Risk of Venous Thromboembolism in Grade II-IV Gliomas as a Function of Molecular Subtype

Neurology. 2021 Feb 16;96(7):e1063-e1069. doi: 10.1212/WNL.0000000000011414. Epub 2020 Dec 22.

Abstract

Objective: To determine the incidence of venous thromboembolism (VTE) in lower-grade gliomas (LGGs, WHO grades II-III) and to stratify the risk of VTE by molecular subtype in gliomas grade II-IV, we performed a retrospective review of a large cohort of patients with glioma.

Methods: We performed a retrospective analysis of a cohort of 635 adult patients with glioma with molecular testing seen at the University of Virginia with a diagnosis of diffuse glioma established from January 2005 to August 2017. Estimates of cumulative incidence of VTE were calculated with death as competing risk; significance was determined using the Fine and Gray model.

Results: Of 256 patients with LGG, 81 were isocitrate dehydrogenase (IDH) wild-type; 113 IDH mutant, 1p/19q codeleted; and 62 IDH mutant, 1p/19q intact. With a median follow-up of 17.9 months, the overall cumulative incidence of VTE was 8.2% for grade II (147 patients), 9.2% for grade III (109 patients), and 30.5% for grade IV (334 patients). In grade II-IV patients, absence of an IDH mutation was associated with a threefold increase in VTE risk when compared to IDH-mutant patients (hazard ratio 3.06, 95% confidence interval 2.03-4.64). In patients with glioblastoma, there was no difference in VTE incidence according to O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status.

Conclusion: Patients with LGG have a higher VTE risk compared to the general population, which is decreased, but not eliminated, in the presence of an IDH mutation. MGMT promoter methylation in glioblastoma does not affect the incidence of VTE.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / complications*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Female
  • Glioma / complications*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Incidence
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Promoter Regions, Genetic
  • Retrospective Studies
  • Risk
  • Venous Thromboembolism / epidemiology*
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / genetics

Substances

  • Isocitrate Dehydrogenase