Early versus late venous thromboembolism in patients with newly diagnosed high-grade gliomas

Abstract Background Venous thromboembolism (VTE) occurs in 20-30% and 9.2% of patients with glioblastoma and grade 3 IDH mutant (IDHmut) gliomas respectively, with highest risk during the first months post-surgery. We sought to identify risk factors for early versus late VTE in high-grade gliomas and evaluated the recently proposed ‘GliomaPredictVTE’ tool. Methods We included 894 patients with newly-diagnosed glioblastoma and grade 3-4 IDHmut gliomas from 2010-2023. Competing-risk analysis estimated VTE cumulative incidence (CumInc), segmented linear regression model identified the change-point between early versus late VTE, and competing-risk regression model identified significant risk factors. GliomaPredictVTE-predicted 6- and 12-month VTE risks were compared to observed CumInc. Results The estimated 6- and 12-month VTE CumInc was 21.5% and 26.4%, respectively for IDHwt glioblastoma versus 6.3% and 8.3%, respectively for IDHmut gliomas. The VTE CumInc increased rapidly during the first 6 months post-surgery, followed by a more gradual rise thereafter, with a change-point around 6 months. On multivariable analyses, ‘Early VTE’ (within 6 months post-surgery) was significantly associated with older age, limb weakness, ambulation dependence, and radiotherapy alone; ‘Late VTE’ (6 months to 5 years) with older age and smoking. GliomaPredictVTE substantially underestimated VTE incidence in our population, with a mean predicted 6- and 12-month risks of 11.0% and 17.4%, versus observed CumInc of 19.9% (p < 0.001) and 23% (p = 0.008), respectively. Conclusions Distinct risk profiles between early and late VTE support prospective studies of primary prophylaxis in high-risk patients, particularly in the first 6 months post-surgery. GliomaPredictVTE significantly underestimates VTE incidence in this population.