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Pediatric Thyroid Cancer: Should Molecular Subtype Be Included in Risk Stratification?

By: Joseph Fanelli
Posted: Wednesday, November 10, 2021

According to findings presented in bioRxiv (a preprint platform of preliminary reports that have not undergone peer review), classifying pediatric differentiated thyroid cancers by genetic subtype may more accurately predict clinical behavior than relying solely on pathologic classification. In fact, patients with RET or NTRK fusions appeared to have worse outcomes than those with BRAF-mutant disease, concluded Andrew J. Bauer, MD, of the Children’s Hospital of Philadelphia, and colleagues, suggesting consideration of including molecular subtype into risk stratification for future clinical trials.

“Categorizing pediatric differentiated thyroid cancer into RAS-mutant, BRAF-mutant, and RET/NTRK fusion variants more accurately separates the higher risk of invasive behavior for RET/NTRK fusion–driven papillary thyroid cancer compared to papillary thyroid cancer harboring BRAF p.V600E mutations,” the authors said. “RET/NTRK fusion tumors metastasize to lateral neck lymph nodes at a significantly higher frequency than BRAF p.V600E papillary thyroid cancer.”

The authors conducted a somatic cancer gene panel on differentiated thyroid cancer samples from 131 pediatric patients in this trial. The samples were categorized into RAS-mutant, BAF-mutant, and RET/NTRK fusion to determine the differences between subtype classification regarding pathologic data, as well as the response to therapy 1 year after the initial therapy was completed.

The research team found that mutation-based subtype categories were “significant” in most variables, including the patient's age at diagnosis, metastatic behavior, and the likelihood of remission 1 year after diagnosis. For example, patients with RET/NTRK fusions were most likely to have advanced lymph node and distant metastasis and less likely to achieve remission at 1 year, compared with patients within RAS-mutant and BRAF-mutant subgroups.

Additionally, RET/NTRK and PAX8-PPARG fusions were more commonly associated with the follicular variant of papillary thyroid cancer and follicular thyroid cancer than other genotypes. The BRAF p.V600E mutation was most associated with classic papillary thyroid cancer, seen in 26 samples (19.8%).

Disclosure: For full disclosures of the study authors, visit

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