The Role of Targeted Therapies in the Overall Survival of Patients Receiving Stereotactic Radiosurgery for Brain Metastases

Abstract

Objectives: In resources limited settings, accurate selection of patients with potential long survival for stereotactic radiosurgery (SRS) is important. Targeted therapies, which provide effective extracranial disease control, may be an important predictor of overall survival (OS) in patients who receive SRS for brain metastases. Methods: Consecutive patients with brain metastases who received SRS from 1998 to July 2012 in a single institution were retrospectively reviewed. Treatment was done with LINAC based SRS system. Competing risk analysis on overall CNS disease control was performed. Multivariate analysis of prognostic factors of OS was performed. Results: Sixty-two patients received SRS with 104 lesions treated. Mean dose given at tumor periphery was 15.1Gy. Mean size of PTV was 4.9cc (range 0.3-25.5cc). Non-small cell lung cancer accounted for 56% of patients, while CA breast and colorectal CA accounted for 12.8 and 11.3% respectively. Distribution of diagnosis-specific graded prognostic assessment indices of patients was 26.4% with 0-1.0, 49.1% with 1.5-2.0, 18.9% with 2.5-3.0, 5.6% with 3.5-4.0. Twelve patients (19.4%) received targeted therapies, including small molecules inhibitors and monoclonal antibodies, after SRS. Forty-four patients (44%) had active extracranial disease. One year local control of SRS treated lesions was 71.8%. The use of whole brain RT in conjunction with SRS was associated with higher overall CNS disease control (HR 0.40, 95% CI 0.20-0.81, p=0.01) in competing risk analysis. Median OS of patients treated with and without targeted therapies after SRS was 167 and 456 days respectively [hazard ratio (HR) 0.37, 95% confident interval (CI) 0.18-0.76, p=0.007]. In multivariate analysis, the use of targeted therapy after SRS (HR 0.36, 95% CI 0.17-0.79, p=0.01), female gender (HR 0.43, 95% CI 0.25-0.75, p=0.003), no active extracranial disease (HR 0.48, 95% CI 0.26-0.90, p=0.02) and KPS ≥70 (HR 0.34, 95% CI 0.18-0.66, p=0.001) were independent predictors of longer OS. Conclusion: The use of targeted therapies post SRS is an independent predictor of OS. Effective intracranial control with SRS, together with effective extracranial disease control with targeted therapies, both contribute to the improved OS of patients with brain metastases. To select patients who may benefit the most from SRS, multi-disciplinary assessment with special regard to extracranial disease control is important.