Epidermal Growth Factor Receptor Mutational Status and Brain Metastases in Non–Small-Cell Lung Cancer

Abstract

IntroductionEpidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancers (NSCLC) may be more common in patients with brain metastases. Previous studies, however, did not adjust for effects of confounding variables.MethodsThis retrospective study included 1,522 consecutive patients with NSCLC, whose tumors were diagnosed and tested for EGFR mutations at the University of Nebraska Medical Center (Omaha, NE) and Tata Memorial Hospital (Mumbai, India). Multivariate logistic regression was used to identify any association between EGFR status and clinical factors.ResultsEGFR mutations were more common in females than males (38.7% v 24.8%), Asians than whites (31.3% v 13.4%), nonsmokers than smokers (40.2% v 14.6%), alcohol nonconsumers than users (32.4% v 15.8%), adenocarcinoma than other histology types (32.7% v 10.3%), and patients with brain metastases than extracranial or no metastases (39.4% v 29.8% v 15.1%; P < .001 for all comparisons). There was a higher likelihood of an EGFR mutation among patients with brain metastases (odds ratio, 1.8; P < .001). The median overall survival (OS) was 19.8 months. Patients with brain metastases had a shorter median OS (15 v 20.6 months; P = .02). However, in the cohort of EGFR mutation–positive patients, there was no difference in median OS between patients with and without brain metastases (20.8 v 25.1 months; P = .11).ConclusionThere is a nearly two-fold higher incidence of EGFR mutations in NSCLC among patients with brain metastases at diagnosis. EGFR mutations did not predict for outcomes from brain metastases.

Risk factors for brain metastases in patients with non–small‐cell lung cancer

“…However, this study had small sample sizes, which may have limitations. In 2016, a retrospective study including 1522 consecutive NSCLC patients reported that patients with EGFR mutations at the time of diagnosis have a nearly twofold higher risk of brain metastases . The results above suggest that the EGFR mutation status could have an influence on the CNS progression of NSCLC.…”

Lung cancer—A global perspective

“…The frequency and distribution of these mutations quite variable across the globe. EGFR mutations occur at a much higher rate in adenocarcinoma in East Asia than in the United States and Europe and are also more common in women than men . However, the frequency of other mutations ( ERBB2 , RET , BRAF , ROS1) are similar among Asian and white populations .…”

“…While the treatment of lung cancer follows the same principles around the world, the differences in the epidemiology of lung cancer and the genetic variations in the patients lead to some variations in the exact treatments received by patients. As a result, since an increased proportion of patients in Asia have activating EGFR mutations, there is an increased prevalence in the use of EGFR tyrosine kinase inhibitors in these countries.…”

Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer

“…Considering the high heterogeneity, analyses stratified by study design ( Figure 2D) suggested that association was significant between EGFR mutations and the incidence of BMs in cohort (16)(17)(18)(19)(25)(26)(27)(28)(29)(30)(31)(36)(37)(38)(39)(40)(41)(42) (P=0.381, I 2 =6.1%) ( Figure 3A). Patients with EGFR mutations were more susceptible to BMs than wild type cases either in adenocarcinoma patients (OR =1.93; 95% CI, 1.59-2.35; P=0.000) or in advanced (stage IV) NSCLC patients (OR =1.83; 95% CI, 1.43-2.36; P=0.000).…”

“…The NOS was used to perform quality assessment on all 22 studies and 14 (17,18,(25)(26)(27)(28)30,(32)(33)(34)(35)(36)38,42) high-quality and 8 (16,19,29,31,37,(39)(40)(41) as low-quality.…”