BACKGROUND
Thyroid cancer is the most common endocrine cancer seen in children and young adults. In United States, it is the second most common cancer in people younger than the age of 45 years. Until recent years, these cancers were routinely treated with removing the thyroid gland followed by radioactive iodine therapy to prevent the cancer from coming back. As our knowledge about these cancers grew, it was found that majority of these cancers already had very low risk of causing death, so for many patients radioactive iodine therapy did not really offer much benefit.

In 2015, American Thyroid Association guidelines recommended not to use radioactive iodine therapy treatment after surgery for cancers less than 1 cm. Currently, radioactive iodine therapy is recommended only for patients that have higher risk of being harmed by the cancer, for example those who have larger cancers extending outside of the thyroid or if the cancer has already spread to lymph nodes. Whether this approach would also be better for pediatric patients is controversial. Children diagnosed with thyroid cancer have a higher risk of having the thyroid cancer coming back years later compared to adults.

There has also been growing concern about unwanted effects of radioactive iodine therapy, such as risk of developing other cancers. This concern is especially for children and young adults since radiation has a stronger effect on younger tissue and life expectancy is much longer providing enough time for the harmful effects to show up. There have been studies that reported increased risk of leukemia and solid organ cancers, like cancers of salivary glands, kidneys, or breast. However, past studies were sometimes too small or did not follow the patients for a long time.

The aim of this study was to find out whether radioactive iodine therapy for thyroid cancer in childhood or young adulthood is associated with increased risk of developing a second cancer other than thyroid cancer.

THE FULL ARTICLE TITLE
Pasqual E et al 2022 Association between radioactive iodine treatment for pediatric and young adulthood differentiated thyroid cancer and risk of second primary malignancies. J Clin Oncol. Epub 2022 Jan 19. PMID: 35044839.

SUMMARY OF THE STUDY
The study used information from 9 US SEER cancer registries and included patients who were diagnosed with thyroid cancer before age 45 between 1975 and 2017. Patients whose cancer had already spread outside of thyroid at the time of diagnosis were excluded. Patients who later developed solid organ cancers (other than thyroid) and blood-related cancers (leukemia, lymphoma and myeloma) were identified.

There were 36,311 patients diagnosed with thyroid cancer, 45% of whom had received radioactive iodine therapy. Radioactive iodine therapy was used more often in patients younger than 15 years of age. Patients were followed on average for 15 years and up to 43 years. Radioactive iodine therapy was associated with a 51% increased risk of total blood-related cancers including leukemia and 23% increased risk of solid cancers. The risk increased with time after the diagnosis, particularly over 20 years. The most common second cancer was breast cancer and had 1.46-fold increased risk more than 20 years after radioactive iodine therapy. The researchers estimated that 6% of all solid cancers, 5% of breast cancers, 14% of blood-related cancers that were found in thyroid cancer survivors may be attributable to radioactive iodine therapy. The cumulative incidence of a second solid cancer at 20 years after the diagnosis of DTC was 5.6% for radioactive iodine therapy treated patients and 5% for patients who were not treated with radioactive iodine therapy.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that radioactive iodine therapy for thyroid cancer diagnosed in children and young adults less than 45 years age was associated with increased risk of leukemia and several solid cancers, especially more than 20 years after exposure. However, a second cancer was relatively rare in thyroid cancer survivors. These findings support the recommendations in the recent guidelines to avoid radioactive iodine therapy in patients who are at very low risk of being harmed from thyroid cancer. In contrast, patients with high-risk thyroid cancers will still benefit from radioactive iodine therapy and they should not be scared to receive this treatment. It is important to weigh the risks of radioactive iodine therapy against benefits for each individual patient with thyroid cancer. Patients should have an open discussion with their physicians to understand their specific situation and have a clear treatment and long-term care plan including regular medical check-ups after completing the initial treatment.

— Ebru Sulanc, MD

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