Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by a Five Circulating Tumor DNA Methylation Signature in Colorectal Cancer

2021 ◽  
Author(s):  
Wei Wang ◽  
Zhicheng Zeng ◽  
Xuecong Zhang ◽  
Chengyong Lei ◽  
Shaowan Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Therapeutic Efficacy ◽  
Circulating Tumor Dna ◽  
Metastatic Relapse ◽  
Tumor Dna

scholarly journals Early Detection of Circulating Tumor DNA Postoperatively Enables Discovery of Resectable Metastatic Disease in a Patient with Colon Cancer

2021 ◽  
pp. 1748-1753
Author(s):  
Benjamin A. Weinberg ◽  
Emily R. Winslow ◽  
Mohammed Bayasi ◽  
Michael R. Krainock ◽  
Perry M. Olshan ◽  
...  
Keyword(s):  
Early Detection ◽  
Residual Disease ◽  
Colon Adenocarcinoma ◽  
Circulating Tumor Dna ◽  
Close Monitoring ◽  
Curative Intent ◽  
Contrast Enhanced ◽  
Metastatic Relapse ◽  
Invasive Method ◽  
Tumor Dna

Currently, serum carcinoembryonic agent (CEA) along with contrast-enhanced imaging and colonoscopy are used for evaluation of recurrence of colorectal cancer. However, CEA is an unreliable and nonspecific biomarker that may fail to rise and signal relapse. Analysis of circulating tumor DNA (ctDNA) in patients offers a minimally invasive method to assess risk of relapse several months ahead of conventional clinical means. Here, we report the case of a colon adenocarcinoma with postoperative liver metastasis diagnosed early by ctDNA measurement, using a personalized NGS-mPCR assay. While ctDNA levels continued to rise, CEA levels tested negative. Metastatic relapse to the liver was promptly confirmed by PET/CT scan. The patient underwent a successful metastasectomy with curative intent. Following surgery, the patient exhibited no evidence of disease and ctDNA levels remained negative. Our case report suggests that the early detection of postoperative molecular residual disease by means of ctDNA measurement can accurately predict mCRC relapse in cases where CEA levels fail to increase. Close monitoring of ctDNA levels during the postoperative period can allow for earlier intervention and more favorable outcomes in relapsing mCRC patients.

scholarly journals The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Martin Widschwendter ◽  
Michal Zikan ◽  
Benjamin Wahl ◽  
Harri Lempiäinen ◽  
Tobias Paprotka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Circulating Tumor Dna ◽  
Methylation Analysis ◽  
Dna Methylation Analysis ◽  
Tumor Dna

scholarly journals Clinical correlates of circulating cell-free DNA tumor fraction

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256436
Author(s):  
Joerg Bredno ◽  
Jafi Lipson ◽  
Oliver Venn ◽  
Alexander M. Aravanis ◽  
Arash Jamshidi
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Metabolic Activity ◽  
Linear Models ◽  
Circulating Tumor Dna ◽  
Cell Free Dna ◽  
Clinical Correlates ◽  
Cancer Early Detection ◽  
Free Dna ◽  
Tumor Dna

Background Oncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated. Methods and findings Circulating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test. Conclusions Prognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.

scholarly journals Detection of Circulating Tumor DNA Methylation in Diagnosis of Colorectal Cancer

2021 ◽  
Vol 12 (8) ◽  
pp. e00386
Author(s):  
Fei Xu ◽  
Shanshan Yu ◽  
Junyi Han ◽  
Ming Zong ◽  
Qi Tan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Circulating Tumor Dna ◽  
Tumor Dna
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