Concurrent Stereotactic Radiotherapy and Immune Checkpoint Inhibitors for Multiple Brain Metastases in Non-Small Cell Lung Cancer - A Multi-Center Retrospective Analysis.

BACKGROUND: This study aimed to evaluate the efficacy and safety of concurrent versus sequential stereotactic radiotherapy (SRT) and immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients with multiple brain metastases (BM). METHODS: We retrospectively analyzed 198 NSCLC patients with BM who underwent SRT and ICIs treatment between 2017 and 2024. Of 136 eligible patients, were assigned to two cohorts and subcohorts through propensity score matching. The concurrent cohort consisted of 68 patients receiving ICIs within 14 days of SRT (post-SRT 34 cases and pre-SRT 34 cases). The sequential cohort included another 68 patients undergoing sequential treatment > 14 days apart (post-SRT1 31 cases and pre-SRT1 37 cases). Overall survival (OS) and intracranial progression-free survival (iPFS) were the primary endpoints. Secondary endpoints were intracranial objective response rate (iORR), disease control rate (DCR) and adverse events (AEs). RESULTS: Concurrent group achieved significantly superior median OS (24.5 months vs. 18.3 months, HR = 0.68, 95% CI 0.49-0.94, p = 0.001) and median iPFS (14.2 months vs. 9.8 months, HR = 0.62, 95% CI 0.45-0.86, p < 0.001) compared to the sequential group. Subgroup analysis, the post-SRT group showed significantly improved median OS (27.1 months vs. 17.2, 19.2, 13.2 months, p < 0.05) and median iPFS (20.1 months vs. 10.5, 12.1, 5.3 months, p < 0.05) compared to the other three groups (pre-SRT, post-SRT1 and pre-SRT1). Multivariate analysis revealed that a treatment interval ≤ 14 days was an independent protective factor for both iPFS (p = 0.004) and OS (p = 0.019). Subgroup analysis demonstrated that a treatment interval ≤ 7 days was superior to an interval of 8-14 days or > 14 days. Furthermore, ICIs following SRT was associated with improved OS (p = 0.003) and iPFS (p < 0.001). No significant differences were observed in radionecrosis (RN) and AEs. CONCLUSION: Concurrent SRT with ICI, especially ICIs following SRT, provides superior survival outcomes for NSCLC patients with multiple BM, without increasing AEs. The timing of therapy is a critical factor influencing the efficacy of the combined regimen.