BACKGROUND
Neuroblastoma is a cancer that starts in developing nerve cells and is the most common solid cancer outside the brain in children. Most cases are diagnosed in infancy or before age 5. About one-third of patients have high-risk neuroblastoma (HRNB) at diagnosis. HRNB is one of the most difficult cancers to treat, so it is managed with a combination of intensive therapies. These treatments have made a real difference, and more children are surviving HRNB. But the same treatments can have side effects that may appear years later. The developing thyroid gland is especially vulnerable to their side effects.

This study was done to examine how often HRNB survivors develop thyroid problems long after treatment and to identify the associated risk factors.

THE FULL ARTICLE TITLE
Deodati A et al. Long-term thyroid toxicity burden in children who received treatment for high-risk neuroblastoma. Thyroid 2026;36(3):259–267; doi: 10.1177/10507256261425684. PMID: 41735800

SUMMARY OF THE STUDY
The study was done at a specialized children’s hospital in Italy. Researchers reviewed records of children treated for HRNB who were followed for at least 5 years after diagnosis. The patients had thyroid exams every year that included blood tests for thyroid function and an ultrasound to image the thyroid. The researchers collected information on each child’s treatment history. Treatments were chemotherapy, surgery, radiotherapy, immunotherapy, and 131 I-MIBG. 131 I-MIBG is a radioactive medicine that can be used in small doses for scanning and at higher doses for treatment. Researchers recorded whether children received it as treatment and the number of diagnostic scans they had. Some children also received a more intense chemotherapy (MAT) which also damages bone marrow, so their own stem cells were collected before treatment and returned afterwards to rebuild the bone marrow. Some had this done once and others twice (tandem MAT). Thyroid toxicity was defined as underactive thyroid, overactive thyroid, thyroid nodules, or thyroid cancer.

The study included 45 long-term HRNB survivors with an average follow-up of 10.6 years after diagnosis (range, 5-25.8 years), meaning half of the patients were diagnosed less than 10.6 years. The average age was 13.3 years (range 7.5-27) at last visit. Long-term thyroid toxicity occurred in 24 of the 45 survivors (53%) at an average of 7.5 years from the diagnosis (range 1.2-18.2). The most common thyroid problem was underactive thyroid, diagnosed in 12 of the 24 patients who had thyroid toxicity. Thyroid ultrasound showed smallerthan- expected thyroid glands in 11 of these 24 patients (45%), and 9 patients had one or more thyroid nodules measuring 0.6–14 mm. One patient was diagnosed with papillary thyroid cancer 10 years after a neuroblastoma diagnosis. This patient was treated with chemotherapy but had not received radiation or 131 I-MIBG therapy. The chances of remaining free from thyroid toxicity 10 years after treatment was 62%. Children treated with tandem MAT were significantly more likely to develop thyroid toxicity. Children treated with immunotherapy, chemotherapy drug busulfan, or 131 I-MIBG developed thyroid toxicity earlier than those who did not receive these treatments.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that HRNB survivors have an increased risk of developing thyroid problems years after treatment. The most common thyroid problem was an underactive thyroid. In the past, fewer children survived HRNB, so limited information was available. This was a small study, but the patients had detailed thyroid evaluations over many years at a single center. The findings are useful for understanding long-term thyroid risks in HRNB survivors as well as risk factors and timing of thyroid disease. These thyroid problems are detectable and treatable. As more children survive cancer and live into adulthood, it is important for patients and their care teams to be aware of thyroid problems that could happen years after treatment and plan for long-term follow-up and screening.

— Ebru Sulanc, MD

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