Abstract

Introduction: Glioma is the most common malignant type of brain tumours. Glioma patients are at higher risk for cerebrovascular mortality compared to the general population and other cancer types. Whether the risk differs by the grade, a marker of aggressiveness in gliomas, remains unclear. Methods: Using the US National Cancer Institute’s Surveillance Epidemiology and End Results program, we identified adult patients with a primary diagnosis of malignant gliomas in 2000 to 2018 (N=72,252). Age-, sex-, and calendar-year- adjusted standardized mortality ratios (SMRs) were calculated for cerebrovascular mortality comparing glioma patients with the general population. Gliomas were classified into four grades based on WHO definition in which increasing grade indicates the higher degrees of invasiveness. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox regression model to examine cerebrovascular mortality in patients with different grades of gliomas. Results: Over 80% of patients were diagnosed with high grade gliomas (Grade 3 & 4). Patients with gliomas in all grades had excess cerebrovascular mortality compared with the general population (SMRs 2.64-4.18, p<0.001). Younger patients (< 50 years) with glioblastoma (Grade 4), the most aggressive type, had substantially greater risk (SMR 12.73, p<0.001) than the general population compared to those with lower grades (SMR 7.14 & 6.31 in Grade 2 & 3, p<0.001). In grade 4, Hispanic patients had highest risk (SMR 6.23, p<0.001) than other ethnic groups (SMR 3.67 & 4.92 in White and Black respectively, p<0.001). In case-only analysis, patients with Grade 4 were significantly associated with increased cerebrovascular mortality compared to the lower grade (HR=1.41, 95% CI 1.01-1.97, p<0.01) after adjustment of socio-demographic and treatment (surgery, radiation and chemotherapy) characteristics. Conclusions: The findings of higher grades of gliomas associated with cerebrovascular mortality support further research to understand the role of aggressiveness and other risk factors in brain cancer-associated fatal stroke.

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