Improved childhood cancer survival rates call for novel strategies to reduce acute and
long-term physical complications of anti-cancer treatment.
Children with cancer have markedly impaired muscle strength, cardiorespiratory fitness, and
physical function occurring few days after diagnosis - further declining because of
anti-cancer treatment and physical inactivity during the treatment trajectory. Moreover,
these impairments persist years after ended treatment. Further, the children become
physically illiterate, which include a lack of confidence, competence and motivation to
engage in physical activities. The combination of persistent physical complications and
physical illiteracy predispose for metabolic- as well as musculoskeletal dysfunction that
lead to severe medical conditions such as metabolic syndrome, diabetes and cardiovascular
disease with reduced life-expectancy.
Studies indicate that structured exercise aimed to optimize both muscle and neuronal
functions ('integrative neuromuscular training'), should be explored further to effectively
counteract the impairment in physical function caused by childhood cancer and its treatment
and found a more healthy lifestyle after ended treatment. This age-adjusted, strength-based
exercise concept, based on games and play, is hypothesized to improve physical function in
children and adolescents diagnosed with cancer.
The primary objective of this study is to investigate the effects of a 6-months integrative
neuromuscular training intervention on knee extension strength in children and adolescents,
ages 6-18 years, with cancer during anti-cancer treatment, compared with an active control
group. Our secondary objectives are to investigate the effects of the intervention on markers
of metabolic syndrome, hospitalized days, health-related quality of life, upper body muscle
strength, cardiorespiratory fitness, physical function, physical activity behavior and body
composition.
All outcomes, except hospitalized days, will be measured within 2 weeks of treatment
initiation, 3-months after inclusion, after 6-months after inclusion, one month after ended
treatment and 1 year after ended treatment.
The primary endpoint for the primary objective and secondary objectives, besides metabolic
syndrome, are 6 months after treatment initiation. The primary endpoint for markers of
metabolic syndrome will be 1 year after cessation of treatment
The INTERACT study is a national multicenter, two arm parallel group, randomized controlled
superiority trial with 12 months follow-up after ended treatment, based in all national
centers for pediatric oncology: University Hospital of Copenhagen (Rigshospitalet), Aarhus
University Hospital and Odense University Hospital.
The study will include 127 children aged 6-18 years with any type of cancer that will be
randomized (2:2) to either the intervention group (integrative neuromuscular training +
motivational-counseling sessions + usual care) or active control group (home-based training
program + motivational-counseling sessions + usual care) and stratified by sex, pubertal
stage and diagnosis as 1) treatment for extracranial solid tumors and CNS-tumors; 2)
treatment for hematologic malignancy 3) stem cell transplantation, within each hospital.
This intervention, integrative neuromuscular training (INT), contains a multifaceted range of
developmentally appropriate activities that incorporate general and specific strength and
conditioning elements such as strength, power, motor skill training, dynamic stability,
core-focused strength, plyometric and agility. INT can be camouflaged as games and play or
performed as structured strength and conditioning program, depending on the participant's
age, motor skill level and diagnosis. The intervention is designed to enhance health- and
skill-related components of physical fitness.
The integrative neuromuscular training group will in addition to usual care receive the
intervention for six months.
All participants are recommended to participate in a minimum of 2 training session per week
the first 7 weeks, and a minimum of three session per week from week 8-24. During the intense
phase of treatment (first six months of treatment), all participants indifferent of cancer
type will receive combinations of treatment requiring either hospitalization or visits to the
outpatient clinic at least once per week. The participants, therefore, receives supervised
training at least once per week. All other training session is conducted as home-based
training. If there are weeks, without any visits to the hospital or outpatient clinic, all
training session will be conducted at home. In this case, the participants will receive a
phone call from the intervention physiotherapist concerning questions, exercise choice and
intensity of exercises.
Parents or guardians will receive education in conducting INT at home, alongside an
exercise-kit consisting of training equipment corresponding to the child's age and fitness
level (fitness ropes, medicine ball, dumbbells).
The active control group is, in addition to usual care, offered a home-based training program
consisting of combined aerobic, strength and stretching exercises.
Participants in both groups will receive a monthly 30-minute motivational-counseling session
to adjust the intervention and training program according to the child's physical capacity
and preferences. Further, the session will determine potential barriers towards performing
physical exercise using the Self-efficacy for Exercise Scale.
Both groups receive standardized hospital care, usual care, including physiotherapy if needed
Sample size:
A difference of 10 % as a result of physical exercise is regarded as a clinically relevant
change (1). Based on a mean 41.4 +/- 7.6 (2) and a 10% increase, an alpha level of 0.05 and
power of 80%, 106 children are needed. Approximately, 60 children with cancer at the age of
6-18 years will be diagnosed pr. year at Copenhagen University Hospital, Rigshospitalet
Aarhus University Hospital and Odense University Hospital. Assuming a 20 % dropout rate, a
total of 2.2 years is needed to include the required number of children with cancer (n=127).
A blinded statistician will randomize participants to either intervention or active control
group using a computer-generated concealed allocation procedure, to secure a proportionate
stratified random sample.
Due to the nature of the intervention, neither participants, nor assessors, will be blinded
to the allocation.