Long-term risk and characteristics of cerebrovascular events after upper body radiotherapy among childhood cancer survivors in the DCCSS-LATER cohort

Abstract

Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed <age 18 years in the period 1963-2001. Data about CVEs were retrieved from medical records of survivors treated with upper body radiotherapy (n = 1633). Multivariable Cox and logistic regression models were used to identify potential risk factors for developing a symptomatic CVE. In 107 survivors with upper body radiotherapy, a CVE emerged, at a median age of 35.5 years. Cumulative incidence 40 years after diagnosis was 9.1% (95% CI: 7.2%-11.6%). A cranial radiotherapy prescription dose >50 Gy was associated with 6-fold increased risk, compared to upper body radiotherapy not involving the cranium (hazard ratio = 6.3, 95%CI: 3.3-12.1). In a subgroup with available data on lifestyle and comorbidities, hypertension (odds ratio[OR] = 6.2, 95%CI: 1.6-23.8) and obesity (BMI≥30 vs. <30 = 2.95, 95%CI: 1.1-8.0) significantly increased CVE risk. During CVE episode, 17 (16%) had a life-threatening situation, and two (2%) others died. In 28%, a second CVE developed during follow-up. At end of follow-up, 29% were deceased, and 40% of those alive were unable to carry out normal activities/active work. Childhood cancer survivors treated with higher doses of cranial radiotherapy are at highest risk for developing CVEs. CVEs occur at a young age and cause a high morbidity. Studies to investigate risk-reducing secondary preventive interventions are warranted.