Chemotherapy and Thyroid Cancer Risk: a Report from the Childhood Cancer Survivor Study

• Authors: Lene H. S. Veiga, National Cancer Institute; Parveen Bhatti, National Cancer Institute; Cecile M. Ronckers, National Cancer Institute; Alice J. Sigurdson, National Cancer Institute; Marilyn Stovall, University of Texas M. D. Anderson Cancer Center; Susan A. Smith, University of Texas M. D. Anderson Cancer Center; Rita Weathers, University of Texas M. D. Anderson Cancer Center; Wendy Leisenring, Fred Hutchinson Cancer Research Center; Ann Mertens, Emory University; Sue Hammond, Children's Hospital; Joseph P. Neglia, University of Minnesota; Anna T. Meadows, Children's Hospital of Philadelphia; Sarah S. Donaldson, Stanford Cancer Center; Charles A. Sklar, Memorial Sloan-Kettering Cancer Center; Debra L. Friedman, Vanderbilt-Ingram Cancer Center; Leslie L. Robison, St. Jude Children’s Research Hospital; Peter D. Inskip, National Cancer Institute
• Journal Title: Cancer Epidemiology, Biomarkers and Prevention
• Volume: Volume 21, Number 1
• Publisher: American Association for Cancer Research | 2012-01-01, Pages 92-101
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1158/1055-9965.EPI-11-0576
• Subjects: Health Sciences, Oncology; Physics, Radiation; Health Sciences, Epidemiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Public, Environmental & Occupational Health; 2ND MALIGNANT NEOPLASMS; ALKYLATING-AGENTS; SOLID TUMORS; RADIATION; RADIOTHERAPY; EXPERIENCE; LEUKEMIA; THERAPY; DISEASE; COHORT

Abstract

Background: Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy. Methods: The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose. Results: Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P trend = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy. Conclusions: Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing. Impact: Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy.