Emilie Le Rhun1,2,3,4,5, Patrick Devos6, Johannes Weller7, Katharina Seystahl4, Francesca Mo8, Annette Compter9, Anna S Berghoff10, Joost L M Jongen11, Fabian Wolpert4, Roberta Rudà8, Dieta Brandsma9, Martin van den Bent11, Matthias Preusser10, Ulrich Herrlinger7, Michael Weller4. 1. University of Lille, Inserm, Lille, France. 2. Neuro-oncology, General and Stereotaxic Neurosurgery Service, University Hospital of Lille, Rue Emile Laine, Lille, France. 3. Breast Cancer Department, Oscar Lambret Center, Lille, France. 4. Department of Neurology, Clinical Neuroscience Center and Comprehensive Cancer Center, University Hospital and University of Zurich, Zurich, Switzerland. 5. Department of Neurosurgery, Clinical Neuroscience Center and Comprehensive Cancer Center, University Hospital and University of Zurich, Zurich, Switzerland. 6. University of Lille, CHU Lille, ULR 2694 - METRICS: Évaluation des technologies de santé et des pratiques médicales, Lille, France. 7. Department of Neurology, Division of Clinical Neurooncology, University Hospital Bonn, Bonn, Germany. 8. Department of Neuro-oncology, City of Health and Science and University of Turin, Turin, Italy. 9. Department of Neuro-oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands. 10. Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria. 11. Brain Tumor Center at Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Abstract
BACKGROUND: The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes. PATIENTS AND METHODS: We retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan-Meier method and compared by Log-rank test. RESULTS: Median age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (P = 0.006). Type I patients had inferior outcome than type II patients (P = 0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (P = 0.014), but not in type I LM. Administration of either intrathecal pharmacotherapy (P = 0.020) or systemic pharmacotherapy (P = 0.0004) was associated with improved outcome in type I LM, but not in type II LM. CONCLUSION: The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.
BACKGROUND: The EANO ESMO guidelines have proposed a classification of leptomeningeal metastases (LM) from solid cancers based on clinical, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) cytology presentation. MRI patterns are classified as linear, nodular, both, or neither. Type I LM is defined by positive CSF cytology (confirmed LM) whereas type II LM is defined by typical clinical and MRI signs (probable or possible LM). Here we explored the clinical utility of these LM subtypes. PATIENTS AND METHODS: We retrospectively assembled data from 254 patients with newly diagnosed LM from solid tumors. Survival curves were derived using the Kaplan-Meier method and compared by Log-rank test. RESULTS: Median age at LM diagnosis was 56 years. Typical clinical LM features were noted in 225 patients (89%); 13 patients (5%) were clinically asymptomatic. Tumor cells in the CSF were observed in 186 patients (73%) whereas the CSF was equivocal in 24 patients (9.5%) and negative in 44 patients (17.5%). Patients with confirmed LM had inferior outcome compared with patients with probable or possible LM (P = 0.006). Type I patients had inferior outcome than type II patients (P = 0.002). Nodular disease on MRI was a negative prognostic factor in type II LM (P = 0.014), but not in type I LM. Administration of either intrathecal pharmacotherapy (P = 0.020) or systemic pharmacotherapy (P = 0.0004) was associated with improved outcome in type I LM, but not in type II LM. CONCLUSION: The EANO ESMO LM subtypes are highly prognostic and should be considered for stratification and overall design of clinical trials.
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