The primary objective of this study is to assess the added value of surgical exploration with intention for resection compared to MRI guided stereotactic ablative radiotherapy (SABR) in improving overall survival in patients with locally advanced pancreatic carcinoma (LAPC) who show a favourable biological response to systemic induction chemotherapy.
Age: ≥18 years.
RECIST non-progressive disease on cross-sectional imaging;
No radiological downstaging to a borderline resectable tumour;
Surgical resection seems potentially feasible according to the local multidisciplinary team*;
None
Parallel
Pancreatic surgery
Procedure/SurgerySurgical exploration starts with a staging laparoscopy, unless already performed previsouly. Hereafter, exploration is typically performed via laparotomy. Although heterogeneity exist in surgical techniques, the following general surgical principles are considered state-of-the-art: 1. Artery-first approach in case of potential arterial involvement 2. Arterial divestment in case of radiological signs of (former) involvement without current signs of arterial wall ingrowth (and negative biopsy of peri-arterial tissue) during surgery to remove all (former) tumour tissue. 3. In case of vascular reconstruction that requires a patch or interposition graft, an autol-ogous (e.g., veins, peritoneal / falciform patch, splenic artery) or biological (e.g., bovine patch) graft is strongly preferred over synthetic prosthesis
MRI guided stereotactic ablative radiotherapy
RadiationMRI-guided SABR must be initiated within four weeks after randomization and is delivered in a hypofractioned regimen of 50 Gy in five fractions of 10 Gy, prescribed to 95% of the planning target volume (PTV). Treatment will be administered on alternative days, two or three times per week, with an intended overall treatment duration of two weeks (i.e., 14 days). All patients will undergo an MR (and CT scan at the department's discretion) for radiotherapy planning. The gross tumour volume (GTV) will be defined based on those imaging datasets and the restaging imaging. A PTV margin of 3mm is applied. Two MRI-guided SABR platforms are allowed. 1.5 Tesla MR-Linac and MRIdian system (0.35 Tesla MR-Linac). All patients will receive a proton pump inhibitor (oral) once daily during MRI-guided SABR, continued for three months afterwards to reduce gastrointestinal toxicity.
Overall survival
This will be measured in days. Participants receive systemic induction therapy before randomization, with a minimum duration of 3 months but no fixed duration. Therefore, overall survival is measured from the date of randomization.
Failure free survival
To compare the failure free survival (FFS) between surgical exploration with intention for resection and MRI guided stereotactic ablative radiotherapy. Failure is defined as any of the following: local relapse/recurrence, local progression, regional relapse/recurrence, regional progression, development of distant metastases, or occurrence of a second primary pancreatic cancer.
Quality of life
functioning, and symptoms scores and the summary score during the first two years from randomization, using the EORTC QLQ-C30 (version 3.0). The higher the score, means more complaints. Scale 1-4. 30 questions.
serious adverse events
defined following the NCI Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) (grade ≥III),71 expressed as the number of patients with serious adverse event(s), the number of events, and type of events.
Global quality of life
Functioning, and symptoms scores and the summary score during the first two years from randomization using the EORTC PAN26 questionnaires. The higher the score, the more complaints. Scale 1-4. 25 questions.
in hospital/90 day major morbidity
defined as Clavien-Dindo classification grade ≥IIIa
in hospital/90 day clinically relevant pancreatic surgery specific complications
including post pancreatectomy hemorrhage, postoperatove pancreatic fistula, post pancreatectomy acute pancreatitis, delayed gastric emptying, chyle leak, and bile leak (grade B/C)
R0 resection rate
R0 resection status will be determined based on the final histopathological examination of the pancreatic resection specimen. Defined according to the 1mm rule following th royal collega of pathologists and international collaboration on cancer reporting, except for the anterior surface where a 0mm rule will be applied, and strtified for surgical and pathological margins in accordance with the 2025 ISGPS-ISGPP statement
Overall survival
This will be measured in days.
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Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Lead sponsor
Erasmus Medical Center
Collaborator
University Hospital Verona, Italy
Collaborator
University Hospital Heidelberg
Collaborator
Catharina Ziekenhuis Eindhoven
Collaborator
St. Antonius Hospital
Collaborator
Leiden University Medical Center
Collaborator
Radboud University Medical Center
Collaborator
University Medical Center Groningen
Collaborator
Maastricht University Medical Center
Collaborator
San Raffaele University Hospital, Italy
Collaborator
West China Hospital
Collaborator
Institut Paoli-Calmettes
Collaborator
University Hospital, Essen
Collaborator
Copenhagen University Hospital, Denmark
Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Collaborator
University Hospital Padova
Collaborator
University Hospital Ulm
Collaborator
Assistance Publique - Hôpitaux de Paris
Collaborator
Ruijin Hospital
Collaborator
Tubingen University Hospital
Collaborator
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