Association of Radioactive Iodine Treatment With Cancer Mortality in Patients With Hyperthyroidism

Abstract

IMPORTANCE Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hypothyroidism. OBJECTIVE To determine whether greater organ-or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. DESIGN, SETTING, AND PARTICIPANTS This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18 805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. EXPOSURES Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). MAIN OUTCOMES AND MEASURES Site-specific and all solid-cancer mortality. RESULTS A total of 18 805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14 671 [78.0%]), and most had a Graves disease diagnosis (17 615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984

Should radioiodine now be first line treatment for Graves’ disease?

“…In addition, the dosimetric model used in the study was based on a series of assumptions which resulted in uncertainties in the tissue dose estimates. Also, the study did not adjust for relevant confounders for cancer risk including smoking, obesity, alcohol intake, and thyroid status [11]. Lastly, the association with breast or solid cancer risk seems implausible given that the mean radioiodine dose in the study was < 500 MBq which is about a tenth of the usual treatment doses administered to thyroid cancer patients [25].…”

“…A more varied picture is seen with cancer mortality, with reports of increased [11,14,18], similar [12] or even decreased [16], overall cancer mortality risk in radioiodine-treated patients with hyperthyroidism. In positive studies, increased cancer risk was dose dependent [11,14,18] and attributable to upper gastroesophageal [14,18], respiratory tract [14] or breast tumours [11] suggesting that the malignancies were a consequence of internal exposure to radioactivity in iodide accumulating organs. Cancer mortality risk was also increased in younger versus older patients and in patients with toxic nodules compared to Graves' disease patients [14].…”

“…Of interest is the recent study by Kitahara et al which evaluated cancer mortality in 18,805 radioiodine-treated patients from the Cooperative Thyrotoxicosis Therapy Follow-up study cohort (CTTFUS) [11]. The CTTFUS is a long-running longitudinal cohort of more than 35,000 hyperthyroid patients enrolled between 1946 and 1964 in the United States and United Kingdom.…”

“…The importance of treatment efficacy has also been highlighted by a number of recent observational studies that have shown an increase in longterm cardiovascular mortality in poorly controlled patients with hyperthyroidism [7][8][9][10]. However, a recent large-scale study in patients with hyperthyroidism reported increased cancer mortality in association with radioiodine treatment [11]. This study has raised concern regarding the safety of radioiodine and hence the implications of the NICE guidance.…”

Is There a Risk of Cancer Following Radioactive Iodine Therapy for Hyperthyroidism?

“…Previous studies on this topic have shown mixed results (1-6); one of the key methodological concerns in these studies has been the control group, which typically is drawn from the general population rather than from groups of patients with the same condition but who are treated with a different method. A recent provocative study that indicated a 12% higher relative risk of breast cancer after RAI therapy per 100 mGy to the breast has again sparked the debate about the potential risks of RAI (1). The current study (7) aimed to investigate the association of RAI therapy as compared with treatment with antithyroid drugs for hyperthyroidism.…”