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

Background: Immune checkpoint inhibitors (ICIs) plus thoracic radiotherapy may magnify the radiation pneumonitis (RP) risk. Data on the risk for symptomatic RP in small cell lung cancer (SCLC) patients following radiotherapy after induction immune-chemotherapy are limited. Patients and methods : This multicenter retrospective study included patients with SCLC from two hospitals who started thoracic intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) between April 1, 2022 and March 31, 2025. The primary endpoint was grade 2 or worse (grade 2+) RP according to the Common Terminology Criteria for Adverse Events v5.0. Logistic regression analyses and receiver operating characteristic (ROC) analysis were used to assess the correlated parameters with grade 2+ RP. Results : A total of 443 patients were reviewed. The median follow-up period was 3 months after radiotherapy. In detail, 87 [19.6%], 35 [7.9%], and 6 [1.4%] developed grade 2, grade 3, and grade 4 RP in this cohort, respectively. No patients recorded grade 0 or 5 RP. On multivariable analysis, male, concurrent chemoradiotherapy (CCRT), VO2max and FEV1 significantly predicted the incidence of grade 2+ RP, with odd ratios (OR) and 95% confidence interval (CI) of 2.408 (1.406-4.125), 2.249 (1.193-4.240), 0.897 (0.828-0.972) and 0.369 (0.161-0.846), respectively(all P<0.05); whereas prior immune-chemotherapy, preexisting pulmonary co-morbidities and smoking history were not significant predictors (P> 0.05, respectively). Furthermore, the area under the ROC curve established using these parameters was 0.766 (95% CI: 0.718-0.815) for predicting the occurrence of grade 2+ RP. Conclusions : Prior immune-chemotherapy (ranging from 0 to 4 cycles) is not correlated with the onset of grade 2+ RP. The incidence of grade 2+ RP was relatively high in this multicenter study, and its risk increased remarkably at decreased VO ₂ max and FEV ₁ . Male and CCRT were independent risk factor of grade 2+ RP. Our findings can aid in RP risk prediction and radiotherapy planning.