ctDNA applications and integration in colorectal cancer: an NCI Colon and Rectal–Anal Task Forces whitepaper

Dasari, Arvind; Morris, Van K.; Allegra, Carmen J.; Atreya, Chloé E.; Benson, Al B.; Boland, Patrick M.; Chung, Ki Young; Copur, Mehmet Sitki; Corcoran, Ryan B.; Deming, Dustin A.; Dwyer, Andrea; Diehn, Maximilian; Eng, Cathy; George, Thomas J.; Gollub, Marc J.; Goodwin, Rachel; Hamilton, Stanley R.; Hechtman, Jaclyn F.; Hochster, Howard S.; Hong, Theodore S.; Innocenti, Federico; Iqbal, Atif; Jacobs, Samuel A.; Kennecke, Hagen F.; Lee, James J.; Lieu, Christopher H.; Lenz, Heinz Josef; Lindwasser, O. Wolf; Montagut, Clara; Odisio, Bruno C.; Ou, Fang Shu; Porter, Laura; Raghav, Kanwal; Schrag, Deborah; Scott, Aaron J.; Shi, Qian; Strickler, John H.; Venook, Alan P.; Yaeger, Rona; Yothers, Greg; You, Y. Nancy; Zell, Jason A.; Kopetz, Scott

doi:10.1038/s41571-020-0392-0

Cited by 255 publications

(251 citation statements)

References 117 publications

(142 reference statements)

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“…The proportion of CRC patients in whom ctDNA can be identified depends on the tumor volume and ranges from 50% to 90% in those with non-metastatic or metastatic disease, respectively [ 76 ]. There is evidence that after CRC curative resection, the detection rate of ctDNA could range from 8–15% in stage II to 50% in stage IV [ 31 , 32 , 77 ]. Serum DNA concentrations and integrity index may play an important role not only in early complementary diagnosis but also in monitoring of progression and prognosis of CRC.…”

Section: Clinical Utility Of Liquid Biopsies In Patients With Colomentioning

confidence: 99%

“…Limitations of NGS, principally with regard to the overall clinical sensitivity, could be overtaken implementing NGS with mutant allele enrichment or using digital PCR to improve reliability [ 96 , 114 ]. Mass-spectrometry and Real-Time PCR are other promising techniques for ctDNA assessment, which are rapid and cheap, require small quantities of input material, and have high sensitivity and specificity [ 77 , 115 ]. If possible, ctDNA should be analyzed in combination with CTCs and exosomal miRNAs, to obtain as much data as possible from a single blood sample [ 116 ].…”

Section: Current Issues and Limitations Of Liquid Biopsymentioning

confidence: 99%

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The Liquid Biopsy in the Management of Colorectal Cancer: An Overview

et al. 2020

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Currently, there is a crucial need for novel diagnostic and prognostic biomarkers with high specificity and sensitivity in patients with colorectal cancer. A “liquid biopsy” is characterized by the isolation of cancer-derived components, such as circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs, and proteins, from peripheral blood or other body fluids and their genomic or proteomic assessment. The liquid biopsy is a minimally invasive and repeatable technique that could play a significant role in screening and diagnosis, and predict relapse and metastasis, as well as monitoring minimal residual disease and chemotherapy resistance in colorectal cancer patients. However, there are still some practical issues that need to be addressed before liquid biopsy can be widely used in clinical practice. Potential challenges may include low amounts of circulating tumor cells and circulating tumor DNA in samples, lack of pre-analytical and analytical consensus, clinical validation, and regulatory endorsement. The aim of this review was to summarize the current knowledge of the role of liquid biopsy in the management of colorectal cancer.

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Section: Clinical Utility Of Liquid Biopsies In Patients With Colomentioning

confidence: 99%

Section: Current Issues and Limitations Of Liquid Biopsymentioning

confidence: 99%

The Liquid Biopsy in the Management of Colorectal Cancer: An Overview

et al. 2020

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“…Although promising, ct-DNA based profiling of BTC has several limitations related to the technology itself and its applicability. Wide variations exist in the preanalytical variables, assay characteristics (PCR-based versus NGS-based techniques), bioinformatic analysis methods, sensitivity, and specificity [40]. These factors pose significant challenges in the interpretation of clinical trial data utilizing different ctDNA platforms.…”

Section: Circulating Tumor Dna (Ctdna)-based Molecular Profilingmentioning

confidence: 99%

Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm

Chakrabarti

Kamgar

Mahipal

2020

Cancers

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Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas that originate from the epithelial lining of the biliary tree. BTCs are characterized by presentation with advanced disease precluding curative surgery, rising global incidence, and a poor prognosis. Chemotherapy is the mainstay of the current treatment, which results in a median overall survival of less than one year, underscoring the need for novel therapeutic agents and strategies. Next-generation sequencing-based molecular profiling has shed light on the underpinnings of the complex pathophysiology of BTC and has uncovered numerous actionable targets, leading to the discovery of new therapies tailored to the molecular targets. Therapies targeting fibroblast growth factor receptor (FGFR) fusion, isocitrate dehydrogenase (IDH) mutations, the human epidermal growth factor receptor (HER) family, DNA damage repair (DDR) pathways, and BRAF mutations have produced early encouraging results in selected patients. Current clinical trials evaluating targeted therapies, as monotherapies and in combination with other agents, are paving the way for novel treatment options. Genomic profiling of cell-free circulating tumor DNA that can assist in the identification of an actionable target is another exciting area of development. In this review, we provide a contemporaneous appraisal of the evolving targeted therapies and the ongoing clinical trials that will likely transform the therapeutic paradigm of BTC.

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“…The study result showed an error rate that would have implications for clinical decision-making [ 70 ]. Recently the Colon and Rectal–Anal Task Forces of the United States National Cancer Institute has published a whitepaper providing detailed guidance in standardization and efficient development of the ctDNA technology [ 71 ].…”

Section: Future Perspective and Conclusionmentioning

confidence: 99%

The Promise of Circulating Tumor DNA (ctDNA) in the Management of Early-Stage Colon Cancer: A Critical Review

Chakrabarti

Xie

Urrutia

et al. 2020

Cancers

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The current standard treatment for patients with early-stage colon cancer consists of surgical resection, followed by adjuvant therapy in a select group of patients deemed at risk of cancer recurrence. The decision to administer adjuvant therapy, intended to eradicate the clinically inapparent minimal residual disease (MRD) to achieve a cure, is guided by clinicopathologic characteristics of the tumor. However, the risk stratification based on clinicopathologic characteristics is imprecise and results in under or overtreatment in a substantial number of patients. Emerging research indicates that the circulating tumor DNA (ctDNA), a fraction of cell-free DNA (cfDNA) in the bloodstream that originates from the neoplastic cells and carry tumor-specific genomic alterations, is a promising surrogate marker of MRD. Several recent studies suggest that ctDNA-guided risk stratification for adjuvant therapy outperforms existing clinicopathologic prognostic indicators. Preliminary data also indicate that, aside from being a prognostic indicator, ctDNA can inform on the efficacy of adjuvant therapy, which is the underlying scientific rationale for several ongoing clinical trials evaluating ctDNA-guided therapy escalation or de-escalation. Furthermore, serial monitoring of ctDNA after completion of definitive therapy can potentially detect cancer recurrence much earlier than conventional surveillance methods that may provide a critical window of opportunity for additional curative-intent therapeutic interventions. This article presents a critical overview of published studies that evaluated the clinical utility of ctDNA in the management of patients with early-stage colon cancer, and the potential of ctDNA to transform the adjuvant therapy strategies.

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ctDNA applications and integration in colorectal cancer: an NCI Colon and Rectal–Anal Task Forces whitepaper

Cited by 255 publications

References 117 publications

The Liquid Biopsy in the Management of Colorectal Cancer: An Overview

The Liquid Biopsy in the Management of Colorectal Cancer: An Overview

Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm

The Promise of Circulating Tumor DNA (ctDNA) in the Management of Early-Stage Colon Cancer: A Critical Review

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