Academic Journal
Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial
| العنوان: | Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial |
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| المؤلفون: | Lueong, Smiths S, Herbst, Andreas, Liffers, Sven-Thorsten, Bielefeld, Nicola, Horn, Peter A, Tannapfel, Andrea, Reinacher-Schick, Anke, Hinke, Axel, Hegewisch-Becker, Susanna, Kolligs, Frank T, Siveke, Jens T |
| المساهمون: | German Cancer Consortium, B. Braun Foundation |
| المصدر: | Clinical Chemistry ; volume 66, issue 12, page 1510-1520 ; ISSN 0009-9147 1530-8561 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2020 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/clinchem/hvaa223 |
| DOI: | 10.1093/clinchem/hvaa223/34602984/hvaa223.pdf |
| الاتاحة: | http://dx.doi.org/10.1093/clinchem/hvaa223 http://academic.oup.com/clinchem/advance-article-pdf/doi/10.1093/clinchem/hvaa223/34602984/hvaa223.pdf http://academic.oup.com/clinchem/article-pdf/66/12/1510/34671947/hvaa223.pdf |
| Rights: | https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| رقم الانضمام: | edsbas.D0347927 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/clinchem/hvaa223 |
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