Circulating Tumor DNA: An Emerging Tool in Gastrointestinal Cancers

Abstract

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that has come from primary or metastatic cancer sites. Neoplasm-specific genetic and epigenetic abnormalities are increasingly being identified through liquid biopsy: a novel, minimally invasive technique used to isolate and analyze ctDNA in the peripheral circulation. Liquid biopsy and other emerging ctDNA technologies represent a paradigm shift in cancer diagnostics because they allow for the detection of minimal residual disease in patients with early-stage disease, improve risk stratification, capture tumor heterogeneity and genomic evolution, and enhance ctDNA-guided adjuvant and palliative cancer therapy. Moreover, ctDNA can be used to monitor the tumor response to neoadjuvant and postoperative therapy in patients with metastatic disease. Using clearance of ctDNA as an endpoint for escalation/de-escalation of adjuvant chemotherapy for patients considered to have high-risk disease has become an important area of research. The possibility of using ctDNA as a surrogate for treatment response–including for overall survival, progression-free survival, and disease-free survival–is an attractive concept; this surrogate will arguably reduce study duration and expedite the development of new therapies. In this review, we summarize the current evidence on the applications of ctDNA for the diagnosis and management of gastrointestinal tumors. Gastrointestinal cancers–including tumors of the esophagus, stomach, colon, liver, and pancreas–account for one-quarter of global cancer diagnoses and contribute to more than one-third of cancer-related deaths. Given the prevalence of gastrointestinal malignancies, ctDNA technology represents a powerful tool to reduce the global burden of disease.

The Novel Prognostic Index Model of Combining Circulating Tumor DNA and PINK-E Predicts the Clinical Outcomes for Newly Diagnosed Extranodal NK/T-cell Lymphoma

“…39 The possibility of using ctDNA as a surrogate for treatment response and survival is an attractive concept; this surrogate will arguably reduce study duration and expedite the development of new therapies. 40 Some studies have reported that monitoring ctDNA can reflect treatment response, monitor disease progression, and facilitate prediction of prognosis in some solid cancers. 39,[41][42][43] Recently, some research reported that ctDNA had prognostic value in lymphoma patients.…”

“… 33 ctDNA analysis has increased sensitivity and specificity compared with the analysis of other circulating biomarkers and SUVmax. 28 , 50 , 51 Moreover, ctDNA provides a dynamic real-time profiling and identifies these novel mutations in a timely manner on serial monitoring independently, making it the ideal tool for monitoring minimal residual disease (MRD) in ENKTL, 40 , 52 and could correct tumor heterogeneity and biopsy site bias. Recently, a new model of a 7-SNP-based classifier based on the status of seven single-nucleotide polymorphisms (SNPs) was constructed for ENKTL, which initiated the use of molecular mutations to construct prognostic model for ENKTL.…”

Comparison of the Clinical Value of the Geriatric Nutritional Risk Index and Prognostic Nutritional Index as Determinants of Survival Outcome in Patients with Gastric Cancer

“…Detection of MRD by measuring circulating tumor DNA (ctDNA) levels may facilitate individualized adjuvant therapy and improve survival outcomes in patients with GC. However, data on the clinical use of ctDNA in GC are limited, requiring further studies for its clinical application [6]. Given the dissatisfaction with the established biomarkers, further research to develop accurate and novel biomarkers are necessary.…”

ASO Author Reflections: Challenges of Circulating Tumor DNA in the Management of Gastrointestinal Peritoneal Carcinomatosis

“…1 Several ongoing clinical studies have been designed to expand the scope of ctDNA-informed treatment decisions in gastrointestinal (GI) cancers. 1,2 Although expansion of ctDNA-based treatment decisions is a necessary advancement in cancer care, it is crucial to understand the limitations of this test and thereby the clinical situations in which ctDNA liquid biopsy may not be entirely reliable. A growing body of evidence shows the interaction of tumor type, tumor burden, and site of metastases on the amount of ctDNA detected in the blood.…”

“… 1 Several ongoing clinical studies have been designed to expand the scope of ctDNA-informed treatment decisions in gastrointestinal (GI) cancers. 1 , 2 …”