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

From The University of Texas Southwestern Medical Center at Dallas, Dallas; The M.D. Anderson Cancer Center, Houston, TX; US Food and Drug Administration, Rockville, MD; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Minnesota, Minneapolis, MN; St Jude Children's Research Hospital, Memphis, TN; Stanford University School of Medicine, Stanford, CA; Children's National Medical Center, Washington, DC, and the Childhood Cancer Survivor Study (see online Appendix)

Address reprint requests to Daniel Bowers, MD, Department of Pediatrics, 5323 Harry Hines Blvd, Dallas, TX 75390-9063; e-mail: Daniel.Bowers{at}utsouthwestern.edu

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.

Supported by grant No. 5U01-CA-55727-05 from the Department of Health and Human Services and funding to the University of Minnesota from the Children's Cancer Research Fund.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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