Navigating Multidisciplinary Care in Pediatric Thyroid Carcinoma: Insights from Children’s Oncology Group Sites

Pediatric thyroid carcinoma is rare, with an incidence of 1.2 per 100,000 individuals under 20 years of age, increasing to 3.5 per 100,000 among adolescents aged 15–19 years¹. Although the overall prognosis is excellent, pediatric patients with thyroid carcinoma may not achieve a complete response with the current management approach. Furthermore, the unique molecular and clinical characteristics of pediatric thyroid carcinoma can influence its clinical behavior and prognosis². Papillary thyroid carcinoma (PTC) constitutes 80–90% of pediatric cases, with cervical lymph node metastasis present in 30–40% and lung metastasis in approximately 20%. While patients experience a survival rate >95%, less than 20% of patients with lung metastasis achieve a complete response to therapy and have recurrence rates of 20–30%^1–5. Follicular thyroid carcinoma (FTC) is the second most common pediatric thyroid carcinoma, occurring in approximately 10% of cases and is more likely to metastasize to the lungs and bones⁴.

PTC is typically associated with single pathogenic/likely pathogenic oncogenic variants, including mutations in BRAF, PTEN, DICER1 and RAS as well as kinase fusions involving RET, NTRK, PAX8, and ALK. FTC is characterized by PTEN, DICER1, and RAS mutations, as well as PAX8 fusions⁶. Based largely on adult experience, the Food and Drug Administration has approved the use of tyrosine kinase inhibitors (RET and NTRK inhibitors), as well as BRAF/MEK inhibitors in patients with advanced metastatic disease, in RAI-refractory cases, or in patients where surgical resection would result in significant morbidity^2,7. These agents are being used with increased frequency for adjuvant and neoadjuvant therapy in select patients. In pediatrics, there is limited data and no consensus on which patients with thyroid carcinoma would benefit from these agents, the optimal time to initiate treatment, or the duration of therapy². Efforts are being made within the Children’s Oncology Group (COG) to bridge this knowledge gap.

Given the involvement of various pediatric specialists—including oncologists, endocrinologists, surgeons, pathologists, and nuclear medicine experts—understanding current clinical practices is vital for developing future clinical trials and fostering multidisciplinary collaboration.

Pediatric oncology provider survey data:

A 9-question survey was sent to all 214 COG site principal investigators (PIs) with responses from 71 (33%) PIs regarding clinical practice patterns for patients ≤ 25 years diagnosed with thyroid carcinoma. Fifty (70%) of the responding PIs reported their institution treats patients aged ≤ 25 years with thyroid carcinoma. Most institutions report their pediatric oncologists (n=54; 77%) are referred 0–5 patients per year, 7 (10%) institutions report 6–10 referrals, an additional 7 report 11–20 referrals, with only 2 (3%) institutions having more than 20 cases referred per year. Of those referrals, an estimated cumulative total of 130 patients had lymph node metastasis, 53 had lung metastases, 5 had bone metastases, 2 had brain metastases, with one reported “other” site of metastasis (Fig. 1).

Figure 1:

Reported number of metastatic disease sites for patients referred to COG institutions.

Most PIs report referrals to pediatric oncology come from pediatric endocrinology (n=45) and pediatric otolaryngology (n=30). Notably, 17 (24%) institutions reported patients ≤ 25 years were not referred to pediatric oncology. When patients are not referred to pediatric oncology, they are instead managed by pediatric otolaryngology and endocrinology in most cases. Most referrals to pediatric oncology occur at the time of pathologic confirmation of thyroid carcinoma (n=27).

Germline and somatic genetic testing patterns vary amongst COG institutions. Twenty-seven (41%) institutions reported performing germline testing on all patients with thyroid carcinoma, 35 (53%) performed germline testing based on clinical indications, and 4 (6%) did not perform germline testing at all. Thirteen (22%) institutions perform somatic testing at the time of the diagnostic fine needle aspiration, 30 (50%) at the time of thyroid surgery, and 17 (28%) did not perform somatic testing at all.

These findings highlight variability in referral patterns and management of pediatric thyroid carcinoma. While surgery and radioactive iodine remain the standard of care for treating pediatric thyroid carcinoma with metastasis, there is growing interest in expanding treatment and care options. This is particularly relevant for patients with metastatic disease that is not amenable to surgery given that less than 20% of patients with distant metastasis will obtain a complete response with the current standard of care⁸. The COG/National Cancer Institute Molecular Characterization Initiative (MCI) is providing the option for paired somatic and germline testing for pediatric patients with newly diagnosed, sporadic thyroid carcinoma across all COG institutions. Locally, this may help to identify possible patients eligible for targeted therapies. Furthermore, this clinically annotated next generation sequencing (NGS) data is being made publicly available, providing a unique opportunity to expand our understanding of the molecular genetics of pediatric thyroid carcinoma. When asked about their interest in participating in a COG-led clinical trial optimizing medical treatment for metastatic thyroid carcinoma, 42 (59%) sites responded “yes” and 23 (32%) responded “maybe”. This underscores strong collective support for the development of prospective clinical trials aimed at optimizing treatment for pediatric patients with metastatic thyroid carcinoma.