NRTK fusions were found to occur more frequently in pediatric tumors than adult tumors, according to research from a team of researchers from The Children’s Hospital of Philadelphia. The data, published in the Journal of Precision Oncology, also demonstrated a broader panel of NTRK fusion partners and a wider range of tumors than previously reported.

“With the recent (US) Food and Drug Administration approval of larotrectinib and entrectinib for the treatment of adult and pediatric NTRK-positive, unresectable solid tumors, identification of these fusions directly affects patient care,” the investigators wrote.

The team studied 1347 consecutive pediatric tumors from 1217 patients who underwent tumor genomic profiling using custom-designed DNA and RNA next-generation sequencing panels. The age of NTRK-positivepatients ranged from 0.1 to 17 years.

NTRK fusions were found in 2.22% of all tumors and in 3.08% of solid tumors. Of the 27 NTRK fusions identified, 5 were novel at the time of discovery.


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NTRK2 fusions were found exclusively in central nervous system tumors, NTRK1 fusions were highly enriched in papillary thyroid carcinomas (PTCs), and NTRK3 fusions were identified in all tumor categories. The ETV6-NTRK3 fusion was found in 10 patients with various different types of tumors. Several novel NTRK fusions were observed in rare tumors types including ganglioglioma and PTCs.

According to the researchers, identification of the NTRK fusions allowed for more precise diagnosis, and in almost all cases, detection of an NTRK fusion confirmed morphological diagnosis. In 5 cases, the final tumor diagnosis was largely based on discovery of the fusion.

In 1 patient, diagnosis was changed based on the discovery of a specific NTRK fusion. One patient with infantile fibrosarcoma was treated with larotrectinib and achieved complete pathologic remission.

Cumulatively, findings from the analysis, conducted in the “largest cohort of unselected pediatric tumors to date,” indicate “the clinical utility of screening [for] NTRK fusions [in] all pediatric tumors,” Zhao et al concluded.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.

Reference

Zhao X, Kotch C, Fox E, et al. NTRK fusions identified in pediatric tumors: the frequency, fusion partners, and clinical outcome. JCO Precis Oncol. Published online January 14, 2021. doi:10.1200/PO.20.00250