“Prior studies of patients with hyperthyroidism compared cancer rates across different treatment groups (those treated with radioactive iodine, surgery, antithyroid drugs, or some combination of these),” Dr Kitahara wrote to Cancer Therapy Advisor in an email. “These types of studies are susceptible to bias because the reason a patient might receiving one type of treatment or another may be related to her/his baseline risk of cancer.”
“Our study was the first to evaluate the dose-response relationship between radioactive iodine treatment and cancer using high-quality estimates of radiation absorbed doses to multiple organs and tissues. This was important because although most of the dose from the treatment is absorbed by the thyroid gland, other organs are exposed to various degrees based on their proximity to the thyroid and ability to take up iodine.”
But the data in this study may not be sufficient for making a causal inference about the relationship between RAI and cancer-related mortality.
“Radioactive iodine may result in increased risk of cancer, just like any other types of radiation, through inhibition of DNA repair,” Angela M. Leung, MD, associate professor of medicine at the UCLA David Geffen School of Medicine in Los Angeles, California, told Cancer Therapy Advisor in an email. “The controversy has been whether the relatively low radioactive iodine doses that we typically use to treat hyperthyroidism … are enough to result in this damage, since even the much higher doses of radioactive iodine that we use to treat thyroid cancer have themselves had mixed results in terms of a secondary malignancy.”
She added, however, that “with any retrospective data, one cannot make causal inferences, and we can only posit that a relationship may be present between RAI therapy and mortality due to the development of solid cancers.”
In the present study, furthermore, the researchers did not adjust for other cancer risks, including lifestyle factors like smoking and having a high body mass index.
Dr Kitahara acknowledged that the research team did not adjust for other cancer risks; this is a confounding variable that may affect the strength of the study’s conclusions. “The major limitation was the observational study design, which leaves open the possibility that our results may have been influenced by other cancer risk factors that we did not collect in our study (eg, smoking, obesity, alcohol use, reproductive factors.)”
However, Dr Kitahara continued, “it seems implausible that these other ‘confounding’ factors could fully explain the dose-response relationships we observed for all solid cancer mortality and breast cancer mortality. Confounding seemed unlikely to explain our breast cancer mortality, because our risk estimates were similar to those of other studies of radiation-exposed populations, such as the Japanese atomic bomb survivors.”
She added that RAI use for hyperthyroidism should, based on these results, depend on patient preferences, as well as a “careful assessment” of the benefits and risks of all other options.
- Ron E, Doody MM, Becker DV, et al. Cancer mortality following treatment for adult hyperthyroidism: Cooperative Thyrotoxicosis Therapy Follow-up Study Group. JAMA. 1998;280(4):347-55.
- Holm LE, Hall P, Wiklund K, et al. Cancer risk after iodine-131 therapy for hyperthyroidism. J Natl Cancer Inst. 1991;83(15):1072-1077.
- 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. 2019;179(8):1034-1042.
- Melo DR, Brill AB, Zanzonico P, et al. Organ dose estimates for hyperthyroid patients treated with (131)i: an update of the thyrotoxicosis follow-up study. Radiat Res. 2015;184(6):595-610.