Abstract
BackgroundThe 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).MethodsForty-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).ResultsThe 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.ConclusionsMutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases.
Highlights
The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro
Consistent with prior studies [23,24,25], the proportion of females and never-smokers was higher in patients with mutant EGFR (57% and 73%, respectively)
We found that NSCLC with mutant EGFR is associated with prolonged intracranial radiological progression-free survival (RPFS) (21 vs. 12 months; p = 0.009) in patients with brain metastases, as compared with wild-type EGFR
Summary
The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. Many prognostic factors have been explored in patients with brain metastases [4,5,6,7,8,9,10,11,12] including age, performance status, control of primary tumor, extent of extracranial disease, primary site of cancer, number of brain metastases, and treatment modalities These parameters have been incorporated in commonly used indices in radiation oncology such as the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and the Graded Prognostic Assessment (GPA). Incorporation of biomarkers such as the expression level of epidermal growth factor receptor (EGFR), vascular endothelial growth factor, and cyclooxygenase-2 has been correlated with treatment outcome after RT [13] Among these biomarkers, amplification of EGFR has been extensively studied and is regarded as a poor prognostic factor in cancer [13,14,15,16]. 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 RT
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