Factors associated with fatal stroke in glioma patients: a population analysis

Importance Brain tumour patients have the highest stroke mortality rates among all cancer types, but the factors associated with fatal stroke in brain tumour remain unknown. Objective We aimed to examine to what extent brain tumour grade, a marker of biological aggressiveness, tumour size and cancer treatment each associated with stroke mortality in glioma. Gliomas include the most common malignant types of brain cancer. Design, setting, participants A retrospective, observational cohort study 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). The primary outcome of interest was death from cerebrovascular disease. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were calculated using cause-specific Cox regression model to determine associations with tumour characteristics: grades II-IV, tumour size and cancer treatment (surgery, radiotherapy, chemotherapy) associated with stroke mortality after adjustment for age, sex, race, marital status and calendar years. Results In patients with glioma, increased risk for stroke mortality was observed in patients with higher grade (Grade III: aHR=1.19, 95% CI=0.88-1.61, p>0.05; Grade IV: aHR=1.94, 95% CI=1.39-2.71 compared to Grade II, p<0.001), and those with larger brain tumours (size=3-6 cm: aHR=1.93, 95%CI 1.31 -2.85, p9cm: aHR=2.07, 95% CI=1.40-3.06, p<0.001 compared to size < 3cm). Having treatment was associated with decreased risk: surgery (yes VS no: aHR= 0.65; p<0.01), radiation (yes VS no: aHR= 0.66, p<0.01), chemotherapy (yes VS no: aHR=0.49, p<0.001). Conclusions Higher grade and tumour size are strongly associated with increased stroke mortality. This implicates tumour biology and/or the systemic tumour response which require further investigation in prospective studies to determine strategies to mitigate this risk.