Greater organ-absorbed doses of radioactive iodine (RAI) seem to be positively associated with risk for death from solid cancer in patients with hyperthyroidism, according to study results published in JAMA Internal Medicine.
Researchers conducted this 24-year extension study to examine how RAI treatment affects overall and site-specific cancer mortality in patients with hyperthyroidism. The cohort consisted of 18,805 patients (average age at entry, 49 years; 78% women) from the United States and United Kingdom who were treated with RAI and had no history of cancer upon first treatment. Graves disease was present in 93.7% of the population and the remaining patients had toxic nodular goiter or an unknown diagnosis.
The most common treatment combination was RAI and antithyroid drugs (46.1%), followed by RAI alone (38.2%); RAI, surgical procedure, and drugs (12.0%); and RAI and surgery (3.7%). Mean total administered activity of sodium iodide I 131 was 375 MBq in patients with Graves disease and 653 MBq in patients with toxic nodular goiter.
Over a mean follow-up of 26 years, 15,484 deaths occurred. Excluding deaths within the first 5 years after the last RAI treatment, researchers discovered significant positive associations between RAI and all solid cancer mortality (n=1984; relative risk [RR] at 100-mGy dose to the stomach, 1.06; P =.002), female breast cancer (n=291; RR at 100-mGy dose to the breast, 1.12; P =.04) and all other solid cancers combined (n=1693; RR at 100-mGy dose to the stomach, 1.05; P =.01).
A 100-mGy dose to the stomach and breast corresponded to an average administered activity of 243 MBq and 266 MBq, respectively, in patients with Graves disease. The researchers estimated that 13 excess solid cancer deaths, including 3 from breast cancer, would occur for every 1000 patients receiving 100 mGy to the stomach or breast at age 40 years. Furthermore, for every 1000 patients receiving a typical dose to the stomach at age 40 years (given higher administered activities of 370-555 MBq in Graves disease), researchers reported that there was potential for an estimated lifetime excess of 19 to 32 solid cancer deaths.
Study limitations included potential bias because of “major uncertainties” in organ dose estimations.
“We believe the results of this study provide quantitative estimates of the risks of radiation-associated cancer deaths in RAI-treated patients with hyperthyroidism, which were previously not well understood,” said the researchers, “and suggest that the risk of death from solid cancer (including breast cancer) increases with the greater absorbed dose to exposed organs and tissues.”
Kitahara CM, Berrington de Gonzalez A, Bouville A, et al. Association of radioactive iodine treatment with cancer mortality in patients with hyperthyroidism [published online July 1, 2019]. JAMA Intern Med. doi:10.1001/jamainternmed.2019.0981