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

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 trop...

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Main Authors: Demetri, George D. (Author) , Antonescu, C. R. (Author) , Bjerkehagen, B. (Author) , Bovée, J. V. M. G. (Author) , Boye, K. (Author) , Chacón, M. (Author) , Dei Tos, A. P. (Author) , Desai, J. (Author) , Fletcher, J. A. (Author) , Gelderblom, H. (Author) , George, S. (Author) , Gronchi, A. (Author) , Haas, R. L. (Author) , Hindi, N. (Author) , Hohenberger, Peter (Author) , Joensuu, H. (Author) , Jones, R. L. (Author) , Judson, I. (Author) , Kang, Y. -K. (Author) , Kawai, A. (Author) , Lazar, A. J. (Author) , Le Cesne, A. (Author) , Maestro, R. (Author) , Maki, R. G. (Author) , Martín, J. (Author) , Patel, S. (Author) , Penault-Llorca, F. (Author) , Premanand Raut, C. (Author) , Rutkowski, P. (Author) , Safwat, A. (Author) , Sbaraglia, M. (Author) , Schaefer, I. -M. (Author) , Shen, L. (Author) , Serrano, C. (Author) , Schöffski, P. (Author) , Stacchiotti, S. (Author) , Sundby Hall, K. (Author) , Tap, W. D. (Author) , Thomas, D. M. (Author) , Trent, J. (Author) , Valverde, C. (Author) , van der Graaf, W. T. A. (Author) , von Mehren, M. (Author) , Wagner, A. (Author) , Wardelmann, E. (Author) , Naito, Y. (Author) , Zalcberg, J. (Author) , Blay, J. -Y. (Author)
Format: Article (Journal)
Language:English
Published: 2020
In: Annals of oncology
Year: 2020, Volume: 31, Issue: 11, Pages: 1506-1517
ISSN:1569-8041
DOI:10.1016/j.annonc.2020.08.2232
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.annonc.2020.08.2232
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0923753420422975
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Author Notes: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. Kawai, A.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

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520 |a 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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