Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Reliable on-treatment prognostication and target identification with a customized assay for circulating tumor DNA in patients with newly diagnosed pancreatic cancer

Petersson, Alexandra ; Svensson, Maja LU ; Hau, Sofie Olsson LU ; Bergström, Rebecka ; Lindberg, Johan ; Mayrhofer, Markus ; Chattopadhyay, Subhayan LU orcid ; Eberhard, Jakob LU ; Heidenblad, Markus LU orcid and Leandersson, Karin LU orcid , et al. (2025) In Scientific Reports 15(1).
Abstract

The vast majority of patients with pancreatic cancer present with unresectable disease and precision medicine is lagging behind. Circulating tumor DNA (ctDNA) has emerged as a promising tool, both as a proxy for tumor burden and for capturing tumor heterogeneity, but optimal gene panels and prognostic cutoffs remain to be determined. Herein, we applied ultra-deep ctDNA sequencing using a customized panel targeting 23 genes and six frequently altered chromosomes on plasma samples obtained before, during and after chemotherapy from 60 patients enrolled in a prospective clinical study. At baseline, positive versus negative ctDNA was not prognostic, neither in the adjuvant nor in the palliative setting, but in palliative patients, an... (More)

The vast majority of patients with pancreatic cancer present with unresectable disease and precision medicine is lagging behind. Circulating tumor DNA (ctDNA) has emerged as a promising tool, both as a proxy for tumor burden and for capturing tumor heterogeneity, but optimal gene panels and prognostic cutoffs remain to be determined. Herein, we applied ultra-deep ctDNA sequencing using a customized panel targeting 23 genes and six frequently altered chromosomes on plasma samples obtained before, during and after chemotherapy from 60 patients enrolled in a prospective clinical study. At baseline, positive versus negative ctDNA was not prognostic, neither in the adjuvant nor in the palliative setting, but in palliative patients, an independent prognostic cutoff could be calculated from the absolute number of mutated DNA molecules. Median overall survival was 3.7 months in the ctDNAhigh compared to 11.9 months in the ctDNAlow group (p < 0.0001), and the cutoff remained prognostic at one and three months. Moreover, relevant genetic alterations were highly concordant in ctDNA and paired tumor tissue. These findings demonstrate the potential clinical utility of a customized and focused gene panel for prognostication and target identification over time in patients with newly diagnosed pancreatic cancer, in particular in the palliative setting.ClinicalTrials.gov number: NCT03724994.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Pancreatic Neoplasms/genetics, Circulating Tumor DNA/blood, Male, Female, Prognosis, Aged, Middle Aged, Biomarkers, Tumor/genetics, Prospective Studies, High-Throughput Nucleotide Sequencing, Aged, 80 and over, Adult, Mutation
in
Scientific Reports
volume
15
issue
1
article number
34481
publisher
Nature Publishing Group
external identifiers
  • pmid:41044171
ISSN
2045-2322
DOI
10.1038/s41598-025-22369-5
project
Chemotherapy, Host response And Molecular dynamics in Periampullary cancer
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
0aa3819f-afa4-4169-8582-db4df009900c
date added to LUP
2025-10-04 08:50:18
date last changed
2025-10-07 03:15:37
@article{0aa3819f-afa4-4169-8582-db4df009900c,
  abstract     = {{<p>The vast majority of patients with pancreatic cancer present with unresectable disease and precision medicine is lagging behind. Circulating tumor DNA (ctDNA) has emerged as a promising tool, both as a proxy for tumor burden and for capturing tumor heterogeneity, but optimal gene panels and prognostic cutoffs remain to be determined. Herein, we applied ultra-deep ctDNA sequencing using a customized panel targeting 23 genes and six frequently altered chromosomes on plasma samples obtained before, during and after chemotherapy from 60 patients enrolled in a prospective clinical study. At baseline, positive versus negative ctDNA was not prognostic, neither in the adjuvant nor in the palliative setting, but in palliative patients, an independent prognostic cutoff could be calculated from the absolute number of mutated DNA molecules. Median overall survival was 3.7 months in the ctDNAhigh compared to 11.9 months in the ctDNAlow group (p &lt; 0.0001), and the cutoff remained prognostic at one and three months. Moreover, relevant genetic alterations were highly concordant in ctDNA and paired tumor tissue. These findings demonstrate the potential clinical utility of a customized and focused gene panel for prognostication and target identification over time in patients with newly diagnosed pancreatic cancer, in particular in the palliative setting.ClinicalTrials.gov number: NCT03724994.</p>}},
  author       = {{Petersson, Alexandra and Svensson, Maja and Hau, Sofie Olsson and Bergström, Rebecka and Lindberg, Johan and Mayrhofer, Markus and Chattopadhyay, Subhayan and Eberhard, Jakob and Heidenblad, Markus and Leandersson, Karin and Gisselsson, David and Jirström, Karin}},
  issn         = {{2045-2322}},
  keywords     = {{Humans; Pancreatic Neoplasms/genetics; Circulating Tumor DNA/blood; Male; Female; Prognosis; Aged; Middle Aged; Biomarkers, Tumor/genetics; Prospective Studies; High-Throughput Nucleotide Sequencing; Aged, 80 and over; Adult; Mutation}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Reliable on-treatment prognostication and target identification with a customized assay for circulating tumor DNA in patients with newly diagnosed pancreatic cancer}},
  url          = {{http://dx.doi.org/10.1038/s41598-025-22369-5}},
  doi          = {{10.1038/s41598-025-22369-5}},
  volume       = {{15}},
  year         = {{2025}},
}