Hypothyroidism after Radiation Therapy for Childhood Cancer: A Report from the Childhood Cancer Survivor Study

被引:38
作者
Inskip, Peter D. [1 ]
Veiga, Lene H. S. [1 ,3 ]
Brenner, Alina V. [1 ]
Sigurdson, Alice J. [1 ]
Ostroumova, Evgenia [1 ,4 ]
Chow, Eric J. [5 ,6 ]
Stovall, Marilyn [7 ]
Smith, Susan A. [7 ]
Weathers, Rita E. [7 ]
Leisenring, Wendy [5 ,6 ]
Robison, Leslie L. [8 ]
Armstrong, Gregory T. [8 ]
Sklar, Charles A. [9 ]
Lubin, Jay H. [2 ]
机构
[1] NCI, Radiat Epidemiol, NIH, US Dept HHS, Bethesda, MD 20892 USA
[2] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA
[3] Brazilian Nucl Energy Commiss, Inst Radiat Protect & Dosimetry, Rio De Janeiro, Brazil
[4] Int Agcy Res Canc, Lyon, France
[5] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA
[6] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA
[7] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA
[8] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St, Memphis, TN 38105 USA
[9] Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA
基金
美国国家卫生研究院;
关键词
THYROID-CANCER; ADULT SURVIVORS; POOLED ANALYSIS; RADIOTHERAPY; HYPOPITUITARISM; ABNORMALITIES; DYSFUNCTION; DISEASES; RISK; HEAD;
D O I
10.1667/RR14888.1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
While thyroid cancer risks from exposure to ionizing radiation early in life are well characterized quantitatively, the association of radiation with nonmalignant, functional thyroid disorders has been less studied. Here, we report on a risk analysis study of hypothyroidism with radiation dose to the thyroid gland and the hypothalamic-pituitary axis among survivors of childhood cancer. Utilizing data from the Childhood Cancer Survivor Study, a cohort of 14,364 fiveyear survivors of childhood cancer diagnosed at 26 hospitals in the U.S. and Canada between 1970 and 1986 and followed through 2009, the occurrence of hypothyroidism was ascertained among 12,015 survivors through serial questionnaires. Radiation doses to the thyroid gland and pituitary gland were estimated from radiotherapy records. Binary outcome regression was used to estimate prevalence odds ratios for hypothyroidism at five years from diagnosis of childhood cancer and Poisson regression to model incidence rate ratios (RR) after the first five years. A total of 1,193 cases of hypothyroidism were observed, 777 (65%) of which occurred five or more years after cancer diagnosis. The cumulative proportion affected with hypothyroidism (prevalence at five years after cancer diagnosis plus incidence through 30 years after cancer diagnosis) was highest among five-year survivors of Hodgkin lymphoma (323%; 95% CI: 29.5-34.9) and cancers of the central nervous system (17.7%; 95% CI: 15.2-20.4). The incidence rate was significantly associated with radiation dose to the thyroid and pituitary. The joint association of hypothyroidism with thyroid and pituitary dose was sub-additive for pituitary doses greater than 16 Gy. In particular, a very strong thyroid radiation dose dependence at low-to-moderate pituitary/hypothalamic doses was diminished at high pituitary doses. Radiation-related risks were higher in males than females and inversely associated with age at exposure and time since exposure but remained elevated more than 25 years after exposure. Our findings indicated that hypothyroidism was significantly associated with treatment with bleomycin (RR = 3.4; 95% CI: 1.6-7.3) and the alkylating agents cyclohexyl-chloroethylnitrosourea (CCNU) (RR = 3.0; 95% CI: 1.5-5.3) and cyclophosphamide (RR = 1.3; 95% CI: 1.0-1.8), with a significant dose response for CCNU (P < 0.01). The risk of hypothyroidism among childhood cancer survivors treated with radiation depends both on direct, dose-dependent radiation-induced damage to the thyroid gland and on dose-dependent indirect effects secondary to irradiation of the hypothalamic-pituitary axis. The dose-response relationship for each site depends on dose to the other. Radiation-related risk persists for more than 25 years after treatment. Treatment with certain chemotherapy agents may increase the risk of hypothyroidism. (C) 2018 by Radiation Research Society
引用
收藏
页码:117 / 132
页数:16
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