Preoperative identification of response to neoadjuvant chemoradiotherapy for esophageal cancer

Esophageal cancer remains one of the most lethal cancers, with an average
5-year survival of 15-20%. Furthermore, the incidence of esophageal cancer has
doubled over the past two decades. For resectable esophageal cancer the
standard therapy is 5 weeks of neoadjuvant chemoradiotherapy (nCRT) followed by
surgery 6-8 weeks afterwards. Surgery is performed independent of the response
to nCRT and is associated with substantial morbidity. A pathological complete
response (pCR) after nCRT is seen in 28-34% of patients. Pathological
non-responders (pNR) most probably do not benefit from nCRT but are exposed to
its toxicity and delay from surgical therapy inevitably occurs in this group.
Accurate identification of non-responders early during nCRT would allow
individualized decision making in continuation or discontinuation of nCRT.
Furthermore, a tool is desirable to accurately assess the treatment response
after nCRT to identify patients with a complete response. Studies in rectal
cancer reported that tumor resection could be omitted in patients with
persisting clinical complete response after 12 months. Also, in some esophageal
cancer studies, complete responders in surgical and non-surgical treatment
groups had comparable overall survival. These findings indicate the possibility
to perform nCRT as sole treatment in patients with a complete response. On the
contrary, if residual tumor is demonstrated, this will support the decision to
move to surgery.

The objective of this explorative study is to assess the value of anatomical
and functional magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose
positron emission tomography and computed tomography (PET-CT) in the evaluation
of treatment response to nCRT for patients with esophageal cancer.

Single-center diagnostic pilot study investigating the value of MRI and PET-CT
in the imaging before, during and after nCRT for assessment of response to nCRT
for resectable esophageal cancer. Imaging response measurements will be
compared with the pathological specimen as gold standard.

For study purposes the patients will undergo three MRI scans and two PET-CT
scans in addition to the standard pre-nCRT PET-CT scan. MRI scanning is a safe
procedure, no ionizing radiation is used. During the 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 of an
allergic reaction to the contrast medium.

Before the MRI exam can take place, the glomerular filtration rate (GFR) needs
to be known. If no recent value (<3 months) is known, a venous punction is
required. The majority of patients, however, will have a recent GFR value
available as it is required for conventional treatment planning
(contrast-enhanced planning CT).

Both the MRI and PET-CT scans will be scheduled in combination with standard
diagnostic scans, radiation treatment or standard follow-up appointments. The
scans will be performed before nCRT, after 2 weeks of the nCRT regimen and 5-7
weeks after the end of the preoperative treatment (1-2 weeks prior to surgery).
The PET-CT scans will be planned on the same day as and preceding the MRI
scans. For the patients included in the study, there is no individual benefit.
For each PET-CT there is an irradiation load of approximately 6.1 mSv, which
involves moderate risk for the patient of developing a second malignancy.
Therefore patients will be excluded from later studies involving additional
irradiation unless patients directly benefit from these studies.