EGFR-Driven Mutation in Non-Small-Cell Lung Cancer (NSCLC) Influences the Features and Outcome of Brain Metastases

Daniele Armocida; Alessandro Pesce; Mauro Palmieri; Fabio Cofano; Giuseppe Palmieri; Paola Cassoni; Carla Letizia Busceti; Francesca Biagioni; Diego Garbossa; Francesco Fornai; Antonio Santoro; Alessandro Frati

doi:10.3390/jcm12103372

EGFR-Driven Mutation in Non-Small-Cell Lung Cancer (NSCLC) Influences the Features and Outcome of Brain Metastases

J Clin Med. 2023 May 9;12(10):3372. doi: 10.3390/jcm12103372.

Authors

Affiliations

¹ Human Neurosciences Department, Neurosurgery Division, "Sapienza" University, 00161 Rome, RM, Italy.
² IRCCS "Neuromed", 86077 Pozzilli, IS, Italy.
³ Neurosurgery Unit, "Santa Maria Goretti" University Hospital, 04100 Latina, LT, Italy.
⁴ Neurosurgery Unit, Department of Neuroscience "Rita Levi Montalcini", University of Turin, 10126 Turin, TO, Italy.
⁵ Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, TO, Italy.

Abstract

Background: Brain metastases (BMs) is one of the most frequent metastatic sites for non-small-cell lung cancer (NSCLC). It is a matter of debate whether EGFR mutation in the primary tumor may be a marker for the disease course, prognosis, and diagnostic imaging of BMs, comparable to that described for primary brain tumors, such as glioblastoma (GB). This issue was investigated in the present research manuscript. Methods: We performed a retrospective study to identify the relevance of EGFR mutations and prognostic factors for diagnostic imaging, survival, and disease course within a cohort of patients affected by NSCLC-BMs. Imaging was carried out using MRI at various time intervals. The disease course was assessed using a neurological exam carried out at three-month intervals. The survival was expressed from surgical intervention. Results: The patient cohort consisted of 81 patients. The overall survival of the cohort was 15 ± 1.7 months. EGFR mutation and ALK expression did not differ significantly for age, gender, and gross morphology of the BM. Contrariwise, the EGFR mutation was significantly associated with MRI concerning the occurrence of greater tumor (22.38 ± 21.35 cm³ versus 7.68 ± 6.44 cm³, p = 0.046) and edema volume (72.44 ± 60.71 cm³ versus 31.92 cm³, p = 0.028). In turn, the occurrence of MRI abnormalities was related to neurological symptoms assessed using the Karnofsky performance status and mostly depended on tumor-related edema (p = 0.048). However, the highest significant correlation was observed between EGFR mutation and the occurrence of seizures as the clinical onset of the neoplasm (p = 0.004). Conclusions: The presence of EGFR mutations significantly correlates with greater edema and mostly a higher seizure incidence of BMs from NSCLC. In contrast, EGFR mutations do not affect the patient's survival, the disease course, and focal neurological symptoms but seizures. This contrasts with the significance of EGFR in the course and prognosis of the primary tumor (NSCLC).

Keywords: ALK; EGFR; NSCLC; brain metastases; brain tumor; lung cancer.

Grants and funding

This work was supported by the Italian Ministry of Health (Current Research 2023).