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Demetri GD , Antonescu CR , Bjerkehagen B , Bovee Jvmg , Boye K , Chacon M , Dei Tos AP , Desai J , Fletcher JA , Gelderblom H , George S , Gronchi A , Haas RL , Hindi N , Hohenberger P , Joensuu H , Jones RL , Judson I , Kang YK , Kawai A , Lazar AJ , Le Cesne A , Maestro R , Maki RG , Martin J , Patel S , Penault-Llorca F , Premanand Raut C , Rutkowski P , Safwat A , Sbaraglia M , Schaefer IM , Shen L , Serrano C , Schoffski P , Stacchiotti S , Sundby Hall K , Tap WD , Thomas DM , Trent J , Valverde C , van der Graaf WTA , von Mehren M , Wagner A , Wardelmann E , Naito Y , Zalcberg J , Blay JY
Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network
Ann Oncol. 2020 Nov;31(11) :1506-1517
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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.
Demetri, G D Antonescu, C R Bjerkehagen, B Bovee, J V M G 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 eng K08 CA241085/CA/NCI NIH HHS/ Review England Ann Oncol. 2020 Nov;31(11):1506-1517. doi: 10.1016/j.annonc.2020.08.2232. Epub 2020 Sep 3.