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EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases

Hsin-Lun Lee1, Tao-Sang Chung1,3, Lai-Lei Ting4, Jo-Ting Tsai5, Shang-Wen Chen4,6, Jeng-Fong Chiou4, Henry WC Leung1 and H E Liu2,7*

Author Affiliations

1 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

2 Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

3 Department of Radiation Oncology, Landseed Hospital, Pingzhen, Taiwan

4 Department of Radiation Oncology, Taipei Medical University Hospital, Taichung, Taiwan

5 Department of Radiation Oncology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan

6 Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan

7 Graduate Institute of Clinical Medicine, Taipei Medical University, 250 Wushing Street, Taipei, Taiwan

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Radiation Oncology 2012, 7:181 doi:10.1186/1748-717X-7-181

Published: 30 October 2012

Abstract

Background

The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT).

Methods

Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS).

Results

The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS.

Conclusions

Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases.

Keywords:
Epidermal growth factor receptor; Non-small cell lung cancer; Brain metastases; Radiotherapy