Exploring the Feasibility of Utilizing Limited Gene Panel Circulating Tumor DNA Clearance as a Biomarker in Patients With Locally Advanced Non-Small Cell Lung Cancer.

Autor:	Knapp B; Department of Medicine, Division of General Medicine, Washington University School of Medicine, St. Louis, MO, United States., Mezquita L; Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France., Devarakonda S; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States., Aldea M; Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France., Waqar SN; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States., Pepin K; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States., Ward JP; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States., Botticella A; Radiation Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France., Howarth K; Department of Clinical Genomics, Inivata Limited, Cambridge, United Kingdom., Knape C; Inivata Inc, Research Triangle Park, Durham, NC, United States., Morris C; Department of Clinical Genomics, Inivata Limited, Cambridge, United Kingdom., Govindan R; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States., Besse B; Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France., Morgensztern D; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Mar 28; Vol. 12, pp. 856132. Date of Electronic Publication: 2022 Mar 28 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.856132
Abstrakt:	Introduction: Circulating tumor DNA (ctDNA) testing may identify patients at high risk for recurrence following chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). We evaluated the feasibility of ctDNA testing on a readily available commercial fixed-gene panel to predict outcomes in patients with LA-NSCLC. Methods: Plasma of 43 patients was collected at CRT initiation (pre-CRT), completion (post-CRT1), quarterly follow up for 12 months (post-CRT2, 3, 4, 5 respectively) after CRT, and at disease progression. ctDNA analysis was performed using InVisionFirst ® -Lung to detect mutations in 36 cancer-related genes. ctDNA clearance was defined as absence of pre-CRT variants at post-CRT1. Patients without detectable pre-CRT variants or no post-CRT1 samples were excluded. Results: Twenty eight of 43 patients (65%) had detectable variants pre-CRT. Nineteen of 43 patients (44%) had detectable pre-CRT variants and post-CRT1 samples and were included in analysis. Median age at diagnosis was 65 years (43-82), and most patients had stage IIIB disease (10/19, 53%). Two patients died from non-cancer related causes before post-CRT2 and were excluded from further analysis. All three patients who did not clear ctDNA had tumor relapse with a median time to relapse of 74 days (30-238), while 50% (7/14) of those who cleared ctDNA have remained disease free. Progression free survival was longer in patients who cleared ctDNA compared to those who did not (median 567 vs 74 d, p = 0.01). Conclusions: Although it is feasible to use ctDNA testing on a limited gene panel to identify patients with LA-NSCLC who are at high risk for disease recurrence following CRT, further studies will be necessary to optimize these assays before they can be used to inform clinical care in patients with lung cancer. Competing Interests: LM: Lectures and educational activities: Bristol-Myers Squibb, Tecnofarma, AstraZeneca, Roche, Takeda. Consulting/advisory role: Roche, Takeda. Research Grants: Bristol-Myers Squibb, Boehringer Ingelheim. Travel, Accommodations, Expenses: Bristol-Myers Squibb, Roche. Others: International Mentorship Program funded by AstraZeneca. SW: Research grant support from -2% effort on “Duke-UNC Wash U Partnership for Early Phase Clinical Trials in Cancer” 1UM1 CA186704-01 grant as mentored faculty, DSMB Chair for Hoosier Cancer Research Network study, and institutional PI for studies with support from Hoffmann-La Roche Ltd, Ariad, Pfizer Pharmaceuticals, Inc., Hengrui Therapeutics, Xcovery, EMD Serono Research & Development Institute, Inc., Checkpoint Therapeutics, Inc., Genentech, Inc., Lilly, Stemcentrx, Inc., Ignyta, Inc., Bristol-Myers Squibb Pharmaceutical, Synermore Biologics Co., Ltd., Novartis Pharmaceuticals Corporation, Merck & Company, Inc., NewLink Genetics Corporation, and Celgene. JW: Advisory board for Novocure, Consultant for Novoure, Employment for Millipore (Spouse), Travel/Expenses from Halozyme. KH: employee and stockholder for Inivata. CK: employee and stockholder for Inivata. CM: employee and stockholder for Inivata. RG: Advisory Board for Achilles, Consulting for GenePlus, Horizon Pharmaceuticals (Spouse). BB: Research support from 4D Pharma, Abbvie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Inivata, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals. DM: Advisory board for Abbvie, Takeda, PharmaMar, Gilead, Boehringer Ingelheim; Consultant for Abbvie, Takeda, Boehringer Ingelheim, PharmaMar, Gilead. The study received funding from Inivata. The funder had the following involvement in the study: study design, analysis and data interpretation, the writing of this article, and the decision to submit it for publication. (Copyright © 2022 Knapp, Mezquita, Devarakonda, Aldea, Waqar, Pepin, Ward, Botticella, Howarth, Knape, Morris, Govindan, Besse and Morgensztern.)
Databáze:	MEDLINE
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