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Objective  The aim of the study was to identify patients with  NTRK  fusion-positive or  RET  fusion/mutation-positive thyroid cancers, who could benefit from neurotrophic tyrosine kinase receptor (NTRK) or receptor tyrosine kinase (RET) inhibitors.    Methods  Patients were identified in the Calgary prospective thyroid cancer database ( N = 482). Patients were ‘pre-screened’ with clinically available MassARRAY® BRAF test, Colon Panel, Melanoma Panel, or ThyroSPEC™. Mutation-negative tumors were ‘screened’ for  NTRK  fusions and  RET  fusions/mutations with the Oncomine™ Comprehensive Assay v3 (OCAv3).    Results  A total of 86 patients were included in 1 of 2 separate analyses. Analysis A included 42 patients with radioactive iodine (RAI)-resistant distant metastases. After pre-screening, 20  BRAF  and  RAS  mutation-negative patients underwent OCAv3 screening, resulting in the detection of 4 patients with  NTRK fusions and 4 patients with  RET  fusions (8/20, 40% of analyzed patients). Analysis B included 44 patients, 42 with American Thyroid Association (ATA) high and intermediate risk of recurrence and 2 with medullary thyroid carcinoma. During pre-screening, 1 patient with an  NTRK  fusion, 1 patient with a  RET  fusion, and 30 patients with  BRAF  mutations were identified. The remaining 9 patients received OCAv3 screening, resulting in detection of 1 patient with an  NTRK fusion and 1 with a  RET  fusion (4/11, 36% of analyzed patients).    Conclusions  Our findings indicate a higher rate of  NTRK  fusions and  RET fusions in patients with thyroid cancer with RAI-resistant distant metastases and ATA high or intermediate risk of recurrence. This highlights the importance of early screening to enable intervention with a NTRK or RET inhibitor.

Systematic population-based identification of NTRK and RET fusion-positive thyroid cancers