Radiographic patterns and survival of patients with early and late brain metastases in EGFR wild type and mutant non small cell lung cancer.

Brain metastasis (BM) in NSCLC is a negative prognostic indicator. In the era of EGFR mutations we evaluated the difference between early (≤6 months from diagnosis) versus late BM (>6 months), in EGFR wild type (WT) and mutant (MT) NSCLC patients with respect to radiographic patterns and overall survival (OS). A retrospective study was conducted of referred patients with non-squamous NSCLC with known EGFR mutation status treated for BM from Mar 2010-Dec 2012. Radiographic patterns, treatment and survival were collected. 430 patients were identified: 327 WT (207 early vs. 120 late) and 103 MT (65 early vs. 38 late). Early and late BM radiographic patterns were similar in EGFR WT patients. In EGFR MT there was a trend towards multiple lesions in the late compared to early BM group. OS from initial diagnosis early BM: WT 7.1 months versus MT 19.9 months (p < 0.001). OS from initial diagnosis late BM: WT 24.9 months versus MT 25.6 months (p = 0.51). In multivariate analysis chemotherapy, single lesion and late BM were associated with better survival in WT patients whereas age, and systemic treatment but not BM timing or single lesion were predictive of better outcomes in MT patients. In early BM, EGFR MT have an OS comparable to late BM. In contrast, early BM EGFR WT have a significantly reduced survival compared to late BM. The positive outcome in EGFR MT may be secondary to systemic control and EGFR TKI penetrance across the blood brain barrier.