{"entity":{"id":"paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999","kind":"paper","name":"Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission","aka":[],"tldr":"Pooling 987 patients from seven trials showed that irradiating the brain of people whose small-cell lung cancer had gone into remission, before any brain secondaries appeared, made them live longer.","summary":"Aupérin, Arriagada, Pignon, Le Péchoux and the Prophylactic Cranial Irradiation Overview Collaborative Group analysed individual data on 987 patients with small-cell lung cancer in complete remission from seven trials comparing prophylactic cranial irradiation with none. Survival was the main endpoint.\n\nIt is one of the few interventions in oncology that treats an organ with no detectable disease in it and extends life, and the principle it established, that micrometastatic sanctuary sites can be treated pre-emptively, is the direct ancestor of the brain metastasis prevention question that next-generation ALK and EGFR inhibitors now raise.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1999","url":"https://doi.org/10.1056/NEJM199908123410703"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/10441603/"}],"tags":["lung-evidence"],"related":["paper-slotman-n-engl-j-med","paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999","idea-bio2-brain-met-prevention-trials"],"cancers":["lung-cancer","sclc","limited-stage-sclc","extensive-stage-sclc"],"sections":["radiation"],"technologies":["radiotherapy","stereotactic-radiosurgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["brain-metastases","prophylactic-cranial-irradiation","mrd"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-dormancy-mrd","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1999,"doi":"10.1056/NEJM199908123410703","pmid":"10441603","authors":"Aupérin A, Arriagada R, Pignon JP, et al.","paperType":"meta-analysis","findings":["Relative risk of death 0.84 (95 percent confidence interval 0.73 to 0.97; P equals 0.01), corresponding to a 5.4 percentage point increase in three-year survival, from 15.3 percent to 20.7 percent.","Relative risk of recurrence or death 0.75 (0.65 to 0.86).","Individual data on 987 patients in complete remission from seven randomised trials."],"whatItMeans":"Treating the brain before the cancer gets there works in small-cell lung cancer, and it is the proof of principle behind every later attempt to prevent rather than treat brain metastases.","caveats":["Trials from before routine brain MRI, so some patients classified as having no brain disease would today be found to have it.","Neurocognitive effects were not measured with modern instruments, and hippocampal-avoidance techniques did not exist; the risk-benefit calculation has shifted.","Extensive-stage disease was addressed separately and remains contested, with the Japanese trial finding no survival benefit when MRI surveillance is used instead."],"changedPractice":true,"participants":987},"route":"/key-papers/paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999/","neighbours":{"paper":[{"id":"paper-slotman-n-engl-j-med","kind":"paper","name":"Prophylactic cranial irradiation in extensive small-cell lung cancer","route":"/key-papers/paper-slotman-n-engl-j-med/"},{"id":"paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999","kind":"paper","name":"Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide","route":"/key-papers/paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999/"}],"idea":[{"id":"idea-lung-brain-metastasis-prevention-as-a-primary-endpoint","kind":"idea","name":"Measure brain metastasis prevention as a primary endpoint, not as a secondary one","route":"/ideas/idea-lung-brain-metastasis-prevention-as-a-primary-endpoint/"},{"id":"idea-bio2-brain-met-prevention-trials","kind":"idea","name":"Prevention trials aimed only at brain metastasis","route":"/ideas/idea-bio2-brain-met-prevention-trials/"}],"cancer":[{"id":"extensive-stage-sclc","kind":"cancer","name":"Extensive-stage small-cell lung cancer","route":"/cancers/extensive-stage-sclc/"},{"id":"limited-stage-sclc","kind":"cancer","name":"Limited-stage small-cell lung cancer","route":"/cancers/limited-stage-sclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"section":[{"id":"radiation","kind":"section","name":"Radiation Therapy","route":"/fronts/radiation/"}],"term":[{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","route":"/terms/brain-metastases/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"radiotherapy","kind":"term","name":"Radiotherapy","route":"/terms/radiotherapy/"},{"id":"stereotactic-radiosurgery","kind":"term","name":"Stereotactic radiosurgery (SRS)","route":"/terms/stereotactic-radiosurgery/"}],"technology":[{"id":"prophylactic-cranial-irradiation","kind":"technology","name":"Prophylactic cranial irradiation vs MRI surveillance","route":"/technologies/prophylactic-cranial-irradiation/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}]}}