title: 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.
authors.affiliation: Pappas Center for Neuro-Oncology, Massachusetts General Hospital, 55 Fruit Street, Yawkey 9E, Boston, MA 02114, USA. aeichler@partners.org
authors.forename: April F
authors.initials: AF
authors.lastname: Eichler
authors.forename: Kristopher T
authors.initials: KT
authors.lastname: Kahle
authors.forename: Daphne L
authors.initials: DL
authors.lastname: Wang
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Joshi
authors.forename: Henning
authors.initials: H
authors.lastname: Willers
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Engelman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D009367:Neoplasm Staging; D019635:Neurosurgical Procedures; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011878:Radiotherapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors