Circulating tumor DNA (ctDNA) as an early marker to monitor clinical benefit of regorafenib and TAS-102 in patients with metastatic colorectal cancer (mCRC).

Pereira, Allan Andresson Lima; Lam, Michael; Marie, Preeti Kanikarla; Raghav, Kanwal; Morris, Van K.; Brown, Hiromi; Windham, Justin; Overman, Michael J.; Sanchez, Eduardo Vilar; Wistuba, Ignacio I.; Kipp, Peter; Janků, Filip; Sinha, Sudhir K.; Kopetz, Scott

doi:10.1200/jco.2018.36.15_suppl.3533

Cited by 3 publications

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“…Patients with metastatic CRC who have a longer PFS on regorafenib and TAS-102 have an early decline in mutant DNA fraction, in contrast to those with a shorter PFS who either have an increase or minimal early change in mutant DNA fraction 65,66 . In patients with metastatic CRC with ctDNA progression, defined as any increase in VAF on regorafenib or TAS-102, the sensitivity, specificity and positive predictive value of ctDNA progression for the detection of subsequent radiographic progressive disease were 61.5%, 100% and 100%, respectively 67 . Thus, based on the data from these studies, establishing the validity of early changes in ctDNA as surrogate markers for clinical response in patients on later lines of therapy, in whom the prior probability of benefit is low and the risk of harm is high, is imperative.…”

Section: Box 4 | Key Recommendations On the Management Of Rectal Cancermentioning

confidence: 99%

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

et al. 2020

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An increasing number of studies are describing potential uses of circulating tumour DNA (ctDNA) in the care of patients with colorectal cancer. Owing to this rapidly developing area of research, the Colon and Rectal–Anal Task Forces of the United States National Cancer Institute convened a panel of multidisciplinary experts to summarize current data on the utility of ctDNA in the management of colorectal cancer and to provide guidance in promoting the efficient development and integration of this technology into clinical care. The panel focused on four key areas in which ctDNA has the potential to change clinical practice, including the detection of minimal residual disease, the management of patients with rectal cancer, monitoring responses to therapy, and tracking clonal dynamics in response to targeted therapies and other systemic treatments. The panel also provides general guidelines with relevance for ctDNA-related research efforts, irrespective of indication.

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Section: Box 4 | Key Recommendations On the Management Of Rectal Cancermentioning

confidence: 99%

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

et al. 2020

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“…The researchers found that higher proportion of ctDNA mutation positive patients (27.8%) experienced disease progression compared to those who were ctDNA mutation negative (4.4%) after surgery (25). Another study showed the reliability of ctDNA in predicting the response to regorafenib or TAS-102 in patients with metastatic CRC using different PCR based methods (26). Cabel et al conducted a study on 36 anal cancer patients in France and reported that post-chemoradiotherapy detection of ctDNA is associated with worse outcomes.…”

Section: Ctdna As a Prognostic Biomarkermentioning

confidence: 99%

Role of Circulating Tumor DNA in Gastrointestinal Cancers: Update From Abstracts and Sessions at ASCO 2018

2019

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Background: The promising aspect of circulating tumor DNA (ctDNA) is its rapid turnaround and non-invasive nature. According to the American Society of Clinical Oncology (ASCO) and College of American Pathologists joint ctDNA review published in March 2018, there is not sufficient evidence to support the use of ctDNA in practice for GI cancers. However, there were numerous studies presented at ASCO Annual Meeting supporting its value. We aimed to summarize on its role in the management of gastrointestinal cancers based on the studies presented recently, and future directions. Methods: We limited our search to keywords “ctDNA,” “circulating tumor DNA,” “cell-free DNA (cfDNA)” and/or “liquid biopsy,” at the 2018 ASCO Annual Meeting library abstracts and presentations. Results: There were 35 studies that revolved around ctDNA as a diagnostic tool, prognostic marker and/or a measure of tumor heterogeneity in gastrointestinal cancers. Depending on the assay used, the results of several studies showed that ctDNA was able to identify relevant mutations or fusions including RAS, HER2/Neu, BRAF, MET, BRCA2, APC, TP53, ALK, ROS1, PTEN , and NF1 . The prognosis in terms of tumor mutation burden, objective response rate, metastasis and survival were also estimated by various studies based on ctDNA. The findings showed that higher baseline ctDNA levels and/or increased number of mutations detected in ctDNA were associated with poor survival and multi-site metastasis. Right-sided colon cancer was associated with higher number of mutations in ctDNA than left-sided colon and rectal cancers. Similarly, tubular adenocarcinoma subtype of gastric cancer was more likely to have higher ctDNA levels than signet-ring cell subtype. The feasibility of assessing response to therapy and residual metastatic disease by using ctDNA which was otherwise not detected on imaging was also presented. Conclusions: The studies presented at ASCO 2018 report on the many ways ctDNA is of value in patients with gastrointestinal malignancies. Experts and discussants at the meeting argued that this may well indeed be ready for prime time for certain GI malignancies including colorectal cancers, especially in the metastatic setting. These findings alongside ongoing studies showing its feasibility into practice would likely lead to revision of the current guidelines for metastatic GI cancers.

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“…Studies were also performed to assess the response to regorafenib and TAS-102 by ctDNA analysis. Patients who had an early decline in this analyte in the plasma experienced better PFS in contrast with those with a minimal change or increase in the ctDNA levels [111][112][113].…”

Section: Therapeutic Response Evaluationmentioning

confidence: 97%

“…ctDNA could be crucial to assess the response to standard chemotherapy, as it can facilitate the early discontinuation of ineffective therapies, especially considering the last lines where preserving the patient's quality of life is crucial [111][112][113]. In the meantime, it could provide information on the possible mechanisms of resistance in particular when using anti-EGFRs to guide clinicians in the choice of rechallenge [144].…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Liquid Biopsy in Advanced Colorectal Cancer: Clinical Applications of Different Analytes

Delcuratolo,

Modrego-Sánchez,

Bungaro

et al. 2023

JMP

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Colorectal cancer is one of the most prevalent cancers nowadays. In the metastatic setting, diagnosis and treatment have relied on tumor tissue analysis. However, the different limitations of this approach have recently opened the door to the introduction of liquid biopsy in the clinical setting. Liquid biopsy provides real-time information about the tumor and its heterogeneity in a simple, non-invasive, and repeatable way. There are several analytes that can be sought: exosomes, circulating tumor cells, and circulating tumor DNA, showing promising results in the areas of early detection, minimal residual disease, prognosis, or response to treatment. Here, we review the clinical applications of liquid biopsy in advanced colorectal cancer patients, focusing on metastatic diagnosis, prognostic assessment, drug sensitivity, treatment response, and acquired resistance monitoring.

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Circulating tumor DNA (ctDNA) as an early marker to monitor clinical benefit of regorafenib and TAS-102 in patients with metastatic colorectal cancer (mCRC).

Cited by 3 publications

References 0 publications

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

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

Role of Circulating Tumor DNA in Gastrointestinal Cancers: Update From Abstracts and Sessions at ASCO 2018

Liquid Biopsy in Advanced Colorectal Cancer: Clinical Applications of Different Analytes

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