A Comparison of Hypofractionated and Twice-Daily Thoracic Irradiation in Limited-Stage Small-Cell Lung Cancer: An Overlap-Weighted Analysis

SIMPLE SUMMARY: The optimal thoracic radiotherapy schedule for limited-stage small cell lung cancer (LS-SCLC) patients remains controversial. We conducted a propensity score adjusted analysis of LS-SCLC patients treated at our institutions with 40Gy/15 fractions versus 45Gy/30 twice daily. After overlap weighting for clinical and treatment variables and attaining good balance, we did not find a significant difference in overall survival, locoregional recurrence risk, thoracic response, or ≥grade 3 toxicity. Moderate hypofractionation, with its similar outcomes and logistical advantages, may present a reasonable alternative to twice daily radiotherapy. ABSTRACT: Despite evidence for the superiority of twice-daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited-stage small-cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules. A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45 Gy/30 fractions) or HFRT (40 Gy/15 fractions) schedules from 2007 to 2019. Overlap weighting using propensity scores was performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any ≥grade 3 (including lung, and esophageal) toxicity were determined using multivariable regression modelling. A total of 173 patients were included in the overlap-weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The median follow-up was 20.4 months. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, p = 0.38), LRR risk (HR 1.48, p = 0.38), thoracic response (odds ratio [OR] 0.23, p = 0.21), any ≥grade 3+ toxicity (OR 1.67, p = 0.33), ≥grade 3 pneumonitis (OR 1.14, p = 0.84), or ≥grade 3 esophagitis (OR 1.41, p = 0.62). HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.