherwise; NICE: 6 months, or screening questions and no test if they are negative), on oral fluids (NICE encourages them; ESUR rejects them as the only measure) and on ACE inhibitors and ARBs (ESUR: need not be stopped, Level B; NICE: consider stopping when eGFR is below 30).","sources":["esur-2026","esur-2018-pcaki","acr-nkf-2020","nice-ng148"]},"variants":[{"name":"NICE: screening questions instead of a routine blood test","differs":"Uses an eGFR from the past 6 months; if there is none, asks whether the person has kidney disease or a transplant, sees a kidney specialist or urologist, or has an acute illness, and proceeds without a blood test if all answers are no and the person is stable (NG148 1.1.9 to 1.1.12, 2024). ESUR offers measuring eGFR in all patients or only in those with a listed history, within 7 days for inpatients and the acutely ill and within 3 months for others.","evidence":"NICE's 2024 update rests on its evidence review of eGFR and risk tools for predicting contrast-associated kidney injury (not read here). ESUR's timing is a consensus recommendation.","sources":["nice-ng148","esur-2026"]},{"name":"Stopping ACE inhibitors and ARBs before contrast","differs":"NICE recommends considering temporarily stopping ACE inhibitors and angiotensin receptor blockers in adults with chronic kidney disease and an eGFR below 30 having iodine-based contrast (1.2.9, [2013, amended 2024]). ESUR says they do not have to be stopped.","evidence":"ESUR: meta-analyses of trials found no lower risk; withholding them may be associated with a slightly lower risk, but not strongly enough to recommend it (Level of evidence B).","sources":["nice-ng148","esur-2018-pcaki"]},{"name":"Oral hydration encouraged (NICE)","differs":"NICE encourages oral hydration before and after intravenous contrast in adults at increased risk (1.2.7 [2019]) and reserves intravenous volume expansion for inpatients at particularly high risk (eGFR below 30, a kidney transplant, a large contrast volume, first-pass intra-arterial injection). ESUR supports unrestricted oral fluids only alongside intravenous volume expansion.","evidence":"ESUR graded oral hydration as the only preventive measure as not recommended (Level of evidence D).","sources":["nice-ng148","esur-2018-pcaki"]},{"name":"Withholding metformin at eGFR 30 to 59 (US labelling)","differs":"The US Food and Drug Administration label advice, as reported by ACR/NKF, withholds metformin before iodinated contrast at eGFR 30 to 59 as well as below 30. ACR/NKF say decisions at 30 to 59 should be individualised by the referring clinician; ESUR continues metformin normally above 30 and notes its advice may differ from EMA and FDA recommendations.","evidence":"ACR/NKF: metformin does not raise the risk of contrast-associated kidney injury, and the risk of contrast-induced injury at eGFR 30 to 59 is low. The FDA text was not read directly.","sources":["acr-nkf-2020","esur-2026","esur-2018-pcaki"]},{"name":"Stopping metformin for every contrast scan (EANM PET-CT guideline)","differs":"The EANM FDG PET/CT procedure guideline (2015) stops metformin at the time of any intravenous contrast and withholds it for 48 hours, restarting without a kidney test when nephrotoxicity risk is low and only after a normal result when it is high. ESUR, ACR/NKF and the later ESUR handbook stop it only below eGFR 30, in acute kidney injury or with first-pass intra-arterial contrast.","evidence":"EANM states it as procedure advice without a grade; it predates the 2018 ESUR and 2020 ACR/NKF revisions, which rest on metformin not raising the risk of kidney injury.","sources":["eanm-fdg-2015","esur-2026","acr-nkf-2020"]}],"grades":[{"claim":"Preventive hydration in at-risk patients","grade":"Level of evidence B","source":"esur-2018-pcaki"},{"claim":"Intravenous saline and bicarbonate are equally effective","grade":"Level of evidence A","source":"esur-2018-pcaki"},{"claim":"Oral hydration alone is not recommended","grade":"Level of evidence D","source":"esur-2018-pcaki"},{"claim":"ACE inhibitors and ARBs need not be stopped","grade":"Level of evidence B","source":"esur-2018-pcaki","quote":"ACE inhibitors and angiotensin receptor blockers do not have to be stopped before CM administration."},{"claim":"Insufficient evidence to withhold nephrotoxic drugs, including chemotherapy, before contrast","grade":"Level of evidence C","source":"esur-2018-pcaki"},{"claim":"Stop metformin at contrast when eGFR is below 30, in acute kidney injury or with first-pass intra-arterial contrast; restart after eGFR at 48 hours","grade":"Level of evidence D","source":"esur-2018-pcaki"},{"claim":"Prophylaxis is indicated in acute kidney injury or eGFR below 30 (not on maintenance dialysis), may be considered at 30 to 44 in high-risk circumstances, and when given is isotonic normal saline","grade":"Consensus statement (ungraded)","source":"acr-nkf-2020","quote":"When prophylaxis is indicated, isotonic volume expansion with normal saline is the preferred method."},{"claim":"Contrast needed for a life-threatening diagnosis should not be withheld on kidney function","grade":"Consensus statement (ungraded)","source":"acr-nkf-2020","quote":"If contrast media administration is required for a life-threatening diagnosis, then it should not be withheld based on kidney function."},{"claim":"Metformin does not increase the risk of contrast-associated kidney injury","grade":"Consensus statement (ungraded)","source":"acr-nkf-2020","quote":"Metformin does not increase risk of CA-AKI."},{"claim":"Encourage oral hydration before and after intravenous contrast in adults at increased risk","grade":"[2019]","source":"nice-ng148","quote":"Encourage oral hydration before and after procedures using intravenous iodine-based contrast media in adults at increased risk of contrast-associated acute kidney injury"},{"claim":"For inpatients at particularly high risk, consider intravenous isotonic bicarbonate or 0.9% saline","grade":"[2019]","source":"nice-ng148","quote":"For inpatients having iodine-based contrast media, consider intravenous volume expansion with either isotonic sodium bicarbonate or 0.9% sodium chloride if they are at particularly high risk, for example, if:"},{"claim":"Consider temporarily stopping ACE inhibitors and ARBs when eGFR is below 30 (the unit after the figure breaks in the raw text and is left out of the quote)","grade":"[2013, amended 2024]","source":"nice-ng148","quote":"Consider temporarily stopping ACE inhibitors and ARBs in adults having iodine-based contrast media if they have chronic kidney disease with an eGFR less than 30"},{"claim":"Do not test for Bence Jones protein before contrast in myeloma","grade":"ungraded (handbook)","source":"esur-2026","quote":"Assessment for Bence Jones proteinuria before contrast medium administration is not recommended."}],"sources":[{"key":"esur-2026","label":"Contrast Media Safety Committee Guidelines 2026 (successor to ESUR Guidelines on Contrast Agents 10.0)","publisher":"European Society of Urogenital Radiology (ESUR) Contrast Media Safety Committee","year":2026,"url":"https://www.esur.org/wp-content/uploads/2026/10/Guidelines-2026.pdf","gradingScheme":"The handbook prints no grades; it summarises the committee's published guidelines, whose levels of evidence are given in the papers behind them.","read":"full-text","accessed":"2026-11-11"},{"key":"esur-2018-pcaki","label":"Post-contrast acute kidney injury. Part 2: risk stratification, role of hydration and other prophylactic measures, patients taking metformin and chronic dialysis patients","publisher":"ESUR Contrast Media Safety Committee (van der Molen et al., European Radiology)","year":2018,"url":"https://doi.org/10.1007/s00330-017-5247-4","doi":"10.1007/s00330-017-5247-4","gradingScheme":"Oxford Centre for Evidence Based Medicine levels: A established scientific evidence, B scientific presumption, C low level of evidence, D expert opinion (working group consensus), printed as 'Level of evidence A' to 'D'.","read":"full-text","accessed":"2026-11-11"},{"key":"acr-nkf-2020","label":"Use of Intravenous Iodinated Contrast Media in Patients With Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation","publisher":"American College of Radiology and National Kidney Foundation (Davenport et al., Kidney Medicine; also published in Radiology, 10.1148/radiol.2019192094)","year":2020,"url":"https://doi.org/10.1016/j.xkme.2020.01.001","doi":"10.1016/j.xkme.2020.01.001","gradingScheme":"Consensus statements without formal grades.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng148","label":"Acute kidney injury: prevention, detection and management (NG148), recommendations (last updated 16 October 2024)","publisher":"NICE","year":2024,"url":"https://www.nice.org.uk/guidance/ng148/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended ([2013], [2019], [2024]).","read":"full-text","accessed":"2026-11-11"},{"key":"eanm-fdg-2015","label":"FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0 (contrast and metformin section)","publisher":"European Association of Nuclear Medicine (Boellaard et al., European Journal of Nuclear Medicine and Molecular Imaging)","year":2015,"url":"https://doi.org/10.1007/s00259-014-2961-x","doi":"10.1007/s00259-014-2961-x","gradingScheme":"Procedure guideline; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"acr-manual-contrast","label":"ACR Manual on Contrast Media","publisher":"American College of Radiology","year":2024,"url":"https://www.acr.org/Clinical-Resources/Contrast-Manual","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-pu-contrast-ct-screening-questions","idea-pu-no-fasting-before-contrast"],"gaps":["ESUR lists its guidelines on preventing contrast-associated kidney injury and on metformin as being updated; the 2026 handbook still carries the 2018 recommendations, and the levels of evidence quoted come from the 2018 paper.","The ACR Manual on Contrast Media could not be read: its address served a JavaScript shell to a script. The ACR position is taken from the ACR/NKF consensus paper only.","The risk of kidney injury caused by the contrast itself, as distinct from injury that happens around the same time for other reasons, is uncertain below eGFR 30; ACR/NKF report estimates from 0% to 17% from observational studies and no randomised trial separating the two.","The best timing, volume and rate of intravenous fluid is uncertain (ACR/NKF); the ESUR regimens are expert opinion (Level D).","No source read addresses people having contrast during chemotherapy that is itself nephrotoxic (cisplatin, high-dose methotrexate) beyond ESUR's finding of insufficient evidence to withhold such drugs.","The FDA metformin label was not read directly; its position is as reported by ACR/NKF."]},{"id":"irinotecan-early-cholinergic-syndrome-and-late-diarrhoea","kind":"protocol","name":"Irinotecan: early cholinergic syndrome and late diarrhoea","aka":["irinotecan cholinergic syndrome","atropine with irinotecan","irinotecan late diarrhoea","high-dose loperamide after irinotecan","sacituzumab govitecan diarrhoea","CPT-11 diarrhoea"],"tldr":"Irinotecan can cause two kinds of diarrhoea. The first comes during or soon after the drip, with sweating, watery eyes and cramps; an atropine injection stops it. The second starts a day or more later and can be serious: take 4 mg of loperamide at the first loose stool, then 2 mg every 2 hours, and call your team if it is not controlled in 24 hours, or with blood, fever or faintness.","summary":"Irinotecan causes an early diarrhoea during or shortly after the infusion, part of an acute cholinergic syndrome (rhinitis, salivation, miosis, lacrimation, sweating, flushing, cramps, sometimes bradycardia), and a late diarrhoea, generally more than 24 hours after the dose (median onset 5 days with 3-weekly and 11 days with weekly dosing), which can be prolonged and life-threatening. The US label advises considering atropine 0.25 to 1 mg intravenously or subcutaneously as prophylaxis or treatment for the cholinergic syndrome; eviQ gives 0.3 to 0.6 mg, repeated to a maximum of 1.2 mg. For late diarrhoea the label and eviQ agree on high-dose loperamide (4 mg at the first loose stool, then 2 mg every 2 hours until 12 hours free of diarrhoea, 4 mg every 4 hours at night), not for more than 48 hours because of paralytic ileus. Fever, dehydration or melaena means admission, stool tests, intravenous fluids and antibiotics; diarrhoea unresolved after a second 12 to 24 hour review is treated with octreotide. The next dose waits until bowel function has been normal without antidiarrhoeals for 24 hours, and the dose is reduced if grade 2 to 4 late diarrhoea recurs. eviQ applies the same algorithm to sacituzumab govitecan, whose label caps loperamide at 16 mg a day.","asOf":"2026-11-11","links":[],"tags":["protocol","diarrhoea","supportive-care"],"related":["treatment-induced-diarrhoea-grading-and-management","octreotide-lanreotide","febrile-neutropenia-first-hour"],"cancers":[],"sections":["supportive-care"],"technologies":["ugt1a1-genotyping"],"targets":["ugt1a1"],"drugs":["irinotecan","sacituzumab-govitecan","folfiri","folfoxiri"],"companies":["pfizer"],"institutions":["nci"],"pathways":[],"terms":["ctcae-grading","febrile-neutropenia","chemotherapy-side-effects-colorectal","chemotherapy-side-effects-pancreatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"This drug can give you runny poo during the drip and days later. Nurses have a medicine for the first. For the second, take your tablets and call your team.","domain":"chemotherapy-administration","setting":{"who":["nurse","doctor","pharmacist","patient-or-carer"],"where":["chemotherapy-day-unit","home","telephone-triage","acute-oncology-service","ward"]},"population":"Adults receiving irinotecan alone or in combination (for example FOLFIRI or FOLFOXIRI), and, by the eviQ algorithm, sacituzumab govitecan. The label read is for conventional irinotecan; liposomal irinotecan has its own label, not read here. People with reduced UGT1A1 activity (UGT1A1*28/*28, *6/*6 or *6/*28) are at higher risk of severe neutropenia.","trigger":"A course of irinotecan or sacituzumab govitecan is planned; and any diarrhoea or cholinergic symptoms during or after a dose.","steps":[{"action":"Before the first dose, consider a reduced starting dose for people known to have UGT1A1*28/*28, *6/*6 or *6/*28","why":"People with these gene variants clear the drug's active form more slowly and are more likely to have severe side effects.","source":"camptosar-label-2026","quote":"When administered in combination with other agents, or as a single-agent, consider a reduction in the starting dose by at least one level of CAMPTOSAR for patients known to be homozygous for the UGT1A1*28 or *6 alleles (*28/*28, *6/*6) or compound heterozygous for the UGT1A1*28 and *6 alleles (*6/*28)"},{"action":"Teach the difference between early and late diarrhoea, and make sure the person has loperamide at home before the first dose","why":"Late diarrhoea can start days after the drip, at home; starting loperamide at the first loose stool stops it becoming dangerous.","source":"camptosar-label-2026","quote":"Patients should have loperamide readily available to begin treatment for late diarrhea (generally occurring more than 24 hours after administration of CAMPTOSAR)."},{"action":"During and shortly after the infusion, watch for the cholinergic syndrome: runny nose, salivation, small pupils, watery eyes, sweating, flushing, cramps, diarrhoea and slow heart rate","why":"These come from a direct effect of the drug on the nerves of the gut and glands, and are quickly relieved by treatment.","source":"camptosar-label-2026","quote":"It may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping. Bradycardia may also occur."},{"action":"Give atropine intravenously or subcutaneously to treat the cholinergic syndrome, and consider it before later doses as prevention, unless contraindicated","why":"Atropine blocks the nerve signal that causes the symptoms; giving it before the next dose usually prevents them.","source":"camptosar-label-2026","quote":"Consider prophylactic or therapeutic administration of 0.25 mg to 1 mg of intravenous or subcutaneous atropine (unless clinically contraindicated)."},{"action":"For late diarrhoea, start loperamide at the first poorly formed or loose stool, or at the first sign of more frequent bowel movements","why":"Late diarrhoea can last days and cause dehydration and infection; it is easiest to control at the start.","source":"camptosar-label-2026","quote":"Begin loperamide at the first episode of poorly formed or loose stools or the earliest onset of bowel movements more frequent than normal."},{"action":"Take loperamide 4 mg, then 2 mg every 2 hours (4 mg every 4 hours overnight) until 12 hours free of diarrhoea, and for no longer than 48 hours at these doses","why":"This higher dose is needed for irinotecan diarrhoea; beyond 48 hours it risks stopping the bowel altogether (paralytic ileus).","source":"camptosar-label-2026","quote":"One dosage regimen for loperamide is 4 mg at the first onset of late diarrhea and then 2 mg every 2 hours until the patient is diarrhea-free for at least 12 hours. Loperamide is not recommended to be used for more than 48 consecutive hours at these doses, because of the risk of paralytic ileus."},{"action":"Call the team for diarrhoea for the first time during treatment, black or bloody stools, dizziness or faintness, being unable to drink, or diarrhoea not controlled within 24 hours","why":"These are signs that the diarrhoea is becoming dangerous and needs assessment the same day.","source":"camptosar-label-2026","quote":"Patients should contact their physician if any of the following occur: diarrhea for the first time during treatment; black or bloody stools; symptoms of dehydration such as lightheadedness, dizziness, or faintness; inability to take fluids by mouth due to nausea or vomiting; or inability to get diarrhea under control within 24 hours."},{"action":"Admit if there is fever, dehydration or melaena; replace fluid and electrolytes, send stool for infection and C. difficile, and give antibiotics for ileus, fever or severe neutropenia; avoid diuretics and laxatives","why":"Infection and dehydration on top of irinotecan diarrhoea can be fatal and need hospital treatment.","source":"camptosar-label-2026","quote":"Monitor and replace fluid and electrolytes. Use antibiotic support for ileus, fever, or severe neutropenia."},{"action":"If diarrhoea is still unresolved at the second review 12 to 24 hours later, start octreotide 100 to 150 micrograms subcutaneously three times daily, escalating to 500 micrograms if dehydration is severe","why":"Octreotide reduces the fluid the bowel secretes when loperamide has not worked.","source":"eviq-3238","quote":"Octreotide 100 to 150 mcg SC three times daily (if dehydration severe, escalate dose up to 500 mcg three times daily)."},{"action":"Delay the next dose until bowel function has been back to normal for 24 hours without antidiarrhoeal medicine, and reduce later doses if grade 2 to 4 late diarrhoea recurs","why":"Giving the next dose while the bowel is still recovering makes severe diarrhoea more likely.","source":"camptosar-label-2026","quote":"Subsequent weekly chemotherapy treatments should be delayed in patients until return of pretreatment bowel function for at least 24 hours without anti-diarrhea medication."}],"bestInClass":{"statement":"The product label is the authority for this drug-specific toxicity, and eviQ's 2024-reviewed algorithm turns it into a nurse-led pathway with review points at 12 to 24 hours, admission criteria and octreotide as the next step. The two agree on high-dose loperamide (4 mg, then 2 mg every 2 hours, at most 48 hours) and on antibiotics for fever, ileus or severe neutropenia. They differ slightly on atropine: the label gives 0.25 to 1 mg as prophylaxis or treatment, eviQ 0.3 to 0.6 mg repeated to 1.2 mg as treatment. No graded guideline for irinotecan-specific diarrhoea was found.","sources":["camptosar-label-2026","eviq-3238","pdq-gi-2025"]},"variants":[{"name":"eviQ atropine dose and the same algorithm for sacituzumab govitecan","differs":"Atropine 0.3 to 0.6 mg intravenously or subcutaneously, repeated to a maximum of 1.2 mg; the whole algorithm applies to sacituzumab govitecan, with a note that its product information caps loperamide at 16 mg a day, though higher doses may be considered in severe diarrhoea.","evidence":"Australian state cancer agency algorithm, reviewed by its medical oncology reference committee in June 2024; not graded.","sources":["eviq-3238"]},{"name":"Scopolamine butylbromide as prophylaxis before later doses (Japanese single-centre practice)","differs":"Gives scopolamine butylbromide, another antimuscarinic, before the next irinotecan dose to people who had the cholinergic syndrome, instead of atropine.","evidence":"Single-centre study of 59 outpatients: the syndrome occurred in 50.8 per cent, and prophylaxis at the next dose reduced it to 3.4 per cent; an irinotecan dose of 150 mg/m2 or more was the only risk factor identified. Not randomised.","sources":["scopolamine-2019"]}],"grades":[{"claim":"Grade 3 to 4 late diarrhoea with weekly irinotecan dosing","grade":"Label incidence from the registration trials (23 to 31 per cent)","source":"camptosar-label-2026","quote":"Grade 3–4 late diarrhea occurred in 23–31% of patients receiving weekly dosing."},{"claim":"Scopolamine butylbromide prophylaxis reduced irinotecan-related cholinergic syndrome","grade":"single-centre before-and-after study, P < 0.01","source":"scopolamine-2019","quote":"Scopolamine butylbromide administration significantly reduced the incidence to 3.4% (P < 0.01)."}],"sources":[{"key":"camptosar-label-2026","label":"CAMPTOSAR (irinotecan hydrochloride) injection: US prescribing information","publisher":"Pfizer (Pharmacia & Upjohn), via DailyMed, US National Library of Medicine","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e518dfc6-7e93-4fee-a66c-51e1ab71c056","gradingScheme":"Product labelling; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"eviq-3238","label":"Algorithm: irinotecan and sacituzumab govitecan induced diarrhoea management (ID 3238, version 3)","publisher":"eviQ, Cancer Institute NSW","year":2024,"url":"https://www.eviq.org.au/p/3238","gradingScheme":"Algorithm endorsed by eviQ reference committees; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"pdq-gi-2025","label":"Gastrointestinal Complications (PDQ), Health Professional Version: Diarrhea","publisher":"National Cancer Institute","year":2025,"url":"https://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq","gradingScheme":"PDQ levels of evidence I to IV, attached to statements.","read":"full-text","accessed":"2026-11-11"},{"key":"scopolamine-2019","label":"Prophylactic effect of scopolamine butylbromide, a competitive antagonist of muscarinic acetylcholine receptor, on irinotecan-related cholinergic syndrome","publisher":"Cancer Chemotherapy and Pharmacology","year":2019,"url":"https://europepmc.org/abstract/MED/30564875","doi":"10.1007/s00280-018-3736-z","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-tr1-pre-emptive-pharmacogenomic-testing"],"gaps":["No graded guideline specific to irinotecan diarrhoea was found; the label and eviQ are the sources, and the 2018 ESMO diarrhoea guideline could not be read.","The EU summary of product characteristics (Campto) and the liposomal irinotecan label were not read; their atropine and loperamide wording may differ.","Whether atropine should be given routinely before every dose, or only after a first episode, is not settled in the sources read: the label says prophylactic or therapeutic use should be considered.","The sacituzumab govitecan label itself was not read; its loperamide limit is reported here as eviQ states it.","Which antibiotic to use is not specified; local febrile neutropenia policy applies."]},{"id":"irae-rheumatological","kind":"protocol","name":"Joint, muscle and other rheumatic side effects of checkpoint inhibitors","aka":["checkpoint inhibitor arthritis","ICI inflammatory arthritis","rheumatic irAEs","immune-related polymyalgia rheumatica","checkpoint inhibitor myositis","immune-related sicca syndrome","musculoskeletal irAEs"],"tldr":"Immunotherapy can cause joint pain and swelling, stiffness in the shoulders and hips, a dry mouth and eyes, or, rarely, muscle inflammation. Mild cases are treated with painkillers or anti-inflammatories; others need steroids and a rheumatologist, and immunotherapy often continues. Muscle weakness, trouble swallowing or breathlessness is urgent, because muscle inflammation can affect the heart.","summary":"Inflammatory arthritis affects 1 to 7% of trial participants; polymyalgia-like syndromes, sicca syndrome, vasculitis and myositis are less common (SITC 2021). Myositis (about 1% on PD-(L)1 inhibitors) is the dangerous one: it overlaps with myocarditis and myasthenia gravis and can involve the breathing muscles.\n\nSITC 2021: refer grade 2 or persistent events to a rheumatologist; for arthritis, ESR, CRP, rheumatoid factor, anti-CCP, ANA, a joint count and imaging; prednisone 10 to 20 mg/day for grade 2 and 40 to 60 mg/day for grade 3 or more (LE: 1); TNF inhibitors, methotrexate, leflunomide, hydroxychloroquine, sulfasalazine or IL-6 receptor inhibitors when steroids fail or long-term treatment is needed (LE: 1). Myositis: grade 3 holds the checkpoint inhibitor and starts prednisone 1 mg/kg, with any myocardial involvement meaning permanent discontinuation.\n\nEULAR 2021, the rheumatologists' statement, differs in emphasis: NSAIDs or analgesics first for mild to moderate symptoms; glucocorticoids only when these fail, tapered to the lowest effective dose; no methylprednisolone pulses or high-dose oral steroids outside life-threatening disease and myositis, because of concern for the anti-tumour response; a conventional DMARD when more than 10 mg/day prednisone is needed; TNF or IL-6 inhibitors preferred for refractory arthritis; holding immunotherapy as a shared decision; and withdrawal always for life-threatening myositis.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","rheumatology"],"related":["irae-myocarditis","irae-neurological","idea-bio2-steroid-sparing-irae"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab","prednisone","methotrexate","tocilizumab","human-normal-immunoglobulin"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can cause painful, stiff or swollen joints. Tell your team, as there are treatments that let many people carry on with immunotherapy. New muscle weakness or difficulty swallowing needs urgent help.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","patient-or-carer","multidisciplinary-team"],"where":["outpatient-clinic","acute-oncology-service","ward"]},"population":"Adults receiving or who have received an immune checkpoint inhibitor who develop joint, muscle, salivary or vessel inflammation, including those with pre-existing autoimmune rheumatic disease, who are at risk of a flare. Children are not addressed by these sources.","trigger":"New joint pain, swelling or stiffness, shoulder and hip girdle pain, dry mouth or eyes, muscle pain or weakness, or a raised creatine kinase during or after checkpoint inhibitor treatment.","steps":[{"action":"Consider cancer spread, paraneoplastic syndromes and unrelated joint disease, and look for objective evidence of inflammation in the affected organ","why":"New pain in someone with advanced cancer may be the cancer itself, not the immunotherapy.","source":"eular-2021","quote":"Metastases, paraneoplastic syndromes and unrelated rheumatic diseases should be considered as a potential differential diagnosis of rheumatic immune-related events.","grade":"LoE 4; LoA 9.5"},{"action":"For possible inflammatory arthritis, check ESR, CRP, rheumatoid factor, anti-CCP and ANA, count the swollen joints and image them where useful","why":"These tests and scans confirm inflammation and help choose treatment.","source":"sitc-2021","quote":"Initial diagnostic evaluation for patients with possible inflammatory arthritis should include ESR, CRP, rheumatoid factor, anti-CCP and ANA, and joint count and radiological investigation of the affected joint(s) where appropriate (with X-ray, MRI, or ultrasound) in consultation with a rheumatologist."},{"action":"Refer grade 2 or persistent rheumatic side effects to a rheumatologist","why":"A rheumatologist can choose treatments that control symptoms while keeping immunotherapy going.","source":"sitc-2021","quote":"Patients with grade ≥2 (or persistent) rheumatological irAEs such as inflammatory arthritis, PMR/GCA, vasculitis, myositis, or sicca syndrome should be referred to a rheumatologist for choice and interpretation of diagnostic testing as well as management recommendations."},{"action":"Start with NSAIDs or simple painkillers for mild to moderate symptoms if there is no reason not to","why":"Many mild cases settle without steroids.","source":"eular-2021","quote":"In the absence of contraindications, symptomatic treatment including non-steroidal anti-inflammatory drugs and/or analgesics should be the initial treatment for mild-to-moderate rheumatic manifestations."},{"action":"If that is not enough, give steroids: prednisone 10 to 20 mg/day for grade 2 arthritis or polymyalgia, and 40 to 60 mg/day for grade 3 or more","why":"Steroids calm joint inflammation; the dose rises with severity.","source":"sitc-2021","quote":"Corticosteroid dosing for inflammatory arthritis and PMR may start at 10–20 mg/day of prednisone equivalents for grade 2 symptoms. For grade ≥3 symptoms, higher dosages of 40–60 mg/day of prednisone equivalents may be required","grade":"LE: 1"},{"action":"Once symptoms improve, taper steroids to the lowest dose that controls them","why":"Long or high steroid doses carry their own harms and may blunt the immunotherapy.","source":"eular-2021","quote":"When improvement is achieved, systemic glucocorticoids should be tapered to the lowest effective dose to control the symptoms","grade":"LoE 4; LoA 9.4"},{"action":"Add a conventional DMARD, such as methotrexate, hydroxychloroquine or sulfasalazine, when steroids are not enough or more than 10 mg/day prednisone is needed","why":"These drugs let the steroid dose come down.","source":"eular-2021","quote":"csDMARD should be considered in patients with insufficient response to acceptable dose of glucocorticoids or requiring glucocorticoid-sparing","grade":"LoE 4; LoA 9"},{"action":"For severe or DMARD-refractory disease, consider a biological DMARD, preferring a TNF or IL-6 inhibitor for inflammatory arthritis","why":"These have been used in refractory immune-related arthritis without clear harm to the cancer response.","source":"eular-2021","quote":"For patients experiencing severe rheumatic and systemic immune-related adverse events or with insufficient response to csDMARD, bDMARD may be considered, with TNF or IL-6 inhibitors being the preferred options for inflammatory arthritis","grade":"LoE 4; LoA 8.8"},{"action":"Decide with the patient whether to hold or continue immunotherapy, weighing severity, the treatment needed and how well the cancer is responding","why":"Most arthritis can be treated while immunotherapy carries on; the choice depends on the person's cancer and goals.","source":"eular-2021","quote":"The decision to hold or to continue the cancer immunotherapy should be based on the severity of rheumatic immune-related adverse events, the extent of required immunosuppressive regimen, the tumour response and its duration, as well as the future oncology treatment plan, in a shared decision with the patient","grade":"LoE 5; LoA 9.4"},{"action":"For myositis, check the heart and the nerve-muscle junction, and for grade 3 hold the checkpoint inhibitor and give prednisone 1 mg/kg; stop it permanently if the heart is involved","why":"Muscle inflammation often comes with myocarditis or myasthenia, which can be fatal.","source":"sitc-2021","quote":"For patients with grade 3 myositis, ICIs should be held until myositis is grade ≤1 while off immune suppression and permanently discontinued if there is any evidence of myocardial involvement. Prednisone should be initiated at 1 mg/kg or equivalent."},{"action":"For life-threatening myositis (swallowing or speech problems, breathlessness or myocarditis), give high-dose steroids and consider IVIG or plasma exchange, and withdraw immunotherapy","why":"Severe myositis can stop the breathing and swallowing muscles working.","source":"eular-2021","quote":"In the presence of life-threatening manifestations (bulbar symptoms (dysphagia, dysarthria, dysphonia), dyspnoea and myocarditis), high dose of glucocorticoids, IVIg and/or plasma exchange should be considered; immunotherapy withdrawal is always necessary","grade":"LoE 4; LoA 8.9"}],"bestInClass":{"statement":"SITC 2021 and EULAR 2021 agree on early rheumatology referral, excluding cancer and other causes, steroid-sparing drugs when steroids fail, and full-strength treatment with withdrawal of immunotherapy for life-threatening myositis. They differ on how hard to treat arthritis with steroids. SITC allows 40 to 60 mg/day prednisone for grade 3 or more (LE: 1, with the grade resting on evidence from rheumatic disease outside immunotherapy). EULAR starts with NSAIDs or analgesics, did not recommend methylprednisolone pulses or high-dose oral steroids outside life-threatening disease and myositis because of concern for the anti-tumour response, and adds a conventional DMARD once more than 10 mg/day prednisone is needed. EULAR is the specialist rheumatology statement and the more recent of the two on this question; both rest on case series and expert opinion, with no randomised trials.","sources":["sitc-2021","eular-2021"]},"variants":[{"name":"Steroid-sparing first (EULAR 2021)","differs":"NSAIDs or analgesics first; intra-articular steroid for one or a few joints; systemic steroids only when these fail, tapered within weeks; no pulses or high-dose oral steroids outside life-threatening complications and myositis; conventional DMARD above 10 mg/day prednisone.","evidence":"LoE 4 to 5; task force level of agreement 8.8 to 9.5 out of 10.","sources":["eular-2021"]},{"name":"Dose by CTCAE grade (SITC 2021)","differs":"Prednisone 10 to 20 mg/day for grade 2 and 40 to 60 mg/day for grade 3 or more, with sicca syndrome of grade 2 or more treated with 20 to 40 mg/day tapered over 4 to 6 weeks.","evidence":"LE: 1 for both dosing recommendations.","sources":["sitc-2021"]}],"grades":[{"claim":"Prednisone 10 to 20 mg/day for grade 2 and 40 to 60 mg/day for grade 3 or more arthritis or polymyalgia","grade":"LE: 1","source":"sitc-2021"},{"claim":"TNF inhibitors, methotrexate, leflunomide, hydroxychloroquine, sulfasalazine or IL-6 receptor inhibitors for refractory or long-term arthritis","grade":"LE: 1","source":"sitc-2021"},{"claim":"Grade 2 or more sicca syndrome: prednisone 20 to 40 mg/day tapered over 4 to 6 weeks","grade":"LE: 1","source":"sitc-2021","quote":"Patients with grade ≥2 sicca syndrome may be treated with 20–40 mg/day of prednisone equivalents, subsequently tapered over 4–6 weeks"},{"claim":"No methylprednisolone pulses or high-dose oral steroids outside life-threatening complications and myositis","grade":"task force text (not a numbered point)","source":"eular-2021","quote":"Because of concerns of glucocorticoids on antitumour responses, the task force did not recommend using methylprednisolone pulses or high-dose oral glucocorticoids in the absence of life-threatening complications and myositis, even in severe presentations, and favoured the concept of glucocorticoid sparing where rheumatologists have extensive experience with alternative options."},{"claim":"Pre-existing autoimmune rheumatic disease does not preclude immunotherapy; keep baseline prednisone below 10 mg/day if possible","grade":"LoE 4; LoA 9","source":"eular-2021","quote":"A pre-existing autoimmune rheumatic and/or systemic disease should not preclude the use of cancer immunotherapy."},{"claim":"No routine autoantibody testing before immunotherapy","grade":"LoE 5; LoA 9","source":"eular-2021","quote":"Before initiation of cancer immunotherapy, there is no indication to test every patient for the presence of autoantibodies."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"eular-2021","label":"EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors","publisher":"European Alliance of Associations for Rheumatology (EULAR), Annals of the Rheumatic Diseases","year":2021,"url":"https://europepmc.org/article/PMC/PMC7788064","doi":"10.1136/annrheumdis-2020-217139","gradingScheme":"Oxford Centre for Evidence-Based Medicine levels of evidence (2009), printed as LoE 1 to 5 (na where not applicable), with the task force's mean level of agreement (LoA) on a 0 to 10 scale.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline was read only as its abstract and its musculoskeletal table is not compared here.","The guidelines disagree on steroid dose for severe arthritis, and no trial has tested whether a steroid-sparing approach protects the anti-tumour response.","Long-term TNF inhibitor use for arthritis, unlike one or two infliximab doses for colitis, is of unclear significance for the cancer, as EULAR notes."]},{"id":"irae-nephritis","kind":"protocol","name":"Kidney inflammation (immune-related nephritis) from checkpoint inhibitors","aka":["checkpoint inhibitor nephritis","ICI-associated acute kidney injury","ICI-AKI","immune-related acute interstitial nephritis","checkpoint inhibitor tubulointerstitial nephritis","immunotherapy kidney damage"],"tldr":"Immunotherapy can occasionally inflame the kidneys. It usually causes no symptoms and is found when the creatinine on a routine blood test rises. Other causes are looked for first, some medicines may be stopped, immunotherapy is paused, and steroids are given if the immunotherapy is the cause. Some people can later restart.","summary":"Acute kidney injury is common on checkpoint inhibitors (up to 20% in observational data) but only about 2 to 5% is caused by the checkpoint inhibitor (ADQI 2026). Tubulointerstitial nephritis is the commonest lesion (80 to 90% of biopsies); glomerular disease is rarer. Pooled-trial incidence is about 2% on PD-(L)1 inhibitors or ipilimumab and 5% on the combination (SITC 2021).\n\nSITC 2021: urinalysis and spot urine protein to creatinine ratio (a normal urinalysis does not exclude nephritis); stop drugs known to cause interstitial nephritis, including NSAIDs and proton pump inhibitors; hold the checkpoint inhibitor at KDIGO stage 1 while reversible causes are treated, restarting if the injury resolves; at stage 2 or 3 or significant proteinuria, withhold and refer urgently to nephrology; strongly consider biopsy. Glucocorticoids are first-line (LE: 3); infliximab or mycophenolate for steroid-refractory nephritis (LE: 4).\n\nADQI 2026 (abstract): no clinical feature reliably separates ICI-AKI from other causes and biopsy remains the gold standard; starting glucocorticoids within 3 days of diagnosis is associated with more kidney recovery; recurrence after rechallenge is under 20%, and the panel supports cautious rechallenge in selected patients.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","nephrology"],"related":["irae-rechallenge","checkpoint-inhibitor-baseline-and-monitoring"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["irae","rechallenge"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can sometimes affect the kidneys. Your blood tests check for this. If it happens, immunotherapy is paused and you may need steroids.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","pharmacist","multidisciplinary-team"],"where":["outpatient-clinic","chemotherapy-day-unit","acute-oncology-service","ward"]},"population":"Adults receiving or who have received an immune checkpoint inhibitor whose kidney function falls. Kidney transplant recipients are a separate high-risk group: SITC allows checkpoint inhibitors only after counselling about the high chance of rejection and dialysis. Children are not addressed by these sources.","trigger":"A rise in serum creatinine (KDIGO stage 1: a rise of more than 0.3 mg/dL or 1.5 to 1.9 times baseline), new proteinuria or blood in the urine, during or after checkpoint inhibitor treatment.","steps":[{"action":"Send a urinalysis and a spot urine protein to creatinine ratio","why":"The urine helps separate nephritis from glomerular disease, though a normal result does not rule nephritis out.","source":"sitc-2021","quote":"Patients with possible ICI-related AKI should have a urinalysis and quantification of proteinuria with a spot urine protein:Cr ratio. It should be noted that normal urinalysis does not exclude TIN."},{"action":"Stop other medicines that can cause interstitial nephritis, such as NSAIDs, proton pump inhibitors and some antibiotics","why":"These drugs cause the same kidney inflammation and may be the real culprit.","source":"sitc-2021","quote":"In cases of potential ICI-related AKI, concomitant medications known to cause TIN (eg, NSAIDs, proton pump inhibitors, and some antibiotics) should be discontinued."},{"action":"At stage 1 kidney injury, hold the checkpoint inhibitor while reversible causes such as dehydration are treated; restart if the injury resolves","why":"Most kidney injury in people on immunotherapy has another cause that can be fixed.","source":"sitc-2021","quote":"In patients with stage I AKI (Cr increase of >0.3 mg/dL or 1.5–1.9 times baseline), the ICI should be held while the patient undergoes evaluation and treatment of reversible causes (eg, hypovolemia). ICI therapy can be restarted if the AKI resolves."},{"action":"At stage 2 or 3 (creatinine at least twice baseline) or grade 2 or more proteinuria, withhold the checkpoint inhibitor and get an urgent nephrology review","why":"Larger falls in kidney function need specialist assessment and often a biopsy.","source":"sitc-2021","quote":"Patients with stage II or III AKI (Cr ≥2 times baseline) and/or significant (grade ≥2) proteinuria should have ICIs temporarily withheld and undergo expedited evaluation by a nephrologist."},{"action":"Strongly consider a kidney biopsy where it is feasible","why":"No blood or urine test reliably proves the immunotherapy is the cause; a biopsy does.","source":"sitc-2021","quote":"Given the lack of specific clinical features for ICI-related AKI, renal biopsy should be strongly considered when feasible, particularly when a plausible alternative etiology for AKI exists or urine studies are suggestive of glomerular disease."},{"action":"Treat immune-related interstitial nephritis with glucocorticoids, starting early","why":"Most cases respond to steroids, and recovery is better when they start within 3 days of diagnosis.","source":"sitc-2021","quote":"The first-line treatment for ICI-related TIN is glucocorticoids","grade":"LE: 3"},{"action":"Aim to start glucocorticoids within 3 days of diagnosis","why":"Earlier steroids were associated with more kidney recovery.","source":"adqi-2026","quote":"Early glucocorticoid initiation (within 3 days of ICI-AKI diagnosis versus >3 days after diagnosis) is associated with higher rates of kidney recovery, although optimal dosing and duration remain uncertain."},{"action":"If nephritis does not respond to glucocorticoids, consider infliximab or mycophenolate mofetil","why":"A second immunosuppressant can rescue kidneys that do not respond to steroids.","source":"sitc-2021","quote":"Patients with interstitial nephritis that does not respond to glucocorticoid therapy may receive infliximab or mycophenolate mofetil","grade":"LE: 4"},{"action":"Once the kidneys have recovered, discuss restarting the checkpoint inhibitor in selected patients","why":"The kidney injury comes back in fewer than 1 in 5 people who restart.","source":"adqi-2026","quote":"Recurrent ICI-AKI occurs in fewer than 20% of patients undergoing ICI rechallenge."}],"bestInClass":{"statement":"SITC 2021 (full text) gives the stepwise protocol: urine studies, stop drugs that cause interstitial nephritis, hold at KDIGO stage 1 and refer at stage 2 or 3, strongly consider biopsy, glucocorticoids first-line (LE: 3), infliximab or mycophenolate if refractory (LE: 4). The ADQI 2026 consensus, the most recent and the only nephrology-led statement, agrees and adds from its abstract that steroids started within 3 days are associated with more recovery, that biopsy is the diagnostic gold standard, and that cautious rechallenge is reasonable in selected patients because recurrence is under 20%. Neither sets a steroid dose or duration with confidence: ADQI says the optimal dosing and duration remain uncertain.","sources":["sitc-2021","adqi-2026","asco-2021","esmo-2022"]},"variants":[{"name":"KDIGO staging instead of CTCAE grading (SITC 2021)","differs":"Stages the kidney injury with KDIGO creatinine and urine output criteria, which use both a rise above baseline and absolute thresholds, rather than the CTCAE grade; SITC notes that most trials use CTCAE, which may underestimate kidney injury.","evidence":"Expert consensus.","sources":["sitc-2021"]},{"name":"Checkpoint inhibitors in kidney transplant recipients (SITC 2021)","differs":"Allows treatment only after extensive counselling about the high probability of rejection and dialysis dependence, particularly with PD-(L)1 antibodies.","evidence":"LE: 4.","sources":["sitc-2021"]}],"grades":[{"claim":"Glucocorticoids first-line for immune-related interstitial nephritis","grade":"LE: 3","source":"sitc-2021"},{"claim":"Infliximab or mycophenolate mofetil for steroid-refractory interstitial nephritis","grade":"LE: 4","source":"sitc-2021"},{"claim":"Checkpoint inhibitors in kidney transplant recipients only after counselling on rejection risk","grade":"LE: 4","source":"sitc-2021","quote":"Patients with renal allografts may receive ICIs, but only after extensive counseling on the associated risks and high probability of rejection and subsequent dialysis dependence"},{"claim":"Cautious rechallenge in selected patients","grade":"consensus statement (modified Delphi)","source":"adqi-2026","quote":"these consensus statements provide a framework for diagnosis and management, support cautious ICI rechallenge in selected patients, and identify priorities for future research."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"adqi-2026","label":"Immune Checkpoint Inhibitor-Associated Acute Kidney Injury: A Report from the 34th Acute Disease Quality Initiative (ADQI) Consensus Conference","publisher":"Acute Disease Quality Initiative, Journal of the American Society of Nephrology","year":2026,"url":"https://europepmc.org/article/PMC/PMC13641466","doi":"10.1681/ASN.0000001232","gradingScheme":"Consensus statements reached by a modified Delphi method after systematic PubMed searches; the abstract does not give grades.","read":"abstract","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ADQI 2026 consensus was read only as its abstract: the publisher does not allow the full text to be downloaded from PubMed Central. Its individual consensus statements, steroid regimen and rechallenge criteria are not given here.","The ASCO 2021 guideline was read only as its abstract and its renal table is not compared here.","No source read gives a steroid dose or duration for immune-related nephritis that rests on more than observational data; ADQI states that the optimal dosing and duration remain uncertain."]},{"id":"car-t-apheresis","kind":"protocol","name":"Leukapheresis to collect T cells for CAR T-cell manufacture","aka":["leukapheresis for CAR T","T-cell collection","apheresis for CAR-T","starting material collection","unmobilised leukapheresis"],"tldr":"Every CAR T-cell treatment made from your own cells starts with leukapheresis: over a few hours, blood is taken from a vein, a machine keeps the white cells it needs, and the rest is returned. The date is booked with the manufacturer. Where possible it is done before more chemotherapy, which can weaken the T cells, and some recent treatments need a gap before collection.","summary":"EBMT/JACIE 2019: book leukapheresis only once the manufacturer has confirmed a manufacturing slot. Any approved leukapheresis device may be used; the procedure resembles unmobilised collection for donor lymphocytes or photopheresis, and no device-specific protocol has been issued by device or CAR T-cell manufacturers. Sites must be qualified by the manufacturer; FACT-JACIE accreditation confirms a quality system. Collection is possible with absolute lymphocyte counts as low as 0.1 x 10^9/L, but manufacturing success is likelier above 0.5 x 10^9/L. Where disease allows, collect before salvage chemotherapy, because cumulative chemotherapy harms T-cell quality, and respect washout periods after recent treatments (EBMT Table 4, not read). Prior blinatumomab does not rule out anti-CD19 CAR T. Infectious disease markers are tested on the day of collection; sterility and cell counts (white cells, haematocrit, CD3+, viable CD45+) are reasonable quality control. Fresh products are kept at 2 to 8 degrees until shipped; one manufacturer (Novartis) requires on-site cryopreservation and accepts cells collected within the preceding 18 months.\n\nSITC 2020 (LE: 4): prior allogeneic transplant, bispecific T-cell engagers or anti-CD19 or other antibodies do not exclude CAR T-cell therapy if the target antigen is still expressed. Bridging therapy starts only after collection (see the bridging protocol).","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t"],"related":["car-t-bridging","car-t-lymphodepletion"],"cancers":[],"sections":[],"technologies":["car-t","apheresis-starting-material","car-t-manufacturing-process"],"targets":[],"drugs":["axicabtagene-ciloleucel","tisagenlecleucel","lisocabtagene-maraleucel","brexucabtagene-autoleucel","idecabtagene-vicleucel","ciltacabtagene-autoleucel","obecabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["apheresis","lymphoma-tx-car-t-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"To make CAR T cells, a machine collects some of your white blood cells over a few hours. The date is planned with the company that makes the cells.","domain":"cell-therapy-toxicity","setting":{"who":["nurse","doctor","multidisciplinary-team"],"where":["outpatient-clinic"]},"population":"Adults and children referred for a commercial autologous CAR T-cell product. Children may need different vascular access (Cytotherapy 2022 abstract names this as a challenge). Allogeneic and investigational products follow their own protocols.","trigger":"A treating centre has accepted the patient for CAR T-cell therapy and the manufacturer has offered a slot.","steps":[{"action":"Book leukapheresis only after the manufacturer has confirmed a manufacturing slot","why":"Manufacturing capacity is limited, and collected cells must go straight into a booked production run.","source":"ebmt-2019","quote":"Confirmation of an agreed manufacturing slot is therefore mandatory prior to deciding on a date for apheresis."},{"action":"Collect before starting salvage chemotherapy where the disease allows","why":"The more chemotherapy a person has had, the poorer the T cells tend to be.","source":"ebmt-2019","quote":"Depending on the disease burden, it may be possible to arrange for leukapheresis before starting salvage chemotherapy to treat disease relapse."},{"action":"Check the lymphocyte count; aim to collect when it is above 0.5 x 10^9/L where possible","why":"Collection works at lower counts, but making the product is more likely to succeed with more lymphocytes.","source":"ebmt-2019","quote":"Although apheresis can be performed in patients with absolute lymphocyte counts as low as 0.1×109/L, the likelihood of reaching the target number of autologous lymphocytes and successfully manufacturing the drug product is higher in individuals with absolute lymphocyte counts exceeding 0.5×109/L."},{"action":"Allow washout periods after recent chemotherapy, antibodies or radiotherapy before collecting","why":"Recent treatment can reduce the number and fitness of the T cells collected.","source":"ebmt-2019","quote":"In addition, the choice of salvage therapy (chemotherapy, serotherapy and radiotherapy) may adversely affect subsequent attempts at leukapheresis and washout periods need to be considered."},{"action":"Do not exclude a patient because of earlier transplant, blinatumomab or anti-CD19 antibodies, provided the cancer still carries the target","why":"These treatments do not stop CAR T cells working if the target is still there.","source":"sitc-iec-2020","quote":"Patients who have previously undergone allo-HSCT, bispecific T cell engager (BiTE) therapy, anti-CD19 monoclonal antibody (mAb) therapy, and mAbs against other targets (eg, rituximab) may be treated with CAR T cells, provided the patient’s disease still expresses the target antigen","grade":"LE: 4"},{"action":"Test infectious disease markers on the day of collection and run sterility and cell-count quality control on the product","why":"Regulations require the markers, and a contaminated or poor product cannot be manufactured.","source":"ebmt-2019","quote":"In addition to testing for infectious disease markers in peripheral blood samples on the day of collection, reasonable quality control should include sterility testing as well as some hemocytometric parameters (white blood cell count, hematocrit, CD3+, and viable CD45+ counts)."},{"action":"Store a fresh product refrigerated at 2 to 8 degrees until shipping, or cryopreserve it on site where the manufacturer requires","why":"Each manufacturer sets how the cells must travel; one requires freezing at the collection centre.","source":"ebmt-2019","quote":"The other commercial manufacturers will collect fresh apheresis product packed in their own specified shipping containers. Until shipping, these apheresis products are stored refrigerated (2-8°C)."}],"bestInClass":{"statement":"EBMT/JACIE 2019 is the only guideline on collection read in full and is the basis here; it is ungraded and says no apheresis-specific protocol has been proposed by device or CAR T-cell manufacturers. Its points are practical and uncontested in the sources read: confirm the manufacturing slot, collect before further chemotherapy where possible, aim for a lymphocyte count above 0.5 x 10^9/L, observe washout periods, and follow each manufacturer's handling requirements. The European 2022 update, a 2022 guidance drawn from tisagenlecleucel manufacturing and a French SFGM-TC consensus could be read only as abstracts. Accreditation (FACT-JACIE) and manufacturer site qualification govern the detail.","sources":["ebmt-2019","ebmt-eha-2022","cytotherapy-2022","sfgm-tc-2021"]},"variants":[{"name":"Leukapheresis guidance from tisagenlecleucel manufacturing (Cytotherapy 2022)","differs":"Recommendations on timing, location, vascular access in small patients, T-cell yield, contaminating cells, washout periods and adverse events at collection, based on tisagenlecleucel trial and real-world manufacturing.","evidence":"Experience-based review; only the abstract was read, so its specific recommendations are not given here.","sources":["cytotherapy-2022"]},{"name":"Prospective collection and storage of cells in high-risk patients (EBMT/JACIE 2019, under debate)","differs":"Collecting and cryopreserving mononuclear cells in advance from selected patients at high risk of relapse, before CAR T-cell therapy is needed.","evidence":"Named by EBMT as under debate; no evidence cited.","sources":["ebmt-2019"]}],"grades":[{"claim":"EBMT/JACIE 2019 recommendations","grade":"not graded (consensus)","source":"ebmt-2019"},{"claim":"Prior allogeneic transplant, BiTE or antibody therapy is not a bar if the target is expressed","grade":"LE: 4","source":"sitc-iec-2020"}],"sources":[{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-eha-2022","label":"Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)","publisher":"EBMT, JACIE and EHA, Annals of Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/34923107","doi":"10.1016/j.annonc.2021.12.003","read":"abstract","accessed":"2026-11-11"},{"key":"cytotherapy-2022","label":"Leukapheresis guidance and best practices for optimal chimeric antigen receptor T-cell manufacturing","publisher":"Cytotherapy (International Society for Cell and Gene Therapy journal)","year":2022,"url":"https://europepmc.org/abstract/MED/35718701","doi":"10.1016/j.jcyt.2022.05.003","gradingScheme":"Experience-based recommendations; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"sfgm-tc-2021","label":"How to perform leukapheresis for procurement of the starting material used for commercial CAR T-cell manufacturing: a consensus from experts convened by the SFGM-TC","publisher":"Société francophone de greffe de moelle et de thérapie cellulaire, Bulletin du Cancer","year":2021,"url":"https://europepmc.org/abstract/MED/33610284","doi":"10.1016/j.bulcan.2020.11.014","gradingScheme":"Expert consensus; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The EBMT 2019 washout table (Table 4, adapted from Kansagra et al.) is an image and was not read, so no washout interval for any drug is stated here.","The EBMT 2019 online supplement on apheresis technique, the Cytotherapy 2022 guidance and the SFGM-TC consensus were not read beyond their abstracts.","FACT-JACIE standards and individual manufacturers' collection manuals were not read.","Several manufacturers have changed their requirements since 2019; which still require on-site cryopreservation was not checked."]},{"id":"linear-accelerator-quality-assurance","kind":"protocol","name":"Linear accelerator quality assurance: daily, weekly, monthly and annual machine checks","aka":["linac QA","linac quality control","machine QA","morning QA","daily output check","TG-142","MPPG 8.b","IPEM Report 81","Winston-Lutz test","picket fence test"],"tldr":"Before patients are treated each day, the radiotherapy team checks that the treatment machine gives the right dose, points at the right place and stops when it should. Bigger checks follow every week, month and year, and after every repair. These checks are why a machine fault very rarely reaches a patient.","summary":"The AAPM's current list (MPPG 8.b, 2023) sets the minimum: the qualified medical physicist (QMP) designs the programme, chooses tests that fit how the machine is used, and owns the results. Daily, on the beams in use that day: photon and electron output within 3% of the device baseline, profile constancy, the patient-positioning system (lasers within 2 mm if used for final set-up, or the imaging or surface system that replaces them), the distance indicator and a jaw setting, and safety: door interlock, audio and video monitoring of the patient, beam-on indicators and one anti-collision system in rotation. Weekly: quantitative multileaf collimator leaf-position accuracy within 0.5 mm at several gantry angles (a measured picket-fence test; log files alone are not enough). Monthly: output within 2%, energy and profile constancy, couch and angle readouts, a holistic dynamic-delivery (sliding window or VMAT) test within 2%. Annually: absolute calibration in water to TG-51 with a chamber calibrated at an accredited standards laboratory within two years, output within 1% of nominal, beam data compared with the planning system model within 1 to 2%, radiation isocentre by a Winston-Lutz test (all axes within 1 mm), small-field output factors, a full review of machine settings and the emergency procedures. After repairs the QMP's written return-to-service checks apply, and manufacturers' technical bulletins are reviewed at once. SRS and SBRT need the tighter stereotactic tests (MPPG 9).\n\nIn the UK, IPEM Report 81 (2018) informs practice in 91% of centres; a 2025 IPEM survey found most centres meeting or exceeding it, with 26% still measuring standard output weekly against the report's monthly recommendation. MPPG 8.b deliberately did not repeat a failure mode analysis and asks each centre to do its own, using its tests as the floor.","asOf":"2026-11-11","links":[],"tags":[],"related":["radiotherapy-patient-identification-and-time-out"],"cancers":[],"sections":[],"technologies":["c-arm-linac","radiotherapy-qa-phantoms-dosimeters","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"The radiotherapy machine is tested every morning before anyone is treated. Physicists test it more deeply each month and each year. If a test fails, the machine is not used until it is fixed and checked again.","domain":"radiotherapy","setting":{"who":["radiographer","multidisciplinary-team"],"where":["radiotherapy-department"]},"population":"C-arm medical linear accelerators giving external beam photon or electron radiotherapy. On-board imaging equipment, ring-gantry, helical, robotic and MR-guided machines and stereotactic-specific tolerances are outside MPPG 8.b's scope and are named, not detailed. The checks are made by medical physicists and therapeutic radiographers (radiation therapists); patients are affected by them but do not take part.","trigger":"Every treatment day, and on the weekly, monthly and annual schedule; also after any maintenance, repair, software update or manufacturer's technical bulletin.","steps":[{"action":"Put a qualified medical physicist in charge of the machine QA programme, with defined tests, frequencies and action limits","why":"One accountable expert has to decide what is tested and judge whether the machine is safe to treat on.","source":"aapm-mppg8b","quote":"The qualified medical physicist (QMP) must establish routine testing to ensure that the linac's current performance has not deviated from the clinical parameters acquired at the time of acceptance and commissioning of the machine.","grade":"must"},{"action":"Choose tests that match what the machine is used for (for example, add stereotactic tests if it treats SRS or SBRT)","why":"A machine that treats tiny brain targets needs tighter checks than one that gives broad palliative fields.","source":"aapm-mppg8b","quote":"Performance tests on each linac must be selected to fit the clinical patterns of use of the accelerator, and care must be given to selecting and performing tests that are relevant to detecting errors related to the specific use of the accelerator.","grade":"must"},{"action":"Every treatment day, before patients, check the output of each beam to be used; act if it is more than 3% from the baseline","why":"The dose the machine gives per unit can drift; a morning check catches it before anyone is treated.","source":"aapm-mppg8b","quote":"Daily output checks must be performed on all clinically used beams and must fall within 3% of that dosimetry system's nominal device baseline that correlates to the reference dose output at TG-51","grade":"must"},{"action":"Every day, check that the patient-positioning system (lasers, imaging or surface guidance) is accurate; lasers used for final set-up must be within 2 mm of the isocentre","why":"A correct dose in the wrong place is still an error; the positioning tools are checked before they are trusted.","source":"aapm-mppg8b","quote":"The accuracy of the device(s) used to position the patients must be evaluated daily.","grade":"must"},{"action":"Every day, check that the door interlock stops the beam, that the patient can be seen and heard, that beam-on lights work, and one anti-collision system in rotation","why":"These are the safeguards that protect patients and staff if something goes wrong in the room.","source":"aapm-mppg8b","quote":"Daily, the functionality of the door interlock must be checked to ensure that the radiation beam will terminate if the door is opened.","grade":"must"},{"action":"Do not treat without at least one working audio channel and one working video channel to the patient","why":"The patient is alone in the room during the beam; staff must be able to see and hear them throughout.","source":"aapm-mppg8b","quote":"At least one channel of audio and one channel of video monitoring are required for clinical use of the machine.","grade":"required"},{"action":"Every week, measure the position of every multileaf collimator leaf at several gantry angles, to within 0.5 mm, with a quantitative test such as a picket fence","why":"The leaves shape every modern treatment; small leaf errors add up to dose errors in intensity-modulated plans.","source":"aapm-mppg8b","quote":"The test must be performed at different gantry angles or in arc mode to detect any gravity-induced positional errors.","grade":"must"},{"action":"Do not rely on the machine's own log files alone to check leaf positions; measure the radiation field","why":"Log files record what the machine thinks it did, which can miss a fault in the leaf position itself.","source":"aapm-mppg8b","quote":"At this time, log file analysis alone is not an adequate replacement for testing that measures the radiation field to detect leaf position.","grade":"must (as worded in the guideline)"},{"action":"Every month, check the output of every clinical beam to within 2% of baseline, and review the daily results","why":"A tighter monthly check with better equipment catches slow drift the daily device might miss.","source":"aapm-mppg8b","quote":"Monthly output checks must be performed on all clinically used beams and must fall within 2% of that dosimetry system's nominal baseline that correlates to the reference dose output at TG-51 reference conditions.","grade":"must"},{"action":"Every year, calibrate the absolute dose in water to TG-51 (or an equivalent protocol) with equipment calibrated by an accredited standards laboratory in the past two years","why":"All the other checks are relative to this one; it ties the machine to the national standard of dose.","source":"aapm-mppg8b","quote":"Annual output measurements must be performed in accordance with TG-51, a comparable protocol, or successors in water with equipment calibrated by an accredited secondary standards laboratory within the previous two years.","grade":"must"},{"action":"Every year, test the radiation isocentre with a Winston-Lutz test, so that collimator, gantry and couch rotate about the same point within 1 mm","why":"Beams from different angles must meet at the same spot, or the target is partly missed.","source":"aapm-mppg8b","quote":"Annually, the radiation isocentricity must be tested to ensure all axes (collimator, gantry, and couch) rotate about the same location within 1 mm.","grade":"must"},{"action":"After maintenance or repair, follow written return-to-service checks before the machine treats again","why":"Repairs can change the beam; a set list of checks means nothing is forgotten before patients return.","source":"aapm-mppg8b","quote":"The QMP must create a summary of the return-to-service QA for typical machine maintenance activities that includes the vendor recommendations and any other tests the QMP deems necessary, thereby providing consistency in returning a linac to clinical service.","grade":"must"},{"action":"Read manufacturers' technical bulletins and service reports promptly and decide whether they affect your machine","why":"Manufacturers warn of faults found elsewhere; acting on them prevents the same fault here.","source":"aapm-mppg8b","quote":"Therefore, customer technical bulletins or other documents that alert the linac operator to known potential issues or malfunctions of the machine must be reviewed immediately.","grade":"must"},{"action":"When a result is out of limits, consider every test of that parameter before adjusting the machine or resetting a baseline","why":"A failed output check may really be an energy change; fixing the wrong thing can hide the fault.","source":"aapm-mppg8b","quote":"Therefore, the QMP must ensure that all tests being performed for a clinical parameter are considered before making any machine adjustments and potentially changing any device baseline or reference values.","grade":"must"},{"action":"For machines treating SRS or SBRT, add the stereotactic tests and tighter limits","why":"Very high doses to small targets leave almost no room for error.","source":"aapm-mppg8b","quote":"In these instances, the QMP must refer to protocols specifically designed for performance tests in a stereotactic setting in order to achieve a higher degree of accuracy than that needed for regularly fractionated patients.","grade":"must"}],"bestInClass":{"statement":"The AAPM's MPPG 8.b (2023) is the most recent published list of minimum linac performance tests found: daily output within 3% and safety checks, weekly quantitative leaf-position testing within 0.5 mm, monthly output within 2%, annual TG-51 calibration and Winston-Lutz isocentre testing within 1 mm, plus written return-to-service checks and immediate review of technical bulletins. It updates TG-142 (2009), MPPG 8.a (2017) and TG-198 (2021), returning some tests 8.a had dropped. In the UK the reference is IPEM Report 81 (2018), not read here; a 2025 IPEM survey found most UK centres meeting or exceeding it. MPPG 8.b asks every centre to treat its list as the floor for a local risk analysis (TG-100) rather than a ceiling.","sources":["aapm-mppg8b","uk-survey-2025","aapm-tg142"]},"variants":[{"name":"AAPM TG-142 (2009) with the TG-198 implementation guide (2021)","differs":"The older and longer AAPM task group list, with separate tables for non-IMRT, IMRT and stereotactic machines and for imaging devices (kV, MV and cone-beam CT), and action levels for inspection, scheduled action and immediate action. TG-198 gives step-by-step methods, staff time and sample forms for TG-142 tests and adds VMAT tests.","evidence":"Consensus of the task groups (abstracts read). MPPG 8.b reviewed each TG-142 test and kept a shorter minimum set.","sources":["aapm-tg142","aapm-tg198","aapm-mppg8b"]},{"name":"AAPM MPPG 8.a (2017): risk-ranked minimum set","differs":"Chose tests from an FMEA by the committee, dropping some that scored low; 8.b reinstated some and requires a quantitative leaf-position test, finding the previously recommended visual tests insufficient.","evidence":"Committee FMEA and consensus. 8.b chose not to repeat the FMEA because risk analysis is specific to each centre.","sources":["aapm-mppg8a","aapm-mppg8b"]},{"name":"UK practice under IPEM Report 81 (2018)","differs":"UK centres follow IPEM Report 81, for which the 2025 survey reports a monthly recommendation for standard output; 26% of responding centres still measured standard output weekly. The survey also found a shift towards QC outside normal working hours and wide variation in the time spent per linac (median 18 hours a month on C-arm machines).","evidence":"National survey of 43 of 68 UK centres (63%), 2025. Report 81 itself was not read.","sources":["uk-survey-2025"]},{"name":"Manufacturer integrated quality control (Varian Machine Performance Check, Elekta machine QA and others)","differs":"Automated, mostly EPID-based tests built into the machine, used for some daily and monthly checks. IPEM's 2025 topical report covers commissioning them: independence review, repeatability, baselines and tolerances, concordance with existing QC, sensitivity testing and risk assessment. MPPG 8.b allows vendor tools where the QMP understands what they measure.","evidence":"Working party experience, existing guidance and a 2022 UK survey (IPEM abstract read).","sources":["ipem-miqc-2025","aapm-mppg8b"]}],"grades":[{"claim":"Daily output of each clinical beam within 3% of the device baseline","grade":"must","source":"aapm-mppg8b"},{"claim":"Use the guideline's tests and frequencies as a minimum for any local risk analysis","grade":"recommendation (committee)","source":"aapm-mppg8b","quote":"We recommend using the tests and frequencies outlined in this report as a minimum for any risk analysis performed and that full consideration be given to the implication of removing any of the recommended minimum components."},{"claim":"Weekly quantitative leaf position accuracy within 0.5 mm; log files alone not adequate","grade":"must","source":"aapm-mppg8b"},{"claim":"Most UK centres meet or exceed IPEM Report 81; 26% still check standard output weekly against a monthly recommendation","grade":"survey finding (no grade)","source":"uk-survey-2025","quote":"Standard output was still performed weekly in 26% of centres compared to monthly recommendation in Report 81."}],"sources":[{"key":"aapm-mppg8b","label":"AAPM Medical Physics Practice Guideline 8.b: Linear accelerator performance tests","publisher":"American Association of Physicists in Medicine (Krauss et al., Journal of Applied Clinical Medical Physics)","year":2023,"url":"https://doi.org/10.1002/acm2.14160","doi":"10.1002/acm2.14160","gradingScheme":"AAPM practice guideline wording: 'must' (necessary to conform to the guideline) and 'should' (prudent practice with occasional exceptions); no evidence grades.","read":"full-text","accessed":"2026-11-11"},{"key":"aapm-mppg8a","label":"AAPM Medical Physics Practice Guideline 8.a.: Linear accelerator performance tests","publisher":"American Association of Physicists in Medicine (Journal of Applied Clinical Medical Physics)","year":2017,"url":"https://doi.org/10.1002/acm2.12080","doi":"10.1002/acm2.12080","gradingScheme":"As MPPG 8.b ('must' and 'should').","read":"abstract","accessed":"2026-11-11"},{"key":"aapm-tg142","label":"Task Group 142 report: quality assurance of medical accelerators","publisher":"American Association of Physicists in Medicine (Klein et al., Medical Physics)","year":2009,"url":"https://doi.org/10.1118/1.3190392","doi":"10.1118/1.3190392","gradingScheme":"Tolerances with action levels (inspection, scheduled action, immediate action); no evidence grades.","read":"abstract","accessed":"2026-11-11"},{"key":"aapm-tg198","label":"AAPM Task Group 198 Report: An implementation guide for TG 142 quality assurance of medical accelerators","publisher":"American Association of Physicists in Medicine (Medical Physics)","year":2021,"url":"https://doi.org/10.1002/mp.14992","doi":"10.1002/mp.14992","read":"abstract","accessed":"2026-11-11"},{"key":"uk-survey-2025","label":"A survey and analysis of radiotherapy linear accelerator quality control in the United Kingdom, for c-arm and ring gantry systems and associated patient specific quality control","publisher":"IPEM Radiotherapy Special Interest Group and Interdepartmental Dosimetry Audit Sub-committee (Tassano-Smith et al., British Journal of Radiology)","year":2025,"url":"https://doi.org/10.1093/bjr/tqaf140","doi":"10.1093/bjr/tqaf140","gradingScheme":"Survey; no grades.","read":"full-text","accessed":"2026-11-11"},{"key":"ipem-miqc-2025","label":"IPEM topical report: guidance for the use of linac manufacturer integrated quality control","publisher":"Institute of Physics and Engineering in Medicine (Physics in Medicine and Biology)","year":2025,"url":"https://doi.org/10.1088/1361-6560/adc8f7","doi":"10.1088/1361-6560/adc8f7","read":"abstract","accessed":"2026-11-11"},{"key":"ipem-report-81","label":"Physics Aspects of Quality Control in Radiotherapy, IPEM Report 81, 2nd edition","publisher":"Institute of Physics and Engineering in Medicine","year":2018,"url":"https://www.ipem.ac.uk/","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["IPEM Report 81 (2018), the UK reference, is a priced book and was not read; UK recommendations are given only as the 2025 IPEM survey reports them.","The full TG-142 and TG-198 reports are behind the Medical Physics paywall; only their abstracts were read, so their tolerance tables are not quoted.","MPPG 8.b excludes on-board imaging QA and non-C-arm machines (ring-gantry, helical, robotic, MR-linac); those have their own reports, not covered here.","There is no trial evidence that any particular test frequency prevents patient harm; frequencies and limits are consensus. A survey of physicists cited by MPPG 8.b (184 responses) found they did not agree on the risk of common delivery failures."]},{"id":"car-t-lymphodepletion","kind":"protocol","name":"Lymphodepleting chemotherapy before CAR T-cell infusion","aka":["lymphodepletion","LD chemotherapy","Flu/Cy","fludarabine and cyclophosphamide conditioning","lymphodepleting conditioning"],"tldr":"A few days before CAR T cells are given, a short course of chemotherapy, usually fludarabine and cyclophosphamide, lowers your own white cells to make room for the CAR T cells to grow. The team first checks that your CAR T cells are ready and that you have no uncontrolled infection. The doses and timing follow the instructions for your product.","summary":"EBMT/JACIE 2019: lymphodepletion favours CAR T-cell expansion and persistence; fludarabine-cyclophosphamide is the most widely used regimen, usually over 3 to 5 days before infusion, with admission unless the centre has a safe outpatient pathway. If more than about 3 weeks pass between lymphodepletion and infusion and the white count is above 1.0 x 10^9/L, consider repeating it (SITC 2020: consider after 4 weeks). Infections must be treated and controlled first; SITC 2020 does not give lymphodepletion while a suspected fungal infection is uncontrolled.\n\nThe regimen and dose come from each product's label. YESCARTA (axicabtagene ciloleucel, US label revised 07/2026): cyclophosphamide 500 mg/m2 and fludarabine 30 mg/m2 intravenously on days 5, 4 and 3 before infusion. KYMRIAH (tisagenlecleucel, revised 6/2025): for adult DLBCL and follicular lymphoma, fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 daily for 3 days, with bendamustine 90 mg/m2 for 2 days as the alternative after grade 4 haemorrhagic cystitis or cyclophosphamide resistance, and lymphodepletion may be omitted if the white count is under 1 x 10^9/L in the week before; for children and young adults with B-ALL, fludarabine 30 mg/m2 for 4 days and cyclophosphamide 500 mg/m2 for 2 days. Both labels: confirm the product is available before starting; no live vaccines for at least 6 weeks before lymphodepletion.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t"],"related":["car-t-bridging","car-t-infection-prevention","icaht-prolonged-cytopenia"],"cancers":["dlbcl","follicular-lymphoma","all-leukemia"],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["fludarabine","cyclophosphamide","bendamustine","axicabtagene-ciloleucel","tisagenlecleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphodepletion","lymphoma-tx-car-t-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before CAR T cells, you have a few days of chemotherapy to make space for them. It starts only when your cells are ready and you are free of serious infection.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","nurse","pharmacist"],"where":["ward","chemotherapy-day-unit"]},"population":"Adults and children receiving a commercial autologous CAR T-cell product for B-cell lymphoma, B-cell ALL or myeloma. Regimens and doses differ by product and indication; the two US labels read here are examples, not the full set.","trigger":"The CAR T-cell product has been manufactured and an infusion date is set.","steps":[{"action":"Confirm the CAR T-cell product is available before starting lymphodepletion","why":"Lymphodepletion without a product to follow leaves the person with low counts and no treatment.","source":"yescarta-label-2026","quote":"Confirm availability of YESCARTA prior to starting the lymphodepleting regimen."},{"action":"Treat and control any active infection first; do not give lymphodepletion while a suspected fungal infection is uncontrolled","why":"Lymphodepletion and the cytokine surge after CAR T cells make an existing infection much worse.","source":"sitc-iec-2020","quote":"If a fungal infection is suspected, lymphodepleting chemotherapy should not be administered until appropriate antifungals have been initiated and fungal infection is controlled."},{"action":"Make sure no live vaccine has been given in the 6 weeks before lymphodepletion","why":"Live vaccines can cause infection when the immune system is suppressed.","source":"yescarta-label-2026","quote":"Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment with YESCARTA."},{"action":"Use fludarabine with cyclophosphamide unless the product label or the patient's history says otherwise","why":"This combination gave better CAR T-cell persistence and disease control than older regimens.","source":"ebmt-2019","quote":"Fludarabine-cyclophosphamide is the most widely used LD conditioning regimen."},{"action":"Give the dose and schedule in the product's label; for axicabtagene ciloleucel, cyclophosphamide 500 mg/m2 and fludarabine 30 mg/m2 on days 5, 4 and 3 before infusion","why":"Each product was tested with its own regimen, and the doses differ between products.","source":"yescarta-label-2026","quote":"Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously on the fifth, fourth, and third day before infusion of YESCARTA."},{"action":"Admit for lymphodepletion unless the centre has an established, safe outpatient pathway","why":"Close monitoring and good hydration are needed during these days.","source":"ebmt-2019","quote":"If the center does not have established policies and infrastructure to allow for safe outpatient-based administration, hospitalization is recommended during this period to ensure close monitoring and optimal hydration."},{"action":"Delay the infusion if there are unresolved serious reactions to earlier chemotherapy, uncontrolled infection, active GVHD or worsening leukaemia after lymphodepletion","why":"These raise the risk of severe cytokine release syndrome and other harm.","source":"kymriah-label-2025","quote":"Delay the infusion of KYMRIAH if a patient has unresolved serious adverse reactions (including pulmonary reactions, cardiac reactions, or hypotension) from preceding chemotherapies, active uncontrolled infection, active graft versus host disease (GVHD), or worsening of leukemia burden following lymphodepleting chemotherapy"},{"action":"If the infusion is delayed by more than about 3 weeks and the white count has recovered above 1.0 x 10^9/L, consider repeating lymphodepletion","why":"Once the person's own lymphocytes come back, the CAR T cells lose the space they need to expand.","source":"ebmt-2019","quote":"If there is a long delay (in general, more than 3 weeks) between completing LD conditioning and the subsequent CAR T-cell infusion, and the white blood cell count is >1.0×109/L, then consideration should be given to re-treating the patient with LD chemotherapy prior to administration of the CAR T cells."}],"bestInClass":{"statement":"For the regimen and dose, the product's own label is the authority, and labels differ (fludarabine 30 mg/m2 with cyclophosphamide 500 mg/m2 for three days for axicabtagene ciloleucel; fludarabine 25 mg/m2 with cyclophosphamide 250 mg/m2 for three days, or bendamustine, for tisagenlecleucel in lymphoma). For the checks around it, EBMT/JACIE 2019 and SITC 2020 agree: control infection first, confirm the product, monitor closely, and consider repeating lymphodepletion after a long delay. They differ slightly on that delay: EBMT says more than 3 weeks with a white count above 1.0 x 10^9/L; SITC says consider repeating after 4 weeks. Neither is graded on this point. The 2022 EBMT/JACIE/EHA update was read only as an abstract.","sources":["yescarta-label-2026","kymriah-label-2025","ebmt-2019","sitc-iec-2020","ebmt-eha-2022"]},"variants":[{"name":"Bendamustine instead of fludarabine-cyclophosphamide (tisagenlecleucel label, lymphoma)","differs":"Bendamustine 90 mg/m2 daily for 2 days when a patient had grade 4 haemorrhagic cystitis with cyclophosphamide or shows resistance to a cyclophosphamide regimen.","evidence":"Label instruction; in the pivotal DLBCL trial 22 of 107 patients given lymphodepletion received bendamustine.","sources":["kymriah-label-2025"]},{"name":"Omitting lymphodepletion when counts are already very low (tisagenlecleucel label, lymphoma)","differs":"Lymphodepletion may be omitted if the white count is under 1 x 10^9/L within a week before infusion.","evidence":"Label instruction, reflecting trial eligibility.","sources":["kymriah-label-2025"]},{"name":"Repeat lymphodepletion after 4 weeks (SITC 2020)","differs":"Considers repeating lymphodepletion after a delay of 4 weeks, without a white count threshold.","evidence":"Panel recommendation without a level of evidence.","sources":["sitc-iec-2020"]}],"grades":[{"claim":"EBMT/JACIE 2019 recommendations","grade":"not graded (consensus)","source":"ebmt-2019"},{"claim":"Regimen and dose","grade":"product label (regulatory instruction)","source":"yescarta-label-2026"}],"sources":[{"key":"yescarta-label-2026","label":"YESCARTA (axicabtagene ciloleucel) US prescribing information, revised 07/2026","publisher":"Kite Pharma; US Food and Drug Administration","year":2026,"url":"https://www.fda.gov/media/108377/download","gradingScheme":"Regulatory prescribing information; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"kymriah-label-2025","label":"KYMRIAH (tisagenlecleucel) US prescribing information, revised 6/2025","publisher":"Novartis; US Food and Drug Administration","year":2025,"url":"https://www.fda.gov/media/107296/download","gradingScheme":"Regulatory prescribing information; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-eha-2022","label":"Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)","publisher":"EBMT, JACIE and EHA, Annals of Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/34923107","doi":"10.1016/j.annonc.2021.12.003","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["Only two US labels were read; the lymphodepletion instructions for lisocabtagene maraleucel, brexucabtagene autoleucel, idecabtagene vicleucel, ciltacabtagene autoleucel and obecabtagene autoleucel, and the European SmPCs, were not read and may differ.","The EBMT 2019 checklists before conditioning (Tables 5A and 5B) are images and were not read.","The EBMT/JACIE/EHA 2022 update and the adult B-ALL Delphi consensus (Blood 2026), which includes lymphodepletion statements, were read only as abstracts.","Dose adjustment of fludarabine for reduced kidney function is set in the labels of the chemotherapy drugs and was not read here."]},{"id":"lymphoedema-risk-reduction-surveillance-and-treatment","kind":"protocol","name":"Lymphoedema after breast cancer: risk reduction, surveillance, early compression and treatment","aka":["breast cancer-related lymphoedema","BCRL","BCRL prevention","breast cancer-related lymphoedema prevention","lymphedema risk reduction","lymphoedema precautions","prospective surveillance for lymphoedema","bioimpedance spectroscopy","L-Dex","arm precautions after lymph node surgery","arm care after axillary surgery","complete decongestive therapy"],"tldr":"After surgery or radiotherapy to the armpit nodes, the arm can swell (lymphoedema). Measuring the arm before surgery and at check-ups can find swelling early, when a compression sleeve may stop it becoming permanent. Exercise, including weights, is safe. Infection raises the risk; the old bans on blood pressure, needles or flying are not well supported. Report arm swelling, heaviness or redness.","summary":"MASCC 2024 (Delphi, 55 experts, statements based on randomised trials and systematic reviews): prioritise people with axillary node dissection, axillary radiotherapy, early relative arm volume increase, many nodes removed and BMI of 30 or more; run prospective surveillance where resources allow (93.8% agreement), with a pre-surgical baseline, starting within 3 months of surgery, every 3 to 4 months in year 1 then every 6 to 12 months for at least 24 months; bioimpedance spectroscopy (L-Dex rise of 6.5 or more) or a 5 to under 10% volume increase or any arm symptom triggers a compression sleeve for at least 4 to 6 weeks; 10% or more triggers more intensive treatment; prophylactic compression sleeves, axillary reverse mapping and prophylactic lymphatic reconstruction are options where expertise and resources allow.\n\nThe APTA interventions guideline (2020) recommends prospective surveillance in high-risk groups (Grade C): a preoperative measurement with bioimpedance spectroscopy or volume, then every 3 months for the first year and twice a year for up to 5 years. Subclinical (ISL stage 0) lymphoedema may be treated with education, self-massage and compression garments (Grade C), escalating to complete decongestive therapy (CDT) if it persists. For early (stage I) lymphoedema, an individually fitted compression garment, an exercise programme and education are first-line (Grade A); CDT is used for moderate and late lymphoedema (stages II and III, Grade B), followed by home care with self-massage, a fitted garment and exercise (Grade B). Supervised progressive resistance training from at least one month after surgery is safe (Grade A) and aerobic exercise should be provided (Grade A); therapist manual lymphatic drainage may not reduce risk (Grade C), and a fitted compression garment for high-risk patients with exercise may reduce it (Grade B). PAL (n=154): slowly progressive weight lifting did not increase lymphoedema.\n\nIn the PREVENT trial (963 randomised, 879 analysed), surveillance by bioimpedance spectroscopy triggered a four-week compression sleeve less often than tape measurement (20.1 against 27.5 per cent), and fewer of those treated progressed to chronic lymphoedema needing CDT (7.9 against 19.2 per cent, relative risk 0.41). New cases kept appearing in years two and three, so the authors advise monitoring for at least three years. The APTA diagnosis guideline (2017) set bioimpedance cut-offs of an L-Dex above 7.1 without a baseline or more than 10 above baseline (Grade B); its authors updated the bioimpedance advice in 2018, which was not read.\n\nOn the traditional precautions, in a 3,041-measurement cohort blood draws, injections, blood pressure readings and flights were not associated with arm volume increase, while cellulitis was a risk; a 2024 evidence map prepared for the American Cancer Society and Lymphology Association of North America summit found the evidence sufficient to refute many of the previously claimed risk factors, and called a 'just in case' approach to education possibly inappropriate.","asOf":"2026-11-11","links":[],"tags":["protocol","lymphoedema","survivorship","breast-cancer"],"related":["exercise-during-and-after-cancer-treatment","breast-cancer-follow-up-after-treatment","sentinel-node-tracers-and-blue-dye-safety"],"cancers":["breast-cancer"],"sections":["supportive-care"],"technologies":["lymphoedema-decongestive-therapy","lymphoedema-surgery-and-early-detection","rejuv-measure-lymphoedema","pneumatic-compression-lymphoedema","sentinel-node"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["breast-cancer-related-lymphoedema","lymphoedema-after-breast-cancer"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your arm can swell after breast cancer treatment. Ask to have both arms measured before surgery and at check-ups for at least two years; regular measuring finds swelling early, and a sleeve can help. Tell your team at once about swelling, heaviness or tightness in the arm, or redness and heat that could be infection. Keep exercising: it is safe.","domain":"survivorship","setting":{"who":["nurse","doctor","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","community","home"]},"population":"People treated for breast cancer with surgery, axillary node surgery (sentinel node biopsy or axillary dissection) or axillary radiotherapy, or taxane chemotherapy, as in MASCC, PREVENT and the APTA guidelines. The guidelines read are limited to upper-limb breast cancer-related lymphoedema; leg lymphoedema after groin node surgery for vulval, cervical, endometrial, penile cancer or melanoma, and lymphoedema after head and neck and other cancers, have too little evidence for their own recommendations (ACS/LANA 2024), and the breast steps should not be assumed to transfer without the team's advice.","trigger":"A plan for breast or axillary surgery or radiotherapy (baseline), then follow-up for at least three years; and whenever arm, hand or chest swelling, heaviness or tightness is reported.","steps":[{"action":"Identify who is at highest risk: axillary node dissection, axillary radiotherapy, an early increase in arm volume, many nodes removed, and a high body mass index","why":"Prevention and surveillance can be concentrated on the people most likely to develop swelling.","source":"mascc-2024","quote":"Axillary lymph node dissection, use of post-operative radiotherapy, relative within-arm volume increase one month after surgery, greater number of lymph nodes dissected, and high body mass index were recommended as the most important risk factors to guide selection of patients for interventions to prevent BCRAL.","grade":"Delphi consensus (MASCC)"},{"action":"Measure both arms before surgery, with bioimpedance spectroscopy or limb volume, as a baseline","why":"Small changes are only meaningful against the person's own starting point.","source":"apta-2020","quote":"Monitoring with bioelectric impedance spectroscopy or volume measures may begin with a preoperative assessment, repeated every 3 months for the first year postoperatively, and then biannually for up to 5 years. (Grade C)","grade":"Grade C"},{"action":"Repeat the measurement every 3 months for the first year after surgery, then every 6 months, for at least 3 and up to 5 years, using the same method each time","why":"Most early swelling appears within the first nine months, but new cases keep appearing in years two and three; changing methods makes readings incomparable.","source":"prevent-timing-2024","quote":"Patients should continue to be monitored for a minimum of 3 years following completion of cancer treatment. Specifically, careful targeted monitoring over the initial 9-month period is important."},{"action":"Measure with bioimpedance spectroscopy where available, or arm circumference or volume where it is not","why":"Bioimpedance detects fluid build-up before the arm looks swollen; a tape measure still works when a machine is not available.","source":"mascc-2024","quote":"2.3 In a prospective surveillance program, arm circumference (or volumetric) or lymphangiography/lymphoscintigraphy measurement is an alternative method to identify patients with subclinical/early stage lymphoedema for early treatment when bioimpedance spectroscopy is not available or there are resource limitations Consensus achieved in round 1 82.8% (53/64)","grade":"Consensus 82.8% (alternatives); 89.8% (bioimpedance as an option)"},{"action":"Ask at each visit about swelling, heaviness and numbness in the arm, and investigate them","why":"What the person feels often comes before a measurable change.","source":"apta-dx-2017","quote":"Self-reported symptoms of swelling, heaviness, and numbness should be investigated for early diagnosis (Grade B)","grade":"Grade B"},{"action":"Start treatment when L-Dex rises by 6.5 or more, arm volume rises by 5 to under 10%, or the person reports swelling, heaviness, tightness or numbness: a fitted compression sleeve for at least 4 to 6 weeks","why":"A sleeve worn early reduced progression to lasting lymphoedema in a randomised trial.","source":"mascc-2024","quote":"2.17 When subclinical/early stage lymphoedema is detected in a prospective surveillance program, compression sleeves are suggested to be prescribed for at least 4–6 weeks. A longer duration can be considered depending on clinical response and the individual judgement of the treating therapist. Consensus achieved in round 2 96.2% (50/52)","grade":"Consensus 96.2%"},{"action":"For subclinical swelling found on surveillance, wear the compression sleeve with a gauntlet (in PREVENT, 12 hours a day for 4 weeks), with education and self-massage; escalate to decongestive therapy if it persists or progresses","why":"Treating swelling before it is visible lowered the chance of it becoming long-lasting in a randomised trial.","source":"prevent-2022","quote":"S-BCRL detection triggered a 4-week, 12-hour per day, compression sleeve, and gauntlet intervention."},{"action":"Refer for more intensive treatment such as complete decongestive therapy when arm volume has risen by 10% or more","why":"Larger swelling needs specialist lymphoedema treatment rather than a sleeve alone.","source":"mascc-2024","quote":"2.8 In a prospective surveillance program, more intensive treatment (e.g., congestive decompressive therapy) is indicated when a difference in volume measurements is ≥ 10% compared to pre-surgery values Consensus achieved in round 2 91.7% (44/48)","grade":"Consensus 91.7%"},{"action":"For early visible lymphoedema, fit a compression garment individually, teach an exercise programme and give education as first-line treatment","why":"A well-fitted garment with exercise controls early swelling for most people.","source":"apta-2020","quote":"If early signs and/or symptoms of lymphedema are noted, the patient should be individually fitted with a compression garment, instructed in an exercise program, and provided education as first-line treatment. (Grade A)","grade":"Grade A"},{"action":"For moderate or late lymphoedema, give complete decongestive therapy with compression bandaging and exercise, then a home programme of self-massage, a fitted garment, night compression if needed, and exercise","why":"Bandaging reduces the swelling; the home programme keeps it down.","source":"apta-2020","quote":"CDT should be used to reduce limb volume in those diagnosed with moderate and late BCRL. (Grade B) • Compression bandaging and exercise are key components of CDT and should be used. (Grade A)","grade":"Grade B (CDT); Grade A (bandaging and exercise within CDT)"},{"action":"Encourage aerobic exercise and supervised, progressive resistance training from at least one month after surgery, with weekly checks at first","why":"Lifting weights, built up gradually, does not cause or worsen lymphoedema and improves strength.","source":"apta-2020","quote":"Progressive resistance training is safe when an individualized program is supervised beginning at least 1 month postsurgery. (Grade A) Individualized aerobic exercise programs should be provided. (Grade A) Monitoring for exercise tolerance and adverse effects should initially occur at least weekly and then taper according to clinical presentation. (Grade A)","grade":"Grade A"},{"action":"Teach the person to look after the skin of the arm and to seek treatment quickly for redness, heat or other signs of infection","why":"Cellulitis in the at-risk arm was linked to arm swelling in a large cohort.","source":"ferguson-2016","quote":"This study suggests that although cellulitis increases risk of lymphedema, ipsilateral blood draws, injections, blood pressure readings, and air travel may not be associated with arm volume increases.","grade":"Prospective cohort (not a guideline grade)"},{"action":"Give risk-reduction advice that matches the evidence: protect the skin and treat infection promptly, rather than forbidding all blood pressure readings, blood tests or flights by rule","why":"Skin infection (cellulitis) is a proven risk; many of the traditional prohibitions are not supported by research and can make people anxious.","source":"precautions-2024","quote":"Patient education about precautionary risks needs to be concordant with what is currently evidenced in the literature."}],"bestInClass":{"statement":"Prospective surveillance from a preoperative baseline, with a compression sleeve when subclinical change appears, is the best-supported approach: MASCC 2024 recommends it by consensus on trial evidence (93.8% agreement), APTA 2020 recommends it (Grade C, because the evidence then was mostly observational) and the PREVENT randomised trial (2022) showed bioimpedance-triggered compression reduced progression to chronic lymphoedema against tape-measure-triggered compression. Exercise, including progressive resistance training, is safe (APTA Grade A). Treatment of established lymphoedema follows APTA 2020 by stage (Grade A for garment, exercise and education in early disease; Grade B for CDT later). On the arm precautions, the 2024 summit evidence map and consensus move away from blanket prohibitions on the same evidence: blood draws, injections, blood pressure readings and air travel were not associated with arm volume increase in the largest cohort, whereas infection was. The 2017 ASBrS panel, which also addressed them, could not be read, so the two cannot be set side by side here. MASCC and APTA differ on prophylactic sleeves: MASCC offers them as an option to anyone at risk, while APTA grades a fitted garment for high-risk patients, paired with exercise, at B.","sources":["mascc-2024","apta-2020","prevent-2022","prevent-timing-2024","apta-dx-2017","precautions-2024","summit-consensus-2024","ferguson-2016","asbrs-2017"]},"variants":[{"name":"Traditional arm precautions (no blood pressure, blood draws, injections or cannulas in the at-risk arm; compression for flights)","differs":"Teaches every person at risk to avoid any procedure or exposure on the treated side, for life.","evidence":"Common practice. In the Ferguson cohort none of blood draws, injections, blood pressure readings or flying was associated with arm volume increase. The 2024 evidence map (37 studies, 2008 to 2023) found evidence sufficient to refute many previously claimed risk factors for developing lymphoedema, and little evidence either way on progression once it exists. The 2024 ACS/LANA consensus updated recommendations on blood pressure, skin puncture, blood draws, air travel and heat; its specific wording could not be read (abstract only).","sources":["ferguson-2016","precautions-2024","summit-consensus-2024"]},{"name":"Tape-measure surveillance instead of bioimpedance","differs":"Circumference measured with a tape at set points, converted to volume, instead of a bioimpedance device.","evidence":"In PREVENT, tape measurement triggered intervention more often (27.5 against 20.1 per cent) and more of those treated progressed (19.2 against 7.9 per cent). Tape measurement needs no device and is widely available, and MASCC accepts it where bioimpedance is not available.","sources":["prevent-2022","mascc-2024"]},{"name":"MASCC surveillance schedule","differs":"Starts within 3 months of surgery, measures every 3 to 4 months in the first year, then every 6 to 12 months, for at least 24 months (APTA: every 3 months in the first year, then twice a year for up to 5 years).","evidence":"MASCC 2024 Delphi consensus: 85.9% (interval), 82.8% (start within 3 months), 89.1% (at least 24 months). PREVENT's timing analysis advises at least 3 years.","sources":["mascc-2024","apta-2020","prevent-timing-2024"]},{"name":"Prospective surveillance plus a supervised exercise programme","differs":"Adds a 12-week supervised multimodal exercise programme to surveillance in high-risk women having adjuvant chemotherapy.","evidence":"Single-centre randomised trial of 116 women: the combination reduced arm volume and improved grip strength, walking distance and quality of life over surveillance alone. Read as an abstract.","sources":["apmr-2025"]},{"name":"Prophylactic compression sleeve for everyone at high risk","differs":"Fits a sleeve from the first day after surgery until 3 months after the end of chemotherapy or radiotherapy (not hormone therapy), at least 8 hours a day.","evidence":"Offered as an option by MASCC 2024 (80% agreement, on a single randomised trial; experts who disagreed said one trial should not set routine practice); APTA 2020 Grade B for a fitted garment with exercise in high-risk patients.","sources":["mascc-2024","apta-2020"]},{"name":"Preventive manual lymphatic drainage","differs":"Adds therapist-delivered lymphatic drainage massage after surgery to prevent lymphoedema.","evidence":"APTA 2020: may not reduce the risk (Grade C).","sources":["apta-2020"]},{"name":"Surgical prevention: axillary reverse mapping and prophylactic lymphatic reconstruction","differs":"Spares the arm's lymphatics during dissection, or joins divided lymphatics to a vein at the time of dissection.","evidence":"MASCC 2024: an option where expertise is available and resources allow; reverse mapping not for people at high risk of axillary recurrence.","sources":["mascc-2024"]}],"grades":[{"claim":"Prospective surveillance is recommended where feasible","grade":"Consensus 93.8% (MASCC)","source":"mascc-2024","quote":"2.1 A prospective surveillance program is recommended to reduce risks of chronic lymphoedema after breast cancer surgery where feasible and resources allow Consensus achieved in round 1 93.8% (60/64)"},{"claim":"Prospective surveillance in high-risk groups","grade":"Grade C","source":"apta-2020","quote":"Early identification of subclinical lymphedema in high-risk groups through prospective surveillance may improve outcomes. (Grade C)"},{"claim":"A pre-surgical baseline is required for surveillance","grade":"Consensus 89.1% (MASCC)","source":"mascc-2024","quote":"2.11 Pre-surgical assessment of lymphoedema is required in a prospective surveillance program for better comparison of measurements after surgery Consensus achieved in round 1 89.1% (57/64)"},{"claim":"Surveillance every 3 to 4 months in year 1, then every 6 to 12 months","grade":"Consensus 85.9% (MASCC)","source":"mascc-2024","quote":"2.12 The surveillance interval for a prospective surveillance program is recommended to be every 3–4 months in the first year then every 6–12 months thereafter where feasible and resources allow Consensus achieved in round 1 85.9% (55/64)"},{"claim":"Bioimpedance cut-offs for diagnosis","grade":"Grade B","source":"apta-dx-2017","quote":"Cutpoint of >7.1 L-Dex score should be used for diagnosis of breast cancer–related lymphedema when preoperative baseline measures are not available (Grade B) – Cutpoint of >10 L-Dex score above preoperative baseline should be used for diagnosis of breast cancer–related lymphedema (Grade B)"},{"claim":"Bioimpedance-triggered compression reduced progression against tape measure","grade":"randomised trial, P = 0.016","source":"prevent-2022","quote":"Overall, 14.4% ( n = 30) progressed post-intervention, with reduced likelihood for BIS patients than TM patients (7.9%, n  = 7 vs. 19.2%, n  = 23; relative risk = 0.41; 95% CI, 0.13-0.81; absolute reduction 11.3%; 95% CI, 2.3-20.3; p  = 0.016)."},{"claim":"Prophylactic sleeves offered as an option","grade":"Consensus 80% (MASCC)","source":"mascc-2024","quote":"3.1 Prophylactic compression sleeves should be offered as an option to prevent breast cancer- related arm lymphoedema Consensus achieved in round 2 80% (40/50)"},{"claim":"Fitted compression garment with exercise for high-risk patients","grade":"Grade B (APTA)","source":"apta-2020","quote":"Provision of a fitted compression garment to patients at high risk of developing lymphedema, when paired with upper extremity exercise and diaphragmatic breathing, may reduce development of lymphedema. (Grade B)"},{"claim":"Manual lymphatic drainage after axillary dissection does not clearly prevent lymphoedema","grade":"Grade C","source":"apta-2020","quote":"The addition of therapist-provided manual lymphatic drainage (MLD) to the postoperative care plan may not reduce the risk of developing BCRL. (Grade C)"},{"claim":"Weight lifting does not increase lymphoedema","grade":"Randomised equivalence trial, n=154 (PAL)","source":"pal-2010","quote":"In breast cancer survivors at risk for lymphedema, a program of slowly progressive weight lifting compared with no exercise did not result in increased incidence of lymphedema."},{"claim":"Evidence too thin for other cancers","grade":"Consensus statement (ACS/LANA)","source":"summit-consensus-2024","quote":"More high-quality evidence is required to allow the development of risk reduction recommendations for other cancer types such as gynecological, melanoma, and head and neck."}],"sources":[{"key":"mascc-2024","label":"Wong et al., MASCC clinical practice guidance for the prevention of breast cancer-related arm lymphoedema: international Delphi consensus-based recommendations (eClinicalMedicine 2024)","publisher":"Multinational Association of Supportive Care in Cancer","year":2024,"url":"https://doi.org/10.1016/j.eclinm.2024.102441","doi":"10.1016/j.eclinm.2024.102441","gradingScheme":"Modified Delphi; each statement printed with the round and percentage agreement (consensus at 75% or more).","read":"full-text","accessed":"2026-11-11"},{"key":"apta-2020","label":"Interventions for Breast Cancer-Related Lymphedema: Clinical Practice Guideline From the Academy of Oncologic Physical Therapy of APTA","publisher":"APTA Academy of Oncologic Physical Therapy, Physical Therapy","year":2020,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7412854/","doi":"10.1093/ptj/pzaa087","gradingScheme":"Grade A (strong) to D (theoretical), plus Best Practice and Expert Opinion statements.","read":"full-text","accessed":"2026-11-11"},{"key":"apta-dx-2017","label":"Diagnosis of Upper Quadrant Lymphedema Secondary to Cancer: Clinical Practice Guideline From the Oncology Section of the American Physical Therapy Association","publisher":"APTA Oncology Section, Physical Therapy","year":2017,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5803775/","doi":"10.1093/ptj/pzx050","gradingScheme":"Grade A (strong: Level I studies) to D (theoretical), plus Expert Opinion.","read":"full-text","accessed":"2026-11-11"},{"key":"prevent-2022","label":"A Comparison of Bioimpedance Spectroscopy or Tape Measure Triggered Compression Intervention in Chronic Breast Cancer Lymphedema Prevention (PREVENT)","publisher":"Lymphatic Research and Biology","year":2022,"url":"https://europepmc.org/abstract/MED/35099283","doi":"10.1089/lrb.2021.0084","read":"abstract","accessed":"2026-11-11"},{"key":"prevent-timing-2024","label":"Timing of Breast Cancer Related Lymphedema Development Over 3 Years: Observations from a Large, Prospective Randomized Screening Trial Comparing Bioimpedance Spectroscopy Versus Tape Measure","publisher":"Annals of Surgical Oncology","year":2024,"url":"https://europepmc.org/abstract/MED/38965099","doi":"10.1245/s10434-024-15706-x","read":"abstract","accessed":"2026-11-11"},{"key":"precautions-2024","label":"Current evidence on patient precautions for reducing breast cancer-related lymphedema manifestation and progression risks","publisher":"Medical Oncology (2023 ACS/LANA Lymphedema Summit)","year":2024,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11486782/","doi":"10.1007/s12032-024-02408-3","gradingScheme":"Evidence map of 37 studies; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"summit-consensus-2024","label":"Evidence-based recommendations regarding risk reduction practices for people at risk of or with breast cancer-related lymphedema: consensus from an expert panel","publisher":"Medical Oncology (2023 ACS/LANA Lymphedema Summit)","year":2024,"url":"https://europepmc.org/abstract/MED/39438352","doi":"10.1007/s12032-024-02510-6","gradingScheme":"Expert consensus on the evidence; grades not visible in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"ferguson-2016","label":"Ferguson et al., Impact of Ipsilateral Blood Draws, Injections, Blood Pressure Measurements, and Air Travel on the Risk of Lymphedema for Patients Treated for Breast Cancer (J Clin Oncol 2016)","publisher":"Journal of Clinical Oncology","year":2016,"url":"https://doi.org/10.1200/JCO.2015.61.5948","doi":"10.1200/JCO.2015.61.5948","gradingScheme":"Prospective cohort; no recommendation grade.","read":"abstract","accessed":"2026-11-11"},{"key":"pal-2010","label":"Schmitz et al., Weight Lifting for Women at Risk for Breast Cancer-Related Lymphedema: a randomized trial (JAMA 2010)","publisher":"JAMA","year":2010,"url":"https://doi.org/10.1001/jama.2010.1837","doi":"10.1001/jama.2010.1837","gradingScheme":"Randomised controlled equivalence trial; no recommendation grade.","read":"abstract","accessed":"2026-11-11"},{"key":"apmr-2025","label":"Randomized Trial Assessing Prospective Surveillance and Exercise for Preventing Breast Cancer-Related Lymphedema in High-Risk Patients","publisher":"Archives of Physical Medicine and Rehabilitation","year":2025,"url":"https://europepmc.org/abstract/MED/40081785","doi":"10.1016/j.apmr.2025.03.002","read":"abstract","accessed":"2026-11-11"},{"key":"asbrs-2017","label":"Considerations for Clinicians in the Diagnosis, Prevention, and Treatment of Breast Cancer-Related Lymphedema: Recommendations from a Multidisciplinary Expert ASBrS Panel, Parts 1 and 2","publisher":"American Society of Breast Surgeons, Annals of Surgical Oncology","year":2017,"url":"https://doi.org/10.1245/s10434-017-5982-4","doi":"10.1245/s10434-017-5982-4","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-acc-lymphoedema-prospective-surveillance","idea-upgrade-evidence-based-arm-precautions-after-breast-cancer"],"gaps":["The 2018 update to the APTA bioimpedance recommendations was not read (Europe PMC holds only the title), so the L-Dex cut-offs given here are the 2017 ones and may have been revised; MASCC's 2024 trigger of an L-Dex rise of 6.5 or more differs from them.","The ACS/LANA 2024 risk-reduction consensus was read only as an abstract; its specific wording on blood pressure, blood draws, injections, air travel, heat and saunas is not given here.","The ASBrS 2017 expert panel recommendations could not be read: Europe PMC holds no abstract.","PREVENT was read only as abstracts; its exact measurement thresholds for triggering compression are not given here.","Which surveillance method is best (bioimpedance or measurement) and the right threshold are not fully settled; MASCC accepts both, while PREVENT favoured bioimpedance.","Whether prophylactic sleeves help everyone at risk rests on one randomised trial with one year of follow-up (MASCC 2024).","No UK guideline (British Lymphology Society, NICE) and no NCCN survivorship guideline was read; NICE breast cancer guidance was not checked for lymphoedema surveillance in this round. The International Society of Lymphology 2023 consensus was read only as an abstract.","There is too little evidence for leg lymphoedema after groin node surgery (vulval, cervical, endometrial, penile cancer, melanoma), or for lymphoedema after head and neck cancers, to set out their own steps (ACS/LANA 2024)."]},{"id":"malignant-ascites-drainage","kind":"protocol","name":"Malignant ascites: paracentesis and indwelling peritoneal catheter drainage","aka":["ascitic drain","abdominal paracentesis for cancer","ascitic tap","PeritX drain","Rocket peritoneal catheter","tunnelled peritoneal catheter","draining fluid from the abdomen in cancer","day-case paracentesis"],"tldr":"When cancer causes fluid to build up in the abdomen, draining it through a thin tube (paracentesis) quickly relieves bloating and breathlessness, often as a day case. Treating the cancer can slow it down. If the fluid keeps coming back, a soft tube can be left in place so it can be drained at home in small amounts. The evidence for the details of drainage is weak, so practice varies.","summary":"The evidence for draining malignant ascites is weak: a 2006 systematic review found no randomised trials of paracentesis, diuretics or shunts, and the 2019 Cochrane update found one high-risk-of-bias trial (catumaxomab) and concluded there is insufficient evidence to recommend how drainage should be managed in gynaecological cancer. Paracentesis gives good, temporary relief and is the first-line treatment (Japanese guideline 2021). Practice carried over from cirrhosis (intermittent clamping, routine intravenous fluids or albumin, admission for several days) is not supported in malignant ascites: a UK hospice guideline (2002) drained up to 5 litres without clamping, removed drains within 6 hours and gave fluids only when indicated, and a UK series (2012) drained 21 people without clamping (4 had an asymptomatic fall in systolic pressure below 95 mm Hg, none felt unwell) and then drained to dryness as a day case, without intravenous fluids, in 18 of 19 procedures. Diuretics should be considered and judged individually (Becker 2006). Systemic treatment is strongly recommended for ovarian cancer with massive ascites (strong, evidence A) and weakly for gastric cancer. For treatment-resistant, recurrent ascites NICE recommends an indwelling peritoneal catheter (PeritX) drained into 1-litre vacuum bottles at home, which saves an estimated £1,095 a person against inpatient large-volume paracentesis. The Japanese guideline recommends against peritoneovenous (Denver) shunts because of frequent, sometimes fatal complications, and supports cell-free and concentrated ascites reinfusion (CART) with a weak grade.","asOf":"2026-11-11","links":[],"tags":[],"related":["care-in-the-last-days-of-life","indwelling-pleural-catheter-drainage-at-home"],"cancers":["ovarian","gastric","pancreatic","peritoneal-mesothelioma"],"sections":[],"technologies":["indwelling-peritoneal-catheters","pleural-and-peritoneal-shunts"],"targets":[],"drugs":["catumaxomab"],"companies":[],"institutions":[],"pathways":[],"terms":["peritoneal-metastasis","colorectal-peritoneal-metastases","pleural-effusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Fluid in the belly from cancer can be drained with a thin tube, usually in a day. If it keeps coming back, a tube can stay in so a nurse or your family can drain it at home. Tell your team about fever, belly pain or fluid leaking around the tube.","domain":"palliative","setting":{"who":["doctor","nurse","patient-or-carer","multidisciplinary-team"],"where":["chemotherapy-day-unit","ward","home","community","outpatient-clinic"]},"population":"Adults with symptomatic ascites caused by cancer in the peritoneum, most often ovarian, gastric, pancreatic, colorectal or breast cancer. Ascites from cirrhosis, including in people with liver cancer, is managed differently and is not covered.","trigger":"Abdominal swelling, discomfort, breathlessness, nausea or early fullness from malignant ascites.","steps":[{"action":"Offer paracentesis as the first treatment for symptomatic, massive malignant ascites","why":"Draining the fluid relieves bloating and breathlessness quickly, and it can be done almost anywhere.","source":"jp-2021","quote":"However, since it can be easily performed at any facility, it can be considered as the first-line treatment for massive ascites.","grade":"Not graded (general statement in the guideline)"},{"action":"Treat the underlying cancer where it is likely to respond, above all in ovarian cancer","why":"Shrinking the cancer can stop the fluid coming back, and people with ovarian cancer can live a long time even with a lot of fluid.","source":"jp-2021","quote":"Ovarian cancer is extremely sensitive to chemotherapy. Although most patients with advanced PD have a large amount of ascites, long-term survival can be expected even from this condition. Chemotherapy is strongly recommended.","grade":"Strength of recommendation: Strong; strength of evidence: A (ovarian). Gastric cancer: weak, C. Other cancers: not recommended, D."},{"action":"Let the drain run freely rather than clamping it at set volumes, watching blood pressure and how the person feels","why":"Clamping comes from liver disease, where large drainage can drop blood pressure; in cancer, free drainage has been safe in the studies done so far.","source":"harding-2012","quote":"Free drainage of malignant ascites is safe.","grade":"Observational study (no grade)"},{"action":"Give intravenous fluids only when there is a specific reason, not routinely","why":"Routine drips keep people in hospital and have not been shown to help in malignant ascites.","source":"stephenson-2002","quote":"giving intravenous fluids only when specifically indicated","grade":"Local guideline based on limited evidence (no grade)"},{"action":"Plan paracentesis as a day case where possible, with the drain placed early in the day under image guidance and removed the same day","why":"Most people can be drained completely in a working day and go home, which is what most patients prefer.","source":"harding-2012","quote":"Daycase paracentesis is feasible, cost-effective and reduces hospital admissions, and potentially represents the standard of care for patients with malignant ascites.","grade":"Observational study (no grade)"},{"action":"Consider diuretics, but judge their use person by person","why":"Some people's ascites responds to diuretics and many do not; the trials have not been done.","source":"becker-2006","quote":"The use of diuretics therefore should be considered in all patients, but has to be evaluated individually.","grade":"Systematic review; evidence weak (no randomised trials)"},{"action":"For ascites that keeps coming back despite treatment, offer an indwelling peritoneal catheter","why":"Draining small amounts often at home avoids repeated hospital visits and long drainage stays.","source":"nice-htg282","quote":"The PeritX system is recommended as an option for drainage of treatment-resistant, recurrent malignant peritoneal ascites.","grade":"Not graded (NICE HealthTech guidance 1.1, 'recommended as an option')"},{"action":"Drain the catheter at home into the vacuum bottles, in smaller amounts more often, by a community nurse, the patient or a carer","why":"Frequent small drainages keep symptoms down instead of waiting for the abdomen to fill.","source":"nice-htg282","quote":"Better symptom control by frequent drainage of smaller quantities of ascitic fluid.","grade":"Not graded (NICE committee's statement of expected benefit)"},{"action":"Ask the patient and carers to report fever, abdominal pain, redness or leakage at the exit site, and drainage that stops","why":"Infection, leakage and blockage are the common catheter problems, and most can be treated.","source":"nice-htg282","quote":"adverse events (catheter site infections, peritonitis, catheter occlusion, and haemorrhage or bowel perforation when the device is inserted)","grade":"Not graded (outcomes the NICE evidence review collected)"}],"bestInClass":{"statement":"There is no high-grade guideline for draining malignant ascites, and the sources agree that the evidence is weak. The best supported approach now combines: paracentesis as first-line relief (Japanese guideline 2021); free drainage as a day case without routine clamping or intravenous fluids (UK hospice guideline 2002 and UK series 2012, both small and non-randomised); treatment of the cancer where it responds (strong for ovarian cancer); and, for treatment-resistant recurrent ascites, an indwelling peritoneal catheter drained at home (NICE HealthTech guidance 282). The Japanese guideline and NICE differ in emphasis: Japan grades CART as an option and recommends against Denver shunts; NICE assessed only the PeritX catheter.","sources":["jp-2021","harding-2012","stephenson-2002","nice-htg282","cochrane-2019","becker-2006"]},"variants":[{"name":"Intermittent clamping and limited volumes","differs":"Clamps the drain after set volumes, or drains small amounts (1 to 3 litres) at a time.","evidence":"Derived from cirrhosis practice (Harding 2012). The Japanese Society of Palliative Medicine guidance cited in the 2021 guideline drains 1 to 3 litres, while noting small drainages relieve symptoms poorly and refill quickly; free drainage was safe in the UK series.","sources":["harding-2012","jp-2021"]},{"name":"Hospice protocol: up to 5 litres, drain out within 6 hours","differs":"Ultrasound only when the diagnosis is uncertain, up to 5 litres without clamping, drain left no more than 6 hours.","evidence":"Exeter hospice guideline (2002); after its introduction, ultrasound use, drain time and length of stay fell, with no symptomatic hypotension. Before-and-after case note review, abstract read.","sources":["stephenson-2002"]},{"name":"Cell-free and concentrated ascites reinfusion therapy (CART)","differs":"Filters and concentrates the drained fluid and returns its protein to the person intravenously; widely used in Japan.","evidence":"Japanese guideline 2021: weak recommendation, evidence C (the statement's wording says 'strongly recommended', the printed grade says weak).","sources":["jp-2021"]},{"name":"Peritoneovenous (Denver) shunt","differs":"A permanent shunt returns ascites to the bloodstream.","evidence":"Japanese guideline 2021 recommends against it because complications are frequent and can be fatal (weak against, evidence C). Becker 2006: can control ascites but must be balanced against the risks.","sources":["jp-2021","becker-2006"]},{"name":"Intraperitoneal catumaxomab after paracentesis","differs":"Gives the antibody catumaxomab into the abdomen after drainage.","evidence":"One randomised trial (245 participants) in the Cochrane review: longer time to deterioration in quality of life, very low certainty, high risk of bias.","sources":["cochrane-2019"]}],"grades":[{"claim":"Chemotherapy for gastric cancer with massive ascites","grade":"Strength of recommendation: Weak; strength of evidence: C","source":"jp-2021","quote":"Chemotherapy is recommended after careful evaluation of general condition of patients."},{"claim":"CART for massive malignant ascites","grade":"Strength of recommendation: Weak; strength of evidence: C; consensus 100%","source":"jp-2021","quote":"It is strongly recommended to perform CART for patients with massive cancerous ascites."},{"claim":"No peritoneovenous shunt","grade":"Strength of recommendation: Weak; strength of evidence: C; consensus 70%","source":"jp-2021","quote":"However, the complications are frequent and can be fatal and thus abdominal-venous shunting is strongly recommended not to be performed."},{"claim":"Intraperitoneal triamcinolone","grade":"Not recommended; strength of evidence: D","source":"jp-2021","quote":"It is a treatment option that is easy to operate and accessible to patients, but no clear recommendations can be made."},{"claim":"Evidence on drainage management in gynaecological cancer","grade":"Very low certainty (Cochrane)","source":"cochrane-2019","quote":"Currently, there is insufficient evidence to recommend the most appropriate management of drainage for malignant ascites among women with gynaecological cancer, as there was only very low-certainty evidence from one small RCT at overall high risk of bias."},{"claim":"Speed of drainage and intravenous hydration","grade":"Not sufficiently studied (systematic review)","source":"becker-2006","quote":"Fluid withdrawal speed and concurrent intravenous hydration is not sufficiently studied."},{"claim":"Cost of the indwelling catheter against inpatient paracentesis","grade":"NICE cost model","source":"nice-htg282","quote":"The PeritX system can lead to an estimated cost saving of £1,095 per person compared with inpatient large-volume paracentesis."}],"sources":[{"key":"nice-htg282","label":"PeritX peritoneal catheter drainage system for vacuum-assisted drainage of treatment-resistant, recurrent malignant ascites (HealthTech guidance 282, formerly MTG9)","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/htg282","gradingScheme":"NICE does not grade recommendations; medical technologies guidance recommends a device as an option or not.","read":"full-text","accessed":"2026-11-11"},{"key":"jp-2021","label":"Clinical practice guideline for the treatment of malignant ascites: section summary in Clinical Practice Guideline for peritoneal dissemination 2021 (Matsusaki et al., Int J Clin Oncol)","publisher":"Japanese Society for Peritoneal Dissemination guideline committee (International Journal of Clinical Oncology)","year":2021,"url":"https://doi.org/10.1007/s10147-021-02077-6","doi":"10.1007/s10147-021-02077-6","gradingScheme":"Minds 2017 and GRADE: strength of recommendation strong or weak, for or against, or not graded; strength of evidence A to D; consensus rate printed.","read":"full-text","accessed":"2026-11-11"},{"key":"cochrane-2019","label":"Management of drainage for malignant ascites in gynaecological cancer (Cochrane Database Syst Rev 2019 update)","publisher":"Cochrane","year":2019,"url":"https://doi.org/10.1002/14651858.CD007794.pub3","doi":"10.1002/14651858.cd007794.pub3","gradingScheme":"GRADE certainty of evidence.","read":"abstract","accessed":"2026-11-11"},{"key":"becker-2006","label":"Malignant ascites: systematic review and guideline for treatment (Becker et al., Eur J Cancer 2006)","publisher":"European Journal of Cancer","year":2006,"url":"https://doi.org/10.1016/j.ejca.2005.11.018","doi":"10.1016/j.ejca.2005.11.018","gradingScheme":"Systematic review; evidence described as weak, no formal grades in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"stephenson-2002","label":"The development of clinical guidelines on paracentesis for ascites related to malignancy (Stephenson and Gilbert, Palliat Med 2002)","publisher":"Palliative Medicine","year":2002,"url":"https://doi.org/10.1191/0269216302pm509oa","doi":"10.1191/0269216302pm509oa","gradingScheme":"Local hospice guideline with before-and-after audit; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"harding-2012","label":"Safety, cost-effectiveness and feasibility of daycase paracentesis in the management of malignant ascites with a focus on ovarian cancer (Harding et al., Br J Cancer 2012)","publisher":"British Journal of Cancer","year":2012,"url":"https://doi.org/10.1038/bjc.2012.343","doi":"10.1038/bjc.2012.343","gradingScheme":"Single-centre audit and prospective series; no grade.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No randomised trial has compared drainage volumes, drainage speed, clamping, albumin or intravenous fluids in malignant ascites; the 2006 systematic review and the 2019 Cochrane update both found the evidence insufficient.","No European, US or UK national clinical guideline specific to malignant ascites was found; the British Society of Gastroenterology ascites guidance is written for cirrhosis and was not read or used.","The Japanese guideline's wording and printed grades disagree for CART and for shunts ('strongly recommended' beside a weak grade); the printed grades are given here.","The full texts of the Cochrane review, Becker 2006 and Stephenson 2002 were not read; only their abstracts.","NICE assessed the PeritX system alone; other tunnelled peritoneal catheters (Rocket, Aspira) were not part of the guidance, and the manufacturers' home drainage instructions were not read.","Who should have a catheter rather than repeated day-case paracentesis (for example platinum-sensitive versus platinum-resistant ovarian cancer) has not been tested in a trial."]},{"id":"malignant-bowel-obstruction","kind":"protocol","name":"Malignant bowel obstruction in advanced cancer: medicines, decompression, stents, surgery and nutrition","aka":["MBO","bowel obstruction in advanced cancer","inoperable bowel obstruction","octreotide for bowel obstruction","venting gastrostomy"],"tldr":"Advanced bowel, ovarian or other abdominal cancer can block the bowel. Cramping pain, a swollen tummy, being sick and not passing wind or stools need urgent assessment; a CT scan confirms it. Treatment depends on what you want from care and how well you are: some people have a stent or an operation, many have medicines for sickness and pain, sometimes with a tube to drain the stomach.","summary":"MASCC 2022 is the most complete recent guideline: a systematic review to March 2021 producing 25 graded suggestions and recommendations (MASCC levels I to V and grades A to D). MBO is a clinical diagnosis confirmed by contrast CT, which is more valuable than plain X-ray. Decisions are framed by goals of care, prognosis, performance status and where care is given, and a surgical opinion should be considered at diagnosis.\n\nMedicines: a somatostatin analogue (octreotide, lanreotide) is the only recommendation at level I, grade A (to reduce vomiting); MASCC 2021 calls octreotide the drug of choice in non-operable MBO. Haloperidol is suggested, particularly in complete obstruction (IV, B); metoclopramide or domperidone in partial obstruction only, avoided in complete obstruction because of perforation risk (III, B); steroids for short-term benefit (III, B), dexamethasone 4 to 16 mg daily, with discontinuation considered after 3 to 5 days without benefit; hyoscine butylbromide is probably inferior to octreotide for vomiting (III, D); opioids are standard for pain without trial evidence (V, D); osmotic laxatives only in partial obstruction.\n\nDecompression and procedures: nasogastric tube for temporary decompression (V, D); endoscopic or percutaneous venting gastrostomy (IV, B); self-expanding metal stents preferred for single-level large bowel obstruction without perforation (II, B); palliative surgery for multi-level obstruction only in highly selected people (IV, B), given high complication rates. Nutrition: nil by mouth at first, then a slow, symptom-led reintroduction of a low-fibre diet (IV, B); parenteral hydration does not relieve thirst or dry mouth and is not started routinely in the last days of life (III, B); home parenteral nutrition only for a very selected group (IV, D).","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency","palliative"],"related":[],"cancers":["colorectal","ovarian"],"sections":[],"technologies":["enteral-parenteral-nutrition","palliative-care","ct","self-expanding-metal-stents"],"targets":[],"drugs":["octreotide-lanreotide","dexamethasone"],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["colorectal-palliation-obstruction-pain","feeding-tube"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you have cancer and get bad tummy cramps, a swollen tummy and keep being sick, ring your cancer team or go to hospital the same day.","domain":"emergencies","setting":{"who":["doctor","nurse","surgical-team","multidisciplinary-team","pharmacist"],"where":["emergency-department","acute-oncology-service","ward","home"]},"population":"Adults with advanced cancer, most often colorectal, ovarian or other intra-abdominal cancer, with mechanical obstruction of the small or large bowel by the cancer. MASCC excludes the use of stents as a bridge to curative surgery. Children are not covered.","trigger":"Colicky abdominal pain, distension, nausea and vomiting, and absent or reduced passage of wind or stool in a person with advanced intra-abdominal cancer.","steps":[{"action":"Confirm suspected bowel obstruction with contrast CT rather than a plain abdominal X-ray","why":"CT shows where and why the bowel is blocked, and whether there is a complication such as perforation.","source":"mascc-2022","quote":"Contrast computed tomography (CT) is more valuable as it provides diagnostic precision [4]."},{"action":"Before offering any intervention, discuss goals of care, and weigh prognosis, performance status, other illnesses and where care will be given","why":"The choices range from surgery to comfort care, and the right one depends on what the person wants and how well they are.","source":"mascc-2022","quote":"Before offering interventions for MBO management, clinicians should take into consideration the risks associated with the interventions in addition to the patient’s estimated prognosis, performance status, comorbidities, location of care and ease of further assessment and support (e.g., home parenteral nutrition programs may not be universally available)."},{"action":"Ask for a surgical opinion at diagnosis","why":"A stent, stoma or bypass may be possible and should be considered early, before the person becomes too unwell.","source":"mascc-2022","quote":"Obtaining a surgical opinion should be considered at the time of MBO diagnosis."},{"action":"Make the person nil by mouth at first, and give medicines subcutaneously or intravenously in complete obstruction","why":"Food and tablets cannot pass a complete blockage and make vomiting worse.","source":"mascc-2022","quote":"In complete MBO, medication should be administered intravenously or subcutaneously if available."},{"action":"Give a somatostatin analogue such as octreotide to reduce vomiting","why":"It reduces the fluid the gut produces, which is what fills the blocked bowel and causes vomiting.","source":"mascc-2022","quote":"Recommendation: Somatostatin analog (octreotide, lanreotide) may reduce vomiting in MBO (levels of evidence: I; grade A).","grade":"Level I; grade A"},{"action":"For nausea, use haloperidol, particularly in complete obstruction; use metoclopramide only in partial obstruction","why":"Metoclopramide pushes the bowel to contract and may risk perforation when it is completely blocked.","source":"mascc-2022","quote":"Due to the potential increased risk of bowel perforation, it likely should be avoided in complete MBO.","grade":"Level III; grade B"},{"action":"Consider a short course of dexamethasone (4 to 16 mg daily), and consider stopping it if there is no improvement within 3 to 5 days","why":"Steroids may reduce swelling of the bowel wall and help the obstruction settle, but the evidence is limited.","source":"mascc-2022","quote":"Suggestion: The use of steroids may help with the acute symptoms of MBO and can be used for short-term benefit (level of evidence: III; grade: B).","grade":"Level III; grade B"},{"action":"Treat pain with parenteral or transdermal opioids, and use hyoscine butylbromide for colic","why":"Most people with obstruction have pain, and tablets may not be absorbed.","source":"mascc-2022","quote":"Suggestion: Opioids are commonly used to treat pain associated with MBO, but there is no evidence to support their use (level of evidence: V; grade D).","grade":"Level V; grade D"},{"action":"Use a nasogastric tube for temporary decompression; consider an endoscopic or percutaneous venting gastrostomy for longer-term decompression","why":"Draining the stomach relieves vomiting; a gastrostomy avoids a tube in the nose for weeks.","source":"mascc-2022","quote":"Suggestion: Endoscopic or percutaneous gastrostomy tube may be used for gastric decompression in MBO (level of evidence: IV; grade B evidence).","grade":"Level IV; grade B"},{"action":"For a single blockage of the large bowel without perforation, prefer a self-expanding metal stent where technically feasible","why":"A stent can reopen the bowel without an operation, with lower early death rates than emergency surgery.","source":"mascc-2022","quote":"Self-expanding metallic stents are the preferred alternative for the management of single-level large bowel obstruction when technically feasible and in the absence of colonic perforation (level of evidence: II; grade: B).","grade":"Level II; grade B"},{"action":"Keep palliative surgery for highly selected people, preferring the least invasive operation","why":"Surgery for obstruction in advanced cancer has high complication and re-obstruction rates.","source":"mascc-2022","quote":"Patients with advanced cancer that undergo palliative surgery for MBO are at high risk of surgical complications, and less invasive surgical interventions should be considered (level of evidence: IV; grade: B).","grade":"Level IV; grade B"},{"action":"Do not start intravenous or subcutaneous fluids routinely in the last days of life","why":"Drip fluids do not ease thirst or a dry mouth at this stage and can cause swelling and breathlessness; mouth care helps more.","source":"mascc-2022","quote":"Parenteral hydration should not be initiated routinely in the last days of life (level of evidence: III; grade: B).","grade":"Level III; grade B"}],"bestInClass":{"statement":"MASCC 2022 is the most recent graded, multidisciplinary guideline that could be read in full; its strongest recommendation is a somatostatin analogue to reduce vomiting (level I, grade A), consistent with the MASCC 2021 medical update, which calls octreotide the drug of choice in non-operable MBO. Its next strongest is self-expanding metal stents for single-level large bowel obstruction (II, B). Almost everything else (haloperidol, steroids, venting gastrostomy, limits on surgery and on parenteral hydration) rests on level III to V evidence. The North American Delphi consensus (Annals of Surgical Oncology, October 2026) is newer, with 49 statements on assessment, medical, surgical and palliative management, but was read only as an abstract, so where it differs from MASCC is not known.","sources":["mascc-2022","mascc-2021","delphi-2026"]},"variants":[{"name":"Hyoscine butylbromide instead of octreotide as the antisecretory","differs":"Uses hyoscine butylbromide, cheaper and widely available, as the first drug to reduce secretions and vomiting.","evidence":"MASCC 2022 suggests it may be inferior to octreotide for vomiting (III, D); MASCC 2021 found it inferior to octreotide at the doses compared.","sources":["mascc-2022","mascc-2021"]},{"name":"Home parenteral nutrition for selected people","differs":"Feeds intravenously at home, through a central line, for someone with inoperable obstruction who is otherwise well enough to live for months.","evidence":"MASCC 2022: may help quality of life in a very selected group (IV, D); central access preferred (III, B); stop, or do not start, at the end of life (V, D).","sources":["mascc-2022"]}],"grades":[{"claim":"Somatostatin analogue to reduce vomiting","grade":"Level I; grade A","source":"mascc-2022"},{"claim":"Octreotide in non-operable MBO","grade":"recommendation (MASCC level and category not given in the abstract)","source":"mascc-2021","quote":"The panel recommends octreotide in non-operable MBO."},{"claim":"Haloperidol, particularly in complete MBO","grade":"Level IV; grade B","source":"mascc-2022","quote":"Suggestion: Haloperidol, a butyrophenone antipsychotic, may be an effective anti-emetic in MBO, particularly for complete MBO (level of evidence: IV; grade: B),"},{"claim":"Nasogastric tube for temporary decompression","grade":"Level V; grade D","source":"mascc-2022","quote":"Suggestion: Nasogastric tube may be used for temporary decompression in acute MBO (level of evidence: V; grade: D)."},{"claim":"Self-expanding metal stent for single-level large bowel obstruction","grade":"Level II; grade B","source":"mascc-2022"},{"claim":"Nil by mouth, then slow symptom-led reintroduction of diet","grade":"Level IV; grade B","source":"mascc-2022"}],"sources":[{"key":"mascc-2022","label":"MASCC multidisciplinary evidence-based recommendations for the management of malignant bowel obstruction in advanced cancer","publisher":"MASCC, Supportive Care in Cancer","year":2022,"url":"https://europepmc.org/article/PMC/PMC9046338","doi":"10.1007/s00520-022-06889-8","gradingScheme":"MASCC 2018 policy: level of evidence I (meta-analysis or high-powered randomised trials) to V (case reports), and grade A (type I evidence or consistent findings) to D (little or no systematic evidence). Each item is printed as a 'Recommendation' or a 'Suggestion' with its level and grade.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-2021","label":"Medical management of malignant bowel obstruction in patients with advanced cancer: 2021 MASCC guideline update","publisher":"MASCC, Supportive Care in Cancer","year":2021,"url":"https://europepmc.org/abstract/MED/34390398","doi":"10.1007/s00520-021-06438-9","gradingScheme":"MASCC levels and categories of evidence; only randomised trials were admitted. The abstract does not print the grade for each recommendation.","read":"abstract","accessed":"2026-11-11"},{"key":"delphi-2026","label":"Recommendations for the Multimodal Management of Malignant Bowel Obstructions: Results of a North American Multidisciplinary Delphi Consensus","publisher":"Annals of Surgical Oncology","year":2026,"url":"https://europepmc.org/abstract/MED/42926303","doi":"10.1245/s10434-026-20614-3","gradingScheme":"Modified Delphi consensus with an 80% agreement threshold; statements are not graded in the abstract.","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The North American Delphi consensus (October 2026) was read only as its abstract: its 49 statements on steroid timing, surgery contraindications, gastrostomy and fluids at the end of life are not compared with MASCC here.","The WSES-PSOGI-SICO 2026 guidelines on surgical emergencies in peritoneal surface malignancy were found but not read.","Only one MASCC 2022 item (somatostatin analogues for vomiting) rests on level I evidence; most of the rest are suggestions on level III to V evidence.","No randomised trial has shown that surgery helps people with malignant bowel obstruction from gynaecological or colorectal cancer; a Cochrane review of 43 mostly retrospective studies could not conclude.","No UK national guideline on malignant bowel obstruction was read."]},{"id":"malignant-pericardial-effusion","kind":"protocol","name":"Malignant pericardial effusion: tamponade, drainage, cytology and preventing recurrence","aka":["MPE","pericardial effusion in cancer","cardiac tamponade in cancer","pericardiocentesis","balloon pericardiotomy","pericardial window"],"tldr":"Cancer can cause fluid to build up in the sac around the heart. When there is a lot, the heart cannot fill properly: breathlessness, a fast heartbeat, feeling faint or low blood pressure need emergency care. A heart ultrasound finds the fluid, and a needle and drain remove it. Because it often comes back, doctors may leave a drain in for a few days or make an opening in the sac.","summary":"Malignant pericardial effusion occurs in up to 21% of people with metastatic cancer (PMAP), most often from lung and breast cancer and lymphomas. In a systematic review of 41 published cases (CJC Open 2024), breathlessness was the leading symptom (90%) and 78% had tamponade. Echocardiography is the first-line test; cytology of drained fluid is the diagnostic standard (sensitivity 92%). Pericardiocentesis is immediate if there is tamponade; the review reports that guidelines (the 2015 ESC guideline) also recommend drainage of large confirmed or suspected malignant effusions without tamponade, with extended catheter drainage, systemic treatment of the cancer, and pericardiotomy or sclerosing agents as adjuncts.\n\nRecurrence is the problem. Observational data quoted by the review: 38% after pericardiocentesis alone, 12.1% with extended drainage, 10.8% with sclerosis, 10.3% with balloon pericardiotomy and under 7% with a surgical window. The PMAP trial (Hong Kong, 50 patients, 98% with features of tamponade) is the first randomised comparison: balloon pericardiotomy with extended drainage cut 6-month recurrence from 60% to 12% (HR 0.15) and tamponade from 40% to 4%, without improving survival or quality of life. Median survival with malignant pericardial effusion is short, so the aim is fewer procedures, not longer life. The 2025 ESC pericarditis guideline and the 2022 ESC cardio-oncology guideline could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency"],"related":[],"cancers":["nsclc","breast-cancer","non-hodgkin-lymphoma"],"sections":[],"technologies":["cardio-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you have cancer and become very breathless or faint, with a fast heartbeat, call 999. Fluid around the heart can be drained.","domain":"emergencies","setting":{"who":["doctor","nurse","emergency-team","multidisciplinary-team"],"where":["emergency-department","acute-oncology-service","ward","intensive-care"]},"population":"Adults with active cancer (most often lung or breast cancer, or lymphoma) who develop a pericardial effusion. PMAP enrolled adults with histologically confirmed active cancer and an effusion of 10 mm or more reachable from below the breastbone. Effusions after radiotherapy or from drug toxicity, and children, are not covered here.","trigger":"New or worsening breathlessness, chest discomfort, a fast heart rate, low blood pressure or raised neck veins in a person with cancer, or an effusion found on a scan.","steps":[{"action":"Suspect a pericardial effusion in a person with cancer who becomes breathless, and look for signs of tamponade","why":"Breathlessness is the commonest symptom, and most people are already in tamponade when they present.","source":"cjc-2024","quote":"Dyspnea was the leading symptom (90%), and cardiac tamponade was present in 78% of cases."},{"action":"Do a transthoracic echocardiogram to confirm the effusion and judge its effect on the heart","why":"Ultrasound shows the fluid and whether it is stopping the heart from filling.","source":"cjc-2024","quote":"Transthoracic echocardiography remains the first-line imaging test to detect pericardial disease."},{"action":"If there is tamponade, drain the fluid immediately by pericardiocentesis","why":"Tamponade can stop the heart from pumping; draining even some fluid relieves it.","source":"cjc-2024","quote":"Immediate treatment with pericardiocentesis is indicated if cardiac Tamp is present."},{"action":"Send the drained fluid for cytology","why":"Finding cancer cells confirms the cause and guides treatment.","source":"cjc-2024","quote":"Cytologic evaluation remains the gold standard for diagnosing malignant pericardial Effs, with a sensitivity of 92%, and a specificity of nearly 100%, although the diagnosis may be made with pericardial or epicardial biopsy as well.14"},{"action":"Leave a drain in for extended drainage rather than draining once and removing the needle","why":"Fluid comes back in more than a third of people after a single drainage.","source":"cjc-2024","quote":"Guidelines recommend management of malignant pericardial disease with systemic antineoplastic therapy, pericardiocentesis, and extended pericardial drainage.14,20"},{"action":"For a large malignant effusion, consider balloon pericardiotomy with extended drainage to prevent the fluid returning","why":"In a randomised trial it cut recurrence from 60% to 12% and tamponade from 40% to 4% over 6 months.","source":"pmap-2025","quote":"In patients with metastatic malignancy and large MPE, upfront intervention using PBP with extended drainage significantly reduces MPE recurrence and incidence of cardiac tamponade at 6 months compared with PC with extended drainage."},{"action":"Treat the underlying cancer where possible","why":"Drainage relieves the pressure, but only treating the cancer stops the fluid being made.","source":"cjc-2024","quote":"Definitive treatment, however, requires systemic treatment of the underlying malignancy with chemotherapy, radiation, and surgery (Fig. 3)."},{"action":"Plan with the person for fewer procedures and time at home, since survival is often short","why":"Preventing repeat drainage matters more than any effect on survival, which none of these procedures has shown.","source":"pmap-2025","quote":"Despite the reduction in recurrence and cardiac tamponade with PBP, overall survival and QoL among patients with MPE remained poor, underscoring that the primary goal in managing MPE is to reduce the frequency of interventions rather than to extend survival."}],"bestInClass":{"statement":"The current European guidelines (2025 ESC myocarditis and pericarditis; 2022 ESC cardio-oncology) could not be read, so the guideline position here is second-hand: the 2024 systematic review reports that guidelines (the 2015 ESC guideline) recommend pericardiocentesis, extended pericardial drainage and systemic treatment, with pericardiotomy or sclerosing agents as adjuncts, and drainage of large malignant effusions even without tamponade. The strongest direct evidence is now the PMAP randomised trial (2025), the first to compare procedures: balloon pericardiotomy plus extended drainage was superior to pericardiocentesis plus extended drainage for recurrence and tamponade, though small (50 patients, short of its planned 148), open-label and from one region, with no survival or quality-of-life benefit. A surgical pericardial window had the lowest recurrence (under 7%) in observational data but has not been compared in a trial.","sources":["pmap-2025","cjc-2024","esc-2025","esc-cardio-onc-2022"]},"variants":[{"name":"Surgical pericardial window","differs":"A surgeon makes an opening in the pericardium so that fluid drains away continuously, instead of a needle and drain.","evidence":"Lowest recurrence (under 7%) in a systematic review of 31 observational studies quoted by the 2024 review; not tested in a randomised trial against the other methods.","sources":["cjc-2024"]},{"name":"Intrapericardial sclerosing or cytotoxic agents","differs":"Instils a cytotoxic or sclerosing drug into the pericardium after drainage to stop fluid re-forming.","evidence":"Recurrence 10.8% in observational data; the review notes many clinicians avoid it because of high rates of chest pain and constrictive pericarditis.","sources":["cjc-2024"]}],"grades":[{"claim":"Balloon pericardiotomy with extended drainage against pericardiocentesis with extended drainage: 6-month recurrence","grade":"randomised trial (n = 50, open-label)","source":"pmap-2025","quote":"At 6 months, MPE recurred in 12% of PBP patients compared with 60% in the PC group (hazard ratio (HR) 0.15, 95% CI 0.05–0.51, P = .001)."},{"claim":"Recurrence by method in observational studies","grade":"systematic review of 31 observational studies (quoted)","source":"cjc-2024","quote":"In a systematic review of 31 observational studies, isolated pericardiocentesis was associated with a recurrence rate of 38%, and extended catheter drainage, pericardial sclerosis, and balloon pericardiotomy had recurrence rates of 12.1%, 10.8%, and 10.3%, respectively.18"}],"sources":[{"key":"pmap-2025","label":"Balloon pericardiotomy for malignant pericardial effusion: the PMAP trial","publisher":"European Heart Journal","year":2025,"url":"https://europepmc.org/article/PMC/PMC13017577","doi":"10.1093/eurheartj/ehaf516","gradingScheme":"A randomised controlled trial (NCT04472468); not a graded guideline.","read":"full-text","accessed":"2026-11-11"},{"key":"cjc-2024","label":"Malignant Pericardial Effusion: A Systematic Review","publisher":"CJC Open","year":2024,"url":"https://europepmc.org/article/PMC/PMC11357784","doi":"10.1016/j.cjco.2024.05.003","gradingScheme":"A systematic review of 41 case reports, with a discussion citing guidelines; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"esc-2025","label":"2025 ESC Guidelines for the management of myocarditis and pericarditis","publisher":"European Society of Cardiology, European Heart Journal","year":2025,"url":"https://doi.org/10.1093/eurheartj/ehaf192","doi":"10.1093/eurheartj/ehaf192","read":"not-reachable","accessed":"2026-11-11"},{"key":"esc-cardio-onc-2022","label":"2022 ESC Guidelines on cardio-oncology developed in collaboration with EHA, ESTRO and IC-OS","publisher":"European Society of Cardiology, European Heart Journal","year":2022,"url":"https://doi.org/10.1093/eurheartj/ehac244","doi":"10.1093/eurheartj/ehac244","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 2025 ESC Guidelines for myocarditis and pericarditis, the current European standard, and the 2022 ESC cardio-oncology guideline could not be read: the publisher refused a script and Europe PMC holds no abstract. Their recommendations and classes are not stated here; the guideline statements on this page come second-hand from the 2024 review, which cites the 2015 ESC guideline.","PMAP is small (50 of a planned 148 patients), open-label and from Hong Kong; seven patients crossed over. A larger trial is needed before balloon pericardiotomy is standard.","No randomised trial compares a surgical pericardial window with balloon pericardiotomy or extended drainage.","The 2024 systematic review is drawn entirely from case reports and is likely to over-represent severe cases.","How long to leave a drain in is not settled; PMAP drained until output was below 100 mL a day."]},{"id":"chemotherapy-extravasation-management","kind":"protocol","name":"Management of chemotherapy extravasation by drug class","aka":["Extravasation management","Vesicant extravasation","Anthracycline extravasation","Chemotherapy leak into tissue"],"tldr":"If a chemotherapy drug leaks out of the vein into the skin around a drip or port, the nurse stops the drip at once, draws back what they can, marks the area and then treats it according to the drug, with an antidote or a cold or warm pack. Tell the team straight away if the site stings, burns, swells or changes colour, during treatment or in the days after.","summary":"Extravasation is leakage of an intravenous anticancer drug into the surrounding tissue. Management starts the same way for every drug: stop the infusion, leave the cannula or port needle in place, aspirate what can be withdrawn without flushing, mark and photograph the area, inform the senior nurse and doctor, then remove the device and elevate the limb.\n\nThe specific measures depend on the drug's class. Vesicants are split into DNA-binding agents (anthracyclines, mitomycin, dactinomycin, mechlorethamine), which are localised and neutralised with cold, and non-DNA-binding agents (vinca alkaloids, taxanes), which are dispersed with warmth and hyaluronidase. The ONS/ASCO 2025 guideline, the newest GRADE-based one, recommends antidotes where available: dexrazoxane for doxorubicin, daunorubicin, epirubicin and idarubicin; hyaluronidase for vinca alkaloids, and conditionally for paclitaxel and docetaxel; topical dimethyl sulfoxide for mitomycin and mitoxantrone, or for an anthracycline when dexrazoxane is unavailable or contraindicated; sodium thiosulfate for more than 20 ml of high-concentration cisplatin and for bendamustine. Thermal compresses are used three to four times daily for 48 to 72 hours: cold for most vesicants, warm for vinca alkaloids, etoposide and oxaliplatin, and for taxanes when hyaluronidase is given.\n\nDexrazoxane is given intravenously in the opposite limb, 1000 mg/m2 on days 1 and 2 and 500 mg/m2 on day 3, the first dose within six hours, with cooling removed 15 minutes beforehand and no dimethyl sulfoxide alongside. Extravasation from a central venous access device, and high-risk cases, are referred early for surgical review. The Japanese 2024 guideline differs on heat (it weakly recommends against warm compresses alone) and makes no recommendation on aspiration; it weakly recommends against local steroid injection and against debriding an ulcer without necrosis. Documentation, patient teaching and follow-up for weeks complete the protocol.","asOf":"2026-11-11","links":[],"tags":[],"related":["dmso-dimethyl-sulfoxide","sodium-thiosulfate"],"cancers":[],"sections":[],"technologies":["implanted-ports","picc-lines"],"targets":[],"drugs":["dexrazoxane","doxorubicin","daunorubicin","epirubicin","idarubicin","vincristine","vinblastine","vinorelbine","paclitaxel","docetaxel","mitomycin","mitoxantrone","dactinomycin","mechlorethamine","trabectedin","oxaliplatin","etoposide","cisplatin","bendamustine","carmustine","dacarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":["extravasation-infusion-reaction","central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"domain":"chemotherapy-administration","setting":{"who":["nurse","doctor","pharmacist","surgical-team","patient-or-carer"],"where":["chemotherapy-day-unit","ward","outpatient-clinic","home"]},"population":"Adults receiving intravenous anticancer drugs through a peripheral cannula or a central venous access device. Children are outside every source read here; the Savene label says safety and efficacy below 18 have not been established and does not recommend it in elderly patients, in whom it was not studied.","trigger":"During or after an intravenous anticancer infusion, the patient reports pain, burning or swelling at the site, or the nurse sees redness, swelling, a change in skin colour or blanching around the site, or loss of blood return from the device.","steps":[{"action":"Recognise it: check the site and the line for loss of blood return, pain, redness, swelling, and skin colour change or blanching","why":"Early signs are often subtle, and treatment works best when it starts as soon as extravasation is suspected.","source":"ons-asco-algorithm-2025"},{"action":"Stop the infusion at once and leave the cannula or port needle in place","why":"Leaving the device in gives a route to draw back drug still sitting in the line or tissue.","source":"ons-voice-2025","quote":"Stop the infusion immediately but leave the needle or catheter in place to allow for the possibility of aspirating any residual drug from the line or tissue."},{"action":"Gently aspirate as much drug as possible through the device with a syringe, without flushing and without pressing on the area, then disconnect the tubing","why":"Less drug left in the tissue means less damage; flushing or pressure would push more of it in.","source":"ons-voice-2025","quote":"Attempt to withdraw as much of the drug as possible using a syringe, then disconnect the tubing."},{"action":"Call for help: inform a doctor straight away, and a consultant for any vesicant or any extravasation from a central line","why":"Antidotes and referrals need a prescriber, and some have to start within hours.","source":"wm-eag-2017","quote":"A doctor should be informed of the incident immediately; in the case of vesicants or an extravasation via a CVAD a consultant should be informed."},{"action":"Measure the area, outline it with a pen and photograph it","why":"A marked outline and a photograph show later whether the injury is spreading or settling.","source":"wm-eag-2017","quote":"Mark the extravasated area with a pen, take a digital image if possible."},{"action":"Remove the peripheral cannula or the port needle without pressing hard on the site, and raise a peripheral limb","why":"Raising the limb helps the fluid be absorbed; firm pressure spreads the drug.","source":"ons-asco-algorithm-2025"},{"action":"Identify the drug and its class: DNA-binding vesicant, non-DNA-binding vesicant, irritant or non-vesicant","why":"The class decides whether the area is cooled to keep the drug in one place or warmed to spread it, and which antidote applies.","source":"wm-eag-2017","quote":"DNA – binding: these drugs are absorbed locally, enter cells and bind to their DNA, precipitating the death of the cell. Following this, the drug can then be re-released to further destroy healthy cells leading to deeper erosion of cells within the tissue"},{"action":"Cold compresses for anthracyclines, alkylating agents, antimetabolites, and taxanes when hyaluronidase is not given","why":"Cold narrows the vessels, which keeps the drug in a small area.","source":"ons-voice-2025","quote":"Cold compresses vasoconstrict and reduce spread and are best for alkylating agents, anthracyclines, taxanes (without hyaluronidase use), and antimetabolites."},{"action":"Warm compresses for vinca alkaloids, etoposide and oxaliplatin, and for paclitaxel or docetaxel when hyaluronidase is given","why":"Warmth spreads the drug so that it is diluted and absorbed.","source":"ons-voice-2025","quote":"Warm compresses disperse the agent and should be used for vinca alkaloids, etoposide, oxaliplatin, paclitaxel, and docetaxel (when coadministering hyaluronidase)."},{"action":"Apply the compress for 15 to 20 minutes at a time, three to four times a day, for 48 to 72 hours","why":"The guideline panel preferred this longer course to a single day.","source":"ons-voice-2025","quote":"Using compresses use three to four times daily over 48–72 hours is recommended over shorter durations (e.g., 24 hours)."},{"action":"Anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin): give dexrazoxane, the first dose as soon as possible and within six hours","why":"Dexrazoxane is the antidote licensed for anthracycline extravasation, and the window for the first dose is short.","source":"savene-smpc","quote":"The first infusion should be initiated as soon as possible, within the first six hours after the accident."},{"action":"Anthracyclines: dose dexrazoxane at 1000 mg/m2 on day 1, 1000 mg/m2 on day 2 and 500 mg/m2 on day 3, each at the same hour plus or minus 3 hours, no single dose above 2000 mg, and halved if creatinine clearance is below 40 ml/min","why":"This is the licensed three-day schedule used in the trials that supported it.","source":"savene-smpc","quote":"Treatment should be given once daily for 3 consecutive days. The recommended dose is: Day 1: 1000 mg/m2 Day 2: 1000 mg/m2 Day 3: 500 mg/m2"},{"action":"Anthracyclines: infuse dexrazoxane over 1 to 2 hours into a large vein of another limb, and take cold packs off the area at least 15 minutes before","why":"The drug has to reach the injured tissue through the blood, which cold slows.","source":"savene-smpc","quote":"Cooling procedures such as ice packs should have been removed from the area at least 15 minutes before the Savene administration in order to allow sufficient blood flow."},{"action":"Anthracyclines: do not apply dimethyl sulfoxide to a patient receiving dexrazoxane","why":"In animal studies the combination caused skin wounds that dexrazoxane alone prevented.","source":"savene-smpc","quote":"Dimethylsulfoxide (DMSO) should not be used in patients who are administered dexrazoxane to treat anthracycline extravasation"},{"action":"Mitomycin, mitoxantrone, or an anthracycline when dexrazoxane is unavailable or contraindicated: use topical dimethyl sulfoxide","why":"Dimethyl sulfoxide is thought to protect tissue by scavenging free radicals.","source":"ons-voice-2025","quote":"Dimethyl sulfoxide for extravasation occurring with mitomycin C and mitoxantrone as well as when dexrazoxane is not available or is contraindicated"},{"action":"Dimethyl sulfoxide: paint a thin layer over the marked area only, let it dry, and stop if it blisters","why":"It should treat the injured area without irritating healthy skin.","source":"wm-eag-2017","quote":"Carefully apply a thin layer of DMSO topically to the marked area avoiding contact with unaffected areas"},{"action":"Dimethyl sulfoxide: start within 10 to 25 minutes, using a 50 to 99 per cent solution every 8 hours for 7 days over an area twice the size of the extravasation","why":"This is the schedule the ONS/ASCO algorithm gives; see the variants for a six-hourly one.","source":"ons-asco-algorithm-2025"},{"action":"Vinca alkaloids (vincristine, vinblastine, vinorelbine): give hyaluronidase and use warm compresses","why":"Hyaluronidase breaks down the tissue's binding substance so the drug spreads and is absorbed.","source":"ons-voice-2025","quote":"Hyaluronidase for extravasation occurring with vinca alkaloids, paclitaxel, and docetaxel"},{"action":"Hyaluronidase: inject 1 ml (150 units) as five 0.2 ml injections under the skin around the edge of the area","why":"Ringing the area spreads the enzyme evenly through it.","source":"wm-eag-2017","quote":"Subcutaneously (or intradermally) inject 1 ml (150 IU) of hyaluronidase as 5 separate 0.2 ml injections around the periphery of extravasation site."},{"action":"Taxanes (paclitaxel, docetaxel): consider hyaluronidase with warm compresses; without it, use cold","why":"Taxane leaks may not cause severe injury, but the panel judged the possible benefit worth the low risk.","source":"ons-voice-2025","quote":"Although paclitaxel or docetaxel extravasations may not result in severe tissue injury, the experts made a conditional recommendation that patients receive hyaluronidase as an antidote because of a potential benefit in minimizing injury and the low potential for harm.","grade":"conditional recommendation"},{"action":"Cisplatin (more than 20 ml at above 0.5 mg/ml) and bendamustine: give sodium thiosulfate","why":"The ONS/ASCO panel names it as the antidote for these two drugs.","source":"ons-voice-2025","quote":"Sodium thiosulfate for extravasation occurring with > 20 ml of cisplatin in high concentration (greater than 0.5 mg/ml) and bendamustine"},{"action":"Mechlorethamine (chlormethine), carmustine, dacarbazine and other DNA-binding vesicants with no antidote named: manage on the DNA-binding pathway, with cold to localise","why":"The UK network guideline classes these as DNA-binding vesicants and puts them on the cold, localise pathway.","source":"wm-eag-2017"},{"action":"Irritants, non-vesicants and drugs not listed: choose a compress by the drug's mechanism, the pain or swelling, and the patient's comfort","why":"Irritants rarely break the skin down, so comfort and the drug's action guide the choice.","source":"ons-voice-2025","quote":"For extravasation of agents not listed, consider the mechanism of action, presence of pain or swelling, and patient comfort when selecting a compress."},{"action":"Do not inject steroids into the site","why":"In the evidence the Japanese panel reviewed, injected steroids were linked to worse injury and slower recovery.","source":"jscn-jsmo-jaspo-2024","quote":"It is weakly recommended not to inject local steroids for EV of anticancer drugs.","grade":"Not recommend (weak), certainty D"},{"action":"Refer for surgical review promptly after any central line extravasation of a vesicant, and consider it for DNA-binding vesicants, large volumes and grade 2 or worse symptoms","why":"The panel judged these patients the likeliest to benefit from early specialist review.","source":"ons-voice-2025","quote":"The panel suggested that patients with central line extravasation of vesicants or irritants with vesicant properties be referred for surgical evaluation or escalation of care in addition to conservative management when indicated."},{"action":"Do not debride an ulcer that has no dead tissue; refer for surgery where necrosis or pain persists beyond 10 days","why":"Ulcers without necrosis can heal without surgery, and it is hard to judge early how deep the damage goes.","source":"jscn-jsmo-jaspo-2024","quote":"It is weakly recommended not to debride EV-induced skin ulcer lesions without necrosis.","grade":"Not recommend (weak), certainty C"},{"action":"Document the drug, dose, volume, site, device, timings, every measure taken and the response, and report the incident","why":"A full record guides follow-up and lets the service learn from each event.","source":"ons-voice-2025","quote":"Document the event carefully, including the drug, dose, timing, interventions taken, and the patient’s response."},{"action":"Teach the patient or carer to keep the area clean and dry, raise the limb, keep up the compresses, and report redness, pain, blistering, peeling or fever","why":"Damage can appear days or weeks later, at home.","source":"ons-voice-2025","quote":"Monitor the area for changes such as redness, pain, blistering, peeling, or streaks and report any delayed reactions such as fever higher than 100.4º F."},{"action":"Review the site within a week, booked before the patient leaves","why":"A planned review catches injury that is getting worse.","source":"wm-eag-2017","quote":"All patients must have a review of their extravasation injury within 1 week, this appointment must be arranged prior to the patient leaving clinic"},{"action":"Keep following up DNA-binding vesicant injuries for at least three weeks, in person or remotely, starting within a day","why":"Injury from DNA-binding drugs has a history of appearing late.","source":"ons-asco-algorithm-2025"}],"bestInClass":{"statement":"The strongest current recommendation is the ONS/ASCO guideline (2025, GRADE): stop, aspirate and mark; use the drug's antidote where one exists (dexrazoxane for anthracyclines, hyaluronidase for vinca alkaloids and conditionally for taxanes, dimethyl sulfoxide for mitomycin and mitoxantrone or when dexrazoxane cannot be used, sodium thiosulfate for concentrated cisplatin and bendamustine); thermal compresses for 48 to 72 hours, cold for most vesicants and warm for vinca alkaloids, etoposide and oxaliplatin; and early surgical referral after a central line extravasation. Dexrazoxane follows its licensed three-day schedule, started within six hours. Guidelines disagree on two points. ONS/ASCO recommends warm compresses for the dispersing drugs and its algorithm advises aspiration; the Japanese JSCN/JSMO/JASPO guideline (2024) weakly recommends against warm compresses used alone, partly because hyaluronidase is not approved for extravasation in Japan, and makes no recommendation on aspiration because the evidence could not be weighed.","sources":["ons-voice-2025","ons-asco-algorithm-2025","savene-smpc","jscn-jsmo-jaspo-2024"]},"variants":[{"name":"UK network pathway: localise and neutralise, or disperse and dilute (West Midlands, 2017)","differs":"Sorts vesicants by DNA binding: DNA-binding drugs get cold compresses and antidotes, non-DNA-binding drugs get warmth and hyaluronidase. Compresses for 20 minutes four times daily for 1 to 2 days. Chooses the anthracycline antidote by volume: topical dimethyl sulfoxide under 3 ml, dexrazoxane over 3 ml. Starts hyaluronidase within 1 hour (ONS/ASCO says within 2 to 4 hours). Refers vesicant and irritant extravasations to the local plastics or flush-out team for a saline flush-out as soon as possible. Its dimethyl sulfoxide appendix says every 6 hours for 7 days while its own antidote table says every 8 hours.","evidence":"Expert consensus with no grades; the guideline describes the antidote evidence as often inconclusive. It passed its own review date in July 2019.","sources":["wm-eag-2017"]},{"name":"Japanese multidisciplinary guideline (JSCN, JSMO and JASPO, 2024)","differs":"Cold compresses weakly recommended; warm compresses alone weakly recommended against; topical steroids weakly recommended and injected steroids weakly recommended against; no recommendation on aspiration. Classifies oxaliplatin, docetaxel, paclitaxel and mitoxantrone as vesicants on its own systematic review, where the UK network list calls oxaliplatin and mitoxantrone irritants.","evidence":"GRADE with the Minds handbook; certainty very low (D) for most local measures and moderate (B) for dexrazoxane.","sources":["jscn-jsmo-jaspo-2024"]}],"grades":[{"claim":"Give dexrazoxane for anthracycline extravasation","grade":"Recommend (weak), certainty B","source":"jscn-jsmo-jaspo-2024","quote":"Administration of dexrazoxane for EV induced by an anthracycline cancer drug is weakly recommended."},{"claim":"Use cold compresses as local therapy","grade":"Recommend (weak), certainty D","source":"jscn-jsmo-jaspo-2024","quote":"Cold compression is weakly recommended as local therapy to prevent aggravation/progression of tissue injury and inflammation induced by EV."},{"claim":"Avoid warm compresses used alone","grade":"Not recommend (weak), certainty D","source":"jscn-jsmo-jaspo-2024","quote":"Avoidance of warm compresses (heat) is weakly recommended to prevent EV-induced skin damage and aggravation/progression of inflammation."},{"claim":"Aspirating residual drug or blood","grade":"None, certainty D","source":"jscn-jsmo-jaspo-2024","quote":"No recommendation (no vote)."},{"claim":"Do not inject steroids locally","grade":"Not recommend (weak), certainty D","source":"jscn-jsmo-jaspo-2024","quote":"It is weakly recommended not to inject local steroids for EV of anticancer drugs."},{"claim":"Apply topical steroids","grade":"Recommend (weak), certainty D","source":"jscn-jsmo-jaspo-2024","quote":"Applying topical steroids for EV of anticancer drugs is weakly recommended."},{"claim":"Do not debride an ulcer without necrosis","grade":"Not recommend (weak), certainty C","source":"jscn-jsmo-jaspo-2024","quote":"It is weakly recommended not to debride EV-induced skin ulcer lesions without necrosis."},{"claim":"Give hyaluronidase after paclitaxel or docetaxel extravasation","grade":"conditional recommendation","source":"ons-voice-2025","quote":"the experts made a conditional recommendation that patients receive hyaluronidase as an antidote"}],"sources":[{"key":"ons-asco-2025","label":"ONS/ASCO Guideline on the Management of Antineoplastic Extravasation, Clinical Journal of Oncology Nursing 29(5):384-399","publisher":"Oncology Nursing Society and American Society of Clinical Oncology","year":2025,"url":"https://www.ons.org/publications-research/cjon/29/5/onsasco-guideline-management-antineoplastic-extravasation","doi":"10.1188/25.CJON.384-399","gradingScheme":"GRADE: recommendations are strong or conditional, with certainty of evidence high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"ons-voice-2025","label":"New Extravasation Guidelines Provide Recommendations for Protecting Patients and Standardizing Care, ONS Voice","publisher":"Oncology Nursing Society","year":2025,"url":"https://www.ons.org/publications-research/voice/news-views/10-2025/new-extravasation-guidelines-provide-recommendations","gradingScheme":"Reports the ONS/ASCO GRADE recommendations; prints a grade only for the taxane hyaluronidase recommendation.","read":"public-summary","accessed":"2026-11-11"},{"key":"ons-asco-algorithm-2025","label":"Algorithm on the Management of Antineoplastic Extravasation of Vesicant or Irritant with Vesicant Properties in Adults","publisher":"Oncology Nursing Society and American Society of Clinical Oncology","year":2025,"url":"https://www.ons.org/sites/default/files/2025-09/ons-asco-algorithm-on-antineoplastic-extravasation_09.2025.pdf","read":"full-text","accessed":"2026-11-11"},{"key":"jscn-jsmo-jaspo-2024","label":"Extravasation associated with cancer drug therapy: multidisciplinary guideline of the Japanese Society of Cancer Nursing, Japanese Society of Medical Oncology, and Japanese Society of Pharmaceutical Oncology, ESMO Open 9:103932","publisher":"Japanese Society of Cancer Nursing, Japanese Society of Medical Oncology and Japanese Society of Pharmaceutical Oncology","year":2024,"url":"https://europepmc.org/article/PMC/PMC11490930","doi":"10.1016/j.esmoop.2024.103932","gradingScheme":"GRADE and Minds: strength Recommend or Not recommend, strong or weak; certainty A high, B moderate, C low, D very low.","read":"full-text","accessed":"2026-11-11"},{"key":"savene-smpc","label":"Savene 20 mg/ml powder and solvent for concentrate for solution for infusion: Summary of Product Characteristics","publisher":"European Medicines Agency","year":2024,"url":"https://www.ema.europa.eu/en/documents/product-information/savene-epar-product-information_en.pdf","read":"full-text","accessed":"2026-11-11"},{"key":"wm-eag-2017","label":"Guidelines for the Management of Extravasation of a Systemic Anti-Cancer Therapy including Cytotoxic Agents, version 1","publisher":"West Midlands Expert Advisory Group for Systemic Anti-Cancer Therapy, NHS England","year":2017,"url":"https://www.england.nhs.uk/midlands/wp-content/uploads/sites/46/2019/05/management-extravasation-of-a-systemic-anti-cancer-therapy-including-cytotoxic-agents.pdf","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-eons-2012","label":"Management of chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines, Annals of Oncology 23 Suppl 7:vii167-vii173","publisher":"ESMO and European Oncology Nursing Society","year":2012,"url":"https://doi.org/10.1093/annonc/mds294","doi":"10.1093/annonc/mds294","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The full text of the ONS/ASCO guideline could not be read (bot checks on PubMed Central and the publisher), so the strength and certainty of each of its recommendations are not quoted, except the conditional recommendation for hyaluronidase after taxane extravasation that ONS's own summary prints.","The ESMO-EONS guideline (2012) could not be read: the publisher's site returned a bot check and no abstract is indexed. No step rests on it. No newer ESMO edition was found.","No source that could be read recommends sodium thiosulfate for mechlorethamine (chlormethine) extravasation. ONS/ASCO recommends it for concentrated cisplatin and bendamustine; the UK network guideline lists mechlorethamine as a DNA-binding vesicant without naming an antidote.","The ONS Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (2023) is a paid book and was not read.","Hyaluronidase timing differs: within 2 to 4 hours in the ONS/ASCO algorithm, within 1 hour in the UK network guideline. Neither gives evidence for its window.","The dimethyl sulfoxide schedule differs between every 8 hours (ONS/ASCO algorithm) and every 6 hours (the UK network guideline's appendix, which contradicts its own table). Dimethyl sulfoxide is unlicensed for this use in the UK.","The Savene label has no data on extravasation from central venous access devices: those patients were excluded from its efficacy evaluation.","The West Midlands guideline passed its review date in July 2019, and an Irish national guideline (NCCP, 2023) could not be retrieved, so no UK or Irish guidance newer than 2017 was read."]},{"id":"medicines-reconciliation-in-cancer-care","kind":"protocol","name":"Medicines reconciliation at the start of anticancer treatment and at each move between care settings","aka":["medication reconciliation","med rec","MedRec","best possible medication history","BPMH","drug history before chemotherapy","medicines reconciliation on admission"],"tldr":"Medicines reconciliation means making one accurate list of every medicine you take, including ones you buy and herbal remedies, and checking it against what the hospital thinks you take. It should happen before cancer treatment starts, when you go into hospital, when you move wards and when you go home.","summary":"NICE NG5 (2015) uses the Institute for Healthcare Improvement's definition: identify an accurate list of a person's current medicines, compare it with the list in use, recognise and document discrepancies, and communicate the result; 'medicines' includes over-the-counter and complementary products. In an acute setting reconciliation should be done within 24 hours of a move between settings, or sooner if clinically necessary, may need repeating on admission, transfer and discharge, and should be done in primary care within a week of the practice receiving discharge information. It should be done by a trained, competent professional, ideally a pharmacist, pharmacy technician, nurse or doctor, and involve the patient and family.\n\nCancer-specific standards add the anticancer start point. ASCO-ONS (2024) requires the medication list, with over-the-counter medicines, herbal products and supplements, to be updated at every encounter and reviewed when it changes; BOPA (2025) puts the drug history and interaction check into the pharmacist's verification of the first cycle. Practice lags: across 21 Canadian cancer centres most collected a best possible medication history but full reconciliation was uncommon, and one centre's improvement project reached a documented history in 26.6% of patients starting systemic therapy and full reconciliation in 4.7%. Where it is done, it finds things: before early-phase trials, pharmacist reconciliation in 501 patients uncovered 35% of the medicines patients were taking and 51% of prohibited or monitored drugs that oncologists had missed.","asOf":"2026-11-11","links":[],"tags":[],"related":["anticancer-drug-interaction-review","sact-prescribing-and-pharmacy-verification","oral-anticancer-medicines-at-home"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Bring all your medicines, or a list, to your first appointment and every hospital stay. Someone will check the list with you so nothing is missed or doubled.","domain":"pharmacy","setting":{"who":["pharmacist","pharmacy-technician","nurse","doctor","patient-or-carer"],"where":["outpatient-clinic","ward","chemotherapy-day-unit","community"]},"population":"Adults and children with cancer starting systemic anticancer treatment, and any person with cancer admitted to hospital, transferred between wards or settings, or discharged. NICE NG5 covers all people taking medicines in any setting.","trigger":"A new anticancer regimen is planned, or the person is admitted, transferred or discharged.","steps":[{"action":"On admission or any move into hospital, list every medicine the person takes, including over-the-counter and complementary products, and reconcile within 24 hours, sooner if clinically necessary","why":"Medicines are most often lost, doubled or changed by mistake when people move between settings.","source":"nice-ng5","quote":"1.3.1 In an acute setting, accurately list all of the person's medicines (including prescribed, over‑the‑counter and complementary medicines) and carry out medicines reconciliation within 24 hours or sooner if clinically necessary, when the person moves from one care setting to another – for example, if they are admitted to hospital."},{"action":"Compare the list with what is currently prescribed, find and resolve every difference, and document the changes","why":"A list only helps if the differences between it and the prescription chart are found and settled.","source":"nice-ng5","quote":"Medicines reconciliation, as defined by the Institute for Healthcare Improvement, is the process of identifying an accurate list of a person's current medicines and comparing them with the current list in use, recognising any discrepancies, and documenting any changes, thereby resulting in a complete list of medicines, accurately communicated."},{"action":"Involve the patient and their family or carers in building the list","why":"They know what is actually taken, including things bought without a prescription.","source":"nice-ng5","quote":"1.3.6 Involve patients and their family members or carers, where appropriate, in the medicines reconciliation process."},{"action":"Before the first cycle of a new regimen, take a full drug history, including previous anticancer treatment, and check it against the planned treatment","why":"Previous treatment and current medicines can change which regimen is safe and what dose is right.","source":"bopa-2025","quote":"Check for potential interactions, contra-indications and duplication between all planned SACT & supportive medication and patient’s concurrent medication."},{"action":"Update the medication list, with herbal products and supplements, at every encounter during treatment, and have it reviewed when it changes","why":"People with cancer see many specialists, and medicines change often during treatment.","source":"asco-ons-2024","quote":"The patient's medication list inclusive of prescribed and over-the-counter medications, herbal products, and supplements is updated and documented in the medical record at every encounter and reviewed by a licensed practitioner when a change occurs"},{"action":"Repeat reconciliation when the person is transferred between wards and at discharge","why":"Each handover is a new chance for a medicine to be stopped or restarted by mistake.","source":"nice-ng5","quote":"1.3.2 Recognise that medicines reconciliation may need to be carried out on more than one occasion during a hospital stay – for example, when the person is admitted, transferred between wards or discharged."},{"action":"If medicines are stopped during an acute illness, write and share a clear plan for when to restart them","why":"Medicines paused in hospital are often never restarted unless someone plans it.","source":"kdigo-2024","quote":"If medications are discontinued during an acute illness, communicate a clear plan of when to restart the discontinued medications to the affected person and healthcare providers, and ensure documentation in the medical record.","grade":"Practice Point 4.3.2"},{"action":"Send complete, accurate medicines information to the next care setting, ideally within 24 hours of transfer","why":"The GP, community pharmacy or next hospital team needs to know what changed and why.","source":"nice-ng5","quote":"1.2.2 For all care settings, health and social care practitioners should proactively share complete and accurate information about medicines: ideally within 24 hours of the person being transferred, to ensure that patient safety is not compromised and in the most effective and secure way, such as by secure electronic communication, recognising that more than one approach may be needed."},{"action":"In primary care, reconcile medicines for everyone discharged from hospital before issuing a new prescription, within a week of receiving the information","why":"Discharge changes, such as a new anticoagulant or a stopped medicine, have to reach the GP record.","source":"nice-ng5","quote":"1.3.3 In primary care, carry out medicines reconciliation for all people who have been discharged from hospital or another care setting."}],"bestInClass":{"statement":"NICE NG5 (2015) sets the process and the clocks for every setting: a full list including over-the-counter and complementary medicines, reconciled within 24 hours of a move into an acute setting, repeated at transfer and discharge, done by a trained professional with the patient, and completed in primary care within a week of discharge information. For cancer treatment, ASCO-ONS (2024) adds a list updated at every encounter, and BOPA (2025) a drug history and interaction check in the first-cycle verification. None of these is graded.","sources":["nice-ng5","asco-ons-2024","bopa-2025"]},"variants":[{"name":"Pharmacist reconciliation before trial enrolment","differs":"A pharmacist reconciles medicines against each trial's prohibited and monitored lists before a patient starts an investigational drug.","evidence":"In 501 patients at one French centre it uncovered 35% of the medicines patients were taking, found 158 prohibited interactions (more than half with herbal products) and caught 51% of prohibited or monitored drugs missed by oncologists (Malifarge 2024).","sources":["malifarge-2024"]},{"name":"Best possible medication history at the start of systemic therapy (Canadian centres)","differs":"Collects a structured best possible medication history for people starting systemic therapy, with full reconciliation as a later step.","evidence":"81% of 21 Canadian cancer centres had a process for the history but full reconciliation was uncommon; one centre's improvement project reached 26.6% documented histories and 4.7% full reconciliations within 30 days of starting treatment (Powis 2023).","sources":["powis-2023"]}],"grades":[],"sources":[{"key":"nice-ng5","label":"Medicines optimisation: the safe and effective use of medicines to enable the best possible outcomes (NG5), recommendations","publisher":"NICE","year":2015,"url":"https://www.nice.org.uk/guidance/ng5/chapter/recommendations","gradingScheme":"NICE does not grade recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and ONS (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded; developed from a systematic review (2015 to 2023), expert panel consensus and public comment.","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"kdigo-2024","label":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","publisher":"KDIGO (Kidney International)","year":2024,"url":"https://doi.org/10.1016/j.kint.2023.10.018","doi":"10.1016/j.kint.2023.10.018","gradingScheme":"Recommendations graded 1 or 2 with evidence quality A to D; practice points are ungraded expert judgement.","read":"full-text","accessed":"2026-11-11"},{"key":"powis-2023","label":"Implementation of medication reconciliation in outpatient cancer care","publisher":"BMJ Open Quality (Powis et al.)","year":2023,"url":"https://doi.org/10.1136/bmjoq-2022-002211","doi":"10.1136/bmjoq-2022-002211","read":"abstract","accessed":"2026-11-11"},{"key":"malifarge-2024","label":"Impact of Medication Reconciliation in Oncology Early Phase Studies: A Drug-Drug Interaction Retrospective Study","publisher":"JCO Oncology Practice (Malifarge et al.)","year":2024,"url":"https://doi.org/10.1200/OP.22.00281","doi":"10.1200/OP.22.00281","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No cancer-specific guideline sets a deadline for reconciliation before a first cycle; NICE NG5's 24-hour clock applies to moves into an acute setting, and ASCO-ONS and BOPA require the list without a time limit.","NICE NG5 dates from 2015 and has not been updated; its recommendations are ungraded.","The two oncology studies were read as abstracts only, and neither measured harm prevented.","The WHO High 5s medication reconciliation protocol was not read."]},{"id":"metastatic-spinal-cord-compression-emergency","kind":"protocol","name":"Metastatic spinal cord compression: recognition, MSCC coordinator, MRI, dexamethasone, radiotherapy and surgery","aka":["MSCC protocol","malignant spinal cord compression","spinal cord compression emergency","cauda equina compression in cancer","NICE NG234"],"tldr":"Cancer that has spread to the spine can press on the spinal cord. New back or neck pain that is severe, worse at night or on coughing, or any weakness, numbness, or trouble passing urine or stools, needs a same-day call to your cancer team. The hospital should do an MRI of the whole spine within 24 hours, give dexamethasone, and plan radiotherapy or surgery quickly, to keep you walking.","summary":"NICE NG234 (2023) sets out the UK pathway. Anyone with a past or current cancer who develops symptoms or signs of cord compression (bladder or bowel dysfunction, gait disturbance, limb weakness, sensory loss, radicular pain) is an oncological emergency: contact the MSCC coordinator immediately, a service that must be covered 24 hours a day. Pain suggesting spinal metastases alone (severe, progressive, mechanical, worse on straining, waking at night, localised tenderness) needs coordinator advice within 24 hours and an MRI within a week.\n\nSuspected MSCC: MRI as soon as possible and always within 24 hours, locally, with sagittal T1 and/or STIR of the whole spine; overnight MRI only if treatment would start immediately; CT if MRI is contraindicated; never a plain X-ray. Immobilise without delay if there are neurological signs or suspected instability, lying flat. Give dexamethasone 16 mg as soon as possible and daily until surgery or radiotherapy, then taper, with glucose monitoring and a proton pump inhibitor; stop it if MSCC is ruled out.\n\nTreatment is planned by the MSCC multidisciplinary team. Surgery to halt or reverse neurological decline as soon as possible after onset (Patchell 2005: 84% walking after surgery plus radiotherapy against 57% after radiotherapy alone). Otherwise urgent radiotherapy within 24 hours, 8 Gy in one fraction unless at high risk of side effects; NICE excludes people with complete paralysis for 2 weeks or more with controlled pain, or a poor prognosis. SCORAD III found single-fraction 8 Gy narrowly missed non-inferiority to 20 Gy in 5 fractions for walking at 8 weeks (69.3% against 72.7%). ASTRO 2024 recommends 8 Gy/1, 16 Gy/2, 20 Gy/5 or 30 Gy/10 for patients not having surgery, and conditionally recommends surgery with postoperative radiotherapy over radiotherapy alone.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency"],"related":[],"cancers":["prostate","breast-cancer","lung-cancer","multiple-myeloma"],"sections":[],"technologies":["palliative-radiotherapy","sbrt","mri"],"targets":[],"drugs":["dexamethasone"],"companies":[],"institutions":["nice","astro"],"pathways":[],"terms":["metastatic-spinal-cord-compression","bone-metastases"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hoskin-jama"],"journals":[],"dependsOn":[],"notes":[],"simple":"If cancer is in your spine, it can squeeze the nerves. Back pain that keeps you awake, weak or numb legs, or trouble with your bladder or bowels is an emergency. Ring your cancer team at once.","domain":"emergencies","setting":{"who":["patient-or-carer","nurse","doctor","radiographer","surgical-team","multidisciplinary-team","emergency-team"],"where":["home","telephone-triage","acute-oncology-service","emergency-department","ward","radiotherapy-department","theatre"]},"population":"Adults with a past, current or suspected cancer who develop back or neck pain suggesting spinal metastases or symptoms and signs of spinal cord or cauda equina compression. NICE NG234 applies also to direct malignant infiltration of the spine. People with haematological cancers (lymphoma, myeloma) have specific steroid advice. Children are not covered by NG234.","trigger":"A person with cancer reports new or worsening back pain with the features in NICE's box 1, or any limb weakness, numbness, unsteadiness, or bladder or bowel change.","steps":[{"action":"Make sure people with spinal metastases, and their families, know which symptoms to report and whom to contact","why":"Most cord compression starts at home, and time to treatment decides whether someone keeps walking.","source":"nice-ng234","quote":"Ensure that people with suspected or confirmed spinal metastases or MSCC and their families and carers know who to contact if they develop new symptoms or signs (see box 1 ) or if their existing symptoms worsen."},{"action":"If a person with cancer has symptoms or signs of cord compression, contact the MSCC coordinator immediately and treat it as an emergency","why":"Weakness, numbness or bladder and bowel problems mean the cord is already under pressure.","source":"nice-ng234","quote":"Immediately contact the MSCC coordinator if a person with a past or current diagnosis of cancer presents with the symptoms or signs of cord compression listed in box 1. Treat this as an oncological emergency."},{"action":"If there is only pain suggesting spinal metastases, seek advice through the MSCC coordinator within 24 hours","why":"Pain often comes before compression; finding the metastasis early allows treatment before nerves are damaged.","source":"nice-ng234","quote":"Seek advice through the MSCC coordinator (within 24 hours) if a person with a past or current diagnosis of cancer presents with pain with the characteristics suggesting spinal metastases listed in box 1."},{"action":"Immobilise without delay, including for transfer, anyone with suspected MSCC and neurological signs or signs of spinal instability, nursing them flat","why":"An unstable spine can collapse further with movement.","source":"nice-ng234","quote":"Start immobilisation without delay (including for transfer to hospital) for people with: suspected or confirmed MSCC and neurological symptoms or signs suggesting spinal instability"},{"action":"Give pain relief straight away, including while waiting for scans or treatment","why":"Pain is usually severe and should not wait for the diagnosis.","source":"nice-ng234","quote":"Ensure pain relief is provided promptly for people with suspected or confirmed spinal metastases or MSCC, including while the person is waiting for investigations or treatment."},{"action":"Give dexamethasone 16 mg by mouth (or the equivalent by injection) as soon as possible to people with neurological symptoms or signs, then 16 mg daily until surgery or radiotherapy","why":"Dexamethasone reduces swelling around the cord while definitive treatment is arranged.","source":"nice-ng234","quote":"Offer 16 mg of oral dexamethasone (or equivalent parenteral dose) as soon as possible."},{"action":"While on dexamethasone, monitor blood glucose and give a proton pump inhibitor; reduce it gradually after surgery or once radiotherapy starts, and stop it if MSCC is ruled out","why":"High-dose steroids raise blood sugar and irritate the stomach, and are not needed once the cause is treated or excluded.","source":"nice-ng234","quote":"If dexamethasone is given before imaging, and spinal metastases and MSCC are subsequently ruled out, discontinue it."},{"action":"Arrange an MRI as soon as possible and always within 24 hours, at the local hospital where possible","why":"MRI shows where and how badly the cord is compressed, which decides surgery or radiotherapy.","source":"nice-ng234","quote":"Offer an MRI scan to people with suspected MSCC (see recommendation 1.3.2 ), to be done: as soon as possible (and always within 24 hours) at the local hospital or appropriate centre with direct access to imaging facilities."},{"action":"Scan the whole spine, with sagittal T1 and/or STIR, sagittal T2 and axial images through any abnormality","why":"Metastases are often at more than one level.","source":"nice-ng234","quote":"MRI of the spine should include: sagittal T1 and/or short TI inversion recovery (STIR) sequences of the whole spine, to identify spinal metastases"},{"action":"Do overnight MRI only when treatment would start immediately; use CT if MRI is contraindicated, and never a plain X-ray","why":"Plain X-rays miss most spinal metastases and cord compression.","source":"nice-ng234","quote":"Do not do a plain X-ray of the spine to diagnose or rule out spinal metastases or MSCC."},{"action":"Plan treatment in the MSCC multidisciplinary team, including an oncologist and a spinal surgeon","why":"The choice between surgery and radiotherapy depends on stability, neurology, the cancer and prognosis.","source":"nice-ng234","quote":"Before an invasive intervention is offered, make a treatment plan in discussion with the appropriate specialists (such as an oncologist and spinal surgeon) within the MSCC service multidisciplinary team."},{"action":"Offer surgery intended to halt or reverse neurological decline as soon as possible after neurological symptoms start, where suitable","why":"In a randomised trial, more people walked after surgery followed by radiotherapy than after radiotherapy alone.","source":"nice-ng234","quote":"Offer surgical intervention intended to halt or reverse neurological decline as soon as possible after the onset of neurological symptoms or signs indicating MSCC."},{"action":"If surgery is not suitable, give urgent radiotherapy within 24 hours, usually 8 Gy in a single fraction","why":"Radiotherapy shrinks the tumour pressing on the cord; a single dose means one visit.","source":"nice-ng234","quote":"Use 8 Gy single fraction radiotherapy for people with MSCC having radiotherapy unless they are at high risk of side effects."},{"action":"After surgery, give postoperative radiotherapy once the person has recovered","why":"Radiotherapy after surgery treats the tumour left behind.","source":"nice-ng234","quote":"Offer postoperative radiotherapy after the person has recovered from surgery for spinal metastases or MSCC."},{"action":"Test spinal stability with graded sitting and then weight bearing, watching neurology and pain throughout","why":"Getting up safely and early prevents the harms of bed rest; a rise in pain or new weakness means stop and reassess.","source":"nice-ng234","quote":"If assessment, including imaging, suggests spinal stability is likely (before or after treatment), start testing this by graded sitting followed by weight bearing."},{"action":"Plan discharge and rehabilitation from admission","why":"Many people need equipment, carers' training and community support to go home.","source":"nice-ng234","quote":"Start planning for discharge and ongoing care, including rehabilitation, on admission to hospital."}],"bestInClass":{"statement":"NICE NG234 (2023) is the most recent full guideline that could be read: immediate MSCC coordinator contact for neurological signs, MRI of the whole spine within 24 hours, dexamethasone 16 mg as soon as possible, immobilisation for suspected instability, surgery as soon as possible after neurological onset where suitable, and otherwise radiotherapy within 24 hours as 8 Gy in one fraction. ASTRO 2024 agrees on dexamethasone for cord compression and conditionally recommends surgery with postoperative radiotherapy over radiotherapy alone, but accepts four schedules (8 Gy/1, 16 Gy/2, 20 Gy/5, 30 Gy/10) for those not having surgery, where NICE prefers the single fraction. The trial evidence behind the choice: SCORAD III found 8 Gy in one fraction did not formally meet non-inferiority against 20 Gy in 5 fractions for walking at 8 weeks (69.3% against 72.7%; lower confidence bound -11.5% against a -11% margin), and Patchell 2005 found surgery plus radiotherapy kept more people walking than radiotherapy alone (84% against 57%).","sources":["nice-ng234","astro-2024","scorad-2019","patchell-2005"]},"variants":[{"name":"Four accepted radiotherapy schedules (ASTRO 2024)","differs":"For cord or cauda equina compression in people not eligible for surgery, recommends 8 Gy in 1 fraction, 16 Gy in 2, 20 Gy in 5 or 30 Gy in 10, chosen after a whole-person assessment and shared decision making, rather than a default single fraction.","evidence":"Recommendation strength and evidence quality assessed by the ASTRO task force from an AHRQ systematic review; only the abstract was read, so the printed grades are not quoted.","sources":["astro-2024"]},{"name":"Multiple fractions for people at high risk of side effects (NICE NG234)","differs":"Considers multiple-fraction radiotherapy when a large treatment field is needed or there has been previous radiotherapy.","evidence":"NICE recommendation; NICE does not grade.","sources":["nice-ng234"]},{"name":"Single fraction against five fractions (SCORAD III trial)","differs":"Randomised 686 people in UK and Australian centres to 8 Gy once or 20 Gy in 5 daily fractions. Walking at 8 weeks was 69.3% against 72.7%, narrowly missing the non-inferiority criterion; at 1, 4 and 12 weeks single fraction met it, and survival at 12 weeks was similar.","evidence":"Randomised controlled trial (abstract read).","sources":["scorad-2019"]}],"grades":[{"claim":"MRI within 24 hours for suspected MSCC","grade":"not graded (NICE uses wording, 'offer')","source":"nice-ng234"},{"claim":"Dexamethasone 16 mg as soon as possible for neurological symptoms or signs","grade":"not graded (NICE uses wording, 'offer')","source":"nice-ng234"},{"claim":"8 Gy single fraction unless at high risk of side effects","grade":"not graded (NICE uses wording, 'use')","source":"nice-ng234"},{"claim":"Surgery and postoperative radiotherapy over radiotherapy alone for cord or cauda equina compression","grade":"conditional recommendation","source":"astro-2024","quote":"Regarding other modalities with RT, for patients with spine metastases causing spinal cord or cauda equina compression, surgery and postoperative RT are conditionally recommended over RT alone."},{"claim":"Dexamethasone for spine metastases with cord or cauda equina compression","grade":"recommended (strength not stated in abstract)","source":"astro-2024","quote":"Furthermore, dexamethasone is recommended for spine metastases with spinal cord or cauda equina compression."}],"sources":[{"key":"nice-ng234","label":"Spinal metastases and metastatic spinal cord compression (NG234), recommendations","publisher":"NICE","year":2023,"url":"https://www.nice.org.uk/guidance/ng234/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; strength is in the wording ('offer', 'consider', 'do not'). Each is dated [2023] or [2008]. Published September 2023, replacing CG75; minor changes August 2024 and March 2026.","read":"full-text","accessed":"2026-11-11"},{"key":"astro-2024","label":"External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline","publisher":"ASTRO, Practical Radiation Oncology","year":2024,"url":"https://europepmc.org/abstract/MED/38788923","doi":"10.1016/j.prro.2024.04.018","gradingScheme":"ASTRO consensus methodology with evidence quality and recommendation strength (strong or conditional); grades per recommendation were not read, only the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"scorad-2019","label":"Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial","publisher":"JAMA","year":2019,"url":"https://europepmc.org/abstract/MED/31794625","doi":"10.1001/jama.2019.17913","read":"abstract","accessed":"2026-11-11"},{"key":"patchell-2005","label":"Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial","publisher":"The Lancet","year":2005,"url":"https://europepmc.org/abstract/MED/16112300","doi":"10.1016/S0140-6736(05)66954-1","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["NICE's bisphosphonate recommendations for spinal metastases were last reviewed in 2008, and NICE says it will review them later; they are not used as steps here.","The ASTRO 2024 guideline was read only as its abstract, so the evidence quality and strength printed beside each schedule are not quoted.","The ESMO guideline on bone health in cancer was not looked at for this page; a European position on MSCC is therefore missing.","NICE gives no evidence grade for the 16 mg dexamethasone dose; trials comparing lower doses were not read here.","The best timing of surgery after complete paraplegia is unsettled; NICE says not to use a time limit as the only factor."]},{"id":"midline-catheters-for-anticancer-therapy","kind":"protocol","name":"Midline catheters in cancer care: when to use one, insertion, care and limits","aka":["midline","midline catheter","MC","extended dwell peripheral catheter","midline for chemotherapy","midline vs PICC"],"tldr":"A midline is a longer drip tube put into a vein in the upper arm, with its tip still in the arm rather than near the heart. It avoids repeated needles, and it carries fewer bloodstream infections than a PICC. Whether it is safe for chemotherapy that can damage tissue if it leaks has not been settled.","summary":"A midline is a peripheral device: its tip lies in the upper arm or axillary vein, not in a central vein. CDC/HICPAC (2011) advises a midline or PICC instead of a short cannula when intravenous therapy will likely exceed six days (Category II), daily site checks, replacement only for a specific indication (II), and prompt removal when it is no longer essential (IA). The Italian SIMiC bundle (2026) sets seven insertion steps: ultrasound assessment of the arm and chest veins, choice of an upper-arm vein, hand hygiene, antisepsis and maximal barrier precautions, ultrasound-guided puncture, intra-procedural ultrasound tip location, sutureless securement and glue with a transparent dressing.\n\nAgainst PICCs, a 2026 meta-analysis of 15 studies (over 27,000 patients) found PICCs had about four times the risk of catheter-related bloodstream infection (RR 4.18), with no difference in thrombosis, failure, occlusion or phlebitis; a second 2026 meta-analysis (29,680 catheters) found similar venous thromboembolism rates (3.5% against 3.8%). In cancer, a Japanese prospective study of 59 patients having continuous fluorouracil for at least four days found no phlebitis with a midline; and a systematic review found midlines and PICCs safe for symptom control in palliative care. The open question is vesicants: no guideline read says whether continuous or repeated vesicant chemotherapy may run through a midline, and the Japanese extravasation guideline cites a case report of oxaliplatin extravasation from one.","asOf":"2026-11-11","links":[],"tags":[],"related":["peripheral-cannula-for-anticancer-therapy","venous-access-device-selection-for-anticancer-therapy","central-venous-catheter-insertion-for-anticancer-therapy"],"cancers":[],"sections":[],"technologies":["infusion-devices-vascular-access","catheter-securement-devices"],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A midline is a longer tube in an upper-arm vein for drips over days or weeks. Ask your team whether your treatment can go through one.","domain":"vascular-access","setting":{"who":["nurse","doctor"],"where":["ward","chemotherapy-day-unit","outpatient-clinic","community"]},"population":"Adults with cancer needing intravenous access for more than about six days without a central device, for supportive treatment, antibiotics, symptom control or selected anticancer infusions. Children and long courses of chemotherapy, where a port or PICC is usually chosen (see the device-selection protocol), are not covered.","trigger":"Intravenous therapy is expected to last more than about six days and a central device is not needed or not wanted.","steps":[{"action":"Choose a midline or PICC rather than a short cannula when intravenous treatment will likely last more than six days","why":"A short cannula usually fails within days; a longer device avoids repeated needles.","source":"cdc-hicpac-2011","quote":"Use a midline catheter or peripherally inserted central catheter (PICC), instead of a short peripheral catheter, when the duration of IV therapy will likely exceed six days.","grade":"Category II"},{"action":"Insert it as a bundle: ultrasound assessment of the veins, an upper-arm vein, hand hygiene, skin antisepsis and maximal barriers, ultrasound-guided puncture, ultrasound tip location, sutureless securement and a sealed transparent dressing","why":"Each step lowers the chance of a failed attempt, an infection, a clot or the line falling out.","source":"simic-2026","quote":"The SIMiC bundle includes seven steps: (1) systematic ultrasound evaluation of the veins of the arms and the supra/infra-clavicular area; (2) choice of the most appropriate vein of the upper arm; (3) appropriate hand hygiene, proper skin antisepsis, and maximal barrier precautions; (4) ultrasound-guided venipuncture; (5) intra-procedural tip location, using infra/supraclavicular ultrasound scan; (6) sutureless securement, preferably using subcutaneous anchorage; (7) protection of the exit site with cyanoacrylate glue and semipermeable transparent membrane."},{"action":"Check the site every day, through the dressing, for tenderness, redness or swelling","why":"Early signs of infection, phlebitis or a leak are found by looking and feeling.","source":"cdc-hicpac-2011","quote":"Evaluate the catheter insertion site daily by palpation through the dressing to discern tenderness and by inspection if a transparent dressing is in use.","grade":"Category II"},{"action":"Do not replace a working midline on a schedule; replace it only for a specific reason","why":"Routine replacement adds procedures without benefit.","source":"cdc-hicpac-2011","quote":"Replace midline catheters only when there is a specific indication.","grade":"Category II"},{"action":"Take the midline out as soon as it is no longer needed","why":"Every day a line stays in adds to the risk of infection and clots.","source":"cdc-hicpac-2011","quote":"Promptly remove any intravascular catheter that is no longer essential [69–72].","grade":"Category IA"}],"bestInClass":{"statement":"Use a midline (or PICC) when intravenous therapy will likely exceed six days (CDC Category II), insert it with an ultrasound-guided bundle (SIMiC 2026), check it daily, replace it only for a reason (CDC II) and remove it promptly (CDC IA). Compared with PICCs, midlines carry fewer bloodstream infections and similar thrombosis risk (2026 meta-analyses). For anticancer drugs, the only cancer-specific evidence read is for continuous fluorouracil (Sakakida 2025); whether vesicants may be given through a midline is unresolved in the sources read, and the INS Standards that address it could not be read.","sources":["cdc-hicpac-2011","simic-2026","aljameie-2026","santagata-2026","sakakida-2025"]},"variants":[{"name":"Midline for continuous fluorouracil","differs":"Gives continuous fluorouracil over four days or more through an upper-arm midline with its tip in the axillary vein, instead of a short cannula or a central line.","evidence":"In a prospective Japanese study of 59 patients (mostly oesophageal and head and neck cancer), no phlebitis occurred (0%, 95% CI 0 to 6.2%), insertion succeeded in 98.3% and complications occurred in 6.8%; median dwell 5.5 days.","sources":["sakakida-2025"]},{"name":"Midline for symptom control in palliative care","differs":"Uses a midline or PICC for weeks of intravenous symptom treatment or parenteral nutrition in people with advanced cancer.","evidence":"A systematic review of 17 studies (moderate or weak quality) found complications of 0 to 2.46 per 1,000 catheter days and high patient satisfaction.","sources":["gravdahl-2024"]}],"grades":[],"sources":[{"key":"cdc-hicpac-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"simic-2026","label":"A GAVeCeLT-IVAS bundle for the Safe Insertion of Midline Catheters: The SIMiC protocol","publisher":"Journal of Vascular Access (GAVeCeLT and IVAS)","year":2026,"url":"https://doi.org/10.1177/11297298261445794","doi":"10.1177/11297298261445794","read":"abstract","accessed":"2026-11-11"},{"key":"magic-onc-2025","label":"The Michigan Appropriateness Guide for Intravenous Catheters in Adult Patients With Cancer (MAGIC-ONC)","publisher":"Annals of Internal Medicine","year":2025,"url":"https://doi.org/10.7326/ANNALS-25-02523","doi":"10.7326/ANNALS-25-02523","gradingScheme":"RAND/UCLA Appropriateness Method: scenarios rated appropriate, neutral/uncertain or inappropriate.","read":"abstract","accessed":"2026-11-11"},{"key":"sakakida-2025","label":"Midline catheter use for cancer patients receiving 5-FU chemotherapy: prospective study of safety and outcomes","publisher":"The Oncologist (Sakakida et al.)","year":2025,"url":"https://doi.org/10.1093/oncolo/oyaf108","doi":"10.1093/oncolo/oyaf108","read":"abstract","accessed":"2026-11-11"},{"key":"aljameie-2026","label":"Comparative safety and effectiveness of midline catheters vs. peripherally inserted central catheters: a systematic review and meta-analysis","publisher":"Frontiers in Cardiovascular Medicine (Aljameie et al.)","year":2026,"url":"https://doi.org/10.3389/fcvm.2026.1890087","doi":"10.3389/fcvm.2026.1890087","read":"abstract","accessed":"2026-11-11"},{"key":"santagata-2026","label":"Venous Thromboembolism Risk Associated with MIDLINE Catheters and Peripherally Inserted Central Catheters, a Systematic Review and Meta-Analysis","publisher":"Thrombosis and Haemostasis (Santagata et al.)","year":2026,"url":"https://doi.org/10.1055/a-2810-4737","doi":"10.1055/a-2810-4737","read":"abstract","accessed":"2026-11-11"},{"key":"gravdahl-2024","label":"Use of peripherally inserted central venous catheters and midline catheters for palliative care in patients with cancer: a systematic review","publisher":"Supportive Care in Cancer (Gravdahl et al.)","year":2024,"url":"https://doi.org/10.1007/s00520-024-08664-3","doi":"10.1007/s00520-024-08664-3","read":"abstract","accessed":"2026-11-11"},{"key":"ins-2024","label":"Infusion Therapy Standards of Practice, 9th Edition","publisher":"Infusion Nurses Society (Journal of Infusion Nursing)","year":2024,"url":"https://doi.org/10.1097/NAN.0000000000000532","doi":"10.1097/NAN.0000000000000532","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-midline-vesicant-safety-study"],"gaps":["Whether vesicant or irritant chemotherapy may be given through a midline is not answered by any source read; the INS Standards (2024), which address infusate limits for midlines, and MAGIC-ONC's full ratings could not be read. The Japanese extravasation guideline (2024) cites a case report of oxaliplatin extravasation from a midline.","OnCo has no technology record for midline catheters; this protocol links the general vascular access record.","All the midline evidence here was read as abstracts; the meta-analyses mix inpatients and intensive care with few people having cancer treatment."]},{"id":"head-and-neck-radiotherapy-oral-mucositis","kind":"protocol","name":"Mouth care and oral mucositis prevention during head and neck radiotherapy","aka":["oral mucositis during radiotherapy","radiation mucositis","sore mouth during head and neck radiotherapy","mouth care during radiotherapy","photobiomodulation for mucositis","benzydamine mouthwash","Difflam during radiotherapy"],"tldr":"Radiotherapy to the head and neck makes the lining of the mouth and throat sore, usually from the second or third week. Keeping the mouth clean on a regular routine, a benzydamine mouthwash, and in many centres a low-level light treatment inside the mouth help prevent it; pain relief and help with eating matter as much as anything else.","summary":"The MASCC/ISOO 2020 guideline (the latest full edition) is the reference. For head and neck radiotherapy it suggests a multiagent combination oral care protocol (level III), recommends benzydamine mouthwash for moderate-dose radiotherapy below 50 Gy (level I) and suggests it with chemoradiotherapy (level II), and recommends intraoral photobiomodulation with low-level laser for radiotherapy alone (level II) and for chemoradiotherapy (level I), following the parameters of one of the protocols in its Table 2 and telling patients that animal data on tumour effects conflict. It suggests against chlorhexidine for prevention (level III), recommends against sucralfate, suggests honey (level II) and, with caution, oral glutamine with chemoradiotherapy (level II), and suggests topical morphine 0.2% mouthwash for pain with chemoradiotherapy (level III). Professional oral care, patient education and saline or bicarbonate rinses carry expert opinion only: dental assessment before treatment, education to support self-care, and bland rinses for clearance and comfort. The MASCC/ISOO Delphi (2024) adds how to assess: the WHO scale by the clinician, weekly or more often in high-grade mucositis, with a patient-reported measure (OMWQ and OMDQ, or PRO-CTCAE items). Where no intervention is recommended, pain relief, dietary support and preventing secondary infection carry management.","asOf":"2026-11-11","links":[],"tags":[],"related":["idea-moon-mucositis-taste-programme","head-and-neck-radiotherapy-dental-assessment-osteoradionecrosis","oral-mucositis-prevention-and-oral-care"],"cancers":["head-and-neck","oral-cavity-cancer","oropharyngeal-cancer"],"sections":[],"technologies":["photobiomodulation-mucositis","honey-radiation-mucositis","glutamine-mucositis-neuropathy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mucositis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Radiotherapy to the mouth or throat often makes the mouth very sore. Brush gently, rinse often, and use the mouthwash your team gives you. Tell them early if it hurts to eat or swallow, so they can help with pain and food.","domain":"radiotherapy","setting":{"who":["nurse","doctor","radiographer","patient-or-carer","multidisciplinary-team"],"where":["radiotherapy-department","outpatient-clinic","home"]},"population":"Adults having radiotherapy, with or without concurrent chemotherapy, to the head and neck. The MASCC/ISOO statements are scoped by treatment (radiotherapy alone, chemoradiotherapy) and by dose for benzydamine (below 50 Gy for the level I recommendation). Children are not covered: a MASCC/ISOO paediatric sub-analysis (2021) found too little evidence to make recommendations beyond basic oral care, and advised extrapolating from adults. Mucositis from chemotherapy alone or from stem cell transplant conditioning follows other statements in the same guideline and is not covered here.","trigger":"Radiotherapy to the head and neck is planned; the protocol starts before the first fraction and runs to the end of treatment and the weeks after.","steps":[{"action":"Arrange a dental assessment, and any treatment needed, before radiotherapy starts","why":"Bad teeth or gums are a source of infection during treatment, and some dental work is safer done before the jaw is irradiated.","source":"mascc-isoo-2020","quote":"An expert opinion complements this guideline: Although there was insufficient evidence to support the use of professional oral care for OM prevention, the panel is of the opinion that dental evaluation and treatment as indicated before cancer therapy are desirable to reduce risk for local and systemic infections from odontogenic sources.","grade":"III (expert opinion)"},{"action":"Start a combined oral care routine (brushing, flossing where possible and regular rinses) and support the patient to keep to it throughout treatment","why":"A regular routine of cleaning the mouth lowers the chance and severity of a sore mouth, mostly by making daily mouth care happen.","source":"mascc-isoo-2020","quote":"The panel suggests that implementation of multiagent combination oral care protocols is beneficial for the prevention of OM during H&N RT.","grade":"III (suggestion)"},{"action":"Teach the patient and carer why mouth care matters and how to do it","why":"People who understand the routine are more likely to keep to it when the mouth is sore.","source":"mascc-isoo-2020","quote":"An expert opinion complements this guideline: The panel is of the opinion that educating patients about the benefits of BOC strategies is still appropriate because this may improve self‐management and adherence to the recommended oral care protocol during cancer treatment.","grade":"III (expert opinion)"},{"action":"Offer bland rinses (salt water or sodium bicarbonate) for cleaning and comfort","why":"They are harmless, wash debris away and can make the mouth feel better, though they have not been shown to prevent mucositis.","source":"mascc-isoo-2020","quote":"An expert opinion complements this guideline: Despite the limited data available for both saline and sodium bicarbonate, the panel recognizes that these are inert, bland rinses that increase oral clearance, which may be helpful for maintaining oral hygiene and improving patient comfort.","grade":"III (expert opinion)"},{"action":"Give benzydamine mouthwash from the start of radiotherapy where the dose is moderate (below 50 Gy)","why":"Benzydamine is an anti-inflammatory rinse that reduces mucositis in trials of moderate-dose head and neck radiotherapy.","source":"mascc-isoo-2020","quote":"The panel recommends benzydamine mouthwash for the prevention of OM in patients with H&N cancer receiving a moderate dose RT (<50 Gy).","grade":"I (recommendation)"},{"action":"Consider benzydamine mouthwash as well when chemotherapy is given with the radiotherapy","why":"The evidence is weaker with chemoradiotherapy, but points the same way.","source":"mascc-isoo-2020","quote":"The panel suggests the use of benzydamine mouthwash for the prevention of OM in patients with H&N cancer who receive RT‐CT.","grade":"II (suggestion)"},{"action":"Where available, give intraoral photobiomodulation (low-level laser) through the course, using the exact parameters of a published protocol","why":"Low-energy red light inside the mouth reduces how severe mucositis gets; the benefit depends on using settings that were tested.","source":"mascc-isoo-2020","quote":"The panel recommends the use of intraoral PBM therapy using low‐level laser therapy for the prevention of OM in adults receiving RT‐CT for H&N cancer (Table 2); safety considerations unique to patients with oral cancer should be considered.","grade":"I (recommendation, chemoradiotherapy); II (recommendation, radiotherapy alone)"},{"action":"Before photobiomodulation, explain the expected benefit and the uncertain risk of light shone on or near a tumour","why":"Animal studies disagree on whether the light affects tumour cells; follow-up of treated patients has not shown more recurrence, but the data are hard to analyse.","source":"mascc-isoo-2020","quote":"Considering the conflicting evidence from animal models regarding the effect of PBM on tumor behavior, the clinician is advised to inform patients about the expected benefits and potential risks of PBM."},{"action":"Do not use chlorhexidine mouthwash to prevent mucositis, unless it is needed to treat an infection","why":"Trials found it does not prevent radiation mucositis; it remains acceptable for a mouth infection.","source":"mascc-isoo-2020","quote":"The panel suggests that CHX not be used in the prevention of OM in patients undergoing H&N RT.","grade":"III (suggestion against)"},{"action":"Check the mouth at least weekly with the WHO mucositis scale, more often once it is severe, and ask the patient to score it too","why":"Regular scoring catches worsening early, and the patient's own report shows how much it affects eating and pain.","source":"mascc-delphi-2024","quote":"Weekly or more in high grade mucositis","grade":"Delphi consensus (more than 80% agreement)"},{"action":"Treat the pain early and step it up as needed; with chemoradiotherapy, consider a topical morphine 0.2% mouthwash","why":"Pain is what stops people eating and drinking; a morphine rinse can help where chemotherapy is part of treatment.","source":"mascc-isoo-2020","quote":"Topical morphine 0.2% mouthwash is suggested for the treatment of OM‐associated pain in patients with H&N cancer who receive RT‐CT.","grade":"III (suggestion)"},{"action":"Do not use sucralfate to prevent or treat mucositis pain during head and neck radiotherapy","why":"Trials found the combined mouth-and-swallowed form did not help.","source":"mascc-isoo-2020","quote":"Sucralfate (combined topical and systemic) is not recommended for the prevention of OM‐associated pain in patients with H&N cancer who receive RT.","grade":"II (recommendation against)"},{"action":"Keep the patient eating and drinking with dietetic support, and watch for and treat mouth infection","why":"Where no treatment prevents mucositis, nutrition, pain relief and stopping infection are what carry people through.","source":"mascc-isoo-2020","quote":"Until more research is available, pain relief, dietary support, and secondary infection prevention are key elements in patient management."}],"bestInClass":{"statement":"MASCC/ISOO 2020 is the only current international guideline read and the reference for this protocol: a combination oral care routine with dental assessment beforehand, benzydamine mouthwash (level I below 50 Gy, level II with chemotherapy), intraoral photobiomodulation with the tested parameters (level I with chemoradiotherapy, level II with radiotherapy alone) after explaining its uncertain tumour safety, no chlorhexidine or sucralfate for prevention, weekly WHO-scale assessment with a patient-reported measure (MASCC/ISOO Delphi 2024), and early pain relief and dietary support. Honey (level II) and oral glutamine with chemoradiotherapy (level II, with caution) are suggestions, not recommendations.","sources":["mascc-isoo-2020","mascc-delphi-2024"]},"variants":[{"name":"Honey","differs":"Adds honey, applied in the mouth and swallowed, through radiotherapy or chemoradiotherapy.","evidence":"MASCC/ISOO 2020 suggests it (level II); the trials were small, mixed radiotherapy and chemoradiotherapy, and used different honeys, so only a suggestion was possible.","sources":["mascc-isoo-2020"]},{"name":"Oral glutamine with chemoradiotherapy","differs":"Adds oral glutamine during chemoradiotherapy.","evidence":"MASCC/ISOO 2020 suggests it (level II) on two randomised trials, with caution: \"The suggestion is with caution because of the higher mortality rate seen in patients undergoing HSCT who receive parenteral glutamine.\" The dose printed in the guideline's discussion is not reproduced here because it could not be checked against the trials.","sources":["mascc-isoo-2020"]},{"name":"Zinc, misoprostol and other agents once suggested","differs":"Some centres still give zinc or a misoprostol rinse.","evidence":"MASCC/ISOO 2020 withdrew the 2014 suggestion for zinc and the 2014 suggestion against misoprostol, reversing both to no guideline possible: \"The previous suggestion made for zinc in the 2014 MASCC/ISOO guidelines for patients with H&N cancer who received RT or RT‐CT was reversed in the current guidelines to NGP.\"","sources":["mascc-isoo-2020"]},{"name":"Chlorhexidine as the routine mouthwash","differs":"Uses chlorhexidine as the standard rinse through radiotherapy.","evidence":"MASCC/ISOO 2020 suggests against it for preventing mucositis (level III) but keeps it for infection: \"If CHX is indicated because of concurrent oral infection and OM, it is acceptable to use it for the oral infection.\"","sources":["mascc-isoo-2020"]}],"grades":[{"claim":"Multiagent combination oral care protocols during head and neck radiotherapy","grade":"III (suggestion)","source":"mascc-isoo-2020"},{"claim":"Benzydamine mouthwash with moderate-dose radiotherapy (below 50 Gy)","grade":"I (recommendation)","source":"mascc-isoo-2020"},{"claim":"Benzydamine mouthwash with chemoradiotherapy","grade":"II (suggestion)","source":"mascc-isoo-2020"},{"claim":"Intraoral photobiomodulation with radiotherapy alone","grade":"II (recommendation)","source":"mascc-isoo-2020","quote":"The panel recommends the use of intraoral PBM therapy using low‐level laser therapy for prevention of OM in adults receiving RT to the H&N (without CT) (Table 2); safety considerations unique to patients with oral cancer should be considered."},{"claim":"Intraoral photobiomodulation with chemoradiotherapy","grade":"I (recommendation)","source":"mascc-isoo-2020"},{"claim":"Follow the specific parameters of the selected photobiomodulation protocol","grade":"Recommendation (ungraded note to the table)","source":"mascc-isoo-2020","quote":"For all PBM guidelines, it is recommended that the specific PTPs of the selected protocol will be followed for optimal therapy."},{"claim":"Chlorhexidine not to be used to prevent mucositis in head and neck radiotherapy","grade":"III (suggestion against)","source":"mascc-isoo-2020"},{"claim":"Topical morphine 0.2% mouthwash for pain with chemoradiotherapy","grade":"III (suggestion)","source":"mascc-isoo-2020"},{"claim":"Sucralfate not recommended for prevention or treatment of pain with radiotherapy","grade":"II (recommendation against)","source":"mascc-isoo-2020"},{"claim":"Oral glutamine with chemoradiotherapy","grade":"II (suggestion, with caution)","source":"mascc-isoo-2020","quote":"The panel suggests oral glutamine for the prevention of OM in patients with H&N cancer who receive receiving RT‐CT."},{"claim":"Honey with radiotherapy or chemoradiotherapy","grade":"II (suggestion)","source":"mascc-isoo-2020","quote":"Honey is suggested for the prevention of OM in patients with H&N cancer who receive treatment with either RT or RT‐CT."},{"claim":"Patient-reported measure for head and neck (chemo)radiotherapy in practice","grade":"Delphi consensus (more than 80% agreement)","source":"mascc-delphi-2024","quote":"OMWQ and OMDQ or PRO-CTCAE questions related to mucositis"}],"sources":[{"key":"mascc-isoo-2020","label":"MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy (2019 update)","publisher":"MASCC and ISOO (Cancer; Elad et al.)","year":2020,"url":"https://doi.org/10.1002/cncr.33100","doi":"10.1002/cncr.33100","gradingScheme":"Level of evidence I to V (Somerfield and McCrae criteria); each statement is a recommendation, a suggestion or no guideline possible (NGP), and expert opinion is marked as such. Negative guidelines mean lack of efficacy, not harm.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-delphi-2024","label":"Guidance on mucositis assessment from the MASCC Mucositis Study Group and ISOO: an international Delphi study","publisher":"MASCC Mucositis Study Group and ISOO (eClinicalMedicine; Abdalla-Aslan et al.)","year":2024,"url":"https://doi.org/10.1016/j.eclinm.2024.102675","doi":"10.1016/j.eclinm.2024.102675","gradingScheme":"Delphi consensus, defined as agreement by more than 80% of respondents; not graded by evidence level.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-isoo-paediatric-2021","label":"MASCC/ISOO clinical practice guidelines for the management of mucositis: sub-analysis of current interventions for the management of oral mucositis in pediatric cancer patients","publisher":"MASCC and ISOO (Supportive Care in Cancer)","year":2021,"url":"https://doi.org/10.1007/s00520-020-05803-4","doi":"10.1007/s00520-020-05803-4","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-photobiomodulation-every-head-neck-centre"],"gaps":["MASCC/ISOO 2020 remains the latest full edition; an erratum was published in 2021 (Cancer, doi 10.1002/cncr.33549) whose text could not be retrieved, so what it corrects was not checked.","The 2014 statements carried forward unchanged (including the doxepin rinse for pain) sit in the 2020 paper's Supporting Table 1, which was not read; nothing here rests on them.","Photobiomodulation parameters (wavelength, power, time per spot, number of sites) are in Table 2 of the guideline and in the PBM systematic review; they are not reproduced here, and the guideline asks that a tested protocol be followed exactly. Access to photobiomodulation varies widely between centres.","The guideline's discussion gives the oral glutamine dose as '10 to 30 mg daily', which does not match the gram doses used in glutamine trials; the figure was not checked against the trials and is not used.","No national guideline (NICE, ESMO) on radiation mucositis newer than MASCC/ISOO 2020 was found. The UK Oral Mucositis in Cancer Group guidance was not located to read.","Children: the evidence is too thin for recommendations beyond basic oral care (paediatric sub-analysis, abstract read)."]},{"id":"mri-safety-screening-implants","kind":"protocol","name":"MRI safety screening for implants, devices and medicine patches","aka":["MRI safety checklist","MRI screening form","MRI with a port","MRI with a pacemaker","MR conditional implant","MRI and fentanyl patch","metal and MRI","MRI implant card"],"tldr":"An MRI scanner is a very strong magnet, so before every scan you will be asked about any implant, device, patch or metal in or on your body, even if you have had MRI before. Bring any implant card. Many implants, including most ports, can be scanned safely under set conditions, but the team needs to know the exact device. Tell the radiographer at once if you feel warmth or tingling.","summary":"MHRA guidance version 5.0 (2026) recommends four screening stages: targeted MRI questions on the referral (the referrer must identify implants and contraindications), questions at booking, a full screening form reviewed with the patient by an MR Authorised Person on arrival, and visual and verbal screening just before entering the magnet room; screening is repeated at every visit and completed before any sedation. Implant make and model should be in the operation notes and on an implant card, and the information should reach the unit before the appointment. Sites should have generic implant safety procedures for low-risk passive implants that do not need make and model, and otherwise identify the device and follow the manufacturer's MR Conditional terms. Where a condition cannot be met, the device is MR Unsafe, unlabelled or unknown, scanning may still proceed if benefit outweighs risk, after a documented multidisciplinary risk assessment (MR radiographer, MR safety expert, MR clinician, and a specialist such as a cardiologist for cardiac devices) with precautions and post-scan checks. Medicine patches with metal can burn, and heated fentanyl patches can cause overdose, so sites need a process for removing and replacing them. Patients with tattoos or permanent make-up report warmth at once. Burns can occur without immediate pain and are reported to the MHRA. Advice about specific devices is left to manufacturers and professional bodies (for cardiac devices, the Joint British Societies' recommendations, which were not read here).","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mri","implanted-ports"],"targets":[],"drugs":["fentanyl"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before an MRI you fill in a safety form every time. Tell them about ports, pumps, pacemakers, clips, skin patches, tattoos and any metal. Bring your implant card. If anything feels warm or tingly in the scanner, press the call button.","domain":"screening-diagnostics","setting":{"who":["radiographer","doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","ward"]},"population":"Adults and children referred for MRI, including people with cancer who have implanted ports, central lines, drug pumps, cardiac devices, surgical clips, markers or other implants, or who use medicine patches. Specific devices are not covered: their manufacturer's MR safety information and the relevant professional body guidance decide whether and how they are scanned.","trigger":"An MRI is requested.","steps":[{"action":"On the referral, answer the MRI safety questions and name any implanted device, so the unit can check it before the appointment","why":"Finding out about a device early gives time to confirm it is safe rather than cancelling on the day.","source":"mhra-2026","quote":"It is the responsibility of the referrer to identify those patients with implants and/or contraindications to MR before referral.","grade":"ungraded"},{"action":"Record the make and model of every implant in the operation notes, and give the patient the implant card","why":"Whether a device can go in a scanner depends on its exact make and model.","source":"mhra-2026","quote":"Surgeons and other medical practitioners should provide patients with accurate documentation and information about the medical devices implanted into them, for example, providing them with an implant card and patient information provided by the implant manufacturer.","grade":"ungraded"},{"action":"Screen at booking, again with a full form reviewed with the patient on arrival, and again in person just before the magnet room, and do it at every visit","why":"Several checks give several chances to catch something missed, and things change between scans.","source":"mhra-2026","quote":"Screening must take place every time the patient attends the MRI unit, even if the patient has already had a previous MRI examination either locally or at another facility.","grade":"ungraded"},{"action":"Complete screening before any sedation or anaesthetic, and for people who cannot answer, use family, records, previous imaging or an X-ray to find implants","why":"Once someone is asleep or cannot speak for themselves, they cannot warn staff about metal.","source":"mhra-2026","quote":"If a patient is to undergo sedation or anaesthesia for the scan, all required safety screening should be completed prior to its administration.","grade":"ungraded"},{"action":"For a low-risk passive implant, follow the site's generic implant safety procedure; otherwise identify the make and model and follow the manufacturer's MR conditions","why":"Many common implants are safe under known conditions; others need their own settings or limits.","source":"mhra-2026","quote":"Where a local GISP does not exist, sites should have a process for identifying the make and model of the implant.","grade":"ungraded"},{"action":"If a condition cannot be met, or the device is unsafe, unlabelled or unknown, scan only after a documented multidisciplinary risk assessment shows benefit outweighs risk, with precautions and a check of the patient and device afterwards","why":"Some people need an MRI that their device was not tested for; a team decision with safeguards makes that possible without ruling them out.","source":"mhra-2026","quote":"If the benefit to the patient of this off-label procedure outweighs the potential risk, then scanning can be undertaken.","grade":"ungraded"},{"action":"Remove medicine patches that contain metal, following the site's process for taking them off and replacing them","why":"Metal in a patch can heat up and burn, and a heated fentanyl patch can release too much drug.","source":"mhra-2026","quote":"For example, patches containing fentanyl may result in a serious overdose if exposed to heat","grade":"ungraded"},{"action":"Remove anything removable before entering the scanner room, and change the person into the unit's clothing","why":"Loose metal can be pulled into the magnet, and some fabrics heat up.","source":"mhra-2026","quote":"Patients should be scanned in appropriate MR SAFE clothing. Ideally, patients should be changed into clothing provided by the MRI unit to minimise the risk of burns.","grade":"ungraded"},{"action":"Ask the person to report any warmth or tingling straight away, especially over tattoos or permanent make-up, and give them the call button","why":"Burns can start before they hurt, so an early warning matters.","source":"mhra-2026","quote":"However, patients should be instructed to inform staff immediately if they feel any focal warming or tingling on their skin.","grade":"ungraded"},{"action":"Report any burn through the local incident system and to the MHRA, and consider an aftercare leaflet because a burn can appear later","why":"Reporting finds patterns that make scanning safer for others.","source":"mhra-2026","quote":"Any patient burns must be reported via local incident reporting systems, and also to the MHRA.","grade":"ungraded"}],"bestInClass":{"statement":"MHRA Safety Guidelines for MRI Equipment in Clinical Use, version 5.0 (2026): four-stage screening repeated at every visit; implant make and model documented and known before the appointment; generic implant safety procedures for low-risk passive implants; manufacturer MR Conditional terms otherwise; a documented multidisciplinary risk assessment for off-label or unknown devices so that people with implants are not refused MRI by default; removal of metal-containing medicine patches; and instructions to report warmth. The guidance is ungraded and defers device-specific advice to manufacturers and professional bodies.","sources":["mhra-2026"]},"variants":[],"grades":[{"claim":"Generic implant safety procedures for low-risk implants","grade":"ungraded (key recommendation box)","source":"mhra-2026","quote":"It is recommended that sites establish local generic implant safety procedures (GISPs) to allow scanning of low-risk implants without needing to establish the make and model."},{"claim":"Off-label scanning decided by a multidisciplinary team","grade":"ungraded","source":"mhra-2026","quote":"As a minimum this should involve an MR RADIOGRAPHER, an MR SAFETY EXPERT and the MR CLINICIAN."},{"claim":"Do not rely on generative AI for MR safety advice","grade":"ungraded (key recommendation box)","source":"mhra-2026","quote":"Caution is advised regarding use of MR safety advice obtained using generative artificial intelligence"}],"sources":[{"key":"mhra-2026","label":"Safety Guidelines for Magnetic Resonance Imaging Equipment in Clinical Use, version 5.0","publisher":"Medicines and Healthcare products Regulatory Agency (MHRA)","year":2026,"url":"https://www.gov.uk/government/publications/safety-guidelines-for-magnetic-resonance-imaging-equipment-in-clinical-use","gradingScheme":"Guidance, not graded; key recommendations are printed in boxes.","read":"full-text","accessed":"2026-11-11"},{"key":"acr-mr-safety","label":"ACR Manual on MR Safety (and the 2025 Radiology commentary on its update)","publisher":"American College of Radiology","year":2024,"url":"https://doi.org/10.1148/radiol.242954","doi":"10.1148/radiol.242954","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The MHRA guidance names no cancer-specific device. Whether a particular implanted port, PICC, breast tissue expander with a magnetic port, intrathecal drug pump or radiotherapy marker can be scanned depends on its manufacturer's MR safety information, which is not summarised here.","The Joint British Societies' recommendations for MRI with cardiac implantable devices, cited by MHRA, were not read.","The ACR Manual on MR Safety and the 2025 Radiology commentary on it could not be read (the ACR site served a JavaScript shell; Europe PMC holds no abstract for the commentary).","The guidance is ungraded consensus."]},{"id":"nausea-and-vomiting-in-advanced-cancer","kind":"protocol","name":"Nausea and vomiting in advanced cancer not caused by cancer treatment","aka":["palliative nausea and vomiting","chronic nausea in advanced cancer","nausea not related to chemotherapy","antiemetic choice in palliative care","malignant bowel obstruction nausea"],"tldr":"In advanced cancer, nausea and vomiting often have a cause that can be found and treated, such as constipation, a high calcium level, a medicine, or a blocked bowel. Your team will look for the cause, stop medicines that may worsen it, and choose an anti-sickness medicine that suits it, under the skin or by a small pump if tablets will not stay down. Say if it is not improving.","summary":"MASCC/ESMO (2016, the latest statement) found the evidence minimal and of low quality, and recommend metoclopramide titrated to effect as the drug of choice, with haloperidol, levomepromazine or olanzapine as alternatives; for bowel obstruction, octreotide with an antiemetic (haloperidol), or an anticholinergic antisecretory agent where octreotide is not an option. MASCC's 2021 update keeps octreotide as the drug of choice in inoperable bowel obstruction and suggests olanzapine or metoclopramide for partial obstruction. The Scottish Palliative Care Guidelines (2025) take a cause-based approach: identify and treat reversible causes, deprescribe, choose the antiemetic for the likely mechanism (haloperidol first for chemical or drug causes, metoclopramide for gastric stasis once complete obstruction is excluded, cyclizine for raised intracranial pressure or vestibular causes, levomepromazine as a broad-spectrum agent), use non-oral routes when needed, avoid combining prokinetics with anticholinergics, consider an ECG for QTc, and start olanzapine or mirtazapine only on specialist advice. In the one randomised comparison of the two approaches (185 people), a cause-based regimen worked faster at 24 hours but was no better than haloperidol alone at 72 hours. Methotrimeprazine (levomepromazine) was no better than haloperidol in a double-blind trial, and olanzapine 5 mg markedly reduced chronic nausea against placebo in a pilot trial of 30 people.","asOf":"2026-11-11","links":[],"tags":["protocol","nausea-and-vomiting","palliative"],"related":["antiemetic-therapy","octreotide-lanreotide","anticipatory-nausea-and-vomiting","antiemetic-prophylaxis-by-emetic-risk"],"cancers":[],"sections":["supportive-care"],"technologies":["palliative-care","syringe-drivers"],"targets":[],"drugs":["dexamethasone"],"companies":[],"institutions":["mascc","esmo"],"pathways":[],"terms":["qt-prolongation"],"trials":[],"people":[],"bottlenecks":["b-palliative"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"When cancer is advanced, feeling sick often has a cause that can be fixed. Your team will look for it and choose the right medicine. Tell them if it does not help.","domain":"palliative","setting":{"who":["doctor","nurse","pharmacist","multidisciplinary-team"],"where":["ward","home","community","outpatient-clinic"]},"population":"Adults with advanced cancer and nausea or vomiting not caused by chemotherapy or radiotherapy. The Scottish guideline asks for specialist palliative care advice before use in people with Parkinson's disease or Parkinson's-plus syndromes, myasthenia gravis, porphyria, hormone-secreting neuroendocrine tumours such as phaeochromocytoma, or past serious reactions to antipsychotics. Children are not covered by the sources read.","trigger":"A person with advanced cancer reports nausea or vomiting, especially when persistent or not linked to recent anticancer treatment.","steps":[{"action":"Take a history and examine to find the likely cause: pattern (constant or intermittent), triggers, vomit volume, bowel habit, medicines, hydration, and signs of raised intracranial pressure or obstruction","why":"The cause decides which medicine works best, and some causes can be removed altogether.","source":"scottish-palliative-nv-2025","quote":"Always try to identify the underlying causes of nausea and vomiting and treat if possible"},{"action":"Correct reversible causes, such as kidney failure, high calcium, low sodium, high blood sugar, constipation, ascites or raised intracranial pressure","why":"Treating the cause can stop the nausea without long-term antiemetics.","source":"scottish-palliative-nv-2025","quote":"Correct any reversible causes of nausea and vomiting when possible (eg renal failure, hypercalcaemia, hyponatraemia, hyperglycaemia, constipation, symptomatic ascites, cerebral oedema or raised intracranial pressure)."},{"action":"Review all medicines and stop those that may cause nausea or are no longer needed","why":"Opioids, antibiotics, antidepressants and many other drugs can cause nausea, and fewer tablets are easier to keep down.","source":"scottish-palliative-nv-2025","quote":"Deprescribe potentially inappropriate medication to reduce tablet burden and polypharmacy where possible"},{"action":"Look for bowel obstruction (colicky pain, large or faeculent vomits, distension, absent flatus); if it is present and inoperable, give octreotide with an antiemetic","why":"Obstruction needs a different treatment: octreotide reduces the fluid in the gut that causes vomiting, and some antiemetics can worsen colic.","source":"mascc-esmo-2016-advanced","quote":"For bowel obstruction, the recommendation is to use octreotide given alongside an antiemetic (haloperidol) and where octreotide is not an option to use an anticholinergic antisecretory agent."},{"action":"Choose an antiemetic for the likely cause, and give it before meals where that helps","why":"Different causes act through different nerve pathways, each blocked best by a different drug.","source":"scottish-palliative-nv-2025","quote":"Select an antiemetic appropriate to the likely identified cause."},{"action":"Before starting a prokinetic such as metoclopramide, make sure there is no complete bowel obstruction and no colic","why":"A drug that pushes the gut forward can cause severe cramping pain against a complete blockage.","source":"scottish-palliative-nv-2025","quote":"Before commencing a prokinetic it is important to ensure that the patient is not in complete obstruction and is not experiencing colic."},{"action":"Where no specific choice applies, use metoclopramide titrated to effect; haloperidol, levomepromazine or olanzapine are alternatives","why":"Metoclopramide is the agent MASCC/ESMO prefer, though the trials behind every choice are small.","source":"mascc-esmo-2016-advanced","quote":"The drug of choice for managing N & V in advanced cancer is metoclopramide titrated to effect. Alternative options include haloperidol, levomepromazine, or olanzapine."},{"action":"If tablets are not absorbed or cannot be kept down, use the subcutaneous, transdermal or buccal route, or a continuous subcutaneous infusion","why":"Nausea slows the stomach and vomiting loses tablets, so medicine by mouth may not work.","source":"scottish-palliative-nv-2025","quote":"the transdermal or parenteral route may be used if the oral route is not appropriate or to reduce tablet burden."},{"action":"Avoid giving a prokinetic (such as metoclopramide) together with an anticholinergic (such as cyclizine)","why":"The anticholinergic cancels out the prokinetic's effect on the gut.","source":"scottish-palliative-nv-2025","quote":"Try to avoid the concurrent prescribing of prokinetics (eg metoclopramide) and anticholinergics (eg cyclizine) medication. The anticholinergics will diminish the prokinetic effect."},{"action":"Consider an ECG to check the QTc interval, since many antiemetics prolong it","why":"Several antiemetics can disturb the heart rhythm, especially in combination or at higher doses.","source":"scottish-palliative-nv-2025","quote":"Consider the appropriateness of performing an electrocardiogram (ECG) to measure QTc as many antiemetics increase the risk of QTc prolongation."},{"action":"Use non-drug measures alongside medicines: mouth care, small palatable meals, avoiding cooking smells, regular bowels, a calm setting and loose clothing","why":"Simple measures reduce triggers and make eating and drinking easier.","source":"scottish-palliative-nv-2025","quote":"Non-pharmacological measures should be considered alongside the prescribing of appropriate antiemetics."},{"action":"If nausea persists, reassess the cause and seek specialist palliative care advice; start olanzapine or mirtazapine only on specialist advice","why":"Persistent nausea often has more than one cause, and specialists can add drugs whose use in this setting is less established.","source":"scottish-palliative-nv-2025","quote":"Olanzapine and mirtazapine should only be commenced on specialist advice."}],"bestInClass":{"statement":"Two current approaches disagree on the first drug. MASCC/ESMO (2016, the latest international statement) recommend metoclopramide titrated to effect for most people, with haloperidol, levomepromazine or olanzapine as alternatives. The Scottish Palliative Care Guidelines (2025, the most recent national guideline read) choose by cause: haloperidol first for chemical and drug-induced nausea, metoclopramide for gastric stasis, cyclizine for intracranial or vestibular causes, levomepromazine for multifactorial nausea. Both rest on weak evidence: the one randomised comparison found a cause-based regimen faster at 24 hours but no better than haloperidol alone at 72 hours. They agree on finding and correcting reversible causes, on octreotide with an antiemetic for inoperable bowel obstruction (reaffirmed by MASCC in 2021), and on keeping olanzapine for when first-line drugs fail. NICE's Clinical Knowledge Summary could not be read.","sources":["mascc-esmo-2016-advanced","scottish-palliative-nv-2025","hardy-2018","mascc-mbo-2021","nice-cks-nv"]},"variants":[{"name":"Cause-based antiemetic choice (Scottish Palliative Care Guidelines 2025)","differs":"First line by mechanism: haloperidol for chemical or drug-induced nausea; metoclopramide or domperidone for gastric stasis, with erythromycin second line; cyclizine or prochlorperazine for raised intracranial pressure, vestibular or oral and oesophageal causes; levomepromazine second line or for multifactorial nausea; lorazepam for anxiety-related nausea. Dexamethasone for raised intracranial pressure or extrinsic compression.","evidence":"National guideline based on an evidence review and, where evidence was lacking, the expert opinion of its development group; recommendations are not individually graded.","sources":["scottish-palliative-nv-2025"]},{"name":"A single agent, haloperidol, for everyone","differs":"Gives haloperidol to all, titrated, instead of choosing by cause.","evidence":"Open-label randomised trial of 185 people: response at 24 hours was higher with cause-based treatment (49 against 32 per cent among those completing each day), but at 72 hours the intention-to-treat response was 49 and 53 per cent, with no significant difference. The Cochrane review of haloperidol (2015) found only one eligible randomised trial.","sources":["hardy-2018","cochrane-haloperidol-2015"]},{"name":"Levomepromazine (methotrimeprazine) as the first drug","differs":"Uses the broad-spectrum antipsychotic levomepromazine first.","evidence":"Double-blind trial at 11 Australian palliative care sites: response at 72 hours 63 per cent with methotrimeprazine 6.25 mg and 75 per cent with haloperidol 1.5 mg, with no difference, and a trend to more sedation with methotrimeprazine. The 2015 Cochrane review found no published randomised trial.","sources":["hardy-2019","cochrane-levomepromazine-2015"]},{"name":"Olanzapine 5 mg for chronic nausea","differs":"Olanzapine 5 mg by mouth daily.","evidence":"Placebo-controlled pilot trial of 30 outpatients with chronic nausea not related to recent treatment: median nausea scores fell from 9 to 1 out of 10 at one week with olanzapine against 9 on placebo; no excess sedation reported. MASCC/ESMO list it as an alternative, and the Scottish guideline keeps it for specialist use.","sources":["olanzapine-2020","mascc-esmo-2016-advanced","scottish-palliative-nv-2025"]}],"grades":[{"claim":"The quality of evidence for antiemetics in advanced cancer","grade":"MASCC/ESMO: low level of evidence in most studies","source":"mascc-esmo-2016-advanced","quote":"The evidence base in this field is minimal with largely poor quality trials or uncontrolled trials and case studies. The level of evidence in most studies is low."},{"claim":"Octreotide in inoperable malignant bowel obstruction","grade":"MASCC recommendation (level and category not shown in the abstract read)","source":"mascc-mbo-2021","quote":"The panel recommends octreotide in non-operable MBO."},{"claim":"Cause-based treatment against single-agent haloperidol at 72 hours","grade":"open-label randomised trial, n = 185, p = 0.59","source":"hardy-2018","quote":"Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59)."},{"claim":"No randomised trial of levomepromazine in palliative care","grade":"Cochrane systematic review, 2015","source":"cochrane-levomepromazine-2015","quote":"As in the initial review, we identified no published randomised controlled trials examining the use of levomepromazine for the management of nausea and vomiting in adults receiving palliative care"}],"sources":[{"key":"mascc-esmo-2016-advanced","label":"2016 Updated MASCC/ESMO consensus recommendations: Management of nausea and vomiting in advanced cancer","publisher":"MASCC/ESMO, Supportive Care in Cancer","year":2017,"url":"https://europepmc.org/abstract/MED/27534961","doi":"10.1007/s00520-016-3371-3","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-mbo-2021","label":"Medical management of malignant bowel obstruction in patients with advanced cancer: 2021 MASCC guideline update","publisher":"MASCC, Supportive Care in Cancer","year":2021,"url":"https://europepmc.org/abstract/MED/34390398","doi":"10.1007/s00520-021-06438-9","gradingScheme":"MASCC level of evidence and category of guideline; not shown in the abstract read.","read":"abstract","accessed":"2026-11-11"},{"key":"scottish-palliative-nv-2025","label":"Scottish Palliative Care Guidelines: Nausea and vomiting","publisher":"Healthcare Improvement Scotland (Right Decision Service)","year":2025,"url":"https://www.palliativecareguidelines.scot.nhs.uk/scottish-palliative-care-guidelines/symptoms/non-pain-symptoms/nausea-and-vomiting/","gradingScheme":"Evidence review with SIGN methodology ratings for references; recommendations are not individually graded.","read":"full-text","accessed":"2026-11-11"},{"key":"hardy-2018","label":"A randomized open-label study of guideline-driven antiemetic therapy versus single agent antiemetic therapy in patients with advanced cancer and nausea not related to anticancer treatment","publisher":"BMC Cancer","year":2018,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5932901/","doi":"10.1186/s12885-018-4404-8","read":"full-text","accessed":"2026-11-11"},{"key":"hardy-2019","label":"Methotrimeprazine versus haloperidol in palliative care patients with cancer-related nausea: a randomised, double-blind controlled trial","publisher":"BMJ Open","year":2019,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6747674/","doi":"10.1136/bmjopen-2019-029942","read":"full-text","accessed":"2026-11-11"},{"key":"olanzapine-2020","label":"Olanzapine for the Treatment of Advanced Cancer-Related Chronic Nausea and/or Vomiting: A Randomized Pilot Trial","publisher":"JAMA Oncology","year":2020,"url":"https://europepmc.org/abstract/MED/32379269","doi":"10.1001/jamaoncol.2020.1052","read":"abstract","accessed":"2026-11-11"},{"key":"cochrane-haloperidol-2015","label":"Haloperidol for the treatment of nausea and vomiting in palliative care patients","publisher":"Cochrane Database of Systematic Reviews","year":2015,"url":"https://europepmc.org/abstract/MED/26524474","doi":"10.1002/14651858.CD006271.pub3","read":"abstract","accessed":"2026-11-11"},{"key":"cochrane-levomepromazine-2015","label":"Levomepromazine for nausea and vomiting in palliative care","publisher":"Cochrane Database of Systematic Reviews","year":2015,"url":"https://europepmc.org/abstract/MED/26524693","doi":"10.1002/14651858.CD009420.pub3","read":"abstract","accessed":"2026-11-11"},{"key":"nice-cks-nv","label":"Palliative care: nausea and vomiting (Clinical Knowledge Summary)","publisher":"NICE","year":2021,"url":"https://cks.nice.org.uk/topics/palliative-care-nausea-vomiting/","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The MASCC/ESMO 2016 statement and the MASCC 2021 bowel obstruction update were read only as abstracts; their grades, doses and the reasoning behind preferring metoclopramide are not shown here.","NICE's Clinical Knowledge Summary on palliative nausea and vomiting refused a script (403) and was not read; its year (2021) is as the Scottish guideline cites it.","MASCC/ESMO and the Scottish guideline disagree on the first-line drug, and no trial has compared metoclopramide with haloperidol as first-line treatment in this setting.","The olanzapine evidence for nausea not caused by treatment is one pilot trial of 30 people; no larger trial was found in the sources read.","MASCC/ESMO could make no recommendation for opioid-induced nausea.","Doses in the Scottish guideline include unlicensed routes and uses; they are a national palliative care formulary and are not repeated here as instructions.","The sources read do not cover children."]},{"id":"neratinib-diarrhoea-prophylaxis-and-dose-escalation","kind":"protocol","name":"Neratinib: diarrhoea prevention with loperamide or dose escalation","aka":["neratinib diarrhoea prophylaxis","Nerlynx loperamide schedule","neratinib dose escalation","CONTROL trial strategies"],"tldr":"Neratinib, a tablet for HER2-positive breast cancer, causes diarrhoea in almost everyone. Prevent it in one of two ways agreed before you start: loperamide on a fixed schedule from the first tablet for eight weeks, or a lower starting dose built up over two weeks. Drink about two litres a day, and call your team at once if diarrhoea is severe or comes with weakness, dizziness or fever.","summary":"Without prophylaxis, diarrhoea occurred in 95 per cent of people in ExteNET, grade 3 in 40 per cent, with a median onset of grade 3 or worse at day 8. The US label now offers two strategies from the first dose. Either loperamide prophylaxis for the first 56 days (4 mg three times daily in weeks 1 and 2, 4 mg twice daily in weeks 3 to 8, then as needed up to 16 mg a day, titrated to one or two bowel movements a day), or a two-week neratinib dose escalation (120 mg a day in week 1, 160 mg in week 2, 240 mg from week 3) with loperamide as needed. In the open-label phase II CONTROL trial, six non-comparative cohorts of 563 people starting extended adjuvant neratinib all had less grade 3 diarrhoea than historical controls; it was lowest with the two-week escalation (13 per cent) and highest with colestipol plus loperamide as needed (33 per cent), and diarrhoea-related discontinuations were 3 per cent with the two-week escalation against 20 per cent with loperamide alone. The label's dose modification table sets when to adjust antidiarrhoeals, interrupt, reduce or stop.","asOf":"2026-11-11","links":[],"tags":["protocol","diarrhoea","supportive-care"],"related":["treatment-induced-diarrhoea-grading-and-management","capecitabine"],"cancers":["breast-her2-positive"],"sections":["supportive-care"],"technologies":["her2-tyrosine-kinase-inhibitors"],"targets":[],"drugs":["neratinib"],"companies":["puma-biotechnology"],"institutions":[],"pathways":[],"terms":["ctcae-grading"],"trials":["nala"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"This cancer tablet often gives runny poo. Your team will either give you a medicine to take every day at the start or start with a smaller dose. Call them if it is bad.","domain":"oral-anticancer-therapy","setting":{"who":["doctor","pharmacist","nurse","patient-or-carer"],"where":["outpatient-clinic","home","telephone-triage"]},"population":"Adults starting neratinib for HER2-positive breast cancer: extended adjuvant treatment of early-stage disease, or with capecitabine for metastatic disease. CONTROL enrolled only people starting extended adjuvant neratinib after trastuzumab-based therapy. The label's dose modification table read here is for neratinib monotherapy; with capecitabine, capecitabine has its own rules.","trigger":"Neratinib is prescribed.","steps":[{"action":"Before the first tablet, agree one strategy: loperamide prophylaxis for the first 56 days, or a two-week neratinib dose escalation","why":"Diarrhoea usually starts in the first weeks; either strategy, started on day one, makes severe diarrhoea much less likely.","source":"nerlynx-label-2026","quote":"Alternatively, a 2-week NERLYNX dose escalation approach prior to initiation of the recommended treatment regimen with NERLYNX can also be considered for diarrhea management"},{"action":"If using prophylaxis, start loperamide with the first dose: 4 mg three times daily for days 1 to 14, 4 mg twice daily for days 15 to 56, then 4 mg as needed up to 16 mg a day","why":"Taking loperamide on a schedule from the start keeps diarrhoea mild while the bowel adapts.","source":"nerlynx-label-2026","quote":"Weeks 1–2 (days 1–14) 4 mg three times daily Weeks 3–8 (days 15–56) 4 mg twice daily Weeks 9–Discontinuation of NERLYNX 4 mg as needed, not to exceed 16 mg per day; titrate dosing to achieve 1–2 bowel movements per day"},{"action":"If using dose escalation, give 120 mg daily in week 1, 160 mg daily in week 2 and 240 mg daily from week 3, with antidiarrhoeals as needed","why":"A lower dose at first lets the bowel adjust before the full dose; in the CONTROL trial it gave the least severe diarrhoea.","source":"nerlynx-label-2026","quote":"Week 1 (days 1–7) 120 mg daily (three 40 mg tablets) Week 2 (days 8–14) 160 mg daily (four 40 mg tablets) Week 3 and onwards 240 mg daily (six 40 mg tablets, recommended dose)"},{"action":"Titrate loperamide to one or two bowel movements a day, and ask the person to keep to that target","why":"One or two bowel movements a day shows the dose is right: fewer suggests too much loperamide, more that diarrhoea is building.","source":"nerlynx-label-2026","quote":"Instruct patients to maintain 1–2 bowel movements per day and on how to use antidiarrheal treatment regimens."},{"action":"For grade 1, grade 2 lasting up to 5 days, or grade 3 lasting up to 2 days, adjust antidiarrhoeals, change diet and keep fluid intake around 2 litres a day","why":"Most diarrhoea on neratinib settles with more antidiarrhoeal medicine and fluids without stopping the drug.","source":"nerlynx-label-2026","quote":"Adjust antidiarrheal treatment Diet modifications Fluid intake of ~2 L/day should be maintained to avoid dehydration"},{"action":"Interrupt neratinib for diarrhoea with complicating features (dehydration, fever, low blood pressure, kidney failure, grade 3 or 4 neutropenia), grade 2 lasting more than 5 days or grade 3 more than 2 days despite treatment; resume at the same dose if it settles within a week, otherwise at a reduced dose","why":"Stopping briefly lets the bowel recover; restarting at a lower dose after a slow recovery prevents a repeat.","source":"nerlynx-label-2026","quote":"If diarrhea resolves to ≤Grade 1 in one week or less, then resume NERLYNX treatment at the same dose If diarrhea resolves to ≤Grade 1 in longer than one week, then resume NERLYNX treatment at reduced dose"},{"action":"Stop neratinib permanently for grade 4 diarrhoea, or if grade 2 or worse diarrhoea recurs at 120 mg a day","why":"Life-threatening diarrhoea, or diarrhoea that persists at the lowest dose, means the drug cannot be given safely.","source":"nerlynx-label-2026","quote":"Permanently discontinue NERLYNX treatment Diarrhea recurs to Grade 2 or higher at 120 mg per day Permanently discontinue NERLYNX treatment"},{"action":"Ask the person to call immediately for severe diarrhoea, or diarrhoea with weakness, dizziness or fever","why":"Severe diarrhoea on neratinib has led to dehydration, low blood pressure and kidney failure.","source":"nerlynx-label-2026","quote":"Advise patients to inform their healthcare provider immediately if severe (≥Grade 3) diarrhea or diarrhea associated with weakness, dizziness, or fever occurs during treatment with NERLYNX"}],"bestInClass":{"statement":"The current US label (July 2026) makes both strategies standard from the first dose: scheduled loperamide for 56 days, or a two-week dose escalation with loperamide as needed. On the evidence read, the two-week escalation gave the lowest rates of grade 3 diarrhoea (13 per cent) and of diarrhoea-related discontinuation (3 per cent) in CONTROL, against 31 and 20 per cent with loperamide alone; but CONTROL's cohorts were not randomised against each other, so the comparison is indirect. No graded guideline on neratinib diarrhoea was found.","sources":["nerlynx-label-2026","control-2023"]},"variants":[{"name":"Four-week dose escalation (CONTROL DE2)","differs":"Neratinib 160 mg a day on days 1 to 14 and 200 mg a day on days 15 to 28, then 240 mg, with loperamide as needed.","evidence":"Grade 3 diarrhoea 27 per cent and diarrhoea-related discontinuation 6 per cent, both higher than the two-week schedule; not in the label. Open-label, non-comparative cohort.","sources":["control-2023"]},{"name":"Loperamide plus budesonide (CONTROL BL)","differs":"Adds budesonide 9 mg once daily on days 1 to 28 to scheduled loperamide.","evidence":"Grade 3 diarrhoea 28 per cent and diarrhoea-related discontinuation 11 per cent, against 31 and 20 per cent with loperamide alone. Open-label, non-comparative cohort.","sources":["control-2023"]},{"name":"Loperamide plus colestipol (CONTROL CL and CL-PRN)","differs":"Adds the bile acid binder colestipol 2 g twice daily on days 1 to 28, to scheduled loperamide (CL) or to loperamide as needed (CL-PRN).","evidence":"Grade 3 diarrhoea 21 per cent with scheduled loperamide and 33 per cent with loperamide as needed; discontinuations 4 and 8 per cent. Open-label, non-comparative cohorts. The label says other agents may be added to loperamide as clinically indicated.","sources":["control-2023","nerlynx-label-2026"]}],"grades":[{"claim":"Grade 3 diarrhoea and discontinuation by strategy in CONTROL","grade":"open-label phase II, six non-comparative cohorts (n = 563)","source":"control-2023","quote":"All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%)."},{"claim":"Without required prophylaxis (ExteNET), grade 3 diarrhoea occurred in 40 per cent","grade":"Label incidence from the registration trial","source":"nerlynx-label-2026","quote":"In the NERLYNX arm, Grade 3 diarrhea occurred in 40% and Grade 4 diarrhea occurred in 0.1% of patients."}],"sources":[{"key":"nerlynx-label-2026","label":"NERLYNX (neratinib) tablets: US prescribing information","publisher":"Puma Biotechnology, via DailyMed, US National Library of Medicine","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d1e41dcf-e82a-47c2-a0ad-6c6eef621834","gradingScheme":"Product labelling; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"control-2023","label":"Final findings from the CONTROL trial: strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer","publisher":"The Breast","year":2023,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9982309/","doi":"10.1016/j.breast.2022.12.003","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-neratinib-two-week-dose-escalation-by-default"],"gaps":["No randomised comparison of the strategies exists in the sources read: CONTROL's cohorts were enrolled one after another and compared with historical controls.","The EU summary of product characteristics was not read; whether it includes the dose escalation option is not shown here.","No graded guideline on neratinib diarrhoea was found; the general ESMO diarrhoea guideline (2018) could not be read.","CONTROL studied extended adjuvant neratinib only; in metastatic disease with capecitabine (NALA), anti-diarrhoeal prophylaxis was required in the first cycle and the strategies were not compared."]},{"id":"irae-neurological","kind":"protocol","name":"Neurological side effects of checkpoint inhibitors: myasthenia gravis, Guillain-Barré syndrome, meningitis and encephalitis","aka":["neurologic irAEs","irAE-N","checkpoint inhibitor myasthenia gravis","immune-related Guillain-Barré syndrome","checkpoint inhibitor encephalitis","immune-related aseptic meningitis","immune-related neuropathy"],"tldr":"Immunotherapy rarely inflames the nerves, the brain or the junction between nerve and muscle. Drooping eyelids, double vision, trouble swallowing or speaking, weakness spreading up the legs, numbness, severe headache with a stiff neck, confusion or a seizure need urgent assessment. Treatment is quick high-dose steroids, often with immunoglobulin or plasma exchange, and a neurologist.","summary":"Neurological irAEs occur in about 6% on PD-(L)1 inhibitors, 4% on CTLA-4 inhibitors and 12% on combinations, mostly grade 1 to 2; grade 3 or more is under 1% but can be fatal or permanent, usually within the first 3 months (SITC 2021). Myasthenia gravis carries about 20% mortality and clusters with myositis and myocarditis.\n\nSITC 2021: refer every neurological irAE to a specialist whatever the grade. Myasthenia: antibody testing, a search for myositis, myocarditis and thyroid dysfunction, negative inspiratory force and vital capacity; stop the checkpoint inhibitor; steroids (prednisone 1 to 1.5 mg/kg for grade 2), pyridostigmine, and IVIG or plasma exchange (LE: 1); admission and possibly intensive care for grade 3 to 4. Guillain-Barré: spine MRI, lumbar puncture, EMG and nerve conduction; permanent discontinuation with IVIG or plasma exchange plus steroids (LE: 1). Encephalitis: MRI, lumbar puncture, EEG, autoimmune and paraneoplastic panels and infection PCR, empirical antivirals; pulse methylprednisolone 1000 mg for 3 to 5 days with IVIG or plasma exchange, then rituximab if refractory (LE: 1). Aseptic meningitis: MRI, lumbar puncture, cortisol and ACTH, antibiotics until bacterial meningitis is excluded, prednisone 0.5 to 1 mg/kg (LE: 4). The 2021 neurologic consensus definitions (seven core disorders, graded by certainty) standardise the diagnosis and advise brain imaging before lumbar puncture.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","acute-oncology","neurology"],"related":["irae-myocarditis","irae-hypophysitis-adrenal","irae-ocular"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab","methylprednisolone","human-normal-immunoglobulin","rituximab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Rarely, immunotherapy affects the nerves or brain. Drooping eyelids, double vision, new weakness, confusion or a bad headache with a stiff neck need urgent help.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","emergency-team","patient-or-carer","multidisciplinary-team"],"where":["emergency-department","acute-oncology-service","telephone-triage","ward","intensive-care","outpatient-clinic"]},"population":"Adults who have received an immune checkpoint inhibitor, alone or in combination. Guillain-Barré syndrome and meningitis are more frequent with CTLA-4 or combined blockade; myasthenia gravis and encephalitis with PD-(L)1 blockade. People with pre-existing neurological autoimmune disease are at risk of a flare. Children are not addressed by these sources.","trigger":"New weakness, drooping eyelids, double vision, difficulty swallowing or speaking, breathlessness from weakness, ascending numbness or weakness, severe headache with neck stiffness or fever, confusion, behaviour change or seizure during or after checkpoint inhibitor treatment.","steps":[{"action":"Refer every neurological side effect to a neurologist, whatever its grade","why":"These conditions overlap, can worsen quickly and need specialist tests to tell apart.","source":"sitc-2021","quote":"Patients diagnosed with neurological irAEs should be referred to a specialist, regardless of severity."},{"action":"For any myasthenia symptoms, test myasthenia antibodies, look for myositis, myocarditis and thyroid disease, and measure negative inspiratory force and vital capacity","why":"Myasthenia often comes with heart and muscle inflammation, and weak breathing muscles can fail.","source":"sitc-2021","quote":"Workup should include diagnostic antibody testing for myasthenia gravis and evaluation for concurrent myositis, myocarditis, and thyroid dysfunction. Electrodiagnostic studies may be performed to distinguish myasthenia gravis from myositis. Pulmonary function should be assessed with negative inspiratory force (NIF) and vital capacity (VC)."},{"action":"For myasthenia gravis, stop the checkpoint inhibitor and give IVIG or plasma exchange with steroids and pyridostigmine, with frequent breathing assessments","why":"Prompt immune treatment and close watch on breathing reduce the risk of respiratory failure.","source":"sitc-2021","quote":"Patients diagnosed with myasthenia gravis should discontinue ICI therapy and should receive IVIG or PLEX with corticosteroid therapy and pyridostigmine. These patients should receive frequent pulmonary assessments","grade":"LE: 1"},{"action":"Admit grade 3 to 4 myasthenia, possibly to intensive care, stop the checkpoint inhibitor permanently and review daily","why":"Severe myasthenia can stop the breathing muscles working.","source":"sitc-2021","quote":"Patients with grade 3 or 4 myasthenia gravis should be admitted to the hospital and may need ICU-level monitoring. ICIs should be permanently discontinued, and frequent pulmonary function assessments and daily neurological review should be performed."},{"action":"For suspected Guillain-Barré syndrome, obtain spine MRI, lumbar puncture, EMG, nerve conduction studies and ganglioside antibodies","why":"These exclude spinal cord compression and confirm nerve root inflammation.","source":"sitc-2021","quote":"Workup for patients with suspected Guillain-Barré syndrome should include MRI of the spine to rule out a compressive lesion, LP, EMG, nerve conduction studies, and ganglioside antibody panel of blood and CSF."},{"action":"For Guillain-Barré syndrome, stop the checkpoint inhibitor permanently and give IVIG or plasma exchange with steroids","why":"Ascending weakness can reach the breathing muscles; immunoglobulin or plasma exchange is the standard treatment.","source":"sitc-2021","quote":"Patients diagnosed with Guillain-Barré syndrome should always permanently discontinue ICI therapy, and should receive IVIG or PLEX with corticosteroid therapy","grade":"LE: 1"},{"action":"Image the brain before lumbar puncture","why":"A mass in the brain can make lumbar puncture dangerous, and the puncture can itself alter the scan.","source":"neuro-definitions-2021","quote":"Head imaging (CT or MRI) should be performed prior to lumbar puncture (LP) to exclude mass lesions that may cause herniation and because LP can cause pachymeningeal enhancement."},{"action":"For suspected aseptic meningitis, obtain brain and pituitary MRI, lumbar puncture, cortisol and ACTH, and give antibiotics until bacterial meningitis is excluded","why":"Infection, cancer in the meninges and hypophysitis can all look the same.","source":"sitc-2021","quote":"Workup for patients with suspected aseptic meningitis should include MRI of the brain and pituitary with and without contrast, lumbar puncture (LP), cortisol, and ACTH."},{"action":"For suspected encephalitis, obtain brain MRI, lumbar puncture, EEG, blood tests, autoimmune and paraneoplastic panels and infection PCR, and give an antiviral until viral encephalitis is excluded","why":"Viral encephalitis must be treated while the cause is found.","source":"sitc-2021","quote":"Workup for patients with suspected encephalitis should include MRI of the brain, LP, CBC, CMP, autoimmune encephalopathy and paraneoplastic panels of blood and cerebrospinal fluid (CSF), PCR for infectious encephalitis, thyroid panel, and electroencephalogram (EEG)."},{"action":"For encephalitis or Guillain-Barré syndrome of any grade, give pulse methylprednisolone 1000 mg IV daily for 3 to 5 days plus IVIG or plasma exchange","why":"These are the most dangerous neurological side effects and are treated at full strength from the start.","source":"sitc-2021","quote":"Patients with any grade of encephalitis or Guillain-Barré syndrome should receive pulse-dose methylprednisolone at 1000 mg IV daily for 3–5 days, and should additionally receive IVIG or PLEX."},{"action":"If encephalitis does not respond to pulse steroids, give IVIG, plasma exchange or rituximab","why":"Steroid-resistant encephalitis needs another immune treatment.","source":"sitc-2021","quote":"If ICI-related encephalitis does not respond to pulse-dose corticosteroids, patients may receive IVIG (2 g/kg in divided doses over the course of 5 days), PLEX (one session every other day for 5–7 cycles), or rituximab (375 mg/m2 weekly infusion for 4 weeks)","grade":"LE: 1"}],"bestInClass":{"statement":"SITC 2021 is the guideline read in full, and it grades its key treatments LE: 1: IVIG or plasma exchange with steroids and pyridostigmine for myasthenia gravis, IVIG or plasma exchange with steroids and permanent discontinuation for Guillain-Barré syndrome, and IVIG, plasma exchange or rituximab for steroid-refractory encephalitis. These grades describe the evidence for the treatments in the non-immunotherapy forms of these diseases; there are no trials in checkpoint inhibitor patients. The 2021 neurologic consensus definitions do not give treatment but standardise the diagnosis into seven core disorders with a certainty level, and note that treatment often starts at probable or possible certainty. ASCO 2021 (abstract) makes neurological toxicity an exception to continuing treatment at grade 1. ESMO 2022 could not be read.","sources":["sitc-2021","neuro-definitions-2021","asco-2021","esmo-2022"]},"variants":[{"name":"Seven core disorders with diagnostic certainty (2021 neurologic consensus definitions)","differs":"Classifies each event as immune-related meningitis, encephalitis, demyelinating disease, vasculitis, neuropathy, neuromuscular junction disorder or myopathy, each as definite, probable or possible, with severity, antibody status and any concurrent irAE recorded.","evidence":"Modified Delphi consensus of 27 panellists from 15 academic centres; definitions, not graded recommendations.","sources":["neuro-definitions-2021"]}],"grades":[{"claim":"Myasthenia gravis: stop the checkpoint inhibitor; IVIG or plasma exchange with steroids and pyridostigmine","grade":"LE: 1","source":"sitc-2021"},{"claim":"Guillain-Barré syndrome: permanent discontinuation; IVIG or plasma exchange with steroids","grade":"LE: 1","source":"sitc-2021"},{"claim":"Steroid-refractory encephalitis: IVIG, plasma exchange or rituximab","grade":"LE: 1","source":"sitc-2021"},{"claim":"Ocular myasthenia or non-Guillain-Barré polyneuropathy of grade 2 or less: prednisone 0.5 to 1 mg/kg/day","grade":"LE: 2","source":"sitc-2021"},{"claim":"Aseptic meningitis: prednisone 0.5 to 1 mg/kg/day","grade":"LE: 4","source":"sitc-2021"},{"claim":"Painful peripheral neuropathy: gabapentin, pregabalin or duloxetine until it resolves","grade":"LE: 1","source":"sitc-2021","quote":"Patients diagnosed with painful peripheral neuropathy should receive neuropathic pain medication such as gabapentin, pregabalin, or duloxetine until neuropathy resolves"},{"claim":"Neurological toxicity is an exception to continuing treatment at grade 1","grade":"expert consensus","source":"asco-2021"}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"neuro-definitions-2021","label":"Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors","publisher":"Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8291304","doi":"10.1136/jitc-2021-002890","gradingScheme":"Modified Delphi consensus using the RAND/UCLA Appropriateness Method; disease definitions, not graded recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline was read only as its abstract and its neurological tables are not compared here.","There are no randomised trials in checkpoint inhibitor neurological toxicity; SITC's LE: 1 grades rest on evidence from the same diseases outside immunotherapy.","Whether a checkpoint inhibitor can ever be restarted after myasthenia gravis, encephalitis or Guillain-Barré syndrome is not addressed beyond SITC's permanent discontinuation for Guillain-Barré and grade 3 to 4 myasthenia."]},{"id":"neutropenic-enterocolitis","kind":"protocol","name":"Neutropenic enterocolitis (typhlitis): imaging, cultures, antibiotics and conservative care","aka":["typhlitis","NEC","neutropenic colitis","ileocaecal syndrome","chemotherapy-associated bowel syndrome"],"tldr":"During intensive chemotherapy, when white cells are very low, the bowel wall can become inflamed and infected. Fever with tummy pain, diarrhoea or bloating is an emergency: ring your treatment helpline at once. In hospital it is confirmed with an ultrasound or CT scan and treated with strong antibiotics through a drip, fluids, pain relief and resting the bowel, with surgeons asked to see you.","summary":"Neutropenic enterocolitis complicates intensive chemotherapy, above all for acute leukaemia; AGIHO cites a pooled incidence of 5.3% in hospitalised patients with haematological cancers, aplastic anaemia or high-dose chemotherapy, and mortality from under 20% to 82%. High-dose cytarabine with anthracyclines is the main risk factor. A 2025 cohort of 178 episodes found it in 13.8% of AML induction courses and 9.5% of autologous transplants (higher with 7+3 induction and BEAM conditioning) with lower 30-day mortality than earlier reports.\n\nAGIHO 2017: proposed diagnostic criteria are fever, abdominal pain and bowel wall thickening over 4 mm across more than 30 mm on ultrasound or CT; a clinical definition (temperature 37.8 °C or more with abdominal pain and/or no bowel movement for 72 hours or more) identifies neutropenic patients at risk earlier. Imaging confirms it and excludes perforation; blood and stool cultures and a C. difficile toxin test are recommended; endoscopy is discouraged because of perforation risk. Conservative therapy (bland diet, hydration, pain control; BIII); piperacillin-tazobactam, imipenem-cilastatin or meropenem (BIII), continued until clinical signs and neutropenia resolve; no evidence on adding metronidazole or vancomycin (CIII); empirical antifungal therapy may be discussed (BIII); growth factors might be considered (BIII). Surgical consultation early; surgery reserved for severe cases such as perforation (BIII).","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency","neutropenic-sepsis"],"related":["febrile-neutropenia-first-hour"],"cancers":["aml","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["cytarabine","filgrastim"],"companies":[],"institutions":[],"pathways":[],"terms":["febrile-neutropenia","neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Fever with tummy pain or diarrhoea while your blood count is low after chemotherapy is an emergency. Ring your cancer helpline at once.","domain":"emergencies","setting":{"who":["doctor","nurse","surgical-team","patient-or-carer"],"where":["ward","emergency-department","acute-oncology-service","intensive-care","telephone-triage"]},"population":"Adults with neutropenia after intensive chemotherapy, above all for acute leukaemia or high-dose chemotherapy before autologous stem cell transplant. AGIHO's guideline covers adults; children have a separate literature (noted in gaps).","trigger":"Fever with abdominal pain, diarrhoea, distension or absent bowel movements in a person who is neutropenic after chemotherapy.","steps":[{"action":"Suspect it early: a temperature of 37.8 °C or more with abdominal pain and/or no bowel movement for 72 hours or more in a neutropenic patient","why":"The formal definition describes late disease; this earlier clinical picture already predicts complications and death.","source":"agiho-2017","quote":"Neutropenic patients with chemotherapy-associated bowel syndrome (T ≥ 37.8 °C and abdominal pain and/or lack of bowel movement for ≥ 72 h) were more likely to suffer complications and death [27]."},{"action":"Confirm with ultrasound or CT, looking for bowel wall thickening over 4 mm and for perforation","why":"Imaging shows the thickened bowel and whether it has burst, which changes treatment.","source":"agiho-2017","quote":"Non-invasive imaging is generally recommended to confirm the diagnosis of NEC and to exclude bowel wall perforation."},{"action":"Send blood cultures, stool cultures and a C. difficile toxin test","why":"Bacteria often enter the blood from the damaged bowel, and C. difficile colitis looks similar but is treated differently.","source":"agiho-2017","quote":"Blood cultures, stool cultures, and a C. difficile toxin test for exclusion of NEC-associated bacteremia and colitis due to C. difficile, respectively, are recommended."},{"action":"Do not do endoscopy to take biopsies","why":"The inflamed bowel wall can tear.","source":"agiho-2017","quote":"Endoscopy to obtain biopsies is discouraged, due to the increased risk of bowel wall perforation."},{"action":"Treat conservatively in most cases: bland diet, hydration and effective pain relief","why":"Most episodes settle as the blood count recovers, if the person is supported until then.","source":"agiho-2017","quote":"Conservative therapy is preferred in most cases, consisting of a bland diet, hydration, and an effective pain treatment (BIII).","grade":"BIII"},{"action":"Give piperacillin-tazobactam, imipenem-cilastatin or meropenem, and continue until clinical signs and neutropenia have resolved","why":"These broad antibiotics cover the gut bacteria, Gram-negative Enterobacteriaceae above all, most often found in the blood in this condition.","source":"agiho-2017","quote":"Antimicrobial therapy should be administered until resolution of clinical signs and neutropenia.","grade":"BIII"},{"action":"Discuss empirical antifungal treatment if it has not already been started for persistent neutropenic fever","why":"Fungal infection is found in a minority of cases and is easily missed.","source":"agiho-2017","quote":"Empirical antifungal therapy may be discussed if it has not yet been administered for the indication of persistent febrile neutropenia [68, 83, 84] (BIII).","grade":"BIII"},{"action":"Ask surgeons to see the person early, but keep operations for severe cases such as perforation","why":"Surgery while the blood count is low is risky, so it is reserved for when the bowel has burst or is failing.","source":"agiho-2017","quote":"While a surgical consultation should be obtained at an early stage of disease evolution, surgical interventions in the neutropenic and/or thrombocytopenic patient are reserved to severe cases, e.g., patients with bowel wall perforation (BIII).","grade":"BIII"}],"bestInClass":{"statement":"The AGIHO/DGHO 2017 update is the only guideline read that addresses neutropenic enterocolitis directly; every recommendation it makes is grade B or C on level III evidence (expert opinion), because there are no trials. Its approach: early recognition, imaging to confirm and exclude perforation, cultures and a C. difficile test, no endoscopy, conservative care, piperacillin-tazobactam or a carbapenem until the neutropenia recovers, antifungal therapy considered, and early surgical review with surgery kept for perforation. Newer cohort data (Clinical Infectious Diseases 2025) refine who is at risk (7+3 AML induction, high-dose steroids, high blast counts, azacitidine, BEAM conditioning) but do not change management.","sources":["agiho-2017","cid-2025"]},"variants":[{"name":"Adding metronidazole or vancomycin to the beta-lactam","differs":"Adds metronidazole for extra anaerobic cover, or vancomycin, to piperacillin-tazobactam or a carbapenem.","evidence":"AGIHO found no studies of their effect on outcome and grades the question CIII.","sources":["agiho-2017"]},{"name":"Granulocyte colony-stimulating factor","differs":"Gives G-CSF to speed recovery of the neutrophil count.","evidence":"AGIHO: might be considered, though corresponding evidence is not available (BIII).","sources":["agiho-2017"]}],"grades":[{"claim":"Conservative therapy: bland diet, hydration, pain control","grade":"BIII","source":"agiho-2017"},{"claim":"Piperacillin-tazobactam, imipenem-cilastatin or meropenem","grade":"BIII","source":"agiho-2017","quote":"In accordance with IDSA guidelines for patients with complicated abdominal infections in non-neutropenic patients [81] and the guideline for antimicrobial therapy of unexplained fever in neutropenic patients of the AGIHO [82], we recommend administration of piperacillin/tazobactam or imipenem/cilastatin or meropenem (BIII)."},{"claim":"Additional metronidazole or vancomycin","grade":"CIII","source":"agiho-2017","quote":"There are no studies assessing the effect of additional metronidazole or vancomycin on patient outcome (CIII)."},{"claim":"Haematopoietic growth factors","grade":"BIII","source":"agiho-2017","quote":"The use of hematopoietic growth factors might be considered, even though corresponding evidence is not available (BIII)."},{"claim":"Surgery reserved for severe cases such as perforation","grade":"BIII","source":"agiho-2017"}],"sources":[{"key":"agiho-2017","label":"Diagnosis and management of gastrointestinal complications in adult cancer patients: 2017 updated evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)","publisher":"AGIHO/DGHO, Annals of Hematology","year":2017,"url":"https://europepmc.org/article/PMC/PMC5748412","doi":"10.1007/s00277-017-3183-7","gradingScheme":"ESCMID criteria: strength of recommendation A (strongly supports) to D (supports a recommendation against), quality of evidence I (randomised trial) to III (expert opinion), printed together as 'BIII'.","read":"full-text","accessed":"2026-11-11"},{"key":"cid-2025","label":"Epidemiology, Risk Factors, and Outcomes of Neutropenic Enterocolitis in Onco-Hematological Patients According to Chemotherapy Regimen","publisher":"Clinical Infectious Diseases","year":2025,"url":"https://europepmc.org/abstract/MED/40112243","doi":"10.1093/cid/ciaf134","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The AGIHO guideline dates from 2017 and no later edition was found; every recommendation in it rests on level III evidence.","No randomised trial has tested any treatment for neutropenic enterocolitis, including the choice and duration of antibiotics or the timing of surgery.","Children are not covered: a 2022 review of typhlitis in children with cancer (Pediatric Infectious Disease Journal) was found but not read, and paediatric oncology groups may differ.","The ultrasound threshold for bowel wall thickening (over 4 mm across more than 30 mm) is a proposed definition that, as AGIHO notes, describes disease at a late stage."]},{"id":"nutrition-screening-and-support-during-cancer-treatment","kind":"protocol","name":"Nutrition screening and support during cancer treatment","aka":["malnutrition screening in cancer","MUST screening","dietitian referral in cancer","oral nutritional supplements in cancer","ESPEN cancer nutrition"],"tldr":"Weight loss and poor eating are common in cancer and make treatment harder. Your weight and eating should be checked from diagnosis onwards. If you are losing weight or eating less, you should get dietary advice, help with symptoms that stop you eating, and drinks or other supplements if needed. Staying active helps keep your muscles.","summary":"ESPEN (2021) recommends regular evaluation of nutritional intake, weight change and body mass index from cancer diagnosis onwards, repeated according to how stable the situation is (strong, very low evidence, strong consensus); NICE CG32 screens all hospital inpatients on admission and all outpatients at the first clinic appointment, weekly for inpatients and on clinical concern for outpatients, with a tool such as MUST. An abnormal screen leads to assessment of intake, nutrition impact symptoms, muscle mass, physical performance and systemic inflammation (ESPEN).\n\nTargets are energy of about 25 to 30 kcal/kg/day and protein above 1 g/kg/day, up to 1.5 g/kg/day if possible; vitamins and minerals at about the recommended daily allowance, without high-dose micronutrients; and no energy-restricting diets in people with or at risk of malnutrition. Support is stepped: dietary advice, treatment of symptoms that impair eating and oral nutritional supplements first (strong, moderate); enteral nutrition if oral intake remains inadequate, parenteral if enteral is not sufficient or feasible (strong, moderate); slow increase with precautions against refeeding syndrome after prolonged poor intake. Physical activity is maintained or increased (strong, high evidence). During radiotherapy to the head and neck, thorax and gut, intake is protected by individual counselling and supplements to avoid treatment interruptions. In advanced cancer, nutrition is offered after weighing prognosis, benefit and burden with the patient; in the dying, care is for comfort.","asOf":"2026-11-11","links":[],"tags":["protocol","nutrition","supportive-care"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["cachexia-therapy","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":["espen","nice"],"pathways":[],"terms":["cachexia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer can make you lose weight. Your team should check your weight and eating. If you are losing weight, ask for help from a dietitian.","domain":"nutrition","setting":{"who":["nurse","doctor","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","ward","chemotherapy-day-unit","radiotherapy-department","community"]},"population":"Adults with cancer from diagnosis through treatment, survivorship and advanced disease. Perioperative immunonutrition and ERAS, nutrition during stem cell transplant and paediatric nutrition are covered in the ESPEN guideline but only touched on here.","trigger":"A cancer diagnosis; then at each stage of treatment and whenever weight, appetite or intake changes.","steps":[{"action":"From diagnosis, check intake, weight change and body mass index regularly, more often when the situation is changing","why":"Malnutrition is easier to prevent than to reverse, and it is often missed when someone still looks well.","source":"espen-2021","quote":"To detect nutritional disturbances at an early stage, we recommend to regularly evaluate nutritional intake, weight change, and body mass index (BMI), beginning with cancer diagnosis and repeated depending on the stability of the clinical situation.","grade":"strong; level of evidence very low; strong consensus"},{"action":"Screen outpatients at the first clinic appointment and again when there is concern, with a validated tool such as MUST","why":"A short screen at a fixed point makes sure nobody is missed.","source":"nice-cg32","quote":"All hospital inpatients on admission and all outpatients at their first clinic appointment should be screened. Screening should be repeated weekly for inpatients and when there is clinical concern for outpatients."},{"action":"If the screen is abnormal, assess intake, symptoms that stop eating, muscle mass, physical performance and inflammation","why":"These show why the person is losing weight and what can be treated.","source":"espen-2021","quote":"In patients with abnormal screening, we recommend objective and quantitative assessment of nutritional intake, nutrition impact symptoms, muscle mass, physical performance and the degree of systemic inflammation.","grade":"strong; level of evidence very low; consensus"},{"action":"Aim for about 25 to 30 kcal/kg/day and protein above 1 g/kg/day, up to 1.5 g/kg/day where possible","why":"People with cancer need at least as much energy as healthy people and more protein to keep muscle.","source":"espen-2021","quote":"We recommend that protein intake should be above 1 g/kg/day and, if possible up to 1.5 g/kg/day.","grade":"strong; level of evidence moderate; strong consensus"},{"action":"Give dietary advice, treat symptoms that get in the way of eating, and offer oral nutritional supplements to people who can eat but are malnourished or at risk","why":"Nausea, a sore mouth, constipation or low mood can all stop someone eating, and many can be treated.","source":"espen-2021","quote":"We recommend nutritional intervention to increase oral intake in cancer patients who are able to eat but are malnourished or at risk of malnutrition.","grade":"strong; level of evidence moderate; consensus"},{"action":"Do not use diets that restrict energy in people who are malnourished or at risk","why":"In someone already losing weight, cutting energy makes malnutrition worse.","source":"espen-2021","quote":"We recommend not to use dietary provisions that restrict energy intake in patients with or at risk of malnutrition.","grade":"strong; level of evidence low; strong consensus"},{"action":"If eating and supplements are still not enough, use tube feeding, and intravenous nutrition only if tube feeding is not enough or not possible","why":"Feeding through the gut is safer than through a vein when the gut works.","source":"espen-2021","quote":"If a decision has been made to feed a patient, we recommend EN if oral nutrition remains inadequate despite nutritional interventions (counseling, ONS), and PN if EN is not sufficient or feasible.","grade":"strong; level of evidence moderate; strong consensus"},{"action":"After a long period of very poor intake, build feeding up slowly and take precautions against refeeding syndrome","why":"Feeding too fast after starvation can cause dangerous shifts in salts in the blood.","source":"espen-2021","quote":"If oral food intake has been decreased severely for a prolonged period, we recommend to increase (oral, enteral or parenteral) nutrition only slowly over several days and to take additional precautions to prevent a refeeding syndrome.","grade":"strong; level of evidence low; consensus"},{"action":"Encourage the person to stay active or become more active, with resistance as well as aerobic exercise where possible","why":"Activity helps keep muscle and strength, which food alone cannot do.","source":"espen-2021","quote":"We recommend maintenance or an increased level of physical activity in cancer patients to support muscle mass, physical function, and metabolic pattern.","grade":"strong; level of evidence high; consensus"},{"action":"In advanced cancer, decide on nutrition support with the person, weighing prognosis, expected benefit and burden; in the last days, care for comfort","why":"Artificial nutrition rarely helps in the last days of life, and the decision belongs with the person.","source":"espen-2021","quote":"In dying patients, we recommend that treatment be based on comfort.","grade":"strong; level of evidence low; strong consensus"}],"bestInClass":{"statement":"ESPEN's 2021 practical guideline, read in full, is the most detailed and recent: screening from diagnosis with intake, weight change and BMI; assessment of the cause when the screen is abnormal; energy of 25 to 30 kcal/kg/day and protein above 1 g/kg/day; a stepped approach from counselling and supplements to enteral and then parenteral nutrition; and maintained physical activity. Most of its screening recommendations are strong but rest on very low evidence, by its own grading. NICE CG32 (2006, updated 2017) applies to all adults rather than to cancer, and sets the fixed screening points (first outpatient appointment, admission, weekly for inpatients) and the BMI and weight-loss criteria for starting support.","sources":["espen-2021","nice-cg32"]},"variants":[{"name":"NICE criteria for starting nutrition support (CG32)","differs":"Considers nutrition support for anyone with a BMI below 18.5 kg/m², unintentional weight loss above 10 per cent in 3 to 6 months, or a BMI below 20 with weight loss above 5 per cent; and for those at risk, such as having eaten little or nothing for more than 5 days.","evidence":"NICE recommendations are not graded; CG32 applies to all adults, not only people with cancer.","sources":["nice-cg32"]},{"name":"Medicines to stimulate appetite in advanced cancer (ESPEN)","differs":"Suggests considering corticosteroids for 1 to 3 weeks or progestins to improve appetite in advanced cancer, aware of their side effects, and long-chain omega-3 fatty acids or fish oil for people on chemotherapy at risk of weight loss.","evidence":"ESPEN grades these weak recommendations (high evidence for corticosteroids and progestins; low for omega-3).","sources":["espen-2021"]}],"grades":[{"claim":"Nutritional counselling and supplements during radiotherapy to head and neck, thorax and gut","grade":"strong; level of evidence moderate; strong consensus","source":"espen-2021"},{"claim":"Maintain or increase physical activity","grade":"strong; level of evidence high; consensus","source":"espen-2021"},{"claim":"Regular screening from diagnosis","grade":"strong; level of evidence very low; strong consensus","source":"espen-2021"}],"sources":[{"key":"espen-2021","label":"ESPEN practical guideline: Clinical Nutrition in cancer","publisher":"ESPEN, Clinical Nutrition","year":2021,"url":"https://www.espen.org/files/ESPEN-Guidelines/ESPEN-practical-guideline-clinical-nutrition-in-cancer.pdf","doi":"10.1016/j.clnu.2021.02.005","gradingScheme":"Each recommendation printed with its strength (strong or weak), level of evidence (high, moderate, low, very low) and consensus (strong consensus or consensus).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-cg32","label":"Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition (CG32), recommendations","publisher":"NICE","year":2006,"url":"https://www.nice.org.uk/guidance/cg32/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations. Published February 2006, last updated August 2017.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-nutrition-risk-screening-at-treatment-start"],"gaps":["ESPEN does not name a single screening tool in the recommendations read; NICE gives MUST as an example for all adults.","ASCO's 2020 guideline on cancer cachexia and ESMO's 2021 cachexia guideline were not read for this protocol.","The evidence for screening itself is very low by ESPEN's own grading; the recommendations rest on consensus.","Perioperative nutrition and immunonutrition, nutrition in stem cell transplant, and children are covered only in passing.","Who delivers the assessment (dietitian, nurse or doctor) and how quickly after a positive screen are not fixed in the sources read."]},{"id":"opioid-switching-and-conversion","kind":"protocol","name":"Opioid switching and dose conversion in adults with cancer pain","aka":["opioid rotation","opioid conversion","opioid switch","equianalgesic dose","converting oral morphine to subcutaneous","morphine to fentanyl patch conversion","opioid conversion ratio"],"tldr":"Sometimes a strong painkiller has to be changed for another, or given a different way, for example by injection under the skin when swallowing becomes hard. Doses do not swap one for one, so the team works out the new dose from the total taken over 24 hours, often starts a little lower to be safe, and checks closely in the first days.","summary":"Switching is considered when pain stays uncontrolled despite an appropriate dose, when side effects are unacceptable (Australian guideline 2025, citing ESMO, NCCN, NICE and ASCO; NICE CG140 1.1.25 for persistent central nervous system effects with uncontrolled pain), or when the oral route is lost. WHO (2018) makes no recommendation for or against switching because no randomised trial has tested it, and presents its conversion tables only as examples. The conversion is done on the total 24-hour dose, looked up in a recognised table or calculator. Ratios in the WHO annex (from the Palliative Care Formulary) include oral to subcutaneous morphine 2:1 and oral morphine to subcutaneous hydromorphone 10:1; oral oxycodone is listed at 1.5 times morphine (manufacturer 2). WHO advises reducing the calculated dose of the new opioid by about 50% when switching at high doses, in older or frail people, because of intolerable side effects such as delirium, or after a rapid recent escalation; the Australian guideline says a dose lower than the equivalent should be used when changing drug. The 2025 MASCC-ASCO-AAHPM-HPNA-NICSO guideline, the first international consensus guideline on conversion, reached agreement on 58 of 84 statements and is described in a 2026 review as challenging traditional dose-reduction protocols; it could be read only as an abstract. Methadone is converted by specialists only.","asOf":"2026-11-11","links":[],"tags":[],"related":["strong-opioids-for-cancer-pain"],"cancers":[],"sections":[],"technologies":["pain-management","syringe-drivers"],"targets":[],"drugs":["fentanyl"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Changing from one strong painkiller to another, or from tablets to a pump or a patch, needs careful sums. Your team works out a safe new dose and checks on you closely afterwards. Tell them if you feel very sleepy or muddled, or if the pain comes back.","domain":"palliative","setting":{"who":["doctor","pharmacist","nurse"],"where":["ward","home","community","outpatient-clinic"]},"population":"Adults with cancer pain already taking a strong opioid. Children, and conversions to or from methadone or intrathecal opioids, need specialist teams and are outside this record.","trigger":"Pain not controlled despite an appropriate opioid dose, side effects that cannot be managed, or the current route (usually swallowing) no longer possible.","steps":[{"action":"Before switching for side effects, rule out other causes and optimise what is already in place: laxatives for constipation, anti-emetics for nausea, a dose reduction if pain is controlled","why":"Many side effects can be treated without changing the painkiller that is working.","source":"nice-cg140","quote":"Optimise laxative treatment for managing constipation before considering switching strong opioids.","grade":"Not graded (NICE 1.1.20)"},{"action":"Consider switching opioid when pain is not controlled despite an appropriate dose, or side effects are unacceptable","why":"People respond differently to different opioids, and another one may give better relief with fewer side effects.","source":"aus-2025","quote":"Optimal pain relief cannot be achieved despite appropriate dose. (ESMO, NCCN, NICE)","grade":"Adopted from ESMO, NCCN and NICE"},{"action":"If the person can no longer swallow, switch to subcutaneous morphine, hydromorphone, oxycodone or fentanyl, or a fentanyl patch if pain is stable","why":"Injection under the skin is less painful than into muscle and works when tablets cannot be taken.","source":"aus-2025","quote":"If the oral route is no longer possible, switch to subcutaneous morphine, hydromorphone, oxycodone, or fentanyl. Transdermal fentanyl is another alternative in stable pain.","grade":"Adopted from source guidelines"},{"action":"Add up the total opioid taken in the last 24 hours, regular and rescue, and convert that total using a recognised conversion table or calculator","why":"Conversion ratios apply to the daily total, and leaving out rescue doses underestimates what the person needs.","source":"aus-2025","quote":"If switching to a different formulation or route of administration with the same agent, look up conversion for total 24‐h opioid dose (ESMO, NCCN, NICE) (e.g., via the eviQ Opioid Conversion Calculator).","grade":"Adopted from ESMO, NCCN and NICE"},{"action":"When changing to a different opioid, start below the calculated equivalent dose","why":"Tolerance to one opioid does not fully carry over to another, so an exactly equivalent dose can be too strong.","source":"aus-2025","quote":"If switching to a different agent, a starting dose lower than the equivalent total 24‐h opioid dose of the previous agent should be used.","grade":"Adopted from source guidelines"},{"action":"Reduce the calculated dose by about half when switching at high doses (around 1 g oral morphine a day or more), in older or frail people, for delirium or other intolerable effects, or after a rapid recent dose rise, and use rescue doses to cover any shortfall","why":"These are the situations where an equivalent dose is most likely to cause overdose.","source":"who-2018","quote":"A dose reduction of around 50% of the calculated equivalent dose of the new opioid is prudent when switching at high doses (e.g. morphine or equivalent doses of ≥ 1 g/24h), in elderly or frail patients, because of intolerable undesirable effects (e.g. delirium), or when there has been a recent rapid escalation of the first opioid (possibly due to opioid-induced hyperalgesia).","grade":"Not graded (annex guidance; WHO does not recommend the tables)"},{"action":"Leave conversion to or from methadone to specialists","why":"Methadone's long and variable action means its effective strength rises with regular use far beyond what a single-dose table suggests.","source":"aus-2025","quote":"P4 Methadone should be initiated and titrated only by specialists familiar with its use. (ESMO, NCCN, ASCO 2016, ASCO 2022)","grade":"Adopted from ESMO, NCCN and ASCO"},{"action":"Monitor closely in the first days after a switch for too much opioid (drowsiness, confusion, slow breathing) and too little (returning pain), and re-titrate","why":"Conversion ratios are only approximate and people vary widely, so the new dose is a starting point.","source":"who-2018","quote":"Thus, careful clinical monitoring during conversion is necessary to avoid under-dosing, excessive dosing and adverse effects, especially when switching at high doses, when rapidly increasing the dose of the first opioid, and when switching to methadone.","grade":"Not graded (annex guidance)"}],"bestInClass":{"statement":"Convert on the total 24-hour dose using a recognised table or calculator, start below the calculated equivalent when changing drug, reduce by about 50% in the high-risk situations WHO lists, keep methadone with specialists, and monitor closely afterwards (WHO 2018 annex; Australian guideline 2025 adopting ESMO, NCCN, NICE and ASCO). The evidence is weak throughout: WHO found no randomised trial of switching and makes no recommendation for or against it. The 2025 MASCC-ASCO-AAHPM-HPNA-NICSO guideline is the first international consensus on conversion ratios and, by the account of a 2026 review, questions routine dose reduction; it could be read only as an abstract, so where it differs from WHO and the Australian guideline on the size of the reduction cannot be stated here.","sources":["who-2018","aus-2025","mascc-2025","mascc-insights-2026"]},"variants":[{"name":"Fixed routine reduction of 25 to 50% for every switch","differs":"Reduces the calculated dose of the new opioid by a set percentage on every change of drug, regardless of the reason or dose.","evidence":"WHO reserves its reduction of about 50% for named high-risk situations; the Australian guideline asks for a starting dose below the equivalent without setting a figure. A 2026 review of the MASCC-ASCO-AAHPM-HPNA-NICSO guideline says it challenges traditional dose-reduction protocols; its exact position could not be read.","sources":["who-2018","aus-2025","mascc-insights-2026"]},{"name":"Oral to subcutaneous hydromorphone at 2:1 rather than 3:1","differs":"Some centres convert oral to subcutaneous hydromorphone at 2:1; the manufacturer's ratio in the WHO annex is 3:1. Some centres likewise convert oral to subcutaneous methadone 1:1 rather than 2:1.","evidence":"WHO annex notes, based on mean oral bioavailability (hydromorphone 50%, range 35 to 60%; methadone 80%, range 40 to 100%). No trial.","sources":["who-2018"]},{"name":"Calculator-based conversion","differs":"Uses an online conversion calculator, such as eviQ's in Australia, rather than a printed table.","evidence":"Named by the Australian guideline as the reference for its dose equivalences. A calculator is only as good as the ratios built into it; studies of calculators were not read.","sources":["aus-2025"]}],"grades":[{"claim":"Opioid switching or rotation","grade":"No recommendation","source":"who-2018","quote":"In the absence of evidence, WHO makes no recommendation for or against the practice of opioid switching or rotation."},{"claim":"Conversion tables are examples to inform judgement, not WHO recommendations","grade":"Not graded (annex)","source":"who-2018","quote":"They are presented merely as examples and should not be construed as recommended by WHO."},{"claim":"Consensus reached on conversion statements","grade":"58 of 84 statements met the 75% agreement threshold","source":"mascc-2025","quote":"In consensus voting, 58 of 84 statements met or exceeded the required 75% level of agreement and were accepted."},{"claim":"Strength of the evidence behind conversion","grade":"Modest (as stated by the panel)","source":"mascc-2025","quote":"The strength of the evidence from the trials is modest, and there are large clinical practice and research gaps."},{"claim":"Switch opioid for persistent or moderate to severe central nervous system effects when pain is not controlled","grade":"Not graded (NICE 1.1.25)","source":"nice-cg140","quote":"consider switching opioids if pain is not controlled."}],"sources":[{"key":"who-2018","label":"WHO guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents (section 6.2.3 and Annex 6)","publisher":"World Health Organization","year":2018,"url":"https://iris.who.int/handle/10665/279700","gradingScheme":"GRADE: strong or conditional recommendations with quality of evidence high to very low; best practice statements; 'no recommendation' where evidence is absent. Annex tables are examples, not recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"aus-2025","label":"Update of the Australian Guideline for the Management of Cancer Pain in Adults (Cancer Council Australia)","publisher":"Asia-Pacific Journal of Clinical Oncology","year":2025,"url":"https://doi.org/10.1111/ajco.70047","doi":"10.1111/ajco.70047","gradingScheme":"Recommendations adopted from source guidelines carry the strength of the source, named in brackets; de novo ones rest on Level 1 evidence or consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-cg140","label":"Palliative care for adults: strong opioids for pain relief (CG140), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg140/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations. Last updated August 2016.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-2025","label":"Opioid conversion in adults with cancer: MASCC-ASCO-AAHPM-HPNA-NICSO guideline","publisher":"Supportive Care in Cancer","year":2025,"url":"https://doi.org/10.1007/s00520-025-09286-z","doi":"10.1007/s00520-025-09286-z","gradingScheme":"Systematic review plus modified Delphi consensus; statements accepted at 75% agreement or more.","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-insights-2026","label":"Opioid Conversion in Adults With Cancer: MASCC-ASCO-AAHPM-HPNA-NICSO Guideline Clinical Insights","publisher":"Journal of Pain and Symptom Management","year":2026,"url":"https://doi.org/10.1016/j.jpainsymman.2025.10.027","doi":"10.1016/j.jpainsymman.2025.10.027","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 2025 MASCC-ASCO-AAHPM-HPNA-NICSO guideline, the most specific and most recent source, could be read only as an abstract (the publisher served a bot challenge). Its conversion ratios and its position on routine dose reduction are not on this page.","No randomised trial of opioid switching exists (WHO 2018). Every conversion ratio rests on retrospective, observational or single-dose studies.","The WHO conversion tables lose their layout when extracted as text; ratios given in the summary were read against the worked examples beside each row, and are WHO's examples, not recommendations.","Methadone conversion, intrathecal conversion and conversion in children are outside this record."]},{"id":"oral-anticancer-medicines-at-home","kind":"protocol","name":"Oral anticancer medicines at home: prescribing, teaching, adherence, storage, handling and disposal","aka":["oral chemotherapy at home","cancer tablets","oral anticancer medication adherence","OAM","capecitabine at home","missed dose of chemotherapy tablets","oral SACT","oral SACT at home","oral chemotherapy safety at home","storing chemotherapy tablets","disposing of chemotherapy tablets","safe handling of oral chemotherapy","chemotherapy body fluid precautions at home"],"tldr":"Many cancer treatments are now tablets taken at home. Ask for a written plan: what to take and when, what to do about a missed dose, what to avoid, and which side effects mean stopping and calling. Keep tablets in their labelled container away from children; carers should not touch them bare-handed; take care with toilets and laundry for two days after a dose; return leftovers to the pharmacy.","summary":"ASCO-ONS (2024) sets the safety standards, and extends them to home administration. Oral anticancer medicines are ordered on electronic or preprinted forms, with the quantity to dispense, the number of refills (zero as the preferred default) and the schedule. Labels give the dosage form, quantity, pills per dose, the schedule with days on and off, food instructions and handling warnings. Before the first dose, patients receive verbal and written education in their preferred language covering the schedule, missed doses, interactions with drugs, herbal products and foods, side effects that require stopping self-administered treatment and calling, safe handling at home including disposal, body secretions and spills, and whom to contact; carers are included where needed. Adherence is assessed at the start and during treatment (standard 4.4).\n\nThe ONS adherence guideline (2022, GRADE) makes conditional recommendations, mostly on very low-certainty evidence, for an adherence risk assessment at the start, education addressing adherence, ongoing assessment, proactive follow-up for those at risk, coaching and motivational interviewing (low certainty), and a structured oral anticancer medication programme; it makes no recommendation on reminder technology (knowledge gap). Product information adds handling rules, such as not crushing or cutting capecitabine tablets.\n\nNo graded guideline sets out the household detail of storage, handling and disposal; that rests on nursing and patient guidance. ACS (2025, ASCO-reviewed) and Macmillan (2022) say to read the labels before leaving hospital, store tablets as instructed (some away from light or in a fridge), keep them in the original container and out of reach of children, ask whether tablets can be crushed or opened, and report missed doses. ACS and the ONS safe handling toolkit (2018) describe body-fluid precautions for at least 48 hours after a dose: sit to use the toilet, lid down and flush (twice for a low-volume flush), wipe the seat, wash hands, carers wear gloves (ACS says two pairs) for fluids, wash soiled laundry separately and twice in hot water, and double-bag disposable waste. For leftover medicine, ONS says never put cancer drugs in the bin, drain or toilet and to return them to the pharmacy or clinic; the FDA's general advice for medicines (take-back first, then the flush list, then the household bin) is not written for cancer drugs and conflicts with this.","asOf":"2026-11-11","links":[],"tags":[],"related":["hazardous-drug-handling-in-clinical-areas","dpyd-testing-before-fluoropyrimidines","idea-acc-pharmacist-interaction-review-oral-anticancer"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","cdk46-inhibitor"],"targets":[],"drugs":["capecitabine","cyclophosphamide","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Ask for a written plan for your cancer tablets: when to take them, what to do if you miss one, and when to stop and call. Keep them in the box or bottle they came in, where children and pets cannot reach. Do not crush or split them unless you are told you can. If someone helps you, they should tip the tablet into the cap or wear gloves. For two days after a dose, put the toilet lid down before flushing and wash your hands. Take any tablets you do not use back to the pharmacy.","domain":"oral-anticancer-therapy","setting":{"who":["pharmacist","nurse","doctor","patient-or-carer"],"where":["outpatient-clinic","home","telephone-triage"]},"population":"Adults taking oral anticancer medicines at home (chemotherapy tablets such as capecitabine, cyclophosphamide or etoposide, kinase inhibitors, CDK4/6 inhibitors and other oral drugs the team classes as hazardous), and the people they live with. Hormonal therapies are covered by ASCO-ONS only where listed as antineoplastic. Children's oral chemotherapy, people unable to manage their own medicines, and drugs with their own pregnancy prevention programmes need carer-centred arrangements or additional rules from the prescriber beyond these sources.","trigger":"An oral anticancer medicine is prescribed or dispensed for use at home for the first time, its dose changes, or a patient reports difficulty taking it.","steps":[{"action":"Order oral anticancer medicines on an electronic or preprinted form with the quantity, schedule and number of refills, with no refills as the default","why":"Automatic repeat prescriptions let people keep taking a drug after it should have been stopped or the dose changed.","source":"asco-ons-2024","quote":"Number of refills, with zero being the preferred default value for oral antineoplastics"},{"action":"Label each container with how many to take, how often, the days on and off, and when follow-up is due","why":"Cycles with days off are a common cause of taking too much or too little.","source":"asco-ons-2024","quote":"Administration schedule, including number of times per day to take medication and days on or off medication (cycle length) when applicable, and when follow-up is scheduled"},{"action":"Before the first dose, teach the schedule, what to do about a missed dose, and interactions with other medicines, herbal products and foods","why":"Patients at home make these decisions without a nurse present.","source":"asco-ons-2024","quote":"Planned duration of treatment, schedule of treatment administration, plan for missed doses, drug names and supportive medications, and drug interactions with prescribed drugs, integrative therapies, over the counter drugs, and foods"},{"action":"Tell the patient which symptoms mean stopping the tablets and calling the team straight away","why":"Severe diarrhoea, mouth sores, fever or hand-foot skin damage can become dangerous if tablets are continued.","source":"asco-ons-2024","quote":"Symptoms or events that require immediate discontinuation of oral or other self-administered treatments"},{"action":"Teach safe handling at home: storage, handling, disposal of unused tablets, body fluids and cleaning up spills","why":"The drugs that harm cancer cells can harm others in the household who touch them.","source":"asco-ons-2024","quote":"Procedures for safe handling medications in the home, including disposal of waste, handling body secretions, storage, safe handling, and management of unused medication, and clean-up of drug spills"},{"action":"Include family or carers in the teaching where the patient needs help to manage treatment","why":"Carers often handle the tablets and notice side effects first.","source":"asco-ons-2024","quote":"Education includes family, caregivers, or others on the basis of the patient's ability to assume responsibility for managing therapy."},{"action":"Read the labels before leaving the hospital or pharmacy, and ask about anything unclear, including whether tablets may be crushed, split or opened","why":"Taking the right dose at the right time matters, and crushing or opening some tablets releases drug into the air or onto skin.","source":"macmillan-how-chemo-given","quote":"read the labels on the drug boxes before you leave the hospital and speak to your nurse, doctor or pharmacist if any instructions are unclear","grade":"Not graded (patient information)"},{"action":"Do not crush, split or open tablets or capsules unless the product information or pharmacist says this is safe","why":"Crushing releases drug dust that the patient or carer can inhale or absorb.","source":"xeloda-smpc","quote":"Xeloda tablets should not be crushed or cut."},{"action":"Store the medicine exactly as instructed (for example away from light or in a fridge), in the bottle or box it came in","why":"Some drugs spoil if stored wrongly, and the original container keeps the label and warnings with the medicine.","source":"macmillan-how-chemo-given","quote":"Some chemotherapy tablets, capsules or injections may need to be stored in a certain way, such as away from direct light or in a fridge. Always follow the instructions given by your nurse or pharmacist.","grade":"Not graded (patient information)"},{"action":"Keep every dose out of the reach of children and pets","why":"A dose meant for an adult with cancer can seriously harm a child who swallows it.","source":"macmillan-how-chemo-given","quote":"All drugs must be stored out of the reach of children, as they could cause serious harm if taken by accident.","grade":"Not graded (patient information)"},{"action":"Carers who help should not touch tablets with bare hands: tip the dose into the container cap, or wear gloves","why":"Many oral anticancer drugs are hazardous to the people who handle them, not only to the person taking them.","source":"ons-safe-handling-toolkit","quote":"When assisting patients with oral HDs, family members should use “no-touch” technique (e.g., pour tablets into the cap of the container) or wear gloves for handling.","grade":"Not graded (nursing toolkit)"},{"action":"If a dose is missed or taken late, tell the team rather than making it up on your own","why":"Doses are timed to keep a steady level of drug; the team decides whether to change anything.","source":"acs-oral-chemo","quote":"If you miss a dose or are late taking one, tell your doctor or nurse about it.","grade":"Not graded (patient information)"},{"action":"For at least 48 hours after a dose, sit to use the toilet, put the lid down before flushing, wipe the seat, and wash hands with soap and water","why":"Most of the drug leaves the body in urine and stools over about two days, and splashes can reach other people.","source":"acs-chemo-safety","quote":"It generally takes at least 48 hours for your body to break down and/or get rid of most chemo.","grade":"Not graded (patient information)"},{"action":"Anyone handling body fluids, vomit or soiled items should wear disposable gloves and wash their hands afterwards","why":"Drug in body fluids can irritate or harm skin with repeated exposure.","source":"acs-chemo-safety","quote":"If others need to touch any of your body fluids or something that has been in contact with your body fluids (like a bucket or basin), they should wear 2 pairs of throw-away gloves.","grade":"Not graded (patient information)"},{"action":"Wash clothes or sheets soiled with body fluids in a machine, separately, twice in hot water; seal them in a plastic bag if they cannot be washed straight away","why":"Washing separately and twice removes drug residue without spreading it to other laundry.","source":"acs-chemo-safety","quote":"Wash them twice in hot water with regular laundry detergent. Do not wash them with other clothes.","grade":"Not graded (patient information)"},{"action":"Double-bag used gloves, pads and other contaminated waste before putting it in the household bin, and do not reuse or recycle empty medicine bottles","why":"Bagging keeps others from touching drug residue; empty containers still carry traces of the drug.","source":"ons-safe-handling-toolkit","quote":"Before putting this waste in the trash, double bag it to help make sure others don’t inadvertently come into contact with it.","grade":"Not graded (nursing toolkit)"},{"action":"Return any leftover or stopped medicine to the pharmacy, clinic or treatment centre; do not put it in the bin, down the drain or down the toilet","why":"Leftover anticancer drugs are a hazard to others and to the environment, and pharmacies can destroy them safely.","source":"ons-safe-handling-toolkit","quote":"Never throw cancer drugs in the trash or down the drain, and don’t flush them down the toilet.","grade":"Not graded (nursing toolkit)"},{"action":"At the start, assess the risk that the person will struggle to take the medicine as prescribed","why":"Cost, complex schedules, low mood and side effects all make missed doses more likely and can be planned for.","source":"ons-oam-2022","quote":"In patients starting a new OAM, the ONS Guidelines panel suggests an adherence risk assessment in addition to usual care rather than usual care alone (conditional recommendation, very low certainty of evidence).","grade":"conditional recommendation, very low certainty of evidence"},{"action":"Ask about missed or extra doses at every contact, and follow up proactively between visits for people at higher risk","why":"Problems with tablets often show up between clinic visits.","source":"ons-oam-2022","quote":"In patients with additional risk factors for nonadherence taking OAMs, the ONS Guidelines panel suggests proactive follow-up addressing adherence in addition to usual care, rather than usual care alone (conditional recommendation, very low certainty of evidence).","grade":"conditional recommendation, very low certainty of evidence"},{"action":"Offer coaching or motivational interviewing to support adherence","why":"Talking through goals and barriers helped some patients keep taking their treatment in small trials.","source":"ons-oam-2022","quote":"In patients taking OAMs, the ONS Guidelines panel suggests motivational interviewing in addition to usual care rather than usual care alone (conditional recommendation, low certainty of evidence).","grade":"conditional recommendation, low certainty of evidence"}],"bestInClass":{"statement":"A structured oral anticancer medicine programme (ONS 2022, conditional, very low certainty): order and label to the ASCO-ONS standards (2024), with zero refills as the default and the schedule, days off and food instructions on the label; teach patient and carer before the first dose, in writing, including missed doses, interactions, stop-and-call symptoms and safe handling and disposal at home; assess adherence risk at the start and adherence at every contact; follow up proactively those at risk; offer coaching and motivational interviewing. The evidence for each adherence intervention is low or very low in certainty, and ONS makes no recommendation on reminder technology. For the household detail ASCO-ONS requires to be taught but does not specify, the convergent nursing and patient guidance (ACS 2025, ASCO-reviewed; Macmillan 2022; NCI 2023; the ONS safe handling toolkit 2018) agrees on original containers, storage as labelled, keeping drugs from children, a no-touch technique or gloves for carers, 48 hours of body-fluid precautions, and returning leftovers to the pharmacy. The ISOPP 2022 standards cover handling but could not be read, so their wording is not used here.","sources":["asco-ons-2024","ons-oam-2022","acs-oral-chemo","acs-chemo-safety","macmillan-how-chemo-given","nci-chemo-and-you","ons-safe-handling-toolkit"]},"variants":[{"name":"Reminder apps and text messages","differs":"Uses automated reminders or interactive apps to support taking oral anticancer medicines.","evidence":"ONS (2022) makes no recommendation, citing a knowledge gap; it notes adherence improved in studies only where technology came with follow-up from a healthcare worker.","sources":["ons-oam-2022"]},{"name":"General medicine disposal (FDA)","differs":"For most unused medicines, use a take-back option first; if there is none, flush medicines on the FDA flush list, and put others in the household bin.","evidence":"FDA consumer guidance (content current 31 October 2024), written for medicines in general and not for anticancer drugs. It conflicts with ONS, which says never to bin or flush cancer drugs; for anticancer drugs, the team's or pharmacy's return route comes first.","sources":["fda-disposal"]},{"name":"Separate toilet for 48 hours (ONS toolkit)","differs":"Asks household members to use a different toilet from the patient for 48 hours after a dose; ACS says to do this if possible and otherwise to wipe the seat after each use.","evidence":"Nursing toolkit, not graded; ONS gives the 48-hour period, citing a nursing text. No study compares the two approaches.","sources":["ons-safe-handling-toolkit","acs-chemo-safety"]},{"name":"Length of body-fluid precautions set by the treating centre (NCI)","differs":"Lists the same precautions (lid closed and flush twice, sit to urinate, gloves for body fluids, separate laundry, condoms during sex) but leaves the duration to the centre and the drug.","evidence":"NCI booklet: the time 'might differ depending on the policy where you receive treatment and the drugs that you receive.'","sources":["nci-chemo-and-you"]}],"grades":[{"claim":"Education addressing adherence in addition to standard education","grade":"conditional recommendation, very low certainty of evidence","source":"ons-oam-2022","quote":"In patients taking OAMs, the ONS Guidelines panel suggests education addressing adherence in addition to standard education rather than standard education alone (conditional recommendation, very low certainty of evidence)."},{"claim":"Ongoing assessment of adherence","grade":"conditional recommendation, very low certainty of evidence","source":"ons-oam-2022","quote":"In patients taking OAMs, the ONS Guidelines panel suggests ongoing assessment of adherence in addition to usual care rather than usual care alone (conditional recommendation, very low certainty of evidence)."},{"claim":"Coaching","grade":"conditional recommendation, very low certainty of evidence","source":"ons-oam-2022","quote":"In patients taking OAMs, the ONS Guidelines panel suggests coaching in addition to usual care, rather than usual care alone (conditional recommendation, very low certainty of evidence)."},{"claim":"A structured oral anticancer medication programme","grade":"Conditional; very low certainty","source":"ons-oam-2022","quote":"The ONS Guidelines panel suggests implementation of a structured OAM program rather than no structured OAM program."},{"claim":"Reminder technology","grade":"No recommendation; knowledge gap","source":"ons-oam-2022","quote":"The ONS Guidelines panel makes no recommendation for the use of technology, either interactive or noninteractive, based on a knowledge gap."},{"claim":"Organisation policy for monitoring adherence","grade":"Standard (not graded)","source":"asco-ons-2024","quote":"The health care organization policy outlines the procedure to monitor initial and subsequent assessment and documentation of patients' adherence to antineoplastic therapy"},{"claim":"Home administration within the scope of the ASCO-ONS safety standards","grade":"Standards (expert panel and literature review); not graded","source":"asco-ons-2024","quote":"The standards presented here include clarification and expansion of existing standards to include home administration and other changes in processes of ordering, preparing, and administering antineoplastic therapy; the advent of immune effector cellular therapy; the importance of social determinants of health; fertility preservation; and pregnancy avoidance."},{"claim":"Home storage, handling and disposal steps","grade":"Not graded: patient information and a nursing toolkit, without a grading scheme","source":"ons-safe-handling-toolkit"},{"claim":"Body-fluid precautions for 48 hours after a dose","grade":"Not graded (ONS toolkit, citing a nursing text)","source":"ons-safe-handling-toolkit","quote":"Family members should use separate toilets from the patient for 48 hours after HD administration to eliminate the risk of contact with contaminated body waste."}],"sources":[{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and the Oncology Nursing Society (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ons-oam-2022","label":"ONS Guidelines to Support Patient Adherence to Oral Anticancer Medications","publisher":"Oncology Nursing Society (Oncology Nursing Forum, Belcher et al.)","year":2022,"url":"https://doi.org/10.1188/22.ONF.279-295","doi":"10.1188/22.ONF.279-295","gradingScheme":"GRADE: recommendations strong, conditional, no recommendation or knowledge gap; certainty of evidence high, moderate, low or very low.","read":"full-text","accessed":"2026-11-11"},{"key":"xeloda-smpc","label":"Xeloda (capecitabine): summary of product characteristics, section 4.4","publisher":"European Medicines Agency (EPAR product information)","year":2026,"url":"https://www.ema.europa.eu/en/documents/product-information/xeloda-epar-product-information_en.pdf","gradingScheme":"Product information; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-how-chemo-given","label":"How chemotherapy is given","publisher":"Macmillan Cancer Support","year":2022,"url":"https://www.macmillan.org.uk/cancer-information-and-support/treatment/types-of-treatment/chemotherapy/how-chemotherapy-is-given","gradingScheme":"Patient information page; not graded. Reviewed 1 March 2022.","read":"full-text","accessed":"2026-11-11"},{"key":"acs-oral-chemo","label":"Getting Oral Chemotherapy","publisher":"American Cancer Society (with ASCO medical review)","year":2025,"url":"https://www.cancer.org/cancer/treatment-types/chemotherapy/oral-chemotherapy.html","gradingScheme":"Patient information page; not graded. Last revised 15 May 2025.","read":"full-text","accessed":"2026-11-11"},{"key":"acs-chemo-safety","label":"Chemotherapy Safety","publisher":"American Cancer Society (with ASCO medical review)","year":2025,"url":"https://www.cancer.org/cancer/treatment-types/chemotherapy/chemotherapy-safety.html","gradingScheme":"Patient information page; not graded. Last revised 15 May 2025.","read":"full-text","accessed":"2026-11-11"},{"key":"ons-safe-handling-toolkit","label":"Toolkit for Safe Handling of Hazardous Drugs for Nurses in Oncology","publisher":"Oncology Nursing Society","year":2018,"url":"https://www.ons.org/sites/default/files/2018-06/ONS_Safe_Handling_Toolkit_0.pdf","gradingScheme":"Nursing toolkit; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nci-chemo-and-you","label":"Chemotherapy and You: Support for People with Cancer","publisher":"National Cancer Institute (US)","year":2023,"url":"https://www.cancer.gov/publications/patient-education/chemotherapy-and-you.pdf","gradingScheme":"Patient booklet; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"fda-disposal","label":"Disposal of Unused Medicines: What You Should Know","publisher":"US Food and Drug Administration","year":2024,"url":"https://www.fda.gov/drugs/safe-disposal-medicines/disposal-unused-medicines-what-you-should-know","gradingScheme":"Consumer guidance; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"isopp-2022","label":"ISOPP Standards for the Safe Handling of Cytotoxics","publisher":"International Society of Oncology Pharmacy Practitioners (J Oncol Pharm Pract)","year":2022,"url":"https://doi.org/10.1177/10781552211070933","doi":"10.1177/10781552211070933","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-oral-anticancer-medicine-adherence-programme"],"gaps":["Every ONS adherence recommendation is conditional and rests on low or very low certainty evidence; no single intervention is proven to improve outcomes such as survival or toxicity.","No graded guideline covers storage, handling and disposal of oral anticancer medicines at home: ASCO-ONS requires it to be taught but does not specify it, so every household step rests on patient information or a nursing toolkit.","The ISOPP 2022 standards, which address household safe handling, and the 2018 pan-Canadian community pharmacy consensus could not be read at all (bot check; the PMC full text did not return).","The ONS toolkit read here is the 2018 edition; ACS cites a 2024 ONS book on safe handling that is not freely available.","The 48-hour period is a general figure; how long a particular drug stays in body fluids varies, and the sources leave the exact period to the drug's label and the treating centre. Gloves for carers and pregnancy in the household are not settled by any source read.","Missed-dose rules are drug-specific and come from each product's label; none is reproduced here.","No UK national standard for oral anticancer medicines (for example, from NHS England or BOPA) was read, and the sources do not give a UK-specific return route for anticancer drugs beyond returning them to the pharmacy or clinic."]},{"id":"oral-mucositis-prevention-and-oral-care","kind":"protocol","name":"Oral care and oral mucositis prevention during cancer treatment","aka":["mouth care during chemotherapy","oral care during chemotherapy","mouth care at home during cancer treatment","mouth sores from chemo","oral mucositis prevention","mouthwash during chemotherapy","salt and baking soda mouth rinse","ice chips during chemotherapy","oral cryotherapy","benzydamine mouthwash","photobiomodulation for mucositis","low-level laser for mouth sores","basic oral care"],"tldr":"Some cancer treatments cause painful mouth sores. See a dentist first if you can, check your mouth daily, keep brushing gently with a soft brush even when counts are low, rinse with salt and baking soda rather than an alcohol mouthwash, and tell your team early about pain or sores. Depending on treatment, the team may add ice chips during the drip, a benzydamine mouthwash or a low-level laser.","summary":"MASCC/ISOO (2020) build prevention on basic oral care: a multiagent combination oral care protocol (brushing, flossing, bland rinses, moisturising) is suggested during chemotherapy, head and neck radiotherapy and haematopoietic stem cell transplant (level III), with dental evaluation and treatment before cancer therapy as expert opinion. Their 2024 practice statement says toothbrushing with a soft or very soft brush twice daily should continue through neutropenia and thrombocytopenia, and that brushes are preferred over foam swabs. Chlorhexidine is not to be used to prevent mucositis during head and neck radiotherapy.\n\nTargeted measures depend on the treatment. Oral cryotherapy (ice chips) is recommended for 30 minutes during bolus 5-fluorouracil and during high-dose melphalan conditioning before autologous transplant (level II). Benzydamine mouthwash is recommended for head and neck radiotherapy at moderate dose, below 50 Gy (level I), and suggested with chemoradiotherapy (level II). Intraoral photobiomodulation with low-level laser is recommended for adults having high-dose conditioning for transplant (level I), head and neck radiotherapy alone (level II) and head and neck chemoradiotherapy (level I), using one of the protocols the guideline specifies. For children, the 2021 paediatric guideline uses cryotherapy only for older cooperative children on short melphalan or 5-fluorouracil infusions and photobiomodulation across transplant and head and neck radiotherapy. Topical 0.2% morphine mouthwash is suggested for mucositis pain in head and neck chemoradiotherapy (level III), and honey for head and neck radiotherapy or chemoradiotherapy (level II).\n\nThe NCI patient guide (2024) gives the home routine: dentist at least two weeks before, check the mouth daily, extra-soft brush after meals and at bedtime, fluoride toothpaste, no alcohol mouthwash, a baking soda and salt rinse three to four times a day, gentle flossing (ask if platelets are low), keep the mouth moist, soft cool foods, and call if it hurts a lot.","asOf":"2026-11-11","links":[],"tags":["protocol","mucositis","oral-care","supportive-care"],"related":["palifermin","head-and-neck-radiotherapy-oral-mucositis","paediatric-oral-mucositis-prevention","bleeding-precautions-when-platelets-are-low","head-and-neck-radiotherapy-dental-assessment-osteoradionecrosis"],"cancers":["head-and-neck"],"sections":["supportive-care"],"technologies":["oral-cryotherapy-mucositis","photobiomodulation-mucositis"],"targets":[],"drugs":["fluorouracil","melphalan"],"companies":[],"institutions":["mascc"],"pathways":[],"terms":["mucositis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer treatments make the mouth sore. Look in your mouth every day. Brushing gently with a soft toothbrush helps. Rinse with salty water a few times a day and avoid mouthwash with alcohol. Call your team if your mouth is very sore or you cannot eat or drink. For some treatments, sucking ice during the drip or using a special mouthwash or light treatment helps more.","domain":"supportive-care","setting":{"who":["patient-or-carer","nurse","doctor"],"where":["chemotherapy-day-unit","ward","radiotherapy-department","home"]},"population":"Adults having chemotherapy, radiotherapy to the head and neck, or high-dose conditioning before a haematopoietic stem cell transplant, as MASCC/ISOO scope each measure. Each targeted measure applies only to the treatment named for it. Children are covered by the separate 2021 paediatric guideline, summarised as a variant. Treatment of established mucositis beyond the home routine and pain relief, and gastrointestinal mucositis, are not covered here; head and neck radiotherapy has its own record with the treatment and assessment steps.","trigger":"Before the first cycle of chemotherapy, the first fraction of head and neck radiotherapy, or transplant conditioning, and every day of treatment after.","steps":[{"action":"Before treatment starts, arrange a dental check and any needed dental treatment","why":"Infected teeth and gums can cause infections when the immune system is weak; the panel advises this although trials have not proved it prevents mucositis.","source":"mascc-isoo-2020","quote":"the panel is of the opinion that dental evaluation and treatment as indicated before cancer therapy are desirable to reduce risk for local and systemic infections from odontogenic sources.","grade":"III (no guideline possible; expert opinion)"},{"action":"Start a combined oral care routine and teach it: brushing, cleaning between the teeth, bland rinses and moisturising the mouth","why":"A routine that the patient and staff follow keeps the mouth cleaner and is linked with fewer and milder sores.","source":"mascc-isoo-2020","quote":"The panel suggests that implementation of multiagent combination oral care protocols is beneficial for the prevention of OM during CT.","grade":"III (suggestion)"},{"action":"Check your mouth and tongue every day and tell the team at once about sores, white spots or signs of infection","why":"Sores and thrush are easier to treat when caught early.","source":"nci-2024","quote":"Check your mouth and tongue every day.","grade":"Not graded (patient guide)"},{"action":"Brush teeth, gums and tongue after each meal and at bedtime with an extra-soft toothbrush and fluoride toothpaste","why":"Gentle, frequent cleaning removes food and germs without damaging the lining of the mouth.","source":"nci-2024","quote":"Brush your teeth, gums, and tongue after each meal and at bedtime.","grade":"Not graded (patient guide)"},{"action":"Brush at least twice a day with a soft or very soft toothbrush, and keep brushing when blood counts are low","why":"Stopping brushing lets plaque build up, which causes more gum bleeding and infection, not less.","source":"mascc-isoo-2024-boc","quote":"It is advised for patients to continue toothbrushing during leukopenia, neutropenia, or thrombocytopenia."},{"action":"Use a toothbrush rather than foam swabs, and do not replace the brush every day","why":"Swabs remove debris but do not clean plaque off the teeth.","source":"mascc-isoo-2024-boc","quote":"Toothbrushes do not need to be replaced daily and are preferred over cleansing swabs."},{"action":"Keep flossing or using interdental brushes only if already used to them; do not start during low counts","why":"Careful cleaning between the teeth helps, but someone new to it is more likely to injure the gums while counts are low.","source":"mascc-isoo-2024-boc","quote":"However, it should be noted that for inexperienced patients who do not routinely use interproximal cleaning devices, episodes of leukopenia and/or thrombocytopenia are not the best times to initiate their use."},{"action":"Do not use mouthwash containing alcohol; rinse three to four times a day with a bland rinse of baking soda and salt in warm water, then plain water","why":"Alcohol stings and dries a sore mouth; a bland rinse washes the mouth and is soothing.","source":"nci-2024","quote":"Do not use mouthwash that has alcohol. Instead, rinse your mouth three to four times a day with a solution of baking soda, salt, and warm water followed by a plain water rinse.","grade":"Not graded (patient guide); MASCC/ISOO: no guideline possible, expert opinion supports bland rinses"},{"action":"Do not use chlorhexidine to prevent mucositis during head and neck radiotherapy","why":"Chlorhexidine did not prevent mucositis in head and neck radiotherapy.","source":"mascc-isoo-2020","quote":"The panel suggests that CHX not be used in the prevention of OM in patients undergoing H&N RT.","grade":"III (suggestion against)"},{"action":"Keep the mouth moist by sipping water, ice chips or sugar-free sweets, and ask about saliva substitutes for a persistently dry mouth","why":"A dry mouth is sore and more prone to infection and tooth decay.","source":"nci-2024","quote":"Ask your doctor or nurse about saliva substitutes if your mouth is always dry.","grade":"Not graded (patient guide)"},{"action":"When the mouth is sore, choose soft, moist, cool foods and avoid sharp, spicy, acidic or sugary foods, alcohol and tobacco","why":"Rough, hot or acidic food hurts and damages the sore lining further.","source":"nci-2024","quote":"Choose foods that are moist, soft, and easy to chew or swallow.","grade":"Not graded (patient guide)"},{"action":"During bolus 5-fluorouracil, have the patient hold ice chips in the mouth for 30 minutes","why":"Cold narrows the blood vessels in the mouth, so less of the drug reaches the lining while the level in the blood is highest.","source":"mascc-isoo-2020","quote":"The panel recommends using 30 min of oral cryotherapy to prevent OM in patients receiving bolus 5‐FU CT during the infusion of the CT.","grade":"II (recommendation)"},{"action":"Use oral cryotherapy during high-dose melphalan conditioning before an autologous transplant","why":"Melphalan is given as a short infusion and clears quickly, so cooling during it protects the mouth.","source":"mascc-isoo-2020","quote":"The panel recommends using oral cryotherapy to prevent OM in patients undergoing autologous HSCT when the conditioning includes high‐dose melphalan.","grade":"II (recommendation)"},{"action":"During head and neck radiotherapy, use benzydamine mouthwash to prevent mucositis","why":"Benzydamine is an anti-inflammatory rinse; trials showed fewer and milder sores at moderate radiotherapy doses.","source":"mascc-isoo-2020","quote":"The panel recommends benzydamine mouthwash for the prevention of OM in patients with H&N cancer receiving a moderate dose RT (<50 Gy).","grade":"I (recommendation)"},{"action":"Offer intraoral photobiomodulation with low-level laser to adults having high-dose conditioning for transplant or head and neck chemoradiotherapy, following a published set of laser settings","why":"Low-level light reduces the inflammation that leads to sores; it works only with the right wavelength, dose and schedule.","source":"mascc-isoo-2020","quote":"For all PBM guidelines, it is recommended that the specific PTPs of the selected protocol will be followed for optimal therapy.","grade":"I (recommendation) for transplant and for head and neck chemoradiotherapy; II for head and neck radiotherapy alone"},{"action":"In head and neck cancer, weigh photobiomodulation with the radiotherapy team where the tumour is in the mouth","why":"The guideline asks for care because the light is aimed at tissue near the tumour.","source":"mascc-isoo-2020","quote":"safety considerations unique to patients with oral cancer should be considered."},{"action":"Call the team if the mouth hurts a lot or you cannot eat or drink","why":"Severe mucositis may need prescribed pain relief, treatment for infection, feeding support or a change to treatment.","source":"nci-2024","quote":"Call your doctor, nurse, or dentist if your mouth hurts a lot.","grade":"Not graded (patient guide)"}],"bestInClass":{"statement":"MASCC/ISOO (2020) is the only international guideline on mucositis prevention and its most recent full update; no later update was found. It grades the targeted measures by treatment: benzydamine mouthwash in head and neck radiotherapy below 50 Gy (level I) and photobiomodulation in transplant conditioning and head and neck chemoradiotherapy (level I) have the strongest evidence; ice chips during bolus 5-fluorouracil and high-dose melphalan are level II recommendations. Basic oral care is a level III suggestion in every setting, and its 2024 practice statement settles the common disputes in haematology: keep brushing through low counts, prefer a brush over swabs, and do not count chlorhexidine as mucositis prevention. The 2021 paediatric guideline agrees on cryotherapy and photobiomodulation and differs on who can use cryotherapy and on palifermin (see variants). For the daily routine at home, the NCI patient guide (2024) gives the practical detail: dental check beforehand, daily self-checks, a soft brush after meals, bland rinses instead of alcohol mouthwash, and early reporting; saline and bicarbonate rinses have too little evidence for a guideline but are supported as bland and comforting.","sources":["mascc-isoo-2020","mascc-isoo-2024-boc","paediatric-2021","nci-2024"]},"variants":[{"name":"Children (2021 paediatric guideline)","differs":"Uses cryotherapy only for older cooperative children receiving short infusions of melphalan or 5-fluorouracil, because young children cannot keep ice in the mouth; uses intraoral photobiomodulation (620 to 750 nm) for autologous or allogeneic transplant and for head and neck carcinoma treated with radiotherapy; advises against routine palifermin.","evidence":"Systematic reviews of randomised trials in children and adults: severe mucositis risk ratio 0.49 with cryotherapy and 0.40 with photobiomodulation; palifermin 0.81 but with adverse effects. Read as an abstract only.","sources":["paediatric-2021"]},{"name":"Palifermin (keratinocyte growth factor) before transplant","differs":"Gives palifermin intravenously to adults with blood cancers having autologous transplant with high-dose chemotherapy and total body irradiation.","evidence":"MASCC/ISOO recommend it at level I in that setting only; the paediatric guideline advises against routine use in children because of adverse effects.","sources":["mascc-isoo-2020","paediatric-2021"]},{"name":"Chlorhexidine rinse in haematology and transplant","differs":"Many haematology units use chlorhexidine mouthwash routinely.","evidence":"The 2024 MASCC/ISOO statement says chlorhexidine may reduce the risk of oral infections but was not found to reduce the risk of oral mucositis; the 2020 guideline suggests against it for mucositis prevention in head and neck radiotherapy (level III). It remains in use for other purposes, such as dental plaque control, in some local protocols.","sources":["mascc-isoo-2024-boc","mascc-isoo-2020"]},{"name":"Honey","differs":"Uses honey, topically or swallowed, to prevent mucositis.","evidence":"Suggested by MASCC/ISOO 2020 for head and neck radiotherapy or chemoradiotherapy only (level II); trials were small and used different honeys.","sources":["mascc-isoo-2020"]},{"name":"Flossing every day and sponge swabs when brushing hurts (NCI home guide)","differs":"The NCI patient guide tells everyone to floss gently every day, asking the team first if platelets are low, and to use a sponge swab if brushing hurts.","evidence":"Patient guide, not graded. The 2024 MASCC/ISOO statement prefers a toothbrush over swabs and advises people not used to cleaning between the teeth not to start during low counts.","sources":["nci-2024","mascc-isoo-2024-boc"]}],"grades":[{"claim":"Multiagent combination oral care protocols during chemotherapy, head and neck radiotherapy and transplant","grade":"III (suggestion)","source":"mascc-isoo-2020"},{"claim":"No chlorhexidine for mucositis prevention during head and neck radiotherapy","grade":"III (suggestion against)","source":"mascc-isoo-2020","quote":"The panel suggests that CHX not be used in the prevention of OM in patients undergoing H&N RT."},{"claim":"Saline or bicarbonate rinses","grade":"No guideline possible, LoE III (expert opinion supports them as bland rinses)","source":"mascc-isoo-2020","quote":"No guideline was possible regarding the use of saline or sodium bicarbonate rinses in the prevention or treatment of OM in patients undergoing cancer therapy because of limited data."},{"claim":"Topical 0.2% morphine mouthwash for mucositis pain in head and neck chemoradiotherapy","grade":"Suggestion, LoE III","source":"mascc-isoo-2020","quote":"Topical morphine 0.2% mouthwash is suggested for the treatment of OM‐associated pain in patients with H&N cancer who receive RT‐CT."},{"claim":"Dental visit at least two weeks before chemotherapy","grade":"Not graded (patient guide)","source":"nci-2024","quote":"Visit a dentist at least two weeks before starting chemotherapy."},{"claim":"Benzydamine mouthwash, head and neck radiotherapy below 50 Gy","grade":"I (recommendation)","source":"mascc-isoo-2020"},{"claim":"Benzydamine mouthwash, head and neck chemoradiotherapy","grade":"II (suggestion)","source":"mascc-isoo-2020","quote":"The panel suggests the use of benzydamine mouthwash for the prevention of OM in patients with H&N cancer who receive RT‐CT."},{"claim":"Intraoral photobiomodulation, adults having transplant with high-dose conditioning","grade":"I (recommendation)","source":"mascc-isoo-2020","quote":"The panel recommends the use of intraoral PBM therapy using low‐level laser therapy for the prevention of OM in adult patients receiving HSCT conditioned with high‐dose CT, with or without TBI, using one of the selected protocols listed in Table 2 ."},{"claim":"Intraoral photobiomodulation, head and neck radiotherapy without chemotherapy","grade":"II (recommendation)","source":"mascc-isoo-2020"},{"claim":"Intraoral photobiomodulation, head and neck chemoradiotherapy","grade":"I (recommendation)","source":"mascc-isoo-2020"},{"claim":"30 minutes of oral cryotherapy during bolus 5-fluorouracil","grade":"II (recommendation)","source":"mascc-isoo-2020"},{"claim":"Oral cryotherapy with high-dose melphalan before autologous transplant","grade":"II (recommendation)","source":"mascc-isoo-2020","quote":"The panel recommends using oral cryotherapy to prevent OM in patients undergoing autologous HSCT when the conditioning includes high‐dose melphalan."},{"claim":"Intravenous palifermin, autologous transplant with high-dose chemotherapy and total body irradiation","grade":"I (recommendation)","source":"mascc-isoo-2020","quote":"The use of KGF‐1 intravenously is recommended for the prevention of OM in patients with hematologic cancer undergoing autologous HSCT with a conditioning regimen that includes high‐dose CT and TBI."}],"sources":[{"key":"mascc-isoo-2020","label":"MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy","publisher":"MASCC and ISOO, Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7540329","doi":"10.1002/cncr.33100","gradingScheme":"Each statement carries a level of evidence (I to V, after Somerfield and McCrae) and one of three determinations: recommendation, suggestion, or no guideline possible; negative guidelines mean lack of efficacy, not harm.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-isoo-2024-boc","label":"MASCC/ISOO clinical practice statement: Current understanding on controversies in basic oral care in hemato-oncology and hematopoietic cell transplantation","publisher":"MASCC and ISOO, Supportive Care in Cancer","year":2024,"url":"https://europepmc.org/article/PMC/PMC11269443","doi":"10.1007/s00520-024-08690-1","gradingScheme":"Expert practice statement; statements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nci-2024","label":"Chemotherapy and You: Support for People Who Have Cancer (NIH Publication No. 24-7157)","publisher":"National Cancer Institute","year":2024,"url":"https://www.cancer.gov/publications/patient-education/chemotherapy-and-you.pdf","gradingScheme":"Patient guide; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"paediatric-2021","label":"Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem cell transplant patients: 2021 update","publisher":"European Journal of Cancer","year":2021,"url":"https://europepmc.org/abstract/MED/34252760","doi":"10.1016/j.ejca.2021.05.013","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-oral-cryotherapy-with-bolus-chemotherapy"],"gaps":["The photobiomodulation settings (wavelength, power, energy and schedule) that MASCC/ISOO require are in Table 2 of the 2020 guideline, which is an image in the text read; they are not given here, and a team should take them from the guideline itself.","No later full MASCC/ISOO mucositis update than 2020 was found, so evidence published since 2019 has not been graded by the panel.","MASCC/ISOO could make no guideline on patient education or professional oral care alone, nor on saline or bicarbonate rinses; these rest on expert opinion.","The guideline gives no length of time for ice chips with high-dose melphalan, and neither source read gives a benzydamine dose or schedule.","The cryotherapy recommendations name bolus 5-fluorouracil and high-dose melphalan only; the sources read say nothing about combination regimens that include other drugs given at the same visit.","The 2021 paediatric guideline was read only as an abstract.","The evidence for the general oral care routine is weak (level III), and the exact recipe and frequency of bland rinses rest on practice rather than trials; the NCI recipe is one example among many.","The 2021 erratum to the MASCC/ISOO guideline was not read; it may correct a statement used here.","Mouth sores from targeted drugs and immunotherapy are not separately addressed in what was read and are outside this record."]},{"id":"palliative-sedation-for-refractory-suffering","kind":"protocol","name":"Palliative sedation for refractory suffering at the end of life","aka":["terminal sedation","continuous deep sedation","proportional sedation","respite sedation","sedation for refractory symptoms","midazolam infusion at the end of life"],"tldr":"Very occasionally, near the end of life, suffering cannot be relieved by any other treatment. Palliative sedation uses medicines to make the person sleepy, only as deeply as needed to relieve the suffering. It is decided together with the person and their family, after specialist advice, and checked often.","summary":"The revised EAPC framework (2024; 42 statements, all with high or very high Delphi consensus) defines palliative sedation as the proportionate, monitored lowering of consciousness for refractory suffering, refractory meaning that the professionals can no longer relieve it by other means and the patient finds it intolerable. Suffering includes physical and psychological symptoms and existential suffering. Consultation with palliative care or other experts to confirm refractoriness is strongly recommended before sedation. Proportionality governs both depth (titrate to the lowest dose that relieves suffering, keeping interaction where possible, rather than aiming straight at unconsciousness) and timing (intermittent, transient or respite sedation earlier in the illness; deep continuous sedation generally in the final stages). No life-expectancy threshold is set, and hydration is decided separately. Apart from emergencies, a planned interruption to reassess is recommended. The framework's stepwise drugs: midazolam first (deep sedation bolus 5 to 10 mg SC or 2.5 to 5 mg IV, then about 1 mg/h, titrated; halved with risk factors), lorazepam as an alternative, levomepromazine (or chlorpromazine) added at step 2, and propofol at step 3 under an anaesthetist's supervision. The Korean guideline (2020) grades palliative sedation for severe symptoms unresponsive to available treatments D IIb.","asOf":"2026-11-11","links":[],"tags":[],"related":["care-in-the-last-days-of-life"],"cancers":[],"sections":[],"technologies":["syringe-drivers","palliative-care"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["palliative-sedation","last-days-of-life-care"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If someone at the end of life is suffering in a way nothing else can ease, the team may give medicine to make them sleepy so they are comfortable. They use the smallest amount that works, check often, and talk with the person and family first.","domain":"palliative","setting":{"who":["doctor","nurse","multidisciplinary-team"],"where":["ward","home","community"]},"population":"Adults with life-limiting disease, in any setting (EAPC 2024). The framework is written for adults; children are outside this record.","trigger":"Suffering judged refractory: the professionals can no longer relieve it by other means after appropriate attempts, and the patient finds it intolerable.","steps":[{"action":"Confirm that the suffering is refractory, with advice from palliative care or other experts before starting","why":"Sedation is a last resort, and a specialist may find another way to relieve the suffering.","source":"eapc-2024","quote":"The consultation of palliative care experts and/or other healthcare experts to determine the untreatable nature of the suffering is strongly recommended before applying palliative sedation (stat. 13).","grade":"Delphi statement 13 (high or very high consensus)"},{"action":"Discuss with the patient, and with their consent those close to them, which form of sedation fits their situation, and record the shared decision","why":"The person's own view of what is intolerable is part of deciding that suffering is refractory.","source":"eapc-2024","quote":"The physician will therefore first discuss with the patient the form of sedation which is appropriate to their individual situation.","grade":"Delphi statements 16, 18 and 19 (high or very high consensus)"},{"action":"Choose intermittent or transient sedation earlier in the illness, and continuous deep sedation generally only in the final stages of life","why":"A temporary rest from suffering can be enough while other treatments start to work, and lets the person wake and talk again.","source":"eapc-2024","quote":"Secondly, it also encompasses proportionality in terms of timing, as intermittent sedation will be more appropriate than continuous sedation earlier in the course of the illness to provide temporary relief whilst waiting for treatment benefit from other therapeutic approaches (transient sedation) or to give the patient a break from the current burdensome situation (respite sedation) before regaining consciousness (stat. 1).","grade":"Delphi statement 1 (high or very high consensus)"},{"action":"Titrate the sedative to the lowest dose that relieves the suffering, keeping the person able to interact where possible, rather than aiming straight for unconsciousness","why":"Deeper sedation than needed takes away time the person could still be aware of those around them.","source":"eapc-2024","quote":"First in terms of depth of sedation, with the administration of sedative medications being titrated to the lowest dosage that will provide adequate relief of suffering and maintain interactive function as far as possible, instead of aiming straight at unconsciousness (stats. 1 and 5).","grade":"Delphi statements 1 and 5 (high or very high consensus)"},{"action":"Start with midazolam, by bolus and then about 1 mg an hour subcutaneously or intravenously, adjusting every 1 to 2 hours to effect; halve the doses where there are risk factors such as age over 60, low weight or severe kidney or liver disease","why":"Midazolam acts quickly, wears off quickly and can be given under the skin, so the depth can be adjusted.","source":"eapc-2024","quote":"Use 1 mg/h (SC and IV) and then adjust as needed.","grade":"Delphi statements 27 and 28, Table 5 (high or very high consensus)"},{"action":"If midazolam is not enough, add levomepromazine (or chlorpromazine); if that fails, consider propofol under an anaesthetist's supervision","why":"Some people need a second drug of a different kind to settle; propofol is powerful and needs expert supervision.","source":"eapc-2024","quote":"Administration under the supervision of an anaesthesiologist is advisable.","grade":"Delphi statements 27 and 28, Table 5 (high or very high consensus)"},{"action":"Decide on fluids separately from the decision to sedate","why":"Whether to give fluids is its own decision, based on the person's wishes and condition, not something that follows automatically from sedation.","source":"eapc-2024","quote":"No specific period of remaining life expectancy has been defined for the use of palliative sedation based on the three key principles of (1) refractoriness of suffering, (2) proportionality, which has been explicitly introduced in the definition of palliative sedation and (3) independent decision-making for hydration.","grade":"Delphi statements 1 and 35 (high or very high consensus)"},{"action":"Outside emergencies, plan an interruption of sedation to reassess with the patient","why":"Things change; waking the person lets the team check whether sedation is still needed and still what they want.","source":"eapc-2024","quote":"Apart from emergency situations at the end of life, a planned interruption of the sedation is recommended, whenever possible, to reassess the situation with the patient.","grade":"Not a numbered statement in the text read"},{"action":"Monitor comfort and depth of sedation with a validated tool, such as the Richmond Agitation Sedation Scale palliative version","why":"Regular, structured checks show whether the person is comfortable and whether the dose needs to change.","source":"eapc-2024","quote":"These 42 statements with their explanatory text are organised into 12 distinct domains ( Table 4 ) and include a table of medications ( Table 5 ) and four assessment tools for monitoring","grade":"Framework content"}],"bestInClass":{"statement":"The revised EAPC framework (2024) is the most recent international standard: confirm refractoriness with expert consultation, decide with the patient, apply proportionality in depth and timing, start with midazolam and escalate stepwise, decide hydration separately, reassess through planned interruptions, and monitor with validated tools. It sets no life-expectancy threshold, unlike several earlier national guidelines. The Korean guideline (2020) agrees but grades the evidence low (D IIb). The ESMO 2014 guideline could not be read.","sources":["eapc-2024","korea-2020"]},"variants":[{"name":"A life-expectancy threshold for continuous deep sedation","differs":"Allows continuous deep sedation only when death is expected within a set period, such as hours to days or up to two weeks.","evidence":"The EAPC 2024 framework notes that life expectancy is handled very differently across guidelines and deliberately sets no period; its Delphi panel could not agree a definition of the final stages of life. The national guidelines it compared were not read here.","sources":["eapc-2024"]},{"name":"Mandatory specialist palliative care consultation","differs":"Requires a palliative care specialist to agree before any palliative sedation starts.","evidence":"Some EAPC experts called for it and others rejected it because access to specialist palliative care is uneven; the framework strongly recommends consultation with palliative care and/or other experts rather than making it mandatory.","sources":["eapc-2024"]}],"grades":[{"claim":"Palliative sedation may be considered for severe symptoms that do not improve with available treatments in the dying process","grade":"D IIb","source":"korea-2020","quote":"For severe symptoms that do not improve with available treatments in patients in the dying process, palliative sedation may be considered."},{"claim":"All 42 EAPC statements reached high or very high consensus after two Delphi rounds","grade":"32 high, 10 very high consensus","source":"eapc-2024","quote":"Following the second Delphi round, 32 statements reached a high and 10 a very high level of consensus ( Table 3 )."},{"claim":"Evidence base for palliative sedation","grade":"Lack of clinical trials and prospective studies (as stated by the authors)","source":"eapc-2024","quote":"The updated literature shows that there is still a lack of clinical trials and prospective studies."}],"sources":[{"key":"eapc-2024","label":"Revised European Association for Palliative Care (EAPC) recommended framework on palliative sedation: an international Delphi study","publisher":"Palliative Medicine (EAPC)","year":2024,"url":"https://doi.org/10.1177/02692163231220225","doi":"10.1177/02692163231220225","gradingScheme":"Delphi consensus: low (<60% agreement), moderate (60 to 79%), high (80 to 89%), very high (>90%). Statements are not graded for evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"korea-2020","label":"Clinical Practice Guideline for Care in the Last Days of Life","publisher":"Korean Journal of Hospice and Palliative Care","year":2020,"url":"https://doi.org/10.14475/kjhpc.2020.23.3.103","doi":"10.14475/kjhpc.2020.23.3.103","gradingScheme":"Evidence level (A to D) and recommendation class (I, IIa, IIb), printed in that order.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2014","label":"ESMO Clinical Practice Guidelines for the management of refractory symptoms at the end of life and the use of palliative sedation","publisher":"ESMO (Annals of Oncology)","year":2014,"url":"https://doi.org/10.1093/annonc/mdu238","doi":"10.1093/annonc/mdu238","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 42 EAPC statements are printed in an image table in the open copy and could not be read as text; the steps rest on the article's own description of them and on its medication table.","The ESMO 2014 guideline on refractory symptoms and palliative sedation could not be read.","The evidence behind palliative sedation is consensus: the EAPC authors note a continuing lack of clinical trials and prospective studies.","National law and practice differ, for example on the role of the legal representative; the framework says it may need local adaptation."]},{"id":"radiotherapy-patient-identification-and-time-out","kind":"protocol","name":"Patient identification and pre-treatment time-out in radiotherapy","aka":["radiotherapy ID check","patient ID check at the linac","radiotherapy time-out","pause and check radiotherapy","wrong patient radiotherapy","wrong site radiotherapy","correct side check radiotherapy","positive patient identification"],"tldr":"Every time you come for radiotherapy, even on the last day and even when the staff know you well, they will ask you to say your full name, date of birth and often your address, rather than asking you to confirm them. They also check that the plan on the machine is yours and that the right side is being treated. This is one of the most important safety checks in radiotherapy.","summary":"In the UK the check is a legal requirement: IR(ME)R 2017 Schedule 2 requires the employer's written procedures to include procedures to identify correctly the individual to be exposed. Towards Safer Radiotherapy (RCR, SCoR, IPEM, NPSA, BIR, 2008) sets the method: open questions that elicit an active response (full name, date of birth, address), never closed yes/no questions; formal identification for every procedure even when the patient is well known, because mistakes are more likely later in treatment than at the beginning; a specified procedure for patients who cannot identify themselves; and confirmation of the correct side at set-up for each fraction. It recommends exploring technology such as bar codes, photographs in the record and verify system and biometrics. The WHO Radiotherapy Risk Profile (2008) rates incorrect patient identification as a high-impact risk at every stage and lists open questions with an active response, a minimum of three points of identification, photo identification and a unique identifier as solutions.\n\nThe time-out is less settled. AAPM TG-100 (2016) includes two forms of identification and a time-out in its example day-1 checklist, notes that the Joint Commission requires a time-out for procedures, and says there is no specific guidance requiring one at every treatment session, though it is a good idea; at day 1, it suggests the radiation oncologist take part. ASTRO's Safety is No Accident (2019) could not be read.","asOf":"2026-11-11","links":[],"tags":[],"related":["radiotherapy-pregnancy-and-breastfeeding-enquiry"],"cancers":[],"sections":[],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Each day the radiographers will ask you to say your name, date of birth and address. They do this every time, on purpose, so the right treatment goes to the right person.","domain":"radiotherapy","setting":{"who":["radiographer","doctor","patient-or-carer"],"where":["radiotherapy-department"]},"population":"Every patient at every radiotherapy planning and treatment attendance, external beam and brachytherapy, adults and children. Children and adults who cannot identify themselves need the department's own written alternative (for example a parent, carer or wristband), which the sources require but do not specify.","trigger":"Each time a patient is called for a planning scan or a treatment, before any exposure.","steps":[{"action":"Have a written procedure for identifying patients before any exposure, including what to do when a patient cannot identify themselves","why":"In the UK this is the law, and a written procedure means every member of staff does the check the same way.","source":"irmer-2017","quote":"to identify correctly the individual to be exposed to ionising radiation;","grade":"Statutory requirement (IR(ME)R 2017, Schedule 2, 1(a))"},{"action":"Ask open questions the patient must answer in their own words (full name, date of birth, address), never questions they can say yes to","why":"A person who is nervous, hard of hearing or expecting to be called can easily say yes to someone else's name; saying their own details out loud avoids that.","source":"towards-safer-radiotherapy-2008","quote":"It is vital that identification verification is performed by asking open questions, which elicit a positive response from the patient (see Table 5.1).","grade":"Recommendation (consensus of RCR, SCoR, IPEM, NPSA and BIR)"},{"action":"Match the answers against the treatment record on the machine every time, using at least three identifiers, a unique patient number and the photograph in the record where available","why":"Checking several details against the record, not just the name, catches two patients with similar names and records opened in error.","source":"who-risk-profile-2008","quote":"ID check open questions, eliciting an active response","grade":"Listed solution to a high-impact risk"},{"action":"Do the full check at every attendance, including the last, even when the patient is well known to the staff","why":"Familiarity makes people skip the check, and errors are more likely later in a course than at the start.","source":"towards-safer-radiotherapy-2008","quote":"Formal identification must be carried out for all procedures even when the patient is well known.","grade":"Recommendation (consensus)"},{"action":"Confirm the side and site to be treated at set-up for every fraction, and confirming it with the patient is good practice","why":"Treating the wrong side is one of the errors a patient can help prevent.","source":"towards-safer-radiotherapy-2008","quote":"Treatment of the correct side should also be confirmed at the set-up for each fraction during a course of treatment.","grade":"Recommendation (consensus)"},{"action":"Before the first treatment, pause as a team to confirm the patient, the plan loaded on the machine, the site and side, and any changes in the prescription","why":"A short shared check before the first fraction catches the wrong plan or an unsigned change before any dose is given.","source":"aapm-tg100-2016","quote":"Patient and treatment plan to be used are identified correctly using two forms of identification check and time-out procedure","grade":"Example checklist item (TG-100 is a method, not a standard)"},{"action":"Consider a time-out at every treatment session, not only the first","why":"The same errors can happen on any day; no standard read requires it, but the AAPM report calls it a good idea.","source":"aapm-tg100-2016","quote":"Although there is no specific guidance that a time out should be required for each treatment session, it is a good idea.","grade":"Suggestion in a task group report"}],"bestInClass":{"statement":"Positive identification by open questions eliciting an active response (name, date of birth, address) against the record on the machine, at every attendance including when the patient is well known, with a written alternative for patients who cannot identify themselves, and confirmation of the treated side at each fraction (Towards Safer Radiotherapy 2008; a legal requirement in the UK under IR(ME)R 2017; WHO 2008 adds a minimum of three identifiers, photo identification and a unique identifier). A time-out before the first fraction is in the AAPM TG-100 example checklist; whether one is needed at every fraction is not settled by any source read, TG-100 calling it a good idea without a requirement. The sources do not disagree; they differ in how much they specify.","sources":["towards-safer-radiotherapy-2008","irmer-2017","who-risk-profile-2008","aapm-tg100-2016"]},"variants":[{"name":"Biometric or bar-code identification linked to the treatment record","differs":"A fingerprint, bar-coded wristband or card calls up the patient's record and confirms the match at the room door.","evidence":"Towards Safer Radiotherapy describes one department using fingerprint identification at the department entrance and the room entrance, and bar-coded wristbands in two UK departments, and recommends that such technology be explored; it notes that these systems compel the identification step. No comparative study was read.","sources":["towards-safer-radiotherapy-2008"]},{"name":"Patient photograph in the record and verify system","differs":"The set-up screen shows a photograph of the patient taken at planning, checked against the person on the couch.","evidence":"Named by Towards Safer Radiotherapy as a feature of some record and verify systems and by WHO 2008 as a solution (photo ID); no study of its effect was read.","sources":["towards-safer-radiotherapy-2008","who-risk-profile-2008"]},{"name":"Day-one time-out with the radiation oncologist","differs":"The doctor joins the radiographers at the machine for the first treatment to confirm the plan matches their intent.","evidence":"Suggested by AAPM TG-100 as a guard against deviations from physician intent; not required by any source read.","sources":["aapm-tg100-2016"]}],"grades":[{"claim":"Correct patient identification at every step, with procedures eliciting an active response; explore new technology","grade":"Recommendation (consensus)","source":"towards-safer-radiotherapy-2008","quote":"Correct patient identification is essential at every step. Procedures eliciting an active response from the patient must be used. The use of new technology to assist patient identification should be explored."},{"claim":"Errors are more likely later in treatment than at the beginning","grade":"Observation from UK incident data","source":"towards-safer-radiotherapy-2008","quote":"Mistakes are more likely later in treatment than at the beginning."},{"claim":"The employer must specify the steps for patients who cannot identify themselves","grade":"Recommendation (consensus)","source":"towards-safer-radiotherapy-2008","quote":"Patients who cannot identify themselves pose particular problems and the employer must specify the steps to be taken in these circumstances."},{"claim":"Written procedures to identify correctly the individual to be exposed","grade":"Statutory requirement","source":"irmer-2017"}],"sources":[{"key":"towards-safer-radiotherapy-2008","label":"Towards Safer Radiotherapy","publisher":"The Royal College of Radiologists, Society and College of Radiographers, Institute of Physics and Engineering in Medicine, National Patient Safety Agency and British Institute of Radiology","year":2008,"url":"https://www.rcr.ac.uk/media/zbtjvtsr/rcr-publications_towards-safer-radiotherapy_april-2008.pdf","gradingScheme":"Not graded: each section ends with a boxed recommendation agreed by the five bodies.","read":"full-text","accessed":"2026-11-11"},{"key":"irmer-2017","label":"The Ionising Radiation (Medical Exposure) Regulations 2017, Schedule 2: Employer's procedures","publisher":"UK Government (SI 2017/1322)","year":2017,"url":"https://www.legislation.gov.uk/uksi/2017/1322/schedule/2/made","gradingScheme":"Law: the employer's written procedures must include these.","read":"full-text","accessed":"2026-11-11"},{"key":"who-risk-profile-2008","label":"Radiotherapy Risk Profile: technical manual (WHO/IER/PSP/2008.12)","publisher":"World Health Organization","year":2008,"url":"https://web.archive.org/web/2015/http://www.who.int/patientsafety/activities/technical/radiotherapy_risk_profile.pdf","gradingScheme":"Risks rated by impact (high, medium, low) with potential solutions listed; no recommendation grades.","read":"full-text","accessed":"2026-11-11"},{"key":"aapm-tg100-2016","label":"The report of Task Group 100 of the AAPM: application of risk analysis methods to radiation therapy quality management","publisher":"American Association of Physicists in Medicine (Medical Physics; Huq et al.)","year":2016,"url":"https://doi.org/10.1118/1.4947547","doi":"10.1118/1.4947547","gradingScheme":"A method (failure modes and effects analysis) with example checklists; not graded recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"astro-safety-2019","label":"Safety is No Accident: a framework for quality radiation oncology care (2019 edition)","publisher":"American Society for Radiation Oncology","year":2019,"url":"https://www.astro.org/patient-care-and-research/patient-safety/safety-is-no-accident","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["ASTRO's Safety is No Accident (2019), the main US framework, could not be read (bot challenge), and the Joint Commission Universal Protocol is reported here only as TG-100 describes it.","Towards Safer Radiotherapy dates from 2008 and the WHO Radiotherapy Risk Profile from 2008; no newer UK or international document on radiotherapy patient identification was found. The UK Health Security Agency's annual IR(ME)R reports, which count identification errors, were not read.","No source read gives evidence that a time-out at every fraction reduces errors beyond the daily identity check; TG-100 suggests it without requiring it.","How departments should identify patients who cannot answer for themselves (children, people with dementia, people who do not share a language with staff) is left to local procedure by every source read.","No comparative study of photographs, wristbands or biometrics in radiotherapy was read."]},{"id":"peripheral-cannula-for-anticancer-therapy","kind":"protocol","name":"Peripheral cannula for anticancer treatment: vein choice, siting and checks, including vesicants","aka":["peripheral IV for chemotherapy","cannulation for chemotherapy","peripheral venous catheter for chemotherapy","PIVC for vesicants","short peripheral catheter chemotherapy","venflon for chemo"],"tldr":"If your chemotherapy goes in through a small tube (cannula) in a vein in your arm, the nurse should choose a good vein in the forearm, avoid joints and the back of the hand, put in a fresh cannula, check it works before and during the drip, and ask you to say at once if it stings, burns or swells.","summary":"Most guidance on peripheral cannulas comes from infection prevention, and much of the chemotherapy-specific detail from extravasation guidelines. The most recent graded guideline on the subject, the Japanese JSCN/JSMO/JASPO extravasation guideline (2024, GRADE), weakly recommends a central venous device rather than peripheral veins for people starting anticancer drugs (certainty B), recommends siting a peripheral cannula upstream (closer to the heart) of any previous puncture (weak, C), recommends against routine timed replacement of a peripheral cannula during anticancer treatment (weak, C), and, unless strict rate control is needed, weakly recommends against an infusion pump for peripheral anticancer infusions (C).\n\nCDC/HICPAC (2011, updated 2017) asks for an upper-limb site in adults (Category II), never a steel needle for anything that can cause necrosis if it leaks (IA), and a midline or PICC rather than a short cannula when therapy will likely exceed six days (II); it finds no need to replace peripheral catheters more often than every 72 to 96 hours (IB) and makes no recommendation on replacing only when clinically indicated. epic3 asks for 2% chlorhexidine in 70% alcohol, allowed to dry, before insertion (Class D/GPP). Practice detail comes from UK network guidance (West Midlands, 2017): avoid joints, the antecubital fossa and the back of the hand; prefer large forearm veins; use a new cannula, the smallest gauge in the largest vein; repeat attempts above the previous site; check for blood return before and throughout; give vesicants first; consider central access for long vesicant infusions or after a previous extravasation.","asOf":"2026-11-11","links":[],"tags":[],"related":["chemotherapy-extravasation-management","venous-access-device-selection-for-anticancer-therapy","sact-administration-checks-at-the-chair"],"cancers":[],"sections":[],"technologies":["infusion-devices-vascular-access","smart-infusion-pumps"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["extravasation-infusion-reaction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A thin tube is put into a vein in your arm for the treatment. Tell the nurse straight away if it hurts, stings, burns or swells, during the drip or after.","domain":"vascular-access","setting":{"who":["nurse","patient-or-carer"],"where":["chemotherapy-day-unit","ward","outpatient-clinic"]},"population":"Adults receiving intravenous anticancer drugs through a short peripheral cannula. Children have their own site rules (CDC allows lower limb and scalp in infants). People who will need treatment for more than about six days, a continuous vesicant infusion, or who have had a previous extravasation are usually better served by a central device (see the device-selection protocol).","trigger":"Intravenous anticancer treatment is to be given through a peripheral vein.","steps":[{"action":"Check whether a central venous device would be better before using a peripheral vein, especially for vesicants, long infusions or a course of many cycles","why":"Central devices avoid repeated needle sticks and make it less likely a drug leaks into the arm.","source":"jscn-2024","quote":"It is weakly recommended to place a CV device in patients planning to receive anticancer drugs.","grade":"Recommend (weak), certainty B"},{"action":"Use a vein in the arm; in adults do not use the legs","why":"Arm veins carry less risk of infection and clots than leg veins.","source":"cdc-hicpac-2011","quote":"In adults, use an upper-extremity site for catheter insertion.","grade":"Category II"},{"action":"Choose a large, straight forearm vein, and avoid joints, the inner elbow and the back of the hand, and any arm with lymphoedema","why":"If a drug leaks where there is little soft tissue, tendons and nerves can be damaged; a big vein dilutes the drug quickly.","source":"west-midlands-2017","quote":"Cannulating over joints, the anticubital fossa or dorsum of the hand should be avoided as tissue damage due to extravasation may have serious consequences as there is little soft tissue for the protection of underlying nerves and tissues."},{"action":"Clean the skin with 2% chlorhexidine in 70% alcohol and let it dry before inserting the cannula","why":"It kills skin bacteria that could otherwise enter the vein with the cannula.","source":"epic3","quote":"Decontaminate the skin at the insertion site with a single-use application of 2% chlorhexidine gluconate in 70% isopropyl alcohol (or povidone iodine in alcohol for patients with sensitivity to chlorhexidine) and allow to dry before inserting a peripheral vascular access device.","grade":"Class D/GPP"},{"action":"Never give anticancer drugs through a steel (butterfly) needle; use a plastic cannula","why":"Steel needles slip out of the vein more easily, and a drug that leaks can destroy tissue.","source":"cdc-hicpac-2011","quote":"Avoid the use of steel needles for the administration of fluids and medication that might cause tissue necrosis if extravasation occurs [33, 34]. Category IA","grade":"Category IA"},{"action":"If an attempt fails, site the next cannula upstream (closer to the heart) of the earlier puncture","why":"A drug given below a fresh puncture can leak out through the hole higher up the vein.","source":"jscn-2024","quote":"It is weakly recommended to place a peripheral venous catheter centrally (upstream) from the site of preceding puncture for patients receiving anticancer drug therapy from the peripheral veins.","grade":"Recommend (weak), certainty C"},{"action":"Check the cannula works before and throughout the treatment: blood comes back, it flushes without resistance and a compatible fluid runs freely","why":"A cannula that has slipped out of the vein lets the drug leak into the tissue.","source":"west-midlands-2017","quote":"Venous access should be assessed and tested immediately prior to and frequently throughout administration of any cytotoxic drugs, checking for backflow, no resistance on syringe plunger on administration and acceptance of free flowing compatible infusion fluid"},{"action":"Do not replace the cannula on a fixed timetable during treatment; replace it when there is a reason","why":"Routine re-siting causes pain and uses up veins without reducing leaks.","source":"jscn-2024","quote":"It is weakly recommended not to replace peripheral venous catheters with specific time interval in patients receiving anticancer drugs.","grade":"Not recommend (weak), certainty C"},{"action":"Unless the drug needs strict rate control, consider running peripheral anticancer infusions by gravity rather than a pump","why":"A pump keeps pushing fluid even if the cannula has slipped, so a leak can grow before anyone notices.","source":"jscn-2024","quote":"Unless strict dose rate control is required, avoidance of infusion pump is weakly recommended when administering anticancer drugs via the peripheral vein.","grade":"Recommend or not recommend (weak), certainty C"},{"action":"Ask the person to report at once any stinging, burning, pain or change in feeling at the cannula during treatment","why":"The person often feels a leak before anyone can see it.","source":"west-midlands-2017","quote":"Patients should be informed of the importance of reporting immediately any change in sensation, stinging or burning during the administration of chemotherapy"}],"bestInClass":{"statement":"Consider a central device first (JSCN 2024, weak, B; MAGIC-ONC 2025 for device choice). If a peripheral vein is used: an upper-limb site (CDC II), chlorhexidine-alcohol skin preparation allowed to dry (epic3 D/GPP), never a steel needle (CDC IA), repeat attempts upstream of earlier punctures (JSCN weak, C), no routine timed replacement (JSCN weak, C), gravity rather than a pump unless strict rate control is needed (JSCN weak, C), and patency checks before and throughout. Guidelines differ on replacement: CDC sees no need to replace more often than every 72 to 96 hours and makes no recommendation on replacing only when clinically indicated, while JSCN recommends against timed replacement during anticancer treatment. Vein choice within the arm (forearm, avoiding joints, the antecubital fossa and the back of the hand) rests on UK network guidance and expert sources, not trials.","sources":["jscn-2024","cdc-hicpac-2011","epic3","west-midlands-2017","magic-onc-2025"]},"variants":[{"name":"UK network practice for vesicants (West Midlands, 2017)","differs":"Adds a new cannula sited immediately before treatment, the smallest gauge in the largest vein, no more than two attempts by one practitioner, vesicants given first while the vein is at its best, a clear dressing with the site always visible, and central access for vesicant infusions of 12 to 24 hours or after a previous extravasation.","evidence":"Network guidance citing nursing texts and expert sources, not trials; past its own review date (July 2019).","sources":["west-midlands-2017"]},{"name":"Insertion bundle for short peripheral catheters (GAVeCeLT-IVAS SISPeC, 2026)","differs":"Six steps for every short cannula: examine both arms with and without a tourniquet, avoid areas of flexion and prefer forearm veins or the upper-arm cephalic vein, hand hygiene and skin antisepsis, cannula-over-needle insertion with a tourniquet, connection, and securement with protection of the exit site.","evidence":"An Italian society consensus bundle described as evidence-based, not specific to anticancer drugs; read as an abstract.","sources":["sispec-2026"]},{"name":"Timed replacement every 72 to 96 hours","differs":"Re-sites peripheral cannulas at a fixed interval to reduce infection and phlebitis.","evidence":"CDC (IB) says there is no need to replace more often than every 72 to 96 hours in adults, and leaves replacement only when clinically indicated as an unresolved issue. JSCN 2024 found routine replacement reduced infiltration but not extravasation and judged that its harms outweigh its benefit during anticancer treatment.","sources":["cdc-hicpac-2011","jscn-2024"]}],"grades":[{"claim":"Use a midline or PICC instead of a short peripheral cannula when IV therapy will likely exceed six days","grade":"Category II","source":"cdc-hicpac-2011","quote":"Use a midline catheter or peripherally inserted central catheter (PICC), instead of a short peripheral catheter, when the duration of IV therapy will likely exceed six days."},{"claim":"No need to replace peripheral catheters more often than every 72 to 96 hours in adults","grade":"Category IB","source":"cdc-hicpac-2011","quote":"There is no need to replace peripheral catheters more frequently than every 72-96 hours to reduce risk of infection and phlebitis in adults [36, 140, 141]."},{"claim":"Replacing peripheral catheters in adults only when clinically indicated","grade":"Unresolved issue","source":"cdc-hicpac-2011","quote":"No recommendation is made regarding replacement of peripheral catheters in adults only when clinically indicated [142–144]."}],"sources":[{"key":"jscn-2024","label":"Multidisciplinary clinical practice guidelines for the management of extravasation of anticancer drugs (JSCN, JSMO, JASPO)","publisher":"ESMO Open (Japanese Society of Cancer Nursing, Japanese Society of Medical Oncology, Japanese Society of Pharmaceutical Oncology)","year":2024,"url":"https://doi.org/10.1016/j.esmoop.2024.103932","doi":"10.1016/j.esmoop.2024.103932","gradingScheme":"GRADE and Minds 2020: recommend or not recommend, strong or weak; certainty of evidence A (strong) to D (very weak).","read":"full-text","accessed":"2026-11-11"},{"key":"cdc-hicpac-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"epic3","label":"epic3: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England","publisher":"Journal of Hospital Infection (Loveday et al., commissioned by the Department of Health)","year":2014,"url":"https://doi.org/10.1016/S0195-6701(13)60012-2","doi":"10.1016/S0195-6701(13)60012-2","gradingScheme":"SIGN-style classes A to D, GPP (good practice point), H&S (health and safety legislation).","read":"full-text","accessed":"2026-11-11"},{"key":"west-midlands-2017","label":"Guidelines for the Management of Extravasation of a Systemic Anti-Cancer Therapy including Cytotoxic Agents (v1)","publisher":"West Midlands Expert Advisory Group for SACT (NHS England)","year":2017,"url":"https://www.england.nhs.uk/midlands/wp-content/uploads/sites/46/2019/05/management-extravasation-of-a-systemic-anti-cancer-therapy-including-cytotoxic-agents.pdf","read":"full-text","accessed":"2026-11-11"},{"key":"magic-onc-2025","label":"The Michigan Appropriateness Guide for Intravenous Catheters in Adult Patients With Cancer (MAGIC-ONC)","publisher":"Annals of Internal Medicine","year":2025,"url":"https://doi.org/10.7326/ANNALS-25-02523","doi":"10.7326/ANNALS-25-02523","gradingScheme":"RAND/UCLA Appropriateness Method: scenarios rated appropriate, neutral/uncertain or inappropriate by a 9-member panel.","read":"abstract","accessed":"2026-11-11"},{"key":"sispec-2026","label":"A GAVeCeLT-IVAS bundle for safe insertion of short peripheral catheters: The SISPeC protocol","publisher":"Journal of Vascular Access (GAVeCeLT and IVAS)","year":2026,"url":"https://doi.org/10.1177/11297298261442098","doi":"10.1177/11297298261442098","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-eons-2012","label":"Management of chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines","publisher":"ESMO and EONS (Annals of Oncology)","year":2012,"url":"https://doi.org/10.1093/annonc/mds294","doi":"10.1093/annonc/mds294","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO-EONS extravasation guideline (2012) and the INS Infusion Therapy Standards (2024), which both address peripheral cannulation for vesicants, could not be read.","Vein choice within the arm (forearm rather than hand or antecubital fossa), cannula gauge, the limit on attempts and giving vesicants first rest on expert and network guidance, not trials.","Whether a cannula should be sited on the side of a previous mastectomy without lymphoedema is unsettled; the West Midlands guidance calls it 'still a matter of discussion'.","MAGIC-ONC and the SISPeC bundle were read as abstracts only."]},{"id":"picc-and-tunnelled-line-care","kind":"protocol","name":"PICC and tunnelled central line care: dressing, hub cleaning, flushing and living with the line","aka":["PICC care","PICC dressing change","Hickman line care","tunnelled line care","central line dressing","scrub the hub","needleless connector care","bionector change","line flush","CVC maintenance","CHG dressing"],"tldr":"A PICC (a thin tube in the arm) or a tunnelled line (in the chest) needs regular care: a clear sealed dressing changed about once a week, the end cap cleaned before every use, and a salt-water flush to keep it open. Keep it dry and out of baths and swimming pools, and call your team if it gets red, sore, leaks, will not flush or you get a fever.","summary":"Line care rests on general central line infection-prevention guidance rather than oncology trials. Hand hygiene (CDC IB) and aseptic technique (NICE CG139). Skin antisepsis at dressing changes with 2% chlorhexidine in 70% alcohol, allowed to dry (epic3 Class A; CDC IA for above 0.5% chlorhexidine with alcohol). A sterile transparent or gauze dressing covers the site (CDC IA); gauze while the site oozes or the patient sweats (CDC II). Transparent dressings are changed at least every 7 days and gauze every 2 days, or sooner if damp, loose or soiled (SHEA, moderate quality, non-tunnelled lines; NICE; epic3); for tunnelled or implanted lines CDC says no more than weekly until the site heals (II), and neither CDC nor epic3 settles whether a healed tunnelled exit site needs a dressing at all.\n\nChlorhexidine-containing dressings are an essential practice in SHEA 2022 (high quality, acute care), epic3 says consider them (Class B) and NICE supports Tegaderm CHG in critically ill adults; SHEA says their value for long-term catheters with healed sites is unclear. Hubs, needleless connectors and injection ports are disinfected before every access (CDC IA; SHEA moderate), with at least 5 seconds of friction (SHEA) or 15 seconds (epic3). Antiseptic caps are an additional practice in SHEA; NICE found insufficient evidence for routine use of Curos. Flush with saline after every use (ESMO [II, B]) and lock frequently accessed lumens with saline (epic3 Class A); the Cochrane review (2022) found heparin locks may reduce occlusion on low-certainty evidence. Sutureless securement (CDC II). No submersion; showers with the line covered (CDC IB). No antibiotic ointment on the site (CDC IB). Remove the line when it is no longer needed (SHEA moderate).","asOf":"2026-11-11","links":[],"tags":[],"related":["implanted-port-access-and-care","suspected-central-line-infection","catheter-related-thrombosis-in-cancer","central-line-maintenance-bundle","community-care-of-vascular-access-devices"],"cancers":[],"sections":[],"technologies":["picc-lines","catheter-securement-devices","needleless-connector-disinfecting-caps","catheter-lock-solutions","infusion-devices-vascular-access"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Keep your line's dressing clean and dry, and let trained staff change it weekly. Do not swim or soak it. Call your team at once for a fever, redness, swelling or a leak.","domain":"vascular-access","setting":{"who":["nurse","patient-or-carer"],"where":["chemotherapy-day-unit","ward","home","community"]},"population":"Adults with cancer who have a PICC or a tunnelled, cuffed central venous catheter. Most recommendations come from infection-prevention guidance for all central lines, much of it from intensive care; SHEA's dressing interval is for non-tunnelled lines. Children, neonates and dialysis catheters follow their own guidance.","trigger":"Routine care of a PICC or tunnelled line: each access, each dressing change and each maintenance flush.","steps":[{"action":"Clean your hands before and after touching the line, the site or the dressing","why":"Hands are the commonest route by which germs reach a line.","source":"cdc-hicpac-2011","quote":"Hand hygiene should be performed before and after palpating catheter insertion sites as well as before and after inserting, replacing, accessing, repairing, or dressing an intravascular catheter.","grade":"Category IB"},{"action":"Use aseptic technique for site care and whenever the line is accessed","why":"The tip of the line sits in a large vein near the heart, so anything touching the connector must stay sterile.","source":"nice-cg139","quote":"An aseptic technique must be used for vascular access device catheter site care and when accessing the system","grade":"[new 2012]"},{"action":"At each dressing change, look at the site for redness, swelling, discharge or a line that has moved","why":"Infection and a line slipping out are easiest to catch at the dressing change.","source":"cdc-hicpac-2011","quote":"Monitor the catheter sites visually when changing the dressing or by palpation through an intact dressing on a regular basis, depending on the clinical situation of the individual patient.","grade":"Category IB"},{"action":"Clean the site with 2% chlorhexidine in 70% alcohol and let it dry completely","why":"Chlorhexidine with alcohol kills skin bacteria best, and works fully only once dry.","source":"epic3","quote":"Use a single-use application of 2% chlorhexidine gluconate in 70% isopropyl alcohol (or povidone iodine in alcohol for patients with sensitivity to chlorhexidine) to clean the central catheter insertion site during dressing changes, and allow to air dry.","grade":"Class A"},{"action":"Cover the site with a sterile transparent dressing, or sterile gauze while it oozes or the person sweats heavily","why":"A clear dressing lets the site be checked without removing it; gauze absorbs blood or sweat that would lift a clear one.","source":"cdc-hicpac-2011","quote":"Use either sterile gauze or sterile, transparent, semipermeable dressing to cover the catheter site","grade":"Category IA"},{"action":"Change transparent dressings every 7 days and gauze every 2 days, and sooner if damp, loose or soiled","why":"A lifted or wet dressing lets germs in; changing a sound one too often irritates the skin and disturbs the line.","source":"shea-clabsi-2022","quote":"For non-tunneled CVCs in adults and children, change transparent dressings and perform site care with a chlorhexidine-based antiseptic at least every 7 days or immediately if the dressing is soiled, loose, or damp. Change gauze dressings every 2 days or earlier if the dressing is soiled, loose, or damp (Quality of Evidence: MODERATE)","grade":"Quality of Evidence: MODERATE"},{"action":"Consider a chlorhexidine-containing dressing","why":"In trials, mostly in intensive care, these dressings reduced line bloodstream infections.","source":"shea-clabsi-2022","quote":"Use chlorhexidine-containing dressings for CVCs in patients over 2 months of age (Quality of Evidence: HIGH)","grade":"Quality of Evidence: HIGH"},{"action":"Secure a PICC with a sutureless securement device","why":"A line that moves in and out carries germs in and can slip out of position.","source":"cdc-hicpac-2011","quote":"Use a sutureless securement device to reduce the risk of infection for intravascular catheters","grade":"Category II"},{"action":"Scrub the hub or needleless connector with an antiseptic before every use, and access it only with sterile devices","why":"The connector is touched many times a day; it is a main route for germs into a long-term line.","source":"cdc-hicpac-2011","quote":"Minimize contamination risk by scrubbing the access port with an appropriate antiseptic (chlorhexidine, povidone iodine, an iodophor, or 70% alcohol) and accessing the port only with sterile devices","grade":"Category IA"},{"action":"Scrub with friction for at least 5 seconds (epic3 says 15) and let it dry before connecting","why":"Rubbing removes the film of germs on the connector; a few seconds are not enough.","source":"shea-clabsi-2022","quote":"Apply mechanical friction for a minimum of 5 seconds to reduce contamination."},{"action":"Change needleless connectors no more often than every 72 hours, or as the maker recommends","why":"Changing connectors more often adds handling without reducing infection.","source":"cdc-hicpac-2011","quote":"Change needleless connectors no more frequently than every 72 hours or according to manufacturers’ Recommendations for the purpose of reducing infection rates","grade":"Category II"},{"action":"Flush with 0.9% saline after every infusion or blood sample, and lock frequently used lumens with saline","why":"Flushing clears blood and drugs that would otherwise block the line or mix in it.","source":"epic3","quote":"Use sterile normal saline for injection to flush and lock catheter lumens that are accessed frequently.","grade":"Class A"},{"action":"Do not put antibiotic ointment or cream on the site","why":"It encourages fungal infection and resistant bacteria.","source":"cdc-hicpac-2011","quote":"Do not use topical antibiotic ointment or creams on insertion sites, except for dialysis catheters, because of their potential to promote fungal infections and antimicrobial resistance","grade":"Category IB"},{"action":"Keep the line out of baths and swimming pools; shower only with the line and connector under a waterproof cover","why":"Soaking the site lets water and germs under the dressing.","source":"cdc-hicpac-2011","quote":"Do not submerge the catheter or catheter site in water. Showering should be permitted if precautions can be taken to reduce the likelihood of introducing organisms into the catheter (e.g., if the catheter and connecting device are protected with an impermeable cover during the shower)","grade":"Category IB"},{"action":"Ask the patient to report any change at the site or new discomfort, and to call at once with a fever","why":"Problems usually start between visits, and the person with the line sees them first.","source":"cdc-hicpac-2011","quote":"Encourage patients to report any changes in their catheter site or any new discomfort to their provider.","grade":"Category II"},{"action":"Take the line out when it is no longer needed","why":"Every day a line stays in carries a risk of infection and clots.","source":"shea-clabsi-2022","quote":"Remove nonessential catheters (Quality of Evidence: MODERATE)","grade":"Quality of Evidence: MODERATE"}],"bestInClass":{"statement":"Hand hygiene and aseptic technique; 2% chlorhexidine in alcohol on the skin, dried (epic3 Class A); a sterile transparent dressing (gauze while oozing) changed at least every 7 days, gauze every 2 days, sooner if compromised (SHEA moderate; NICE; CDC IB for damp or loose dressings); a chlorhexidine-containing dressing where available (SHEA high quality, acute care; epic3 Class B, consider); sutureless securement (CDC II); hub scrubbed before every access (CDC IA), for at least 5 seconds (SHEA) or 15 seconds (epic3); saline flush after every use (ESMO [II, B]; epic3 Class A); no submersion. The guidance differs on chlorhexidine dressings for long-term lines in healed sites (SHEA: benefit unclear) and on antiseptic caps (SHEA additional practice; NICE: insufficient evidence for routine use).","sources":["cdc-hicpac-2011","shea-clabsi-2022","epic3","nice-cg139","esmo-2015","nice-htg379","nice-htg510"]},"variants":[{"name":"Antiseptic (disinfecting) caps on needleless connectors","differs":"A cap holding alcohol is left on each needleless connector between uses, replacing or adding to the manual scrub.","evidence":"SHEA 2022 lists antiseptic-containing caps as an additional practice despite high-level evidence, because they are not considered superior to manual disinfection, and lists as unresolved whether a scrub is still needed under a cap. NICE (HealthTech guidance 510, 2019) found Curos promising but the evidence insufficient for routine NHS adoption, and recommended research including people managed in the community.","sources":["shea-clabsi-2022","nice-htg510"]},{"name":"Chlorhexidine gel or sponge dressings","differs":"Uses a dressing that releases chlorhexidine at the insertion site instead of a standard transparent dressing.","evidence":"SHEA 2022: essential practice, high quality, but unclear for long-term catheters in well-healed sites. epic3 IVAD20: consider (Class B). NICE HealthTech guidance 379 supports Tegaderm CHG for central and arterial lines in critically ill adults, estimating a saving of £93 per patient at a baseline infection rate of 1.48 per 1,000 catheter days.","sources":["shea-clabsi-2022","epic3","nice-htg379"]},{"name":"Heparin lock","differs":"Locks the line with heparinised saline after the saline flush, instead of saline alone; common for tunnelled lines.","evidence":"Cochrane 2022 (12 RCTs, 2422 adults, two oncology studies): heparin may give fewer occlusions (RR 0.70, 95% CI 0.51 to 0.95, low certainty), with no clear difference in patency duration, line infection, bleeding or heparin-induced thrombocytopenia (very low certainty). epic3 recommends saline for frequently accessed lumens (Class A).","sources":["cochrane-heparin-saline-2022","epic3"]},{"name":"No dressing on a healed tunnelled exit site","differs":"Leaves the well-healed exit site of a cuffed tunnelled line uncovered.","evidence":"epic3 says a dressing may no longer be required once the site has healed (Class D/GPP); CDC makes no recommendation (unresolved issue).","sources":["epic3","cdc-hicpac-2011"]}],"grades":[{"claim":"Replace a dressing that becomes damp, loosened or visibly soiled","grade":"Category IB","source":"cdc-hicpac-2011","quote":"Replace catheter site dressing if the dressing becomes damp, loosened, or visibly soiled"},{"claim":"Tunnelled or implanted sites: transparent dressings no more than weekly until healed","grade":"Category II","source":"cdc-hicpac-2011","quote":"Replace transparent dressings used on tunneled or implanted CVC sites no more than once per week (unless the dressing is soiled or loose), until the insertion site has healed."},{"claim":"No recommendation on dressing well-healed exit sites of long-term tunnelled lines","grade":"Unresolved issue","source":"cdc-hicpac-2011","quote":"No recommendation can be made regarding the necessity for any dressing on well- healed exit sites of long-term cuffed and tunneled CVCs."},{"claim":"Tunnelled or implanted sites: dressing every 7 days until healed; may not be needed once healed","grade":"Class D/GPP","source":"epic3","quote":"Dressings used on tunnelled or implanted catheter insertion sites should be replaced every 7 days until the insertion site has healed unless there is an indication to change them sooner. A dressing may no longer be required once the insertion site has healed."},{"claim":"Consider a chlorhexidine-impregnated sponge dressing in adults with a central line","grade":"Class B","source":"epic3","quote":"Consider the use of a chlorhexidine-impregnated sponge dressing in adult patients with a central venous catheter as a strategy to reduce catheter-related bloodstream infection."},{"claim":"Disinfect hubs, needleless connectors and injection ports before access","grade":"Quality of Evidence: MODERATE","source":"shea-clabsi-2022","quote":"Disinfect catheter hubs, needleless connectors, and injection ports before accessing the catheter (Quality of Evidence: MODERATE)"},{"claim":"Saline flush after any infusion or blood sample","grade":"[II, B]","source":"esmo-2015","quote":"Routine flushing with saline, after the completion of any infusion or blood sampling, is recommended"},{"claim":"Daily 2% chlorhexidine skin wash","grade":"Category II","source":"cdc-hicpac-2011","quote":"Use a 2% chlorhexidine wash for daily skin cleansing to reduce CRBSI"},{"claim":"Curos disinfecting cap: insufficient evidence for routine adoption","grade":"NICE HealthTech recommendation (not graded)","source":"nice-htg510","quote":"Curos disinfecting cap shows promise for preventing infections when using needleless connectors, but there is currently insufficient evidence to support the case for routine adoption in the NHS."}],"sources":[{"key":"cdc-hicpac-2011","label":"Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011 (last update October 2017)","publisher":"CDC/HICPAC","year":2011,"url":"https://www.cdc.gov/infection-control/media/pdfs/Guideline-BSI-H.pdf","gradingScheme":"Category IA (strongly recommended, strongly supported by well-designed studies), IB (strongly recommended, some studies and strong rationale, or accepted practice), IC (required by regulation), II (suggested), Unresolved issue (insufficient evidence or no consensus).","read":"full-text","accessed":"2026-11-11"},{"key":"shea-clabsi-2022","label":"Strategies to prevent central line-associated bloodstream infections in acute-care hospitals: 2022 Update","publisher":"SHEA, IDSA, APIC (Infection Control and Hospital Epidemiology, Buetti et al.)","year":2022,"url":"https://doi.org/10.1017/ice.2022.87","doi":"10.1017/ice.2022.87","gradingScheme":"Quality of evidence HIGH, MODERATE or LOW, with each recommendation classed as an essential practice, an additional approach or an unresolved issue.","read":"full-text","accessed":"2026-11-11"},{"key":"epic3","label":"epic3: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England","publisher":"Journal of Hospital Infection (Loveday et al., commissioned by the Department of Health)","year":2014,"url":"https://doi.org/10.1016/S0195-6701(13)60012-2","doi":"10.1016/S0195-6701(13)60012-2","gradingScheme":"SIGN-style classes A (1++ or consistent 1+ evidence) to D (level 3 or 4 evidence), GPP (good practice point from the guideline group's experience), H&S (health and safety legislation).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-cg139","label":"Healthcare-associated infections: prevention and control in primary and community care (CG139), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg139/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended ([2003], [2012], [new 2012]).","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology, Sousa et al.)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I (large good-quality RCT or meta-analysis) to V (no control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-htg379","label":"3M Tegaderm CHG IV securement dressing for central venous and arterial catheter insertion sites (HealthTech guidance 379, formerly MTG25; published 2015, updated 2019)","publisher":"NICE","year":2019,"url":"https://www.nice.org.uk/guidance/htg379/chapter/1-Recommendations","gradingScheme":"NICE technology recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-htg510","label":"Curos for preventing infections when using needleless connectors (HealthTech guidance 510, formerly MTG44, 2019)","publisher":"NICE","year":2019,"url":"https://www.nice.org.uk/guidance/htg510/chapter/1-Recommendations","gradingScheme":"NICE technology recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"cochrane-heparin-saline-2022","label":"Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults","publisher":"Cochrane Database of Systematic Reviews","year":2022,"url":"https://doi.org/10.1002/14651858.CD008462.pub4","doi":"10.1002/14651858.CD008462.pub4","gradingScheme":"GRADE certainty of evidence: high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"ins-2024","label":"Infusion Therapy Standards of Practice, 9th Edition","publisher":"Infusion Nurses Society (Journal of Infusion Nursing)","year":2024,"url":"https://doi.org/10.1097/NAN.0000000000000532","doi":"10.1097/NAN.0000000000000532","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-antiseptic-caps-for-long-term-lines-at-home"],"gaps":["Almost all the evidence comes from intensive care and acute hospital wards; trials of dressing type, interval and hub care in people with cancer living at home with a PICC or tunnelled line are few. SHEA's 7-day dressing interval is stated for non-tunnelled lines.","The INS Infusion Therapy Standards of Practice, 9th edition (2024), the most detailed nursing standard on PICC and tunnelled line care, could not be read. Nothing here rests on it.","CDC's July 2017 update on chlorhexidine-impregnated dressings sits on a separate page that could not be read; the 2011 guideline text marks its earlier recommendation as superseded.","Scrub time differs between sources (at least 5 seconds in SHEA, at least 15 seconds in epic3); no trial in oncology settles it.","Whether a healed tunnelled exit site needs a dressing is unresolved in CDC and left to judgement in epic3.","No source read addresses masks on the patient or the nurse during PICC or tunnelled line dressing changes; the implanted port protocol records the same finding for ports."]},{"id":"paediatric-platelet-transfusion-thresholds","kind":"protocol","name":"Platelet transfusion thresholds for children with cancer","aka":["paediatric platelet transfusion","prophylactic platelet transfusion children","platelet threshold lumbar puncture","platelet count 10 transfusion"],"tldr":"Chemotherapy can lower platelets, the blood cells that stop bleeding. A child who is not bleeding is usually given a platelet transfusion only when the count falls below 10, because giving them earlier does not prevent more bleeding. Higher counts are needed before a lumbar puncture or surgery, and for a child who is bleeding.","summary":"The 2025 AABB and ICTMG international guidelines (GRADE, 21 randomised trials and 13 observational studies), endorsed by the Children's Oncology Group in February 2026, favour restrictive platelet use. For non-bleeding patients with hypoproliferative thrombocytopenia receiving chemotherapy or undergoing allogeneic stem cell transplant, transfuse at a platelet count below 10 × 10³/μL (strong, moderate). Before lumbar puncture, transfuse below 20 × 10³/μL (strong, moderate), recognising an extremely low rate of spinal haematoma. Preterm neonates without major bleeding are transfused below 25 × 10³/μL (strong, high). A good practice statement asks clinicians to weigh symptoms, bleeding history, medicines, values and the whole clinical picture. NICE NG24 (children over 1 year, extrapolated from adults) agrees on prophylaxis below 10 × 10⁹/L, gives a threshold of 30 × 10⁹/L for clinically significant (WHO grade 2) bleeding and up to 100 for severe or critical-site bleeding, considers raising the count above 50 for invasive procedures or surgery, and advises no prophylactic platelets for bone marrow aspiration and trephine. One dose at a time, then reassess the child and recheck the count.","asOf":"2026-11-11","links":[],"tags":["protocol","paediatric","transfusion"],"related":[],"cancers":["childhood-cancers","all-leukemia","aml"],"sections":["supportive-care"],"technologies":["transfusion-support","allogeneic-hsct"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["nice"],"pathways":[],"terms":["thrombocytopenia","intrathecal-therapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Platelets help blood clot. If chemotherapy makes them very low, the child gets a platelet transfusion. The team gives them when the count is very low or before some procedures, not every time it drops.","domain":"paediatric","setting":{"who":["doctor","nurse"],"where":["ward","chemotherapy-day-unit","outpatient-clinic"]},"population":"Children with cancer who have low platelets because of chemotherapy or allogeneic stem cell transplant (hypoproliferative thrombocytopenia), as the AABB and ICTMG recommendations endorsed by COG for children scope them. NICE NG24 excludes children under 1 year; preterm neonates have their own AABB and ICTMG threshold. The guideline's recommendations on autologous transplant and aplastic anaemia are for adults only.","trigger":"A child having chemotherapy or after transplant has a low platelet count, is bleeding, or is due for a procedure.","steps":[{"action":"Decide on each transfusion with the whole picture in mind: symptoms, signs, other blood tests, bleeding history, medicines, the family's values and other treatments","why":"The count is a guide, not the only reason to transfuse or not.","source":"cog-platelet-2026","quote":"Consider symptoms, signs, other laboratory parameters, bleeding history, medications, patients’ values and preferences, alternative therapies, and overall clinical context when deciding to perform a platelet transfusion on a particular patient.","grade":"Good practice statement"},{"action":"For a child who is not bleeding during chemotherapy or after allogeneic transplant, transfuse platelets when the count is below 10 × 10³/μL","why":"Transfusing at higher counts did not reduce bleeding or deaths in the trials, and each transfusion carries a risk of reactions.","source":"metcalf-2025","quote":"Evidence demonstrated that restrictive transfusion strategies probably did not cause increases in mortality or bleeding relative to liberal strategies across predefined clinical populations.","grade":"Strong / Moderate"},{"action":"Before a lumbar puncture, transfuse if the count is below 20 × 10³/μL","why":"Bleeding into the spine after a lumbar puncture with low platelets was found to be extremely rare, so a lower threshold spares children transfusions.","source":"metcalf-2025","quote":"Exceedingly low incidence of spinal hematoma was identified in patients with thrombocytopenia undergoing lumbar puncture.","grade":"Strong / Moderate"},{"action":"Do not give prophylactic platelets for a bone marrow aspirate and trephine","why":"NICE classes it as a procedure with a low risk of bleeding, so platelets are not given just for it.","source":"nice-ng24","quote":"Do not offer prophylactic platelet transfusions to people having procedures with a low risk of bleeding, such as adults having central venous cannulation or any people having bone marrow aspiration and trephine biopsy."},{"action":"For other invasive procedures or surgery, consider raising the count above 50 × 10⁹/L, and above 100 for surgery in critical sites such as the brain or the back of the eye","why":"Riskier procedures need a higher count, and the brain and the back of the eye are where bleeding does most harm.","source":"nice-ng24"},{"action":"For a child with clinically significant bleeding (WHO grade 2) and a count below 30 × 10⁹/L, transfuse platelets","why":"Bleeding with a low count is the clearest reason to give platelets.","source":"nice-ng24"},{"action":"For severe bleeding or bleeding in a critical site such as the brain or eyes, use a higher threshold, up to 100 × 10⁹/L","why":"Bleeding in these places can cause lasting harm, so the count is kept higher.","source":"nice-ng24"},{"action":"Give one dose at a time, then reassess the child and recheck the count before giving more","why":"A single dose is usually enough, and checking avoids giving more than needed.","source":"nice-ng24","quote":"Reassess the person's clinical condition and check their platelet count after each platelet transfusion, and give further doses if needed."}],"bestInClass":{"statement":"For prophylaxis during chemotherapy or after allogeneic transplant the guidelines agree: transfuse a non-bleeding child below 10 (AABB and ICTMG 2025, strong, moderate, endorsed by COG for children; NICE NG24, for people over 1 year). They differ before lumbar puncture: AABB and ICTMG recommend a threshold of 20 × 10³/μL (strong, moderate), on evidence that spinal haematoma is exceedingly rare, while NICE NG24 has no lumbar puncture threshold and considers raising the count above 50 × 10⁹/L for invasive procedures in general, a 2015 recommendation extrapolated from adults. The 2025 international guideline is the newer and the one COG endorses for children.","sources":["cog-platelet-2026","metcalf-2025","nice-ng24"]},"variants":[{"name":"Platelets above 50 before lumbar puncture (NICE NG24 general procedure threshold)","differs":"Treats a lumbar puncture as an invasive procedure and considers raising the count above 50 × 10⁹/L, rather than transfusing only below 20.","evidence":"NICE does not grade recommendations and wrote this one in 2015 for invasive procedures in general, extrapolated to children from adult evidence. AABB and ICTMG 2025 give a strong recommendation, moderate certainty, for a threshold of 20 × 10³/μL specifically for lumbar puncture.","sources":["nice-ng24","metcalf-2025"]}],"grades":[{"claim":"Prophylactic transfusion below 10 × 10³/μL during chemotherapy or after allogeneic transplant","grade":"Strong / Moderate","source":"cog-platelet-2026"},{"claim":"Transfusion below 20 × 10³/μL before lumbar puncture","grade":"Strong / Moderate","source":"cog-platelet-2026"},{"claim":"Preterm neonates without major bleeding transfused below 25 × 10³/μL","grade":"Strong / High","source":"cog-platelet-2026"},{"claim":"No prophylactic platelets for non-bleeding adults after autologous transplant or with aplastic anaemia","grade":"conditional recommendation, low/very low-certainty evidence","source":"metcalf-2025","quote":"For hypoproliferative thrombocytopenia in nonbleeding adults undergoing autologous stem cell transplant or with aplastic anemia, prophylactic platelet transfusion is not recommended."}],"sources":[{"key":"cog-platelet-2026","label":"Platelet Transfusion 2025 AABB and ICTMG International Clinical Practice Guidelines (COG endorsement, version date 26 March 2026)","publisher":"Children's Oncology Group","year":2026,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/07/COG_SC_Platelet_Transfusion_Guideline_Document_26MARCH2026.pdf","gradingScheme":"GRADE, reprinted from the source guideline as strength of recommendation / certainty of evidence (for example Strong / Moderate).","read":"full-text","accessed":"2026-11-11"},{"key":"metcalf-2025","label":"Platelet Transfusion: 2025 AABB and ICTMG International Clinical Practice Guidelines","publisher":"AABB and the International Collaboration for Transfusion Medicine Guidelines, JAMA","year":2025,"url":"https://europepmc.org/abstract/MED/40440268","doi":"10.1001/jama.2025.7529","gradingScheme":"GRADE: strong or conditional recommendations; certainty high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"nice-ng24","label":"Blood transfusion (NG24): platelet transfusion recommendations","publisher":"NICE","year":2015,"url":"https://www.nice.org.uk/guidance/ng24/chapter/Platelet-transfusion","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'consider', 'do not offer'), and each is dated, here [2015]. The guideline was last updated in February 2026 (tranexamic acid).","read":"full-text","accessed":"2026-11-11"},{"key":"bsh-2016","label":"Guidelines on transfusion for fetuses, neonates and older children (with 2020 addendum)","publisher":"British Society for Haematology, British Journal of Haematology","year":2016,"url":"https://doi.org/10.1111/bjh.14233","doi":"10.1111/bjh.14233","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The full text of the 2025 AABB and ICTMG guideline is not open access; the recommendations here come from its abstract and the COG endorsement document, which lists only those applicable to children.","The British Society for Haematology paediatric transfusion guideline (2016, 2020 addendum), the main UK source for children, could not be read: the publisher refused a script and Europe PMC holds no abstract.","No guideline read here gives a platelet threshold for central line insertion in children; the AABB and ICTMG threshold of 10 for compressible central venous catheter sites is for adults.","The thresholds for children who are bleeding come from NICE, extrapolated from adult evidence.","Whether a fever, infection or a falling count should raise the prophylactic threshold in children is not addressed in the sources read."]},{"id":"pneumocystis-pneumonia-prophylaxis","kind":"protocol","name":"Pneumocystis pneumonia (PJP) prophylaxis with co-trimoxazole","aka":["PJP prophylaxis","PCP prophylaxis","Pneumocystis prophylaxis","co-trimoxazole prophylaxis","Septrin prophylaxis","TMP-SMX prophylaxis","trimethoprim-sulfamethoxazole prophylaxis"],"tldr":"Pneumocystis is a fungus that can cause a dangerous pneumonia in people whose immune system is weakened by some cancer treatments, steroids or a stem cell transplant. An inexpensive antibiotic, co-trimoxazole, taken a few times a week or daily, prevents it very well. People who cannot take it have other options: atovaquone, dapsone or an inhaled medicine once a month.","summary":"AGIHO (2020) strongly recommends chemoprophylaxis for the groups its Table 7 lists at significant risk: acute lymphoblastic leukaemia, allogeneic stem cell transplant, long-term steroids above 20 mg prednisone equivalent daily for more than 4 weeks, and fludarabine with cyclophosphamide and rituximab (prevent PJP A-I, reduce mortality A-IIr), and for idelalisib, alemtuzumab and temozolomide with radiotherapy (A-IIu,t). Intermediate risk (R-CHOP14, escalated BEACOPP, nucleoside analogues, brain irradiation with high-dose steroids, CD4 below 200/µl) may or may not receive it (C-III). ASCO/IDSA (2018) set the threshold at regimens with more than 3.5% risk, for example 20 mg or more prednisone equivalent daily for a month or more, or purine analogues. ECIL-5 (2016) lists ALL, allogeneic HSCT, alemtuzumab, fludarabine with cyclophosphamide and rituximab, more than 4 weeks of corticosteroids and primary immune deficiencies in children, for the entire period at risk.\n\nCo-trimoxazole (trimethoprim-sulfamethoxazole) is first choice (AGIHO A-IIt,r; ECIL-5 A-II adults, A-I children), at one single-strength tablet daily or one double-strength tablet daily or thrice weekly (B-IIt); ECIL-5 gives it 2 to 3 times weekly and notes children may do equally well once weekly (B-II). Second line: atovaquone 1500 mg daily with a fatty meal (A-IIt), dapsone 100 mg daily after G6PD testing (A-IIt), or aerosolised pentamidine 300 mg monthly (B-IIt), which is probably less effective and needs staff protection. For idelalisib the label asks for prophylaxis from the start and for 2 to 6 months after stopping.","asOf":"2026-11-11","links":[],"tags":["protocol","pneumocystis","infection-prevention"],"related":["lymphoma-tx-pjp-and-infection-prophylaxis"],"cancers":["all-leukemia","cll","non-hodgkin-lymphoma","glioblastoma","childhood-cancers"],"sections":["supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":["idelalisib","alemtuzumab","temozolomide","fludarabine","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-pjp-and-infection-prophylaxis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer treatments raise the risk of a rare but serious lung infection. A cheap antibiotic tablet, often taken only three days a week, prevents it.","domain":"infection-prevention","setting":{"who":["doctor","pharmacist","nurse","patient-or-carer"],"where":["outpatient-clinic","ward","home"]},"population":"People with cancer who are not living with HIV and are having treatment that suppresses cell-mediated immunity: haematological cancers, stem cell transplant, long-term corticosteroids, temozolomide with radiotherapy. AGIHO and ASCO/IDSA address adults; ECIL-5 grades adults and children separately; a 2017 guideline addresses children with solid tumours.","trigger":"A regimen or steroid course that carries a significant risk of Pneumocystis pneumonia is being planned.","steps":[{"action":"Identify the people at significant risk: ALL, allogeneic stem cell transplant, steroids above 20 mg prednisone equivalent a day for more than 4 weeks, or fludarabine with cyclophosphamide and rituximab","why":"In these groups the pneumonia is common enough, and deadly enough, that prevention clearly pays.","source":"agiho-2020","quote":"Oncologic patients at significant risk for PcP are those treated for acute lymphoblastic leukemia, those treated with a combination of fludarabine, cyclophosphamide, and rituximab [129], and patients undergoing allogeneic HSCT [128, 130]."},{"action":"Give these patients prophylaxis","why":"It prevents the pneumonia and reduces deaths from it.","source":"agiho-2020","quote":"The administration of chemoprophylaxis in patients with one of these three risk factors is thus strongly recommended to prevent PcP (A-I) and reduce mortality (A-IIr).","grade":"A-I (prevent PcP); A-IIr (reduce mortality)"},{"action":"Give prophylaxis with idelalisib, alemtuzumab, or temozolomide given with radiotherapy","why":"These treatments carry a documented high risk, and for idelalisib the drug label requires it.","source":"agiho-2020","quote":"Based on the documented high-risk situation, we strongly recommend chemoprophylaxis against PcP for patients receiving temozolomide (in combination with radiotherapy), idelalisib, or alemtuzumab (A-IIu,t) (Tables 7 and 8).","grade":"A-IIu,t"},{"action":"Decide case by case for intermediate risk, such as R-CHOP14, escalated BEACOPP, nucleoside analogues, brain radiotherapy with high-dose steroids, or a CD4 count below 200","why":"These patients occasionally get the infection, but no study shows prophylaxis helps them and many more would need treating to prevent one case.","source":"agiho-2020","quote":"Such patients at moderate risk may or may not receive chemoprophylaxis to prevent PcP (C-III) and to reduce mortality (C-III).","grade":"C-III"},{"action":"Use co-trimoxazole (trimethoprim-sulfamethoxazole) first","why":"It is the most effective option, and also protects against toxoplasmosis, nocardiosis and actinomycosis.","source":"agiho-2020","quote":"For these reasons, TMP-SMX is the first-choice agent for PcP prophylaxis (A-IIt,r).","grade":"A-IIt,r"},{"action":"Give one single-strength tablet daily, or one double-strength tablet daily or three times a week","why":"The schedules work equally well; three times a week caused fewer stoppings for side effects in a study in people with HIV.","source":"agiho-2020","quote":"We recommend using any of these dosing regimens (B-IIt).","grade":"B-IIt"},{"action":"Continue it for the whole time the person is at risk","why":"The risk lasts as long as the immune suppression, not just the days of chemotherapy.","source":"ecil5-2016","quote":"Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk.","grade":"A-II (adults); A-I (children)"},{"action":"If co-trimoxazole is not tolerated, use atovaquone 1500 mg once daily with a fatty meal","why":"It worked well and does not lower blood counts; lower doses were less effective, and fat helps it absorb.","source":"agiho-2020","quote":"Low-dose atovaquone has been described to be less effective in PcP prophylaxis [164]; thus, 1500 mg atovaquone should be administered once daily (off-label use) (A-IIt).","grade":"A-IIt"},{"action":"Or use dapsone 100 mg daily, after testing for G6PD deficiency","why":"Dapsone works as well as co-trimoxazole but can break down red cells in G6PD deficiency and cause methaemoglobinaemia.","source":"agiho-2020","quote":"Testing for glucose-6-phosphat dehydrogenase deficiency is recommended prior to administration of dapsone.","grade":"A-IIt"},{"action":"Keep aerosolised pentamidine, 300 mg once a month, for when the tablets cannot be used, and protect the staff giving it","why":"It has no blood or drug interactions but probably works less well, gives no protection against toxoplasmosis, and exposes staff to the drug.","source":"agiho-2020","quote":"Our recommendation to use aerosolized pentamidine (300 mg once/month) is moderate (B-IIt) (Table 9).","grade":"B-IIt"}],"bestInClass":{"statement":"Co-trimoxazole for the whole period of risk is the agreed first choice (AGIHO 2020 A-IIt,r; ECIL-5 2016 A-II adults, A-I children). The guidelines agree on the core indications (ALL, allogeneic transplant, fludarabine-based chemoimmunotherapy, alemtuzumab, prolonged steroids) but draw the line differently: AGIHO names significant, intermediate and special-indication groups and leaves intermediate risk to judgement (C-III); ASCO/IDSA (2018) use a numerical threshold of more than 3.5% risk, with 20 mg or more prednisone equivalent daily for a month or longer as the example; ECIL-5 adds primary immune deficiencies in children and other regimens case by case. On the schedule, AGIHO accepts daily or thrice-weekly dosing (B-IIt), ECIL-5 recommends 2 to 3 times weekly and allows once weekly in children (B-II). For children with solid tumours, a 2017 guideline suggests offering prophylaxis to all children having immunosuppressive therapy unless contraindicated.","sources":["agiho-2020","ecil5-2016","asco-idsa-2018","jpho-2017"]},"variants":[{"name":"Numerical risk threshold (ASCO/IDSA 2018)","differs":"Recommends prophylaxis for chemotherapy regimens associated with more than 3.5% risk of Pneumocystis pneumonia, for example 20 mg or more prednisone equivalents daily for a month or more, or purine analogues.","evidence":"Read as an abstract only, so the grade is not given here.","sources":["asco-idsa-2018"]},{"name":"Once-weekly co-trimoxazole in children (ECIL-5)","differs":"Uses a single weekly dose instead of 2 to 3 times weekly in children.","evidence":"ECIL-5 says recent data indicate children may benefit equally, graded B-II.","sources":["ecil5-2016"]},{"name":"Prophylaxis for every child on immunosuppressive therapy for a solid tumour","differs":"Offers co-trimoxazole to all children with malignancies on immunosuppressive therapy unless there are clear contraindications, rather than only those in named high-risk groups.","evidence":"A paediatric guideline read as an abstract only; it argues from the high mortality of the pneumonia and the safety and low cost of co-trimoxazole.","sources":["jpho-2017"]}],"grades":[{"claim":"Prophylaxis for significant-risk groups, to prevent PJP","grade":"A-I","source":"agiho-2020"},{"claim":"Prophylaxis for significant-risk groups, to reduce mortality","grade":"A-IIr","source":"agiho-2020"},{"claim":"Prophylaxis with idelalisib, alemtuzumab or temozolomide with radiotherapy","grade":"A-IIu,t","source":"agiho-2020"},{"claim":"Intermediate-risk groups may or may not receive prophylaxis","grade":"C-III","source":"agiho-2020"},{"claim":"Co-trimoxazole as first choice","grade":"A-IIt,r","source":"agiho-2020"},{"claim":"Co-trimoxazole 2 to 3 times weekly for the entire period at risk","grade":"A-II (adults); A-I (children)","source":"ecil5-2016"},{"claim":"Once-weekly co-trimoxazole in children","grade":"B-II","source":"ecil5-2016","quote":"Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: )."},{"claim":"Aerosolised pentamidine 300 mg monthly as second choice","grade":"B-IIt","source":"agiho-2020"}],"sources":[{"key":"agiho-2020","label":"Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO)","publisher":"AGIHO/DGHO, Annals of Hematology","year":2021,"url":"https://europepmc.org/article/PMC/PMC8116237","doi":"10.1007/s00277-021-04452-9","gradingScheme":"Strength of recommendation A (strongly supports use) to D (supports a recommendation against use) and quality of evidence I to III, with indices r (meta-analysis), t (transferred evidence), h (historical control), u (uncontrolled trial), a (abstract), printed as A-IIt,r.","read":"full-text","accessed":"2026-11-11"},{"key":"ecil5-2016","label":"ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients","publisher":"European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy","year":2016,"url":"https://europepmc.org/abstract/MED/27550992","doi":"10.1093/jac/dkw157","gradingScheme":"IDSA grading: strength A to C, evidence I to III.","read":"abstract","accessed":"2026-11-11"},{"key":"asco-idsa-2018","label":"Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update","publisher":"ASCO and IDSA, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/abstract/MED/30179565","doi":"10.1200/JCO.18.00374","read":"abstract","accessed":"2026-11-11"},{"key":"jpho-2017","label":"Guidelines for the Prophylaxis of Pneumocystis jirovecii Pneumonia (PJP) in Children With Solid Tumors","publisher":"Journal of Pediatric Hematology/Oncology","year":2017,"url":"https://europepmc.org/abstract/MED/28267082","doi":"10.1097/mph.0000000000000771","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ECIL-5 full text could not be read: the publisher's page returned a bot challenge to a script. Its paediatric doses and the additional regimen-specific indications it proposes are not given here.","ASCO/IDSA 2018 was read only as an abstract, so its grade and drug choices for PJP prophylaxis are not stated.","No source read here gives a duration after treatment ends beyond 'the entire period at risk', except the idelalisib label's 2 to 6 months cited by AGIHO.","Evidence for co-trimoxazole schedules comes largely from people living with HIV and is transferred to cancer (AGIHO grades it B-IIt).","Whether prophylaxis helps intermediate-risk groups, such as people on long-term anti-CD20 antibodies or R-CHOP14, has not been studied."]},{"id":"radiotherapy-pregnancy-and-breastfeeding-enquiry","kind":"protocol","name":"Pregnancy and breastfeeding checks before radiotherapy","aka":["pregnancy check before radiotherapy","pregnancy status enquiry","IR(ME)R pregnancy enquiry","ten-day rule","28-day rule","breastfeeding and molecular radiotherapy","radiotherapy in pregnancy","fetal dose radiotherapy"],"tldr":"Radiation can harm an unborn baby, so before your planning scan and your first treatment, anyone who could be pregnant is asked whether they might be, and before a radioactive medicine is given, whether they are breastfeeding. The answer is recorded; if pregnancy cannot be ruled out a test may be done, and if you are pregnant the team reconsiders the plan with you.","summary":"In the UK, IR(ME)R 2017 regulation 11(1)(f) requires the operator to enquire about pregnancy where relevant, and the RCR guidance (second edition, October 2026, with UKHSA) sets out how. The employer's written procedure defines who is asked (commonly people of childbearing potential aged 12 to 55, some departments 10 to 55), when (asking before the first planning exposure and before the first treatment may be sufficient), exceptions (for example after total abdominal hysterectomy), sedated or anaesthetised patients, under-16s (local safeguarding procedure), trans and gender-diverse people, and irregular cycles, where the ten-day rule and menstrual history may not predict pregnancy and routine testing may be specified. The answer is documented; a refusal to answer is documented and the unknown-status procedure followed. If pregnancy is possible or confirmed, the practitioner reconsiders justification, deferral is considered and a test is done where it cannot be excluded. For molecular radiotherapy menstrual history alone is not adequate to exclude pregnancy, and breastfeeding is completely contraindicated where the radionuclide enters milk. Deliberately treating a pregnant patient is rare, case by case, with a prior risk assessment by the medical physics expert, and AAPM TG-36 (1995) gives the physics for estimating and shielding fetal dose; an unintended fetal exposure may be notifiable.","asOf":"2026-11-11","links":[],"tags":[],"related":["radiotherapy-patient-identification-and-time-out","radiotherapy-consent"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-in-pregnancy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before radiotherapy you will be asked if you could be pregnant or are breastfeeding. Please answer honestly and tell the team straight away if this changes during treatment.","domain":"radiotherapy","setting":{"who":["radiographer","doctor","multidisciplinary-team"],"where":["radiotherapy-department"]},"population":"People of childbearing potential having radiotherapy planning or treatment, including external beam, brachytherapy, intraoperative radiotherapy and molecular radiotherapy, and people who are breastfeeding before molecular radiotherapy. The procedure and wording are UK (IR(ME)R 2017); other countries have their own regulations, which were not read. Under-16s are included with safeguarding procedures.","trigger":"A radiotherapy planning scan, the first treatment, or a molecular radiotherapy administration is due for a person who could be pregnant or is breastfeeding; and any time during a course that pregnancy becomes possible.","steps":[{"action":"Before the planning scan and before the first treatment, the operator asks every person of childbearing potential in the locally agreed age range whether they could be pregnant","why":"Radiation to an unborn baby can cause harm, and the law requires the person giving the exposure to ask where it is relevant.","source":"rcr-irmer-2026","quote":"Regulation 11(1)(f) requires operators to enquire about pregnancy status where relevant.","grade":"Legal requirement (IR(ME)R 2017)"},{"action":"Use the age range set in the local procedure (commonly 12 to 55) and ask at least before the first planning exposure and the first treatment exposure","why":"A clear rule means nobody who could be pregnant is missed and the check is not forgotten on the day treatment starts.","source":"rcr-irmer-2026","quote":"It may be considered sufficient to ask prior to initial planning exposure and prior to initial treatment exposure."},{"action":"Explain why the question is asked, in appointment letters, leaflets and in person, and ask privately and with sensitivity","why":"People can only declare a possible pregnancy if they understand why it matters; some fear asking or answering in front of others.","source":"rcr-irmer-2026","quote":"It is therefore essential to provide every individual with adequate information relating to the benefits and risks associated with the radiation dose prior to the procedure, as this gives them the opportunity to ask questions and to declare any possibility of pregnancy."},{"action":"For anyone under 16, follow the local safeguarding procedure when asking","why":"A disclosed pregnancy in a young person can raise safeguarding concerns that need a set response.","source":"rcr-irmer-2026","quote":"When checking the possibility of pregnancy with individuals under 16 years of age, operators must follow the local safeguarding procedure.","grade":"Must (RCR guidance)"},{"action":"Where cycles are irregular (because of illness or chemotherapy), do not rely on the ten-day rule or the last period; test if the local procedure says so","why":"Cancer treatment and illness can stop or disturb periods, so the usual questions may not show a pregnancy.","source":"rcr-irmer-2026","quote":"In these cases, the traditional ten-day rule and enquiries about menstruation may be ineffective in predicting pregnancy."},{"action":"Set out who confirms pregnancy status before a patient is sedated or anaesthetised (for example for intraoperative radiotherapy)","why":"A patient who is asleep cannot be asked at the time of the exposure.","source":"rcr-irmer-2026","quote":"The employer’s procedure must specify whose responsibility it is to confirm pregnancy status prior to the patient being anaesthetised or sedated.","grade":"Must (RCR guidance)"},{"action":"Record the answer every time; if the person declines to answer, record that and follow the procedure for unknown pregnancy status","why":"The record shows the question was asked and lets the team act on the answer.","source":"rcr-irmer-2026","quote":"The response to pregnancy enquiries must be documented as evidence that the appropriate questions have been asked.","grade":"Must (RCR guidance)"},{"action":"If pregnancy cannot be excluded, do the pregnancy test set out in the local procedure, and consider deferring if doubt remains or treatment is not urgent; before molecular radiotherapy, never rely on menstrual history alone","why":"A test settles the question; a radioactive medicine cannot be taken back once given.","source":"rcr-irmer-2026","quote":"The confirmation of menstrual history alone is not considered adequate to exclude pregnancy."},{"action":"If the person is or may be pregnant, before or during the course, stop and tell the practitioner, who reconsiders whether the exposure is justified, with the medical physics expert","why":"The balance of benefit and risk changes when a pregnancy is involved, and treatment may be deferred, changed or, rarely, given with fetal shielding.","source":"rcr-irmer-2026","quote":"If the possibility of pregnancy is discovered before the exposure takes place, the operator should alert the practitioner, who should reconsider justification of the exposure."},{"action":"If a pregnant patient is to be treated deliberately, decide case by case, with a prior fetal dose risk assessment by the medical physics expert and, where needed, an obstetrician","why":"Planning and shielding can lower the dose to the fetus; the physics for estimating it is published.","source":"rcr-irmer-2026","quote":"The MPE must be involved in a prior risk assessment of exposures to such individuals.","grade":"Must (RCR guidance)"},{"action":"Before molecular radiotherapy, ask anyone who has recently given birth whether they are breastfeeding, and do not give a radionuclide excreted in milk while breastfeeding continues","why":"The radioactive medicine passes into breast milk and to the baby.","source":"rcr-irmer-2026","quote":"Breastfeeding is completely contraindicated for MRT using radionuclides that are excreted in breast milk."}],"bestInClass":{"statement":"The RCR IR(ME)R guidance for radiotherapy (second edition, October 2026, with UKHSA) is the most current and detailed source read: a written employer's procedure; an operator enquiry, documented, for all people of childbearing potential in a set age range before the first planning and first treatment exposures; sensitive, private questioning with information in advance; safeguarding for under-16s; testing where pregnancy cannot be excluded or cycles are irregular; reconsideration of justification by the practitioner with the medical physics expert if pregnancy is possible; and, for molecular radiotherapy, exclusion of pregnancy by more than menstrual history and no breastfeeding with radionuclides excreted in milk. Fetal dose estimation and shielding, where a pregnant patient is treated, rest on AAPM TG-36 (1995).","sources":["rcr-irmer-2026","irmer-2017-schedule-2","aapm-tg36-1995"]},"variants":[{"name":"Age range for asking","differs":"Most departments ask people of childbearing potential aged 12 to 55; some have agreed 10 to 55 with their obstetric team to fit local patients.","evidence":"Both are described by the RCR guidance as in use (12 to 55 in many departments); neither rests on a trial.","sources":["rcr-irmer-2026"]},{"name":"Routine pregnancy testing","differs":"Tests everyone in the age range, or everyone with irregular cycles, rather than asking and testing only where pregnancy cannot be excluded.","evidence":"The RCR guidance leaves this to the employer's procedure after a risk assessment, and requires an appropriate test for molecular radiotherapy where pregnancy must be excluded. No comparison of approaches was found.","sources":["rcr-irmer-2026"]}],"grades":[{"claim":"Operators must enquire about pregnancy where relevant","grade":"Legal requirement, IR(ME)R 2017 regulation 11(1)(f)","source":"rcr-irmer-2026"},{"claim":"The employer's written procedures must cover enquiries about pregnancy and breastfeeding","grade":"Legal requirement, IR(ME)R 2017 Schedule 2, paragraph 1(c)","source":"irmer-2017-schedule-2","quote":"for making enquiries of individuals of childbearing potential to establish whether the individual is or may be pregnant or breastfeeding;"},{"claim":"Making pregnancy or breastfeeding enquiries is an operator task","grade":"RCR guidance statement","source":"rcr-irmer-2026","quote":"Making pregnancy or breastfeeding enquiries in advance of an exposure is an operator task."},{"claim":"A newly discovered pregnancy during a course leads the practitioner to reconsider justification","grade":"RCR guidance (should)","source":"rcr-irmer-2026","quote":"If the possibility of pregnancy is discovered after the exposure has been justified or during the course of treatment, the operator should alert the practitioner, who should reconsider justification of the exposure."},{"claim":"Deliberate treatment of a pregnant patient is rare and case by case","grade":"RCR guidance (must)","source":"rcr-irmer-2026","quote":"These occasions are rare and must always be considered on a case-by-case basis."},{"claim":"An unintended fetal exposure may need notifying","grade":"RCR guidance","source":"rcr-irmer-2026","quote":"If an unintended fetal exposure occurs, this may require notification to the relevant enforcing authority in accordance with published guidance."},{"claim":"After molecular radiotherapy, patients are advised to avoid conception for set periods","grade":"RCR guidance (should), periods set by ARSAC","source":"rcr-irmer-2026","quote":"Male and female patients who wish to conceive following treatment should be advised to avoid getting pregnant for set periods of time as recommended by ARSAC."}],"sources":[{"key":"rcr-irmer-2026","label":"IR(ME)R: Implications for clinical practice in radiotherapy, second edition. Guidance from the Radiotherapy Board (chapter 13, Pregnancy and breastfeeding enquiries)","publisher":"The Royal College of Radiologists, in association with the UK Health Security Agency","year":2026,"url":"https://www.rcr.ac.uk/our-services/all-our-publications/clinical-oncology-publications/ionising-radiation-medical-exposure-regulations-implications-for-clinical-practice-in-radiotherapy/","gradingScheme":"Not graded: guidance interpreting the Ionising Radiation (Medical Exposure) Regulations 2017; 'must' marks a legal or procedural requirement, 'should' and 'may' mark recommended and permitted practice.","read":"full-text","accessed":"2026-11-11"},{"key":"irmer-2017-schedule-2","label":"The Ionising Radiation (Medical Exposure) Regulations 2017 (SI 2017/1322), Schedule 2: Employer's Procedures","publisher":"UK Government (legislation.gov.uk)","year":2017,"url":"https://www.legislation.gov.uk/uksi/2017/1322/schedule/2/made","gradingScheme":"Statutory instrument: binding in Great Britain, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"aapm-tg36-1995","label":"Fetal dose from radiotherapy with photon beams: report of AAPM Radiation Therapy Committee Task Group No. 36","publisher":"AAPM (Medical Physics; Stovall et al.)","year":1995,"url":"https://doi.org/10.1118/1.597525","doi":"10.1118/1.597525","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-pregnancy-test-or-ask-before-radiotherapy"],"gaps":["Only UK guidance and IR(ME)R Schedule 2 were read. US, EU and other national rules on pregnancy enquiries before radiotherapy, the body of the IR(ME)R regulations and the ARSAC notes for guidance (which set conception and breastfeeding intervals after molecular radiotherapy) were not read.","AAPM TG-36, the standard reference for fetal dose estimation and shielding, dates from 1995 and was read as an abstract only; no update was found.","Consent for radiotherapy, which the census row pairs with this check, is a separate protocol (radiotherapy-consent); no consent guidance was read for this record.","No study compares asking alone with routine testing for missed pregnancies in radiotherapy; the age range and testing rules are local decisions."]},{"id":"premedication-before-reaction-prone-anticancer-drugs","kind":"protocol","name":"Premedication against infusion reactions before taxanes, antibodies and other reaction-prone anticancer drugs","aka":["chemotherapy premedication","taxane premedication","paclitaxel premeds","docetaxel dexamethasone","rituximab premedication","daratumumab premedication","pre-meds before chemotherapy"],"tldr":"Before some cancer drugs you are given other medicines, usually a steroid such as dexamethasone and an antihistamine, to lower the chance of a reaction during the drip. For docetaxel the steroid tablets start the day before, so it matters that you take them as told. Many drugs need no premedication at all.","summary":"ESMO (2017) recommends premedication with corticosteroids plus antihistamines before every taxane [IV, A]. For paclitaxel it gives intravenous dexamethasone with diphenhydramine 50 mg and an H2 antagonist 30 minutes before [II, A], noting a randomised trial in which short intravenous dexamethasone matched oral dexamethasone for reactions with fewer side effects [II, A]; the US label gives oral dexamethasone 20 mg 12 and 6 hours before, with diphenhydramine and an H2 antagonist 30 to 60 minutes before. For docetaxel the label and ESMO give oral dexamethasone 8 mg twice daily for 3 days starting the day before (8 mg at 12, 3 and 1 hours before in prostate cancer), against fluid retention as well as reactions.\n\nFor platinums ESMO does not routinely recommend premedication (consider in high-risk patients; it may not prevent a reaction) [IV, B]. For antibodies it varies by drug: rituximab always with an antipyretic and antihistamine [IV, A], with glucocorticoids considered in lymphoma and CLL; cetuximab with a corticosteroid plus antihistamine [IV, B], which can stop after the second infusion if no reaction; daratumumab with an intravenous corticosteroid, an antipyretic and an antihistamine before every infusion and oral corticosteroid on the two days after [IV, B]; none recommended for trastuzumab, bevacizumab, panitumumab or atezolizumab [IV, B]. Bleomycin in lymphoma starts with two doses of 2 units or less [IV, B]. ESMO asks nurses to check that oral premedication was taken [V, C]. Severe reactions still occur despite premedication (paclitaxel 2 to 4%).","asOf":"2026-11-11","links":[],"tags":[],"related":["infusion-reaction-management","sact-prescribing-and-pharmacy-verification"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["paclitaxel","docetaxel","rituximab","cetuximab","daratumumab","carboplatin","oxaliplatin","bleomycin","dexamethasone"],"companies":[],"institutions":[],"pathways":[],"terms":["extravasation-infusion-reaction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer drips need tablets or injections beforehand to stop a reaction. If you were given steroid tablets to take before treatment, take them exactly as told and say if you forgot.","domain":"chemotherapy-administration","setting":{"who":["doctor","pharmacist","nurse","patient-or-carer"],"where":["chemotherapy-day-unit","ward","home"]},"population":"Adults receiving intravenous anticancer drugs. Regimens for children, for cell therapies and for bispecific antibodies with step-up dosing follow their own protocols and product labels. Premedication against nausea and vomiting is a separate protocol.","trigger":"A reaction-prone anticancer drug is prescribed.","steps":[{"action":"Give every patient a corticosteroid and an antihistamine before a taxane","why":"Without premedication about three in ten people react to paclitaxel or docetaxel; with it, severe reactions fall to a few in a hundred.","source":"esmo-2017","quote":"All patients should receive premedication with corticosteroids plus antihistamines before taxane administration","grade":"[IV, A]"},{"action":"Before paclitaxel, give dexamethasone, an H1 antihistamine such as diphenhydramine 50 mg and an H2 antagonist, 30 minutes before the infusion","why":"Paclitaxel reactions are mostly caused by histamine release, so blocking both histamine receptors and adding a steroid prevents most of them.","source":"esmo-2017","quote":"One dose of i.v. dexamethasone plus diphenhydramine (50 mg i.v.) and a H2 receptor antagonist (ranitidine 50 mg or cimetidine 300 mg i.v.) 30 min before paclitaxel infusion","grade":"[II, A]"},{"action":"Before docetaxel, start oral dexamethasone 8 mg twice a day the day before, for 3 days (in prostate cancer, 8 mg at 12, 3 and 1 hours before)","why":"The steroid lowers both the risk of an allergic reaction and the fluid build-up docetaxel can cause.","source":"docetaxel-label","quote":"All patients should be premedicated with oral corticosteroids (see below for prostate cancer) such as dexamethasone 16 mg per day (e.g., 8 mg twice daily) for 3 days starting 1 day prior to docetaxel injection administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions"},{"action":"If premedication is taken by mouth, check on the day that the patient took it","why":"Missed tablets are a common and avoidable reason for a reaction.","source":"esmo-2017","quote":"If premedications are to be taken orally, oncology nurses should check that the patient has actually taken them","grade":"[V, C]"},{"action":"Before rituximab, always give an antipyretic and an antihistamine, consider a glucocorticoid in lymphoma and CLL, and start the first infusion slowly","why":"Most people react to the first rituximab dose, mainly through cytokine release; a slow start and premedication make reactions milder.","source":"esmo-2017","quote":"Premedication consisting of an antipyretic and an antihistamine should always be given","grade":"[IV, A]"},{"action":"Before daratumumab, give an intravenous corticosteroid, an antipyretic and an antihistamine one hour before every infusion, and oral corticosteroid on the two days after","why":"Reactions affect up to half of patients, mostly at the first infusion.","source":"esmo-2017","quote":"Premedication 1 h before every infusion: i.v. corticosteroid [(methyl)prednisolone 100 mg, or equivalent], oral antipyretics (paracetamol 650–1000 mg) and oral or i.v. antihistamine (diphenhydramine 25–50 mg or equivalent).","grade":"[IV, B]"},{"action":"Do not routinely premedicate before carboplatin or oxaliplatin; consider it for high-risk patients, knowing it may not prevent a reaction","why":"Platinum reactions are true allergies that build up over many cycles, and steroids and antihistamines do not reliably stop them.","source":"esmo-2017","quote":"Corticosteroids and H1/H2 antagonists not routinely recommended. Consider in high-risk patients. Premedication may not prevent an IR.","grade":"[IV, B]"},{"action":"In lymphoma, give the first two doses of bleomycin at 2 units or less, then the usual dose if there is no reaction","why":"Bleomycin can rarely cause a sudden severe reaction in people with lymphoma, so small first doses test for it.","source":"esmo-2017","quote":"Because of the possibility of an anaphylactoid reaction, lymphoma patients should be treated with 2 units or less for the first 2 doses. If no IR occurs, then the regular dosage schedule may be followed","grade":"[IV, B]"}],"bestInClass":{"statement":"Premedicate by drug, not by habit: corticosteroid plus antihistamine before every taxane (ESMO [IV, A]); for paclitaxel a single intravenous dexamethasone dose with H1 and H2 blockade 30 minutes before (ESMO [II, A]), where the US label instead gives oral dexamethasone 12 and 6 hours before; for docetaxel three days of oral dexamethasone from the day before (label; ESMO [IV, B]); antipyretic and antihistamine always before rituximab (ESMO [IV, A]); per-infusion steroid, antipyretic and antihistamine before daratumumab (ESMO [IV, B]); none routinely before platinums, trastuzumab, bevacizumab, panitumumab or PD-L1 antibodies (ESMO [IV, B]). Check oral premedication was taken.","sources":["esmo-2017","paclitaxel-label","docetaxel-label"]},"variants":[{"name":"Oral dexamethasone the night before and morning of paclitaxel","differs":"Gives dexamethasone 20 mg by mouth about 12 and 6 hours before paclitaxel instead of one intravenous dose just before.","evidence":"This is the US label's regimen. ESMO cites a randomised trial that found no difference in reaction rates between oral and short-term intravenous dexamethasone before a first paclitaxel cycle, with fewer side effects from the intravenous dose [II, A].","sources":["paclitaxel-label","esmo-2017"]},{"name":"Stopping cetuximab premedication after two infusions","differs":"Gives corticosteroid and antihistamine before the first two cetuximab infusions only, if neither causes a reaction.","evidence":"ESMO [IV, B]; it reports corticosteroids plus antihistamines reduced grade 3 or 4 reactions to 1%, compared with 4.7% with antihistamines alone.","sources":["esmo-2017"]}],"grades":[{"claim":"Corticosteroid plus antihistamine before every taxane","grade":"[IV, A]","source":"esmo-2017"},{"claim":"Paclitaxel: one intravenous dexamethasone dose with H1 and H2 antagonists 30 minutes before","grade":"[II, A]","source":"esmo-2017"},{"claim":"Short intravenous dexamethasone as effective as oral, with fewer side effects","grade":"[II, A]","source":"esmo-2017","quote":"However, short-term i.v. dexamethasone was associated with fewer side-effects than oral dexamethasone"},{"claim":"Antipyretic and antihistamine always before rituximab","grade":"[IV, A]","source":"esmo-2017"},{"claim":"Cetuximab: corticosteroid plus antihistamine; may stop after the second infusion without a reaction","grade":"[IV, B]","source":"esmo-2017","quote":"Premedication can be discontinued after the second infusion if no IR is observed"},{"claim":"Platinums: premedication not routinely recommended","grade":"[IV, B]","source":"esmo-2017"},{"claim":"Trastuzumab: premedication not recommended","grade":"[IV, B]","source":"esmo-2017","quote":"Loading dose in 90 min. Subsequent doses in 30 min. Premedication is not recommended."},{"claim":"Paclitaxel: all patients premedicated (US label)","grade":"Product labelling (not graded)","source":"paclitaxel-label","quote":"All patients should be premedicated prior to paclitaxel injection administration in order to prevent severe hypersensitivity reactions."}],"sources":[{"key":"esmo-2017","label":"Management of infusion reactions to systemic anticancer therapy: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology, Roselló et al.)","year":2017,"url":"https://doi.org/10.1093/annonc/mdx216","doi":"10.1093/annonc/mdx216","gradingScheme":"[level, grade]: levels I (large randomised trial or meta-analysis) to V (studies without control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"},{"key":"paclitaxel-label","label":"Paclitaxel injection prescribing information (Teva Parenteral Medicines)","publisher":"US Food and Drug Administration label (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e4be6cbf-72b9-4f7f-9b1b-459b2d35961a","gradingScheme":"Product labelling; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"docetaxel-label","label":"Docetaxel injection prescribing information (Mylan Institutional)","publisher":"US Food and Drug Administration label (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2fb017fd-e55e-43ef-9024-07f2d412b37b","gradingScheme":"Product labelling; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["ESMO's infusion reaction guideline dates from 2017 and most of its drug-by-drug advice is level IV; antibody premedication now follows each product's label, and newer antibodies (bispecifics, amivantamab and others) are not covered by it.","ESMO names ranitidine as the H2 antagonist; it has since been withdrawn in several countries, and no source read names the replacement.","Whether dexamethasone can be reduced or stopped after several uneventful weekly paclitaxel doses was not settled by any source read.","No ASCO, NCCN or UK national guidance on reaction premedication was read."]},{"id":"paediatric-chemotherapy-nausea-vomiting-prevention","kind":"protocol","name":"Preventing chemotherapy sickness (nausea and vomiting) in children","aka":["paediatric CINV","pediatric chemotherapy-induced nausea and vomiting","antiemetics in children","POGO CINV guidelines","breakthrough nausea children","anticipatory nausea children"],"tldr":"How likely a child's chemotherapy is to cause sickness decides which anti-sickness medicines they get, given before the chemotherapy, not after the child is sick. The strongest chemotherapy gets three medicines together. If a child is still sick, the team steps up the medicines straight away and for the next cycle, because sickness that is not controlled makes the next cycle worse.","summary":"Children's Oncology Group endorses four POGO guidelines (GRADE) and the ASCO 2020 antiemetics update. First classify the acute emetogenicity of the chemotherapy using the POGO 2019 paediatric classification (high, moderate, low, minimal; for example cisplatin 12 mg/m2 per dose or more is highly emetogenic). Acute prophylaxis: highly emetogenic, a 5-HT3 antagonist plus dexamethasone plus aprepitant or fosaprepitant (strong, high), with palonosetron-based alternatives where dexamethasone or the NK1 antagonist cannot be given, and olanzapine to be considered (conditional, moderate); moderately emetogenic, a 5-HT3 antagonist plus dexamethasone (strong, moderate); low, a 5-HT3 antagonist (strong, low); minimal, no routine prophylaxis (strong, very low). Delayed phase after highly emetogenic chemotherapy: oral aprepitant if started acutely (strong, high), dexamethasone after ondansetron or granisetron (strong, moderate), continue olanzapine, and no 5-HT3 antagonists (strong, low). Breakthrough nausea: escalate to the prophylaxis for the next emetogenic level (strong, low) or, on highly emetogenic regimens, consider switching to palonosetron and adding dexamethasone, an NK1 antagonist or olanzapine; next cycle, use what worked. Anticipatory nausea: control acute and delayed nausea from the start (strong, moderate); consider hypnosis, systematic desensitisation or relaxation and lorazepam; not ginger routinely; never clonidine.","asOf":"2026-11-11","links":[],"tags":["protocol","paediatric","nausea-and-vomiting"],"related":[],"cancers":["childhood-cancers"],"sections":["supportive-care"],"technologies":["antiemetic-therapy"],"targets":[],"drugs":["ondansetron","granisetron","palonosetron","aprepitant","dexamethasone","cisplatin"],"companies":["childrens-oncology-group"],"institutions":["asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Anti-sickness medicines are chosen by how strong the chemotherapy is. They are given before it starts. If they do not work, the team adds more.","domain":"paediatric","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["ward","chemotherapy-day-unit","home"]},"population":"Children and adolescents receiving chemotherapy, aged 1 month to 18 years for the emetogenicity classification and up to 18 for the prevention and treatment guidelines, including haematopoietic stem cell transplant recipients for anticipatory and breakthrough nausea. Adults are covered by adult antiemetic guidelines.","trigger":"A child is due to start a chemotherapy block.","steps":[{"action":"Before each chemotherapy block, classify how likely it is to cause sickness, using the paediatric emetogenicity classification","why":"The level decides which anti-sickness medicines are needed, and the paediatric classification is built from studies in children.","source":"pogo-classification-2019","quote":"This information is critically important for the appropriate selection of antiemetic prophylaxis.","grade":"Strong recommendation (very low to high quality evidence, by regimen)"},{"action":"For highly emetogenic chemotherapy, give a 5-HT3 antagonist, dexamethasone and aprepitant or fosaprepitant before the chemotherapy","why":"For the strongest chemotherapy this three-drug combination has the best evidence, rated high quality.","source":"cog-cinv-2024","quote":"a. Use a 5HT3RA + dexamethasone + (fos)aprepitant","grade":"Strong recommendation, High quality evidence"},{"action":"If a child cannot have dexamethasone or aprepitant, use palonosetron-based combinations instead","why":"Some children cannot be given dexamethasone or an NK1 antagonist, and the guideline names palonosetron combinations for each of those cases.","source":"cog-cinv-2024","grade":"Strong recommendation, Low to Moderate quality evidence (by combination)"},{"action":"Consider adding olanzapine to the other antiemetics for highly emetogenic chemotherapy","why":"Olanzapine can add to the other medicines; the recommendation is conditional, so it is offered rather than required.","source":"cog-cinv-2024","quote":"e. Consider adding olanzapine to other CPG-consistent antiemetics","grade":"Conditional recommendation, Moderate quality evidence"},{"action":"For moderately emetogenic chemotherapy, give a 5-HT3 antagonist with dexamethasone","why":"Two medicines are enough for most children at this level.","source":"cog-cinv-2024","quote":"a. Use a 5HT3RA + dexamethasone","grade":"Strong recommendation, Moderate quality evidence"},{"action":"For low emetogenic chemotherapy, give a 5-HT3 antagonist alone, and for minimally emetogenic chemotherapy give no routine prophylaxis","why":"Children on mild chemotherapy are rarely sick, and extra medicines add side effects.","source":"cog-cinv-2024","quote":"a. Do not use prophylaxis routinely","grade":"Strong recommendation, Very low quality evidence (minimal); Strong recommendation, Low quality evidence (low)"},{"action":"In the days after highly emetogenic chemotherapy, continue oral aprepitant if it was started on day one, add dexamethasone if ondansetron or granisetron was used, and continue olanzapine if started","why":"Sickness can come on a day or more after chemotherapy, and these medicines cover that delayed phase.","source":"cog-cinv-2024","grade":"Strong recommendation, High quality evidence (aprepitant); Strong recommendation, Moderate quality evidence (dexamethasone, olanzapine)"},{"action":"Do not use 5-HT3 antagonists such as ondansetron in the delayed phase","why":"They work for the first day's sickness, not for the delayed phase.","source":"cog-cinv-2024","quote":"g. Do not use 5HT3RAs in the delayed phase","grade":"Strong recommendation, Low quality evidence"},{"action":"If a child is sick despite prophylaxis for minimal, low or moderate chemotherapy, step up straight away to the medicines for the next level of chemotherapy","why":"Breakthrough sickness means the level of cover was too low.","source":"pogo-breakthrough-2023","quote":"In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended.","grade":"Strong recommendation, Low-quality evidence"},{"action":"On highly emetogenic chemotherapy, for breakthrough sickness consider switching to palonosetron and adding dexamethasone, aprepitant or olanzapine if not already given; consider metoclopramide if olanzapine cannot be used","why":"There is no higher level to step up to, so the team adds or swaps medicines instead.","source":"cog-cinv-2024","grade":"Conditional recommendation, Low to Moderate quality evidence"},{"action":"For the next block, use the antiemetics that controlled the breakthrough sickness last time","why":"Sickness that was hard to control once is likely to happen again; preventing it is easier than treating it.","source":"pogo-breakthrough-2023","quote":"A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.","grade":"Strong recommendation, Low-quality evidence"},{"action":"Control acute and delayed sickness well from the first block, to stop the child becoming sick at the thought of chemotherapy","why":"Children who were sick in earlier cycles are the ones who later feel sick before treatment even starts.","source":"cog-cinv-2024","grade":"Strong recommendation, Moderate-quality evidence"},{"action":"For a child with anticipatory sickness, consider hypnosis, systematic desensitisation or relaxation, and consider lorazepam; do not use ginger routinely, and do not use clonidine","why":"The psychological methods carry little risk; lorazepam helped adults; ginger's results were inconsistent; clonidine has a poor safety record and no clear benefit.","source":"cog-cinv-2024","quote":"2.4 Do not use clonidine for secondary prevention of anticipatory CINV.","grade":"Strong recommendation, Low-quality evidence (clonidine); Conditional recommendation (others)"}],"bestInClass":{"statement":"The POGO paediatric guidelines endorsed together by the Children's Oncology Group (summary dated 15 January 2024) are the current standard for children: classify emetogenicity with the paediatric classification, then three-drug prophylaxis (5-HT3 antagonist, dexamethasone and an NK1 antagonist) for highly emetogenic chemotherapy, two drugs for moderate, one for low, none for minimal, with olanzapine considered; escalate for breakthrough sickness and carry the effective regimen into the next block. COG also endorses the adult ASCO 2020 antiemetics update for acute prevention; that guideline was not read here, so any difference between them is not stated. Where paediatric data for a regimen are lacking, the classification guideline says adult guidelines may be consulted.","sources":["cog-cinv-2024","pogo-classification-2019","pogo-acute-delayed-2022","pogo-breakthrough-2023","pogo-anticipatory-2021"]},"variants":[{"name":"Palonosetron as the 5-HT3 antagonist for highly emetogenic chemotherapy","differs":"Uses palonosetron rather than ondansetron or granisetron in the acute phase for children at high risk of delayed sickness, and may then add dexamethasone in the delayed phase rather than routinely.","evidence":"Strong recommendation, moderate quality evidence, for palonosetron in patients at high risk of delayed-phase CINV; conditional, moderate, for adding delayed dexamethasone after palonosetron.","sources":["cog-cinv-2024"]},{"name":"Dietary counselling and yoga for refractory sickness","differs":"Adds sickness-focused dietary counselling or yoga for a child who stays sick despite every suitable antiemetic.","evidence":"Conditional recommendation, low-quality evidence.","sources":["cog-cinv-2024"]}],"grades":[{"claim":"5-HT3 antagonist, dexamethasone and (fos)aprepitant for highly emetogenic chemotherapy","grade":"Strong recommendation, High quality evidence","source":"cog-cinv-2024"},{"claim":"Olanzapine considered with highly emetogenic chemotherapy","grade":"Conditional recommendation, Moderate quality evidence","source":"cog-cinv-2024"},{"claim":"5-HT3 antagonist with dexamethasone for moderately emetogenic chemotherapy","grade":"Strong recommendation, Moderate quality evidence","source":"cog-cinv-2024"},{"claim":"5-HT3 antagonist for low emetogenic chemotherapy","grade":"Strong recommendation, Low quality evidence","source":"cog-cinv-2024","quote":"a. Use a 5HT3RA"},{"claim":"No routine prophylaxis for minimally emetogenic chemotherapy","grade":"Strong recommendation, Very low quality evidence","source":"cog-cinv-2024"},{"claim":"Oral aprepitant in the delayed phase if started acutely (highly emetogenic)","grade":"Strong recommendation, High quality evidence","source":"cog-cinv-2024"},{"claim":"No 5-HT3 antagonists in the delayed phase","grade":"Strong recommendation, Low quality evidence","source":"cog-cinv-2024"},{"claim":"Escalate to the next level's prophylaxis for breakthrough sickness","grade":"Strong recommendation, Low-quality evidence","source":"cog-cinv-2024"},{"claim":"Lorazepam considered for secondary prevention of anticipatory sickness","grade":"Conditional recommendation, Very low-quality evidence","source":"cog-cinv-2024"},{"claim":"No clonidine for anticipatory sickness","grade":"Strong recommendation, Low-quality evidence","source":"cog-cinv-2024"}],"sources":[{"key":"cog-cinv-2024","label":"COG-endorsed guidelines on chemotherapy-induced nausea and vomiting: classification, acute, delayed, anticipatory, breakthrough and refractory (version date 15 January 2024)","publisher":"Children's Oncology Group","year":2024,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_CINV_Guidelines_Document_15JAN2024-new-logo.pdf","gradingScheme":"GRADE, reprinted from the source guidelines: strong or conditional recommendation, with high, moderate, low or very low quality evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"pogo-classification-2019","label":"Classification of the acute emetogenicity of chemotherapy in pediatric patients: a clinical practice guideline","publisher":"Pediatric Oncology Group of Ontario, Pediatric Blood & Cancer","year":2019,"url":"https://europepmc.org/abstract/MED/30729654","doi":"10.1002/pbc.27646","read":"abstract","accessed":"2026-11-11"},{"key":"pogo-acute-delayed-2022","label":"Prevention of acute and delayed chemotherapy-induced nausea and vomiting in pediatric cancer patients: a clinical practice guideline","publisher":"Pediatric Oncology Group of Ontario, Pediatric Blood & Cancer","year":2022,"url":"https://europepmc.org/abstract/MED/36221901","doi":"10.1002/pbc.30001","read":"abstract","accessed":"2026-11-11"},{"key":"pogo-anticipatory-2021","label":"Prevention and treatment of anticipatory chemotherapy-induced nausea and vomiting in pediatric cancer patients and hematopoietic stem cell recipients: clinical practice guideline update","publisher":"Pediatric Oncology Group of Ontario, Pediatric Blood & Cancer","year":2021,"url":"https://europepmc.org/abstract/MED/33686754","doi":"10.1002/pbc.28947","read":"abstract","accessed":"2026-11-11"},{"key":"pogo-breakthrough-2023","label":"Treatment of breakthrough and prevention of refractory chemotherapy-induced nausea and vomiting in pediatric cancer patients: clinical practice guideline update","publisher":"Pediatric Oncology Group of Ontario, Pediatric Blood & Cancer","year":2023,"url":"https://europepmc.org/abstract/MED/37178438","doi":"10.1002/pbc.30395","read":"abstract","accessed":"2026-11-11"},{"key":"asco-antiemetics-2020","label":"Antiemetics: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2020,"url":"https://europepmc.org/abstract/MED/32658626","doi":"10.1200/JCO.20.01296","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-moon-olanzapine-antiemetic-everywhere"],"gaps":["Doses of the antiemetics for children are not given in the COG summary and were not read in the full source guidelines, which are not open access; the source guidelines name optimal dosing and safety as evidence gaps.","The ASCO 2020 antiemetics update, endorsed by COG for acute prevention, was not read; how it differs from the paediatric guidelines is not set out here.","Many chemotherapies given to children have no paediatric emetogenicity data; the classification guideline says adult guidelines may be consulted for them.","No recommendation could be made for treating anticipatory sickness once it has started.","Several recommendations wrap across the grade column of the COG PDF; their grades were read from the layout text and they carry no quote."]},{"id":"paediatric-oral-mucositis-prevention","kind":"protocol","name":"Preventing mouth sores (oral mucositis) in children having cancer treatment or a stem cell transplant","aka":["paediatric oral mucositis prevention","pediatric mucositis prophylaxis","cryotherapy ice chips children","photobiomodulation children transplant","mouth care during chemotherapy children"],"tldr":"Some chemotherapy and transplants cause painful sores in the mouth and throat. Older children who can manage it suck ice during short infusions of certain drugs, and children having a stem cell transplant or radiotherapy to the head and neck have gentle red-light treatment inside the mouth. Good daily mouth care and a dental check before treatment help too.","summary":"The Pediatric Oncology Group of Ontario 2021 update (seven systematic reviews, 107 studies, GRADE), endorsed by the Children's Oncology Group, covers patients aged 0 to 18. Cryotherapy: use for older, cooperative children receiving short infusions of melphalan or 5-fluorouracil (strong, high), consider for short infusions of other mucotoxic chemotherapy (conditional, moderate); the panel thought it not feasible for infusions longer than 1 hour or in young children. Intraoral photobiomodulation in the red spectrum (620 to 750 nm): use for children having autologous or allogeneic transplant and for head and neck carcinoma radiotherapy (strong, high), consider for radiotherapy to other head and neck cancers such as rhabdomyosarcoma (conditional, moderate). Do not give palifermin routinely (strong, high), because its benefit was modest (risk ratio for severe mucositis 0.81) against short-term harms, possible long-term effects on cancer outcomes, cost and availability; do not give G-CSF to prevent mucositis (strong, high). The adult MASCC/ISOO 2020 guideline adds multiagent basic oral care protocols during chemotherapy, radiotherapy and transplant (level III), dental assessment before treatment (expert opinion), and differs on palifermin, which it recommends for autologous transplant with high-dose chemotherapy and total body irradiation.","asOf":"2026-11-11","links":[],"tags":["protocol","paediatric","mucositis"],"related":["oral-mucositis-prevention-and-oral-care"],"cancers":["childhood-cancers"],"sections":["supportive-care"],"technologies":["oral-cryotherapy-mucositis","photobiomodulation-mucositis","allogeneic-hsct","autologous-stem-cell-transplant"],"targets":[],"drugs":["palifermin","filgrastim"],"companies":["childrens-oncology-group"],"institutions":["mascc"],"pathways":[],"terms":["mucositis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer treatment can make the mouth very sore. Sucking ice during some drips, and a red-light treatment in the mouth for children having a transplant, can lower the chance of bad sores.","domain":"paediatric","setting":{"who":["nurse","doctor","patient-or-carer","multidisciplinary-team"],"where":["ward","chemotherapy-day-unit","radiotherapy-department","home"]},"population":"Children and adolescents aged 0 to 18 receiving treatment for cancer or undergoing haematopoietic stem cell transplant, as the paediatric guideline scopes it. The basic oral care steps rest on the MASCC/ISOO guideline, which is written mainly from adult evidence.","trigger":"A child is due to start chemotherapy, radiotherapy to the head and neck, or transplant conditioning likely to cause mucositis.","steps":[{"action":"Arrange a dental assessment, and any treatment needed, before cancer treatment starts","why":"Bad teeth and gums can become a source of infection once the white count falls.","source":"mascc-isoo-2020","quote":"the panel is of the opinion that dental evaluation and treatment as indicated before cancer therapy are desirable to reduce risk for local and systemic infections from odontogenic sources.","grade":"Expert opinion"},{"action":"Put a daily oral care routine in place, with tooth brushing and bland rinses, and teach the child and family to keep it up","why":"Combined mouth care routines lowered mucositis in trials of chemotherapy, radiotherapy and transplant, mostly in adults.","source":"mascc-isoo-2020","quote":"The panel suggests that implementation of multiagent combination oral care protocols is beneficial for the prevention of OM during CT.","grade":"LoE III (suggestion)"},{"action":"For an older, cooperative child having a short infusion of melphalan or 5-fluorouracil, give ice chips or ice water to hold in the mouth during the infusion","why":"In trials it halved severe mucositis (risk ratio 0.49), with no documented harms and little cost; it suits infusions of 30 minutes or less.","source":"patel-mucositis-2021","quote":"Cryotherapy should be used for older cooperative pediatric patients who will receive short infusions of melphalan or 5-fluorouracil.","grade":"Strong recommendation, High-quality evidence"},{"action":"Consider ice for short infusions of other chemotherapy that causes mucositis, and tell families that sores can still happen","why":"The benefit is likely to carry over to other drugs, but there is no direct evidence; cooling is not practical for infusions longer than an hour.","source":"cog-mucositis-2022","quote":"Consider using cryotherapy for older, cooperative pediatric patients receiving treatment for cancer or undergoing HSCT who will receive short infusions of chemotherapy associated with mucositis other than melphalan or 5-fluorouracil.","grade":"Conditional recommendation, Moderate-quality evidence"},{"action":"For a child having an autologous or allogeneic transplant, or radiotherapy for head and neck carcinoma, give intraoral red-light photobiomodulation (620 to 750 nm)","why":"It reduced severe mucositis by more than half in trials and was workable in children of all ages, though it needs trained staff, equipment and eye protection.","source":"cog-mucositis-2022","quote":"Use intraoral photobiomodulation therapy in the red light spectrum (620–750 nm) for pediatric patients undergoing autologous or allogeneic HSCT and for pediatric patients who will receive radiotherapy for head and neck carcinoma.","grade":"Strong recommendation, High-quality evidence"},{"action":"Consider photobiomodulation for radiotherapy to other head and neck cancers, such as rhabdomyosarcoma","why":"The benefit is expected to be similar, but there are no direct data in these cancers.","source":"cog-mucositis-2022","quote":"Consider using intraoral photobiomodulation therapy in the red light spectrum (620–750 nm) for pediatric patients who will receive radiotherapy for head and neck cancers other than carcinoma.","grade":"Conditional recommendation, Moderate-quality evidence"},{"action":"Do not give palifermin routinely","why":"It reduced severe mucositis only modestly, has short-term side effects, may affect cancer outcomes in the long term, and is costly and hard to get.","source":"cog-mucositis-2022","quote":"Do not administer palifermin routinely to pediatric patients with cancer receiving treatment for cancer or undergoing HSCT.","grade":"Strong recommendation, High-quality evidence"},{"action":"Do not give G-CSF to prevent mucositis","why":"It did not prevent mucositis; children may still have it for other reasons, such as shortening neutropenia.","source":"cog-mucositis-2022","quote":"Do not administer GCSFs to pediatric patients receiving treatment for cancer or undergoing HSCT for the purpose of mucositis prevention.","grade":"Strong recommendation, High-quality evidence"}],"bestInClass":{"statement":"For children, the POGO 2021 update endorsed by the Children's Oncology Group is the current guideline: cryotherapy for older, cooperative children on short melphalan or 5-fluorouracil infusions, red-light intraoral photobiomodulation for transplant and head and neck radiotherapy, and no routine palifermin or G-CSF. The adult MASCC/ISOO 2020 guideline agrees on cryotherapy (melphalan conditioning and bolus 5-fluorouracil, level II) and photobiomodulation (adult transplant, level I) and adds basic oral care protocols, but differs on palifermin: MASCC/ISOO recommends intravenous KGF-1 (palifermin) for haematological cancers having autologous transplant with high-dose chemotherapy and total body irradiation (level I), where the paediatric panel advises against routine use because of harms, possible long-term effects on cancer outcomes and cost.","sources":["cog-mucositis-2022","patel-mucositis-2021","mascc-isoo-2020"]},"variants":[{"name":"Palifermin in autologous transplant with total body irradiation (MASCC/ISOO, adults)","differs":"Gives intravenous palifermin to prevent mucositis in people with haematological cancers having autologous transplant with high-dose chemotherapy and total body irradiation.","evidence":"MASCC/ISOO level I recommendation in adults. The paediatric guideline makes a strong recommendation against routine use in children (risk ratio for severe mucositis 0.81).","sources":["mascc-isoo-2020","cog-mucositis-2022"]},{"name":"Chlorhexidine mouthwash","differs":"Some units use chlorhexidine rinses as part of mouth care to prevent mucositis.","evidence":"MASCC/ISOO suggests chlorhexidine not be used to prevent mucositis during head and neck radiotherapy (level III); the paediatric guideline makes no recommendation on it.","sources":["mascc-isoo-2020"]}],"grades":[{"claim":"Cryotherapy for short melphalan or 5-fluorouracil infusions in older, cooperative children","grade":"Strong recommendation, High-quality evidence","source":"cog-mucositis-2022"},{"claim":"Cryotherapy considered for other short mucotoxic infusions","grade":"Conditional recommendation, Moderate-quality evidence","source":"cog-mucositis-2022"},{"claim":"Photobiomodulation for transplant and head and neck carcinoma radiotherapy","grade":"Strong recommendation, High-quality evidence","source":"cog-mucositis-2022"},{"claim":"No routine palifermin in children","grade":"Strong recommendation, High-quality evidence","source":"cog-mucositis-2022"},{"claim":"No G-CSF for mucositis prevention","grade":"Strong recommendation, High-quality evidence","source":"cog-mucositis-2022"},{"claim":"Multiagent oral care protocols during chemotherapy (adults)","grade":"LoE III","source":"mascc-isoo-2020"},{"claim":"Palifermin for autologous transplant with high-dose chemotherapy and total body irradiation (adults)","grade":"LoE I","source":"mascc-isoo-2020","quote":"The use of KGF‐1 intravenously is recommended for the prevention of OM in patients with hematologic cancer undergoing autologous HSCT with a conditioning regimen that includes high‐dose CT and TBI."},{"claim":"Chlorhexidine not to be used to prevent mucositis during head and neck radiotherapy (adults)","grade":"LoE III","source":"mascc-isoo-2020","quote":"The panel suggests that CHX not be used in the prevention of OM in patients undergoing H&N RT."}],"sources":[{"key":"cog-mucositis-2022","label":"Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem cell transplant patients: 2021 update (COG endorsement, version date 7 February 2022)","publisher":"Children's Oncology Group","year":2022,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_Mucositis_Guideline_Document_07FEB2022-new-logo.pdf","gradingScheme":"GRADE, reprinted from the source guideline: strong or conditional recommendation, with high, moderate, low or very low quality evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"patel-mucositis-2021","label":"Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem cell transplant patients: 2021 update","publisher":"Pediatric Oncology Group of Ontario, European Journal of Cancer","year":2021,"url":"https://europepmc.org/abstract/MED/34252760","doi":"10.1016/j.ejca.2021.05.013","gradingScheme":"GRADE: strong or conditional recommendations; evidence high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-isoo-2020","label":"MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy","publisher":"MASCC and ISOO, Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7540329","doi":"10.1002/cncr.33100","gradingScheme":"Level of evidence I to V printed beside each statement; 'recommends' for stronger and 'suggests' for weaker evidence; expert opinion where no guideline was possible.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-oral-cryotherapy-with-bolus-chemotherapy"],"gaps":["The full text of the paediatric 2021 guideline is not open access and was read through the COG endorsement document and the abstract; the photobiomodulation settings (wavelength apart) and the cryotherapy method used in the trials are not given here.","The paediatric guideline makes no recommendation on basic oral care, chlorhexidine or other mouthwashes; the oral care steps rest on adult MASCC/ISOO evidence.","Cryotherapy was not feasible in young children, and no prevention is recommended for them during chemotherapy other than in transplant.","Photobiomodulation needs equipment and trained staff that many centres do not have; access has not been measured here."]},{"id":"paediatric-procedural-pain-and-sedation","kind":"protocol","name":"Procedural pain and sedation for children with cancer: needles, lumbar punctures and marrow tests","aka":["sedation for lumbar puncture in children","general anaesthetic for LP","needle pain in children with cancer","numbing cream before port access","procedural distress paediatric oncology","bone marrow aspirate sedation"],"tldr":"Children with cancer have many needles, lumbar punctures and bone marrow tests. An international guideline says every needle procedure should use numbing cream and distraction, and every child having a lumbar puncture should be offered deep sedation or a general anaesthetic. Sedation is given by a trained team with monitoring, after the child and family are prepared for what will happen.","summary":"The international clinical practice guideline on needle procedures in children with cancer (Loeffen et al., Eur J Cancer 2020; GRADE, 48 randomised trials, 2,271 participants, evidence very low to moderate) makes strong recommendations for topical anaesthetics in all needle procedures, for offering deep sedation or general anaesthesia to all children undergoing lumbar puncture, for deep sedation or general anaesthesia in major procedures in children of all ages, and for hypnosis and active distraction in all needle procedures. NICE CG112 (sedation in under 19s) sets the safety frame: trained pre-sedation assessment and documented consent, psychological preparation suited to the child's development, parents offered the chance to be present, a team with life support skills (advanced life support for deep sedation), an anaesthetist available for propofol, sevoflurane or opioids with ketamine, continuous monitoring including capnography for deep sedation, and discharge criteria. Fasting is not needed for minimal sedation, nitrous oxide or moderate sedation with verbal contact; for deeper sedation professional fasting guidance applies, with the 2018 move to 1 hour for clear fluids. For painful procedures NICE suggests considering a local anaesthetic as well as a sedative.","asOf":"2026-11-11","links":[],"tags":["protocol","paediatric","procedural-pain","sedation"],"related":["hand-hygiene-in-cancer-care","implanted-port-access-and-care"],"cancers":["childhood-cancers","all-leukemia"],"sections":["supportive-care"],"technologies":["implanted-ports"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["nice","who"],"pathways":[],"terms":["intrathecal-therapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Needles and spinal taps should not have to hurt. Ask for numbing cream, distraction such as games or videos, and for a lumbar puncture, a sleep medicine or anaesthetic. A trained team watches your child closely.","domain":"paediatric","setting":{"who":["nurse","doctor","anaesthetist","patient-or-carer"],"where":["outpatient-clinic","ward","theatre","chemotherapy-day-unit"]},"population":"Children and young people with cancer having needle procedures (port access, venepuncture, cannulation, injections), lumbar punctures and bone marrow aspiration or biopsy (Loeffen 2020); NICE CG112 covers sedation for diagnostic and therapeutic procedures in anyone under 19.","trigger":"A needle procedure, lumbar puncture or bone marrow test is planned for a child having cancer care.","steps":[{"action":"Use a topical anaesthetic for every needle procedure, including port access","why":"Children with cancer have many needles during treatment; numbing the skin reduces pain each time and the fear that builds up.","source":"loeffen-2020","quote":"Strong recommendations were made for the use of topical anesthetics in all needle procedures, for offering deep sedation (DS)/general anesthesia (GA) to all children undergoing lumbar puncture, for the use of DS/ GA in major procedures in children of all ages, for the use of hypnosis in all needle procedures and for the use of active distraction in all needle procedures.","grade":"Strong recommendation"},{"action":"Use active distraction, and hypnosis where staff are trained in it, for every needle procedure","why":"Psychological methods reduce pain and distress at little cost and work alongside numbing cream.","source":"loeffen-2020","grade":"Strong recommendation"},{"action":"Offer every child having a lumbar puncture deep sedation or a general anaesthetic","why":"Lumbar punctures are repeated many times in leukaemia treatment; deep sedation lets the child keep still and avoids the procedure becoming traumatic.","source":"loeffen-2020","grade":"Strong recommendation"},{"action":"Before sedation, have a trained professional assess the child, including airway, medicines, previous sedation and development, and document it","why":"The assessment picks out children who need a specialist or an anaesthetist, such as those with airway problems or ASA grade 3 or above.","source":"nice-cg112","quote":"Ensure that trained healthcare professionals (see section 1.4) carry out pre‑sedation assessments and document the results in the healthcare record."},{"action":"Give the child and family spoken and written information on the sedation, its alternatives, risks and benefits, and record consent","why":"Families decide better, and children cope better, when they know what will happen.","source":"nice-cg112","quote":"Obtain and document informed consent for sedation."},{"action":"Prepare the child psychologically: what will happen, what they will feel and how to cope, in words suited to their age","why":"Preparation lowers distress, and checking understanding shows whether the explanation worked.","source":"nice-cg112","quote":"Ensure that the information is appropriate for the developmental stage of the child or young person and check that the child or young person has understood the information."},{"action":"Offer parents the chance to be present, with advice on their role","why":"Many children are calmer with a parent there, and parents cope better when they know what to do.","source":"nice-cg112","quote":"Offer parents and carers the opportunity to be present during sedation if appropriate. If a parent or carer decides to be present, offer them advice about their role during the procedure."},{"action":"Record the time of the last food and drink; fast only for deep sedation or moderate sedation without verbal contact, following current anaesthetic guidance","why":"Fasting protects the airway under deep sedation but is not needed for lighter sedation; long fasts are distressing for small children.","source":"nice-cg112","quote":"Before starting sedation, confirm and record the time of last food and fluid intake in the healthcare record."},{"action":"Make sure the team has the right life support skills, and an anaesthetist for propofol, sevoflurane or opioids with ketamine","why":"Deep sedation can stop a child breathing; the person giving it must be able to rescue the airway.","source":"nice-cg112","quote":"Ensure that all members of the sedation team have basic life support skills for minimal, moderate and deep sedation. At least 1 team member should have intermediate life support skills for moderate sedation and advanced life support skills for deep sedation."},{"action":"Clean hands before the lumbar puncture and before putting on gloves","why":"A lumbar puncture enters a sterile space; gloves alone may not prevent contamination.","source":"who-2009","quote":"For some tasks on clean sites (lumbar puncture, surgical procedures, tracheal suctioning, etc.), the use of gloves is standard procedure. In this case, hand hygiene is required before donning gloves because gloves alone may not entirely prevent contamination"},{"action":"During deep sedation, continuously monitor depth of sedation, breathing, oxygen saturation, heart rate and ECG, with capnography and blood pressure every 5 minutes where possible","why":"Monitoring catches slowed breathing or low oxygen early; the person giving sedation does nothing else.","source":"nice-cg112","quote":"The healthcare professional administering sedation should be involved only in continuously monitoring, interpreting and responding to all of the above."},{"action":"Discharge only when vital signs are normal, the child is awake with no risk of drowsiness returning, and nausea, vomiting and pain are controlled","why":"Some sedatives last longer than the procedure; going home too early risks a drowsy child with no one watching.","source":"nice-cg112","quote":"the child or young person is awake (or returned to baseline level of consciousness) and there is no risk of further reduced level of consciousness"}],"bestInClass":{"statement":"Follow the international paediatric oncology needle-procedure guideline (Loeffen 2020): topical anaesthetic, active distraction and hypnosis for every needle procedure, and deep sedation or general anaesthesia offered for every lumbar puncture and major procedure, all strong recommendations. Deliver the sedation within NICE CG112's safety frame of assessment, consent, preparation, a skilled team, continuous monitoring and discharge criteria. NICE CG112 is general rather than oncology-specific, and for painful procedures it suggests lighter options first (nitrous oxide or oral or intranasal midazolam for minimal or moderate sedation, then ketamine or intravenous midazolam with or without fentanyl, then propofol) where the oncology guideline offers deep sedation for every lumbar puncture.","sources":["loeffen-2020","nice-cg112"]},"variants":[{"name":"Stepped sedation for painful procedures (NICE CG112)","differs":"For painful procedures at minimal or moderate target depth, considers nitrous oxide and/or oral or intranasal midazolam first, then intravenous or intramuscular ketamine or intravenous midazolam with or without fentanyl, then a specialist technique such as propofol, with a local anaesthetic in all cases.","evidence":"NICE does not grade recommendations; the guideline is for all procedures in under 19s, not oncology, and its examples are suturing and fracture manipulation.","sources":["nice-cg112"]}],"grades":[{"claim":"Topical anaesthetics in all needle procedures","grade":"Strong recommendation","source":"loeffen-2020"},{"claim":"Offer deep sedation or general anaesthesia to all children undergoing lumbar puncture","grade":"Strong recommendation","source":"loeffen-2020"},{"claim":"Hypnosis and active distraction in all needle procedures","grade":"Strong recommendation","source":"loeffen-2020"},{"claim":"Quality of evidence across the recommendations","grade":"very low to moderate (GRADE)","source":"loeffen-2020","quote":"Quality of evidence supporting the recommendations ranged from very low to moderate."}],"sources":[{"key":"loeffen-2020","label":"Reducing pain and distress related to needle procedures in children with cancer: A clinical practice guideline","publisher":"International inter-disciplinary guideline panel (Loeffen et al.), European Journal of Cancer","year":2020,"url":"https://europepmc.org/article/MED/32302949","doi":"10.1016/j.ejca.2020.02.039","gradingScheme":"GRADE with evidence-to-decision frameworks: strong or weak recommendations, evidence high to very low.","read":"abstract","accessed":"2026-11-11"},{"key":"nice-cg112","label":"Sedation in under 19s: using sedation for diagnostic and therapeutic procedures (CG112), recommendations","publisher":"NICE","year":2010,"url":"https://www.nice.org.uk/guidance/cg112/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; strength is in the wording ('ensure', 'consider', 'do not').","read":"full-text","accessed":"2026-11-11"},{"key":"cog-sedation-review-2020","label":"Evidence-Based Recommendations for the Appropriate Level of Sedation to Manage Pain in Pediatric Oncology Patients Requiring Procedures: A Systematic Review From the Children's Oncology Group","publisher":"Children's Oncology Group nursing, Journal of Pediatric Oncology Nursing","year":2020,"url":"https://europepmc.org/article/MED/31303100","doi":"10.1177/1043454219858610","read":"abstract","accessed":"2026-11-11"},{"key":"who-2009","label":"WHO Guidelines on Hand Hygiene in Health Care","publisher":"World Health Organization","year":2009,"url":"https://www.who.int/publications/i/item/9789241597906","gradingScheme":"CDC/HICPAC categories IA, IB, IC and II.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The 2020 international guideline was read only as an abstract, so its weak recommendations, its advice on specific drugs and its grades for each strong recommendation are not given here.","The Children's Oncology Group nursing review makes a recommendation on the level of sedation for bone marrow aspirates and biopsies that its abstract does not state; it was not read in full.","No guideline read sets doses for sedative or topical anaesthetic drugs in children with cancer; these come from local protocols and product licences.","The Children's Oncology Group archived its guideline on atraumatic (pencil-point) needles for lumbar puncture in August 2024; no current guideline on needle type was read.","Intrathecal chemotherapy safety, including the separation of vinca alkaloids from intrathecal drugs, is not covered by this protocol."]},{"id":"icaht-prolonged-cytopenia","kind":"protocol","name":"Prolonged low blood counts after CAR T-cell therapy (ICAHT): grading, work-up and treatment","aka":["ICAHT","immune effector cell-associated hematotoxicity","prolonged cytopenia after CAR T","post-CAR T neutropenia","CAR-HEMATOTOX","stem cell boost after CAR T"],"tldr":"Low blood counts are the commonest side effect of CAR T-cell therapy. Most recover within weeks, but in some people counts stay low for months, raising infection risk. Teams check counts often, give growth factor injections, transfusions and infection-preventing tablets, and look at the bone marrow if counts stay low after about a month. Some need their own stored stem cells.","summary":"EHA/EBMT 2023 named immune effector cell-associated haematotoxicity (ICAHT) and graded it by depth and duration of neutropenia, separately for early (day 0 to 30) and late (after day +30) cytopenia; it also set out risk factors, the pre-infusion CAR-HEMATOTOX score and recommendations on growth factors, prophylaxis, transfusion, autologous stem cell boost and allogeneic transplant. Only its abstract could be read. ASTCT's 2026 consensus grading update also addresses ICAHT (abstract only).\n\nSITC 2020 (LE: 4 unless stated): for cytopenias in the first 28 days, follow blood counts without marrow biopsy; for cytopenias beyond 28 days, bone marrow aspirate and biopsy with viral studies; consider holding G-CSF until day 14 or CRS has resolved; consider growth factors for ANC under 500 per microlitre after day 28; no GM-CSF in the CRS window (LE: 5); antibacterial and antifungal prophylaxis for all with persistent neutropenia. The Haematologica 2025 review (Beyar-Katz, Rejeski, Shouval): watch and wait for early cytopenias; irradiated red cells and platelets because of fludarabine exposure; red cell threshold 7 to 8 g/dL; platelets at 10 or below (20 with bleeding, fever or infection); thrombopoietin receptor agonists for persistent thrombocytopenia (retrospective data only); autologous CD34+ boost for G-CSF-refractory ICAHT, with 70 to 100% neutrophil recovery in retrospective series, and allogeneic transplant as a last option. No prospective or randomised trial of any ICAHT treatment exists.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t"],"related":["car-t-infection-prevention","crs-grading-and-management","iec-hs-management"],"cancers":[],"sections":[],"technologies":["car-t","rejuv-tx-prolonged-cytopenias"],"targets":[],"drugs":["filgrastim","eltrombopag","romiplostim"],"companies":[],"institutions":["eha","sitc"],"pathways":[],"terms":["cytopenias","lymphodepletion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After CAR T-cell therapy, blood counts can stay low for a long time. Your team will check them, may give injections or transfusions, and will help protect you from infection.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","nurse","multidisciplinary-team"],"where":["ward","outpatient-clinic"]},"population":"Adults and children after CD19- or BCMA-directed CAR T-cell therapy for lymphoma, leukaemia or myeloma. The ICAHT grading was built for CAR T cells; its use after bispecific antibodies is not established (Haematologica 2025 review).","trigger":"Neutropenia, thrombocytopenia or anaemia after CAR T-cell infusion, especially beyond day 28 or recurring after initial recovery.","steps":[{"action":"Before lymphodepletion, assess bone marrow reserve and inflammation, for example with the CAR-HEMATOTOX score","why":"Knowing who is at high risk lets the team plan growth factors, back-up stem cells or a gentler conditioning regimen.","source":"haematologica-2025","quote":"The use of the recently introduced and widely applied CAR-HEMATOTOX score, evaluating these parameters, allows for early identification of patients at high risk of developing ICAHT."},{"action":"Grade neutropenia by depth and duration, separately for days 0 to 30 and after day 30","why":"A shared grading lets teams compare and decide when to escalate.","source":"eha-ebmt-icaht-2023","quote":"For the grading of ICAHT, a classification system based on depth and duration of neutropenia was developed for early (day 0-30) and late (after day +30) cytopenia."},{"action":"In the first 28 days, follow blood counts with a differential; a marrow biopsy is usually not needed","why":"Early low counts are expected after lymphodepletion and often recover on their own.","source":"sitc-iec-2020","quote":"For cytopenias occurring within the first 28 days after IEC infusion, a bone marrow biopsy may not be indicated—complete blood counts with differential may be adequate for follow-up","grade":"LE: 4"},{"action":"If cytopenias persist beyond 28 days, perform bone marrow aspirate and biopsy, including tests for viruses","why":"Relapse, infection of the marrow or a new marrow disorder can each cause low counts and need different treatment.","source":"sitc-iec-2020","quote":"For cytopenias persisting >28 days after IEC infusion, bone marrow biopsy and bone marrow aspiration should be performed in addition to the standard work-up to assess response and cellularity, including assessment of viral pathogens","grade":"LE: 4"},{"action":"Consider holding G-CSF until day 14 or until CRS has resolved","why":"Growth factor during peak CAR T-cell expansion was feared to worsen cytokine release syndrome.","source":"sitc-iec-2020","quote":"To avoid interaction with the peak CRS risk and CART expansion period, consider holding growth factors until day 14 from infusion of CAR T cells or once CRS has resolved","grade":"LE: 4"},{"action":"For neutrophils persistently below 500 per microlitre after day 28, consider G-CSF; avoid GM-CSF in the CRS window","why":"Growth factor shortens severe neutropenia; GM-CSF in particular may aggravate CRS.","source":"sitc-iec-2020","quote":"For persistent neutropenia (ANC<500 cells/µL) after day 28 following CAR T cell infusion, growth factors should be considered","grade":"LE: 4"},{"action":"Give antibacterial and antifungal prophylaxis to everyone with persistent neutropenia","why":"Long neutropenia is when serious bacterial and fungal infections happen.","source":"sitc-iec-2020","quote":"All patients who develop persistent neutropenia should have antibacterial and antifungal prophylaxis."},{"action":"Transfuse irradiated red cells and platelets","why":"Fludarabine in the lymphodepletion raises the risk of transfusion-associated graft-versus-host disease.","source":"haematologica-2025","quote":"Blood products are typically administered based on a patient’s blood counts, and it is imperative that red blood cells and platelets be irradiated, in part because of the prior exposure to fludarabine, which can increase the risk of transfusion-associated graft-versus-host disease (Table 3)."},{"action":"For persistent transfusion-dependent thrombocytopenia, a thrombopoietin receptor agonist (eltrombopag or romiplostim) may be considered","why":"These drugs stimulate platelet production; the evidence is retrospective and uncontrolled.","source":"haematologica-2025","quote":"Thrombopoietin receptor agonists, such as eltrombopag and romiplostim, are potential treatment options for patients with persistent thrombocytopenia after CAR T-cell therapy, as they stimulate platelet production and may reduce transfusion dependence."},{"action":"For G-CSF-refractory, persistent ICAHT, give an autologous stem cell boost if the person's own stem cells are stored","why":"In retrospective series most patients recovered neutrophils within one to three weeks of a boost, without conditioning.","source":"haematologica-2025","quote":"For patients with G-CSF-refractory and persistent ICAHT, an autologous stem cell boost is emerging as a promising therapeutic option."},{"action":"Where no stored stem cells exist, consider allogeneic transplant only after other options and only if the person is not critically ill","why":"It can restore blood production but carries its own serious risks.","source":"haematologica-2025","quote":"In cases in which autologous stem cells are not available, allogeneic SCT may be considered, although this option is typically reserved for patients who have exhausted other treatment options and are not critically ill."}],"bestInClass":{"statement":"The EHA/EBMT 2023 consensus is the reference for grading and managing ICAHT, but only its abstract could be read, so its recommendations are not reproduced step by step here. The steps rest on SITC 2020 (graded LE: 4 and LE: 5) and on a 2025 review co-written by the EHA/EBMT consensus's first author, which describes the same toolkit (CAR-HEMATOTOX, grading by depth and duration, G-CSF, transfusion, thrombopoietin receptor agonists, autologous boost, allogeneic transplant). The sources disagree on the timing of G-CSF: SITC 2020 says consider holding it until day 14 or until CRS has resolved; the 2025 review describes G-CSF from day +2 for high-risk patients and cites retrospective data that early G-CSF did not increase CRS progression. EBMT/JACIE 2019 notes that about a third of patients have neutropenia beyond day 30 and that growth factor support may be indicated early.","sources":["eha-ebmt-icaht-2023","sitc-iec-2020","haematologica-2025","ebmt-2019"]},"variants":[{"name":"Prophylactic G-CSF from day +2 in high-risk patients (Haematologica 2025 review)","differs":"Starts G-CSF on day +2 after infusion when CAR-HEMATOTOX predicts high risk, rather than holding it until day 14 or CRS resolution.","evidence":"Retrospective: in 197 patients given prophylactic G-CSF or pegylated G-CSF, progression from grade 1 CRS to higher grades did not increase, and neutrophil recovery was faster. A myeloma series found more CRS with cumulative G-CSF above 1,500 micrograms or more than 5 days.","sources":["haematologica-2025"]},{"name":"Bendamustine instead of fludarabine-cyclophosphamide lymphodepletion for high-risk patients (Haematologica 2025 review)","differs":"Uses bendamustine, described as less myelosuppressive in some cases, for patients at high risk of ICAHT.","evidence":"Described as an option by the review; no comparative trial is cited for ICAHT outcomes.","sources":["haematologica-2025"]},{"name":"Back-up stem cell collection before CAR T-cell therapy (Haematologica 2025 review)","differs":"Collects and stores haematopoietic stem cells before CAR T-cell therapy in patients at significant risk, so a boost is possible later.","evidence":"Number needed to treat and cost-effectiveness unknown; a worldwide survey found a boost available in under 30% of patients, or not at all for 61% of responders.","sources":["haematologica-2025"]},{"name":"Low-dose prednisone for late ICAHT (Haematologica 2025 review)","differs":"Prednisone 0.5 mg/kg/day for prolonged cytopenia, mainly after CAR T cells for B-cell ALL, when G-CSF fails.","evidence":"Described by the review as very circumstantial; one small series of 17 patients.","sources":["haematologica-2025"]}],"grades":[{"claim":"No marrow biopsy needed for cytopenias in the first 28 days","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Marrow aspirate and biopsy with viral studies for cytopenias beyond 28 days","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Growth factors for ANC below 500 after day 28","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"No GM-CSF until the CRS risk period is over","grade":"LE: 5","source":"sitc-iec-2020","quote":"If growth factors are administered, GM-CSF is not recommended until the risk period for CRS is over (usually 2 weeks) (LE: 5)."},{"claim":"Evidence base for ICAHT treatments overall","grade":"expert opinion","source":"haematologica-2025","quote":"There are no prospective or randomized clinical trials specifically focused on ICAHT therapeutic approaches, and current recommendations are largely based on expert opinion."}],"sources":[{"key":"eha-ebmt-icaht-2023","label":"Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations","publisher":"European Hematology Association and EBMT, Blood","year":2023,"url":"https://europepmc.org/abstract/MED/37300386","doi":"10.1182/blood.2023020578","gradingScheme":"Consensus of an international panel of 36 CAR T-cell experts; the abstract gives no grades.","read":"abstract","accessed":"2026-11-11"},{"key":"haematologica-2025","label":"Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies (Beyar-Katz, Rejeski and Shouval, review)","publisher":"Haematologica","year":2025,"url":"https://europepmc.org/article/PMC/PMC12130777","doi":"10.3324/haematol.2024.286027","gradingScheme":"Narrative review; recommendations are not graded and the authors state current recommendations are largely expert opinion.","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"astct-2026","label":"ASTCT Consensus Grading for Toxicities after Immune Effector Cell Therapy","publisher":"American Society for Transplantation and Cellular Therapy, Transplantation and Cellular Therapy","year":2026,"url":"https://europepmc.org/abstract/MED/42711241","doi":"10.1016/j.jtct.2026.05.020","gradingScheme":"Consensus definitions and grading criteria; the abstract gives no grades.","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The EHA/EBMT 2023 ICAHT consensus could not be read beyond its abstract: it is not in PubMed Central and the publisher refused a script. Its grade thresholds (neutrophil count and duration for each grade), and its own recommendations on G-CSF timing, are therefore not stated here.","The ASTCT 2026 consensus grading update, which considered ICAHT among emerging toxicities, was read only as its abstract.","The Haematologica 2025 review's tables (grading systems, risk factors, management) are images and were not read; figures quoted are from its prose.","No prospective or randomised trial of any ICAHT treatment exists in the sources read, and the sources disagree on when G-CSF may start.","The optimal CD34+ dose for an autologous boost is unknown, and the risk of tumour cells in the boost product is unproven either way."]},{"id":"prostate-biopsy-route-and-antibiotic-prophylaxis","kind":"protocol","name":"Prostate biopsy: transperineal or transrectal route, antibiotic prophylaxis and aftercare","aka":["prostate biopsy","transperineal biopsy","LATP","local anaesthetic transperineal biopsy","TRUS biopsy","transrectal ultrasound-guided biopsy","antibiotics before prostate biopsy","MRI-targeted prostate biopsy","post-biopsy sepsis"],"tldr":"If an MRI suggests prostate cancer, needle samples are taken. The European urology guideline now recommends going through the skin between the scrotum and the back passage (transperineal) rather than through the back passage, because infections are rarer, and says most men having it this way need no antibiotics. Blood in urine and semen afterwards is common; fever or shivering needs urgent help.","summary":"Biopsy follows a multiparametric MRI in suspected clinically localised prostate cancer and is offered when the MRI score is 3 or more (NICE NG131 1.2.2 to 1.2.4 [2019]). The EAU 2026 guideline recommends the transperineal route (Strong), with surgical disinfection of the perineal skin (Strong), and omitting antibiotic prophylaxis for transperineal biopsy in men without risk factors for infection such as diabetes or a history of urinary retention (Weak). Where transrectal biopsy is done, it recommends povidone-iodine rectal cleansing (Strong) and either targeted prophylaxis from a rectal swab or stool culture or augmented prophylaxis with two or more antibiotic classes (Strong), and avoiding fluoroquinolones (Strong, because of European restrictions). Both routes can be done under local anaesthetic; a periprostatic block is the standard for transrectal biopsy.\n\nThe evidence: EAU pooled eight randomised trials (1,596 men) with more infections after transrectal biopsy (48 of 789 against 22 of 807, RR 2.48); a review of 165 studies gave sepsis rates of 0.1% transperineal and 0.9% transrectal. Two later trials found no significant difference against transrectal biopsy with targeted or standard prophylaxis (PREVENT: 0 against 4 infections in 658 men, p = 0.059; ProBE-PC: 2.7% against 2.6%). TRANSLATE (1,126 men, 10 UK hospitals) found more grade group 2 or higher cancer with local anaesthetic transperineal biopsy (60% against 54%) and 2 against 9 admissions for infection, at the cost of more immediate pain and embarrassment (38% against 27%). A 2026 meta-analysis of 10 trials (4,188 biopsies) found lower odds of admission for infection with transperineal biopsy (OR 0.23) and no difference with or without antibiotics for transperineal biopsy. NICE (2019) found no evidence to separate the two routes and says \"prostate biopsy\" throughout; it advises against mapping transperineal template biopsy as an initial test. Low-dose aspirin is not an absolute contraindication (EAU).","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["transperineal-prostate-biopsy-devices","mri","ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":["nice"],"pathways":[],"terms":["biopsy","template-mapping-biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A prostate biopsy takes tiny samples with a needle. It is usually done awake with a numbing injection. The needle can go through the skin behind the scrotum or through the back passage. Through the skin causes fewer infections. Blood in your pee or semen for a few weeks is common. If you get a fever or feel shivery and unwell, get help straight away.","domain":"screening-diagnostics","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic"]},"population":"Adults with suspected clinically localised prostate cancer having a first or repeat MRI-directed or systematic prostate biopsy. Men with risk factors for infection (diabetes, a history of urinary retention, immunosuppression, a recent urinary infection) are named as exceptions to omitting antibiotics. Template mapping biopsy under general anaesthetic and biopsy after treatment are not covered.","trigger":"An MRI or clinical findings lead to a decision to biopsy the prostate.","steps":[{"action":"Use multiparametric MRI first, and offer an MRI-influenced biopsy when the Likert score is 3 or more","why":"The MRI shows where to aim the needle and lets some men with a reassuring scan avoid a biopsy.","source":"nice-ng131","quote":"Offer multiparametric MRI-influenced prostate biopsy to people whose Likert score is 3 or more.","grade":"[2019]"},{"action":"Explain the common after-effects and the rare serious ones (infection and sepsis, retention of urine, heavy bleeding) before consent","why":"Most men get some bleeding afterwards and knowing what is normal makes it easier to spot what is not.","source":"nice-ng131","quote":"The most serious is sepsis, which develops in a bit fewer than 1 out of 100 people.","grade":"[2019]"},{"action":"Do the biopsy through the perineum (transperineal) rather than through the rectum where it can be done","why":"Going through skin that can be cleaned, rather than through the bowel, leads to fewer infections.","source":"eau-2026","quote":"Perform prostate biopsy using the transperineal approach due to the low risk of infectious complications and better antibiotic stewardship.","grade":"Strong"},{"action":"Give local anaesthetic into the perineal skin and around the prostate; the biopsy does not need a general anaesthetic","why":"Numbing the area makes the procedure tolerable as a clinic appointment.","source":"eau-2026","quote":"Local anaesthesia can also be used effectively for MRI-targeted and systematic transperineal biopsy","grade":"Summary of evidence (no strength rating)"},{"action":"Disinfect the perineal skin as for surgery before a transperineal biopsy","why":"Clean skin keeps skin bacteria from being carried in by the needle.","source":"eau-2026","quote":"Use routine surgical disinfection of the perineal skin for transperineal biopsy.","grade":"Strong"},{"action":"For a transperineal biopsy in a man without risk factors for infection, do not give routine antibiotics","why":"Trials and reviews found infection rates just as low without them, and unnecessary antibiotics breed resistant bacteria.","source":"eau-2026","quote":"Omit perioperative antibiotic prophylaxis in transperineal biopsy in patients without risk factors for infectious complications.","grade":"Weak"},{"action":"If the biopsy is done through the rectum, clean the rectum with povidone-iodine first","why":"Reducing the bacteria in the bowel lowers the chance the needle carries them into the prostate.","source":"eau-2026","quote":"Use rectal cleansing with povidone-iodine prior to transrectal prostate biopsy.","grade":"Strong"},{"action":"For a transrectal biopsy, give antibiotics targeted to a rectal swab or stool culture, or augmented prophylaxis with two or more classes; avoid fluoroquinolones","why":"Bowel bacteria are often resistant to the old standard antibiotic, and choosing by culture or covering more widely prevents more infections.","source":"eau-2026","quote":"First option: Targeted prophylaxis based on rectal swab or stool culture. Second option: Augmented prophylaxis (using two or more different classes of antibiotics).","grade":"Strong"},{"action":"Send cores from different sites separately to the laboratory","why":"Knowing where each sample came from tells the team where the cancer is and how much there is.","source":"eau-2026","quote":"Ensure that prostate core biopsies from different sites are submitted separately for processing and pathology reporting.","grade":"Strong"},{"action":"Do not stop low-dose aspirin as a matter of routine; plan other blood thinners with the team","why":"Aspirin on its own does not rule out a biopsy; stronger blood thinners need an individual plan.","source":"eau-2026","quote":"Low-dose aspirin is not an absolute contra-indication","grade":"Text statement (no strength rating)"},{"action":"Tell the man that blood in the urine, stool and especially semen is common and can last weeks, and that fever, shivering or being unable to pass urine needs urgent care","why":"Bleeding is expected and settles; infection and urinary retention are the after-effects that need treatment quickly.","source":"nice-ng131","quote":"90 out of 100 people have blood in their semen; in 60 of them, it will last for at least 2 weeks; 25 will consider it a moderate or serious problem.","grade":"[2019]"}],"bestInClass":{"statement":"Transperineal biopsy under local anaesthetic, with surgical skin disinfection and without routine antibiotics in men without risk factors (EAU 2026: route Strong, skin disinfection Strong, omitting antibiotics Weak). The route recommendation rests on fewer infections in pooled randomised trials and large cohorts, a higher detection of significant cancer in TRANSLATE, and antibiotic stewardship; EAU notes the certainty for the infection benefit is low but rates it strong for its clinical significance. Where transrectal biopsy is used, povidone-iodine rectal cleansing and targeted or augmented prophylaxis without fluoroquinolones (EAU Strong). NICE NG131 (2019) does not choose a route: its committee found no evidence to separate them, and it predates PREVENT, ProBE-PC and TRANSLATE. The two later trials comparing transperineal biopsy with transrectal biopsy under antibiotics did not show a significant difference in infection, so the size of the advantage over well-protected transrectal biopsy is uncertain.","sources":["eau-2026","nice-ng131","translate-2025","prevent-2024","euf-meta-2026"]},"variants":[{"name":"Transrectal biopsy with targeted prophylaxis (PREVENT comparator)","differs":"Rectal culture screening for fluoroquinolone-resistant bacteria and antibiotics chosen from the culture, then transrectal biopsy, instead of transperineal biopsy without antibiotics.","evidence":"PREVENT (658 men): 4 infections (1.4%) after transrectal biopsy with targeted prophylaxis against none after transperineal biopsy, p = 0.059; cancer detection similar (53% against 50%). The authors say it achieves similar infection rates but needs rectal cultures and careful antibiotic selection.","sources":["prevent-2024","eau-2026"]},{"name":"NICE: no preference of route","differs":"NICE NG131 refers to \"prostate biopsy\" throughout and recommends against mapping transperineal template biopsy as part of an initial assessment unless in a trial (1.2.5 [2019]); it does not recommend one route of non-mapping biopsy over the other, and its box 1 harms figures come from transrectal biopsy in PROMIS and ProtecT.","evidence":"The 2019 committee found no evidence to separate transperineal (non-mapping) and transrectal biopsy and made a research recommendation on the transperineal route.","sources":["nice-ng131"]},{"name":"Antibiotic prophylaxis for transperineal biopsy","differs":"Many centres still give a single antibiotic dose before transperineal biopsy.","evidence":"EAU summarises meta-analyses of non-randomised cohorts and two randomised trials showing comparable infection rates with and without prophylaxis (for example 1.35% of 29,880 with against 1.22% of 4,772 without); the 2026 meta-analysis of randomised trials found no significant difference. EAU keeps prophylaxis for men with risk factors such as diabetes or a history of urinary retention.","sources":["eau-2026","euf-meta-2026"]},{"name":"AUA/SUO Early Detection of Prostate Cancer guideline (2026 amendment)","differs":"The United States guideline was amended in 2025 to 2026 with revised statements on biopsy technique. Its statements could not be read for this page.","evidence":"Only the abstract was reachable; it reports revised strength of evidence on biopsy techniques without stating them.","sources":["aua-2026"]}],"grades":[{"claim":"Transperineal route","grade":"Strong","source":"eau-2026","quote":"Although data showing the lower risk of infection via the transperineal approach is low in certainty, its statistical and clinical significance warrants its strong rating."},{"claim":"Omit antibiotics for transperineal biopsy in men without risk factors","grade":"Weak","source":"eau-2026"},{"claim":"Surgical disinfection of perineal skin","grade":"Strong","source":"eau-2026"},{"claim":"Povidone-iodine rectal cleansing before transrectal biopsy","grade":"Strong","source":"eau-2026"},{"claim":"Targeted or augmented antibiotic prophylaxis for transrectal biopsy","grade":"Strong","source":"eau-2026"},{"claim":"Avoid fluoroquinolones for prostate biopsy","grade":"Strong","source":"eau-2026","quote":"A ‘Strong’ rating is given for avoiding fluoroquinolones in prostate biopsy due to its legal implications in Europe."},{"claim":"Offer MRI-influenced biopsy when the Likert score is 3 or more","grade":"[2019]","source":"nice-ng131"},{"claim":"Do not offer mapping transperineal template biopsy at initial assessment, unless in a trial","grade":"[2019]","source":"nice-ng131","quote":"Do not offer mapping transperineal template biopsy as part of an initial assessment, unless as part of a clinical trial."}],"sources":[{"key":"eau-2026","label":"EAU Guidelines on Prostate Cancer, chapter 5: Diagnostic evaluation (2026 edition, presented at the EAU Annual Congress, London 2026)","publisher":"European Association of Urology (EAU)","year":2026,"url":"https://uroweb.org/guidelines/prostate-cancer/chapter/diagnostic-evaluation","gradingScheme":"Levels of evidence 1a to 4 (modified Oxford) for each summary of evidence; recommendations rated Strong or Weak (modified GRADE).","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng131","label":"Prostate cancer: diagnosis and management (NG131), recommendations (last updated 15 December 2021)","publisher":"NICE","year":2021,"url":"https://www.nice.org.uk/guidance/ng131/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended.","read":"full-text","accessed":"2026-11-11"},{"key":"prevent-2024","label":"Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial","publisher":"Hu et al., European Urology","year":2024,"url":"https://doi.org/10.1016/j.eururo.2023.12.015","doi":"10.1016/j.eururo.2023.12.015","gradingScheme":"Randomised trial; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"translate-2025","label":"Local anaesthetic transperineal biopsy versus transrectal prostate biopsy in prostate cancer detection (TRANSLATE): a multicentre, randomised, controlled trial","publisher":"Lancet Oncology","year":2025,"url":"https://doi.org/10.1016/s1470-2045(25)00100-7","doi":"10.1016/s1470-2045(25)00100-7","gradingScheme":"Randomised trial; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"euf-meta-2026","label":"Infectious Complications After Transrectal Versus Transperineal Prostate Biopsy: A Systematic Review and Meta-analysis","publisher":"European Urology Focus","year":2026,"url":"https://doi.org/10.1016/j.euf.2025.07.005","doi":"10.1016/j.euf.2025.07.005","gradingScheme":"Systematic review and meta-analysis of randomised trials (RoB 2); not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"aua-2026","label":"Updates to Early Detection of Prostate Cancer: AUA/SUO Guideline (2026)","publisher":"American Urological Association and Society of Urologic Oncology (Journal of Urology)","year":2026,"url":"https://doi.org/10.1097/ju.0000000000004995","doi":"10.1097/ju.0000000000004995","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The AUA/SUO guideline statements on biopsy route and antibiotics were not read: the guideline page returned 404 to a script and only the abstract of the 2026 amendment was available.","PREVENT, TRANSLATE and the 2026 meta-analysis were read as abstracts only; figures on this page are those the abstracts and the EAU text state.","Which risk factors should keep antibiotics for transperineal biopsy is not settled: EAU names diabetes and a history of urinary retention as examples, and the trials excluded men with immunocompromise or a need for enhanced prophylaxis.","Management of anticoagulants other than low-dose aspirin before prostate biopsy is not addressed by the sources read.","NICE NG131 has not been updated on biopsy route since 2019 and its harm figures describe transrectal biopsy only."]},{"id":"neutropenic-precautions-and-daily-life","kind":"protocol","name":"Protective measures and daily life during neutropenia: hand hygiene, visitors, pets, plants, school and swimming","aka":["neutropenic precautions","reverse barrier nursing","protective isolation","safe living during chemotherapy","social restrictions for children with cancer","pets during chemotherapy","gardening during chemotherapy","school during chemotherapy"],"tldr":"Clean hands, for everyone, matter most. A 2024 guideline for children with cancer says many old restrictions can go: children can keep pets, go to school even when their white count is low, keep plants and swim, unless they have a PICC line. Still avoid building sites and digging in soil, bath toys that hold water, cleaning pet litter or cages, and ill visitors. Transplant units are stricter.","summary":"For children with cancer on curative treatment as outpatients (not after stem cell transplant), the Dutch Children's Oncology Group guideline (2024, GRADE, endorsed by the Children's Oncology Group in March 2025) makes hand hygiene for patients, carers and staff a strong good practice statement; recommends school or kindergarten attendance irrespective of neutropenia unless a classmate has a serious contagious disease such as varicella (strong, very low); suggests keeping domestic pets (weak, very low) but not letting children clean litter boxes or cages (weak, expert); suggests swimming irrespective of neutropenia (weak, very low) but not with a non-tunnelled line such as a PICC (strong, expert); recommends against reservoir bath toys (strong, very low) and public warm bubble baths (weak); suggests against chlorhexidine bathing or wipes (weak, very low); allows indoor plants (strong, expert); and, following ASCO/IDSA, recommends avoiding prolonged contact with environments high in fungal spores such as construction, demolition, gardening or digging (strong). It advises against crowded places and public transport with neutropenia during viral seasons (weak, expert).\n\nFor HCT recipients the CDC/IDSA/ASBMT guideline (2009) is stricter: no plants or flowers in hospital rooms (DIII), avoid gardening, soil and plants while immunosuppressed (CIII), avoid construction areas, screen visitors and keep symptomatic visitors away (BIII), vaccinate VZV-susceptible contacts (AIII), and do not ask patients to part with pets but avoid reptiles, chicks, exotic and young or ill animals, with someone else changing cat litter.","asOf":"2026-11-11","links":[],"tags":["protocol","neutropenic-precautions","paediatric","safe-living"],"related":["central-line-maintenance-bundle","food-safety-and-neutropenic-diet"],"cancers":["childhood-cancers"],"sections":["supportive-care"],"technologies":["allogeneic-hsct","picc-lines"],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":["asco"],"pathways":[],"terms":["neutropenia","febrile-neutropenia","thrombocytopenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Wash hands often. Children with cancer can usually go to school, keep pets and swim. Stay away from building work and soil. Do not let ill people visit. Ask your team, because transplant patients have extra rules.","domain":"infection-prevention","setting":{"who":["patient-or-carer","nurse","doctor","multidisciplinary-team"],"where":["home","community","ward","outpatient-clinic"]},"population":"Children aged 0 to 18 with cancer receiving treatment with curative intent, at home and in outpatient care (the Dutch guideline excludes hospitalised children, palliative care, care after treatment ends and stem cell transplant); and adult and child recipients of haematopoietic cell transplant (the CDC/IDSA/ASBMT guideline). For adults on chemotherapy outside transplant, only the ASCO/IDSA environmental recommendation was read.","trigger":"Treatment that can lower the white cell count starts, or a family asks what their child can and cannot do.","steps":[{"action":"Make hand hygiene the first measure for the patient, family, visitors and staff, following local protocols","why":"Hands carry most of the germs that cause infection at home and on the ward; this matters more than any restriction on activities.","source":"dcog-2024","quote":"Proper hand hygiene should be performed by patients, caregivers, and medical personnel (STRONG recommendation, GOOD PRACTICE STATEMENT).","grade":"STRONG recommendation, GOOD PRACTICE STATEMENT"},{"action":"Ask visitors to clean their hands before and after visiting, and keep away anyone with fever, rash, vomiting, diarrhoea, a cold or conjunctivitis","why":"Visitors can bring in infections that are mild for them and serious for someone with no white cells.","source":"hct-2009","quote":"All visitors should be screened for symptoms of infection: fever, rash, vomiting, diarrhea, upper respiratory symptoms, or conjunctivitis, and should not be allowed to visit a HCT recipient while they are symptomatic (BIII).","grade":"BIII"},{"action":"Vaccinate family members, household contacts and visitors who have not had chickenpox before they have close contact with a transplant recipient","why":"Chickenpox can be severe in people with weak immunity; protecting those around them reduces exposure.","source":"hct-2009","quote":"Health care workers (HCWs), family members, household contacts, and visitors who are healthy and do not have a reported history of varicella infection or who are VZV-seronegative should receive VZV vaccination before being allowed to visit or have direct contact with an HCT recipient (AIII).","grade":"AIII"},{"action":"Avoid prolonged time near building sites, demolition, house renovation, gardening or digging in soil while neutropenic","why":"These places put large amounts of mould spores into the air, which can cause serious lung infection when neutrophils are low.","source":"dcog-2024","quote":"We recommend that children with cancer and neutropenia should avoid prolonged contact with environments that have high concentrations of fungal spores (i.e., construction or demolition sites, exposure to soil through gardening or digging, household renovation) (STRONG recommendation, ASCO and IDSA guideline [21]).","grade":"STRONG recommendation, ASCO and IDSA guideline"},{"action":"Let children with cancer go to school or nursery whatever their neutrophil count, unless someone in their class has a serious contagious illness such as chickenpox","why":"School matters for a child's life and learning, and the infection risk from attending is small; chickenpox in the class is the exception to discuss with the team.","source":"dcog-2024","quote":"We recommend allowing children with cancer to attend school or kindergarten irrespective of neutropenia (unless someone in their class or group has a contagious disease with potential severe consequences, e.g., varicella zoster) (STRONG recommendation, VERY LOW quality evidence).","grade":"STRONG recommendation, VERY LOW quality evidence"},{"action":"Let families keep their pets, but do not let the child clean the litter box or cage","why":"Pets help a child's wellbeing and no study found they raise infection; cleaning up after them is the task with the most germs and is easy to hand to someone else.","source":"dcog-2024","quote":"We suggest allowing to keep domestic pets in the households of children with cancer (WEAK recommendation, VERY LOW quality of evidence).","grade":"WEAK recommendation, VERY LOW quality of evidence"},{"action":"Allow swimming whatever the neutrophil count, but not with a non-tunnelled line such as a PICC","why":"Swimming was not linked to more infection in children with tunnelled lines; a PICC carries a higher infection risk and the panel advises against it.","source":"dcog-2024","quote":"We strongly believe children with cancer with a non-tunneled central venous catheter such as PICC line should not swim (STRONG recommendation, EXPERT opinion).","grade":"STRONG recommendation, EXPERT opinion"},{"action":"Do not use bath toys that hold water inside or cannot be dried thoroughly","why":"Water trapped inside bath toys grows Pseudomonas, and such toys have been linked to infections and an outbreak on a children's cancer ward.","source":"dcog-2024","quote":"We recommend against the use of bath toys that have a reservoir (in which water can be retained) or bath toys that cannot be dried thoroughly (STRONG recommendation, VERY LOW quality of evidence).","grade":"STRONG recommendation, VERY LOW quality of evidence"},{"action":"Do not add chlorhexidine bathing or antiseptic wipes at home to ordinary hygiene","why":"Studies in children with cancer did not show it adds anything to normal washing, and it is a burden.","source":"dcog-2024","quote":"We suggest not to use chlorhexidine bathing or other bath wipes as it does not seem to have an added value to basic hygiene measures (WEAK recommendation, VERY LOW quality of evidence).","grade":"WEAK recommendation, VERY LOW quality of evidence"},{"action":"Allow indoor flowers and plants at home, changing flower water often and keeping the child away from the soil","why":"The risk from having plants in the house is very small, provided the child does not handle the soil.","source":"dcog-2024","quote":"We strongly believe that indoor flowers or plants at home should be allowed (STRONG recommendation, EXPERT opinion).","grade":"STRONG recommendation, EXPERT opinion"},{"action":"When neutropenic during a season of high viral infection, avoid crowded places and public transport","why":"Crowds at those times raise the chance of catching a respiratory virus; outside those times crowds and public transport are allowed with hand hygiene.","source":"dcog-2024","quote":"We believe that it is not advisable for children with cancer with neutropenia to use public transport or visit crowded places when there is a higher incidence of viral infections and thereby a higher chance of getting infected (WEAK recommendation, EXPERT opinion).","grade":"WEAK recommendation, EXPERT opinion"},{"action":"Encourage exercise and sport, avoiding contact sports and activities with a risk of falling while platelets are below 50","why":"Exercise helps children through treatment; a low platelet count raises the risk of bleeding from a knock or fall.","source":"dcog-2024","grade":"WEAK recommendation, EXPERT opinion"}],"bestInClass":{"statement":"For children with cancer outside transplant, the Dutch Children's Oncology Group guideline (2024), endorsed by the Children's Oncology Group, is the only evidence-graded guideline on daily-life restrictions and sets the standard: hand hygiene first, school regardless of neutropenia, pets, indoor plants and swimming allowed (not with a PICC), and a short list of exposures to avoid (construction and soil, reservoir bath toys, public bubble baths, cleaning litter or cages, crowds during viral seasons when neutropenic). Most of its recommendations rest on very low quality evidence or expert opinion, which the panel says openly. For transplant recipients, the CDC/IDSA/ASBMT guideline (2009) remains the reference and is stricter: no plants or flowers in hospital rooms (DIII), avoiding gardening and soil while immunosuppressed (CIII), visitor screening (BIII) and restrictions on certain animals. The two guidelines differ on plants, and the transplant guideline's restrictions are graded mainly on expert opinion (III).","sources":["dcog-2024","cog-lifestyles-2025","hct-2009","asco-idsa-2018"]},"variants":[{"name":"Stricter rules after stem cell transplant (CDC/IDSA/ASBMT 2009)","differs":"No plants or dried or fresh flowers in hospital rooms during conditioning or after transplant; avoid gardening, soil and plants while on immunosuppressive therapy, or wear an N95 mask and gloves if continuing; avoid construction areas; do not adopt young, ill or stray animals, reptiles, chicks or exotic pets; someone other than the patient changes cat litter daily for the first 6 months.","evidence":"Graded mainly on expert opinion: plants and flowers in rooms DIII, gardening and soil CIII, reptiles BII, litter boxes BIII; the guideline notes plants and flowers have not conclusively caused mould infection.","sources":["hct-2009"]},{"name":"Protective environment rooms and HEPA filtration in transplant units","differs":"Transplant centres house patients at highest risk of mould infection in rooms with HEPA-filtered air and, when such rooms run short, use portable HEPA filters; laminar air flow rooms are not recommended for new builds.","evidence":"HEPA filtration AIII and room allocation BIII; laminar air flow DII because it has not shown an overall survival benefit.","sources":["hct-2009"]},{"name":"Swimming with a tunnelled line","differs":"Where Dutch practice previously discouraged it, children with an external tunnelled line may swim if the site and dressing can be cleaned and dried and there is no needle in a port; a tight shirt can hold the line against the body.","evidence":"One retrospective cohort found no significant difference in infection between swimmers and non-swimmers; the recommendation is weak, very low quality.","sources":["dcog-2024"]}],"grades":[{"claim":"Hand hygiene by patients, carers and staff","grade":"STRONG recommendation, GOOD PRACTICE STATEMENT","source":"dcog-2024"},{"claim":"School or kindergarten irrespective of neutropenia","grade":"STRONG recommendation, VERY LOW quality evidence","source":"dcog-2024"},{"claim":"Avoid environments high in fungal spores when neutropenic","grade":"STRONG recommendation, ASCO and IDSA guideline","source":"dcog-2024"},{"claim":"Keep domestic pets","grade":"WEAK recommendation, VERY LOW quality of evidence","source":"dcog-2024"},{"claim":"No plants or flowers in hospital rooms after HCT","grade":"DIII","source":"hct-2009"},{"claim":"Avoid gardening, soil and plants while on immunosuppressive therapy after HCT","grade":"CIII","source":"hct-2009","quote":"Patients should be advised to avoid gardening, soil, and plants while receiving immunosuppressive therapy (CIII)."},{"claim":"Water-retaining bath toys should not be used by HCT recipients","grade":"DII","source":"hct-2009","quote":"Water-retaining bath toys should not be used by immunocompromised HCT recipients and candidates as they have been associated with an outbreak of Pseudomonas aeruginosa in a pediatric oncology ward (DII)"},{"claim":"Do not routinely advise HCT recipients to part with their pets","grade":"not graded in the sentence; reptiles BII, juvenile and stray animals BIII","source":"hct-2009","quote":"HCT physicians should advise recipients and candidates undergoing conditioning therapy of the potential infection risks posed by pet ownership; however, they should not routinely advise HCT recipients to part with their pets, with limited exceptions."}],"sources":[{"key":"dcog-2024","label":"Less restrictions in daily life: a clinical practice guideline for children with cancer","publisher":"Dutch Children's Oncology Group (DCOG), Supportive Care in Cancer","year":2024,"url":"https://europepmc.org/article/PMC/PMC11162397","doi":"10.1007/s00520-024-08537-9","gradingScheme":"GRADE: STRONG or WEAK recommendation with quality of evidence HIGH to VERY LOW; recommendations worded 'we believe' rest on EXPERT opinion; good practice statements are separate.","read":"full-text","accessed":"2026-11-11"},{"key":"cog-lifestyles-2025","label":"Less restrictions in daily life for children with cancer (COG endorsement, version date 28 April 2025)","publisher":"Children's Oncology Group","year":2025,"url":"https://childrensoncologygroup.org/wp-content/uploads/2026/05/COG_SC_Lifestyles_Guideline_Document_28APRIL2025-new-logo.pdf","gradingScheme":"Endorses the source guideline's GRADE recommendations and good practice statement; the expert opinion statements are not part of the endorsement table.","read":"full-text","accessed":"2026-11-11"},{"key":"hct-2009","label":"Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective","publisher":"CDC, IDSA, ASBMT and international partners (Biology of Blood and Marrow Transplantation)","year":2009,"url":"https://europepmc.org/article/PMC/PMC3103296","doi":"10.1016/j.bbmt.2009.06.019","gradingScheme":"Strength A (always offer) to E (never offer); quality of evidence I (randomised trial), II (non-randomised or observational), III (expert opinion); printed together, for example BIII.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-idsa-2018","label":"Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update","publisher":"ASCO and IDSA, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/article/MED/30179565","doi":"10.1200/JCO.18.00374","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The COG endorsement covers only the Dutch guideline's GRADE recommendations and good practice statement; the expert opinion statements (litter boxes, plants, crowds, sport, swimming with a PICC) are the Dutch panel's alone.","There is no equivalent graded guideline for adults having chemotherapy outside transplant; the ASCO/IDSA 2018 environmental recommendation was read only in its abstract, which mentions it without its wording or grade.","The CDC/IDSA/ASBMT transplant guideline dates from 2009 and no later edition was found; most of its environmental measures are graded on expert opinion.","Protective isolation in a single room for neutropenic patients outside transplant units is not addressed by either guideline read; NICE CG151 and epic3 were not checked for it.","Masks for patients in public places are mentioned only in the transplant guideline (N95 near construction, CIII), which notes no mask has been tested for reducing mould exposure and surgical masks give negligible protection."]},{"id":"permanent-prostate-seed-brachytherapy-home-radiation-safety","kind":"protocol","name":"Radiation precautions at home after permanent prostate seed brachytherapy","aka":["prostate seed implant precautions","LDR brachytherapy precautions","iodine-125 seeds at home","palladium-103 seeds precautions","after seed brachytherapy","seed implant and children","seed implant and pregnancy","passing a seed","seed brachytherapy cremation"],"tldr":"The seeds stay in the prostate and give off most of their radiation in the first few months, almost all of it absorbed inside you. You can be around other people normally. For about two months, avoid having children on your lap for long and avoid long close contact with anyone pregnant, use a condom for the first few ejaculations in case a seed comes out, and carry the card you are given.","summary":"Release follows the same framework as other radioactive treatments: before discharge the physicist or radiation protection officer confirms that doses to others will stay within public limits and carer constraints, with assumptions matching the written instructions (IAEA SSG-46 5.258; in the US no other person likely to exceed 5 mSv, 10 CFR 35.75). ICRP 98 found that in the vast majority of cases the dose to carers stays well below 1 mSv a year, and that only a partner who is pregnant at the time of implantation may need specific precautions. Measured dose rates from 1,279 patients (Dauer 2010) found no precautions needed for a typical palladium-103 patient, and for a typical iodine-125 patient only avoiding sleeping in contact with a pregnant partner and long periods holding a child on the lap, for about two months; Prostate Cancer UK gives the same two months, with 50 cm from children beyond a few minutes a day and from pregnant women beyond three hours.\n\nWritten instructions also cover a seed coming out (rare; most likely in the first month) and what to do (SSG-46 5.260; ICRP 98); UK patients are told to use a condom for the first five ejaculations and not to pick up a seed passed in urine but to flush it away. A wallet card carries the implant details for later pelvic or abdominal surgery, for radiation security monitors and in case of death (SSG-46 5.261; ICRP 98). Cremation is the one point where sources differ widely: ICRP 98 allows it once 12 months have passed after iodine-125 (3 months after palladium-103), while Prostate Cancer UK says cremation is not possible in the first 20 months and to carry the card for at least 20 months. ICRP 98 notes that fathering a child remains possible after an implant.","asOf":"2026-11-11","links":[],"tags":[],"related":["radionuclide-therapy-patient-release-criteria","prostate-radiotherapy-bladder-and-rectal-preparation"],"cancers":["prostate"],"sections":[],"technologies":["ldr-seed-brachytherapy","brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":["prostate-cancer-uk"],"pathways":[],"terms":["brachytherapy-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"It is safe to be around other people. For about two months, do not hold children on your lap for long and do not sit close to a pregnant woman for hours. Use a condom the first few times you ejaculate. Carry your seed card, and tell any surgeon you have seeds.","domain":"radiotherapy","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","home"]},"population":"Men with prostate cancer who have had permanent low-dose-rate seed brachytherapy with iodine-125 or palladium-103 seeds, alone or as a boost, and the people they live with. Caesium-131 seeds, temporary high-dose-rate brachytherapy and seed implants elsewhere in the body are not covered. The day counts are typical values; centres may set them from a dose-rate measurement on the patient.","trigger":"A permanent prostate seed implant has been placed and the patient is about to go home.","steps":[{"action":"Before the patient leaves, have the physicist or radiation protection officer confirm that doses to the public and to carers will stay within limits, using assumptions that match the written instructions","why":"The precautions given only need to be as strict as the measured activity requires.","source":"iaea-ssg46","quote":"In the case of carers and comforters, the assumptions made for the calculations should be consistent with the written instructions that will be given at the time the patient is discharged from the facility."},{"action":"Give the patient written instructions on keeping doses to others low, with particular attention to children and a pregnant partner","why":"Children and unborn babies are the most sensitive to radiation; for adults the dose is very small.","source":"iaea-ssg46","quote":"Individuals of particular concern are children and pregnant partners of patients."},{"action":"Reassure the patient that being around other people is safe, and that a partner who is pregnant at the time of the implant is the case that may need specific precautions","why":"Measured doses to the people around a patient with seeds are well below the yearly public limit.","source":"icrp-98","quote":"The available data show that, in the vast majority of cases, the dose to comforters and carers remains well below the recommended limit of 1 mSv/year. Only the (rare) case where the patient's partner is pregnant at the time of implantation may need specific precautions."},{"action":"With iodine-125 seeds, for about two months avoid sleeping pressed against a pregnant partner and avoid holding children on the lap for long periods; with palladium-103 seeds a typical patient needs no precautions","why":"Palladium-103 decays faster and gives a lower dose rate; for iodine-125 only long, very close contact matters.","source":"dauer-2010","quote":"For the typical Pd-103 patient, no radiation-safety precautions are required."},{"action":"Include in the instructions what to do if a seed comes out","why":"Seeds occasionally come out in urine or semen, most often in the first month; a single seed is low in activity but should be handled properly.","source":"iaea-ssg46","quote":"There is a low probability of an implanted seed being expelled, for example with prostate treatment. The written instructions should cover this possibility and should provide guidance on what to do and what not to do."},{"action":"Give the patient a wallet card with the implant details, and tell them to inform any surgeon before later pelvic or abdominal surgery","why":"A surgeon needs to know about the seeds, and the card explains a radiation detector alarm at an airport.","source":"iaea-ssg46","quote":"The patient with permanent brachytherapy implants should be informed that, if he or she is to undergo subsequent surgery, the surgeon should be informed of the presence of the implants; for example, a prostate cancer patient undergoing subsequent pelvic or abdominal surgery."},{"action":"Tell the patient and family how death and cremation are handled in the first months after an implant, and that the card is needed then","why":"Ashes may hold radioactivity if cremation happens soon after the implant, so it may need to wait.","source":"icrp-98","quote":"Review of available data shows that cremation can be allowed if 12 months have elapsed since implantation with I-125 (3 months for Pd-103)."},{"action":"Explain that the implant reduces fertility but that fathering a child is still possible","why":"Men who do not want a child need to know contraception still matters.","source":"icrp-98","quote":"However, although the therapy-related modifications of the semen reduce fertility, patients must be aware of the possibility of fathering children after such a permanent implantation, with a limited risk of genetic effects for the child."}],"bestInClass":{"statement":"Release after a physicist's check that doses to others stay within public limits and carer constraints, with written instructions focused on children and a pregnant partner, advice on a seed being expelled, and a wallet card for later surgery, security monitors and death (IAEA SSG-46 2018; ICRP 98 2005; 10 CFR 35.75). Measured dose rates support short, light precautions: none for a typical palladium-103 patient and about two months of avoiding long close contact with children and pregnant women for iodine-125 (Dauer 2010; Prostate Cancer UK 2026). The sources disagree on cremation: ICRP 98 allows it 12 months after iodine-125 and 3 months after palladium-103; UK patient information says not within 20 months. None of the sources grades its advice.","sources":["iaea-ssg46","icrp-98","dauer-2010","nrc-10cfr35-75","pcuk-seeds"]},"variants":[{"name":"UK patient advice (Prostate Cancer UK, 2026)","differs":"For the first two months: no closer than 50 cm to children for more than a few minutes a day (a quick cuddle is fine, not on the lap), not this close to pregnant women for more than three hours, and no pets on the lap. Avoid sex for a few days, use a condom for the first five ejaculations and double-wrap used condoms in the bin. A seed passed in urine at home is flushed away, not picked up. No cremation within 20 months; carry the card for at least 20 months.","evidence":"Patient information reviewed by a consultant clinical scientist; it gives no evidence grades. The 20-month cremation interval is longer than the ICRP's 12 months for iodine-125, and the page does not say why.","sources":["pcuk-seeds"]},{"name":"Patient-specific precautions from a dose-rate measurement","differs":"The dose rate at 30 cm from the skin is measured after the implant and put into an equation that gives the precaution time for each situation (pregnant partner, children on the lap), keeping doses to others below half the public limits. Most patients then need far shorter precautions than a fixed rule; a rare iodine-125 patient at the highest measured rate would need much longer ones.","evidence":"Measurements from 1,279 patients at one US centre; the authors found the resulting precaution times significantly less restrictive than those generally prescribed, which they report as 1 to 3 months for palladium-103 and 2 to 6 months for iodine-125.","sources":["dauer-2010"]}],"grades":[{"claim":"Release with written instructions; children and pregnant partners of particular concern","grade":"Safety Guide recommendation (ungraded)","source":"iaea-ssg46","quote":"As indicated in para. 5.258, the patient or the legal guardian of the patient should be provided with written instructions on how to keep doses to members of the public and carers and comforters as low as reasonably achievable."},{"claim":"Systematic dose monitoring of family members is not necessary after permanent prostate implants","grade":"Safety Guide recommendation (ungraded)","source":"iaea-ssg46","quote":"Published data suggest that systematic dose monitoring, at least in the case of permanent brachytherapy implanted sources for the treatment of prostate cancer, is not necessary"},{"claim":"A wallet card with the implant details","grade":"Consensus (ungraded)","source":"icrp-98","quote":"A 'wallet card' with all relevant information about the implant is useful."},{"claim":"Release where no other individual is likely to exceed 5 mSv (US), which covers implants as well as unsealed sources","grade":"Regulatory requirement (ungraded)","source":"nrc-10cfr35-75","quote":"A licensee may authorize the release from its control of any individual who has been administered unsealed byproduct material or implants containing byproduct material if the total effective dose equivalent to any other individual from exposure to the released individual is not likely to exceed 5 mSv (0.5 rem)."}],"sources":[{"key":"iaea-ssg46","label":"Radiation Protection and Safety in Medical Uses of Ionizing Radiation, Specific Safety Guide No. SSG-46 (release of patients after permanent brachytherapy implants)","publisher":"International Atomic Energy Agency, jointly sponsored by PAHO and WHO","year":2018,"url":"https://www-pub.iaea.org/MTCD/Publications/PDF/PUB1775_web.pdf","gradingScheme":"An IAEA Safety Guide: recommendations ('should'); not graded by evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"icrp-98","label":"ICRP Publication 98: Radiation Safety Aspects of Brachytherapy for Prostate Cancer using Permanently Implanted Sources","publisher":"International Commission on Radiological Protection (Annals of the ICRP 35(3))","year":2005,"url":"https://www.icrp.org/publication.asp?id=ICRP%20Publication%2098","gradingScheme":"ICRP recommendations; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"dauer-2010","label":"Less-restrictive, patient-specific radiation safety precautions can be safely prescribed after permanent seed implantation","publisher":"Dauer et al., Brachytherapy (NIH author manuscript PMC3819139)","year":2010,"url":"https://doi.org/10.1016/j.brachy.2009.06.006","doi":"10.1016/j.brachy.2009.06.006","gradingScheme":"Single-centre measurement study; not a guideline.","read":"full-text","accessed":"2026-11-11"},{"key":"nrc-10cfr35-75","label":"10 CFR 35.75 Release of individuals containing unsealed byproduct material or implants containing byproduct material","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2007,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-C/section-35.75","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"pcuk-seeds","label":"Permanent seed brachytherapy (patient information, updated September 2026)","publisher":"Prostate Cancer UK","year":2026,"url":"https://prostatecanceruk.org/prostate-information-and-support/treatments/permanent-seed-brachytherapy","gradingScheme":"Patient information; not graded.","read":"public-summary","accessed":"2026-11-11"},{"key":"acr-abs-astro-ldr-2022","label":"ACR-ABS-ASTRO Practice Parameter for Transperineal Permanent Brachytherapy of Prostate Cancer","publisher":"American College of Radiology, American Brachytherapy Society and ASTRO (American Journal of Clinical Oncology)","year":2022,"url":"https://doi.org/10.1097/coc.0000000000000915","doi":"10.1097/coc.0000000000000915","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["ICRP 98 was read only as its abstract; its sample information sheet, which SSG-46 points to for detail, was not read.","The condom advice (first five ejaculations) and the instruction to flush a seed passed in urine come from UK patient information; no guideline text read states either, and the number of ejaculations is not explained.","The sources disagree on cremation (12 months for iodine-125 in ICRP 98, 20 months in UK patient information), and the reason for the UK figure was not found.","The ACR-ABS-ASTRO practice parameter (2022), the most recent US professional standard for the procedure, could not be read.","The measurement study behind the patient-specific precautions is from one centre, with patients treated from 1995 to 2008."]},{"id":"lutetium-177-therapy-home-radiation-safety","kind":"protocol","name":"Radiation safety at home after lutetium-177 PSMA or dotatate therapy","aka":["Pluvicto radiation precautions","Lutathera radiation precautions","177Lu-PSMA home precautions","PRRT home precautions","radioligand therapy precautions","after lutetium treatment at home","radiation safety after radionuclide therapy"],"tldr":"After a lutetium-177 treatment your body gives off a small amount of radiation for some days, and most of the radioactivity leaves in your urine. For a short time you are asked to keep some distance from others, especially children and anyone pregnant, to sleep apart, to be careful with the toilet and washing, and to drink plenty. Your team will give you written instructions with the exact days.","summary":"Release follows national law: the EANM/SNMMI 2023 guideline notes that up to 48 to 72 hours of ward isolation may be needed to reach a local discharge threshold, and that where outpatient treatment is allowed the patient should stay about 2 hours to be monitored, hydrated and to pass urine first. In the United States 10 CFR 35.75 allows release where no other person is likely to receive more than 5 mSv, with written instructions where anyone could receive more than 1 mSv. Precautions: drink more for 3 to 4 days and void often (EANM/SNMMI; both US labels); rigorous toilet hygiene, a double flush and hand washing, with particular care in the first 2 days and against soiling for a week (IAEA/EANM/SNMMI 2013 for PRRT); catheterise incontinent patients and keep the catheter for 2 days (IAEA 2013), and EANM/SNMMI suggests considering a catheter. The Pluvicto label gives the most specific contact limits after each dose: under 3 feet from others for 2 days and from children and pregnant women for 7 days, no sexual activity for 7 days, and separate sleeping for 3, 7 and 15 days (others, children, pregnant women). The Lutathera label gives no day counts and notes radioactivity in urine for up to 30 days. Contraception figures differ by source: Pluvicto men 14 weeks after the last dose; Lutathera women 7 months and men 4 months, no breastfeeding for 2.5 months; EANM/SNMMI 3 months for PSMA; IAEA 2013 at least 6 months avoiding pregnancy for women after PRRT. A medical emergency is never delayed for radiation reasons.","asOf":"2026-11-11","links":[],"tags":[],"related":[],"cancers":["prostate","neuroendocrine"],"sections":[],"technologies":["lu177-radioligand-therapy"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":["castration-resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"For a few days after this treatment, keep a little distance from other people, especially children and pregnant women, sleep on your own, and flush the toilet twice and wash your hands after using it. Drink plenty of water. Follow the written sheet your hospital gives you.","domain":"radiotherapy","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["outpatient-clinic","ward","home"]},"population":"Adults treated with lutetium-177 vipivotide tetraxetan (PSMA) for prostate cancer or lutetium-177 dotatate (PRRT) for neuroendocrine tumours, and the people they live with. The day counts quoted are from the US Pluvicto label; the Lutathera label and the guidelines read leave the exact numbers to institutional and national rules, which vary by country and by the dose rate measured at discharge. Children treated with PRRT, and other radionuclide therapies (radioactive iodine, radium-223), follow their own instructions.","trigger":"A lutetium-177 radioligand treatment has been given and the patient is being prepared for discharge, after each cycle.","steps":[{"action":"Decide on release by national rules: keep the patient on a shielded ward until the dose rate is below the local discharge threshold where the law requires it, or for about 2 hours after outpatient treatment","why":"The rules on when someone can go home after a radioactive treatment differ between countries; the short stay also lets the team check side effects and that the patient can pass urine.","source":"eanm-snmmi-psma-2023","quote":"Where out-patient therapy is allowed, patients should nevertheless be kept in isolation for approx. 2 h to monitor side effects, ensure sufficient hydration, and complete first urination before release."},{"action":"Give written instructions on reducing radiation to other people before the patient leaves","why":"People remember little of what is said on treatment day; a written sheet with the dates lets the household follow it.","source":"nrc-10cfr35-75","quote":"A licensee shall provide the released individual, or the individual's parent or guardian, with instructions, including written instructions, on actions recommended to maintain doses to other individuals as low as is reasonably achievable if the total effective dose equivalent to any other individual is likely to exceed 1 mSv (0.1 rem)."},{"action":"Ask the patient to drink more for the first 3 to 4 days and to pass urine often, especially in the first hours","why":"Most of the radioactivity leaves in urine; drinking and emptying the bladder often clears it faster and lowers the dose to the bladder and kidneys.","source":"eanm-snmmi-psma-2023","quote":"To support kidney clearance, the patient is encouraged to increase fluid intake during the first 3–4 days following treatment."},{"action":"Teach toilet hygiene: flush twice after passing urine, wash hands every time, and wash heavily soiled clothing separately","why":"Urine is the main source of contamination in the home for the first days, and others may use the same toilet.","source":"iaea-eanm-snmmi-prrnt-2013","quote":"Patients should be advised to observe rigorous hygiene to avoid contaminating persons using the same toilet facilities. A double toilet flush is recommended after urination. Patients should wash their hands after urination."},{"action":"For the first week, take care not to soil underclothing or the area around the toilet","why":"Small amounts of radioactive urine on clothes or surfaces are the commonest way others are exposed.","source":"iaea-eanm-snmmi-prrnt-2013","quote":"Once discharged, patients should be cautioned to avoid soiling underclothing or areas around toilet bowls for 1 week following PRRNT. Considerably contaminated clothing should be washed separately."},{"action":"If the patient is incontinent, place a urinary catheter before treatment and keep it for 2 days, emptying the bag often and with gloves","why":"A catheter keeps radioactive urine contained when the bladder cannot be controlled.","source":"iaea-eanm-snmmi-prrnt-2013","quote":"Incontinent patients should be catheterized prior to PRRNT and the catheter should be kept for 2 days thereafter."},{"action":"Keep a distance from other people, and more so from children and pregnant women, for the days set out in the instructions (after Pluvicto: under 3 feet from others for 2 days, and from children and pregnant women for 7 days)","why":"The treatment gives off some gamma radiation for several days, and distance cuts the dose to others sharply; children and unborn babies are more sensitive.","source":"pluvicto-uspi","quote":"Limit close contact (less than 3 feet) with others for 2 days or with children and pregnant women for 7 days."},{"action":"Sleep in a separate room for the days set out (after Pluvicto: 3 days from other adults, 7 days from children, 15 days from a pregnant woman), and avoid sexual activity for 7 days","why":"Hours spent close together at night account for much of a partner's dose.","source":"pluvicto-uspi","quote":"Sleep in a separate room from others for 3 days, from children for 7 days, or from pregnant women for 15 days."},{"action":"Use effective contraception during treatment and afterwards for the period the product and the team set, and do not breastfeed after Lutathera","why":"Radiation can harm an unborn baby and sperm and eggs; the advised gap differs between the drugs and the guidelines.","source":"lutathera-uspi","quote":"Advise females of reproductive potential to use effective contraception during treatment with LUTATHERA and for 7 months after the last dose."},{"action":"Give a discharge letter stating the radionuclide, the drug, the activity given, the date, the aftercare and the next appointment","why":"Other clinicians need to know what was given, and urine can carry detectable radioactivity for weeks (up to 30 days after Lutathera, by its US label).","source":"eanm-snmmi-psma-2023","quote":"The discharge letter should contain relevant patient data, date of therapy, the administered radionuclide (177Lu) and radiopharmaceutical, administered activity, details on necessary aftercare, and next follow-up appointment."},{"action":"In a medical emergency, give care at once; radiation precautions come second","why":"The dose to staff from a treated patient is small compared with the harm of delayed treatment.","source":"iaea-eanm-snmmi-prrnt-2013","quote":"In a medical emergency, concerns about radiation exposure should not hinder the prompt delivery of appropriate medical care to the patient."}],"bestInClass":{"statement":"Release under national rules (EANM/SNMMI 2023: up to 48 to 72 hours' isolation where the law requires it, otherwise about 2 hours' observation; US 10 CFR 35.75: release where no one else is likely to receive more than 5 mSv, with written instructions above 1 mSv), followed by written home precautions: plenty to drink and frequent voiding, rigorous toilet hygiene with a double flush and hand washing (IAEA/EANM/SNMMI 2013), catheterisation for incontinence, distance and separate sleeping for set periods (the US Pluvicto label is the most specific: 2 and 7 days of limited close contact, 3, 7 and 15 days of separate sleeping, 7 days without sexual activity), and contraception. The sources disagree on contraception after treatment: for Lutathera, 7 months for women and 4 months for men (US label) against at least 6 months avoiding pregnancy (IAEA 2013); for PSMA, 14 weeks for men (US label) against 3 months (EANM/SNMMI). Patients should follow the figure their own team gives, which is set by the product licence in their country.","sources":["eanm-snmmi-psma-2023","iaea-eanm-snmmi-prrnt-2013","pluvicto-uspi","lutathera-uspi","nrc-10cfr35-75"]},"variants":[{"name":"Inpatient isolation until a dose-rate threshold","differs":"Keeps the patient on a shielded radioisotope ward for up to 48 to 72 hours rather than treating as an outpatient.","evidence":"Set by national law rather than by evidence about outcomes: EANM/SNMMI 2023 says that, depending on national legislation, up to 48 to 72 hours of isolation on a radioisotope ward may be needed to reach the local discharge threshold. The United States allows outpatient release under the 5 mSv rule.","sources":["eanm-snmmi-psma-2023","nrc-10cfr35-75"]},{"name":"Contraception periods by source","differs":"Pluvicto (US label): men with female partners, 14 weeks after the last dose. Lutathera (US label): women 7 months, men 4 months, and no breastfeeding for 2.5 months. EANM/SNMMI (PSMA): 3 months. IAEA/EANM/SNMMI (PRRT, 2013): women to avoid pregnancy for at least 6 months, and men to consider sperm banking before therapy.","evidence":"No trial compares them; the label periods derive from the drug's half-life and genotoxicity, and EANM/SNMMI states its 3 months is \"Without specific evidence for 177Lu-PSMA-RLT, but according to general knowledge of radiopharmaceuticals\".","sources":["pluvicto-uspi","lutathera-uspi","eanm-snmmi-psma-2023","iaea-eanm-snmmi-prrnt-2013"]}],"grades":[{"claim":"Release where no other person is likely to receive more than 5 mSv","grade":"US federal regulation (10 CFR 35.75(a))","source":"nrc-10cfr35-75","quote":"if the total effective dose equivalent to any other individual from exposure to the released individual is not likely to exceed 5 mSv (0.5 rem)."},{"claim":"Instruct patients how to minimise exposure to others, such as avoiding prolonged close contact with pregnant women or infants","grade":"Procedure guideline statement (not graded)","source":"eanm-snmmi-psma-2023","quote":"Patients should be instructed how to minimize exposure to others (e.g., avoiding prolonged close contact with pregnant women or infants)."},{"claim":"Contraception during and for 3 months after lutetium-177 PSMA therapy","grade":"Procedure guideline statement, stated to be without specific evidence","source":"eanm-snmmi-psma-2023","quote":"Due to the pro-mutagenic characteristics of any radioactive drug, sufficient contraception is needed during and for 3 months after therapy."},{"claim":"Contraception for men after Pluvicto, 14 weeks after the last dose","grade":"US prescribing information (FDA label)","source":"pluvicto-uspi","quote":"Advise males with female partners of reproductive potential to use effective contraception during treatment with PLUVICTO and for 14 weeks after the last dose"},{"claim":"No breastfeeding during Lutathera and for 2.5 months after the last dose","grade":"US prescribing information (FDA label)","source":"lutathera-uspi","quote":"Because of the potential risk for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LUTATHERA and for 2.5 months after the last dose."},{"claim":"Radioactivity in urine for up to 30 days after Lutathera","grade":"US prescribing information (FDA label)","source":"lutathera-uspi","quote":"Radiation can be detected in the urine for up to 30 days following LUTATHERA administration."}],"sources":[{"key":"eanm-snmmi-psma-2023","label":"Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT)","publisher":"EANM and SNMMI (European Journal of Nuclear Medicine and Molecular Imaging; Kratochwil et al.)","year":2023,"url":"https://doi.org/10.1007/s00259-023-06255-8","doi":"10.1007/s00259-023-06255-8","gradingScheme":"Indications are graded strong or weak by level of evidence; the radiation protection and aftercare statements quoted here are procedure guidance and carry no grade.","read":"full-text","accessed":"2026-11-11"},{"key":"iaea-eanm-snmmi-prrnt-2013","label":"The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours","publisher":"IAEA, EANM and SNMMI (European Journal of Nuclear Medicine and Molecular Imaging)","year":2013,"url":"https://doi.org/10.1007/s00259-012-2330-6","doi":"10.1007/s00259-012-2330-6","gradingScheme":"Not graded: practical guidance.","read":"full-text","accessed":"2026-11-11"},{"key":"pluvicto-uspi","label":"PLUVICTO (lutetium Lu 177 vipivotide tetraxetan) injection, US prescribing information (sections 5.1, 8.3 and 17)","publisher":"Novartis, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14908037-2892-4d98-a053-253ce35afb1a","gradingScheme":"Regulatory label: not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"lutathera-uspi","label":"LUTATHERA (lutetium Lu 177 dotatate) injection, US prescribing information (sections 5.1, 8.2, 8.3 and 17)","publisher":"Advanced Accelerator Applications, via DailyMed (US National Library of Medicine)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72d1a024-00b7-418a-b36e-b2cb48f2ab55","gradingScheme":"Regulatory label: not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nrc-10cfr35-75","label":"10 CFR 35.75: Release of individuals containing unsealed byproduct material or implants containing byproduct material","publisher":"US Nuclear Regulatory Commission (Electronic Code of Federal Regulations)","year":2007,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-C/section-35.75","gradingScheme":"Federal regulation: binding on US licensees, not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":["idea-pu-lutetium-177-family-planning-table"],"gaps":["The European product information for Pluvicto and Lutathera could not be read (ema.europa.eu refused a script with HTTP 429), so the European and UK day counts and contraception periods are not given here; patients in Europe should follow the leaflet supplied with their treatment.","The Lutathera US label and both guidelines leave the number of days of distance and separate sleeping to institutional rules; only the Pluvicto US label states them. Hospital instruction sheets set them from the dose rate measured at discharge.","No newer IAEA, EANM or SNMMI procedure guideline for lutetium-177 dotatate than 2013 was found; an erratum to the 2013 guidance exists and could not be read.","Contraception periods differ between the labels and the guidelines (3 months, 14 weeks, 4 months, 6 months, 7 months); no study compares them.","UK release rules (Ionising Radiations Regulations 2017, IR(ME)R and environmental permitting) were not read.","The precautions rest on dose modelling and regulation, not on trials measuring harm to household members."]},{"id":"radioiodine-therapy-home-radiation-safety","kind":"protocol","name":"Radiation safety at home after radioactive iodine (I-131) for thyroid cancer","aka":["radioactive iodine precautions","RAI precautions","I-131 home precautions","radioiodine ablation precautions","after radioiodine treatment at home","radioiodine isolation","radioactive iodine and children","radioiodine and pregnancy","radioiodine and breastfeeding"],"tldr":"After radioactive iodine your body gives off radiation for some days, and some leaves in urine, saliva and sweat. For a while you keep your distance from others, especially babies, young children and anyone pregnant, sleep apart, take care in the toilet and with cups and towels, and stop breastfeeding completely. Your team works out how many days apply to you and writes them down.","summary":"Before treatment the patient is told how to protect others and how long it will last, so they can plan (IAEA SRS-63; ICRP 94). Pregnancy is excluded and breastfeeding is stopped completely; ICRP says mothers must cease breastfeeding immediately, and some physicians ask for it to stop two to three weeks before treatment so the breast takes up less iodine (SRS-63). Release is an individual decision: the IAEA and ICRP base it on the dose others could receive rather than on a fixed amount left in the body; the US allows release where no one else is likely to receive more than 5 mSv, with written instructions where anyone could receive more than 1 mSv (10 CFR 35.75); in the UK the patient must have written instructions on restricting others' dose before leaving (IR(ME)R 2017 reg 12(6) and (7)). Many European countries also set a maximum retained activity, mostly 400 to 600 MBq (SRS-63), and thyroid cancer treatment is usually given with a hospital stay there; in the US most patients are now treated as outpatients (87% of survey respondents treated after 2011, Wu 2020).\n\nAt home the effort goes on pregnant women, infants and children, because measured doses to adults who follow the advice rarely approach a few millisieverts (SRS-63). The example IAEA leaflet asks for a distance of at least one metre, two metres for longer than an hour, a separate bed two metres apart, close contact limited to half an hour a day, under-twos cared for by someone else, seated urination with flushing and hand washing, a daily shower especially on the first two days, and no sharing of cutlery, crockery, towels or laundry. Durations depend on the activity and on whether the treatment is a first ablation or a later follow-up treatment; the ICRP 94 table reproduced by SRS-63 gives, for 3,700 MBq, 4 days of sleeping apart after a follow-up treatment and 20 days after ablation. Patients carry a card for unplanned admissions and for radiation detectors at airports and borders, which can pick up radioiodine for weeks. ICRP advises women to avoid pregnancy for 4 months after iodine-131 for thyroid cancer; ARSAC in the UK says 6 months; men are commonly advised to avoid fathering a child for some months, on prudence rather than evidence (SRS-63). UK guidance from 2023 found wide variation and some unnecessarily burdensome restrictions, and recommends personalising them.","asOf":"2026-11-11","links":[],"tags":[],"related":["lutetium-177-therapy-home-radiation-safety","radionuclide-therapy-patient-release-criteria"],"cancers":["thyroid","papillary-thyroid-cancer","follicular-thyroid-cancer"],"sections":[],"technologies":["radioiodine-therapy"],"targets":[],"drugs":["radioactive-iodine"],"companies":[],"institutions":["iaea"],"pathways":[],"terms":["radioiodine-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"For some days after this treatment, keep away from babies, small children and pregnant women, sleep on your own, sit down to pass urine, flush and wash your hands, and do not share cups, cutlery or towels. Breastfeeding must stop. Drink plenty. Carry the card the hospital gives you.","domain":"radiotherapy","setting":{"who":["doctor","nurse","patient-or-carer"],"where":["ward","outpatient-clinic","home"]},"population":"Adults treated with iodine-131 (sodium iodide) for differentiated thyroid cancer, after thyroidectomy (ablation, adjuvant treatment or treatment of persistent or metastatic disease), and the people they live and work with. The day counts are examples: each centre sets them from the activity given, measured dose rate, home circumstances and national rules. Children treated with iodine-131, iodine-131 MIBG and treatment for an overactive thyroid follow their own instructions; lutetium-177 therapy is a separate protocol.","trigger":"Radioactive iodine treatment is planned, and again when the patient is released from hospital or from the department.","steps":[{"action":"Before treatment, tell the patient how they will protect others afterwards and for how long, in time for them to plan childcare, work and travel","why":"Knowing in advance how many days of precautions apply makes them easier to follow and less frightening.","source":"iaea-srs63","quote":"Patients should be given information about their own safety and that of others before their treatment is started."},{"action":"Confirm the patient is not pregnant before giving the iodine","why":"Radioactive iodine crosses the placenta and can damage the baby's thyroid; thyroid cancer treatment can usually wait until after pregnancy.","source":"iaea-srs63","quote":"Pregnancy is a strong contraindication to unsealed radionuclide therapy, unless the therapy is life saving."},{"action":"Make sure breastfeeding has stopped completely before treatment and does not restart for this child","why":"Radioactive iodine passes into breast milk and could destroy the baby's thyroid.","source":"iaea-srs63","quote":"Thus, therapeutic radiopharmaceuticals, regardless of the route of administration, are potentially hazardous, and therefore breast-feeding must be discontinued indefinitely"},{"action":"Decide on release for this patient individually, from the dose other people could receive and their home circumstances, within national rules","why":"A fixed rule can keep people in hospital who could safely go home, or send home someone who lives with a baby.","source":"iaea-srs63","quote":"The decision to hospitalize or release a patient should be determined on an individual basis."},{"action":"Give written instructions on protecting others, and the risks of radiation, before the patient leaves the department","why":"Instructions on paper are there when questions come up at home.","source":"irmer-2017-reg12","quote":"be provided to the patient or other person specified in paragraph (6) as appropriate prior to the patient leaving the radiological installation where the exposure was carried out."},{"action":"Focus the restrictions on pregnant women, babies and children","why":"Adults at home who follow the advice receive very small doses; the young and the unborn are most sensitive.","source":"iaea-srs63","quote":"Restrictions, once families and carers have been well instructed, should thus focus on the special consideration groups (i.e. pregnant women, infants and children)."},{"action":"Keep at least one metre from other people, and two metres for anything longer than an hour, for the days set by the team","why":"Radiation falls off quickly with distance, so a little space cuts the dose a lot.","source":"iaea-srs63","quote":"Do not sit or stay close to any person either at home or at work. Try to maintain a distance of at least one metre. For long periods (more than one hour), stay two metres away."},{"action":"Sleep in a separate bed two metres away, and limit hugging or sex to half an hour a day, for the days set by the team","why":"A night beside someone is the longest close contact of the day; house walls do not block this radiation well.","source":"iaea-srs63","quote":"Close contact such as hugging or sex should be limited to half an hour a day. You should sleep in a separate bed. Beds should be two metres apart, even if there is a wall separating them."},{"action":"Arrange for someone else to look after children under two where possible","why":"Babies are the most sensitive to radiation and need the longest, closest contact.","source":"iaea-srs63","quote":"Children under two years old should be looked after by someone else."},{"action":"Sit to pass urine (men too), dry with toilet paper and flush, wash hands every time, and shower daily, especially in the first two days","why":"Most of the iodine not taken up by the thyroid leaves in urine; careful toilet habits keep it off surfaces others touch.","source":"iaea-srs63","quote":"Therefore, pass urine while seated (including men). Always dry your genitals with toilet paper and flush the toilet."},{"action":"Do not share cutlery, crockery, towels, face cloths or toothbrushes; wash your clothes and bedding separately","why":"Some iodine leaves in saliva and sweat; washing removes it.","source":"iaea-srs63","quote":"Therefore, cutlery, crockery, towels, bed linen, etc., should not be shared with others."},{"action":"Drink plenty and pass urine often","why":"Emptying the bladder often moves the iodine out of the body sooner and lowers the dose to nearby organs.","source":"iaea-srs63","quote":"The dose can be reduced by orally hydrating the patient and by encouraging frequent voiding. This is a common recommendation for all patients whether pregnant or not."},{"action":"Carry the treatment card, show it if admitted to any hospital, and take it when travelling","why":"Staff need to know about the radioactivity, and airport and border detectors can pick it up for weeks.","source":"iaea-srs63","quote":"Environmental or other radiation detection devices are sensitive enough that they will usually detect patients who have received radioiodine treatment for weeks after administration."},{"action":"Avoid pregnancy for at least 4 months (ICRP) or 6 months (ARSAC, UK) after treatment","why":"The wait protects a future baby from radiation and lets the team confirm the cancer is controlled before a pregnancy.","source":"iaea-srs63","quote":"the ICRP recommends that female patients be advised to avoid pregnancy for the time periods indicated in Table 13."}],"bestInClass":{"statement":"An individual release decision based on the dose others could receive, with written instructions before leaving (IAEA SRS-63 and SSG-46; ICRP 94; 10 CFR 35.75; IR(ME)R 2017 reg 12), and restrictions focused on pregnant women, infants and children, whose length is set for the person from the activity given and their household rather than taken from a single table. None of these sources grades its advice: the IAEA and ICRP documents are consensus built on measured and modelled doses, and the US and UK texts are law. They differ on two points shown below: how release is decided (dose to others in the US and in IAEA and ICRP advice, a retained-activity limit in many European countries) and how long to avoid pregnancy (4 months ICRP, 6 months ARSAC, 6 to 12 months in some practice). The 2023 UK multidisciplinary guidance adds the case against over-restriction, which its authors found widespread.","sources":["iaea-srs63","iaea-ssg46","icrp-94","nrc-10cfr35-75","irmer-2017-reg12","uk-rai-2023"]},"variants":[{"name":"Release by retained activity (many European countries)","differs":"A patient is kept in hospital until the iodine left in the body falls below a set amount: the old IAEA Basic Safety Standards guidance level was 1,100 MBq; most EU member states use 400 to 600 MBq (range about 95 to 800); Germany 250 MBq, based on 3.5 microsieverts an hour at one metre; the European Thyroid Association favours outpatient treatment up to 800 MBq (SRS-63 tables 9 and 10). Thyroid cancer treatment is usually given with a hospital stay in the EU.","evidence":"SRS-63 says some retained-activity models are unduly conservative and may cause unnecessary hospital stays, and that where the two approaches conflict the ICRP regards the dose-based one as more fundamental.","sources":["iaea-srs63"]},{"name":"Release by dose to others (United States)","differs":"Release is allowed when no other person is likely to receive more than 5 mSv; written instructions are required when anyone could receive more than 1 mSv, with breastfeeding guidance where a nursing infant could. In practice most US patients with thyroid cancer are treated as outpatients.","evidence":"In a 2018 survey of 1,111 US patients treated between 2011 and 2018, 87% were treated as outpatients (66% before 2009), 67% were able to discuss and individualise their instructions, and 2% did not recall receiving any.","sources":["nrc-10cfr35-75","wu-2020-survey"]},{"name":"UK guidance (2023): personalised, less burdensome restrictions","differs":"A UK multidisciplinary group convened at the instigation of patient support groups, with the British Thyroid Association, British Nuclear Medicine Society, IPEM, BIR and RCR among the authors, wrote guidance and a patient leaflet focused on personalising the advice, including for patients on haemodialysis.","evidence":"Its abstract reports significant variation across the UK and that some patients are asked to observe unnecessarily burdensome restrictions. Only the abstract was read; its specific day counts are not reproduced here.","sources":["uk-rai-2023"]},{"name":"Stopping breastfeeding weeks before treatment","differs":"Some physicians ask women to stop breastfeeding two to three weeks before radioiodine, so that the breast takes up less iodine and there is no risk of restarting; the general rule is only that breastfeeding stops and does not resume.","evidence":"SRS-63 describes it as a practice some find helpful, without a grade or data.","sources":["iaea-srs63"]},{"name":"American Thyroid Association tables (2011)","differs":"Gives example tables for working out the number of days of precautions for an individual patient, built on US NRC rules and NCRP Report 155, with a checklist for the patient's circumstances.","evidence":"Its authors state there are insufficient data on long-term outcomes for evidence-based guidelines. Only the abstract was read.","sources":["ata-2011"]}],"grades":[{"claim":"Decide hospital stay or release individually","grade":"Consensus (ungraded)","source":"icrp-94","quote":"The decision to hospitalise or release a patient should be determined on an individual basis."},{"claim":"Stop breastfeeding immediately after radioiodine","grade":"Consensus (ungraded)","source":"icrp-94","quote":"After radioiodine therapy, mothers must cease breastfeeding immediately."},{"claim":"Release allowed if no other person is likely to receive more than 5 mSv; written instructions if anyone could receive more than 1 mSv","grade":"Regulatory requirement (ungraded)","source":"nrc-10cfr35-75","quote":"A licensee may authorize the release from its control of any individual who has been administered unsealed byproduct material or implants containing byproduct material if the total effective dose equivalent to any other individual from exposure to the released individual is not likely to exceed 5 mSv (0.5 rem)."},{"claim":"Written instructions to the patient on restricting others' doses","grade":"Regulatory requirement (ungraded)","source":"irmer-2017-reg12","quote":"specify how doses resulting from the patient’s exposure can be restricted as far as reasonably possible so as to protect persons in contact with the patient;"},{"claim":"Written instructions to carers after radioiodine, including time and proximity, physical contact and not sharing food or drinks","grade":"Safety Guide recommendation (ungraded)","source":"iaea-ssg46","quote":"carer or comforter of the patient (including for example, instructions on time spent with the patient and proximity to the patient, minimizing of physical contact and not sharing food or drinks)."},{"claim":"Dose constraint of 5 mSv per episode for an adult carer, 1 mSv for children and for the embryo or fetus of a pregnant carer","grade":"Safety Guide recommendation (ungraded)","source":"iaea-ssg46","quote":"For an adult carer or comforter, a value of dose constraint commonly used is 5 mSv effective dose per episode."}],"sources":[{"key":"iaea-srs63","label":"Release of Patients After Radionuclide Therapy, Safety Reports Series No. 63 (with contributions from the ICRP)","publisher":"International Atomic Energy Agency","year":2009,"url":"https://www-pub.iaea.org/MTCD/Publications/PDF/pub1417_web.pdf","gradingScheme":"A safety report built on measured and modelled doses and on ICRP, EU and national guidance; its advice is not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"iaea-ssg46","label":"Radiation Protection and Safety in Medical Uses of Ionizing Radiation, Specific Safety Guide No. SSG-46","publisher":"International Atomic Energy Agency, jointly sponsored by PAHO and WHO","year":2018,"url":"https://www-pub.iaea.org/MTCD/Publications/PDF/PUB1775_web.pdf","gradingScheme":"An IAEA Safety Guide: recommendations ('should') on meeting the Safety Requirements; not graded by evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"icrp-94","label":"ICRP Publication 94: Release of Patients after Therapy with Unsealed Radionuclides","publisher":"International Commission on Radiological Protection (Annals of the ICRP 34(2))","year":2004,"url":"https://www.icrp.org/publication.asp?id=ICRP%20Publication%2094","doi":"10.1016/j.icrp.2004.08.001","gradingScheme":"ICRP recommendations; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"nrc-10cfr35-75","label":"10 CFR 35.75 Release of individuals containing unsealed byproduct material or implants containing byproduct material","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2007,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-C/section-35.75","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"irmer-2017-reg12","label":"The Ionising Radiation (Medical Exposure) Regulations 2017, regulation 12 (optimisation), latest revised text","publisher":"UK legislation (legislation.gov.uk)","year":2017,"url":"https://www.legislation.gov.uk/uksi/2017/1322/regulation/12","gradingScheme":"Statutory instrument; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"uk-rai-2023","label":"Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK","publisher":"Wadsley et al. with the British Thyroid Association, British Thyroid Foundation, BNMS, IPEM, BIR, RCR and patient groups (Clinical Oncology)","year":2023,"url":"https://doi.org/10.1016/j.clon.2022.07.002","doi":"10.1016/j.clon.2022.07.002","gradingScheme":"Multidisciplinary consensus guidance; grading not known (only the abstract was read).","read":"abstract","accessed":"2026-11-11"},{"key":"ata-2011","label":"Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I: practice recommendations of the American Thyroid Association","publisher":"American Thyroid Association Taskforce on Radioiodine Safety (Sisson et al., Thyroid)","year":2011,"url":"https://doi.org/10.1089/thy.2010.0403","doi":"10.1089/thy.2010.0403","gradingScheme":"Practice recommendations; the authors state the data are insufficient for evidence-based guidelines.","read":"abstract","accessed":"2026-11-11"},{"key":"wu-2020-survey","label":"Nationwide Survey on Implementation of 2011 Nuclear Regulatory Commission Policy on Release of Patients After 131I Therapy for Thyroid Cancer","publisher":"Wu et al., Journal of Nuclear Medicine","year":2020,"url":"https://doi.org/10.2967/jnumed.119.230730","doi":"10.2967/jnumed.119.230730","gradingScheme":"Patient survey; not a guideline.","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The example leaflet quoted in the steps is the IAEA's for radioiodine treatment of an overactive thyroid, adapted from European Commission guidance; SRS-63 says thyroid cancer needs its own leaflet. The behaviours are the same, but the number of days after cancer treatment is longer and is set by each centre.","The 2023 UK guidance, the most recent national guidance found, was read only as its abstract: the publisher's page refused a script. Its recommended durations, and its advice for patients on haemodialysis, are not reproduced here.","The ICRP 94 report itself, the American Thyroid Association recommendations (2011) and the SNMMI/EANM procedure standard (2022) were not read in full; the last could not be reached at all.","Whether men should avoid fathering a child after radioiodine, and for how long, has no strong evidence base (SRS-63); centres differ.","The day counts in the ICRP 94 table reproduced by SRS-63 come from dose models from the 1990s and 2000s; SRS-63 notes that calculated doses tended to be higher than measured ones and that some contact restrictions in use could be eased.","SRS-63 dates from 2009. A newer IAEA safety report on release was not looked for beyond SSG-46 (2018), which defers to it for detail."]},{"id":"radiotherapy-dose-fractionation-reference","kind":"protocol","name":"Radiotherapy dose and fractionation by cancer site: UK reference schedules","aka":["dose fractionation","RCR dose fractionation fourth edition","fractionation schedules","radiotherapy prescription","how many fractions","hypofractionation schedules","26 Gy in 5 fractions","60 Gy in 20 fractions","8 Gy single fraction"],"tldr":"Radiotherapy is given as a total dose split into a number of treatments (fractions). For most common cancers there is a standard schedule backed by trials: for example one week for early breast cancer, four weeks for prostate cancer, and often a single treatment for painful bone metastases. Fewer, larger treatments are now standard for many cancers because trials showed they work as well.","summary":"The RCR's Radiotherapy dose fractionation (fourth edition, January 2024) is the UK reference: evidence-based schedules for 22 sites, each graded on the Oxford CEBM scale (A consistent level 1 studies to D expert opinion). It covers external beam only (brachytherapy is excluded), avoids recommending fields, volumes or technique, and states that inclusion does not mean a schedule is commissioned by the NHS in any of the four nations. It also sets out what a complete prescription contains.\n\nExamples, as printed: adjuvant non-nodal breast or chest wall without immediate reconstruction 26 Gy in 5 fractions over 1 week (A), the same for external beam partial breast (A), regional nodes 40 Gy in 15 (B); prostate only 60 Gy in 20 fractions over 4 weeks (A); radical bladder 55 Gy in 20 (A); short-course preoperative rectal 25 Gy in 5 (A); medically inoperable peripheral T1 to T2b N0 lung SABR 54 Gy in 3 (B); glioblastoma with good performance status under 70, 60 Gy in 30 with or without temozolomide (A); painful bone metastases 8 Gy single dose (A); spinal cord compression in non-ambulant patients or a prognosis under 6 months 8 Gy single dose (A), and 20 Gy in 5 or 30 Gy in 10 for ambulant patients with a good prognosis or after surgery (B).\n\nASTRO differs in places: its 2018 whole-breast guideline prefers 40 Gy in 15 or 42.5 Gy in 16 (not 26 Gy in 5); its 2024 bone metastasis guideline lists 8 Gy in 1, 20 Gy in 5, 24 Gy in 6 or 30 Gy in 10 as equally recommended and conditionally prefers SBRT for selected patients with good performance status; its October 2026 prostate guideline recommends moderate hypofractionation over conventional fractionation for all risk groups and ultrahypofractionation as a standard option for low and intermediate risk.","asOf":"2026-11-11","links":[],"tags":[],"related":["prostate-radiotherapy-bladder-and-rectal-preparation","breast-radiotherapy-positioning-and-setup"],"cancers":["breast-cancer","prostate","urothelial","rectal-cancer","nsclc","glioblastoma"],"sections":[],"technologies":["sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":["astro"],"pathways":[],"terms":["hypofractionation","bone-metastases","metastatic-spinal-cord-compression"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your radiotherapy dose is split into a set number of visits. UK specialists publish a list of the standard schedules for each cancer, based on trials. Ask your team which schedule you are having and why.","domain":"radiotherapy","setting":{"who":["doctor","multidisciplinary-team"],"where":["radiotherapy-department","outpatient-clinic"]},"population":"Adults having external beam radiotherapy in the UK, for the indications the RCR lists. Brachytherapy, children's schedules beyond the RCR paediatric chapter, technique and target volumes are outside this reference. The schedules are a prescribing reference for clinical oncologists, not advice for an individual patient.","trigger":"A clinical oncologist prescribing a course of external beam radiotherapy.","steps":[{"action":"Write a complete prescription: patient identity, diagnosis, site and side, prescriber, intent, date, modality, volumes, dose and fractionation, normal tissue limits, overall time, technique and associated treatments (including chemotherapy, pacemakers and prostheses)","why":"The prescription is the legal record of the treatment and is used as evidence that the treatment was justified and checked.","source":"rcr-dose-fx-2024","quote":"The legal record of the radiotherapy treatment to be delivered is the radiotherapy treatment prescription.","grade":"ungraded (introduction)"},{"action":"For adjuvant whole breast or chest wall radiotherapy without nodes and without immediate reconstruction, prescribe 26 Gy in 5 fractions over 1 week","why":"Since the UK FAST-Forward trial in 2020, one week has replaced three weeks as standard for early breast cancer.","source":"rcr-dose-fx-2024","quote":"For adjuvant radiotherapy of non-nodal breast or chest wall without immediate reconstruction: • 26 Gy in 5 fractions over 1 week (Grade A)","grade":"Grade A"},{"action":"For regional nodal irradiation in breast cancer, prescribe 40 Gy in 15 fractions over 3 weeks","why":"Three weeks remains the standard when the lymph node areas are treated.","source":"rcr-dose-fx-2024","quote":"For regional nodal irradiation: • 40 Gy in 15 fractions over 3 weeks (Grade B)","grade":"Grade B"},{"action":"For radiotherapy to the prostate only, prescribe 60 Gy in 20 fractions over 4 weeks","why":"Four weeks controls the cancer as well as the older seven-and-a-half-week course.","source":"rcr-dose-fx-2024","quote":"Prostate-only RT: • 60 Gy in 20 fractions over 4 weeks (Grade A)","grade":"Grade A"},{"action":"For radical bladder radiotherapy, prescribe 55 Gy in 20 fractions over 4 weeks as the regimen of choice","why":"Four weeks is the UK regimen of choice for curative bladder radiotherapy, graded on the strongest level of evidence.","source":"rcr-dose-fx-2024","quote":"For radical radiotherapy to the bladder: • 55 Gy in 20 fractions over 4 weeks is the regimen of choice (Grade A)","grade":"Grade A"},{"action":"For short-course preoperative rectal radiotherapy, prescribe 25 Gy in 5 daily fractions","why":"One week of radiotherapy before surgery lowers the chance of the cancer returning in the pelvis.","source":"rcr-dose-fx-2024","quote":"Short-course preoperative radiotherapy: • 25 Gy in 5 daily fractions (Grade A)","grade":"Grade A"},{"action":"For medically inoperable small peripheral lung cancer (T1 to T2b, 5 cm or less, N0) in a favourable position, prescribe SABR 54 Gy in 3 fractions over 5 to 8 days","why":"A few very precise high doses control small lung cancers in people who cannot have surgery.","source":"rcr-dose-fx-2024","quote":"SABR using: • 54 Gy in 3 fractions over 5–8 days (Grade B)","grade":"Grade B"},{"action":"For glioblastoma (IDH wild-type) in people under 70 with good performance status and minimal residual tumour, prescribe 60 Gy in 30 daily fractions over 6 weeks, with or without temozolomide","why":"Six weeks of radiotherapy, usually with temozolomide, is the standard for fit people with this tumour.","source":"rcr-dose-fx-2024","quote":"Good performance status (KPS 80–100) and aged <70 with minimal residual tumour: • 60 Gy in 30 daily fractions over 6 weeks ± temozolomide (Grade A)","grade":"Grade A"},{"action":"For pain from bone metastases, prescribe a single 8 Gy treatment","why":"Trials and their meta-analyses support a single treatment for pain; around a quarter of people need a further treatment later.","source":"rcr-dose-fx-2024","quote":"For the initial treatment of pain from bone metastases: • 8 Gy single dose (Grade A)","grade":"Grade A"},{"action":"For spinal cord compression in people who cannot walk or have a prognosis under 6 months, prescribe 8 Gy single dose; for those who can walk with a good prognosis, or after spinal surgery, 20 Gy in 5 or 30 Gy in 10","why":"A single treatment spares people with little time from extra visits; longer courses suit those expected to live longer.","source":"rcr-dose-fx-2024","quote":"Metastatic spinal cord compression: non-ambulant patients or ambulant patients with a prognosis <6 months: • 8 Gy single dose (Grade A)","grade":"Grade A (single dose); Grade B (20 Gy in 5 or 30 Gy in 10)"},{"action":"Check that the schedule is commissioned locally before offering it; inclusion in the RCR reference is not a commissioning decision","why":"A schedule can be evidence-based and still not yet funded in a given UK nation.","source":"rcr-dose-fx-page","quote":"However, inclusion in this guidance does not imply that a particular treatment or schedule is commissioned by the national health services in the four UK nations.","grade":"ungraded"}],"bestInClass":{"statement":"For UK practice, the RCR fourth edition (January 2024) is the current graded reference, with Grade A schedules for the commonest indications (26 Gy in 5 for non-nodal breast, 60 Gy in 20 for prostate, 55 Gy in 20 for bladder, 25 Gy in 5 short-course rectal, 60 Gy in 30 for fit glioblastoma, 8 Gy single dose for painful bone metastases and for cord compression with poor mobility or prognosis). Where the US guideline differs, both are shown: ASTRO (2018) prefers 40 Gy in 15 or 42.5 Gy in 16 for whole breast, predating the five-year FAST-Forward results the RCR grades A; ASTRO (2024) recommends 8 Gy in 1, 20 Gy in 5, 24 Gy in 6 or 30 Gy in 10 for painful bone metastases, conditionally preferring SBRT for selected fit patients, where the RCR names 8 Gy single dose; ASTRO (October 2026) recommends moderate hypofractionation for localized prostate cancer across risk groups and ultrahypofractionation as a standard option at low and intermediate risk, consistent with the RCR's 60 Gy in 20.","sources":["rcr-dose-fx-2024","astro-breast-2018","astro-bone-2024","astro-prostate-2026"]},"variants":[{"name":"ASTRO whole-breast guideline (2018)","differs":"Preferred whole-breast schedule is 40 Gy in 15 fractions or 42.5 Gy in 16 fractions; 26 Gy in 5 is not the preferred option.","evidence":"Systematic review and graded consensus (abstract read). Published before the five-year FAST-Forward results on which the RCR's Grade A rests.","sources":["astro-breast-2018","rcr-dose-fx-2024"]},{"name":"ASTRO palliative bone metastasis guideline (2024)","differs":"Recommends 8 Gy in 1, 20 Gy in 5, 24 Gy in 6 or 30 Gy in 10 for symptomatic bone metastases; for cord or cauda equina compression in people ineligible for surgery, 8 Gy in 1, 16 Gy in 2, 20 Gy in 5 or 30 Gy in 10; conditionally recommends SBRT over conventional radiotherapy for selected patients with good performance status without surgery or neurological signs; surgery then radiotherapy conditionally over radiotherapy alone for cord compression.","evidence":"Based on an AHRQ systematic review with graded consensus (abstract read).","sources":["astro-bone-2024"]},{"name":"ASTRO prostate hypofractionation guideline (October 2026)","differs":"Recommends moderate hypofractionation over conventional fractionation for all risk groups and ultrahypofractionation as a standard option for low- and intermediate-risk disease, to be considered in selected high-risk patients, preferably in trials; moderate hypofractionation may be preferred with significant baseline urinary problems.","evidence":"Systematic review with graded consensus; high-quality randomised data (abstract read). The schedules it lists were not read.","sources":["astro-prostate-2026"]}],"grades":[{"claim":"Non-nodal breast or chest wall without immediate reconstruction: 26 Gy in 5 fractions","grade":"Grade A","source":"rcr-dose-fx-2024"},{"claim":"Partial breast external beam: 26 Gy in 5 fractions","grade":"Grade A","source":"rcr-dose-fx-2024","quote":"For partial breast radiotherapy using external beam radiotherapy: • 26 Gy in 5 fractions over 1 week (Grade A)"},{"claim":"Prostate only: 60 Gy in 20 fractions","grade":"Grade A","source":"rcr-dose-fx-2024"},{"claim":"Ambulant cord compression with a good prognosis, or after surgery: 20 Gy in 5 or 30 Gy in 10","grade":"Grade B","source":"rcr-dose-fx-2024","quote":"Metastatic spinal cord compression: ambulant patients with a good prognosis or post-spinal surgery: • 20 Gy in 5 daily fractions over 1 week (Grade B) or • 30 Gy in 10 daily fractions over 2 weeks (Grade B)"},{"claim":"Reirradiation of bone metastases: 8 Gy single dose or 20 Gy in 5","grade":"Grade B","source":"rcr-dose-fx-2024","quote":"For the reirradiation of bone metastases: • 8 Gy single dose (Grade B) • 20 Gy in 5 daily fractions (or 8 fractions over the spinal cord) over 1 week (Grade B)"}],"sources":[{"key":"rcr-dose-fx-2024","label":"Radiotherapy dose fractionation, fourth edition (January 2024)","publisher":"The Royal College of Radiologists","year":2024,"url":"https://www.rcr.ac.uk/media/0d4mrqi5/radiotherapy-dose-fractionation-fourth-edition.pdf","gradingScheme":"Oxford Centre for Evidence-Based Medicine (2009): levels 1a to 5; grades A (consistent level 1 studies), B (consistent level 2 or 3, or extrapolations from level 1), C (level 4, or extrapolations from level 2 or 3), D (level 5, or inconsistent or inconclusive studies).","read":"full-text","accessed":"2026-11-11"},{"key":"rcr-dose-fx-page","label":"Radiotherapy dose fractionation, Fourth edition (publication page)","publisher":"The Royal College of Radiologists","year":2024,"url":"https://www.rcr.ac.uk/our-services/all-our-publications/clinical-oncology-publications/radiotherapy-dose-fractionation-fourth-edition/","read":"full-text","accessed":"2026-11-11"},{"key":"astro-prostate-2026","label":"Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO Clinical Practice Guideline","publisher":"American Society for Radiation Oncology (Practical Radiation Oncology)","year":2026,"url":"https://doi.org/10.1016/j.prro.2026.09.017","doi":"10.1016/j.prro.2026.09.017","gradingScheme":"ASTRO grading of quality of evidence and strength of recommendation (full text not read).","read":"abstract","accessed":"2026-11-11"},{"key":"astro-bone-2024","label":"External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline","publisher":"American Society for Radiation Oncology (Practical Radiation Oncology)","year":2024,"url":"https://doi.org/10.1016/j.prro.2024.04.018","doi":"10.1016/j.prro.2024.04.018","gradingScheme":"ASTRO evidence quality and recommendation strength (full text not read).","read":"abstract","accessed":"2026-11-11"},{"key":"astro-breast-2018","label":"Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline","publisher":"American Society for Radiation Oncology (Practical Radiation Oncology)","year":2018,"url":"https://doi.org/10.1016/j.prro.2018.01.012","doi":"10.1016/j.prro.2018.01.012","gradingScheme":"ASTRO evidence quality and recommendation strength (full text not read).","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-five-fraction-breast-default","idea-pu-prostate-hypofractionation-default","idea-acc-single-fraction-palliative-radiotherapy-default"],"gaps":["Only a selection of the RCR's schedules is shown as steps; the reference covers 22 sites and many more indications, including head and neck, gynaecological, lymphoma, paediatric, skin and oligometastatic disease.","The ASTRO guidelines were read as abstracts; their full texts (and so their grades and the full lists of schedules) are behind the Practical Radiation Oncology paywall.","The ASTRO whole-breast guideline (2018) predates the five-year FAST-Forward results; no newer ASTRO whole-breast guideline was found in Europe PMC.","ESTRO and ESMO site-specific fractionation recommendations were not compared here.","The RCR reference excludes brachytherapy and does not cover technique or target volumes."]},{"id":"radiotherapy-planning-ct-simulation","kind":"protocol","name":"Radiotherapy planning scan (CT simulation): positioning, skin marks and what the patient does","aka":["CT simulation","CT sim","planning CT","radiotherapy planning appointment","simulation","virtual simulation","radiotherapy tattoos","reference marks","mould room"],"tldr":"Before radiotherapy starts you have a planning appointment, usually a CT scan. You lie in the exact treatment position, sometimes with a mask, mould or cushion, and keep very still. Small skin marks (permanent dots or temporary ink) may be made to line you up each day. Depending on the area, you may need a full or empty bladder, a dye injection, or breath-hold practice.","summary":"The NCI booklet (2021) describes the planning session for patients: the radiation oncologist and therapist define the treatment area while the patient lies very still for scans; small permanent tattoos or ink dots are placed to line the patient up daily; a body mould or, for the head and neck, a mask may be made. The ESTRO ACROP head and neck guideline (2017) gives the radiographer's procedure: identification and consent checked before scanning; diagnosis, prescription and scan margins known in advance to keep imaging dose as low as reasonably achievable; contrast screened for, kidney function checked and the patient observed for at least 15 minutes after; nodes and scars marked and bolus placed before scanning; the couch set so all immobilisation is in the field of view; orientation entered correctly; slice thickness of 3 mm or less; dose-length product recorded; a photograph of the set-up taken if needed.\n\nOn skin marks, ESTRO-ACROP breast (2023) reports a randomised trial (176 against 166 patients) with no difference in set-up error between permanent tattoos and temporary marks on weekly portal imaging, notes that tattoos may affect wellbeing, and considers that surface guidance may allow marks to be omitted if validated locally. A randomised trial in 196 women found that a virtual-reality explanation before breast radiotherapy planning reduced anxiety immediately and improved knowledge of the procedure compared with the standard explanation. Site-specific preparation (bladder and bowel filling, breath-hold, 4D CT, masks) is in linked protocols.","asOf":"2026-11-11","links":[],"tags":[],"related":["breast-radiotherapy-positioning-and-setup","breath-hold-left-breast-radiotherapy","prostate-radiotherapy-bladder-and-rectal-preparation","head-and-neck-radiotherapy-immobilisation-mask","respiratory-motion-management-4d-ct-and-gating","iodinated-contrast-kidney-and-metformin","radiotherapy-patient-identification-and-time-out","radiotherapy-pregnancy-and-breastfeeding-enquiry"],"cancers":["head-and-neck","breast-cancer"],"sections":[],"technologies":["ct","surface-guided-radiotherapy","treatment-planning-systems","iodinated-contrast-media","respiratory-motion-management"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"The planning scan maps exactly where the treatment will go. You lie very still in the same position you will be treated in. The team may make tiny marks on your skin.","domain":"radiotherapy","setting":{"who":["radiographer","doctor","patient-or-carer"],"where":["radiotherapy-department"]},"population":"Adults having a CT planning scan for external beam radiotherapy at any site. MR simulation, PET-CT planning and children's preparation are not covered by the sources read. The detailed CT steps come from a head and neck guideline and apply generally where marked as such.","trigger":"The first planning appointment after the decision to give external beam radiotherapy.","steps":[{"action":"Explain the planning session to the patient beforehand: what the scan is for, that they must keep very still, and that skin marks may be made","why":"Knowing what will happen makes the appointment easier and helps people stay still.","source":"nci-rt-and-you","quote":"You will be asked to lie very still while x-rays or scans are taken.","grade":"Patient information (ungraded)"},{"action":"Confirm the patient's identity and consent by departmental procedure before scanning, and complete the pregnancy enquiry where it applies","why":"The planning scan is the first exposure in a course of treatment, and every later step depends on it being the right person.","source":"estro-acrop-hn-2017","quote":"All departmental procedures in relation to patient informed consent and identification should be adhered to prior to commencing the CT scanning procedure.","grade":"Guideline (ungraded)"},{"action":"Know the diagnosis, prescription and required scan margins before scanning, and scan no more than is needed","why":"This keeps the radiation from the scan itself as low as possible.","source":"estro-acrop-hn-2017","quote":"The patient diagnosis, prescription and required scanning margins should be known to the RTTs before commencing CT, so as to adhere to the ALARA principle.","grade":"Guideline (ungraded)"},{"action":"If contrast is to be given, screen for previous reactions, check kidney function, keep the emergency trolley ready, and observe the patient for at least 15 minutes afterwards","why":"Contrast helps the team see the tumour, but reactions, though rare, need to be prepared for.","source":"estro-acrop-hn-2017","quote":"If contrast is to be used, the RTTs must screen the patient for potential anaphylaxis as per departmental protocol, document this screening procedure and ensure that the emergency trolley is prepared and fully stocked.","grade":"Guideline (ungraded)"},{"action":"Position the patient in the treatment position with all immobilisation in place, mark any scars or nodes and place any planned bolus before the scan","why":"The plan is calculated on this scan, so anything present at treatment must be present now.","source":"estro-acrop-hn-2017","quote":"If bolus is planned for the patient’s treatment, this should be in situ prior to CT scanning so as to account for the actual bolus to be used at treatment in the dose calculations.","grade":"Guideline (ungraded)"},{"action":"Set the couch so all immobilisation devices are in the field of view, and enter patient orientation correctly at the console","why":"Devices must be in the scan to be accounted for in the dose, and a wrong orientation could flip the plan.","source":"estro-acrop-hn-2017","quote":"The RTTs must ensure that both patient orientation and the orientation of the topogram or pilot scan are correctly entered at the CT console.","grade":"Guideline (ungraded)"},{"action":"Use thin slices (3 mm or less for head and neck) and record the scan dose (dose-length product) in the chart","why":"Thin slices show small structures clearly, and recording the dose is a legal requirement for imaging.","source":"estro-acrop-hn-2017","quote":"It is recommended to use axial slice thickness of 3 mm or less for head and neck cases.","grade":"Guideline (ungraded)"},{"action":"Place reference marks for daily set-up, discussing with the patient permanent tattoos or temporary marks, or omit marks where a validated surface-guidance workflow allows","why":"Marks help line you up each day; permanent tattoos are not the only option.","source":"estro-acrop-breast-2023","quote":"Temporary skin marks may be an alternative to permanent tattoos with a lesser impact on patient well-being [70] .","grade":"Consideration (ESTRO-ACROP: practice the evidence could not support as a recommendation)"},{"action":"Tell the patient to keep their marks and to say if they fade","why":"The marks are used every day of treatment.","source":"nci-rt-and-you","quote":"Be careful not to remove them and tell the radiation therapist if they have faded or lost color.","grade":"Patient information (ungraded)"},{"action":"Before the patient leaves, take a photograph of the set-up if needed and record the position and devices in the chart","why":"Every radiographer who treats the patient later must be able to reproduce the position exactly.","source":"estro-acrop-hn-2017","quote":"If needed, a photograph of the patient position can be taken and added to the patient chart.","grade":"Guideline (ungraded)"}],"bestInClass":{"statement":"Prepare the patient (an explanation in advance; a staff-led preview such as a virtual-reality walkthrough reduced anxiety and improved understanding in one randomised trial), confirm identity, consent and pregnancy status, scan in the treatment position with all devices and bolus in place and the scan limits known in advance, screen for contrast and observe afterwards, use thin slices, record the scan dose, and document the set-up (ESTRO ACROP head and neck 2017; NCI 2021). Skin marks may be permanent or temporary (no difference in accuracy in one randomised trial reported by ESTRO-ACROP breast 2023), or omitted where surface guidance is validated. No single international guideline covers CT simulation across all sites; site-specific steps are in the linked protocols.","sources":["estro-acrop-hn-2017","estro-acrop-breast-2023","nci-rt-and-you","shin-vr-2023"]},"variants":[{"name":"Virtual-reality or guided preview before planning","differs":"The patient sees the room, the machine and the sequence of the session in a headset (or on a visit) before the planning appointment, instead of a verbal or written explanation only.","evidence":"Randomised trial, 196 women before breast radiotherapy: immediate anxiety reductions of 26.0%, 16.1% and 55.8% on three scales against 8.1%, 8.5% and 13.7%, with only one scale showing a lasting difference; knowledge 81.9 against 76.8 out of 100 (P = .006).","sources":["shin-vr-2023"]},{"name":"Tattoo-free set-up with surface guidance","differs":"No permanent marks: the patient is aligned with a surface camera, or temporary marks are used.","evidence":"ESTRO-ACROP breast (2023) reports one randomised trial with no difference in set-up error between tattoos and temporary marks on weekly portal imaging, and considers that surface guidance may allow marks to be omitted after local validation.","sources":["estro-acrop-breast-2023"]}],"grades":[{"claim":"Virtual-reality explanation reduces anxiety at radiotherapy planning","grade":"Single randomised trial (196 patients)","source":"shin-vr-2023","quote":"Immersive VR applied to the current procedure reduces anxiety during RT planning for patients with breast cancer."},{"claim":"Surface guidance may allow skin marks to be omitted","grade":"Consideration (ESTRO-ACROP)","source":"estro-acrop-breast-2023","quote":"SGRT may improve setup accuracy and enable the omission of skin marks entirely, though this must be validated in the context of a department’s local workflow."},{"claim":"Patient remains at least 15 minutes after contrast","grade":"Guideline (ungraded)","source":"estro-acrop-hn-2017","quote":"As a minimum requirement, the patient must remain in the department for a further fifteen minutes."}],"sources":[{"key":"nci-rt-and-you","label":"Radiation Therapy and You: Support for People With Cancer (April 2021)","publisher":"US National Cancer Institute","year":2021,"url":"https://www.cancer.gov/publications/patient-education/radiation-therapy-and-you","read":"full-text","accessed":"2026-11-11"},{"key":"estro-acrop-hn-2017","label":"ESTRO ACROP guidelines for positioning, immobilisation and position verification of head and neck patients for radiation therapists","publisher":"ESTRO ACROP (Leech et al., Technical Innovations and Patient Support in Radiation Oncology)","year":2017,"url":"https://doi.org/10.1016/j.tipsro.2016.12.001","doi":"10.1016/j.tipsro.2016.12.001","gradingScheme":"Guidance based on a literature review, a European survey and committee experience; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"estro-acrop-breast-2023","label":"ESTRO-ACROP guideline for positioning, immobilisation and setup verification for local and loco-regional photon breast cancer irradiation","publisher":"ESTRO-ACROP (Mast et al., Technical Innovations and Patient Support in Radiation Oncology)","year":2023,"url":"https://doi.org/10.1016/j.tipsro.2023.100219","doi":"10.1016/j.tipsro.2023.100219","gradingScheme":"Recommendations where the evidence supported them; considerations for relevant practice the evidence could not support.","read":"full-text","accessed":"2026-11-11"},{"key":"shin-vr-2023","label":"An Investigation of the Effect of Virtual Reality on Alleviating Anxiety in Patients With Breast Cancer Undergoing Radiation Therapy: A Randomized Controlled Trial","publisher":"International Journal of Radiation Oncology, Biology, Physics (Shin et al.)","year":2023,"url":"https://doi.org/10.1016/j.ijrobp.2023.06.275","doi":"10.1016/j.ijrobp.2023.06.275","read":"abstract","accessed":"2026-11-11"}],"upgrades":["idea-pu-radiotherapy-walkthrough-before-planning","idea-pu-tattoo-free-set-up"],"gaps":["No international guideline covering CT simulation for all tumour sites was found; the detailed procedure is taken from the ESTRO ACROP head and neck guideline (2017), which is ungraded and site-specific.","AAPM Task Group 66 on CT simulator quality assurance (2003) was not read: it is paywalled, and an identifier tried for it resolved to an unrelated paper.","MR simulation and PET-CT planning were not examined.","The virtual-reality trial was in breast cancer at one institution and read as an abstract; effects in other sites are not known.","The randomised trial of tattoos against temporary marks is reported through the ESTRO-ACROP breast guideline and was not read directly."]},{"id":"radiotherapy-with-pacemaker-or-defibrillator","kind":"protocol","name":"Radiotherapy with a pacemaker or implanted defibrillator","aka":["CIED and radiotherapy","pacemaker and radiotherapy","ICD and radiotherapy","cardiac implantable electronic device radiotherapy","TG-203","defibrillator radiotherapy","pacing-dependent radiotherapy"],"tldr":"Radiotherapy can occasionally upset a pacemaker or an implanted defibrillator, usually by resetting it. Tell the team about your device at your first appointment. They will contact your heart device clinic, plan the treatment to keep dose to the device low, and may watch your heart rhythm during treatment. Your device is checked within two weeks of finishing.","summary":"The UK Radiotherapy Board guidance (January 2025, with the British Cardio-Oncology Society and the British Heart Rhythm Society) and the JASTRO/JCS guideline (2021) take the same approach: identify the device at referral, obtain the last device check and pacing dependency from the device clinic, consent the patient to the risk of malfunction, and stratify risk by pacing dependency, cumulative device dose and neutron production. Risk of malfunction rises with neutron-producing beams (photons of 10 MV or more, electrons of 20 MeV or more, protons and heavy ions), with high dose rates (flattening-filter-free beams) and with cumulative dose. A meta-analysis of 17 retrospective studies (2,454 patients) found ICDs more often affected than pacemakers (odds ratio 2.75) and reset more likely with neutron-producing radiotherapy.\n\nUK planning rules: energies below 10 MV where possible (otherwise high risk), no direct irradiation of the device including exit beam, the device outlined with a margin (CIED PRV) when within 10 cm of a field edge, and a near-maximum dose (D0.035cc) to the CIED PRV below 5 Gy; a device more than 10 cm from the field edge can be assumed to receive under 2 Gy. Cumulative dose includes previous radiotherapy and cone-beam CT (about 0.01 Gy per scan). Relocating the device is not recommended below 5 Gy. A defibrillator, an AED able to pace and trained staff must be available; continuous ECG monitoring is strongly recommended for pacing-dependent patients, a device nearing end of battery life and ICDs, with an extra trained person on the first day. The device is interrogated weekly once it has received more than 5 Gy and checked within 2 weeks of the course. JASTRO/JCS classify high risk as any of: photons of 10 MV or more, electrons of 20 MeV or more, protons or carbon ions, pacing dependency, device dose above 10 Gy, previous ventricular fibrillation or ICD therapy; low risk needs all of: lower energies, not pacing dependent, no chest irradiation, device dose below 2 Gy and no ventricular tachycardia. None of this is graded; the evidence is case series and laboratory studies.","asOf":"2026-11-11","links":[],"tags":[],"related":["mri-safety-screening-implants","radiotherapy-patient-identification-and-time-out"],"cancers":[],"sections":[],"technologies":["imrt-igrt","in-room-imaging-systems"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you have a pacemaker or a defibrillator, tell the radiotherapy team straight away. They will talk to your heart team, keep the rays away from the device, and get it checked after treatment.","domain":"radiotherapy","setting":{"who":["doctor","radiographer","multidisciplinary-team","patient-or-carer"],"where":["radiotherapy-department","outpatient-clinic"]},"population":"Adults with a permanent pacemaker, implantable cardioverter-defibrillator (including subcutaneous ICD), cardiac resynchronisation device (CRT-P managed as a pacemaker, CRT-D as an ICD) or leadless pacemaker who are referred for external beam radiotherapy, kilovoltage radiotherapy or brachytherapy. MR simulation and MR-linac treatment follow MR conditional rules for the device and are noted, not detailed. Children are not addressed by the sources read.","trigger":"Referral for radiotherapy of a person who has, or may have, a cardiac implantable electronic device.","steps":[{"action":"At referral, confirm whether the patient has a cardiac device and which type, identify their device clinic, and find out whether they are pacing dependent","why":"Whether the heart relies on the device decides how serious a malfunction would be.","source":"rcr-cied-2025","quote":"It is imperative to identify patients with CIEDs as early as possible within the radiotherapy pathway.","grade":"Guidance (ungraded)"},{"action":"Contact the device clinic for the last device check report and all programmed settings, and ask about previous ventricular arrhythmia or ICD shocks","why":"The team needs to know how the device is set and how the heart behaves before any treatment.","source":"rcr-cied-2025","quote":"Ensure the CIED is under regular follow-up and request a report of the last device check and documentation of all programmed parameters","grade":"Guidance (ungraded)"},{"action":"Discuss the small risk of device malfunction with the patient and record it on the referral and the consent form","why":"The patient should know what could happen and what the team will do about it before agreeing to treatment.","source":"rcr-cied-2025","quote":"Ensure an appropriately trained practitioner has had a risk-benefit discussion with the patient regarding possible device malfunction and management during radiotherapy.","grade":"Guidance (ungraded)"},{"action":"At the planning scan, ask every patient whether they have a cardiac device, and leave a device more than 10 cm from any field edge out of the scan unless it is needed for planning","why":"Small or leadless devices are easy to miss, and a short CT scan carries very little risk to the device.","source":"rcr-cied-2025","quote":"If a device is more than 10cm from a potential field edge it is not necessary to include in the planning CT scan (radiotherapy dose will be <2Gy).","grade":"Guidance (ungraded)"},{"action":"Plan with photon energies below 10 MV, avoid direct irradiation of the device including the exit beam, and prefer flattened beams over high dose-rate beams","why":"Higher energies make neutrons that can scramble the device's memory; keeping the beam off the device keeps its dose low.","source":"rcr-cied-2025","quote":"Use energies <10MV to minimise neutron production. If energies at 10MV and above cannot be avoided, then the patient must be managed within the high-risk category.","grade":"Guidance (ungraded)"},{"action":"Outline the device with a margin when it is within 10 cm of the field, record the near-maximum cumulative dose (including earlier radiotherapy and imaging), and aim for less than 5 Gy","why":"The total dose the device receives over the whole course is what raises the chance of a fault.","source":"rcr-cied-2025","quote":"Recommended near-maximum dose (eg. D0.035cc) to CIED PRV is <5Gy.","grade":"Guidance (ungraded)"},{"action":"Do not compromise the cancer treatment plan to spare the device; if the device would receive too much dose, discuss other techniques or moving the device with the cardiologist, but do not move it for a dose below 5 Gy","why":"Treating the cancer properly comes first, and moving a device is an operation with its own risks.","source":"rcr-cied-2025","quote":"The quality of the treatment plan should not be significantly compromised for the sake of sparing the device.","grade":"Guidance (ungraded)"},{"action":"Before the first treatment, check that the dose estimate, device report and consent are in place, that a defibrillator able to pace is in the department, and that trained staff are arranged if monitoring is needed","why":"If the device fails, the team must be able to support the heart at once.","source":"rcr-cied-2025","quote":"A cardiac arrest trolley equipped with an automated external defibrillator (AED) capable of delivering external pacing is available within the department and staff are adequately trained to use the equipment.","grade":"Guidance (ungraded)"},{"action":"Monitor the heart continuously by ECG during treatment for pacing-dependent patients, devices near the end of battery life and ICDs, with an extra trained person on the first day","why":"Watching the heart rhythm lets staff stop the beam the moment something goes wrong.","source":"rcr-cied-2025","quote":"There is a lack of data on the benefit of continuous cardiac monitoring during radiotherapy2, but it is strongly recommended to use cardiac monitoring for patients who are pacing dependent, those whose device battery is nearing end of life or those with ICDs24.","grade":"Guidance (ungraded)"},{"action":"If an ICD shocks inappropriately, place a magnet over it to stop shocks and call a cardiologist urgently; remove the magnet if the patient becomes unstable with a fast heart rhythm","why":"A magnet pauses the defibrillator's shocks without stopping its pacing, but the shocks may be needed if the rhythm is truly dangerous.","source":"rcr-cied-2025","quote":"If an ICD appears to be delivering shocks inappropriately, a magnet positioned over the device will stop the delivery of shocks and anti-tachycardia therapy but will not affect the pacemaker function of the ICD.","grade":"Guidance (ungraded)"},{"action":"Have the device interrogated weekly once it has received more than 5 Gy, and arrange a device check at the referring hospital within 2 weeks of the last treatment, with an advice letter by the last day","why":"Some faults appear only later, so the device is checked again after treatment ends.","source":"rcr-cied-2025","quote":"The patient must have their CIED checked at their referring hospital within 2 weeks of completing treatment.","grade":"Guidance (ungraded)"},{"action":"Record any unexpected device event in the incident reporting system and explain it to the patient","why":"Faults are rare, and reporting them is how guidance improves.","source":"rcr-cied-2025","quote":"All unexpected CIED events detected during the radiotherapy course and in the follow-up period must be systematically recorded using the centre’s incident reporting system and explained to the patient.","grade":"Guidance (ungraded)"}],"bestInClass":{"statement":"Identify the device at referral, obtain its settings and pacing dependency from the device clinic, consent to the risk, and stratify risk by pacing dependency, cumulative device dose and neutron production (UK Radiotherapy Board 2025; JASTRO/JCS 2021; AAPM TG-203 2019 frames the same process as a failure-mode analysis). Plan below 10 MV with flattened beams, keep the beam off the device and aim for a near-maximum cumulative device dose below 5 Gy (UK), without compromising the cancer plan; monitor pacing-dependent patients, ICDs and devices near end of life by ECG with resuscitation and external pacing to hand; check the device within 2 weeks of the course. The guidelines differ on thresholds: the UK counts any treatment at 10 MV or above as high risk and sets 5 Gy as the dose aim, while JASTRO/JCS calls a device dose above 10 Gy high risk and below 2 Gy (with no chest irradiation) low risk, and raises risk one level for flattening-filter-free beams; Italian AIAC/AIRO/AIFM draws its energy line at 6 MV. None of these is graded, because the evidence is case series and laboratory studies.","sources":["rcr-cied-2025","jastro-jcs-2021","aapm-tg203-2019","meta-hrthm-2023"]},"variants":[{"name":"JASTRO/JCS (Japan): three risk levels with a 10 Gy high-risk threshold and monitoring by risk","differs":"Low risk requires photons below 10 MV or electrons below 20 MeV, no pacing dependency, no chest irradiation, device dose below 2 Gy and no history of ventricular tachycardia; high risk is any of photons of 10 MV or more, electrons of 20 MeV or more, protons, carbon ions, pacing dependency, device dose above 10 Gy, previous ventricular fibrillation or ICD therapy. Medium-risk patients are monitored by ECG or pulse oximeter at the first session and as needed after; high-risk patients at every session. FFF beams can raise the category by one level.","evidence":"Consensus of the Japanese radiation oncology and cardiology societies, based on case reports and laboratory studies; ungraded.","sources":["jastro-jcs-2021"]},{"name":"Italian AIAC/AIRO/AIFM and ANMCO: a 6 MV energy line","differs":"As tabulated by the UK and JASTRO/JCS documents, the Italian classification counts as low risk only photons or electrons of 6 MV or less with device dose of 2 Gy or less and no pacing dependency, and as high risk a device dose above 10 Gy; the 2025 ANMCO statement adds timing of cardiology assessments during and after treatment.","evidence":"Expert consensus. The ANMCO statement was read as an abstract only.","sources":["rcr-cied-2025","anmco-2025"]},{"name":"Emergency palliative radiotherapy without dose or device information (UK)","differs":"Use continuous cardiac monitoring where available, keep doses below 2 Gy (departments set rules for a safe distance from field edge to device when dose is not calculated), and refer for a device check within 2 weeks.","evidence":"Pragmatic guidance; ungraded.","sources":["rcr-cied-2025"]}],"grades":[{"claim":"Implantable defibrillators are more often affected by radiotherapy than pacemakers","grade":"Meta-analysis of 17 retrospective observational studies (2,454 patients)","source":"meta-hrthm-2023","quote":"The meta-analysis showed that RT was associated with an increased risk of ICD malfunctions (odds ratio [OR] 2.75; 95% confidence interval [CI] 1.74-4.33)."},{"claim":"Neutron-producing radiotherapy raises the risk of device malfunction","grade":"Meta-analysis of observational studies","source":"meta-hrthm-2023","quote":"Neutron-generating RT significantly increased the risk of CIED malfunctions (OR 3.97; 95% CI 1.70-9.26), especially the risk of reset (OR 5.79; 95% CI 2.37-14.12; P = .0001)."},{"claim":"Continuous monitoring for high-risk patients at every session","grade":"Guideline (ungraded)","source":"jastro-jcs-2021","quote":"For high-risk patients, monitor the circulation using an electrocardiogram or pulse oximeter for pulse abnormalities in every radiotherapy session."},{"claim":"Flattening-filter-free beams raise the risk category","grade":"Guideline (ungraded)","source":"jastro-jcs-2021","quote":"When using flattening filter-free (FFF) beams, consider raising the risk classification by one level depending on the patient’s condition."},{"claim":"A device more than 10 cm from the field edge can be assumed to receive under 2 Gy","grade":"Guidance (ungraded)","source":"rcr-cied-2025","quote":"If the CIED is >10cm superiorly or inferiorly from the edge of the treatment beam, it can be assumed that the near-maximum dose (eg. D0.035cc) to the CIED PRV will be <2Gy."}],"sources":[{"key":"rcr-cied-2025","label":"Guidance on the management of patients with cardiac implantable electronic devices receiving radiotherapy (January 2025)","publisher":"Radiotherapy Board (IPEM, Society and College of Radiographers, Royal College of Radiologists), with the British Cardio-Oncology Society and the British Heart Rhythm Society","year":2025,"url":"https://rcr.ac.uk/media/0mdltaed/management-of-patients-with-cieds-receiving-rt_jan2025_.pdf","gradingScheme":"Guidance without graded recommendations.","read":"full-text","accessed":"2026-11-11"},{"key":"jastro-jcs-2021","label":"JASTRO/JCS Guidelines for radiotherapy in patients with cardiac implantable electronic devices","publisher":"Japanese Society for Radiation Oncology and Japanese Circulation Society (Journal of Radiation Research)","year":2021,"url":"https://doi.org/10.1093/jrr/rraa102","doi":"10.1093/jrr/rraa102","gradingScheme":"Consensus guideline; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"aapm-tg203-2019","label":"Management of radiotherapy patients with implanted cardiac pacemakers and defibrillators: A Report of the AAPM TG-203","publisher":"American Association of Physicists in Medicine (Miften et al., Medical Physics)","year":2019,"url":"https://doi.org/10.1002/mp.13838","doi":"10.1002/mp.13838","gradingScheme":"Task group report; recommendations are not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"meta-hrthm-2023","label":"Radiotherapy-induced malfunctions of cardiac implantable electronic devices: A meta-analysis","publisher":"Heart Rhythm","year":2023,"url":"https://doi.org/10.1016/j.hrthm.2023.01.024","doi":"10.1016/j.hrthm.2023.01.024","read":"abstract","accessed":"2026-11-11"},{"key":"anmco-2025","label":"Management of cardiac implantable electronic devices in cancer patients undergoing radiotherapy. An Italian Association of Hospital Cardiologists (ANMCO) statement","publisher":"ANMCO (Giornale Italiano di Cardiologia)","year":2025,"url":"https://doi.org/10.1714/4531.45340","doi":"10.1714/4531.45340","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The AAPM TG-203 report could not be read in full: the publisher returned 403 to a script. Its position is taken from its abstract and from the UK and Japanese documents that summarise it.","Thresholds differ between guidelines (UK aim below 5 Gy; JASTRO/JCS high risk above 10 Gy, low risk below 2 Gy; Italian energy line at 6 MV) because the evidence is case reports, retrospective series and laboratory irradiation of devices; no prospective trial compares the strategies.","The UK guidance itself says there is a lack of data on the benefit of continuous cardiac monitoring; it recommends monitoring anyway for those at greatest risk.","The UK risk flowchart (Figure 1) is an image and was not read; the categories here are taken from the guidance text and appendix.","Proton and heavy ion therapy are treated as high risk by both guidelines read; device-specific evidence for particle therapy was not examined.","The 2017 HRS expert consensus on MRI and radiation exposure in patients with cardiac devices and the 2022 ESC cardio-oncology guideline were not read; the UK guidance cites the HRS statement for its 5 Gy relocation rule."]},{"id":"raised-intracranial-pressure","kind":"protocol","name":"Raised intracranial pressure in cancer: recognition, urgent scan, dexamethasone and referral","aka":["raised ICP","cerebral oedema from brain metastases","brain swelling in cancer","peritumoral oedema","dexamethasone for brain metastases"],"tldr":"Cancer in or spreading to the brain can raise the pressure inside the skull. A headache that is worse in the morning or on coughing, being sick without feeling sick, new confusion, a fit or a change in vision needs a same-day call to your cancer team. Usually a brain scan is done and a steroid called dexamethasone is started to reduce the swelling, then lowered as soon as it can be.","summary":"Raised intracranial pressure in cancer is usually from brain metastases or a primary brain tumour with surrounding oedema, or a bleed into or around a tumour. The Scottish Palliative Care Guidelines list a headache gradually increasing, classically worse in the morning and on coughing, sneezing or bending, vomiting often without nausea, visual disturbance, dizziness, personality change and seizures; signs (raised blood pressure, altered consciousness, ocular palsies, papilloedema) are often late. Management there: urgent CT brain may be necessary; a trial of corticosteroids with gastroprotection, dexamethasone 8 to 16 mg immediately, then 4 to 8 mg twice daily with the second dose before 2 pm, stopped promptly if there is no benefit and reduced gradually in responders; raise the head of the bed; stop anticoagulants if a bleed is suspected; analgesia and antiemetics (ondansetron); referral to oncology and consideration of neurosurgery.\n\nThe Congress of Neurological Surgeons (2019, Level 3) recommends steroids for temporary relief of symptoms from raised pressure, a starting dose of 4 to 8 mg/day of dexamethasone for mild symptoms and 16 mg/day or more for severe symptoms, dexamethasone as the steroid of choice, and tapering as rapidly as tolerated; it finds insufficient evidence for steroids in people without symptoms or mass effect. The trial behind the lower dose (Vecht 1994) found 4 mg/day gave the same improvement at one week as 16 mg/day, with fewer toxic effects, in people without signs of impending herniation. NICE NG122 (lung cancer) offers dexamethasone for symptomatic brain metastases, reduced to the minimum dose that keeps symptoms controlled. EANO-ESMO 2021 could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency"],"related":["metastatic-spinal-cord-compression-emergency","acute-oncology-telephone-triage"],"cancers":["secondary-brain-tumours","brain-tumours","glioblastoma"],"sections":[],"technologies":["ct","mri","palliative-radiotherapy"],"targets":[],"drugs":["dexamethasone","ondansetron"],"companies":[],"institutions":["nice"],"pathways":[],"terms":["brain-metastases","stereotactic-radiosurgery","wbrt"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you have cancer and get a new headache that is worse in the morning, keep being sick, or become confused, ring your cancer team the same day.","domain":"emergencies","setting":{"who":["doctor","nurse","patient-or-carer","emergency-team"],"where":["home","telephone-triage","acute-oncology-service","emergency-department","ward"]},"population":"Adults with a known or suspected brain tumour or brain metastases, or any cancer that can bleed into the brain, who develop symptoms of raised intracranial pressure. The Scottish guideline is written for palliative care; the CNS guideline for adults with brain metastases. Children and people with hydrocephalus needing a shunt or drain are not covered here.","trigger":"A person with cancer reports a new or worsening headache with the features below, vomiting, new confusion or personality change, visual disturbance or a seizure.","steps":[{"action":"Suspect raised intracranial pressure when a person with cancer has a headache that is worse in the morning or on coughing, sneezing or bending, or vomits without nausea","why":"Pressure in the skull rises when lying flat overnight and when straining, so the pattern of the headache is a clue.","source":"scot-pcg","quote":"Headache often worse on coughing, sneezing and bending over"},{"action":"Do not wait for signs on examination before acting","why":"Signs such as swelling at the back of the eye often appear late.","source":"scot-pcg","quote":"Diagnosis is usually based on the history. Signs are often late but can include:"},{"action":"Arrange an urgent CT scan of the brain where it would change management","why":"A scan shows whether there is a tumour, swelling or bleeding, and guides treatment.","source":"scot-pcg","quote":"Urgent CT Brain may be necessary."},{"action":"Remember that a bleed into or around a tumour can cause it, and stop anticoagulants if a bleed is suspected","why":"Blood thinners can make bleeding inside the skull worse.","source":"scot-pcg","quote":"If intracranial bleed suspected stop anticoagulants"},{"action":"Start dexamethasone with a proton pump inhibitor: 8 to 16 mg at once, then 4 to 8 mg twice daily, giving the second dose before 2 pm","why":"Steroids reduce the swelling around the tumour; the earlier afternoon dose helps sleep, and the stomach protection reduces ulcers.","source":"scot-pcg","quote":"Consider a trial of corticosteroids with gastroprotection (usually proton pump inhibitor),"},{"action":"Match the starting dose to the symptoms: 4 to 8 mg a day for mild symptoms, 16 mg a day or more for severe symptoms of raised pressure","why":"Lower doses work as well for many people and cause fewer side effects; severe symptoms need more.","source":"cns-2019","quote":"If patients exhibit severe symptoms consistent with increased intracranial pressure, it is recommended that higher doses such as 16 mg/d or more be considered.","grade":"Level 3"},{"action":"Stop dexamethasone promptly if it does not help, and reduce it gradually, as fast as symptoms allow, if it does","why":"Long courses of steroids cause diabetes, muscle weakness, mood change and infection.","source":"scot-pcg","quote":"Discontinue promptly if no benefit and reduce gradually in responders."},{"action":"Raise the head of the bed and treat pain and vomiting; ondansetron can help","why":"Sitting up helps the pressure fall, and controlling symptoms matters while other treatment is planned.","source":"scot-pcg","quote":"Raise the head of the patient’s bed"},{"action":"Refer to oncology, and consider neurosurgery, to decide on treatment of the cause","why":"Surgery, radiotherapy or drug treatment may treat the cause; the team also needs to know what this means for the future.","source":"scot-pcg","quote":"Referral to oncology is important to understand the implications for the patient’s prognosis, and whether disease-modifying therapy would be offered"}],"bestInClass":{"statement":"No graded guideline read for this page addresses raised intracranial pressure in cancer as an emergency in its own right. The Congress of Neurological Surgeons 2019 guideline is the graded source for steroids (Level 3, from a systematic review that found only two eligible studies): dexamethasone, 4 to 8 mg/day for mild symptoms and 16 mg/day or more for severe ones, tapered as fast as tolerated, and no recommendation either way when there are no symptoms. The Scottish Palliative Care Guidelines give the practical bedside sequence (CT, dexamethasone with gastroprotection, head up, anticoagulant review, referral). Their starting dose (8 to 16 mg, then 4 to 8 mg twice daily) is higher than the CNS lower range; the randomised evidence (Vecht 1994) supports 4 mg/day for people without signs of impending herniation. NICE NG122 adds that the dose should be reduced to the minimum needed. The EANO-ESMO 2021 guideline, the current European standard for brain metastases, could not be read.","sources":["cns-2019","scot-pcg","vecht-1994","nice-ng122","eano-esmo-2021"]},"variants":[{"name":"Lower starting dose of dexamethasone (4 to 8 mg a day)","differs":"Starts at 4 to 8 mg a day for mild symptoms rather than 8 to 16 mg as a first dose followed by 8 to 16 mg a day.","evidence":"CNS 2019, Level 3; Vecht 1994 double-blind randomised trials in 96 patients: 4 or 8 mg/day gave the same improvement in performance status at one week as 16 mg/day, and toxic effects were more frequent at 16 mg/day.","sources":["cns-2019","vecht-1994"]},{"name":"No steroids for people without symptoms","differs":"Withholds dexamethasone from people whose brain metastases cause no symptoms or mass effect.","evidence":"CNS 2019 found insufficient evidence to recommend for or against; NICE NG122 offers dexamethasone only to people with symptomatic brain metastases.","sources":["cns-2019","nice-ng122"]}],"grades":[{"claim":"Corticosteroids for temporary relief of symptoms from raised intracranial pressure and oedema","grade":"Level 3","source":"cns-2019","quote":"Corticosteroids are recommended to provide temporary symptomatic relief of symptoms related to increased intracranial pressure and edema secondary to brain metastases."},{"claim":"Dexamethasone as the steroid of choice","grade":"Level 3","source":"cns-2019","quote":"If corticosteroids are given, dexamethasone is the best drug choice given the available evidence."},{"claim":"Offer dexamethasone for symptomatic brain metastases and reduce to the minimum maintenance dose","grade":"not graded (NICE; dated 2011)","source":"nice-ng122","quote":"Offer dexamethasone to people with symptomatic brain metastases and reduce to the minimum necessary maintenance dose for symptomatic response."}],"sources":[{"key":"scot-pcg","label":"Scottish Palliative Care Guidelines: Raised intracranial pressure (ICP)","publisher":"NHS Scotland, Scottish Palliative Care Guidelines (Right Decisions platform)","year":2026,"url":"https://www.palliativecareguidelines.scot.nhs.uk/scottish-palliative-care-guidelines/palliative-emergencies/raised-intracranial-pressure-icp/","gradingScheme":"National consensus palliative care guidance; not graded. The page carries no publication or review date: the year given is the year it was read.","read":"full-text","accessed":"2026-11-11"},{"key":"cns-2019","label":"Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Steroids in the Treatment of Adults With Metastatic Brain Tumors","publisher":"Congress of Neurological Surgeons, Neurosurgery","year":2019,"url":"https://europepmc.org/abstract/MED/30629207","doi":"10.1093/neuros/nyy546","gradingScheme":"CNS levels of recommendation, printed as Level 1 to Level 3 before each recommendation; the abstract read does not define them, and every recommendation in it is Level 3.","read":"abstract","accessed":"2026-11-11"},{"key":"vecht-1994","label":"Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day","publisher":"Neurology","year":1994,"url":"https://europepmc.org/abstract/MED/8164824","doi":"10.1212/WNL.44.4.675","read":"abstract","accessed":"2026-11-11"},{"key":"nice-ng122","label":"Lung cancer: diagnosis and management (NG122), palliative interventions and supportive and palliative care","publisher":"NICE","year":2019,"url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care","gradingScheme":"NICE does not grade recommendations; strength is in the wording ('offer', 'consider'). Each recommendation is dated by the year it was written. Published March 2019, last updated March 2024.","read":"full-text","accessed":"2026-11-11"},{"key":"eano-esmo-2021","label":"EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours","publisher":"EANO and ESMO, Annals of Oncology","year":2021,"url":"https://doi.org/10.1016/j.annonc.2021.07.016","doi":"10.1016/j.annonc.2021.07.016","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The EANO-ESMO 2021 guideline on brain metastases could not be read: Europe PMC holds no abstract and the publisher refused a script. Its steroid and emergency advice is not compared here.","The CNS 2019 guideline was read only as its abstract; its full text and evidence tables were not read.","No source read gives a threshold for emergency neurosurgery or for osmotic therapy (mannitol or hypertonic saline) in raised pressure from a tumour; the Scottish guideline says only to consider referral to neurosurgery.","The steroid evidence is thin: the CNS systematic review found two eligible studies, and its recommendations are Level 3.","Whether to withhold dexamethasone before a biopsy when lymphoma of the brain is possible is not addressed by any source read here."]},{"id":"drug-desensitisation-after-anticancer-hypersensitivity","kind":"protocol","name":"Rapid drug desensitisation after an allergic reaction to a platinum, taxane or antibody","aka":["chemotherapy desensitization","rapid drug desensitisation","RDD","carboplatin desensitisation","paclitaxel desensitisation","12-step desensitization","3-bag protocol","rituximab desensitisation","carboplatin allergy"],"tldr":"If you have had a true allergic reaction to a cancer drug that is still your best treatment, allergy specialists can often give it again safely by desensitisation: starting with a tiny, very diluted dose and building up slowly over several hours, under close watch. The protection lasts only while the drug is in your body, so it is repeated at every treatment.","summary":"After a hypersensitivity reaction, the choices are desensitisation, skin testing to stratify risk, risk stratification and a drug challenge without testing, or avoiding the drug if an equally effective alternative exists (AAAAI/ACAAI practice parameter 2022). The first task is phenotyping: non-IgE reactions to chemotherapy or biologics can be managed with slower infusion, graded dose escalation or premedication without desensitisation (a conditional suggestion), while candidates for desensitisation include type I (mast-cell or IgE-mediated) reactions, including anaphylaxis. Empiric desensitisation is described as reasonable and safe even without skin testing; for platinums, skin testing can stratify risk and show when desensitisation is unnecessary; for antibodies it should be considered when the drug is the preferred therapy.\n\nOncology guidance is more cautious. ESMO (2017) says rechallenge after a CTCAE grade 3 or higher reaction or true anaphylaxis should not be attempted [V, B], and that desensitisation has been used for some drugs with varying success in experienced centres, with no standard protocol. The method gives an initial small, diluted dose over a prolonged infusion with gradual escalation; tolerance is temporary, so it is repeated at every course. The best-known protocol, a standardised 12-step, three-bag regimen, gave 413 desensitisations in 98 patients with 94% mild or no reactions and no deaths. One-bag protocols appear similarly safe, with less data after severe reactions. In 241 women with gynaecological cancers, survival after desensitisation for platinum or taxane reactions was comparable to that without reactions.","asOf":"2026-11-11","links":[],"tags":[],"related":["infusion-reaction-management","premedication-before-reaction-prone-anticancer-drugs"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","cisplatin","oxaliplatin","paclitaxel","docetaxel","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["extravasation-infusion-reaction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After an allergic reaction to a cancer drug, you may still be able to have it by starting with tiny amounts and building up slowly, under close watch, at every treatment.","domain":"chemotherapy-administration","setting":{"who":["doctor","nurse","pharmacist","multidisciplinary-team"],"where":["chemotherapy-day-unit","ward","intensive-care","outpatient-clinic"]},"population":"Adults with cancer who have had an immediate hypersensitivity reaction to a platinum (carboplatin, cisplatin, oxaliplatin), a taxane or a monoclonal antibody that remains their preferred treatment. Delayed reactions and severe skin reactions are outside this protocol; the sources read describe desensitisation for immediate reactions. Children are less studied.","trigger":"A person has had an infusion or hypersensitivity reaction to an anticancer drug and further doses are planned.","steps":[{"action":"Decide what kind of reaction it was: a true allergic (type I, mast-cell or IgE) reaction, or a non-allergic infusion reaction","why":"Non-allergic reactions can usually be managed by slowing the drip and premedication; desensitisation is for true allergy.","source":"jtf-2022","quote":"Suggestion that patients with non-IgE chemotherapy or biologic reactions be treated with slowed infusion rate, graded dose escalation, and/or pre-medications without desensitization","grade":"Suggestion"},{"action":"After a severe reaction or anaphylaxis, do not simply give the drug again in the usual way","why":"A second full-speed exposure after a severe allergic reaction can be fatal.","source":"esmo-2017","quote":"Rechallenge in IRs with CTCAE severity grade 3 or higher or in true anaphylaxis should not be attempted [V, B].","grade":"[V, B]"},{"action":"Choose with the person among desensitisation, skin testing, risk stratification with a drug challenge, or an equally effective alternative drug","why":"Each route has different risks, time costs and chances of keeping the best treatment.","source":"jtf-2022","quote":"The main approaches to care after a presumed hypersensitivity reaction (HSR) to a chemotherapeutic include (1) desensitization, (2) skin testing to assist with risk stratification, (3) risk stratification without skin testing and drug challenge or (4) avoidance of the offending agent if an equally efficacious alternative exists."},{"action":"Offer desensitisation for a true allergic reaction, including anaphylaxis, when the drug remains the best treatment; it can be done without skin testing","why":"Desensitisation lets people keep their most effective treatment instead of switching to a weaker one.","source":"jtf-2022","quote":"If the clinical assessment is consistent with a HSR, then empiric desensitization is a reasonable and safe approach to care and can be performed even when skin testing is not possible (i.e., outpatient clinic without access to chemotherapy drugs for skin testing)."},{"action":"For platinum reactions, consider skin testing to stratify risk; it can show that desensitisation is not needed","why":"Some people with a reaction history are not truly allergic and can be treated more simply.","source":"jtf-2022","quote":"Skin testing may be useful in the management of patients with platin HSRs and also identifies cases where desensitization may be unnecessary despite a clinical history suggestive of an HSR."},{"action":"Give the drug by a stepwise protocol: a small, diluted first dose over a long infusion, increasing gradually to the full dose","why":"Building up slowly lets the immune cells that cause the reaction be quietened step by step.","source":"esmo-2017","quote":"In desensitisation protocols, an initial small diluted dose of the agent with a prolonged infusion time and gradual escalation of the dose is administered."},{"action":"Do it in a centre experienced in desensitisation, with staff and treatment for anaphylaxis at hand","why":"Breakthrough reactions happen, most often on the first desensitisation and the last step, and need treating at once.","source":"esmo-2017","quote":"For patients who have recurrent IRs despite premedication, desensitisation protocols have been used with certain drugs with varying success in experienced centres."},{"action":"Repeat the desensitisation for every course of the drug","why":"The tolerance wears off once the drug has cleared from the body; the person is still allergic.","source":"esmo-2017","quote":"Patients remain allergic to the drug and must be desensitised for every course of treatment."},{"action":"For an immediate reaction to a monoclonal antibody, consider desensitisation when that antibody is the preferred therapy","why":"Antibodies often have no equal alternative.","source":"jtf-2022","quote":"In contrast, for patients with immediate reactions including anaphylactic reactions to mAbs, drug desensitization should be considered when the implicated drug is the preferred therapy."}],"bestInClass":{"statement":"Phenotype the reaction first; manage non-IgE reactions with slower infusion, graded escalation or premedication (AAAAI/ACAAI 2022, conditional suggestion); for true type I reactions, including anaphylaxis, offer desensitisation in an experienced centre when the drug is still the best treatment, with skin testing as an option for platinums, and repeat it at every course. The guidelines differ in emphasis: the allergy practice parameter calls empiric desensitisation reasonable and safe, while ESMO 2017, written for oncologists, says rechallenge after grade 3 or higher reactions or anaphylaxis should not be attempted [V, B] and that desensitisation has varying success, with no standard protocol. These are compatible if 'rechallenge' means re-exposure at the usual rate rather than desensitisation.","sources":["jtf-2022","esmo-2017","castells-2008","eaaci-2022"]},"variants":[{"name":"Standardised 12-step, three-bag protocol (Brigham and Women's)","differs":"Three bags of increasing concentration infused in 12 steps; the first desensitisations were done in intensive care and later ones as outpatients, intravenously or intraperitoneally.","evidence":"413 desensitisations in 98 patients reacting to carboplatin, cisplatin, oxaliplatin, paclitaxel, doxorubicin (including liposomal) or rituximab: 94% mild or no reactions, no life-threatening reactions or deaths, and every patient received the full dose (Castells 2008).","sources":["castells-2008"]},{"name":"One-bag protocols","differs":"Uses a single bag with a stepped infusion rate, which is simpler and quicker to prepare.","evidence":"The 2022 practice parameter says increasing evidence suggests similar safety and efficacy to three-bag protocols, with more data needed after severe initial reactions.","sources":["jtf-2022"]},{"name":"Same-day desensitisation after the reaction","differs":"Desensitises on the day of the initial reaction rather than at a later, planned session.","evidence":"A Spanish retrospective cohort (570 desensitisations in 120 patients with platinum or taxane reactions) found breakthrough reactions in 15% with same-day and 24% with planned rapid desensitisation; a Bayesian model estimated a 14.6-point lower probability with same-day. Observational and single-centre.","sources":["torres-gorriz-2026"]}],"grades":[{"claim":"For immediate taxane reactions, the severity of the initial reaction may assist risk stratification and management","grade":"Suggestion","source":"jtf-2022","quote":"Suggestion that for patients with immediate reactions to taxanes, the severity of the initial reaction may assist in risk stratification and management"},{"claim":"Non-IgE reactions to monoclonal antibodies may be managed with slowed infusion, graded escalation or premedication without desensitisation","grade":"Suggestion","source":"jtf-2022","quote":"Suggestion that patients with non-IgE reactions to monoclonal antibodies (mAb) may be treated with a slowed infusion, graded dose escalation, and/or premedication without desensitization"}],"sources":[{"key":"jtf-2022","label":"Drug allergy: A 2022 practice parameter update","publisher":"AAAAI/ACAAI Joint Task Force on Practice Parameters (Journal of Allergy and Clinical Immunology, Khan et al.)","year":2022,"url":"https://doi.org/10.1016/j.jaci.2022.08.028","doi":"10.1016/j.jaci.2022.08.028","gradingScheme":"Consensus-based statements, worded with GRADE terms: 'recommendation' (strong) or 'suggestion' (conditional).","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2017","label":"Management of infusion reactions to systemic anticancer therapy: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology, Roselló et al.)","year":2017,"url":"https://doi.org/10.1093/annonc/mdx216","doi":"10.1093/annonc/mdx216","gradingScheme":"[level, grade]: levels I (large randomised trial or meta-analysis) to V (studies without control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"},{"key":"eaaci-2022","label":"Hypersensitivity reactions to chemotherapy: an EAACI Position Paper","publisher":"European Academy of Allergy and Clinical Immunology (Allergy, Pagani et al.)","year":2022,"url":"https://doi.org/10.1111/all.15113","doi":"10.1111/all.15113","read":"abstract","accessed":"2026-11-11"},{"key":"castells-2008","label":"Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases","publisher":"Journal of Allergy and Clinical Immunology (Castells et al.)","year":2008,"url":"https://doi.org/10.1016/j.jaci.2008.02.044","doi":"10.1016/j.jaci.2008.02.044","read":"abstract","accessed":"2026-11-11"},{"key":"zwimpfer-2024","label":"Desensitization in patients with hypersensitivity to platinum and taxane in gynecological cancers","publisher":"Cancer Medicine (Zwimpfer et al.)","year":2024,"url":"https://doi.org/10.1002/cam4.6840","doi":"10.1002/cam4.6840","read":"abstract","accessed":"2026-11-11"},{"key":"torres-gorriz-2026","label":"Comparison of rapid and same-day desensitization protocols in hypersensitivity reactions to platinum and taxanes: a retrospective cohort study","publisher":"Frontiers in Allergy (Torres Gorriz et al.)","year":2026,"url":"https://doi.org/10.3389/falgy.2026.1751512","doi":"10.3389/falgy.2026.1751512","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The EAACI position paper (2022), the European allergy statement on chemotherapy reactions, was read only as an abstract; its recommendations and grades are not quoted.","No randomised trial compares desensitisation with switching to an alternative drug; outcome evidence is observational, such as the 241-patient cohort in which survival after desensitisation matched that without reactions (Zwimpfer 2024).","Who should be skin tested, the exact step schedules, and whether desensitisation can move from allergy units to ordinary day units are not settled by the sources read.","ESMO's infusion reaction guideline dates from 2017; no newer ESMO edition was found."]},{"id":"red-cell-and-platelet-transfusion-thresholds","kind":"protocol","name":"Red cell and platelet transfusion thresholds in cancer care","aka":["restrictive transfusion threshold","when to transfuse in cancer","platelet transfusion threshold during chemotherapy","blood transfusion for anaemia in cancer","prophylactic platelet transfusion"],"tldr":"During cancer treatment your red cells or platelets may fall. Blood or platelet transfusions are given when the levels fall below set points, or when you are bleeding, rather than to bring the numbers back to normal. Giving less blood at higher thresholds has proved just as safe in trials, and spares people the risks of transfusion.","summary":"For red cells, NICE NG24 recommends a restrictive threshold for people without major haemorrhage, acute coronary syndrome or regular transfusion for chronic anaemia: consider transfusing at haemoglobin 70 g/L, aiming for 70 to 90 g/L afterwards, with a threshold of 80 g/L and target 80 to 100 g/L in acute coronary syndrome. AABB (2023) suggests the same 7 g/dL threshold for hospitalised adults with haematological and oncological disorders (conditional, low certainty), within its strong recommendation for stable hospitalised adults generally; clinicians may use 8 g/dL with pre-existing cardiovascular disease. Give single units to adults who are not bleeding, and reassess after each.\n\nFor platelets, prophylactic transfusion is given below 10 × 10⁹/L in people not bleeding and not having procedures (NICE; AABB/ICTMG 2025 strong recommendation for chemotherapy and allogeneic transplant), with no routine prophylaxis in chronic bone marrow failure, immune thrombocytopenia, heparin-induced thrombocytopenia or TTP. Adults having autologous transplant may be transfused at the first sign of bleeding rather than prophylactically (ASCO 2018; AABB/ICTMG 2025 conditional). For bleeding, NICE offers platelets for WHO grade 2 bleeding below 30 × 10⁹/L and allows up to 100 × 10⁹/L for severe or critical-site bleeding. Before procedures, NICE considers raising the count above 50 × 10⁹/L (100 × 10⁹/L for the central nervous system or back of the eye), while AABB/ICTMG (2025) set lower thresholds for some, such as 10 × 10⁹/L for central venous catheters in compressible sites and 20 × 10⁹/L for lumbar puncture. Give a single dose and recheck.","asOf":"2026-11-11","links":[],"tags":["protocol","transfusion","supportive-care"],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["transfusion-support"],"targets":[],"drugs":[],"companies":[],"institutions":["nice","asco"],"pathways":[],"terms":["thrombocytopenia","anaemia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer treatment can lower blood cells. You may need a transfusion if levels fall low or you bleed. Doctors use set levels to decide.","domain":"transfusion","setting":{"who":["doctor","nurse"],"where":["ward","chemotherapy-day-unit","outpatient-clinic"]},"population":"Adults with cancer, including those having chemotherapy or a stem cell transplant, who are anaemic or thrombocytopenic. NICE NG24 excludes children under 1 year, pregnant women, people with haemoglobinopathies and major haemorrhage protocols; anaemia management before transfusion (iron, erythropoiesis-stimulating agents) is a separate question.","trigger":"A low haemoglobin or platelet count during cancer care, bleeding, or a planned invasive procedure.","steps":[{"action":"Use a restrictive red cell threshold unless the person has major bleeding, acute coronary syndrome or regular transfusions for chronic anaemia","why":"Trials found that transfusing at a lower haemoglobin is as safe as transfusing at a higher one, and avoids unneeded blood.","source":"nice-ng24-rbc","quote":"Use restrictive red blood cell transfusion thresholds for people who need red blood cell transfusions and who do not: have major haemorrhage or have acute coronary syndrome or need regular blood transfusions for chronic anaemia."},{"action":"Consider transfusing at a haemoglobin of 70 g/L and aim for 70 to 90 g/L afterwards","why":"This is the threshold used in most trials and in both NICE and AABB.","source":"nice-ng24-rbc","quote":"When using a restrictive red blood cell transfusion threshold, consider a threshold of 70 g/litre and a haemoglobin concentration target of 70 to 90 g/litre after transfusion."},{"action":"Apply the same 7 g/dL threshold to hospitalised adults with blood cancers or other cancers","why":"AABB looked at people with haematological and oncological disorders separately and suggests the same threshold, on weaker evidence.","source":"aabb-rbc-2023","quote":"Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence).","grade":"conditional recommendation, low certainty evidence"},{"action":"Give one unit at a time to adults who are not bleeding, then reassess and recheck the haemoglobin","why":"One unit is often enough, and each extra unit adds risk.","source":"nice-ng24-rbc","quote":"Consider single‑unit red blood cell transfusions for adults (or equivalent volumes calculated based on body weight for children or adults with low body weight) who do not have active bleeding."},{"action":"Give prophylactic platelets when the count is below 10 × 10⁹/L in someone not bleeding and not having a procedure","why":"This is the threshold both NICE and AABB/ICTMG use for people who are not bleeding; transfusing at higher counts adds risk without shown benefit.","source":"nice-ng24-platelets"},{"action":"Do not give routine prophylactic platelets in chronic bone marrow failure, immune thrombocytopenia, heparin-induced thrombocytopenia or thrombotic thrombocytopenic purpura","why":"In these conditions the low count has other causes and its own treatment; NICE advises against routine prophylaxis.","source":"nice-ng24-platelets","quote":"Do not routinely offer prophylactic platelet transfusions to people with any of the following: chronic bone marrow failure autoimmune thrombocytopenia heparin‑induced thrombocytopenia thrombotic thrombocytopenic purpura."},{"action":"For adults having an autologous stem cell transplant at an experienced centre, consider transfusing platelets at the first sign of bleeding rather than prophylactically","why":"Randomised trials in this group showed that a bleeding-triggered approach is reasonable.","source":"asco-2018","quote":"Based on data from randomized controlled trials, adult patients who undergo autologous stem-cell transplantation at experienced centers may receive a platelet transfusion at the first sign of bleeding, rather than prophylactically."},{"action":"For clinically significant bleeding (WHO grade 2), offer platelets if the count is below 30 × 10⁹/L; for severe or critical-site bleeding, use a threshold up to 100 × 10⁹/L","why":"Bleeding in the brain or eye is dangerous at counts that would otherwise be safe.","source":"nice-ng24-platelets"},{"action":"Do not give platelets before low-risk procedures such as central line insertion or bone marrow biopsy","why":"These procedures rarely bleed, and the platelets carry their own risks.","source":"nice-ng24-platelets","quote":"Do not offer prophylactic platelet transfusions to people having procedures with a low risk of bleeding, such as adults having central venous cannulation or any people having bone marrow aspiration and trephine biopsy."},{"action":"Give a single dose of platelets, then reassess and recheck the count before giving more","why":"One dose is usually enough; more doses add risk without benefit except in severe bleeding at a critical site.","source":"nice-ng24-platelets","quote":"Do not routinely transfuse more than a single dose of platelets."}],"bestInClass":{"statement":"NICE NG24 and AABB agree on restrictive thresholds. For red cells both use 70 g/L (7 g/dL); AABB's 2023 recommendation for people with haematological and oncological disorders is conditional on low-certainty evidence, while its recommendation for stable hospitalised adults overall is strong. For prophylactic platelets both use 10 × 10⁹/L in people having chemotherapy or allogeneic transplant (AABB/ICTMG 2025, strong, high or moderate certainty). They differ on procedures: NICE considers a count above 50 × 10⁹/L before invasive procedures generally and advises against platelets for central venous cannulation, whereas AABB/ICTMG (2025) set procedure-specific thresholds (10 × 10⁹/L for central lines in compressible sites, 20 × 10⁹/L for lumbar puncture and low-risk interventional radiology, 50 × 10⁹/L for high-risk interventional radiology and major non-neuraxial surgery). On autologous transplant, ASCO (2018) and AABB/ICTMG (2025, conditional) support a bleeding-triggered rather than prophylactic approach in adults.","sources":["nice-ng24-rbc","nice-ng24-platelets","aabb-rbc-2023","aabb-ictmg-platelets-2025","asco-2018"]},"variants":[{"name":"Procedure-specific platelet thresholds (AABB and ICTMG 2025)","differs":"Sets thresholds by procedure: below 10 × 10⁹/L for central venous catheters in compressible sites, below 20 × 10⁹/L for lumbar puncture and low-risk interventional radiology, below 50 × 10⁹/L for high-risk interventional radiology and major non-neuraxial surgery.","evidence":"GRADE; strong with high or moderate certainty for lumbar puncture, conditional with low or very low certainty for the others; read as an abstract.","sources":["aabb-ictmg-platelets-2025"]},{"name":"Higher red cell threshold with cardiovascular disease (AABB 2023)","differs":"Allows 8 g/dL for people with pre-existing cardiovascular disease or having orthopaedic surgery, and 7.5 g/dL in cardiac surgery, in line with the trials' restrictive arms; NICE uses 80 g/L only for acute coronary syndrome.","evidence":"AABB recommendation 1, strong, moderate certainty; read as an abstract.","sources":["aabb-rbc-2023","nice-ng24-rbc"]}],"grades":[{"claim":"Restrictive red cell threshold (7 g/dL) for stable hospitalised adults","grade":"strong recommendation, moderate certainty evidence (GRADE)","source":"aabb-rbc-2023"},{"claim":"Restrictive red cell threshold (7 g/dL) for adults with haematological and oncological disorders","grade":"conditional recommendation, low certainty evidence (GRADE)","source":"aabb-rbc-2023"},{"claim":"Platelets below 10 × 10⁹/L for non-bleeding people on chemotherapy or having allogeneic transplant","grade":"strong recommendation, high or moderate certainty (GRADE)","source":"aabb-ictmg-platelets-2025"},{"claim":"No prophylactic platelets for non-bleeding adults having autologous transplant or with aplastic anaemia","grade":"conditional recommendation, low or very low certainty (GRADE)","source":"aabb-ictmg-platelets-2025","quote":"For hypoproliferative thrombocytopenia in nonbleeding adults undergoing autologous stem cell transplant or with aplastic anemia, prophylactic platelet transfusion is not recommended."}],"sources":[{"key":"nice-ng24-rbc","label":"Blood transfusion (NG24): red blood cell transfusion","publisher":"NICE","year":2015,"url":"https://www.nice.org.uk/guidance/ng24/chapter/Red-blood-cell-transfusion","gradingScheme":"NICE does not grade recommendations; each is dated, here [2015]. Published November 2015, last updated February 2026.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng24-platelets","label":"Blood transfusion (NG24): platelet transfusion","publisher":"NICE","year":2015,"url":"https://www.nice.org.uk/guidance/ng24/chapter/Platelet-transfusion","gradingScheme":"NICE does not grade recommendations; each is dated, here [2015].","read":"full-text","accessed":"2026-11-11"},{"key":"aabb-rbc-2023","label":"Red Blood Cell Transfusion: 2023 AABB International Guidelines","publisher":"AABB, JAMA","year":2023,"url":"https://europepmc.org/abstract/MED/37824153","doi":"10.1001/jama.2023.12914","gradingScheme":"GRADE: strong or conditional recommendation, with certainty of evidence high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"aabb-ictmg-platelets-2025","label":"Platelet Transfusion: 2025 AABB and ICTMG International Clinical Practice Guidelines","publisher":"AABB and the International Collaboration for Transfusion Medicine Guidelines, JAMA","year":2025,"url":"https://europepmc.org/abstract/MED/40440268","doi":"10.1001/jama.2025.7529","gradingScheme":"GRADE: strong or conditional recommendation, with certainty of evidence.","read":"abstract","accessed":"2026-11-11"},{"key":"asco-2018","label":"Platelet Transfusion for Patients With Cancer: ASCO Clinical Practice Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/abstract/MED/29182495","doi":"10.1200/JCO.2017.76.1734","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The AABB, AABB/ICTMG and ASCO guidelines were read only as abstracts; their thresholds for solid tumours, for chronic stable severe thrombocytopenia and for platelet refractoriness are not given here.","NICE's thresholds date from 2015; its February 2026 update did not change the red cell or platelet recommendations read here.","The platelet threshold steps carry no quotation because the raw text prints the powers of ten incorrectly; the numbers are taken from NICE recommendations 1.7.1 to 1.7.3 and checked against the text.","No source read covers transfusion thresholds for children with cancer, or the use of irradiated or CMV-negative products after transplant or purine analogues."]},{"id":"car-t-referral-and-eligibility","kind":"protocol","name":"Referral and eligibility assessment for CAR T-cell therapy","aka":["CAR-T referral","CAR T eligibility","CAR-T candidacy","who can have CAR T","CAR-T indications"],"tldr":"CAR T-cell therapy is given at specialist centres, and a team there decides. For large B-cell lymphoma that does not respond to first treatment or returns within a year, CAR T cells are now the standard next step, so early referral matters. The centre checks your fitness, heart, brain and blood, and you will need to stay near the hospital, with someone to help, for at least two weeks after.","summary":"EBMT 2025 indications (Table 1, adults; category/evidence level as printed): in large B-cell lymphoma, CAR T cells are standard of care (S/I) for primary refractory disease, early relapse with untested or chemoresistant disease and early chemosensitive relapse, where axicabtagene ciloleucel or lisocabtagene maraleucel beat salvage chemotherapy and autologous transplant in two phase III trials; for late relapse autologous transplant remains standard (S/II) and CAR T a clinical option (CO/II); after a failed autograft CAR T is standard (S/II). Follicular lymphoma: CAR T within the EMA labels, standard for refractory relapse (S/II). Mantle cell lymphoma: not first line outside trials; a clinical option second line after primary BTK inhibitor failure. Myeloma: idecabtagene vicleucel and ciltacabtagene autoleucel within their labels. Primary CNS lymphoma relapse: clinical option. Hodgkin lymphoma: not convincingly better than other options to date.\n\nEBMT/JACIE 2019: the decision is made by a multidisciplinary team in a designated centre; cumulative chemotherapy harms T-cell quality, so plan collection early. SITC 2020: prior allogeneic transplant, BiTE or antibody therapy is no bar if the target antigen is expressed (LE: 4); weigh ECOG performance status; recent or active intracranial haemorrhage excludes (LE: 4); refer for neurological review if there is inflammatory neurological disease or CNS involvement; baseline CRP, ferritin, LDH, blood count, chemistry and echocardiogram or MUGA (LE: 4). FDA 2025: the REMS ended; labels now ask patients to stay near a healthcare facility for at least two weeks and not to drive for two weeks.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t"],"related":["car-t-apheresis","car-t-bridging","car-t-lymphodepletion","car-t-infection-prevention"],"cancers":["dlbcl","primary-mediastinal-b-cell-lymphoma","follicular-lymphoma","mantle-cell-lymphoma","all-leukemia","multiple-myeloma"],"sections":[],"technologies":["car-t","autologous-stem-cell-transplant"],"targets":[],"drugs":["axicabtagene-ciloleucel","lisocabtagene-maraleucel","tisagenlecleucel","brexucabtagene-autoleucel","idecabtagene-vicleucel","ciltacabtagene-autoleucel","obecabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-car-t-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A specialist team decides whether CAR T-cell therapy is right for you. If it is, you will need to stay close to the hospital, with a helper, for at least two weeks afterwards.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","multidisciplinary-team","nurse","patient-or-carer"],"where":["outpatient-clinic"]},"population":"Adults with relapsed or refractory B-cell lymphoma, B-cell ALL or multiple myeloma, and children and young adults with B-cell ALL, being considered for a licensed CAR T-cell product. Indications and reimbursement differ by country; the EBMT categories are European. CAR T cells for autoimmune disease and solid tumours are outside this protocol.","trigger":"Relapse or refractoriness in a disease for which a CAR T-cell product is licensed, or a referring team asking whether a patient is a candidate.","steps":[{"action":"Refer to a designated CAR T-cell centre, where the decision is made by its multidisciplinary team","why":"The treatment and its side effects need a specialist team and hospital set up for them.","source":"ebmt-2019","quote":"The decision to treat a patient with CAR T cells therapy should be made collectively at a multidisciplinary team meeting in a designated center for CAR T-cell therapy."},{"action":"For large B-cell lymphoma that is primary refractory or relapses early, refer for second-line CAR T-cell therapy","why":"In two phase III trials CAR T cells kept the lymphoma controlled for longer than chemotherapy and transplant in this group.","source":"ebmt-2025","quote":"For patients with primary refractory disease or early relapse with untested or chemorefractory disease, treatment with axi-cel or liso-cel represents the current standard of care.","grade":"S/I"},{"action":"For late relapse of large B-cell lymphoma, consider autologous transplant first, with CAR T cells after a failed transplant","why":"Autologous transplant still works well for late relapse and has not been beaten in a trial.","source":"ebmt-2025","quote":"Patients with late relapses face reasonable outcomes with auto-HCT and this standard has not been challenged by a clinical trial as of today.","grade":"S/II"},{"action":"In mantle cell lymphoma, do not use CAR T cells first line outside trials; consider them second line after BTK inhibitor failure","why":"The licence and the evidence are for disease that has failed earlier treatment.","source":"ebmt-2025","quote":"With Bruton’s TKIs moving to 1st-line treatment, CAR-T has become a clinical option as 2nd-line therapy in patients with primary Bruton’s TKIs failure."},{"action":"Refer early, before further lines of chemotherapy where possible","why":"Each course of chemotherapy weakens the T cells from which the product is made.","source":"ebmt-2019","quote":"There is evidence that cumulative chemotherapy exposure adversely affects the quality of circulating T cells."},{"action":"Do not exclude a patient for earlier allogeneic transplant, bispecific T-cell engager or antibody therapy if the cancer still expresses the target","why":"These do not stop CAR T cells working if the target is still present.","source":"sitc-iec-2020","quote":"Patients who have previously undergone allo-HSCT, bispecific T cell engager (BiTE) therapy, anti-CD19 monoclonal antibody (mAb) therapy, and mAbs against other targets (eg, rituximab) may be treated with CAR T cells, provided the patient’s disease still expresses the target antigen","grade":"LE: 4"},{"action":"Assess performance status, and do not proceed with recent or active bleeding in the brain","why":"Side effects can be severe; a recent brain bleed makes neurotoxicity especially dangerous.","source":"sitc-iec-2020","quote":"Patients with evidence of recent or active intracranial hemorrhage should not undergo CAR T cell therapy","grade":"LE: 4"},{"action":"Refer for neurological review if there is inflammatory neurological disease or lymphoma in the brain or spinal cord","why":"Existing brain disease changes the risk and the monitoring plan for neurotoxicity.","source":"sitc-iec-2020","quote":"Patients with history of inflammatory neurological conditions or current CNS disease involvement should be referred for additional neurological consultation prior to initiating CAR T cell therapy."},{"action":"Take baseline CRP, ferritin, LDH, blood count, kidney, liver and mineral chemistry, and an echocardiogram or MUGA scan","why":"Baselines make it possible to recognise toxicity early, and heart function must be adequate.","source":"sitc-iec-2020","quote":"Prior to CAR T cell therapy, treating physicians should order CRP, ferritin, lactate dehydrogenase (LDH), complete blood counts, comprehensive metabolic panel (including Mg/Pho), and transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) scan.","grade":"LE: 4"},{"action":"Plan for the patient to stay near a healthcare facility for at least two weeks after infusion, and not to drive for two weeks","why":"Cytokine release syndrome and neurotoxicity usually start in the first two weeks and can come on fast.","source":"fda-rems-2025","quote":"Specifically, labeling update included revision to language to monitor patients for at least two weeks including daily monitoring for at least one week; to instruct patients to remain within proximity of a healthcare facility for at least two weeks; and to advise patients to avoid driving for two weeks following product administration"}],"bestInClass":{"statement":"For who should be referred, the EBMT 2025 indications are the most recent guideline read in full: CAR T cells are standard of care (S/I) for large B-cell lymphoma that is primary refractory or relapses early, on the strength of two randomised phase III trials, and the standard after a failed autograft (S/II); autologous transplant stays standard for late relapse (S/II). For the eligibility work-up, SITC 2020 (LE: 4) and EBMT/JACIE 2019 (ungraded) agree on a specialist multidisciplinary decision, performance status, baseline inflammatory markers and cardiac function, and neurological assessment. EBMT 2025 and its retrospective evidence leave one open point: for early chemosensitive relapse that reaches complete remission on salvage, EBMT rates CAR T S/I but also calls autologous transplant a valid clinical option (CO/II). In the US the FDA ended the REMS in June 2025 and relaxed proximity and driving restrictions to two weeks; European labels were not read.","sources":["ebmt-2025","sitc-iec-2020","ebmt-2019","fda-rems-2025","ebmt-eha-2022"]},"variants":[{"name":"Autologous transplant for early chemosensitive relapse in complete remission (EBMT 2025)","differs":"For large B-cell lymphoma relapsing early but reaching complete remission on salvage, consolidates with high-dose therapy and autologous transplant rather than CAR T cells.","evidence":"Rated CO/II; a retrospective analysis found better progression-free survival with autologous transplant than CAR T in this group, but included no second-line CAR T and mostly tisagenlecleucel.","sources":["ebmt-2025"]},{"name":"US monitoring after the REMS (FDA 2025)","differs":"Removes the requirement for specially certified hospitals with immediate on-site tocilizumab; labels require monitoring for at least two weeks with daily monitoring for at least one, proximity for two weeks and no driving for two weeks.","evidence":"Regulatory decision based on established management guidelines and stable adverse event reporting.","sources":["fda-rems-2025"]}],"grades":[{"claim":"CAR T for primary refractory or early relapsed large B-cell lymphoma","grade":"S/I (standard of care; EBMT evidence level I)","source":"ebmt-2025"},{"claim":"Autologous transplant for late relapse of large B-cell lymphoma","grade":"S/II; CAR T CO/II","source":"ebmt-2025"},{"claim":"Prior allogeneic transplant, BiTE or antibody therapy is no bar if the antigen is expressed","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"No CAR T with recent or active intracranial haemorrhage","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Baseline CRP, ferritin, LDH, blood count, chemistry and echocardiogram or MUGA","grade":"LE: 4","source":"sitc-iec-2020"}],"sources":[{"key":"ebmt-2025","label":"Indications for haematopoietic cell transplantation and CAR-T for haematological diseases, solid tumours and immune disorders: 2025 EBMT practice recommendations","publisher":"European Society for Blood and Marrow Transplantation, Bone Marrow Transplantation","year":2025,"url":"https://europepmc.org/article/PMC/PMC12583170","doi":"10.1038/s41409-025-02701-3","gradingScheme":"Each indication is categorised S (standard of care), CO (clinical option after careful assessment of risks and benefits), D (developmental) or GNR (generally not recommended), with an evidence level I, II or III; the evidence levels are defined in a supplementary table that was not read.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"fda-rems-2025","label":"FDA Eliminates Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies (FDA Safety Communication, 26 June 2025)","publisher":"US Food and Drug Administration","year":2025,"url":"https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-eliminates-risk-evaluation-and-mitigation-strategies-rems-autologous-chimeric-antigen-receptor","gradingScheme":"A regulatory safety communication; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-eha-2022","label":"Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)","publisher":"EBMT, JACIE and EHA, Annals of Oncology","year":2022,"url":"https://europepmc.org/abstract/MED/34923107","doi":"10.1016/j.annonc.2021.12.003","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The EBMT 2025 supplementary table that defines evidence levels I to III was not read; levels are given as printed in Table 1.","The EBMT/JACIE 2019 eligibility criteria (Table 1) and minimum screening tests (Table 2) are images and were not read; the EBMT/JACIE/EHA 2022 update was read only as an abstract.","NICE technology appraisals and other national reimbursement decisions, which decide who can actually be referred in each country, were not read.","No organ-function thresholds (creatinine clearance, ejection fraction, oxygen saturation) are given here: SITC leaves them to institutional standards and the trial criteria were not read.","The proximity and driving advice is from US labelling; European SmPCs were not read."]},{"id":"radionuclide-therapy-patient-release-criteria","kind":"protocol","name":"Release of patients after radionuclide therapy or a permanent implant: criteria, instructions and records","aka":["patient release criteria","discharge after radionuclide therapy","release after radioiodine","release after Lutathera","release after Pluvicto","10 CFR 35.75","dose constraints for carers and comforters","retained activity limit","radioactive patient discharge","release of patients with permanent implants"],"tldr":"After some treatments with radioactive medicines or seeds, you give off a little radiation for a while. Before you go home, the team checks that the people around you will receive only a small, safe dose, taking your home and family into account, and gives you written instructions. If that is not yet possible you stay in a single room until it is.","summary":"Release is governed by dose to other people. Members of the public are subject to the public dose limit (1 mSv a year); family and friends who knowingly help are carers and comforters, whose exposure is controlled by a dose constraint, commonly 5 mSv per episode for an adult and 1 mSv for children and for the embryo or fetus of a pregnant carer, with more lenient values possible for elderly people (IAEA SSG-46 para 2.49). Before release, the medical physicist or radiation protection officer establishes that retained activity is low enough to stay within those limits and constraints, for example by integrating the measured dose rate over the activity, energy and effective half-life, taking into account the patient's living conditions, children and pregnant women at home, excreta and incontinence; the assumptions must match the written instructions given (SSG-46 4.247, 5.258). Carers must have received and understood information on radiation risks before they provide care (GSR Part 3 para 3.153, quoted in SSG-46). Written instructions go to the patient or guardian (SSG-46 4.248; UK IR(ME)R 2017 reg 12(6) and (7), before leaving).\n\nThe US rule allows release when no other individual is likely to receive more than 5 mSv, requires written instructions when anyone could receive more than 1 mSv, and requires breastfeeding guidance when a nursing infant could exceed 1 mSv (10 CFR 35.75); the basis for release must be recorded when it uses retained activity, an occupancy factor below 0.25 at 1 m, an effective half-life or tissue shielding, and kept for 3 years (35.2075). A patient who cannot be released is kept in a private room with a private toilet, the door posted, visitor time noted and items leaving the room surveyed or treated as radioactive waste (35.315), by staff given annual radiation safety instruction (35.310). Many countries also use a retained-activity limit for iodine-131 (most EU member states 400 to 600 MBq; Germany 250 MBq; Japan 500 MBq or under 30 microsieverts an hour at 1 m) (IAEA SRS-63). The IAEA and ICRP advise that the decision is individual and that dose limits and constraints, not secondary limits such as retained activity, should drive it; SSG-46 notes that systematic dose monitoring of family members is not necessary. Permanent implants follow the same framework (SSG-46 5.257 to 5.261), with a wallet card and advice about seed expulsion, later surgery and death.","asOf":"2026-11-11","links":[],"tags":[],"related":["radioiodine-therapy-home-radiation-safety","lutetium-177-therapy-home-radiation-safety","permanent-prostate-seed-brachytherapy-home-radiation-safety"],"cancers":[],"sections":[],"technologies":["radioiodine-therapy","lu177-radioligand-therapy","radioligand-therapy","mibg-theranostics","ldr-seed-brachytherapy"],"targets":[],"drugs":["radioactive-iodine","pluvicto","lutathera","radium-223"],"companies":[],"institutions":["iaea"],"pathways":[],"terms":["radioiodine-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Before you leave after a radioactive treatment, the team checks it is safe for the people you live with and gives you written instructions. Tell them about babies, children or anyone pregnant at home.","domain":"radiotherapy","setting":{"who":["doctor","nurse","multidisciplinary-team"],"where":["ward","outpatient-clinic"]},"population":"Patients of any age treated with unsealed radiopharmaceuticals (iodine-131 for thyroid disease, lutetium-177 PSMA or dotatate, iodine-131 MIBG, radium-223 and others) or given permanent radioactive implants (iodine-125 or palladium-103 seeds), and the members of the public, family members and carers around them. Medical physicists or radiation protection officers usually make the calculation; the treating physician (in the UK the IR(ME)R practitioner, in the US the authorised user) is responsible for the release. What the patient does at home is covered by the protocol for each treatment.","trigger":"A therapeutic radiopharmaceutical has been given, or a permanent radioactive implant placed, and the patient is ready to leave the department or the ward.","steps":[{"action":"Use the national dose limits and dose constraints: the public dose limit for members of the public, and a constraint per episode for carers and comforters (commonly 5 mSv for an adult, 1 mSv for a child or for the fetus of a pregnant carer)","why":"These limits keep the dose to the people around the patient small, while letting family help and comfort them.","source":"iaea-ssg46","quote":"For an adult carer or comforter, a value of dose constraint commonly used is 5 mSv effective dose per episode."},{"action":"Base the decision on the dose others could receive, decided for this patient, rather than on retained activity alone","why":"Fixed retained-activity limits rest on worst-case models and can keep people in hospital who could safely go home.","source":"iaea-srs63","quote":"The control arrangements should focus on the dose limits or dose constraints that are generally applied, rather than on secondary limits, such as retained activity."},{"action":"Before release, have the medical physicist or radiation protection officer establish that the retained activity keeps doses to others within limits and constraints","why":"A qualified person checks the numbers for each patient before they leave.","source":"iaea-ssg46","quote":"The medical physicist or RPO at the nuclear medicine facility should establish prior to the release of a patient that the retained radioactivity in the patient is such that the doses that could be received by members of the public would not exceed public dose limits, and would be unlikely to exceed the relevant dose constraints for both members of the public and carers and comforters."},{"action":"Estimate the dose from the measured dose rate integrated over time, using the activity, energy and effective half-life of the radionuclide","why":"A measurement on the patient, decayed forward, gives a realistic estimate rather than a worst case.","source":"iaea-ssg46","quote":"An acceptable method of estimating the acceptable retained activity for patients being discharged from hospitals is to calculate the time integral of the ambient dose equivalent rate, considering the activity, energy and effective half-life of the radionuclides."},{"action":"Take account of the patient's home: whether they can keep apart from children and pregnant women, how excreta will be managed, and incontinence","why":"The same treatment is safe to go home with in one household and not yet in another.","source":"iaea-ssg46","quote":"Special consideration should be given to incontinent patients."},{"action":"Make sure carers have been told about the radiation risks and how to limit them, and have understood, before they provide care","why":"A carer's exposure is accepted because they choose to help knowing what it involves.","source":"iaea-ssg46","quote":"Registrants and licensees shall ensure that no individual incurs a medical exposure as a carer or comforter unless he or she has received, and has indicated an understanding of, relevant information on radiation protection and information on the radiation risks prior to providing care and comfort to an individual undergoing a radiological procedure."},{"action":"Give the patient, or their parent, guardian or representative, written instructions on keeping others' doses low and on the risks, before they leave, consistent with the assumptions used in the calculation","why":"The calculation only holds if the patient knows and follows the precautions it assumed.","source":"irmer-2017-reg12","quote":"In the case of patients undergoing treatment or diagnosis with radioactive substances, the employer’s procedures must provide that, where appropriate, written instructions and information are provided to—"},{"action":"If the patient is breastfeeding and the infant could receive more than 1 mSv, include guidance on interrupting or stopping breastfeeding and what happens if it is not followed (US rule)","why":"Some radioactive medicines pass into breast milk.","source":"nrc-10cfr35-75","quote":"If the total effective dose equivalent to a nursing infant or child could exceed 1 mSv (0.1 rem) assuming there were no interruption of breast-feeding, the instructions must also include—"},{"action":"Record the basis for release where it used retained activity, an occupancy factor below 0.25 at one metre, an effective half-life or tissue shielding, and keep the record (US: 3 years)","why":"A record shows how the decision was made if it is questioned later.","source":"nrc-10cfr35-2075","quote":"The records required by paragraphs (a) and (b) of this section must be retained for 3 years after the date of release of the individual."},{"action":"If the patient cannot yet be released, keep them in a private room with its own toilet, post the door, note how long visitors may stay, and survey items leaving the room or treat them as radioactive waste","why":"This protects other patients, visitors and staff until the activity falls.","source":"nrc-10cfr35-315","quote":"A private room with a private sanitary facility; or"},{"action":"Give staff who care for patients who cannot be released radiation safety instruction when they start and at least yearly, and tell the radiation safety officer at once if such a patient has a medical emergency or dies","why":"Nurses need to know how to care for the patient safely, and an emergency or death needs specific precautions.","source":"nrc-10cfr35-310","quote":"A licensee shall provide radiation safety instruction, initially and at least annually, to personnel caring for patients or human research subjects who cannot be released under § 35.75."},{"action":"Give the patient a card with the treatment details and the department's contact, to show if admitted elsewhere or if they die soon after treatment","why":"Staff elsewhere, or funeral directors, need to know what was given and whom to call.","source":"iaea-srs63","quote":"To facilitate this, the patient should be given a small card with details of their treatment and contact details for a radiation protection specialist/medical physicist associated with the department responsible for the therapy"}],"bestInClass":{"statement":"An individual decision based on the dose others could receive, using dose limits for the public and dose constraints for carers (commonly 5 mSv per episode for adults and 1 mSv for children and for the fetus of a pregnant carer), estimated by a physicist from measured dose rates and the patient's home circumstances, with written instructions consistent with that estimate, given before the patient leaves (IAEA SSG-46 2018; IAEA SRS-63 2009; ICRP 94; 10 CFR 35.75; IR(ME)R 2017 reg 12). The IAEA and ICRP favour the dose approach over retained-activity limits and say that where they conflict the dose approach is the more fundamental; many European countries still apply retained-activity limits in law, and a patient there is bound by them. None of these sources grades its recommendations.","sources":["iaea-ssg46","iaea-srs63","icrp-94","nrc-10cfr35-75","irmer-2017-reg12"]},"variants":[{"name":"Retained-activity limits (many European and Asian countries)","differs":"A patient stays until the activity left in the body is below a set value. For iodine-131: most EU member states 400 to 600 MBq (range about 95 to 800), Germany 250 MBq (3.5 microsieverts an hour at 1 m) in table 10 but 75 MBq in table 9 of the same report, Japan 500 MBq or under 30 microsieverts an hour at 1 m, Sweden 600, Finland 800, Australia 600, the former IAEA guidance level 1,100 MBq (SRS-63 tables 9 and 10). EU recommendations then set how long instructions apply by dose rate at release, from 24 hours under 3 microsieverts an hour at 1 m to 3 weeks under 40 (table 11).","evidence":"SRS-63 reports that some retained-activity models are unduly conservative, overstate doses and lead to unnecessary hospital stays.","sources":["iaea-srs63"]},{"name":"United States: 5 mSv to any other individual","differs":"Release is allowed when no other person is likely to exceed 5 mSv, with written instructions above 1 mSv; NUREG-1556 Volume 9 gives default activity tables and methods for patient-specific calculation. This allows considerably higher activities to be released than retained-activity limits do.","evidence":"SRS-63 reports that competent and cooperative US patients are routinely discharged with up to 8 or 9 GBq of iodine-131, and that this has produced some previously unreported practices that need to be kept under review. NUREG-1556 itself could not be read.","sources":["nrc-10cfr35-75","iaea-srs63"]},{"name":"A 1 mSv constraint per administration and a stay of 4 to 6 hours","differs":"A 2025 modelling study comparing release approaches for lutetium-177 PSMA and dotatate, iodine-131, iodine-131 MIBG and samarium-153 recommends a dose constraint of 1 mSv per administration for people in contact with the patient, and keeping patients in the department for at least 4 to 6 hours, because exposure of other passengers on public transport should be considered.","evidence":"A single modelling study; abstract read only.","sources":["chipiga-2025"]}],"grades":[{"claim":"Release where no other individual is likely to exceed 5 mSv","grade":"Regulatory requirement (ungraded)","source":"nrc-10cfr35-75","quote":"A licensee may authorize the release from its control of any individual who has been administered unsealed byproduct material or implants containing byproduct material if the total effective dose equivalent to any other individual from exposure to the released individual is not likely to exceed 5 mSv (0.5 rem)."},{"claim":"Written instructions when another individual could exceed 1 mSv","grade":"Regulatory requirement (ungraded)","source":"nrc-10cfr35-75","quote":"A licensee shall provide the released individual, or the individual's parent or guardian, with instructions, including written instructions, on actions recommended to maintain doses to other individuals as low as is reasonably achievable if the total effective dose equivalent to any other individual is likely to exceed 1 mSv (0.1 rem)."},{"claim":"Children as carers, and the fetus of a pregnant carer, constrained to 1 mSv per episode","grade":"Safety Guide recommendation (ungraded)","source":"iaea-ssg46","quote":"The same approach of constraining the effective dose to the embryo or fetus to 1 mSv per episode is often taken."},{"claim":"Decide hospital stay or release on an individual basis","grade":"Consensus (ungraded)","source":"icrp-94","quote":"The decision to hospitalise or release a patient should be determined on an individual basis."},{"claim":"Young children, infants and visitors not giving care treated as members of the public","grade":"Consensus (ungraded)","source":"icrp-94","quote":"The present report recommends that young children and infants, as well as visitors not engaged in direct care or comforting, should be treated as members of the public (i.e. be subject to the public dose limit)."},{"claim":"Systematic dose monitoring of others is not necessary","grade":"Safety Guide recommendation (ungraded)","source":"iaea-ssg46","quote":"Published data suggest that systematic dose monitoring is not necessary"}],"sources":[{"key":"iaea-ssg46","label":"Radiation Protection and Safety in Medical Uses of Ionizing Radiation, Specific Safety Guide No. SSG-46","publisher":"International Atomic Energy Agency, jointly sponsored by PAHO and WHO","year":2018,"url":"https://www-pub.iaea.org/MTCD/Publications/PDF/PUB1775_web.pdf","gradingScheme":"An IAEA Safety Guide: recommendations ('should') on meeting the Safety Requirements (GSR Part 3, whose requirements it quotes as 'shall'); not graded by evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"iaea-srs63","label":"Release of Patients After Radionuclide Therapy, Safety Reports Series No. 63 (with contributions from the ICRP)","publisher":"International Atomic Energy Agency","year":2009,"url":"https://www-pub.iaea.org/MTCD/Publications/PDF/pub1417_web.pdf","gradingScheme":"A safety report built on measured and modelled doses and on ICRP, EU and national guidance; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"icrp-94","label":"ICRP Publication 94: Release of Patients after Therapy with Unsealed Radionuclides","publisher":"International Commission on Radiological Protection (Annals of the ICRP 34(2))","year":2004,"url":"https://www.icrp.org/publication.asp?id=ICRP%20Publication%2094","doi":"10.1016/j.icrp.2004.08.001","gradingScheme":"ICRP recommendations; not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"nrc-10cfr35-75","label":"10 CFR 35.75 Release of individuals containing unsealed byproduct material or implants containing byproduct material","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2007,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-C/section-35.75","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nrc-10cfr35-2075","label":"10 CFR 35.2075 Records of the release of individuals containing unsealed byproduct material or implants containing byproduct material","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2005,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-L/section-35.2075","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nrc-10cfr35-315","label":"10 CFR 35.315 Safety precautions (patients who cannot be released)","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2003,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-E/section-35.315","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nrc-10cfr35-310","label":"10 CFR 35.310 Safety instruction (staff caring for patients who cannot be released)","publisher":"US Nuclear Regulatory Commission (Code of Federal Regulations, via eCFR)","year":2003,"url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-E/section-35.310","gradingScheme":"Federal regulation; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"irmer-2017-reg12","label":"The Ionising Radiation (Medical Exposure) Regulations 2017, regulation 12 (optimisation), latest revised text","publisher":"UK legislation (legislation.gov.uk)","year":2017,"url":"https://www.legislation.gov.uk/uksi/2017/1322/regulation/12","gradingScheme":"Statutory instrument; requirements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"chipiga-2025","label":"Harmonization of practice of release of patients after radiopharmaceutical therapy","publisher":"Chipiga et al., Journal of Radiological Protection","year":2025,"url":"https://doi.org/10.1088/1361-6498/adba70","doi":"10.1088/1361-6498/adba70","gradingScheme":"Modelling study; not a guideline.","read":"abstract","accessed":"2026-11-11"},{"key":"nrc-nureg-1556-v9","label":"NUREG-1556 Volume 9, Program-Specific Guidance About Medical Use Licenses (patient release methods and default tables)","publisher":"US Nuclear Regulatory Commission","year":2019,"url":"https://www.nrc.gov/reading-rm/doc-collections/nuregs/staff/sr1556/","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No source read grades these requirements; they are safety standards, consensus and regulation built on measured and modelled doses.","NUREG-1556 Volume 9 and NRC Regulatory Guide 8.39, which give the US default release tables and calculation methods, could not be read: nrc.gov returned HTTP 403 to a script. The US activity thresholds are therefore not reproduced here.","The EU Basic Safety Standards Directive (2013/59/Euratom), European Commission Radiation Protection 97, the UK Ionising Radiations Regulations 2017 and the UK Medical and Dental Guidance Notes were not read; the European retained-activity figures come from the 2009 IAEA tables and may have changed.","ICRP Publication 94 was read only as its abstract. ICRP and IAEA guidance on release predates the wide use of lutetium-177 therapies; SRS-63 itself says there is a lack of good data on which to base advice for most radionuclides other than iodine-131.","The IAEA tables disagree with each other for Germany (250 MBq in table 10, 75 MBq in table 9); the current German limit was not checked against German law.","SRS-63 reports a lack of audit data on how patients behave after early release and on its consequences."]},{"id":"renal-dose-adjustment-of-anticancer-drugs","kind":"protocol","name":"Renal dose adjustment of anticancer drugs in reduced kidney function","aka":["renal dosing of chemotherapy","chemotherapy in kidney impairment","anticancer drug dosing in kidney dysfunction","ADDIKD","chemotherapy dose reduction for renal impairment","eGFR vs creatinine clearance for chemotherapy"],"tldr":"Many cancer drugs leave the body through the kidneys, so if your kidneys work less well the dose may need changing. The newest international guidance (2025) says to measure kidney function the same way the rest of medicine does, with the eGFR on your blood test, to use a more exact kidney test for a few drugs, and to think hard before cutting doses, because a lower dose can work less well.","summary":"No randomised trials guide anticancer dosing in kidney dysfunction, because reduced kidney function usually excludes people from trials. ADDIKD (2025), an international GRADE-and-consensus guideline from 38 working-group members covering 59 drugs, makes three general recommendations, all clinical consensus and strong: assess kidney function with eGFR by CKD-EPI, except where measured GFR is clinically necessary; use eGFR CKD-EPI to guide dosing of kidney-dependent drugs, preferring measured GFR for initial dosing of carboplatin, cisplatin and high-dose methotrexate (500 mg/m2 or more) and at extremes of body size or muscle mass, amputation or paraplegia; and use the KDIGO CKD categories to step doses. Standardised (1.73 m2) eGFR is used for every drug except carboplatin, where BSA-adjusted eGFR goes into the Calvert formula.\n\nThis departs from long practice: product information and older references use Cockcroft-Gault creatinine clearance, and BOPA (2025) still allows measured or calculated methods by local policy. ADDIKD also warns that dose cuts can harm: for cisplatin, several studies found poorer survival in people with eGFR below 60 given reduced doses, and it splits cisplatin into high and low dose at 50 mg/m2. Before deciding, weigh patient factors (hydration, performance status, liver disease, a single kidney), treatment factors (intent, an alternative regimen not dependent on the kidneys, tumour lysis risk, therapeutic drug monitoring, nephrotoxic co-medicines) and access to measured GFR. KDIGO 2024 adds that creatinine-based estimates are unreliable when kidney function is changing, and that medicines should be reviewed at transitions of care.","asOf":"2026-11-11","links":[],"tags":[],"related":["carboplatin-dose-calculation","sact-prescribing-and-pharmacy-verification"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","cisplatin","methotrexate"],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Your blood tests show how well your kidneys work. For some cancer drugs the team changes the dose if your kidneys are slower, and for a few they may do a special kidney test first.","domain":"pharmacy","setting":{"who":["doctor","pharmacist"],"where":["outpatient-clinic","ward","aseptic-unit"]},"population":"Adults with cancer prescribed systemic anticancer drugs whose kidney function is reduced or uncertain. ADDIKD states eGFR CKD-EPI is unsuitable in kidney replacement therapy, pregnancy and people under 18, and does not cover dialysis dosing; those patients need nephrology and specialist pharmacy input.","trigger":"A new anticancer regimen is planned, or eGFR is below 60 ml/min/1.73 m2, or kidney function changes during treatment.","steps":[{"action":"Assess kidney function with eGFR from the CKD-EPI equation, as laboratories report it, unless measured GFR is clinically necessary","why":"CKD-EPI eGFR is closer to true kidney function than older estimates and is the measure the rest of medicine uses.","source":"addikd-part1-2025","quote":"We recommend the use of estimated glomerular filtration rate calculated via the Chronic Kidney Disease—Epidemiology Collaboration (eGFR CKD-EPI ) equation to guide the assessment of kidney function, except where directly measured glomerular filtration rate (GFR) is clinically necessary.","grade":"clinical consensus; strong"},{"action":"Use a directly measured GFR to set the first dose of carboplatin, cisplatin and high-dose methotrexate, and of any kidney-dependent drug in people with extremes of body size or muscle mass, amputation or paraplegia","why":"For drugs where a small error matters, or bodies where creatinine misleads, a measured GFR avoids under- or overdosing.","source":"addikd-part1-2025","quote":"Directly measured GFR is preferred to guide the initial dosing: • for a select group of anticancer drugs including, but not limited to, carboplatin, cisplatin, and methotrexate (≥500 mg/m 2 ).","grade":"clinical consensus; strong"},{"action":"Use the standard (per 1.73 m2) eGFR for dosing every drug except carboplatin","why":"Most doses are already scaled to body size; adjusting the eGFR for body size too would count it twice.","source":"addikd-part1-2025","quote":"eGFR CKD-EPI adjusted to an individual’s body surface area (BSA) is not routinely advised to guide dosing of anticancer drugs over standardised eGFR CKD-EPI , except for carboplatin.","grade":"clinical consensus; strong"},{"action":"Do not rely on a creatinine-based estimate when kidney function is changing quickly, for example after an acute kidney injury","why":"Blood creatinine can take one to three days to rise after the kidneys are injured, so the estimate can look better than the kidneys are.","source":"addikd-part1-2025","quote":"eGFR CKD-EPI requires stable kidney function and should be performed as close as possible to the time of administering the anticancer drug(s) to ensure it is a reflective estimation of the patient’s steady state kidney function.","grade":"clinical consensus; strong"},{"action":"Place the patient in a KDIGO CKD category and use it to step the dose and the monitoring for each drug","why":"Common bands across all of medicine make dosing rules consistent and easier to check.","source":"addikd-part1-2025","quote":"We recommend the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) 9 , 10 categories to guide the stepwise dose adjustment of anticancer drugs in reduced kidney function and the monitoring of drug-related adverse events.","grade":"clinical consensus; strong"},{"action":"Before cutting a dose, weigh the patient's condition, the aim of treatment, whether an equally effective regimen avoids kidney-dependent drugs, the drug's properties and any other medicines that harm the kidneys","why":"A lower dose can mean a less effective treatment, so the decision depends on the person and the goal, not on a number alone.","source":"addikd-part1-2025","quote":"Treatment factors—treatment protocol (e.g., intent of treatment, appropriate alternative treatment protocols with similar efficacy and without drugs dependent on kidney function for dosing), risk of adverse events (e.g., tumour lysis syndrome), anticancer drug properties (e.g., pharmacokinetics, pharmacodynamics, formulation, availability of therapeutic drug monitoring), and concomitant drugs (especially with nephrotoxic potential).","grade":"clinical consensus; strong"},{"action":"Check kidney function at every cycle at pharmacy verification and modify doses as the regimen's literature directs, knowing which method the organisation uses","why":"Kidney function changes during treatment, and the pharmacist is the second check that the dose still fits.","source":"bopa-2025","quote":"Check renal function and ensure drug doses are modified accordingly where appropriate as per drug/regimen literature."},{"action":"Review all medicines, including over-the-counter and herbal products, for kidney harm and interactions, and repeat at each transition of care","why":"Other medicines can damage the kidneys or raise the levels of kidney-cleared cancer drugs.","source":"kdigo-2024","quote":"Perform thorough medication review periodically and at transitions of care to assess adherence, continued indication, and potential drug interactions because people with CKD often have complex medication regimens and are seen by multiple specialists.","grade":"Practice Point 4.3.1"}],"bestInClass":{"statement":"ADDIKD (2025) is the only international guideline on the subject and the most recent: eGFR CKD-EPI to assess kidney function and guide dosing, measured GFR for carboplatin, cisplatin, high-dose methotrexate and unusual body composition, KDIGO categories to step doses, and a deliberate weighing of patient and treatment factors before any reduction (all clinical consensus, strong). KDIGO 2024 agrees on CKD-EPI eGFR for most drug dosing and on measured GFR or cystatin C where accuracy matters. It conflicts with product labels and older references (Krens 2019/2023, BC Cancer monographs, the Renal Drug Database), which mostly use Cockcroft-Gault creatinine clearance and sometimes different cut-offs; UK pharmacy standards (BOPA 2025) leave the method to local policy.","sources":["addikd-part1-2025","addikd-method-2025","addikd-integration-2025","kdigo-2024","bopa-2025"]},"variants":[{"name":"Cockcroft-Gault creatinine clearance with label or reference-book cut-offs","differs":"Estimates creatinine clearance by Cockcroft-Gault and applies the dose bands in the product information or a reference such as the Lancet Oncology recommendations (Krens et al.), BC Cancer monographs or the Renal Drug Database.","evidence":"ADDIKD notes Cockcroft-Gault overestimates GFR by 10 to 20% and was not validated after creatinine assays were standardised in 2010, and that existing references disagree with one another: for cisplatin some advise 25 to 50% reductions at 30 to 59 ml/min and others contraindicate it below 40. BOPA 2025 accepts measured or calculated methods (including Cockcroft-Gault) by local policy.","sources":["addikd-part1-2025","addikd-integration-2025","bopa-2025","krens-2023"]},{"name":"Cisplatin split into high and low dose (ADDIKD)","differs":"Treats cisplatin above 50 mg/m2 (counting fractionated doses together) as high dose, and in the eGFR 45 to 59 category reduces high-dose cisplatin or considers another regimen, taking performance status and nephrotoxic co-medicines into account.","evidence":"Based on the link between high free-platinum peaks and kidney injury, and on studies showing poorer overall survival when people with eGFR below 60 were given reduced doses; low to moderate certainty in the ADDIKD tables.","sources":["addikd-integration-2025","addikd-method-2025"]}],"grades":[{"claim":"eGFR CKD-EPI to guide dosing of kidney-dependent anticancer drugs, except in specific situations","grade":"Evidence quality/certainty: clinical consensus; strength of recommendation: strong","source":"addikd-part1-2025","quote":"We recommend eGFR CKD-EPI to guide the dosing of anticancer drugs whose dose is dependent on kidney function, except in specific clinical situations or for a select group of anticancer drugs where eGFR CKD-EPI may be unsuitable."},{"claim":"Consider GFR when dosing medicines cleared by the kidneys","grade":"Practice Point 4.2.1","source":"kdigo-2024","quote":"Consider GFR when dosing medications cleared by the kidneys."},{"claim":"Validated creatinine-based eGFR equations are appropriate for drug dosing for most people","grade":"Practice Point 4.2.2","source":"kdigo-2024","quote":"For most people and clinical settings, validated eGFR equations using SCr are appropriate for drug dosing."}],"sources":[{"key":"addikd-part1-2025","label":"Aligning kidney function assessment in patients with cancer to global practices in internal medicine (ADDIKD, Part 1)","publisher":"eClinicalMedicine (Sandhu et al., ADDIKD Working Group, eviQ / Cancer Institute NSW)","year":2025,"url":"https://doi.org/10.1016/j.eclinm.2025.103102","doi":"10.1016/j.eclinm.2025.103102","gradingScheme":"GRADE-informed consensus: evidence quality or certainty (here 'clinical consensus') and strength of recommendation, strong or conditional.","read":"full-text","accessed":"2026-11-11"},{"key":"addikd-method-2025","label":"A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney function (ADDIKD)","publisher":"eClinicalMedicine (Sandhu et al.)","year":2025,"url":"https://doi.org/10.1016/j.eclinm.2025.103101","doi":"10.1016/j.eclinm.2025.103101","gradingScheme":"GRADE certainty (very low to high) and strength (strong or conditional) for each drug and question, set by anonymous consensus voting.","read":"full-text","accessed":"2026-11-11"},{"key":"addikd-integration-2025","label":"Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practice","publisher":"eClinicalMedicine (Sandhu et al.)","year":2025,"url":"https://doi.org/10.1016/j.eclinm.2025.103161","doi":"10.1016/j.eclinm.2025.103161","read":"full-text","accessed":"2026-11-11"},{"key":"kdigo-2024","label":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","publisher":"KDIGO (Kidney International)","year":2024,"url":"https://doi.org/10.1016/j.kint.2023.10.018","doi":"10.1016/j.kint.2023.10.018","gradingScheme":"Recommendations graded 1 (we recommend) or 2 (we suggest) with evidence quality A to D; practice points are ungraded expert judgement.","read":"full-text","accessed":"2026-11-11"},{"key":"bopa-2025","label":"Standards for the Pharmacy Verification of Prescriptions for Cancer Medicines, version 5.0","publisher":"British Oncology Pharmacy Association","year":2025,"url":"https://www.bopa.org.uk/wp-content/uploads/2019/07/BOPA-Standards-for-the-Pharmacy-Verification-of-Prescriptions-for-Cancer-Medicines-Version-5.0-3-june-2025.pdf","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"krens-2023","label":"Dose recommendations for anticancer drugs in patients with renal or hepatic impairment: an update","publisher":"The Lancet Oncology (Krens et al.)","year":2023,"url":"https://doi.org/10.1016/S1470-2045(23)00216-4","doi":"10.1016/S1470-2045(23)00216-4","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The drug-by-drug ADDIKD recommendations (dose by KDIGO category for each of 59 drugs) sit in the eviQ quick reference tool and supplementary appendices, which were not read; this protocol does not give individual drug doses.","The Lancet Oncology recommendations (Krens et al., 2019 and the 2023 update), the reference UK pharmacists name most often, could not be read.","ADDIKD rests on consensus and observational data; no randomised trial compares eGFR-based with creatinine-clearance-based dosing on outcomes, and its uptake outside Australia is not yet measured.","Dosing on dialysis and after kidney transplant is outside ADDIKD's scope and is not covered here."]},{"id":"irae-rechallenge","kind":"protocol","name":"Restarting a checkpoint inhibitor after an immune-related side effect","aka":["immunotherapy rechallenge","ICI rechallenge","checkpoint inhibitor retreatment after irAE","resuming immunotherapy after toxicity","re-challenge after immune-related adverse event"],"tldr":"After an immunotherapy side effect has settled, your team may offer to restart the same treatment. About 3 in 10 people who restart have the same side effect again, and some side effects (such as heart or nerve inflammation, or very severe reactions) usually mean stopping for good. It is a shared decision that weighs the cancer benefit against the risk.","summary":"Rechallenge is considered once the toxicity has resolved to grade 1 or less and the patient needs no more than 10 mg prednisone a day (SITC 2021). SITC: after grade 2 irAEs, rechallenge may proceed once resolved or controlled on 10 mg/day or less (LE: 3); after grade 3 to 4, the decision is risk-adjusted (LE: 3). Factors against: severe or life-threatening irAEs, prolonged or multiple immunosuppressants, long prior treatment, and complete response or prolonged benefit. ASCO 2021 (abstract): consider resuming most grade 2 toxicities when grade 1 or less; permanently discontinue after grade 4, except endocrinopathies controlled by hormone replacement. ESE 2022: a controlled endocrinopathy is no contraindication (++00).\n\nOrgan rules in SITC: colitis needs a repeat endoscopy before resuming; pneumonitis after grade 2 only after complete resolution (LE: 4); myocarditis, Guillain-Barré syndrome and grade 3 to 4 myasthenia gravis lead to permanent or seriously considered permanent discontinuation. ADQI 2026 supports cautious rechallenge after kidney injury (recurrence under 20%).\n\nEvidence: a WHO pharmacovigilance cohort found the same irAE recurred in 28.8% of informative rechallenges, more often after colitis, hepatitis and pneumonitis and less often after adrenal events; two small SITC-cited series found 26 to 43% recurrence and 13 to 26% new irAEs.","asOf":"2026-11-11","links":[],"tags":["protocol","irae"],"related":["irae-colitis","irae-pneumonitis","irae-hepatitis","irae-myocarditis","irae-neurological","irae-nephritis","io-rechallenge-caution-rcc"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["rechallenge","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"After a side effect from immunotherapy has settled, it may be possible to restart. Your team will talk through the benefits and risks with you.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","patient-or-carer","multidisciplinary-team","nurse"],"where":["outpatient-clinic"]},"population":"Adults whose checkpoint inhibitor was paused for an immune-related adverse event that has since improved. Children are not addressed by these sources.","trigger":"An immune-related adverse event has improved to grade 1 or less and the patient's steroid dose is down to about 10 mg prednisone a day or less.","steps":[{"action":"Consider restarting once the side effect is grade 1 or less and the steroid dose is 10 mg prednisone a day or less","why":"Restarting while the inflammation is still active or on high-dose steroids risks a flare.","source":"sitc-2021","quote":"Once the toxicity has sufficiently resolved (generally to grade 1 symptoms or lower with ≤10 mg prednisone equivalents per day), patients may be re-challenged."},{"action":"After a grade 2 side effect, restart if it has resolved or is controlled on 10 mg prednisone a day or less","why":"Most moderate side effects can be managed if they return.","source":"sitc-2021","quote":"Unless otherwise specified, patients who have experienced grade 2 irAEs may be re-challenged with ICI therapy if their signs and symptoms have resolved or are controlled with ≤10 mg of prednisone (or equivalent) per day","grade":"LE: 3"},{"action":"After a grade 3 or 4 side effect, decide case by case, weighing the expected cancer benefit against the risk","why":"Severe side effects are more likely to return, but restarting may still be worthwhile for some.","source":"sitc-2021","quote":"The decision to re-challenge a patient who has experienced grade 3 or 4 irAEs should be risk-adjusted based on anticipated benefit with therapy versus the potential for toxicity","grade":"LE: 3"},{"action":"Weigh the factors against restarting: a severe or life-threatening side effect, long or multiple immunosuppressants, long prior treatment, and a complete or lasting response","why":"Someone whose cancer has already responded well may gain little from restarting and risk a lot.","source":"sitc-2021","quote":"Factors that may cause clinicians to lean away from re-challenge include severe or life-threatening irAEs, requirement for prolonged or multiple immunosuppressants, and a history of long-term ICI therapy and/or patients with complete responses or prolonged clinical benefit."},{"action":"Continue or restart treatment when an endocrine side effect is controlled with hormone replacement","why":"A hormone shortage that is replaced does not get worse with more immunotherapy.","source":"ese-2022","quote":"We recommend that a controlled endocrinopathy is not a contraindication for initiation and/or continuation of ICI therapy","grade":"++00"},{"action":"After colitis, repeat the endoscopy before restarting","why":"Bowel inflammation can persist without symptoms and is one of the side effects most likely to return.","source":"sitc-2021","quote":"Repeat endoscopy should be performed prior to resuming ICI therapy."},{"action":"After grade 2 pneumonitis, restart only once symptoms have completely resolved, with more frequent reviews","why":"Lung inflammation can recur and is among the commonest to come back.","source":"sitc-2021","quote":"If patients have experienced grade 2 pneumonitis, they may be re-challenged with ICIs upon complete resolution of symptoms. These patients should be monitored through more frequent consultations with their physician","grade":"LE: 4"},{"action":"Do not restart after Guillain-Barré syndrome, and seriously consider never restarting after myocarditis","why":"These side effects can be fatal if they return.","source":"sitc-2021","quote":"Patients diagnosed with Guillain-Barré syndrome should always permanently discontinue ICI therapy, and should receive IVIG or PLEX with corticosteroid therapy","grade":"LE: 1"},{"action":"Tell the patient that about 3 in 10 people have the same side effect again, more often after colitis, hepatitis or pneumonitis","why":"Knowing the size of the risk helps the patient decide and spot a recurrence early.","source":"vigibase-2020","quote":"This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI."},{"action":"After restarting, monitor closely for the side effect returning and treat it as before","why":"A recurrence caught early is easier to treat.","source":"sitc-2021","quote":"Close monitoring for recurrence of diarrhea or colitis symptoms is recommended after re-challenging patients with ICI therapy."}],"bestInClass":{"statement":"SITC 2021 (full text) gives the clearest rule: rechallenge after grade 2 once resolved or controlled on 10 mg prednisone a day or less (LE: 3), a risk-adjusted decision after grade 3 to 4 (LE: 3), and organ-specific exceptions. ASCO 2021 (abstract) is stricter at the top: permanent discontinuation after grade 4 in general, with controlled endocrinopathies the exception. ESE 2022 grades continuing through a controlled endocrinopathy ++00. ADQI 2026 supports cautious rechallenge after kidney injury. All rest on retrospective series and pharmacovigilance data; there are no randomised trials of rechallenge. ESMO 2022 could not be read.","sources":["sitc-2021","asco-2021","ese-2022","adqi-2026","vigibase-2020","esmo-2022"]},"variants":[{"name":"Permanent discontinuation after grade 4 (ASCO 2021)","differs":"Recommends permanent discontinuation after grade 4 toxicities in general, except endocrinopathies controlled by hormone replacement, where SITC leaves grade 3 to 4 as a risk-adjusted decision.","evidence":"Informal consensus of an expert panel after a systematic review; read as abstract only.","sources":["asco-2021"]},{"name":"Cautious rechallenge after kidney injury (ADQI 2026)","differs":"A nephrology consensus that supports rechallenge in selected patients after ICI-associated kidney injury, citing recurrence in fewer than 20%.","evidence":"Modified Delphi consensus; read as abstract only.","sources":["adqi-2026"]}],"grades":[{"claim":"Rechallenge after grade 2 once resolved or controlled on 10 mg prednisone a day or less","grade":"LE: 3","source":"sitc-2021"},{"claim":"Risk-adjusted rechallenge after grade 3 or 4","grade":"LE: 3","source":"sitc-2021"},{"claim":"Permanent discontinuation after grade 4, except controlled endocrinopathies","grade":"expert consensus","source":"asco-2021","quote":"In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, except for endocrinopathies that have been controlled by hormone replacement."},{"claim":"A controlled endocrinopathy is no contraindication to continuing","grade":"++00","source":"ese-2022"},{"claim":"Recurrence of the same irAE after rechallenge","grade":"observational (pharmacovigilance cohort)","source":"vigibase-2020","quote":"One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"ese-2022","label":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline","publisher":"European Society of Endocrinology, European Journal of Endocrinology","year":2022,"url":"https://europepmc.org/article/PMC/PMC9641795","doi":"10.1530/EJE-22-0689","gradingScheme":"GRADE: quality of evidence printed as +000 (very low), ++00 (low), +++0 (moderate) or ++++ (strong); 'recommend' is a strong and 'suggest' a weak recommendation; recommendations not formally graded are marked good clinical practice.","read":"full-text","accessed":"2026-11-11"},{"key":"vigibase-2020","label":"Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer","publisher":"JAMA Oncology","year":2020,"url":"https://europepmc.org/abstract/MED/32297899","doi":"10.1001/jamaoncol.2020.0726","gradingScheme":"An observational pharmacovigilance cohort study (WHO VigiBase); not a guideline.","read":"abstract","accessed":"2026-11-11"},{"key":"adqi-2026","label":"Immune Checkpoint Inhibitor-Associated Acute Kidney Injury: A Report from the 34th Acute Disease Quality Initiative (ADQI) Consensus Conference","publisher":"Acute Disease Quality Initiative, Journal of the American Society of Nephrology","year":2026,"url":"https://europepmc.org/article/PMC/PMC13641466","doi":"10.1681/ASN.0000001232","gradingScheme":"Consensus statements reached by a modified Delphi method; the abstract does not give grades.","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline was read only as its abstract; its organ-by-organ resumption criteria are not compared here.","No randomised trial of rechallenge versus permanent discontinuation exists among the sources read; recurrence figures come from pharmacovigilance and small retrospective series, which may over- or under-count.","Whether switching to a different checkpoint inhibitor (for example from a combination to a PD-1 inhibitor alone) lowers the risk is not addressed by the sources read here."]},{"id":"radiotherapy-risk-analysis-fmea","kind":"protocol","name":"Risk-based quality management of the radiotherapy process (TG-100 failure mode and effects analysis)","aka":["FMEA radiotherapy","failure mode and effects analysis","TG-100","prospective hazard analysis","risk priority number","RPN","fault tree analysis","process map radiotherapy","risk-based QA","STPA"],"tldr":"Most radiotherapy errors come not from broken machines but from steps in the process: a wrong image, a mistyped number, a missed message. Departments therefore map every step of the treatment pathway, ask what could go wrong at each, score how likely, how harmful and how hard to spot each failure would be, and put their safety checks where the risk is highest.","summary":"AAPM Task Group 100 (2016) set out the reference method, starting from the observation that many errors are failures of workflow and process rather than of devices and software. A multidisciplinary team maps the process in detail, lists the failure modes at each step, scores occurrence (O), severity (S) and lack of detectability (D), usually from 1 to 10, and ranks them by the risk priority number (RPN = O x S x D). TG-100 looked at the top 20% to 25% by RPN and by severity, leaving each team to set its own threshold; studies commonly treat the top quartile of RPN and any severity of 8 or more as high risk. Fault tree analysis traces how failures propagate, and the quality management programme is then designed around the high-risk failure modes. MPPG 8.b (2023) asks every centre to run its own analysis, with published RPNs used only as a guide.\n\nA 2025 systematic review found 62 prospective hazard analyses in external beam radiotherapy: FMEA in 75%, STPA in 10%; 579 high-risk failure modes, half in treatment delivery sessions and a quarter in contouring and planning; and mitigations that tended to add workload and sit low on the hierarchy of effective interventions. A 2026 Ontario multi-institution exercise by nine physicists found the automotive-industry 'action priority' table, which weights severity and occurrence over detectability, picked out the same critical failures with less scoring disagreement. Incident learning, checklists, training and staffing are the commonest other safety recommendations across seven international documents.","asOf":"2026-11-11","links":[],"tags":[],"related":["linear-accelerator-quality-assurance","radiotherapy-patient-identification-and-time-out"],"cancers":[],"sections":[],"technologies":["c-arm-linac","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"The radiotherapy team looks at every step of your treatment, from the first scan to the last session, and asks what could go wrong. They fix the riskiest steps first, and check again after the fix.","domain":"radiotherapy","setting":{"who":["multidisciplinary-team","radiographer","doctor"],"where":["radiotherapy-department"]},"population":"Radiotherapy departments: the whole treatment process (referral, simulation, contouring, planning, checking, delivery) or a new technique or machine before it is introduced. It concerns staff and systems; patients benefit but do not take part.","trigger":"Introducing a new technique, machine or software; redesigning a quality management programme; or a periodic review of an existing process.","steps":[{"action":"Analyse the whole process, not only the equipment, because most errors happen in workflow and process","why":"Machine checks alone miss the commonest causes of error, such as wrong data passed between steps.","source":"aapm-tg100","quote":"Many errors that occur in radiation oncology are not due to failures in devices and software; rather they are failures in workflow and process.","grade":"ungraded (task group report)"},{"action":"Assemble a multidisciplinary team (physicists, doctors, radiographers or dosimetrists, and ideally a facilitator) to do the analysis","why":"Each profession sees different ways a step can go wrong.","source":"pha-review-2025","quote":"Disciplines involved in the studies were physicists (92%), physicians (75%), radiation therapists or dosimetrists (71%), external experts (38%), and facilitators (33%).","grade":"systematic review finding"},{"action":"Draw a detailed process map, list the failure modes at each step, and score each for occurrence, detectability and severity","why":"Writing every step down makes hidden weak points visible before they hurt anyone.","source":"pha-review-2025","quote":"involves generating a process map detailing the linear sequence of events involved in the process through analytical reduction, identifying the failure modes (FM) in each step of the process, assessing the effects of each FM in terms of their occurrence (O), detectability (D) and severity (S), and generating the risk priority number (RPN = O × S × D).","grade":"method as described (TG-100)"},{"action":"Rank failure modes by RPN (each score from 1 to 10) and treat the top quartile, and any with severity 8 or more, as high risk; set the threshold for your own system","why":"A rare but catastrophic failure needs attention even when its overall score is modest.","source":"fmea-ap-2026","quote":"As suggested in TG-100, PFMs that were in the top quartile of RPN scores and/or with a severity score greater than or equal to eight were deemed to be high risk profile PFMs.","grade":"method as described (TG-100)"},{"action":"Use fault tree analysis alongside FMEA to see how failures combine and spread","why":"Some harms happen only when two small failures line up; a fault tree shows where one check can block both.","source":"pha-review-2025","quote":"Of the included studies, 11 used fault tree analysis, however, only two studies used FTA alone, the rest of the studies used it alongside FMEA in the way described in TG-100.","grade":"systematic review finding"},{"action":"Do your own analysis of your own process; use published scores only as a guide","why":"Departments differ in equipment, staffing and workflow, so another centre's risk scores do not transfer.","source":"aapm-mppg8b","quote":"Each center should conduct their own risk analysis of their site-specific QA procedures.","grade":"should"},{"action":"Choose mitigations that prevent the failure (forcing functions, automation) before ones that only try to detect it, and avoid piling on extra manual checks","why":"Preventing an error is more reliable than hoping a busy person spots it later.","source":"fmea-ap-2026","quote":"The AP framework's emphasis on prevention over detection aligns with established hierarchies of intervention effectiveness.","grade":"study discussion (no grade)"},{"action":"Re-score the process after the mitigations are in place","why":"A fix can fail or create a new risk; checking again shows whether it worked.","source":"pha-review-2025","quote":"PHA involves the use of a formalized method of assessing and/or defining a system, technology, or technique, evaluating it for hazards, prioritizing the identified hazards and reassessment following the development of mitigation strategies to reduce the risk of the identified hazards.","grade":"method as described"},{"action":"Run the analysis before a new technique or machine treats patients","why":"Risks can be found and designed out before anyone is exposed to them.","source":"pha-review-2025","quote":"A benefit of PHA is that it can be performed during development of a system, technology, or technique.","grade":"review statement"},{"action":"Keep the other safety foundations in place alongside risk analysis: training, staffing, documentation, incident learning, communication and checklists","why":"Risk analysis is one of several layers; across international safety reports these others are named more often.","source":"dunscombe-2012","quote":"They are, in order of most to least cited: training, staffing, documentation, incident learning, communication, check lists, quality control and preventive maintenance, dosimetric audit, accreditation, minimizing interruptions, prospective risk assessment, and safety culture.","grade":"mapping of seven documents (no grade)"}],"bestInClass":{"statement":"AAPM TG-100 (2016) is the reference method: a multidisciplinary team maps the process, scores failure modes for occurrence, severity and detectability, ranks them, adds fault tree analysis, and builds the quality management programme around the high-risk failures; MPPG 8.b (2023) asks each centre to do this locally rather than borrow published scores. The 2025 systematic review shows FMEA in three-quarters of published analyses and warns that mitigations often add workload and sit low on the hierarchy of interventions. Where methods differ, both are shown: TG-100's RPN with a severity threshold, or the action priority table that weights severity and occurrence over detectability (Ontario multi-institution exercise, 2026). No trial shows that any risk analysis method reduces patient harm; the evidence is methodological and observational.","sources":["aapm-tg100","aapm-mppg8b","pha-review-2025","fmea-ap-2026"]},"variants":[{"name":"Action priority (AP) instead of the risk priority number","differs":"Uses a look-up table from the automotive industry's updated FMEA that ranks failures High, Medium or Low, weighting occurrence over detectability, rather than multiplying O x S x D and applying a quartile and severity cut-off.","evidence":"In an exercise by nine physicists from different Ontario cancer centres on 63 failure modes, AP selected 7 high-risk failures and RPN 30; all 7 were among the RPN set; AP was less affected by scoring variability and easier to apply.","sources":["fmea-ap-2026"]},{"name":"System theoretic process analysis (STPA)","differs":"A top-down method based on system theory: it starts from the events to be prevented and works through how they could come about, focusing on control loops and feedback, instead of listing failure modes step by step.","evidence":"Used in 10% of the 62 studies in the 2025 systematic review.","sources":["pha-review-2025"]},{"name":"Risk and benefit balance impact template (RABBIT)","differs":"A high-level assessment, developed in Australia, of the risks and benefits of a new technology or process before work to introduce it starts.","evidence":"Described in the 2025 systematic review; no comparative outcome data.","sources":["pha-review-2025"]},{"name":"Prescriptive QA lists without local risk analysis","differs":"Following task group tolerance tables (TG-142, MPPG 8.b) as written, without a local FMEA. MPPG 8.b treats its list as the minimum and asks for local risk analysis on top.","evidence":"TG-100 argues prescriptive device-focused QA cannot keep pace with complex modern processes; MPPG 8.b keeps a minimum list and cites a survey in which physicists did not agree on the risk of common failures.","sources":["aapm-tg100","aapm-mppg8b"]}],"grades":[{"claim":"TG-100 considered the top 20% to 25% of failure modes by RPN and severity, leaving the threshold to each team","grade":"method as reported","source":"pha-review-2025","quote":"TG-100 chose to consider the top 20%–25% of RPN and severity ranked failure modes but indicates that it is up to each individual team to determine the threshold appropriate for their system."},{"claim":"Published mitigations tend to add workload","grade":"systematic review finding","source":"pha-review-2025","quote":"The mitigation strategies recommended by studies tended to add to the departmental workload."},{"claim":"Use the MPPG 8.b tests as a minimum for any local risk analysis","grade":"recommendation (committee)","source":"aapm-mppg8b","quote":"We recommend using the tests and frequencies outlined in this report as a minimum for any risk analysis performed and that full consideration be given to the implication of removing any of the recommended minimum components."}],"sources":[{"key":"aapm-tg100","label":"The report of Task Group 100 of the AAPM: Application of risk analysis methods to radiation therapy quality management","publisher":"American Association of Physicists in Medicine (Huq et al., Medical Physics)","year":2016,"url":"https://doi.org/10.1118/1.4947547","doi":"10.1118/1.4947547","gradingScheme":"Task group report; consensus, not graded.","read":"abstract","accessed":"2026-11-11"},{"key":"pha-review-2025","label":"Systematic review of prospective hazard analysis in radiation therapy","publisher":"Medical Physics (open access)","year":2025,"url":"https://doi.org/10.1002/mp.18110","doi":"10.1002/mp.18110","gradingScheme":"Systematic review (PRISMA); no grades.","read":"full-text","accessed":"2026-11-11"},{"key":"fmea-ap-2026","label":"Application of an updated severity-based FMEA approach to Radiation Therapy QA: A multi-institutional exercise","publisher":"Rangel et al., Journal of Applied Clinical Medical Physics","year":2026,"url":"https://doi.org/10.1002/acm2.70674","doi":"10.1002/acm2.70674","read":"full-text","accessed":"2026-11-11"},{"key":"aapm-mppg8b","label":"AAPM Medical Physics Practice Guideline 8.b: Linear accelerator performance tests (sections 6.2 to 6.5, risk assessment)","publisher":"American Association of Physicists in Medicine (Krauss et al., Journal of Applied Clinical Medical Physics)","year":2023,"url":"https://doi.org/10.1002/acm2.14160","doi":"10.1002/acm2.14160","gradingScheme":"AAPM practice guideline wording: 'must' and 'should'.","read":"full-text","accessed":"2026-11-11"},{"key":"dunscombe-2012","label":"Recommendations for safer radiotherapy: what's the message?","publisher":"Dunscombe, Frontiers in Oncology","year":2012,"url":"https://doi.org/10.3389/fonc.2012.00129","doi":"10.3389/fonc.2012.00129","read":"full-text","accessed":"2026-11-11"},{"key":"towards-safer-rt","label":"Towards Safer Radiotherapy","publisher":"The Royal College of Radiologists, Society and College of Radiographers, IPEM, National Patient Safety Agency and British Institute of Radiology","year":2008,"url":"https://www.rcr.ac.uk/","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The full TG-100 report was not read: PubMed Central holds it as a non-open PDF and the publisher's copy is paywalled. Its method is described from its abstract and from open papers that quote it.","Towards Safer Radiotherapy (UK, 2008) and the IAEA risk matrix publications were not read; the UK document is known here only through a 2012 mapping paper.","No study shows that prospective risk analysis reduces patient harm; the evidence is that it finds failure modes, not that outcomes improve.","Scoring is subjective: published studies vary in scales, thresholds and team make-up, and physicists in one survey did not agree on the risk of common failures."]},{"id":"routine-preoperative-tests","kind":"protocol","name":"Routine tests before planned surgery, by size of operation and fitness","aka":["preoperative tests","pre-op bloods","pre-assessment tests","preoperative investigations","routine chest X-ray before surgery","preoperative ECG"],"tldr":"Before a planned operation, tests should be chosen for the person and the size of the operation, not done for everyone. A blood count is offered before major surgery; a heart tracing and kidney tests depend on age, health and the operation; a chest X-ray, urine dipstick or heart scan is not done routinely.","summary":"NICE NG45 (2016) sets which routine tests to offer before elective surgery by surgery grade (minor, intermediate, major or complex) and ASA grade. Not routinely before any surgery: chest X-ray, resting echocardiography (consider it for a murmur with cardiac symptoms, or signs of heart failure, after an ECG and anaesthetic discussion), urine dipstick (consider midstream urine culture if a urinary infection would change the decision), sickle cell testing (ask about it instead), and HbA1c in people without diabetes. Offer HbA1c to people with diabetes not tested in the last 3 months. Before major or complex surgery: full blood count for all ASA grades; ECG for ASA 2 and above, and considered over 65 at ASA 1 without an ECG in the last year; kidney function for ASA 2 and above, and considered in ASA 1 at risk of acute kidney injury. Clotting tests are not routine; consider them in chronic liver disease, and make an individual plan for anticoagulants, noting that DOAC effects cannot be measured by routine tests. Ask about pregnancy on the day of surgery and test with consent if in doubt. Take existing medicines into account. People with cancer often have recent blood tests from their treatment; NG45 does not address chemotherapy or recent cancer treatment.","asOf":"2026-11-11","links":[],"tags":[],"related":["enhanced-recovery-after-liver-surgery","vte-prophylaxis-after-cancer-surgery"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"You may have blood tests or a heart tracing before your operation. Which ones depends on how big the operation is and on your health. Tests that will not change your care are not needed.","domain":"surgery-perioperative","setting":{"who":["anaesthetist","nurse","surgical-team"],"where":["outpatient-clinic"]},"population":"People aged over 16 having elective surgery, as NICE NG45 scopes it. It does not cover pregnant women or people having cardiothoracic procedures or neurosurgery (so not lung cancer surgery), and it is not about tests to diagnose or stage the cancer itself.","trigger":"Preoperative assessment before a planned operation.","steps":[{"action":"Take the person's current medicines into account when deciding on any test","why":"Some medicines, such as diuretics or anticoagulants, make particular tests worthwhile.","source":"nice-ng45","quote":"Take into account any medicines people are taking when considering whether to offer any preoperative test.","grade":"Not graded (NICE 1.2.1)"},{"action":"Do not routinely offer a chest X-ray, resting echocardiogram or urine dipstick before surgery","why":"These tests rarely change the plan when done routinely, and abnormal results can lead to delays and more tests.","source":"nice-ng45","quote":"Do not routinely offer chest X‑rays before surgery.","grade":"Not graded (NICE 1.8.1)"},{"action":"Consider an echocardiogram only for a heart murmur with cardiac symptoms, or signs of heart failure, after a resting ECG and discussion with an anaesthetist","why":"In these people a heart scan can change how the anaesthetic is given.","source":"nice-ng45","quote":"Before ordering the resting echocardiogram, carry out a resting electrocardiogram (ECG) and discuss the findings with an anaesthetist.","grade":"Not graded (NICE 1.9.2)"},{"action":"Offer HbA1c to people with diabetes who have not been tested in the last 3 months; do not test routinely in people without diabetes","why":"Poorly controlled diabetes raises the risk of complications and can often be improved before planned surgery.","source":"nice-ng45","quote":"Offer HbA1c testing to people with diabetes having surgery if they have not been tested in the last 3 months.","grade":"Not graded (NICE 1.6.2)"},{"action":"Before major or complex surgery, offer a full blood count to everyone; offer kidney function tests and an ECG to people with ASA grade 2 or above, and consider them in fit people at risk of kidney injury or over 65","why":"Anaemia, kidney problems and heart rhythm problems matter more as the operation gets bigger.","source":"nice-ng45","grade":"Table 3 (major or complex surgery): full blood count Yes at every ASA grade; kidney function and ECG Yes at ASA 2 and ASA 3 or 4, Consider at ASA 1"},{"action":"Do not test clotting routinely; consider it in chronic liver disease, and make an individual plan for anyone on anticoagulants","why":"Clotting tests rarely change care unless the liver is affected; blood thinners need their own plan, and newer ones do not show on routine tests.","source":"nice-ng45","quote":"Note that currently the effects of direct oral anticoagulants (DOACs) cannot be measured by routine testing.","grade":"Table 2 and Table 3: Not routinely at ASA 1 and 2; Consider in people with chronic liver disease"},{"action":"Ask about sickle cell disease rather than testing for it routinely","why":"Asking finds people who need specialist planning without testing everyone.","source":"nice-ng45","quote":"Ask the person having surgery if they or any member of their family have sickle cell disease.","grade":"Not graded (NICE 1.4.2)"},{"action":"On the day of surgery, sensitively ask anyone who could be pregnant whether they might be, and test with consent if there is any doubt","why":"Anaesthesia and surgery can harm a pregnancy, and some cancer surgery would be planned differently.","source":"nice-ng45","quote":"Carry out a pregnancy test with the woman's consent if there is any doubt about whether she could be pregnant.","grade":"Not graded (NICE 1.3.4)"}],"bestInClass":{"statement":"NICE NG45 (2016): tests chosen by surgery grade and ASA grade, with chest X-ray, echocardiography, urine dipstick, sickle cell testing and HbA1c in people without diabetes not done routinely, and a full blood count before all major or complex surgery. It is the only guideline read here, so no disagreement can be shown.","sources":["nice-ng45"]},"variants":[],"grades":[{"claim":"No routine resting echocardiography","grade":"Not graded (NICE 1.9.1)","source":"nice-ng45","quote":"Do not routinely offer resting echocardiography before surgery."},{"claim":"No routine urine dipstick","grade":"Not graded (NICE 1.7.1)","source":"nice-ng45","quote":"Do not routinely offer urine dipstick tests before surgery."},{"claim":"No routine HbA1c in people without diagnosed diabetes","grade":"Not graded (NICE 1.5.1)","source":"nice-ng45","quote":"Do not routinely offer HbA1c testing before surgery to people without diagnosed diabetes."},{"claim":"No routine sickle cell testing","grade":"Not graded (NICE 1.4.1)","source":"nice-ng45","quote":"Do not routinely offer testing for sickle cell disease or sickle cell trait before surgery."}],"sources":[{"key":"nice-ng45","label":"Routine preoperative tests for elective surgery (NG45), recommendations","publisher":"NICE","year":2016,"url":"https://www.nice.org.uk/guidance/ng45/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations. Tables mark each test 'Yes' (offer), 'Not routinely' or 'Consider' by surgery grade and ASA grade.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["Only one guideline (NICE NG45, 2016) was read. Other national guidance (for example US or European preoperative evaluation guidelines) was not, so the page cannot show where they differ.","NG45 does not address people who are having or have recently had chemotherapy, radiotherapy or immunotherapy, who may need blood counts, thyroid or other tests for that reason; those come from the cancer team's own protocols.","Tests to diagnose or stage the cancer, and cardiopulmonary exercise testing before major cancer surgery, are outside NG45 and this record."]},{"id":"hazardous-drug-handling-in-clinical-areas","kind":"protocol","name":"Safe handling of hazardous anticancer drugs where they are given: protective equipment, closed systems, spills, waste and body fluids","aka":["cytotoxic safe handling","chemotherapy PPE","chemo gloves","chemotherapy gown","USP 800","closed-system transfer device","CSTD","chemotherapy spill","cytotoxic spill kit","cytotoxic waste","hazardous drugs in healthcare","NIOSH hazardous drug list"],"tldr":"Many cancer drugs harm the staff who handle them every day, even in tiny amounts. So nurses wear special gloves and gowns when giving them, use sealed connectors, and handle spills and waste in a set way. For a day or two after treatment some drug is in the patient's body fluids, so staff wear gloves for those too. The protection is for repeated exposure at work; you are not dangerous to be near.","summary":"The US framework is NIOSH (the 2004 Alert and the 2024 hazardous drug list), USP chapter 800 and OSHA, which ASCO's consensus standards (2019) endorse; the UK framework is COSHH, applied by HSE, with a hierarchy of control: enclosed systems, control at source, then PPE. Employers should keep a facility-specific hazardous drug list, because the NIOSH list (2024, 25 drugs added and 7 removed since 2016) may not include newer drugs.\n\nNIOSH (2004) asks for double chemotherapy-tested gloves, a disposable gown with a closed front and closed cuffs, and goggles for all administration activities, from opening the outer bag to disposal; preparation belongs in a ventilated cabinet, tubing is primed with a non-drug fluid, and closed-system transfer devices (CSTDs) supplement but do not replace the cabinet. ASCO (2019) reports that USP chapter 800 requires CSTDs for administration and recommends them for compounding, while a Cochrane review (2018, 24 observational studies) found the evidence of benefit very low in certainty and drew no firm conclusions. Linen and excreta from patients treated within 48 hours (sometimes 7 days) are handled with two pairs of gloves and a gown. Spills follow written procedures with spill kits nearby; large spills need trained staff and a respirator, as surgical masks do not protect. ASCO asks for an alternative-duty policy for staff who are trying to conceive, pregnant or breastfeeding, and finds routine medical surveillance unsupported by evidence; HSE says monitoring is normally needed under COSHH where carcinogens are handled.","asOf":"2026-11-11","links":[],"tags":[],"related":["sact-administration-checks-at-the-chair"],"cancers":[],"sections":[],"technologies":["closed-system-transfer-devices","pharmacy-automation","cytotoxic-chemotherapy"],"targets":[],"drugs":["cyclophosphamide","ifosfamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Nurses wear gloves and gowns with chemotherapy because they handle it every day. It is about their repeated exposure, not about you being unsafe to touch or hug.","domain":"hazardous-drug-safety","setting":{"who":["nurse","pharmacist","pharmacy-technician"],"where":["chemotherapy-day-unit","ward","aseptic-unit","home"]},"population":"Healthcare workers who receive, prepare, give or dispose of hazardous drugs, including most cytotoxic anticancer drugs and some hormonal and targeted drugs, and those who handle patients' body fluids and linen after treatment. Aseptic compounding in pharmacy has further requirements (USP chapter 800, ISOPP) not covered here. Guidance for patients and carers at home is a separate subject.","trigger":"A hazardous drug is received, prepared, given, spilled or disposed of, or a patient's body fluids are handled after treatment.","steps":[{"action":"Keep a list of the hazardous drugs used in your own unit, starting from the NIOSH list and adding new drugs as they arrive","why":"New cancer drugs reach wards before national lists are updated.","source":"niosh-2024","quote":"Therefore, this list may not be all-inclusive, and employers should consider creating a facility-specific hazardous drug list."},{"action":"Assess the risk of each handling task and control exposure in order: enclosed systems first, control at source next, protective equipment last","why":"Protective equipment is the last line of defence; engineering controls protect everyone at once.","source":"hse-cytotoxics","quote":"Under COSHH, employers must assess the risks from handling cytotoxic drugs for employees and anyone else affected by this type of work, and take suitable precautions to protect them."},{"action":"Label hazardous drugs as hazardous when they are prepared","why":"Everyone who touches the bag later, including porters and cleaners, needs to know.","source":"asco-ons-2024","quote":"A label denoting HAZARDOUS DRUG, if applicable"},{"action":"Prepare, crush or pour hazardous drugs only inside a ventilated cabinet; a closed-system device is an addition, not a substitute","why":"Opening vials and powders releases droplets and particles that a cabinet captures.","source":"niosh-2004","quote":"closed-system transfer device is not an acceptable substitute for a ventilated cabinet and should be used only within a ventilated cabinet."},{"action":"Wear double chemotherapy gloves, a protective gown and goggles for every step of giving the drug, from opening the outer bag to disposal","why":"Skin contact with contaminated bags, tubing and surfaces is the main route of exposure for nurses.","source":"niosh-2004","quote":"Wear PPE (including double gloves, goggles, and protective gowns) for all activities associated with drug administration—opening the outer bag, assembling the delivery system, delivering the drug to the patient, and disposing of all equipment used to administer drugs."},{"action":"Use gloves tested and labelled for chemotherapy, and gowns with a closed front, long sleeves and closed cuffs, disposed of after each use","why":"Ordinary gloves and cloth gowns let some drugs through.","source":"niosh-2004","quote":"Make sure gowns have closed fronts, long sleeves, and elastic or knit closed cuffs."},{"action":"Have tubing primed in pharmacy or with a non-drug fluid, never with the drug at the bedside","why":"Priming with the drug can spray it into the air or onto hands.","source":"niosh-2004","quote":"Have pharmacy personnel prime the IV tubing and syringes inside the ventilated cabinet, or prime them in-line with nondrug solutions—never in the patient’s room."},{"action":"Use closed-system transfer devices for administration where your standards require them","why":"They are designed to stop drug escaping when lines are connected and disconnected; whether they improve health is unproven.","source":"asco-2018","quote":"USP 800 requires use of CSTDs for nursing administration of hazardous drugs and recommends use for sterile product compounding of hazardous drugs."},{"action":"Wear two pairs of gloves and a gown to handle linen, urine or faeces from patients treated in the last 48 hours (for some drugs, 7 days)","why":"Some drugs leave the body unchanged in urine, stool, vomit and sweat for a day or more.","source":"niosh-2004","quote":"Wear two pairs of protective gloves and a disposable gown if you must handle linens, feces, or urine from patients who have received hazardous drugs within the last 48 hours—or in some cases, within the last 7 days"},{"action":"Dispose of drug waste and contaminated equipment by the written local procedure for cytotoxic waste","why":"Waste bins are handled by many people who never see the drug.","source":"hse-cytotoxics","quote":"Procedures must be in place for the safe disposal of waste."},{"action":"Keep spill kits where drugs are handled and clean spills by the written procedure; leave large spills to trained staff","why":"A prepared response limits spread and exposure.","source":"niosh-2004","quote":"Manage hazardous drug spills according to the established, written policies and procedures for each workplace."},{"action":"For spills that can make airborne particles, use a fitted respirator; a surgical mask does not protect","why":"Surgical masks stop splashes to the mouth, not fine droplets or powder.","source":"niosh-2004","quote":"Surgical masks do not provide adequate protection."},{"action":"Offer alternative duties to staff who are trying to conceive, pregnant or breastfeeding, and tell staff about this when they are hired","why":"Exposure to some drugs has been linked to miscarriage in staff who handled them without protection.","source":"asco-2018","quote":"The health care setting has a policy that identifies potential alternative work options, where possible, for workers who are actively trying to conceive, are pregnant, or are breastfeeding."},{"action":"Report any exposure or health concern to occupational health when it happens","why":"Acute exposures, such as a spill on skin, need assessment and a record.","source":"asco-2018","quote":"Workers should be encouraged to report occupational health issues to employee health services at the time that they are experienced."}],"bestInClass":{"statement":"In the US, USP chapter 800 with NIOSH and OSHA, as endorsed by ASCO (2019): a facility hazardous drug list, ventilated-cabinet preparation, double chemotherapy gloves, impermeable gown and eye protection for administration, CSTDs for administration (required by USP chapter 800, according to ASCO), written spill and waste procedures, precautions with body fluids for 48 hours, and an alternative-duty policy. In the UK, COSHH as applied by HSE: risk assessment and a hierarchy of enclosure, control at source, then PPE. The sources differ on CSTDs (required by USP chapter 800; Cochrane 2018 found the evidence of benefit very low in certainty) and on monitoring (ASCO: routine medical surveillance has no supporting data; HSE: monitoring is normally necessary under COSHH where carcinogens are handled). USP chapter 800 and the ISOPP standards could not be read directly.","sources":["asco-2018","niosh-2004","niosh-2024","hse-cytotoxics","cochrane-cstd-2018"]},"variants":[{"name":"Closed-system transfer devices for every hazardous drug connection","differs":"Uses a CSTD for all preparation and every connection and disconnection at the bedside, rather than standard needles and open connections with PPE.","evidence":"Cochrane (2018): 24 observational cluster studies, no randomised trials, all at serious risk of bias; very low certainty evidence was insufficient to show differences in staff urine tests or surface contamination, and no firm conclusions could be drawn. ASCO (2019) calls the literature low quality and notes no standard test of CSTD performance exists. USP chapter 800 requires them for administration (as reported by ASCO).","sources":["cochrane-cstd-2018","asco-2018"]},{"name":"Routine medical surveillance of exposed staff","differs":"Regular health checks, blood counts or urine tests for staff who handle hazardous drugs.","evidence":"ASCO (2019) finds no data that routine surveillance improves outcomes and prefers a registry approach; HSE says monitoring is normally necessary under COSHH where there is potential exposure to carcinogens.","sources":["asco-2018","hse-cytotoxics"]}],"grades":[{"claim":"ASCO endorses OSHA, USP chapter 800, the NIOSH 2004 Alert and ONS standards","grade":"Consensus-based standard","source":"asco-2018","quote":"The Expert Panel endorses a majority of the standards for safe handling of hazardous drugs as issued by the US Occupational Safety and Health Administration,"},{"claim":"Routine ongoing medical surveillance: role unclear","grade":"Consensus-based standard","source":"asco-2018","quote":"The role of routine ongoing medical surveillance programs that include medical screening, laboratory testing, or other biologic monitoring is unclear, because there are no published data to reliably inform a standard or best practice."},{"claim":"CSTD plus safe handling versus safe handling alone","grade":"very low certainty (GRADE)","source":"cochrane-cstd-2018","quote":"Currently, no firm conclusions can be drawn on the effect of CSTD combined with safe handling versus safe handling alone due to very low certainty evidence available for the main outcomes."},{"claim":"Order of control measures under COSHH","grade":"UK regulation (COSHH)","source":"hse-cytotoxics","quote":"Measures to control exposure should be applied in the following order: use totally enclosed systems where reasonably practicable control exposure at source, for example, by using adequate extraction systems and appropriate organisational measures issue personal protective equipment where adequate control cannot be achieved by other measures alone"}],"sources":[{"key":"asco-2018","label":"Safe Handling of Hazardous Drugs: ASCO Standards","publisher":"ASCO (Journal of Clinical Oncology, Celano et al.)","year":2019,"url":"https://doi.org/10.1200/JCO.18.01616","doi":"10.1200/JCO.18.01616","gradingScheme":"Consensus-based standards developed by weighing benefits and harms, because the evidence base was limited; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"niosh-2004","label":"NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings (DHHS (NIOSH) Publication No. 2004-165)","publisher":"National Institute for Occupational Safety and Health (CDC)","year":2004,"url":"https://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf","gradingScheme":"Not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"niosh-2024","label":"NIOSH List of Hazardous Drugs in Healthcare Settings, 2024 (DHHS (NIOSH) Publication No. 2025-103)","publisher":"National Institute for Occupational Safety and Health (CDC)","year":2024,"url":"https://doi.org/10.26616/NIOSHPUB2025103","doi":"10.26616/NIOSHPUB2025103","gradingScheme":"Not graded; advisory.","read":"full-text","accessed":"2026-11-11"},{"key":"hse-cytotoxics","label":"Safe handling of cytotoxic drugs in the workplace","publisher":"Health and Safety Executive (UK)","year":2026,"url":"https://www.hse.gov.uk/healthservices/safe-use-cytotoxic-drugs.htm","gradingScheme":"Regulatory guidance under COSHH; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"cochrane-cstd-2018","label":"Closed-system drug-transfer devices plus safe handling of hazardous drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff","publisher":"Cochrane Database of Systematic Reviews (Gurusamy et al.)","year":2018,"url":"https://doi.org/10.1002/14651858.CD012860.pub2","doi":"10.1002/14651858.CD012860.pub2","gradingScheme":"GRADE certainty of evidence: high, moderate, low or very low.","read":"abstract","accessed":"2026-11-11"},{"key":"asco-ons-2024","label":"Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards","publisher":"ASCO and the Oncology Nursing Society (JCO Oncology Practice)","year":2024,"url":"https://doi.org/10.1200/OP.24.00216","doi":"10.1200/OP.24.00216","gradingScheme":"Standards are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"usp-800","label":"USP General Chapter <800> Hazardous Drugs: Handling in Healthcare Settings","publisher":"United States Pharmacopeia","year":2020,"url":"https://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare","read":"not-reachable","accessed":"2026-11-11"},{"key":"isopp-2022","label":"ISOPP Standards for the Safe Handling of Cytotoxics","publisher":"International Society of Oncology Pharmacy Practitioners (Journal of Oncology Pharmacy Practice)","year":2022,"url":"https://doi.org/10.1177/10781552211070933","doi":"10.1177/10781552211070933","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-upgrade-closed-system-transfer-device-outcome-trial"],"gaps":["USP chapter 800 (usp.org refused a script) and the ISOPP Standards for the Safe Handling of Cytotoxics (2022, paywalled) could not be read; what USP chapter 800 requires is stated here only as ASCO (2019) reports it.","NIOSH moved its PPE-by-activity guidance from the hazardous drug list into 'Managing Hazardous Drug Exposures: Information for Healthcare Settings' (2023), which could not be retrieved; the PPE steps here come from the 2004 NIOSH Alert, which is older.","No European Union or NHS-specific standard for chair-side PPE could be read; UK waste colour coding for cytotoxic waste is not stated by any source read.","Whether CSTDs improve staff health is unknown: the Cochrane review found only observational studies at serious risk of bias.","The 48-hour period for precautions with body fluids comes from a 1992 source cited by NIOSH; drug-specific excretion times are not given by any source read.","Which newer agents (antibody-drug conjugates, some targeted tablets) count as hazardous depends on the NIOSH table and local assessment; the 2024 list was read but its drug tables are not reproduced here."]},{"id":"scalp-cooling-during-chemotherapy","kind":"protocol","name":"Scalp cooling during chemotherapy: suitability, preparation and cooling times","aka":["cold cap","cool cap","scalp hypothermia","Paxman","DigniCap","post-infusion cooling time","PICT","preventing hair loss during chemotherapy"],"tldr":"A cold cap worn before, during and after a chemotherapy drip can help some people keep much of their hair, especially with taxanes such as paclitaxel and docetaxel. It is not suitable for blood cancers or for people very sensitive to cold. For taxanes, trials show 20 minutes afterwards works as well as longer. It does not always work, and results depend on the chemotherapy.","summary":"Machine scalp cooling (DigniCap, Paxman) is FDA-authorised to reduce the likelihood of chemotherapy-induced alopecia in women with breast cancer (the 2015 De Novo and 2017 510(k) decisions read); later extensions were not read. In the SCALP randomised trial (Paxman, 142 evaluable), 50.5 per cent of cooled women kept their hair against 0 per cent of controls. Contraindications in the DigniCap instructions are cold sensitivity, cold agglutinin disease, cryoglobulinaemia and cryofibrinogenaemia, and haematological malignancy treated with curative intent. A 2025 meta-analysis of 67 studies found scalp metastasis in 0.15 per cent; common effects were chills (42 per cent), cap heaviness (35 per cent) and headache (30 per cent), and 18 per cent stopped cooling.\n\nThere is no guideline-defined schedule. Pre-cooling of 30 minutes is the accepted standard. Post-infusion cooling time depends on the regimen: randomised trials found 20 minutes as effective as 45 minutes after docetaxel and after weekly paclitaxel (the 2022 authors call 20 minutes the new standard of care), while with FEC extending from 90 to 150 minutes did not significantly reduce head-cover use; the Dutch registry (4680 patients) found under 85 minutes as effective as longer for the taxane and anthracycline regimens studied. Wetting hair before cooling lowers scalp temperature but, in the Dutch registry of 1825 patients, added little and slightly raised discontinuation for intolerance. Results are poorer with anthracyclines and with taxane plus anthracycline regimens.","asOf":"2026-11-11","links":[],"tags":["protocol","alopecia","scalp-cooling","supportive-care"],"related":[],"cancers":["breast-cancer"],"sections":["supportive-care"],"technologies":["scalp-cooling","manual-cold-caps","wigs-cranial-prosthesis"],"targets":[],"drugs":["paclitaxel","docetaxel","doxorubicin","epirubicin","cyclophosphamide"],"companies":["paxman","dignitana"],"institutions":[],"pathways":[],"terms":["hair-loss-and-scalp-cooling-breast","anthracycline"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A cold cap can help you keep your hair during some chemotherapy. It goes on before the drip and stays on a while after. It does not suit everyone.","domain":"supportive-care","setting":{"who":["nurse","patient-or-carer"],"where":["chemotherapy-day-unit"]},"population":"Adults with solid tumours receiving chemotherapy that causes hair loss, above all taxanes, in whom cooling is available. The FDA decisions read and most trials are in women with breast cancer; the Dutch registry and later studies include other solid tumours. Not for people with haematological cancers (the DigniCap instructions limit this to curative-intent treatment; Macmillan says not suitable for any blood cancer), or with cold sensitivity disorders.","trigger":"Chemotherapy likely to cause hair loss is planned and the person wants to try to keep their hair; cooling starts at the first cycle.","steps":[{"action":"Before the first cycle, check that cooling is suitable: not for blood cancers treated to cure, or for cold sensitivity, cold agglutinin disease, cryoglobulinaemia or cryofibrinogenaemia","why":"In blood cancers, cancer cells may circulate in the scalp, and cooling could shelter them from the drugs; cold-sensitive conditions make cooling unsafe.","source":"dignicap-den150010","quote":"“Contraindications are cold sensitivity, cold agglutinin disease, cryoglobulinemia and cryofibrinogenemia.”","grade":"FDA De Novo decision summary (device instructions)"},{"action":"Explain how likely it is to work with the planned regimen, and that results are poorer with anthracyclines and with taxane and anthracycline combinations","why":"Success varies with the drugs, dose and infusion time; knowing this helps people decide whether the time and discomfort are worth it.","source":"dignicap-den150010","quote":"“Attention: Clinical studies have produced variable success rates in patient reduction of chemotherapy induced alopecia with scalp cooling since the outcome is dependent on several factors including chemotherapy regimen, dose, duration of drug infusion, chemotherapy drug metabolism, and concomitant comorbidities.”","grade":"FDA De Novo decision summary (device instructions)"},{"action":"Explain that the risk of cancer spreading to the scalp is very low","why":"People worry that cooling could protect cancer cells in the scalp; in pooled studies this happened in about 1 or 2 people in 1000.","source":"sc-ae-ma-2025","quote":"Secondary analysis of scalp metastases yielded an incidence of 0.15% (95% CI 0.05-0.47%).","grade":"systematic review and meta-analysis of 67 studies"},{"action":"For Afro hair, remove weaves or braids before cooling so the cap sits close to the scalp","why":"The cap must touch the scalp evenly to cool it enough.","source":"macmillan","quote":"If you have Afro hair, you will need to remove any weaves or braids before trying scalp cooling.","grade":"patient information, ungraded"},{"action":"Treat wetting the hair before fitting the cap as optional rather than required","why":"Damp hair conducts cold better, but in a large registry it made little difference to hair kept, and a few more people stopped because they could not tolerate it.","source":"sc-wet-2023","quote":"In a large patient group with mainly a European hair type and a high hair mass, no convincing evidence was found whether wetting hair prior to scalp cooling contributes to better prevention of CIA.","grade":"observational registry study, n = 1825"},{"action":"Start cooling at least 30 minutes before the chemotherapy and keep it running throughout the infusion","why":"The scalp must already be cold, with its blood vessels narrowed, when the drug levels in the blood are highest.","source":"paxman-k163484","quote":"Scalp cooling will begin a minimum of 30 minutes pre-infusion administration of chemotherapy.","grade":"FDA 510(k) summary (SCALP trial procedure)"},{"action":"After taxanes (docetaxel, or weekly paclitaxel), continue cooling for 20 minutes after the infusion ends","why":"Two randomised trials found 20 minutes kept hair as well as 45 or 90 minutes, which spares the person cold and chair time.","source":"lugtenberg-2022","quote":"A 20 min PICT is as effective as 45 and 90 min to prevent weekly paclitaxel-induced alopecia and should be the new standard of care.","grade":"randomised multi-centre trial (n = 74 analysed for the primary outcome)"},{"action":"After anthracycline regimens, continue cooling for about 90 minutes after the infusion, as in the trials","why":"Anthracyclines are harder on the hair; trials used 90 minutes, and going longer did not clearly help.","source":"sc-fec-2019","quote":"Extending the duration of 90-min post-infusion scalp cooling to 150 min in patients treated with adjuvant FEC chemotherapy was well-tolerated but did not significantly diminish the need for head covering.","grade":"randomised multi-centre trial, n = 102"},{"action":"Prepare the person for cold, heaviness of the cap and headache, and offer warmth and distraction","why":"These are the commonest effects and the main reasons people stop; most are worst in the first part of the first session.","source":"sc-ae-ma-2025","quote":"The most common AEs were generalized chills (42%, 95% confidence interval (CI) 26-58%), cap heaviness (35%, 95% CI 18-52%), and headache (30%, 95% CI 21-39%).","grade":"systematic review and meta-analysis of 67 studies"}],"bestInClass":{"statement":"No society guideline sets a scalp cooling procedure; the best-supported version comes from the device authorisations and randomised trials of timing. Offer cooling to people with solid tumours on regimens where it works best (taxanes), after excluding haematological cancers treated to cure and cold-sensitivity disorders; pre-cool for 30 minutes; cool throughout; then 20 minutes after docetaxel or weekly paclitaxel (two randomised trials) and about 90 minutes after anthracyclines (trial standard, with no significant gain from 150 minutes). The Dutch registry suggests under 85 minutes suffices across the regimens it studied, but it is observational. Wetting the hair is optional. Manufacturers' instructions and many units use longer post-infusion times than these trials support.","sources":["dignicap-den150010","paxman-k163484","lugtenberg-2022","sc-docetaxel-2016","sc-fec-2019","sc-dutch-pict-2025","sc-wet-2023","sc-ae-ma-2025","sc-variability-2025","onf-overview-2022"]},"variants":[{"name":"Manual frozen gel caps","differs":"A cap filled with frozen gel, changed every 20 to 40 minutes by a nurse or carer, instead of a machine-cooled cap.","evidence":"Macmillan describes the method; the 2025 review notes that gel caps must be pre-frozen, often with dry ice, and changed every 25 to 30 minutes by a caregiver. No head-to-head comparison with machine cooling was read.","sources":["macmillan","sc-variability-2025"]},{"name":"Longer pre-cooling of 30 to 45 minutes","differs":"Macmillan tells patients both types of cap need to be worn for 30 to 45 minutes before chemotherapy, longer than the 30-minute minimum in the SCALP trial.","evidence":"No trial of pre-cooling time was read; the 2025 review reports pre-cooling of 5 to 30 minutes in studies, with 30 minutes the generally accepted standard.","sources":["macmillan","sc-variability-2025"]},{"name":"Fixed 90-minute post-infusion cooling for every regimen","differs":"The SCALP trial and many units cool for at least 90 minutes after every infusion, whatever the drug.","evidence":"Used in the SCALP trial that supported FDA clearance. For taxanes, two randomised trials found 20 minutes as effective; the 2025 review notes that institutions often follow manufacturer guidance or internal protocols because there is no guideline.","sources":["paxman-k163484","sc-docetaxel-2016","lugtenberg-2022","sc-variability-2025"]}],"grades":[{"claim":"Paxman cooling preserved hair in 50.5 per cent against 0 per cent of controls (SCALP)","grade":"randomised trial, n = 142 evaluable, p < 0.0001","source":"paxman-k163484","quote":"Results show 48 (50.5%) out of 95 in the cooling group and 0 (0%) out of 47 in the control group had hair preservation."},{"claim":"20 minutes of post-infusion cooling was as effective as 45 minutes with docetaxel","grade":"randomised multi-centre trial, n = 134, p = 0.5","source":"sc-docetaxel-2016","quote":"A 20-min post-infusion cooling time is effective and tolerable for patients treated with scalp cooling to prevent docetaxel-induced alopecia."},{"claim":"Shorter post-infusion cooling (under 85 minutes) was as effective as longer across taxane and anthracycline regimens","grade":"observational registry study, 4680 patients, 68 hospitals","source":"sc-dutch-pict-2025","quote":"For all anthracycline and taxane-based chemotherapy regimens studied, shorter PICTs delivered comparable results to longer PICTs."},{"claim":"Guideline recommendations on scalp cooling are lacking","grade":"overview of 14 systematic reviews (poor quality by AMSTAR 2)","source":"onf-overview-2022","quote":"There is a lack of guideline recommendations about the use of scalp cooling for preventing chemotherapy-induced alopecia (CIA)."}],"sources":[{"key":"dignicap-den150010","label":"De Novo classification request DEN150010: DigniCap Scalp Cooling System, decision summary","publisher":"US Food and Drug Administration","year":2015,"url":"https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN150010.pdf","gradingScheme":"Regulatory decision summary, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"paxman-k163484","label":"510(k) summary K163484: Paxman Scalp Cooler","publisher":"US Food and Drug Administration","year":2017,"url":"https://www.accessdata.fda.gov/cdrh_docs/pdf16/K163484.pdf","gradingScheme":"Regulatory decision summary, not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"lugtenberg-2022","label":"Comparable effectiveness of 45- and 20-min post-infusion scalp cooling time in preventing paclitaxel-induced alopecia: a randomized controlled trial","publisher":"Supportive Care in Cancer","year":2022,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9213299/","doi":"10.1007/s00520-022-07090-7","read":"full-text","accessed":"2026-11-11"},{"key":"sc-docetaxel-2016","label":"Results of 20- versus 45-min post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia","publisher":"Supportive Care in Cancer","year":2016,"url":"https://europepmc.org/abstract/MED/26805558","doi":"10.1007/s00520-016-3084-7","read":"abstract","accessed":"2026-11-11"},{"key":"sc-fec-2019","label":"Prolonging the duration of post-infusion scalp cooling in the prevention of anthracycline-induced alopecia: a randomised trial in patients with breast cancer treated with adjuvant chemotherapy","publisher":"Supportive Care in Cancer","year":2019,"url":"https://europepmc.org/abstract/MED/30206728","doi":"10.1007/s00520-018-4432-6","read":"abstract","accessed":"2026-11-11"},{"key":"sc-dutch-pict-2025","label":"Shorter post-infusion cooling times at least as effective as longer cooling times: an observational study of taxane- and anthracycline-based chemotherapies in the Dutch Scalp Cooling Registry","publisher":"Supportive Care in Cancer","year":2025,"url":"https://europepmc.org/abstract/MED/40434428","doi":"10.1007/s00520-025-09526-2","read":"abstract","accessed":"2026-11-11"},{"key":"sc-wet-2023","label":"Minimal added value of wetting hair before scalp cooling to prevent chemotherapy-induced alopecia in cancer patients: results from the Dutch Scalp Cooling Registry","publisher":"Supportive Care in Cancer","year":2023,"url":"https://europepmc.org/abstract/MED/37067605","doi":"10.1007/s00520-023-07687-6","read":"abstract","accessed":"2026-11-11"},{"key":"sc-ae-ma-2025","label":"Adverse effects of scalp cooling for the reduction of chemotherapy-induced alopecia: a systematic review and meta-analysis","publisher":"Breast Cancer Research and Treatment","year":2025,"url":"https://europepmc.org/abstract/MED/41269388","doi":"10.1007/s10549-025-07858-5","read":"abstract","accessed":"2026-11-11"},{"key":"sc-variability-2025","label":"Scalp cooling therapy in chemotherapy-induced alopecia: addressing variability in cooling duration and efficacy","publisher":"Supportive Care in Cancer","year":2025,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12578718/","doi":"10.1007/s00520-025-10058-y","read":"full-text","accessed":"2026-11-11"},{"key":"onf-overview-2022","label":"Effectiveness, Safety, and Tolerance of Scalp Cooling for Chemotherapy-Induced Alopecia","publisher":"Oncology Nursing Forum","year":2022,"url":"https://europepmc.org/abstract/MED/35788740","doi":"10.1188/22.ONF.369-384","read":"abstract","accessed":"2026-11-11"},{"key":"macmillan","label":"Scalp cooling","publisher":"Macmillan Cancer Support","year":2026,"url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/hair-loss/scalp-cooling","gradingScheme":"Patient information, not graded.","read":"public-summary","accessed":"2026-11-11"}],"upgrades":["idea-moon-hair-preservation-for-all","idea-upgrade-twenty-minute-post-infusion-scalp-cooling-after-taxanes","idea-mach-cooling-off-the-chair"],"gaps":["No ESMO, ASCO, MASCC, ONS or NICE guideline on scalp cooling was found; the ESMO 2021 dermatological toxicity guideline, which covers alopecia, could not be read (the publisher refused a script).","Hair care during and after cooling (gentle washing, avoiding heat styling, colouring and tight hairstyles) is widely advised by manufacturers and units, but no independent source setting it out could be read; Paxman's hair care page returned no usable text and the Breast Cancer Now and Breastcancer.org pages tried were not found.","The FDA decisions read are limited to women with breast cancer; later extensions to other solid tumours were not read.","The timing trials were read as abstracts, except the 2022 paclitaxel trial; post-infusion times for other drugs (for example antibody-drug conjugates such as trastuzumab deruxtecan or sacituzumab govitecan) were not covered by the trials read.","Whether wetting the hair helps people with dense or Afro-textured hair is not known: the Dutch registry was mainly European hair type, and its authors call for a randomised trial.","The SCALP result is from the 510(k) summary of the trial, not the published paper, which was not read here."]},{"id":"sentinel-node-tracers-and-blue-dye-safety","kind":"protocol","name":"Sentinel node tracers and blue dye: injection, allergic reaction readiness and aftercare","aka":["sentinel lymph node mapping tracer","blue dye anaphylaxis","isosulfan blue reaction","patent blue anaphylaxis","dual technique sentinel node biopsy","lymphatic mapping dye safety"],"tldr":"To find the sentinel lymph node, a radioactive tracer and often a blue dye are injected near the tumour. Severe allergic reactions to the blue dye are rare (about 2 in 1,000 in the largest pooled study) but can come late, so the team asks about allergies beforehand and watches you closely for at least an hour. Your urine may be blue for a day and the skin can stay blue-stained for a while.","summary":"NICE NG101 tells UK breast teams to perform SLNB 'using the dual technique with isotope and blue dye' (2009 recommendation, unchanged in the current guideline). In a systematic review of 24 prospective studies, adding blue dye to isotope raised the identification rate (OR 2.03) but did not lower the false-negative rate. Isosulfan blue: hypersensitivity in about 2% (label), with life-threatening anaphylaxis possible; risk is higher with asthma, allergies, drug reactions or a previous reaction to triphenylmethane dyes; monitor for at least 60 minutes with trained staff and resuscitation available; do not mix with lidocaine in the same syringe; pulse oximetry reads falsely low (maximal at 30 minutes). A 2025 meta-analysis (8 studies, 19,183 breast patients) found 11.65 adverse events per 1,000 and 1.86 per 1,000 needing vasopressors, with no deaths; intraparenchymal injection had more events than peritumoral. NAP6 (UK, 266 severe perioperative anaphylaxis cases) identified Patent Blue as the culprit in 9 of 199, with delayed onset compared with antibiotics and neuromuscular blockers. Technetium tilmanocept: ask about dextran reactions and have resuscitation ready. Indocyanine green fluorescence was equivalent to isotope and superior to dual isotope and blue dye for identification in a 2020 meta-analysis.","asOf":"2026-11-11","links":[],"tags":[],"related":["surgical-site-infection-prevention"],"cancers":[],"sections":[],"technologies":["sentinel-node","magnetic-sentinel-node-tracer"],"targets":[],"drugs":["isosulfan-blue","tilmanocept-tc99m","technetium-sulfur-colloid"],"companies":[],"institutions":[],"pathways":[],"terms":["sentinel-lymph-node-biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Tell the team about any allergy, asthma, or reaction to a dye or to dextran. After the blue dye, you will be watched for at least an hour. Blue or green urine for a day is expected.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","radiographer","nurse","patient-or-carer"],"where":["theatre","outpatient-clinic","ward"]},"population":"Adults having sentinel lymph node biopsy, chiefly for early breast cancer and melanoma, also vulval, cervical, endometrial, penile and oral cancers where the operation is offered. The sources read are mainly about breast cancer; tracer choice and injection site differ by cancer and are set by the team.","trigger":"A planned sentinel lymph node biopsy.","steps":[{"action":"For early breast cancer, use the dual technique: radioisotope plus blue dye (UK, NICE)","why":"Using two tracers finds the sentinel node more often than isotope alone.","source":"nice-ng101","quote":"Perform SLNB using the dual technique with isotope and blue dye. [2009]","grade":"Not graded (NICE NG101 1.4.10, 'perform', 2009)"},{"action":"Before injecting blue dye, ask about asthma, allergies, previous drug reactions and any earlier reaction to a blue dye","why":"Allergic reactions to the dye are more likely in these people, and the team can plan for that or choose another tracer.","source":"isosulfan-us","quote":"Reactions are more likely to occur in patients with a history of bronchial asthma, allergies, drug reactions or previous reactions to tri-phenylmethane dyes.","grade":"Label warning (no grade)"},{"action":"Before a tilmanocept (Lymphoseek) injection, ask about reactions to dextran or iron dextran","why":"This tracer is chemically similar to dextran, which can cause serious allergic reactions.","source":"lymphoseek-us","quote":"Before administering Lymphoseek, ask patients about prior hypersensitivity reactions to drugs, especially to dextran and modified forms of dextran.","grade":"Label warning (no grade)"},{"action":"Have resuscitation equipment and staff trained to use it immediately available when any tracer is injected","why":"A severe allergic reaction needs treatment within minutes.","source":"lymphoseek-us","quote":"Have resuscitation equipment and trained personnel immediately available at the time of Lymphoseek administration.","grade":"Label warning (no grade)"},{"action":"Draw up isosulfan blue in its own syringe, never mixed with lidocaine","why":"Mixed in one syringe, the two form a solid deposit at once.","source":"isosulfan-us","quote":"The admixture of isosulfan blue injection 1% (with local anesthetics (i.e. lidocaine)) in the same syringe results in an immediate precipitation of 4% to 9% drug complex. Use a separate syringe to administer a local anesthetic.","grade":"Label warning (no grade)"},{"action":"Watch the patient closely for at least 60 minutes after blue dye, remembering that reactions to it can start late","why":"Unlike reactions to antibiotics, reactions to blue dye often appear well after the injection, sometimes after surgery has moved on.","source":"isosulfan-us","quote":"Monitor patients closely for at least 60 minutes after administration of isosulfan blue injection 1%. Trained personnel should be available to administer emergency care including resuscitation.","grade":"Label warning (no grade)"},{"action":"Expect pulse oximetry to read falsely low after blue dye; confirm a low reading with an arterial blood gas","why":"The blue colour in the blood fools the finger probe for up to a few hours.","source":"isosulfan-us","quote":"Isosulfan blue injection 1% interferes with measurements of oxygen saturation in peripheral blood by pulse oximetry and can cause falsely low readings. The interference effect is maximal at 30 minutes and minimal generally by 4 hours after administration.","grade":"Label warning (no grade)"},{"action":"Tell the patient their urine may be blue for 24 hours and the skin at the injection site may stay blue","why":"Knowing in advance prevents alarm; the skin staining can last a long time.","source":"isosulfan-us","quote":"Inform patients that urine color may be blue for 24 hours following administration of isosulfan blue injection 1%.","grade":"Label instruction (no grade)"}],"bestInClass":{"statement":"In the UK, NICE NG101 sets the dual technique (isotope plus blue dye) for breast cancer. The evidence for blue dye is a higher identification rate without a lower false-negative rate (BMC Cancer 2016), at the cost of rare severe allergic reactions (1.86 per 1,000 needing vasopressors in the 2025 meta-analysis; 9 of 199 culprit agents in NAP6). Safety readiness comes from the product labels: ask about risk factors, have resuscitation ready, observe for at least 60 minutes, and allow for late onset and false pulse oximetry readings. The EANM/SNMMI procedure guideline, which sets injection technique and imaging, could not be read.","sources":["nice-ng101","blue-dye-meta-2016","isosulfan-meta-2025","nap6-epidemiology","isosulfan-us","lymphoseek-us"]},"variants":[{"name":"Indocyanine green (ICG) fluorescence instead of blue dye","differs":"Uses a fluorescent dye seen with a near-infrared camera, alone or with isotope, avoiding blue dye's allergy risk and tattooing.","evidence":"Meta-analysis of 10 studies: ICG equivalent to isotope and superior to dual isotope and blue dye for identification; not yet the NICE standard.","sources":["icg-meta-2020"]},{"name":"Isotope alone","differs":"Omits blue dye where lymphoscintigraphy shows a node, to avoid dye reactions and staining.","evidence":"Dual tracers' advantage was not significant in studies with a high proportion of positive lymphoscintigraphy (OR 1.41, not significant), and dual tracers did not lower the false-negative rate.","sources":["blue-dye-meta-2016"]},{"name":"Peritumoral rather than intraparenchymal blue dye injection","differs":"Injects isosulfan blue around the tumour rather than into the breast tissue.","evidence":"Fewer adverse events (7.04 vs 15.16 per 1,000, p=0.02) in a meta-analysis of observational studies; no dose-response with volume.","sources":["isosulfan-meta-2025"]}],"grades":[{"claim":"Isosulfan blue hypersensitivity rate","grade":"Case series reported in the label","source":"isosulfan-us","quote":"Hypersensitivity Reactions: Hypersensitivity reactions occur in approximately 2% of patients and include life threatening anaphylactic reactions with respiratory distress, shock, angioedema, urticaria, pruritus."},{"claim":"Severe reactions to isosulfan blue are uncommon","grade":"Meta-analysis of 8 observational studies, 19,183 patients","source":"isosulfan-meta-2025","quote":"The rate of Grade I reactions was 7.96 per 1,000 (95% CI 4.08-15.46); Grade II 0.08 per 1,000 (95% CI 0.00-1.31), Grade III 1.86 per 1,000 (95% CI 0.94-3.66), with no reported mortalities."},{"claim":"Patent Blue is a recognised cause of perioperative anaphylaxis, with delayed onset","grade":"National audit, 266 reports (NAP6)","source":"nap6-epidemiology","quote":"Onset was rapid for neuromuscular blocking agents and antibiotics, but delayed with chlorhexidine and Patent Blue dye."},{"claim":"Adding blue dye raises identification but not the false-negative rate","grade":"Systematic review of 24 prospective studies","source":"blue-dye-meta-2016","quote":"Dual tracers did not significantly lower the false-negative rate compared with radioisotope alone (OR = 0.76, 95% CI 0.44-1.29, P > 0.05)."},{"claim":"Management of perioperative anaphylaxis could be better","grade":"National audit (NAP6)","source":"nap6-management","quote":"Management of perioperative anaphylaxis could be improved, especially with respect to administration of epinephrine, cardiac compressions, and i.v. fluid."}],"sources":[{"key":"nice-ng101","label":"Early and locally advanced breast cancer: diagnosis and management (NG101), recommendations","publisher":"NICE","year":2018,"url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'perform', 'consider') signals strength, and the year in brackets is when each was written.","read":"full-text","accessed":"2026-11-11"},{"key":"isosulfan-us","label":"Isosulfan blue injection 1% US prescribing information, DailyMed (Mylan Institutional, version of 25 May 2026)","publisher":"US FDA (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0391e544-3633-48df-9f3a-ed16183125b1","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"lymphoseek-us","label":"Lymphoseek (technetium Tc 99m tilmanocept) US prescribing information, DailyMed (version of 2 September 2026)","publisher":"US FDA (DailyMed)","year":2026,"url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=72f31b09-4d7b-475c-b37a-9daf2ad80240","gradingScheme":"Regulatory label; no grading.","read":"full-text","accessed":"2026-11-11"},{"key":"nap6-epidemiology","label":"Harper et al., Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6) (Br J Anaesth 2018)","publisher":"Royal College of Anaesthetists (British Journal of Anaesthesia)","year":2018,"url":"https://doi.org/10.1016/j.bja.2018.04.014","doi":"10.1016/j.bja.2018.04.014","gradingScheme":"National audit; no recommendation grade.","read":"abstract","accessed":"2026-11-11"},{"key":"nap6-management","label":"Harper et al., Anaesthesia, surgery, and life-threatening allergic reactions: management and outcomes in the 6th National Audit Project (NAP6) (Br J Anaesth 2018)","publisher":"Royal College of Anaesthetists (British Journal of Anaesthesia)","year":2018,"url":"https://doi.org/10.1016/j.bja.2018.04.015","doi":"10.1016/j.bja.2018.04.015","gradingScheme":"National audit; no recommendation grade.","read":"abstract","accessed":"2026-11-11"},{"key":"isosulfan-meta-2025","label":"Adverse Effects of Intraparenchymal and Peritumoral Application of Isosulfan Blue Dye in Sentinel Lymph Node Mapping in Breast Cancer: a systematic review and meta-analysis (Eur J Breast Health 2025)","publisher":"European Journal of Breast Health","year":2025,"url":"https://doi.org/10.4274/ejbh.galenos.2024.2024-8-1","doi":"10.4274/ejbh.galenos.2024.2024-8-1","gradingScheme":"Meta-analysis; no recommendation grade.","read":"full-text","accessed":"2026-11-11"},{"key":"blue-dye-meta-2016","label":"The combination of blue dye and radioisotope versus radioisotope alone during sentinel lymph node biopsy for breast cancer: a systematic review (BMC Cancer 2016)","publisher":"BMC Cancer","year":2016,"url":"https://doi.org/10.1186/s12885-016-2137-0","doi":"10.1186/s12885-016-2137-0","gradingScheme":"Systematic review; no recommendation grade.","read":"full-text","accessed":"2026-11-11"},{"key":"icg-meta-2020","label":"Meta-analysis Comparing Fluorescence Imaging with Radioisotope and Blue Dye-Guided Sentinel Node Identification for Breast Cancer Surgery (Ann Surg Oncol 2020)","publisher":"Annals of Surgical Oncology","year":2020,"url":"https://doi.org/10.1245/s10434-020-09288-7","doi":"10.1245/s10434-020-09288-7","gradingScheme":"Meta-analysis; no recommendation grade.","read":"full-text","accessed":"2026-11-11"},{"key":"eanm-snmmi-2013","label":"The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer (Eur J Nucl Med Mol Imaging 2013)","publisher":"EANM and SNMMI","year":2013,"url":"https://doi.org/10.1007/s00259-013-2544-2","doi":"10.1007/s00259-013-2544-2","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-pu-sentinel-node-without-blue-dye"],"gaps":["The EANM/SNMMI procedure guideline (2013), which sets tracer dose, injection site and imaging timing, could not be read; injection technique is therefore not given step by step here.","The UK product information for Patent Blue V, the blue dye used in the UK, was not reachable; the safety steps here come from the US isosulfan blue label, a closely related triphenylmethane dye, and from NAP6.","How to treat anaphylaxis once it starts (adrenaline dose and route, fluids, referral for allergy testing) follows resuscitation and anaesthetic guidance not read here.","Methylene blue is used as a cheaper dye in some countries; its safety relative to isosulfan and patent blue rests on a paper whose abstract could not be read here.","Whether ICG or magnetic tracers should replace blue dye in the UK standard has not been settled by NICE in the sources read."]},{"id":"sex-and-contraception-during-chemotherapy","kind":"protocol","name":"Sex, contraception and barrier protection during and after chemotherapy","aka":["contraception during chemotherapy","condoms after chemotherapy","pregnancy prevention during cancer treatment","sex during chemotherapy","birth control and cancer treatment"],"tldr":"Chemotherapy can harm an unborn baby, and pregnancy is still possible even when fertility is affected, so anyone who could get pregnant, or get a partner pregnant, needs contraception during treatment and for a time after. Condoms are usually advised, and they also protect a partner from traces of drug in body fluids after some treatments. Ask your team which method suits you and for how long.","summary":"Patient guidance from Macmillan (2018), the NHS (2025) and NCI (2023) agrees that chemotherapy can harm a pregnancy, that contraception is needed by anyone who could get pregnant or make a partner pregnant during treatment and for a time after, that a pregnancy test may be done before treatment, and that pregnancy remains possible even when fertility is reduced. Macmillan says barrier methods are usually best during treatment, condoms (or a dental dam for oral sex) for a few days after certain drugs protect partners from drug in body fluids, and breastfeeding is not advised. NCI says to prevent pregnancy for a year after chemotherapy and that some teams suggest two methods. The Society of Family Planning (2025) recommends offering a discussion of contraception before treatment to everyone who is pregnancy-capable, says emergency contraception is safe, recommends nonhormonal contraception first line after breast cancer (GRADE 1B) and avoiding oestrogen-containing methods with oestrogen-blocking therapy (best practice), and supports access to all methods for most other cancers. US MEC 2024 lists breast cancer among conditions in which pregnancy carries added risk. ASCO 2025 says fertility preservation should be discussed before treatment. The ESMO 2020 fertility and pregnancy guideline could not be read.","asOf":"2026-11-11","links":[],"tags":[],"related":["idea-acc-default-fertility-preservation-referral","oral-anticancer-medicines-at-home"],"cancers":[],"sections":[],"technologies":["fertility-preservation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cancer-in-pregnancy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Most people can have sex during chemotherapy, but ask your team first. Use contraception during treatment and for as long afterwards as your team says, because the drugs can harm a baby. Condoms are usually best. After some drugs, use a condom for a few days to protect your partner. Tell your team straight away if you might be pregnant.","domain":"supportive-care","setting":{"who":["patient-or-carer","doctor","nurse"],"where":["home","outpatient-clinic"]},"population":"Adults having chemotherapy who are sexually active and could become pregnant or make a partner pregnant, and their partners. Advice differs for people with hormone-sensitive cancers (breast cancer in particular), people after a stem cell transplant, and people with very low blood counts; those differences are named in the steps.","trigger":"Before chemotherapy starts, and again at any change of treatment.","steps":[{"action":"Before treatment, talk with the team about contraception, pregnancy and fertility, including storing eggs or sperm","why":"Choices about fertility must be made before treatment, and the right contraceptive depends on the cancer and the drugs.","source":"sfp-2025-part1","quote":"No test reliably rules out pregnancy potential in cancer survivors; clinicians should offer to discuss contraception with individuals who are pregnancy-capable before cancer treatment.","grade":"Committee statement (Society of Family Planning); not graded in the abstract"},{"action":"Use contraception during treatment and for as long afterwards as the team advises, if you could get pregnant or get a partner pregnant","why":"Chemotherapy can harm a developing baby, and pregnancy can still happen even if fertility has been reduced.","source":"nhs-chemotherapy","quote":"It's important to use contraception during treatment if you could get pregnant or you could get your partner pregnant.","grade":"Not graded (patient information)"},{"action":"Ask which method is best; barrier methods such as condoms or a cap are usually advised during treatment","why":"Some hormonal methods are unsuitable with some cancers and drugs, and barrier methods are safe for almost everyone.","source":"macmillan-chemo-side-effects","quote":"During treatment, it is usually best to use barrier methods of contraception, such as condoms or the cap (diaphragms). Ask your cancer doctor or specialist nurse which type is best for you to use.","grade":"Not graded (patient information)"},{"action":"After breast cancer, use a nonhormonal method first line, and avoid oestrogen-containing contraception if taking oestrogen-blocking therapy","why":"Breast cancer is often hormone-sensitive, and oestrogen-containing methods work against oestrogen-blocking treatment.","source":"sfp-2025-part2","quote":"For individuals with a history of breast cancer, we recommend nonhormonal contraceptives as the first-line option (GRADE 1B); additional guidance is provided for hormonal contraception depending on breast cancer hormone receptor status.","grade":"GRADE 1B (nonhormonal first line after breast cancer); Best Practice (avoid oestrogen with oestrogen-blocking therapy)"},{"action":"If the team advises it, use a condom for vaginal or anal sex, and a condom or dental dam for oral sex, for a few days after certain drugs","why":"Small amounts of some drugs reach semen and vaginal fluid, and a barrier protects a partner from them.","source":"macmillan-chemo-side-effects","quote":"To protect partners, your cancer doctor may advise that for a few days after certain drugs you use a condom for vaginal or anal sex and a condom (or a latex barrier such as a dental dam) for oral sex.","grade":"Not graded (patient information)"},{"action":"Ask the team whether sex is safe for you during treatment, especially when blood counts are low or after a stem cell transplant","why":"Most people can have sex, but very low platelets or white cells change the risks of bleeding and infection.","source":"nci-chemo-and-you","quote":"Ask your doctor or nurse if it is okay for you to have sex during chemotherapy.","grade":"Not graded (patient booklet)"},{"action":"Use emergency contraception if needed; it is safe for people with cancer","why":"A missed or failed method should not be left uncovered during treatment.","source":"sfp-2025-part1","quote":"Clinicians should counsel individuals with cancer that it is safe for them to use emergency contraception.","grade":"Committee statement (Society of Family Planning); not graded in the abstract"},{"action":"Tell the team straight away if you are, or might be, pregnant","why":"The team can explain the risks and options, which depend on the drugs and the stage of pregnancy.","source":"macmillan-chemo-side-effects","quote":"If you know you are pregnant before starting treatment, or become pregnant during treatment, tell your cancer doctor or nurse straight away.","grade":"Not graded (patient information)"},{"action":"Do not breastfeed during chemotherapy","why":"The drugs can pass to a baby in breast milk.","source":"macmillan-chemo-side-effects","quote":"Breastfeeding during chemotherapy is not advised.","grade":"Not graded (patient information)"},{"action":"For vaginal dryness, use a water-based lubricant, and ask about other treatments if sex is still painful","why":"Chemotherapy can lower hormone levels and cause dryness, which makes sex uncomfortable.","source":"nci-chemo-and-you","quote":"If sex is still painful because of dryness, ask your doctor or nurse about medications to help restore moisture in your vagina.","grade":"Not graded (patient booklet)"}],"bestInClass":{"statement":"Contraception for anyone pregnancy-capable, or with a pregnancy-capable partner, during chemotherapy and for a period after is agreed by every source read (NHS 2025, NCI 2023, Macmillan 2018, Society of Family Planning 2025). The Society of Family Planning 2025 series is the most recent specialist guidance: discuss contraception before treatment with everyone pregnancy-capable, emergency contraception is safe, nonhormonal methods first after breast cancer (GRADE 1B), no oestrogen with oestrogen-blocking therapy (best practice), and access to all methods for most other cancers. How long to continue after treatment is not agreed: NCI says a year, Macmillan says 'for a time after', and the real figure depends on the drug's label, which the team gives.","sources":["sfp-2025-part1","sfp-2025-part2","sfp-2025-part3","nhs-chemotherapy","nci-chemo-and-you","macmillan-chemo-side-effects"]},"variants":[{"name":"A year of pregnancy prevention, possibly with two methods (NCI)","differs":"Sets a fixed year after chemotherapy for women and says some teams suggest two forms of birth control.","evidence":"NCI booklet, not graded: 'It is very important to prevent pregnancy while having chemotherapy and for a year afterwards.' Other sources leave the period to the drug and the team.","sources":["nci-chemo-and-you"]},{"name":"Hormonal and intrauterine methods for most cancers other than breast (Society of Family Planning)","differs":"Supports access to all contraceptive methods for most other cancers, with shared decision-making for some hormone-sensitive tumours (for example adult granulosa cell, low-grade serous and endometrioid ovarian tumours, melanoma, meningioma, follicular lymphoma), and advises against an IUD with active cervical cancer.","evidence":"Society of Family Planning 2025 parts 2 and 3: GRADE 1B to 2C depending on the cancer, as printed in the abstracts.","sources":["sfp-2025-part2","sfp-2025-part3"]},{"name":"Avoiding close contact after high-dose chemotherapy or stem cell transplant (Macmillan)","differs":"After high-dose chemotherapy or a stem cell transplant, the team may advise no close physical contact for a while, to prevent infection.","evidence":"Patient information, not graded.","sources":["macmillan-chemo-side-effects"]}],"grades":[{"claim":"Nonhormonal contraception first line after breast cancer","grade":"GRADE 1B","source":"sfp-2025-part2","quote":"For individuals with a history of breast cancer, we recommend nonhormonal contraceptives as the first-line option (GRADE 1B); additional guidance is provided for hormonal contraception depending on breast cancer hormone receptor status."},{"claim":"No oestrogen-containing contraception with oestrogen-blocking therapy","grade":"Best Practice","source":"sfp-2025-part2","quote":"Estrogen-containing contraceptives should be avoided by individuals treated with estrogen-blocking therapy (Best Practice)."},{"claim":"Access to all methods after colorectal, pancreatic, oesophageal and gastric cancer","grade":"GRADE 1C","source":"sfp-2025-part3","quote":"For individuals with a history of colorectal, pancreatic, esophageal, and gastric cancer, we recommend clinicians provide access to all available contraceptive methods (GRADE 1C)."},{"claim":"Breast cancer is hormonally sensitive; LNG-IUD may carry less concern than combined or higher-dose progestogen methods","grade":"US MEC 2024 classification comment","source":"us-mec-2024","quote":"Breast cancer is a hormonally sensitive tumor. Concerns about progression of the disease might be less with LNG-IUDs than with COCs or higher-dose POCs."},{"claim":"Fertility preservation discussed before treatment","grade":"ASCO guideline recommendation (strength not shown in the abstract)","source":"asco-fp-2025","quote":"FP approaches should be discussed before cancer-directed therapy."}],"sources":[{"key":"macmillan-chemo-side-effects","label":"Side effects of chemotherapy","publisher":"Macmillan Cancer Support","year":2018,"url":"https://www.macmillan.org.uk/cancer-information-and-support/treatment/types-of-treatment/chemotherapy/side-effects-of-chemotherapy","gradingScheme":"Patient information page; not graded. Reviewed September 2018, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"nhs-chemotherapy","label":"Chemotherapy","publisher":"NHS","year":2025,"url":"https://www.nhs.uk/tests-and-treatments/chemotherapy/","gradingScheme":"Patient information page; not graded. Reviewed 14 February 2025.","read":"full-text","accessed":"2026-11-11"},{"key":"nci-chemo-and-you","label":"Chemotherapy and You: Support for People with Cancer","publisher":"National Cancer Institute (US)","year":2023,"url":"https://www.cancer.gov/publications/patient-education/chemotherapy-and-you.pdf","gradingScheme":"Patient booklet; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"us-mec-2024","label":"U.S. Medical Eligibility Criteria for Contraceptive Use, 2024","publisher":"CDC (MMWR Recommendations and Reports)","year":2024,"url":"https://doi.org/10.15585/mmwr.rr7304a1","doi":"10.15585/mmwr.rr7304a1","gradingScheme":"Categories 1 to 4 for each method and condition (1 no restriction, 4 unacceptable health risk).","read":"full-text","accessed":"2026-11-11"},{"key":"sfp-2025-part1","label":"Society of Family Planning Committee Statement: Contraceptive considerations for individuals with cancer and cancer survivors part 1, key considerations for clinical care","publisher":"Society of Family Planning and Society of Gynecologic Oncology (Contraception)","year":2025,"url":"https://doi.org/10.1016/j.contraception.2025.110870","doi":"10.1016/j.contraception.2025.110870","gradingScheme":"Committee statement; not graded in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"sfp-2025-part2","label":"Society of Family Planning Clinical Recommendation: Contraceptive considerations for individuals with cancer and cancer survivors part 2, breast, ovarian, uterine and cervical cancer","publisher":"Society of Family Planning and Society of Gynecologic Oncology (Contraception)","year":2025,"url":"https://doi.org/10.1016/j.contraception.2025.110867","doi":"10.1016/j.contraception.2025.110867","gradingScheme":"GRADE strength (1 strong, 2 weak) and certainty (A to C), printed after each recommendation in the abstract; some statements are labelled Best Practice.","read":"abstract","accessed":"2026-11-11"},{"key":"sfp-2025-part3","label":"Society of Family Planning Clinical Recommendation: Contraceptive considerations for individuals with cancer and cancer survivors part 3, skin, blood, gastrointestinal, liver, lung, central nervous system and other cancers","publisher":"Society of Family Planning and Society of Gynecologic Oncology (Contraception)","year":2025,"url":"https://doi.org/10.1016/j.contraception.2025.110869","doi":"10.1016/j.contraception.2025.110869","gradingScheme":"GRADE strength (1 strong, 2 weak) and certainty (A to C), printed after each recommendation in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"asco-fp-2025","label":"Fertility Preservation in People With Cancer: ASCO Guideline Update","publisher":"ASCO (Journal of Clinical Oncology)","year":2025,"url":"https://doi.org/10.1200/JCO-24-02782","doi":"10.1200/JCO-24-02782","gradingScheme":"ASCO evidence quality and recommendation strength; not shown in the abstract.","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-fertility-2020","label":"Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2020,"url":"https://doi.org/10.1016/j.annonc.2020.09.006","doi":"10.1016/j.annonc.2020.09.006","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["How long to continue contraception after treatment depends on each drug's label; the patient sources give a year (NCI) or 'a time' (Macmillan), and no source read here gives drug-by-drug periods.","How much drug reaches semen or vaginal fluid, and for how long, is poorly measured; the 'few days' of condom use is expert advice.","The ESMO 2020 guideline on fertility preservation and pregnancy after treatment could not be read (bot check on the journal page, no abstract in PubMed).","The Society of Family Planning 2025 series and the ASCO 2025 fertility guideline were read as abstracts only.","Macmillan's chemotherapy side effects page was last reviewed in 2018 and is marked as under review.","Advice for trans and non-binary people, and for same-sex partners, is not addressed in the patient sources beyond the Society of Family Planning's call for person-centred care."]},{"id":"sexual-health-assessment-and-interventions","kind":"protocol","name":"Sexual health after cancer: assessment and interventions for women and men","aka":["sexual dysfunction after cancer","sexual problems in people with cancer","vaginal dryness after cancer treatment","erectile dysfunction after cancer","psychosexual counselling","vaginal dilators","penile rehabilitation"],"tldr":"Cancer and its treatment often change sex, desire, body image and relationships, for women and men. Guidelines say your team should raise it so you do not have to. Help includes counselling, alone or as a couple; moisturisers, lubricants and then low-dose vaginal oestrogen for dryness; dilators and pelvic floor physiotherapy; and tablets, devices or injections for erection problems.","summary":"The Cancer Care Ontario guideline (2016, published 2017), adapted by ASCO in 2018 with added statements, makes one overarching recommendation: a member of the healthcare team should start a discussion about sexual health and dysfunction caused by the cancer or its treatment, ideally including a partner, at diagnosis and periodically through follow-up. ASCO adds that medical and treatable contributing factors should be found and addressed first, and that psychosocial or psychosexual counselling should be offered to all patients.\n\nFor women, CCO recommends psychosocial counselling for problems with sexual response, body image, intimacy and overall function (couples-based where partnered), with exercise or pelvic floor physiotherapy as possible additions; vaginal moisturisers and lubricants first for vaginal atrophy, then vaginal oestrogen, which can be considered after discussion in hormone-receptor-positive breast cancer when conservative measures fail and is of uncertain safety with aromatase inhibitors; vaginal dilators for vaginismus or stenosis, and to prevent stenosis after radiotherapy for cervical cancer; and pelvic floor physiotherapy for pain. For men, PDE5 inhibitors first for erectile dysfunction regardless of type of surgery, then a vacuum device, urethral medication or intracavernosal injection; counselling combined with PDE5 inhibitors, ideally for the couple; and daily vacuum device use to prevent loss of penile length. The evidence is mostly low to moderate quality.\n\nA 2025 comparison of ASCO 2018, ESO-ESMO 2022, NCCN 2024 and SOGC 2024 for women found consensus on non-hormonal moisturisers and lubricants first and low-dose vaginal oestrogen second, and on multidisciplinary and psychological care; ESO-ESMO alone did not include recommendations on drugs for low desire, for which the data are limited.","asOf":"2026-11-11","links":[],"tags":["protocol","survivorship","sexual-health"],"related":["fertility-preservation-before-cancer-treatment","hot-flushes-on-endocrine-therapy-non-hormonal-options"],"cancers":[],"sections":["supportive-care"],"technologies":["sexual-function-after-cancer","vaginal-oestrogen-after-breast-cancer","menopause-after-cancer-treatment"],"targets":[],"drugs":[],"companies":[],"institutions":["ontario-health-cancer-care-ontario","asco","esmo"],"pathways":[],"terms":["erectile-dysfunction-after-prostate-cancer","sex-fertility-after-bowel-cancer","quality-of-life","late-effects"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer can change your sex life. Your team should ask about it. There are treatments and counselling that help.","domain":"survivorship","setting":{"who":["doctor","nurse","multidisciplinary-team","patient-or-carer"],"where":["outpatient-clinic","community"]},"population":"Adults with any cancer, during and after treatment, and their partners. The guideline's evidence is mostly from breast, gynaecological and prostate cancer. Children and adolescents, and fertility questions, are outside it (fertility has its own protocol).","trigger":"At diagnosis, and periodically through treatment and follow-up.","steps":[{"action":"Raise sexual health with every patient at diagnosis and periodically through follow-up, including the partner where the patient wishes","why":"Many people never mention sexual problems unless asked; nothing else can help until someone opens the conversation.","source":"cco-2017","quote":"The issue should be raised at the time of diagnosis and should continue to be reassessed periodically throughout follow-up."},{"action":"Find and treat medical and treatable contributing causes first","why":"Some problems have a direct physical cause that can be treated.","source":"asco-2018","quote":"Medical and treatable contributing factors should be identified and addressed first."},{"action":"Offer psychosocial or psychosexual counselling to all patients, as a couple where they are partnered","why":"Counselling improved sexual response, body image and intimacy in the studies reviewed, and helps couples adapt.","source":"asco-2018","quote":"Psychosocial and/or psychosexual counseling should be offered to all patients with cancer, aiming to improve sexual response, body image, intimacy and relationship issues, and overall sexual functioning and satisfaction."},{"action":"For vaginal dryness, start with vaginal moisturisers for daily comfort and lubricants for sex","why":"These are safe, need no prescription in most countries, and help many women.","source":"cco-2017","quote":"Women with symptoms from vaginal atrophy should be managed in the same way as women without cancer: vaginal moisturizers for daily comfort or lubricants with sexual activity, or both."},{"action":"If dryness persists or is severe, consider low-dose vaginal oestrogen; in hormone-receptor-positive breast cancer only after discussion of the uncertainty","why":"Vaginal oestrogen works well, but whether it is safe with aromatase inhibitors is not known from the data available.","source":"cco-2017","quote":"For women with hormone-positive breast cancer who are symptomatic and not responding to conservative measures, vaginal estrogen can be considered after a discussion. Whether vaginal estrogen can be used safely in women with breast cancer on aromatase inhibitors is uncertain because of limited data."},{"action":"Offer vaginal dilators for vaginismus or narrowing, including after pelvic radiotherapy for cervical cancer, and pelvic floor physiotherapy for pain","why":"Radiotherapy and surgery can narrow the vagina and cause pain; dilators and physiotherapy can prevent or ease this.","source":"cco-2017","quote":"Vaginal dilators can be of benefit in the management of vaginismus or vaginal stenosis. The expert panel felt that there was a role for vaginal dilators in the prevention of stenosis for patients with cervical cancer treated with radiation."},{"action":"For erectile dysfunction, offer a PDE5 inhibitor first, whatever the type of surgery, unless the man takes nitrates","why":"These tablets help many men after cancer treatment; they must not be combined with nitrate heart medicines.","source":"cco-2017","quote":"And although pde 5i medications might be most effective for men whose radical prostatectomy used a nerve-sparing approach, it is recommended that those agents be used as a first-line approach regardless of the type of surgery."},{"action":"If tablets do not work, consider a vacuum erection device, urethral medication or penile injections, and a daily vacuum device to prevent loss of penile length","why":"Other treatments work where tablets do not, and starting early may give a better result.","source":"cco-2017","quote":"For men who do not respond to pde 5i medications, alternative interventions such as a vacuum erectile device, a medicated urethral system for erection, or intracavernosal injection should be considered."}],"bestInClass":{"statement":"The CCO guideline (2016), adapted by ASCO (2018), remains the most complete cancer-specific guideline read: raise the subject routinely, treat contributing causes, offer counselling to all, and use the women's and men's interventions above. Later guidelines for women (ESO-ESMO 2022, NCCN 2024, SOGC 2024), as compared in 2025, agree on moisturisers and lubricants first and low-dose vaginal oestrogen second and on counselling; they differ on drugs for low desire, which all but ESO-ESMO include despite limited data, and on dilators and pelvic physiotherapy, recommended by ASCO, NCCN and SOGC. Those three later guidelines were not read directly.","sources":["cco-2017","asco-2018","nice-ng23","compare-2025"]},"variants":[{"name":"NICE NG23 (2024): vaginal oestrogen after breast cancer, with specialist input on aromatase inhibitors","differs":"Sets the same order as CCO (non-hormonal moisturisers or lubricants first, then vaginal oestrogen if symptoms continue) for anyone with a personal history of breast cancer, and for people currently on adjuvant aromatase inhibitors asks the team to work with a breast cancer specialist rather than prescribe directly.","evidence":"NICE evidence reviews on genitourinary symptoms and breast cancer recurrence; NICE says it is unknown whether vaginal oestrogen affects the risk of recurrence, that systemic absorption is minimal compared with HRT, and that it is likely to be safe after oestrogen receptor-negative breast cancer. Vaginal oestrogen after breast cancer was off-label in November 2024.","sources":["nice-ng23"]},{"name":"Regular self-stimulation to improve sexual response (CCO and ASCO)","differs":"Adds regular stimulation, including masturbation, as advice for both women and men.","evidence":"Expert opinion of the CCO working group; ASCO includes it; NCCN and SOGC recommend sexual aids such as vibrators, per the 2025 comparison.","sources":["cco-2017","compare-2025"]},{"name":"Drugs for low sexual desire in women (NCCN 2024, SOGC 2024)","differs":"Includes androgens, bupropion, flibanserin, bremelanotide or buspirone for low desire.","evidence":"Included by ASCO, NCCN and SOGC and not by ESO-ESMO; the 2025 comparison notes limited data. CCO made no recommendation for drugs to improve women's sexual response.","sources":["compare-2025","cco-2017"]},{"name":"Daily against on-demand PDE5 inhibitor","differs":"A daily dose instead of tablets taken before sex.","evidence":"CCO: whether effectiveness differs may depend on the drug, but compliance and side effects may be better with daily use.","sources":["cco-2017"]}],"grades":[{"claim":"PDE5 inhibitors and counselling for men's sexual response","grade":"39 publications of low-to-moderate quality (CCO)","source":"cco-2017","quote":"The evidence base for these recommendations consists of thirty-nine publications of low-to-moderate quality"},{"claim":"Daily vacuum device to prevent loss of penile length","grade":"three publications of moderate quality (CCO)","source":"cco-2017","quote":"The evidence base for these recommendations consists of three publications of moderate quality"},{"claim":"Vaginal oestrogen after breast cancer when non-hormonal treatment fails","grade":"NICE does not grade recommendations ('consider')","source":"nice-ng23","quote":"Consider vaginal oestrogen for people with a personal history of breast cancer and genitourinary symptoms that have continued despite trying non-hormonal treatments"},{"claim":"Counselling for overall sexual function in women","grade":"16 publications of moderate quality and four systematic reviews (CCO)","source":"cco-2017","quote":"The evidence base for this recommendation consists of sixteen publications of moderate quality"}],"sources":[{"key":"cco-2017","label":"Interventions to address sexual problems in people with cancer (Cancer Care Ontario guideline)","publisher":"Cancer Care Ontario, Current Oncology","year":2017,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5486385/","doi":"10.3747/co.24.3583","gradingScheme":"Recommendations are not graded; each states the number and quality of the publications behind it (low, moderate or high).","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2018","label":"Interventions to Address Sexual Problems in People With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Adaptation of Cancer Care Ontario Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/abstract/MED/29227723","doi":"10.1200/JCO.2017.75.8995","read":"abstract","accessed":"2026-11-11"},{"key":"nice-ng23","label":"Menopause: identification and management (NG23), recommendations 1.5.14 to 1.5.19","publisher":"NICE","year":2026,"url":"https://www.nice.org.uk/guidance/ng23/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider', 'do not offer') signals the strength.","read":"full-text","accessed":"2026-11-11"},{"key":"compare-2025","label":"2024 SOGC, 2024 NCCN, 2022 ESO-ESMO, and 2018 ASCO: a comparison of female cancer survivorship guidelines for the management of sexual health concerns","publisher":"Supportive Care in Cancer","year":2025,"url":"https://europepmc.org/abstract/MED/40518469","doi":"10.1007/s00520-025-09640-1","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ASCO 2018 adaptation was read only as an abstract, so its added statements beyond those in the abstract are not given here.","The ESO-ESMO 2022, NCCN 2024 and SOGC 2024 guidelines were not read directly; their positions are as reported in a 2025 comparison, read as an abstract.","No updated CCO or Ontario Health edition after 2016 was found; whether one is in progress was not checked.","The safety of vaginal oestrogen with aromatase inhibitors is uncertain in the CCO guideline; OnCo's `vaginal-oestrogen-after-breast-cancer` page sets out the later evidence.","The evidence is mostly in breast, gynaecological and prostate cancer and in heterosexual couples; sexual health for LGBTQ+ people with cancer, and after head and neck or colorectal cancer, is thinly covered by the sources read."]},{"id":"skin-and-nail-care-during-cancer-drug-treatment","kind":"protocol","name":"Skin and nail care during chemotherapy and targeted therapy","aka":["skin care on chemotherapy","EGFR inhibitor rash care","acneiform rash prevention","paronychia prevention","hand-foot syndrome skin care","nail care during chemotherapy","dry skin on targeted therapy"],"tldr":"Many cancer drugs dry the skin; some cause an acne-like rash, sore nail folds or red, painful hands and feet. Gentle washing in lukewarm water, a thick fragrance-free moisturiser, gloves for housework and careful nail trimming help; with some targeted drugs the team prescribes preventive creams from day one. Tell the team early about a rash or sore nails, and urgently about a rash with wheezing.","summary":"The MASCC EGFR inhibitor guideline (2011, the most recent MASCC guideline on this that could be read) is the only graded source read in full. For acne-like rash it recommends prevention from the start of treatment: hydrocortisone 1% with moisturiser and sunscreen, plus doxycycline 100 mg twice daily (or minocycline 100 mg daily) for the first 6 weeks, on randomised data (systemic tetracyclines level II, grade A; topical regimen level II, grade C). For dry skin it recommends tepid bathing with mild moisturising soap or bath oil, regular moisturising creams, and avoiding extreme temperatures and direct sun (level III, grade B); thick occlusive emollients in a tub, avoiding alcohol-containing lotions, retinoids and benzoyl peroxide. For fissures, protective footwear and avoiding friction (level III, grade B). For paronychia, dilute bleach soaks (level II, grade A), comfortable shoes, careful nail trimming and gloves for cleaning. For hand-foot syndrome, a 2026 comparison of six guidelines found five of six advise avoiding chemical and physical stress to the hands and feet and using alcohol-free moisturiser; only ESMO, BC Cancer and eviQ recommend oral celecoxib for capecitabine. NCI's patient booklet (2023) gives matching ungraded advice. The ESMO 2021 dermatological toxicity guideline could not be read.","asOf":"2026-11-11","links":[],"tags":[],"related":["sun-protection-during-and-after-cancer-treatment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["cetuximab","panitumumab","erlotinib","gefitinib","afatinib","capecitabine","fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["hand-foot-syndrome","rash-skin-toxicity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Wash with lukewarm water and a mild soap, pat dry, and use a thick moisturiser without perfume. Avoid products with alcohol. Wear gloves for cleaning and comfortable shoes, and trim nails gently. Tell your team about any rash, sore nails or sore hands and feet, and get help at once if a rash comes with wheezing.","domain":"supportive-care","setting":{"who":["patient-or-carer","nurse","doctor","pharmacist"],"where":["home","outpatient-clinic","chemotherapy-day-unit"]},"population":"Adults having chemotherapy or targeted therapy that affects the skin or nails, including EGFR inhibitors (cetuximab, panitumumab, erlotinib, gefitinib, afatinib) and fluoropyrimidines (capecitabine, fluorouracil) that cause hand-foot syndrome. Skin reactions to immunotherapy, radiotherapy skin care, and severe reactions (blistering, peeling, mouth or eye involvement) are outside this protocol and need the team.","trigger":"Starting a drug known to affect the skin or nails, or new dryness, rash, nail fold redness or soreness of the hands and feet.","steps":[{"action":"Before an EGFR inhibitor starts, ask whether preventive skin treatment is planned: a mild steroid cream with moisturiser and sunscreen, and doxycycline or minocycline, for the first 6 weeks","why":"The acne-like rash appears in the first weeks in most people on these drugs, and starting treatment before it appears makes it milder.","source":"mascc-egfri-2011","quote":"Hydrocortisone 1% combined with moisturizer, sunscreen, and doxycycline 100 mg bid for the first 6 weeks is recommended based on randomized data.","grade":"Systemic (minocycline or doxycycline): II A; topical (hydrocortisone 1% with moisturiser and sunscreen): II C (MASCC Table 3)"},{"action":"Wash in lukewarm rather than hot water, keep baths and showers short, use a mild moisturising soap or bath oil, and pat the skin dry","why":"Hot water and long soaks strip the skin's oils and make dryness and cracking worse.","source":"mascc-egfri-2011","quote":"Avoiding bathing in excess and using tepid water as opposed to hot water is recommended.","grade":"III B (MASCC Table 8, xerosis prevention)"},{"action":"Moisturise regularly with a thick, fragrance-free cream from a tub or jar, applied while the skin is still damp","why":"Thick creams hold water in the skin better than thin lotions.","source":"mascc-egfri-2011","quote":"Moisturizers should be occlusive, emollient creams that are generally packaged in a jar or tub rather than a lotion that can be pumped or poured.","grade":"III B (MASCC Table 8, xerosis treatment)"},{"action":"Avoid alcohol-based lotions, perfumes and aftershaves, and do not use acne products such as retinoids or benzoyl peroxide unless the team prescribes them","why":"Alcohol and acne treatments dry the skin further; the rash from these drugs is not ordinary acne.","source":"mascc-egfri-2011","quote":"Topical retinoids and benzoyl peroxide gels are not recommended due to their drying effect","grade":"III B (MASCC Table 8: alcohol-containing lotions, retinoids and benzoyl peroxide listed as not recommended)"},{"action":"Protect the nails: wear gloves for washing up, cleaning and gardening, wear comfortable shoes, and trim nails without aggressive manicuring","why":"Pressure and small injuries around the nails trigger painful inflammation of the nail folds.","source":"mascc-egfri-2011","quote":"Wearing comfortable shoes, trimming nails but avoiding aggressive manicuring, and wearing gloves while cleaning (e.g., household, dishes) are recommended to minimize periungual trauma.","grade":"Expert opinion (MASCC: no randomised trials of paronychia treatment)"},{"action":"Protect hands and feet from friction, pressure and heat, with well-fitting shoes or covered fingertips, and moisturise them with an alcohol-free cream","why":"Friction and heat worsen hand-foot syndrome and the deep cracks that some drugs cause in fingertips and heels.","source":"hfs-guidelines-2026","quote":"Regarding prevention, five of six guidelines (83%) advised avoiding chemical and physical stressors to the hands and feet and using alcohol-free moisturizer.","grade":"Consensus across five of six guidelines (comparison study; recommendation grades not given in the abstract)"},{"action":"Tell the team if cuticles become red and painful, or if hands and feet become red, sore or blistered","why":"Nail fold infection needs checking, and hand-foot syndrome of grade 2 or worse usually means pausing the drug until it settles.","source":"nci-chemo-and-you","quote":"Let your doctor or nurse know if your cuticles are red and painful.","grade":"Not graded (patient booklet)"},{"action":"Get urgent help if a rash, hives or sudden severe itching comes with wheezing or difficulty breathing, or if there is burning or pain at the drip site during treatment","why":"These can be signs of an allergic reaction or of the drug leaking out of the vein, which need treating straight away.","source":"nci-chemo-and-you","quote":"Tell your doctor or nurse right away if you wheeze or have trouble breathing along with:","grade":"Not graded (patient booklet)"}],"bestInClass":{"statement":"For EGFR inhibitors, preventive treatment from the first day (hydrocortisone 1% with moisturiser and sunscreen, plus a tetracycline for 6 weeks) is the best-supported step, on randomised data (MASCC 2011: systemic II A, topical II C). General skin and nail care (tepid bathing, thick fragrance-free emollients, no alcohol-based products, gloves, comfortable shoes, careful nail trimming) rests on level III evidence and expert opinion, and the guidelines agree on it. For hand-foot syndrome the guidelines agree on avoiding friction and heat and using alcohol-free moisturiser, and on pausing the drug at grade 2 or 3 (all but ONS), but disagree on drugs: only ESMO, BC Cancer and eviQ recommend oral celecoxib to prevent capecitabine hand-foot syndrome. The ESMO 2021 guideline, which is the most recent comprehensive one, could not be read, so its grades are not reproduced here.","sources":["mascc-egfri-2011","hfs-guidelines-2026","nci-chemo-and-you"]},"variants":[{"name":"Oral celecoxib to prevent capecitabine hand-foot syndrome","differs":"Adds a prescribed anti-inflammatory tablet to prevent hand-foot syndrome on capecitabine.","evidence":"Recommended by ESMO, BC Cancer and eviQ but not by ONS, UKONS or the UK North Cancer Alliance, according to the 2026 comparison of six guidelines.","sources":["hfs-guidelines-2026"]},{"name":"Cooling the hands and feet","differs":"Cools the hands and feet during infusion to prevent hand-foot syndrome.","evidence":"ESMO and ONS recommend cooling for taxanes; BC Cancer and eviQ for all agents (2026 comparison abstract).","sources":["hfs-guidelines-2026"]},{"name":"Dilute bleach soaks for nail fold inflammation","differs":"Soaks fingers or toes in very dilute bleach (about 0.005%) to prevent infection of inflamed nail folds.","evidence":"MASCC 2011 Table 10: level II, grade A for prevention of paronychia, from a non-EGFR, non-cancer study.","sources":["mascc-egfri-2011"]},{"name":"Cornstarch and colloidal oatmeal baths (NCI)","differs":"For itchy, dry or peeling skin, sprinkle cornstarch and take a colloidal oatmeal bath when the whole body itches.","evidence":"Patient booklet advice, not graded; MASCC lists colloidal oatmeal among occlusive emollients for dry skin (level III, grade B).","sources":["nci-chemo-and-you","mascc-egfri-2011"]}],"grades":[{"claim":"Preventive tetracycline (minocycline or doxycycline) for EGFR inhibitor rash","grade":"Level II, grade A (MASCC Table 3)","source":"mascc-egfri-2011"},{"claim":"Preventive hydrocortisone 1% with moisturiser and sunscreen for EGFR inhibitor rash","grade":"Level II, grade C (MASCC Table 3)","source":"mascc-egfri-2011"},{"claim":"Tepid bathing and regular moisturiser to prevent dry skin; avoid extreme temperatures and direct sun","grade":"Level III, grade B (MASCC Table 8)","source":"mascc-egfri-2011"},{"claim":"Protective footwear and avoiding friction to prevent fissures","grade":"Level III, grade B (MASCC Table 9)","source":"mascc-egfri-2011","quote":"Wearing protective footwear or covering the fingertips to avoid friction can prevent skin fissures and aid healing."},{"claim":"No randomised trials of paronychia treatment; recommendations are expert opinion","grade":"As stated by MASCC","source":"mascc-egfri-2011","quote":"Similarly, there have been no randomized controlled studies evaluating therapies for paronychia."},{"claim":"No randomised trials of prevention or treatment of EGFR inhibitor dry skin","grade":"As stated by MASCC","source":"mascc-egfri-2011","quote":"To date, there are no existing randomized clinical trials assessing the prevention or treatment of EGFRI-induced xerosis."},{"claim":"Pause the drug for grade 2 or 3 hand-foot syndrome and continue when it improves","grade":"Agreed by five of six guidelines (all except ONS), per the 2026 comparison","source":"hfs-guidelines-2026","quote":"All guidelines except ONS recommended dose suspension with grade 2 or 3 HFS and continuation when resolved or improved."}],"sources":[{"key":"mascc-egfri-2011","label":"Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities","publisher":"MASCC Skin Toxicity Study Group (Supportive Care in Cancer)","year":2011,"url":"https://doi.org/10.1007/s00520-011-1197-6","doi":"10.1007/s00520-011-1197-6","gradingScheme":"Levels of evidence I to V (I meta-analyses or high-powered randomised trials, V case reports) and grades A to D (A level I or consistent findings, D little or no evidence).","read":"full-text","accessed":"2026-11-11"},{"key":"hfs-guidelines-2026","label":"Comparing clinical practice guidelines on the prevention and management of chemotherapy-induced hand-foot syndrome","publisher":"Supportive Care in Cancer","year":2026,"url":"https://doi.org/10.1007/s00520-026-10809-5","doi":"10.1007/s00520-026-10809-5","gradingScheme":"A comparison of six guidelines appraised with AGREE II; it reports which guidelines make each recommendation, not grades.","read":"abstract","accessed":"2026-11-11"},{"key":"nci-chemo-and-you","label":"Chemotherapy and You: Support for People with Cancer","publisher":"National Cancer Institute (US)","year":2023,"url":"https://www.cancer.gov/publications/patient-education/chemotherapy-and-you.pdf","gradingScheme":"Patient booklet; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-derm-2021","label":"Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2021,"url":"https://doi.org/10.1016/j.annonc.2020.11.005","doi":"10.1016/j.annonc.2020.11.005","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2021 dermatological toxicity guideline, the most recent comprehensive guideline, could not be read (bot check on the journal page, no abstract in PubMed); its grades are not reproduced.","The MASCC EGFR inhibitor guideline read here dates from 2011 and describes itself as first-generation recommendations; newer targeted drugs are not covered by it.","Most general skin and nail care steps rest on level III evidence or expert opinion; there are no randomised trials for dry skin or paronychia on EGFR inhibitors (MASCC).","The 2026 hand-foot syndrome comparison was read as an abstract; the six guidelines it compares were not read directly.","Afatinib is listed because it is an EGFR inhibitor; the MASCC 2011 guideline predates it and names cetuximab, panitumumab, erlotinib and gefitinib."]},{"id":"radiation-dermatitis-skin-care","kind":"protocol","name":"Skin care during radiotherapy and acute radiation dermatitis","aka":["radiation dermatitis","radiodermatitis","radiotherapy skin reaction","radiotherapy skin care","moist desquamation","Mepitel film","StrataXRT","mometasone for radiotherapy skin","can I wash during radiotherapy","deodorant during radiotherapy"],"tldr":"Radiotherapy often makes the treated skin pink or darker, dry, itchy and sore, and sometimes it peels. Wash the area gently with water and mild soap, use your usual moisturiser and keep using deodorant unless it stings. If your risk is high, as with breast or head and neck treatment, your team may suggest a thin film dressing or a steroid cream from the start. Report blisters or pain.","summary":"Prevention. The MASCC 2023 Delphi guideline (42 experts, interventions reaching 75% consensus) recommends six interventions for prevention: photobiomodulation and Mepitel film in breast cancer, Hydrofilm, mometasone, betamethasone and olive oil; most others were not recommended for lack or conflict of evidence. Its systematic review found that washing with water and soap and deodorant use do not worsen dermatitis but did not find enough evidence to recommend them for prevention. Two 2023 meta-analyses go further: washing with or without soap reduced severe dermatitis (OR 0.32) and moist desquamation (OR 0.25), and deodorant made no difference, so the evidence does not support advising against it. The Canadian breast Delphi (2025) reached consensus for education, moisturising and washing for every patient, and Mepitel film and mometasone for high-risk patients. MASCC clinical practice statements since then recommend Mepitel film or Hydrofilm prophylaxis in breast and selected head and neck cancers (2025), medium-potency topical steroid such as mometasone furoate 0.1% for high-risk head and neck and breast patients (2026), and barrier-forming agents, StrataXRT having the most evidence, where the contour is irregular (2026). The ONS guideline (2020, GRADE) made a conditional recommendation for deodorant and suggested against emu oil, calendula and non-steroidal agents.\n\nManagement. MASCC 2023 recommends Mepilex Lite dressings for established dermatitis; the 2026 steroid statement allows topical steroid for early dermatitis without moist desquamation and asks for weekly skin review, stopping the steroid if moist desquamation appears. Most of this rests on abstracts; the full MASCC 2023 text and the UK Society of Radiographers guideline could not be read.","asOf":"2026-11-11","links":[],"tags":[],"related":["breast-radiotherapy-positioning-and-setup"],"cancers":["breast-cancer","head-and-neck"],"sections":[],"technologies":["photobiomodulation-mucositis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radiation-dermatitis","radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"The treated skin can get red, dry, itchy or sore. You can wash it gently, moisturise and use deodorant. Tell your team if it blisters, peels or hurts.","domain":"radiotherapy","setting":{"who":["radiographer","nurse","doctor","patient-or-carer"],"where":["radiotherapy-department","home"]},"population":"Adults having external beam radiotherapy, in any cancer; most trials are in breast and head and neck cancer, and the film dressings, topical steroid and barrier-agent statements are scoped to those sites or to high-risk patients. Children, late radiation skin changes and fibrosis, and dermatitis with EGFR inhibitors (cetuximab) are not covered here.","trigger":"The start of a course of external beam radiotherapy, and each weekly review during it.","steps":[{"action":"Before treatment starts, explain how the skin may react and how to care for it, and assess whether the patient is at high risk of a severe reaction","why":"Knowing what to expect helps people look after their skin and report changes early; some treatments, like film dressings, only help if started at the beginning.","source":"canadian-delphi-breast-2025","quote":"After the four rounds, consensus for recommendation was reached for 3 prevention interventions in both low- and high-risk patients: prevention care education, moisturizing, and washing.","grade":"Delphi consensus (19 Canadian experts, breast cancer)"},{"action":"Tell the patient they can wash the treated skin gently with water, with or without mild soap, and pat it dry","why":"Pooled trials found washing led to fewer severe skin reactions and less peeling, and people feel better for it.","source":"chan-washing-2023","quote":"Given the QoL benefits of washing, it should be advocated as part of routine skin care during RT.","grade":"Systematic review and meta-analysis of randomised trials"},{"action":"Let the patient keep using their usual deodorant or antiperspirant unless it irritates the skin","why":"Trials found deodorant did not make skin reactions, itching or pain worse.","source":"salvestrini-deodorant-2023","quote":"As such, the current evidence does not support recommendation against antiperspirant/deodorant use during RT.","grade":"Meta-analysis of five randomised trials"},{"action":"For patients with breast cancer, and selected head and neck patients, consider a thin film dressing (Mepitel film or Hydrofilm) over the treated skin from the start of treatment","why":"A thin film protects the skin from friction and has reduced the severity of reactions, especially peeling, in several trials.","source":"mascc-film-cps-2025","quote":"Prophylactic use of Mepitel Film and Hydrofilm is recommended for reducing the severity of ARD in breast cancer and selected head and neck cancer patients.","grade":"MASCC clinical practice statement (expert consensus on a literature review)"},{"action":"For head and neck or breast patients at high risk, consider a medium-strength steroid cream such as mometasone furoate 0.1% on the treated skin during treatment","why":"A steroid cream calms the inflammation that causes redness and itching, and several trials found fewer and milder reactions with it.","source":"mascc-steroid-cps-2026","quote":"TCs are recommended for the prevention of ARD in selected patients with head and neck and breast cancers at a high risk of ARD.","grade":"MASCC clinical practice statement (expert consensus on a literature review)"},{"action":"Where the treated area has an irregular shape, such as the head and neck, consider a barrier-forming gel for patients at high risk","why":"A gel that dries into a film can cover curved or folded skin where a dressing will not stay on.","source":"mascc-barrier-cps-2026","quote":"Barrier-forming topical agents are recommended for patients undergoing radiotherapy who are at considerable risk of developing high‑grade ARD, particularly in treatment sites with irregular anatomical contours, such as head and neck cancers.","grade":"MASCC clinical practice statement (expert consensus on a literature review)"},{"action":"Look at the skin at least weekly during treatment, and stop a steroid cream if the skin starts to weep or peel (moist desquamation)","why":"Reactions build up over the course and often peak after it ends; once the skin is broken a steroid cream is no longer the right treatment.","source":"mascc-steroid-cps-2026","quote":"Healthcare professionals should monitor patients' skin weekly during radiation and guide steroid use, discontinuing it if moist desquamation or other complications arise.","grade":"MASCC clinical practice statement (expert consensus on a literature review)"},{"action":"For established dermatitis, especially moist desquamation, use a soft silicone foam dressing such as Mepilex Lite","why":"A soft dressing protects broken skin, eases pain and lets it heal without sticking to the wound.","source":"mascc-delphi-2023","quote":"Mepilex Lite dressings were recommended for the management of acute radiation dermatitis.","grade":"Delphi consensus (at least 75% of 42 experts)"}],"bestInClass":{"statement":"For everyone: education before treatment, gentle washing with water with or without mild soap, a moisturiser the patient likes, and their usual deodorant (Chan 2023 and Salvestrini 2023 meta-analyses; Canadian Delphi 2025; ONS 2020 conditional for deodorant). For high-risk patients, prophylaxis chosen by site: Mepitel film or Hydrofilm in breast cancer (MASCC 2023, 2025), medium-potency topical steroid such as mometasone furoate 0.1% in breast or head and neck cancer (MASCC 2023, 2026), photobiomodulation in breast cancer where available (MASCC 2023), or a barrier-forming agent on irregular contours (MASCC 2026). Weekly skin review; Mepilex Lite for established dermatitis (MASCC 2023). Where the sources differ: the MASCC 2023 systematic review found that washing and deodorant do not worsen dermatitis but judged the evidence insufficient to recommend them for prevention, while the 2023 washing meta-analysis found a reduction in severe dermatitis and recommends washing as routine care; the Canadian panel recommended washing for all. None of the sources read advises against washing or deodorant.","sources":["mascc-delphi-2023","mascc-systematic-review-2023","mascc-film-cps-2025","mascc-steroid-cps-2026","mascc-barrier-cps-2026","chan-washing-2023","salvestrini-deodorant-2023","canadian-delphi-breast-2025","ons-radiodermatitis-2020"]},"variants":[{"name":"Advice not to wash the treated area or use deodorant","differs":"Older patient information told people to keep the treated skin dry, avoid soap and stop deodorant for the whole course.","evidence":"Not supported by any source read: washing reduced severe dermatitis in pooled trials (OR 0.32, 95% CI 0.19 to 0.55), and deodorant did not change grade 1 or worse, grade 2 or worse, or grade 3 dermatitis in five trials. How many departments still give this advice was not measured by any source read.","sources":["chan-washing-2023","salvestrini-deodorant-2023","mascc-systematic-review-2023"]},{"name":"Topical steroid for every patient rather than only those at high risk","differs":"Some departments prescribe a steroid cream such as mometasone from the first day for all patients.","evidence":"MASCC 2023 recommends mometasone and betamethasone for prevention without restricting them to high-risk patients in its abstract; the 2026 MASCC statement and the Canadian panel recommend them for high-risk patients. The systematic review found mometasone effective across eight randomised trials of mixed quality.","sources":["mascc-delphi-2023","mascc-steroid-cps-2026","canadian-delphi-breast-2025","mascc-systematic-review-2023"]},{"name":"Photobiomodulation","differs":"Low-level red or near-infrared light is applied to the treated skin from the start of treatment.","evidence":"Recommended by MASCC 2023 for prevention in breast cancer. Needs a device and staff time; one trial in 46 head and neck patients found grade 2 to 3 dermatitis in 28.6% with it against 77.8% without (reported in the MASCC systematic review).","sources":["mascc-delphi-2023","mascc-systematic-review-2023"]},{"name":"Aloe vera, calendula and other creams","differs":"Many departments and patients use aloe vera, calendula, emu oil or other non-steroidal creams to prevent reactions.","evidence":"ONS 2020 suggested against emu oil, calendula and non-steroidal interventions and recommended aloe vera only within a trial; the MASCC 2023 systematic review found most such interventions unsupported, and MASCC 2023 recommended olive oil as the only one of these to reach consensus.","sources":["ons-radiodermatitis-2020","mascc-delphi-2023","mascc-systematic-review-2023"]}],"grades":[{"claim":"Prevention: photobiomodulation and Mepitel film in breast cancer, Hydrofilm, mometasone, betamethasone and olive oil","grade":"Delphi consensus (at least 75% of 42 experts)","source":"mascc-delphi-2023","quote":"Six interventions could be recommended for the prevention of acute radiation dermatitis: photobiomodulation therapy and Mepitel film in people with breast cancer, Hydrofilm, mometasone, betamethasone, and olive oil."},{"claim":"Most interventions were not recommended","grade":"Delphi consensus","source":"mascc-delphi-2023","quote":"Most interventions were not recommended due to insufficient evidence, conflicting evidence, or lack of consensus to support use, suggesting a need for further research."},{"claim":"Washing and deodorant do not worsen dermatitis but are not proven to prevent it","grade":"Systematic review (149 randomised trials among 235 studies)","source":"mascc-systematic-review-2023","quote":"Based on evidence from multiple RCTs, aluminum/deodorant use and washing with water and soap do not worsen ARD, but there is insufficient evidence to support their use in the prevention of ARD."},{"claim":"Washing with or without soap reduces severe dermatitis and moist desquamation","grade":"Meta-analysis of two randomised trials","source":"chan-washing-2023","quote":"Washing with or without soap significantly reduced the incidence of severe RD (OR: 0.32, 95% CI: 0.19-0.55, p < 0.01) and moist desquamation (OR: 0.25, 95% CI: 0.12-0.52, p < 0.01)."},{"claim":"Medium-potency steroid preferred","grade":"MASCC clinical practice statement","source":"mascc-steroid-cps-2026","quote":"Medium potency TCs, such as mometasone furoate 0.1% cream, are preferred."},{"claim":"Among barrier-forming agents, StrataXRT has the most evidence","grade":"MASCC clinical practice statement","source":"mascc-barrier-cps-2026","quote":"Among these agents, StrataXRT currently has the most robust supporting evidence."},{"claim":"Conditional recommendation for deodorant; aloe vera and oral curcumin only within a trial; against emu oil, calendula and non-steroidal interventions","grade":"GRADE (ONS); the individual grades are in the full text, not read","source":"ons-radiodermatitis-2020","quote":"The panel agreed on eight recommendations and made a conditional recommendation for deodorant/antiperspirant."}],"sources":[{"key":"mascc-delphi-2023","label":"Multinational Association of Supportive Care in Cancer (MASCC) clinical practice guidelines for the prevention and management of acute radiation dermatitis: international Delphi consensus-based recommendations","publisher":"MASCC (Lancet Oncology; Behroozian et al.)","year":2023,"url":"https://doi.org/10.1016/S1470-2045(23)00067-0","doi":"10.1016/S1470-2045(23)00067-0","gradingScheme":"Four-round Delphi of 42 international experts; an intervention was recommended when it reached at least 75% consensus.","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-systematic-review-2023","label":"MASCC clinical practice guidelines for the prevention and management of acute radiation dermatitis: part 1) systematic review","publisher":"MASCC (EClinicalMedicine)","year":2023,"url":"https://doi.org/10.1016/j.eclinm.2023.101886","doi":"10.1016/j.eclinm.2023.101886","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-film-cps-2025","label":"MASCC oncodermatology clinical practice statement: prevention and management of acute radiation dermatitis with Mepitel Film and Hydrofilm","publisher":"MASCC (Supportive Care in Cancer)","year":2025,"url":"https://doi.org/10.1007/s00520-025-10218-0","doi":"10.1007/s00520-025-10218-0","gradingScheme":"Clinical practice statement: literature review and expert consensus of the MASCC Oncodermatology Study Group, without formal grades.","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-steroid-cps-2026","label":"MASCC clinical practice statement: prevention and management of acute radiation dermatitis using topical corticosteroids","publisher":"MASCC (Supportive Care in Cancer)","year":2026,"url":"https://doi.org/10.1007/s00520-026-10659-1","doi":"10.1007/s00520-026-10659-1","gradingScheme":"Clinical practice statement: MEDLINE search to 23 November 2025 and structured expert discussion, without formal grades.","read":"abstract","accessed":"2026-11-11"},{"key":"mascc-barrier-cps-2026","label":"MASCC oncodermatology clinical practice statement: prevention of acute radiation dermatitis using barrier-forming topical agents","publisher":"MASCC (Supportive Care in Cancer)","year":2026,"url":"https://doi.org/10.1007/s00520-026-11244-2","doi":"10.1007/s00520-026-11244-2","gradingScheme":"Clinical practice statement: literature search to 23 April 2026 and structured expert discussion, without formal grades.","read":"abstract","accessed":"2026-11-11"},{"key":"canadian-delphi-breast-2025","label":"Modified Delphi consensus on interventions for acute radiation dermatitis in breast cancer: a Canadian expert perspective","publisher":"International Journal of Radiation Oncology, Biology, Physics","year":2025,"url":"https://doi.org/10.1016/j.ijrobp.2024.12.037","doi":"10.1016/j.ijrobp.2024.12.037","read":"abstract","accessed":"2026-11-11"},{"key":"ons-radiodermatitis-2020","label":"ONS Guidelines for Cancer Treatment-Related Radiodermatitis","publisher":"Oncology Nursing Society (Oncology Nursing Forum)","year":2020,"url":"https://doi.org/10.1188/20.ONF.654-670","doi":"10.1188/20.ONF.654-670","gradingScheme":"GRADE: recommendations strong or conditional, certainty high to very low.","read":"abstract","accessed":"2026-11-11"},{"key":"chan-washing-2023","label":"Prevention of radiation dermatitis with skin hygiene and washing: a systematic review and meta-analysis","publisher":"Supportive Care in Cancer (Chan et al.)","year":2023,"url":"https://doi.org/10.1007/s00520-023-07720-8","doi":"10.1007/s00520-023-07720-8","read":"abstract","accessed":"2026-11-11"},{"key":"salvestrini-deodorant-2023","label":"The effect of antiperspirant and deodorant use on acute radiation dermatitis in breast cancer patients during radiotherapy: a systematic review and meta-analysis","publisher":"Supportive Care in Cancer (Salvestrini et al.)","year":2023,"url":"https://doi.org/10.1007/s00520-023-07657-y","doi":"10.1007/s00520-023-07657-y","read":"abstract","accessed":"2026-11-11"},{"key":"scor-dermatitis-2020","label":"Radiation dermatitis guidelines for radiotherapy healthcare professionals","publisher":"Society and College of Radiographers","year":2020,"url":"https://www.sor.org/learning-advice/professional-body-guidance-and-publications/documents-and-publications/policy-guidance-document-library/radiation-dermatitis-guidelines-for-radiotherapy-h","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":["idea-pu-washing-and-deodorant-during-radiotherapy"],"gaps":["The full text of the MASCC 2023 Delphi guideline is paywalled and was not read; the recommendations here are those its abstract names, and any conditions or grading in the full text are not stated.","The UK Society and College of Radiographers radiation dermatitis guideline (2020) could not be read: its page on sor.org returns 404 and the PDF is not in the Internet Archive. Whether it has been withdrawn or replaced is not known.","The ONS 2020 guideline was read as an abstract; its eight recommendations and their GRADE certainty are not listed here.","Who counts as high risk is defined in the full texts of the MASCC statements and the Canadian consensus, not in their abstracts; the abstracts name breast and head and neck cancer, skin folds and irregular contours.","The washing meta-analysis pooled only two trials, and the MASCC review judged the same evidence insufficient for a prevention recommendation; the sources agree that washing does no harm.","The technology record linked for photobiomodulation describes its use for oral mucositis; no OnCo record covers photobiomodulation for the skin.","Sun protection after treatment and long-term skin care (late effects, fibrosis) are not covered."]},{"id":"stereotactic-radiosurgery-and-sbrt-delivery-safeguards","kind":"protocol","name":"Stereotactic radiosurgery and SBRT: planning and delivery safeguards","aka":["SRS safety","SBRT safety","SABR safeguards","stereotactic ablative radiotherapy","radiosurgery checklist","MPPG 9.b","TG-101","frameless radiosurgery","Gamma Knife frame","CyberKnife"],"tldr":"Stereotactic treatment gives a very high dose in one to a few sessions to a small target, so a small error matters more than in ordinary radiotherapy. The team uses a firm head frame or a close-fitting mask or body cushion, checks the plan with an independent calculation, takes images to confirm the target's position before every treatment, and has a physicist present for the first session.","summary":"AAPM-RSS MPPG 9.b (2025) sets minimum practice for linac SRS and SBRT in the United States. The service needs standard operating procedures for every step, a safety checklist, participation in an incident learning system, at least two radiation therapists at every session (one trained in the technique), 4D CT for thoracic and abdominal SBRT, and MRI and PET fusion. At simulation the therapists prepare immobilisation and document set-up after the radiation oncologist approves position, images and target localisation. In planning, prior radiotherapy plans are obtained for re-irradiation and cumulative dose reported; brain metastases are named with the MRI date so new and old targets cannot be confused; a calculation grid of 2 mm or finer is used (1 mm for targets of 1 cc or less); the radiation oncologist signs the plan; an independent dose calculation and a physicist's plan and chart review are done before treatment. At delivery a pre-treatment QA check including a dry-run collision check is done, target localisation is verified by imaging before every treatment, imaging-to-treatment isocentre coincidence must be within 1 mm for SRS and 1.5 mm for SBRT (tested daily on treatment days), and a qualified medical physicist personally supervises the first session and directly supervises the rest (new in 9.b). For frameless intracranial SRS, open-face masks let surface guidance use the face. In one randomised trial of SRS for brain metastases, a 1 mm margin around the visible tumour gave similar local control to 3 mm with less radionecrosis (5 of 6 biopsy-proven cases in the 3 mm arm, P=.10), and the authors judged 1 mm more appropriate.","asOf":"2026-11-11","links":[],"tags":[],"related":["respiratory-motion-management-4d-ct-and-gating","head-and-neck-radiotherapy-immobilisation-mask","radiotherapy-patient-identification-and-time-out"],"cancers":["nsclc"],"sections":[],"technologies":["radiosurgery-srs","sbrt","sabr-oligometastases","gamma-knife","cyberknife","in-room-imaging-systems","surface-guided-radiotherapy","respiratory-motion-management","treatment-planning-systems"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stereotactic-radiosurgery","sbrt-term","brain-metastases","planning-target-volume"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kirkpatrick-srs-margin-trial-ijrobp-2015"],"journals":[],"dependsOn":[],"notes":[],"simple":"Stereotactic radiotherapy is very precise and very strong. You are held very still, scans check your position before each treatment, and extra people check the plan.","domain":"radiotherapy","setting":{"who":["doctor","radiographer","multidisciplinary-team"],"where":["radiotherapy-department"]},"population":"Adults having linac-based stereotactic radiosurgery to the brain (single or few fractions) or stereotactic body radiotherapy to the lung, liver, spine, prostate, oligometastases or other body sites. Gamma Knife and particle therapy have their own physics guidance not read here. Disease-specific doses and selection are outside this protocol.","trigger":"A decision to treat with SRS or SBRT.","steps":[{"action":"Run the service by written procedures for every step, with a safety checklist covering the whole process","why":"Checklists catch the slips that matter most when the whole dose is given in one or a few sessions.","source":"aapm-mppg-9b-2025","quote":"Establishment of a comprehensive safety checklist to act as a guide for the entire treatment process, and determine appropriate methods for the clinic's QA committee to monitor the SRS-SBRT program.","grade":"Minimum practice guideline (ungraded)"},{"action":"At simulation, prepare the immobilisation, position the patient and acquire the planning images, and record the set-up only after the radiation oncologist approves the position, images and target","why":"The position at the planning scan has to be repeatable to within a millimetre or two at treatment.","source":"aapm-mppg-9b-2025","quote":"For each simulation session, prepare immobilization devices, position the patient, and acquire images for treatment planning in accordance with the clinic's SRS-SBRT procedure and the patient-specific instructions, and document treatment setup parameters after the radiation oncologist has approved the positioning, images, and target localization.","grade":"Minimum practice guideline (ungraded)"},{"action":"For lung and upper abdominal SBRT, have 4D CT available to measure breathing motion, and MRI and PET fusion for target definition","why":"Tumours in the chest and upper abdomen move with breathing, and the plan must account for it.","source":"aapm-mppg-9b-2025","quote":"Four-dimensional computed tomography (4D CT) capability (for thoracic and abdominal SBRT services).","grade":"Minimum practice guideline (ungraded)"},{"action":"For re-irradiation or multiple brain metastases, obtain the previous plans and name targets so new and old lesions cannot be confused, for example with the date of the MRI","why":"Treating the wrong lesion, or overdosing an area treated before, are known stereotactic errors.","source":"aapm-mppg-9b-2025","quote":"In the case of multiple brain metastases and re-irradiation, a target naming convention that makes clear which targets are new and which are old must be utilized; for example, include the date of the MR scan at the end of the target structure's name.","grade":"Minimum practice guideline (ungraded)"},{"action":"Calculate the plan on a grid of 2 mm or finer (1 mm for very small targets or targets beside critical organs)","why":"Small targets and steep dose fall-off need a fine calculation to be accurate.","source":"aapm-mppg-9b-2025","quote":"The use of an isotropic calculation grid size of 2 mm or finer should be utilized.","grade":"Minimum practice guideline (ungraded)"},{"action":"Have the radiation oncologist sign off target coverage, dose fall-off and organ doses, then perform an independent dose calculation and a physicist's plan and chart review before the first treatment","why":"A second, separate check of a high-dose plan is the main protection against a planning error reaching the patient.","source":"aapm-mppg-9b-2025","quote":"An independent dose calculation check must be performed prior to treatment.","grade":"Minimum practice guideline (ungraded)"},{"action":"Before treatment, perform the defined pre-treatment QA check, including a dry run for collisions where the machine could touch the patient or couch","why":"Stereotactic beams often come from unusual angles close to the patient.","source":"aapm-mppg-9b-2025","quote":"This should include a “dry run” collision check where the potential for collision exists.","grade":"Minimum practice guideline (ungraded)"},{"action":"Verify the target's position by imaging before every treatment, with written criteria for imaging during treatment and for any motion management","why":"A few millimetres off can mean missing the tumour or hitting a nearby organ with a very high dose.","source":"aapm-mppg-9b-2025","quote":"Pre-treatment verification of target localization must always be performed; the criteria for intra-treatment image guidance should be clearly described.","grade":"Minimum practice guideline (ungraded)"},{"action":"On treatment days, confirm that the imaging and treatment isocentres coincide within 1 mm for SRS and 1.5 mm for SBRT","why":"The images are only useful if the machine treats exactly where the images say.","source":"aapm-mppg-9b-2025","quote":"AAPM MPPG 2.b states that the composite tolerance of the imaging-treatment isocenter coincidence and table repositioning accuracy must be ≤1 mm for SRS and ≤1.5 mm for SBRT, tested daily when SRS-SBRT treatments are conducted.","grade":"Minimum practice guideline (ungraded)"},{"action":"Have at least two radiation therapists at every session, one trained in the technique, and a qualified medical physicist personally present for the first treatment and directly supervising later ones","why":"Experienced eyes at the machine catch problems before the beam is switched on.","source":"aapm-mppg-9b-2025","quote":"For the first treatment session the QMP must provide personal supervision of the session.","grade":"Minimum practice guideline (ungraded)"},{"action":"Report near misses and errors in an incident learning system, and tell the physicist about any unexpected side effect so its cause can be looked for","why":"Learning from near misses prevents the next real error.","source":"aapm-mppg-9b-2025","quote":"Facilitation and management of the clinic's participation in an incident learning system to ensure a transparent, structured evaluation of all “near miss” and actual deviations in the planning and treatment delivery process.","grade":"Minimum practice guideline (ungraded)"}],"bestInClass":{"statement":"AAPM-RSS MPPG 9.b (2025) is the most recent and most detailed guideline read: written procedures and a checklist for every step, an independent dose calculation and physicist plan review before treatment, imaging verification of the target before every treatment, daily isocentre coincidence within 1 mm (SRS) or 1.5 mm (SBRT), at least two trained therapists at every session and a physicist personally present at the first, and participation in incident learning. For brain metastases treated with image-guided linac SRS, one randomised trial supports a 1 mm rather than a 3 mm margin. European and UK guidance (ESTRO ACROP for lung SBRT, the UK SABR Consortium) cover the same ground; they were read only as an abstract or not at all, so differences in detail could not be compared.","sources":["aapm-mppg-9b-2025","kirkpatrick-2015","estro-acrop-lung-sbrt-2017","aapm-tg101-2010"]},"variants":[{"name":"Frame-based versus frameless intracranial radiosurgery","differs":"A stereotactic head frame is fixed to the skull under local anaesthetic on the day of treatment; frameless SRS uses a thermoplastic mask (often open-face, with surface guidance on the exposed face) and image guidance. MPPG 9.b requires the procedure, tolerances and supervision for each treatment type to be written down and notes that open-face masks let the face serve as a reference surface for frameless SRS.","evidence":"No comparative trial was read here; MPPG 9.b treats both as acceptable when commissioned and verified.","sources":["aapm-mppg-9b-2025"]},{"name":"ESTRO ACROP consensus for peripheral early-stage lung SBRT","differs":"A European consensus of eight institutions found only 8 of 57 technologies and techniques mandatory and 32 optional, but half of quality assurance items mandatory, and agreed risk-adapted doses of 3 x 15 Gy for peripheral lesions and 4 x 12 Gy for lesions with broad chest wall contact.","evidence":"Questionnaire-based expert consensus; read as an abstract.","sources":["estro-acrop-lung-sbrt-2017"]}],"grades":[{"claim":"A 1 mm margin is more appropriate than 3 mm for image-guided SRS of brain metastases","grade":"Single randomised trial (49 patients, 80 metastases)","source":"kirkpatrick-2015","quote":"However, given the higher potential risk of RN with a 3-mm margin, a 1-mm GTV expansion is more appropriate."},{"claim":"Personal physicist supervision for the first session is new in the 2025 guideline","grade":"Minimum practice guideline (ungraded)","source":"aapm-mppg-9b-2025","quote":"The new language requires personal supervision for the first treatment session of SRS-SBRT and direct treatment supervision after the initial fraction."},{"claim":"European consensus treats few techniques but many QA items as mandatory","grade":"Expert consensus (questionnaire, 8 institutions)","source":"estro-acrop-lung-sbrt-2017","quote":"Only 8/57 technologies and techniques were identified as mandatory for SBRT while 32/57 were considered as optional."}],"sources":[{"key":"aapm-mppg-9b-2025","label":"AAPM-RSS Medical Physics Practice Guideline 9.b: SRS-SBRT","publisher":"American Association of Physicists in Medicine and Radiosurgery Society (Journal of Applied Clinical Medical Physics)","year":2025,"url":"https://doi.org/10.1002/acm2.14624","doi":"10.1002/acm2.14624","gradingScheme":"Minimum practice guideline using 'must' and 'should'; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"kirkpatrick-2015","label":"Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial","publisher":"International Journal of Radiation Oncology, Biology, Physics (Kirkpatrick et al.)","year":2015,"url":"https://doi.org/10.1016/j.ijrobp.2014.09.004","doi":"10.1016/j.ijrobp.2014.09.004","read":"abstract","accessed":"2026-11-11"},{"key":"estro-acrop-lung-sbrt-2017","label":"ESTRO ACROP consensus guideline on implementation and practice of stereotactic body radiotherapy for peripherally located early stage non-small cell lung cancer","publisher":"ESTRO ACROP (Guckenberger et al., Radiotherapy and Oncology)","year":2017,"url":"https://doi.org/10.1016/j.radonc.2017.05.012","doi":"10.1016/j.radonc.2017.05.012","gradingScheme":"Consensus by agreement of more than 50% of institutions; items classed as mandatory or optional.","read":"abstract","accessed":"2026-11-11"},{"key":"aapm-tg101-2010","label":"Stereotactic body radiation therapy: the report of AAPM Task Group 101","publisher":"American Association of Physicists in Medicine (Benedict et al., Medical Physics)","year":2010,"url":"https://doi.org/10.1118/1.3438081","doi":"10.1118/1.3438081","read":"abstract","accessed":"2026-11-11"},{"key":"acr-astro-sbrt","label":"ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy","publisher":"American College of Radiology and American Society for Radiation Oncology","year":2024,"url":"https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The guideline read in full is a United States physics minimum-practice document; the UK SABR Consortium guidance could not be found by URL and the ACR-ASTRO practice parameter refused a script, so UK and clinical-practice detail is missing.","AAPM TG-101 and the ESTRO ACROP lung SBRT guideline were read as abstracts only.","No source read sets patient-facing steps for frame placement (local anaesthetic, pin sites, frame removal) or gives evidence comparing frame-based and frameless radiosurgery.","Margins for SBRT outside the brain are set by local motion studies; no randomised evidence was read.","None of the safeguards is graded; their support is error and incident experience rather than trials, which is normal for physics quality assurance."]},{"id":"irae-steroid-taper-and-pjp","kind":"protocol","name":"Steroid taper after immunotherapy side effects, with Pneumocystis prophylaxis and adrenal checks","aka":["irAE steroid taper","corticosteroid taper for immune-related adverse events","PJP prophylaxis on steroids","PCP prophylaxis immunotherapy","co-trimoxazole prophylaxis on steroids","steroid weaning after immunotherapy toxicity"],"tldr":"Steroids for an immunotherapy side effect are reduced slowly, usually over at least 4 to 6 weeks, because stopping too fast can bring it back. A month or more of higher-dose steroids weakens defences against Pneumocystis pneumonia, so a preventive antibiotic (usually co-trimoxazole) is often given. Your body's own steroid production may need checking before the last tablets stop.","summary":"Steroids are the first-line treatment for most irAEs, and their own harms (hyperglycaemia, mood change, insomnia, gastritis, weight gain, osteoporosis and opportunistic infection including Pneumocystis pneumonia) need counselling (SITC 2021, LE: 1). ASCO 2021 (abstract): taper over at least 4 to 6 weeks. SITC tapers over 4 to 6 weeks for hepatitis, pneumonitis and myocarditis, but within 4 weeks for colitis (LE: 1).\n\nPneumocystis prophylaxis: ASCO/IDSA 2018 recommends it for regimens carrying more than 3.5% risk, for example 20 mg prednisone equivalent or more daily for a month or longer. ECIL-5 (haematological patients) lists more than 4 weeks of corticosteroids as a main indication and makes trimethoprim/sulfamethoxazole the drug of choice, with pentamidine, atovaquone and dapsone second-line.\n\nAdrenal axis: doses equivalent to 7.5 mg prednisolone or more for over 3 weeks can suppress the adrenal glands, so ESE 2022 advises at least a morning cortisol (with ACTH, and a Synacthen test if needed) before stopping. The 2024 ESE/Endocrine Society guideline on glucocorticoid-induced adrenal insufficiency tapers faster in the supraphysiological range and more slowly at physiological doses.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","infection-prevention"],"related":["irae-colitis","irae-hepatitis","irae-pneumonitis","irae-hypophysitis-adrenal","irae-rechallenge","idea-bio2-steroid-sparing-irae"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["prednisone","methylprednisolone","hydrocortisone","pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Steroids are reduced slowly over several weeks. If you are on them for a month or more, you may be given an antibiotic to prevent a lung infection.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","acute-oncology-service","ward","home"]},"population":"Adults taking systemic corticosteroids for an immune-related adverse event of a checkpoint inhibitor. The ECIL-5 Pneumocystis guidance was written for people with haematological cancers and transplant recipients and is applied here by analogy; the ASCO/IDSA guideline covers adults with cancer-related immunosuppression generally. Hypophysitis and primary adrenal insufficiency, which need lifelong replacement, are covered by their own protocol.","trigger":"Starting systemic corticosteroids for an immune-related adverse event, and each step of the taper.","steps":[{"action":"When starting steroids, explain their side effects, including high blood sugar, mood change, insomnia, stomach irritation, weight gain and infections such as Pneumocystis pneumonia","why":"Knowing what to look for lets the patient report problems early.","source":"sitc-2021","quote":"When beginning corticosteroid therapy, patients should be specifically counseled about potential toxicities, including hyperglycemia, mood disturbances, insomnia, gastritis, weight gain, and opportunistic infections (eg, Pneumocystis pneumonia)","grade":"LE: 1"},{"action":"Taper the steroids over at least 4 to 6 weeks once the side effect has settled","why":"Reducing too quickly can make the inflammation come back.","source":"asco-2021","quote":"Corticosteroids should be tapered over the course of at least 4-6 weeks."},{"action":"Start Pneumocystis prophylaxis for anyone taking 20 mg prednisone or equivalent a day or more for a month or longer","why":"At this dose and duration the risk of a serious Pneumocystis lung infection is high enough to justify prevention.","source":"asco-idsa-2018","quote":"Pneumocystis jirovecii prophylaxis is recommended for patients receiving chemotherapy regimens that are associated with a > 3.5% risk for pneumonia as a result of this organism (eg, those with ≥ 20 mg prednisone equivalents daily for ≥ 1 month or on the basis of purine analog usage)."},{"action":"Use trimethoprim/sulfamethoxazole (co-trimoxazole) as first choice, and pentamidine, atovaquone or dapsone if it cannot be taken","why":"Co-trimoxazole is the most effective preventive; the others are alternatives for allergy or intolerance.","source":"ecil-2016","quote":"All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated."},{"action":"Taper faster while the dose is above the body's own replacement level, and more slowly once it nears physiological doses","why":"Withdrawal symptoms and adrenal insufficiency mostly appear at the low end of the taper.","source":"ese-es-2024","quote":"In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing."},{"action":"Before stopping steroids after 3 weeks or more at 7.5 mg prednisolone or above, check a morning cortisol (with ACTH, and a Synacthen test if needed)","why":"Long steroid courses can switch off the adrenal glands, and stopping suddenly can cause an adrenal crisis.","source":"ese-2022","quote":"Use of doses equivalent to 7.5 mg prednisolone or higher for more than 3 weeks can lead to secondary adrenal insufficiency. Thus, at least a medication fasting morning cortisol (plus ACTH) and if needed a 250 µg Synacthen® test should be considered if glucocorticoids are considered to be stopped."},{"action":"If the side effect does not respond to steroids, move to a second-line immunosuppressant rather than continuing high doses","why":"Prolonged high-dose steroids add harm without benefit when the toxicity is steroid-refractory.","source":"sitc-2021","quote":"However, in patients who do not respond to initial corticosteroid therapy, second-line immunosuppressive therapy should be considered."}],"bestInClass":{"statement":"On the taper, ASCO 2021 (abstract) sets at least 4 to 6 weeks and SITC 2021 agrees for most organs (LE: 1 for hepatitis) but tapers colitis within 4 weeks (LE: 1). On Pneumocystis, the ASCO/IDSA 2018 threshold (20 mg prednisone equivalent or more daily for 1 month or more) is the guideline written for adults with cancer in general and is the clearest trigger; ECIL-5 uses more than 4 weeks of corticosteroids in haematological patients and makes co-trimoxazole the drug of choice (graded A-II for adults in its abstract). SITC 2021 names Pneumocystis among the risks to counsel about but sets no prophylaxis threshold in the text read. On the adrenal axis, ESE 2022 advises a morning cortisol before stopping after more than 3 weeks at 7.5 mg prednisolone or more, and the 2024 ESE/Endocrine Society guideline tapers more slowly at physiological doses. None of these is a trial in checkpoint inhibitor patients.","sources":["asco-2021","sitc-2021","asco-idsa-2018","ecil-2016","ese-2022","ese-es-2024"]},"variants":[{"name":"Shorter taper for colitis (SITC 2021)","differs":"Tapers corticosteroids within 4 weeks after colitis improves to grade 1 or less, instead of over 4 to 6 weeks as for hepatitis and pneumonitis.","evidence":"LE: 1.","sources":["sitc-2021"]},{"name":"Prophylaxis after more than 4 weeks of corticosteroids (ECIL-5, haematological patients)","differs":"Uses duration (more than 4 weeks) rather than a dose threshold, and gives co-trimoxazole 2 to 3 times weekly for the whole period at risk.","evidence":"IDSA grading; co-trimoxazole as drug of choice in adults graded A-II.","sources":["ecil-2016"]},{"name":"Lowest effective dose, tapered within weeks (EULAR 2021, rheumatic irAEs)","differs":"For rheumatic irAEs, tapers to the lowest effective dose that controls symptoms rather than to zero over a fixed period, with a conventional DMARD above 10 mg/day prednisone.","evidence":"LoE 4; level of agreement 9.4 out of 10.","sources":["eular-2021"]}],"grades":[{"claim":"Counsel about steroid toxicities, including Pneumocystis pneumonia","grade":"LE: 1","source":"sitc-2021"},{"claim":"Taper over at least 4 to 6 weeks","grade":"expert consensus","source":"asco-2021"},{"claim":"Taper within 4 weeks after colitis improves to grade 1 or less","grade":"LE: 1","source":"sitc-2021","quote":"Corticosteroids should be tapered within 4 weeks after improvement of diarrhea or colitis symptoms to grade ≤1"},{"claim":"Co-trimoxazole 2 to 3 times weekly as the drug of choice for Pneumocystis prophylaxis in adults","grade":"A-II","source":"ecil-2016","quote":"Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults"},{"claim":"More than 4 weeks of corticosteroids as a main indication for prophylaxis","grade":"not graded in the abstract","source":"ecil-2016","quote":"The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"asco-idsa-2018","label":"Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update","publisher":"ASCO and Infectious Diseases Society of America, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/abstract/MED/30179565","doi":"10.1200/JCO.18.00374","gradingScheme":"Recommendations based on an expert panel's review of a systematic review; the abstract does not print grades.","read":"abstract","accessed":"2026-11-11"},{"key":"ecil-2016","label":"ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients","publisher":"European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy","year":2016,"url":"https://europepmc.org/abstract/MED/27550992","doi":"10.1093/jac/dkw157","gradingScheme":"IDSA grading: strength A to C and quality of evidence I to III (for example A-II).","read":"abstract","accessed":"2026-11-11"},{"key":"ese-2022","label":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline","publisher":"European Society of Endocrinology, European Journal of Endocrinology","year":2022,"url":"https://europepmc.org/article/PMC/PMC9641795","doi":"10.1530/EJE-22-0689","gradingScheme":"GRADE: quality of evidence printed as +000 (very low), ++00 (low), +++0 (moderate) or ++++ (strong); 'recommend' is a strong and 'suggest' a weak recommendation; recommendations not formally graded are marked good clinical practice.","read":"full-text","accessed":"2026-11-11"},{"key":"ese-es-2024","label":"European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency","publisher":"European Society of Endocrinology and Endocrine Society, European Journal of Endocrinology","year":2024,"url":"https://europepmc.org/abstract/MED/38714321","doi":"10.1093/ejendo/lvae029","gradingScheme":"The abstract does not print grades.","read":"abstract","accessed":"2026-11-11"},{"key":"eular-2021","label":"EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors","publisher":"European Alliance of Associations for Rheumatology (EULAR), Annals of the Rheumatic Diseases","year":2021,"url":"https://europepmc.org/article/PMC/PMC7788064","doi":"10.1136/annrheumdis-2020-217139","gradingScheme":"Oxford Centre for Evidence-Based Medicine levels of evidence (2009), printed as LoE 1 to 5, with the task force's mean level of agreement (LoA) on a 0 to 10 scale.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline update was read only as its abstract, which gives the general rules (continue for grade 1, hold for most grade 2, high-dose steroids for grade 3, taper over at least 4 to 6 weeks, stop for grade 4) but not its organ-by-organ tables.","No source read sets a Pneumocystis prophylaxis rule written specifically for checkpoint inhibitor toxicity; the ASCO/IDSA threshold covers adults with cancer generally and ECIL-5 covers haematological patients. SITC 2021 names the risk but gives no threshold in the text read.","The ASCO/IDSA 2018 update, ECIL-5 and the 2024 ESE/Endocrine Society guideline were read only as abstracts; their dosing, duration and stopping rules for prophylaxis and their taper schedules are not given here. Whether ASCO/IDSA has issued a newer edition was checked only through Europe PMC.","Bone protection, gastric protection and glucose monitoring during long steroid courses are named as harms by SITC but no source read gives an irAE-specific recommendation on them."]},{"id":"strong-opioids-for-cancer-pain","kind":"protocol","name":"Strong opioids for cancer pain: starting, titrating, rescue doses and preventing constipation","aka":["starting morphine for cancer pain","opioid titration","breakthrough cancer pain","rescue dose","PRN morphine","opioid-induced constipation prevention","laxative with opioids","WHO analgesic ladder"],"tldr":"When cancer pain needs a strong painkiller, morphine by mouth is usually the first choice: a regular dose plus extra 'rescue' doses for pain that breaks through, adjusted until the pain is controlled with side effects you can live with. A laxative should be prescribed from the start, because almost everyone taking strong opioids gets constipated.","summary":"NICE CG140 (2012, updated 2016) and WHO (2018) agree on the core: oral morphine first, regular dosing with immediate-release oral morphine for rescue (WHO strong recommendation, moderate-quality evidence). NICE gives a starting schedule for adults without renal or hepatic impairment of 20 to 30 mg oral morphine a day with 5 mg immediate-release rescue doses during titration, and asks for specialist advice before strong opioids in moderate to severe renal or hepatic impairment. ASCO 2023 starts PRN at the lowest dose with early assessment and frequent titration; the Australian guideline (2025) adds ASCO's minimum dose increase of 25 to 50% and NCCN's practice of folding the previous 24 hours of rescue doses into the regular dose.\n\nRescue doses are where the sources differ most in their numbers: WHO suggests 50 to 100% of the regular 4-hourly dose; the Australian guideline, citing ASCO 2022, 5 to 20% of the daily regular dose, up to hourly; NICE gives a fixed 5 mg during titration and says not to use fast-acting fentanyl as first-line rescue. Every patient starting a strong opioid should be prescribed a regular laxative (NICE 1.1.18); NICE says to optimise laxatives before switching opioids, and points to naldemedine and naloxegol appraisals for constipation that persists despite laxatives. Nausea and drowsiness at the start or after a dose rise are usually transient; persistent central nervous system effects call for dose reduction if pain is controlled or a switch if it is not.\n\nThe ESMO 2018 guideline, which the Australian guideline draws on heavily, could not be read directly.","asOf":"2026-11-11","links":[],"tags":[],"related":["opioid-switching-and-conversion"],"cancers":[],"sections":[],"technologies":["pain-management","palliative-care"],"targets":[],"drugs":["fentanyl","methylnaltrexone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Strong painkillers like morphine are safe and work well for cancer pain when the dose is set carefully. You take a regular dose, and an extra dose when pain breaks through. Take a laxative every day too. Tell your team if you are very sleepy, muddled or the pain is not controlled.","domain":"palliative","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["home","ward","outpatient-clinic","community"]},"population":"Adults with pain from cancer or its treatment that needs a strong opioid (WHO also covers adolescents). NICE CG140 is written for adults with advanced and progressive disease; ASCO 2023 covers adults with pain from cancer or cancer treatment. People with moderate to severe kidney or liver impairment, people with a substance use disorder, and children need specialist advice and are not covered by the starting doses here.","trigger":"Pain from cancer that is moderate or severe, or that persists despite paracetamol or an anti-inflammatory.","steps":[{"action":"Before starting, ask about worries such as addiction, tolerance, side effects and what starting morphine means","why":"Fear that morphine is addictive or means the end is near stops many people taking enough to control their pain.","source":"nice-cg140","quote":"When offering pain treatment with strong opioids to a patient with advanced and progressive disease, ask them about concerns such as:","grade":"Not graded (NICE 1.1.1)"},{"action":"Give spoken and written information on how and when to take regular and rescue doses, side effects, safe storage and who to call out of hours","why":"Most of the work of pain control happens at home, and people need to know what to do when pain breaks through at night.","source":"nice-cg140","quote":"Provide verbal and written information on strong opioid treatment to patients and carers, including the following:","grade":"Not graded (NICE 1.1.2)"},{"action":"Start regular oral morphine, sustained-release or immediate-release by the patient's preference, with immediate-release oral morphine for breakthrough pain","why":"Morphine by mouth works for most people, is cheap and widely available, and a fast-acting rescue dose covers pain between regular doses.","source":"who-2018","quote":"Regularly-dosed immediate-release oral morphine, or regularly-dosed slow-release morphine, should be used to maintain effective and safe pain relief whenever oral dosing is possible. With either formulation, immediate-release oral morphine should be used as rescue medicine.","grade":"Strong recommendation; moderate-quality evidence"},{"action":"Where kidneys and liver work normally, start at 20 to 30 mg oral morphine a day (for example 10 to 15 mg sustained-release twice daily) with 5 mg immediate-release rescue doses","why":"A low starting dose with rescue doses lets the right dose be found safely within a few days.","source":"nice-cg140","quote":"For patients with no renal or hepatic comorbidities, offer a typical total daily starting dose schedule of 20 mg to 30 mg of oral morphine (for example, 10 mg to 15 mg oral sustained-release morphine twice daily), plus 5 mg oral immediate-release morphine for rescue doses during the titration phase.","grade":"Not graded (NICE 1.1.5)"},{"action":"Get specialist advice before starting a strong opioid in moderate to severe kidney or liver impairment","why":"Morphine and its breakdown products build up when the kidneys or liver are failing, which can cause drowsiness, confusion and twitching.","source":"nice-cg140","quote":"Seek specialist advice before prescribing strong opioids for patients with moderate to severe renal or hepatic impairment.","grade":"Not graded (NICE 1.1.7)"},{"action":"Review often while titrating and adjust the dose until pain control and side effects are in balance; seek specialist advice if that balance is not reached after a few adjustments","why":"The right dose is the one that controls the pain with side effects you can live with, and it differs from person to person.","source":"nice-cg140","quote":"Adjust the dose until a good balance exists between acceptable pain control and side effects. If this balance is not reached after a few dose adjustments, seek specialist advice. Offer patients frequent review, particularly in the titration phase.","grade":"Not graded (NICE 1.1.6)"},{"action":"When raising the regular dose, take account of the rescue doses used over the previous 24 hours, and reassess pain and side effects within 48 hours","why":"The rescue doses a person needed show how much more regular opioid they need.","source":"aus-2025","quote":"Regular dose of opioid may be increased to incorporate the rescue doses taken in previous 24 h (NCCN), then reassess pain severity and adverse effects within 48 h. (Consensus)","grade":"Consensus (NCCN source)"},{"action":"Use immediate-release oral morphine for breakthrough pain, not fast-acting fentanyl, as the first-line rescue","why":"Oral morphine works for most breakthrough pain; fast-acting fentanyl products cost much more and are kept for when morphine does not work.","source":"nice-cg140","quote":"Do not offer fast-acting fentanyl as first-line rescue medication.","grade":"Not graded (NICE 1.1.15)"},{"action":"Prescribe a regular laxative at an effective dose for everyone starting a strong opioid, and explain that it takes time to work","why":"Constipation affects nearly everyone on strong opioids and does not wear off with time.","source":"nice-cg140","quote":"Prescribe laxative treatment (to be taken regularly at an effective dose) for all patients starting strong opioids.","grade":"Not graded (NICE 1.1.18)"},{"action":"Optimise laxatives before switching opioid for constipation, and consider a peripherally acting opioid antagonist where laxatives have failed","why":"Changing the laxative usually works and keeps the pain control that has been found; antagonists such as naldemedine or naloxegol block opioids in the gut only.","source":"nice-cg140","quote":"Optimise laxative treatment for managing constipation before considering switching strong opioids.","grade":"Not graded (NICE 1.1.20)"},{"action":"Warn that nausea and mild drowsiness are common at the start or after a dose rise and usually pass; treat persistent nausea with an anti-emetic before switching opioid","why":"Knowing the early side effects usually fade helps people keep taking the medicine; drowsiness can affect driving.","source":"nice-cg140","quote":"If nausea persists, prescribe and optimise anti-emetic treatment before considering switching strong opioids.","grade":"Not graded (NICE 1.1.23)"},{"action":"For persistent or moderate to severe drowsiness or confusion, reduce the dose if pain is controlled, or switch opioid if it is not","why":"These are signs of too much opioid for this person; lowering the dose or changing the drug usually clears them.","source":"nice-cg140","quote":"consider dose reduction if pain is controlled or","grade":"Not graded (NICE 1.1.25)"},{"action":"If breathing is slow and the person cannot be roused, withhold opioid and give naloxone in small, repeated doses aimed at restoring consciousness without bringing back the pain","why":"A full reversing dose in someone on long-term opioids brings on severe pain and withdrawal; small doses reverse the danger and keep some pain relief.","source":"aus-2025","quote":"If respiratory rate ≤ 8/min and the person is unrousable, use the appropriate dose of naloxone in frequent small doses with the aim to improve consciousness without worsening pain (diluting ampoule to 10 mL). (ESMO, NCCN)","grade":"Adopted from ESMO and NCCN"}],"bestInClass":{"statement":"Oral morphine first, regular dosing plus immediate-release oral morphine as rescue (WHO 2018, strong recommendation, moderate-quality evidence; NICE CG140), titrated with frequent review, with a regular laxative from day one (NICE CG140; Australian guideline 2025 citing ESMO, NICE and NCCN). The starting dose for adults without renal or hepatic impairment is NICE's 20 to 30 mg a day; ASCO 2023 starts as needed at the lowest effective dose. The size of the rescue dose differs between sources and is stated side by side: WHO 50 to 100% of the 4-hourly dose; ASCO 2022 (via the Australian guideline) 5 to 20% of the daily dose, up to hourly; NICE a fixed 5 mg while titrating. None of these rests on strong trial evidence: WHO calls its rescue statement best practice and found one small trial.","sources":["who-2018","nice-cg140","aus-2025","asco-2023"]},"variants":[{"name":"Start as needed rather than regularly","differs":"Starts immediate-release opioid only as needed (PRN) at the lowest dose, with early assessment and frequent titration, adding a long-acting opioid once three or four doses a day are needed consistently.","evidence":"ASCO 2023 recommends PRN initiation at the lowest possible dose; the Australian guideline applies it to intermittent pain and adds NCCN's threshold of 3 to 4 doses a day. NICE and WHO start regular dosing. No trial comparing the two starts was found in the sources read.","sources":["asco-2023","aus-2025"]},{"name":"Rescue dose as a fraction of the daily dose","differs":"Sets the rescue dose at 5 to 20% of the daily regular morphine-equivalent dose, available hourly, with advice to seek help if three doses in a row have not worked (Australian guideline, citing ASCO 2022 and NCCN). WHO suggests 50 to 100% of the regular 4-hourly dose, which is roughly 8 to 17% of the daily dose.","evidence":"Consensus in all sources. WHO found one small trial (68 patients) on breakthrough pain and could not make a recommendation, issuing a best practice statement instead.","sources":["aus-2025","who-2018"]},{"name":"Transdermal patch first","differs":"Starts with a fentanyl or buprenorphine patch instead of oral morphine.","evidence":"NICE does not routinely offer patches as first-line maintenance where oral opioids are suitable, and considers them where oral opioids are not suitable and pain is stable. The Australian guideline notes a reduced risk of constipation with transdermal preparations and that they suit stable pain only, because of slow onset and long action.","sources":["nice-cg140","aus-2025"]},{"name":"Oxycodone with naloxone, or methylnaltrexone, for constipation","differs":"Where constipation persists despite stimulant and softening laxatives, switches to a less constipating opioid, to oxycodone combined with naloxone (below its maximum dose), or uses methylnaltrexone short term in palliative care.","evidence":"Adopted by the Australian guideline from ESMO, NCCN and NICE; NICE refers to its technology appraisals of naldemedine (TA651) and naloxegol (TA345) for people who have had laxatives.","sources":["aus-2025","nice-cg140"]}],"grades":[{"claim":"NSAIDs, paracetamol and opioids, alone or together, at the start of cancer pain management","grade":"Strong recommendation; low-quality evidence","source":"who-2018"},{"claim":"Any opioid may be considered for maintenance of pain relief","grade":"Strong recommendation; low-quality evidence","source":"who-2018"},{"claim":"Regular oral morphine (immediate or slow release) with immediate-release oral morphine as rescue","grade":"Strong recommendation; moderate-quality evidence","source":"who-2018"},{"claim":"Breakthrough pain treated with an immediate-release opioid rescue medicine","grade":"Best Practice statement","source":"who-2018","quote":"Breakthrough pain should be treated with a rescue medicine, which should be an opioid such as morphine in its immediate-release formulation."},{"claim":"Subcutaneous rather than intramuscular route when oral or transdermal routes are not possible","grade":"Best Practice statement","source":"who-2018","quote":"When oral or transdermal routes are not possible for administration of opioids, the subcutaneous route is preferred over intramuscular injection, as this route is less painful for the patient."},{"claim":"Taper gradually if physical dependence has developed","grade":"Best Practice statement","source":"who-2018","quote":"If a patient has developed physical dependence on opioids over the course of the management of their pain, opioid dosages should be decreased gradually to avoid withdrawal symptoms."},{"claim":"A regular laxative for all patients starting strong opioids","grade":"Not graded (NICE does not grade recommendations)","source":"nice-cg140"},{"claim":"Laxatives routinely for prophylaxis and management of opioid-induced constipation","grade":"Adopted from ESMO, NICE and NCCN (strength as in the source guidelines, not printed beside the recommendation)","source":"aus-2025","quote":"Laxatives must be routinely prescribed for both the prophylaxis and the management of opioid‐induced constipation (ESMO, NICE, NCCN)"}],"sources":[{"key":"nice-cg140","label":"Palliative care for adults: strong opioids for pain relief (CG140), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg140/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider', 'do not offer') signals strength. Published May 2012, last updated August 2016.","read":"full-text","accessed":"2026-11-11"},{"key":"who-2018","label":"WHO guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents","publisher":"World Health Organization","year":2018,"url":"https://iris.who.int/handle/10665/279700","gradingScheme":"GRADE: strong or conditional recommendations with high, moderate, low or very low quality of evidence; best practice statements where the guideline group judged the benefit clear without graded evidence.","read":"full-text","accessed":"2026-11-11"},{"key":"aus-2025","label":"Update of the Australian Guideline for the Management of Cancer Pain in Adults (Cancer Council Australia)","publisher":"Asia-Pacific Journal of Clinical Oncology","year":2025,"url":"https://doi.org/10.1111/ajco.70047","doi":"10.1111/ajco.70047","gradingScheme":"Recommendations adopted from source guidelines (ESMO, NCCN, NICE, WHO, ASCO) carry the strength of the source, named in brackets after each; de novo recommendations rest on Level 1 evidence or on consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2023","label":"Use of Opioids for Adults With Pain From Cancer or Cancer Treatment: ASCO Guideline","publisher":"ASCO (Journal of Clinical Oncology)","year":2023,"url":"https://doi.org/10.1200/JCO.22.02198","doi":"10.1200/JCO.22.02198","read":"abstract","accessed":"2026-11-11"},{"key":"eapc-2012","label":"Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC","publisher":"European Association for Palliative Care (Lancet Oncology)","year":2012,"url":"https://doi.org/10.1016/S1470-2045(12)70040-2","doi":"10.1016/S1470-2045(12)70040-2","gradingScheme":"GRADE (16 recommendations).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2018","label":"Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2018,"url":"https://doi.org/10.1093/annonc/mdy152","doi":"10.1093/annonc/mdy152","read":"not-reachable","accessed":"2026-11-11"},{"key":"nccn-2025","label":"Adult Cancer Pain, Version 2.2025, NCCN Clinical Practice Guidelines in Oncology","publisher":"NCCN (Journal of the National Comprehensive Cancer Network)","year":2025,"url":"https://doi.org/10.6004/jnccn.2025.0032","doi":"10.6004/jnccn.2025.0032","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2018 cancer pain guideline could not be read: Europe PMC holds no abstract, the publisher refused a script and no archived copy was found. What ESMO says is known here only through the Australian guideline (2025), which names ESMO as the source of several recommendations.","The ASCO 2023 opioid guideline and the EAPC 2012 recommendations were read as abstracts only; the full NCCN guideline needs a login and was not read.","The size of the rescue dose rests on consensus in every source read; WHO found a single small trial on breakthrough pain. No source read compares a fixed rescue dose with a percentage of the daily dose.","NICE CG140 dates from 2012 (updated 2016) and the WHO guideline from 2018. No newer edition of either was found.","Children, people with moderate to severe kidney or liver impairment, and people with a substance use disorder need specialist plans that are outside this record."]},{"id":"sun-protection-during-and-after-cancer-treatment","kind":"protocol","name":"Sun protection during and after cancer treatment","aka":["photosensitivity during chemotherapy","sunscreen during cancer treatment","sun protection after radiotherapy","sun sensitivity on targeted therapy","radiation recall sun protection"],"tldr":"Some chemotherapy, many targeted and immunotherapy drugs, and radiotherapy make the skin burn more easily; treated skin stays sensitive for years. Stay in the shade at midday, cover up with a wide-brimmed hat and long sleeves, use sunscreen of at least SPF 30 with high UVA protection and reapply it, avoid sunbeds, and ask before putting anything on skin being treated with radiotherapy.","summary":"No graded guideline sets out sun protection during anticancer treatment; the advice comes from national patient guidance and general sun-safety guidance. NCI's chemotherapy booklet (2023) says chemotherapy can cause sensitivity to the sun even in people with very dark skin, and advises avoiding direct sun from 10 a.m. to 4 p.m., sunscreen of SPF 15 or higher, lip balm with SPF, covering clothing and no tanning beds, and protecting skin previously treated with radiotherapy from the sun (radiation recall). NCI's radiotherapy booklet (2021) advises daily protection of the treated area, a broad-brimmed hat and long sleeves, sunscreen that the team may suggest at SPF 30 or higher, no tanning beds, protection continuing after treatment ends, and checking with the team before using sunscreen or other products on the treated skin. Macmillan (2023) says many targeted and immunotherapy drugs make skin sun-sensitive and that radiotherapy skin stays sensitive for many years, especially in the first year. The NHS (2026) recommends shade from 11 a.m. to 3 p.m. in the UK from March to October, at least SPF 30 and at least 4-star UVA protection, applied generously and reapplied. The MASCC EGFR inhibitor guideline (2011) includes sunscreen in its preventive rash regimen and recommends avoiding direct sun to prevent dry skin (level III, grade B). The sources differ on the SPF figure (15 in NCI's chemotherapy booklet, 30 in the others).","asOf":"2026-11-11","links":[],"tags":[],"related":["skin-and-nail-care-during-cancer-drug-treatment","driving-flying-and-travel-during-cancer-treatment"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sun-protection-after-skin-cancer","radiation-dermatitis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer treatment can make your skin burn quickly. Keep in the shade at midday, wear a hat and long sleeves, use sunscreen of at least SPF 30 and put more on often. Never use sunbeds. Keep skin that has had radiotherapy out of the sun, especially in the first year, and ask your team before using sunscreen on it during treatment.","domain":"supportive-care","setting":{"who":["patient-or-carer","nurse"],"where":["home","radiotherapy-department","outpatient-clinic"]},"population":"Adults having chemotherapy, targeted therapy, immunotherapy or radiotherapy, and survivors with skin previously treated with radiotherapy. Which drugs cause photosensitivity is set out in each drug's label; this protocol does not list them.","trigger":"Starting a treatment the team says makes the skin sun-sensitive, any course of radiotherapy, or going into strong sun during or after treatment.","steps":[{"action":"Ask the team whether your treatment makes your skin sensitive to the sun","why":"Some chemotherapy and many targeted and immunotherapy drugs make the skin burn faster, and the team knows which ones.","source":"macmillan-holiday","quote":"Many targeted therapy and immunotherapy drugs can make your skin sensitive to the sun. Your skin may burn more easily than normal. Ask your doctor or nurse whether you need to take special care to protect your skin.","grade":"Not graded (patient information)"},{"action":"Stay in the shade when the sun is strongest, between 11 a.m. and 3 p.m. in the UK from March to October","why":"Most of the burning ultraviolet light reaches the ground in the middle of the day.","source":"nhs-sun-safety","quote":"Spend time in the shade when the sun is strongest. In the UK, this is between 11am and 3pm from March to October.","grade":"Not graded (public health guidance)"},{"action":"Cover up outdoors with a broad-brimmed hat, a long-sleeved shirt and long trousers, and cover a bald or thinning scalp","why":"Clothing protects more reliably than sunscreen, which is often applied too thinly.","source":"nci-radiation-and-you","quote":"Wear a broad-brimmed hat, long-sleeved shirt, and long pants when you are outside.","grade":"Not graded (patient booklet)"},{"action":"Use sunscreen of at least SPF 30 with at least 4-star UVA protection, apply plenty 30 minutes before going out and again just before, and reapply every 2 hours and after swimming or sweating","why":"Most people put on too little sunscreen, and it wears off with water, sweat and time.","source":"nhs-sun-safety","quote":"use at least factor 30 sunscreen – make sure to use enough and re-apply frequently","grade":"Not graded (public health guidance)"},{"action":"During radiotherapy, check with the team before putting sunscreen, creams or any other product on the treated skin","why":"Some products on the treated area can increase the skin reaction or interfere with treatment.","source":"nci-radiation-and-you","quote":"Check with your doctor or nurse before using any of the following skin products:","grade":"Not graded (patient booklet)"},{"action":"Keep skin treated with radiotherapy out of the sun after treatment ends, with extra care in the first year","why":"Treated skin stays sensitive for years and has a higher risk of burning and of later skin cancer.","source":"macmillan-holiday","quote":"The skin in the area treated by radiotherapy stays sensitive for many years. You need to take extra care to protect it from the sun, especially for the first year.","grade":"Not graded (patient information)"},{"action":"If chemotherapy is given after radiotherapy, protect the previously treated skin from the sun and tell the team if it turns red or sore","why":"Some drugs can bring back a skin reaction in an area treated before (radiation recall), and sun makes it worse.","source":"nci-chemo-and-you","quote":"Protect the area of your skin that received radiation therapy from the sun.","grade":"Not graded (patient booklet)"},{"action":"Do not use sunbeds","why":"Sunbeds give the same harmful ultraviolet light as the sun.","source":"nci-radiation-and-you","quote":"Do not use tanning beds. Tanning beds expose you to the same harmful effects as the sun.","grade":"Not graded (patient booklet)"}],"bestInClass":{"statement":"No graded guideline exists for sun protection during anticancer treatment. The best available version combines the NHS sun-safety guidance (2026: shade at midday, covering clothing, at least SPF 30 and 4-star UVA, generous application and reapplication) with the cancer-specific points that NCI (2021, 2023) and Macmillan (2023) agree on: ask whether the treatment is photosensitising, protect radiotherapy skin daily during and for years after treatment, check with the team before using products on skin under treatment, protect previously irradiated skin during chemotherapy, and avoid sunbeds. The sources disagree on the sunscreen figure: NCI's chemotherapy booklet says SPF 15 or higher; its radiotherapy booklet, the NHS and Macmillan say 30 or higher.","sources":["nhs-sun-safety","nci-radiation-and-you","nci-chemo-and-you","macmillan-holiday"]},"variants":[{"name":"SPF 15 or higher (NCI chemotherapy booklet)","differs":"Gives SPF 15 or higher, or a zinc oxide sunblock, and avoids direct sun from 10 a.m. to 4 p.m.","evidence":"Patient booklet, not graded: 'Use sunscreen lotion with an SPF (skin protection factor) of 15 or higher.' The NHS, Macmillan and NCI's own radiotherapy booklet give 30.","sources":["nci-chemo-and-you"]},{"name":"Sunscreen within the preventive regimen for EGFR inhibitor rash (MASCC)","differs":"Sunscreen is applied twice daily with hydrocortisone 1% and moisturiser as part of preventive treatment in the first 6 weeks of an EGFR inhibitor; sunscreen alone is listed as not recommended for preventing the rash.","evidence":"MASCC 2011 Table 3: topical regimen level II, grade C; avoiding direct sun to prevent dry skin level III, grade B.","sources":["mascc-egfri-2011"]},{"name":"Avoiding chlorinated pools and hot tubs (Macmillan)","differs":"Adds that some people's skin becomes sensitive to chlorine during chemotherapy and that hot tubs and saunas are best avoided.","evidence":"Patient information, not graded.","sources":["macmillan-holiday"]}],"grades":[{"claim":"All sun protection steps","grade":"Not graded: patient booklets and public health guidance, without a grading scheme","source":"nhs-sun-safety"},{"claim":"Avoid extreme temperatures and direct sunlight to prevent dry skin on EGFR inhibitors","grade":"Level III, grade B (MASCC Table 8)","source":"mascc-egfri-2011"},{"claim":"Chemotherapy can cause sun sensitivity even in very dark skin","grade":"Not graded (patient booklet)","source":"nci-chemo-and-you","quote":"This problem can happen even to people who have very dark skin color."},{"claim":"Protection of radiotherapy skin continues after treatment ends","grade":"Not graded (patient booklet)","source":"nci-radiation-and-you","quote":"You will need to protect your skin from the sun even after radiation therapy is over."}],"sources":[{"key":"nhs-sun-safety","label":"Sunscreen and sun safety","publisher":"NHS","year":2026,"url":"https://www.nhs.uk/live-well/seasonal-health/sunscreen-and-sun-safety/","gradingScheme":"Public health information page; not graded. Reviewed 24 March 2026.","read":"full-text","accessed":"2026-11-11"},{"key":"nci-radiation-and-you","label":"Radiation Therapy and You: Support for People with Cancer","publisher":"National Cancer Institute (US)","year":2021,"url":"https://www.cancer.gov/publications/patient-education/radiation-therapy-and-you.pdf","gradingScheme":"Patient booklet; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nci-chemo-and-you","label":"Chemotherapy and You: Support for People with Cancer","publisher":"National Cancer Institute (US)","year":2023,"url":"https://www.cancer.gov/publications/patient-education/chemotherapy-and-you.pdf","gradingScheme":"Patient booklet; recommendations are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"macmillan-holiday","label":"Taking care on holiday (travel and cancer)","publisher":"Macmillan Cancer Support","year":2023,"url":"https://www.macmillan.org.uk/cancer-information-and-support/impacts-of-cancer/travel/taking-care-on-holiday","gradingScheme":"Patient information page; not graded. Reviewed 1 March 2023, page marked as under review.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-egfri-2011","label":"Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities","publisher":"MASCC Skin Toxicity Study Group (Supportive Care in Cancer)","year":2011,"url":"https://doi.org/10.1007/s00520-011-1197-6","doi":"10.1007/s00520-011-1197-6","gradingScheme":"Levels of evidence I to V and grades A to D.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-derm-2021","label":"Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology)","year":2021,"url":"https://doi.org/10.1016/j.annonc.2020.11.005","doi":"10.1016/j.annonc.2020.11.005","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No trial has tested sun protection advice during anticancer treatment; every step is expert or public health advice, and none is graded.","The sources disagree on the minimum SPF (15 in NCI's 2023 chemotherapy booklet, 30 in its 2021 radiotherapy booklet, the NHS and Macmillan) and give different hours (10 a.m. to 4 p.m. for NCI, 11 a.m. to 3 p.m. for the NHS in the UK).","Which drugs are photosensitising, and how long the sensitivity lasts after the last dose, is in each drug's label and was not compiled here.","The ESMO 2021 dermatological toxicity guideline could not be read (bot check).","How to balance sun avoidance with vitamin D during long treatment is not addressed by the cancer sources; the NHS page mentions the balance in general terms only."]},{"id":"svc-obstruction","kind":"protocol","name":"Superior vena cava obstruction in cancer: recognition, imaging, stenting and treatment of the cause","aka":["SVCO","SVC syndrome","superior vena cava syndrome","malignant SVC obstruction","SVC stent"],"tldr":"A cancer in the chest, most often lung cancer or lymphoma, can squeeze the large vein that brings blood back from the head and arms. The face, neck and arms swell, and breathing can become difficult: this needs urgent hospital assessment the same day. A CT scan confirms it; a small metal tube (stent) in the vein can relieve symptoms within days, and chemotherapy or radiotherapy treats the cancer.","summary":"Malignant SVCO is caused by external compression, thrombosis or direct invasion of the superior vena cava; lung cancer accounts for 65 to 80%, lymphoma for 2 to 10% (Scottish Palliative Care Guidelines). It may be the first presentation of the cancer. Symptoms are those of venous hypertension: breathlessness, headache worse on stooping, swelling of the face, neck and arms, visual change and dizziness; signs include non-pulsatile distended neck veins, chest wall collaterals and, late, stridor and papilloedema. A chest X-ray and CT confirm it; CT venography and MR venography are the primary imaging studies (Sen 2026).\n\nNICE NG122 (2005 recommendations, still current) offers chemotherapy and radiotherapy according to stage and performance status, and considers a stent for immediate relief of severe symptoms or after failure of earlier treatment. The Scottish guideline adds loosening clothing and supporting the arms, urgent discussion with oncology, radiotherapy or respiratory medicine, chemotherapy and radiotherapy for small-cell lung cancer, consideration of stenting, thrombectomy, thrombolysis and anticoagulation, and dexamethasone 16 mg then 8 mg twice daily, noting that steroids may help despite the absence of evidence. A systematic review (Rowell and Gleeson 2002) found chemotherapy and/or radiotherapy relieved SVCO in 77% with small-cell and 60% with non-small-cell lung cancer, and a stent in 95%, more rapidly; the effectiveness of steroids and the best timing of a stent were uncertain. A 2026 vascular review calls stenting first-line for symptomatic SVC syndrome of any cause (pooled clinical success 96.8% in 2249 patients; fatal complications 1 to 2%), and the Annals of Palliative Medicine 2024 review reserves immediate stenting for airway compromise, laryngeal oedema or cerebral oedema, after complete staging to decide whether treatment is curative or palliative.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency"],"related":["metastatic-spinal-cord-compression-emergency"],"cancers":["nsclc","sclc","non-hodgkin-lymphoma"],"sections":[],"technologies":["ct","palliative-radiotherapy"],"targets":[],"drugs":["dexamethasone"],"companies":[],"institutions":["nice"],"pathways":[],"terms":["superior-vena-cava-obstruction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If your face, neck or arms swell or you become breathless, and you have a cancer in your chest, ring your cancer team or 999 the same day.","domain":"emergencies","setting":{"who":["doctor","nurse","multidisciplinary-team","radiographer","emergency-team","patient-or-carer"],"where":["emergency-department","acute-oncology-service","ward","radiotherapy-department","home","telephone-triage"]},"population":"Adults with a known or suspected cancer in the chest (lung cancer, lymphoma, other mediastinal or metastatic disease) who develop obstruction of the superior vena cava. Benign causes (central venous catheters, pacemaker leads) are noted only where the sources compare them. Children are not covered.","trigger":"Swelling of the face, neck or arms, breathlessness, headache worse on bending, or distended neck and chest wall veins in a person with cancer in the chest, or as a first presentation of cancer.","steps":[{"action":"Recognise the symptoms of venous congestion: breathlessness, swelling of the face, neck and arms, headache worse on stooping, visual change and dizziness","why":"The blocked vein raises pressure in the head, neck and arms; this can be the first sign of a cancer.","source":"scot-pcg-svco","quote":"This condition may be the first presentation of malignancy or can occur in those with known malignancy."},{"action":"Confirm the diagnosis with a chest X-ray and CT, ideally CT venography","why":"The scan shows where the vein is blocked, whether there is a clot, and what is pressing on it.","source":"sen-2026","quote":"Central vein obstruction can be suspected based on Duplex ultrasound of the neck and arm veins, but computed tomography venography (CTV) (Fig 1) and/or magnetic resonance venography are the primary imaging studies to diagnose and ascertain the extent of the central venous obstruction."},{"action":"Loosen tight clothing and support the arms on pillows","why":"This eases the pressure in the veins of the head and arms while treatment is arranged.","source":"scot-pcg-svco","quote":"Ensure restricting clothing is loosened and upper arms are supported on pillows."},{"action":"Discuss urgently with oncology, clinical oncology (radiotherapy) or respiratory medicine","why":"The right treatment depends on the type of cancer, its stage and how fit the person is.","source":"scot-pcg-svco","quote":"Discuss with or refer urgently to oncologist, radiotherapist, respiratory physician as appropriate."},{"action":"Complete staging, including the type of cancer where it is not yet known, before deciding whether treatment aims to cure","why":"The type and extent of the cancer decide whether chemotherapy or radiotherapy comes first, and whether cure is possible.","source":"apm-2024","quote":"When evaluating patients, a complete staging workup is recommended, as it will determine whether treatment should be definitive/curative or palliative in intent."},{"action":"Offer chemotherapy and radiotherapy according to the stage of the cancer and the person's performance status","why":"Treating the cancer relieves the obstruction in most people with lung cancer.","source":"nice-ng122","quote":"For people who present with superior vena cava obstruction, offer chemotherapy and radiotherapy based on the stage of disease and performance status. [2005]"},{"action":"Consider a stent for immediate relief of severe symptoms, or when earlier treatment has failed","why":"A stent opens the vein within days, faster than chemotherapy or radiotherapy.","source":"nice-ng122","quote":"Consider stent insertion for the immediate relief of severe symptoms of superior vena caval obstruction or following failure of earlier treatment. [2005]"},{"action":"Treat the vein urgently with a stent, with thrombolysis if there is clot, when there is airway compromise, laryngeal oedema or reduced consciousness from brain swelling","why":"These complications can kill before cancer treatment has time to work.","source":"apm-2024","quote":"If the patient requires urgent treatment of venous obstruction, such as in the cases of acute central airway obstruction, severe laryngeal edema and/or coma from cerebral edema, direct opening of the occlusion by endovascular stenting and angioplasty with thrombolysis should be considered."},{"action":"If dexamethasone is tried, stop it promptly if there is no benefit","why":"Steroids are widely given, but there is no good evidence that they help, and they have side effects.","source":"scot-pcg-svco","quote":"Steroids may be helpful despite the absence of evidence to support their use."},{"action":"Offer supportive care to everyone: benzodiazepines, opioids and oxygen for breathlessness and distress","why":"Breathlessness is frightening, and these ease it whatever else is done.","source":"scot-pcg-svco","quote":"Offer benzodiazepines, opioids, oxygen and supportive care to all patients in addition to the above measures."}],"bestInClass":{"statement":"No current graded guideline on malignant SVCO was found. NICE NG122 is the most recent national guideline that addresses it, with two 2005 recommendations: chemotherapy and radiotherapy by stage and performance status, and a stent for immediate relief of severe symptoms or after earlier treatment fails. The evidence since has moved towards earlier stenting: the 2002 systematic review found stents relieved SVCO in 95% (against 60 to 77% with chemotherapy or radiotherapy) and more rapidly, and a 2026 vascular surgery review of literature to April 2025 calls stenting first-line for symptomatic SVC syndrome of any cause, with covered stents probably safer. The positions differ on when to stent: NICE and the Scottish guideline consider it for severe symptoms or failure of other treatment; the vascular review puts it first for anyone symptomatic. In either case complete staging comes first, because the histology decides between chemotherapy and radiotherapy (Annals of Palliative Medicine 2024). Steroids are unsupported by evidence in every source read.","sources":["nice-ng122","rowell-2002","sen-2026","scot-pcg-svco","apm-2024"]},"variants":[{"name":"Stent first for all symptomatic SVC obstruction","differs":"Puts balloon angioplasty and stenting first for every symptomatic patient, before or alongside cancer treatment, rather than reserving it for severe symptoms or failure.","evidence":"Sen 2026 review: pooled clinical success 96.8% and 1-year patency over 90% in a meta-analysis of 2249 patients (benign and malignant); total complications about 9%, fatal 1 to 2%, rupture with tamponade the most severe.","sources":["sen-2026"]},{"name":"Dexamethasone 16 mg, then 8 mg twice daily (Scottish Palliative Care Guidelines)","differs":"Gives dexamethasone 16 mg immediately and 8 mg twice daily from the next day, with the second dose before 2 pm, stopped if there is no benefit.","evidence":"No evidence of benefit: the guideline says so itself, and the 2002 systematic review found the effectiveness of steroids uncertain.","sources":["scot-pcg-svco","rowell-2002"]}],"grades":[{"claim":"Chemotherapy and radiotherapy based on stage and performance status","grade":"not graded (NICE; dated 2005)","source":"nice-ng122"},{"claim":"Stent for immediate relief of severe symptoms or after failure of earlier treatment","grade":"not graded (NICE; dated 2005)","source":"nice-ng122"},{"claim":"Relief rates by treatment","grade":"systematic review (2 randomised and 44 non-randomised studies)","source":"rowell-2002","quote":"Insertion of an SVC stent relieved SVCO in 95%; 11% of those treated had further SVCO but recanalization was possible in the majority resulting in a long-term patency rate of 92%."}],"sources":[{"key":"scot-pcg-svco","label":"Scottish Palliative Care Guidelines: Superior vena cava obstruction","publisher":"NHS Scotland, Scottish Palliative Care Guidelines (Right Decisions platform)","year":2026,"url":"https://www.palliativecareguidelines.scot.nhs.uk/scottish-palliative-care-guidelines/palliative-emergencies/superior-vena-cava-obstruction/","gradingScheme":"National consensus palliative care guidance; not graded. The page carries no publication or review date: the year given is the year it was read.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng122","label":"Lung cancer: diagnosis and management (NG122), palliative interventions and supportive and palliative care","publisher":"NICE","year":2019,"url":"https://www.nice.org.uk/guidance/ng122/chapter/Palliative-interventions-and-supportive-and-palliative-care","gradingScheme":"NICE does not grade recommendations; strength is in the wording ('offer', 'consider'). Each recommendation is dated by the year it was written. Published March 2019, last updated March 2024.","read":"full-text","accessed":"2026-11-11"},{"key":"rowell-2002","label":"Steroids, radiotherapy, chemotherapy and stents for superior vena caval obstruction in carcinoma of the bronchus: a systematic review","publisher":"Clinical Oncology (Royal College of Radiologists)","year":2002,"url":"https://europepmc.org/abstract/MED/12555872","doi":"10.1053/clon.2002.0095","read":"abstract","accessed":"2026-11-11"},{"key":"sen-2026","label":"Contemporary management of superior vena cava syndrome","publisher":"Journal of Vascular Surgery: Venous and Lymphatic Disorders","year":2026,"url":"https://europepmc.org/article/PMC/PMC13098589","doi":"10.1016/j.jvsv.2026.102491","gradingScheme":"A narrative review with a systematic literature search (to April 2025); not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"apm-2024","label":"Management of malignant superior vena cava syndrome","publisher":"Annals of Palliative Medicine","year":2024,"url":"https://europepmc.org/abstract/MED/38600814","doi":"10.21037/apm-23-573","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No current graded guideline on malignant SVCO was found. NICE's recommendations date from 2005, and the Cochrane review of steroids, radiotherapy, chemotherapy and stents (CD001316) has been withdrawn.","Whether to stent at diagnosis or only after cancer treatment fails is unsettled: the 2002 systematic review called the optimal timing uncertain, and no randomised trial of stent first against chemotherapy or radiotherapy first was found.","Anticoagulation after a stent for malignant SVCO varies between centres; a 2025 retrospective series (Current Oncology) was found but not read, and no guideline read sets a regimen.","Whether steroids before a biopsy can obscure a diagnosis of lymphoma is not addressed by any source read here.","SIGN 137 (2014), the source of the Scottish guideline, was not read."]},{"id":"surgical-site-infection-prevention","kind":"protocol","name":"Surgical site infection prevention: skin preparation, antibiotic timing, warming and wound care","aka":["SSI prevention","SSI bundle","wound infection prevention","surgical antibiotic prophylaxis","chlorhexidine skin prep","preoperative shower","hair clipping before surgery"],"tldr":"Wound infections after an operation are common and mostly preventable. Before surgery you shower, hair is clipped rather than shaved if it has to go, a single dose of antibiotic is given shortly before the cut when the operation needs it, and the skin is cleaned with chlorhexidine in alcohol. You are kept warm during the operation, and the wound is covered and cared for cleanly afterwards.","summary":"NICE NG125 (2019, updated 2020) and the WHO global guidelines (2nd edition, 2018) agree on the core. Shower or bathe with soap before surgery (WHO conditional, moderate quality: plain or antimicrobial soap). Do not remove hair routinely; if needed, use clippers, never razors (WHO strong, moderate). Give antibiotic prophylaxis for clean-contaminated and contaminated operations and implants, before incision (WHO strong, low quality) and within 120 minutes of it (WHO strong, moderate), repeating it if the operation outlasts the drug's half-life; do not continue it after the operation (WHO strong, moderate) or because a drain is in place (WHO conditional, low). Prepare the skin with alcohol-based chlorhexidine (WHO strong, low to moderate; NICE first choice unless next to a mucous membrane). Keep the patient warm, consider triclosan-coated sutures (both), and cover the wound at the end of the operation; shower after 48 hours (NICE).\n\nThey differ in places. On oxygen, WHO suggests 80% inspired oxygen during and for 2 to 6 hours after intubated general anaesthesia (conditional, moderate), while NICE asks for enough oxygen to keep saturation above 95%. For elective colorectal surgery, WHO suggests oral antibiotics combined with mechanical bowel preparation (conditional, moderate) and recommends against bowel preparation alone (strong, moderate); NICE says not to use mechanical bowel preparation routinely and does not address oral antibiotics. On wound irrigation, NICE says do not irrigate, while WHO suggests considering aqueous povidone-iodine irrigation (conditional, low). WHO suggests prophylactic negative pressure dressings on high-risk closed wounds (conditional, low); NICE NG125's recommendations do not mention them. Nasal mupirocin for Staphylococcus aureus carriers is recommended by WHO for cardiothoracic and orthopaedic surgery (strong) and suggested for others; NICE leaves it to local decision.","asOf":"2026-11-11","links":[],"tags":[],"related":["vte-prophylaxis-after-cancer-surgery"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"To stop the wound getting infected: shower before surgery, do not shave the area yourself, and keep the dressing on as advised. You can usually shower two days after surgery. Tell your team if the wound gets red, hot, swollen, leaks pus, or you get a fever.","domain":"surgery-perioperative","setting":{"who":["surgical-team","anaesthetist","nurse","patient-or-carer"],"where":["ward","theatre","home"]},"population":"People having surgery that involves a cut through the skin, including cancer surgery. NICE NG125 covers adults, young people and children; several WHO recommendations are stated for adults only (oxygen, bowel preparation, negative pressure dressings). Not specific to cancer: no source read gives separate SSI rules for people with cancer, though chemotherapy, steroids, malnutrition and previous radiotherapy all raise risk.","trigger":"A planned operation.","steps":[{"action":"Tell the patient the risk of wound infection, what is being done to reduce it, how to care for the wound at home and whom to call","why":"People who know the signs of infection come back early, when it is easier to treat.","source":"nice-ng125","quote":"Offer patients and carers information and advice about how to recognise a surgical site infection and who to contact if they are concerned.","grade":"[2008]"},{"action":"Shower or bathe with soap the day before or on the day of surgery","why":"Washing lowers the number of germs on the skin; plain soap works as well as antiseptic soap in the trials WHO reviewed.","source":"who-ssi-2018","quote":"It is good clinical practice for patients to bathe or shower prior to surgery. The panel suggests that either a plain or antimicrobial soap may be used for this purpose.","grade":"Conditional recommendation, moderate quality of evidence"},{"action":"Do not remove hair unless necessary; if it must go, use clippers on the day of surgery, never a razor","why":"Shaving makes tiny cuts in the skin where germs grow.","source":"who-ssi-2018","quote":"The panel recommends that in patients undergoing any surgical procedure, hair should either not be removed or, if absolutely necessary, it should be removed only with a clipper. Shaving is strongly discouraged at all times, whether preoperatively or in the operating room (OR).","grade":"Strong recommendation, moderate quality of evidence"},{"action":"Give antibiotic prophylaxis when the operation calls for it (clean-contaminated or contaminated surgery, or an implant), before the incision and within 120 minutes of it, allowing for the drug's half-life","why":"The antibiotic needs to be in the tissues when the skin is cut; given too early or after the cut, it protects less.","source":"who-ssi-2018","quote":"The panel recommends the administration of SAP within 120 minutes before incision, while considering the half-life of the antibiotic.","grade":"Strong recommendation, moderate quality of evidence"},{"action":"Repeat the antibiotic dose if the operation lasts longer than the drug's half-life","why":"A long operation can outlast the protection of one dose.","source":"nice-ng125","quote":"Give a repeat dose of antibiotic prophylaxis when the operation is longer than the half-life of the antibiotic given.","grade":"[2008]"},{"action":"Clean the operation site immediately before incision with an alcohol-based chlorhexidine solution, unless contraindicated or next to a mucous membrane, and let it dry fully if diathermy will be used","why":"Chlorhexidine in alcohol kills skin germs best; alcohol left pooled or wet can catch fire with diathermy.","source":"who-ssi-2018","quote":"The panel recommends alcohol-based antiseptic solutions based on CHG for surgical site skin preparation in patients undergoing surgical procedures.","grade":"Strong recommendation, low to moderate quality of evidence"},{"action":"Keep the patient warm during the operation","why":"Even mild cooling reduces blood flow to the wound and the body's defences against infection.","source":"who-ssi-2018","quote":"The panel suggests the use of warming devices in the operating room and during the surgical procedure for patient body warming with the purpose of reducing SSI.","grade":"Conditional recommendation, moderate quality of evidence"},{"action":"Consider triclosan-coated sutures","why":"Sutures coated with an antiseptic reduce infection a little across many types of surgery.","source":"who-ssi-2018","quote":"The panel suggests the use of triclosan-coated sutures for the purpose of reducing the risk of SSI, independent of the type of surgery.","grade":"Conditional recommendation, moderate quality of evidence"},{"action":"Cover the incision with a suitable dressing at the end of the operation, and change dressings with aseptic non-touch technique","why":"A clean covering protects the wound while it seals over in the first days.","source":"nice-ng125","quote":"Cover surgical incisions with an appropriate interactive dressing at the end of the operation.","grade":"[2008]"},{"action":"Stop prophylactic antibiotics when the operation ends, including when a drain is left in","why":"Continuing antibiotics does not prevent more infections and adds side effects and resistance.","source":"who-ssi-2018","quote":"The panel recommends against the prolongation of SAP administration after completion of the operation for the purpose of preventing SSI.","grade":"Strong recommendation/moderate quality of evidence"},{"action":"Clean the wound with sterile saline for the first 48 hours, then tell the patient they can shower","why":"After two days a closed wound is sealed enough to get wet.","source":"nice-ng125","quote":"Advise patients that they may shower safely 48 hours after surgery.","grade":"[2008]"},{"action":"If infection is suspected from spreading redness, give an antibiotic that covers the likely organisms, guided by local resistance and microbiology","why":"Early treatment stops a wound infection spreading or opening the wound.","source":"nice-ng125","quote":"When surgical site infection is suspected by the presence of cellulitis, either by a new infection or an infection caused by treatment failure, give the patient an antibiotic that covers the likely causative organisms.","grade":"[2008]"}],"bestInClass":{"statement":"Soap shower, no shaving (clippers if needed), timed single-dose antibiotic prophylaxis before incision and within 120 minutes, alcohol-based chlorhexidine skin preparation, active warming, triclosan-coated sutures considered, no prophylaxis after the operation ends, a dressing at closure and showering from 48 hours (WHO 2018 and NICE NG125 agree; WHO grades as listed). Where they disagree, both are shown: inspired oxygen 80% (WHO, conditional, moderate) against saturation above 95% (NICE); oral antibiotics with bowel preparation before elective colorectal surgery (WHO, conditional, moderate) against no routine bowel preparation (NICE, which does not address oral antibiotics); povidone-iodine wound irrigation considered (WHO, conditional, low) against no irrigation (NICE); prophylactic negative pressure dressings on high-risk wounds (WHO, conditional, low), which NICE NG125's recommendations do not mention.","sources":["who-ssi-2018","nice-ng125"]},"variants":[{"name":"High inspired oxygen (80%) during and after anaesthesia","differs":"Gives 80% oxygen through the breathing tube during surgery and, where feasible, for 2 to 6 hours afterwards, rather than enough to keep saturation above 95%.","evidence":"WHO conditional recommendation, moderate quality of evidence. NICE asks only for saturation above 95% during major surgery and recovery.","sources":["who-ssi-2018","nice-ng125"]},{"name":"Oral antibiotics with mechanical bowel preparation before elective colorectal surgery","differs":"Gives oral antibiotics together with bowel preparation the day before elective colorectal cancer surgery.","evidence":"WHO suggests the combination (conditional, moderate quality) and recommends against bowel preparation alone (strong, moderate). NICE NG125 (2008 wording) says not to use mechanical bowel preparation routinely and does not mention oral antibiotics.","sources":["who-ssi-2018","nice-ng125"]},{"name":"Povidone-iodine wound irrigation before closure","differs":"Washes the incision with aqueous povidone-iodine before closing, particularly in clean and clean-contaminated wounds.","evidence":"WHO conditional, low quality of evidence; WHO found insufficient evidence for or against saline irrigation and suggests against antibiotic irrigation. NICE says not to use wound irrigation to reduce SSI, and to apply antiseptics or antibiotics to the wound before closure only within a trial.","sources":["who-ssi-2018","nice-ng125"]},{"name":"Prophylactic negative pressure wound therapy","differs":"Puts a negative pressure (vacuum) dressing on a closed high-risk incision.","evidence":"WHO conditional, low quality of evidence, taking resources into account. NICE NG125's recommendations do not mention it.","sources":["who-ssi-2018"]},{"name":"Nasal mupirocin and chlorhexidine wash for Staphylococcus aureus carriers","differs":"Treats known nasal carriers of S. aureus with mupirocin ointment, with or without a chlorhexidine body wash, around surgery.","evidence":"WHO recommends it for cardiothoracic and orthopaedic surgery (strong, moderate) and suggests considering it for other surgery (conditional, moderate). NICE says consider it where S. aureus is a likely cause, decided locally, with resistance surveillance.","sources":["who-ssi-2018","nice-ng125"]}],"grades":[{"claim":"Antibiotic prophylaxis before incision when indicated","grade":"Strong recommendation, low quality of evidence","source":"who-ssi-2018","quote":"The panel recommends the administration of SAP prior to the surgical incision when indicated (depending on the type of operation)."},{"claim":"Antibiotic prophylaxis within 120 minutes before incision","grade":"Strong recommendation, moderate quality of evidence","source":"who-ssi-2018"},{"claim":"Alcohol-based chlorhexidine for skin preparation","grade":"Strong recommendation, low to moderate quality of evidence","source":"who-ssi-2018"},{"claim":"No shaving; clippers only if hair must be removed","grade":"Strong recommendation, moderate quality of evidence","source":"who-ssi-2018"},{"claim":"No prolongation of prophylaxis after the operation","grade":"Strong recommendation/moderate quality of evidence","source":"who-ssi-2018"},{"claim":"Prophylaxis not continued because a drain is present","grade":"Conditional recommendation, low quality of evidence","source":"who-ssi-2018","quote":"The panel suggests that perioperative antibiotic prophylaxis should not be continued to the presence of a wound drain for the purpose of preventing SSI."},{"claim":"80% inspired oxygen during intubated general anaesthesia and 2 to 6 hours after","grade":"Conditional recommendation, moderate quality of evidence","source":"who-ssi-2018","quote":"The panel suggests that adult patients undergoing general anaesthesia with tracheal intubation for surgical procedures should receive an 80% fraction of inspired oxygen (FiO2) intraoperatively and, if feasible, in the immediate postoperative period for 2-6 hours to reduce the risk of SSI."},{"claim":"Oral antibiotics with mechanical bowel preparation in elective colorectal surgery","grade":"Conditional recommendation, moderate quality evidence","source":"who-ssi-2018","quote":"The panel suggests that preoperative oral antibiotics combined with mechanical bowel preparation (MBP) should be used to reduce the risk of SSI in adult patients undergoing elective colorectal surgery."},{"claim":"No mechanical bowel preparation alone in elective colorectal surgery","grade":"Strong recommendation, moderate quality evidence","source":"who-ssi-2018","quote":"The panel recommends that MBP alone (without administration of oral antibiotics) should not be used for the purpose of reducing SSI in adult patients undergoing elective colorectal surgery."},{"claim":"Prophylactic negative pressure wound therapy on high-risk closed incisions","grade":"Conditional recommendation, low quality of evidence","source":"who-ssi-2018","quote":"The panel suggests the use of prophylactic negative pressure wound therapy (pNPWT) in adult patients on primarily closed surgical incisions in high-risk wounds, for the purpose of the prevention of SSI, while taking resources into account."},{"claim":"Do not use wound irrigation to reduce SSI","grade":"[2008] (NICE does not grade)","source":"nice-ng125","quote":"Do not use wound irrigation to reduce the risk of surgical site infection."},{"claim":"Maintain oxygen saturation above 95% during major surgery and recovery","grade":"[2008] (NICE does not grade)","source":"nice-ng125","quote":"Maintain optimal oxygenation during surgery. In particular, give patients sufficient oxygen during major surgery and in the recovery period to ensure that a haemoglobin saturation of more than 95% is maintained."}],"sources":[{"key":"who-ssi-2018","label":"Global guidelines for the prevention of surgical site infection, second edition","publisher":"World Health Organization","year":2018,"url":"https://iris.who.int/handle/10665/277399","gradingScheme":"GRADE: strong or conditional recommendations, with quality of evidence high, moderate, low or very low.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng125","label":"Surgical site infections: prevention and treatment (NG125), recommendations","publisher":"NICE","year":2019,"url":"https://www.nice.org.uk/guidance/ng125/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; each is tagged with the year it was written or amended. Published April 2019, last updated August 2020.","read":"full-text","accessed":"2026-11-11"},{"key":"who-lancet-2016","label":"New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective","publisher":"The Lancet Infectious Diseases (Allegranzi et al.)","year":2016,"url":"https://doi.org/10.1016/S1473-3099(16)30398-X","doi":"10.1016/S1473-3099(16)30398-X","read":"abstract","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The CDC/HICPAC 2017 SSI guideline could not be read (cdc.gov refuses scripts) and is not cited. The ERAS Society colorectal guideline (2025), which also covers bowel preparation and oral antibiotics, could not be read (bot check on the publisher's site).","The choice of antibiotic, dose and redosing interval come from local formularies and are not given here.","No source read gives SSI measures specific to people with cancer, for example after radiotherapy to the operative field or during chemotherapy or immunotherapy.","Most of NICE NG125's recommendations date from 2008; the WHO guideline is from 2018. No newer edition of either was found."]},{"id":"suspected-central-line-infection","kind":"protocol","name":"Suspected central line infection in a person with cancer: paired blood cultures, first antibiotics and line removal or salvage","aka":["CRBSI","catheter-related bloodstream infection","line infection","port infection","PICC infection","Hickman line infection","tunnel infection","port pocket infection","differential time to positivity","line salvage","antibiotic lock"],"tldr":"A fever, shivering, or redness, pain or pus where a central line goes in can mean the line is infected. Blood is taken from the line and from an arm vein before antibiotics start, and antibiotics should not wait for the results. Some line infections can be cleared with the line left in; others, such as a serious infection or certain germs, mean the line has to come out.","summary":"IDSA (2009, the current edition) and ESMO (2015) agree on the core. Take paired blood cultures, one through the catheter and one from a peripheral vein, before antibiotics, labelled by site (IDSA A-II; ESMO [II, A]); if no peripheral sample is possible, take at least two through different lumens (IDSA B-III; ESMO [III, B]). Clean the hub or skin with alcohol, iodine tincture or alcoholic chlorhexidine above 0.5% and let it dry (A-I). Swab any exit-site exudate (B-III). Growth from the catheter sample at least 2 hours before the peripheral sample (differential time to positivity) supports catheter-related bloodstream infection (A-II).\n\nStart empirical antibiotics without waiting for cultures (ESMO): vancomycin where MRSA is common (IDSA A-II; ESMO [II, A]), with Gram-negative cover chosen from local susceptibility data, and combination cover for resistant Gram-negative bacilli such as Pseudomonas when the patient is neutropenic or septic (IDSA A-II). Suspect candidaemia in septic patients with haematological cancer, transplant or parenteral nutrition (B-II).\n\nRemove a long-term catheter for severe sepsis, suppurative thrombophlebitis, endocarditis, bacteraemia persisting beyond 72 hours of appropriate antibiotics, or infection with S. aureus, P. aeruginosa, fungi or mycobacteria (IDSA A-II); ESMO adds tunnel infection and port abscess. Otherwise salvage can be tried with systemic antibiotics plus an antibiotic lock (B-II), with repeat cultures and removal if they are still positive at 72 hours (B-II). A single positive culture for coagulase-negative staphylococci should be repeated, paired, before treatment or removal (A-II).","asOf":"2026-11-11","links":[],"tags":[],"related":["febrile-neutropenia-first-hour","implanted-port-access-and-care","catheter-related-thrombosis-in-cancer"],"cancers":[],"sections":[],"technologies":["implanted-ports","picc-lines","catheter-lock-solutions"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["central-venous-access","febrile-neutropenia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"If you have a fever, shivers after your line is flushed, or redness or pus at your line, call your chemotherapy helpline straight away. Blood tests are taken from the line and your arm, then antibiotics start.","domain":"vascular-access","setting":{"who":["doctor","nurse"],"where":["acute-oncology-service","emergency-department","ward","chemotherapy-day-unit"]},"population":"Adults with cancer and a central venous catheter. A person with a temperature during chemotherapy is first managed as possible neutropenic sepsis (see the febrile neutropenia protocol), within which these steps apply. IDSA covers adults and children; haemodialysis catheters and paediatric specifics are not covered here.","trigger":"Fever, rigors (especially just after the line is flushed), low blood pressure or sepsis in a person with a central line, or redness, tenderness, swelling or pus at the exit site, along the tunnel or over the port.","steps":[{"action":"Suspect line infection with fever, chills or low blood pressure after the line is used, or redness, pain, hardness or discharge at the site","why":"Line infections can start suddenly and become serious quickly, especially when white cells are low.","source":"esmo-2015","quote":"Clinical manifestations of CVC infection may include: fever, inflammation or purulence at the insertion site (erythema, tenderness, pain, induration and drainage), catheter dysfunction, hypotension, chills and signs of sepsis of sudden onset, after catheter use."},{"action":"Clean the catheter hub, or the skin for the vein sample, with alcohol, iodine tincture or alcoholic chlorhexidine above 0.5%, and let it dry","why":"Germs on the skin or hub can contaminate the bottle and give a false result.","source":"idsa-2009","quote":"If a blood sample is obtained through a catheter, clean the catheter hub with either alcohol or tincture of iodine or alcoholic chlorhexidine (>0.5%) and allow adequate drying time to mitigate blood culture contamination (A-I).","grade":"A-I"},{"action":"Before antibiotics, take paired blood cultures, one through the line and one from an arm vein, and label each bottle with where it came from","why":"Comparing the two shows whether the line is the source of the infection, which decides whether it must come out.","source":"idsa-2009","quote":"For suspected CRBSI, paired blood samples drawn from the catheter and from a peripheral vein should be cultured before initiation of antimicrobial therapy, and the bottles should be appropriately marked to reflect the site from which the cultures were obtained (A-II).","grade":"A-II"},{"action":"If no vein sample can be taken, take at least two samples through different lumens","why":"Two samples still allow a comparison.","source":"idsa-2009","quote":"If a blood sample for culture cannot be drawn from a peripheral vein, it is recommended that ≥2 blood samples should be obtained through different catheter lumens (B-III).","grade":"B-III"},{"action":"If there is discharge at the exit site, swab it for culture and Gram stain","why":"It can identify the germ before the blood cultures grow.","source":"idsa-2009","quote":"When catheter-related infection is suspected and there is a catheter exit site exudate, swab the drainage to obtain samples for culture and Gram staining (B-III).","grade":"B-III"},{"action":"Start empirical antibiotics at once; do not wait for culture results","why":"Delay increases the risk of sepsis becoming life-threatening.","source":"esmo-2015","quote":"Antibiotic therapy onset should not be delayed for blood culture results to be available."},{"action":"Cover staphylococci with vancomycin where MRSA is common, and add Gram-negative cover chosen from local resistance data, with combination cover for resistant organisms if the patient is neutropenic or septic","why":"Skin staphylococci are the commonest cause; people with low white cells or sepsis can also be infected by more dangerous bowel organisms.","source":"idsa-2009","quote":"Empirical combination antibiotic coverage for multi-drug-resistant (MDR) gram-negative bacilli, such as Pseudomonas aeruginosa, should be used when CRBSI is suspected in neutropenic patients, severely ill patients with sepsis, or patients known to be colonized with such pathogens, until the culture and susceptibility data are available and deescalation of the antibiotic regimen can be done (A-II).","grade":"A-II"},{"action":"Read the cultures together: growth from the line sample at least 2 hours before the vein sample points to the line","why":"Germs living in the line reach detectable levels sooner in blood drawn through it.","source":"idsa-2009","quote":"For DTP, growth of microbes from blood drawn from a catheter hub at least 2 h before microbial growth is detected in blood samples obtained from a peripheral vein best defines CRBSI (A-II).","grade":"A-II"},{"action":"If a single culture grows coagulase-negative staphylococci, repeat paired cultures before treating or removing the line","why":"These skin germs often contaminate a sample without causing infection.","source":"idsa-2009","quote":"If a catheterized patient has a single positive blood culture that grows coagulase-negative Staphylococcus species, then additional cultures of blood samples obtained through the suspected catheter and from a peripheral vein should be performed before the initiation of antimicrobial therapy and/or catheter removal to be certain that the patient has true bloodstream infection and that the catheter is the likely source (A-II).","grade":"A-II"},{"action":"Remove the line for severe sepsis, infected clot, endocarditis, bacteraemia lasting more than 72 hours on the right antibiotics, or infection with S. aureus, Pseudomonas, fungi or mycobacteria","why":"These infections rarely clear with the line in place and can spread to the heart valves or bones.","source":"idsa-2009","quote":"Long-term catheters should be removed from patients with CRBSI associated with any of the following conditions: severe sepsis; suppurative thrombophlebitis; endocarditis; bloodstream infection that continues despite >72 h of antimicrobial therapy to which the infecting microbes are susceptible; or infections due to S. aureus, P. aeruginosa, fungi, or mycobacteria (A-II).","grade":"A-II"},{"action":"Remove the line for a tunnel infection or a port pocket abscess","why":"Pus in the tunnel or around the port cannot be cleared by antibiotics while the device is there.","source":"esmo-2015","quote":"Indications to remove the CVC are: severe sepsis, suppurative (septic) thrombophlebitis, endocarditis, tunnel infection, port abscess"},{"action":"Otherwise, consider keeping the line, with systemic antibiotics plus an antibiotic lock","why":"People with cancer may need the line for months, and replacing it has its own risks.","source":"idsa-2009","quote":"Antibiotic lock therapy should be used for catheter salvage (B-II); however, if antibiotic lock therapy cannot be used in this situation, systemic antibiotics should be administered through the colonized catheter (C-III).","grade":"B-II"},{"action":"If the line is kept, repeat blood cultures and remove it if they are still positive 72 hours into appropriate treatment","why":"Persistent positive cultures mean the line is still seeding the blood.","source":"idsa-2009","quote":"For patients with CRBSI for whom catheter salvage is attempted, additional blood cultures should be obtained, and the catheter should be removed if blood culture results (e.g., 2 sets of blood cultures obtained on a given day; 1 set of blood cultures is acceptable for neonates) remain positive when blood samples are obtained 72 h after the initiation of appropriate therapy (B-II).","grade":"B-II"},{"action":"If a port is removed, send the reservoir contents and the catheter tip for culture","why":"The material inside the port is more likely to grow the germ than the tip alone.","source":"idsa-2009","quote":"If a venous access subcutaneous port is removed because of suspected CRBSI, send the port to the microbiology laboratory for qualitative culture of the port reservoir contents, in addition to the catheter tip (B-II).","grade":"B-II"}],"bestInClass":{"statement":"Paired, labelled blood cultures from the line and a peripheral vein before antibiotics (IDSA A-II; ESMO [II, A]) after hub and skin antisepsis allowed to dry (A-I); empirical antibiotics without delay, vancomycin where MRSA is common (A-II) and Gram-negative cover by local data, combination cover in neutropenia or sepsis (A-II); removal of a long-term line for severe sepsis, suppurative thrombophlebitis, endocarditis, persistent bacteraemia beyond 72 hours, S. aureus, P. aeruginosa, fungi or mycobacteria (IDSA A-II), and for tunnel infection or port abscess (ESMO); otherwise salvage with antibiotic lock (B-II) and repeat cultures. IDSA (2009) and ESMO (2015) agree on these points; both are old, and no newer edition of either was found.","sources":["idsa-2009","esmo-2015"]},"variants":[{"name":"Salvage of an uncomplicated infection in a line that is hard to replace","differs":"Keeps a long-term catheter infected with organisms other than S. aureus, Pseudomonas, Bacillus, Micrococcus, Propionibacteria, fungi or mycobacteria, treating with systemic antibiotics and an antibiotic lock.","evidence":"IDSA B-II, framed for patients with limited access sites; ESMO's algorithm (Figure 1) follows the same logic. No randomised trial of salvage against removal in cancer was cited.","sources":["idsa-2009","esmo-2015"]}],"grades":[{"claim":"Blood cultures before antibiotics","grade":"[I, A]","source":"esmo-2015","quote":"In the diagnostic assessment, blood cultures are indicated before starting antibiotic treatment [I, A]"},{"claim":"Paired cultures, catheter and peripheral vein, labelled","grade":"A-II","source":"idsa-2009"},{"claim":"Vancomycin empirically where MRSA is prevalent","grade":"A-II","source":"idsa-2009","quote":"Vancomycin is recommended for empirical therapy in heath care settings with an elevated prevalence of methicillin-resistant Staphylococcus aureus (MRSA)"},{"claim":"Vancomycin as empirical treatment","grade":"[II, A]","source":"esmo-2015","quote":"Since the most frequent infectious agents are Staphylococcus coagulase-negative and S. aureus methicillin-resistant (MRSA), the recommended treatment is vancomycin [II, A]"},{"claim":"Linezolid not for empirical therapy","grade":"AI","source":"idsa-2009","quote":"Linezolid should not be used for empirical therapy (i.e., for patients suspected but not proven to have bacteremia) (AI)."},{"claim":"Removal of long-term catheters for complicated infection or high-risk organisms","grade":"A-II","source":"idsa-2009"},{"claim":"Thrombolytics not recommended as adjunctive therapy","grade":"B-I","source":"idsa-2009","quote":"Urokinase and other thrombolytic agents are not recommended as adjunctive therapy for patients with CRBSI (B-I)."}],"sources":[{"key":"idsa-2009","label":"Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America","publisher":"IDSA (Clinical Infectious Diseases, Mermel et al.)","year":2009,"url":"https://doi.org/10.1086/599376","doi":"10.1086/599376","gradingScheme":"Strength A (good evidence) to C (poor evidence); quality I (at least one randomised trial), II (non-randomised trials, cohort or case-control studies) or III (expert opinion), from the Canadian Task Force scheme.","read":"full-text","accessed":"2026-11-11"},{"key":"esmo-2015","label":"Central venous access in oncology: ESMO Clinical Practice Guidelines","publisher":"ESMO (Annals of Oncology, Sousa et al.)","year":2015,"url":"https://doi.org/10.1093/annonc/mdv296","doi":"10.1093/annonc/mdv296","gradingScheme":"[level, grade]: levels I (large good-quality RCT or meta-analysis) to V (no control group, case reports, expert opinion); grades A (strongly recommended) to E (never recommended), adapted from the IDSA/USPHS system.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["Both guidelines are old: IDSA 2009 and ESMO 2015. No newer edition of either was found, and IDSA notes its diagnostic definition differs from surveillance definitions of central line-associated bloodstream infection.","Antibiotic choices depend on local resistance; the guideline examples (vancomycin, daptomycin, fourth-generation cephalosporins, carbapenems) are not a substitute for local policy.","The ECIL and other haematology-specific guidance on line infections in neutropenic patients was not read.","Duration of antibiotics by organism is set out in IDSA's figures and pathogen sections, which are not reproduced here."]},{"id":"febrile-neutropenia-first-hour","kind":"protocol","name":"Suspected febrile neutropenia (neutropenic sepsis): the first hour","aka":["neutropenic sepsis first hour","febrile neutropenia door-to-needle","neutropenic fever emergency management","suspected neutropenic sepsis"],"tldr":"Anyone having cancer treatment who feels unwell, with or without a high temperature, should ring their 24-hour cancer line and be seen in hospital straight away. There they should be given a strong antibiotic through a drip within about an hour, without waiting for the blood count to come back.","summary":"Suspect neutropenic sepsis in any adult having anticancer treatment who becomes unwell (NICE CG151 1.3.1.1); NICE NG253 widens this to systemic anticancer treatment within the last 30 days and to people on immunosuppressants, and warns that people having treatment for cancer may not develop a raised temperature. NICE confirms the diagnosis later, at a neutrophil count of 0.5 × 10⁹/L or lower with a temperature higher than 38 °C or other signs of clinically significant sepsis; SEOM uses a temperature above 38 °C or clinical signs of sepsis with neutrophils below 500/mm³, or below 1000/mm³ before the nadir.\n\nTreatment does not wait for the count. NICE says to offer empiric antibiotics immediately and sets no clock, because its committee found the evidence on timing very low quality; ASCO/IDSA (2018) endorse the first dose within 1 hour of triage, and SEOM (2018) within the first hour of arrival in the emergency department, after cultures. NICE's first choice is piperacillin with tazobactam alone, with no routine aminoglycoside or glycopeptide; SEOM allows any anti-pseudomonal beta-lactam and adds amikacin, preferably with a carbapenem, when severity criteria are met. Bloods include full blood count, renal and liver function with albumin, C-reactive protein, lactate and blood cultures, with a peripheral culture as well as a line culture where there is a central venous device, which stays in.\n\nWithin 24 hours a competent clinician scores the risk of septic complications with a validated tool (MASCC; CISNE for stable patients with solid tumours on moderate-intensity chemotherapy in SEOM). A MASCC score of 21 or more marks those who may go home on oral antibiotics; under 21 is high risk and stays on the standard pathway. Under NG253, a high-risk patient who does not respond within 1 hour of any intervention needs a senior decision maker in person and a critical care discussion.","asOf":"2026-11-11","links":[],"tags":["protocol","neutropenic-sepsis","acute-oncology"],"related":["idea-acc-hospital-at-home-oncology","idea-acc-acute-oncology-assessment-units"],"cancers":[],"sections":["supportive-care"],"technologies":["implanted-ports","picc-lines"],"targets":[],"drugs":[],"companies":[],"institutions":["nice","asco","mascc"],"pathways":[],"terms":["febrile-neutropenia","neutropenia","central-venous-access","neutropenic-sepsis-breast-chemotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Cancer medicines can lower the white cells that fight germs. If you feel ill during treatment, even without a fever, ring your cancer helpline at once. The hospital should give you antibiotics quickly, usually within an hour.","domain":"emergencies","setting":{"who":["patient-or-carer","nurse","doctor","emergency-team"],"where":["home","telephone-triage","emergency-department","acute-oncology-service","ward"]},"population":"Adults having anticancer treatment, chemotherapy above all, who become unwell or have a fever. NICE CG151 covers people of any age with age-specific recommendations marked; this protocol follows its adult recommendations and NG253, which covers people aged 16 or over. Children, and people after stem cell transplant or with acute leukaemia where local haematology protocols differ, are not covered here.","trigger":"A person having anticancer treatment (NICE NG253: systemic anticancer treatment within the last 30 days) becomes unwell, with or without a temperature above 38 °C.","steps":[{"action":"Before treatment starts, give the patient and carer written and spoken information on neutropenic sepsis and the 24-hour number","why":"Most episodes start at home between visits, so the person needs to know the signs and whom to ring before they need to.","source":"nice-cg151","quote":"Provide patients having anticancer treatment and their carers with written and oral information, both before starting and throughout their anticancer treatment, on:"},{"action":"On the phone or at the door, suspect neutropenic sepsis in anyone having anticancer treatment who is unwell","why":"The trigger is feeling unwell during treatment, not a number on a thermometer.","source":"nice-cg151","quote":"Suspect neutropenic sepsis in patients having anticancer treatment who become unwell."},{"action":"Do not rule sepsis out because the temperature is normal","why":"People having cancer treatment may be septic without a raised temperature, and steroids or paracetamol can hide one.","source":"nice-ng253","quote":"Do not rely on fever or hypothermia alone to rule sepsis either in or out."},{"action":"Send the person to hospital at once; do not book a routine appointment","why":"Assessment and the first antibiotic happen in hospital, so any delay at the telephone stage adds to the time before treatment.","source":"nice-cg151","quote":"Refer patients with suspected neutropenic sepsis immediately for assessment in secondary or tertiary care."},{"action":"Treat it as an emergency on arrival and start empiric intravenous antibiotics immediately","why":"Without neutrophils an infection can spread fast, and the antibiotic is the one step that changes the outcome.","source":"nice-cg151","quote":"Treat suspected neutropenic sepsis as an acute medical emergency and offer empiric antibiotic therapy immediately."},{"action":"Give the first dose within one hour of arrival, and record when the clock started","why":"The one-hour target is the one most guidelines and audits use; writing down the start time is what lets a team see whether it was met.","source":"seom-2018","quote":"Empirical antibiotic therapy should be initiated within the first hour of arrival at the ED (after sampling for cultures)","grade":"II, A"},{"action":"Do not wait for the neutrophil count before giving the antibiotic","why":"NICE's antibiotic recommendation applies to suspected neutropenic sepsis; the count is used afterwards to confirm the diagnosis (CG151 1.4.4.1), not to decide the first dose.","source":"nice-cg151"},{"action":"Take a history, examine, and send full blood count, kidney and liver tests with albumin, C-reactive protein, lactate and blood cultures","why":"These find the likely source and show how unwell the person is, which decides the next steps.","source":"nice-cg151"},{"action":"Take two sets of blood cultures before the antibiotic, inside the hour, plus other samples the history points to","why":"Cultures taken after the first dose are less likely to grow the germ, but taking them must not push the antibiotic past the hour.","source":"seom-2018","quote":"Two pairs of blood cultures and microbiological specimens, as clinically indicated, should be obtained prior to initiating empirical antibiotic therapy","grade":"III, A"},{"action":"If there is a central line, port or PICC, take a peripheral culture as well and leave the line in","why":"A second culture from a vein helps show whether the line is the source; taking the line out is not part of the first hour.","source":"nice-cg151","quote":"Do not remove central venous access devices as part of the initial empiric management of suspected neutropenic sepsis."},{"action":"Give piperacillin with tazobactam on its own as the first antibiotic, unless allergy or local resistance rules it out","why":"NICE's analysis found lower mortality and less kidney harm with this single drug than with a carbapenem or with an added aminoglycoside.","source":"nice-cg151","quote":"Offer beta lactam monotherapy with piperacillin with tazobactam as initial empiric antibiotic therapy to patients with suspected neutropenic sepsis who need intravenous treatment unless there are patient-specific or local microbiological contraindications."},{"action":"Do not add an aminoglycoside or a glycopeptide routinely","why":"NICE limits them to patient-specific or local microbiological reasons, such as a line infection or known resistant organisms.","source":"nice-cg151","quote":"Do not offer an aminoglycoside, either as monotherapy or in dual therapy, for the initial empiric treatment of suspected neutropenic sepsis unless there are patient-specific or local microbiological indications."},{"action":"Do a chest X-ray only if the history or examination points to the chest","why":"NICE found no reason to X-ray every patient; SEOM includes one in the first assessment (see variants).","source":"nice-cg151","quote":"Do not perform a chest X-ray unless clinically indicated."},{"action":"If a high-risk patient has not responded within an hour of any intervention, get the senior decision maker in person and talk to critical care","why":"Failure to respond to antibiotics and fluids in the first hour is the point to bring in intensive care, not after a further wait.","source":"nice-ng253","quote":"If a person aged 16 years or over who is at high risk of severe illness or death from sepsis does not respond within 1 hour of any intervention:"},{"action":"Within 24 hours, have a competent clinician score the risk of complications with a validated tool such as MASCC","why":"The score separates people who can finish treatment at home from those who need to stay in hospital.","source":"nice-cg151","quote":"A healthcare professional with competence in managing complications of anticancer treatment should assess the patient's risk of septic complications within 24 hours of presentation to secondary or tertiary care, basing the risk assessment on presentation features and using a validated risk scoring system."},{"action":"Treat a MASCC score under 21 as high risk on the standard inpatient pathway, and consider 21 or more for outpatient care","why":"In the original validation a score of 21 or more picked out low-risk patients with a positive predictive value of 91 per cent.","source":"mascc-2026","quote":"Patients treated with chemotherapy/ICI presenting with febrile neutropenia and a MASCC risk index < 21 are high risk and require standard neutropenic sepsis management.","grade":"A"},{"action":"For outpatient treatment, give the first dose intravenously within the hour, observe for at least 4 hours, then switch to oral antibiotics","why":"The observation period catches people who look well at first but are not; ASCO/IDSA name an oral fluoroquinolone with amoxicillin and clavulanate unless a fluoroquinolone was already being taken as prevention.","source":"seom-2018","quote":"In low-risk patients for whom ambulatory treatment has been decided on, the first dose of antibiotic should be administered via IV within the first hour and the patient should remain in observation at the hospital for at least 4 h","grade":"III, B"}],"bestInClass":{"statement":"Start empiric intravenous antibiotics on suspicion, without waiting for the neutrophil count. On timing the guidelines differ in wording and in where the clock starts: NICE CG151 says immediately and sets no clock, judging the evidence too weak to name a period while noting the one-hour pathway of the National Cancer Peer Review Programme; ASCO/IDSA (2018) endorse the first dose within 1 hour of triage; SEOM (2018) within the first hour of arrival in the emergency department, after cultures. NICE NG253 times its general sepsis antibiotic from the NEWS2 score at initial assessment but sends neutropenic sepsis back to CG151. On the trigger, NICE confirms the diagnosis at neutrophils of 0.5 × 10⁹/L or lower with a temperature higher than 38 °C or other signs of clinically significant sepsis, and both NICE guidelines warn that people having cancer treatment may not run a temperature; SEOM uses above 38 °C or clinical signs of sepsis with neutrophils below 500/mm³, or below 1000/mm³ before the nadir. On the first drug, NICE recommends piperacillin with tazobactam alone; SEOM allows any anti-pseudomonal beta-lactam (piperacillin with tazobactam, meropenem, imipenem with cilastatin or cefepime) and adds amikacin when severity criteria are met. Risk scoring with MASCC (score of 21 or more is low risk) or, for stable patients with solid tumours, CISNE then decides who can continue at home.","sources":["nice-cg151","nice-cg151-full","nice-ng253","asco-idsa-2018","seom-2018","mascc-2026"]},"variants":[{"name":"Clock started at presentation, with nurse-given first dose (Cardiff and Vale University Health Board)","differs":"Sets a local standard of intravenous antibiotics within 60 minutes of presentation, suspects neutropenic sepsis after anticancer treatment in the last 6 weeks with a temperature over 38 °C or under 36 °C, tells staff not to wait for blood count results, and in haematology lets assessed nurses give the first dose of piperacillin with tazobactam under a patient group direction. MASCC scoring is used for solid tumours only.","evidence":"A local policy that cites NICE CG151; it is not graded evidence.","sources":["cardiff-vale-2025"]},{"name":"Broader anti-pseudomonal choice and combination for severe cases (SEOM)","differs":"Allows piperacillin with tazobactam, meropenem, imipenem with cilastatin or cefepime as the first beta-lactam, and for high-risk patients meeting severity criteria a beta-lactam, preferably a carbapenem, with amikacin; adds a gram-positive agent for suspected line or skin infection, pneumonia or haemodynamic instability.","evidence":"SEOM grades the beta-lactam choice I, A and the carbapenem with amikacin II, A. NICE advises against a routine aminoglycoside and keeps to piperacillin with tazobactam unless there are patient-specific or local reasons.","sources":["seom-2018","nice-cg151"]},{"name":"Chest X-ray for everyone (SEOM)","differs":"Includes a chest X-ray in every initial assessment, where NICE advises one only when clinically indicated.","evidence":"SEOM grades its initial evaluation including chest X-ray III, B; NICE makes the opposite recommendation without a grade.","sources":["seom-2018","nice-cg151"]},{"name":"CISNE instead of MASCC for stable patients with solid tumours (SEOM)","differs":"Uses the Clinical Index of Stable Febrile Neutropenia (0 low, 1 to 2 intermediate, 3 or more high risk) in people with solid tumours on moderate-intensity chemotherapy who look clinically stable, and never in haematological cancers or lymphoma.","evidence":"SEOM grades CISNE II, B. In the CISNE validation cohort of 1,133 patients the area under the curve was 0.868 for CISNE against 0.721 for MASCC.","sources":["seom-2018","cisne-2015"]}],"grades":[{"claim":"Empirical antibiotics within the first hour of arrival in the emergency department, after cultures","grade":"II, A","source":"seom-2018","quote":"Empirical antibiotic therapy should be initiated within the first hour of arrival at the ED (after sampling for cultures)"},{"claim":"First intravenous antibiotic is an anti-pseudomonal beta-lactam","grade":"I, A","source":"seom-2018","quote":"Initial parenteral antibiotherapy should include a beta-lactam with activity against Pseudomonas spp. (piperacillin/tazobactam, meropenem, imipenem–cilastatin, cefepime)"},{"claim":"Blood cultures before the first antibiotic","grade":"III, A","source":"seom-2018","quote":"Two pairs of blood cultures and microbiological specimens, as clinically indicated, should be obtained prior to initiating empirical antibiotic therapy"},{"claim":"Severe cases: beta-lactam, preferably a carbapenem, with amikacin","grade":"II, A","source":"seom-2018","quote":"In high-risk patients meeting criteria for severity, initial parenteral antibiotherapy should include a beta-lactam with activity against Pseudomonas spp. (preferably a carbapenem) in combination with amikacin"},{"claim":"CISNE score for clinically stable patients with solid tumours on moderate-intensity chemotherapy","grade":"II, B","source":"seom-2018","quote":"The application of the CISNE score is recommended in patients with apparent clinical stability and solid tumors on moderate-intensity chemotherapy"},{"claim":"Outpatient route: first intravenous dose within the hour and at least 4 hours of observation","grade":"III, B","source":"seom-2018"},{"claim":"First dose of empirical antibiotic within 1 hour of triage and at least 4 hours of monitoring before discharge","grade":"consensus recommendations (ASCO/IDSA Expert Panel)","source":"asco-idsa-2018","quote":"The panel continued to endorse consensus recommendations from the previous version of this guideline that patients with febrile neutropenia receive initial doses of empirical antibacterial therapy within 1 hour of triage and be monitored for ≥ 4 hours before discharge."},{"claim":"MASCC score of 21 or more is likely to be suitable for outpatient or ambulatory care","grade":"A","source":"mascc-2026","quote":"The MASCC score is a well-validated score for risk stratification in febrile neutropenia and patients with a score ≥ 21 are likely to be suitable for outpatient or ambulatory emergency care"},{"claim":"MASCC score under 21 is high risk and needs standard neutropenic sepsis management","grade":"A","source":"mascc-2026"},{"claim":"Evidence on how fast antibiotics must be given in suspected neutropenic sepsis","grade":"very low (GRADE)","source":"nice-cg151-full","quote":"The overall quality of the evidence classified by GRADE was ‘very low’."},{"claim":"Evidence for piperacillin with tazobactam monotherapy on mortality and treatment failure","grade":"moderate (GRADE)","source":"nice-cg151-full","quote":"The overall quality of the evidence as classified by GRADE was ‘moderate’ in addressing mortality and treatment failure, and low or very low in relation to adverse effects."}],"sources":[{"key":"nice-cg151","label":"Neutropenic sepsis: prevention and management in people with cancer (CG151), recommendations","publisher":"NICE","year":2012,"url":"https://www.nice.org.uk/guidance/cg151/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the strength is in the wording ('offer', 'do not offer', 'consider'). Published September 2012, recommendations 1.2.1.1 and 1.2.1.2 updated January 2020 and September 2024.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-cg151-full","label":"Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients, full guideline and evidence review","publisher":"NICE (National Collaborating Centre for Cancer)","year":2012,"url":"https://www.nice.org.uk/guidance/cg151/evidence/full-guideline-pdf-188303581","gradingScheme":"Evidence for each question rated with GRADE as high, moderate, low or very low; recommendations themselves are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"nice-ng253","label":"Suspected sepsis in people aged 16 or over: recognition, assessment and early management (NG253)","publisher":"NICE","year":2025,"url":"https://www.nice.org.uk/guidance/ng253","gradingScheme":"NICE does not grade recommendations; each is dated by the year it was written or amended, for example [2016, amended 2024].","read":"full-text","accessed":"2026-11-11"},{"key":"seom-2018","label":"SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018)","publisher":"Spanish Society of Medical Oncology (SEOM), Clinical and Translational Oncology","year":2019,"url":"https://europepmc.org/article/PMC/PMC6339667","doi":"10.1007/s12094-018-1983-4","gradingScheme":"Infectious Diseases Society of America-US Public Health Service grading system, printed as level of evidence (I to III) and grade of recommendation (letter), for example II, A.","read":"full-text","accessed":"2026-11-11"},{"key":"mascc-2026","label":"Febrile neutropenia in patients treated with chemotherapy/immune checkpoint inhibition: a MASCC consensus statement","publisher":"MASCC, Supportive Care in Cancer","year":2026,"url":"https://europepmc.org/article/PMC/PMC13421288","doi":"10.1007/s00520-026-11045-7","gradingScheme":"Ten expert-consensus position points, each graded on what the authors call the standard A to D scoring system; the grade is printed after the point.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-idsa-2018","label":"Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: ASCO and IDSA Clinical Practice Guideline Update","publisher":"ASCO and IDSA, Journal of Clinical Oncology","year":2018,"url":"https://europepmc.org/abstract/MED/29461916","doi":"10.1200/JCO.2017.77.6211","read":"abstract","accessed":"2026-11-11"},{"key":"idsa-2010","label":"Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America","publisher":"IDSA, Clinical Infectious Diseases","year":2011,"url":"https://europepmc.org/abstract/MED/21258094","doi":"10.1093/cid/cir073","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2016","label":"Management of febrile neutropaenia: ESMO Clinical Practice Guidelines","publisher":"ESMO, Annals of Oncology","year":2016,"url":"https://doi.org/10.1093/annonc/mdw325","doi":"10.1093/annonc/mdw325","read":"not-reachable","accessed":"2026-11-11"},{"key":"mascc-index-2000","label":"The Multinational Association for Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying Low-Risk Febrile Neutropenic Cancer Patients","publisher":"Journal of Clinical Oncology","year":2000,"url":"https://europepmc.org/abstract/MED/10944139","doi":"10.1200/JCO.2000.18.16.3038","read":"abstract","accessed":"2026-11-11"},{"key":"cisne-2015","label":"Prediction of Serious Complications in Patients With Seemingly Stable Febrile Neutropenia: Validation of the Clinical Index of Stable Febrile Neutropenia in a Prospective Cohort of Patients From the FINITE Study","publisher":"Journal of Clinical Oncology","year":2015,"url":"https://europepmc.org/abstract/MED/25559804","doi":"10.1200/JCO.2014.57.2347","read":"abstract","accessed":"2026-11-11"},{"key":"cardiff-vale-2025","label":"Policy for the management of suspected and proven neutropenic sepsis in adults (UHB 529)","publisher":"Cardiff and Vale University Health Board","year":2025,"url":"https://cavuhb.nhs.wales/files/policies-procedures-and-guidelines/patient-safety-and-quality/uhb-529-neutropenic-sepsis-policy-final-version-1-2-1-pdf/","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2016 guideline could not be read: it has no abstract in Europe PMC and the publisher's page refused a script. Its fever threshold, time target and antibiotic choice are not stated here.","The ASCO/IDSA 2018 update and the IDSA 2010 guideline were read only as abstracts, so their temperature definitions and full lists of first-line drugs are not given; the 2010 abstract says only that empirical antibiotic therapy should be immediate.","No guideline read here gives evidence that one hour is better than another short interval; NICE judged the evidence on timing very low quality and declined to name a period.","The UKONS 24-hour telephone triage toolkit (version 3, December 2024), which most UK cancer helplines use, returned a page-not-found to a script and is not cited.","NICE gives no specific first antibiotic for people with a penicillin allergy and leaves it to clinical judgement and local policy.","The MASCC score has not been validated in people having chemotherapy combined with immune checkpoint inhibitors (MASCC 2026), and SEOM says CISNE must not be used in haematological cancers or lymphoma."]},{"id":"syringe-driver-continuous-subcutaneous-infusion","kind":"protocol","name":"Syringe driver (syringe pump): setting up and checking a continuous subcutaneous infusion in palliative care","aka":["syringe driver","syringe pump","CSCI","continuous subcutaneous infusion","McKinley T34","BD BodyGuard T","palliative infusion pump","24-hour subcutaneous infusion"],"tldr":"A syringe driver is a small battery pump that pushes medicines for pain, sickness, agitation or chest secretions slowly under the skin over 24 hours, when swallowing is hard or tablets are not working. A nurse sets it up, refills it every day and checks it regularly; you or your family should not adjust it, and should call the nurses if it alarms, the skin is sore, or symptoms are not controlled.","summary":"NICE NG31 (2015) says to consider a syringe pump for continuous symptom control in the last days of life if more than 2 or 3 as-needed doses have been given in 24 hours, to avoid intramuscular injections, to start at the lowest effective dose and to reassess at least daily. The Scottish Palliative Care Guidelines (2023 version, BD BodyGuard T) give the procedure: discuss the reasons and offer the leaflet; choose a site with loose subcutaneous tissue (outer arm, upper thigh, abdomen, chest wall, scapula for a confused person) and avoid oedema, ascites, bony prominences and irradiated or broken skin; use a dedicated cannula for the pump and a second one for breakthrough doses; mix only medicines known to be compatible, no more than three without specialist or pharmacy advice, dilute to the maximum volume and add dexamethasone or cyclizine last; change the battery in the community if it is below 50%; prime the line by hand and never connect the line to the patient while loading; keep the pump level with or below the site; select Start Infusion, not Resume, for a new syringe; lock the keypad; check 15 to 30 minutes after set-up, then 4-hourly in hospital and at least daily at home; renew the syringe every 24 hours; and report any infusion finishing more than an hour early or late. About a quarter of palliative medication incidents reported in England and Wales involve these infusions, most from failures of monitoring and supply, administration and prescribing.","asOf":"2026-11-11","links":[],"tags":[],"related":["care-in-the-last-days-of-life","strong-opioids-for-cancer-pain","opioid-switching-and-conversion"],"cancers":[],"sections":[],"technologies":["syringe-drivers","hospice-end-of-life"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["last-days-of-life-care"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"A small pump in a pouch gives your medicines through a fine tube under the skin, all day and night. A nurse changes it every day and checks it. Do not touch the buttons. Call the nurses if it beeps, the skin around the tube is red or sore, or you still have symptoms.","domain":"palliative","setting":{"who":["nurse","doctor","pharmacist","patient-or-carer"],"where":["home","ward","community"]},"population":"Adults receiving palliative or end of life care who need a continuous subcutaneous infusion of symptom control medicines. Children and young people are excluded by the Scottish guideline, which points to the PELiCaN guideline for them (not read).","trigger":"The oral route is failing or not working (difficulty swallowing, persistent vomiting, bowel obstruction or malabsorption), or more than 2 or 3 as-needed doses of a medicine have been given in 24 hours.","steps":[{"action":"Consider a syringe pump when more than 2 or 3 as-needed doses of a medicine have been needed in 24 hours, or the oral route is failing","why":"A steady infusion keeps symptoms controlled without repeated injections.","source":"nice-ng31","quote":"Consider using a syringe pump to deliver medicines for continuous symptom control if more than 2 or 3 doses of any 'as required' medicines have been given within 24 hours.","grade":"Not graded (NICE NG31 1.5.6, 'consider')"},{"action":"Explain why the pump is being used, how it works and what to do if something goes wrong, and offer the written leaflet","why":"Many people link a syringe driver with dying; talking it through first avoids fear and lets the family know who to call.","source":"scot-spcg","quote":"Before setting up the syringe pump, it is important to discuss the reasons for use with the patient, family and carer.","grade":"Not graded (national guideline)"},{"action":"With the patient, choose a site with loose subcutaneous tissue, avoiding swollen or lymphoedematous areas, ascites, bony prominences, skin folds, irradiated and broken skin","why":"Medicine is absorbed poorly from swollen or damaged skin, and a cannula over bone or a waistband is uncomfortable and falls out.","source":"scot-spcg","quote":"Where possible, involve the patient in the choice of suitable site(s). Ensure the area chosen has loose, subcutaneous tissue.","grade":"Not graded (national guideline)"},{"action":"Use a single-port cannula for the pump only, and insert a separate cannula for breakthrough injections","why":"Giving extra doses through the pump line interrupts the infusion and can flush a bolus of the pump medicines in.","source":"scot-spcg","quote":"A single port, subcutaneous infusion device should be used for the administration of medicines via a syringe pump. An additional device should be inserted for the administration of bolus subcutaneous medications.","grade":"Not graded (Key Point)"},{"action":"Mix only medicines known to be compatible, and no more than three without specialist palliative care or pharmacy advice; dilute to the maximum volume and add dexamethasone or cyclizine last","why":"Some combinations crystallise in the syringe, which blocks the line and means the person does not get their medicine.","source":"scot-spcg","quote":"Do not mix more than three medicines without seeking advice from specialist palliative care and / or pharmacy unless this has already been agreed by your health board.","grade":"Not graded (national guideline)"},{"action":"Check the battery before starting; at home, fit a new battery if less than 50% remains","why":"A pump that stops overnight at home leaves the person without symptom control until a nurse can come.","source":"scot-spcg","quote":"In the community setting, if the battery power has less than 50% life remaining at the start of an infusion, then a new battery should be installed","grade":"Not graded (national guideline)"},{"action":"Prime the line by hand, load the syringe with the line disconnected from the patient, then connect it","why":"Loading a syringe while connected can push a sudden dose into the person.","source":"scot-spcg","quote":"To prevent an accidental bolus of medicines being given, please ensure the line is not attached to the patient's cannula when placing the syringe in the pump.","grade":"Not graded (national guideline)"},{"action":"Keep the pump at the same level as the infusion site or lower","why":"A pump held above the site can siphon medicine in faster than intended.","source":"scot-spcg","quote":"To reduce the risk of siphonage the syringe pump should be placed at the same level or lower than the infusion site.","grade":"Not graded (Key Point)"},{"action":"For every new or changed syringe, select Start Infusion rather than Resume, and renew the syringe every 24 hours","why":"Resume continues the old programme, so a new syringe would not run over a full 24 hours.","source":"scot-spcg","quote":"When renewing or changing the syringe it is important to select ' START INFUSION ' instead of ' RESUME ' as this will ensure that the syringe pump delivers the infusion over a new 24 hour period.","grade":"Not graded (Key Point)"},{"action":"Lock the keypad, use a lockbox or cover as local policy says, and ask the patient and family to call the nurses rather than touch the pump","why":"Accidental button presses change the rate or stop the infusion.","source":"scot-spcg","quote":"The patient/family/carer should be discouraged from interacting with the pump and advised to contact the nursing team caring for them if any issues occur.","grade":"Not graded (Key Point)"},{"action":"Check 15 to 30 minutes after set-up, then every 4 hours in hospital and at every visit (at least daily) at home: volume infused, syringe contents, the site and the battery","why":"Checking volume against time shows whether the pump is running to schedule; cloudy contents or a sore site need action.","source":"scot-spcg","quote":"When set up, reloaded or resited an initial check should be carried out within the first 15-30 minutes to ensure the infusion is running correctly. Then every 4 hours in an inpatient setting and at every visit (at least daily) in the community setting.","grade":"Not graded (national guideline)"},{"action":"Prescribe a breakthrough dose of each medicine in the pump and give it when symptoms break through","why":"The pump takes hours to reach a steady level, and symptoms can flare in between.","source":"scot-spcg-practice","quote":"If the patient has uncontrolled symptoms before the infusion is started or during the infusion period, give breakthrough doses of medication as required.","grade":"Not graded (practice point)"},{"action":"Reassess symptoms at least daily, and seek specialist palliative care advice if they do not improve promptly or there are unwanted effects such as sedation","why":"Doses usually need adjusting, and a specialist can help when they do not work.","source":"nice-ng31","quote":"Regularly reassess, at least daily, the dying person's symptoms during treatment to inform appropriate titration of medicine.","grade":"Not graded (NICE NG31 1.5.8)"},{"action":"Report every incident, including an infusion finishing more than an hour early or late, and take the pump out of use","why":"Pump faults and errors are common enough that every one needs to be found and fixed.","source":"scot-spcg","quote":"infusions completing ahead of intended time (finishing > 1 hour early)","grade":"Not graded (national guideline)"}],"bestInClass":{"statement":"NICE NG31 (2015) decides when a syringe pump is used in the last days of life; the Scottish Palliative Care Guidelines (2023) give the most detailed public national procedure for setting it up and checking it. Neither grades its recommendations, and the procedure rests on device instructions, compatibility data and safety reporting rather than trials. National incident data (Palliat Med 2024) show where it fails: supply and monitoring, administration and prescribing, worsened by gaps in continuity and unfamiliar staff.","sources":["nice-ng31","scot-spcg","cssi-incidents-2024"]},"variants":[{"name":"Other pump models (McKinley T34 version 2, CME version 3)","differs":"Different menus and alarms from the BD BodyGuard T on which the Scottish guideline is written.","evidence":"The Scottish guideline names them as in use and points to local standard operating procedures for the differences; no comparative outcome data.","sources":["scot-spcg"]},{"name":"Extension line change every 72 hours","differs":"Changes the extension line on a fixed 72-hour schedule rather than only when needed.","evidence":"A manufacturer recommendation cited by the Scottish guideline, which notes the evidence on line duration in palliative CSCI is limited.","sources":["scot-spcg"]},{"name":"More than three medicines in one syringe","differs":"Some health boards mix four or more medicines in a single pump.","evidence":"Allowed by the Scottish guideline only on specialist or pharmacy advice or local agreement; mixing in a syringe is unlicensed but supported by practice.","sources":["scot-spcg"]},{"name":"Regular as-needed subcutaneous injections instead of a pump","differs":"Gives each dose by separate injection, usually through an indwelling cannula.","evidence":"NICE NG31 reserves the pump for when more than 2 or 3 as-needed doses are needed in 24 hours; below that, separate doses are the default.","sources":["nice-ng31"]}],"grades":[{"claim":"Avoid intramuscular injections in the last days of life","grade":"Not graded (NICE NG31 1.5.5)","source":"nice-ng31","quote":"Avoid giving intramuscular injections and give either subcutaneous or intravenous injections."},{"claim":"Seek specialist advice when symptoms do not settle","grade":"Not graded (NICE NG31 1.5.9)","source":"nice-ng31","quote":"Seek specialist palliative care advice if the dying person's symptoms do not improve promptly with treatment or if there are undesirable side effects, such as unwanted sedation."},{"claim":"Cannula dwell time","grade":"Not graded (national guideline)","source":"scot-spcg","quote":"The cannula can remain in place for up to 7 days."},{"claim":"Share of palliative medication incidents involving CSCI","grade":"National incident data, England and Wales 2016-2021","source":"cssi-incidents-2024","quote":"About 25% of palliative medication incidents involve continuous subcutaneous infusions."}],"sources":[{"key":"nice-ng31","label":"Care of dying adults in the last days of life (NG31), recommendations","publisher":"NICE","year":2015,"url":"https://www.nice.org.uk/guidance/ng31/chapter/Recommendations","gradingScheme":"NICE does not grade recommendations; the wording ('offer', 'consider', 'avoid') signals strength.","read":"full-text","accessed":"2026-11-11"},{"key":"scot-spcg","label":"Scottish Palliative Care Guidelines: Syringe pump / driver guidelines (guideline sections: before setting up, setting up, loading, monitoring and maintaining, safety and risk management)","publisher":"Scottish Palliative Care Guidelines (Healthcare Improvement Scotland, Right Decision Service)","year":2023,"url":"https://www.palliativecareguidelines.scot.nhs.uk/scottish-palliative-care-guidelines/medicines/syringe-pump-driver-guidelines/","gradingScheme":"Not graded; national consensus guidance first produced by NHS Education for Scotland in 2011, updated 2018 and 2023.","read":"full-text","accessed":"2026-11-11"},{"key":"scot-spcg-practice","label":"Scottish Palliative Care Guidelines: Syringe pump / driver practice points","publisher":"Scottish Palliative Care Guidelines (Healthcare Improvement Scotland, Right Decision Service)","year":2023,"url":"https://www.palliativecareguidelines.scot.nhs.uk/scottish-palliative-care-guidelines/medicines/syringe-pump-driver-guidelines/syringe-pump-driver-practice-points/","gradingScheme":"Not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"cssi-incidents-2024","label":"Multiple points of system failure underpin continuous subcutaneous infusion safety incidents in palliative care: a mixed methods analysis (Brown et al., Palliat Med 2024)","publisher":"Palliative Medicine","year":2024,"url":"https://doi.org/10.1177/02692163241287639","doi":"10.1177/02692163241287639","gradingScheme":"Analysis of national incident reports; no grade.","read":"full-text","accessed":"2026-11-11"},{"key":"npsa-2010","label":"Safer ambulatory syringe drivers, Rapid Response Report NPSA/2010/RRR019","publisher":"National Patient Safety Agency (England and Wales)","year":2010,"url":"https://webarchive.nationalarchives.gov.uk/ukgwa/20171030131208/http://www.nrls.npsa.nhs.uk/resources/?entryid45=92908","gradingScheme":"Patient safety alert; not graded.","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The NPSA 2010 Rapid Response Report that moved UK services to syringe drivers with alarms, lockboxes and rates set in millilitres could not be read (the archive refused the script); nothing here rests on it.","No source read grades any step; the procedure is national consensus built on device instructions and incident learning, not on trials.","Drug choices, doses and compatibility tables are in the Scottish guideline's compatibility pages and local formularies and are not reproduced here.","The evidence on how often to change the extension line in palliative CSCI is limited, as the Scottish guideline says.","Children are outside these sources; the PELiCaN guideline for syringe pumps in children and young people was not read."]},{"id":"bispecific-step-up-dosing","kind":"protocol","name":"T-cell engaging bispecific antibodies: step-up dosing, monitoring and outpatient delivery","aka":["bispecific step-up dosing","BCMA bispecific outpatient dosing","teclistamab step-up","elranatamab step-up","bispecific CRS prevention","T-cell engager monitoring"],"tldr":"Bispecific antibodies such as teclistamab and elranatamab for myeloma, or glofitamab and epcoritamab for lymphoma, link T cells to cancer cells. The first doses are built up in steps to lower the risk of cytokine release syndrome (fever, low blood pressure) and confusion. Some countries do this in hospital; others let chosen patients go home between doses with a trained carer and a 24-hour number.","summary":"Step-up dosing (a small priming dose, then one or more intermediate doses before the full dose) is the standard way to start T-cell engaging bispecifics; the schedule, premedication and observation period are set by each product's label, which was not read here. The European Myeloma Network (2023) recommends premedication, frequent assessment for CRS and step-up dosing, with corticosteroids and tocilizumab for CRS and anakinra for refractory cases. CRS and ICANS are graded on the ASTCT scale.\n\nThe 2026 European Delphi consensus on BCMA bispecifics in myeloma (84 statements, 75% or more agreement; Pfizer-funded) restricts outpatient step-up dosing to patients with ECOG 0 to 2, low tumour burden, stable organ function, a neutrophil count of at least 1000/mm3, no neurological symptoms or active infection, a trained adult carer available 24 hours a day, and a home within 60 minutes of a centre with haematology and intensive care. Centres must have a clinician experienced in CRS and ICANS during dosing hours, two doses of tocilizumab in a known place, dexamethasone, high-dose steroids and anakinra, written escalation protocols and access to intensive care. Neutropenia from high tumour burden should not be corrected with G-CSF before step-up dosing. Antiviral and Pneumocystis prophylaxis are mandatory for all, with baseline CMV testing and immunoglobulin replacement when IgG is under 400 mg/dL or infections recur. Transfer to a community centre only after the full step-up phase, afebrile for 24 hours and with no toxicity, with a written handover.\n\nA 2026 viewpoint notes that current US labels recommend inpatient administration during step-up dosing. The CD3xCD20 consensus (2024) covers the lymphoma bispecifics separately and was read only as an abstract.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","bispecific"],"related":["crs-grading-and-management","icans-grading-and-management"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["bispecific-antibody"],"targets":[],"drugs":["teclistamab","elranatamab","linvoseltamab","talquetamab","glofitamab","epcoritamab","mosunetuzumab","tocilizumab","dexamethasone","human-normal-immunoglobulin"],"companies":[],"institutions":[],"pathways":[],"terms":["crs","icans","lymphoma-tx-bispecific-step-up","lymphoma-tx-immunoglobulin-replacement"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"These drugs are started at low doses that are stepped up over the first week or two, with close checks for fever and confusion. You will need a carer with you and a hospital nearby while this happens.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer","multidisciplinary-team"],"where":["ward","outpatient-clinic","chemotherapy-day-unit","home"]},"population":"Adults starting a T-cell engaging bispecific antibody, above all BCMA-directed bispecifics for relapsed or refractory multiple myeloma (teclistamab, elranatamab, linvoseltamab). CD3xCD20 bispecifics for lymphoma (glofitamab, epcoritamab, mosunetuzumab) and other T-cell engagers (blinatumomab, tarlatamab, talquetamab, tebentafusp) follow the same principles under their own labels and consensus papers.","trigger":"A decision to start a T-cell engaging bispecific antibody.","steps":[{"action":"Start with step-up doses and premedication, and assess often for cytokine release syndrome","why":"Building up the dose lets the immune system adjust and lowers the risk and severity of CRS.","source":"emn-2023","quote":"Recommended measures include premedication, frequent assessing for symptoms and severity of cytokine release syndrome, step-up dosing for several BsAbs and some CAR T-cell therapies; corticosteroids; and tocilizumab in the case of cytokine release syndrome."},{"action":"Follow the product label for the step-up schedule, premedication and how long to observe after each dose","why":"Each bispecific has its own licensed schedule; outpatient observation must match it.","source":"eu-bcma-2026","quote":"Following each step‐up dose, patients must be observed for vital signs and neurological function for a minimum defined period as specified in the SmPC."},{"action":"Before the first dose, test for CMV and start antiviral and Pneumocystis prophylaxis","why":"Infections are the main cause of serious harm on these drugs; prophylaxis lowers the risk.","source":"eu-bcma-2026","quote":"Antiviral (e.g., acyclovir) and PJP prophylaxis (e.g., co‐trimoxazole) are mandatory for all patients."},{"action":"Check IgG at baseline and every 4 weeks, and give immunoglobulin replacement if IgG is under 400 mg/dL or infections recur","why":"BCMA bispecifics deplete antibody-making cells, leaving people unable to fight bacteria.","source":"eu-bcma-2026","quote":"Patients with trough IgG < 400 mg/dL should receive IV or SC Ig every 4 weeks and be retested every month until IgG recovers (including after completion of treatment)."},{"action":"Do not use G-CSF to correct neutropenia before step-up dosing","why":"Growth factors may raise the risk of CRS, and neutropenia from heavy marrow involvement itself signals higher CRS risk.","source":"eu-bcma-2026","quote":"Neutropenia (defined as an absolute neutrophil count < 1000/mm 3 ) should not be resolved with G‐CSF prior to SUD due to the risk of CRS."},{"action":"Offer outpatient step-up dosing only to stable patients with low tumour burden, ECOG 0 to 2 and no neurological symptoms or active infection","why":"High tumour burden and frailty raise the risk of severe CRS, which is safer to manage on a ward.","source":"eu-bcma-2026","quote":"Outpatient SUD should only be considered for patients with low tumor burden (where high tumor burden is defined as BMPCs ≥ 60%, presence of ≥ 1 focal lesion ≥ 5 mm [bone or soft tissue] on MRI or PET–CT, M‐spike ≥ 30 g/L, LDH > ULN) and stable disease status."},{"action":"For outpatient dosing, require a trained adult carer available day and night and a home within 60 minutes of a centre with haematology and intensive care","why":"Someone must notice fever or confusion and get the patient back quickly.","source":"eu-bcma-2026","quote":"Patients must reside within 60 min (by ambulance, car, etc.) of a treatment center that provides both hematology or internal medicine expertise and ICU‐level care."},{"action":"Keep two doses of tocilizumab in a known place, with dexamethasone, high-dose steroids and anakinra, wherever step-up doses are given","why":"CRS and ICANS can begin within hours and must be treated without delay.","source":"eu-bcma-2026","quote":"Outpatient SUD centers must have tocilizumab (two doses) available in a known and accessible location."},{"action":"Write standard procedures that set observation times and escalation thresholds using ASTCT and ICE grading","why":"Clear triggers mean every nurse escalates at the same point.","source":"eu-bcma-2026","quote":"SOPs must define observation duration and escalation thresholds for CRS and ICANS, using established grading systems such as ASTCT and ICE."},{"action":"Grade any CRS on the ASTCT scale","why":"The same scale is used for CAR T cells and bispecifics, so treatment algorithms can be shared.","source":"astct-2019","quote":"CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause."},{"action":"Teach patients and carers, in their own language and in writing, the early signs of CRS, ICANS and infection, and give a 24-hour contact","why":"Fever, confusion and breathlessness at home need an immediate call.","source":"eu-bcma-2026","quote":"Education on CRS/ICANS must include both verbal explanations and written materials tailored to BCMA‐BsAb toxicities."},{"action":"Transfer care to a community centre only after the full step-up phase, with the patient afebrile for 24 hours and free of toxicity","why":"Most CRS happens during step-up; moving care earlier risks it starting away from the team that knows the drug.","source":"eu-bcma-2026","quote":"Patients must be afebrile (≥ 24 h) and hemodynamically stable before being considered for transition to community care."}],"bestInClass":{"statement":"Step-up dosing with premedication and close CRS monitoring is common ground (European Myeloma Network 2023; IMWG 2024). Where step-up doses are given is not: a 2026 viewpoint notes that current US labels recommend inpatient administration during step-up dosing, while the 2026 European Delphi consensus sets criteria for doing it as an outpatient in selected patients (low tumour burden, ECOG 0 to 2, trained carer, within 60 minutes of intensive care, tocilizumab on site). That consensus is the most detailed source read and it was funded by Pfizer, a manufacturer of a BCMA bispecific. Infection prophylaxis (antiviral and Pneumocystis for all, immunoglobulin when IgG is under 400 mg/dL) is shared across the myeloma sources. The product labels, which set the schedules, were not read.","sources":["emn-2023","imwg-2024","eu-bcma-2026","rpm-2026"]},"variants":[{"name":"Inpatient step-up dosing (US labels)","differs":"Current US labelling recommends inpatient administration during step-up dosing, which concentrates treatment in academic centres.","evidence":"Regulatory labelling, as described in a 2026 viewpoint; the labels themselves were not read.","sources":["rpm-2026"]},{"name":"Outpatient step-up dosing with remote monitoring (2026 viewpoint)","differs":"Uses remote patient monitoring to support outpatient step-up dosing in academic and community practices.","evidence":"Authors' real-world experience and case examples; not a trial.","sources":["rpm-2026"]},{"name":"Lymphoma bispecifics (CD3xCD20 consensus, 2024)","differs":"An international panel of physicians, advanced practitioners, nurses and pharmacists set recommendations specific to CD3xCD20 bispecifics, noting that the timing, nature and severity of their toxicities differ from CAR T cells.","evidence":"Consensus recommendations; abstract read only.","sources":["cd20-2024"]}],"grades":[{"claim":"Antiviral and Pneumocystis prophylaxis for all patients on BCMA bispecifics","grade":"consensus, 100% agreement","source":"eu-bcma-2026"},{"claim":"Outpatient step-up dosing only for low tumour burden and stable disease","grade":"consensus, 84% agreement","source":"eu-bcma-2026"},{"claim":"Live within 60 minutes of a centre with haematology and intensive care","grade":"consensus, 100% agreement","source":"eu-bcma-2026"},{"claim":"Two doses of tocilizumab on site for outpatient step-up dosing","grade":"consensus, 97% agreement","source":"eu-bcma-2026"},{"claim":"No G-CSF to correct neutropenia before step-up dosing","grade":"consensus, 79% agreement","source":"eu-bcma-2026"}],"sources":[{"key":"eu-bcma-2026","label":"European Recommendations for Transitioning the Care of Patients With Multiple Myeloma Treated With B-Cell Maturation Antigen Bispecific Antibodies From Academic Hospitals to Community-Based Centers and for Outpatient Step-Up Dosing","publisher":"eJHaem (European Delphi panel; funded by Pfizer)","year":2026,"url":"https://europepmc.org/article/PMC/PMC13172755","doi":"10.1002/jha2.70290","gradingScheme":"Modified Delphi: a statement reached consensus at 75% or more agreement among 38 to 53 haematologists, nurses and pharmacists from six countries; the percentage agreeing is printed beside each statement.","read":"full-text","accessed":"2026-11-11"},{"key":"emn-2023","label":"Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network","publisher":"European Myeloma Network, The Lancet Oncology","year":2023,"url":"https://europepmc.org/abstract/MED/37269857","doi":"10.1016/S1470-2045(23)00159-6","read":"abstract","accessed":"2026-11-11"},{"key":"imwg-2024","label":"International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma","publisher":"International Myeloma Working Group, The Lancet Oncology","year":2024,"url":"https://europepmc.org/abstract/MED/38697166","doi":"10.1016/S1470-2045(24)00043-3","read":"abstract","accessed":"2026-11-11"},{"key":"cd20-2024","label":"Consensus recommendations on the management of toxicity associated with CD3xCD20 bispecific antibody therapy","publisher":"Blood (international panel)","year":2024,"url":"https://europepmc.org/abstract/MED/38252906","doi":"10.1182/blood.2023022432","read":"abstract","accessed":"2026-11-11"},{"key":"rpm-2026","label":"Practical Recommendations for Implementing Remote Patient Monitoring for Patients Receiving Bispecific Antibodies for Multiple Myeloma","publisher":"JMIR (viewpoint)","year":2026,"url":"https://europepmc.org/abstract/MED/42987260","doi":"10.2196/95949","read":"abstract","accessed":"2026-11-11"},{"key":"astct-2019","label":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","publisher":"American Society for Transplantation and Cellular Therapy, Biology of Blood and Marrow Transplantation","year":2019,"url":"https://europepmc.org/article/PMC/PMC12180426","doi":"10.1016/j.bbmt.2018.12.758","gradingScheme":"A consensus grading system (grades 1 to 4), not a set of graded recommendations.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The product labels (SmPC and US prescribing information) for teclistamab, elranatamab, linvoseltamab, talquetamab, glofitamab, epcoritamab and mosunetuzumab, which set each step-up schedule, premedication and observation period, were not read; no dose or schedule is given here.","The IMWG 2024 guideline, the European Myeloma Network 2023 consensus and the CD3xCD20 consensus 2024 were read only as abstracts.","The most detailed source, the 2026 European Delphi consensus, was funded by Pfizer and its panel members were paid honoraria; no independent source of the same detail was found.","No randomised comparison of inpatient and outpatient step-up dosing was found."]},{"id":"irae-thyroid","kind":"protocol","name":"Thyroid inflammation and underactive thyroid from checkpoint inhibitors","aka":["checkpoint inhibitor thyroiditis","ICI thyroiditis","immune-related hypothyroidism","immunotherapy thyroid problems","ir-thyroiditis","immune-related thyrotoxicosis"],"tldr":"Immunotherapy often inflames the thyroid gland. It can briefly make the thyroid overactive (racing heart, sweating, shakiness) and then underactive (tiredness, feeling cold), and the underactive phase is often permanent. It is found on routine blood tests, treated with tablets rather than steroids, and immunotherapy usually carries on.","summary":"The commonest endocrine irAE. Hypothyroidism occurs in about 8% on PD-(L)1 inhibitors, 3% on CTLA-4 inhibitors and 15% on combinations (SITC 2021); ESE 2022 gives 3.9 to 8.5%, 2.5 to 3.8% and 10.2 to 16.4%, with onset at a median 8 to 12 weeks. A thyrotoxic phase, typically 4 to 6 weeks after starting and lasting about 6 weeks, often precedes it, and hypothyroidism is often permanent.\n\nMonitoring: TSH and free T4 every 4 to 6 weeks on treatment and every 6 to 12 months after (SITC; ESE suggests before every cycle for the first 6 months). Thyrotoxicosis is treated with beta-blockers for symptoms; persistent thyrotoxicosis needs assessment for Graves' disease with TSH receptor antibodies. Morning cortisol is checked before levothyroxine, because replacing thyroid hormone in untreated adrenal insufficiency can precipitate a crisis. High-dose glucocorticoids are not used for thyroiditis (ESE, +000). Immunotherapy is usually continued.\n\nThe two guidelines differ on when and how much levothyroxine to start: SITC considers it for a persistently raised TSH with normal free T4 and starts at 1.5 to 1.6 µg/kg/day in young healthy patients; ESE suggests it when free T4 is low and TSH above 10 mIU/L (++00), advises against routine treatment for TSH 4 to 10 with normal free T4 (+000), and starts at 1.0 µg/kg/day. ESMO 2022 could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","endocrine"],"related":["irae-hypophysitis-adrenal","checkpoint-inhibitor-baseline-and-monitoring"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","tremelimumab","avelumab","dostarlimab"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["immune-endocrinopathy","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can upset your thyroid gland. Your blood tests check for this. If it happens, it is treated with tablets and you can usually keep having immunotherapy.","domain":"immunotherapy-toxicity","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","chemotherapy-day-unit","community"]},"population":"Adults receiving or who have received an immune checkpoint inhibitor (PD-1, PD-L1 or CTLA-4), alone or in combination. Central hypothyroidism from hypophysitis is a different condition and is covered by the hypophysitis protocol. Children are not addressed by these sources.","trigger":"An abnormal TSH or free T4 on routine monitoring, or symptoms of an overactive or underactive thyroid, during or after checkpoint inhibitor treatment.","steps":[{"action":"Test TSH and free T4 every 4 to 6 weeks during treatment and every 6 to 12 months after it ends","why":"Thyroid problems are often silent and can start months after the last dose.","source":"sitc-2021","quote":"Thyroid function (TSH, fT4) should be tested every 4–6 weeks during ICI treatment, and should continue to be tested every 6–12 months following the conclusion of ICI treatment."},{"action":"Keep giving the checkpoint inhibitor once the patient is stable, treating the thyroid with hormone replacement or symptom relief","why":"A controlled thyroid problem is not a reason to stop cancer treatment.","source":"sitc-2021","quote":"Patients experiencing endocrine toxicities should be treated with hormone replacement, and immunotherapy should generally be continued as soon as patients are stable (often without interruption)."},{"action":"Do not give high-dose steroids for thyroiditis, except for severe thyrotoxicosis or severe thyroid eye disease","why":"Steroids have not been shown to save the thyroid, and they bring their own side effects.","source":"ese-2022","quote":"We recommend against the use of high-dose glucocorticoids for the treatment of thyroiditis; except in severe thyrotoxicosis and severe thyroid eye disease","grade":"+000"},{"action":"Watch mild thyrotoxicosis or mild hypothyroidism without treatment, rechecking TSH and free T4 every 3 to 6 weeks early on","why":"Most cases are mild, and the overactive phase usually passes on its own.","source":"ese-2022","quote":"We suggest that cases of clinically and biochemically mild thyrotoxicosis or hypothyroidism can be monitored without treatment","grade":"good clinical practice"},{"action":"Give a beta-blocker for symptoms of an overactive thyroid; use a cardioselective one such as atenolol or metoprolol in asthma or COPD","why":"A beta-blocker calms a racing heart and shakiness while the inflammation settles.","source":"sitc-2021","quote":"Patients with low TSH and normal fT4 should receive repeat TSH and fT4 testing routinely, and if symptoms of hyperthyroidism or high fT4 develop patients should be treated with beta-blockers. Patients with asthma or chronic obstructive pulmonary disease should be treated with cardioselective beta-blockers such as atenolol or metoprolol."},{"action":"If TSH stays low with a high free T4, assess for Graves' disease, including TSH receptor antibodies","why":"Graves' disease is rare after immunotherapy but needs different treatment (anti-thyroid drugs) from thyroiditis.","source":"sitc-2025-endocrine","quote":"TSH receptor antibody should be considered in patients with suspected ir-Graves’ disease, as the condition is managed differently from ir-thyroiditis."},{"action":"Before starting levothyroxine for symptoms or a high TSH with low free T4, check a morning cortisol","why":"Replacing thyroid hormone when adrenal insufficiency is untreated can trigger an adrenal crisis.","source":"sitc-2021","quote":"Patients with symptoms of hypothyroidism and/or with elevated TSH and low fT4 should be tested for morning cortisol to identify possible concurrent adrenal insufficiency."},{"action":"Start levothyroxine for overt primary hypothyroidism: free T4 below the reference range with TSH above 10 mIU/L","why":"Treating an underactive thyroid improves tiredness and other symptoms.","source":"ese-2022","quote":"We suggest replacement with levothyroxine in primary hypothyroidism in cases with fT4 below the lower reference limit and TSH > 10 mIU/L.","grade":"++00"},{"action":"Do not routinely start levothyroxine for TSH between 4 and 10 mIU/L with a normal free T4; repeat the tests and weigh symptoms","why":"A mildly raised TSH often settles or stays harmless.","source":"ese-2022","quote":"We recommend against routine replacement with levothyroxine of ICI-treated patients with a TSH between 4–10 mIU/L and a normal fT4","grade":"+000"},{"action":"Adjust the levothyroxine dose on TSH and free T4 no more often than every 6 weeks","why":"Levothyroxine takes weeks to reach a steady level, so earlier changes overshoot.","source":"ese-2022","quote":"Regular monitoring of thyroid hormones (TSH and fT4) is needed in order to titrate levothyroxine dosage at intervals of at least 6 weeks."},{"action":"After immunotherapy stops, keep checking thyroid function every 6 to 12 months, and sooner if symptoms appear","why":"Thyroid problems can develop late and the symptoms are vague.","source":"ese-2022","quote":"In case of ICI cessation, ongoing monitoring of thyroid function (TSH and fT4) is still indicated, albeit less frequently (e.g. every 6–12 months and in case of symptoms and signs of thyroid dysfunction)."}],"bestInClass":{"statement":"SITC 2021 and ESE 2022 agree on regular TSH and free T4 testing, beta-blockers for symptomatic thyrotoxicosis, a check for adrenal insufficiency before levothyroxine, no high-dose steroids for thyroiditis, and continuing immunotherapy. They disagree on when and how much levothyroxine to start. SITC considers levothyroxine for a persistently raised TSH with a normal free T4 (subclinical hypothyroidism) and starts at 1.5 to 1.6 µg/kg/day in young healthy patients (25 or 50 µg/day if older than 65 or with heart disease), without a grade. ESE suggests replacement only when free T4 is below range and TSH above 10 mIU/L (++00), recommends against routine replacement for TSH 4 to 10 with a normal free T4 (+000), and starts at 1.0 µg/kg/day (25 µg/day in older people or those with heart disease). ESE is a GRADE-based endocrine guideline with a systematic review behind it, so its thresholds are the better supported; SITC's are expert consensus. The SITC 2025 endocrine definitions take a middle line: replacement for a TSH above 10 mIU/L whatever the free T4.","sources":["ese-2022","sitc-2021","sitc-2025-endocrine"]},"variants":[{"name":"Testing before every cycle for the first 6 months (ESE 2022)","differs":"Tests TSH and free T4 before every treatment cycle for the first 6 months, then every 2 to 3 months for 6 months, then every 6 months, instead of a flat every 4 to 6 weeks.","evidence":"Described in the text as general advice; not a graded recommendation.","sources":["ese-2022"]},{"name":"Levothyroxine for any TSH above 10 mIU/L (SITC 2025 endocrine definitions)","differs":"Defines overt hypothyroidism as a high TSH with low free T4, or a TSH above 10 mIU/L regardless of free T4, and starts replacement in either case.","evidence":"Modified Delphi consensus (RAND/UCLA appropriateness method) of an expert panel; not graded.","sources":["sitc-2025-endocrine"]},{"name":"Higher starting dose of levothyroxine (SITC 2021)","differs":"Starts 1.5 to 1.6 µg/kg/day for young, healthy patients and 25 or 50 µg/day above 65 or with heart disease, and considers treating a persistent raised TSH with normal free T4.","evidence":"Expert consensus; no level of evidence printed for this recommendation.","sources":["sitc-2021"]}],"grades":[{"claim":"A controlled endocrinopathy is not a contraindication to starting or continuing checkpoint inhibitors","grade":"++00","source":"ese-2022","quote":"We recommend that a controlled endocrinopathy is not a contraindication for initiation and/or continuation of ICI therapy"},{"claim":"No high-dose glucocorticoids for thyroiditis, except severe thyrotoxicosis or thyroid eye disease","grade":"+000","source":"ese-2022"},{"claim":"Beta-blockers in symptomatic thyrotoxicosis","grade":"good clinical practice","source":"ese-2022","quote":"We recommend using beta-blockers in symptomatic thyrotoxicosis"},{"claim":"Levothyroxine when free T4 is below range and TSH above 10 mIU/L","grade":"++00","source":"ese-2022"},{"claim":"No routine levothyroxine for TSH 4 to 10 mIU/L with normal free T4","grade":"+000","source":"ese-2022"},{"claim":"Consider tapering and stopping low-dose levothyroxine periodically to see whether the thyroid has recovered","grade":"+000","source":"ese-2022","quote":"We suggest considering tapering and stopping levothyroxine periodically in patients with low-dose replacement to assess whether thyroid function has recovered"}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"ese-2022","label":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline","publisher":"European Society of Endocrinology, European Journal of Endocrinology","year":2022,"url":"https://europepmc.org/article/PMC/PMC9641795","doi":"10.1530/EJE-22-0689","gradingScheme":"GRADE: quality of evidence printed as +000 (very low), ++00 (low), +++0 (moderate) or ++++ (strong); 'recommend' is a strong and 'suggest' a weak recommendation; recommendations not formally graded are marked good clinical practice.","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-2025-endocrine","label":"Consensus-based disease definitions for endocrine immune-related adverse events of immune checkpoint inhibitors","publisher":"Journal for ImmunoTherapy of Cancer","year":2025,"url":"https://europepmc.org/article/PMC/PMC12530408","doi":"10.1136/jitc-2025-011865","gradingScheme":"RAND/UCLA Appropriateness Method (modified Delphi) consensus of a multidisciplinary panel; statements are not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline was read only as its abstract, which says permanent discontinuation after grade 4 toxicity does not apply to endocrinopathies controlled by hormone replacement, but does not give its thyroid table.","The guidelines disagree on whether to treat a raised TSH (4 to 10 mIU/L) with a normal free T4, and on the levothyroxine starting dose; no trial compares the approaches in people on immunotherapy.","Recovery is uncommon and the proportion of transient versus permanent hypothyroidism cannot be defined from the studies ESE reviewed."]},{"id":"tumour-lysis-syndrome-prevention-and-treatment","kind":"protocol","name":"Tumour lysis syndrome: risk assessment, prophylaxis and treatment","aka":["TLS prophylaxis","tumor lysis syndrome management","rasburicase or allopurinol","laboratory TLS","clinical TLS","Cairo-Bishop"],"tldr":"When a fast-growing cancer such as some leukaemias and lymphomas is first treated, many cancer cells can die at once and flood the blood with potassium, phosphate and uric acid, which can damage the kidneys and heart. Teams check who is at risk, give extra fluids and a medicine (allopurinol, or rasburicase for higher risk) before treatment, and check blood tests often in the first days.","summary":"TLS is laboratory (two or more of raised uric acid, potassium or phosphate, or low calcium, by 25% from baseline or past fixed thresholds, from three days before to seven days after starting treatment) or clinical (laboratory TLS with renal failure, arrhythmia or seizure) (Italian consensus 2008). Risk rises with bulky or highly chemosensitive disease (Burkitt and lymphoblastic lymphoma, acute lymphoblastic leukaemia, bulky small cell lung cancer), LDH over twice normal, pre-existing renal impairment, dehydration and high uric acid. The Cairo 2010 expert panel assigns low, intermediate and high risk with a decision tree.\n\nPrevention (Cairo 2008): close monitoring for low risk, hydration with allopurinol or rasburicase for intermediate risk, hydration with prophylactic rasburicase for high risk. The Italian consensus gives low-risk patients oral allopurinol and hydration and high-risk patients rasburicase 0.20 mg/kg/day over 30 minutes as inpatients, starting at least 4 hours before treatment and continuing 3 to 5 days, without allopurinol at the same time; rasburicase is contraindicated in G6PD deficiency and methaemoglobinaemia. Hydration ideally starts 48 hours ahead, keeping urine output at least 100 mL an hour in adults. Monitor LDH, uric acid, sodium, potassium, creatinine, urea, phosphate and calcium every 12 hours for 3 days in high-risk patients.\n\nEstablished TLS: hydration and rasburicase, observations and electrolytes every 6 hours for the first 24 hours, calcium only for symptomatic hypocalcaemia, and renal replacement for persistent hyperkalaemia, severe acidosis, refractory overload or uraemia. Cairo 2008 does not recommend urine alkalinisation; the Italian consensus keeps it only for low-risk patients and those who cannot have rasburicase. The BSH 2015 guideline could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","acute-oncology","oncological-emergency","metabolic"],"related":[],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["rasburicase","allopurinol","venetoclax"],"companies":[],"institutions":[],"pathways":[],"terms":["tumor-lysis-syndrome","lymphoma-tx-tumour-lysis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Some cancer treatments kill cancer cells so quickly that the waste can harm the kidneys. Drinking plenty, extra fluids through a drip, a tablet or drip to lower uric acid, and regular blood tests prevent this.","domain":"emergencies","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["ward","chemotherapy-day-unit","outpatient-clinic","intensive-care"]},"population":"Adults and children starting treatment for a cancer at risk of rapid cell kill, above all haematological cancers (acute leukaemias, Burkitt and other high-grade lymphomas, CLL starting venetoclax) and bulky chemosensitive solid tumours. CAR T-cell recipients and venetoclax ramp-up have specific variants.","trigger":"Planning the first cycle of treatment for a cancer at risk of TLS, or a rise in potassium, phosphate, uric acid or creatinine, or a fall in calcium, in the days after treatment starts.","steps":[{"action":"Before treatment, assess TLS risk from the cancer, its bulk and expected response, kidney function, hydration and baseline uric acid","why":"Prevention is matched to risk; the highest-risk patients need inpatient care and rasburicase.","source":"haematologica-2008","quote":"Patients at high risk of developing TLS carry at least one of the following factors: (i) Host-related factors (comorbidities): dehydration; hyponatremia (limited to solid tumors); pre-existing renal impairment (including renal infiltration by hematologic malignancies which induce a reduction in renal function); obstructive uropathy; hyperuricemia (uric acid >8 mg/dL in children and >10 mg/dL in adults)."},{"action":"Match prophylaxis to risk: monitoring for low risk, hydration with allopurinol or rasburicase for intermediate risk, hydration with rasburicase for high risk","why":"The cheaper drug is enough when risk is lower; rasburicase removes existing uric acid quickly when it is high.","source":"cairo-2008","quote":"Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients."},{"action":"Start hydration, where possible, 48 hours before treatment and keep adult urine output at least 100 mL an hour","why":"Good urine flow washes out uric acid, potassium and phosphate before they build up.","source":"haematologica-2008","quote":"When possible, hydration should start at least 48 hours before tumor-specific therapy; however, the use of rasburicase with subsequent rapid degradation of uric acid allows earlier administration of chemotherapy, if needed."},{"action":"For high risk, give rasburicase 0.20 mg/kg/day over 30 minutes, the first dose at least 4 hours before treatment, for 3 to 5 days, then switch to oral allopurinol","why":"Rasburicase breaks down uric acid already in the blood; allopurinol only stops new uric acid forming.","source":"haematologica-2008","quote":"Rasburicase should be administered at the dose of 0.20 mg/kg/day, infused over 30 minutes, administering the first dose at least four hours before the start of tumor-specific therapy and continuing for at least 3-5 days."},{"action":"Do not give allopurinol at the same time as rasburicase","why":"Allopurinol causes xanthine to build up and starves rasburicase of uric acid to act on.","source":"haematologica-2008","quote":"In order to avoid xanthine accumulation and lack of substrate for rasburicase, concomitant allopurinol should not be administered."},{"action":"Do not give rasburicase to people with G6PD deficiency or methaemoglobinaemia; use allopurinol and hydration instead","why":"Rasburicase can cause severe haemolysis and methaemoglobinaemia in these patients.","source":"haematologica-2008","quote":"Rasburicase is contraindicated in patients with metahemoglobinemia, G6PDH deficiency or other metabolic disorders that can potentially cause hemolytic anemia; these patents should be treated with oral allopurinol, hydration and urine alkalinization."},{"action":"In high-risk patients, check LDH, uric acid, sodium, potassium, creatinine, urea, phosphate and calcium every 12 hours for 3 days, then daily","why":"TLS usually develops within the first days of treatment, and early changes can be corrected before harm.","source":"haematologica-2008","quote":"In patients at high risk of TLS, levels of LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus and calcium should be monitored every 12 hours for the first three days, and every 24 hours subsequently."},{"action":"Diagnose laboratory TLS from two or more abnormal values among uric acid, potassium, phosphate and calcium, and clinical TLS when there is also kidney failure, arrhythmia or a seizure","why":"A shared definition triggers treatment at the same point everywhere.","source":"haematologica-2008","quote":"Clinical TLS is defined by the presence of laboratory TLS and at least one of the following clinical alterations: renal failure (estimated glomerular filtration rate ≤ 60 mL/min), cardiac arrhythmia, seizure."},{"action":"Treat established TLS with intravenous hydration and rasburicase","why":"Clearing uric acid quickly protects the kidneys and lets cancer treatment continue.","source":"haematologica-2008","quote":"Hydration through a central venous access and rasburicase should be administrated to all patients with clinical TLS."},{"action":"Do not give calcium for mild, symptom-free low calcium; reserve it for symptoms or for heart rhythm problems from high potassium","why":"Calcium given when phosphate is high can deposit as crystals in the kidneys and tissues.","source":"haematologica-2008","quote":"Asymptomatic hypocalcemia does not require treatment."},{"action":"Refer for renal replacement therapy for persistent high potassium, severe acidosis, fluid overload that does not respond to diuretics, or uraemic symptoms","why":"Dialysis removes potassium, phosphate and uric acid when the kidneys cannot.","source":"haematologica-2008","quote":"Indications for the start-up of renal replacement therapy in TLS include persistent hyperkalemia, severe metabolic acidosis, volume overload unresponsive to diuretic therapy, and overt uremic symptoms, including pericarditis and severe encephalopathy."}],"bestInClass":{"statement":"Risk-adapted prophylaxis is common ground: hydration for everyone at risk, allopurinol at lower risk and rasburicase at high risk, given before treatment starts (Cairo 2008; Cairo 2010 risk model; Italian consensus 2008). The sources disagree on urine alkalinisation: Cairo 2008 does not recommend it, while the Italian consensus still lists it for low-risk patients and for those who cannot have rasburicase, although it also says alkalinisation brings no biochemical advantage and has been progressively abandoned. Rasburicase dosing and schedule here are from the Italian consensus (0.20 mg/kg/day for 3 to 5 days); lower and single fixed doses are in use but were described as under evaluation in 2008. The UK guideline (BSH 2015), the most recent national guideline in the census, could not be read, so this page does not say how the UK position differs.","sources":["cairo-2008","cairo-2010","haematologica-2008","bsh-2015"]},"variants":[{"name":"No urine alkalinisation (Cairo 2008)","differs":"States that alkalinisation is not recommended for prevention or treatment.","evidence":"Expert panel evidence-based review (abstract read).","sources":["cairo-2008"]},{"name":"Alkalinisation for low-risk patients (Italian consensus 2008)","differs":"Gives low-risk children and adults oral allopurinol, hydration and urine alkalinisation, and uses alkalinisation for those who cannot have rasburicase.","evidence":"Consensus conference endorsed by SIE, AIEOP and AIOM; the same document says alkalinisation does not improve the biochemistry of TLS.","sources":["haematologica-2008"]},{"name":"Venetoclax ramp-up in CLL (UK practice review)","differs":"Stratifies TLS risk before a five-week ramp-up of venetoclax (20, 50, 100, 200, 400 mg), starts allopurinol two to three days ahead and oral fluids of 1.5 to 2 litres a day for the two days before, admits high-risk patients for intravenous fluids, and checks blood chemistry before, and 8 and 24 hours after, each dose increase. The author gives the first dose early in the morning so the 6 to 8 hour blood test is seen while staff are present.","evidence":"A single clinician's practical review following the product label; medical writing support was funded by the manufacturer.","sources":["gribben-2020"]},{"name":"Around CAR T-cell therapy (SITC 2020)","differs":"Monitors disease burden and potassium, phosphate, calcium, uric acid and creatinine, gives allopurinol as prophylaxis before CAR T cells, and considers rasburicase for established TLS.","evidence":"LE: 3 for monitoring, LE: 4 for allopurinol and rasburicase.","sources":["sitc-iec-2020"]}],"grades":[{"claim":"Risk-adapted prophylaxis: rasburicase for high risk, allopurinol or rasburicase for intermediate, monitoring for low","grade":"expert panel consensus (grades not in abstract)","source":"cairo-2008"},{"claim":"Alkalinisation not recommended","grade":"expert panel consensus (grades not in abstract)","source":"cairo-2008","quote":"Alkalinization is not recommended."},{"claim":"Hydration and rasburicase for high-risk adults; hydration and oral allopurinol for low risk","grade":"consensus conference recommendation (not graded)","source":"haematologica-2008"},{"claim":"Allopurinol before CAR T cells","grade":"LE: 4","source":"sitc-iec-2020","quote":"For prophylaxis against TLS prior to CAR T cell therapy, allopurinol should be administered"}],"sources":[{"key":"haematologica-2008","label":"Consensus conference on the management of tumor lysis syndrome","publisher":"Italian Society of Hematology (SIE), Italian Association of Pediatric Oncologists (AIEOP) and Italian Society of Medical Oncology (AIOM), Haematologica","year":2008,"url":"https://doi.org/10.3324/haematol.13290","doi":"10.3324/haematol.13290","gradingScheme":"Consensus statements from an expert panel; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"cairo-2008","label":"Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review","publisher":"Journal of Clinical Oncology (expert panel)","year":2008,"url":"https://europepmc.org/abstract/MED/18509186","doi":"10.1200/JCO.2007.15.0177","read":"abstract","accessed":"2026-11-11"},{"key":"cairo-2010","label":"Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus","publisher":"British Journal of Haematology (international expert panel)","year":2010,"url":"https://europepmc.org/abstract/MED/20331465","doi":"10.1111/j.1365-2141.2010.08143.x","read":"abstract","accessed":"2026-11-11"},{"key":"bsh-2015","label":"Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology","publisher":"British Society for Haematology, British Journal of Haematology","year":2015,"url":"https://doi.org/10.1111/bjh.13403","doi":"10.1111/bjh.13403","read":"not-reachable","accessed":"2026-11-11"},{"key":"gribben-2020","label":"Practical management of tumour lysis syndrome in venetoclax-treated patients with chronic lymphocytic leukaemia","publisher":"British Journal of Haematology (review)","year":2020,"url":"https://europepmc.org/article/PMC/PMC7154710","doi":"10.1111/bjh.16345","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The BSH 2015 guideline, the UK standard, could not be read: Europe PMC holds no abstract and the Wiley page returned 403 to a script.","The Cairo 2008 and 2010 papers were read as abstracts only, so their risk tables, drug doses and grades are not given here.","The fullest source read is from 2008; no newer international guideline on TLS was found in Europe PMC. Lower or single fixed doses of rasburicase are in use, and the evidence for them was not reviewed for this page.","Venetoclax, and other targeted drugs with their own ramp-up schedules, follow their product labels, which were not read here."]},{"id":"vaccination-around-cancer-treatment","kind":"protocol","name":"Vaccination before, during and after cancer treatment","aka":["vaccines during chemotherapy","flu jab during chemotherapy","live vaccines and cancer","immunisation and chemotherapy","household contacts vaccination","vaccination of children with cancer"],"tldr":"Before cancer treatment, the team should check which vaccines a person has had and bring them up to date, ideally two to four weeks before. Non-live vaccines such as the flu jab can still be given during treatment. Live vaccines, such as MMR, chickenpox and the nasal flu spray for the patient, must be avoided during treatment and for months after. Family vaccines protect the patient too.","summary":"ASCO (2024, adults) asks clinicians to determine vaccination status and bring newly diagnosed adults up to date on seasonal and age- and risk-based vaccines (moderate, strong), ideally 2 to 4 weeks before treatment, with non-live vaccines allowed during or after chemotherapy, immunotherapy, hormonal treatment, radiation or surgery (moderate, strong). The Green Book (UK, all ages) gives inactivated vaccines at least two weeks before immunosuppressive treatment where possible, and otherwise at any time with re-immunisation considered after recovery. Live vaccines are contraindicated in acute and chronic leukaemia and lymphoma, during and for 6 months after immunosuppressive chemotherapy or radiotherapy, for 12 months after immunosuppressive biologics such as rituximab, for 24 months after a stem cell transplant (and longer with GVHD or ongoing immunosuppression), and for 3 months after high-dose corticosteroids (above 40 mg prednisolone a day, or 2 mg/kg/day in children under 20 kg, for more than a week). Live attenuated nasal influenza vaccine cannot be given to patients with cancer (ASCO).\n\nRevaccination after transplant starts at 6 to 12 months (influenza, COVID-19 and pneumococcal from 3 months), after CD19 or BCMA CAR-T no sooner than 3 months for influenza and COVID-19 and 6 months for other non-live vaccines (very low, weak), and after B-cell depleting therapy COVID-19 only, at 6 months (moderate, strong). Household contacts should be fully vaccinated, including MMR, varicella and rotavirus, with hand washing after nappy changes for rotavirus; contacts of severely immunocompromised patients such as transplant recipients in isolation get inactivated rather than live influenza vaccine. Children with immunodeficiency attending school do not need to be kept away when classmates are immunised. For children, ASCO does not apply (it covers 19 and over); the Indian Academy of Pediatrics advises against live vaccines during and up to 6 months after chemotherapy and recommends only annual inactivated influenza vaccine for all children during chemotherapy.","asOf":"2026-11-11","links":[],"tags":["protocol","vaccination","infection-prevention","paediatric"],"related":["rejuv-tx-revaccination","lymphoma-living-vaccinations"],"cancers":["childhood-cancers","all-leukemia","non-hodgkin-lymphoma","hodgkin-lymphoma","multiple-myeloma"],"sections":["supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t"],"targets":[],"drugs":["rituximab"],"companies":[],"institutions":["asco"],"pathways":[],"terms":["hypogammaglobulinaemia"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"Ask your cancer team which vaccines you need before treatment starts. Flu and other injected vaccines are usually safe during treatment. Some vaccines that use live germs are not. Your family should have their normal vaccines too.","domain":"infection-prevention","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["outpatient-clinic","community","home"]},"population":"Adults with solid tumours or haematological cancers, including after stem cell transplant, CAR-T and B-cell depleting therapy, and long-term survivors (ASCO 2024, which excludes people under 19 and gives no separate advice for people living with HIV); people of all ages in the UK (Green Book); children having chemotherapy (Indian Academy of Pediatrics); and the household contacts of all of them.","trigger":"A new cancer diagnosis with treatment planned, each influenza season during treatment, and the end of treatment.","steps":[{"action":"At the first visit, find out which vaccines the person has had and bring them up to date with seasonal, age-based and risk-based vaccines","why":"People with cancer catch infections more easily and more severely, and vaccines work best before treatment weakens the immune system.","source":"asco-2024","quote":"Clinicians should determine vaccination status and ensure that adults newly diagnosed with cancer and about to start treatment are up to date on seasonal vaccines as well as age- and risk-based vaccines (see Tables 2-4)","grade":"Evidence quality: moderate; strength of recommendation: strong"},{"action":"Give vaccines 2 to 4 weeks before treatment where possible, but do not withhold non-live vaccines during or after treatment","why":"The response is best before treatment, yet a non-live vaccine cannot cause infection and still gives some protection later.","source":"asco-2024","quote":"Vaccination should ideally precede any planned cancer treatment by 2-4 weeks. However, nonlive vaccines can be administered during or after chemotherapy or immunotherapy, hormonal treatment, radiation, or surgery","grade":"Evidence quality: moderate; strength of recommendation: strong"},{"action":"Do not give live vaccines to anyone with leukaemia or lymphoma, or within 6 months of immunosuppressive chemotherapy or radiotherapy","why":"A weakened vaccine germ can multiply out of control when the immune system is suppressed.","source":"green-book-ch6","quote":"those who are receiving, or have received in the past 6 months, immunosuppressive chemotherapy or radiotherapy for malignant disease or non-malignant disorders"},{"action":"Extend the live-vaccine bar to 12 months after immunosuppressive biologics such as rituximab, unless a specialist directs otherwise","why":"B-cell depleting antibodies weaken immunity for longer than chemotherapy does.","source":"green-book-ch6","quote":"those who are receiving or have received in the past 12 months immunosuppressive biological therapy (e.g. anti-TNF therapy such as alemtuzumab, ofatumumab and rituximab) unless otherwise directed by a specialist"},{"action":"Use the injected flu vaccine every year for the patient, never the nasal spray","why":"The nasal spray contains live virus.","source":"asco-2024","quote":"Live attenuated influenza vaccine, which is administered as a nasal spray, cannot be given to patients with cancer."},{"action":"Record past measles and chickenpox, and the vaccines for them, so an exposure can be acted on quickly","why":"After contact with chickenpox or measles, a protective antibody injection or aciclovir has to be given promptly, and the history decides who needs it.","source":"green-book-ch7","quote":"As administration of these products should be undertaken promptly, it is important to ensure that any past history of measles and varicella disease and/or vaccination is documented, and antibody testing may be indicated."},{"action":"After a stem cell transplant, offer a full revaccination course starting 6 to 12 months later, with live vaccines delayed at least 2 years","why":"A transplant wipes out most of the protection from earlier vaccines.","source":"asco-2024","quote":"Complete revaccination starting 6-12 months after hematopoietic stem-cell transplant should be offered in order to restore vaccine-induced immunity.","grade":"Evidence quality: moderate; strength of recommendation: strong"},{"action":"After CAR-T against CD19 or BCMA, give influenza and COVID-19 vaccines no sooner than 3 months after treatment and other non-live vaccines no sooner than 6 months","why":"Too early and the vaccine produces little protection; there is very little evidence on the best timing.","source":"asco-2024","quote":"Adults with hematopoietic malignancies receiving CAR-T therapy directed against B-cell antigens (CD19, BCMA) should receive influenza and COVID-19 vaccine no sooner than 3 months after the completion of therapy.","grade":"Evidence quality: very low; strength of recommendation: weak"},{"action":"Make sure everyone the patient lives with, and close contacts, are up to date on their own vaccines, including the yearly flu vaccine","why":"Vaccinated family members are less likely to bring infection home.","source":"asco-2024","quote":"It is recommended that all household members and close contacts, where feasible, be up to date on vaccinations","grade":"Evidence quality: moderate; strength of recommendation: strong"},{"action":"Let household contacts have live vaccines such as MMR, varicella and rotavirus, with careful hand washing after nappy changes for rotavirus","why":"These vaccine viruses are not known to harm close contacts, and the family's immunity protects the patient from the real infections.","source":"green-book-ch6","quote":"Where household contacts of immunosuppressed individuals receive rotavirus vaccine, careful hand washing should be used to minimize the risk of transmission of vaccine virus."},{"action":"For contacts of very severely immunocompromised patients, such as transplant recipients in isolation, use inactivated flu vaccine instead of the nasal spray","why":"Nasal vaccine virus can be shed for up to two weeks.","source":"green-book-ch6","quote":"Household members and others who cannot avoid contact with very severely immunocompromised patients (e.g. bone marrow transplant patients and others who require isolation) should not be offered live attenuated influenza vaccine but given appropriate alternative inactivated influenza vaccines."},{"action":"Do not keep a child having cancer treatment off school because classmates are being vaccinated","why":"Vaccinated classmates do not pass vaccine viruses on in a way that harms the child.","source":"green-book-ch6","quote":"Children with immunodeficiency who are attending school do not require exclusion when other children are being immunised."},{"action":"For a child having chemotherapy, give the yearly inactivated flu vaccine and hold live vaccines until at least 6 months after chemotherapy ends","why":"Most routine childhood vaccines give a weaker, shorter response during chemotherapy and are better given or repeated afterwards.","source":"iap-2019","quote":"Live vaccines are contraindicated during and up to 6 months after end of chemotherapy."}],"bestInClass":{"statement":"For adults, ASCO 2024 is the most recent graded guideline: check vaccination status at diagnosis, vaccinate 2 to 4 weeks before treatment where possible, give non-live vaccines during or after any treatment, avoid live vaccines, and revaccinate after transplant, CAR-T and B-cell depletion on its timetable. The UK Green Book agrees on the principle but times inactivated vaccines at least two weeks before immunosuppression and sets explicit live-vaccine intervals: 6 months after immunosuppressive chemotherapy or radiotherapy, 12 months after biologics such as rituximab, 24 months after transplant, 3 months after high-dose steroids. For children, no graded international guideline was readable: the Green Book applies at every age, and the Indian Academy of Pediatrics consensus holds live vaccines until 6 months after chemotherapy, gives only inactivated influenza vaccine to all children during treatment, and prefers to give other non-live vaccines from 6 months after the end of treatment for durable immunity. Everyone agrees that household contacts should be fully vaccinated; the Green Book and ASCO both allow MMR, varicella and nasal influenza vaccine in contacts, except contacts of transplant recipients or patients in isolation.","sources":["asco-2024","green-book-ch6","green-book-ch7","iap-2019"]},"variants":[{"name":"UK Green Book intervals and timing","differs":"Inactivated vaccines at least two weeks before immunosuppressive treatment (ASCO: 2 to 4 weeks); live vaccines barred for fixed periods after each kind of treatment, with steroid doses that count as immunosuppressive given in milligrams and by weight for children under 20 kg.","evidence":"Ungraded national guidance from Public Health England, now the UK Health Security Agency.","sources":["green-book-ch6","green-book-ch7"]},{"name":"Non-live vaccines deferred until after chemotherapy in children (Indian Academy of Pediatrics)","differs":"Gives only annual inactivated influenza vaccine to all children during chemotherapy, hepatitis B only to unimmunised children at risk from transfusion, and other non-live vaccines from 6 months after the end of treatment; a catch-up or re-immunisation schedule depends on what the child had before; siblings continue their vaccines but switch oral polio to the injected vaccine.","evidence":"A national consensus guideline; read here as an abstract only.","sources":["iap-2019"]},{"name":"Rotavirus vaccine with immunodeficiency other than SCID (Green Book)","differs":"Although rotavirus vaccine is live, the Green Book notes that outside severe combined immunodeficiency the benefit may exceed the risk.","evidence":"Stated in a footnote to the live-vaccine list; ungraded.","sources":["green-book-ch6"]}],"grades":[{"claim":"Determine vaccination status and update seasonal, age- and risk-based vaccines at diagnosis","grade":"Evidence quality: moderate; strength of recommendation: strong","source":"asco-2024"},{"claim":"Vaccinate 2 to 4 weeks before treatment; non-live vaccines allowed during or after treatment","grade":"Evidence quality: moderate; strength of recommendation: strong","source":"asco-2024"},{"claim":"Full revaccination from 6 to 12 months after stem cell transplant","grade":"Evidence quality: moderate; strength of recommendation: strong","source":"asco-2024"},{"claim":"Timing after CD19 or BCMA CAR-T","grade":"Evidence quality: very low; strength of recommendation: weak","source":"asco-2024"},{"claim":"After B-cell depleting therapy, revaccinate for COVID-19 only, no sooner than 6 months after treatment","grade":"Evidence quality: moderate; strength of recommendation: strong","source":"asco-2024","quote":"Adults who receive B-cell–depleting therapy should be revaccinated for COVID-19 only, no sooner than 6 months after completion of treatment"},{"claim":"Household members and close contacts up to date on vaccinations","grade":"Evidence quality: moderate; strength of recommendation: strong","source":"asco-2024"}],"sources":[{"key":"asco-2024","label":"Vaccination of Adults With Cancer: ASCO Guideline","publisher":"ASCO, Journal of Clinical Oncology","year":2024,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11095883/","doi":"10.1200/JCO.24.00032","gradingScheme":"Evidence quality (high, moderate, low, very low) and strength of recommendation (strong, weak), printed beside each recommendation in Table 1.","read":"full-text","accessed":"2026-11-11"},{"key":"green-book-ch6","label":"Contraindications and special considerations: the Green Book, chapter 6 (August 2017)","publisher":"Public Health England (now UK Health Security Agency)","year":2017,"url":"https://www.gov.uk/government/publications/contraindications-and-special-considerations-the-green-book-chapter-6","gradingScheme":"Not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"green-book-ch7","label":"Immunisation of individuals with underlying medical conditions: the Green Book, chapter 7 (January 2020)","publisher":"Public Health England (now UK Health Security Agency)","year":2020,"url":"https://www.gov.uk/government/publications/immunisation-of-individuals-with-underlying-medical-conditions-the-green-book-chapter-7","gradingScheme":"Not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"iap-2019","label":"Immunization of Children with Cancer in India Treated with Chemotherapy: Consensus Guideline from the Pediatric Hematology-Oncology Chapter and the Advisory Committee on Vaccination and Immunization Practices of the Indian Academy of Pediatrics","publisher":"Indian Academy of Pediatrics, Indian Pediatrics","year":2019,"url":"https://europepmc.org/abstract/MED/31884436","doi":"10.1007/s13312-019-1678-0","read":"abstract","accessed":"2026-11-11"},{"key":"ecil7-2019","label":"Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7)","publisher":"ECIL, Lancet Infectious Diseases","year":2019,"url":"https://europepmc.org/abstract/MED/30744964","doi":"10.1016/S1473-3099(18)30601-7","read":"abstract","accessed":"2026-11-11"},{"key":"sfce-2025","label":"Vaccination of children and adolescents treated for acute leukemia, excluding HSCT recipients: recommendations of the French Society for Childhood and Adolescent Cancer and Leukemia (SFCE)","publisher":"SFCE, Bulletin du Cancer","year":2025,"url":"https://europepmc.org/abstract/MED/39706725","doi":"10.1016/j.bulcan.2024.10.013","read":"abstract","accessed":"2026-11-11"},{"key":"idsa-2013","label":"2013 IDSA clinical practice guideline for vaccination of the immunocompromised host","publisher":"IDSA, Clinical Infectious Diseases","year":2014,"url":"https://doi.org/10.1093/cid/cit684","doi":"10.1093/cid/cit684","read":"not-reachable","accessed":"2026-11-11"}],"upgrades":[],"gaps":["No current graded guideline on vaccinating children during and after chemotherapy could be read in full. The ECIL 7 (2019) and SFCE (2025) recommendations for children with leukaemia were read only as abstracts that state no recommendation, and the IDSA 2013 guideline, which covers children, returned a bot challenge to a script.","The Green Book chapter 6 on gov.uk is dated August 2017 and its list of live vaccines still names Zostavax; later changes to the UK shingles programme are not reflected in that chapter and were not checked in chapter 28a.","ASCO notes that the best timing of inactivated influenza vaccine within chemotherapy cycles is not settled; trials gave varied results.","Evidence on vaccine timing after CAR-T is very limited (ASCO grades it very low).","The detailed revaccination schedule after transplant is on the revaccination page, not repeated here."]}]