Predictive markers for individualized biology-driven treatment for esophageal cancer

Esophageal cancer (EC) is the eight most common cancer and one of the leading
causes of cancer related death in the western world. Worldwide approximately
460.000 patients are diagnosed annually and incidence rates have increased
6-fold in the last 30 years. EC has one of the highest mortality rates among
solid tumors with a 5-years survival rate of only 10-15%. One important
determinant of the poor survival is that treatment response is unsatisfactory.
Treated patients suffer from local recurrence and distant metastasis while no
signs of advanced or metastatic disease are present at initial diagnose .
Biomarkers that assist in predicting risk of progressive disease and poor
response will prevent major surgical procedures in patients with short life
expectancy that might have more benefit from chemotherapeutic treatment.
Difference between patients in tumor behavior and respons to therapy might be
explained by differences in genetic and epigenetic alterations as well as the
tumor immune microenvironment that influence tumor biology. We hypothesize that
by unraveling genetic and epigenetic alterations involved in biological
processes that are important for sensitivity to chemo-radiotherapy, we will
identify biomarkers for response to treatment that might guide individualized-
biology driven esophageal cancer treatment that will increase survival.

This project aims to unravel genetic and epigenetic alterations as well as
characteristics of the tumor immune microenvironment that influence important
biological processes in esophageal cancer and determine response or resistance
to chemo-radiotherapy. These alterations might serve as biomarkers for response
to therapy and tailor treatment decisions.

This is a prospective cohort study in which we collect biopsy specimens from
normal and tumor tissue of all patient that undergo endoscopic ultrasound for
tumor staging during diagnostic work-up, before treatment is started.
Furthermore we collect blood samples before start and after finishing of the
treatment. The patient will be treated according to the current (international)
treatment standard in VUmc. Detailed information on clinicopathologic
characteristics such as tumor stage, treatment, response rate, pathological
response to chemo-radiotherapy after surgery, disease or progression free
survival will be collected. The biopsy specimen will be used for DNA- and RNA
isolation for genetic and epigenetic analysis as well as immune analyses by
immune histochemistry and flow cytometry.

For biopsy purposes a different endoscope is necessary. This will cause minimal
physical discomfort for the patient because the patient is sedated during the
procedure. There is only a small risk of complication, which includes bleeding
at the biopsy side that may or may not require treatment and perforation of
esophagus which may require surgical repair.