High-dose versus standard dose twice-daily thoracic radiotherapy in limited stage small-cell lung cancer: final survival data, long-term toxicity and relapse patterns in a randomised, open-label, phase II trial

Chemoradiotherapy is standard treatment for limited stage (LS) small-cell lung cancer (SCLC). A majority of patients relapse and there is a need for better treatment. We investigated whether twice-daily thoracic radiotherapy (TRT) of 60 Gy/40 fractions improve survival compared with the established schedule of 45 Gy/30 fractions. Here we report final survival data and long-term toxicity. Randomised, open-label, phase II trial. Eligible patients had PS 0-2, were ≥18 years, underwent FDG-PET/CT and brain MRI for staging and were randomised 1:1 to TRT of 60 or 45 Gy. Patients were to receive four courses of platinum/etoposide chemotherapy and responders were offered prophylactic cranial irradiation. 170 patients were randomized (60 Gy: n=89, 45 Gy: n=81). Median age was 65, 31% ≥70 years, 57% women, 89% had PS 0-1, 83% stage III disease, median planning target volume was 305 cm3, and 67% were treated with three-dimensional conformal radiotherapy (3D CRT). Median OS in the 60 Gy group was significantly longer (43.5 vs. 22.5 months, HR 0.68, 95% CI 0.48-0.98, p=0.037). The 60 Gy group did not experience more acute grade 3-4 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 oesophageal strictures, while eleven patients (60 Gy: n=5, 45 Gy: n=6) developed severe long-term eating and swallowing dysfunction. Twice-daily TRT of 60 Gy/40 fractions was well tolerated and prolonged survival compared with 45 Gy/30 fractions in LS SCLC patients.