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

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).

Brain metastases: Comparing clinical radiological differences in patients with lung and breast cancers treated with surgery

“…7 ). 23 , 24 , 25 , 26 In this study, the natural histories of breast and lung cancer patients are consistent with those reported by others. 27 , 28 Still, under clinical, radiological and surgical aspects, there are some interesting differences especially regarding age, clinical debut, timing, extracranial metastases and surgical features.…”

“…It is reported that the median survival of breast cancer patients with BM varies according to HER-2 subtype with the triple-negative forms having worse prognosis (about 6 months), than HER 2 positive HR (about 21 months). 56 In patients with metastasis from lung carcinoma, seems that the EGFR expression correlates with prognosis, 57 although our recent study 23 on this collection did not confirm this finding. Patients with metastasis from breast carcinoma present with more advanced intracranial disease than patients with metastasis from NSCLC but after treatment, no differences are reported between the two groups.…”

“…BMs from lung and breast cancer are the most frequent types of secondary intracranial lesions in adults since melanoma patients were nowadays excluded as they have seen significant progress in the development of systemic therapies to improve control of the primary disease, reducing the percentage who develop BM. 20 , 21 , 22 , 23 Biologically and prognostically, the two types cannot be comparable since they are two different clinical entities, but at the time of acute clinical onset where there is radiological evidence of a surgically treatable contrast capturing lesion their appearance can be very similar and difficult to distinguish to other tumors ( Fig. 7 ).…”

Preoperative Prognostic Index for Patients with Brain Metastases—A Population-Based Multi-Centre Study

“…For a high fraction of patients such molecular data is unknown at the time of evaluation for craniotomy. In addition, while the above mutations are associated with survival, the association is uncertain in patients with BM [ 38 , 39 ], and more studies are warranted to establish the role of oncogenic mutations in these patients. Further, studies have also shown discrepancies between mutation status in primary tumors and their BM [ 40 , 41 ].…”

Effect of Different Timing of Local Brain Radiotherapy on Survival of EGFR-Mutated NSCLC Patients with Limited Brain Metastases

“…The synchronous brain metastases, defined as the BM lesions occurring within 2 months of the primary cancer diagnosis and the prognosis is reported to be poor compared with metachronous lesions, which were defined as brain metastases found 2 months or more after the detection of the primary cancer [ 21 ]. A previous study suggested that the presence of EGFR mutations significantly correlates with greater edema and mostly a higher seizure incidence of BMs from NSCLC [ 22 ]. However, in clinical practice, patients diagnosed with treatment-naïve EGFR-mutant NSCLC without severe BM symptoms tend to choose EGFR-TKIs as first-line therapy and defer brain RT.…”