# Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide

Source: https://onco.cc/key-papers/paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999/  
OnCo record `paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

It 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: New England Journal of Medicine
- Year: 1999
- DOI: 10.1056/NEJM199901283400403
- Authors: Turrisi AT, Kim K, Blum R, et al.
- 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.
- What it means: 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.

## Sources

- N Engl J Med 1999: https://doi.org/10.1056/NEJM199901283400403
- PubMed: https://pubmed.ncbi.nlm.nih.gov/9920950/

## Connected records

- key papers: [Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer](https://onco.cc/key-papers/paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024/), [Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission](https://onco.cc/key-papers/paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999/)
- roadmaps: [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](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/), [Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH](https://onco.cc/roadmaps/radiation-roadmap/)
- cancers: [Limited-stage small-cell lung cancer](https://onco.cc/cancers/limited-stage-sclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)
- fronts: [Radiation Therapy](https://onco.cc/fronts/radiation/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Radiotherapy](https://onco.cc/terms/radiotherapy/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/)
- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Etoposide](https://onco.cc/drugs/etoposide/)
- bottlenecks: [Knowledge reaches practice too slowly](https://onco.cc/bottlenecks/b-knowledge-diffusion/), [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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