Increased cancer risk observed decades after radioactive iodine treatment
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Young adults who received radioactive iodine therapy for differentiated thyroid cancer were at 92% increased risk for leukemia and 23% increased risk for any solid malignancies vs. those who did not receive radioactive iodine therapy.
Among solid cancers, researchers observed elevated risk for uterine, breast, lung and salivary gland cancers; solid malignancy risks increased with greater time since thyroid cancer diagnosis.
“Our results reinforce the notion that treatment decisions regarding the use of radioactive iodine therapy should consider the balance of risks and benefits for individual patients with differentiated thyroid cancer,” Cari Kitahara, PhD, a senior investigator in the division of cancer epidemiology and genetics, radiation epidemiology branch, of the NIH’s National Cancer Institute, told Healio. “This is especially important for younger patients who are much more vulnerable to the carcinogenic effects of ionizing radiation compared with older adults, and patients diagnosed with differentiated thyroid cancers with low risk of recurrence.”
Incidence of differentiated thyroid cancer (DTC) has increased in the U.S. since the 1970s, becoming the second most common cancer in adolescents and young adults, Elisa Pasqual, MD, PhD, a postdoctoral fellow in the division of cancer epidemiology and genetics at the NCI, said during a presentation at the American Thyroid Association annual meeting. In parallel, the use of radioactive iodine (RAI) treatment also increased, including for young patients.
Researchers analyzed data from nine U.S. Surveillance, Epidemiology and End Results cancer registries (1975-2017) to estimate RRs for solid and hematopoietic malignancies associated with RAI therapy (yes vs. no/unknown) among patients diagnosed with nonmetastatic DTC before age 45 years, using Poisson regression analyses among 27,050 5-year survivors and 32,171 2-year survivors, respectively.
During a maximum follow-up of 43 years, RAI therapy was associated with an increased risk for solid cancers (RR= 1.23; 95% CI 1.11-1.37), particularly more than 20 years after DTC diagnosis (RR = 1.47; 95% CI 1.24-1.74). Researchers observed a similar pattern for breast cancer, the most common second cancer, with an overall RR of 1.18 (95% CI, 0.99-1.4) and an RR of 1.46 more than 20 years after RAI therapy (95% CI, 1.1-1.95). Risk was also elevated for uterine cancer (RR = 1.55; 95% CI, 1.03-2.32) and leukemia (RR = 1.92; 95% CI, 1.04-3.56). The researchers also observed nonsignificant increased risks for cancers of the salivary gland and lung.
Researchers estimated that 6% of solid and 14% of hematologic malignancies that occurred among pediatric and young adult DTC survivors during 1975-2017 at least 1 year after RAI therapy may be attributable to RAI.
“Previous studies have consistently linked radioactive iodine therapy for thyroid cancer with an increased risk of leukemia about 2 years after exposure,” Pasqual told Healio. “Quantifying the risks of solid cancers after radioactive iodine therapy has been more challenging, and results have been inconsistent. We know from the radiation epidemiology and radiobiology literature that the effects of radiation on solid cancer development are not observable for at least 5 to 10 years. Also, surprisingly, there has been limited focus on second cancer risks in young thyroid cancer patients, even though younger individuals are more susceptible to the late effects of radiation and have a longer average life expectancy over which these effects might develop.”
Kitahara said the focus on young patients with thyroid cancer and long-term follow-up were important features of the study that allowed researchers to quantify the risks of RAI-associated second cancers more precisely compared with previous studies.
“Future research should determine whether the risks of second cancers after radioactive iodine therapy are dose-dependent,” Kitahara told Healio. “If radioactive iodine therapy for thyroid cancer indeed causes an increased risk of second primary malignancies, then we should expect higher doses to yield higher risks. This research also would help to determine whether lower doses of radioactive iodine could be considered for patients who would otherwise benefit from this treatment.”
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Pasqual E, et al. OR-14. Presented at: American Thyroid Association Annual Meeting; Sept. 30-Oct. 3, 2021 (virtual meeting).
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