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Early assessment of...
Early assessment of circulating tumor DNA after curative-intent resection predicts tumor recurrence in early-stage and locally advanced non-small-cell lung cancer
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Waldeck, Silvia (author)
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Mitschke, Jan (author)
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Wiesemann, Sebastian (author)
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Rassner, Michael (author)
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Andrieux, Geoffroy (author)
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Deuter, Max (author)
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Mutter, Jurik (author)
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Lüchtenborg, Anne Marie (author)
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Kottmann, Daniel (author)
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Titze, Laurin (author)
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Zeisel, Christoph (author)
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- Jolic, Martina (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för biomaterialvetenskap,Institute of Clinical Sciences, Department of Biomaterials
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Philipp, Ulrike (author)
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Lassmann, Silke (author)
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Bronsert, Peter (author)
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Greil, Christine (author)
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Rawluk, Justyna (author)
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Becker, Heiko (author)
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Isbell, Lisa (author)
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Müller, Alexandra (author)
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Doostkam, Soroush (author)
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Passlick, Bernward (author)
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Börries, Melanie (author)
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Duyster, Justus (author)
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Wehrle, Julius (author)
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Scherer, Florian (author)
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von Bubnoff, Nikolas (author)
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- 2021
- 2021
- English.
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In: Molecular Oncology. - 1574-7891 .- 1878-0261.
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
Keyword
- circulating tumor DNA
- early-stage and locally advanced non-small-cell lung cancer
- minimal residual disease
- noninvasive biomarker
- relapse prediction
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Waldeck, Silvia
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Mitschke, Jan
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Wiesemann, Sebas ...
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Rassner, Michael
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Andrieux, Geoffr ...
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Deuter, Max
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show more...
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Mutter, Jurik
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Lüchtenborg, Ann ...
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Kottmann, Daniel
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Titze, Laurin
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Zeisel, Christop ...
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Jolic, Martina
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Philipp, Ulrike
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Lassmann, Silke
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Bronsert, Peter
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Greil, Christine
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Rawluk, Justyna
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Becker, Heiko
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Isbell, Lisa
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Müller, Alexandr ...
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Doostkam, Sorous ...
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Passlick, Bernwa ...
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Börries, Melanie
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Duyster, Justus
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Wehrle, Julius
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Scherer, Florian
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von Bubnoff, Nik ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
- Articles in the publication
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Molecular Oncolo ...
- By the university
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University of Gothenburg