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Osteonecrosis in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Nina S. Kadan-Lottick, Irina Dinu, Karen Wasilewski-Masker, Sue Kaste, Lillian R. Meacham, Anita Mahajan, Marilyn Stovall, Yutaka Yasui, Leslie L. Robison, Charles A. Sklar

From the Section of Pediatric Hematology-Oncology, Yale University School of Medicine, New Haven, CT; Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta; Emory Children's Center, Atlanta, GA; Department of Epidemiology and Cancer Control and Division of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN; The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY; and Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada

Corresponding author: Nina S. Kadan-Lottick, MD, Yale University School of Medicine, 333 Cedar St, LMP 2073, PO Box 208064, New Haven, CT 06520; e-mail: Nina.Kadan-Lottick{at}Yale.Edu

Purpose Osteonecrosis (ON) is a potentially serious complication of therapy in survivors of childhood cancer. Our goals were to describe the incidence of ON and identify patient and treatment characteristics associated with elevated risk.

Patients and Methods The rate of self-reported ON was determined for 9,261 patients enrolled onto the Childhood Cancer Survivor Study, a cohort of 5-year survivors of childhood cancer diagnosed from 1970 to 1986, and compared with the rate in a random sample of 2,872 siblings of survivors. Survivors with positive responses were reinterviewed to confirm the diagnosis.

Results Fifty-two cancer survivors reported ON in 78 joints, yielding 20-year cumulative incidence of 0.43% and a rate ratio (RR) of 6.2 (95% CI, 2.3 to 17.2) compared with siblings, adjusted for age and sex; 44% developed ON in a previous radiation field. The RR was greatest among survivors of stem-cell transplantation for acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (RR = 26.9, 66.5, and 93.1, respectively). Nontransplantation patients with ALL (RR = 6.5; 95% CI, 2.2 to 19.4), AML (RR = 11.2; 95% CI, 2.1 to 61.2), and bone sarcoma (RR = 7.3; 95% CI, 2.0 to 26.2) were at higher risk for ON. Older age at diagnosis, shorter elapsed time, older treatment era, exposure to dexamethasone (± prednisone), and gonadal and nongonadal radiation were independently associated with ON.

Conclusion ON among long-term survivors of childhood cancer is rare. However, compared with siblings, childhood cancer survivors have a significantly increased relative rate of ON, particularly those who were older at diagnosis and who received dexamethasone or radiation therapy. Future studies are needed to better delineate our findings, particularly the increased risk after gonadal radiation.

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. This publication was made possible by Clinical and Translational Science Award Grant No. Number KL2 RR024138 from the National Center for Research Resources, a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of National Center for Research Resources or National Institutes of Health (NIH). Information on Re-engineering the Clinical Research Enterprise can be obtained from the NIH website: http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp.

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

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