Stroke As a Late Treatment Effect of Hodgkin's Disease: A Report From the Childhood Cancer Survivor Study

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Abstract
Purpose: The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors. Patients and Methods: The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings. Results: Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% CI, 3.85 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% CI, 54.5 to 121.7 per 100,000 person-years). The RR of stroke among HD survivors was 4.32 (95% CI, 2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% CI, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P < .0001). Conclusion: Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease.