Determining venous thromboembolism risk in patients with adult-type diffuse glioma

• Published in: Blood 2023-03, Vol.141 (11), p.1322-1336
• Main Authors: Burdett, Kirsten Bell, Unruh, Dusten, Drumm, Michael, Steffens, Alicia, Lamano, Jonathan, Judkins, Jonathan, Schwartz, Margaret, Javier, Rodrigo, Amidei, Christina, Lipp, Eric S., Peters, Katherine B., Lai, Albert, Eldred, Blaine S. C., Heimberger, Amy B., McCortney, Kathleen, Scholtens, Denise M., Horbinski, Craig
• Format: Article
• Language: English
• Subjects: Adult; Anticoagulants - therapeutic use; Biomarkers; Brain Neoplasms - complications; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Glioma - complications; Glioma - drug therapy; Glioma - genetics; Humans; Isocitrate Dehydrogenase - genetics; Mutation; Venous Thromboembolism - diagnosis; Venous Thromboembolism - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2022017858

•VTE is a frequent event in patients with adult-type diffuse glioma, but tools to assess VTE risk are not available.•Using clinical and pathologic variables, including molecular data, we generated a web-based VTE prediction tool for patients with glioma. [Display omitted] Venous thromboembolism (VTE) is a life-threating condition that is common in patients with adult-type diffuse gliomas, yet thromboprophylaxis is controversial because of possible intracerebral hemorrhage. Effective VTE prediction models exist for other cancers, but not glioma. Our objective was to develop a VTE prediction tool to improve glioma patient care, incorporating clinical, blood-based, histologic, and molecular markers. We analyzed preoperative arterial blood, tumor tissue, and clinical-pathologic data (including next-generation sequencing data) from 258 patients with newly diagnosed World Health Organization (WHO) grade 2 to 4 adult-type diffuse gliomas. Forty-six (17.8%) experienced VTE. Tumor expression of tissue factor (TF) and podoplanin (PDPN) each positively correlated with VTE, although only circulating TF and D-dimers, not circulating PDPN, correlated with VTE risk. Gliomas with mutations in isocitrate dehydrogenase 1 (IDH1) or IDH2 (IDHmut) caused fewer VTEs; multivariable analysis suggested that this is due to IDHmut suppression of TF, not PDPN. In a predictive time-to-event model, the following predicted increased VTE risk in newly diagnosed patients with glioma: (1) history of VTE; (2) hypertension; (3) asthma; (4) white blood cell count; (5) WHO tumor grade; (6) patient age; and (7) body mass index. Conversely, IDHmut, hypothyroidism, and MGMT promoter methylation predicted reduced VTE risk. These 10 variables were used to create a web-based VTE prediction tool that was validated in 2 separate cohorts of patients with adult-type diffuse glioma from other institutions. This study extends our understanding of the VTE landscape in these tumors and provides evidence-based guidance for clinicians to mitigate VTE risk in patients with glioma. Venous thromboembolism (VTE) is a common complication of glioblastoma, but physicians are wary of anticoagulation due to the risk of bleeding. Burdett et al present a new prediction model for VTE risk in glioma based on clinical factors and tumor characteristics (including next-generation sequencing) from 258 patients, and the authors validated this model in 2 separate cohorts. They also created a web-based tool that may guide clinic