Abstract

BackgroundLeptomeningeal metastases (LM) remain challenging for patients with non-small cell lung cancer. EGFR mutation shows a higher incidence rate of LM with poor prognosis. 3rd generation TKI has better cerebral-spinal fluid(CSF) penetration and may be a promising treatment. Here we collected LM clinical features and outcome in EGFR-mutant lung adenocarcinoma in high EGFR mutation prevalence area. MethodsThis is a retrospective observational cohort study, conducted in a tertiary medical center in Taiwan. Patients with newly diagnosed advanced lung adenocarcinoma with common EGFR mutation were enrolled. LM were diagnosed by brain imaging study or cytology study of CSF analysis. Patients without initial brain MRI imaging or patients who underwent CNS surgery initially were excluded. All the data is valid up to Dec 31, 2017. ResultsFrom 2013 to 2015, a total of 283 patients was included. All patients were treated with first-line TKIs as systemic treatment initially. Thirty-four patients had LM, accounting for 12.0% (34/283) of this cohort. Only four patients in the LM group (11.7%) received CSF study, and three of them showed malignant cells in their CSF. Patients with LM had median overall survival(OS) 26.2 months, whereas patients with brain tumor progression had median OS 42.3 months. (p = 0.002) For patients with LM, the median OS after LM is 5.1 months. Patients with younger age(HR0.63[0.45-0.90], p = 0.01) and initial M1b(HR 2.86[1.81-4.53], p < 0.001) were associated with higher risk or intracranial progression. Among 34 patients, 6 patients received 3rd generation TKI and revealed significant better OS than those without 3rd TKI. (OS 15.3 months vs 3.7 months, p = 0.03). ConclusionsLM show poor prognosis for patients with EGFR-mutant lung adenocarcinoma, compared with other types of brain metastases. Younger age and initial M1b associated with higher risk. Patients with 3rd generation TKI may bring benefit to these patients. Legal entity responsible for the studyThe authors. FundingTaipei Veterans General Hospital. DisclosureC-H. Chiu: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche. All other authors have declared no conflicts of interest.

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