{"slug":"precision","tag":"precision","variants":["precision"],"description":"Records where care is limited by how precise it is: how precise a test, a beam, a margin or a dose is today, what limits it, and what more precision would buy a patient.","count":101,"kinds":{"technology":40,"term":22,"biomarker":3,"idea":9,"drug":3,"roadmap":2,"paper":21,"trial":1},"related":[{"slug":"radiation","tag":"radiation","shared":13},{"slug":"protocol-upgrade","tag":"protocol-upgrade","shared":9},{"slug":"radiation-wave1","tag":"radiation-wave1","shared":9},{"slug":"upgrade-promising","tag":"upgrade:promising","shared":5},{"slug":"breast","tag":"breast","shared":4},{"slug":"upgrade-proven-unevenly-used","tag":"upgrade:proven-unevenly-used","shared":4},{"slug":"biomarker","tag":"biomarker","shared":3},{"slug":"machines-wave2","tag":"machines-wave2","shared":3},{"slug":"ctdna","tag":"ctdna","shared":2},{"slug":"diagnostic","tag":"diagnostic","shared":2},{"slug":"frontier","tag":"frontier","shared":2},{"slug":"genome-wide","tag":"genome-wide","shared":2}],"records":[{"id":"low-dose-ct-screening","kind":"technology","name":"Low-dose CT lung screening","route":"/technologies/low-dose-ct-screening/","status":"standard-of-care","tldr":"A yearly low-radiation CT scan for current and former heavy smokers that finds lung cancer early enough to cure it."},{"id":"r0-r1-margin-pancreatic","kind":"term","name":"R0 and R1 margins in pancreatic cancer: the 1 mm rule and standardised specimen reporting","route":"/terms/r0-r1-margin-pancreatic/","tldr":"After a pancreatic cancer is removed, the pathologist checks whether cancer reaches the cut edges of the specimen. In the UK, cancer within one millimetre of an edge counts as an incomplete (R1) resection even if it does not touch it. Reported this way most operations are R1, because the tumour creeps along nerves behind the gland; cancer touching the edge carries a worse outlook."},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/","status":"standard-of-care","tldr":"Sequencing the unique genetic barcode of a patient's leukaemia to find one cancer cell in a million."},{"id":"pd-l1-assay-discordance","kind":"term","name":"PD-L1 assay discordance (SP142, SP263 and 22C3 in breast cancer)","route":"/terms/pd-l1-assay-discordance/","tldr":"Three commercial PD-L1 stains give different answers on the same breast tumour: the SP142 assay used with atezolizumab called fewer than half of tumours positive while the 22C3 and SP263 assays called about three quarters. Because the pembrolizumab licence rests on 22C3 combined positive score 10, which test a laboratory runs, and how it scores it, decides who is offered immunotherapy."},{"id":"lung-rads","kind":"term","name":"Lung-RADS and nodule reporting","route":"/terms/lung-rads/","tldr":"The scoring systems that turn a screening CT into an action. Each nodule gets a category from the scan, and the category dictates the next step: rescan in a year, rescan in three months, or go to a lung cancer clinic. They exist so that the same scan gets the same answer in every centre."},{"id":"ctdna-tumour-fraction","kind":"biomarker","name":"Circulating tumour DNA fraction (and what a negative plasma result means)","route":"/biomarkers/ctdna-tumour-fraction/","tldr":"How much of the DNA floating in a blood sample came from the cancer. Above a few per cent, a plasma test finds what a biopsy would find; below it, a negative result means the test could not see, not that there is nothing there."},{"id":"targeted-axillary-dissection","kind":"term","name":"Targeted axillary dissection","route":"/terms/targeted-axillary-dissection/","tldr":"When chemotherapy is given before surgery, the surgeon marks the lymph node that was known to contain cancer with a clip before treatment starts, then removes that exact node afterwards along with the sentinel nodes. It is the difference between missing leftover cancer one time in ten and one time in fifty."},{"id":"breast-margins-and-re-excision","kind":"term","name":"Margins after breast-conserving surgery, and second operations","route":"/terms/breast-margins-and-re-excision/","tldr":"After conserving surgery a pathologist measures how close the cancer came to the edge of the tissue removed. Cancer at the inked edge means another operation is offered; within 1 mm it is considered; and the threshold was lowered in 2024 specifically to spare people a second operation."},{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/","status":"standard-of-care","tldr":"A prostate-cancer-specific PET scan that finds spread far earlier than CT or bone scan, and tells you whether a matched radioactive drug will work."},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/","status":"standard-of-care","tldr":"Sequencing hundreds of cancer genes at once from a biopsy to find the mutations a drug can target."},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/","status":"standard-of-care","tldr":"A blood test that reads fragments of DNA shed by the tumour, so you can genotype or monitor cancer without a needle in the tumour."},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/","status":"established","tldr":"An ultra-sensitive blood test after surgery that detects leftover cancer months before a scan would."},{"id":"mced","kind":"technology","name":"Multi-cancer early detection (MCED)","route":"/technologies/mced/","status":"phase-3","tldr":"A single blood test intended to screen for dozens of cancers at once, including ones with no screening today."},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/","status":"standard-of-care","tldr":"Surgeons operate through small incisions using robotic arms with tremor-free precision and 3D vision."},{"id":"fluorescence-guided-surgery","kind":"technology","name":"Fluorescence-guided surgery","route":"/technologies/fluorescence-guided-surgery/","status":"established","tldr":"Injecting a dye that makes tumour glow so the surgeon can see exactly where to cut."},{"id":"sentinel-node","kind":"technology","name":"Sentinel lymph node biopsy","route":"/technologies/sentinel-node/","status":"standard-of-care","tldr":"Removing just the first lymph node a tumour drains to, instead of all of them, to check for spread."},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/","status":"standard-of-care","tldr":"IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue."},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/","status":"standard-of-care","tldr":"Stereotactic body radiotherapy converges multiple beams with sub-millimetre accuracy to deliver tumour-destroying doses in one to five outpatient sessions, doing the job of surgery for inoperable early lung cancer and for metastases in liver, spine and brain. Tumour size and location limit its use, and late toxicity is a concern near the central airways."},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/","status":"established","tldr":"Radiation using protons, which stop inside the tumour instead of passing through, so tissue behind it gets no dose."},{"id":"mr-linac","kind":"technology","name":"MR-guided adaptive radiotherapy","route":"/technologies/mr-linac/","status":"established","tldr":"An MR-linac is a radiation machine with an MRI scanner built in, so images taken during setup let the plan be re-optimised in minutes to that day's anatomy. It allows tighter margins and higher doses in pancreatic and prostate cancer, but treatment is slow and costly, and whether daily adaptation improves cure rates rather than only toxicity is unproven."},{"id":"flash-rt","kind":"technology","name":"FLASH radiotherapy","route":"/technologies/flash-rt/","status":"phase-1","tldr":"Delivering an entire dose in under a second, which in animals spares healthy tissue while still killing the tumour."},{"id":"ai-pathology-scoring","kind":"technology","name":"AI scoring of biomarkers and grade on pathology slides","route":"/technologies/ai-pathology-scoring/","status":"approved","tldr":"Software that reads digitised biopsy slides to detect cancer, grade it, and score biomarkers such as HER2, PD-L1 and Ki-67 more consistently than the eye alone."},{"id":"oncology-pharmacogenomics","kind":"technology","name":"Pharmacogenomic testing before chemotherapy","route":"/technologies/oncology-pharmacogenomics/","status":"established","tldr":"Testing a patient's inherited genes before certain chemotherapies to spot people who cannot break the drug down and would suffer severe, sometimes fatal, side effects."},{"id":"her2-low","kind":"term","name":"HER2-low and HER2-ultralow","route":"/terms/her2-low/","tldr":"Tumours with a little HER2 (IHC 1+ or 2+ without amplification), or a trace (ultralow), which older HER2 drugs ignored but Enhertu can attack."},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/","tldr":"Circulating tumour DNA (ctDNA) consists of fragments of DNA shed by tumour cells into the blood, detectable with sensitive sequencing."},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/","tldr":"Cancer still present after treatment but too small to see on scans, detected by blood or marrow tests."},{"id":"fragmentomics","kind":"technology","name":"cfDNA fragmentomics","route":"/technologies/fragmentomics/","status":"established","tldr":"Fragmentomics reads the sizes and positions of DNA fragments in blood, not the mutations. Cancer cells die messily and leave a recognisable fragmentation pattern."},{"id":"idea-tr1-pre-emptive-pharmacogenomic-testing","kind":"idea","name":"Test DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhere","route":"/ideas/idea-tr1-pre-emptive-pharmacogenomic-testing/","tldr":"A cheap gene test for DPYD, UGT1A1 and TPMT or NUDT15 before fluoropyrimidines, irinotecan or thiopurines identifies people at risk of severe or fatal toxicity so their dose can be lowered. The EMA has recommended DPD testing since 2020; US uptake remains partial."},{"id":"idea-acc-reflex-genomic-profiling-at-diagnosis","kind":"idea","name":"Pathologists order genomic profiling automatically at diagnosis of advanced cancer","route":"/ideas/idea-acc-reflex-genomic-profiling-at-diagnosis/","tldr":"A substantial share of patients with advanced non-small-cell lung cancer start first-line treatment before their biomarker results arrive, or without full testing, and so miss targeted therapy. Letting the pathologist order the full genomic panel the moment a cancer of a defined type and stage is confirmed shortens time to result and makes testing complete."},{"id":"idea-acc-geriatric-assessment-by-default","kind":"idea","name":"Geriatric assessment by default for every patient over 70 starting cancer treatment","route":"/ideas/idea-acc-geriatric-assessment-by-default/","tldr":"A short structured check of memory, mobility, nutrition and medicines before treatment cuts serious side effects in older patients without reducing benefit. It should be automatic, not optional."},{"id":"auto-contouring-ai","kind":"technology","name":"AI auto-contouring and adaptive planning","route":"/technologies/auto-contouring-ai/","status":"established","tldr":"Software that draws organs and tumours on scans automatically, saving hours per patient and making daily plan adaptation practical."},{"id":"project-optimus","kind":"term","name":"Project Optimus","route":"/terms/project-optimus/","tldr":"An FDA programme pushing companies to find the best dose of a cancer drug, not just the highest tolerable one."},{"id":"pegulicianine","kind":"drug","name":"Pegulicianine","route":"/drugs/pegulicianine/","status":"approved","tldr":"A cavity-imaging dye used during breast lumpectomy to spot leftover tumour before the operation ends; in its main trial it spared a second operation for 9 of 62 patients whose margins were positive."},{"id":"aminolevulinic-acid-gleolan","kind":"drug","name":"5-Aminolevulinic acid (oral, for glioma surgery)","route":"/drugs/aminolevulinic-acid-gleolan/","status":"approved","tldr":"A drink taken before brain surgery that makes high-grade glioma glow under blue light, letting surgeons remove more tumour safely."},{"id":"genomic-profiling","kind":"term","name":"Genomic profiling","route":"/terms/genomic-profiling/","tldr":"Reading the DNA (and sometimes RNA) of a tumour, usually with a panel of a few hundred genes, to list its mutations, fusions and amplifications and match them to approved drugs or trials. Guidelines now require it before first-line treatment in lung, colorectal, breast and prostate cancer, though in several cancer types most tumours still show no actionable finding."},{"id":"sentinel-lymph-node-biopsy","kind":"term","name":"Sentinel node biopsy","route":"/terms/sentinel-lymph-node-biopsy/","tldr":"Finding and removing the first one or two lymph nodes a tumour drains to, to see whether cancer has spread, instead of removing the whole nodal basin."},{"id":"stereotactic-radiosurgery","kind":"term","name":"Stereotactic radiosurgery (SRS)","route":"/terms/stereotactic-radiosurgery/","tldr":"A single high dose of radiation delivered to a brain tumour or metastasis by beams converging from all sides, so the target gets a destructive dose while the surrounding brain gets little; no scalpel is involved despite the name. It treats metastases up to about 3-4 cm and has replaced whole-brain radiotherapy for limited disease because it spares cognition."},{"id":"sbrt-term","kind":"term","name":"Stereotactic body radiotherapy (SBRT / SABR)","route":"/terms/sbrt-term/","tldr":"A course of one to five large, pinpoint-accurate radiation doses that destroy a tumour outside the brain almost like surgery, for patients who cannot or prefer not to have an operation. It is standard for inoperable early lung cancer and the backbone of oligometastatic treatment; toxicity is mostly to whatever lies within a centimetre of the target."},{"id":"imrt-term","kind":"term","name":"IMRT / IGRT / VMAT (modern external beam radiotherapy)","route":"/terms/imrt-term/","tldr":"Radiation beams shaped and varied in intensity from multiple angles, or while the machine rotates around the patient (VMAT), so the dose hugs the tumour and misses healthy tissue, checked against imaging before each session so it lands where planned. It cut dry mouth in head and neck cancer and rectal toxicity in prostate cancer."},{"id":"resection-margins","kind":"term","name":"Resection margins (R0 / R1 / R2)","route":"/terms/resection-margins/","tldr":"Whether the edge of the removed tissue is free of cancer. R0 means clear under the microscope, R1 means microscopic cancer at the edge, R2 means visible tumour left behind. R0 is what 'complete resection' means."},{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/","tldr":"Short pieces of DNA floating in the blood, shed by dying cells all over the body. Most is from normal cells; the small tumour-derived fraction (ctDNA) is what liquid biopsies fish out."},{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/","tldr":"Blood carries fragments of tumour DNA. This roadmap follows the tests that read them, from the first sighting in 1948 to blood tests that now choose a drug, spare chemotherapy, or screen for many cancers at once, and it lists the readouts to watch next."},{"id":"tumour-informed-assay","kind":"term","name":"Tumour-informed versus tumour-naive ctDNA assays","route":"/terms/tumour-informed-assay/","tldr":"A tumour-informed blood test is built for one patient: the tumour is sequenced first and the test then hunts for that patient's own mutations in blood. A tumour-naive test uses the same fixed panel, often of methylation marks, for everyone, so it needs no tumour sample and returns faster."},{"id":"paper-shiva-off-label-targeted-therapy-lancet-oncol-2015","kind":"paper","name":"SHIVA: molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer","route":"/key-papers/paper-shiva-off-label-targeted-therapy-lancet-oncol-2015/","tldr":"The one randomised test of giving people a targeted drug matched to their tumour's mutation but outside its licence found they did no better than with their doctor's choice of treatment."},{"id":"paper-marquart-genome-driven-oncology-benefit-jama-oncol-2018","kind":"paper","name":"Estimation of the percentage of US patients with cancer who benefit from genome-driven oncology","route":"/key-papers/paper-marquart-genome-driven-oncology-benefit-jama-oncol-2018/","tldr":"Counting every drug approved for a gene change up to January 2018, about 8 in 100 Americans with advanced cancer were eligible for one and about 5 in 100 were estimated to benefit."},{"id":"paper-mcgrail-tmb-pan-cancer-response-ann-oncol-2021","kind":"paper","name":"High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types","route":"/key-papers/paper-mcgrail-tmb-pan-cancer-response-ann-oncol-2021/","tldr":"Pooling more than 10,000 tumours, a high mutation count predicted response to immunotherapy in melanoma, lung and bladder cancers but not in breast, prostate or brain tumours."},{"id":"paper-marabelle-keynote-158-tmb-lancet-oncol-2020","kind":"paper","name":"Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of KEYNOTE-158","route":"/key-papers/paper-marabelle-keynote-158-tmb-lancet-oncol-2020/","tldr":"In ten hard-to-treat cancer types, 29 in 100 people whose tumours carried at least 10 mutations per million DNA letters responded to pembrolizumab, against 6 in 100 below that line."},{"id":"paper-cohen-msi-dmmr-misdiagnosis-colorectal-jama-oncol-2019","kind":"paper","name":"Association of primary resistance to immune checkpoint inhibitors in metastatic colorectal cancer with misdiagnosis of microsatellite instability or mismatch repair deficiency status","route":"/key-papers/paper-cohen-msi-dmmr-misdiagnosis-colorectal-jama-oncol-2019/","tldr":"When colorectal cancers labelled mismatch-repair deficient did not respond to immunotherapy, three of five turned out on retesting not to be deficient at all; local results were wrong about one time in ten."},{"id":"paper-razavi-cfdna-variant-sources-clonal-haematopoiesis-nat-med-2019","kind":"paper","name":"High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants","route":"/key-papers/paper-razavi-cfdna-variant-sources-clonal-haematopoiesis-nat-med-2019/","tldr":"Sequencing blood plasma and white blood cells side by side showed that most mutations found in plasma came from ageing blood-forming cells, not from the cancer."},{"id":"paper-bettegowda-ctdna-early-late-stage-stm-2014","kind":"paper","name":"Detection of circulating tumor DNA in early- and late-stage human malignancies","route":"/key-papers/paper-bettegowda-ctdna-early-late-stage-stm-2014/","tldr":"Tumour DNA could be found in the blood of more than three quarters of people with many advanced cancers, but in fewer than half with brain, kidney, prostate or thyroid cancers, and less often when the cancer was localised."},{"id":"paper-abbosh-tracerx-ctdna-relapse-nature-2023","kind":"paper","name":"Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA","route":"/key-papers/paper-abbosh-tracerx-ctdna-relapse-nature-2023/","tldr":"Tracking about 200 of each patient's own tumour mutations in blood after lung cancer surgery found tumour DNA in half of those who later relapsed from one sample, and in more with repeated testing."},{"id":"paper-zviran-whole-genome-cfdna-residual-disease-nat-med-2020","kind":"paper","name":"Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring","route":"/key-papers/paper-zviran-whole-genome-cfdna-residual-disease-nat-med-2020/","tldr":"Reading the whole genome of DNA in the blood, rather than a few genes very deeply, let researchers detect tumour DNA at one part in 100,000 by adding up thousands of mutations."},{"id":"paper-esmo-ctdna-assay-recommendations-ann-oncol-2022","kind":"paper","name":"ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group","route":"/key-papers/paper-esmo-ctdna-assay-recommendations-ann-oncol-2022/","tldr":"Europe's oncology society advised that blood tests for tumour DNA can guide targeted treatment in advanced cancer, that tissue is still preferred for many patients, and that residual disease tests after surgery were not yet ready for routine use."},{"id":"proton-range-uncertainty","kind":"term","name":"Proton range uncertainty and the range margin","route":"/terms/proton-range-uncertainty/","tldr":"A proton beam stops at a depth that cannot be predicted exactly, so planners deliberately aim it a few millimetres past the tumour. At one leading centre the allowance is 3.5 per cent of the beam's range plus 1 millimetre, which for a beam reaching 20 centimetres into soft tissue means overshooting by about 8 millimetres."},{"id":"target-delineation-variability","kind":"term","name":"Variation between clinicians in drawing the radiotherapy target","route":"/terms/target-delineation-variability/","tldr":"Before a radiotherapy plan can be made, a doctor draws the tumour and the organs around it on the planning scan, and two doctors given the same scan do not draw the same outline. A 2016 review found 119 studies measuring this across every major cancer site, and only one in five checked what the differences did to the dose."},{"id":"paper-van-herk-ptv-margin-recipe-ijrobp-2000","kind":"paper","name":"The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy","route":"/key-papers/paper-van-herk-ptv-margin-recipe-ijrobp-2000/","tldr":"The paper behind the margin most radiotherapy departments add around a target. It showed that errors repeated every day matter far more than errors that vary day to day, and turned that into a formula: a margin of 2.5 times the systematic error plus 0.7 times the random error."},{"id":"paper-vinod-delineation-uncertainty-review-radiother-oncol-2016","kind":"paper","name":"Uncertainties in volume delineation in radiation oncology: a systematic review and recommendations for future studies","route":"/key-papers/paper-vinod-delineation-uncertainty-review-radiother-oncol-2016/","tldr":"A review of 119 studies in which several clinicians drew the same radiotherapy targets. The studies measured the disagreement in so many different ways that they could not be combined, and only 21 per cent checked what it did to the dose."},{"id":"paper-kirkpatrick-srs-margin-trial-ijrobp-2015","kind":"paper","name":"Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial","route":"/key-papers/paper-kirkpatrick-srs-margin-trial-ijrobp-2015/","tldr":"Brain metastases treated with radiosurgery were randomly given a 1 millimetre or a 3 millimetre margin. Control of the treated tumours was similar, the larger margin irradiated more healthy brain, and five of the six biopsy-proven cases of radiation damage were in the 3 millimetre group."},{"id":"paper-de-crevoisier-daily-weekly-igrt-ijrobp-2018","kind":"paper","name":"Daily versus weekly prostate cancer image guided radiation therapy: phase 3 multicenter randomized trial","route":"/key-papers/paper-de-crevoisier-daily-weekly-igrt-ijrobp-2018/","tldr":"A French trial of 470 men compared checking the prostate's position with imaging before every radiotherapy session against checking weekly. Daily imaging lowered rectal side effects and PSA-defined progression, but the main endpoint, recurrence-free survival, did not differ, and overall survival was worse in the daily group."},{"id":"paper-flame-focal-boost-prostate-jco-2021","kind":"paper","name":"Focal boost to the intraprostatic tumor in external beam radiotherapy for patients with localized prostate cancer: results from the FLAME randomized phase III trial","route":"/key-papers/paper-flame-focal-boost-prostate-jco-2021/","tldr":"A trial of 571 men with intermediate or high-risk prostate cancer gave half of them an extra dose, up to 95 Gy, to the tumour visible on MRI inside the prostate. After five years 92 per cent of the boosted group were free of PSA relapse against 85 per cent, with no measurable increase in side effects and no difference in survival."},{"id":"paper-liao-proton-vs-imrt-nsclc-jco-2018","kind":"paper","name":"Bayesian adaptive randomization trial of passive scattering proton therapy and intensity-modulated photon radiotherapy for locally advanced non-small-cell lung cancer","route":"/key-papers/paper-liao-proton-vs-imrt-nsclc-jco-2018/","tldr":"The first randomised comparison of protons with modern photon radiotherapy for lung cancer. Protons spared the heart but not the lung overall, and neither severe lung inflammation nor local failure was reduced: 10.5 per cent against 6.5 per cent for lung inflammation, 10.5 against 10.9 per cent for local failure."},{"id":"paper-paganetti-range-uncertainties-pmb-2012","kind":"paper","name":"Range uncertainties in proton therapy and the role of Monte Carlo simulations","route":"/key-papers/paper-paganetti-range-uncertainties-pmb-2012/","tldr":"A review of why the depth at which a proton beam stops cannot be predicted exactly, and how much margin centres add for it. One common recipe, 3.5 per cent of the range plus 1 millimetre, overshoots by about 8 millimetres for a beam reaching 20 centimetres into soft tissue."},{"id":"paper-heartspare-stage-ii-clin-oncol-2017","kind":"paper","name":"The UK HeartSpare Study (Stage II): multicentre evaluation of a voluntary breath-hold technique in patients receiving breast radiotherapy","route":"/key-papers/paper-heartspare-stage-ii-clin-oncol-2017/","tldr":"In ten UK centres, women having radiotherapy for left breast cancer were taught to hold a deep breath during treatment without any machine to help. Ninety-five per cent had a lower heart dose as a result, and the average heart dose fell from 1.8 to 1.1 Gy."},{"id":"paper-smyth-dibh-cardiac-sparing-review-jmrs-2015","kind":"paper","name":"The cardiac dose-sparing benefits of deep inspiration breath-hold in left breast irradiation: a systematic review","route":"/key-papers/paper-smyth-dibh-cardiac-sparing-review-jmrs-2015/","tldr":"A review of ten studies comparing radiotherapy plans for left breast cancer made in deep breath-hold and in free breathing. Breath-hold cut the average heart dose by up to 3.4 Gy, which on published dose-risk estimates corresponds to a 13.6 per cent smaller projected rise in heart disease risk."},{"id":"paper-favaudon-flash-mice-sci-transl-med-2014","kind":"paper","name":"Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice","route":"/key-papers/paper-favaudon-flash-mice-sci-transl-med-2014/","tldr":"The mouse study that started modern FLASH research. Radiation given in a fraction of a second spared the lungs of mice from scarring at doses that scarred them when given at the usual rate, while controlling tumours just as well. It was in mice, and the effect in people has not been shown."},{"id":"paper-open-trial-open-face-masks-sgrt-radiother-oncol-2026","kind":"paper","name":"OPEN: optimising patient experience in head and neck radiotherapy, a phase 3 randomised control trial comparing open versus closed face masks","route":"/key-papers/paper-open-trial-open-face-masks-sgrt-radiother-oncol-2026/","tldr":"People having radiotherapy for head and neck cancer were randomly given the standard closed face mask or one of two open masks, with cameras tracking the face during treatment. The open masks were set up as accurately and were significantly better tolerated."},{"id":"intraoperative-margin-assessment-breast","kind":"technology","name":"Intraoperative margin assessment in breast-conserving surgery","route":"/technologies/intraoperative-margin-assessment-breast/","status":"established","tldr":"Ways of checking, before the operation ends, whether cancer reaches the edge of the breast tissue removed, so the surgeon can take more there and then instead of operating again days later. In randomised trials a radiofrequency probe cut second operations from 25.8 to 19.8 per cent, and routinely shaving an extra layer from the cavity cut them from 21 to 10 per cent."},{"id":"fluorouracil-pharmacokinetic-dosing","kind":"technology","name":"Fluorouracil dosing by measured blood level","route":"/technologies/fluorouracil-pharmacokinetic-dosing/","status":"emerging","tldr":"Fluorouracil is dosed by body size, yet the amount of drug in the blood varies widely between people given the same dose. Measuring the level during the infusion and adjusting the next dose raised the response rate from 18 to 34 per cent in one randomised trial and is recommended by an international pharmacology society, but it is not routine care and no survival gain has been established."},{"id":"carboplatin-calvert-dosing","kind":"technology","name":"Carboplatin dosing by kidney function: the Calvert formula and how kidney function is measured","route":"/technologies/carboplatin-calvert-dosing/","status":"standard-of-care","tldr":"Carboplatin is dosed by kidney function rather than body size, using a formula from 1989 that aims at a set drug exposure. The formula is only as good as the kidney measurement fed into it: in a study of 2,471 people with cancer, the usual blood-test estimates missed the intended dose by more than a fifth in about one person in five to one in four."},{"id":"oral-targeted-therapy-drug-monitoring","kind":"technology","name":"Blood-level monitoring of oral targeted cancer drugs","route":"/technologies/oral-targeted-therapy-drug-monitoring/","status":"emerging","tldr":"Cancer tablets such as kinase inhibitors are given at one dose for everyone, though the amount in the blood differs widely between people. A Dutch study of 600 patients measured trough levels and adjusted when they were low, cutting the share of people with too little drug by 39 per cent, but no trial has yet shown that this improves survival."},{"id":"chemotherapy-dosing-in-obesity","kind":"technology","name":"Full weight-based chemotherapy dosing for people with obesity","route":"/technologies/chemotherapy-dosing-in-obesity/","status":"standard-of-care","tldr":"Chemotherapy doses used to be capped for larger people for fear of overdose. The American Society of Clinical Oncology guideline found that up to 40 per cent of people with obesity were given reduced doses, that the feared extra toxicity is unfounded, and recommends full doses based on actual body weight."},{"id":"precision-roadmap","kind":"roadmap","name":"Precision roadmap: margins measured in millimetres → tests that find a target → doses fitted to the person → precision that changes outcomes","route":"/roadmaps/precision-roadmap/","tldr":"Cancer care is limited by how precise it is: how small a tumour a test can find, how close to it a surgeon can cut, how tightly a beam can be aimed and how well a dose fits the person. This roadmap follows each of those from where it stands now to the next step, and says plainly where more precision has been shown to help a patient and where it has not."},{"id":"idea-pu-breath-hold-left-breast-routine","kind":"idea","name":"Deep-breath-hold radiotherapy for every suitable person with left-sided breast cancer","route":"/ideas/idea-pu-breath-hold-left-breast-routine/","tldr":"Taking and holding a deep breath during each beam moves the heart away from the treated breast and roughly halves the dose it receives. England's national guideline has recommended it for left-sided breast cancer since 2018, yet surveys in Germany, Austria, Switzerland, Australia and the United States found it applied to a fraction of the people who could have it."},{"id":"idea-pu-breath-hold-visual-feedback","kind":"idea","name":"Let the patient see their own breath-hold on a screen or in video glasses","route":"/ideas/idea-pu-breath-hold-visual-feedback/","tldr":"During breath-hold radiotherapy a camera or sensor measures how deep the breath is, but often only the radiographers see the trace. Showing it to the patient, on a screen or in video glasses with a target band to stay inside, made holds steadier and more repeatable in the clinical comparisons OnCo found, though none has yet measured whether it changes side effects."},{"id":"idea-pu-breath-hold-coaching-before-planning","kind":"idea","name":"Breath-hold coaching and home practice a week before the planning scan, in the patient's own language","route":"/ideas/idea-pu-breath-hold-coaching-before-planning/","tldr":"Breath-hold is usually taught on the day of the planning scan. Two hospital series found that teaching it at least five days earlier, with practice at home, went with lower heart doses and shorter set-up times, and a survey of American radiation oncologists found interpreters were present at fewer than one in three first treatments for people who do not speak English."},{"id":"idea-pu-pelvic-filling-protocol","kind":"idea","name":"A measured drink of water before pelvic radiotherapy, and bowel preparation kept to what trials support","route":"/ideas/idea-pu-pelvic-filling-protocol/","tldr":"The bladder and rectum change size from day to day and move the prostate with them. A randomised trial found that drinking about half a litre of water before each treatment kept the bladder more consistent than drinking a litre, and small trials of anti-wind medicines before prostate radiotherapy found no effect."},{"id":"idea-pu-tattoo-free-set-up","kind":"idea","name":"Radiotherapy set-up without permanent ink tattoos, using surface guidance or invisible ink","route":"/ideas/idea-pu-tattoo-free-set-up/","tldr":"Most people having breast radiotherapy are given small permanent ink dots to line them up on the couch. In a United Kingdom survey of 204 people afterwards, half rated the impact of those tattoos as negative, and surface cameras or ultraviolet ink line people up as accurately without leaving a visible mark."},{"id":"idea-upgrade-clot-risk-score-and-preventive-anticoagulation","kind":"idea","name":"A blood clot risk score at the start of chemotherapy, with preventive anticoagulation offered to those at higher risk","route":"/ideas/idea-upgrade-clot-risk-score-and-preventive-anticoagulation/","tldr":"People with cancer get blood clots more often than others. A score built from the cancer type and routine blood tests picks out those at higher risk, and in two placebo-controlled trials a low-dose blood-thinning tablet reduced clots but caused more bleeding. United States guidance says it may be offered; surveys in the Netherlands and China found most specialists do not use the score."},{"id":"paige-prostate","kind":"drug","name":"Paige Prostate Detect","route":"/drugs/paige-prostate/","status":"approved","tldr":"The first AI for reading biopsy slides authorised by the FDA, which points pathologists to prostate cancer they might otherwise miss."},{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/","status":"standard-of-care","tldr":"Tests that show whether a tumour has lost its DNA spell-checker; if so, immunotherapy works unusually well and an inherited syndrome may be present."},{"id":"tmb-testing","kind":"technology","name":"Tumour mutational burden testing","route":"/technologies/tmb-testing/","status":"established","tldr":"Counting how many mutations a tumour carries per stretch of DNA; heavily mutated tumours are more likely to respond to immunotherapy."},{"id":"tmb-high","kind":"biomarker","name":"TMB-high (tumour mutational burden >= 10 mutations per megabase)","route":"/biomarkers/tmb-high/","tldr":"TMB counts how many mutations a tumour carries per million DNA letters. Ten or more, measured by FoundationOne CDx, allows pembrolizumab for almost any solid tumour after other treatment has failed."},{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/","tldr":"A ctDNA MRD test looks for the tumour's own mutations in blood after surgery. Detection predicts relapse months before scans, and in 2026 the FDA approved Signatera as the companion test selecting bladder cancer patients for adjuvant atezolizumab."},{"id":"ct-body-composition-sarcopenia","kind":"technology","name":"CT body composition and sarcopenia measurement","route":"/technologies/ct-body-composition-sarcopenia/","status":"emerging","tldr":"The staging CT scan every cancer patient already has can be measured for muscle and fat at the level of the third lumbar vertebra; low muscle predicts chemotherapy toxicity and shorter survival across cancers, and software now does the measuring automatically."},{"id":"dpyd-genotyping","kind":"technology","name":"DPYD genotyping and DPD phenotyping before fluoropyrimidines","route":"/technologies/dpyd-genotyping/","status":"standard-of-care","tldr":"A one-off blood test done before fluorouracil or capecitabine that finds the roughly one in twenty-five people who break the drug down too slowly. Lowering their starting dose reduces severe and occasionally fatal toxicity, and in the one matched comparison published so far survival was not shortened overall."},{"id":"ugt1a1-genotyping","kind":"technology","name":"UGT1A1 genotyping before irinotecan","route":"/technologies/ugt1a1-genotyping/","status":"established","tldr":"A gene test that finds people who clear irinotecan's active form slowly because of a common variant in the UGT1A1 enzyme, the same variant behind harmless Gilbert syndrome; they run a higher risk of severe diarrhoea and low white cells at full dose."},{"id":"tpmt-nudt15-genotyping","kind":"technology","name":"TPMT and NUDT15 genotyping before thiopurines","route":"/technologies/tpmt-nudt15-genotyping/","status":"standard-of-care","tldr":"Before children and adults with acute lymphoblastic leukaemia start two years of daily mercaptopurine, two genes are checked; carriers of low-activity variants need a fraction of the standard dose or their bone marrow shuts down within weeks."},{"id":"radiosurgery-srs","kind":"technology","name":"Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)","route":"/technologies/radiosurgery-srs/","status":"established","tldr":"A single very high dose, or a few doses, aimed at a small brain or spine target with millimetre precision, replacing whole-brain radiotherapy for most brain metastases."},{"id":"adaptive-radiotherapy","kind":"technology","name":"Adaptive radiotherapy (online replanning)","route":"/technologies/adaptive-radiotherapy/","status":"emerging","tldr":"Re-shaping the treatment plan to the anatomy of the day, using the images taken on the treatment couch, so the dose follows a shrinking tumour or a moving bladder."},{"id":"surface-guided-radiotherapy","kind":"technology","name":"Surface-guided radiotherapy (SGRT)","route":"/technologies/surface-guided-radiotherapy/","status":"established","tldr":"Cameras track the patient's skin surface in three dimensions during treatment, replacing tattoos and pausing the beam if the patient moves."},{"id":"respiratory-motion-management","kind":"technology","name":"Respiratory motion management (4D-CT, gating, breath-hold, tracking)","route":"/technologies/respiratory-motion-management/","status":"established","tldr":"Ways of dealing with tumours that move as the patient breathes: image the motion, treat only in part of the breathing cycle, hold the breath, or chase the tumour with the beam."},{"id":"intensity-modulated-proton-therapy","kind":"technology","name":"Pencil-beam scanning and intensity-modulated proton therapy","route":"/technologies/intensity-modulated-proton-therapy/","status":"established","tldr":"Modern proton machines paint the tumour spot by spot with a magnetically steered pencil beam, so the dose can be shaped in three dimensions and the proton's stop-point is put to full use."},{"id":"dose-painting","kind":"technology","name":"Dose painting and biologically guided radiotherapy","route":"/technologies/dose-painting/","status":"emerging","tldr":"Instead of one uniform dose, the plan gives more to the parts of the tumour that imaging says are most resistant, such as hypoxic or highly active regions on PET."},{"id":"planning-target-volume","kind":"term","name":"GTV, CTV and PTV (target volumes)","route":"/terms/planning-target-volume/","tldr":"The nested outlines a radiation plan is built on: the visible tumour (GTV), the tumour plus the tissue likely to hold microscopic spread (CTV), and a further margin for daily movement and setup error (PTV)."},{"id":"deep-inspiration-breath-hold","kind":"term","name":"Deep inspiration breath-hold (DIBH)","route":"/terms/deep-inspiration-breath-hold/","tldr":"Taking and holding a deep breath during each radiation beam. For left-sided breast cancer it pulls the heart away from the chest wall and cuts heart dose by about half."},{"id":"fiducial-markers","kind":"term","name":"Fiducial markers","route":"/terms/fiducial-markers/","tldr":"Tiny gold seeds or electromagnetic beacons placed in or near a tumour so the treatment machine can see exactly where it is each day."},{"id":"body-surface-area-dosing","kind":"technology","name":"Body-surface-area dosing","route":"/technologies/body-surface-area-dosing/","status":"established","tldr":"Chemotherapy doses are usually written per square metre of body surface, a convention from 1958 that scales drug clearance between species and people; it is imprecise, and for many newer drugs flat or weight-based doses have replaced it."},{"id":"nci-match","kind":"trial","name":"NCI-MATCH (EAY131)","route":"/trials/nci-match/","status":"active","tldr":"NCI-MATCH was the largest trial to sequence tumours from thousands of patients across the United States and give each a drug matched to the mutation rather than to the organ. It proved the system could work at national scale, found real activity for a handful of matches, and showed that most single drugs given for a single mutation do little."},{"id":"flash-research-accelerators","kind":"technology","name":"FLASH research accelerators (Oriatron, Mobetron FLASH, ProBeam FLASH)","route":"/technologies/flash-research-accelerators/","status":"phase-1","tldr":"Machines built or modified to deliver a whole radiation dose in a fraction of a second, so scientists can test whether ultra-fast dosing spares healthy tissue in people the way it does in animals."},{"id":"patient-positioning-surface-guidance-systems","kind":"technology","name":"Patient positioning and surface guidance systems (AlignRT, Catalyst, ExacTrac Dynamic)","route":"/technologies/patient-positioning-surface-guidance-systems/","status":"established","tldr":"Cameras that watch the patient's skin in three dimensions, robotic couches and moulded shells that hold the body still, so each radiotherapy dose lands where the plan says without tattoos and with the beam paused if the patient moves."},{"id":"respiratory-gating-tumour-tracking-systems","kind":"technology","name":"Respiratory gating and tumour tracking systems (RPM, ABC, Calypso, Synchrony)","route":"/technologies/respiratory-gating-tumour-tracking-systems/","status":"established","tldr":"Hardware that copes with tumours that move when the patient breathes: belts and cameras that switch the beam on only in part of the breathing cycle, devices that hold the breath, and implanted beacons or X-ray tracking that let the beam follow the tumour."}]}