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Early change in circulating tumor DNA as a potential predictor of response to chemotherapy in patients with metastatic colorectal cancer
Open accessAbstract
The impact of ctDNA changes after chemotherapy on the clinical outcomes of patients with metastatic colorectal cancer (mCRC) remains unclear. The present study evaluated the clinical implications of the early change in ctDNA levels as a predictor of objective response and clinical outcome in mCRC patients who received chemotherapy. We investigated the effects of after/before ratio of ctDNA levels 2 and 8 weeks after initiation of second-line chemotherapy, on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). ctDNA was detected using amplicon-based deep sequencing with a molecular barcode encompassing >240 hotspot mutations in 14 colon cancer-related genes. In multivariate analysis, as compared to baseline, patients with lower ctDNA level (≤50%) 8 weeks after initiation of chemotherapy showed significantly longer PFS and OS than the patients with higher (>50%) ctDNA level. In patients achieving a partial response or stable disease, the after/before ratio of ctDNA level 8 weeks after initiation of chemotherapy was significantly lower than those in patients with progressive disease. The present study suggests that an early change in the ctDNA level might serve as a biomarker to predict the chemotherapeutic efficacy and clinical outcomes in patients with mCRC.
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“recent data suggests that serial analyses may have clinical value as clearance of ctDNA among patients undergoing systemic chemo- or immunotherapy correlate with progression-free and overall survival.13–17”
From Early Changes in Circulating Cell-Free KRAS G12C Predict Response to Adagrasib in KRAS Mutant Non–Small Cell Lung Cancer Patients (2023) · cites this paper as [14]
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Metadata
- Authors
- Osumi, H., Shinozaki, E., Yamaguchi, K., & Zembutsu, H.
- Affiliations
- Japanese Foundation For Cancer Research (JP)
- Corresponding author
- Zembutsu, Hitoshi
- Venue
- Scientific Reports
- Published
- 2019-11-22
- Volume
- 9
- Issue
- 1
- Pages
- 17358-17358
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6874682
- OpenAlex
- W2991166240
- Cited by
- 114
- References
- 46
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 9 · 2023: 17 · 2022: 21 · 2021: 21 · 2020: 23
- FWCI
- 6.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (18K07310)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- circulating tumor DNA, metastatic colorectal cancer, second-line chemotherapy, objective response rate, predictive biomarkers, progression-free survival, overall survival, mutational hotspots, treatment response prediction
- MeSH terms
- Liquid Biopsy, Circulating Tumor DNA, Adenocarcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Predictive Value of Tests, Prognosis, Biomarkers, Tumor, Colorectal Neoplasms, Early Diagnosis, Biomarkers, Pharmacological, High-Throughput Nucleotide Sequencing
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