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

G D Demetri (1) , Antonescu C R (2) , B Bjerkehagen (3) , Judith V.M.G. Bovee (4) , K Boye (3) , M Chacón (5) , a P Dei Tos (6) , J Desai (7) , Fletcher J A (1) , H Gelderblom (4) , George S (8) , A Gronchi (9) , R L Haas (10) , N Hindi (11) , P Hohenberger (12) , H Joensuu (13) , Jones R L (14) , I Judson (14) , Y-K Kang (15) , A Kawai (16) , Lazar a J (17) , A Le Cesne (18, 19) , R Maestro (20) , Maki R G (21) , J Martín (11) , S Patel (17) , F Penault-Llorca (22) , C Premanand Raut (8, 1) , P Rutkowski (23) , A Safwat (24) , M Sbaraglia (6) , I-M Schaefer (1) , L Shen (25) , C Serrano (26) , Schöffski P (27) , S Stacchiotti (9) , K Sundby Hall (3) , Tap W-D (2) , Thomas D-M (28) , J Trent (29) , C Valverde (26) , W T a van Der Graaf (30) , von Mehren M (31) , A Wagner (1) , E Wardelmann (32) , Y Naito (33) , J Zalcberg (34) , Blay J-y (35, 36)

1 HMS - Harvard Medical School [Boston]
2 Memorial Sloane Kettering Cancer Center [New York]
3 Oslo University Hospital [Oslo]
4 LUMC - Leiden University Medical Center
5 IAF - Instituto Alexander Fleming [Buenos Aires, Argentina]
6 Unipd - Università degli Studi di Padova = University of Padua
7 University of Melbourne
8 Dana-Farber Cancer Institute [Boston]
9 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
10 NKI - Netherlands Cancer Institute
11 Universidad de Sevilla = University of Seville
12 University Medical Center Mannheim
13 University of Helsinki
14 The institute of cancer research [London]
15 University of Ulsan
16 National Cancer Center Research Institute [Tokyo]
17 The University of Texas M.D. Anderson Cancer Center [Houston]
18 IGR - Institut Gustave Roussy
19 Département de médecine oncologique [Gustave Roussy]
20 National Cancer Institute of Aviano
21 University of Pennsylvania
22 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
23 Maria Sklodowska-Curie National Research Institute of Oncology [Krakow, Poland]
24 Aarhus University Hospital
25 PKUPH - People's Hospital of Peking University
26 Vall d'Hebron University Hospital [Barcelona]
27 LKI - Leuven Cancer Institute [Leuven, Belgium]
28 Garvan Institute of medical research
29 S3C - Sylvester Comprehensive Cancer Center [Miami, FL, USA]
30 Radboud University Medical Center [Nijmegen]
31 Fox Chase Cancer Center
32 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
33 NCCJ - National Cancer Center Hospital
34 Monash University [Melbourne]
35 Centre Léon Bérard [Lyon]
36 Centre de Recherche et d’Innovation de Lyon, Solvay

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.

Mots clés: entrectinib; larotrectinib; neurotrophic tyrosine receptor kinase; sarcoma; tropomyosin receptor kinase

Domaines: Sciences du Vivant [q-bio]

G D Demetri, Antonescu C R, B Bjerkehagen, Judith V.M.G. Bovee, K Boye, et al.. Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network. Annals of Oncology, 2020, 31 (11), pp.1506-1517. ⟨10.1016/j.annonc.2020.08.2232⟩. ⟨hal-03046627⟩