Objective:

To compare the clinical efficacy of stereotactic radiotherapy (SRT) plus immune checkpoint inhibitors (ICIs) versus hippocampal avoidance whole-brain radiotherapy (HA-WBRT) plus ICIs in non-small cell lung cancer (NSCLC) patients with multiple brain metastases.

Approach:

• Study Design: Retrospective review of NSCLC patients with multiple brain metastases who underwent RT plus ICIs from 2018 to 2024, with specific exclusion criteria.

Key Findings:

• A total of 124 eligible patients were analyzed after matching, with 62 in each cohort.
• The SRT+ICIs cohort demonstrated significantly longer median OS (21.4 months vs. 15.5 months; P<0.001) and median iPFS (10.5 months vs. 8.1 months; P<0.001) compared to the HA-WBRT+ICIs cohort.
• 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).
• Adverse events were similar between cohorts, with no grade > 3 adverse events reported.

Interpretation:

SRT+ICIs is associated with significantly improved OS and iPFS compared to HA-WBRT+ICIs in NSCLC patients with multiple brain metastases, without an increased risk of adverse events.

Limitations:

• The retrospective nature of the study may introduce bias.
• Generalizability is limited due to specific inclusion and exclusion criteria.

Conclusion:

SRT+ICIs represents a promising approach for NSCLC patients with multiple brain metastases.