Abstract
BackgroundNSCLC patients with EGFR mutation were at a higher incidence of developing brain metastasis (BM). Patients with BM are associated with high mortality. Reducing BM incidence becomes increasingly significant for NSCLC patients to achieve prolonged survival. The aim of the study was to explore the possible risk factors of developing metachronous BM during EGFR-TKIs treatment, and to identify the potential candidates for prophylactic cranial irradiation (PCI) or the first-line Osimertinib treatment.MethodsA total of 157 consecutive EGFR-mutated advanced NSCLC patients without BM at initial diagnosis in our institution from 2012 and 2018 were retrospectively reviewed. Comparisons of OS were performed based on BM status. The cumulative incidence of metachronous BM was calculated by the Kaplan-Meier method, and the independent risk factors of metachronous BM were investigated by multivariate analysis.ResultsPatients developing metachronous BM had worse survival (mOS: 22.1 months) than patients not-developing BM (mOS: 44.8 months). Moreover, the multivariate analysis indicated that age ≤ 49 years (P = 0.035), number of extracranial metastases (P = 0.013), and malignant pleural effusion (P = 0.002) were independent risk factors of metachronous BM. Furthermore, the 1-year actuarial incidence of developing metachronous BM in patients with no risk factor (n = 101), 1 risk factor (n = 46), and 2 risk factors (n = 10) were 7.01, 14.61, and 43.75%, respectively (P < 0.001).ConclusionsPatients developing metachronous BM during EGFR-TKIs treatment have worse outcomes. Our results suggested that EGFR-mutated advanced NSCLC patients with ≥1 risk factors were candidates for PCI or the first-line Osimertinib treatment.
Highlights
non-small cell lung cancer (NSCLC) patients with Epidermal growth factor receptor (EGFR) mutation were at a higher incidence of developing brain metastasis (BM)
Our inclusion criteria are: (1) NSCLC was confirmed by cytology (14 pts), or histology (143 pts) (World Health Organization, WHO); (2) EGFR mutations were detected by real-time quantitative PCR (ARMS, 126 pts) or Generation Sequencing (NGS, 31 pts), using histological or cytological specimens from primary or metastatic lesions; (3) The disease was clinically diagnosed as stage IIIB (10 pts)-IV (147 pts) (American Joint Committee on Cancer, the 7th Edition); (4) Patients had negative results of enhanced magnetic resonance imaging (MRI, 149 pts) or computed tomography (CT, 8 pts) scans of brain before initial treatment; (5) Patients were treatment naive for EGFR-Tyrosine kinase inhibitor (TKI) treatment
Among the 30 patients with metachronous BM, 20 patients (20/30, 66.7%) first progressed in intracranial disease, implying metachronous BM principally correlated with the ability of EGFR-TKIs to pass through blood-brain barrier (BBB)
Summary
NSCLC patients with EGFR mutation were at a higher incidence of developing brain metastasis (BM). Reducing BM incidence becomes increasingly significant for NSCLC patients to achieve prolonged survival. Prevent the occurrence of metachronous BM becomes increasingly significant for EGFRmutated advanced NSCLC patients to achieve prolonged survival. How to reduce incidence of developing metachronous BM for EGFR-mutated advanced NSCLC patients? It was reported to significantly reduce incidence of metachronous BM and improve overall survival (OS) in patients with limitedstage small cell lung cancer (SCLC) [12]. The first-line Osimertinib treatment for EGFR-mutated advanced NSCLC patients is not widely available in most developing countries due to its high cost. It is higher costeffective to apply the first-line Osimertinib treatment for EGFR-mutated NSCLC patients with higher risk of BM. These findings prompted us to identify population subsets with higher risk of BM, who are candidates for PCI or the first-line Osimertinib treatment
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