Abstract PR008: Genome-wide analyses of cfDNA fragmentomes for therapeutic monitoring of patients with pancreatic cancer

• Published in: Clinical cancer research 2024-11, Vol.30 (21_Supplement), p.PR008-PR008
• Main Authors: Hruban, Carolyn A, Bruhm, Daniel C., Chen, Inna M, Koul, Shashikant, Annapragada, Akshaya V, Vulpescu, Nicholas A, Short, Sarah, Theile, Susann, Boyapati, Kavya, Cristiano, Stephen, Adleff, Vilmos, Johannsen, Julia S, Scharpf, Robert B, Foda, Zachariah H, Phallen, Jillian A, Velculescu, Victor E
• Format: Article
• Language: English
• ISSN: 1557-3265; 1557-3265
• DOI: 10.1158/1557-3265.LIQBIOP24-PR008

Determining response to therapy for patients with pancreatic cancer can be challenging using imaging alone, and there is an unmet need for noninvasive assessment of tumor burden. We developed a method for assessing response to therapy using circulating cell-free DNA (cfDNA) and tested it using 217 plasma samples from 40 patients with metastatic pancreatic cancer treated with immune checkpoint inhibition and radiation as part of the CheckPAC trial (NCT02866383). Samples were evaluated before and after initiation of therapy using a mutation-independent and tumor-independent approach (ARTEMIS-DELFI), combining genome-wide cfDNA fragmentation profiles and repeat landscapes. Patients with below median scores (n=16) at the time of the first follow up CT scan at 8 weeks had a longer median progression free survival (PFS) and longer median overall survival (OS) than patients with above median scores (n=17) (PFS: 153 days versus 50 days; HR=0.26, 95% CI=0.11-0.64, p=0.0013) (OS: 375 days versus 121 days; HR=0.12, 95% CI=0.045-0.30, p