Hruban Carolyn, Bruhm Daniel C, Chen Inna M, Koul Shashikant, Annapragada Akshaya V, Vulpescu Nicholas A, Short Sarah, Theile Susann, Boyapati Kavya, Alipanahi Bahar, Skidmore Zachary L, Leal Alessandro, Cristiano Stephen, Adleff Vilmos, Johannsen Julia S, Scharpf Robert B, Foda Zachariah H, Phallen Jillian, Velculescu Victor E
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Oncology, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
Sci Adv. 2025 May 23;11(21):eads5002. doi: 10.1126/sciadv.ads5002. Epub 2025 May 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, = 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, < 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.
确定胰腺癌患者的治疗反应可能具有挑战性。在CheckPAC试验（NCT02866383）中，我们评估了使用转移性胰腺癌患者血浆中的游离DNA（cfDNA）来评估治疗反应的方法。在治疗开始前后，使用肿瘤知情的血浆全基因组测序（WGMAF）以及与肿瘤无关的全基因组cfDNA片段化图谱和重复序列景观（ARTEMIS-DELFI）对患者进行评估。使用WGMAF，分子反应者的中位总生存期（OS）为319天，而无反应者为126天[风险比（HR）=0.29，95%置信区间（CI）=0.11-0.79，P=0.011]。对于ARTEMIS-DELFI，治疗开始后得分低的患者的中位OS比得分高的患者更长（233天对172天，HR=0.12，95%CI=0.046-0.31，P<0.0001）。我们在PACTO试验（NCT02767557）中的胰腺癌患者中验证了ARTEMIS-DELFI。这些分析表明，基于cfDNA的非侵入性突变和片段化方法可以识别胰腺癌个体的治疗反应。
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