Three-pronged Centralized Molecular Analysis to Optimize Detection of NTRK1,2,3 Fusions in Thyroid Cancer

Study Overview
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Brief Summary
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This multi-center study aims at NTRK fusion testing of all patients with advanced thyroid cancer (any histotype and regardless of stage). The primary objective of this study is to assess the frequency of NTRK fusions in thyroid cancer. The secondary objective of this study is to develop an effective tool (testing) strategy for the detection of NTRK fusions in thyroid tumors, comparing the diagnostic tecniques available (IHC, real-time PCR and NGS).

Detailed Description
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Thyroid cancer is the most common neoplasm of the endocrine system. Most thyroid carcinomas originate from the follicular epithelium and are distinguished in differentiated forms (DTC): papillary (PTC) and follicular (FTC) carcinomas. Both have a favorable prognosis and account for approximately 80% and 10% of all thyroid neoplasms, respectively. The undifferentiated form represented by the anaplastic thyroid carcinoma (ATC) is less frequent (about 2%) and represents one of the most aggressive human tumors with a survival that rarely exceeds 6-12 months. Medullary thyroid carcinoma (MTC), deriving from parafollicular C cells, is relatively rare (approximately 5%) and is associated with an intermediate prognosis between differentiated and poorly differentiated forms. As to the prevalence of NTRK lesions, many authoritative papers and reviews claim very high (up to 75%) NTRK fusion frequencies, particularly in the common PTC. However, an extensive PubMed analysis back to year 1990 does not provide convincing support for this claim.Several techniques for NTRK fusion diagnosis exist, including pan-Trk IHC, FISH, reverse transcription PCR, DNA-based next-generation sequencing (NGS), and RNA-based NGS. Each of these assays has unique features, advantages, and limitations, and familiarity with these assays is critical to appropriately screen for NTRK fusions. The aim of this study is to determine the frequency of NTRK fusions in advanced thyroid cancer patients and to compare the diagnostic tecniques available (IHC, real-time PCR and NGS).

Official Title
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A Multi-institutional Effort With a Three-pronged Centralized Molecular Analysis to Optimize Detection of NTRK1,2,3 Fusions in Thyroid Cancer

Conditions
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Thyroid Cancer

Intervention / Treatment
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* Diagnostic Test: NTRK fusion assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of advanced thyroid cancer (any histotype) Informed consent. Exclusion Criteria: Patients with thyroid neoplasms without appropriate material for subsequent immunohistochemical and molecular studies; Patients with non-advanced thyroid cancer
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: NTRK fusion assessment|To evaluate NTRK fusion presence by MCG, Immunohistochemistry or NGS|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of NTRK fusions in thyroid cancer | To assess the frequency of NTRK fusions in histological sample of tumors by patients affected by thyroid cancer, assessed as the number of tumor harboring NTRK fusion on the total of tumor analized | from 01-Jan-2022 to 31-Dec-2023 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assesment of the ability of Immunohistochemistry to identify for NTRK fusion | To assess the ability of Immunohistochemistry to detect NTRK fusion on histological sample (using NGS as comparator) | from 01-Jan-2022 to 31-Dec-2023 | 
| Assesment of the ability of real time PCR to identify for NTRK fusion | To assess the ability of real time PCR to detect NTRK fusion on histological sample (using NGS as comparator) | from 01-Jan-2022 to 31-Dec-2023 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ntrk fusion