Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases

Background Historically, 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 6, 2010. Objectives To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of brain metastases. Search methods In the original review we searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and CancerLit (1975 to 2009) in order to identify trials for inclusion in this review. In this update we searched the following electronic databases in May 2012: Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2012), MEDLINE (2009 to May week 4 2012), and EMBASE (2009 to 2012 week 21) in order to identify trials for inclusion in the review. Selection criteria The review was restricted to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adult patients with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. Data collection and analysis The Generic Inverse Variance method, random-effects model in RevMan 5 was used for the meta-analysis. Main results Ameta-analysis of two trials with a total of 358 participants, found no statistically significant difference in overall survival (OS) between WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.65 to 1.02). For patients with one brain metastasis median survival was significantly longer in WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Patients in the WBRT plus SRS group had decreased local failure compared to patients who received WBRT alone (HR 0.27; 95% CI 0.14 to 0.52). Furthermore, a statistically significant improvement in performance status scores and decrease in steroid use was seen in the WBRT plus SRS group. Unchanged or improved Karnofsky Performance Scale (KPS) at 6 months was seen in 43% of patients in the combined therapy group versus only 28% in WBRT group (P = 0.03). Overall, risk of bias in the included studies was unclear. Authors' conclusions Since the last version of this review no new studies were found that met the inclusion criteria. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. Analysis of all included patients, 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.