Frontiers in oncology · 2026
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.
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Wang Xiaoliang, Zheng Yanan, Wang Aimin, Zhao Xiaolan, Ruan Xudong, Wu Choubin, Han Chunquan
Аннотация
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.
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.