Diagnostic accuracy of contrast-enhanced diffusion-weighted MRI for liver metastases of
pancreatic cancer: towards adequate staging and follow-up of pancreatic cancer

Given the dismal prognosis of pancreatic cancer, detecting liver metastases
early can avoid inappropriate therapy with
associated substantial risks, long-term hospital admissions and high costs, but
without survival benefit. The current standard
of diagnostic workup with contrast-enhanced CT (CECT) has a poor sensitivity
(38-76%) for the detection of liver metastases
As more sophisticated and expensive treatment options emerge, better staging of
pancreatic cancer is needed to
avoid unnecessary procedures and select the most appropriate treatment
strategy. New imaging modalities are available,
but their value in staging of pancreatic cancer has not been evaluated yet.
Therefore prospective imaging studies are
necessary.

The main aim of this study is to determine the diagnostic accuracy of
contrast-enhanced diffusion-weighted MRI (CE-DW-MRI) in the detection of liver
metastases in patients with pancreatic cancer compared to a reference standard
of histopathology and follow up imaging.

Prospective cohort study (inclusion of patients until 138 patients with
metastasis are included, with a maximum total of 465 patients). Patients with
pancreatic cancer will undergo additional CE-DW-MRI within two weeks from the
CECT. CECT and CE-DW-MRI will be read independently by two radiologists.
Suspected liver lesions on CECT and/or CE-DW-MRI will be biopsied to obtain
histopathology as reference standard. For liver lesions without histopathologic
proof of metastases a paired follow-up CECT and CE-DW-MRI serve as a composite
reference standard.
Pancreatic resection will be pursued in patients without proven liver or
distant metastases. Patients with locally advanced or metastatic disease will
be offered palliative treatment. The patients will be asked for informed
consent for part 2 of the study, the follow-up, after the baseline scans.
Follow-up CECT and CE-DW-MRI will be performed in all patients at 3, 6, and 12
months. When disease progression is taken into account about 400-450 paired
follow up scans will be performed. There is also a number of substudies, for
which we refer to the research protocol.

The extent of burden and associated risks are:

- the extra CT en MRI scans. The first MRI will take place within two weeks
after the diagnostic CT. A follow up CT and MRI are scheduled at 3, 6 and 12
months. For these investigations the patient will pay an extra visit to the
hospital. The CT and MRI are scheduled on the same day and will take about 15
minutes and 45 minutes respectively.

- radiation dose of the CT:
a) when the patient will undergo his diagnostic imaging in the Radboudumc, an
additional perfusion CT will be performed during the routine CT scan. With the
CT perfusion scan the enhancement of the tumor can be better evaluated. These
extra scans will not prolong the duration of the routine CT scan. There is
however an additional radiation dose with an almost negligible risk for this
patient category.
b) when the patient will undergo his diagnostic imaging not in the Radboudumc,
only the routine CT scan will be performed without the perfusion CT.

- for the MRI there is no burden from radiation dose.

- extra blood samples. Blood samples will be collected on the first day of the
visit to the clinic and during follow up at 3, 6 and 12 months: two tubes
(3.5ml each) for tumor markers (part of routine diagnostic workup); three tubes
(2 times 10ml and 1 time 6ml only at baseline) for the Biobank for future
scientific research in the Radboudumc and two tubes (10ml each) for
international exosome research (Oslo University Hospital and Champalimaud
Centre for the Unknown, Lisbon). The total amount of blood drawn at baseline
will 53ml and at each follow up visit (3, 6 and 12 months) will be 47ml.