Journal
ANNALS OF ONCOLOGY
Volume 31, Issue 11, Pages 1506-1517Publisher
ELSEVIER
DOI: 10.1016/j.annonc.2020.08.2232
Keywords
entrectinib; larotrectinib; neurotrophic tyrosine receptor kinase; sarcoma; tropomyosin receptor kinase
Categories
Funding
- Ludwig Center at Harvard
- Dr Miriam and Sheldon G. Adelson Medical Research Foundation
- Pan Mass Challenge
- National Institutes of Health/National Cancer Institute [K08 CA241085]
- NetSARC (INCA DGOS)
- RREPS (INCA DGOS)
- RESOS (INCA DGOS)
- EURACAN (EC) [739521]
- LYRICAN (INCA-DGOS-INSERM) [12563]
- LabEx DEvweCAN [ANR-10-LABX-0061]
- Institut Convergence PLASCAN [17CONV-0002]
- RHU4 DEPGYN [ANR-18-RHUS-0009]
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Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.
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