Changes in body composition, dietary intake, and physical activity in children with cancer - a master protocol

Poor nutritional status (which includes both undernutrition and overnutrition)
in children being treated for cancer can result in decreased survival,
increased treatment-related toxicity, and poor quality of life. However,
current evidence is based on studies of low quality, a limited number of
patients, often cross sectional, focus on a specific patient group (mostly
patients with hematological malignancies), or anthropometric data only (body
weight or body mass index). Besides weight and height, especially body
composition (fat mass (FM) and fat free mass (FFM)) is widely believed to
influence clinical outcomes. For example, excess FM may result in inadequate
dosing and diminished efficacy of chemotherapy on short-term, but may also
exacerbate effects associated with obesity, like cardiovascular and metabolic
diseases on long-term.

Till now, the main focus has been on undernutrition in children with cancer.
Emerging evidence shows that many children are also vulnerable to overnutrition
and weight gain (particularly gain of FM) during treatment, for example as side
effect from steroids often used in acute lymphoblastic leukaemia, which often
extends into survivorship.

However, there are a lot of remaining questions:
1. Which anthropometric or body composition variables are most strongly
associated with clinical outcomes: weight and height, or rather FM and FFM?
2. Which personal, clinical, and lifestyle factors are important risk factors
for either over- or undernutrition throughout the course of cancer treatment?
3. Is over- or undernutrition related to toxicity, survival and quality of life
in a heterogeneous group of children with cancer, or only in specific
sub-groups who might benefit from additional supportive care?
4. What are effective strategies to improve nutritional status, and how does it
influence clinical outcomes including toxicity, survival, and quality of life?

The overarching objective of this master protocol is to study the risk factors
(personal, clinical and lifestyle factors) for-, and consequences of- , changes
of nutritional status (both over- and undernutrition) in children with cancer.
Based on the results of this first phase, we will develop and evaluate
interventions aiming to improve the nutritional status, to finally improve
clinical outcomes (i.e., survival, toxicity, and quality of life) for children
with cancer.

This is a master protocol for a longitudinal cohort study focusing on all
relevant aspects of malnutrition, including body composition, dietary intake,
and physical activity in children with cancer. The term master protocol refers
to a study design that uses one overarching protocol to guide multiple,
simultaneously occurring sub-studies to evaluate multiple diseases, therapies,
clinical outcomes, or a combination of those within the same overall study
structure.

During this longitudinal cohort study, measurements will be performed and data
will be collected at diagnosis, and 3, 6, 12, and 24 months after diagnosis.

This study will yield valuable information to enable personalized support
regarding body composition, nutrition, and physical activity for future
children with cancer. Risks and burden of participation within the initial
cohort can be considered as minimal. Measurements of body composition using the
Bodpod can be performed in approximately 5 minutes. The regular evaluations
related to dietary intake (MijnEetmeter application) will take approximately 10
minutes per day for 3 days and the more extensive food frequency questionnaires
(20 minutes) will only be applied at three timepoints (at start of the study,
12 months, and 24 months after diagnosis). The diary which needs to be kept
during the Actigraph is worn takes 2 minutes per day for 7 days. Moreover,
measurements are not painful (the blood withdrawal for research purposes will
be combined with a regular blood draw as part of clinical care) and are always
performed during planned visits to the hospital.

The data obtained in this study will be used to define high risks groups which
might benefit from nutritional or physical interventions and to develop
intervention studies aiming to prevent over- and undernutrition and possible
detrimental changes in body composition during cancer treatment, ultimately
leading to less treatment-related toxicity, better survival, and improved
quality of life, both on the short- and long-term. In this way, future patients
(and their parents) will benefit from the knowledge obtained in this study.