Abstract 5593: The fragment size and levels of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer

Abstract

Purpose: To investigate the prognostic value of cell-free DNA (cfDNA) fragment size and cfDNA levels in patients with advanced pancreatic cancer. Methods: Blood samples were acquired from patients with locally advanced or metastatic pancreatic cancer at baseline (n = 61) and one month (n = 48) after initiation of chemotherapy. All samples were processed by Lymphoprep™ (Axis Shield) density centrifugation followed by DNA isolation from the plasma fraction using the QIAamp Circulating Nucleic Acid kit (Qiagen). The cfDNA fragment size and cfDNA levels were then determined using the High Sensitivity DNA kit on an Agilent 2100 Bioanalyzer. A cohort of healthy age-matched volunteers (n = 28) constituted the control group. Results: Both the cfDNA fragment size (median 167 vs 176.5 bp; p < 0.001) and the cfDNA levels (median 4.48 vs 0.33 ng/mL plasma; p < 0.001) were significantly different between patient and healthy control samples. A pre-treatment cfDNA fragment size of ≤167 bp (median) was associated with both shorter progression-free survival (PFS) (4 vs. 7.7 months; log-rank p = 0.002) and overall survival (OS) (4.6 vs. 10.5 months; log-rank p = 0.001). Similarly, cfDNA levels above the median value were associated with both shorter PFS (3.3 vs. 7.7 months; log-rank p < 0.001) and OS (5.4 vs. 8.8 months; log-rank p = 0.001) for samples obtained before initiation of chemotherapy. Survival analysis on the combination of fragment size and cfDNA levels showed a significantly longer PFS (8.1 vs 4.6 vs 2.6 months; log-rank p < 0.001) and OS (10.6 vs 7.9 vs 3.8 months; log-rank p = 0.001) for patients negative for both parameters compared to patients with 1 or 2 positive parameters, respectively. Analyses of plasma samples obtained one month after initiation of chemotherapy indicated a trend towards an association with PFS (p = 0.066 and p = 0.025), but not OS (p = 0.504 and p = 0.213) for cfDNA fragment size and cfDNA levels, respectively. Univariate cox regression using both the continuous and the categorical variable for cfDNA fragment size and cfDNA levels, and the categorical variable for the combination test, confirmed the results from the Kaplan-Meier estimates. Conclusion: Determination of cfDNA fragment size and cfDNA levels is a non-invasive and simple method for predicting prognosis in patients with advanced pancreatic cancer. Further investigations in larger patient cohorts are needed to elaborate the consistency and clinical impact of this finding. Citation Format: Morten Lapin, Satu Oltedal, Kjersti Tjensvoll, Tove Buhl, Rune Smaaland, Nils Glenjen, Bjørnar Gilje, Oddmund Nordgård. The fragment size and levels of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5593.