Cytokines as predictors on response to preoperative chemoradiotherapy in patients with rectal cancer

Rationale and background: 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. Various cytokines are abnormally expressed in colorectal cancer patients, are associated with colorectal cancer or determine response to chemoradiotherapy. Therefore we want to investigate whether levels of circulating cytokines could predict response to preoperative chemoradiotherapy in patients with rectal cancer.

Hypothesis: Our hypothesis is that the varying levels of circulating cytokines in the blood of rectal cancer patients may predict the response to preoperative chemoradiotherapy.

Study design: This study is an explorative clinical pilot study in which we will collect 4 ml of blood from a selection of rectal cancer patients during a regular venipuncture before, during and after preoperative CRT and before and after surgery. 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 response to identify which cytokines and corresponding levels can predict response to preoperative CRT for 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.

Study population: Thirty patients (≥18 years) with locally advanced rectal adenocarcinoma eligible for preoperative CRT (oral capecitabine and 45-50 gray (Gy) in total; fractions of 1.8-2 Gy) and surgery.

Country of recruitment: The Netherlands

Cancer and cancer treatment result in an inflammatory response thereby cytokines are produced. Cytokines may also themselves influence therapy response. Various cytokines are abnormally 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.

What: cytokine concentrations
Timepoints: 6 blood plasma measurements of cytokines per patient; specifically before, in week 3 and just after preoperative CRT, 1 day before and 2 days and 6 weeks after surgery. Tissue measurements of cytokines will be performed on the resection specimen.
How: multiplex immunoassays (LUMINEX)

N/A