Clinical relevance of next-generation sequencing in patients aged 60 years or younger with pancreatic cancer: A Nationwide prospective cohort study

Gaby J. Strijk; Jelle C. van Dongen; Willem de Koning; Lodewijk A. A. Brosens; Geert A. Cirkel; Michail Doukas; Arantza Farina Sarasqueta; Floris H. Groenendijk; Bas Groot Koerkamp; Ignace H. J. Th de Hingh; Marjolein Y. V. Homs; Sanne R. Martens-de Kemp; Judith de Vos-Geelen; Anja Wagner; Nigel G. Kooreman; Andrew P. Stubbs; Johanna W. Wilmink; Casper H. J. van Eijck

doi:10.1016/j.ejca.2025.116065

Clinical relevance of next-generation sequencing in patients aged 60 years or younger with pancreatic cancer: A Nationwide prospective cohort study

Gaby J. Strijk
, Jelle C. van Dongen
, Willem de Koning
, Lodewijk A. A. Brosens
, Geert A. Cirkel
, Michail Doukas
, Arantza Farina Sarasqueta
, Floris H. Groenendijk
, Bas Groot Koerkamp
, Ignace H. J. Th de Hingh
, Marjolein Y. V. Homs
, Sanne R. Martens-de Kemp
, Judith de Vos-Geelen
, Anja Wagner
, Nigel G. Kooreman
, Andrew P. Stubbs
, Johanna W. Wilmink
, Casper H. J. van Eijck^*

^*Corresponding author for this work

Erasmus University Rotterdam
Utrecht University
Radboud University Nijmegen
Meander Medical Center
University of Amsterdam
Amsterdam UMC
Catharina Hospital
Maastricht University

Research output: Contribution to journal › Article › Academic › peer-review

23 Downloads (Pure)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options and frequent resistance to standard treatments. This study evaluates the feasibility and clinical impact of comprehensive tumor molecular profiling in PDAC patients aged ≤ 60 years. Nationwide prospective cohort study across 13 Dutch hospitals from April 2021 to June 2024. PDAC patients aged ≤ 60 at any disease stage were included regardless of treatment status. DNA and RNA from tumor samples were isolated from representative, formalin-fixed paraffin-embedded (FFPE) slides for whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS). A multidisciplinary molecular tumor board reviewed results monthly. Among 318 patients, 88.7 % (282/318) had tumor samples suitable for sequencing. WES and WTS were completed in 175 patients (55.0 %), with WTS alone in 88 (27.7 %). Complete molecular analysis was more often successful in resection specimens than in biopsy samples (79 % vs 33 %; P < .001). Unknown germline mutations in cancer predisposition genes were identified in 4 % (13/318) of patients. Actionable alterations were detected in 13.2 % (42/318), rising to 22.3 % (39/175) among patients with WES and WTS. Actionable targets were found in 92.3 % (12/13) KRAS-wildtype tumors. Only 11 of 42 (26.2 %) patients received tailored therapies. Complete molecular profiling in PDAC patients ≤ 60 years showed moderate success (55 %) and limited clinical impact, with actionable findings in 13 % and therapy implementation in 3.5 %. Prioritizing KRAS testing and deeper sequencing in KRAS-wildtype tumors, alongside broader access to targeted therapies, may improve outcomes.

Original language	English
Article number	116065
Journal	Eur. J. Cancer
Volume	230
DOIs	https://doi.org/10.1016/j.ejca.2025.116065
Publication status	Published - 17 Nov 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Molecular profiling
Pancreatic neoplasms
Precision medicine
Young adult

Access to Document

10.1016/j.ejca.2025.116065

Clinical-relevance-of-next-generation-sequencing-in-patients-aged-60-years-or-younger-with-pancreatic-cancer.pdfFinal published version, 1.1 MBLicence: CC BY

Cite this

Strijk, G. J., van Dongen, J. C., de Koning, W., Brosens, L. A. A., Cirkel, G. A., Doukas, M., Sarasqueta, A. F., Groenendijk, F. H., Koerkamp, B. G., Th de Hingh, I. H. J., Homs, M. Y. V., Martens-de Kemp, S. R., de Vos-Geelen, J., Wagner, A., Kooreman, N. G., Stubbs, A. P., Wilmink, J. W., & Eijck, C. H. J. V. (2025). Clinical relevance of next-generation sequencing in patients aged 60 years or younger with pancreatic cancer: A Nationwide prospective cohort study. Eur. J. Cancer, 230, Article 116065. https://doi.org/10.1016/j.ejca.2025.116065

@article{229a2931e48d442b98a1dfc4a960f415,

title = "Clinical relevance of next-generation sequencing in patients aged 60 years or younger with pancreatic cancer: A Nationwide prospective cohort study",

abstract = "Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options and frequent resistance to standard treatments. This study evaluates the feasibility and clinical impact of comprehensive tumor molecular profiling in PDAC patients aged ≤ 60 years. Nationwide prospective cohort study across 13 Dutch hospitals from April 2021 to June 2024. PDAC patients aged ≤ 60 at any disease stage were included regardless of treatment status. DNA and RNA from tumor samples were isolated from representative, formalin-fixed paraffin-embedded (FFPE) slides for whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS). A multidisciplinary molecular tumor board reviewed results monthly. Among 318 patients, 88.7 \% (282/318) had tumor samples suitable for sequencing. WES and WTS were completed in 175 patients (55.0 \%), with WTS alone in 88 (27.7 \%). Complete molecular analysis was more often successful in resection specimens than in biopsy samples (79 \% vs 33 \%; P < .001). Unknown germline mutations in cancer predisposition genes were identified in 4 \% (13/318) of patients. Actionable alterations were detected in 13.2 \% (42/318), rising to 22.3 \% (39/175) among patients with WES and WTS. Actionable targets were found in 92.3 \% (12/13) KRAS-wildtype tumors. Only 11 of 42 (26.2 \%) patients received tailored therapies. Complete molecular profiling in PDAC patients ≤ 60 years showed moderate success (55 \%) and limited clinical impact, with actionable findings in 13 \% and therapy implementation in 3.5 \%. Prioritizing KRAS testing and deeper sequencing in KRAS-wildtype tumors, alongside broader access to targeted therapies, may improve outcomes.",

keywords = "Molecular profiling, Pancreatic neoplasms, Precision medicine, Young adult",

author = "Strijk, \{Gaby J.\} and \{van Dongen\}, \{Jelle C.\} and \{de Koning\}, Willem and Brosens, \{Lodewijk A. A.\} and Cirkel, \{Geert A.\} and Michail Doukas and Sarasqueta, \{Arantza Farina\} and Groenendijk, \{Floris H.\} and Koerkamp, \{Bas Groot\} and \{Th de Hingh\}, \{Ignace H. J.\} and Homs, \{Marjolein Y. V.\} and \{Martens-de Kemp\}, \{Sanne R.\} and \{de Vos-Geelen\}, Judith and Anja Wagner and Kooreman, \{Nigel G.\} and Stubbs, \{Andrew P.\} and Wilmink, \{Johanna W.\} and Eijck, \{Casper H. J. van\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors.",

year = "2025",

month = nov,

day = "17",

doi = "10.1016/j.ejca.2025.116065",

language = "English",

volume = "230",

journal = "Eur. J. Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd",

}

Strijk, GJ, van Dongen, JC, de Koning, W, Brosens, LAA, Cirkel, GA, Doukas, M, Sarasqueta, AF, Groenendijk, FH, Koerkamp, BG, Th de Hingh, IHJ, Homs, MYV, Martens-de Kemp, SR, de Vos-Geelen, J, Wagner, A, Kooreman, NG, Stubbs, AP, Wilmink, JW & Eijck, CHJV 2025, 'Clinical relevance of next-generation sequencing in patients aged 60 years or younger with pancreatic cancer: A Nationwide prospective cohort study', Eur. J. Cancer, vol. 230, 116065. https://doi.org/10.1016/j.ejca.2025.116065

TY - JOUR

T1 - Clinical relevance of next-generation sequencing in patients aged 60 years or younger with pancreatic cancer

T2 - A Nationwide prospective cohort study

AU - Strijk, Gaby J.

AU - van Dongen, Jelle C.

AU - de Koning, Willem

AU - Brosens, Lodewijk A. A.

AU - Cirkel, Geert A.

AU - Doukas, Michail

AU - Sarasqueta, Arantza Farina

AU - Groenendijk, Floris H.

AU - Koerkamp, Bas Groot

AU - Th de Hingh, Ignace H. J.

AU - Homs, Marjolein Y. V.

AU - Martens-de Kemp, Sanne R.

AU - de Vos-Geelen, Judith

AU - Wagner, Anja

AU - Kooreman, Nigel G.

AU - Stubbs, Andrew P.

AU - Wilmink, Johanna W.

AU - Eijck, Casper H. J. van

PY - 2025/11/17

Y1 - 2025/11/17

N2 - Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options and frequent resistance to standard treatments. This study evaluates the feasibility and clinical impact of comprehensive tumor molecular profiling in PDAC patients aged ≤ 60 years. Nationwide prospective cohort study across 13 Dutch hospitals from April 2021 to June 2024. PDAC patients aged ≤ 60 at any disease stage were included regardless of treatment status. DNA and RNA from tumor samples were isolated from representative, formalin-fixed paraffin-embedded (FFPE) slides for whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS). A multidisciplinary molecular tumor board reviewed results monthly. Among 318 patients, 88.7 % (282/318) had tumor samples suitable for sequencing. WES and WTS were completed in 175 patients (55.0 %), with WTS alone in 88 (27.7 %). Complete molecular analysis was more often successful in resection specimens than in biopsy samples (79 % vs 33 %; P < .001). Unknown germline mutations in cancer predisposition genes were identified in 4 % (13/318) of patients. Actionable alterations were detected in 13.2 % (42/318), rising to 22.3 % (39/175) among patients with WES and WTS. Actionable targets were found in 92.3 % (12/13) KRAS-wildtype tumors. Only 11 of 42 (26.2 %) patients received tailored therapies. Complete molecular profiling in PDAC patients ≤ 60 years showed moderate success (55 %) and limited clinical impact, with actionable findings in 13 % and therapy implementation in 3.5 %. Prioritizing KRAS testing and deeper sequencing in KRAS-wildtype tumors, alongside broader access to targeted therapies, may improve outcomes.

AB - Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options and frequent resistance to standard treatments. This study evaluates the feasibility and clinical impact of comprehensive tumor molecular profiling in PDAC patients aged ≤ 60 years. Nationwide prospective cohort study across 13 Dutch hospitals from April 2021 to June 2024. PDAC patients aged ≤ 60 at any disease stage were included regardless of treatment status. DNA and RNA from tumor samples were isolated from representative, formalin-fixed paraffin-embedded (FFPE) slides for whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS). A multidisciplinary molecular tumor board reviewed results monthly. Among 318 patients, 88.7 % (282/318) had tumor samples suitable for sequencing. WES and WTS were completed in 175 patients (55.0 %), with WTS alone in 88 (27.7 %). Complete molecular analysis was more often successful in resection specimens than in biopsy samples (79 % vs 33 %; P < .001). Unknown germline mutations in cancer predisposition genes were identified in 4 % (13/318) of patients. Actionable alterations were detected in 13.2 % (42/318), rising to 22.3 % (39/175) among patients with WES and WTS. Actionable targets were found in 92.3 % (12/13) KRAS-wildtype tumors. Only 11 of 42 (26.2 %) patients received tailored therapies. Complete molecular profiling in PDAC patients ≤ 60 years showed moderate success (55 %) and limited clinical impact, with actionable findings in 13 % and therapy implementation in 3.5 %. Prioritizing KRAS testing and deeper sequencing in KRAS-wildtype tumors, alongside broader access to targeted therapies, may improve outcomes.

KW - Molecular profiling

KW - Pancreatic neoplasms

KW - Precision medicine

KW - Young adult

UR - https://www.scopus.com/pages/publications/105020577930

U2 - 10.1016/j.ejca.2025.116065

DO - 10.1016/j.ejca.2025.116065

M3 - Article

C2 - 41129983

SN - 0959-8049

VL - 230

JO - Eur. J. Cancer

JF - Eur. J. Cancer

M1 - 116065

ER -

Clinical relevance of next-generation sequencing in patients aged 60 years or younger with pancreatic cancer: A Nationwide prospective cohort study

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this