Frequency, Risk Factors, and Outcomes of Strokes in Patients With Primary Glioma After Cranial Radiation Therapy

BACKGROUND AND OBJECTIVES: Radiation therapy is the mainstay of therapy for patients with glioma. While this treatment modality can improve survival, treatment-related complications may include radiation-induced vasculopathy and increased risk of stroke. We aimed to evaluate the stroke frequency, associated risk factors, and outcomes after cranial radiation therapy in patients with glioma. METHODS: This is a retrospective cohort study at a single tertiary academic brain tumor center involving patients diagnosed with gliomas between 2005 and 2021 who received cranial radiation therapy. Data were collected from the time of cranial radiation therapy until last follow-up. Logistic regression analyses were used to evaluate the association of clinical and demographic variables with all-cause, ischemic, and hemorrhagic strokes. RESULTS: In a retrospective cohort of 930 patients, 910 received radiation therapy (mean age 53.8 years; 40% women) and were included in the final analysis. A total of 91 patients (10.0%) were diagnosed with stroke (73.6% ischemic; 15.4% with recurrent strokes). The median time to diagnosis of stroke after onset of radiation therapy was 652 days with median time to recurrent stroke of 102 days. In a univariable model, Black race (odds ratio [OR] 3.83, 95% CI 1.94-7.56), radiation necrosis (OR 4.62, 95% CI 2.02-10.55), hypertension (OR 1.93, 95% CI 1.23-3.01), hyperlipidemia (OR 5.93, 95% CI 3.61-9.57), and diabetes mellitus (OR 2.25, 95% CI 1.28-3.95) were associated with higher odds of all-cause stroke. In multivariable analysis, Black race (OR 3.41, 95% CI 1.59-7.33), radiation necrosis (OR 6.42, 95% CI 2.45-16.79), and hyperlipidemia (OR 6.42, 95% CI 3.91-10.57) were significantly associated with increased odds of all-cause stroke. Radiation necrosis and hyperlipidemia were associated with increased odds of ischemic stroke. Black race, hyperlipidemia, and younger age were associated with increased odds of hemorrhagic stroke. Compared with ischemic strokes, hemorrhagic strokes were associated with higher poststroke disability. DISCUSSION: In a large, retrospective cohort of adult patients with glioma treated with cranial radiation therapy, 1 in 10 patients were subsequently diagnosed with stroke with 15.4% suffering recurrent strokes. Factors associated with increased odds of stroke included Black race, radiation necrosis, and hyperlipidemia and should be validated in future prospective cohorts. Study limitations include the retrospective design, incomplete stroke workups, and lack of molecular diagnostics.