Differential Effect of Consolidative Thoracic Radiation Therapy in Extensive-Stage Small Cell Lung Cancer Based on Sex

Abstract

BackgroundThe landmark CREST trial demonstrated that consolidative thoracic radiotherapy (cTRT) improved overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer (ES-SCLC), with potentially increased benefit in women compared to men. It is unknown whether similar findings would apply after chemoimmunotherapy (chemo-IO) became the standard first-line treatment. In this analysis, we report national practice patterns and survival outcomes of cTRT according to patient sex. MethodsWe included patients from a nationwide de-identified electronic health record-derived database diagnosed with stage IV SCLC (2014-2021) who completed 4-6 cycles of first-line systemic therapy (platinum-doublet chemo or chemo-IO). We evaluated OS and PFS using multivariable Cox proportional hazards regression with receipt of cTRT as an independent variable and stratified by sex. As a sensitivity analysis, we weighted the models by the inverse probability of receiving cTRT. ResultsA total of 1,227 patients were included (850 chemo, 377 chemo-IO). There were no statistically significant differences in baseline characteristics between patients who did and did not receive cTRT. Among women, cTRT was associated with superior OS (adjusted hazard ratio (HR) 0.67; 95% confidence interval [CI] 0.52-0.87) and PFS (HR 0.63; 95% CI 0.49-0.82) compared to those not receiving cTRT. Conversely, no OS or PFS benefit with cTRT was observed in men [(OS HR 1.03; 95% CI 0.80-1.31; PFS HR 1.12; 95% CI 0.85-1.47)]. Findings were similar in weighted analyses. ConclusionThe survival efficacy of cTRT may be moderated by sex, with female patients appearing more likely to benefit than male patients. These findings reflect sex-based survival trends with similar effect sizes to those observed in the CREST trial. While the underpinnings of this association need to be elucidated, stratification by sex should be considered for RCTs studying cTRT in ES-SCLC.