Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery

Reinert, Thomas; Schøler, Lone V.; Thomsen, Rie; Tobiasen, Heidi; Vang, Søren; Nordentoft, Iver; Lamy, Pierre‐Jean; Kannerup, Anne Sofie; Mortensen, Frank Viborg; Stribolt, Katrine; Hamilton-Dutoit, Stephen; Nielsen, Hans Jørgen; Laurberg, Søren; Pallisgaard, Niels; Pedersen, Jakob Skou; Ørntoft, Torben F.; Andersen, Claus Lindbjerg

doi:10.1136/gutjnl-2014-308859

Cited by 386 publications

(350 citation statements)

References 24 publications

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“…With WIF1 and NPY markers being found to be hypermethylated in a large fraction of tumor tissues, independently of the stage of the cancer, our results suggest that ctDNA monitoring can be performed without analysis of the tumor DNA (which may be inaccessible or of poor quality). In addition, these results suggest that monitoring of MetctDNA was as efficient as the monitoring of MutctDNA for the detection of CRC recurrence in plasma of patients with localized disease, and for monitoring treatment efficiency for patients with advanced CRC (18,40 ).…”

Section: Discussionmentioning

confidence: 87%

A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker

et al. 2016

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BACKGROUND Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored. METHODS We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up. RESULTS Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution. CONCLUSIONS These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.

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Section: Discussionmentioning

confidence: 87%

A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker

et al. 2016

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“…Posttreatment ctDNA levels may also be useful in detecting previously unrecognized residual disease following definitive therapy. Anecdotal evidence has been reported to support this concept (7,17,123,124), but large, prospective studies will be needed to demonstrate the prognostic value of residual disease detected by ctDNA. Tie and colleagues (125) have reported preliminary results of a prospective trial in stage II colon cancer evaluating the relationship of postoperative ctDNA levels with tumor recurrence.…”

Section: Considerations For Sensitive Detection Of Ctdnamentioning

confidence: 99%

Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility

Ignatiadis

Lee

Jeffrey

2015

Clinical Cancer Research

310

251

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Recent technological advances have enabled the detection and detailed characterization of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) in blood samples from patients with cancer. Often referred to as a "liquid biopsy," CTCs and ctDNA are expected to provide real-time monitoring of tumor evolution and therapeutic efficacy, with the potential for improved cancer diagnosis and treatment. In this review, we focus on these opportunities as well as the challenges that should be addressed so that these tools may eventually be implemented into routine clinical care.

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“…Danish researchers used NGS and droplet digital PCR to identify patient-specific somatic structural variants, which were then used as personalized ctDNA assays to monitor the disease burden after CRC surgery. 94 Their technique enabled efficient temporal assessment of disease status, with detection of metastatic recurrence at a mean of 10 months earlier than conventional follow-up. The authors concluded that ctDNA analysis is an exquisitely specific and highly sensitive approach for monitoring disease load.…”

Section: Monitoring Tumor Burden or Response During Treatmentmentioning

confidence: 99%

Future perspectives of circulating tumor DNA in colorectal cancer

et al. 2017

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Tumor biopsy is currently the gold standard for diagnosis and in determining cell signaling pathways involved in the development of treatment resistance. However, there are major challenges with this technique, including the need for serial sampling to monitor treatment resistance, which is invasive and also has the potential for selection bias due to intra-tumoral and inter-tumoral heterogeneity. These challenges highlight the need for more effective methods for obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells shed into the blood from the primary tumor and metastatic sites and consequently provides a comprehensive, real-time picture of the tumor burden in an individual patient. Indeed, liquid biopsy has the potential to revolutionize cancer management. Here, we review recent studies on the potential clinical applications of liquid biopsy using circulating tumor DNA in colorectal cancer, including screening, diagnosis, detection of minimal residual disease after surgery, detection of recurrence, prognosis, predicting treatment response, monitoring tumor burden or response during treatment, and tracking resistance. We also discuss recent data demonstrating the utility of detecting KRAS-mutated circulating tumor DNA, both at diagnosis to determine an appropriate treatment strategy and during anti-epidermal growth factor receptor therapy to predict treatment resistance. The future integration of liquid biopsy into clinical practice is discussed, together with alternative approaches and key questions that need to be answered in future clinical studies before this technology can be implemented and used routinely.

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Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery

Cited by 386 publications

References 24 publications

A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker

A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker

Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility

Future perspectives of circulating tumor DNA in colorectal cancer

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