Innovative MRI techniques to improve treatment stratification of patients with Esophageal cancer: an optimization and pilot study

The outcome of esophageal cancer is poor, with an overall 5-year survival rate
of 10% worldwide. In resectable esophageal cancer, outcome can be improved by
multimodality treatment. The current standard treatment of resectable
esophageal cancer consists of neoadjuvant chemoradiation followed by resection.
In the Netherlands, the preferred chemoradiation regimen consists of
carboplatin plus paclitaxel with concurrent radiotherapy in 23 fractions of 1.8
Gray.1 In a meta-analysis the benefit of chemoradiation over surgery alone for
both adenocarcinoma and squamous cell carcinoma has been shown.2 However, not
all patients benefit from this preoperative treatment regimen. Some patients
develop recurrent disease despite chemoradiation and additional (systemic)
treatment might have been indicated. In contrast, in other patients a (nearly)
complete response is observed after chemoradiation and those patients could
possibly have been treated with a less extensive treatment regimen.
Furthermore, in patients without a threatened circumferential resection margin
(CRM) and lymph node metastases chemoradiotherapy could possibly be omitted,
reducing patients* risk for complications and unnecessary, expensive treatment.
Thus, stratification of patients with esophageal cancer is urgently needed.
Functional magnetic resonance imaging techniques (MRI) can provide in vivo,
quantitative information on tumor biology and may prove to be a useful
non-invasive tool for this purpose. In this project, ultra-small
superparamagnetic particles of iron oxide (USPIO) enhanced MRI using
iron-dextran nano particles, diffusion weighted MRI (DWI) and T2* MRI will be
developed, both in terms of improvement of acquisition and data processing
techniques. For patients with esophageal cancer, the proposed acquisition
techniques and data processing have not been performed before.

1. To determine the optimal acquisition technique for USPIO enhanced MRI
(without contrast injection), DCE (without contrast injection) and DWI and T2*
MRI of esophageal cancer in terms of signal-to-noise ratio, time resolution and
spatial resolution.
2. To determine the optimal data processing approach for USPIO enhanced MRI,
DCE, DWI and T2* MRI of esophageal cancer.
3. To explore the correlation between lymph node involvement on USPIO enhanced
MRI in relation to results obtained at pathological examination.
4. To explore the correlation of DCE, DWI and T2* MRI of esophageal cancer in
relation to stromal involvement and markers of hypoxia and vasculature obtained
at pathological examination.
5. To explore the accuracy of MRI concerning circumferential tumor delineation
compared to pathological examination.
6. To determine the feasibility to detect lymph node involvement on USPIO
enhanced MRI in initial staging, prior to preoperative chemoradiation therapy.
7. To determine the correlation between lymph node involvement on pre-treatment
USPIO MRI in relation to results obtained at pathology after complete
treatment.

The project will be executed in three steps:
1) Optimization of acquisition and data processing techniques of USPIO MRI
(without contrast injection), DCE (without contrast injection), DWI and T2* in
five healthy volunteers to optimize field of view, number of slices, slice
thickness (objectives 1 and 2).
2) Using the data of (1): assessment of USPIO MRI, DCE, DWI and T2* MRI in 20
esophageal cancer patients with clinically suspect lymph nodes directly before
surgery (objectives 3, 4 and 5).
3) Using the data of (1): assessment of USPIO MRI, DCE, DWI and T2* MRI in 10
esophageal cancer patients with clinically suspect lymph nodes, before initial
start of the treatment (objectives 6 and 7).

Patients will have no direct benefit from the study.

The administration of Gadolinium involves a very small risk of an acute
allergic reaction.

The most important side effects of intravenous iron injection are hypotension
and severe hypersensitivity reactions. These side effects are rare. We try to
further decrease the risk by excluding patients and healthy volunteers that had
hypersensitivity reactions before. Because hypersensitivity reactions will only
occur shortly after administration, we monitor each patients and healthy
volunteer for at least 30minutes after injection. Furthermore, medication to
treat hypersensitivity reactions will be available during the examination.
Other, less severe side-effects of iron administration include nausea,
diarrhea, constipation, dizziness and thickening of the legs.

The administration of Buscopan involves a risk of an adverse reaction. The most
common adverse reactions are accommodation disorders, tachycardia, vertigo and
a dry mouth. Patients who have a contraindication for IV administration of
Buscopan (mega-colon, ileus, myasthenia gravis, glaucoma, prostate hypertrophy
with urine retention, intestinal stenosis and tachycardia), will undergo the
scans without administration of Buscopan.

For injection of the USPIO a temporary IV canule will be injected once.
A group of 30 patients will visit the AMC twice for study purposes. Where
possible these visits will be combined with the visits planned for standard
patient care.
One group of 5 healthy volunteers will visit the AMC once for a MRI scan.
One group of 5 patients will visit the AMC once for a MRI scan.