Rationale: Current standard treatment of localized esophageal cancer (EC) with neoadjuvant
chemoradiotherapy (nCRT) followed by esophagectomy with curative intent results in 30%
complete, 40-60% partial and 20% no-response at pathologic examination. Clinical response of
nCRT is usually evaluated with PET-CT. However, response measurements are currently still
insufficient in optimizing EC treatment. Proper pre-surgical response prediction may allow
individualized treatment with esophagus-preservation in complete responders or switching to
an alternative treatment in non-responders. Interestingly, in many tumors, a subset of cells
has been found to possess cancer stem cell (CSC) properties with associated signaling as
drivers of tumor (re-)growth and therapy resistance. Response of CSC-derived tissue
resembling in vitro cultured tumor organoids may reflect patient's tumors sensitivity to
therapy.
Objective: To create a patient derived organoid model for EC patients to predict the
pathologic tumor response to nCRT in clinical practice. This will allow a more personalized
approach in future treatment of locally advanced EC.
Study design: Fresh esophageal tumor material will be collected during diagnostic endoscopic
ultrasound (EUS) in participating patients. These biopsies will be used to select cancer stem
cells, which will be cultured to derive organoids (esophageal cancer patient derived
organoids; EC-PDO). When the EC-PDO contain sufficient cells, these cells will be treated
with radiotherapy and/or chemotherapy in order to obtain dose-response curves. The response
of these EC-PDOs will be compared to the actual tumor response to nCRT treatment in these EC
patients, which will be assessed at the definitive pathologic examination of the resection
specimen after esophagectomy with curative intent.
Study population: All patients with curatively treatable and resectable esophageal cancer
(adenocarcinoma or squamous cell carcinoma) can be included in this trial.
Main study parameters/endpoints: The main endpoint is response prediction to
chemoradiotherapy by EC-PDO; the steepness of the dose response survival curve in the
organoids in relation to the pathologic response after resection in the clinical situation.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness: The patients will be asked to undergo 3 to 6 additional biopsies during
endoscopic ultrasonography (EUS) for the TNM staging of the tumor. The risk of these
additional biopsies is not greater than the biopsies for the diagnosis of EC. The patient
will not benefit from participation in this trial.
For the future approach we can get more insight into the mechanism of (chemo)radiation
response or resistance to nCRT, which might lead to a better patient selection and more
individualized esophageal cancer treatment in the future. This improvement in selection and
treatment can result in less over or under-treatment of these EC patients.