Treatment and survival of patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastasis: A retrospective cohort analysis

Justine L. Kuiper*, Lizza E. Hendriks, Anthonie J. van der Wekken, Adrianus J. de Langen, Idris Bahce, Erik Thunnissen, Danielle 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, Egbert F. Smit

*Corresponding author for this work

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Objectives: Development 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 (EGER+) NSCLC have a superior prognosis compared to EGFR-wild type NSCLC. Studies in EGFR+ NSCLC-patients with LM are scarce. We retrospectively evaluated a multiinstitutional cohort of EGER+ NSCLC-patients for LM to assess clinical outcome in relation to patient characteristics and treatment modalities. Material and methods: Medical 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. Results: Thirty-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 MM (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% Cl: 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. Conclusion: Although 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.
Original languageEnglish
Pages (from-to)255-261
JournalLung Cancer
Issue number3
Publication statusPublished - Sept 2015


  • EGER
  • Leptomeningeal metastasis
  • TKI

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