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

G. D. Demetri, C. R. Antonescu, B. Bjerkehagen, J. V.M.G. Bovée, K. Boye, M. Chacón, A. P. Dei Tos, J. Desai, J. A. Fletcher, H. Gelderblom, S. George, A. Gronchi, R. L. Haas, N. Hindi, P. Hohenberger, H. Joensuu, R. L. Jones, I. Judson, Y. K. Kang, A. KawaiA. J. Lazar, A. Le Cesne, R. Maestro, R. G. Maki, J. Martín, S. Patel, F. Penault-Llorca, C. Premanand Raut, P. Rutkowski, A. Safwat, M. Sbaraglia, I. M. Schaefer, L. Shen, C. Serrano, P. Schöffski, S. Stacchiotti, K. Sundby Hall, W. D. Tap, D. M. Thomas, J. Trent, C. Valverde, W. T.A. van der Graaf, M. von Mehren, A. Wagner, E. Wardelmann, Y. Naito, J. Zalcberg, J. Y. Blay

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)1506-1517
Number of pages12
JournalAnnals of Oncology
Volume31
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • entrectinib
  • larotrectinib
  • neurotrophic tyrosine receptor kinase
  • sarcoma
  • tropomyosin receptor kinase

ASJC Scopus subject areas

  • Hematology
  • Oncology

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