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

Vikram Jairam; Pamela R Soulos; Madhav K C; Cary P Gross; Ben J Slotman; Anne C Chiang; Henry S Park

doi:10.1016/j.adro.2023.101413

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

Adv Radiat Oncol. 2023 Dec 3;9(4):101413. doi: 10.1016/j.adro.2023.101413. eCollection 2024 Apr.

Authors

Vikram Jairam¹, Pamela R Soulos², Madhav K C², Cary P Gross^{2

3}, Ben J Slotman⁴, Anne C Chiang⁵, Henry S Park^{2

6}

Affiliations

¹ Department of Radiation Oncology, Sutter Medical Group, Sacramento, California.
² Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut.
³ Section of General Internal Medicine, Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
⁴ Department of Radiation Oncology, Amsterdam University Medical Center, De Boelelaan, Amsterdam, The Netherlands.
⁵ Section of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
⁶ Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.

Abstract

Purpose: The landmark randomized trial on chest irradiation in extensive disease small cell lung cancer (CREST) demonstrated that consolidative thoracic radiation therapy (cTRT) improved overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer, with potentially increased benefit in women compared with men. It is unknown whether similar findings would apply after chemoimmunotherapy became the standard first-line treatment. In this analysis, we report national practice patterns and survival outcomes of cTRT according to patient sex.

Methods and materials: We included patients from de-identified electronic health record-derived database diagnosed with stage IV small cell lung cancer (2014-2021) who completed 4 to 6 cycles of first-line systemic therapy (platinum-doublet chemotherapy or chemoimmunotherapy). 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.

Results: A total of 1227 patients were included (850 chemotherapy, 377 chemoimmunotherapy). 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% CI, 0.52-0.87) and PFS (HR, 0.63; 95% CI, 0.49-0.82) compared with 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.

Conclusions: The 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. Although the underpinnings of this association need to be elucidated, stratification by sex should be considered for randomized-controlled trials studying cTRT in extensive-stage small cell lung cancer.