Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2013-09, Vol.81 (3), p.455-461
• Main Authors: Hsiao, Shih-Hsin, Lin, Horng-Chyuan, Chou, Yu-Ting, Lin, Sey-En, Kuo, Chia-Chun, Yu, Ming-Chih, Chung, Chi-Li
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Brain - diagnostic imaging; Brain - pathology; Brain metastases; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - mortality; Brain Neoplasms - secondary; Epidermal growth factor receptor mutations; ErbB Receptors - genetics; Female; Hematology, Oncology and Palliative Medicine; Humans; Lung adenocarcinoma; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Neoplasm Staging; Neurology; Pneumology; Prognosis; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - therapeutic use; Pulmonary/Respiratory; Radiography; Radiotherapy; Survival after brain metastases; Treatment Outcome; Treatment response; Tumor Burden; Tumors; Tumors of the nervous system. Phacomatoses; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2013.06.004

Abstract Introduction 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. Material and 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. Conclusion 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.