What’s the Future Cancer Risk of RAI Treatment?

Re-examining the relationship between dose and response in radioactive iodine treatment

With Cari Kitihara PhD

There have been several research papers that have studied the potential danger of using radioactive iodine (RAI) to treat people with hyperthyroidism. It is one of the first line treatments, and it has been since the 1940s. While generally viewed as safe, there remains a concern about the potential for the radioactivity to cause cancer in patients who receive the treatment.

The first studies that looked at increased cancer risk from RAI treatment found no need for patients to worry about thyroid cancer or leukemia, but the researchers only followed patients for 8 years and did not look at other types of cancer. Later work has been more mixed. A study from 2007 found there was increased risk of stomach, breast, and kidney cancer for patients treated with RAI. The patients in this study were followed for 10 years. But eight years later, a study found no increased risk of cancers related to the treatment.

New research illuminates new risks

Last year, Cari Kitihara, PhD, a radiation and epidemiology researcher at the National Cancer Institute at the National Institutes of Health (NIH) and her team published work using data from more than 70 years of patients treated in the United States and Great Britain to try again to see if there was a clear link between RAI treatment and cancer. 

They looked not just at cancer incidence, but also at the doses of RAI given, and the dose estimates for various organs and tissues. Nearly 19,000 patients were included in the study, which found that there was a modest increased risk of death from solid cancers including breast cancer, based on the doses absorbed by those organs or tissues.

In the current work, they looked again at the same cohort for long-term impacts of RAI, surgery, and anti-thyroid drugs – or combinations of those treatments – related to solid cancer occurrence. Patients were treated for hyperthyroidism between 1946 and 1965, and followed up through 2014. Slightly more than 31,000 patient records met criteria set by researchers for inclusion in this study, and there was a median follow up time of 26 years.

Among those who were treated with radioactive iodine, there was an increased risk of death from a solid cancer as the dosage increased. The rates were similar for those with breast cancer and non-breast solid cancer, and were stronger among those who only received RAI as a treatment than those who had RAI along with other types of treatment. The increased risk was put at an additional 8% to 10% per 370 MBq dose.

Future implications

“Radioactive iodine is given orally, and most of the radiation is taken up by the thyroid gland,” says Kitahara. “There is less awareness that other organs are exposed, although at lower rates than the thyroid.” The breasts, which are extremely sensitive to radioactivity, lungs, and salivary glands are all potential cancer sites because of their proximity to the thyroid, she notes, "and the digestive tract is exposed through the ingestion of the RAI."

The increased absolute risk amounts to an excess of 20 to 30 cancer deaths per 1000 patients that are related to the use of RAI, Kitahara explains. Results were based on the current dosages of RAI. “A lot of the cohort studies are based on lower doses and multiple rounds of treatment,” she says.

Health care providers still have many questions about RAI treatment and the potential risk of death from cancer. Kitara says that they often ask for a “better context for these risks, how to they compare to surgery, antithyroid drugs, or some combination. So we wanted to compare cancer risks across those treatment groups.”

Another question that arose from the study published last year was how does the level of RAI administered compare to the organ dose of radiation, says Kitahara.

Expert discussion

“We had done these initial analyses, but they were not the main focus of our work, so we did not include them in the original paper,” she notes. “But we realized when questions kept arising that we needed to publish this further research. It is also useful because it updates a much older, but similar analysis that came out in 1998.” That study found no increased risk of cancer from RAI use in treating hyperthyroidism.

The positive dose response results did not surprise Kitahara or her coauthors. “Given what we knew about low dose radiation and cancer risk, we expected this.” Kitahara says that the current findings for breast cancer risk are similar to what was found in studies of the atomic bombs dropped on Hiroshima and Nagasaki.

“However, this is a treatment that has a long-term risk associated with it, and that is not necessarily widely understood,” says Kitahara.

RAI has been used for more than 70 years, but there have never been randomized clinical trials of the treatment, just observational studies. Kitahara says the results just published show that risks from radioactive iodine are small, and they are not apparent for the first years after treatment. “I would say that for most patients, the risks probably do not outweigh the benefits.” Still, she thinks it is important to have this data when discussing treatments with patients. “You have to know the full story of risks and benefits to make the best treatment decisions with an individual patient.”

Next steps

She would like to see the results she and her team found replicated in other large studies that have cancer incidence follow-ups. “One of our limitations is that we followed patients for cancer deaths, not cancer incidence or type. And there are definitely implications for cancer survival based on that.”

Kitahara thinks the next step is for the findings to be confirmed, and then evaluated by expert clinical guidelines committees before making wholesale changes to the way patients are treated for hyperthyroidism. “Our results do suggest that this warrants further research, and that we need to better understand the long-term risks of the other treatment options as well.”

Continue Reading:
Axitinib Active in Advanced Radioactive Iodine-Resistant Differentiated Thyroid Cancer and Refractory Medullary Thyroid Cancer
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