Patterns of failure analysis and the role of consolidative thoracic radiotherapy in extensive‑stage small‑cell lung cancer treated with first‑line chemoimmunotherapy

The efficacy of consolidative thoracic radiotherapy (cTRT) for extensive-stage small-cell lung cancer (ES-SCLC) remains controversial in the immunotherapy era, and the failure patterns in these patients require further exploration. This study aimed to investigate the failure pattern and the efficacy of cTRT in ES-SCLC patients treated with first-line chemoimmunotherapy. Brain metastases (BMs)-free ES-SCLC patients treated with first-line chemoimmunotherapy were included and divided into different groups based on whether they received cTRT or not. Failure patterns were recorded. Kaplan-Meier survival curves and log-rank tests were used to compare the survival outcomes between the groups. Additionally, the survival benefits of cTRT were further evaluated through univariable and multivariate analyses. Propensity score matching (PSM) was used to balance the baseline characteristics. A total of 100 eligible BMs-free ES-SCLC patients were enrolled, with 24 (24.0%) in the cTRT group and 76 (76.0%) in the no-cTRT group. Failure pattern analyses revealed that intrathoracic failure remained the primary failure pattern in chemoimmunotherapy-treated ES-SCLC. The addition of cTRT to chemoimmunotherapy reduced the risk of intrathoracic failure (from 60.0% to 29.4%), and both intrathoracic and intracranial progression were delayed by cTRT before and after PSM. Moreover, cTRT significantly improved the overall survival (OS) of ES-SCLC patients compared to no-cTRT (median OS: not reached vs. 14.1 months; HR = 0.40, 95% CI: 0.22–0.70, P = 0.01). Grade 3 pneumonitis was recorded in 9.7% and 3% of patients in the cTRT group and the no-cTRT group, respectively. No cases of grade 4 or 5 pneumonitis occurred. In conclusion, this study characterized the failure patterns in BMs-free ES-SCLC patients treated with chemoimmunotherapy. cTRT significantly reduces intrathoracic and intracranial progression, and these benefits significantly translated into improved progression free survival and OS in chemoimmunotherapy-responsive ES-SCLC. These findings warrant the validation of prospective trials in the immunotherapy era.