Genetic and protein profiling in patients with oesophageal cancer

Improvement in oesophageal cancer treatment requires better selection of
patients with an unfavourable prognosis from the outset (early metastatic
potential) in whom intensive (local) therapy will only do harm. These patients
should be discriminated from those patients who can be cured, preferably after
individualized determination of the best treatment strategy.
Significant progress in the prediction and early identification of responders
to chemoradiation will likely come from further insight into the molecular
biology of oesophageal cancer. The use of biological markers may help to select
patients with early metastatic potential, to earmark patients who will be
unresponsive to (preoperative) (chemo)radiotherapy, and to individualize
choices of chemotherapeutic regimens combined with radiation.

Gene expression analysis
With gene expression analysis a profile can be determined. This genetic profile
shows active genes inside the tumour, including those genes that are associated
with tumoural behaviour such as response to radiation and chemosensitivity and
the process of tumour dissemination.
It is very plausible that the genetic defects involved in oesophageal
tumourigenesis can predict the outcome of disease, and therefore be of
importance in directing individual treatment.

Protein expression analysis
Protein expression profiling is another means by which response to treatment
and the process of tumour dissemination can be explored. If a pattern can be
identified, it could be used for individualization of treatment for the patient
with oesophageal cancer.

So far, both methods have been studied in patients with oesophageal cancer only
on a very limited scale. Available data suggest that gene expression profiling
may provide biomarkers for selection of therapy, but it is generally concluded
that the results are preliminary.

1) To identify a tumour genetic profile that is associated with early
metastatic spread in patients presenting with oesophageal cancer and no
evidence of distant metastasis at the time of diagnosis.

2) To distinguish oesophageal cancer patients who will respond to
(preoperative) (chemo)radiotherapy from those who will not respond with the use
of gene expression profiling.

3) To identify distinctive protein profiles in serum samples that can
discriminate between subgroups of patients with oesophageal cancer (those with
early metastatic spread versus those without, and responders versus non
responders to chemoradiation).

4) To investigate whether serum protein profiling reflects tumour activity in
patients who are treated for oesophageal cancer.

Inclusion criteria:
1) Patients presenting at the NKI-AvL or LUMC for the treatment of oesophageal
cancer.
2) Planned gastroduodenoscopy (for diagnosis, feeding tube insertion,
dilatation, etc.) or endoscopic ultrasonography (for staging) before the start
of therapy.
3) No evidence of distant metastases at presentation (by endoscopic
ultrasonography, computer tomography, and positron emission tomography)
4) Able and willing to undergo tissue sampling for tumour genetic analyses.
5) Age > 18 years.

Exclusion criteria:
1) Any condition that prohibits safe biopsy sampling (e.g. use of
anticoagulants).
2) Incapacity or unwillingness of participant to give (written) informed
consent.

Burden associated with participation:
- Extra biopsies (6) during planned gastroduodenoscopy/endoscopic
ultrasonography before the start of therapy
- Five blood withdrawals (combined with planned blood withdrawals during
therapy):
One sample will be drawn directly before
gastroduodenoscopy/endosonography.
Additional blood samples will be drawn at different time points during
the course of the therapy:
In patients undergoing (neoadjuvant) chemoradiotherapy, two
weeks after the start of the treatment and at
the end of the treatment.
And, in patients undergoing surgery, at postoperative day 1 and
four weeks after the operation.
- To fill in a standardized EORTC questionnaire at five different time points.
- Individual duration of the study will be 4 months (from planned
gastroduodenoscopy/endoscopic ultrasonography until four weeks after the
operation)