Detection of circulating tumor DNA in patients of operative colorectal and gastric cancers

Emerging data suggest that circulating tumor DNA (ctDNA) can detect colorectal cancer (CRC)-specific signals across both non-metastatic and metastatic settings. With the development of multiple platforms, including tumor-informed and tumor-agnostic ctDNA assays and demonstration of their provocative analytic performance to detect minimal residual disease, there are now ongoing, phase III randomized clinical trials to evaluate their role in the management paradigm of CRC. In this review, we highlight landmark studies that have formed the basis for ongoing studies on the clinically applicability of plasma ctDNA assays in resected, stage I–III CRC and metastatic CRC. We discuss clinical settings by which ctDNA may have the most immediate impact in routine clinical practice. These include the potential for ctDNA to (1) guide surveillance and intensification or de-intensification strategies of adjuvant therapy in resected, stage I–III CRC, (2) predict treatment response to neoadjuvant therapy in locally advanced rectal cancer inclusive of total neoadjuvant therapy (TNT), and (3) predict response to systemic and surgical therapies in metastatic disease. We end by considering clinical variables that can influence our ability to reliably interpret ctDNA dynamics in the clinic.

Section: Detection Of Minimal Residual Disease and Recurrences In Resected Stage I–iii Colorectal Cancermentioning

confidence: 93%

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

Gong

Hendifar

Gangi

et al. 2021

“…Indeed, partitioning DNA molecules through the generation of millions of droplets and the possible additivity of reactions reduce template competition and allows to reach a theoretical detection threshold of mutations until 1/100,000 [ 8 ]. Therefore, digital droplet PCR (ddPCR) might appear as the most sensitive, suitable and fast technology [ 7 , 9 , 10 , 11 ]. Several ddPCR platforms are now being commercialized but still contain a restricted number of probes in each run.…”

Section: Molecular Aspectsmentioning

confidence: 99%

Role of Circulating Tumor DNA in Gastrointestinal Cancers: Current Knowledge and Perspectives

Moati¹,

Taly

Garinet

et al. 2021

Gastrointestinal (GI) cancers are major health burdens worldwide and biomarkers are needed to improve the management of these diseases along their evolution. Circulating tumor DNA (ctDNA) is a promising non-invasive blood and other bodily-fluid-based biomarker in cancer management that can help clinicians in various cases for the detection, diagnosis, prognosis, monitoring and personalization of treatment in digestive oncology. In addition to the well-studied prognostic role of ctDNA, the main real-world applications appear to be the assessment of minimal residual disease to further guide adjuvant therapy and predict relapse, but also the monitoring of clonal evolution to tailor treatments in metastatic setting. Other challenges such as predicting response to treatment including immune checkpoint inhibitors could also be among the potential applications of ctDNA. Although the level of advancement of ctDNA development in the different tumor localizations is still inhomogeneous, it might be now reliable enough to be soon used in clinical routine for colorectal cancers and shows promising results in other GI cancers.

“…Liquid biopsy-based post-operative assessments would be able to detect tumor relapse/recurrence a few to several months earlier than current radiological imaging modalities [ 101 , 108 , 109 , 110 ]. According to a recent study, patients with positive ctDNA after their surgery showed a significantly shorter recurrence-free survival than patients without ctDNA [ 111 ]. This implies that screening of ctDNA with liquid biopsy can be useful in identifying patients at high risk of post-operative recurrence, and that serial screening of ctDNA would allow early detection of tumor relapse/recurrence.…”

Section: Detection Of Minimal Residual Disease (Mrd) By Liquid Biopsy After the Curative Resectionmentioning

confidence: 99%

Precision Medicine for Colorectal Cancer with Liquid Biopsy and Immunotherapy

Nagayama

Low

Kiyotani

2021

Self Cite

In the field of colorectal cancer (CRC) treatment, diagnostic modalities and chemotherapy regimens have progressed remarkably in the last two decades. However, it is still difficult to identify minimal residual disease (MRD) necessary for early detection of recurrence/relapse of tumors and to select and provide appropriate drugs timely before a tumor becomes multi-drug-resistant and more aggressive. We consider the leveraging of in-depth genomic profiles of tumors as a significant breakthrough to further improve the overall prognosis of CRC patients. With the recent technological advances in methodologies and bioinformatics, the genomic profiles can be analyzed profoundly without delay by blood-based tests—‘liquid biopsies’. From a clinical point of view, a minimally-invasive liquid biopsy is thought to be a promising method and can be implemented in routine clinical settings in order to meet unmet clinical needs. In this review, we highlighted clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of MRD, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease. In addition, we addressed a possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information.