Risk of Radiation Vasculopathy and Stroke in Pediatric Patients Treated With Proton Therapy for Brain and Skull Base Tumors

Abstract

Purpose: To estimate the rate of and identify risk factors for vasculopathy after proton therapy in pediatric patients with central nervous system and skull base tumors.

Methods and materials: Between 2006 and 2015, 644 pediatric patients with central nervous system and skull base tumors were treated with proton therapy at a single institution. The 3 most common histologies were craniopharyngioma (n = 135), ependymoma (n = 135), and low-grade glioma (n = 131). The median age was 7.6 years (range, 0.7-21.8 years), and the median prescribed dose was 54 cobalt gray equivalent (CGE) (range, 25.2-75.6 CGE). For this analysis, vasculopathy included asymptomatic vessel narrowing identified on imaging, transient ischemic attacks, and cerebrovascular accidents. Serious vasculopathy was defined as events resulting in permanent neurologic complications or requiring revascularization surgery. Multivariate logistic regression (MVA) was used to assess predictors of toxicity. Variables examined included age, neurofibromatosis, extent of surgical resection, chemotherapy, postoperative stroke, total prescribed dose, and dose delivered to the optic nerves, chiasm, and hypothalamus.

Results: With a median follow-up of 3.0 years (range, 0.1-9.6 years), the 3-year cumulative rates of any vasculopathy and serious vasculopathy were 6.4% and 2.6%, respectively. Seven children (1.2%) experienced a stroke with permanent neurologic deficits; 4 required revascularization surgery. On MVA, maximum dose to the optic chiasm ≥ 54 CGE was significantly associated with the development of any vasculopathy (13.1% vs 2.2%; P < .001); age < 5 years was also significant (8.4% vs 5.4%; P < .01). On MVA, maximum dose to the optic chiasm ≥ 54 CGE also predicted serious vasculopathy (3.8% vs 1.7%; P < .05).

Conclusions: Childhood cancer survivors are at risk of vasculopathy after cranial radiation therapy. Young children and those receiving ≥54 CGE to the chiasm are at an increased risk of this toxicity. These findings suggest appropriate follow-up and screening are important in this population.