Practical Guidance on the Detection of NTRK Fusions in Sarcomas: Current Status and Diagnostic Challenges
DOI:
https://doi.org/10.20344/amp.21925Keywords:
Gene Fusion, Oncogene Proteins, Fusion/genetics, Receptor, trkA/genetics, Sarcoma/geneticsAbstract
Sarcomas are a rare and heterogeneous group of mesenchymal malignant tumors and account for approximately 1% of all adult cancers and around 20% of all pediatric solid tumors in Europe. Technology advances have enabled a more accurate and efficient characterization of the molecular mechanisms underlying the pathogenesis of sarcoma subtypes and revealed novel and unexpected therapeutic targets with prognostic/predictive biomarkers, namely the neurotrophic tyrosine receptor kinase (NTRK) gene fusion. The NTRK fusion assessment has recently become a standard part of management for patients with unresectable locally advanced or metastatic cancers and has been identified in various tumor types. In the more prevalent adult and pediatric sarcomas, NTRK fusions are present in 1% and 20%, respectively, and in more than 90% of very rare subsets of tumors. The inhibition of TRK activity with first-generation TRK inhibitors has been found to be effective and well tolerated in adult and pediatric patients, independently of the tumor type. Overall, the therapeutic benefit to those patients compensates for the difficulties of identifying NTRK gene fusions. However, the rarity and diagnostic complexity of NTRK gene fusions raise several questions and challenges for clinicians. To address these issues, an expert panel of medical and pediatric oncologists, radiologists, surgeons, orthopedists, and pathologists reviewed the recent literature and discussed the current status and challenges, proposing a diagnostic algorithm for identifying NTRK fusion sarcomas. The aim of this article is to review the updated information on this issue and to provide the experts’ recommendations and practical guidance on the optimal management of patients with soft tissue sarcomas, infantile fibrosarcoma, gastrointestinal stromal tumors, and osteosarcoma.
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