Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1799-1812
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1799
Cell-free DNA liquid biopsy for early detection of gastrointestinal cancers: A systematic review
Isabelle Uhe, Monika Elisabeth Hagen, Frédéric Ris, Jeremy Meyer, Christian Toso, Jonathan Douissard
Isabelle Uhe, Monika Elisabeth Hagen, Frédéric Ris, Jeremy Meyer, Christian Toso, Jonathan Douissard, Abdominal Surgery Division, Geneva University Hospitals, Geneva 1211, Switzerland
Author contributions: Uhe I and Douissard J designed the review, performed studies selection, data analysis, and wrote the manuscript. All authors performed critical revision of the manuscript and approved its final version.
Conflict-of-interest statement: Dr. Uhe and Dr. Meyer have nothing to disclose. Dr. Hagen reports grants from Intuitive Surgical Inc., grants, personal fees and non-financial support from Johnson&Johnson Inc., personal fees and non-financial support from Verb Surgical Inc., personal fees from Verily, non-financial support from Quantgene Inc., personal fees from I2X, outside the submitted work. Pr. Ris reports personal fees and non-financial support from Stryker Inc., grants from Quantgene Inc., outside the submitted work. Pr. Toso reports grants, personal fees, and non-financial support from Johnson&Johnson Inc., outside the submitted work. Dr. Douissard reports grants and non-financial support from Intuitive Surgical Inc., personal fees from Verb Surgical Inc., grants, personal fees, and non-financial support from Johnson&Johnson Inc., outside the submitted work.
PRISMA 2009 Checklist statement: This systematic review of the literature was performed following the PRISMA 2009 guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jonathan Douissard, MD, Surgeon, Abdominal Surgery Division, Geneva University Hospitals, Rue Gabrielle Perret Gentil 4, Geneva 1211, Switzerland. jonathan.douissard@hcuge.ch
Received: March 1, 2021
Peer-review started: March 1, 2021
First decision: June 23, 2021
Revised: July 6, 2021
Accepted: September 7, 2021
Article in press: September 7, 2021
Published online: November 15, 2021
Processing time: 255 Days and 16.8 Hours
Abstract
BACKGROUND

Gastrointestinal tumors are among the most common cancer types, and early detection is paramount to improve their management. Cell-free DNA (cfDNA) liquid biopsy raises significant hopes for non-invasive early detection.

AIM

To describe current applications of this technology for gastrointestinal cancer detection and screening.

METHODS

A systematic review of the literature was performed across the PubMed database. Articles reporting the use of cfDNA liquid biopsy in the screening or diagnosis of gastrointestinal cancers were included in the analysis.

RESULTS

A total of 263 articles were screened for eligibility, of which 13 articles were included. Studies investigated colorectal cancer (5 studies), pancreatic cancer (2 studies), hepatocellular carcinoma (3 studies), and multi-cancer detection (3 studies), including gastric, oesophageal, or bile duct cancer, representing a total of 4824 patients. Test sensitivities ranged from 71% to 100%, and specificities ranged from 67.4% to 100%. Pre-cancerous lesions detection was less performant with a sensitivity of 16.9% and a 100% specificity in one study. Another study using a large biobank demonstrated a 94.9% sensitivity in detecting cancer up to 4 years before clinical symptoms, with a 61% accuracy in tissue-of-origin identification.

CONCLUSION

cfDNA liquid biopsy seems capable of detecting gastrointestinal cancers at an early stage of development in a non-invasive and repeatable manner and screening simultaneously for multiple cancer types in a single blood sample. Further trials in clinically relevant settings are required to determine the exact place of this technology in gastrointestinal cancer screening and diagnosis strategies.

Keywords: Cell-free DNA; Tumor DNA; Liquid biopsy; Next-generation sequencing; Cancer genomics; Pancreatic cancer; Colorectal cancer; Hepatocellular carcinoma; Multi-cancer detection; Cancer screening; Public health; Precision oncology

Core Tip: Liquid biopsy cell-free DNA represents a promising non-invasive method for detecting various gastrointestinal cancers at an early stage of development. The current literature suggests a high-performance profile for this technology and the potential to improve the global course of gastrointestinal cancers currently diagnosed at an advanced stage, such as pancreatic cancer. Prospective validation studies in relevant clinical settings are required to determine the applicability and added value of these new diagnostic and screening tests in global cancer care.