High-Dose Versus Standard-Dose Twice-Daily Thoracic Radiotherapy in Limited-Stage SCLC: Final Survival Data, Long-Term Toxicity, and Relapse Patterns in a Randomized, Open-Label, Phase II Trial

Abstract Introduction Chemoradiotherapy is standard treatment for limited-stage SCLC. However, most patients relapse and there is a need for better treatment. We investigated whether twice-daily thoracic radiotherapy (TRT) of 60 Gy/40 fractions improves survival compared with the established schedule of 45 Gy/30 fractions. Here, we report final survival data and long-term toxicity. Methods Randomized, open-label, phase II trial. Eligible patients had performance status of 0 to 2, were above or equal to 18 years of age, underwent ¹⁸F-fluorodeoxyglucose positron emission tomography computed tomography and brain magnetic resonance imaging for staging, and were randomized 1:1 to TRT of 60 or 45 Gy. Patients were to receive four courses of platinum and etoposide chemotherapy, and responders were offered prophylactic cranial irradiation. Results A total of 170 patients were randomized (60 Gy: n=89, 45 Gy: n=81). Median age was 65 years, 31% above or equal to 70 years, 57% women, 89% had performance status of 0 to 1, 83% stage III disease, median planning target volume was 305 cm³, and 67% were treated with three-dimensional conformal radiotherapy. Median overall survival in the 60 Gy group was significantly longer (43.5 versus 22.5 mo, hazard ratio 0.68, 95% confidence interval 0.48–0.98, p = 0.037). The 60 Gy group did not experience more acute grades 3 to 4 esophagitis (60 Gy: 21%, 45 Gy: 18%, p = 0.83) or pneumonitis (60 Gy: 3%, 45 Gy: 0%, p = 0.39). Two patients, both in the 60 Gy group, developed esophageal strictures, whereas 11 patients (60 Gy: n=5, 45 Gy: n=6) developed severe long-term eating and swallowing dysfunction. Conclusion Twice-daily TRT of 60 Gy/40 fractions was well tolerated and prolonged survival compared with 45 Gy/30 fractions in patients with limited-stage SCLC. This trial is registered at ClinicalTrials.gov: NCT02041845.