Circulating tumor DNA for diagnosis, prognosis and treatment of gastrointestinal malignancies

Abstract

Minimally invasive detection of circulating tumor DNA (ctDNA) in peripheral blood or other body fluids of patients with gastrointestinal malignancies via liquid biopsy has emerged as a promising biomarker. This is urgently needed, as conventional imaging and plasma protein-derived biomarkers lack sensitivity and specificity in prognosis, early detection of relapse or treatment monitoring. This review summarizes the potential role of liquid biopsy in diagnosis, prognosis and treatment monitoring of gastrointestinal malignancies, including upper gastrointestinal, liver, bile duct, pancreatic and colorectal cancer. CtDNA can now be part of the clinical routine as a promising, highly sensitive and specific biomarker with a broad range of applicability. Liquid-biopsy based postoperative relapse prediction could lead to improved survival by intensification of adjuvant treatment in patients identified to be at risk of early recurrence. Moreover, ctDNA allows monitoring of antineoplastic treatment success, with identification of potentially developed resistance or therapeutic targets during the course of treatment. It may also assist in early change of chemotherapy in metastatic gastrointestinal malignancies prior to imaging findings of relapse. Nevertheless, clinical utility is dependent on the tumor’s entity and burden.

Circulating Tumor DNA and Management of Colorectal Cancer

“…Multiple techniques, such as real-time quantitative polymerase chain reaction (qPCR), digital droplet PCR (ddPCR), and next-generation sequencing (NGS), have been utilized for the detection and analysis of ctDNA [ 26 ]. The detection of ctDNA can either be targeted or untargeted, while DNA may enter the bloodstream through both active and passive mechanisms [ 27 , 28 , 29 , 30 ].…”

“…The ratio between ctDNA and cfDNA can greatly vary anywhere between 1 and 40% due to the characteristics of the primary tumor as well as the presence and location of metastatic disease [17,20,25]. Multiple techniques, such as real-time quantitative polymerase chain reaction (qPCR), digital droplet PCR (ddPCR), and next-generation sequencing (NGS), have been utilized for the detection and analysis of ctDNA [26]. The detection of ctDNA can either be targeted or untargeted, while DNA may enter the bloodstream through both active and passive mechanisms [27][28][29][30].…”

Circulating tumor DNA based minimal residual disease detection and adjuvant treatment decision-making for muscle-invasive bladder cancer guided by modern clinical trials

“…First, the patient's Signatera™ testing was drawn using a mobile phlebotomy station, highlighting improved convenience. Previous studies have indicated that ctDNA changes often precede observable changes on imaging [ 40 ]. Given the positive ctDNA assay and positive imaging findings, a negative ctDNA assay could potentially lead to less frequent imaging and change the standard of care.…”

Circulating tumour DNA in gastrointestinal cancer in clinical practice: Just a dream or maybe not?

“…We read with great interest the minireview by Kirchweger et al [ 1 ], entitled “Circulating tumor DNA (ctDNA) for diagnosis, prognosis and treatment of gastrointestinal malignancies”. This paper provides a comprehensive overview on available literature data regarding the potential role of ctDNA in the management of gastric, biliary tract, liver, pancreatic and colorectal cancer (CRC).…”