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Cited by 191Cancer Genomics and DiagnosticsCircular RNAs in diseasesPrenatal Screening and Diagnostics

Detection of Solid Tumor Molecular Residual Disease (MRD) Using Circulating Tumor DNA (ctDNA)

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Chin, Re-I, Chen, Kevin, Usmani, Abul, Chua, Chanelle, Harris, Peter K., Binkley, Michael S., Azad, Tej D., Dudley, Jonathan C. +1 more·2019·Molecular Diagnosis & Therapy
DOI 10.1007/s40291-019-00390-5PMC PMC6561896
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Abstract

Circulating tumor DNA (ctDNA) is a component of cell-free DNA that is shed by malignant tumors into the bloodstream and other bodily fluids. Levels of ctDNA are typically low, particularly in patients with localized disease, requiring highly sophisticated methods for detection and quantification. Multiple liquid biopsy methods have been developed for ctDNA analysis in solid tumor malignancies and are now enabling detection and assessment of earlier stages of disease, post-treatment molecular residual disease (MRD), resistance to targeted systemic therapy, and tumor mutational burden. Understanding ctDNA biology, mechanisms of release, and clearance and size characteristics, in conjunction with the application of molecular barcoding and targeted error correction, have increased the sensitivity and specificity of ctDNA detection techniques. Combinatorial approaches including integration of ctDNA data with circulating protein biomarkers may further improve assay sensitivity and broaden the scope of ctDNA applications. Circulating viral DNA may be utilized to monitor disease in some virally induced malignancies. In spite of increasingly accurate methods of ctDNA detection, results need to be interpreted with caution given that somatic mosaicisms such as clonal hematopoiesis of indeterminate potential (CHIP) may give rise to genetic variants in the bloodstream unrelated to solid tumors, and the limited concordance observed between different commercial platforms. Overall, highly precise ctDNA detection and quantification methods have the potential to transform clinical practice via non-invasive monitoring of solid tumor malignancies, residual disease detection at earlier timepoints than standard clinical and/or imaging surveillance, and treatment personalization based on real-time assessment of the tumor genomic landscape.

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  • Imaging may lack sensitivity for detecting early molecular relapse or minimal residual disease in pediatric sarcomas, particularly when tumor burden is low.

    “While imaging plays an essential role in disease assessment, it may lack sensitivity for detecting early molecular relapse or minimal residual disease (MRD), particularly when tumor burden is low [9,10].”

    From Circulating Tumor DNA and microRNA–Based Liquid Biopsy for Longitudinal Treatment Monitoring and Recurrence Prediction in Pediatric Sarcomas: A Prospective Cohort Study (2026) · cites this paper as [9]

    The Lung Cancer section (page unavailable) says standard imaging detects only macroscopic recurrence and reports that ctDNA detection preceded radiographic progression. This supports the citing sentence’s general point about imaging and early molecular relapse, but the copy does not establish it specifically for pediatric sarcomas. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Authors
Chin, R.-I., Chen, K., Usmani, A., Chua, C., Harris, P. K., Binkley, M. S., Azad, T. D., Dudley, J. C., & Chaudhuri, A. A.
Affiliations
  • Washington University in St. Louis (US)
  • Stanford Medicine (US)
  • Johns Hopkins University (US)
  • Barnes-Jewish Hospital (US)
Corresponding author
Chaudhuri, Aadel A.
ORCID
Venue
Molecular Diagnosis & Therapy
Publisher
Springer Science and Business Media LLC
Published
2019-04-02
Volume
23
Issue
3
Pages
311-331
ISSN
  • 1177-1062 (ISSN-L)
  • 1179-2000
DOI
10.1007/s40291-019-00390-5
PMC
PMC6561896
OpenAlex
W2929863582
Cited by
191
References
22
Citations by year
2026: 18 · 2025: 27 · 2024: 25 · 2023: 40 · 2022: 29 · 2021: 25 · 2020: 21 · 2019: 6
FWCI
1.94
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Molecular Diagnosis & Therapy (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Society of Clinical Oncology (Young Investigator Award)
  • Takeda Pharmaceuticals U.S.A. (Young Investigator Award)
  • Washington University (SPORE in Pancreatic Cancer Career Enhancement Program)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
Keywords
circulating tumor DNA, liquid biopsy, molecular residual disease, solid tumors, DNA barcoding, clonal hematopoiesis of indeterminate potential, somatic mosaicism, tumor mutational burden, personalized treatment
MeSH terms
Liquid Biopsy, Circulating Tumor DNA, Humans, Neoplasms, Biomarkers, Tumor, Neoplasm, Residual, Genomics, Molecular Diagnostic Techniques, High-Throughput Nucleotide Sequencing

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