Emilie Le Rhun1, Els Genbrugge2, Roger Stupp3, Olivier L Chinot4, L Burt Nabors5, Timothy Cloughesy6, David A Reardon7, Wolfgang Wick8, Thierry Gorlia2, Michael Weller9. 1. University of Lille, U-1192, F-59000, Lille, France; Inserm, U-1192, F-59000, Lille, France; CHU Lille, General and Stereotaxic Neurosurgery Service, F-59000, Lille, France; Department of Neurology & Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland. Electronic address: emilie.lerhun@chru-lille.fr. 2. EORTC Headquarters, Brussels, Belgium. 3. Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. 4. Aix-Marseille University, AP-HM, Service de Neuro-Oncologie, CHU Timone, Marseille, France. 5. University of Alabama at Birmingham, Birmingham, AL, USA. 6. UCLA Neuro-Oncology Program, Los Angeles, CA, USA. 7. Dana-Farber Cancer Research Institute, Boston, MA, USA. 8. Department of Neurology and Neurooncology Programm at the National Center for Tumor Diseases, University Hospital Heidelberg and German Cancer Research Center, Heidelberg, Germany. 9. Department of Neurology & Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland.
Abstract
BACKGROUND: To test the hypothesis that despite bleeding risk, anticoagulants improve the outcome in glioblastoma because of reduced incidence of venous thromboembolic events and modulation of angiogenesis, infiltration and invasion. METHODS: We assessed survival associations of anticoagulant use from baseline up to the start of temozolomide chemoradiotherapy (TMZ/RT) (period I) and from there to the start of maintenance TMZ chemotherapy (period II) by pooling data of three randomised clinical trials in newly diagnosed glioblastoma including 1273 patients. Progression-free survival (PFS) and overall survival (OS) were compared between patients with anticoagulant use versus no use; therapeutic versus prophylactic versus no use; different durations of anticoagulant use versus no use; anticoagulant use versus use of anti-platelet agents versus neither anticoagulant nor anti-platelet agent use. Cox regression models were stratified by trial and adjusted for baseline prognostic factors. RESULTS: Anticoagulant use was documented in 75 patients (5.9%) in period I and in 104 patients (10.2%) in period II. Anticoagulant use during period II, but not period I, was associated with inferior OS than no use on multivariate analysis (p = 0.001, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.18-1.95). No decrease in OS became apparent when only patients with prophylactic anticoagulant use were considered. No survival association was established for anti-platelet agent use. CONCLUSIONS: Anticoagulant use was not associated with improved OS. Anticoagulants may not exert relevant anti-tumour properties in glioblastoma.
BACKGROUND: To test the hypothesis that despite bleeding risk, anticoagulants improve the outcome in glioblastoma because of reduced incidence of venous thromboembolic events and modulation of angiogenesis, infiltration and invasion. METHODS: We assessed survival associations of anticoagulant use from baseline up to the start of temozolomide chemoradiotherapy (TMZ/RT) (period I) and from there to the start of maintenance TMZ chemotherapy (period II) by pooling data of three randomised clinical trials in newly diagnosed glioblastoma including 1273 patients. Progression-free survival (PFS) and overall survival (OS) were compared between patients with anticoagulant use versus no use; therapeutic versus prophylactic versus no use; different durations of anticoagulant use versus no use; anticoagulant use versus use of anti-platelet agents versus neither anticoagulant nor anti-platelet agent use. Cox regression models were stratified by trial and adjusted for baseline prognostic factors. RESULTS: Anticoagulant use was documented in 75 patients (5.9%) in period I and in 104 patients (10.2%) in period II. Anticoagulant use during period II, but not period I, was associated with inferior OS than no use on multivariate analysis (p = 0.001, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.18-1.95). No decrease in OS became apparent when only patients with prophylactic anticoagulant use were considered. No survival association was established for anti-platelet agent use. CONCLUSIONS: Anticoagulant use was not associated with improved OS. Anticoagulants may not exert relevant anti-tumour properties in glioblastoma.
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