EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer

Abstract

A small subset of patients with nonsmall cell lung cancer (NSCLC) harbors mutations in the epidermal growth factor receptor (EGFR) that predict unique sensitivity to EGFR tyrosine kinase inhibitors (TKIs). The characteristics and behavior of brain metastases (BMs) in these patients have not been well described. The longitudinal records of all NSCLC patients who underwent EGFR mutation screening at our center from August 2004 to November 2008 were reviewed for eligibility, and 93 patients were identified who developed BM during the course of their disease. Survival was estimated using the Kaplan-Meier method and the log-rank test. Multivariable predictors were assessed via the Cox proportional hazards model. Among the 93 patients with BM, 41 (44%) had mutations in EGFR, including 13 exon 19 deletions and 12 L858R mutations. Eighty-three percent of patients with BM were treated initially with whole brain radiation, either alone (53%) or in combination with craniotomy for neurosurgical resection (22%) or stereotactic radiosurgery (8%). Median survival from the time of BM was 11.7 months and was longer for patients with an EGFR mutation (14.5 vs 7.6 months, P = .09). On multivariable analysis, EGFR mutation (HR: 0.50, 95% CI: 0.30-0.82), age (HR: 1.03, 95% CI: 1.00-1.05), and active extracranial disease (HR: 3.30, 95% CI: 1.70-6.41) were independently associated with survival. In NSCLC patients with BM, EGFR mutation status is associated with improved survival, independent of age, functional status, extracranial disease status, and number of BMs.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Treatment of Epidermal Growth Factor Receptor–Mutant Non–Small Cell Lung Cancer Metastatic to the Brain

“…The survival of patients treated with WBRT ranges from 4 to 6 months but can be longer depending on several prognostic variables, including functional status, age, sites of disease outside of the brain, and epidermal growth factor receptor (EGFR) mutation status (8)(9)(10). Brain metastases often result in significant clinical deterioration in neurologic and neurocognitive function, and approximately half of these patients die as a direct result of progression within the brain (11).…”

Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor

“…22 There have been a few reports regarding the relationship between BMs and EGFR mutation status. Patients with EGFR-mutated NSCLC have been reported to develop more BMs, in number 23 and frequency, 24 than those with wild-type EGFR NSCLC. Moreover, patients with NSCLC harboring exon 19 deletion of EGFR have been reported to have BMs more often, 25 especially miliary BMs, 26 than those with EGFR L858R mutated NSCLC.…”

Prognostic Factors and Scoring Systems for Non-Small Cell Lung Cancer Patients Harboring Brain Metastases Treated with Gamma Knife Radiosurgery

“…There was also a significant prognostic impact of EGFR TKI medication in our study. Furthermore, Eichler et al found that the EGFR mutation status is associated with improved survival in NSCLC patients with brain metastases, indicating that EGFR-mutant cancer may have increased radiosensitivity compared with wild-type disease 24 . The present study focused on identifying poorer prognostic patients in NSCLC patients with brain metastases who received GKRS.…”