NPY Gene Methylation as a Universal, Longitudinal Plasma Marker for Evaluating the Clinical Benefit from Last-Line Treatment with Regorafenib in Metastatic Colorectal Cancer.

Autor: Jensen LH; Department of Oncology, Vejle University Hospital, 7100 Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.; Danish Colorectal Cancer Center South, Vejle University Hospital, 7100 Vejle, Denmark., Olesen R; Department of Oncology, Aarhus University Hospital, 8000 Aarhus, Denmark., Petersen LN; Department of Oncology 5073, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark., Boysen AK; Department of Oncology, Aarhus University Hospital, 8000 Aarhus, Denmark., Andersen RF; Danish Colorectal Cancer Center South, Vejle University Hospital, 7100 Vejle, Denmark.; Department of Biochemistry, Vejle University Hospital, 7100 Vejle, Denmark., Lindebjerg J; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.; Danish Colorectal Cancer Center South, Vejle University Hospital, 7100 Vejle, Denmark.; Department of Pathology, Vejle University Hospital, 7100 Vejle, Denmark., Nottelmann L; Department of Oncology, Vejle University Hospital, 7100 Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.; Danish Colorectal Cancer Center South, Vejle University Hospital, 7100 Vejle, Denmark., Thomsen CEB; Department of Oncology, Vejle University Hospital, 7100 Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.; Danish Colorectal Cancer Center South, Vejle University Hospital, 7100 Vejle, Denmark., Havelund BM; Department of Oncology, Vejle University Hospital, 7100 Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.; Danish Colorectal Cancer Center South, Vejle University Hospital, 7100 Vejle, Denmark., Jakobsen A; Department of Oncology, Vejle University Hospital, 7100 Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.; Danish Colorectal Cancer Center South, Vejle University Hospital, 7100 Vejle, Denmark., Hansen TF; Department of Oncology, Vejle University Hospital, 7100 Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark.; Danish Colorectal Cancer Center South, Vejle University Hospital, 7100 Vejle, Denmark.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2019 Oct 25; Vol. 11 (11). Date of Electronic Publication: 2019 Oct 25.
DOI: 10.3390/cancers11111649
Abstrakt: There is a need for biomarkers to improve the clinical benefit from systemic treatment of colorectal cancer. We designed a prospective, clinical study where patients receiving regorafenib as last-line treatment had sequential blood samples drawn. Effect and toxicity was monitored. The primary clinical endpoint was progression free survival (PFS). Cell-free circulating tumor (ct) DNA was measured as either the fraction with Neuropeptide Y ( NPY ) methylated DNA or KRAS/NRAS/BRAF mutated ctDNA. One hundred patients were included from three Danish centers. Among 95 patients who received regorafenib for at least two weeks, the median PFS was 2.1 months (95% confidence interval (CI) 1.8-3.3) and the median overall survival (OS) was 5.2 months (95% CI 4.3-6.5). Grade 3-4 toxicities were reported 51 times, most frequently hypertension, hand-food syndrome, and skin rash. In the biomarker population of 91 patients, 49 could be monitored using mutated DNA and 90 using methylated DNA. There was a strong correlation between mutated and methylated DNA. The median survival for patients with a level of methylated ctDNA above the median was 4.3 months compared to 7.6 months with ctDNA below the median, p < 0.001. The median time from increasing methylated ctDNA to disease progression was 1.64 months (range 0.46-8.38 months). In conclusion, NPY methylated ctDNA was a universal liquid biopsy marker in colorectal cancer patients treated with regorafenib. High baseline levels correlated with short survival and changes during treatment may predict early effect and later progression. We suggest plasma NPY methylation analysis as an easy and universally applicable method for longitudinal monitoring of ctDNA in metastatic colorectal cancer patients.
Databáze: MEDLINE
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