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Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network

Abstract

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.

Type Journal
ISBN 1569-8041 (Electronic) 0923-7534 (Linking)
Authors Demetri, G. D.; Antonescu, C. R.; Bjerkehagen, B.; Bovee, Jvmg; Boye, K.; Chacon, M.; Dei Tos, A. P.; Desai, J.; Fletcher, J. A.; Gelderblom, H.; George, S.; Gronchi, A.; Haas, R. L.; Hindi, N.; Hohenberger, P.; Joensuu, H.; Jones, R. L.; Judson, I.; Kang, Y. K.; Kawai, A.; Lazar, A. J.; Le Cesne, A.; Maestro, R.; Maki, R. G.; Martin, J.; Patel, S.; Penault-Llorca, F.; Premanand Raut, C.; Rutkowski, P.; Safwat, A.; Sbaraglia, M.; Schaefer, I. M.; Shen, L.; Serrano, C.; Schoffski, P.; Stacchiotti, S.; Sundby Hall, K.; Tap, W. D.; Thomas, D. M.; Trent, J.; Valverde, C.; van der Graaf, W. T. A.; von Mehren, M.; Wagner, A.; Wardelmann, E.; Naito, Y.; Zalcberg, J.; Blay, J. Y.
Responsible Garvan Author Professor David Thomas
Publisher Name Annals Of Oncology
Published Date 2020-11-01
Published Volume 31
Published Issue 11
Published Pages 1506-1517
Status Published in-print
DOI 10.1016/j.annonc.2020.08.2232
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/32891793