Circulating tumor DNA informs clinical practice in patients with recurrent/metastatic gastroesophageal cancers

Q: What is the clinical purpose of using circulating tumor DNA (ctDNA) in recurrent/metastatic gastroesophageal cancers?

ctDNA is used to assess treatment response and molecular residual disease, and to infer progression risk based on ctDNA dynamics over time.

Q: How was ctDNA testing performed in the study?

Patients underwent commercial ctDNA testing with a personalized, tumor-informed assay (Signatera; Natera, Inc.).

Q: What ctDNA patterns during treatment were most associated with outcomes?

Patients who remained ctDNA-negative throughout treatment showed treatment benefit, while those who converted to ctDNA positivity progressed; ctDNA clearance was linked to favorable outcomes.

Sep 22, 2026

Upload by Theodore

Circulating tumor DNA (ctDNA) is evaluated as a biomarker for treatment response and molecular residual disease in recurrent or metastatic gastroesophageal cancers. A multi-institutional retrospective analysis assessed ctDNA using a personalized, tumor-informed assay (Signatera) in 200 patients, correlating longitudinal ctDNA dynamics with clinical and radiographic findings. Results show that sustained ctDNA negativity during treatment predicts benefit, while conversion to ctDNA positivity signals progression; ctDNA clearance relates to favorable outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Introduction

DOI: 10. 1002/cncr.70242 ORIGINAL ARTICLE Circulating tumor DNA informs clinical practice in patients with recurrent/metastatic gastroesophageal cancers Rutika Mehta MD, MPH1 | Samuel Rivero-Hinojosa PhD2 | Farshid Dayyani MD, PhD3 | Jenifer Ferguson PhD2 | Bushra Shariff DO4 | Vasily N. Aushev PhD2 | Griffin L. Budde PharmD2 | J. Bryce Ortiz PhD2 | Giby V. George MD2 | Shruti Sharma PhD2 | Adham A. Jurdi MD2 | Minetta C. Liu MD2 | Ronald L. Drengler MD5 | Samuel J. Klempner MD6 1Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine/New York Presbyterian Hospital, New York, New York, USA 2Natera, Inc., Austin, Texas, USA 3Chao Family Comprehensive Cancer Center, University of California Irvine Health, Orange, California, USA 4Department of Internal Medicine, H. Lee Moffitt Cancer Center, Tampa, Florida, USA 5Medical Oncology, The START Center for Cancer Care, San Antonio, Texas, USA 6Massachusetts General Hospital, Boston, Massachusetts, USA Correspondence Rutika Mehta, Division of Hematology/ Oncology, Department of Medicine, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY 10021, USA. Email: [rum9028@med.cornell.edu](rum9028@med.cornell.edu) Funding information Natera Inc. Abstract Background: Circulating tumor DNA (ctDNA) is a valuable biomarker for assessing treatment response and molecular residual disease. In advanced esophageal and gastric cancer (gastroesophageal cancer [EGC]), ctDNA dynamics remain poorly understood. The authors investigated ctDNA in patients with advanced EGC to evaluate its clinical utility. Methods: This was a multi-institutional, retrospective analysis of 200 patients with recurrent/metastatic EGCs who underwent commercial ctDNA testing using a personalized, tumor-informed assay (Signatera; Natera, Inc.). Patients were divided into cohort A (N = 36; stage I–III with recurrence) or cohort B (N = 164; metastatic at diagnosis). Longitudinal ctDNA dynamics were correlated with clinical and radiographic findings. Results: In cohort A, 31 of 36 patients (86. 1%) had ctDNA collected ≤90 days before recurrence; of these, 25 of 31 patients (80.65%) were ctDNA-positive before recurrence. In cohort B, baseline ctDNA was available for 29 of 164 patients (17.68%), and all 29 were ctDNA-positive. Among 52 patients who had ontreatment ctDNA assessments, 62 treatment lines were analyzed (N = 6 in cohort A; N = 46 in cohort B). All who remained ctDNA-negative throughout treatment (Neg-Neg) showed treatment benefit (n = 6 of 6). Those who converted to ctDNApositive (Neg-Pos) progressed (n = 2 of 2). Among ctDNA-positive patients (PosPos), 27 of 40 (67.5%) showed treatment benefit, whereas 13 of 40 (32.5%) progressed. Patients who cleared ctDNA (Pos-Neg) had favorable outcomes (12 of 14 patients; 85. 7%). A decrease >90% in ctDNA levels among Pos-Pos patients was linked to superior progression-fee survival. Grouping treatment lines into favorable (Neg-Neg, Pos-Neg, and Pos-Pos with >90% decrease) versus unfavorable (Neg-Pos This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2026 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. Cancer. 2026;e70242. [https://doi.org/10.1002/cncr.70242](https://doi.org/10.1002/cncr.70242) wi[leyonlinelibrary.com/journal/cncr](leyonlinelibrary.com/journal/cncr) 1 of 9 and Pos-Pos with a <90% decrease or an increase) had significantly improved progression-free survival in the favorable group (p < .0001). Conclusions: ctDNA dynamics predicted progression and may guide treatment or imaging. ctDNA offers a minimally invasive, cost-effective adjunct to radiographic surveillance. KEYWORDS circulating tumor DNA (ctDNA), ctDNA dynamics, metastatic

FAQs

What is the clinical purpose of using circulating tumor DNA (ctDNA) in recurrent/metastatic gastroesophageal cancers?

ctDNA is used to assess treatment response and molecular residual disease, and to infer progression risk based on ctDNA dynamics over time.

How was ctDNA testing performed in the study?

Patients underwent commercial ctDNA testing with a personalized, tumor-informed assay (Signatera; Natera, Inc.).

What ctDNA patterns during treatment were most associated with outcomes?

Patients who remained ctDNA-negative throughout treatment showed treatment benefit, while those who converted to ctDNA positivity progressed; ctDNA clearance was linked to favorable outcomes.

Sep 22, 2026

Upload by Theodore