Body composition and colorectal cancer recurrence and survival

  • Topic: Colorectal cancer
  • Institution: Wageningen University and Research Centre
  • Country: Netherlands
  • Status: Ongoing

Scientific abstract

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Background

Colorectal cancer patients who are obese or underweight may experience higher recurrence and mortality rates than normal and overweight patients. However, data are sparse and inconsistent. Part of the inconsistency may be explained by differences in body composition: body fatness is often mainly assessed as body mass index (BMI), which is not a valid measure for abdominal adiposity and body composition. Excess adiposity in combination with low muscle mass – sarcopenic obesity - has been related to worse survival in comparison with obese patients without sarcopenia. These findings underline the need to study the associations of muscle and fat mass both separately and combined on recurrence and overall and CRC-specific survival. Publications on nutritional intake in cancer patients mainly focus on weight loss and underweight, while many patients are overweighed or obese at diagnosis. Few studies assessed the association between diet, physical activity and body composition in cancer patients. Therefore, we additionally aim to assess dietary protein intake, total energy intake and physical (in)activity in association with body composition in CRC patients.

Hypothesis and Objectives

The main objective of this proposal is to assess the association between body composition, recurrence and overall and CRC-specific survival in a pooled dataset of 3 prospective cohort studies including ~2,400 patients.

There are three main hypotheses:

  1. visceral adiposity is associated with increased risk of recurrence and with decreased survival, 
  2. indicators of low muscle quality (low muscle mass, low muscle attenuation and increased inter-muscular fat areas) are associated with decreased survival,
  3. indicators of low muscle quality are associated with decreased survival independent of adipose tissue area, but not with recurrence 

Moreover, in a subgroup of ~800 patients, we will assess whether diet and lifestyle are associated with body composition.

Setting and Methods

Diagnostic CT-images will be retrieved from medical records of CRC patients from 3 cohort studies in the Netherlands: the COLON-study of Wageningen University, the EnCoRe study of Maastricht University, and a cohort of the Comprehensive Cancer Center Netherlands, location Eindhoven. From these CT-images, cross-sectional areas (cm2) of skeletal muscle, subcutaneous, visceral fat and inter-muscular fat will be quantified at the landmark level of the third lumbar vertebra (L3) using Slice-O-matic software. Information on recurrence and survival will be retrieved from medical records and from linkage to national registries. We will use Cox proportional hazard models to assess the associations between body composition and recurrence or survival. Stratification by gender, BMI, age and TNM-stage of disease will be used to assess effect modification. Models will be adjusted for possible confounding factors. We will study the association between diet, lifestyle and body composition cross-sectionally in a subgroup of 800 patients of whom we have data on diet and lifestyle at diagnosis available (COLON- and EnCoRe-study).

Impact

This project will show whether measures of muscle mass and adiposity either separately or combined have an impact on recurrence and survival. It will aid to identify whether future interventions should focus on maintenance of muscle mass, loss of excess fat mass, changes in the distribution of body fat mass or on a combination.


Plain language abstract

Background

Colorectal cancer patients who are obese or underweight may have a higher chance of recurrence of cancer, or of dying in comparison to patients of normal weight. However, data are sparse and inconsistent. Part of the inconsistency may be explained by differences in body composition: body fatness is often mainly assessed as body mass index (BMI), which does not give information about a persons' fat and or muscle mass. Excess fat mass in combination with low muscle mass – sarcopenic obesity - has been related to worse survival in comparison with persons who do not have a low muscle mass. These findings underline the need to study the associations of muscle and fat mass both separately and combined with recurrence and survival. Within the current proposal, these associations will be studied. In addition, we will study whether dietary intake and physical activity are associated with body composition in cancer patients.

Aims and Objectives

The main objective of this proposal is to assess the association between body composition, recurrence and survival in a large combined dataset including ~2,400 colorectal cancer patients. In a subgroup of ~800 patients, we will assess whether dietary protein intake, energy intake and physical (in)activity are associated with body composition.

How It Will Be Done

This study will be performed in a project in which 3 cohort studies from the Netherlands are collaborating: the COLON-study of Wageningen University, the EnCoRe study of Maastricht University, and a cohort of the Comprehensive Cancer Center Netherlands, location Eindhoven. Together, approximately 2,400 patients will be included in the total dataset. From all these patients, the CT-scan that was made at the time of diagnosis will be retrieved from medical records. From these CT-images, information about skeletal muscle mass, subcutaneous fat mass, visceral fat mass (fat surrounding the organs of the abdomen) and inter-muscular fat will be quantified using Slice-O-matic software. Information on recurrence and survival will be retrieved from medical records and from linkage to national registries. We will use specific statistical models - Cox proportional hazard models - to assess the associations between body composition and recurrence or survival.

Potential Impact

This project will show whether measures of muscle mass and adiposity either separately or combined have an impact on recurrence and on overall and colorectal cancer specific survival. It will aid to identify whether future interventions should focus on maintenance of muscle mass, loss of excess fat mass, changes in the distribution of body fat mass or on a combination.

Grant publication

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