Cancer Res Treat.  2023 Oct;55(4):1313-1320. 10.4143/crt.2023.452.

Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection

  • 1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 2Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 3Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 4Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea


There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods
Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.


Circulating-tumor DNA; Borderline resectable pancreatic cancer; Neoadjuvant; mFOLFIRINOX; DNA damage repair; Platinum sensitivity


  • Fig. 1 Study outline. BRPC, borderline resectable pancreatic cancer.

  • Fig. 2 Genomic landscape of alterations detected with baseline plasma cell-free DNA sequencing analysis. OS, overall survival; PFS, progression-free survival.

  • Fig. 3 Kaplan-Meier estimates of survival outcomes according to baseline genomic alterations detected from plasma circulating tumor DNA. Progression-free survival (A) and overall survival (B) according to DNA damage repair (DDR) gene alteration detection. Progression-free survival (C) and overall survival (D) according to KRAS alteration detection. Progression-free survival (E) and overall survival (F) according to TP53 alteration detection.



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