ABSTRACT BACKGROUND Activating fusions of the _NTRK1_, _NTRK2_ and _NTRK3_ genes are drivers of carcinogenesis and proliferation across a broad range of tumour types in both adult and

paediatric patients. Recently, the FDA granted tumour-agnostic approvals of TRK inhibitors, larotrectinib and entrectinib, based on significant and durable responses in multiple primary

tumour types. Unfortunately, testing rates in clinical practice remain quite low. Adding plasma next-generation sequencing of circulating tumour DNA (ctDNA) to tissue-based testing increases

the detection rate of oncogenic drivers and demonstrates high concordance with tissue genotyping. However, the clinical potential of ctDNA analysis to identify _NTRK_ fusion-positive

confirmed in tissue in 88% of cases. Here, we report for the first time that minimally-invasive plasma NGS can detect _NTRK_ fusions with a high positive predictive value. CONCLUSION Plasma

ctDNA represents a rapid, non-invasive screening method for this rare genomic target that may improve identification of patients who can benefit from TRK-targeted therapy and potentially

identify subsequent on- and off-target resistance mechanisms. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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ADJUNCT TO TISSUE RESPONSE ASSESSMENT Article Open access 05 January 2024 GENOMIC ANALYSIS OF PLASMA CIRCULATING TUMOR DNA IN PATIENTS WITH HEAVILY PRETREATED HER2 + METASTATIC BREAST CANCER

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Central  Google Scholar  Download references ACKNOWLEDGEMENTS Not applicable. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai

System & Icahn School of Medicine, Mount Sinai, New York, NY, USA Christian Rolfo * Memorial Sloan Kettering Cancer Center, New York, NY, USA Alexander Drilon & Alison M. Schram *

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA David Hong * University of California, San

Francisco, CA, USA Caroline McCoach * Genentech, South San Francisco, CA, USA Caroline McCoach * University Hospitals Cleveland Medical Center, Cleveland, OH, USA Afshin Dowlati & Timmy

Nguyen * Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA Jessica J. Lin, Neelima Vidula & Aditya Bardia * Thoracic Oncology & Experimental

Therapeutics Program, Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA Alessandro Russo * Lombardi Comprehensive Cancer Center,

Georgetown University, Washington, DC, USA Stephen V. Liu * Keck School of Medicine of USC, Section Head – Solid Tumors, USC/Norris Cancer Center, Los Angeles, CA, USA Jorge J. Nieva * James

R. Berenson, MD, Inc., West Hollywood, CA, USA Shahrooz Eshaghian * Duke Cancer Institute, Division of Medical Oncology, Durham, NC, USA Michael Morse & Thomas Stinchcombe * Yale

Comprehensive Cancer Center, New Haven, CT, USA Scott Gettinger & Sarah Goldberg * ProMedica Bay Park Hospital Cancer, Sylvania, OH, USA Mohammad Mobayed * Kymera Cancer Center and

University of New Mexico, Roswell, NM, USA Emilio Araujo-Mino * Saint Lukes Cancer Institute/University of Missouri, Kansas City, MO, USA Janakiraman Subramanian * US Oncology Network, Texas

Oncology, Baytown, TX, USA Deepa Sashital * Guardant Health, Redwood City, CA, USA Lesli Kiedrowski & Kristin Price * UC Davis Comprehensive Cancer Center, Sacramento, CA, USA David R.

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also search for this author inPubMed Google Scholar * David R. Gandara View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS CR, LK, KP and DRG

conceived the work; LK and KP acquired data; AD, JJL, AMS, LK and KP provided detailed cases information and materials; CR, AR, LK, KP and DRG drafted the manuscript and analysed the data;

all the co-authors revised the manuscript. All the co-authors approved the final version. CORRESPONDING AUTHOR Correspondence to Christian Rolfo. ETHICS DECLARATIONS ETHICS APPROVAL AND

CONSENT TO PARTICIPATE This research was conducted in accordance with the Declaration of Helsinki. Institutional Review Board approval (Advarra IRB Pro00034566/CR00218935) waived the need

for individual informed consent for use of deidentified aggregate data for research purposes. CONSENT TO PUBLISH Not applicable. COMPETING INTERESTS Dr. Rolfo reports grants for Lung Cancer

Research Foundation-Pfizer Grant 2019 NHI U54 grant (Project co-leader); He has received personal fees for attending advisory board with Inivata, ArcherDx, EMD Serono, BMS, Novartis, Boston

Pharmaceuticals, Pfizer, Mirati, and Eisai; fee for speaking bureau: MSD, Astra Zeneca, Roche, and GuardantHealth; Participation in Safety Monitoring Board for EMD Serono Non-financial

conflict included research collaboration: GuardantHealth. Dr. Drilon reports Honoraria/Advisory Boards from Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics,

AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, MORE Health, Abbvie, 14ner/Elevation Oncology, Remedica

Ltd., ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare RX; Associated Research to Institution from Pfizer, Exelixis, GlaxoSmithKlein, Teva, Taiho, PharmaMar; Royalties

from Wolters Kluwer; Other from Merck, Puma, Merus, Boehringer Ingelheim. Dr. Russo reports consultancy for Astra Zeneca, MSD, and Novartis outside the submitted work. Dr. Stinchcombe

reports personal fees from Takeda, AstraZeneca, Genentech/Roche, Foundation Medicine, Pfizer, EMD Serono, Novartis, Daiichi Sankyo, Lilly, Medtronic, Puma Biotechnology, Janssen Oncology,

Regeneron, non-financial support from Genentech/Roche, Blueprint Medicines, AstraZeneca, Takeda, Advaxis, Regeneron, outside the submitted work. Dr. Vidula reports institutional research

funding from Radius, Merck, Daehwa, Pfizer (and travel), and Novartis; advisory board from AbbVie; Dr. Price is an employee and stock holder of Guardant Health. ADDITIONAL INFORMATION

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al._ _NTRK1_ Fusions identified by non-invasive plasma next-generation sequencing (NGS) across 9 cancer types. _Br J Cancer_ 126, 514–520 (2022). https://doi.org/10.1038/s41416-021-01536-1

Download citation * Received: 25 April 2021 * Revised: 10 August 2021 * Accepted: 20 August 2021 * Published: 03 September 2021 * Issue Date: 01 February 2022 * DOI:

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