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Radiotherapy in Lung Adenocarcinoma with Brain Metastases: Effects of Activating Epidermal Growth Factor Receptor Mutations on Clinical Response

Authors' Affiliations: ¹ Department of Internal Medicine, ² Division of Radiation Oncology, Department of Oncology, ³ Department of Pathology, ⁴ Department of Medical Imaging, and ⁵ Department of Oncology, National Taiwan University Hospital; ⁶ Division of Biostatistics, Graduate Institute of Epidemiology and Center of Biostatistics Consultation, College of Public Health, National Taiwan University, Taipei, Taiwan; ⁷ Division of Critical Care Medicine, Department of Emergency and Critical Care Medicine, Lotung Poh-Ai Hospital, Yi-Lan, Taiwan; and ⁸ Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan

Requests for reprints: Jin-Yuan Shih, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan. Phone: 886-2-235-62905; Fax: 886-2-23582867; E-mail: jyshih{at}ntu.edu.tw.

Purpose: Whole-brain radiation therapy (WBRT) has been applied to inoperable brain metastases in lung adenocarcinoma. Recently, an in vitro study showed reduced clonogenic survival of mutant epidermal growth factor receptor (EGFR) lung cancer cell lines in response to ionizing radiation compared with that of the wild type. To elucidate the role of EGFR mutations in radiation treatment, we evaluated the clinical response to WBRT and survival of lung adenocarcinoma patients with brain metastases.

Experimental Design: This was a retrospective analysis of 63 patients with brain metastases from lung adenocarcinoma who were treated with WBRT. Demographic data, EGFR mutation status, response to WBRT, and survival data were collected. Clinical response was assessed 1 month after the start of WBRT. Univariate and logistic regression models were used to test potential predictive factors associated with clinical response. Log-rank test and Cox regression were analyzed to identify factors that affected survival.

Results: Clinical response to WBRT was observed in 29 patients (46%), with 34 nonresponder patients (54%). Patients with EGFR mutations had higher response rates to WBRT compared with those with the wild-type (54% versus 24%; P = 0.045). Both the administration of EGFR tyrosine kinase inhibitor (P = 0.034) and EGFR mutation (P = 0.029) were independently associated with response to WBRT. In Cox regression analysis, WBRT responder (P = 0.010) and absence of extracranial metastases (P = 0.002) were associated with better survival.

Conclusions: Both the EGFR mutations and the administration of EGFR TKI during WBRT were independent predictors of response to WBRT in brain metastases of lung adenocarcinoma.