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 language | English |
|---|---|
| Pages (from-to) | 1506-1517 |
| Number of pages | 12 |
| Journal | Annals of Oncology |
| Volume | 31 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2020 |
Keywords
- entrectinib
- larotrectinib
- neurotrophic tyrosine receptor kinase
- sarcoma
- tropomyosin receptor kinase
ASJC Scopus subject areas
- Hematology
- Oncology
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Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas : expert recommendations from the World Sarcoma Network. / Demetri, G. D.; Antonescu, C. R.; Bjerkehagen, B.; Bovée, J. V.M.G.; Boye, K.; Chacón, 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.; Martín, J.; Patel, S.; Penault-Llorca, F.; Premanand Raut, C.; Rutkowski, P.; Safwat, A.; Sbaraglia, M.; Schaefer, I. M.; Shen, L.; Serrano, C.; Schöffski, 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.
In: Annals of Oncology, Vol. 31, No. 11, 11.2020, p. 1506-1517.Research output: Contribution to journal › Review article › peer-review
}
TY - JOUR
T1 - Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas
T2 - expert recommendations from the World Sarcoma Network
AU - Demetri, G. D.
AU - Antonescu, C. R.
AU - Bjerkehagen, B.
AU - Bovée, J. V.M.G.
AU - Boye, K.
AU - Chacón, M.
AU - Dei Tos, A. P.
AU - Desai, J.
AU - Fletcher, J. A.
AU - Gelderblom, H.
AU - George, S.
AU - Gronchi, A.
AU - Haas, R. L.
AU - Hindi, N.
AU - Hohenberger, P.
AU - Joensuu, H.
AU - Jones, R. L.
AU - Judson, I.
AU - Kang, Y. K.
AU - Kawai, A.
AU - Lazar, A. J.
AU - Le Cesne, A.
AU - Maestro, R.
AU - Maki, R. G.
AU - Martín, J.
AU - Patel, S.
AU - Penault-Llorca, F.
AU - Premanand Raut, C.
AU - Rutkowski, P.
AU - Safwat, A.
AU - Sbaraglia, M.
AU - Schaefer, I. M.
AU - Shen, L.
AU - Serrano, C.
AU - Schöffski, P.
AU - Stacchiotti, S.
AU - Sundby Hall, K.
AU - Tap, W. D.
AU - Thomas, D. M.
AU - Trent, J.
AU - Valverde, C.
AU - van der Graaf, W. T.A.
AU - von Mehren, M.
AU - Wagner, A.
AU - Wardelmann, E.
AU - Naito, Y.
AU - Zalcberg, J.
AU - Blay, J. Y.
N1 - Funding Information: Under the authors' conceptual guidance, medical writing support was provided by Michael Sheldon, PhD and editorial support was provided by Annabel Ola, MSc, both of Scion, London, UK, according to Good Publication Practice guidelines and supported by an independent grant from Bayer HealthCare Pharmaceuticals, Inc. Funding Information: GDD was supported in part by the Ludwig Center at Harvard ; the Dr Miriam and Sheldon G. Adelson Medical Research Foundation ; and the Pan Mass Challenge (no grant numbers). IMS is supported by the National Institutes of Health / National Cancer Institute (grant number K08 CA241085 ). JYB was supported by NetSARC (INCA & DGOS) and RREPS (INCA & DGOS), RESOS (INCA & DGOS), EURACAN (EC 739521), LYRICAN (INCA-DGOS-INSERM 12563), LabEx DEvweCAN (ANR-10-LABX-0061), Institut Convergence PLASCAN (17-CONV-0002), RHU4 DEPGYN (ANR-18-RHUS-0009). Funding Information: KB has received consultant fees from Bayer and Merck, and research support from Bayer, Merck, and Eli Lilly. GDD discloses scientific consultancy with sponsored research to Dana-Farber from Bayer, Pfizer, Novartis, Roche/Genentech, Epizyme, LOXO Oncology, AbbVie, GSK, Janssen, PharmaMar, ZioPharm, Daiichi Sankyo, Adaptimmune, and Mirati; scientific consultancy for GSK, EMD Serono, Sanofi, ICON plc, WCG/Arsenal Capital, Polaris Pharmaceuticals, MJ Hennessy/OncLive, C4 Therapeutics, Synlogic, and MEDSCAPE; consultant/SAB member with minor equity holding for G1 Therapeutics, Caris Life Sciences, Champions Biotechnology, Bessor Pharma, Erasca Pharmaceuticals, RELAY Therapeutics, and Caprion/HistoGeneX; board of directors member and scientific advisory board consultant with minor equity for Blueprint Medicines, Merrimack Pharmaceuticals (ended Oct 2019), and Translate BIO; royalties from Novartis to Dana-Farber for use of patent of imatinib in GIST; non-financial interests with McCann Health, Alexandria Real Estate Equities, and AACR Science Policy and Government Affairs Committee (Chair). JD discloses advisory/consultancy roles for Amgen, Novartis, Lilly, GSK, Pierre Fabre, and Eisai; institutional research funding from Novartis, Lilly, GSK, Roche/Genentech, BMS, AstraZeneca, and BeiGene. PH discloses consultancy fees from Roche and Pfizer, and research support from Novartis. HJ has a co-appointment at Orion Pharma, has received fees from Neutron Therapeutics, and owns stocks of Orion Pharma and Sartar Therapeutics. YKK discloses consultancy for Taiho, Ono, Merck, Daehwa, BMS, Astellas, Zymeworks, ALX ONCOLOGY, Amgen, Novartis, MacroGenics, and Surface Oncology. SP discloses grant support from Blueprint Medicines and Hutchison MediPharma; consultancy for Daiichi Sankyo, Epizyme, Dova, Decimera, Bayer, and Immune Design. FPL discloses advisory/consultancy roles for Bayer and Roche, and institutional research grants from Bayer. PR has received honoraria for lectures and advisory boards from Novartis, MSD, Roche, BMS, Sanofi, Merck, Amgen, Pfizer, Pierre Fabre, and Blueprint Medicines, outside the scope of this report. WDT discloses advisory/consultancy roles for Lilly, EMD Serono, Eisai, Janssen, Immune Design, Daiichi Sankyo, Blueprint Medicines, LOXO Oncology, GSK, Agios Pharmaceuticals, NanoCarrier, Deciphera, Certis Oncology Solutions, and Atropos Therapeutics; patent for CDK4 inhibitor companion diagnostic (14/854 329) pending to MSKCC/SKI; stock ownership in Certis Oncology Solutions and Atropos Therapeutics; participation in FDA ODAC meeting for pexidartinib. DT is the CEO of a non-profit company, Omico, which undertakes precision oncology activities across Australia. He has received honoraria or consultant fees from Roche, Pfizer, Bayer, AstraZeneca, Merck, and the Maine Cancer Genome Initiative. He has received research support from Roche, Pfizer, Bayer, AstraZeneca, Amgen, Eisai, Illumina, and Sun Pharma. JZ discloses honoraria from Pfizer, Merck Serono, Specialized Therapeutics, Targovax, Halozyme, Gilead Sciences, and Bayer; advisory/consultancy roles for Pfizer, Merck Serono, Targovax, MSD, Sirtex Medical, Halozyme, Lipotek, Novella, and Khloris Biosciences; institutional research funding from Bayer, Merck Serono, Roche, BMS, Pfizer, AstraZeneca, Specialized Therapeutics, Baxalta/Shire, Lilly, Boehringer-Ingelheim, and MSD; travel/accommodation/expenses from Merck Serono, AstraZeneca, MSD, Deciphera, and Sirtex; shareholder/stockholder/stock options in GW Pharmaceuticals, Aimmune, Vertex, Bluebird Bio, Alnylam, BioMarin, Sage Therapeutics, Dova Pharmaceuticals, Therapeutics MD, Juno Therapeutics, Kite Pharma, Kiadis Pharma, CSL Ltd, Cochlear, Amarin, Freq Therapeutics, Global Blood Therapeutics, Gilead, uniQure, Sangamo, Acceleron, Zogenix, Myovant Science, and Khloris Biosciences; board of directors for Praxis Australia; non-remunerated activities for Australian Clinical Trials Alliance (Chair), National Oncology Alliance (co-Chair), and All.Can Australia (co-Chair). All other authors have declared no conflicts of interest. Publisher Copyright: © 2020 The Author(s) Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - entrectinib
KW - larotrectinib
KW - neurotrophic tyrosine receptor kinase
KW - sarcoma
KW - tropomyosin receptor kinase
UR - http://www.scopus.com/inward/record.url?scp=85092103764&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092103764&partnerID=8YFLogxK
U2 - 10.1016/j.annonc.2020.08.2232
DO - 10.1016/j.annonc.2020.08.2232
M3 - Review article
C2 - 32891793
AN - SCOPUS:85092103764
VL - 31
SP - 1506
EP - 1517
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 11
ER -