Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial.

Autor:	Lueong SS; Institute for Developmental Cancer Therapeutics, West German Cancer Center, University Medicine Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Herbst A; Institute of Laboratory Medicine, University of Munich, Munich, Germany.; German Cancer Consortium (DKTK, Partner Site Munich) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Liffers ST; Institute for Developmental Cancer Therapeutics, West German Cancer Center, University Medicine Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Bielefeld N; Institute for Developmental Cancer Therapeutics, West German Cancer Center, University Medicine Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany., Horn PA; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany.; Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany., Tannapfel A; Institute for Pathology, Ruhr-University, Bochum, Germany., Reinacher-Schick A; Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital, Ruhr-University Bochum., Hinke A; CCRC: Cancer Clinical Research Consulting, Düsseldorf, Germany., Hegewisch-Becker S; HOPE: Private Practice of Hematology and Oncology, Hamburg, Germany., Kolligs FT; German Cancer Consortium (DKTK, Partner Site Munich) and German Cancer Research Center, DKFZ, Heidelberg, Germany.; Department of Medicine, Division of- Gastroenterology, Hepatology & Infectiology, Helios Clinic Berlin-Buch, Berlin, Germany.; Department of Medicine II, University of Munich, Munich, Germany., Siveke JT; Institute for Developmental Cancer Therapeutics, West German Cancer Center, University Medicine Essen, Essen, Germany.; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Clinical chemistry [Clin Chem] 2020 Dec 01; Vol. 66 (12), pp. 1510-1520.
DOI:	10.1093/clinchem/hvaa223
Abstrakt:	Background: We assessed the usefulness of circulating tumor DNA (ctDNA) pre- or post-treatment initiation for outcome prediction and treatment monitoring in metastatic colorectal cancer (mCRC). Methods: Droplet digital PCR was used to measure absolute mutant V-Ki-ras2 Kirsten rat sarcoma viral oncogene ((mut)KRAS) ctDNA concentrations in 214 healthy controls (plasma and sera) and in 151 tissue-based mutKRAS positive patients with mCRC from the prospective multicenter phase 3 trial AIO KRK0207. Serial mutKRAS ctDNA was analyzed prior to and 2-3 weeks after first-line chemotherapy initiation with fluoropyrimidine, oxaliplatin, and bevacizumab in patients with mCRC and correlated with clinical parameters. Results: mut KRAS ctDNA was detected in 74.8% (113/151) of patients at baseline and in 59.6% (90/151) at follow-up. mutKRAS ctDNA at baseline and follow-up was associated with poor overall survival (OS) (hazard ratio [HR] =1.88, 95% confidence interval [CI] 1.20-2.95; HR = 2.15, 95% CI 1.47-3.15) and progression-free survival (PFS) (HR = 2.53, 95% CI 1.44-4.46; HR = 1.90, 95% CI 1.23-2.95), respectively. mutKRAS ctDNA clearance at follow-up conferred better disease control (P = 0.0075), better OS (log-rank P = 0.0018), and PFS (log-rank P = 0.0018). Measurable positive mutKRAS ctDNA at follow-up was the strongest and most significant independent prognostic factor on OS in multivariable analysis (HR = 2.31, 95% CI 1.40-3.25). Conclusions: Serial analysis of circulating mutKRAS concentrations in mCRC has prognostic value. Post treatment mutKRAS concentrations 2 weeks after treatment initiation were associated with therapeutic response in multivariable analysis and may be an early response predictor in patients receiving first-line combination chemotherapy. Clinicaltrialsgov Identifier: NCT00973609. (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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