The evidence supporting this protocol is provided by two phase 3 multicentre randomised trials Turrisi et al. and Faivre-Finn et al.rr The trial by Turrisi et al.involved 417 patients with limited stage SCLC comparing hyperfractionated accelerated radiation therapy with once-daily radiation therapy in patients receiving concurrent cisplatin and etoposide.r
Between 1989 and 1992, 211 patients were randomised to receive 45Gy in twice daily 1.5Gy fractions over 3 weeks and 206 patients were randomised to receive 45Gy in once daily fractions of 1.8Gy over 5 weeks starting with cycle 1 of chemotherapy. Both arms were delivered with 4, three-weekly cycles of concurrent cisplatin and etoposide chemotherapy. Cisplatin dose was 60mg/m2 (on D1) and etoposide (120mg/m2 D1-3 of each cycle).
The primary end point was overall survival (OS). After a median follow up of almost 8 years, the median OS was 23 vs.19 months, and local failure was 36% vs 52%, both in favour of twice-daily concurrent chemoradiation therapy.
The CONVERT trial involved 547 patients comparing hyperfractionated accelerated radiation therapy with once-daily radiation therapy in patients receiving concurrent cisplatin and etoposide.r Between 2008 and 2017, 274 patients were randomised to receive radiation therapy of 45Gy in 30 twice-daily fractions (1.6Gy over 19 days) and 273 patients were randomised to receive 66Gy in 33 once-daily fractions (2Gy over 45 days). In both arms, the radiation therapy started on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks). The primary end point was OS. A 12% difference in OS at 2 years was considered to be clinically significant and to demonstrate superiority.
After a median follow up of 45 months, the median OS was 30 months (95% CI: 24-34 months) in the twice-daily group versus 25 months (95% CI: 21-31 months) in the once-daily group (hazard ratio for death in the once daily group 1.18 [95% CI: 0.95-1.45]; p=0.14).
Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiation therapy in patients with limited-stage small cell lung cancer. Since the trial was designed to show superiority of once-daily radiation therapy and was not powered to show equivalence, the implication is that twice-daily radiation therapy should continue to be considered the standard of care in this setting.