Brazilian Expert Consensus for NTRK Gene Fusion Testing in Solid Tumors

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Oncogenic neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are rare but actionable biomarkers in various cancers.
• The emergence of targeted therapies necessitates clear diagnostic strategies for NTRK fusions.
• Current optimal screening and diagnostic platforms for NTRK fusions remain debated.

Purpose of the Study:

• To review the latest evidence and international consensus on NTRK gene fusion diagnosis.
• To propose a clinical guideline and testing algorithm for NTRK fusion biomarker diagnosis.
• To adapt diagnostic strategies for the Brazilian healthcare system.

Main Methods:

• Literature review of current evidence and international guidelines on NTRK fusion diagnosis.
• Convening a panel of national experts in molecular cancer diagnosis and treatment.
• Development of a proposed testing algorithm for NTRK gene fusion screening.

Main Results:

• NTRK gene fusions are identified in less than 1% of common cancers.
• Immunohistochemistry (IHC) is proposed as an effective screening method.
• Next-generation sequencing (NGS) is recommended for confirmatory testing in IHC-positive cases.

Conclusions:

• An integrated diagnostic approach utilizing IHC and NGS is recommended for NTRK fusions.
• Testing for NTRK fusions should be considered in advanced metastatic tumors lacking known driver mutations.
• The proposed algorithm aims to standardize NTRK fusion diagnosis within the Brazilian health system.