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
Bjørn Henning Grønberg, Kristin Toftaker Killingberg, Øystein Fløtten, Maria Moksnes Bjaanæs, Odd Terje Brustugun, Tesfaye Madebo, Seppo W. Langer, Signe Lenora Risumlund, Tine Schytte, Nina Helbekkmo, Kirill Neumann, Øyvind Yksnøy, Jens Engleson, Sverre Fluge, Thor Naustdal, Liv Giske, Jan Nyman, Georgios Tsakonas, Tarje Onsøien Halvorsen
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 18 F-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 cm 3 , 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.