ArticleFrontiers in oncology2026
Stereotactic versus hippocampal avoidance whole-brain radiotherapy combined with immune checkpoint inhibitors for multiple brain metastases in non-small cell lung cancer: a multi-center retrospective study.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: The optimal radiotherapy (RT) approach combined with immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) patients with multiple brain metastases (BM) remains controversial. This study compared the clinical efficacy of stereotactic radiotherapy (SRT) plus ICIs versus hippocampal avoidance whole-brain radiotherapy (HA-WBRT) plus ICIs in this population. Methods: We retrospectively reviewed NSCLC patients with multiple BM(>4) who underwent RT plus ICIs from 2018 to 2024. Exclusion criteria included SRT-alone or WBRT-alone, Karnofsky performance status (KPS) <70, suspected leptomeningeal disease, or 1-4 BM lesions. Patients were divided into SRT+ICIs and HA-WBRT+ICIs cohorts by 1:1 propensity score matching (PSM). In the matched datasets, overall survival (OS) was the primary endpoint and intracranial progression-free survival (iPFS) was the secondary endpoint. Survival outcomes were analyzed using Kaplan-Meier and log-rank tests. Cox proportional hazards models identified factors associated with OS and iPFS. Results: Of the 256 patients diagnosed, 124 eligible patients (992 lesions) were analyzed. After 1:1 PSM, each cohort included 62 patients (SRT+ICIs and HA-WBRT+ICIs). The SRT+ICIs cohort demonstrated significantly longer median OS(21.4 vs. 15.5 months; P<0.001) and median iPFS (10.5 vs. 8.1 months; P<0.001) compared to the HA-WBRT+ICIs cohort. On multivariate analysis, SRT+ICIs was independently associated with improved OS (HR 0.381,95% CI 0.241-0.695, P<0.001) and iPFS (HR 0.513, 95% CI 0.297-0.961,P<0.001) versus HA-WBRT+ICIs. Adverse events (AEs) were similar between cohorts. No grade > 3 AEs were found. Conclusions: For NSCLC patients with multiple BM, SRT+ICIs is associated with significantly improved OS and iPFS versus HA-WBRT+ICIs, without an increased risk of AEs. SRT+ICIs represents a promising approach for this population.
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