Grant title: Treatment tolerance and prognosis in survivors with non-metastatic colorectal cancer: a matter of liver fa(c)t?
Liver fat accumulation is an emerging health problem. We are delighted that, with support of this grant, we can now start unravelling the role of liver fat in relation to treatment tolerance and prognosis in individuals with large bowel cancer. – Dr Dieuwertje Kok
Background
Fat accumulation in the liver is common in individuals living in western countries. A fatty liver exists in more than 25% of the general population, and is strongly linked to lifestyle factors, including diet and physical activity. Previous research showed that individuals with large bowel cancer who have a fatty liver had a worse prognosis than those without a fatty liver.
Determinants of liver fat in individuals with large bowel cancer are not clear. This impedes development of effective strategies that could help these individuals and their healthcare professionals to optimise treatment and prognostic outcomes.
The liver plays an important role in the processing of drugs, including chemotherapeutic agents. Therefore, we hypothesise that individuals with a fatty liver may experience more side-effects of chemotherapy and therefore may not be able to complete their treatment as planned.
Also, a fatty liver might be more prone to invasion of cancer cells and could potentially increase the risk of complications of surgery.
Aims and objectives
The overall aim of this project is to unravel the role of liver fat in relation to acute and long-term clinical outcomes in individuals with large bowel cancer.
Specifically, we aim to:
- study the relation between the amount of liver fat and side-effects of chemotherapy and complications of surgery.
- study the relation between the amount of liver fat and return of the disease, either in the large bowel or in other organs (metastases), as well as survival.
- identify lifestyle-related factors determining the amount of liver fat in individuals with large bowel cancer.
How it will be done
This project will be implemented in the COLON study, which is a study among individuals newly diagnosed with large bowel cancer. The COLON study was approved by an ethical review board in 2010. Participants were involved in the definition and prioritizsation of research topics. Prevention of side-effects of treatment was one of the prioritised topics.
More than 2,100 participants were included in the study, and all provided informed consent for collection of clinical data, including computed tomography (CT) scans, from their medical records. These scans can also be used to evaluate the amount of liver fat.
Participants of the study also provided detailed information on dietary habits and lifestyle factors at time of diagnosis.
In this project, the amount of liver fat will be studied in relation to acute or long-term side-effects of chemotherapy, post-operative complications, as well as risk of return of the cancer (local or as metastases) and survival during follow-up.
Potential impact
The substantial impact of side-effects of treatment were explicitly mentioned by COLON participants. We aim for better understanding of liver fat in relation to side-effects and prognosis after a large bowel cancer diagnosis. As we will consider diet- and lifestyle-related factors, this project has the potential to provide valuable information for future interventions aiming at a reduction of liver fat and thereby improved outcomes after diagnosis.