Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer - read online free

Q: How did the study assess therapeutic response in pancreatic cancer patients?

It used plasma cfDNA approaches in the CheckPAC trial, including tumor-informed WGMAF and tumor-independent ARTEMIS-DELFI fragmentation and repeat landscape profiling before and after therapy initiation.

Q: What outcome difference was observed with WGMAF for responders versus nonresponders?

WGMAF molecular responders had a longer median overall survival than nonresponders, with a reported hazard ratio and significance level indicating a measurable separation in outcomes.

Q: How was ARTEMIS-DELFI validated and what did it indicate after therapy start?

ARTEMIS-DELFI was validated in the PACTO trial, showing that patients with low scores after initiation had longer median overall survival than those with high scores.

Sep 23, 2026

Uploaded by Aria Callaghan

Evaluated cfDNA-based methods to assess therapeutic response in metastatic pancreatic cancer patients within the CheckPAC trial, using tumor-informed plasma whole-genome sequencing (WGMAF) and tumor-independent genome-wide cfDNA fragmentation profiles and repeat landscapes (ARTEMIS-DELFI). WGMAF showed molecular responders had longer median overall survival than nonresponders, while ARTEMIS-DELFI linked lower post-initiation scores to improved outcomes. ARTEMIS-DELFI was validated in the PACTO trial, supporting noninvasive mutation- and fragmentation-driven response assessment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

Challenges in early response assessment for pancreatic cancer

Current monitoring tools and limitations

Liquid biopsy and cfDNA-based monitoring approaches

HEALTH AND MEDICINE Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer Carolyn Hruban1†, Daniel C. Bruhm1†, Inna M. Chen2†, Shashikant Koul1, AkshayaV. Annapragada1, Nicholas A. Vulpescu1, Sarah Short1, Susann Theile2, Kavya Boyapati1, Bahar Alipanahi3, Zachary L. Skidmore3, Alessandro Leal1, Stephen Cristiano1, Vilmos Adleff1, Julia S. Johannsen2,4,5, Robert B. Scharpf1, Zachariah H. Foda1,6*, Jillian Phallen1*, Victor E. Velculescu1,6* Determining response to therapy for patients with pancreatic cancer can be challenging. We evaluated methods for assessing therapeutic response using cell-free DNA (cfDNA) in plasma from patients with metastatic pancreatic cancer in the CheckPAC trial (NCT02866383). Patients were evaluated before and after initiation of therapy using tumor-informed plasma whole-genome sequencing (WGMAF) and tumor-independent genome-wide cfDNA fragmentation profiles and repeat landscapes (ARTEMIS-DELFI) . Using WGMAF, molecular responders had a median overall survival (OS) of 319 days compared to 126 days for nonresponders [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.11–0.79, P = 0.011]. For ARTEMIS-DELFI, patients with low scores after therapy initiation had longer median OS than patients with high scores (233 versus 172 days, HR = 0.12, 95% CI = 0.046–0.31, P < 0.0001). We validated ARTEMIS-DELFI in patients with pancreatic cancer in the PACTO trial (NCT02767557). These analyses suggest that noninvasive mutation and fragmentation-based cfDNA approaches can identify therapeutic response of individuals with pancreatic cancer. copyright © 2025 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S. Government Works. distributed under a creative commons Attribution license 4.0 (cc BY) . INTRODUCTION In 2020, more than 450,000 people are estimated to have died from pancreatic cancer worldwide (1). Most pancreatic cancers are ductaladenocarcinomas (PDAC), and patients with PDAC have an extremely poor prognosis, especially when their disease is diagnosed at an advanced stage (2), with a grim 12% survival rate (3) . For patients with metastatic or locally advanced nonresectable PDAC, the standard-of-care treatment is either chemotherapy or symptomatic management (4) . Recent studies, however, suggest that some patients with advanced-stage disease respond to targeted therapies based on somatic mutations in their cancers or to immune checkpoint blockade treatment (5–9) . Unfortunately, determining response early during therapy using currently available imaging techniques is imperfect, especially in small, isoattenuating lesions (10) . Continuing ineffective therapy can be detrimental as tumors can double in size within 5 months in the absence of therapeutic response (11–13). Consequently, there is a need to develop noninvasive approaches that can provide a real-time and accurate assessment of response to therapy for patients with PDAC. Current tools for monitoring PDAC include radiographic Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessment using computed tomography (CT) and evaluation of serum CA19-9 (14) . However, each of these methods has shortcomings. CT scans can be misleading in patients treated with immunotherapy 1the Sidney Kimmel comprehensive cancer center, Johns Hopkins University School of Medicine, Baltimore, Md, USA. 2department of Oncology, copenhagen University Hospital–Herlev and Gentofte, Herlev, denmark. 3delfi diagnostics inc., Baltimore, Md, USA. 4department of Medicine, copenhagen University Hospital– Herlev and Gentofte, Herlev, denmark. 5department of clinical Medicine, Faculty of Health and Medical Sciences, University of copenhagen, copenhagen, denmark. 6department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, USA. *corresponding [author. email:](author. email:) [foda@jhmi.edu](foda@jhmi

FAQs

How did the study assess therapeutic response in pancreatic cancer patients?

It used plasma cfDNA approaches in the CheckPAC trial, including tumor-informed WGMAF and tumor-independent ARTEMIS-DELFI fragmentation and repeat landscape profiling before and after therapy initiation.

What outcome difference was observed with WGMAF for responders versus nonresponders?

WGMAF molecular responders had a longer median overall survival than nonresponders, with a reported hazard ratio and significance level indicating a measurable separation in outcomes.

How was ARTEMIS-DELFI validated and what did it indicate after therapy start?

ARTEMIS-DELFI was validated in the PACTO trial, showing that patients with low scores after initiation had longer median overall survival than those with high scores.

Sep 23, 2026

Uploaded by Aria Callaghan