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This study aimed to evaluate the clinical benefits of stereotactic radiosurgery (SRS) for more than ten brain metastases (BM).

We extracted all the BM patients who underwent SRS without surgery or whole-brain radiotherapy from our institutional disease database from 2016–2021. The exclusion criteria are as follows: Single BM, leptomeningeal disease, and Karnofsky Performance Status (KPS)<60. The raw dataset was divided into two groups according to the number of BMs (BM 2–10 vs BM>10). Given the small population of BM>10 patients who underwent SRS and the different baseline characteristics of the two groups, we performed a propensity score matching to create the 2:1 matched dataset. The non-inferiority comparison between the two groups required a minimum of 237 patients to achieve >70% power in the matched dataset. The non-inferiority margin was considered the adjusted hazard ratio (HR) of 1.3: non-inferiority would be established if the upper limit of the one-sided 95% CI for the difference in mortality was less than the margin at an α level of 0.10. We used multivariable logistic regression to estimate the propensity score for survival outcome on the following covariates: number of BM, GPA, KPS, age, ECM, cancer type, EGFR/ALK mutation, PD-L1, and systemic regimens. Overall survival (OS) and intracranial progression-free survival (PFS) were calculated in the raw and matched datasets using the Log-rank test, and survival curves were constructed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of death and BM progression. All statistical analyses were performed using R software version 3.6.1. Statistical significance was set at P<0.05, and all tests were one-sided.

Of all the 1042 patients assessed for eligibility, 434 were analyzed (BM 2–10: n = 324, BM>10: n = 110). The estimated propensity score was matched 2:1 without replacement (BM 2–10: n = 160, BM>10: n = 80). In the matched dataset, the median OS was 16.5 months in the BM 2–10 group and 20.0 months in the BM>10 group (P = 0.76). The adjusted HR ratio was 0.76 [95% CI: 0.53–1.1], and the upper limit of 95% CI was within the non-inferiority margin of 1.3. Although the median PFS in the BM 2–10 group was better than that of the BM>10 group in the raw dataset, the difference in the matched dataset was not significantly different (5.6 months vs 4.6 months, P = 0.56). The number of BM was not associated with OS and PFS after controlling for significant covariables in a multivariable model: better KPS score, female, ECM absent, cancer type (breast cancer or lung adenocarcinoma), PDL1 positive (50–100%), and use of targeted therapy were independently associated with better OS. Better KPS score, female, and lung adenocarcinoma were independently associated with better PFS.

The results of this study suggest that SRS for patients with >10 BM may be non-inferior in OS to patients with 2–10 BM.