# Circulating nucleic acids are associated with outcomes of patients with pancreatic cancer

Source: https://onco.cc/key-papers/paper-bernard-ctdna-exodna-pancreatic-gastroenterology-2019/  
OnCo record `paper-bernard-ctdna-exodna-pancreatic-gastroenterology-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Tracking tumour DNA both free in the blood and packaged in exosomes across 194 patients showed each carries prognostic information, and together they identified patients with a nearly eightfold risk of death.

## Summary

Liquid biopsies from 194 patients treated for localised or metastatic pancreatic adenocarcinoma (425 samples before and during therapy) and 37 disease controls were analysed by droplet digital PCR for KRAS mutant allele fraction in circulating tumour DNA and exosome DNA, with 123 serial samples from 34 patients. In 34 patients with potentially resectable tumours, a rise in exosome DNA after neoadjuvant therapy was associated with disease progression (P = .003), while ctDNA was not. Concordance of KRAS mutations between resected tissue and liquid biopsy exceeded 95%. In metastatic disease, detectable baseline ctDNA gave a progression-free survival hazard ratio of 1.8 and overall survival hazard ratio of 2.8; exosome DNA allele fraction of 5% or more predicted progression-free (2.28) and overall survival (3.46), and detecting both at 5% or more gave an overall survival hazard ratio of 7.73.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Gastroenterology
- Year: 2019
- DOI: 10.1053/j.gastro.2018.09.022
- Authors: Bernard V, Kim DU, San Lucas FA, et al.
- Findings: Plasma and tissue KRAS concordance above 95%.; Baseline ctDNA in metastatic disease: death hazard ratio 2.8.; Exosome DNA plus ctDNA at 5% or more: overall survival hazard ratio 7.73.
- What it means: Exosome DNA adds signal where free DNA is scarce, particularly after neoadjuvant treatment, and the two together give the strongest published blood-based prognosis in this disease.
- Caveats: KRAS-targeted droplet PCR only, so wild-type tumours are invisible.; Single-centre prospective cohort.

## Sources

- Bernard et al., Gastroenterology 2019: ctDNA and exosome DNA in 194 patients: https://doi.org/10.1053/j.gastro.2018.09.022
- PubMed: https://pubmed.ncbi.nlm.nih.gov/30240661/

## Connected records

- biomarkers: [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/)
- cancers: [Borderline resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/borderline-resectable-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [KRAS](https://onco.cc/targets/kras/)
- institutions: [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/)
- people: [Anirban Maitra](https://onco.cc/people/anirban-maitra/)
- journals: [Gastroenterology](https://onco.cc/journals/gastroenterology/)

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