. 2025 Feb 19;25(1):299.

doi: 10.1186/s12885-025-13554-w.

Nationwide implementation of the international multidisciplinary best-practice for locally advanced pancreatic cancer (PREOPANC-4): study protocol

T F Stoop^#^{1

2

3}, L W F Seelen^#⁴, F R van 't Land^#⁵, A C van der Hout⁶, J C M Scheepens⁴, M Ali^{2

7}, A M Stiggelbout⁸, B M van der Kolk⁹, B A Bonsing¹⁰, D J Lips¹¹, D J A de Groot¹², E van Veldhuisen^{1

2}, E D Kerver¹³, E R Manusama¹⁴, F Daams^{2

7}, G Kazemier^{2

7}, G A Cirkel¹⁵, G van Tienhoven¹⁶, G A Patijn¹⁷, H N Lelieveld-Rier¹⁸, I H de Hingh¹⁹, I E G van Hellemond²⁰, J H Wijsman²¹, J I Erdmann^{1

2}, J S D Mieog¹⁰, J de Vos-Geelen²², J W B de Groot²³, K R D Lutchman^{1

2}, L J Mekenkamp²⁴, L W Kranenburg²⁵, L P M Beuk⁵, M W Nijkamp²⁶, M den Dulk^{27

28}, M B Polée²⁹, M Y V Homs³⁰, M L Wumkes³¹, M W J Stommel⁹, O R Busch^{1

2}, R F de Wilde⁵, R T Theijse^{1

2}, S A C Luelmo³², S Festen³³, T L Bollen³⁴, U P Neumann^{27

35}, V E de Meijer²⁶, W A Draaisma³⁶, B Groot Koerkamp⁵, I Q Molenaar⁴, C L Wolfgang³⁷, M Del Chiaro³, M G H Katz³⁸, T Hackert^{39

40}, J A C Rietjens^#^{6

41}, J W Wilmink^#^{2

42}, H C van Santvoort^#⁴, C H J van Eijck^#⁵, M G Besselink^#^{43

44

45}; Dutch Pancreatic Cancer Group

Collaborators, Affiliations

Collaborators

Dutch Pancreatic Cancer Group:
A Bruynzeel, A Vlijm, A van Asseldonk, B Zonderhuis, A A Javed, A Sterk, A Schoorlemmer, A Stam, C Y Nio, E van Alphen, H W M van Laarhoven, H van Veenendaal, I Griffioen, I F Rompen, J M Klaase, M Los, M F M A Marting, M S L Liem, J Peters, L J Peters, Linda Garms, M Walma, L H J Brada, M Seijbel, N D Hildebrand, N Michiels, R Bax, R M van Dam, S Achten, S Bouwense, S Augustinus, S Rötgerink, T W van Ravens, V B Nieuwenhuijs, W W Te Riele

Affiliations

¹ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
² Cancer Center Amsterdam, Amsterdam, the Netherlands.
³ Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht / St. Antonius Hospital Nieuwegein, Nieuwegein & Utrecht, the Netherlands.
⁵ Department of Surgery and Pulmonology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands.
⁶ Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁷ Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, the Netherlands.
⁸ Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
⁹ Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁰ Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
¹¹ Department of Surgery, Medisch Spectrum Twente, Enschede, the Netherlands.
¹² Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
¹³ Department of Medical Oncology, OLVG, Amsterdam, the Netherlands.
¹⁴ Department of Surgery, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
¹⁵ Department of Medical Oncology, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein, University Medical Center Utrecht, Nieuwegein & Utrecht, the Netherlands.
¹⁶ Amsterdam UMC, Location University of Amsterdam, Department of Radiation Oncology, Amsterdam, the Netherlands.
¹⁷ Department of Surgery, Isala, Zwolle, the Netherlands.
¹⁸ Department of Medical Oncology, Amphia Hospital, Breda, the Netherlands.
¹⁹ Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
²⁰ Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands.
²¹ Department of Surgery, Amphia Hospital, Breda, the Netherlands.
²² Department of Internal Medicine, Division of Medical Oncology, GROW - Research Institute for Oncology & Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands.
²³ Department of Medical Oncology, Isala Oncology Center, Isala, Zwolle, the Netherlands.
²⁴ Department of Medical Oncology, Medisch Spectrum Twente, Enschede, the Netherlands.
²⁵ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
²⁶ Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
²⁷ Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands.
²⁸ Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands.
²⁹ Department of Medical Oncology, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
³⁰ Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
³¹ Department of Medical Oncology, Jeroen Bosch Hospital, 's , Hertogenbosch, the Netherlands.
³² Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
³³ Department of Surgery, OLVG, Amsterdam, the Netherlands.
³⁴ Department of Radiology, St. Antonius Hospital, Nieuwegein, the Netherlands.
³⁵ Department of Surgery, University Hospital Essen, Essen, Germany.
³⁶ Department of Surgery, Jeroen Bosch Hospital, 's, Hertogenbosch, the Netherlands.
³⁷ Department of Surgery, NYU Langone Health, New York, NY, USA.
³⁸ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁹ Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
⁴⁰ Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
⁴¹ Department of Design, Organisation and Strategy, Faculty of Industrial Design Engineering, Delft University of Technology, Delft, the Netherlands.
⁴² Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands.
⁴³ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands. m.g.besselink@amsterdamUMC.nl.
⁴⁴ Cancer Center Amsterdam, Amsterdam, the Netherlands. m.g.besselink@amsterdamUMC.nl.
⁴⁵ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, De Boelelaan 1117 (ZH-7F), Amsterdam, HV, 1081, the Netherlands. m.g.besselink@amsterdamUMC.nl.

^# Contributed equally.

PMID: 39972248
PMCID: PMC11841322
DOI: 10.1186/s12885-025-13554-w

Nationwide implementation of the international multidisciplinary best-practice for locally advanced pancreatic cancer (PREOPANC-4): study protocol

T F Stoop et al. BMC Cancer. 2025.

. 2025 Feb 19;25(1):299.

doi: 10.1186/s12885-025-13554-w.

Authors

Collaborators

Dutch Pancreatic Cancer Group:
A Bruynzeel, A Vlijm, A van Asseldonk, B Zonderhuis, A A Javed, A Sterk, A Schoorlemmer, A Stam, C Y Nio, E van Alphen, H W M van Laarhoven, H van Veenendaal, I Griffioen, I F Rompen, J M Klaase, M Los, M F M A Marting, M S L Liem, J Peters, L J Peters, Linda Garms, M Walma, L H J Brada, M Seijbel, N D Hildebrand, N Michiels, R Bax, R M van Dam, S Achten, S Bouwense, S Augustinus, S Rötgerink, T W van Ravens, V B Nieuwenhuijs, W W Te Riele

Affiliations

¹ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands.
² Cancer Center Amsterdam, Amsterdam, the Netherlands.
³ Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht / St. Antonius Hospital Nieuwegein, Nieuwegein & Utrecht, the Netherlands.
⁵ Department of Surgery and Pulmonology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands.
⁶ Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
⁷ Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, the Netherlands.
⁸ Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
⁹ Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁰ Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
¹¹ Department of Surgery, Medisch Spectrum Twente, Enschede, the Netherlands.
¹² Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
¹³ Department of Medical Oncology, OLVG, Amsterdam, the Netherlands.
¹⁴ Department of Surgery, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
¹⁵ Department of Medical Oncology, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein, University Medical Center Utrecht, Nieuwegein & Utrecht, the Netherlands.
¹⁶ Amsterdam UMC, Location University of Amsterdam, Department of Radiation Oncology, Amsterdam, the Netherlands.
¹⁷ Department of Surgery, Isala, Zwolle, the Netherlands.
¹⁸ Department of Medical Oncology, Amphia Hospital, Breda, the Netherlands.
¹⁹ Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
²⁰ Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands.
²¹ Department of Surgery, Amphia Hospital, Breda, the Netherlands.
²² Department of Internal Medicine, Division of Medical Oncology, GROW - Research Institute for Oncology & Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands.
²³ Department of Medical Oncology, Isala Oncology Center, Isala, Zwolle, the Netherlands.
²⁴ Department of Medical Oncology, Medisch Spectrum Twente, Enschede, the Netherlands.
²⁵ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands.
²⁶ Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands.
²⁷ Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands.
²⁸ Nutrim School for Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands.
²⁹ Department of Medical Oncology, Medical Center Leeuwarden, Leeuwarden, the Netherlands.
³⁰ Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
³¹ Department of Medical Oncology, Jeroen Bosch Hospital, 's , Hertogenbosch, the Netherlands.
³² Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
³³ Department of Surgery, OLVG, Amsterdam, the Netherlands.
³⁴ Department of Radiology, St. Antonius Hospital, Nieuwegein, the Netherlands.
³⁵ Department of Surgery, University Hospital Essen, Essen, Germany.
³⁶ Department of Surgery, Jeroen Bosch Hospital, 's, Hertogenbosch, the Netherlands.
³⁷ Department of Surgery, NYU Langone Health, New York, NY, USA.
³⁸ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁹ Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
⁴⁰ Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
⁴¹ Department of Design, Organisation and Strategy, Faculty of Industrial Design Engineering, Delft University of Technology, Delft, the Netherlands.
⁴² Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands.
⁴³ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands. m.g.besselink@amsterdamUMC.nl.
⁴⁴ Cancer Center Amsterdam, Amsterdam, the Netherlands. m.g.besselink@amsterdamUMC.nl.
⁴⁵ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, De Boelelaan 1117 (ZH-7F), Amsterdam, HV, 1081, the Netherlands. m.g.besselink@amsterdamUMC.nl.

^# Contributed equally.

PMID: 39972248
PMCID: PMC11841322
DOI: 10.1186/s12885-025-13554-w

Abstract

Background: The introduction of (m)FOLFIRINOX and gemcitabine-nab-paclitaxel has changed the perspective for patients with locally advanced pancreatic cancer (LAPC). Consequently, in experienced centres 23% of patients with LAPC undergo a resection with 5-year overall survival (OS) rates of up to 25%. In the Netherlands, the nationwide resection rate for LAPC remains low at 8%. The PREOPANC-4 program aims for a nationwide implementation of the international multidisciplinary best-practice to improve patient outcome.

Methods: Nationwide program implementing the international multidisciplinary best-practice for LAPC. In the training phase, multidisciplinary and surgical webinars are given by 4 international experts, leading to a clinical protocol, followed by surgical off-site and on-site proctoring sessions. In the implementation phase, the clinical protocol will be implemented in all centres, including a nationwide expert panel (2022-2024). Healthcare professionals will be trained in shared decision-making. Consecutive patients diagnosed with pathology-proven LAPC (i.e., arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion [DPCG criteria]) are eligible. Primary outcomes are median and 5-year OS from diagnosis, resection rate, in-hospital/30-day mortality and major morbidity (i.e., Clavien-Dindo grade ≥ IIIa), and radical resection (R0) rate. Secondary outcomes include quality of life, functioning, side effects, and patients' healthcare satisfaction in all included patients. Outcomes will be compared with patients with borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX in the PREOPANC-2 trial (EudraCT: 2017-002036-17) and a historical cohort of patients with LAPC from the PACAP registry (NCT03513705). The existing prospective LAPC Registry and PACAP PROMs (NCT03513705) will be used for data collection. In qualitative interviews, treatment preferences, values, and experiences of LAPC patients, their relatives, and healthcare professionals will be assessed for the development of shared decision-making supportive tools. It is hypothesized that the program will double the nationwide LAPC resection rate to 16% with major morbidity < 50% and mortality ≤ 5%, and OS following resection similar to that observed in patients with BRPC.

Discussion: The PREOPANC-4 program aims to safely implement the international multidisciplinary best-practice for LAPC leading to benchmark outcomes for both short-term morbidity, mortality, and OS.

Trial registration: PREOPANC-4 program was registered at ClinicalTrials.gov (NCT05524090) on September 1, 2022.

Keywords: Implementation program; Induction therapy; Locally advanced pancreatic cancer; Surgery; The Netherlands.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval and consent to participate: The Medical Ethical Committee from the Amsterdam UMC (location Academic Medical Center) has assessed the study protocol (excluding the section about shared decision-making training and the qualitative interview study) and concluded that the Medical Research Involving Human Subjects Act (WMO) does NOT apply to the PREOPANC-4 program (W21_487 # 21.541). The local Medical Ethical Committee from each participating centre has approved their participation. Consent for publication: The manuscript contains no individual person’s data in any form. Consent is not applicable. Competing interests: (1) T.F. Stoop is granted by the Cultuurfonds (Jan de Ruijsscher / Pia Huisman Fonds). (2) M. Del Chiaro has been awarded with an industry grant (Haemonetics, Inc) to conduct a multicentre study to evaluate the prognostic implications of TEG in pancreatic cancer. (3) M. Del Chiaro is co-principal investigator of a Boston Scientific sponsored international multicentre study on the use of intraoperative pancreatoscopy of patients with IPMN. (4) M.G. Besselink has received grants from Ethicon, Medtronic, Intuitive Surgical, Oncosil and is a proctor for Intuitive Surgical. (5) J.W. Wilmink has received grants from MSD, Nordic and Servier and reports an advisory role for MSD, Astra Zeneca and Servier.

Figures

**Fig. 1**
Clinical work-up. *LAPC,* locally advanced pancreatic cancer; *DPCG,* Dutch Pancreatic Cancer Group; *CT,* computed tomography; *CA19-9,* carbohydrate antigen 19–9; *CEA,* carcinoembryonic antigen; U, units; *ml,*millilitres [18]; *F-FDG PET/CT*, 2-deoxy-2-[fluorine-18]-fluoro-D-glucose positron emission tomography; *PACAP,* PAncreatic CAncer Project (NCT03513705); *PROMs,* patient-reported outcome measures; *RECIST,* Response Evaluation Criteria in Solid Tumours [31]; *eCRF,* electronic case report form; *SBRT,* stereotactic body radiotherapy. NB. The LAPC 1–2–3classification concerns the anatomy-based classification system from Johns Hopkins University [32]

See this image and copyright information in PMC

References

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Nationwide implementation of the international multidisciplinary best-practice for locally advanced pancreatic cancer (PREOPANC-4): study protocol

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Nationwide implementation of the international multidisciplinary best-practice for locally advanced pancreatic cancer (PREOPANC-4): study protocol

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Conflict of interest statement

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