• Justine L Kuiper, Lizza E Hendriks, Anthonie J van der Wekken, Adrianus J de Langen, Idris Bahce, Erik Thunnissen, Daniëlle A M Heideman, Yvonne Berk, Ed J M Buijs, Ernst-Jan M Speel, Frans H Krouwels, Hans J M Smit, Harry J M Groen, Anne-Marie C Dingemans, and Egbert F Smit.
• Department of Pulmonary Diseases, VU University Medical Center, Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: jl.kuiper@vumc.nl.
• Lung Cancer. 2015 Sep 1; 89 (3): 255-61.

ObjectivesDevelopment of leptomeningeal metastasis (LM) in non-small cell lung cancer (NSCLC)-patients is associated with a poor prognosis. It has been suggested that LM-patients with epidermal growth factor receptor mutated (EGFR+) NSCLC have a superior prognosis compared to EGFR-wild type NSCLC. Studies in EGFR+ NSCLC-patients with LM are scarce. We retrospectively evaluated a multi-institutional cohort of EGFR+ NSCLC-patients for LM to assess clinical outcome in relation to patient characteristics and treatment modalities.Material And MethodsMedical records of advanced-stage EGFR+ NSCLC-patients (diagnosed between August 2000 and June 2014) from 11 Dutch hospitals were evaluated for LM as diagnosed by MRI and/or cytopathological liquor analysis. Data on patient characteristics, treatment and outcome were collected.ResultsThirty-two of 356 (9.0%) advanced-stage EGFR+ NSCLC-patients (median follow-up 21.0 months), were diagnosed with LM between 2006 and 2014. LM was diagnosed by MRI (59.4%), liquor analysis (9.4%) or by both MRI and liquor analysis (31.3%). Median survival after LM-diagnosis was 3.1 months (95% CI: 0.0-7.3). Six- and 12-month survival rates were 43.8% and 18.8%, respectively. Patients with performance status (PS) 0-1 at time of diagnosis of LM had a significantly higher chance to be alive after 6 months and had a significantly longer survival after diagnosis of LM compared to patients with PS≥2. Age, treatment with high-dose EGFR-TKI, radiotherapy and whether LM was the only site of progressive disease did not influence survival after LM-diagnosis.ConclusionAlthough median survival after LM-diagnosis in EGFR-mutated NSCLC-patients was poor, a substantial part of the patients had a prolonged survival of more than 6 months. PS of 0-1 at time of diagnosis of LM was associated with prolonged survival. No other patient- or treatment-related characteristics were identified. Further research is warranted to identify treatment strategies that improve survival in EGFR+ NSCLC-patients with LM.Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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