Paper of the Month November

Reference:

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

Reply in a letter to the editor in EJNMMI: « Use of anti-thyroid drugs in patients with hyperthyroidism: a case for shared decision-making»

Pubmed link

https://www.ncbi.nlm.nih.gov/pubmed/31260066

Letter to the editor: https://www.ncbi.nlm.nih.gov/pubmed/31399802

Link to Journal

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737319

Letter to the editor: https://link.springer.com/article/10.1007%2Fs00259-019-04476-4

Discussion:

This month, we will discuss the paper “Association of Radioactive Iodine Treatment With Cancer Mortality in Patients With Hyperthyroidism” by Kitahara et al. as well as the reply to this paper by Giovanella and Verburg in a letter to the editor in EJNMMI.

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

Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Postsurgical RAI ablation therapy for differentiated thyroid cancer has been associated with an increased risk of secondary malignant neoplasms. Relatively few cohort studies have evaluated cancer risk after RAI for hyperthyroidism, which involves much lower administered activities (typically 10-15 mCi) and findings have been inconsistent.

The cohort study by Kitahara et al. included 18 805 patients who were treated with RAI for hyperthyroidism and had no history of cancer at the time of the first treatment. 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). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95% CI, 1.02-1.10; P = .002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95% CI, 1.003-1.32; P = .04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95% CI, 1.01-1.10; P = .01). The 100-mGy dose to the stomach and breast corresponded to a mean administered activity of 243 MBq and 266 MBq in patients with Graves disease. Taking these findings into account, the authors calculated that for every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur. Kitahara et al. conclude that greater organ-absorbed doses appear to be modestly positively associated with risk of death from solid cancer, including breast cancer.

Reply in a letter to the editor in EJNMMI: « Use of anti-thyroid drugs in patients with hyperthyroidism: a case for shared decision-making»

In their letter to the editor in EJNMMI, Giovanella and Verburg state that an objective assessment of the paper by Kitahara et al. inevitably leads to the conclusion that a multitude of limitations preclude the assumption offered:

1. The role of thyroid hormones excess in promoting cancerogenesis was ignored despite the well-known positive relationship between hyperthyroidism and the risk of breast, prostate, lung, and colon neoplasia.
2. In an earlier comparison of cancer mortality by treatment in the same sample studied by the Kitahara team, a 1.31 cancer-related standardized mortality ratio (SMR) was found in patients given anti-thyroid drugs (ATD’s), while the subgroup receiving radioiodine had an SMR of 1.02. For breast cancer, SMR was 1.69 for patients given ATDs and 1.08 for patients receiving radioiodine, respectively.
3. Only patients treated with radioiodine were enrolled by Kitahara et al. and, in addition, no correction for any of the typical cancer risk factors (e.g., smoke, diabetes, alcohol) was applied. Considering that the group of patients with the highest radioiodine activity also had the highest rate of coronary heart disease does make one suspect, however, that this group also had the highest rate of smokers, thus more than sufficiently explaining any excess cancer rate.
4. To properly analyze the role of radioiodine, the authors should have included a suitable control group such as hyperthyroid patients treated only with surgery, ATDs, or both.

Giovanella and Verburg conclude that considering these points, one must question whether the study by Kitahara et al. even supports a hypothesis of a relationship between radioiodine therapy and cancer mortality in GD’s patients.