Justine L Kuiper1, Lizza E Hendriks2, Anthonie J van der Wekken3, Adrianus J de Langen4, Idris Bahce4, Erik Thunnissen5, Daniëlle A M Heideman5, Yvonne Berk6, Ed J M Buijs7, Ernst-Jan M Speel8, Frans H Krouwels9, Hans J M Smit10, Harry J M Groen3, Anne-Marie C Dingemans2, Egbert F Smit11. 1. 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. 2. Department of Pulmonary Diseases, GROW-School for Developmental Biology & Oncology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. 3. Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. 4. Department of Pulmonary Diseases, VU University Medical Center, Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands; Department of Pulmonary Diseases, Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. 5. Department of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. 6. Department of Pulmonary Diseases, Canisius Wilhelmina hospital, P.O. Box 9015, 6500 GS Nijmegen, The Netherlands. 7. Department of Pulmonary Diseases, VU University Medical Center, Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. 8. Department of Pathology, GROW-School for Developmental Biology & Oncology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. 9. Department of Pulmonary Diseases, Spaarne Hospital, P.O. Box 770, 2130 AT Hoofddorp, The Netherlands. 10. Department of Pulmonary Diseases, Rijnstate Hospital, P.O. Box 9555, 6800 TA Arnhem, The Netherlands. 11. Department of Pulmonary Diseases, VU University Medical Center, Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands; Department of Pulmonary Diseases, The Netherlands Cancer Institute, P.O. Box 90203, 1006 BE Amsterdam, The Netherlands.
Abstract
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 (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 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 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. 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.
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 (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 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 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. 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.
Authors: Emilie Le Rhun; Patrick Devos; Thomas Boulanger; Marion Smits; Dieta Brandsma; Roberta Rudà; Julia Furtner; Johann-Martin Hempel; Tjeerd J Postma; Patrick Roth; Tom J Snijders; Frank Winkler; Sebastian Winklhofer; Antonella Castellano; Elke Hattingen; Jaume Capellades; Thierry Gorlia; Martin Van den Bent; Patrick Y Wen; Martin Bendszus; Michael Weller Journal: Neuro Oncol Date: 2019-05-06 Impact factor: 12.300
Authors: Emilie Le Rhun; Roberta Rudà; Patrick Devos; Khê Hoang-Xuan; Dieta Brandsma; Pedro Pérez Segura; Riccardo Soffietti; Michael Weller Journal: J Neurooncol Date: 2017-04-28 Impact factor: 4.130