Related Experiment Video
Updated: Oct 8, 2025
Computer-Aided Three-Dimensional Visualization in the Treatment of Locally Advanced Thyroid Cancer
Published on: June 9, 2023
Systematic population-based identification of NTRK and RET fusion-positive thyroid cancers
Markus Eszlinger1,2, Paul Stewardson3, John B McIntyre4
1Departments 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.
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.
Insights
Early screening for NTRK and RET fusions in thyroid cancer patients with distant metastases or high recurrence risk can identify candidates for targeted therapies, improving treatment outcomes.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Thyroid cancer management often relies on radioactive iodine (RAI) therapy.
- Identifying specific genetic alterations like NTRK and RET fusions is crucial for targeted treatment strategies.
- Neurotrophic tyrosine kinase receptor (NTRK) and receptor tyrosine kinase (RET) inhibitors offer novel therapeutic options.
Purpose of the Study:
- To identify patients with thyroid cancer harboring NTRK or RET fusions.
- To determine the prevalence of these fusions in specific patient subgroups, including those with RAI-resistant disease or high recurrence risk.
- To assess the utility of comprehensive genomic profiling assays in detecting these actionable fusions.
Main Methods:
- Retrospective analysis of 482 patients from a prospective thyroid cancer database.
- Initial screening using MassARRAY® BRAF test, Colon Panel, Melanoma Panel, or ThyroSPEC™.
- Subsequent screening for NTRK and RET fusions using the Oncomine™ Comprehensive Assay v3 (OCAv3) in mutation-negative cases.
Main Results:
- In patients with RAI-resistant distant metastases, 40% (8/20) had NTRK or RET fusions detected by OCAv3.
- In patients with high/intermediate ATA risk or medullary thyroid carcinoma, 36% (4/11) had NTRK or RET fusions detected by OCAv3.
- BRAF mutations were also frequently identified in these cohorts.
Conclusions:
- NTRK and RET fusions are more prevalent in thyroid cancer patients with RAI-resistant distant metastases and high ATA risk.
- Early molecular screening is essential for identifying patients who can benefit from NTRK or RET inhibitor therapy.
- Comprehensive genomic assays play a vital role in detecting these targetable fusions for personalized cancer treatment.
