Systematic population-based identification of NTRK and RET fusion-positive thyroid cancers.
Markus Eszlinger, Paul Stewardson, John B McIntyre, Adrian Box, Moosa Khalil, Martin Hyrcza, Konstantin Koro, Dean Ruether, Jiahui Wu, Ralf Paschke
Author Information
Markus Eszlinger: Departments of Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada.
Paul Stewardson: Department of Medical Science and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
John B McIntyre: Precision Oncology Hub Laboratory, Alberta Health Services, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Adrian Box: Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Moosa Khalil: Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Martin Hyrcza: Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Konstantin Koro: Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Dean Ruether: Section of Medical Oncology, Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Jiahui Wu: Department of Medical Science and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Ralf Paschke: Departments of Medicine, Oncology, Pathology and Laboratory Medicine, Biochemistry and Molecular Biology, and Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Heritage Medical Research Building, Calgary, Alberta, Canada.
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 NTRKfusions 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 NTRKfusion and 1 with a RET fusion (4/11, 36% of analyzed patients). Conclusions: Our findings indicate a higher rate of NTRK fusions and RETfusions 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.
