The risk of symptomatic radiation pneumonitis in small cell lung cancer patients following sequential immunochemotherapy and radiotherapy: a multicenter retrospective cohort study.

[OBJECTIVE] Immune checkpoint inhibitors plus thoracic radiotherapy (RT) may magnify the radiation pneumonitis (RP) risk. Data on the risk for symptomatic RP in small cell lung cancer (SCLC) patients following RT after induction immunochemotherapy using anti-programmed cell death protein-1 monoclonal antibody Serplulimab, cisplatin plus etoposide are limited.

[METHODS] This retrospective study included 443 SCLC patients from two hospitals who finished thoracic intensity-modulated radiation therapy or volumetric modulated arc therapy between April 1, 2022 and March 31, 2025. The primary endpoint was the incidence of grade 2 or worse (grade 2+) RP. Fine-Gray competing risks regression analyses were used to identify the potential risk factors of RP2+.

[RESULTS] The follow-up duration was (15.8 ± 4.6) weeks since the end of RT. In detail, 87 (19.6%), 35 (7.9%), and 6 (1.4%) patients developed grade 2, grade 3, and grade 4 RP respectively. Six patients died from non-RP-related diseases were treated as competing events. On univariate analysis, male, pneumoconiosis, ECOG status, concurrent chemoradiotherapy (CCRT) were positively correlated with the incidence of RP2+, with subdistribution hazard ratio (SHR) and 95% confidence interval (CI) of 1.81 (1.29-2.55), 2.56 (1.35-4.87), 1.53 (1.17-1.99) and 2.15 (1.35-3.42), respectively (all P < 0.05), while VO, left ventricular ejection fraction (LVEF), and forced expiratory volume in one second (FEV) were negatively correlated with RP2+, with SHR and 95%CI of 0.89 (0.84-0.935), 0.98 (0.96-1.00), and 0.34 (0.19-0.61), respectively (all P < 0.05). Further multivariate competing risks analysis revealed that male, CCRT, and VO2max were independent predictors of RP2+, with SHR and 95% as 1.84 (1.22-2.78), 1.72 (1.04-2.87), and 0.92 (0.86-0.98), respectively (all P < 0.05). Additionally, immunochemotherapy before RT, preexisting pulmonary co-morbidities and smoking history were not significant indicators of RP2+ (P > 0.05, respectively).

[CONCLUSION] The incidence of RP2 + following sequential immunochemotherapy and RT was positively associated with male and CCRT, but negatively correlated with VO max in SCLC patients.

[CLINICAL TRIAL NUMBER] Not applicable.