Short-course hypofractionated radiotherapy of 4 Gy per fraction for limited-stage small cell lung cancer: a randomized pilot trial.

Background: Local-regional relapse remains high after the standard radiotherapy regimen for limited-stage small cell lung cancer (LS-SCLC). Short-course hypofractionated radiotherapy may improve disease control. In this single-institution open-label pilot trial, we aimed to explore the preliminary safety and efficacy of short-course hypofractionated radiotherapy with 4 Gy per fraction. Methods: LS-SCLC patients (18 to 75 years old) with Karnofsky performance scale score (KPS) over 70 were enrolled. Patients were randomized with a ratio of 1:1 to receive radiotherapy of 48 Gy/12 f once daily (low-dose arm) or 60 Gy/15 f once daily (high-dose arm). Concurrent chemotherapy was administered for 4 to 6 cycles. The primary objective was the radiation-induced toxicity and the secondary objective was 2-year survival outcome. Results: From August 2022 to August 2023, 44 patients with a median age of 63.5 years old were prospectively enrolled with 22 patients in each of the low-dose arm and the high-dose arm. The median follow-up time was 20 months (interquartile range, 15.3-28.0 months). The incidence of Grade 3 and higher toxicity was 13.6% in the low-dose arm and 36.4% in the high-dose arm (P=0.16), among which the predominant one was myelosuppression. The incidence of atelectasis (50.0% Conclusions: Short-course hypofractionated radiotherapy of 4 Gy per fraction was preliminarily safe and efficient for LS-SCLC with high local-regional control. For striking the balance of toxicity and efficacy, the regimen of 48 Gy/12 f might be a novel and promising radiation regimen for future exploration. Trial Registration: Hypofraction Radiotherapy for Limited-Stage Small Cell Lung Cancer: a randomized pilot trial (No. NCT05523908), registered on clinicaltrials.gov in August 2022.