Early assessment of circulating tumor DNA after curative-intent resection predicts tumor recurrence in early-stage and locally advanced non-small-cell lung cancer.

Autor: Waldeck S; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany., Mitschke J; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Wiesemann S; Department of Thoracic Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Rassner M; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Andrieux G; German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Deuter M; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Mutter J; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Lüchtenborg AM; Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Kottmann D; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Titze L; Department of Thoracic Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Zeisel C; Department of Thoracic Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Jolic M; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Philipp U; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Lassmann S; German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Bronsert P; Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Greil C; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Rawluk J; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Becker H; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Isbell L; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Müller A; Institute for Neuropathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Doostkam S; Institute for Neuropathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Passlick B; Department of Thoracic Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Börries M; German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Duyster J; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany., Wehrle J; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Scherer F; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany., von Bubnoff N; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2022 Jan; Vol. 16 (2), pp. 527-537. Date of Electronic Publication: 2021 Oct 31.
DOI: 10.1002/1878-0261.13116
Abstrakt: Circulating tumor DNA (ctDNA) has demonstrated great potential as a noninvasive biomarker to assess minimal residual disease (MRD) and profile tumor genotypes in patients with non-small-cell lung cancer (NSCLC). However, little is known about its dynamics during and after tumor resection, or its potential for predicting clinical outcomes. Here, we applied a targeted-capture high-throughput sequencing approach to profile ctDNA at various disease milestones and assessed its predictive value in patients with early-stage and locally advanced NSCLC. We prospectively enrolled 33 consecutive patients with stage IA to IIIB NSCLC undergoing curative-intent tumor resection (median follow-up: 26.2 months). From 21 patients, we serially collected 96 plasma samples before surgery, during surgery, 1-2 weeks postsurgery, and during follow-up. Deep next-generation sequencing using unique molecular identifiers was performed to identify and quantify tumor-specific mutations in ctDNA. Twelve patients (57%) had detectable mutations in ctDNA before tumor resection. Both ctDNA detection rates and ctDNA concentrations were significantly higher in plasma obtained during surgery compared with presurgical specimens (57% versus 19% ctDNA detection rate, and 12.47 versus 6.64 ng·mL -1 , respectively). Four patients (19%) remained ctDNA-positive at 1-2 weeks after surgery, with all of them (100%) experiencing disease progression at later time points. In contrast, only 4 out of 12 ctDNA-negative patients (33%) after surgery experienced relapse during follow-up. Positive ctDNA in early postoperative plasma samples was associated with shorter progression-free survival (P = 0.013) and overall survival (P = 0.004). Our findings suggest that, in early-stage and locally advanced NSCLC, intraoperative plasma sampling results in high ctDNA detection rates and that ctDNA positivity early after resection identifies patients at risk for relapse.
(© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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