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Alexander Drilon, MD

Gregory J. Riely, MD, PhD


RET/NTRK Fusions and Risk of Metastasis in Pediatric Differentiated Thyroid Cancer

By: Julia Fiederlein
Posted: Tuesday, June 21, 2022

In 2014, data from The Cancer Genome Atlas project suggested the reclassification of adult papillary thyroid cancer into RAS-like and BRAF-like molecular subtypes better reflected phenotypic behavior and outcomes than sole reliance on pathologic classification; however, according to Andrew J. Bauer, MD, of the Children’s Hospital of Philadelphia, and colleagues, a three-tiered classification system comprising RAS-mutated, BRAF-mutated, and NTRK/RET gene fusion–positive subgroups may provide more accurate predictions in pediatric differentiated thyroid cancer. The results of this analysis, which were published in the Journal of Clinical Oncology, highlighted the need to further define differences in the molecular landscape between pediatric and adult patients.

NTRK and RET [gene] fusions are the most prevalent genetic alterations in pediatric differentiated thyroid cancer,” the investigators remarked. “Patients with NTRK/RET [gene] fusions had the highest risk of metastases and were less likely to achieve remission at 1-year post-surgery.”

The investigators conducted a somatic cancer gene panel analysis of pediatric surgical specimens (papillary thyroid cancer: n = 122; follicular thyroid carcinoma: n = 9). Tumors were categorized based on mutational status: RAS-mutant (6.9%); BRAF-mutant (19.8%); NTRK/RET gene fusion–positive (32.8%). Mutation-based subtype categories were found to be significant in most variables, including age at diagnosis, metastatic behavior, and likelihood of remission at 1 year. Compared with patients who harbored RAS or BRAF mutations, those with NTRK/RET gene fusions seemed to be significantly more likely to experience advanced lymph node and distant metastases and less likely to achieve remission at 1 year.

“The combined data set used in this study represents an evolutionary change in the information gained from genetic and molecular analysis over the span of a few short years,” the investigators concluded. “Future trials should consider the inclusion of molecular subtype into risk stratification.” 

Disclosure: For full disclosures of the study authors, visit

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