Stereotactic radiosurgery with immune checkpoint inhibitors for brain metastases: a meta-analysis study

Immune checkpoint inhibitors (ICIs) are an emerging tool in the treatment of brain metastases (BMs), Stereotactic radiosurgery (SRS), traditionally used for BMs, elicits an immune brain response and can act synergistically with ICIs. We aim to investigate the efficacy of ICI administered with SRS and determine the impact of timing on BM response. A systematical search was performed to identify potential studies concerning BMs managed with SRS alone or with SRS + ICI with relative timing administration (ICI concurrent with SRS, ICI nonconcurrent with SRS, SRS before ICI, SRS after ICI). The overall survival (OS), 12-month OS, local progression-free survival (LPFS), 12-month local brain control (LBC), distant progression-free survival (DPFS), 12-month distant brain control (DBC), and adverse events (intracranial hemorrhage, radionecrosis) were analyzed using the random-effects model. A total of 16 retrospective studies with 1356 BM patients were included. Compared to nonconcurrent therapy, concurrent therapy revealed a significantly longer OS (HR= 1.43; <i>p</i> = 0.008) and 12-months LBC (HR = 1.91; <i>p</i> = 0.04), a similar 12-months DBC (HR = 1.12; <i>p</i> = 0.547) and higher complication rate (<i>R</i> = 0.77; <i>p</i> = 0.346). Concurrent therapy leads to a significantly higher OS compared to ICI before SRS (HR = 2.55; <i>p</i> = 0.0003). The combination of SRS with ICI improves patients’ clinical and radiological outcomes. The effectiveness of the combination is subject to the identification of an optimal therapeutic window.