{"entity":{"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","aka":[],"tldr":"Giving the same total radiation dose twice a day over three weeks instead of once a day over five raised five-year survival from 16 to 26 percent, at the cost of a much sorer gullet.","summary":"Turrisi, Kim, Blum and colleagues randomised 417 patients with limited small-cell lung cancer, all receiving four 21-day cycles of cisplatin and etoposide, to 45 Gy of concurrent thoracic radiotherapy given either twice daily over three weeks or once daily over five, starting with cycle 1 of chemotherapy.\n\nIt is the trial that defined limited-stage small-cell treatment for twenty-five years, and it is also a study in why a proven regimen can fail to be adopted: twice-daily radiotherapy needs two hospital visits a day for three weeks and causes grade 3 oesophagitis in more than a quarter of patients, so many centres continued once-daily treatment regardless.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 1999","url":"https://doi.org/10.1056/NEJM199901283400403"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/9920950/"}],"tags":["lung-evidence"],"related":["paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999","paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024","radiation-roadmap"],"cancers":["lung-cancer","sclc","limited-stage-sclc"],"sections":["radiation"],"technologies":["radiotherapy","imrt-igrt"],"targets":[],"drugs":["cisplatin","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":["chemoradiation"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol","b-knowledge-diffusion"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":1999,"doi":"10.1056/NEJM199901283400403","pmid":"9920950","authors":"Turrisi AT, Kim K, Blum R, et al.","paperType":"rct","findings":["Median survival 23 months with twice-daily radiotherapy against 19 months with once-daily, after a median follow-up of almost 8 years (P equals 0.04 by log-rank).","Survival with twice-daily radiotherapy 47 percent at two years and 26 percent at five years; with once-daily, 41 percent and 16 percent.","Grade 3 oesophagitis in 27 percent of the twice-daily group against 11 percent of the once-daily group.","Overall two- and five-year survival across both arms 44 percent and 23 percent, a considerable improvement over previous results in limited small-cell lung cancer."],"whatItMeans":"The standard of care in limited-stage small-cell lung cancer from 1999 until ADRIATIC added immunotherapy in 2024, and a rare example of a curative gain in a disease that has had almost none.","caveats":["45 Gy twice daily is not the only accelerated schedule, and the later CONVERT and higher-dose once-daily trials did not settle the question.","Grade 3 oesophagitis in 27 percent is a substantial cost, and toxicity is part of why adoption has been patchy.","Chemotherapy, staging and supportive care of the 1990s; patients today also receive prophylactic cranial irradiation and, since ADRIATIC, consolidation durvalumab."],"changedPractice":true,"participants":417},"route":"/key-papers/paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999/","neighbours":{"paper":[{"id":"paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024","kind":"paper","name":"Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer","route":"/key-papers/paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024/"},{"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","route":"/key-papers/paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999/"}],"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/"},{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"}],"cancer":[{"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":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"radiotherapy","kind":"term","name":"Radiotherapy","route":"/terms/radiotherapy/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"drug":[{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"etoposide","kind":"drug","name":"Etoposide","route":"/drugs/etoposide/"}],"bottleneck":[{"id":"b-knowledge-diffusion","kind":"bottleneck","name":"Knowledge reaches practice too slowly","route":"/bottlenecks/b-knowledge-diffusion/"},{"id":"b-surgery-radiation-innovation","kind":"bottleneck","name":"Surgery and radiotherapy cure most, get least","route":"/bottlenecks/b-surgery-radiation-innovation/"},{"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/"}]}}