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

PURPOSE/OBJECTIVE(S) 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. MATERIALS/METHODS A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45Gy/30 fractions) or HFRT (40Gy/15 fractions) schedules from 2007-2019. Overlap weighting using propensity scores were 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. E-values were used to assess the sensitivity of effect estimate to unobserved confounding. RESULTS 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 5-year OS for the overlap weighted cohort was 24.3% (95% CI, 16.1-36.6), and specifically 22.1% (95% CI, 12.7-38.5) and 26.6% (95% CI, 14.4-49.0%) when stratified by BID and HFRT cohorts specifically. The 5-year LRR risk for the same cohorts after overlap weighting were 68.9% (95% CI, 59.2-80.1), 68.9% (95% CI, 56.6-83.8), and 69.2% (95% CI, 55.3-86.6), respectively. 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), CRT 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). These effect estimates were consistent between unweighted and overlap weighted cohorts. CONCLUSION HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.