• Chirag G Patil, Katie Pricola, J Manuel Sarmiento, Sachin K Garg, Andrew Bryant, and Keith L Black.
• Department of Neurosurgery, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8631 West Third Street, Suite 800E, Los Angeles, CA, USA, 90048.
• Cochrane Db Syst Rev. 2017 Sep 25; 9: CD006121.

BackgroundHistorically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane Review published in Issue 9, 2012.ObjectivesTo assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of adults with brain metastases.Search MethodsFor the original review, in 2009 we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and CancerLit in order to identify trials for inclusion in this review. For the first update the searches were updated in May 2012.For this update, in May 2017 we searched CENTRAL, MEDLINE, and Embase in order to identify trials for inclusion in the review.Selection CriteriaWe restricted the review to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adults with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer.Data Collection And AnalysisWe used the generic inverse variance method, random-effects model in Review Manager 5 for the meta-analysis.Main ResultsWe identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in performance status scores and decrease in steroid use in the WBRT plus SRS group (risk ratio (RR) 0.64 CI 0.42 to 0.97; 1 study, 118 participants; low-quality evidence). Unchanged or improved Karnofsky Performance Scale (KPS) at six months was seen in 43% of participants in the combined therapy group versus only 28% in the WBRT-alone group (RR 0.78 CI 0.61 to 1.00; P value = 0.05; 1 study, 118 participants; low-quality evidence). Overall, risk of bias in the included studies was unclear.Authors' ConclusionsSince the last version of this review we have identified one new study that met the inclusion criteria. However, due to a lack of data from this study we were not able to include it in a meta-analysis. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. In our analysis of all included participants, SRS plus WBRT did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for recursive partitioning analysis (RPA) Class I patients as well as patients with single metastasis. Most of our outcomes of interest were graded as moderate-quality evidence according to the GRADE criteria and the risk of bias in the majority of included studies was mostly unclear.

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