scholarly journals PD-001 Total cell-free DNA level in plasma as strong prognostic marker in metastatic colorectal cancer

2016 ◽  
Vol 27 ◽  
pp. ii102
Author(s):  
K.-L. Spindler ◽  
C. Demuth ◽  
B. Soerensen ◽  
J. Johansen ◽  
D. Nielsen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Prognostic Marker ◽  
Total Cell ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Total cell-free DNA, carcinoembryonic antigen, and C-reactive protein for assessment of prognosis in patients with metastatic colorectal cancer

Tumor Biology ◽  
2018 ◽  
Vol 40 (11) ◽  
pp. 101042831881120 ◽  
Author(s):  
Karen-Lise Garm Spindler ◽  
Christina Demuth ◽  
Boe Sandahl Sorensen ◽  
Julia S Johansen ◽  
Dorte Nielsen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Metastatic Colorectal Cancer ◽  
Carcinoembryonic Antigen ◽  
Total Cell ◽  
C Reactive Protein ◽  
Cell Free Dna ◽  
Reactive Protein ◽  
Free Dna

In late-stage metastatic colorectal cancer, difficult treatment decisions should incorporate a thorough evaluation of the patient’s general condition and subject for shared decision making. Assessment of the individual patients’ prognosis is valuable in this setting. The aim was to analyze the prognostic value of plasma levels of total cell-free DNA, carcinoembryonic antigen and C-reactive protein in 97 heavily pretreated patients with metastatic colorectal cancer. Patients received irinotecan, cetuximab, and everolimus in a phase-2 clinical trial ( clinicaltrials.gov NCT01387880). Plasma samples were used for DNA purification and quantification of total cell-free DNA by droplet digital polymerase chain reaction. Serum carcinoembryonic antigen and C-reactive protein were analyzed by routine methods. Clinical endpoints were overall survival and progression-free survival. A total of 82 patients had blood samples available for quantification of total cell-free DNA. Patients with pre-treatment cell-free DNA levels higher than the median total cell-free DNA (9800 alleles per milliliter plasma) had a significantly shorter overall survival of 4.3 months (95% confidence interval: 3.6–5.8) compared to patients with cell-free DNA levels below the median with an overall survival of 11.3 months (95% confidence interval: 8.0–14.8, p < 0.0001). When using the upper normal limit from a previously analyzed normal control group, the median overall survival was 11.3 (95% confidence interval: 7.3–14.8) and 4.3 (95% confidence interval: 3.7–6.1) months, respectively (p < 0.0001). Serum carcinoembryonic antigen and C-reactive protein had similar prognostic value with short overall survival and progression-free survival in patients with elevated levels compared to those within normal range. A high-risk profile of elevated cell-free DNA, carcinoembryonic antigen, and C-reactive protein was described, but in combined Cox regression multivariate analysis, only total cell-free DNA preserved a strong prognostic value. In conclusion, total cell-free DNA in plasma, carcinoembryonic antigen, and C-reactive protein could all contribute to assessment of patients’ prognosis and potentially aid in clinical decision making in patients with metastatic colorectal cancer.

scholarly journals Treatment monitoring in metastatic colorectal cancer patients by quantification and KRAS genotyping of circulating cell-free DNA

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0174308 ◽  
Author(s):  
Andreas W. Berger ◽  
Daniel Schwerdel ◽  
Hanna Welz ◽  
Ralf Marienfeld ◽  
Stefan A. Schmidt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Treatment Monitoring ◽  
Cell Free Dna ◽  
Free Dna ◽  
Colorectal Cancer Patients ◽  
Circulating Cell Free Dna

Plasma cell-free DNA and fraction of circulating KRAS mutations as prognostic in patients with metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 490-490 ◽  
Author(s):  
David Sefrioui ◽  
Nasrin Vasseur ◽  
Richard Sesboüé ◽  
France Blanchard ◽  
Alice Oden-Gangloff ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Plasma Cell ◽  
Circulating Tumor Dna ◽  
Dna Fragments ◽  
Wild Type ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna

490 Background: It has been suggested that detection of circulating tumor DNA may be relevant in patients with metastatic colorectal cancer (mCRC). The main objective of the present study was to evaluate a method based on the TaqMan Mutation Detection Assay (TMDA) for the detection of circulating KRAS mutations in mCRC patients. Moreover, we also investigated the prognostic impact of the plasma cell-free DNA and the fraction of circulating KRAS mutations. Methods: The study was conducted from April to July 2013 and plasma samples were prospectively collected in a series of 35 mCRC patients treated with chemotherapy (CT). QIAamp Circulating Nucleic Acid kit was used for DNA extraction and Quant-iT High Sensitivity dsDNA Assay for cf-DNA quantification. Detection of circulating tumor DNA was based on the KRAS mutations detected in tumour and was performed in plasma by the castPCR Technology TMDA. Response to CT was assessed according to RECIST criteria. The results of plasma cf-DNA and level of mutant DNA fragments were correlated with response and 3-months survival. Results: We isolated and quantified plasma cf-DNA in all patients with a mean concentration of 106 ng/mL. Among them, 18 were wild-type and 17 mutated for KRAS in the tumour. Detection of circulating KRAS mutations was performed with TMDA in 23 patients (10 KRAS wild-type and 13 KRAS mutated). The sensitivity was 62% (8/13) and specificity 100% (0/10) with a level of circulating mutant DNA fragments ranging from 0 to 29%. Plasma cf-DNA and level of circulating mutant DNA were both significantly correlated with the 3-months survival (mean 36 versus 524 ng/mL, p=0.0015 and 2% versus 29%, p<0.0001). There was a non significant trend for response to CT (respectively p=0.14 and p=0.12). Conclusions: TMDA method is a simple, accurate and non-invasive tool for the detection of circulating tumor DNA. Our preliminary results also suggest that plasma cf-DNA and fraction of mutant DNA fragments could be prognostic markers in mCRC patients.

scholarly journals Cell‐Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta‐Analysis

2017 ◽  
Vol 22 (9) ◽  
pp. 1049-1055 ◽  
Author(s):  
Karen‐Lise G. Spindler ◽  
Anders K. Boysen ◽  
Niels Pallisgård ◽  
Julia S. Johansen ◽  
Josep Tabernero ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Cell Free Dna ◽  
Free Dna
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