Originally published as JCO Early Release 10.1200/JCO.2006.07.2884 on November 6 2006

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Late-Occurring Stroke Among Long-Term Survivors of Childhood Leukemia and Brain Tumors: A Report From the Childhood Cancer Survivor Study

Daniel C. Bowers, Yan Liu, Wendy Leisenring, Elizabeth McNeil, Marilyn Stovall, James G. Gurney, Leslie L. Robison, Roger J. Packer, Kevin C. Oeffinger

From The University of Texas Southwestern Medical Center at Dallas, Dallas; The University of Texas M.D. Anderson Cancer Center, Houston, TX; Fred Hutchinson Cancer Research Center, Seattle, WA; US Food and Drug Administration, Rockville, MD; University of Michigan, Ann Arbor, MI; St Jude Children's Research Hospital, Memphis, TN; Children's National Medical Center, Washington, DC; and Memorial Sloan-Kettering Cancer Center, New York, NY

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

Purpose This report examines the incidence of and risk factors for strokes that occur in 5-year survivors of childhood leukemia and brain tumors.

Patients and Methods The rate of first occurrence of self-reported late-occurring strokes was determined for leukemia survivors (n = 4,828), brain tumor survivors (n = 1,871), and a comparison group of a random sample of cancer survivor siblings (n = 3,846). Relative risks (RRs) and 95% confidence intervals (CIs) of stroke by treatment exposures were examined by multivariate analyses.

Results Thirty-seven leukemia survivors and 63 brain tumor survivors reported a late-occurring stroke. The rate of late-occurring stroke for leukemia survivors was 57.9 per 100,000 person-years (95% CI, 41.2 to 78.7). The RR of stroke for leukemia survivors compared with the sibling comparison group was 6.4 (95% CI, 3.0 to 13.8; P < .0001). The rate of late-occurring stroke for brain tumor survivors was 267.6 per 100,000 person-years (95% CI, 206.8 to 339.2). The RR of stroke for brain tumor survivors compared with the sibling comparison group was 29.0 (95% CI, 13.8 to 60.6; P < .0001). Mean cranial radiation therapy (CRT) dose of 30 Gy was associated with an increased risk in both leukemia and brain tumor survivors in a dose-dependent fashion, with the highest risk after doses of 50 Gy CRT.

Conclusion Survivors of childhood leukemia and brain tumors, particularly those with brain tumors treated with CRT at doses of greater than 30 Gy, are at an increased risk of stroke.

published online ahead of print at www.jco.org on November 6, 2006.

Supported by Grant No. U24-CA-55727 (L.L.R., Principal Investigator) from the Department of Health and Human Services, funding to the University of Minnesota from the Children's Cancer Research Fund, and funding to St Jude Children's Research Hospital from the American Lebanese Syrian Associated Charities.

Presented at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL.

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

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