Serial circulating tumor DNA as a biomarker for monitoring and prognostication in patients with pancreatic cancer

doi:10.3748/wjg.v32.i22.118323

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Observational Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jun 14, 2026; 32(22): 118323
Published online Jun 14, 2026. doi: 10.3748/wjg.v32.i22.118323

Serial circulating tumor DNA as a biomarker for monitoring and prognostication in patients with pancreatic cancer

Kwangrok Jung, Jongchan Lee, Dayeon Jang, Jinwoo Ahn, Bomi Kim, Soomin Yang, Jae Hyeong Kim, Yuna Youn, Jong-Chan Lee, Jaihwan Kim, Jin-Hyeok Hwang

Kwangrok Jung, Jongchan Lee, Dayeon Jang, Jinwoo Ahn, Bomi Kim, Soomin Yang, Jae Hyeong Kim, Yuna Youn, Jong-Chan Lee, Jaihwan Kim, Jin-Hyeok Hwang, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13620, Gyeonggi-do, South Korea

Co-first authors: Kwangrok Jung and Jongchan Lee.

Author contributions: Jung K and Lee J contributed equally to this work as co-first authors. Jung K and Lee J conceived and designed the study, conducted the investigation and developed the methodology, curated the data and prepared the visualizations; Jung K, Lee J, Jang D, and Ahn J performed the formal analysis; Jung K, Lee J, and Jang D drafted the original manuscript; Ahn J, Kim B, Yang S, Kim JH, and Youn Y participated in data curation and validation; Lee JC and Kim J provided resources; Hwang JH conceptualized and supervised the study, acquired funding, administered the project, and critically reviewed and revised the manuscript; All authors read and approved the final manuscript.

Supported by National Research Foundation of Korea, No. RS-2021-NR059201; and the Seoul National University Bundang Hospital Research Fund, No. 06-2019-0069.

Institutional review board statement: The study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (No. B-1901-517-003) and conducted in accordance with the Declaration of Helsinki.

Informed consent statement: All study participants, or their legal guardians, provided written consent prior to study enrollment.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: To obtain the supporting data from this research, interested parties can submit a reasonable request to the corresponding author (woltoong@snu.ac.kr) for consideration. All requests will be reviewed, and the data will be shared for non-commercial, academic research purposes only, with all patients anonymized to protect patient confidentiality.

Corresponding author: Jin-Hyeok Hwang, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si 13620, Gyeonggi-do, South Korea. woltoong@snu.ac.kr

Received: December 30, 2025
Revised: January 30, 2026
Accepted: March 18, 2026
Published online: June 14, 2026
Processing time: 151 Days and 1.8 Hours

Abstract

BACKGROUND

Despite emerging evidence supporting circulating tumor DNA (ctDNA) as a potential biomarker for pancreatic ductal adenocarcinoma (PDAC), its clinical efficacy for serial monitoring has not been thoroughly explored. We hypothesized that serial monitoring of ctDNA provides clinically relevant information on treatment response and prognosis in patients with PDAC.

AIM

To investigate the feasibility of using longitudinal ctDNA monitoring to predict treatment response and prognostic outcomes in patients with PDAC.

METHODS

This prospective observational study enrolled patients with PDAC confirmed histologically by biopsy. Blood samples were collected at baseline and during follow-up for ctDNA analysis using droplet digital polymerase chain reaction targeting KRAS G12/G13 mutations. Patients with PDAC were divided into resection and chemotherapy groups for further analysis. Radiologic responses were compared with changes in ctDNA (ΔctDNA) and carbohydrate antigen 19-9. Survival outcomes were analyzed based on the baseline ctDNA levels and clearance status.

RESULTS

Of the 200 enrolled patients, 168 were eligible for ctDNA detection rate analysis using the droplet digital polymerase chain reaction and 139 underwent serial ctDNA monitoring (34 resection group, 105 chemotherapy group). The overall ctDNA detection rate was 80.4%. Higher rates were observed in advanced disease stages (P = 0.004) and liver metastasis (P = 0.031). In the resection group, ΔctDNA did not differ significantly between the recurrence and non-recurrence groups. However, in the chemotherapy group, ΔctDNA showed significant differences among response groups (P < 0.001), demonstrating a moderate discriminative ability (area under the curve = 0.630), which was comparable to that of carbohydrate antigen 19-9 (area under the curve = 0.642). Preoperative and postoperative ctDNA detection was not associated with recurrence-free survival or overall survival (OS). However, among patients with metastatic disease, higher baseline ctDNA levels (> 0.418) were associated with shorter progression-free survival (4.7 months vs 7.5 months, P = 0.024) and OS (9.7 months vs 15.9 months, P = 0.039). In addition, ctDNA clearance at 8 weeks after chemotherapy was associated with improved OS (18.8 months vs 11.4 months, P = 0.031).

CONCLUSION

Serial ctDNA monitoring is a promising biomarker for treatment response and prognosis of PDAC, particularly in advanced disease.

Keywords: Circulating tumor DNA; Pancreatic ductal adenocarcinoma; Liquid biopsy; Serial monitoring; Treatment response; Prognosis

Core Tip: This study highlights the emerging role of circulating tumor DNA (ctDNA) as a clinically relevant biomarker in pancreatic ductal adenocarcinoma. ctDNA offers a minimally invasive approach for serial disease monitoring and may provide complementary information to conventional imaging and tumor markers for treatment assessment and prognostication. In the setting of limited effective biomarkers for this malignancy, ctDNA represents a promising tool for improving clinical management.