Distant Metastases From Childhood Differentiated Thyroid Carcinoma: Clinical Course and Mutational Landscape

Area of Science:

• Pediatric Oncology
• Endocrinology
• Molecular Biology

Background:

• Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are rare, with limited published data.
• Understanding the outcomes and molecular characteristics of these rare cases is crucial for improving patient management.

Purpose of the Study:

• To describe the clinical outcomes of patients with DM from childhood DTC.
• To investigate the molecular landscape of these tumors, including oncogenic drivers.

Main Methods:

• Retrospective study at a tertiary cancer center.
• Inclusion of patients diagnosed with pediatric DTC (age ≤ 18 years) and DM between 1946 and 2019.
• Molecular analysis of tumor samples to identify genetic alterations.

Main Results:

• 148 patients identified; 97% had papillary thyroid carcinoma (PTC).
• Common oncogenic drivers in PTC: RET fusion (59%), NTRK1/3 fusions (28%), BRAF V600E (13%).
• Persistent disease was common (93%), but disease-specific death was uncommon (5%), occurring decades after diagnosis.

Conclusions:

• Childhood DTC with DM often shows persistent disease despite radioactive iodine (RAI) therapy.
• Disease-specific mortality is low, with deaths occurring many years post-diagnosis.
• High prevalence of fusion genes in PTC suggests potential for targeted therapies, warranting further research into integrating these into treatment paradigms.