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Background: 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. Methods: 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 noncon-current 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. Results: A total of 16 retrospective studies with 1356 BM patients were included. Compared to noncon-current therapy, concurrent therapy revealed a significantly longer OS (HR= 1.43; p = 0.008) and 12-months LBC (HR = 1.91; p = 0.04), a similar 12-months DBC (HR = 1.12; p = 0.547) and higher complication rate (R = 0.77; p = 0.346). Concurrent therapy leads to a significantly higher OS compared to ICI before SRS (HR = 2.55; p = 0.0003). Conclusion: 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. [ABSTRACT FROM AUTHOR]

To determine the efficacy of stereotactic radiosurgery (SRS) in treating patients with brain metastases (BMs), a network meta-analysis (NMA) of randomized controlled trials (RCTs) and a direct comparison of cohort studies were performed. Relevant literature regarding the effectiveness of SRS alone and in combination with whole-brain radiotherapy (WBRT) and surgery was retrieved using systematic database searches up to April 2019. The patterns of overall survival (OS), one-year OS, progression-free survival (PFS), one-year local brain control (LBC), one-year distant brain control (DBC), neurological death (ND), and complication rate were analyzed. A total of 18 RCTs and 37 cohorts were included in the meta-analysis. Our data revealed that SRS carried a better OS than SRS+WBRT (p = 0.048) and WBRT (p = 0.041). Also, SRS+WBRT demonstrated a significantly improved PFS, LBC, and DBC compared to WBRT alone and SRS alone. Finally, SRS achieved the same LBC as high as surgery, but intracranial relapse occurred considerably more frequently in the absence of WBRT. However, there were not any significant differences in ND and toxicities between SRS and other groups. Therefore, SRS alone may be a better alternative since increased patient survival may outweigh the increased risk of brain tumor recurrence associated with it. [Display omitted] • WBRT+SRS is better than SRS alone in terms of LBC and DBC. • WBRT+SRS carries a prolonged survival with higher LBC, DBC when compared to WBRT. • LBC is high in either surgery or SRS, but it is significantly higher in SRS. • Surgery+SRS achieved higher LBC than surgery+WBRT, but resulted in worse regional control. • SRS+WBRT had longer PFS when compared to SRS alone and WBRT. [ABSTRACT FROM AUTHOR]