Magnetic Resonance Imaging for Better Selection of Pancreatic Cancer Patients for Surgery
Phase: NA
Conditions: Pancreas Cancer
Sponsor: University of Aarhus

 
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MAGIPAC trial: Magnetic Resonance Imaging for Better Selection of 
Pancreatic Cancer Patients for Surgery: A Randomized Clinical Trial. 
 
BACKGROUND AND SIGNIFICANCE 
Pancreatic cancer has a dismal prognosis with a 5-year survival of only 8% [1]. Despite surgery 
being the only chance for cure, only 20% of the patients are eligible for surgical treatment, as most 
have metastatic disease at diagnosis [2]. Pancreatic cancer surgery is a major procedure with a 
substantial morbidity and mortality [3]. Therefore, it is important to avoid futile resections that will 
delay initiation of life-prolonging chemotherapy in patients who will not benefit from surgery. 
Whether the patient can be operated depends on the local extent of the tumor and the presence of 
distant metastases (most often in the liver), which are contraindications to surgery [4-6]. 
Currently, computed tomography (CT) is state-of-the-art for assessing pancreatic cancer 
resectability [7]. However, CT has some shortcomings. Although it performs well in assessing the 
local extent of the tumor, it has limited sensitivity for detecting small liver metastases in pancreatic 
cancer [8]. Relying solely on CT imaging therefore leads to futile resections in patients with 
undetected liver metastases. This will impair survival, as patients will have to recover from surgery 
and the associated complications before they can initiate chemotherapy. These shortcomings may 
be overcome by using liver and pancreatic magnetic resonance imaging (MRI) instead of CT. 
MRI may be superior to CT for detection of liver metastases in pancreatic cancer [9]. As 
liver metastases from resectable pancreatic cancer tend to be small [10], for which MRI (with use of 
diffusion weighted imaging and liver-specific contrast) has a high sensitivity, routine use of 
preoperative MRI could be beneficial. However, the feasibility of using MRI in detection of liver 
metastases in pancreatic cancer patients has been sparsely investigated. One prospective study of 69 
pancreatic cancer patients found that almost 25% had liver metastases on MRI that were not visible 
on CT [11], whereas a retrospective study of 216 patients found that MRI revealed liver metastases 
in only 5% of patients with CT-assessed non-metastatic pancreatic cancer [12]. The latter study also 
found a longer time to recurrence after surgery in patients undergoing preoperative MRI, suggesting 
that preoperative MRI may be beneficial in pancreatic cancer patients. However, they did not 
provide information on why MRI was performed, and findings are unlikely to be generalizable. 
Furthermore, only few studies have examined the use of MRI in assessing the local extent of the 
tumor, suggesting it is not inferior to CT [13, 14]. 
Thus, MRI may provide a superior alternative to conventional CT in order to improve 
treatment allocation for pancreatic cancer patients. However, there is a substantial need for high-

 
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quality research to examine this. Specifically, no randomized clinical trial (RCT) has been 
conducted. 
 
PURPOSE AND OVERALL AIM 
We propose to conduct a nationwide RCT to examine the feasibility of using MRI for tumor staging 
and identification of liver metastases in pancreatic cancer patients. The aim is to improve selection 
of pancreatic cancer patients for surgery in order to increase overall survival. Within this RCT, we 
will conduct three studies outlined below. 
 
STUDY POPULATION AND DESIGN 
Patients 
200 patients with CT-assessed resectable pancreatic cancer allocated to surgery by the local 
multidisciplinary tumor board (MDT) will be included. Patients will be randomized to either the 
intervention (preoperative MRI, n=100) or control/standard-of-care (no preoperative MRI, n=100) 
arm. 
 
Study design and patient flow 
An overview of the proposed study design is shown in Figure 1. 
 
Figure 1. Study design. R: Randomization. 
 
Upon consent, patients will be electronically randomized to one of the two treatment arms. Patients 
in the control arm will proceed directly to surgery. Patients in the intervention arm will have an 
MRI performed after randomization and before treatment. If the interval from CT to MRI is >14 
days, a new CT will be performed to assure a valid comparator. The MRI will be read by an 
experienced gastro-radiologists blinded to the patient’s identity and initial CT scan. Based on the 
MRI, the treatment decision will be made (Figure 2): 

 
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1) No liver metastases on MRI (expected ~75%): Surgery as planned. 
2) Non-specific liver lesions on MRI, not seen on CT (expected ~10%): Surgery as planned. 
3) Liver metastases on MRI (expected ~15%): Referral to liver biopsy and oncological 
treatment if malignancy is verified. If biopsy is inconclusive, repeat liver MRI after one 
month. 
 
Figure 2. Patient flow in the intervention arm. MDT: Multidisciplinary team conference. 
 
Follow-up 
Patients will be followed for up to three years for information on treatment, recurrence, and vital 
status. We will conduct standard-of-care follow-up CT at 3, 6, 9, 12, 18, 24, 30, and 36 months 
postoperatively in all patients. Primary end-point for this project will be one-year survival. For 
subsequent studies, we will also perform analyses of three-year survival. 
 
SPECIFIC STUDY AIMS, HYPOTHESES AND OUTCOMES 
Study I: To compare tumor staging of pancreatic cancer patients assessed by MRI versus upper 
abdominal CT. 
Study II: To assess the ability of MRI to detect liver metastases in pancreatic cancer patients with 
resectable tumor on CT. 
Study III: To assess the impact of MRI on treatment allocation, recurrence, and survival in 
pancreatic cancer patients with a resectable tumor on CT. 
Details of study hypotheses, population, and analytical plans are outlined in Figure 3. 
 
 
 
 

 
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Study I 
Study II 
Study III 
Aim 
To compare tumor 
staging of pancreatic 
cancer patients assessed 
by MRI versus upper 
abdominal CT 
To assess the ability of 
MRI to detect liver 
metastases in pancreatic 
cancer patients with 
resectable tumor on CT 
To assess the impact of 
MRI on treatment 
allocation, recurrence, 
and survival in pancreatic 
cancer patients with a 
resectable tumor on CT 
Hypothesis 
MRI is non-inferior to CT 
with respect to tumor 
staging 
MRI will detect liver 
metastases in patients 
with a resectable tumor 
on CT 
Use of MRI will change 
treatment allocation and 
improve overall survival 
Population 
Patients in the 
intervention arm (N=100) 
Patients in the 
intervention arm (N=100) 
Patients in both arms 
(N=200) 
Analysis 
Agreement assessed by 
intraclass correlation 
coefficient (ICC) 
Agreement assessed by 
intraclass correlation 
coefficient (ICC) 
Treatment allocation and 
recurrence by Chi2 test 
Survival analyses by 
Kaplan-Meier estimation 
Figure 3. Outline of the three studies. 
 
POWER CALCULATIONS AND FEASIBILITY 
Assuming alpha=0.05, power of 80%, and a hazard ratio of death of 1.5, we need 191 patients in 
total. To guard against dropout of 5%, we aim to include 200 patients. On average, all four 
institutions performing pancreatic cancer surgery in Denmark (Rigshospitalet, Aarhus, Aalborg, and 
Odense) shall include 50 patients. We aim to finalize patient enrollment during the first 18 months 
of the study period, equaling to 2.8 patients monthly in each institution. In total, ~300 resections 
will be performed during this 18-month period. We consider it feasible and realistic to include two-
thirds of these patients. 
 
IMAGING PROTOCOLS 
CT imaging protocol 
As a part of the routinely workup for staging pancreatic cancer, all patients referred to the local 
hepato-pancreato-biliary MDT board undergo a pancreas-specific CT scan. All CT scans include a 

 
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portal venous phase (PVP) of the liver. CT scanners from different vendors will be used to acquire 
the images. The PVP will routinely obtained by 120 KV and mAs range from 150 to 290 depending 
of the body mass of the patient and the scan system. Contrast medium will be administered 
intravenously as a bolus injection by weight bases contrast Iodine concentration of 500 – 750 mg 
I/kg and a rate of 3-5 ml/s, followed by a saline flush of 20–40 ml. The scan delay for the PVP will 
be 50 sec (post-threshold, bolus tracking). Axial slice thickness of 2 mm slices will be reconstructed 
with 1 mm increments. 
 
MR imaging protocol 
The MRI will be performed using 1.5 or 3.0 T MR scanners of different vendors. The liver will be 
scanned using axial and coronal T2W single shot (SS) TSE, axial DWI (minimum b-values of 50 
and 800) and axial T1W 3D spoiled gradient echo for gadoxetic acid (Primovist, Bayer Pharma, 
Berlin, Germany) contrast scans. Both a dynamic contrast scan consisted of; pre-contrast phase, 
arterial phase (timed using bolus tracking) followed immediately by porto-venous phase; late phase 
at 2 min and hepato-biliary phase 15 min after contrast injection. The gadoxetic acid contrast will 
be injected at 1 or 2 mL/s depending of using a dilution 1:1 of gadoxetic acid and saline 9mg/ml or 
not. The dose will be 0.025 mmol/kg body weight with a maximum of 2.5 mmol using a power 
injector. 
 
Analysis for metastatic lesions 
Each modality will be read anonymized. Both CT and MRI images will be read independently by 
dedicated radiologist from each participating site as part of the routine work-up in staging 
pancreatic cancer. The CT scan will be performed as the first examination followed by MRI scan 
within 14 days after the CT scanning. For all focal hepatic lesions confidence of malignancy will be 
categorized via a 3-point scale, 1: benign, 2: indeterminate, 3: malignant. 
 
FEASIBILITY 
Time schedule 
The project will begin in January 2022 and end in December 2024. We will include the patients 
within the first 18 months of the project period. In the final year of the study period, we will 
perform data analyses and writing of scientific papers. This will allow for a sufficient follow-up 
period of all patients (please see Figure 4 for detailed time schedule). 

 
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Figure 4. Time schedule. 
 
Scientific and non-scientific personnel 
At each institution, one research nurse will be responsible for identification of potential study 
subjects and, in collaboration with the surgeon, perform the practical work on obtaining informed 
consent and randomize the patients. The research nurse will also be responsible for each patient’s 
path through the project, e.g. schedule the imaging and collect data, and to coordinate the project 
with the research nurses at the other participating sites. 
The applicant is Professor, DMSc, Chief Surgeon Frank Viborg Mortensen. Having 
published over 130 scientific papers, Frank has a strong track-record with clinical, experimental, 
and epidemiological research. Specifically, he has participated in several clinical studies [15-21] 
and has led epidemiological pancreatic cancer projects [22-34]. 
MD, PhD, Resident Surgeon Jakob Kirkegård will be responsible for data analyses and 
paper writing. For this purpose, he will be employed for one year (2024) as buyout from his 
position as surgical registrar. Jakob has a PhD on epidemiological studies of pancreatic cancer and 
has served as PI on a multicentre study on multidisciplinary team assessments of pancreatic cancer 
patients, coordinating the study with seven international collaborating institutions [35]. 
 
Collaborations 
We will collaborate with the Department of Radiology, Aarhus University Hospital, represented by 
MD, DMSc, Consultant Radiologist Erik Morre Pedersen and MD, Associate professor, 
Consultant Radiologist Lars Peter Larsen. Both are experts in imaging of gastrointestinal cancers 
and have published a substantial number of papers within this field. 
At our institutions, we have a strong experience in clinical research [15-21]. Furthermore, 
we are currently conducting another RCT in liver surgery (ARAPS Study, currently enrolling; 
ClinicalTrials.gov ID: NCT04107324) and participate in the ASAC trial (EudraCT: 2014-003601-
15). We thus possess all intellectual expertise and infrastructure needed to conduct this study. 
 

 
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Nationwide collaboration 
This project will be anchored at the Department of Surgery at Aarhus University Hospital and be 
conducted in collaboration between all four centers performing pancreatic cancer surgery in 
Denmark (Rigshospitalet, Aarhus, Odense, and Aalborg). All participating sites are represented in 
the steering committee of the Danish Pancreatic Cancer Group, who has endorsed the project. 
Aarhus will analyze data and draft the scientific papers originating from this study and thus have 
1st, 2nd, and last authorship. Each of the remaining three centers will each have two authors. 
Ordering will be determined the number of included patients (the more patients, the higher order) 
 
FINANCIAL ASPECTS 
Beside the salary for Jakob Kirkegård and two research nurses mentioned above, we apply the 
Danish Cancer Society for expenses related to MRI scans. The departments will hold expenses for 
CT scans for the 50% of the patients that are expected to have more than 14 days between CT and 
MRI. Please see the attached budget for more details. 
 
FUTURE PERSPECTIVES 
We expect this project to substantially improve our ability to tailor the optimal treatment for each 
individual with pancreatic cancer. Underdiagnosis of liver metastases delays the initiation of life-
prolonging chemotherapy. Thus, with proper preoperative detection of liver metastases, our project 
will improve both survival and quality-of-life, as patients will be spared from unnecessary major 
surgery. Thus, findings from our project is expected to have an immediate clinical impact. 
Furthermore, if MRI is non-inferior to CT with respect to tumor staging, it may replace CT in the 
diagnostic workup of pancreatic cancer patients. 
 
ETHICAL CONSIDERATIONS 
This project will be conducted according to the Helsinki Declaration. The project needs to be 
registered at the Danish Data Protection Agency in accordance with the Central Denmark Region 
common registration system and it also requires approval from the Central Denmark Region Ethics 
Committee. We will ensure that all permissions are granted when study starts. All information 
involving patients will be handled according to national law on personal data information. Both 
positive, negative, and inconclusive results will be published, and presented at scientific meetings. 
Results will be presented at international scientific congresses, and we will aim for publications in 

 
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high-impact journals with focus on oncology, radiology, and surgery. The study will be registered at 
ClinicalTrials.gov and monitored by the Good Clinical Practice Unit at Aarhus University Hospital. 
 
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