Implementing circulating tumor DNA as a prognostic biomarker in resectable non-small cell lung cancer
- PMID: 38839544
- DOI: 10.1016/j.trecan.2024.04.004
Implementing circulating tumor DNA as a prognostic biomarker in resectable non-small cell lung cancer
Abstract
Systemic treatment of resectable non-small cell lung cancer (NSCLC) is evolving with emerging neoadjuvant, perioperative, and adjuvant immunotherapy approaches. Circulating tumor DNA (ctDNA) detection at clinical diagnosis, during neoadjuvant therapy, or after resection may discern high-risk patients who might benefit from therapy escalation or switch. This Review summarizes translational implications of data supporting ctDNA-based risk determination in NSCLC and outstanding questions regarding ctDNA validity/utility as a prognostic biomarker. We discuss emerging ctDNA capabilities to refine clinical tumor-node-metastasis (TNM) staging in lung adenocarcinoma, ctDNA dynamics during neoadjuvant therapy for identifying patients deriving suboptimal benefit, and postoperative molecular residual disease (MRD) detection to escalate systemic therapy. Considering differential relapse characteristics in landmark MRD-negative/MRD-positive patients, we propose how ctDNA might integrate with pathological response data for optimal postoperative risk stratification.
Keywords: biomarker; ctDNA; molecular residual disease; non-small cell lung cancer; resectable; staging.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests C.A. was formerly an employee of, and held stocks/shares in, AstraZeneca, and is currently an employee of SAGA Diagnostics. D.H., G.J.D., D.G., L.H., and J.S.R.-F. are employees of, and hold stocks/shares in, AstraZeneca. J.R.M.B. has no conflicts of interest to disclose. D.G. is the cofounder of Inivata, acquired by NeoGenomics in 2021, and holds shares in AstraZeneca and GSK. C.S. is the co-founder of, a Scientific Advisory Board (SAB) member for, and has stock options in Achilles Therapeutics; has stock options in Epic Bioscience, Relay Therapeutics, and Bicycle Therapeutics; held stock options in Apogen Biotechnologies and GRAIL until June 2021; was a member of the American Association for Cancer Research (AACR) Board of Directors until April 2022; is chief investigator of AstraZeneca's MeRmaiD I and II clinical trials and co-chief investigator of the NHS Galleri Trial funded by GRAIL; has received honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Illumina, MSD, Novartis, Pfizer, and Roche; has received consulting fees from Genentech, Sarah Canon Research Institute, GRAIL (SAB), Medicxi, Bicycle Therapeutics (SAB), Metabomed – until June 2021, China Innovation Centre of Roche (CICor) – (formerly Roche Innovation Centre-Shanghai), Relay Therapeutics (SAB), and Saga Diagnostics (SAB); has received grants or funds from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Invitae (formerly Archer Dx), Ono Pharmaceuticals, Personalis, and Pfizer; and holds the following patents – US20190106751A1 – Methods for lung cancer detection; PCT/EP2016/071471 – 'immune checkpoint intervention' in cancer; PCT/EP2016/059401 – Method for treating cancer; PCT/US2017/028013 – Methods for lung cancer detection; PCT/GB2018/051912 – Method for identifying responders to cancer treatment; PCT/GB2018/052004 – Analysis of HLA alleles in tumors and the uses thereof; PCT/GB2020/050221 – Method of predicting survival rates of patients with cancer; PCT/GB2017/053289 – Method of detecting tumor recurrence; PCT/EP2021/059989 – Modulation of T cell cytotoxicity and related therapy; and PCT/EP2022/077987 – Methods and systems for tumor monitoring; PCT/EP2023/059039 – Analysis of HLA alleles transcriptional deregulation.
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