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A prospective multicenter study of venous thromboembolism in patients with newly-diagnosed high-grade glioma: hazard rate and risk factors

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Abstract

Venous thromboembolism (VTE) is a common complication in patients with high-grade gliomas. The purpose of this prospective multicenter study was to determine the hazard rate of first symptomatic VTE in newly-diagnosed glioma patients and identify clinical and laboratory risk factors. On enrollment, demographic and clinical information were recorded and a comprehensive coagulation evaluation was performed. Patients were followed until death. The study end point was objectively-documented symptomatic VTE. One hundred seven patients were enrolled with a median age of 57 years (range 29–85) between June 2005 and April 2008. Ninety-one (85 %) had glioblastoma multiforme (GBM). During an average survival of 17.7 months, 26 patients (24 %) (95 % CI 17–34 %) developed VTE (hazard rate 0.15 per person-year) and 94 patients (88 %) died. Median time to VTE was 14.2 weeks post-operation (range 3–126). Patients with an initial tumor biopsy were 3.0 fold more likely to suffer VTE (p = 0.02). Patients with an elevated factor VIII activity (>147 %) were 2.1-fold more likely to develop VTE. ABO blood group, D dimer and thrombin generation were not associated with VTE. No fatal VTE occurred. VTE is a common complication in patients with newly-diagnosed high grade gliomas, particularly in the first six months after diagnosis. Patients with an initial tumor biopsy and elevated factor VIII levels are at increased risk. However, VTE was not judged to be primarily responsible for any patient deaths. Therefore, outpatient primary VTE prophylaxis remains investigational until more effective primary prophylaxis strategies and therapies for glioma are identified.

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Acknowledgments

The authors would like to acknowledge the efforts of all the investigators and staff at the member institutions of the National Cancer Institute-funded “New Approaches to Brain Tumor Therapy” (NABTT) and Adult Brain Tumor Consortium. (Grant 2UM1 CA137443).

Funding

This study was conducted by the Adult Brain Tumor Consortium (ABTC) which is funded by the National Cancer Institute (Grant #2UM1 CA137443).

Potential conflict of interest

Michael Streiff has received research funding from Bristol Myers Squibb, Portola and the Patient Centered Outcomes Research Institute, honoraria for CME lectures from Sanofi-Aventis and consulted for Sanofi-Aventis, Eisai, Daiichi-Sankyo, Boehringer-Ingelheim, Pfizer and Janssen HealthCare and has given expert witness testimony in various medical malpractice cases.

Thomas Kickler

receives patent fees for inventions licensed to Siemens that are administered thru Johns Hopkins University. He recieves no cost research reagents for performance of the ETP assay.

Conflict of interest

Xiaobu Ye, Serena Desideri, Jayesh Jani, Joy Fisher, Stuart Grossman has no conflicts of interest to report.

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Streiff, M.B., Ye, X., Kickler, T.S. et al. A prospective multicenter study of venous thromboembolism in patients with newly-diagnosed high-grade glioma: hazard rate and risk factors. J Neurooncol 124, 299–305 (2015). https://doi.org/10.1007/s11060-015-1840-z

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  • DOI: https://doi.org/10.1007/s11060-015-1840-z

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