The predictive value of cytokines on response to preoperative chemoradiotherapy in patients with rectal cancer.

Preoperative chemotherapy and radiotherapy are essential parts of rectal cancer
treatment. The selection of patients eligible for preoperative
chemoradiotherapy is currently based on pathological parameters and MRI-scan
findings. However, some of these patients show a good or complete response to
chemoradiation whereas others do not respond at all. Surgery is performed
independent of the response to the therapy and is attended with substantial
morbidity. If complete or good responders to preoperative chemoradiotherapy can
be identified surgery could be omitted or postponed. In contrast, if
non-responders to preoperative chemoradiotherapy can be identified beforehand
or in an early stage, chemoradiotherapy can be omitted or stopped and surgery
can be brought forward.

Cancer and cancer treatment result in an inflammatory response thereby
cytokines are produced. Cytokines may also themselves influence therapy
response. Various cytokines are abnormal expressed in colorectal cancer
patients, are associated with colorectal cancer or determine response to
chemoradiotherapy. Our hypothesis is that the varying levels of these
circulating cytokines in the blood of rectal cancer patients may predict the
response to preoperative chemoradiotherapy. Because of the explorative pilot
study design this is not a hypothesis based study.

Predictive factors are needed to discriminate chemoradiotherapy responders from
non-responders and to individualize the treatment regime. Various cytokines
play a role in processes affecting tumour growth and metastasis. Furthermore,
cytokines might influence treatment response. Therefore we want to investigate
whether levels of circulating cytokines could predict response to preoperative
chemoradiotherapy in patients with rectal cancer.

The main objectives of the study are:
- To identify which cytokines and corresponding levels can predict response to
preoperative chemoradiotherapy in patients with locally advanced rectal cancer
- To determine the influence of surgery on the immune response, which can be
measured by comparing blood plasma cytokine levels before and after tumour
resection
- To determine whether blood plasma cytokine levels reflect tissue cytokine
levels

This study is an explorative clinical pilot study with a duration of 1 year in
which we will collect 5 ml of blood from a selection of rectal cancer patients
during a regular puncture before, during and after preoperative
chemoradiotherapy and before and after surgery. At these time points regular
blood samples are taken thus no extra puncture will be performed. Standard
procedure MRI-scans will be made before and after chemoradiotherapy. Cytokines
will be measured in blood plasma and in tumour and healthy tissue from the
resection specimen using multiplex immunoassays. Plasma cytokine measurements
will be linked to pathological (tissue samples) and clinical response
(MRI-scans) to identify which cytokines and corresponding levels can predict
response to preoperative chemoradiotherapy in patients with locally advanced
rectal cancer. Furthermore, blood plasma cytokine measurements before and after
surgery will be compared to evaluate the effect of tumour resection on the
immune response. In addition, preoperative blood plasma cytokine levels will be
compared with cytokine levels in normal and tumour tissue to test whether
circulating cytokine levels are representative for tissue cytokine levels.

For the patients included in the study there is no individual benefit. During
this study 5 ml of blood from a selection of rectal cancer patients during a
regular puncture before, during and after preoperative chemoradiotherapy and
before and after surgery will be taken. At these time points regular blood
samples are taken thus no extra puncture will be performed. No known risks are
associated with participation.