Assessing stromal architecture with MR Elastography to predict cytotoxic treatment efficacy in pancreatic cancer (ASAP-study)

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer
death worldwide and despite many efforts has retained a very grim overall
5-year survival of 5%. When surgery with curative intent is possible, 5-year
survival increases up to circa 10-20%, but at the time of diagnosis this is
only feasible in 20% of patients. Patients with Locally Advanced (i.e.
non-metastatic, but irresectable) Pancreatic Cancer (LAPC) show increased
progression-free and overall survival after combination chemotherapy such as
5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX), with 20%
even becoming eligible for surgery with curative intent. Stromal deposition is
an important component of PDAC and its amount is related to therapy resistance.
Therefore, the amount of stroma could potentially be used as a biomarker for
the efficacy of the treatment. We hypothesize that Magnetic Resonance
Elastography (MRE) can be used to predict the cytotoxic treatment efficacy.
This new imaging technology provides architectural information on PDAC
composition.

Predict response to FOLFIRINOX treatment in patients with LAPC based on
baseline stiffness values derived with MRE.

This prospective observational study is aimed to determine if MRE can be used
as an imaging biomarker to predict the response to FOLFIRINOX in patients with
LAPC. In this study, a total of 50 adult patients with LAPC who will be treated
with FOLFIRINOX will be scheduled for an MRI scan session which will include an
MRE, DWI and DCE-MRI scan. The MRI scan will take place in the Amsterdam UMC.

Participation in this study does not lead to immediate advantage for the
participant. The overall aim of the ASAP study is to gain further insight in
treatment efficacy of FOLFIRINOX in patients with LAPC using MRE, DWI and
DCE-MRI.

The burden for the patients will consist of a 1 x 45 minutes MRI scan session
including MRE, DWI and DCE-MRI.

During the MRE scan, an external vibration is applied to the body that is not
harmful or painful for the patient. MRI is a safe imaging procedure that does
not use ionizing radiation and has low inherent risks. The subject is asked to
fast for at least 4 hours prior to the scan. Patients with MRI
contraindications are excluded from participation in this study.

For DCE-MRI, MR contrast agent Dotarem (gadoteric acid) will be used. This
product is used daily at the Department of Radiology and Nuclear Medicine of
the Amsterdam UMC. Side-effects of Dotarem administration are rarely observed.
The most common side effects include a short sensation of warmth or very mild
pain in the arm and a strange oral taste, this does not constitute an allergic
reaction. Indeed, allergic reactions are rare (<0.1% of patients). Medications
to treat contrast-induced hypersensitivity reactions are readily available at
our site. In case of known renal insufficiency (eGFR <30 ml/min/1.73m2),
subjects cannot participate.

In summary, given that MRI, MR Elastography and MR contrast administration are
safe with the correct application of our exclusion criteria (which includes MRI
and contrast-agent contra-indications), the risk in participating in this study
is considered negligible.