Predictors of Long-Term Survival Among Patients With Brain Metastases

Abstract

The prognosis for patients with brain metastases (BrM) remains guarded, with population-based data indicating a median survival of 3-12 months. However, a subset of patients with BrM display prolonged survival. We sought to characterize the likelihood and predictors associated with survival ≥ 5 years after BrM diagnosis.We identified 1,370 patients diagnosed with BrM at a tertiary cancer center between 2008 and 2015 who either died or survived ≥ 5 years. Patients censored before 5 years were excluded from the analysis (N = 66). Multivariable logistic regression was used to characterize predictors of long-term (i.e., ≥ 5 years) survival after BrM diagnosis (odds ratios > 1 indicated a greater odds of long-term survival). Median survival for subgroups was calculated with the Kaplan-Meier method; comparisons were made with the log-rank test.Among all 1,304 patients, median survival after BrM diagnosis was 10.8 months. In total, 123 patients (9.4%) survived ≥ 5 years. On multivariable logistic regression, significant predictors of survival ≥ 5 years included: breast as the primary tumor site vs. the reference of non-small cell lung cancer (NSCLC) (OR: 2.44 [95% CI, 1.23-4.83], P = 0.01), high Karnofsky performance score (KPS) (90-100) vs. low KPS (< 90) (OR: 2.32 [95% CI, 1.48-3.62], P < 0.001), and lack of progressive extracranial disease at time of BrM diagnosis (OR: 2.33 [95% CI, 1.47-3.70], P < 0.001). Factors significantly associated with not surviving ≥ 5 years included: receipt of whole brain radiation therapy vs. the reference of SRT as initial management (OR: 0.30 [95% CI, 0.13-0.70], P = 0.005), presence of 2-4 BrM vs. 1 BrM (OR: 0.63 [95% CI, 0.40-1.00], P = 0.05), an increasing number of extracranial sites of disease (OR: 0.73 per additional site [95% CI, 0.59-0.90], P = 0.003), and an increasing number of systemic therapy regimens for metastatic disease prior to diagnosis of BrM (OR: 0.64 per additional regimen [95% CI, 0.50-0.84], P = 0.001). When limiting to patients with NSCLC for whom EGFR and ALK status were known, there were significant differences in survival among patients with an ALK rearrangement, EGFR mutation, or neither (median survival of 30.9, 15.0, and 12.7 months, respectively, P = 0.04). Subsetting patients with breast cancer based on receptor subtype, there were significant differences in survival among patients with HER2-positive, hormone receptor-positive/HER2-negative, or triple-negative breast cancer (median survival of 26.0, 11.2, and 6.5 months, respectively, P < 0.001).Although patients with BrM generally have a poor prognosis, select patients live for ≥ 5 years. Multidisciplinary teams caring for favorable sub-populations should consider the long-term impact of oncologic therapy when formulating treatment recommendations.N. Lamba: None. D.N. Cagney: Research Grant; NhTheraguix, Viewray. P.J. Catalano: None. P. Wen: None. D. Haas-Kogan: Research Grant; Novartis; Cellworks. A.A. Aizer: Research Grant; Varian. Consultant; Novartis. Advisory Board; Seattle Genetics.