title: Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients.
abstract: BACKGROUND
  Brain metastases (BM) commonly occur in patients with lung adenocarcinoma and usually lead to a poor prognosis and quality of life despite of radiotherapy. Epidermal growth factor receptor (EGFR) mutations have been widely demonstrated to be a predictive and prognostic factor for lung adenocarcinoma, however, its impact on BM from lung adenocarcinoma remains inconclusive. The present study aimed to elucidate the predictive role of EGFR mutations in BM treatment response and survival after BM in patients with lung adenocarcinoma.
  
  
  METHODS
  From January 2006 through February 2012, 180 of 505 lung adenocarcinoma patients developed BM during their disease course were reviewed for eligibility, and 139 patients, including 89 EGFR-mutant and 50 EGFR wild-type patients, were identified for analysis.
  
  
  RESULTS
  Of the patients eligible for evaluation of treatment response, up to 85% received radiotherapy and the remaining took EGFR tyrosine kinase inhibitors (TKIs) as the front modality for BM. EGFR-mutant patients, compared with EGFR wild-type patients, had significantly greater intracranial treatment response of BM (84% vs. 48%, P = 0.002), experienced higher therapeutic efficacy to radiotherapy (86% vs. 52%, P = 0.005), and had longer median survival after BM diagnosis (13.2 vs. 6.8 months, P < 0.001). Furthermore, EGFR mutation (P = 0.002) and performance status (P = 0.009) were independently associated with BM treatment response. Additionally, EGFR mutation (P = 0.005), good performance status (P < 0.001) and absence of extracranial metastases (P=0.033) correlated with better survival.
  
  
  CONCLUSIONS
  EGFR mutation is an independent predictive factor for both BM treatment response and survival after BM in patients with lung adenocarcinoma. Further prospective studies on incorporation of EGFR mutation status into therapeutic strategy and survival prediction system for lung adenocarcinoma with BM are warranted.
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, 252 Wu-Xin Street, 110 Taipei, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Hsiao
authors.affiliation: Division of Pulmonary Infectious & Immunological Disease, Department of Thoracic Medicine, Chang Gung Memorial Hospital, No. 5 Fusing Street, Gueishan Township, Taoyuan County 333, Taiwan.
authors.forename: Horng-Chyuan
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Science, Academia Sinica, 128 Sinica Road, 115 Taipei, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chou
authors.affiliation: Department of Pathology, Taipei Medical University Hospital, 252 Wu-Xin Street, 110 Taipei, Taiwan.
authors.forename: Sey-En
authors.initials: SE
authors.lastname: Lin
authors.affiliation: Department of Radiation Oncology, Taipei Medical University Hospital, 252 Wu-Xin Street, 110 Taipei, Taiwan.
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, 250 Wu-Xin Street, 110 Taipei, Taiwan.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Yu
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, 252 Wu-Xin Street, 110 Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wu-Xin Street, 110 Taipei, Taiwan. Electronic address: clchung@tmu.edu.tw.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Chung
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011859:Radiography; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: Brain metastases; Epidermal growth factor receptor mutations; Lung adenocarcinoma; Radiotherapy; Survival after brain metastases; Treatment response