Patients who received radioactive iodine (RAI) treatment for hyperthyroidism had an increased risk of death from solid tumours, including breast cancer, with the risk increasing when treatment was given at higher doses, shows a study*, led by researchers at the National Cancer Institute, part of the National Institutes of Health, published in JAMA Internal Medicine.
"We identified a clear dose-response relationship between this widely used treatment and long-term risk of death from solid cancer, including breast cancer, in the largest cohort study to date of patients treated for hyperthyroidism," said Cari Kitahara, from the Division of Cancer Epidemiology and Genetics, at the National Cancer Institute.
"We estimated that for every 1,000 patients treated currently using a standard range of doses, about 20 to 30 additional solid cancer deaths would occur as a result of the radiation exposure."
RAI is one of the three most commonly used treatments for hyperthyroidism and has been used since the 1940s. The other two are anti-thyroid drugs, which have been rising in popularity, and surgical treatment, which is used least often.
The researchers used data from the Cooperative Thyrotoxicosis Therapy Follow-up Study - a long-term follow-up study of a large cohort of people with hyperthyroidism (mainly Graves' disease) who were treated with radiation between 1946 and 1964.
In the new analysis, which included nearly 19,000 people from the original cohort, all of whom had received RAI and none of whom had had cancer at study entry, the researchers used a novel, comprehensive method of estimating radiation doses to each organ or tissue. Most of the radiation is absorbed by the thyroid gland, but other organs like the breast and stomach are also exposed during treatment.
The researchers observed positive dose-response relationships between the dose absorbed by an organ and mortality from cancer at that site. The relationship was statistically significant for female breast cancer, for which every 100 milligray (mGy) of dose led to a 12% increased relative risk of breast cancer mortality, and for all other solid tumours considered together, for which relative risk of mortality was increased by 5% per every 100 mGy.
Based on these findings, the researchers estimated that for every 1,000 patients aged 40 years with hyperthyroidism who were treated with the radiation doses typical of current treatment, a lifetime excess of 19 to 32 radiation-attributable solid cancer deaths would be expected.
“We found the increased risks of death from solid cancer overall and from breast cancer more specifically to be modest, but RAI is still a widely used treatment for hyperthyroidism," Dr Kitahara said.
"It's important for patients and their physicians to discuss the risks and benefits of each available treatment option. The results of our study may contribute to these discussions."
The researchers wrote that additional research is needed to more comprehensively assess the risk-benefit ratio of radiation versus other available treatment options for hyperthyroidism, particularly current anti-thyroid drugs.
Commenting on the study Professor Jim Smith, professor of environmental science, University of Portsmouth, said: “Extremely high doses to organs required for radiation therapy can cause other parts of the body also to receive much lower, but still significant doses. This study does not in any way mean that radiation therapy is not the best treatment for hyperthyroidism, but it helps evaluate the risks.”
Professor Saad Shakir, director of the Drug Safety Research Unit, said: “The influence of the finding of this study on clinical decisions has to be put in context with the benefits of the use radioactive iodine for hyperactive thyroid disease and with the benefits and risks of different therapies. This fine balance can be discussed by doctors with patients when choosing the best therapy for the treatment of hyperactive thyroid disease.”
*Kitahara CM, Berrington de Gonzalez A, Bouville A, et al. Association of Radioactive Iodine Treatment With Cancer Mortality in Patients With Hyperthyroidism. JAMA Intern Med. Published online July 01, 2019. doi:10.1001/jamainternmed.2019.0981