Hyperthyroidism after radiation therapy for childhood cancer: A report from the Childhood Cancer Survivor study Journal Article


Authors: Inskip, P. D.; Veiga, L. H. S.; Brenner, A. V.; Sigurdson, A. J.; Ostroumova, E.; Chow, E. J.; Stovall, M.; Smith, S. A.; Leisenring, W.; Robison, L. L.; Armstrong, G. T.; Sklar, C. A.; Lubin, J. H.
Article Title: Hyperthyroidism after radiation therapy for childhood cancer: A report from the Childhood Cancer Survivor study
Abstract: Purpose: The association of hyperthyroidism with exposure to ionizing radiation is poorly understood. This study addresses the risk of hyperthyroidism in relation to incidental therapeutic radiation dose to the thyroid and pituitary glands in a large cohort of survivors of childhood cancer. Methods and Materials: Using the Childhood Cancer Survivor Study's cohort of 5-year survivors of childhood cancer diagnosed at hospitals in the United States and Canada between 1970 and 1986, the occurrence of hyperthyroidism through 2009 was ascertained among 12,183 survivors who responded to serial questionnaires. Radiation doses to the thyroid and pituitary glands were estimated from radiation therapy records, and chemotherapy exposures were abstracted from medical records. Binary outcome regression was used to estimate prevalence odds ratios (ORs)for hyperthyroidism at 5 years from diagnosis of childhood cancer and Poisson regression to estimate incidence rate ratios (RRs)after the first 5 years. Results: Survivors reported 179 cases of hyperthyroidism, of which 148 were diagnosed 5 or more years after their cancer diagnosis. The cumulative proportion of survivors diagnosed with hyperthyroidism by 30 years after the cancer diagnosis was 2.5% (95% confidence interval [CI], 2.0%-2.9%)among those who received radiation therapy. A linear relation adequately described the thyroid radiation dose response for prevalence of self-reported hyperthyroidism 5 years after cancer diagnosis (excess OR/Gy, 0.24; 95% CI, 0.06-0.95)and incidence rate thereafter (excess RR/Gy, 0.06; 95% CI, 0.03-0.14)over the dose range of 0 to 63 Gy. Neither radiation dose to the pituitary gland nor chemotherapy was associated significantly with hyperthyroidism. Radiation-associated risk remained elevated >25 years after exposure. Conclusions: Risk of hyperthyroidism after radiation therapy during childhood is positively associated with external radiation dose to the thyroid gland, with radiation-related excess risk persisting for >25 years. Neither radiation dose to the pituitary gland nor chemotherapy exposures were associated with hyperthyroidism among childhood cancer survivors through early adulthood. © 2019 Elsevier Inc.
Keywords: adolescent; adult; cancer chemotherapy; child; major clinical study; united states; cancer radiotherapy; chemotherapy; follow up; cancer diagnosis; radiotherapy dosage; radiotherapy; incidence; prevalence; cohort analysis; alkylating agent; radiation injury; medical record review; retrospective study; childhood cancer; hodgkin disease; radiation exposure; radiation response; confidence interval; nonhodgkin lymphoma; brain; neuroblastoma; dosimetry; diagnosis; soft tissue sarcoma; ionizing radiation; bleomycin; hyperthyroidism; hypothyroidism; anthracycline; childhood leukemia; canada; diseases; nephroblastoma; bone cancer; surveys; pituitary gland; childhood cancer survivor; epipodophyllotoxin derivative; cisplatin derivative; methods and materials; human; male; female; priority journal; article; central nervous system cancer; poisson regression; childhood cancers; external radiation dose; linear relation
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 104
Issue: 2
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2019-06-01
Start Page: 415
End Page: 424
Language: English
DOI: 10.1016/j.ijrobp.2019.02.009
PUBMED: 30769174
PROVIDER: scopus
PMCID: PMC6818231
DOI/URL:
Notes: Article -- Export Date: 3 June 2019 -- Source: Scopus
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MSK Authors
  1. Charles A Sklar
    312 Sklar