{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:13:26Z","timestamp":1787958806058,"version":"build-2784847793"},"reference-count":121,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Liquid biopsy using circulating tumor DNA (ctDNA) is rapidly reshaping gastrointestinal (GI) oncology. The highest-impact applications are molecular residual disease (mRD) detection after curative-intent therapy and early recognition of progression or resistance during systemic treatment. Methods: We performed a structured, clinically oriented narrative synthesis by using explicit search, eligibility, evidence prioritization, and clinical interpretation rules, integrating landmark prospective cohorts, randomized ctDNA-guided strategy trials where available, meta-analyses, key methodological research (e.g., pre-analytics, assay design, and clonal hematopoiesis (CH)\/clonal hematopoiesis of indeterminate potential (CHIP)), and selected trial registries. Results: In resected colorectal cancer (CRC), postoperative ctDNA positivity is among the strongest known biomarkers of recurrence risk; large prospective studies demonstrate clear separation of disease-free survival (DFS)\/overall survival (OS) between mRD+ and mRD\u2212 patients. In stage II colon cancer, randomized data (DYNAMIC) show that a ctDNA-guided strategy reduces adjuvant chemotherapy exposure without compromising long-term outcomes. In metastatic CRC, ctDNA supports early response monitoring and resistance tracking; ctDNA-selected anti-EGFR rechallenge provides a model of biomarker-driven actionability (CHRONOS). In gastroesophageal cancers, longitudinal ctDNA dynamics correlate with relapse risk and treatment efficacy, and in esophageal squamous cell carcinoma, ctDNA after neoadjuvant chemoradiotherapy informs residual disease risk and adjuvant stratification. In pancreatic ductal adenocarcinoma and hepatobiliary malignancies, sensitivity is constrained by low shedding and background cell-free DNA (cfDNA), yet ctDNA positivity remains clinically meaningful, and emerging data in resected extrahepatic cholangiocarcinoma (STAMP-linked analyses) show that ctDNA dynamics during adjuvant therapy predict recurrence. Conclusions: ctDNA is a clinically validated biomarker for mRD in CRC, whereas in other GI cancers, it remains a promising but methodologically heterogeneous tool whose clinical utility is tumor- and context-dependent. The next phase requires interventional trials demonstrating outcome improvement, harmonized sampling and reporting standards, and rigorous control of confounders (notably CH\/CHIP).<\/jats:p>","DOI":"10.3390\/cancers18061014","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:02:43Z","timestamp":1774026163000},"page":"1014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Liquid Biopsy in Gastrointestinal Cancers: Circulating Tumor DNA for Molecular Residual Disease Assessment and Early Treatment Monitoring"],"prefix":"10.3390","volume":"18","author":[{"given":"Kamil","family":"Safiejko","sequence":"first","affiliation":[{"name":"Colorectal Cancer Unit, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Juchimiuk","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Pierko","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0516-3231","authenticated-orcid":false,"given":"Maciej","family":"Maslyk","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Mucha","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Koda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland"},{"name":"Department of General Pathomorphology, Medical University of Bialystok, 15-269 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza","family":"Konczuga-Koda","sequence":"additional","affiliation":[{"name":"Department of Pathology, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4066-7566","authenticated-orcid":false,"given":"Sebastian","family":"Radej","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adem","family":"Akcakaya","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, 34093 \u0130stanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-5455","authenticated-orcid":false,"given":"Lukasz","family":"Szarpak","sequence":"additional","affiliation":[{"name":"Colorectal Cancer Unit, Maria Sklodowska-Curie Bialystok Oncology Center, 15-027 Bialystok, Poland"},{"name":"Institute of Medical Science, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland"},{"name":"Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1001\/jamaoncol.2023.5098","article-title":"Incidence of Recurrence and Time to Recurrence in Stage I to III Colorectal Cancer: A Nationwide Danish Cohort Study","volume":"10","author":"Nors","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1007\/s00384-021-03914-w","article-title":"Disease recurrence after colorectal cancer surgery in the modern era: A population-based study","volume":"36","author":"Qaderi","year":"2021","journal-title":"Int. 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