Survival and prognostic factors in surgically treated brain metastases

Abstract

Purpose: While surgery and radiation remain the mainstays of therapy for all patients with brain metastases (BM), the management is moving to a more individualized approach based on the underlying tumor. We sought to identify prognostic factors of both intracranial progression (IC-PFS) and overall survival (OS) in a surgical cohort.

Methods: We retrospectively reviewed the records of 1015 patients treated surgically for BM at Brigham and Women's Hospital (2007-2017). Kaplan-Meier curves were used for OS and IC-PFS and Cox proportional hazards models were built to assess for predictive factors.

Results: Common origins were lung (43.9%), breast (14.4%), and melanoma (13.8%). Median OS for the cohort was 15.4 months (95% confidence interval [95%CI] 14.1-17.1). Breast cancer (22.1 months, 95%CI 17.8-30.3) and colorectal cancer (10.6 months, 95%CI 7.2-15.4) had the longest and shortest OS, respectively. On multivariable Cox regression, significant prognostic factors of shorter OS were age (HR 1.01, 95%CI 1.01-1.02), number of lesions (HR 1.56, 95%CI 1.28-1.89), extracranial spread at BM diagnosis (HR 1.26, 95%CI 1.05-1.52), and KPS (HR 0.98, 95%CI 0.98-0.99). Regarding molecular factors, all driver mutations in lung adenocarcinoma had a favorable effect (EGFR, HR 0.53, 95%CI 0.31-0.89; ALK, HR 0.28, 95%CI 0.12-0.66; KRAS, HR 0.65, 95%CI 0.47-0.92), triple negative status predicted poor prognosis in breast adenocarcinoma (HR 2.04, 95%CI 1.13-3.69), while no effect of BRAF/NRAS mutations was demonstrated in melanoma BMs.

Conclusions: Our results corroborate the role of tumor origin and systemic as well as intracranial spread in OS. Heterogeneity within histologies was further explained by molecular alterations.

Keywords: Brain metastases; Prognostic factors; Surgery; Treatment outcome.