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Alexander Drilon, MD

Gregory J. Riely, MD, PhD

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How RET/NTRK Fusion Mutations May Impact Outcomes in Pediatric Thyroid Cancer

By: Lauren Harrison, MS
Posted: Tuesday, February 15, 2022

Genetic subtyping of pediatric differentiated thyroid cancer may more accurately predict clinical behavior than pathologic classification alone. A study published in the Journal of Clinical Oncology found that patients with RET/NTRK fusions tend to have worse outcomes than those with mutations in BRAF. According to Andrew J. Bauer, MD, of the Children’s Hospital of Philadelphia, and colleagues, future trials may benefit from including molecular subtype into risk stratification.

“Our results provide greater clarity into the oncogenic alterations in pediatric differentiated thyroid cancer that confer the greatest risk for metastasis and persistent disease,” concluded the authors.

Researchers performed somatic cancer gene panel analysis on surgical specimens from 131 pediatric patients with differentiated thyroid cancer. The cancer samples were categorized into RAS-mutant (6.9%), BRAF-mutant (19.8%), and RET/NTRK fusion (32.8%). Clinical behavior based on these subgroups was analyzed and compared with subtype classification by pathologic data.

Remission was achieved after 1 year by 61.5% of patients with BRAF mutations and 42% of patients with RET/NTRK fusions. Classic papillary thyroid cancer was the most common histology among both the RET-mutant and RET/NTRK fusion groups. Among this pathologic subgroup, distant metastases were noted in 36% of patients with fusions in RET/NTRK and in none of the patients with RET mutations. Persistent disease at 1 year was seen in 36% of patients with RET/NTRK fusions and 17% of those with BRAF mutations. Patients with RET/NTRK mutations were also more likely to have advanced lymph node and distant metastases than patients with BRAF mutations.

Patients younger than 10 were found to be more likely to have RET/NTRK fusions (91%) than those older than 10 (27%). In adults, these fusions were seen in just 9% of patients. In contrast, one patient younger than 10 had a BRAF mutation, whereas 20% of those older than 10 harbored these mutations. In comparison, 58% of adults with papillary thyroid cancer have BRAF mutations.

Disclosure: For a full list of authors’ disclosures, visit ascopubs.org.


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