Genomic Assessment of Blood-Derived Circulating Tumor DNA in Patients With Colorectal Cancers: Correlation With Tissue Sequencing, Therapeutic Response, and Survival
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Purpose Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with colorectal cancers were correlated with clinical outcomes. Patients and Methods Next-generation sequencing of ctDNA (54- to 73-gene panel) was performed in 94 patients with colorectal cancer. Results Most patients (96%) had metastatic or recurrent disease at the time of blood draw. The median number of nonsynonymous alterations per patient was three (range, zero to 30). The most frequently aberrant genes were TP53 (52.1% of patients), KRAS (34%), and APC (28.7%). Concordance between tissue and blood next-generation sequencing ranged from 63.2% ( APC) to 85.5% ( BRAF). Altogether, 74 patients (79%) had one or more nonsynonymous alterations, 69 (73%) had one or more potentially actionable alterations, and 61 (65%) had an alteration actionable by a drug approved by the US Food and Drug Administration (on or off label). Lung metastases correlated with improved survival from diagnosis in univariable analysis. ctDNA of 5% or more from blood tests as well as EGFR and ERBB2 (HER2) nonsynonymous alterations correlated with worse survival (but only ERBB2 remained significant in multivariable analysis). No two patients had identical molecular portfolios. Overall, 65% versus 31% of patients treated with matched (n = 17) versus unmatched therapy (n = 18) after ctDNA testing achieved stable disease for 6 months or more, partial response, or complete response ( P = .045); progression-free survival, 6.1 versus 2.3 months ( P = .08); and survival not reached versus 9.4 months ( P = .146; all by multivariable analysis). Conclusion Patients with colorectal cancer have heterogeneous ctDNA profiles, and most harbor potentially actionable ctDNA alterations. Matched therapy yielded higher rates of stable disease for 6 months or more, partial response, or complete response. ctDNA assessment may have clinical utility and merits further investigation.
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Higher rates of BRAF copy number variants have been observed in other colorectal cancer studies employing blood-based sequencing.
“Higher rates of BRAF copy number variants have been observed in other colorectal cancer studies employing blood-based sequencing. 29,30”
From Sotorasib with panitumumab in chemotherapy-refractory KRASG12C-mutated colorectal cancer: a phase 1b trial (2024) · cites this paper as [29]
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- Authors
- Kato, S., Schwaederlé, M. C., Fanta, P. T., Okamura, R., Leichman, L., Lippman, S. M., Lanman, R. B., Raymond, V. M., Talasaz, A., & Kurzrock, R.
- Affiliations
- Moores Cancer Center (US)
- Shumei Kato, Maria C. Schwaederlé, Paul T. Fanta, Ryosuke Okamura, Lawrence Leichman, Scott M. Lippman, and Razelle Kurzrock, University of California San Diego Moores Cancer Center, La Jolla; and Richard B. Lanman, Victoria M. Raymond, and AmirAli Talasaz, Guardant Health, Redwood City, CA
- Corresponding author
- Kato, Shumei
- ORCID
- Venue
- JCO Precision Oncology
- Published
- 2019-12
- Volume
- 3
- Issue
- 3
- Pages
- 1-16
- ISSN
- 2473-4284 (ISSN-L)
- PMC
- PMC6484865
- OpenAlex
- W2912600727
- Cited by
- 52
- References
- 47
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 13 · 2022: 4 · 2021: 5 · 2020: 12 · 2019: 8
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- JCO Precision Oncology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Cancer Institute (P30CA023100)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- circulating tumor DNA, liquid biopsy, colorectal cancer, TP53, KRAS, APC, BRAF, actionable mutations, EGFR, HER2, progression-free survival, matched therapy, metastatic colorectal cancer, lung metastasis
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