{"id":"precision-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/","eras":[{"era":"2000","title":"Precision in radiotherapy gets a formula","description":"Every radiotherapy plan adds a margin of healthy tissue around the target, because the set-up varies from day to day and the tumour moves. Van Herk and colleagues turned that margin into arithmetic in 2000: to give at least 95 per cent of the dose to the target in 90 per cent of patients, the margin should be about 2.5 times the spread of systematic errors plus 0.7 times the spread of random ones, and because that recipe leaves out rotations and changes of shape the authors called it a lower limit for safe radiotherapy. From then on, a margin was a measured number that better imaging could shrink.","status":"historic","refs":[{"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":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/","tldr":"Radiotherapy cures more people than any drug and has reinvented itself every decade: from crude X-ray fields to beams shaped by computer, delivered in days instead of weeks, and now in fractions of a second. Its future is precision, fewer visits, and combination with drugs that make radiation work better."},{"id":"linear-quadratic-model","kind":"technology","name":"The linear-quadratic model and fractionation","route":"/technologies/linear-quadratic-model/","status":"established","tldr":"The equation radiotherapy uses to compare schedules: cell kill has a part proportional to dose and a part proportional to dose squared, and the ratio between them (alpha over beta) tells you how much a tissue cares about the size of each fraction."}],"trials":[],"papers":[]},{"era":"2013 to 2023","title":"The millimetres matter to the organ next door","description":"The reason to shrink a margin is the tissue beside it. In 2,168 women given radiotherapy for breast cancer in Sweden and Denmark between 1958 and 2001, the rate of major coronary events rose by 7.4 per cent for every gray of mean heart dose, with no apparent threshold, which is the case for breath-holding and motion management that keep the heart out of the beam. The first randomised test of a tighter margin came from MIRAGE: 156 men having stereotactic radiotherapy for prostate cancer were given either a 4 mm margin with CT guidance or a 2 mm margin with MRI guidance, and acute moderate or worse urinary side effects fell from 43.4 to 24.4 per cent, and moderate or worse bowel side effects from 10.5 to 0 per cent. Longer follow-up is needed to show whether the difference lasts.","status":"current","refs":[{"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":"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":"cardio-oncology","kind":"technology","name":"Cardio-oncology","route":"/technologies/cardio-oncology/","status":"established","tldr":"Cardio-oncology builds heart risk assessment, monitoring and prevention into cancer care so patients can finish curative treatment without trading cancer for heart failure. It targets anthracycline and trastuzumab damage, checkpoint-inhibitor myocarditis and radiation heart disease using echocardiography, troponin tests and protective drugs; specialist clinics are concentrated in large centres."},{"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":"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":"paper-kishan-jama-oncol","kind":"paper","name":"Magnetic Resonance Imaging-Guided vs Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial","route":"/key-papers/paper-kishan-jama-oncol/","tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 36633877 and published in JAMA Oncology; the citing page links this DOI, which is how the record was matched."}],"trials":[],"papers":[{"id":"paper-kishan-jama-oncol","name":"Magnetic Resonance Imaging-Guided vs Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial","route":"/key-papers/paper-kishan-jama-oncol/","journal":"JAMA Oncology","year":2023,"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand."}]},{"era":"2015 to 2023","title":"Seeing the edge: the margin, the scan and the second operation","description":"In surgery, imprecision shows up as a second operation. In a randomised trial of 235 patients having a partial mastectomy, funded by the Yale Cancer Center, 34 per cent of those whose surgeon took no extra tissue had a positive margin and 21 per cent needed a second operation; shaving extra tissue from the cavity halved both, to 19 and 10 per cent. Imaging moved in the same direction: in proPSMA, 302 men with high-risk prostate cancer were randomised to PSMA PET-CT or to CT and bone scanning, and PSMA PET-CT was 92 per cent accurate against 65 per cent for finding spread to lymph nodes or further. A dye that lights up tumour left in the cavity followed: in the INSITE trial of pegulicianine it removed tumour left behind after standard lumpectomy in 27 of 357 patients, with a per-margin sensitivity of 49.3 per cent and a specificity of 85.2 per cent, so it helps the surgeon find some residual cancer and misses about half.","status":"current","refs":[{"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":"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":"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":"propsma","kind":"trial","name":"proPSMA","route":"/trials/propsma/","status":"positive","tldr":"Proved PSMA PET is far more accurate than conventional scans for staging, with less radiation."},{"id":"paper-propsma-hofman-lancet-2020","kind":"paper","name":"proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer","route":"/key-papers/paper-propsma-hofman-lancet-2020/","tldr":"PSMA PET-CT was 27 percentage points more accurate than CT and bone scan for finding spread in men with high-risk prostate cancer before treatment, with less radiation and more influence on management, and it has replaced conventional imaging where available."},{"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":"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":"intraoperative-fluorescence-imaging-systems","kind":"technology","name":"Intraoperative fluorescence and Cerenkov imaging systems (SPY, Firefly, LumiSystem, LightPath)","route":"/technologies/intraoperative-fluorescence-imaging-systems/","status":"established","tldr":"Cameras in the operating theatre that see dyes the surgeon's eye cannot: green dye lighting up lymph nodes and blood supply, pink glow marking a brain tumour, and even the faint light from a PET tracer in a removed specimen. They turn the dyes into a picture the surgeon follows."},{"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":"surgery-roadmap","kind":"roadmap","name":"Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work","route":"/roadmaps/surgery-roadmap/","tldr":"Surgery cures more cancers than any other treatment. Its story for a century has been learning how much can safely be left in, and now whether the operation is needed at all once drugs and radiation have cleared the tumour."},{"id":"molecular-imaging-roadmap","kind":"roadmap","name":"Molecular imaging roadmap: FDG → PSMA → FAP → antigen and immune PET","route":"/roadmaps/molecular-imaging-roadmap/","tldr":"From a sugar tracer that lights up most cancers to tracers that show a single protein, a stromal cell type, or the immune cells inside a tumour."}],"trials":[{"id":"propsma","name":"proPSMA","route":"/trials/propsma/","outcomes":[{"endpoint":"Accuracy for pelvic nodal or distant metastases (AUC)","primary":true,"unit":"%","arms":[{"name":"PSMA PET/CT","n":150,"value":92},{"name":"CT + bone scan","n":152,"value":65}],"p":"<0.0001","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30314-7/fulltext"}],"setting":"High-risk localised prostate cancer staging: PSMA PET/CT vs CT + bone scan","enrolled":302,"enrolledBasis":"registry"}],"papers":[{"id":"paper-propsma-hofman-lancet-2020","name":"proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer","route":"/key-papers/paper-propsma-hofman-lancet-2020/","journal":"The Lancet","year":2020,"whatItMeans":"PSMA PET-CT is the preferred staging investigation for high-risk prostate cancer and for biochemical recurrence, though most treatment trials were designed with conventional imaging."}]},{"era":"2018 to 2020","title":"Matching drugs to mutations: precise tests, few matches","description":"Sequencing a tumour is precise; finding a drug that works for what it shows is less often possible. NCI-MATCH sequenced tumours from 5,954 people with cancers that had stopped responding to standard treatment, at 1,117 sites: profiling worked for 93.0 per cent, an actionable alteration was found in 37.6 per cent, and 17.8 per cent were assigned to a matched treatment. The share varied by cancer, from more than 35 per cent for urothelial cancers to under 6 per cent for pancreatic and small-cell lung cancer. A 2018 estimate from FDA approvals put the share of US patients with metastatic cancer eligible for genome-targeted therapy at 8.33 per cent and the share estimated to benefit at 4.90 per cent. The test can be precise and the match still rare, which is why the matrix scores both.","status":"current","refs":[{"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":"paper-flaherty-j-clin-oncol","kind":"paper","name":"Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH)","route":"/key-papers/paper-flaherty-j-clin-oncol/","tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 33048619 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched."},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/","tldr":"Reading millions of DNA fragments in parallel, the engine behind every modern genomic test."},{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/","status":"standard-of-care","tldr":"The test that decides whether a specific drug is right for you, approved together with the drug."},{"id":"variant-knowledgebases","kind":"technology","name":"Cancer variant knowledgebases and molecular tumour boards","route":"/technologies/variant-knowledgebases/","status":"established","tldr":"Curated databases that say what each mutation means for treatment, and the expert meetings that use them to decide on therapy."},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/","tldr":"A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started."},{"id":"diagnostics-roadmap","kind":"roadmap","name":"Diagnostics roadmap: stains → gene panels → blood tests that decide treatment","route":"/roadmaps/diagnostics-roadmap/","tldr":"Cancer diagnosis moved from what a tumour looks like under a microscope to what is driving it, and now to reading it from a blood sample. The next step is tests that tell the doctor what to do, not only what is there."}],"trials":[{"id":"nci-match","name":"NCI-MATCH (EAY131)","route":"/trials/nci-match/","outcomes":[{"endpoint":"Assigned to a treatment arm","primary":false,"unit":"%","arms":[{"name":"Enrolled patients","n":5954,"value":17.8}],"source":"https://doi.org/10.1200/JCO.19.03010"},{"endpoint":"Objective response, dabrafenib plus trametinib in BRAF V600 tumours (arm H)","unit":"%","arms":[{"name":"Treated patients","value":38}],"source":"https://doi.org/10.1200/JCO.20.00762"},{"endpoint":"Objective response, nivolumab in dMMR non-colorectal tumours (arm Z1D)","unit":"%","arms":[{"name":"Treated patients","value":36}],"source":"https://doi.org/10.1200/JCO.19.00818"}],"setting":"Advanced solid tumours, lymphomas and myeloma that have progressed on standard treatment: central tumour sequencing assigns patients to one of nearly 40 single-agent or doublet targeted-therapy arms by molecular alteration regardless of cancer type","enrolled":5954,"enrolledBasis":"registry"}],"papers":[{"id":"paper-flaherty-j-clin-oncol","name":"Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH)","route":"/key-papers/paper-flaherty-j-clin-oncol/","journal":"Journal of Clinical Oncology","year":2020,"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand."}]},{"era":"From 2018","title":"The dose stops being one size for everyone","description":"Chemotherapy doses are calculated from height and weight, and the FDA says the dose of many newer targeted drugs is inadequately characterised before the trials that lead to approval. Two changes have started to move that. In 1,103 patients in 17 Dutch hospitals tested for four DPYD variants before fluoropyrimidine chemotherapy, the 8 per cent who carried one were given a lower starting dose; for carriers of DPYD*2A the relative risk of severe toxicity was 1.31 with genotype-guided dosing against 2.87 in a historical cohort treated at full dose, and the authors concluded that genotype-based dose reductions improved patient safety. For new drugs, the FDA's Project Optimus asks companies to find the best dose rather than the highest tolerable one, because, in its own words, a poorly characterised dose may lead to \"selection of a dose that provides more toxicity without additional efficacy\".","status":"current","refs":[{"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":"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":"paper-henricks-lancet-oncol","kind":"paper","name":"DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis","route":"/key-papers/paper-henricks-lancet-oncol/","tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30348537 and published in The Lancet Oncology; the citing page links this DOI, which is how the record was matched."},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/","status":"approved","tldr":"The 1957 chemotherapy that remains the backbone of treatment for bowel, stomach, pancreatic, anal, head and neck and breast cancers, and as a cream for skin precancers."},{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/","status":"approved","tldr":"Capecitabine (Xeloda) is a tablet form of the chemotherapy fluorouracil. It is a backbone of treatment for bowel cancer and a standard option in advanced breast cancer."},{"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":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/","tldr":"Most drug doses were chosen as the highest a person can tolerate, which is often more than they need."},{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/","status":"approved","tldr":"Sotorasib (Lumakras) was the first drug to hit KRAS, approved in 2021 after four decades of failure."}],"trials":[],"papers":[{"id":"paper-henricks-lancet-oncol","name":"DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis","route":"/key-papers/paper-henricks-lancet-oncol/","journal":"The Lancet Oncology","year":2018,"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand."}]},{"era":"2022 to 2026","title":"A blood test for residual disease starts to decide treatment","description":"Tests that find tumour DNA in the blood after surgery are the molecular form of a margin: they ask whether anything was left behind. In DYNAMIC, 455 people with stage II colon cancer were randomised to have adjuvant chemotherapy decided by a blood test or by the usual pathology features; the blood-test group received chemotherapy less often (15 against 28 per cent) with two-year recurrence-free survival of 93.5 against 92.4 per cent. The ctDNA roadmap follows this in detail, including the first drug approval that depends on a residual disease result. How little tumour DNA a test can find is the precision limit, and it is recorded row by row in the matrix.","status":"current","refs":[{"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":"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":"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":"dynamic","kind":"trial","name":"DYNAMIC","route":"/trials/dynamic/","status":"positive","tldr":"Showed that a blood test can safely halve the number of colon cancer patients given chemotherapy after surgery."},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/","status":"established","tldr":"Signatera is Natera's tumour-informed blood test that tracks 16 mutations from each patient's own tumour to detect residual or returning cancer after surgery. Medicare covers it in colorectal, breast, bladder, lung and ovarian cancer and for immunotherapy monitoring, and in 2026 it selected the bladder cancer patients for the first approval based on circulating tumour DNA."},{"id":"imvigor011","kind":"trial","name":"IMvigor011","route":"/trials/imvigor011/","status":"positive","tldr":"The first trial to use a blood test for leftover cancer to decide who gets immunotherapy, and it worked."},{"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."}],"trials":[{"id":"dynamic","name":"DYNAMIC","route":"/trials/dynamic/","outcomes":[{"endpoint":"Recurrence-free survival at 2 years (non-inferiority)","primary":true,"unit":"%","arms":[{"name":"ctDNA-guided management","n":302,"value":93.5,"note":"Non-inferiority met (margin −8.5 points)"},{"name":"Standard management","n":153,"value":92.4}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2200075"},{"endpoint":"Patients receiving adjuvant chemotherapy","unit":"%","arms":[{"name":"ctDNA-guided management","value":15},{"name":"Standard management","value":28}],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2200075"}],"setting":"Stage II colon cancer: ctDNA-guided adjuvant chemotherapy vs standard management","enrolled":455,"enrolledBasis":"registry"},{"id":"imvigor011","name":"IMvigor011","route":"/trials/imvigor011/","outcomes":[{"endpoint":"Disease-free survival (ctDNA-positive, randomised)","primary":true,"unit":"months","arms":[{"name":"Atezolizumab","n":167,"value":9.9},{"name":"Placebo","n":83,"value":4.8}],"hr":0.64,"ci":[0.47,0.88],"p":"0.005","source":"https://www.roche.com/media/releases/med-cor-2025-10-20b"},{"endpoint":"Overall survival (ctDNA-positive)","unit":"months","arms":[{"name":"Atezolizumab","value":32.8},{"name":"Placebo","value":21.1}],"hr":0.59,"ci":[0.41,0.86],"p":"0.005","source":"https://www.roche.com/media/releases/med-cor-2025-10-20b"},{"endpoint":"Disease-free survival at 12 months, persistently ctDNA-negative (untreated surveillance)","unit":"%","arms":[{"name":"ctDNA-negative, surveillance only","n":357,"value":95.4,"note":"12-month OS 100% in this group"}],"source":"https://www.roche.com/media/releases/med-cor-2025-10-20b"}],"setting":"Muscle-invasive bladder cancer after cystectomy, ctDNA-positive (Signatera): atezolizumab vs placebo","enrolled":761,"enrolledBasis":"registry"}],"papers":[]},{"era":"Next","title":"Adapting to the day: plans and operations that follow the tumour","description":"The next step in radiotherapy and surgery is to measure during treatment rather than before it. Online adaptive radiotherapy redraws the plan on the treatment couch from that day's scan, so the margin can follow a shrinking tumour or a filling bladder; trials are testing whether that reduces side effects in more cancers than prostate. In surgery, the proposals are fluorescent agents, mass spectrometry and rapid digital pathology that read the margin before the wound is closed. Each is available somewhere and routine almost nowhere, and for most of them the outcome a patient would feel, fewer side effects or fewer second operations, has not yet been measured in a randomised trial.","status":"emerging","refs":[{"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":"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":"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":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/","status":"established","tldr":"Scanning microscope slides and letting software measure things a pathologist cannot see, including predictions of who will benefit from a treatment."},{"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":"idea-moon-image-guided-surgery-everywhere","kind":"idea","name":"Real-time margin assessment and image-guided surgery as the global standard","route":"/ideas/idea-moon-image-guided-surgery-everywhere/","tldr":"Surgeons often cannot see where a tumour ends. Fluorescent dyes and AI-read imaging in the operating theatre can show them, cutting repeat operations. Make this routine everywhere."}],"trials":[],"papers":[]},{"era":"Next","title":"Dosing the person rather than the average","description":"Proposals in the corpus would carry dose precision further: dosing chemotherapy by muscle mass measured on routine scans rather than by height and weight, dose-finding designs that count late and lasting side effects rather than the first month only, randomised lower-dose trials for drugs already approved at the highest tolerated dose, and radioligand doses set by measuring what each patient's tumour and kidneys absorb. None has yet changed a label or a guideline. They are listed so that the gap between a dose that is convenient to calculate and one that fits the person stays visible.","status":"emerging","refs":[{"id":"idea-bio2-lean-mass-dosing","kind":"idea","name":"Dose chemotherapy by muscle mass, not body surface area","route":"/ideas/idea-bio2-lean-mass-dosing/","tldr":"Chemotherapy doses are calculated from height and weight, a formula from the 1950s. Doses based on actual muscle mass may cause fewer severe side-effects."},{"id":"idea-tr1-model-based-dose-finding-with-late-toxicity","kind":"idea","name":"Retire the 3+3: model-based dose finding that counts late and chronic side effects","route":"/ideas/idea-tr1-model-based-dose-finding-with-late-toxicity/","tldr":"The traditional way of finding a dose looks only at severe side effects in the first month. Modern statistical designs can use all patients' data and count the grumbling, long-lasting problems that make people quit months later."},{"id":"idea-moon-post-approval-dose-deescalation","kind":"idea","name":"Randomised lower-dose trials for approved drugs with quality of life as the primary endpoint","route":"/ideas/idea-moon-post-approval-dose-deescalation/","tldr":"Many cancer drugs are approved at the highest dose patients could stand, not the best dose. Run trials that test lower doses on approved drugs and measure how patients feel."},{"id":"idea-cost-optimus-legacy-drugs","kind":"idea","name":"Apply Project Optimus to drugs already on the market","route":"/ideas/idea-cost-optimus-legacy-drugs/","tldr":"The FDA now requires new cancer drugs to prove their dose is the right one rather than the highest tolerated; asking the same question of the twenty best-selling approved drugs could cut doses, side effects and cost at once."},{"id":"idea-net-dosimetry-prrt","kind":"idea","name":"Dosimetry-personalised PRRT instead of four fixed cycles","route":"/ideas/idea-net-dosimetry-prrt/","tldr":"Measure the radiation each patient's tumour and kidneys actually absorb and adjust the number and size of doses, instead of giving everyone four identical cycles."},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/","tldr":"Most drug doses were chosen as the highest a person can tolerate, which is often more than they need."}],"trials":[],"papers":[]},{"era":"Further","title":"Testing the drug on the patient's own cells","description":"Matching by mutation predicts which drug might work; testing drugs directly on a patient's living cancer cells measures it. In blood cancers, where cells survive outside the body long enough to be screened against a panel of approved drugs, this has reached small interventional trials. For solid tumours it remains research. If it works at scale it would change the molecular question from whether a target is present to whether a drug kills this cancer.","status":"speculative","refs":[{"id":"functional-precision-medicine-haematology","kind":"technology","name":"Ex vivo drug sensitivity screening in blood cancers (EXALT)","route":"/technologies/functional-precision-medicine-haematology/","status":"phase-2","tldr":"Blood cancer cells taken from a patient's blood or marrow are exposed within days to a panel of approved drugs, and the ones that kill the cancer cells while sparing healthy ones are offered back to the patient; a Vienna trial found this beat the previous treatment in more than half of heavily treated patients."},{"id":"idea-bio2-functional-precision-rare","kind":"idea","name":"Test drugs on the patient's own cancer cells when there is no trial to join","route":"/ideas/idea-bio2-functional-precision-rare/","tldr":"For rare cancers there is often no genetic clue and no trial to join. Testing drugs directly on the patient's fresh tumour cells has guided treatment with reported benefit in a randomised haematology study and in paediatric case series; turnaround and tissue quality are the barriers."}],"trials":[],"papers":[]},{"era":"What sets the pace","title":"Precision is not the same as benefit","description":"Three things limit how fast precision reaches patients, and only one of them is technical. The first is evidence: a tighter margin, a more sensitive test or a fitted dose has to change something a patient feels, and for many technologies that trial has not been run, so the matrix records the outcome as shown, plausible or not established. The second is access: the machines, assays and genotyping tests exist and are unevenly paid for. The third is the honest arithmetic of molecular matching, where a test that finds a target in a third of people leads to a matched treatment in fewer than one in five and a benefit in fewer still. Where precision is marketed beyond what has been shown, the matrix grades it rather than leaving it out.","status":"current","refs":[{"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":"paper-flaherty-j-clin-oncol","kind":"paper","name":"Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH)","route":"/key-papers/paper-flaherty-j-clin-oncol/","tldr":"Paper cited by one trial page, indexed on Europe PMC as PubMed record 33048619 and published in Journal of Clinical Oncology; the citing page links this DOI, which is how the record was matched."},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/","tldr":"Most drug doses were chosen as the highest a person can tolerate, which is often more than they need."},{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/","status":"standard-of-care","tldr":"The test that decides whether a specific drug is right for you, approved together with the drug."},{"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."}],"trials":[{"id":"nci-match","name":"NCI-MATCH (EAY131)","route":"/trials/nci-match/","outcomes":[{"endpoint":"Assigned to a treatment arm","primary":false,"unit":"%","arms":[{"name":"Enrolled patients","n":5954,"value":17.8}],"source":"https://doi.org/10.1200/JCO.19.03010"},{"endpoint":"Objective response, dabrafenib plus trametinib in BRAF V600 tumours (arm H)","unit":"%","arms":[{"name":"Treated patients","value":38}],"source":"https://doi.org/10.1200/JCO.20.00762"},{"endpoint":"Objective response, nivolumab in dMMR non-colorectal tumours (arm Z1D)","unit":"%","arms":[{"name":"Treated patients","value":36}],"source":"https://doi.org/10.1200/JCO.19.00818"}],"setting":"Advanced solid tumours, lymphomas and myeloma that have progressed on standard treatment: central tumour sequencing assigns patients to one of nearly 40 single-agent or doublet targeted-therapy arms by molecular alteration regardless of cancer type","enrolled":5954,"enrolledBasis":"registry"}],"papers":[{"id":"paper-flaherty-j-clin-oncol","name":"Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH)","route":"/key-papers/paper-flaherty-j-clin-oncol/","journal":"Journal of Clinical Oncology","year":2020,"whatItMeans":"One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand."}]}],"watch":[]}