Whole-brain radiation therapy alone vs. combined therapy with stereotactic radiosurgery for the treatment of limited brain metastases: A systematic review

Abstract

Abstract Objective The aim of the study was to compare the efficacy and safety of whole brain radiotherapy (WBRT) used alone and combined with stereotactic radiosurgery (SRS) in the treatment of limited (1-4) brain metastases. Methods We searched for randomized controlled and matched-pair analysis trials comparing WBRT plus SRS versus WBRT alone for brain metastases. The primary outcomes were the overall survival (OS), intracranial control (IC), and localcontrol (LC). The secondary outcome was radiation toxicity. The log hazard ratios (lnHRs) and their variances were extracted from published Kaplan-Meier curves and pooled using the generic inverse variance method in the RevMan 5.3 software. The non-pooled outcome measures were evaluated using descriptive analysis. Results Three randomized controlled trials and two matched-pair analysis studies were included. There was no difference in the OS for limited brain metastases between the two groups [lnHR 0.91 (95% CI 0.76-1.09, P = 0.32) vs. 0.72 (95% CI 0.44-1.19, P = 0.20)]. The LC and IC were significantly higher in the combined treatment group [lnHR 0.69 (95% CI 0.55-0.86, P = 0.001) vs. 0.41 (95% CI 0.29-0.58, P < 0.0001)]. For patients with a single lesion, one trial showed a higher survival in the combined treatment group (median OS: 6.5 months vs. 4.9 months, P = 0.04). The combined treatment was not associated with significantly higher incidence of radiation toxicity. Conclusion Combined treatment with WBRT plus SRS should be recommended for patients with limited brain metastases based on the better LC and IC without increased toxicity. It should also be considered a routine treatment option for patients with solitary brain metastases based on the prolonged OS.