EGFR driving mutation in non-small-cell lung cancer influences the incidence and characteristics of related brain metastases

Abstract Background: Brain metastases (BMs) are the most common intracranial tumors in adults and the brain is one of the most frequent metastatic sites for non-small-cell lung cancer (NSCLC). Some studies have hypothesized that EGFR expression in the primary tumor may result in clinically radiological and prognostic changes in related brain metastases, comparable to EGFR's correlation with prognosis in primary brain tumors. There are no current studies that clinically and radiologically demonstrate a difference between BMs from EGFR-mutated and wild-type NSCLC.Methods: We performed a retrospective study to identify prognostic factors for the survival of patients with NSCLC-BMs by exploring the role of driving mutations in NSCLC, focusing on EGFR mutated status, and comparing all morphological, radiological, and clinical features of NSCLC-BMs with their outcome parameters in a cohort of surgically treated patients. Results: The final cohort consisted of 81 patients. The overall survival of the cohort was 15±17 months. The tumor-related edema was associated with neurological symptoms at the clinical onset of the disease (p=.048). We found that EGFR and ALK mutation status did not reach significant associations with age, sex, and the morphology of the lesions. EGFR mutation in the primary tumor is positively associated with higher edema and tumor volume (respectively 22.38±21.35cm3 versus 7.68±8.44cm3 and 72.44±60.71cm3 versus 31.92cm3 p=.046 and p=.028). Moreover, EGFR mutation is associated with a clinical debut of seizures (p=.004).Conclusions: The role of EGFR and ALK mutations of NSCLC on prognostic characteristics of BMs is still to be fully clarified; however the results retrieved from the present study suggest that the presence of EGFR mutations significantly correlates with bigger edema volume and higher incidence of seizures. In recent studies, while EGFR mutation status did not affect the immune pathway scores of primary lung tumors, the overall immune pathway scores in related BMs indicate a peculiar immunogenic phenotype that could explain a large amount of edema volume. This study could be considered the first clinical and radiological demonstration of this immunological phenotype.