Abstract 2291: Dynamics of genomic instability of circulating tumor DNA in pancreatic cancer patients

Abstract

Abstract Background: Genomic instability of circulating tumor DNA (ctDNA) has been evaluated as a prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). However, we did not investigated the association of dynamics between baseline and follow-up genomic instability level and patients outcome. Methods: CtDNA I-score which low-depth whole-genome wide copy number alterations calculated by Z-score comparing the relative frequency for each bin with healthy control were investigated in total 87 PDAC patients (N=32 in resectable stage and N=55 in metastatic stage). Follow-up period for resectable and metastatic patients was different after one month, and 2 and 4 months, respectively. Then the association between I-score dynamics at follow-up and survivals (progression free survival (PFS) and overall survival (OS)) were analyzed. Results: The mean I-score represented as 7.212 (6.887 ± 0.073 in 32 resectable patients and 7.536 ± 0.123 in 55 metastatic patients, p < 0.01) at baseline. In recetable patients, I-score decreased upto 6.710±0.03 (p=0.03) after 1 month and dynamics (decrease or increase) of I-score did not showed significant association with PFS and OS with hazard ratio (HR) of 3.6 (range 0.16-79.2 95% Cl) and 3.9 (range 0.3-50.7), respectively. I-score of metastatic patients at 2 and 4 moths were decresed to 7.180±0.062 (p= 0.01) and 7.029±0.056 (p < 0.01). The change of I-score represented association with PFS and OS as HR 2.8 (range 0.9-8.5) and 0.5 (range 0.11-2.20) at 2 months and 1.1 (range 0.2-5.5) and 3.3 (range 0.07-142.7) at 4 months, respectively. Conclusion: Overall I-score decreased after treatment in both resectable and metastatic patients. To investigate impact for outcome of dynamics of genomic instability in ctDNA, we will continue to analyze follow-up data for long term results. Citation Format: SooBeen Heo, Jung Won Chun, Eun-Hae Cho, Tae-Rim Lee, Chang-Seok Ki, Yun-Hee Kim, Sang Myung Woo, Sun-Young Kong. Dynamics of genomic instability of circulating tumor DNA in pancreatic cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2291.