PMID- 37296928
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230612
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 11
DP  - 2023 May 29
TI  - NTRK Gene Fusions in Non-Small-Cell Lung Cancer: Real-World Screening Data of 
      1068 Unselected Patients.
LID - 10.3390/cancers15112966 [doi]
LID - 2966
AB  - (1) Background: The main objectives of our study are (i) to determine the 
      prevalence of NTRK (neurotrophic tyrosine kinase) fusions in a routine diagnostic 
      setting in NSCLC (non-small cell lung cancer) and (ii) to investigate the 
      feasibility of screening approaches including immunohistochemistry (IHC) as a 
      first-line test accompanied by fluorescence in situ hybridization (FISH) and 
      RNA-(ribonucleic acid-)based next-generation sequencing (RNA-NGS). (2) Methods: A 
      total of 1068 unselected consecutive patients with NSCLC were screened in two 
      scenarios, either with initial IHC followed by RNA-NGS (n = 973) or direct FISH 
      testing (n = 95). (3) Results: One hundred and thirty-three patients (14.8%) were 
      IHC positive; consecutive RNA-NGS testing revealed two patients (0.2%) with NTRK 
      fusions (NTRK1-EPS15 (epidermal growth factor receptor pathway substrate 15) and 
      NTRK1-SQSTM1 (sequestosome 1)). Positive RNA-NGS was confirmed by FISH, and 
      NTRK-positive patients benefited from targeted treatment. All patients with 
      direct FISH testing were negative. RNA-NGS- or FISH-positive results were 
      mutually exclusive with alterations in EGFR (epidermal growth factor receptor), 
      ALK (anaplastic lymphoma kinase), ROS1 (ROS proto-oncogene 1), BRAF 
      (proto-oncogene B-Raf), RET (rearranged during transfection) or KRAS (kirsten rat 
      sarcoma viral oncogene). Excluding patients with one of these alterations raised 
      the prevalence of NTRK-fusion positivity among panTrk-(tropomyosin receptor 
      kinase-) IHC positive samples to 30.5%. (4) Conclusions: NTRK fusion-positive 
      lung cancers are exceedingly rare and account for less than 1% of patients in 
      unselected all-comer populations. Both RNA-NGS and FISH are suitable to determine 
      clinically relevant NTRK fusions in a real-world setting. We suggest including 
      panTrk-IHC in a diagnostic workflow followed by RNA-NGS. Excluding patients with 
      concurrent molecular alterations to EGFR/ALK/ROS1/BRAF/RET or KRAS might narrow 
      the target population.
FAU - Overbeck, Tobias Raphael
AU  - Overbeck TR
AUID- ORCID: 0000-0002-2579-0171
AD  - Department of Hematology and Medical Oncology, University Medical Center 
      Gottingen, 37075 Gottingen, Germany.
AD  - Gottingen Comprehensive Cancer Center (G-CCC), Lungentumorzentrum Universitat 
      Gottingen, 37075 Gottingen, Germany.
FAU - Reiffert, Annika
AU  - Reiffert A
AD  - Institute of Pathology, University Medical Center Gottingen, 37075 Gottingen, 
      Germany.
FAU - Schmitz, Katja
AU  - Schmitz K
AD  - Institute of Pathology, University Medical Center Gottingen, 37075 Gottingen, 
      Germany.
AD  - Tyrolpath Obrist Brunhuber GmbH and Krankenhaus St. Vinzenz, 6511 Zams, Austria.
FAU - Rittmeyer, Achim
AU  - Rittmeyer A
AUID- ORCID: 0000-0002-5280-6052
AD  - Gottingen Comprehensive Cancer Center (G-CCC), Lungentumorzentrum Universitat 
      Gottingen, 37075 Gottingen, Germany.
AD  - Lungenfachklinik Immenhausen, 34376 Immenhausen, Germany.
FAU - Korber, Wolfgang
AU  - Korber W
AD  - Gottingen Comprehensive Cancer Center (G-CCC), Lungentumorzentrum Universitat 
      Gottingen, 37075 Gottingen, Germany.
AD  - Department of Pneumology Evangelisches Krankenhaus Weende, 37075 Gottingen, 
      Germany.
FAU - Hugo, Sara
AU  - Hugo S
AD  - Institute of Pathology, University Medical Center Gottingen, 37075 Gottingen, 
      Germany.
FAU - Schnalke, Juliane
AU  - Schnalke J
AD  - Institute of Pathology, University Medical Center Gottingen, 37075 Gottingen, 
      Germany.
FAU - Lukat, Laura
AU  - Lukat L
AD  - Institute of Pathology, University Medical Center Gottingen, 37075 Gottingen, 
      Germany.
FAU - Hugo, Tabea
AU  - Hugo T
AD  - Institute of Pathology, University Medical Center Gottingen, 37075 Gottingen, 
      Germany.
AD  - Discovery Life Sciences, 34119 Kassel, Germany.
FAU - Hinterthaner, Marc
AU  - Hinterthaner M
AD  - Gottingen Comprehensive Cancer Center (G-CCC), Lungentumorzentrum Universitat 
      Gottingen, 37075 Gottingen, Germany.
AD  - Department of Heart, Thoracic and Vascular Surgery, University Medical Center 
      Gottingen, 37075 Gottingen, Germany.
FAU - Reuter-Jessen, Kirsten
AU  - Reuter-Jessen K
AD  - Institute of Pathology, University Medical Center Gottingen, 37075 Gottingen, 
      Germany.
FAU - Schildhaus, Hans-Ulrich
AU  - Schildhaus HU
AD  - Institute of Pathology, University Medical Center Gottingen, 37075 Gottingen, 
      Germany.
AD  - Discovery Life Sciences, 34119 Kassel, Germany.
LA  - eng
GR  - financial support/Ignyta (United States)/
GR  - financial support/Roche (Germany)/
PT  - Journal Article
DEP - 20230529
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC10252111
OTO - NOTNLM
OT  - FISH
OT  - NSCLC
OT  - NTRK
OT  - RNA-based next-generation sequencing
OT  - fluorescence in situ hybridization
OT  - immunohistochemistry
OT  - lung cancer
OT  - targeted therapy
COIS- T.R.O. received grants as an advisor or speaker from: AstraZeneca, Boehringer 
      Ingelheim, Daiichi-Sankyo, Roche Pharma, Merck Sharp and Dohme, Novartis Pharma, 
      and Takeda Oncology. T.R.O. received travel support from AstraZeneca and 
      Janssen-Cilag. K.S. received honoraria as advisor or speaker from: Amgen, 
      AstraZeneca, Bayer, Daiichi-Sankyo, Diaceutics, Incyte, Janssen-Cilag, Eli Lilly, 
      Merck Sharp and Dohme, Novartis Pharma, Pfizer, PharmaMar, Roche Pharma, Servier, 
      Stemline, Targos GmbH, and ZytoVision. A.R. received grants as an advisor or 
      speaker from: AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, 
      Eli Lilly, Merck Sharp and Dohme, Novartis Pharma, Pfizer, and Roche Pharma. W.K. 
      received grants as an advisor or speaker from: AstraZeneca, Berlin Chemie, 
      Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Merck Sharp and 
      Dohme, Novartis Pharma, Pfizer, Roche Pharma, and Takeda Oncology. M.H. received 
      grants as an advisor or speaker from: AstraZeneca, Merck Sharp and Dohme, and 
      Roche Pharma. K.R.-J. received grants as a speaker from: AstraZeneca, Roche, and 
      ZytoVision. H.-U.S. received a research grant from Novartis Oncology, served as 
      an advisory board member for Abbott Molecular, Abbvie, Bristol-Myers Squibb, 
      Merck Sharp and Dohme, Novartis Oncology, and Pfizer, and received honoraria from 
      Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Roche Pharma, Zytomed, and 
      ZytoVision. The other authors have no conflicts of interest to declare.
EDAT- 2023/06/10 15:13
MHDA- 2023/06/10 15:14
PMCR- 2023/05/29
CRDT- 2023/06/10 01:03
PHST- 2023/04/13 00:00 [received]
PHST- 2023/05/12 00:00 [revised]
PHST- 2023/05/23 00:00 [accepted]
PHST- 2023/06/10 15:14 [medline]
PHST- 2023/06/10 15:13 [pubmed]
PHST- 2023/06/10 01:03 [entrez]
PHST- 2023/05/29 00:00 [pmc-release]
AID - cancers15112966 [pii]
AID - cancers-15-02966 [pii]
AID - 10.3390/cancers15112966 [doi]
PST - epublish
SO  - Cancers (Basel). 2023 May 29;15(11):2966. doi: 10.3390/cancers15112966.