Circulating Tumor DNA (ctDNA) in Gastroesophageal Adenocarcinoma (GEA): Evidence and Emerging Applications

TL;DR

This paper reviews how circulating tumor DNA (ctDNA) can be used non-invasively to monitor and guide treatment in gastroesophageal cancer patients.

Contribution

The paper provides a comprehensive review of ctDNA's emerging clinical applications in gastroesophageal adenocarcinoma, including recurrence prediction and resistance detection.

Findings

Postoperative ctDNA can detect high recurrence risk in gastroesophageal cancer months before imaging.

ctDNA can reveal actionable biomarkers like ERBB2 and FGFR2 in metastatic gastroesophageal cancer.

ctDNA levels correlate with prognosis and treatment response in advanced gastroesophageal adenocarcinoma.

Abstract

Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive biomarker that can be detected in the blood of patients with gastroesophageal adenocarcinoma (GEA). Measuring ctDNA levels can help identify patients at high risk of recurrence after surgery, evaluate treatment response, and detect molecular changes that signal resistance to therapy. ctDNA can also uncover actionable biomarkers such as ERBB2 or MSI-H and reveal resistance mechanisms. In this review, we summarize recent studies on the clinical applications of ctDNA in resectable and advanced GEA.

The role of circulating tumor DNA (ctDNA) in gastroesophageal adenocarcinoma (GEA) has expanded in recent years. In resectable disease, postoperative ctDNA is able to detect patients at highest risk of recurrence months before scans. Tumor-informed assays provide the best sensitivity and emerging methylation assays are useful when tissue is scarce. In metastatic GEA, baseline ctDNA burden correlates with prognosis, and a decrease in ctDNA level after treatment initiation reflects therapeutic response. It can also uncover actionable targets, including ERBB2, FGFR2, and MSI-H, and detect resistance that can arise after starting treatment. Limitations include variable assay performance, low shedding in some tumors, clonal hematopoiesis confounding, and a lack of randomized data showing that ctDNA-guided changes improve outcomes. Ongoing trials are testing MRD-guided escalation/de-escalation and ctDNA-directed biomarker therapy. In this review, we evaluate the role of ctDNA in GEA cancers over recent years.

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