A combined physical exercise and psychosocial training program to improve physical fitness in children with cancer.

Advances in diagnosis and treatment of childhood cancer have dramatically
increased long-term survival. As a result, the numbers of childhood cancer
survivors (CCS) are growing. A recent study has shown that approximately 75% of
CCS have at least one adverse health effect after a median follow-up of 17
years. Prevention or reduction of acute and long-term adverse health effects
should be pursued in order to maintain or improve health-related quality of
life (HrQOL). Physical fitness has been shown to be reduced both during and
after childhood cancer with physical inactivity being one of the most prominent
causes. Physical inactivity may lead to obesity, fatigue, a poor skeletal
and/or mental health, and ultimately a compromised HrQOL. Therefore, prevention
of inactivity-related health problems by increasing physical fitness both
during and following treatment is essential. Rehabilitation programs in adult
cancer patients report positive effects on physical fitness and HrQOL and have
been introduced as standard care. However, such a program does not exist for
childhood cancer patients (CCP). Limited evidence suggests that it is safe for
CCP to engage in physical activities and that physical exercise programs are
capable of increasing physical fitness both during and following treatment.
However, study groups were small, restricted to children with acute
lymphoblastic leukemia, and effects on health outcomes and HrQOL were rarely
assessed. In addition, the interventions included a physical exercise program
only, thus not addressing the psychosocial factors affecting physical activity
in CCP.

The proposed study is part of a larger KWF program proposal: the Alpe d*HuZes
Cancer Rehabilitation Research Program (A-CaRe) coordinated by the EMGO
Institute. The aim of the study is to evaluate the short- and long-term
effectiveness of a combined physical exercise and psychosocial intervention
program, implemented during or shortly after treatment, in improving the
physical fitness of CCP. In addition, it will be determined whether positive
effects on physical fitness will attenuate or even prevent inactivity-related
health problems (i.e. fatigue, obesity) and improve HrQOL.

The proposed study is a multi-centre randomized clinical trial.

In total, 100 consenting patients will be randomized to either the intervention
or the control group after being stratified according to type of malignancy,
age group, and moment of inclusion into the study (during/after treatment).
Randomization will occur as soon as the clinical condition of the patient
enables him/her to participate in and complete the intervention program.


All patients will be asked to undergo performance tests (Cardiorespiratory
fitness: peak oxygen consumption (VO2-peak), peak work load (Wmax) and peak
heart rate; muscle strength: arms and legs - both left and right side of the
body) and are asked to undergo tests for health examination (1) DEXA scan: both
lumbar spine as full body; 2) Blood: magnesium, phosphate, calcium, 1CTP, PTH,
P1NP, IGF-1, 25 OH vit D; 3) pulmonary function: FEV1 and FEVC; 4)
electrocardiogram; 5) blood pressure) and complete a battery of questionnaires.
These measurements occur prior to randomization (T=0), after 12-14 weeks (T=1)
and at 12 month follow-up (T=3). At T=2 (6-9 months from baseline) only the
questionnaires will be administered.

The 12-week intervention consists of a combined physical exercise (2x/week) and
psychosocial training program followed by an one day booster session. The
physical exercise program includes both cardiorespiratory and muscle strength
training, and the psychosocial training program (6 child and 2 parent sessions)
contains psycho-education and cognitive-behavioral therapy.

The control group will receive care as usual.

Burden
This study will be measured on 3 occasions with a 12 months period.
Measurements include all primary and secundary outcome measures. An additional
measurement will be performed in approximatly in the seventh month following
the start of the study. This measurement includes measurments of questionnaires
only.

Measurments of all primary and secundary outcome measures will occur within a
5,5 hours period. This provides the children with ample apportunity to recover
between the different tests.

Risks
Risks accompanying DEXA scans and blood sampling are minimal. The amount of
radiation during a DEXA scan is equivalent to a persons normal daily
environmental radiation dose. To reduce the number of vena-punctions and
associated burden, blood sampling for research will be recommended with blood
sampling for "usual care" as much as possible. This will also reduce a possible
risk for infections. When available, a central venous access devise will be
used to collect blood.

Risks associated with the intervention are limited. Recent study has shown that
children during cancer treatment are well able to perform physical exercise.
However, due to a decreased bone mineral density during diagnosis and the
intensive fase of the treatment of Acute Lymphoblastic Leukemia (ALL) there may
be an increased risk for bone fractures. To decrease this possible bone
fracture risk, the intensity of the program will slowly increases, sports that
include body contact (judo or rugby) will not be performed, the physical
intervention program is individualist and patients are monitored repeatedly
during the training.