Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer
- Carolyn Hruban
- Daniel C. Bruhm
- Inna M. Chen
- Shashikant Koul
- Akshaya V. Annapragada
- Nicholas A. Vulpescu
- Sarah Short
- Susann Theile
- Kavya Boyapati
- Bahar Alipanahi
- Zachary L. Skidmore
- Alessandro Leal
- Stephen Cristiano
- Vilmos Adleff
- Julia S. Johannsen
- Robert B. Scharpf
- Zachariah H. Foda
- Jillian Phallen
- Victor E. Velculescu
2025-05-21
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.