Radiation-induced cerebral contrast enhancements strongly share ischemic stroke risk factors

BACKGROUND AND PURPOSE:Radiation-induced cerebral contrast enhancements (RICE) are frequent following both photon and particularly proton radiotherapy and are associated with a significant risk for neurologic morbidity. Nevertheless, risk factors are poorly understood. A more robust understanding of RICE risk factors is crucial to improve management and offer adaptive therapy at the outset and during follow-up. MATERIALS AND METHODS:We analyzed the comorbidities in detail of 190 consecutive adult patients treated at a single European national comprehensive cancer center with proton radiotherapy (PRT; 54Gy RBE) for LGG from 2010 to 2020 who were followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years. RESULTS:Classical vascular risk factors including age (≥50 years vs. <50 years: 1.6-fold; p=0.0024), hypertension (2.7-fold; p=0.00012) and diabetes (11.7-fold; p=0.0066) were observed more frequently in the cohort who developed RICE. Dyslipidemia (2.1-fold), overweight (2.0-fold) and smoking (2.6-fold) as well as history of previous stroke (1.7-fold) were also more frequently observed in the RICE cohort, though these factors did not reach threshold for significance. Multivariable regression modelling supported the influence of age (p=0.05), arterial hypertension (p=0.01) and potentially male sex (p=0.02), diabetes (p=0.0008) and smoking (p=0.001) on RICE occurrence over time, independent of each other and further vascular risk factors. If RICE occurred, bevacizumab treatment was two-fold more frequently needed in the cohort with vascular risk factors, but RICE long-term prognosis did not differ between the RICE subcohort with and without vascular risk factors. CONCLUSIONS:This is the first report in the literature demonstrating RICE strongly share vascular risk factors with ischemic stroke, which further enhances the nebulous understanding of the multifactorial pathophysiology of RICE. Classical vascular risk factors, especially age, hypertension and diabetes clearly correlated independently with RICE risk. Risk-adapted screening and management for RICE can be directly derived from this data to assist in clinical management.