{"id":"radiation-roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/","eras":[{"era":"1895-1990s","title":"From X-rays to conformal beams","description":"Röntgen's X-rays were used against cancer within a year of their discovery, and the Curies' radium became brachytherapy. Cobalt units and then linear accelerators (1950s) delivered higher energies deeper; CT planning in the 1980s let beams be shaped to the tumour in three dimensions. Radioactive iodine for thyroid cancer, from the 1940s, was the first targeted radiotherapy and a preview of the radiopharmaceutical field.","status":"historic","refs":[{"id":"institut-curie","kind":"institution","name":"Institut Curie","route":"/institutions/institut-curie/","tldr":"Founded by Marie Curie; a leader in breast cancer, radiotherapy, and proton therapy."},{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","route":"/technologies/brachytherapy/","status":"standard-of-care","tldr":"Brachytherapy places a radioactive source directly inside or next to the tumour."},{"id":"radioactive-iodine","kind":"drug","name":"Radioactive iodine (I-131)","route":"/drugs/radioactive-iodine/","status":"approved","tldr":"The original targeted radiotherapy: thyroid cells soak up iodine, so radioactive iodine destroys leftover thyroid tissue and metastases while sparing everything else."},{"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."}],"trials":[],"papers":[]},{"era":"2000s-2020","title":"Modulation, image guidance and fewer fractions","description":"Intensity-modulated and image-guided radiotherapy shaped dose around organs and checked position daily, cutting late toxicity in prostate and head and neck cancer. Stereotactic body radiotherapy ablated early lung cancers and oligometastases in one to five sessions. Large trials proved that fewer, larger fractions match conventional courses: CHHiP in prostate cancer and FAST-Forward (2020), which delivered breast radiotherapy in five sessions over one week. CONVERT settled the small-cell lung schedule debate. Treatment planning software became the real product.","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":"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":"hypofractionation","kind":"term","name":"Hypofractionation (fewer, larger radiotherapy doses)","route":"/terms/hypofractionation/","tldr":"Giving radiotherapy in fewer, bigger daily doses (fractions) so a course takes one to three weeks instead of five to seven. Randomised trials showed equal control and side effects in breast (START, FAST-Forward) and prostate (CHHiP, PACE-B) cancer, and a single dose suffices for bone pain; adoption lags where health systems are paid per fraction."},{"id":"convert","kind":"trial","name":"CONVERT","route":"/trials/convert/","status":"mixed","tldr":"Settled the radiotherapy schedule debate in limited-stage disease: neither schedule was superior, so twice-daily 45 Gy remains standard and once-daily is an acceptable alternative."},{"id":"treatment-planning-systems","kind":"technology","name":"Radiotherapy treatment planning and QA software","route":"/technologies/treatment-planning-systems/","status":"standard-of-care","tldr":"The software that calculates exactly how radiation beams should be shaped and checks the machine delivered it."},{"id":"varian","kind":"company","name":"Varian (Siemens Healthineers)","route":"/companies/varian/","tldr":"Varian is the largest radiotherapy equipment maker and is running the first human FLASH proton trials."},{"id":"elekta","kind":"company","name":"Elekta","route":"/companies/elekta/","tldr":"Elekta is the Swedish radiotherapy company behind Unity, the leading MR-linac, and Gamma Knife."},{"id":"raysearch","kind":"company","name":"RaySearch Laboratories","route":"/companies/raysearch/","tldr":"RaySearch makes the vendor-neutral RayStation treatment planning system, strong in proton and adaptive planning, with machine-learning planning tools."}],"trials":[{"id":"convert","name":"CONVERT","route":"/trials/convert/","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Twice-daily 45 Gy","n":274,"value":30},{"name":"Once-daily 66 Gy","n":273,"value":25}],"hr":1.18,"ci":[0.95,1.45],"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30318-2/fulltext"}],"setting":"Limited-stage SCLC: twice-daily 45 Gy vs once-daily 66 Gy thoracic radiotherapy with concurrent cisplatin-etoposide","enrolled":547,"enrolledBasis":"registry"}],"papers":[]},{"era":"2017-2026","title":"Radiation plus drugs: what worked and what did not","description":"PACIFIC made a year of durvalumab after chemoradiation the standard in stage III lung cancer; KEYNOTE-A18 added pembrolizumab to curative chemoradiation for cervical cancer with a survival gain; LAURA gave osimertinib after chemoradiation in EGFR-mutant lung cancer; INTERLACE showed that six weeks of cheap chemotherapy before cervical chemoradiation cuts deaths. The failures were as instructive: adding a PD-L1 blocker to head and neck chemoradiation did not help (JAVELIN HN 100), a promising radiosensitiser made things worse (TrilynX), and de-escalating radiation for HPV-positive throat cancer fell short (NRG-HN002 and HN005).","status":"current","refs":[{"id":"pacific","kind":"trial","name":"PACIFIC","route":"/trials/pacific/","status":"positive","tldr":"Made a year of immunotherapy after chemoradiation the standard for stage III lung cancer, with a survival benefit that held at five years."},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/","status":"approved","tldr":"A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers."},{"id":"keynote-a18","kind":"trial","name":"KEYNOTE-A18 / ENGOT-cx11 / GOG-3047","route":"/trials/keynote-a18/","status":"positive","tldr":"Adding immunotherapy to curative chemoradiation for locally advanced cervical cancer improved both control and survival, the first such advance in two decades."},{"id":"laura","kind":"trial","name":"LAURA","route":"/trials/laura/","status":"positive","tldr":"For stage III lung cancers with an EGFR mutation, a targeted pill after chemoradiation cut progression by more than 80%."},{"id":"interlace","kind":"trial","name":"INTERLACE","route":"/trials/interlace/","status":"positive","tldr":"Six weeks of cheap, generic chemotherapy before standard chemoradiation cut deaths by 40%, an advance usable anywhere in the world."},{"id":"cross","kind":"trial","name":"CROSS","route":"/trials/cross/","status":"positive","tldr":"The trial that made chemotherapy plus radiation before surgery the standard for oesophageal cancer; the survival gain was still there ten years later."},{"id":"portec-3","kind":"trial","name":"PORTEC-3","route":"/trials/portec-3/","status":"positive","tldr":"Adding chemotherapy to radiation after surgery helped women with high-risk endometrial cancer, especially those whose tumours have a broken p53 gene."},{"id":"javelin-hn-100","kind":"trial","name":"JAVELIN Head and Neck 100","route":"/trials/javelin-hn-100/","status":"negative","tldr":"Adding a PD-L1 blocker to curative chemoradiation did not help, the first of several such failures in head and neck cancer."},{"id":"trilynx","kind":"trial","name":"TrilynX","route":"/trials/trilynx/","status":"negative","tldr":"TrilynX tested xevinapant, a drug meant to make tumours more sensitive to radiation, with cisplatin chemoradiation in 730 patients with locally advanced head and neck cancer. Despite a striking phase 2 result, the phase 3 was stopped for futility in 2024 with worse outcomes on xevinapant, a reminder that early wins in this disease often do not replicate."},{"id":"nrg-hn002-hn005","kind":"trial","name":"NRG-HN002 & NRG-HN005 (HPV+ de-escalation)","route":"/trials/nrg-hn002-hn005/","status":"mixed","tldr":"Attempts to give HPV-positive throat cancer patients less radiation fell short: the standard dose remained better, so de-escalation is not yet routine."},{"id":"temozolomide","kind":"drug","name":"Temozolomide","route":"/drugs/temozolomide/","status":"standard-of-care","tldr":"The only chemotherapy proven to extend life in glioblastoma, given during and after radiation. It works best when the tumour has switched off a repair gene called MGMT."},{"id":"eortc-26981","kind":"trial","name":"EORTC 26981 / NCIC CE.3 (Stupp trial)","route":"/trials/eortc-26981/","status":"positive","tldr":"The 2005 trial that set the treatment every glioblastoma patient still receives. Nothing has replaced it in twenty years."}],"trials":[{"id":"pacific","name":"PACIFIC","route":"/trials/pacific/","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Durvalumab","n":476,"value":16.8},{"name":"Placebo","n":237,"value":5.6}],"hr":0.52,"ci":[0.42,0.65],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1709937"},{"endpoint":"Overall survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Durvalumab","value":42.9},{"name":"Placebo","value":33.4}],"hr":0.72,"ci":[0.59,0.89],"source":"https://ascopubs.org/doi/10.1200/JCO.21.01308"}],"setting":"Unresectable stage III NSCLC without progression after chemoradiation: durvalumab 1 year vs placebo","enrolled":713,"enrolledBasis":"registry"},{"id":"keynote-a18","name":"KEYNOTE-A18 / ENGOT-cx11 / GOG-3047","route":"/trials/keynote-a18/","outcomes":[{"endpoint":"Progression-free survival at 24 months","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + CRT","n":529,"value":68},{"name":"Placebo + CRT","n":531,"value":57}],"hr":0.7,"ci":[0.55,0.89],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00317-9/fulltext"},{"endpoint":"Overall survival at 36 months","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + CRT","value":82.6},{"name":"Placebo + CRT","value":74.8}],"hr":0.67,"ci":[0.5,0.9],"source":"https://pubmed.ncbi.nlm.nih.gov/39288779/"}],"setting":"Newly diagnosed high-risk locally advanced cervical cancer (FIGO 2014 IB2-IIB node-positive or III-IVA): pembrolizumab + cisplatin chemoradiation + brachytherapy, then pembrolizumab, vs chemoradiation","enrolled":1060,"enrolledBasis":"registry"},{"id":"laura","name":"LAURA","route":"/trials/laura/","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Osimertinib","n":143,"value":39.1},{"name":"Placebo","n":73,"value":5.6}],"hr":0.16,"ci":[0.1,0.24],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2402614"}],"setting":"Unresectable stage III EGFR-mutant NSCLC after chemoradiation: osimertinib until progression vs placebo","enrolled":216,"enrolledBasis":"registry"},{"id":"interlace","name":"INTERLACE","route":"/trials/interlace/","outcomes":[{"endpoint":"Progression-free survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Induction chemo + CRT","n":250,"value":72},{"name":"CRT alone","n":250,"value":64}],"hr":0.65,"ci":[0.46,0.91],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01438-7/fulltext"},{"endpoint":"Overall survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Induction chemo + CRT","value":80},{"name":"CRT alone","value":72}],"hr":0.6,"ci":[0.4,0.91],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01438-7/fulltext"}],"setting":"Locally advanced cervical cancer: 6 weeks of induction carboplatin-paclitaxel before chemoradiation vs chemoradiation alone","enrolled":500,"enrolledBasis":"registry"},{"id":"cross","name":"CROSS","route":"/trials/cross/","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Chemoradiation + surgery","n":178,"value":49.4},{"name":"Surgery alone","n":188,"value":24}],"hr":0.68,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1112088"},{"endpoint":"Overall survival at 10 years","unit":"percent","arms":[{"name":"Chemoradiation + surgery","value":38},{"name":"Surgery alone","value":25}],"source":"https://ascopubs.org/doi/10.1200/JCO.20.03614"}],"setting":"Resectable oesophageal or junctional cancer (squamous and adenocarcinoma): weekly carboplatin/paclitaxel + 41.4 Gy radiation then surgery vs surgery alone","enrolled":366,"enrolledBasis":"registry"},{"id":"portec-3","name":"PORTEC-3","route":"/trials/portec-3/","outcomes":[{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Chemoradiation + chemotherapy","n":330,"value":81.4},{"name":"Radiotherapy alone","n":330,"value":76.1}],"hr":0.7,"ci":[0.51,0.97],"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30395-X/fulltext"}],"setting":"High-risk early or stage III endometrial cancer after surgery: chemoradiation + 4 cycles chemotherapy vs pelvic radiotherapy alone","enrolled":660,"enrolledBasis":"registry"},{"id":"javelin-hn-100","name":"JAVELIN Head and Neck 100","route":"/trials/javelin-hn-100/","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Avelumab + chemoradiotherapy, then avelumab maintenance","n":350,"note":"Median not reached in either arm; stopped for futility at interim analysis"},{"name":"Placebo + chemoradiotherapy","n":347}],"hr":1.21,"ci":[0.93,1.57],"p":"0.92 (one-sided)","source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30737-3/fulltext"}],"setting":"Locally advanced HNSCC: avelumab + chemoradiation then avelumab maintenance vs chemoradiation","enrolled":697,"enrolledBasis":"registry"},{"id":"trilynx","name":"TrilynX","route":"/trials/trilynx/","outcomes":[{"endpoint":"Event-free survival","primary":true,"unit":"months","arms":[{"name":"Xevinapant + CRT","value":19.4},{"name":"Placebo + CRT","value":33.1}],"source":"https://ascopubs.org/doi/10.1200/JCO-25-00272"}],"setting":"Unresected locally advanced HNSCC: xevinapant + cisplatin chemoradiation vs placebo + chemoradiation","enrolled":730,"enrolledBasis":"registry"},{"id":"nrg-hn002-hn005","name":"NRG-HN002 & NRG-HN005 (HPV+ de-escalation)","route":"/trials/nrg-hn002-hn005/","outcomes":[{"endpoint":"HN005: progression-free survival at 2 years (phase II non-inferiority)","primary":true,"unit":"%","arms":[{"name":"70 Gy + cisplatin (standard)","n":136,"value":98.1,"note":"Both de-escalated arms failed non-inferiority (HR vs standard 7.42 and 5.55; non-inferiority margin HR 2.4); the trial did not proceed to phase III"},{"name":"60 Gy + cisplatin","n":116,"value":88.6},{"name":"60 Gy + nivolumab","n":132,"value":90.3}],"source":"https://clinicaltrials.gov/study/NCT03952585"},{"endpoint":"HN002: progression-free survival at 2 years (randomised phase II vs 85% historical control)","unit":"%","arms":[{"name":"60 Gy IMRT + weekly cisplatin","value":90.5,"note":"306 patients; only the cisplatin arm met the PFS and swallowing (MDADI) criteria to advance"},{"name":"60 Gy IMRT alone","value":87.6}],"p":"0.04 (IMRT + cisplatin vs 85%)","source":"https://ascopubs.org/doi/10.1200/JCO.20.03128"}],"setting":"Low-risk HPV-positive oropharyngeal cancer: reduced-dose radiation (60 Gy) with or without cisplatin, or with nivolumab, vs standard 70 Gy chemoradiation","enrolledBasis":"registry"},{"id":"eortc-26981","name":"EORTC 26981 / NCIC CE.3 (Stupp trial)","route":"/trials/eortc-26981/","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Radiotherapy + temozolomide","n":287,"value":14.6},{"name":"Radiotherapy alone","n":286,"value":12.1}],"hr":0.63,"ci":[0.52,0.75],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa043330"},{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Radiotherapy + temozolomide","value":9.8},{"name":"Radiotherapy alone","value":1.9}],"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70025-7/fulltext"}],"setting":"Newly diagnosed glioblastoma: radiotherapy + concurrent and adjuvant temozolomide vs radiotherapy alone","enrolled":575,"enrolledBasis":"registry"}],"papers":[]},{"era":"2010s-2026","title":"Particles, magnets and adaptation","description":"Protons stop inside the tumour rather than passing through, which matters most in children and near critical organs; the Christie opened the UK's first NHS proton centre and compact single-room systems are spreading. Carbon ions kill radioresistant tumours and are available at a handful of centres, with North America's first being built at Mayo Clinic Florida. MR-linacs image soft tissue during treatment and adapt the plan daily; PET-guided systems track the tumour by its own emissions. AI auto-contouring now saves hours per plan in hundreds of centres. Clinical proton dose is still reported at RBE 1.1; whether LET-weighted RBE plus tissue alpha/beta can pick the adults who benefit versus IMRT is untested in the randomised trials now running.","status":"current","refs":[{"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":"the-christie","kind":"institution","name":"The Christie NHS Foundation Trust","route":"/institutions/the-christie/","tldr":"The Christie is Europe's largest single-site cancer centre and the UK's first NHS proton therapy centre."},{"id":"mgh","kind":"institution","name":"Massachusetts General Hospital Cancer Center","route":"/institutions/mgh/","tldr":"Harvard's largest hospital; leaders in lung cancer targeted therapy, proton therapy, and ctDNA research."},{"id":"iba","kind":"company","name":"IBA (Ion Beam Applications)","route":"/companies/iba/","tldr":"IBA (Ion Beam Applications), of Louvain-la-Neuve, Belgium, is the largest supplier of proton therapy equipment: its Proteus One and Proteus Plus systems equip proton centres worldwide, and it also builds cyclotrons for PET isotope production. Proton therapy's capital cost is the problem its compact systems try to answer."},{"id":"mevion","kind":"company","name":"Mevion Medical Systems","route":"/companies/mevion/","tldr":"Mevion Medical Systems, of Littleton, Massachusetts, makes the MEVION S250-FIT, a compact single-room proton therapy system meant to bring protons within reach of community cancer centres. Whether smaller, cheaper proton machines widen access without diluting the evidence base is the open question."},{"id":"carbon-ion","kind":"technology","name":"Carbon-ion therapy","route":"/technologies/carbon-ion/","status":"established","tldr":"Heavier charged particles that kill even radiation-resistant tumours, available at only a handful of centres worldwide."},{"id":"mayo-clinic-florida","kind":"institution","name":"Mayo Clinic Comprehensive Cancer Center in Florida","route":"/institutions/mayo-clinic-florida/","tldr":"Mayo Clinic's Florida campus, building North America's first carbon-ion therapy facility alongside proton therapy and a cancer vaccine programme."},{"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":"elekta","kind":"company","name":"Elekta","route":"/companies/elekta/","tldr":"Elekta is the Swedish radiotherapy company behind Unity, the leading MR-linac, and Gamma Knife."},{"id":"reflexion","kind":"company","name":"RefleXion Medical","route":"/companies/reflexion/","tldr":"RefleXion Medical makes the first PET-guided radiotherapy system, which uses the tumour's own emissions to steer the beam."},{"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":"limbus-ai","kind":"company","name":"Limbus AI","route":"/companies/limbus-ai/","tldr":"Limbus AI provides AI auto-contouring for radiotherapy, FDA-cleared and used across hundreds of centres."},{"id":"therapanacea","kind":"company","name":"TheraPanacea","route":"/companies/therapanacea/","tldr":"TheraPanacea is a Paris AI company whose ART-Plan does auto-contouring and synthetic CT in radiotherapy."},{"id":"linear-energy-transfer","kind":"term","name":"Linear energy transfer (LET)","route":"/terms/linear-energy-transfer/","tldr":"How densely a radiation track dumps energy along its path. Sparse tracks (X-rays, most of a proton beam) are easier to repair; dense tracks (the proton's stop-point, carbon ions, alpha particles) punch clustered holes in DNA."},{"id":"relative-biological-effectiveness","kind":"term","name":"Relative biological effectiveness (RBE)","route":"/terms/relative-biological-effectiveness/","tldr":"How many grays of ordinary X-rays you would need to match the damage from one gray of this radiation. Protons are treated as 1.1 times as damaging as X-rays; that number is a convention, and the true value is higher where the beam stops."},{"id":"idea-bio2-let-rbe-ab-selects-protons","kind":"idea","name":"Use LET, RBE and alpha/beta to decide when protons beat IMRT","route":"/ideas/idea-bio2-let-rbe-ab-selects-protons/","tldr":"Protons cost more than shaped X-ray beams. They are worth it when the extra punch where the beam stops, and the missing exit dose, widen the gap between killing the tumour and harming late-reacting tissue: an alpha/beta and RBE question, not a machine question."}],"trials":[],"papers":[]},{"era":"2016-2026","title":"Doing less: fewer visits and fewer treatments","description":"Single-fraction radiotherapy relieves bone pain as well as ten fractions and is still under-used. ESTIMABL2 showed that most low-risk thyroid cancers can skip radioactive iodine after surgery. ACNS0331 tested lower doses and smaller fields in children with medulloblastoma to reduce cognitive harm. MRI surveillance is replacing prophylactic brain irradiation in small-cell lung cancer. In overloaded systems, one-week hypofractionated courses are the single largest capacity gain available.","status":"current","refs":[{"id":"palliative-radiotherapy","kind":"technology","name":"Palliative radiotherapy","route":"/technologies/palliative-radiotherapy/","status":"standard-of-care","tldr":"Short courses of radiation, often a single treatment, to relieve pain from bone metastases, stop bleeding, open blocked airways or protect the spinal cord. Among the most cost-effective treatments in cancer."},{"id":"idea-acc-single-fraction-palliative-radiotherapy-default","kind":"idea","name":"Single-fraction radiotherapy as the default for painful bone metastases","route":"/ideas/idea-acc-single-fraction-palliative-radiotherapy-default/","tldr":"Randomised trials and meta-analyses show a single 8 Gy radiotherapy session relieves pain from uncomplicated bone metastases as well as ten sessions, with a higher retreatment rate, yet habit and per-fraction payment keep most patients on the longer course. Making one session the default, with an opt-out justification and payment neutrality, would spare patients trips and free machines."},{"id":"estimabl2","kind":"trial","name":"ESTIMABL2","route":"/trials/estimabl2/","status":"positive","tldr":"Proved that most people with small, low-risk thyroid cancers can skip radioactive iodine after surgery without any increase in recurrence."},{"id":"acns0331","kind":"trial","name":"COG ACNS0331","route":"/trials/acns0331/","status":"mixed","tldr":"This trial asked whether children with average-risk medulloblastoma could safely receive less radiation. Shrinking the boost to the tumour bed was safe; cutting the dose to the whole brain and spine in young children was not, so 23.4 Gy remains the floor for most."},{"id":"prophylactic-cranial-irradiation","kind":"technology","name":"Prophylactic cranial irradiation vs MRI surveillance","route":"/technologies/prophylactic-cranial-irradiation/","status":"established","tldr":"Small-cell lung cancer spreads to the brain so often that doctors used to irradiate the whole brain pre-emptively. Regular MRI scans are now challenging that practice."},{"id":"idea-acc-hypofractionation-default-lmic","kind":"idea","name":"Make one-week radiotherapy the default in overloaded systems","route":"/ideas/idea-acc-hypofractionation-default-lmic/","tldr":"Giving radiotherapy in five larger doses over one week instead of 15 to 25 smaller doses is non-inferior for cancer control and late toxicity in breast and prostate cancer, and triples the number of patients each machine can treat. The barriers are guideline inertia and payment per fraction, not hardware."},{"id":"idea-cthpv-adapted-deescalation","kind":"idea","name":"ctHPV-DNA-adapted de-escalation of chemoradiation","route":"/ideas/idea-cthpv-adapted-deescalation/","tldr":"Instead of guessing from HPV status who can get less radiation, measure the virus DNA in blood during treatment and reduce dose only when it clears fast."}],"trials":[{"id":"estimabl2","name":"ESTIMABL2","route":"/trials/estimabl2/","outcomes":[{"endpoint":"Patients without events at 3 years","primary":true,"unit":"%","arms":[{"name":"No radioiodine","value":95.6},{"name":"Radioiodine 1.1 GBq","value":95.9}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2111953"}],"setting":"Low-risk differentiated thyroid cancer (pT1a-T1b N0/Nx) after total thyroidectomy: no radioiodine vs 1.1 GBq ablation","enrolled":776,"enrolledBasis":"registry"},{"id":"acns0331","name":"COG ACNS0331","route":"/trials/acns0331/","outcomes":[{"endpoint":"5-year event-free survival: boost volume","primary":true,"unit":"%","arms":[{"name":"Involved-field boost","value":82.5},{"name":"Posterior fossa boost","value":80.5}],"hr":0.97,"source":"https://doi.org/10.1200/JCO.20.02730"},{"endpoint":"5-year event-free survival: CSI dose (age 3-7)","primary":true,"unit":"%","arms":[{"name":"18 Gy CSI","value":71.4},{"name":"23.4 Gy CSI","value":82.9}],"hr":1.67,"source":"https://doi.org/10.1200/JCO.20.02730"}],"setting":"Average-risk medulloblastoma, age 3-21: involved-field (tumour bed) vs whole posterior fossa boost; and, in children aged 3-7, 18 Gy vs 23.4 Gy craniospinal irradiation","enrolled":549,"enrolledBasis":"registry"}],"papers":[]},{"era":"2026-2032","title":"FLASH, arcs, upright and new particles","description":"FLASH radiotherapy delivers a full dose in under a second and, in animals, spares normal tissue while killing tumour; the first human trials of FLASH protons have been run and dedicated electron machines are being built. Very-high-energy electrons and proton arcs are routes to deep FLASH. Upright treatment chairs could cut the cost of particle therapy; boron neutron capture therapy, approved in Japan for head and neck cancer, needs compact neutron sources; lattice radiotherapy deliberately doses a large tumour unevenly. Each is limited by engineering and dosimetry rather than biology.","status":"emerging","refs":[{"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":"theryq","kind":"company","name":"THERYQ","route":"/companies/theryq/","tldr":"THERYQ, part of the French industrial group ALCEN, builds linear accelerators for FLASH radiotherapy, which delivers a whole radiation dose in under 100 milliseconds; its FLASHDEEP produces 100 to 200 MeV electron beams that reach tumours about 20 cm deep. It is still preclinical, with a 38 million euro France 2030 programme to reach a CE mark."},{"id":"varian","kind":"company","name":"Varian (Siemens Healthineers)","route":"/companies/varian/","tldr":"Varian is the largest radiotherapy equipment maker and is running the first human FLASH proton trials."},{"id":"vhee-radiotherapy","kind":"technology","name":"Very-high-energy electron therapy","route":"/technologies/vhee-radiotherapy/","status":"preclinical","tldr":"VHEE radiotherapy fires electrons at 100 to 250 MeV, energies that reach deep tumours and can be steered by magnets, aiming to deliver FLASH-speed radiation from a machine smaller and cheaper than a proton facility. It is still at the accelerator-development and preclinical stage: no patient had been treated by September 2026."},{"id":"proton-arc-therapy","kind":"technology","name":"Proton arc therapy","route":"/technologies/proton-arc-therapy/","status":"phase-1","tldr":"Rotating the proton beam continuously around the patient instead of firing from a few fixed angles, to spread the entrance dose and sharpen the target dose."},{"id":"leo-cancer-care","kind":"company","name":"Leo Cancer Care","route":"/companies/leo-cancer-care/","tldr":"Leo Cancer Care builds radiotherapy equipment that treats patients sitting upright instead of lying down, so the beam can stay fixed and the room, machine and building can be far smaller and cheaper."},{"id":"p-cure","kind":"company","name":"P-Cure","route":"/companies/p-cure/","tldr":"P-Cure makes a compact proton therapy system in which the patient sits upright in a rotating chair in front of a fixed beam, so the treatment fits inside an ordinary radiotherapy room instead of a purpose-built multi-storey building."},{"id":"bnct","kind":"technology","name":"Boron neutron capture therapy","route":"/technologies/bnct/","status":"approved","tldr":"In boron neutron capture therapy a boron drug accumulates in tumour cells, then a neutron beam makes only those cells explode from inside."},{"id":"tae-life-sciences","kind":"company","name":"TAE Life Sciences","route":"/companies/tae-life-sciences/","tldr":"TAE Life Sciences is developing boron neutron capture therapy, in which a boron drug collects in cancer cells and a hospital-based neutron beam then triggers a tiny nuclear reaction inside those cells to destroy them while sparing nearby healthy tissue."},{"id":"neutron-therapeutics","kind":"company","name":"Neutron Therapeutics","route":"/companies/neutron-therapeutics/","tldr":"Neutron Therapeutics makes a compact particle accelerator that produces the neutron beam needed for boron neutron capture therapy, a form of radiotherapy that targets cancer cells one at a time, so hospitals no longer need a nuclear reactor to offer it."},{"id":"lattice-radiotherapy","kind":"technology","name":"Lattice and GRID radiotherapy","route":"/technologies/lattice-radiotherapy/","status":"phase-2","tldr":"Lattice radiotherapy deliberately treats a bulky tumour unevenly, placing peaks of tumour-destroying dose at spaced points inside it while the tissue between receives far less, relying on bystander and immune effects to extend the kill. It runs on standard linear accelerators, but evidence is mostly palliative and single-arm, and the mechanism is unsettled."},{"id":"radiodynamic-therapy","kind":"technology","name":"Radiodynamic therapy and radiosensitising nanoparticles","route":"/technologies/radiodynamic-therapy/","status":"phase-2","tldr":"Nanoparticles that turn ordinary radiotherapy X-rays into a much bigger dose exactly where they sit."},{"id":"hyperthermia","kind":"technology","name":"Hyperthermia","route":"/technologies/hyperthermia/","status":"established","tldr":"Hyperthermia heats tumours to 40-43 °C to make radiation and chemotherapy work better."}],"trials":[],"papers":[]},{"era":"2028+","title":"Radiation as an immune primer, and radiation from inside","description":"Radiation releases tumour antigens and can switch on the innate immune alarm, or switch it off, depending on dose and fractionation; trials are trying to find the schedule that primes rather than suppresses. Systemic radiation is the radiopharmaceutical roadmap: radioligands, radio-antibodies and alpha emitters that deliver dose to every metastasis, increasingly combined with DNA-repair inhibitors. The two fields are converging on the same question: how to kill the last cell wherever it is.","status":"speculative","refs":[{"id":"idea-bio2-radiotherapy-sting-fractionation","kind":"idea","name":"Pick the radiation dose that switches the immune alarm on, not off","route":"/ideas/idea-bio2-radiotherapy-sting-fractionation/","tldr":"Radiation can alert the immune system through the cGAS-STING pathway, but single doses above roughly 12 to 18 Gy switch on the enzyme TREX1, which destroys the alarm signal. Choosing fractionated schedules around 8 Gy times three for immune priming may add benefit at no extra cost."},{"id":"radiopharma-roadmap","kind":"roadmap","name":"Radiopharmaceutical roadmap: iodine → lutetium → actinium","route":"/roadmaps/radiopharma-roadmap/","tldr":"The radiopharmaceutical roadmap runs eighty years from radioactive iodine for thyroid cancer to alpha-emitting drugs for prostate and neuroendocrine cancers, with isotope supply as the limiting factor."},{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/","status":"phase-2","tldr":"Attaching a radioactive atom to an antibody, so an ADC's targeting is used to deliver radiation instead of chemotherapy."},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/","status":"phase-3","tldr":"Like radioligand therapy but with alpha particles: far more destructive over a much shorter range, so single cells can be killed with less collateral damage."},{"id":"radionuclide-parp-combination","kind":"technology","name":"Radioligand plus DNA-repair inhibitor combinations","route":"/technologies/radionuclide-parp-combination/","status":"phase-1","tldr":"Adding a PARP or ATR inhibitor to a radioactive drug so the tumour cannot repair the damage the radiation causes."},{"id":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/","tldr":"Radical oncology is a horizon map of the wilder ideas in cancer, sorted by how close they are to mattering, with the reason each one might never arrive."}],"trials":[],"papers":[]},{"era":"What sets the pace","title":"Machines, physicists and money","description":"Radiotherapy cures a large share of all cured patients and receives a small share of research funding. Most of the world's population lacks access to a working linear accelerator, and where machines exist they are idle for want of physicists and maintenance. Pooled procurement of machines and service, contracts that pay for uptime rather than hardware, remote planning hubs and remote quality assurance, and low-cost brachytherapy for cervical cancer in every regional centre are the proposals that would change that.","status":"current","refs":[{"id":"b-surgery-radiation-innovation","kind":"bottleneck","name":"Surgery and radiotherapy cure most, get least","route":"/bottlenecks/b-surgery-radiation-innovation/","tldr":"Surgery and radiotherapy cure more people than drugs do, but attract a fraction of the research investment."},{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/","tldr":"Seven in ten cancer deaths happen in low- and middle-income countries, where radiotherapy, pathology, surgery and drugs are scarce."},{"id":"b-workforce","kind":"bottleneck","name":"Not enough oncologists, nurses, pathologists, physicists","route":"/bottlenecks/b-workforce/","tldr":"The number of people with cancer is rising faster than the workforce trained to treat them."},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/","tldr":"A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on."},{"id":"idea-acc-pooled-procurement-radiotherapy","kind":"idea","name":"A Gavi-style pooled purchaser for radiotherapy equipment and service","route":"/ideas/idea-acc-pooled-procurement-radiotherapy/","tldr":"Countries buying radiotherapy machines one at a time pay high prices and get poor service. A single global buyer negotiating for dozens of machines a year could cut prices and demand long-term support."},{"id":"idea-acc-linac-uptime-contracts","kind":"idea","name":"Pay for radiotherapy machine uptime, not for the machine","route":"/ideas/idea-acc-linac-uptime-contracts/","tldr":"Governments and donors should buy guaranteed working hours from radiotherapy vendors, with remote monitoring and regional spare-parts depots, instead of buying machines that then sit broken."},{"id":"idea-acc-remote-planning-hubs","kind":"idea","name":"Round-the-clock remote treatment-planning hubs for clinics without physicists","route":"/ideas/idea-acc-remote-planning-hubs/","tldr":"Hospitals without enough physicists could upload scans to a shared planning centre, where AI drafts the treatment plan and remote experts finish and check it within a day."},{"id":"idea-acc-remote-medical-physics-qa","kind":"idea","name":"One medical physicist covering many radiotherapy machines through remote quality assurance","route":"/ideas/idea-acc-remote-medical-physics-qa/","tldr":"Medical physicists, who keep radiotherapy machines accurate and safe, are in even shorter supply than oncologists in under-resourced systems. Routine linac quality assurance is now largely automated and log-file based, so one physicist could review it remotely while trained radiation therapists take the measurements, covering three to five machines once regulators define the supervision standard."},{"id":"idea-acc-frugal-hdr-brachytherapy","kind":"idea","name":"Low-cost cobalt-60 brachytherapy for cervical cancer in every regional centre","route":"/ideas/idea-acc-frugal-hdr-brachytherapy/","tldr":"Cervical cancer cannot be cured by external radiotherapy alone; it needs brachytherapy, internal radiation that LMIC radiotherapy centres frequently lack or cannot keep running because iridium-192 sources must be replaced every three months. Cobalt-60 sources last about five years and give equivalent doses, so funding cobalt units for every regional centre closes a well-understood cure gap."}],"trials":[],"papers":[]}],"watch":[]}