Isolated Brain Metastases as the First Relapse After the Curative Surgical Resection in Non–Small-Cell Lung Cancer Patients With an EGFR Mutation

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The aim of this study was to clarify the incidence and disease behavior of brain metastases (BM) without extracranial disease (ie, isolated BM) as the first relapse after curative surgery in non–small-cell lung cancer (NSCLC) patients, analyzed according to epidermal growth factor receptor (EGFR) mutation status.

Patients and Methods

A review of the medical charts of consecutive NSCLC patients diagnosed between 2005 and 2016 with BM as the first relapse after curative surgery was performed.


Among 1191 patients evaluated for EGFR mutation status, 28 patients who met the inclusion criteria were divided into 2 groups: EGFR mutation group (16 patients) and wild type group (12 patients). At BM diagnosis, the EGFR-mutation group tended to have more commonly isolated BM compared with that in the wild type group (11 of 16 vs. 3 of 12; P = .054). In the EGFR mutation group, the patients with isolated BM showed longer overall survival than those with non-isolated BM (39.6 vs. 18.7 months; P = .038). Notably, isolated BM in the EGFR mutation group was neurologically asymptomatic in 10 of the 11 patients. With regard to upfront treatment for isolated BM in the EGFR mutation group, 10 of 11 patients were treated with only cranial radiotherapy without EGFR tyrosine kinase inhibitors, but two-thirds of the patients (7 of 11; 64%) developed extracranial disease during the study period.


In curatively resected NSCLC patients with EGFR mutation, isolated BM would be correlated with better prognosis, but regarded as a precursor to systemic disease. Because isolated BM can be neurologically asymptomatic, it would be important to periodically perform cranial evaluation to detect isolated BM.


Isolated brain metastases (BM) tended to be more common as the first relapse in curatively resected non–small-cell lung cancer patients with epidermal growth factor receptor mutation. Because isolated BM in those patients was mostly neurologically asymptomatic and would be regarded as a precursor to systemic disease, it would be preferable to periodically perform appropriate cranial evaluation.

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