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

Kirsten Bell Burdett; Dusten Unruh; Michael Drumm; Alicia Steffens; Jonathan Lamano; Jonathan Judkins; Margaret Schwartz; Rodrigo Javier; Christina Amidei; Eric S. Lipp; Katherine B. Peters; Albert Lai; Blaine S.C. Eldred; Amy B. Heimberger; Kathleen McCortney; Denise M. Scholtens; Craig Horbinski

doi:10.1182/blood.2022017858

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

Kirsten Bell Burdett, Dusten Unruh, Michael Drumm, Alicia Steffens, Jonathan Lamano, Jonathan Judkins, Margaret Schwartz, Rodrigo Javier, Christina Amidei, Eric S. Lipp, Katherine B. Peters, Albert Lai, Blaine S.C. Eldred, Amy B. Heimberger, Kathleen McCortney, Denise M. Scholtens, Craig Horbinski^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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 (IDH^mut) caused fewer VTEs; multivariable analysis suggested that this is due to IDH^mut 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, IDH^mut, 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.

Original language	English (US)
Pages (from-to)	1322-1336
Number of pages	15
Journal	Blood
Volume	141
Issue number	11
DOIs	https://doi.org/10.1182/blood.2022017858
State	Published - Mar 16 2023

Funding

D.U. was supported by the National Institutes of Health (NIH) National Cancer Institute (NCI) grant F32CA216996 . C.H. was supported by NIH National Institute of Neurological Disorders and Stroke grants R01NS102669 , R01NS117104 , and R01NS118039 ; the Northwestern University SPORE in Brain Cancer grant P50CA221747 ; and the Lou and Jean Malnati Brain Tumor Institute . Histology and microscopy services were provided by the Mouse Histology and Phenotyping Laboratory, supported by NCI grant P30CA060553 , awarded to the Robert H. Lurie Comprehensive Cancer Center.

ASJC Scopus subject areas

Hematology
Biochemistry
Cell Biology
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1182/blood.2022017858

Cite this

Burdett, K. B., Unruh, D., Drumm, M., Steffens, A., Lamano, J., Judkins, J., Schwartz, M., Javier, R., Amidei, C., Lipp, E. S., Peters, K. B., Lai, A., Eldred, B. S. C., Heimberger, A. B., McCortney, K., Scholtens, D. M., & Horbinski, C. (2023). Determining venous thromboembolism risk in patients with adult-type diffuse glioma. Blood, 141(11), 1322-1336. https://doi.org/10.1182/blood.2022017858

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title = "Determining venous thromboembolism risk in patients with adult-type diffuse glioma",

abstract = "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.",

author = "Burdett, {Kirsten Bell} and Dusten Unruh and Michael Drumm and Alicia Steffens and Jonathan Lamano and Jonathan Judkins and Margaret Schwartz and Rodrigo Javier and Christina Amidei and Lipp, {Eric S.} and Peters, {Katherine B.} and Albert Lai and Eldred, {Blaine S.C.} and Heimberger, {Amy B.} and Kathleen McCortney and Scholtens, {Denise M.} and Craig Horbinski",

note = "Publisher Copyright: {\textcopyright} 2023 The American Society of Hematology",

year = "2023",

month = mar,

day = "16",

doi = "10.1182/blood.2022017858",

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Burdett, KB, Unruh, D, Drumm, M, Steffens, A, Lamano, J, Judkins, J, Schwartz, M, Javier, R, Amidei, C, Lipp, ES, Peters, KB, Lai, A, Eldred, BSC, Heimberger, AB, McCortney, K, Scholtens, DM & Horbinski, C 2023, 'Determining venous thromboembolism risk in patients with adult-type diffuse glioma', Blood, vol. 141, no. 11, pp. 1322-1336. https://doi.org/10.1182/blood.2022017858

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T1 - Determining venous thromboembolism risk in patients with adult-type diffuse glioma

AU - Burdett, Kirsten Bell

AU - Unruh, Dusten

AU - Drumm, Michael

AU - Steffens, Alicia

AU - Lamano, Jonathan

AU - Judkins, Jonathan

AU - Schwartz, Margaret

AU - Javier, Rodrigo

AU - Amidei, Christina

AU - Lipp, Eric S.

AU - Peters, Katherine B.

AU - Lai, Albert

AU - Eldred, Blaine S.C.

AU - Heimberger, Amy B.

AU - McCortney, Kathleen

AU - Scholtens, Denise M.

AU - Horbinski, Craig

PY - 2023/3/16

Y1 - 2023/3/16

N2 - 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.

AB - 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.

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

Abstract

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ASJC Scopus subject areas

UN SDGs

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