ESPEYB19 3. Thyroid Paediatric thyroid cancer (3 abstracts)
3.13. NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake
Lee YA , Lee H , Im SW , Song YS , Oh DY , Kang HJ , Won JK , Jung KC , Kwon D , Chung EJ , Hah JH , Paeng JC , Kim JH , Choi J , Kim OH , Oh JM , Ahn BC , Wirth LJ , Shin CH , Kim JI & Park YJ
J Clin Invest. 2021 Sep 15;131(18):e144847. doi: 10.1172/JCI144847. PMID: 34237031
Brief Summary: This retrospective analysis of clinical, pathologic, and genetic characteristics of n=106 children with differentiated thyroid carcinoma (DCT) showed that fusion oncogene associated papillary thyroid carcinoma (PTC) is more frequent in young children and is associated with larger tumors, extrathyroidal extension and metastases. They showed decreased radioiodine uptake, which could be successfully restored by selective fusion-targeted therapy.
This important work reveals insights into the genetic alterations in pediatric PTCs: First, fusion oncogenes are very frequent (92.9%) in children aged < 10 years, compared to children aged 10-15 years (27.5%) and 15-20 years old patients (13.5%). In contrast, PTC due to BRAF mutations increased in frequency with age (7.1%, 30.0%, and 65.4%, respectively in children <10 years, 10-15 years, and 15-20 years). Second, comparing PTC due to fusion oncogenes vs. BRAF mutations, fusion oncogene PTCs showed larger tumors, and larger extrathyroidal extension with lymph nodes, and lung metastases with low radioiodine uptake. Gene expression profiles of fusion oncogene PTCs revealed higher degree of dedifferentiation associated with higher expression of MAPK pathway genes, but lower expression of the sodium/iodide symporter gene (SLC5A5), which encodes the molecular basis for radioiodine uptake in the thyrocyte. Based on these results, the authors treated two young children (ages 4 and 7 years) with radioiodine-refractory lung metastases with fusion-targeted therapy and achieved in both patients restored radioiodine uptake of the lung metastases.
These data are of high clinical relevance for treatment of pediatric patients with PTC providing evidence that 1) molecular testing needs to be integrated in routine diagnostics of pediatric PTCs, and 2) PTCs caused by fusion oncogenes can be treated successfully with fusion-targeted therapies. These results were confirmed in a second large study (see paper 3.14 in this chapter) [1].
Reference: 1. Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers. Franco AT, Ricarte-Filho JC, Isaza A, Jones Z, Jain N, Mostoufi-Moab S, Surrey L, Laetsch TW, Li MM, DeHart JC, Reichenberger E, Taylor D, Kazahaya K, Adzick NS, Bauer AJ. J Clin Oncol. 2022 Apr 1;40(10):1081–1090. doi: 10.1200/JCO.21.01861. Epub 2022 Jan 11. PMID: 35015563.
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ESPE Yearbook of Paediatric Endocrinology
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