Concurrent versus non-concurrent immune checkpoint inhibition with stereotactic radiosurgery for metastatic brain disease: a systematic review and meta-analysis


Aurora Neuroscience Innovation Institute, Aurora St. Luke's Medical Center


BACKGROUND: Immune checkpoint inhibition (ICI) is an emerging immunotherapy for metastatic brain disease (MBD). Current management options include stereotactic radiosurgery (SRS), which has been shown to confer prognostic benefit in combination with ICI. However, the effect, if any, of ICI timing on this benefit is currently unclear. The aim of this study was to evaluate the effect of concurrent ICI with SRS on survival outcomes in MBD compared to non-concurrent ICI administered before or after SRS.

METHODS: Searches of 7 electronic databases from inception to April 2018 were conducted following the appropriate guidelines. 1210 articles were identified for screening. Kaplan Meier estimation of 12-month overall survival (OS), local progression free survival (LPFS) and distant progression free survival (DPFS) were pooled as odd ratios (ORs) and analyzed using the random effects model.

RESULTS: A total of 8 retrospective observational cohort studies satisfied selection criteria. Compared to non-concurrent ICI, concurrent ICI with SRS conferred a significant 12-month OS benefit (OR = 1.74; p = 0.011), and comparable 12-month LPFS (OR = 2.09; p = 0.154) and DPFS (OR = 0.88; p = 0.839). These significances were reflected in the subgroup of melanoma metastases.

CONCLUSION: Based on the trends of our findings, there appears to exist an optimal time window around SRS of which ICI may confer the most survival benefit. However, current literature is limited by a number of clinical parameters requiring further delineation which limits the certainty of these findings. Larger, prospective, and randomized studies will assist in identifying the time period for which ICI can provide the best outcome in MBD managed with SRS.

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