Repeated magnetic resonance imaging in esophageal cancer for adaptive radiation treatment planning during chemoradiotherapy.

The role of chemoradiotherapy (CRT) in the management of esophageal cancer is
growing. For resectable esophageal cancer, the standard therapy consists of 5
weeks of neoadjuvant chemoradiotherapy (nCRT) followed by surgery 6-8 weeks
afterwards. The advantage of nCRT followed by a 6-8-week period before surgery
is that this approach can induce significant tumor regression and downstaging,
which leads to an increased rate of microscopically radical resections,
decrease in local recurrences, a pathologic complete response (pCR) in 28-34%
of the patients and an overall survival benefit. For unresectable esophageal
cancer or inoperable patients due to comorbidities, definitive
chemoradiotherapy (dCRT) is the treatment of choice. The current radiotherapy
delivery to the esophageal tumor is not without adverse effect due to dose
delivery to healthy tissues surrounding the tumor. Radiation pneumonitis,
esophageal strictures, hearts failure, ischemic heart disease and postoperative
pulmonary complications, such as anastomotic leakage, pneumonia or ARDS can
directly be related to radiation dose delivered to these tissues.
Applying smaller irradiation margins may reduce short-term and long-term side
effects. However safely reducing radiation fields is only justified when full
tumor coverage is still assured. In order to develop more accurate radiation
treatment plans with limited toxicity the shape of the radiation field needs to
be adapted to the tumor. Therefore information about tumor shrinkage and
movement during therapy is needed. We aim to study these changes with magnetic
resonance imaging (MRI). This imaging modality has proven to provide excellent
soft-tissue contrast and allows for non-invasive visualization of the tumor.
Furthermore, a tool is desirable to accurately identify patients with good or
poor response to nCRT. Functional MRI imaging during the first 2-3 weeks of
nCRT has shown promising result in the prediction of pathological response.
However, the optimal timing of scanning for pathological response prediction is
unclear.
By visualizing both tumor shrinkage and movement during CRT and predicting
pathological response to neoadjuvant treatment, a first step is made to safe
adaptive radiotherapy planning strategies, using MRI. This development is
expected to allow for more personalized treatment for patients with esophageal
cancer.

Primary objective:
- To develop a patient-specific adaptive radiotherapy planning strategy using
MRI with more precise target coverage and critical organ sparing by safely
reducing treatment margins for resectable esophageal cancer irradiation.

Secondary objective:(only applicable to patients with resectable esophageal
cancer)
- To find the optimal timing for MRI guided response assessment to predict
pathological response to nCRT as determined after surgery.
- Assessment of the value of 'dynamic contrast-enhanced MRI' for early
response assessment during nCRT

Single-center prospective diagnostic study investigating the value of MRI in
the imaging before and during CRT for esophageal cancer. The MRI protocol
consists of anatomical MRI for the assessment of tumor movement characteristics
and shrinkage, and functional MRI for treatment response assessment. Imaging
response measurements will be compared with the pathological specimen as
reference standard.

For study purposes patients will undergo six extra MRI scans. The use of MRI
is negligible. Five scans will be scheduled in combination with radiation
treatment and one scan will be scheduled in the first week prior to nCRT when
the patient is in the hospital for radiation planning purposes. During the
course of two MRI exams, an intravenous contrast agent is administered to the
patient. This can lead to mild side effects of headache, nausea, injection site
reaction, disturbed sense of taste and feeling hot. The use of the contrast
agent has a very low risk (<1%) of an allergic reaction to the contrast medium.