Prognostic implication of methylation-based circulating tumor DNA detection prior to surgery in stage I non-small cell lung cancer.

Autor: Bossé Y; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada; Department of Molecular Medicine, Université Laval, Quebec City, Canada. Electronic address: yohan.bosse@criucpq.ulaval.ca., Dasgupta A; Oncology Data Science, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., Abadier M; Translational Medicine Early Oncology, AstraZeneca, Waltham, MA, USA., Guthrie V; Oncology Data Science, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., Song F; Translational Medicine Early Oncology, AstraZeneca, Munich, Germany., Saavedra Armero V; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada., Gaudreault N; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada., Orain M; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada., Lamaze FC; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada., Melton C; GRAIL, LLC, Menlo Park, CA, USA., Nance T; GRAIL, LLC, Menlo Park, CA, USA., Hung T; GRAIL, LLC, Menlo Park, CA, USA., Hodgson D; Translational Medicine Early Oncology, AstraZeneca, Cambridge, United Kingdom., Abbosh C; Translational Medicine Early Oncology, AstraZeneca, Cambridge, United Kingdom., Joubert P; Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, Canada; Department of Molecular Biology, Pathology and Medical Biochemistry, Université Laval, Quebec City, Canada.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2024 Jul 10; Vol. 594, pp. 216984. Date of Electronic Publication: 2024 May 24.
DOI: 10.1016/j.canlet.2024.216984
Abstrakt: Background: Circulating tumor DNA (ctDNA) positivity at diagnosis, which is associated with worse outcomes in multiple solid tumors including stage I-III non-small cell lung cancer (NSCLC), may have utility to guide (neo)adjuvant therapy.
Methods: In this retrospective study, 260 patients with clinical stage I NSCLC (180 adenocarcinoma, 80 squamous cell carcinoma) were allocated (2:1) to high- and low-risk groups based on relapse versus disease-free status ≤5 years post-surgery. We evaluated the association of preoperative ctDNA detection by a plasma-only targeted methylation-based multi-cancer early detection (MCED) test with NSCLC relapse ≤5 years post-surgery in the overall population, followed by histology-specific subgroup analyses.
Results: Across clinical stage I patients, preoperative ctDNA detection did not associate with relapse within 5 years post-surgery. Sub-analyses confined to lung adenocarcinoma suggested a histology-specific association between ctDNA detection and outcome. In this group, ctDNA positivity tended to associate with relapse within 2 years, suggesting prognostic implications of MCED test positivity may be histology- and time-dependent in stage I NSCLC. Preoperative ctDNA detection was associated with upstaging of clinical stage I to pathological stage II-III NSCLC.
Conclusions: Our findings suggest preoperative ctDNA detection in patients with resectable clinical stage I NSCLC using MCED, a pan-cancer screening test developed for use in an asymptomatic population, has no detectable prognostic value for relapse ≤5 years post-surgery. MCED detection may be associated with early adenocarcinoma relapse and increased pathological upstaging rates in stage I NSCLC. However, given the exploratory nature of these findings, independent validation is required.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y. Bossé has received grants (paid to institution) from AstraZeneca and the IUCPQ foundation. A. Dasgupta is a full-time employee of and owns stock in AstraZeneca. M. Abadier is a full-time employee of and owns stock in Moderna Therapeutics. V. Guthrie is a full-time employee of and owns stock in Exact Sciences. F. Song is a full-time employee of and owns stock in AstraZeneca. F.C. Lamaze has a patent pending related to cancer diagnosis (U.S. Application No. 17/612,695; filed November 19, 2021). C. Melton is a full-time employee of GRAIL, LLC and owns stock in Illumina, Inc. T. Nance is a full-time employee of GRAIL, LLC. T. Hung is a full-time employee of GRAIL, LLC and owns stock in Illumina, Inc. D. Hodgson is a full-time employee of and owns stock in AstraZeneca. C. Abbosh is a full-time employee of and owns stock in AstraZeneca, and holds patents in MRD detection (ES2913468T3 and US20200248266A1). P. Joubert has received honoraria and research grants from AstraZeneca. The remaining authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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