Radioactive Iodine Thyroid Treatment Linked to Cancer Mortality

By Will Boggs MD

July 03, 2019

NEW YORK (Reuters Health) - Treatment of hyperthyroidism with radioactive iodine (RAI) is associated with increased cancer mortality later in life, according to an extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study.

"The results of our study suggest a modest dose-dependent relationship between radioactive iodine treatment and solid cancer-related death, including breast cancer death, among patients with hyperthyroidism," Dr. Cari M. Kitahara from National Cancer Institute, Bethesda, Maryland told Reuters Health by email. "Physicians and patients may want to consider these findings when comparing the risks and benefits of different treatment options."

"For decades, radioactive iodine has been the preferred treatment option for uncomplicated cases of Graves' disease by endocrinologists in the United States, but antithyroid medications have gained favor in the United States and have been the preferred option in much of the rest of the world," she said. "However, evidence regarding the long-term effects of these treatments, which could help guide these decisions, has been limited."

The Cooperative Thyrotoxicosis Therapy Follow-up Study of more than 35,000 patients with hyperthyroidism enrolled between 1946 and 1964 found no elevation of total or site-specific cancer mortality rates through 1990 in RAI-treated patients compared with the general population.

Dr. Kitahara and colleagues extended the follow-up of this study by 24 years and evaluated the radiation dose-response relationships for site-specific cancer death among 18,805 RAI-treated patients with hyperthyroidism.

The highest absorbed radiation doses were to the thyroid (130 Gy), followed by the esophagus (1.6 Gy); liver, oral mucosa, lung, stomach, red bone marrow, female breast, pancreas, kidney (100-400 mGy); and uterus, brain, bladder, ovary, prostate, and colon or rectum (20-99 mGy).

During a mean follow-up of 26 years (maximum, 68 years), there was a positive dose-response relationship for mortality from most of the individual solid cancers evaluated, after excluding deaths in the first 5 years after the last RAI treatment, according to the July 1st JAMA Internal Medicine online report.

For example, a 100-mGy dose to the breast was associated with a 12% increased risk of female breast cancer mortality, and a 100-mGy dose to the stomach was associated with a 6% increased risk of all solid cancer mortality.

There was no evidence of a dose-response relationship for mortality from leukemia, non-Hodgkin lymphoma, or multiple myeloma.

The authors estimate that 8% of solid cancer deaths, including 14% of breast cancer and 7% of all other solid cancer deaths, during follow-up were attributable to radiation.

Based on current U.S. mortality rates, this translates into 13 excess solid cancer deaths, including 3 breast cancer deaths, for every 1000 patients treated at age 40 with 100 mGy absorbed dose to the stomach or breast or an excess of 12 radiation-associated solid cancer deaths, including 3 breast cancer deaths, for every 1000 patients treated at age 50.

At higher doses currently recommended for the treatment of patients with Graves' disease, the authors would expect 19 to 32 excess solid cancer deaths per 1000 patients treated at age 40 and 18 to 31 excess solid cancer deaths per 1000 patients treated at age 50.

"Our study, with nearly seven decades of follow-up and estimates of absorbed doses to organs and tissues for nearly 19,000 patients, showed that radioactive iodine treatment for hyperthyroidism was associated with a dose-dependent risk of death from solid cancer, including breast cancer," Dr. Kitahara said. "Although these associations were relatively modest in strength, these risks were previously unknown. The risk estimates could be factored into discussions between physicians and patients during treatment decision-making."


JAMA Intern Med 2019.