Optimal sequencing of brain radiotherapy and immunotherapy for patients with non-small cell lung cancer and driver gene-negative, asymptomatic brain metastases

To investigate the efficacy and safety of combining brain radiotherapy (RT) with immune checkpoint inhibitors (ICIs) across different treatment sequences. A retrospective analysis was performed on 95 patients with non-small cell lung cancer (NSCLC) characterized by negative driver genes and asymptomatic brain metastases (BM) who received ICIs. Patients were divided into three groups based on their receipt of brain RT and the timing relative to ICIs administration: group A (concurrent ICIs and RT), group B (sequential ICIs and RT), and group C (ICIs without RT). The efficacy and safety profiles of each group were assessed. The median follow-up time was 20 months (range: 2–57 months). The median intracranial progression-free survival (miPFS) for groups A, B, and C was 14 (95% CI: 9.139–18.861), 14 (95% CI: 9.213–18.787), and 10 months (95% CI: 5.213–14.787), respectively (P = 0.048). The median overall survival (mOS) for groups A, B, and C was 23 (95% CI: 18.489–27.511), 20 (95% CI: 15.186–24.814), and 15 months (95% CI: 10.390–19.610), respectively (P = 0.076). The incidence rates of RT-induced brain injury in groups A and B were 30.0% and 26.7%, respectively. Univariate and multivariate analyses identified combined bevacizumab treatment and high PD-L1 expression as independent favorable prognostic factors for OS. Among patients with NSCLC with negative driver genes and asymptomatic BM, combining ICIs with brain RT demonstrated superior efficacy compared with ICIs alone. Concurrent administration of ICIs and brain RT resulted in prolonged OS compared with sequential treatment, although the difference did not reach statistical significance, and the concurrent approach did not increase the risk of adverse events (AEs). The combination of immunotherapy and radiotherapy may exert an immune-activating and synergistic effect. This study found that the intracranial progression-free survival(14 months vs. 10 months) and overall survival (23 months vs. 15 months) of patients receiving ICIs combined with radiotherapy were significantly prolonged compared with those without radiotherapy. In patients with asymptomatic brain metastases from non-small cell lung cancer, the optimization of the combination of immunotherapy and brain radiotherapy has always been a critical focus in clinical research. This study systematically evaluated the efficacy and safety of concurrent versus sequential administration of immunotherapy and brain radiotherapy. The findings revealed no significant differences in intracranial progression-free survival (14 months vs. 14 months) or overall survival (23 months vs. 20 months) between the two groups. Additionally, there were no notable differences in the incidence or severity grading of adverse events. In this study, univariate and multivariate analyses found that combined bevacizumab treatment and high PD-L1 expression were independent favorable prognostic factors for overall survival.