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Physical exercise training interventions for children and young adults during and after treatment for childhood cancer

  1. Katja I Braam1,
  2. Patrick van der Torre2,†,*,
  3. Tim Takken2,
  4. Margreet A Veening1,
  5. Eline van Dulmen-den Broeder1,
  6. Gertjan JL Kaspers3

Editorial Group: Cochrane Childhood Cancer Group

Published Online: 30 APR 2013

Assessed as up-to-date: 5 MAR 2012

DOI: 10.1002/14651858.CD008796.pub2

How to Cite

Braam KI, van der Torre P, Takken T, Veening MA, van Dulmen-den Broeder E, Kaspers GJL. Physical exercise training interventions for children and young adults during and after treatment for childhood cancer. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD008796. DOI: 10.1002/14651858.CD008796.pub2.

Author Information

  1. 1

    VU University Medical Center, Department of Pediatrics, Division of Oncology/Hematology, Amsterdam, Netherlands

  2. 2

    Wilhelmina Children's Hospital, University Medical Center Utrecht, Child Development and Exercise Center, Utrecht, Netherlands

  3. 3

    VU University Medical Center, Department of Paediatrics, Division of Paediatric Oncology/Haematology, Amsterdam, Netherlands

  1. Joint first authorship with Katja I. Braam

*Patrick van der Torre, Child Development and Exercise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, PO Box 85090, Utrecht, 3508 AB, Netherlands. p.vandertorre@umcutrecht.nl.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 30 APR 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

 
Summary of findings for the main comparison. Physical exercise training compared with usual care for children and young adults during and after treatment for childhood cancer

Physical exercise training compared with usual care for children and young adults during and after treatment for childhood cancer

Patient or population: children and young adults during and after treatment for childhood cancer

Settings: hospital and non-hospital

Intervention: physical exercise training

Comparison: usual care

OutcomesIllustrative comparative risks* (95% CI)No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Usual care groupExercise group

Cardiorespiratory outcomes

9-minute run-walk test
wheeled distance counter
Follow-up: mean 4 months
The mean 9-minute run-walk test in the control groups was
3304.5 feet (1007.2 m)
The mean 9-minute run-walk test in the intervention groups was
0.33 standard deviations higher
(0.42 lower to 1.07 higher)
28
(1 study)
⊕⊕⊝⊝
low1,2,3
SMD 0.33 (-0.42 to 1.07)

Timed up-and-down stairs test
stopwatch
Follow-up: mean 4 months
The mean timed up-and-down stairs in the control groups was
8.6 seconds
The mean timed up-and-down stairs in the intervention groups was
0.11 standard deviations higher
(0.64 lower to 0.85 higher)
28
(1 study)
⊕⊕⊝⊝
low1,2,3
SMD 0.11 (-0.64 to 0.85)

Body composition outcomes

Bone mineral density
DXA scan
Follow-up: mean 24 months
The mean bone mineral density in the control groups was
-1.1412 standard deviation
The mean bone mineral density in the intervention groups was
1.07 standard deviations higher
(0.48 to 1.66 higher)
51
(1 study)
⊕⊕⊝⊝
low1,2,3
SMD 1.07 (0.48 to 1.66)

Body mass index
Quetlet Index
Follow-up: mean 18 months
The mean body mass index in the intervention groups was
0.59 standard deviations higher
(0.23 lower to 1.41 higher)
64
(2 studies)
⊕⊝⊝⊝
very low1,2,3,4
SMD 0.59 (-0.23 to 1.41)

Muscle endurance/strength outcomes

Ankle Dorsiflexion Strength
Hand-held dynamometer
Follow-up: mean 4 months
The mean ankle dorsiflexion strength in the control groups was
0.22 standard deviation
The mean ankle dorsiflexion strength in the intervention groups was
0.29 standard deviations higher
(0.46 lower to 1.04 higher)
28
(1 study)
⊕⊕⊝⊝
low1,2,3
SMD 0.29 (-0.46 to 1.04)

Health-related quality of life

Health-related quality of life
PedsQl - General questionnaire (version 3.0)
Follow-up: mean 4 months
The mean health-related quality of life in the control groups was
17.5
The mean health-related quality of life in the intervention groups was
0.23 standard deviations lower
(0.98 lower to 0.51 higher)
28
(1 study)
⊕⊕⊝⊝
low1,2,3
SMD -0.23 (-0.98 to 0.51)

Fatigue

General fatigue
PedsQl - fatigue questionnaire
Follow-up: mean 6 weeks
The mean general fatigue in the control groups was
3.4
The mean general fatigue in the intervention group was
0.04 standard deviations lower
(0.88 lower to 0.8 higher)
22
(1 study)
⊕⊕⊝⊝
low1,2,3
SMD -0.04 (-0.88 to 0.8)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in the table. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group.
CI: Confidence interval; SMD: standardised mean difference; DXA: dual-energy x-ray absorptiometry; cmH2O: centimetres of water pressure

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Total population size is less than 400 (a threshold rule-of-thumb value; using the usual α and β, and an effect size of 0.2 SD, representing a small effect).
2 The upper or lower confidence limit crosses an effect size of 0.5 in either direction.
3 Published evidence is limited to a small number of trials.
4 In this study outcome-accessors were not blinded.

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of the condition

Only a small percentage of the total population suffer from childhood cancer; approximately 144 to 148 cases per million children (Cancer Research UK 2011; National Cancer Institute 2012). However the impact of childhood cancer is significant. Many studies report a decreased physical fitness (aerobic capacity and muscle strength) and a poor social functioning, in patients and survivors of acute lymphoblastic leukaemia (ALL), which is the most common type of childhood cancer (Aznar 2006; Hartman 2009; Hovi 1993; Marchese 2004; Moyer-Mileur 2009; San Juan 2008; Warner 1998; Warner 2008; Wright 1998; Wright 2005) and also in childhood cancer patients in general (Arroyave 2008; Cox 2008; De Caro 2006; Hartman 2008; Ness 2005; Ness 2009; Winter 2009). In addition, a considerable number of survivors of childhood cancer suffer from motor function disability (Geenen 2007; Van Brussel 2006). Motor function disability in patients or survivors of childhood cancer is mostly related to negative motor signs, such as insufficient muscle activity, or muscle weakness (Hartman 2008; Wright 2005). A reduced daily energy expenditure and lower levels of physical activity have been described as the most important cause of this reduced state of physical fitness in childhood cancer patients (Warner 2008).

Positive effects of exercise training on physical fitness have been reported in studies with adult cancer patients (Cramp 2008; Oldervoll 2004; Schmitz 2005; Watson 2004). It is hypothesised that similar results are possible in children with cancer, or survivors of childhood cancer (Moyer-Mileur 2009).

 

Description of the intervention

The intervention under consideration was a physical exercise training programme, introduced within the first five years following the diagnosis of childhood cancer. The exercise training should aim to increase physical fitness by aerobic, anaerobic, strength, or mixed fitness training.

 

How the intervention might work

Cancer and cancer treatment induce lean tissue degeneration and can, therefore, potentially cause abnormalities in the cardiac and skeletal muscle (Schneider 2007). A decline in protein synthesis and protein degeneration by cancer and its treatment, can reduce muscle mass, the muscle fibre cross-section, and muscle extensibility. This can result in a decreased oxidative enzyme activity and a decreased number of proteins necessary for metabolism (Schneider 2007). Cancer patients often experience muscle weakness, a decreased functional capacity, decreased flexibility, reduced mobility, and diminished health-related quality of life (HRQoL) (Hartman 2008; Schneider 2007). In addition, a decreased psychosocial functioning and HRQoL as a result of cancer has impact on a person's motivational drive and can result in a poorer self perception of one's ability to perform physical activity (Warner 2008; Wright 1998).

Physical activity can prevent or diminish the negative effects of a sedentary life-style such as obesity, poor skeletal health, fatigue, and poor mental health, thereby increasing HRQoL of the individual. Increasing physical activity is possible by adopting a less inactive life-style and increasing sports participation. Beneficial effects of physical activity during or shortly after cancer therapy are an increase in muscle mass and plasma volume, improved lung ventilation and lung perfusion, and also an increased cardiac reserve, which can lead to a higher concentration of oxidative muscle enzymes.

This was seen in the study by Dimeo et al (2001); the children with cancer who received cancer treatment with glucocorticoids in combination with resistance exercises, showed less muscle mass loss than the children who did not receive the additional physical exercise training intervention (Dimeo 2001).

 

Why it is important to do this review

Despite the positive results of exercise interventions in adult cancer patients, the evidence for benefits in childhood cancer patients is limited. Studies within the population of childhood cancer patients and survivors have been initiated and the first data have been published. However, the number of participants in the various publications is small and the variety in type of cancer limited, making it difficult to draw conclusions. In making healthcare management decisions, participants and clinicians must weigh the benefits and drawbacks of supportive care. Pooled data can help in this decision-making process.

The purpose of this Cochrane review is to summarise the existing literature on the effectiveness of physical exercise training interventions in children with cancer, implemented within the first five years from diagnosis and to provide a best-evidence synthesis or meta-analysis of the reported results.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Primary objective

To evaluate the effect of a physical exercise training intervention on the physical fitness (e.g. aerobic capacity, muscle strength, or functional performance) of children with cancer within the first five years from their diagnosis (performed either during or after cancer treatment), compared to a control group of childhood cancer patients who did not receive an exercise intervention.

 

Secondary objectives

To determine whether physical exercise within the first five years of diagnosis has an effect on fatigue, anxiety, depression, self efficacy, and HRQoL and to determine whether there are any adverse effects of the intervention.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing the effects of physical exercise training within the first five years following the diagnosis of childhood cancer with no training.

A CCT was included in the review when the study included a well-defined and comparable control group. Factors that were taken into account regarding comparability were: being childhood cancer patients or survivors, age, sex, and country of origin.

We included cluster-randomised trials when the intervention and control groups were comparable in each aspect except for the location of cancer treatment and study recruitment.

We included cross-over trials when the study results were available for each separate intervention period. The data of the first randomisation period were then used.

Reviews were not included but were assessed for relevant references. In addition, we excluded observational studies (including case reports, case-control studies) and surveys from this review.

 

Types of participants

Study participants were under 19 years of age at diagnosis of any type of childhood cancer. Participants in the physical exercise training programme needed to be no more than five years from diagnosis. We only included studies that also included adult cancer participants when the results of the childhood and adult study populations were reported separately.

 

Types of interventions

Studies that were included compared a physical exercise training intervention for childhood cancer patients or survivors with a control group receiving care as usual. Care as usual is defined as care when needed, but no specific exercise programme or alternative intervention prescribed to increase physical fitness, HRQoL, self perception, or a combination of these, or to decrease adverse events, fatigue, anxiety, depression, or a combination of these in childhood cancer patients.

The physical exercise training interventions that were offered included different types of training or exercise programmes. For instance, muscle strength or stretching exercises, aerobic exercises, or sports such as gymnastics, swimming, running, or bicycling.

The exercise training intervention could have been additional care during therapy or could have been offered after the standard cancer therapy in a form of rehabilitation. The goals of this exercise training intervention were preventing motor disabilities and a decline in physical fitness, or treating motor function problems which developed during childhood cancer therapy.

The exercise training intervention could have taken place in any setting or location: at home, at a physical therapy centre, in a hospital, or elsewhere. It could either have been a group intervention, or an individual programme.

The duration of the exercise training intervention needed to be at least four weeks, in order to be able to report on exercise training effects. The upper limit of the training duration was not fixed for this review. In addition, the duration of physical activities (daily time spent on activities or sports) could differ per protocol.

 

Types of outcome measures

We included studies evaluating the effect of physical exercise training interventions on physical fitness, HRQoL, fatigue, self efficacy, anxiety and depression. Furthermore adverse effects of the intervention programme were studied.

 

Primary outcomes

The primary outcome of this review was physical fitness measured by:

  1. cardiorespiratory fitness (e.g. peak oxygen uptake (VO2peak), peak work rate (Wmax), endurance time): aerobic or anaerobic exercise capacity tested by ergometry on a cycle ergometer or treadmill, the Wingate anaerobic test, the steep-ramp-test, maximal anaerobic running/cycling test, the Cooper test, or another valid instrument;
  2. muscle endurance/strength: assessed with a hand-held dynamometer, the Biodex, the spring scale, the lateral step-up test, the sit-to-stand test, 10 repetitions maximum, the up-and-down stairs test, the minimum chair height test, the muscle power sprint test, a 10 x 5-m sprint test, the six-minute walk test, the incremental shuttle walking test, or another valid instrument;
  3. body composition: using body mass index (BMI), skin-fold measurement, a dual energy x-ray absorptiometry (DXA) scan, waist circumference, or the waist-to-hip-ratio;
  4. flexibility: conducted with a goniometer, flexometer or with the sit-and-reach test, V-sit test, shoulder or trunk rotation test, straight leg raise, the passive and active ankle dorsiflexion test, or another valid instrument;
  5. activity energy expenditure: for example by using an accelerometer;
  6. level of daily activity: assessed by an exercise diary, questionnaire, or by accelerometry;
  7. time spent exercising (more than daily activity): assessed by an exercise diary, questionnaire, or by accelerometry

 

Secondary outcomes

Secondary outcomes of the review were:

  1. HRQoL: measured by the Paediatric Quality of Life Inventory (PedsQL), Child Health Questionnaire (CHQ), and DISABKIDS;
  2. fatigue: assessed by the PedsQL Multidimensional Fatigue Scale, Childhood Cancer Fatigue Scale (CCFS), or the Fatigue Scale for a child (FS-C), the same scale for adolescents (FS-A), and for parents (FS-P);
  3. anxiety and depression: measured by the Childhood Depression Inventory (CDI) and the Center of Epidemiological Studies Depression Scale (CES-D);
  4. self efficacy: assessed using the Confidence Scale, the Self-Efficacy Questionnaire for Children (SEQ-C), or the Children's Self-Efficacy Scale;
  5. adverse effects during the study period by collecting information on the occurrence of sport injuries, infections, fractures, heart failure, the recurrence of cancer, and fever.

 

Search methods for identification of studies

 

Electronic searches

For this review electronic databases of The Cochrane Central Library of Controlled Trials (CENTRAL) (The Cochrane Library, 6 September 2011, Issue 3), MEDLINE/PubMed (from 1945 to 6 September 2011), EMBASE/Ovid (from 1980 to 6 September 2011), CINAHL (from 1982 to 6 September 2011), and Physiotherapy Evidence Database (PEDro; from 1929 to 6 September 2011) (www.pedro.org.au/) were searched.

The search strategies for the different electronic databases (using a combination of controlled vocabulary and text words) are stated in the appendices (Appendix 1; Appendix 2; Appendix 3; Appendix 4; Appendix 5).

 

Searching other resources

We located information about trials not registered in CENTRAL, MEDLINE, EMBASE, CINAHL, and PEDro, either published or unpublished, by searching the reference lists of relevant articles and reviews. We scanned the conference proceedings of the International Society for Paediatric Oncology (SIOP), the American College of Sports Medicine (ACSM), the International Congress on Physical Activity and Public Health (ICPAPH), and the American Physical Therapy Association (APTA) electronically, or otherwise by handsearching from 2005 to 2011.

A search was performed in the ISRCTN register, the register of the National Institute of Health (both at www.controlled-trials.com), and the clinical trial database (www.clinicaltrials.gov) for ongoing trials on the 26 September 2011. We did not impose language restrictions and will update the searches every two years.

 

Data collection and analysis

 

Selection of studies

After employing the search strategy described previously, identification of studies meeting the inclusion criteria was undertaken by two review authors (KB, PT) independently. We obtained in full any study that seemed to meet the inclusion criteria on title and abstract, for closer inspection. Reasons for exclusion were noted on a separate form. Discrepancies between review authors were solved by reaching consensus. In one case, a third party arbitrator (TT) was needed: we required another opinion on the study of Macedo 2010. This discussion resulted in inclusion of that study because the training corresponded with the described criteria of the protocol.

 

Data extraction and management

Data extraction was performed independently by the two review authors (KB, PT) using standardised forms. For each study we collected information on the study design, participant baseline characteristics, settings, sample size, number of participants in each study arm, type of intervention(s), duration of intervention, randomization and blinding procedure, type of control group, type and duration of cancer treatment and stage of cancer treatment (for example, during or after treatment), and duration of participant follow-up.

The extracted outcome measures included: changes in cardiorespiratory fitness, muscle strength/endurance, body composition, body flexibility, daily energy expenditure per time period (for example, day, week, or month), and changes in the level of daily activity and time spent exercising. In addition, we used a separate form to collect information on psychosocial outcomes such as HRQoL, fatigue, anxiety and depression, and the child's self efficacy. To collect data regarding any other adverse effect of the intervention, we collected all information reported on adverse events during the intervention period in the included studies. Authors of the studies of which only an abstract was available were contacted for additional study information.

In the process of data extraction consensus was reached on all items.

 

Assessment of risk of bias in included studies

The two review authors (KB, PT) independently assessed the risk of bias in the included RCTs and CCT. This was done according to the following criteria: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessor (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other bias, such as significant baseline imbalance between study groups in pre-score or baseline outcome data. We also looked at differential diagnostic activity to observe differences in study protocol for the intervention group and the control group.

For all 'Risk of bias' items of the included studies we used the definitions as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We included a 'Risk of bias' summary figure. This figure shows whether a study had a high, low, or unclear risk of bias; a green plus symbol corresponds with a low risk of bias, a red minus symbol corresponds with a high risk of bias and the yellow question mark symbol corresponds with lack of information or uncertainty over the potential for bias.

Discrepancies between review authors were discussed and solved so consensus was reached. Quality of the outcomes in the different studies was rated by using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria (Guyatt 2008; Guyatt 2008a). For purposes of systematic reviews, GRADE defines the quality of a body of evidence ('High', ‘Moderate’, 'Low', or 'Very Low') as the extent to which we can be confident that an estimate of effect or association is close to the quantity of specific interest. The GRADE system entails an assessment of the quality of a body of evidence for each individual outcome (Guyatt 2008). Factors that may decrease the quality of evidence are: 1) study limitations; 2) inconsistency of results; 3) indirectness of evidence; 4) imprecision; and 5) publication bias. Factors that may increase the quality of evidence are: 1) large magnitude of effect; 2) plausible confounding, which would reduce a demonstrated effect; and 3) dose-response gradient (Guyatt 2008a). The two review authors performed the quality of evidence grading simultaneously. In case of disagreement they discussed even minor aspects to reach consensus on that matter.

 

Measures of treatment effect

The main outcome differences between study groups and pooled data are described in the  Summary of findings for the main comparison. In this table the illustrative comparative risks (with 95% confidence interval (CI)) and differences in standardised mean difference (SMD) are provided. For the Cohen's SMD, data were taken from the post-training/control period measurement. The results of the review also include effect estimates of the intervention per outcome measure. Across the included studies different outcome assessing scales were used. However, in case of BMI we were able to combine data of two studies.

For the interpretation of the Cohen's SMD we used the following criteria (Higgins 2011):

  • less than 0.41 represents a small effect;
  • 0.40 to 0.70 represents a moderate effect;
  • greater than 0.70 represents a large effect.

 

Dealing with missing data

Relevant missing data were sought by contacting the primary study author or the corresponding study author. To optimise the strategy for dealing with missing data, we used an intention-to-treat (ITT) analysis when possible. The ITT analysis includes all participants who did not receive the assigned intervention according to the protocol as well as those who were lost to follow-up. Attrition rates, for example dropouts and withdrawals, were investigated to optimize data analyses.

 

Assessment of heterogeneity

Heterogeneity was assessed both by visual inspection of the forest plots and by a formal statistical test for heterogeneity, that is the I2 statistic. Significant heterogeneity was defined as I2 > 50% (Higgins 2011). In case of heterogeneity, we assessed the following potential sources of clinical heterogeneity: 1) participant characteristics; 2) intervention setting; and 3) stratification methods within studies. When heterogeneity was found, we assessed potential reasons for the differences by examining the study characteristics.

 

Assessment of reporting biases

In the protocol we had planned to perform a funnel plot, however, due to an insufficient number of studies (fewer than 10) included in this review, we were not able to do so (Higgins 2011).

 

Data synthesis

The data of the included studies were entered into Review Manager software (RevMan 2011). The analyses were performed according to the updated Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). By using the GRADE criteria, the quality of the included studies was taken into account when interpreting the results for the review. We used the random-effects model throughout the review. When we were unable to perform meta-analysis, we provided all available effect information from the articles.

 

Subgroup analysis and investigation of heterogeneity

We planned to perform subgroup analyses to evaluate whether the outcome was influenced by differences in the age of the participant, the delivered type of physical exercise training intervention, the duration of the exercise training intervention, the exercise training intervention location, type of childhood cancer, and cancer treatment. However, only a meta-analysis on BMI could be performed and for this outcome it was not possible to perform subgroup analysis. Apart from the intervention and control groups, BMI data were not available per subgroup (Hartman 2009; Moyer-Mileur 2009).

 

Sensitivity analysis

For those studies that assessed similar outcomes and of which data could be pooled, we performed sensitivity analyses. We assessed whether the outcome would have been different when a study with high or unclear risk of bias would have been excluded from the analyses. This method aimed to assess whether the findings were robust to the decisions made in the process of obtaining them.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Description of studies

 

Results of the search

Running the searches in the electronic databases of CENTRAL, MEDLINE, EMBASE, CINAHL, and PEDro; searching the ongoing trial registries; plus searching the abstract books from SIOP, ACSM, ICPAPH, and APTA yielded 743 references.

After removal of duplicates, this search resulted in 710 potentially relevant articles. Initial screening of titles and abstracts excluded a further 700 references that did not meet the criteria for inclusion. The 10 remaining references were read in full text. Two of these 10 studies were ongoing trials, four studies did not meet all eligibility criteria and were thus excluded and four studies were included. Reference list tracking led to two additional articles that could potentially be included: one of these studies met all eligibility criteria and was thus included, whereas it was not possible to decide if the second study was eligible for inclusion based on the currently available information (Figure 1).

 FigureFigure 1. Study flow diagram.

Five studies were included, we also identified two ongoing trials (see Characteristics of ongoing studies) and one study is awaiting classification (see Characteristics of studies awaiting classification table).

 

Included studies

 

Methods

Five articles were included in this review (Hartman 2009; Macedo 2010; Marchese 2004; Moyer-Mileur 2009; Yeh 2011). Four of these studies were RCTs, and one study used a quasi-experimental study design, making it a CCT (Yeh 2011). One study performed a power calculation (Hartman 2009). For trial characteristics and outcomes see the 'Characteristics of included studies' table.

 

Participants

From the five included articles 131 participants were included in the analysis. All were children diagnosed with ALL and studied during chemotherapy for childhood ALL (Hartman 2009; Macedo 2010; Marchese 2004; Moyer-Mileur 2009; Yeh 2011). Of the 131 children, 74 were boys, 54 girls (Hartman 2009; Macedo 2010; Marchese 2004; Moyer-Mileur 2009; Yeh 2011), and the sex of the three children who dropped-out was not reported. The numbers of children per study were small. Hartman 2009 included the most children (n = 51) in their study, with 26 children in the usual care group and 25 in the intervention group. The 14 children in the study of Macedo 2010 were divided in nine children who received care as usual and five who received the intervention. Marchese 2004 included 13 children that performed the exercise intervention and 15 who had care as usual. The 13 children analysed in the study of Moyer-Mileur 2009 were divided in seven who received care as usual and six received the intervention; one child was lost to follow-up. Yeh 2011 included 22 children in the analyses of which 12 children received the intervention training programme and 10 received care as usual; two children were lost to follow-up.

Four studies reported their exclusion criteria; in one study no exclusion criteria were reported (Moyer-Mileur 2009). Cognitive or mental (developmental), or both, impairment were exclusion criteria in three studies (Hartman 2009; Marchese 2004; Yeh 2011). Having difficulties with the national language was described in one study (Hartman 2009). Children with neurological impairment could not participate in three studies (Macedo 2010; Marchese 2004; Yeh 2011). Marchese 2004 excluded children with a genetic disorder, as well as children who were already receiving physiotherapy. Children with a chronic lung disease, neuromuscular disease, or those treated with radiotherapy could not participate in the Brazil study of Macedo 2010.

 

Intervention

Aimed to increase physical fitness, all five studies included a home-based exercise programme, with guidance from a therapist of the treating hospital (Hartman 2009; Macedo 2010; Marchese 2004; Moyer-Mileur 2009; Yeh 2011). However, the duration of the entire intervention, the duration of each training session, the timing and the type of the interventions, differed across studies. The duration of the training sessions ranged from 15 minutes up to 60 minutes. The intervention period ranged from 10 weeks (Macedo 2010; Yeh 2011) to two years (Hartman 2009). Four out of five studies introduced the exercise intervention during the maintenance treatment period (Macedo 2010; Marchese 2004; Moyer-Mileur 2009; Yeh 2011) and in one study it started shortly after diagnosis (Hartman 2009). Four studies determined the effects of an exercise intervention to increase muscle strength of all muscles (Hartman 2009; Marchese 2004; Moyer-Mileur 2009; Yeh 2011). The study of Macedo 2010 investigated the effect of an inspiratory muscle training programme. They studied the effects of a domiciliary inspiratory muscle training, which was performed with a threshold device using a load of 30% of the maximal inspiratory pressure.

For more details see the information in the Characteristics of included studies table

 

Control

The control groups of all five studies received care as usual (Hartman 2009; Macedo 2010; Marchese 2004; Moyer-Mileur 2009; Yeh 2011). With the exception of those of the study of Macedo 2010, all study participants of the control groups were measured at the same time points as the intervention group.

The control group in the study of Macedo 2010 performed the study assessments during the initial evaluation and after 10 weeks, whereas the intervention group performed the measurements at the end of each training week.

 

Outcomes

The studied primary outcomes were: cardiorespiratory fitness, muscle endurance/strength, body composition, flexibility, and level of daily activity. Secondary outcomes of this review that were mentioned in the studies were: HRQoL, fatigue, and adverse events. The other secondary outcomes (anxiety, depression, and self efficacy) were not addressed.

Because of the different aims and study methods of the five included studies, there was little to no overlap in assessed outcomes. Only changes in BMI, which is part of the information concerning body composition, were assessed in two studies (Hartman 2009; Moyer-Mileur 2009). For further information see Characteristics of included studies table and the Data and analyses tables.

 

Excluded studies

Four publications had been retrieved, but were subsequently excluded. One was a non-peer-reviewed conference proceeding, presenting data of a pilot study (Te Winkel 2008). The full study data were reported by Hartman 2009 and were included in this review. The second study used a cross-over design but did not publish the between-group evaluation after the first block (Speyer 2010). Unfortunately the corresponding author did not respond to our requests for these missing data, therefore we had to exclude this report. The last two studies assessed the effects of a training intervention with duration of less than four weeks (Chamorro-Vina 2010; Hinds 2007). Information concerning the excluded references can be found in the Characteristics of excluded studies table.

 

Risk of bias in included studies

See the risk of bias section of the Characteristics of included studies table and Figure 2 for the exact scores per study and the support for the judgements made.

 FigureFigure 2. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

 

Allocation

The random sequence generation was adequately generated in two out of the five studies (Figure 2; Hartman 2009; Marchese 2004). These two studies used block randomisation with sealed envelopes (Hartman 2009; Marchese 2004). Macedo 2010 reported that selection and allocation were random; however, it remained unclear how the randomisation was carried out. A non-randomised design was used in the study of Yeh 2011, leading to a high risk of selection bias. No information on random sequence generation was available for the fifth study (Moyer-Mileur 2009). None of the studies described the quality of the envelopes, how the envelopes were sealed, or whether they were coded. Therefore four out of five studies were judged to have an unclear risk of bias for allocation concealment (Hartman 2009; Macedo 2010; Marchese 2004; Moyer-Mileur 2009). One study did not use a randomisation method and therefore had no allocation concealment (Yeh 2011). In summary, four studies had an unclear risk of selection bias and one study had a high risk of selection bias.

 

Blinding

 

Blinding of participants and personnel (performance bias)

Due to the nature of the interventions blinding was virtually impossible: that is when the participants need to perform an exercise intervention and the children and their parents are well informed about the study purpose, participants cannot be blinded for the study randomisation. This could be a potential performance bias in all studies (Higgins 2011). Therefore, all included studies of this review were thought to have a high risk for performance bias.

 

Blinding of outcome assessors (detection bias)

It is possible to minimise detection bias with blinding the outcome assessor for the randomisation. Two studies used outcome assessors who were blinded for study groups (Figure 2; Hartman 2009; Marchese 2004). In the other three studies the risk was unclear.

 

Incomplete outcome data

All studies reported withdrawals and drop-outs during the intervention period. However, only one study used an ITT analysis to deal with missing data and thus had a low risk of attrition bias (Yeh 2011).

In the study of Marchese 2004, the authors reported missing data for daily logs of activity and heart monitor. Yet no information was reported on methods used for data imputation. For the two other studies, it also remained unclear whether they used a (valid) method for missing data imputation (Macedo 2010; Moyer-Mileur 2009). In all these three studies the risk of attrition bias was thus unclear.

In the final study (Hartman 2009), there was a high risk of attrition bias. The authors used a simple imputation technic to include data for those children who dropped out the study. Yet, they included the data from prior to the elimination. This method is very simple and therefore increases the risk for bias due to incomplete outcome data.

 

Selective reporting

In one study serious selective reporting was detected (Yeh 2011). In this study, 'adherence' was mentioned to be an extra or a secondary outcome. Yet, in the results the authors focused on this item as if it was a primary outcome. In the four other studies the risk of reporting bias was low.

 

Other potential sources of bias

In this review we also looked at differences in baseline outcome data. The absence of significant differences in baseline outcome data were reported in three studies (Hartman 2009; Macedo 2010; Moyer-Mileur 2009). However, in two studies it remained unclear whether all baseline test scores were significantly different between the two study groups (Marchese 2004; Yeh 2011).

The study of Macedo 2010 had a different study measurement regimen for children in the control group compared with those in the intervention group. The control group of this study performed the study assessments during the initial evaluation and after 10 weeks, whereas the intervention group performed the measurements at the end of each training week. This could have led to differential diagnostic activity. We judged this study to be of high risk for this other type of bias. The other studies used the same number of measurements, and they were free of differential diagnostic activity (Hartman 2009; Marchese 2004; Moyer-Mileur 2009; Yeh 2011).

In summary, the combination of these two other biases showed that for two studies the risk of 'other biases' was unclear (Marchese 2004; Yeh 2011), for one study the risk was considered high (Macedo 2010), and for the other two the 'other' risk was low (Hartman 2009; Moyer-Mileur 2009).

 

Effects of interventions

See:  Summary of findings for the main comparison Physical exercise training compared with usual care for children and young adults during and after treatment for childhood cancer

Because of the different aims and study methods of the five included studies there was little to no overlap in assessed outcomes. Only for one item (BMI) pooling of results was possible.

 

Cardiorespiratory fitness

In this review cardiorespiratory fitness could be: peak oxygen uptake (VO2 peak), peak work rate (Wmax), or endurance time. In the included studies physical fitness was assessed by the nine-minute run-walk test (Marchese 2004), timed up-and-down stairs test (Marchese 2004), and by the 20-m shuttle run test (Moyer-Mileur 2009).

The nine-minute run-walk test (SMD 0.33; 95% CI -0.42 to 1.07; P value = 0.39) as well as the timed up-and-down stairs test (SMD 0.11; 95% CI -0.64 to 0.85; P value = 0.78) did not show a significant difference in the SMD for the intervention (n = 13) or the control group (n = 15) ( Analysis 1.1;  Analysis 1.2). Marchese 2004 reported one dropped-out. Data for that child were not taken into account in the analysis, only data for children who completed the trial were used; therefore no ITT analysis was conducted.

Results of the 20-m shuttle run test showed that children who performed home-based exercises during their maintenance chemotherapy for ALL (six children) were able to perform more laps than those in the control group (seven children) (P value = 0.05) (no RevMan data available). ITT analysis was not performed (Moyer-Mileur 2009).

 

Body composition

Bone mineral density (BMD) (Hartman 2009) and BMI (Hartman 2009; Moyer-Mileur 2009) were assessed in order to collect data on body composition.

The study of Hartman 2009 used a DXA scan to determine BMD (lumbar spine and a whole body) changes in childhood ALL participants. The assessments were performed at diagnosis, during chemotherapy for childhood ALL, and one year after the end of treatment. Analysis showed a significant SMD 1.07 (95% CI 0.48 to 1.66; P value < 0.001) ( Analysis 2.1) indicating a large and significant positive effect on the BMD for the intervention group (n = 25) compared to the control group (n = 26). This analysis was performed according to the ITT analysis principles.

Differences in BMI between the intervention group and the control group were studied in two trials, and both studies did not find BMI differences between, or within, either study group (Hartman 2009; Moyer-Mileur 2009). Moyer-Mileur 2009 tested six children with a nutrition and exercise programme compared to seven children who received care as usual. The SMD results showed no effect (SMD 0.02; 95% CI -1.07 to 1.11). In this study the data of the child who dropped out were not taken into analyses, therefore no ITT analysis on this item was performed in this review. The study of Hartman 2009 showed a statistically significant difference on BMI in favour of the exercise group (n = 25) compared to the control group (n = 26) (SMD 0.90; 95% CI 0.32 to 1.48). These BMI analyses were performed according to ITT analysis principles (Hartman 2009).

Analysis of BMI showed a non-significant moderate effect with an SMD of 0.59 (95% CI -0.23 to 1.41; P value = 0.16 ) ( Analysis 2.2) in favour of the intervention group. In addition, analysis also showed no substantial heterogeneity (I2 = 48%) for this item between the studies ( Analysis 2.2).

 

Flexibility

In two studies the ankle dorsiflexion range of motion was measured. However, in one study this was done in a passive way (Hartman 2009) and in the other by active contraction (Marchese 2004). Therefore data could not be pooled.

According to the ITT analysis shown in  Analysis 3.1, the passive ankle dorsiflexion showed a moderate significant positive effect for the 25 children in the intervention group compared to the 26 children in the control group (SMD 0.69; 95% CI: 0.12 to 1.25; P value = 0.02) (Hartman 2009). Analysis of the ankle dorsiflexion range of motion, measured in active contraction, showed a non-significant moderate effect in the intervention group (13 children) compared to the control group (15 children) (SMD 0.46; 95% CI -0.29 to 1.22; P value = 0.23) ( Analysis 3.1) (Marchese 2004). Because Marchese 2004 only provided the data of the children who finished all measurements, no ITT analysis was performed.

The study of Moyer-Mileur 2009 assessed body flexibility by the use of the sit-and-reach distance test. In this study there was no difference in the test results between the six children of the intervention and seven children of the control group. P values and ITT analysis were not stated in the text or provided by the authors.

 

Muscle endurance/strength

Marchese 2004 assessed the knee and ankle strength changes by hand-held dynamometry in both the intervention group (13 children) and the control group (15 children). Over time the authors found a significant effect in favour of the intervention group. Analysis showed that differences between the end scores of the intervention group and the control group were not significantly different for both knee and ankle strength ( Analysis 4.1;  Analysis 4.2). The SMD of the knee strength was 0.25 (95% CI -0.49 to 1.00; P value = 0.51) and the increase of ankle strength was 0.29 (95% CI -0.46 to 1.04; P value = 0.44) (Marchese 2004).

The study of Moyer-Mileur 2009 determined differences in number of completed push-ups (with knees on the ground) and used a peripheral quantitative computed tomography of the tibia to determine the muscle mass of the participants. According to the original study data, there was no significant change in maximal number of push-ups or muscle mass, within or between the intervention (six children) and control group (seven children). The report of this study did not include the data of these results, therefore the RevMan analysis could not be done.

Respiratory muscle strength of the Brazilian ALL population was determined by measuring the maximal inspiratory pressure and maximal expiratory pressure with a digital manometer and a nozzle to dissipate additional pressure caused by the facial muscles and the oropharynx (Macedo 2010). In the intervention group (five children) the authors found a significant improvement over time compared to the control group (nine children). Yet, the end score differences were not significant between the study groups; SMD for inspiratory breathing muscle strength was 0.33 (95% CI -0.77 to 1.43; P value = 0.56), for expiratory breathing muscle strength the SMD was 0.00 (95% CI -1.09 to 1.09; P value = 1.00) ( Analysis 4.3;  Analysis 4.4).

Due to invalid methods used for missing data imputation, an ITT analysis could not be performed for these outcomes.

 

Activity energy expenditure

No information was available for activity energy expenditure as it was not assessed in the included studies.

 

Level of daily activity

Daily physical activity of the participants was assessed in one study (Moyer-Mileur 2009). They used both the pedometer steps-per-day and an activity questionnaire to examine physical activity behaviour. This study showed that the six children of the intervention group increased in approximately the same amount in "reported activity in minutes per day" over time. In the control group three out of seven children increased in their reported activity in minutes per day. According to the original analyses the reported activities at baseline and at six months were not statistically significantly different between the intervention group and the control group (Moyer-Mileur 2009). At 12 months from baseline a higher number of steps was recorded in the intervention group compared with the controls, but this difference was of borderline statistical significance (P value = 0.06) (no RevMan data available) (Moyer-Mileur 2009). This analysis was not performed according to the ITT procedure.

 

Time spent exercising (more than daily activity)

No information was available for activity energy expenditure as it was not assessed in the included studies.

 

Health-related quality of life

HRQoL in general and HRQoL related to cancer were assessed by the PedsQL version 3.0 in the study of Marchese 2004. There were no significant differences on the child cancer PedsQL, child general PedsQL, the parent cancer PedsQL and the parent general PedsQL over the four-month study period between the intervention (13 children) and control group (15 children). The end scores were not significantly different between the groups. The PedsQL Generic showed a non-significant small estimate of effect with an SMD of -0.23 (95% CI -0.98 to 0.51; P value = 0.54) ( Analysis 5.1) and for PedsQL Cancer there was no statistically significant effect (SMD 0.16; 95% CI -0.58 to 0.91; P value = 0.66) ( Analysis 5.2). A small to moderate non-significant effect was seen on the parent Peds-QL general questionnaire (SMD 0.38; 95% CI -0.37 to 1.13; P value = 0.32) ( Analysis 5.3) and for the cancer-specific PedsQl module filled in by parents no statistically significant differences were reported (SMD 0.04; 95% CI -0.70 to 0.79; P value = 0.91) ( Analysis 5.4).

Due to missing data an ITT analysis could not be conducted.

 

Fatigue

Yeh 2011 measured the effect of the exercise intervention on fatigue. This study used the PedsQL multidimensional fatigue scale. They compared the fatigue change patterns between the intervention group (12 children) and the control group (10 children) over eight time points within 10 weeks. There were no significant differences between the intervention and control group using the PedsQL general fatigue scale (SMD -0.04; 95% CI -0.88 to 0.80; P value = 0.92) ( Analysis 6.1), the sleep/rest fatigue items (SMD -0.01; 95% CI -0.85 to 0.83; P value = 0.98) ( Analysis 6.2), or the assessed cognitive fatigue items (SMD 0.07; 95% CI -0.77 to 0.91; P value = 0.86) ( Analysis 6.3). Fatigue was assessed by the an ITT analysis.

 

Anxiety and depression

No information was available for anxiety and depression as these items were not assessed in the included studies.

 

Self efficacy

No information was available for self efficacy as this item was not assessed in the included studies.

 

Adverse events (due to, or not clearly related to, the intervention)

The study of Marchese 2004 reported that no children had any negative effects from the exercises or experienced complications attributed to the physical programme. The other studies did not report on this item (Hartman 2009; Macedo 2010; Moyer-Mileur 2009; Yeh 2011).

 

Sensitivity analysis

Sensitivity analyses were performed for those outcomes for which pooling was possible (i.e. BMI) (Hartman 2009; Moyer-Mileur 2009). We assessed whether the outcome would have been different when a study with high or unclear risk would have been excluded in the review analyses.

For two bias items: random sequence generation (selection bias) and blinding of outcome assessors (detection bias), the study of Hartman 2009 had a low risk, while for the study of Moyer-Mileur 2009 the risk was unclear. For these items sensitivity analyses were possible. For all other risk of bias items the twostudies scored the same (i.e. low, high, or unclear risk) or performed a combination of high and unclear risk.

The outcome of the sensitivity analysis showed the BMI data of Hartman 2009 without Moyer-Mileur 2009 (SMD 0.90; 95% CI 0.32 to 1.48). The results of the pooled data were SMD 0.59 (95% CI -0.23 to 1.41). The results of the sensitivity analyses thus were consistent among the trials and did not differ from the overall analyses.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Summary of main results

Several studies have investigated the effects of exercise interventions on physical fitness in adult cancer patients, showing different benefits. Less frequent are studies assessing these effects in a childhood cancer population, particularly not when looking at RCT or CCT study designs.

This review included five studies. All these studies investigated the effects of a physical exercise training intervention programme of at least four weeks' duration, in children with cancer. They all aimed to improve physical functioning or psychosocial well-being, and had enrolled children with ALL. The five included studies included limited participant numbers and some lacked a well-designed exercise intervention. Therefore the outcomes of this review should be interpreted with care.

Cardiorespiratory fitness was studied by the use of the nine-minute run-walk test, the timed up-and-down stairs test, and the 20-m shuttle run test. Only the 20-m shuttle run test showed significantly better scores in the intervention group compared with the control group (P value = 0.05, no further information available).

For BMD, a statistically significant difference in favour of the exercise group was identified (SMD 1.07; 95% CI 0.48 to 1.66; P value < 0.001). BMI was assessed in two studies. In contrast with the results of one of these studies (SMD 0.90; 95% CI 0.32 to 1.48), the pooled data did not show a statistically significant difference between the combined population in the intervention and control group.

Flexibility was assessed in three studies and each study used different test methods. No (statistically significant) difference between the study groups was identified in two studies, whereas in another study a statistically significant difference in favour of the exercise group was found (SMD 0.69; 95% CI: 0.12 to 1.25; P value = 0.02).

The study of Macedo 2010 focused on muscles of the lung. In this study an inspiratory muscle training programme aimed to increase inspiratory or expiratory muscle strength. No significant effects where found for either inspiratory or expiratory muscle strength. Two other studies using either the knee and ankle strength changes measured by hand-held dynamometry or the number of completed push-ups (with knees on the ground) and a peripheral quantitative computed tomography of the tibia to determine the muscle mass identified no statistically significant differences in muscle strength/endurance.

No statistically significant differences between the study groups were found for the level of daily activity, HRQoL, or fatigue. In addition, only one study reported no complications attributed to the physical exercise intervention programme, whereas the other studies did not address this item.

None of the included studies evaluated the outcomes of activity energy expenditure, time spent exercising, anxiety and depression, or self efficacy.

It should be noted that the exercise interventions were not the same and the quality and quantity of the evidence was limited.

For the future it will be best to assess the effects of one type of exercise intervention in more childhood cancer subgroups. This can be done in well-designed studies with large sample sizes.

 

Overall completeness and applicability of evidence

This review provides evidence for modest but positive effects of physical exercise training interventions for children with cancer. These modest effects could be due to small sample sizes, various interventions, and different outcome measures that were used in the studies included in this review. As a result, only data for BMI could be pooled; therefore, the results of the analysis were instable and weak. Although the meta-analysis and sensitivity analysis outcome on BMI were robust, the patient population was unintentionally homogeneous since ; all included children had ALL. The results of this review, therefore, are not applicable for other types of childhood cancer.

The RevMan analyses results of this review are very different to the analysis performed by the authors of some of the studies, which led to different conclusions. For Macedo 2010, Hartman 2009, and Marchese 2004, the differences were due to different methods of analysis. In this review we assessed the final outcome differences between the study groups ( Analysis 4.1;  Analysis 4.3;  Analysis 4.4) and found no changes over time.

The included studies all had supervised interventions with a duration and intensity in which it was possible to have a physiological response (Hartman 2009; Macedo 2010; Marchese 2004; Moyer-Mileur 2009; Yeh 2011). From literature it is known that supervised exercise interventions in children are more effective compared to non-supervised programmes (Faigenbaum 2010). It is also known that a well-designed exercise programme consists of four parameters: mode (type of exercise), intensity, frequency, and duration (ACSM 2010; Ganley 2011). It would be advisable for new studies to first determine if the planned programme includes all elements of these parameters. This will increase the quality of the trials and also increase the comparability.

Appropriate statistical methods are important. The use of incorrect statistical methods can diminish the likelihood of demonstrating the real effects, also in high-quality interventions. In this review only one of the included studies used a power calculation (Hartman 2009). In the included studies the authors used a Chi2 test or the Mann-Whitney U test (Hartman 2009; Moyer-Mileur 2009), the Kruskal-Wallis (Moyer-Mileur 2009), and the paired sample T-test (Macedo 2010) to assess baseline (pre-score) differences between the study groups. The baseline scores were reported as group average (Hartman 2009; Macedo 2010; Marchese 2004; Yeh 2011), but also per study participant (Moyer-Mileur 2009). These baseline differences might have had a large impact on the results and conclusions of this review. It would have been preferable for all authors to have corrected for baseline differences in their analyses. However this was not done. To increase the quality of evidence of this review we hoped to be able to pool all raw data (baseline and end of study data) in one database. This would have given us the possibility to correct for these differences. Yet, not all researchers responded to our request for additional information.

To investigate changes between participants and changes over time the paired sample T-tests (Hartman 2009; Macedo 2010), Friedman two-way test (Moyer-Mileur 2009), the mixed-effects model (Yeh 2011), and repeated measure analyses (Hartman 2009; Marchese 2004) were used in the included studies. The mixed-effect model and repeated measure analyses are more specific than comparing group mean changes. Therefore, the results of the studies using the better statistical methods are possibly better than the ones using simple statistical techniques. However, in this review we were not able to use this information in the outcome.

 

Quality of the evidence

By grading the evidence according to the GRADE criteria (Guyatt 2008) the overall quality of the studies varied between low and very low. Due to risk of bias, inconsistency, indirectness, imprecision, possible publication bias, or a combination of these, the qualities of the studies were downgraded. None of the articles was eligible for upgrading. The quality of the evidence is summarised in the 'Summary of findings' table ( Summary of findings for the main comparison). The small numbers of participants in the trials was the main reason for the low-quality scores. This is often the case in studies in a paediatric population, and in cases of newly introduced interventions. More and larger well-controlled studies are needed to improve the quality and the quantity of evidence. This also shows the need for a core-set of outcome measures in exercise-related research in childhood chronic conditions (Van Brussel 2011).

This review included five studies, all with small numbers of participants. Between the studies there is a considerable degree of heterogeneity on mode and intensity of the exercise interventions. Only BMI was assessed in two different studies with no substantial heterogeneity (I2 = 48%). None of the other more important outcome measures were assessed in more than one study. This prevented further pooling of the data.

 

Potential biases in the review process

The search strategies for MEDLINE/PubMed, EMBASE/OVID, CENTRAL were formulated by the Cochrane Childhood Cancer Group. In addition, two other databases were searched by the use of a search strategy we developed ourselves: CINAHL and PEDro. The PEDro database was difficult to search. Although it is possible that we missed one or two studies from this database, due to the great overlap between results of the different databases it is very unlikely that studies were missed.

 

Agreements and disagreements with other studies or reviews

In 2010, a review on childhood cancer and physical activity was published by Winter 2010. This review included 28 studies, and almost half had an uncontrolled study design. In eight studies healthy controls were used. Of the four RCTs included in that review, one study included long-term childhood cancer survivors (mean 12 years from diagnosis). Another RCT offered a two- to four-day intervention, which therefore did not match with the inclusion criteria of this Cochrane review (Hinds 2007). The two remaining RCTs of the review by Winter 2010 are also included in this Cochrane review (Hartman 2009; Marchese 2004). A second review on exercise interventions for childhood cancer patients was performed by Huang 2011. They included many of the same studies, but also the study of Chamorro-Vina 2010, which again introduced an intervention of less than four weeks. Both reviews concluded that results are promising, but that there is a need for more and larger RCTs. Both reviews stated that only a subgroup of the childhood cancer population was tested, since almost all studies concerned children with ALL. These findings are consistent with our findings.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

 

Implications for practice

Based on the currently available evidence from the included RCTs and CCTs we are not able to draw conclusions regarding the best physical exercise training intervention, neither can we provide information on the best timing of the intervention during or after cancer treatment. However, the five included studies did show that exercise training is feasible in children with ALL.

Effects of the intervention are not yet convincing due to small numbers of participants and insufficient study methodology. Despite that, first results show somewhat better outcomes in the intervention group than in the control group on physical fitness items such as body composition, flexibility, and cardiorespiratory fitness. However, no significant differences were identified for muscle strength/endurance, the level of daily activity, HRQoL, fatigue, and adverse events and the included studies did not include activity energy expenditure, time spent exercising, anxiety, depression, or self efficacy to the study outcomes.

 
Implications for research

The observed heterogeneity in study findings can be due to differences in the physical exercise training intervention (mode, intensity, frequency, duration, as well as location), different outcome measures (quantitative, qualitative, physical, or psychosocial), and methods to assess the effects of an intervention. Consensus on these items is needed in order to facilitate comparison of results across different studies.

More and high-quality evidence is needed in order to be able to draft exercise and physical activity guidelines for this population. We urge the paediatric oncology community to design national or international multicentre studies, while local and small-scale studies must be discouraged.

In addition, since we could only include five RCTs or CCTs with a total of 131 children, there is a need for additional well-designed studies with large sample sizes. Results of ongoing trials have to be awaited, and further trials with adequate power are needed.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

We would like to thank Edith Leclercq for developing and running the search strategy for CENTRAL, MEDLINE, and EMBASE. We would like to thank Bart Bartels, MSc for translating the Portuguese article and Dr. Annelies Hartman for providing additional data, the results of her study population, and her comments in the reviewing process. Also, we would like to thank Dr. Mariska Leeflang for her remarks, as well as the third external review author. In addition we would like to mention that the editorial base of the Cochrane Childhood Cancer Group is funded by Stichting Kinderen Kankervrij (KIKA), Foundation Children Cancer-free.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
Download statistical data

 
Comparison 1. Cardiorespiratory fitness outcomes after physical exercise training intervention for children and adolescents during or after childhood cancer

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 9-minute run-walk test128Std. Mean Difference (IV, Random, 95% CI)0.33 [-0.42, 1.07]

 2 Timed up-and-down stairs test128Std. Mean Difference (IV, Random, 95% CI)0.11 [-0.64, 0.85]

 
Comparison 2. Body composition outcomes after physical exercise training intervention for children and adolescents during or after childhood cancer

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Bone mineral density151Std. Mean Difference (IV, Random, 95% CI)1.07 [0.48, 1.66]

 2 Body mass index264Std. Mean Difference (IV, Random, 95% CI)0.59 [-0.23, 1.41]

 
Comparison 3. Flexibility outcomes after physical exercise training intervention for children and adolescents during or after childhood cancer

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Flexiblity2Std. Mean Difference (IV, Random, 95% CI)Subtotals only

    1.1 Active ankle dorsiflexion
128Std. Mean Difference (IV, Random, 95% CI)0.46 [-0.29, 1.22]

    1.2 Passive ankle dorsiflexion
151Std. Mean Difference (IV, Random, 95% CI)0.69 [0.12, 1.25]

 
Comparison 4. Muscle endurance/strength outcomes after physical exercise training intervention for children and adolescents during or after childhood cancer

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Knee strength128Std. Mean Difference (IV, Random, 95% CI)0.25 [-0.49, 1.00]

 2 Ankle dorsiflexion strength128Std. Mean Difference (IV, Random, 95% CI)0.29 [-0.46, 1.04]

 3 Inspiratory breathing muscle strength114Std. Mean Difference (IV, Random, 95% CI)0.33 [-0.77, 1.43]

 4 Expiratory breathing muscle strength114Std. Mean Difference (IV, Random, 95% CI)0.0 [-1.09, 1.09]

 
Comparison 5. Health-related quality of life outcomes after physical exercise training intervention for children and adolescents during or after childhood cancer

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PedsQL - general128Std. Mean Difference (IV, Random, 95% CI)-0.23 [-0.98, 0.51]

 2 PedsQL - cancer128Std. Mean Difference (IV, Random, 95% CI)0.16 [-0.58, 0.91]

 3 Parents PedsQL - general128Std. Mean Difference (IV, Random, 95% CI)0.38 [-0.37, 1.13]

 4 Parents PedsQl - cancer128Std. Mean Difference (IV, Random, 95% CI)0.04 [-0.70, 0.79]

 
Comparison 6. Fatigue outcomes after physical exercise training intervention for children and adolescents during or after childhood cancer

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PedsQl - general fatigue122Std. Mean Difference (IV, Random, 95% CI)-0.04 [-0.88, 0.80]

 2 PedsQl - sleep/rest fatigue122Std. Mean Difference (IV, Random, 95% CI)-0.01 [-0.85, 0.83]

 3 PedsQl - cognitive fatigue122Std. Mean Difference (IV, Random, 95% CI)0.07 [-0.77, 0.91]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Appendix 1. Search strategy for MEDLINE/PubMed

1. For children the following MeSH headings and text words were used:

infant OR infan* OR newborn OR newborn* OR new-born* OR baby OR baby* OR babies OR neonat* OR perinat* OR postnat* OR child OR child* OR schoolchild* OR schoolchild OR school child OR school child* OR kid OR kids OR toddler* OR adolescent OR adoles* OR teen* OR boy* OR girl* OR minors OR minors* OR underag* OR under ag* OR juvenil* OR youth* OR kindergar* OR puberty OR puber* OR pubescen* OR prepubescen* OR prepuberty* OR pediatrics OR pediatric* OR paediatric* OR peadiatric* OR schools OR nursery school* OR preschool* OR pre school* OR primary school* OR secondary school* OR elementary school* OR elementary school OR high school* OR highschool* OR school age OR schoolage OR school age* OR schoolage* OR infancy OR schools, nursery OR infant, newborn

2. For cancer and childhood cancer the following MeSH headings and text words were used:

cancer OR oncology OR oncolog* OR neoplasms OR neoplas* OR carcinoma OR carcinom* OR tumor OR tumour OR tumor* OR tumour* OR cancer* OR malignan* OR hematooncological OR hemato oncological OR hemato-oncological OR hematologic neoplasms OR hematolo* OR bone marrow transplantation OR bone marrow transplant* OR lymphoma OR (((leukemia OR leukemi* OR leukaemi* OR (childhood ALL) OR AML OR lymphoma OR lymphom* OR hodgkin OR hodgkin* OR T-cell OR B-cell OR non-hodgkin OR sarcoma OR sarcom* OR sarcoma, Ewing's OR Ewing* OR osteosarcoma OR osteosarcom* OR wilms tumor OR wilms* OR nephroblastom* OR neuroblastoma OR neuroblastom* OR rhabdomyosarcoma OR rhabdomyosarcom* OR teratoma OR teratom* OR hepatoma OR hepatom* OR hepatoblastoma OR hepatoblastom* OR PNET OR medulloblastoma OR medulloblastom* OR PNET* OR neuroectodermal tumors, primitive OR retinoblastoma OR retinoblastom* OR meningioma OR meningiom* OR glioma OR gliom*) OR (pediatric oncology OR paediatric oncology)) OR (childhood cancer OR childhood tumor OR childhood tumors)) OR (brain tumor* OR brain tumour* OR brain neoplasms OR central nervous system neoplasm OR central nervous system neoplasms OR central nervous system tumor* OR central nervous system tumour* OR brain cancer* OR brain neoplasm* OR intracranial neoplasm*) OR (leukemia lymphocytic acute) OR (leukemia, lymphocytic, acute[mh])

3. For physical exercise training therapy the following MeSH headings and text words were used:

exercise OR exercises OR exercis* OR Exercise, Physical OR Exercises, Physical OR Physical Exercise OR Physical Exercises OR Exercise, Isometric OR Exercises, Isometric OR Isometric Exercises OR Isometric Exercise OR Warm-Up Exercise OR Exercise, Warm-Up OR Exercises, Warm-Up OR Warm Up Exercise OR Warm-Up Exercises OR Exercise, Aerobic OR Aerobic Exercises OR Exercises, Aerobic OR Aerobic Exercise OR exercise therapy OR Therapy, Exercise OR Exercise Therapies OR Therapies, Exercise OR physical therapy modalities OR Modalities, Physical Therapy OR Modality, Physical Therapy OR Physical Therapy Modality OR Physiotherapy (Techniques) OR Physiotherapies (Techniques) OR Physical Therapy Techniques OR Physical Therapy Technique OR Techniques, Physical Therapy OR exercise test OR exercise tests OR muscle stretching exercise OR muscle stretching exercises OR physical therapy OR physical therapies OR strengthen* OR stretch* OR physiotherapy[text] OR physiotherap*[text] OR stability training OR training* OR exercise movement technique OR exercise movement techniques OR Movement Techniques, Exercise OR exercise movement technic OR Exercise Movement Technics OR pilates based exercise OR pilates-based exercise OR Pilates Based Exercises OR Pilates-Based Exercises OR Exercises, Pilates-Based OR pilates OR physical exercise OR gymnastics OR gymnastic OR gymnastic* OR swimming OR locomotion OR locomotions OR locomotion* OR treadmill OR walking OR running OR aerobic OR aerobics OR aerobic* OR cycling OR jogging OR Exertion OR disability of function[text] OR occupational therapy OR occupational therapies OR functional therapy[text] OR functional therapies[text] OR training program OR physical education and training OR Physical Education, Training OR Physical Education OR Education, Physical OR fitness OR cardio training OR weight lifting OR power training OR muscle training OR rowing OR sports OR jump OR jumping

4. For outcome the following MeSH headings and text words were used:

quality of life OR Qol OR condition* OR physical fitness OR Fitness, Physical OR Physical Conditioning, Human OR Conditioning, Human Physical OR Conditionings, Human Physical OR Human Physical Conditioning OR Human Physical Conditionings OR Physical Conditionings, Human OR physical effort OR physical skill OR physical activity OR muscle strength OR muscular strength OR lung function OR pulmonary function OR vital capacity OR Depression OR Depressive Disorder OR Depression, involutional OR fear OR recovery of function OR physical endurance OR range of motion OR VO2 OR VO(2peak) OR ventilatory threshold OR heart rate OR endurance OR activity energy expenditure OR DXA scan OR activity participation OR mets score OR DeltaMetS OR Wingate anaerobic test OR steep ramp test OR dynamometer OR Six Minute Walk Distance OR 6MWD OR lateral step up OR Sit-to-Stand OR ten repetition maximum OR minimum chair height OR muscle power OR gross motor function OR GMFCS OR GMFM OR incremental shuttle walking OR sit-and-reach

5. For RCTs and CCTs the following MeSH headings and text words were used:

(randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab]) AND humans[mh] (Higgins 2011)

Final search:

1 AND 2 AND 3 AND 4 AND 5

[pt]=publication type
[tiab]=title or abstract
[sh]=subject heading
[mh]=MeSH term
[text]=text word
[*]=1+ more characters
[RCT]= randomised controlled trial
[CCT]= controlled clinical trial

 

Appendix 2. Search strategy for EMBASE/OVID

1. Forchildren the following Emtree terms and text words were used:    

1. infant/ or infancy/ or newborn/ or baby/ or child/ or preschool child/ or school child/
2. adolescent/ or juvenile/ or boy/ or girl/ or puberty/ or prepuberty/ or pediatrics/
3. primary school/ or high school/ or kindergarten/ or nursery school/ or school/
4. or/1-3
5. (infant$ or newborn$ or (new adj born$) or baby or baby$ or babies or neonate$ or perinat$ or postnat$).mp.
6. (child$ or (school adj child$) or schoolchild$ or (school adj age$) or schoolage$ or (pre adj school$) or preschool$).mp.
7. (kid or kids or toddler$ or adoles$ or teen$ or boy$ or girl$).mp.
8. (minors$ or (under adj ag$) or underage$ or juvenil$ or youth$).mp.
9. (puber$ or pubescen$ or prepubescen$ or prepubert$).mp.
10. (pediatric$ or paediatric$ or peadiatric$).mp.
11. (school or schools or (high adj school$) or highschool$ or (primary adj school$) or (nursery adj school$) or (elementary adj school) or (secondary adj school$) or kindergar$).mp.
12. or/5-11
13. 4 or 12

2. For childhood cancer the following Emtree terms and text words were used:

1. (leukemia or leukemi$ or leukaemi$ or (childhood adj ALL) or acute lymphocytic leukemia).mp.
2. (AML or lymphoma or lymphom$ or hodgkin or hodgkin$ or T-cell or B-cell or non-hodgkin).mp.
3. (sarcoma or sarcom$ or Ewing$ or osteosarcoma or osteosarcom$ or wilms tumor or wilms$).mp.
4. (nephroblastom$ or neuroblastoma or neuroblastom$ or rhabdomyosarcoma or rhabdomyosarcom$ or teratoma or teratom$ or hepatoma or hepatom$ or hepatoblastoma or hepatoblastom$).mp.
5. (PNET or medulloblastoma or medulloblastom$ or PNET$ or neuroectodermal tumors or primitive neuroectodermal tumor$ or retinoblastoma or retinoblastom$ or meningioma or meningiom$ or glioma or gliom$).mp.
6. (pediatric oncology or paediatric oncology).mp.
7. ((childhood adj cancer) or (childhood adj tumor) or (childhood adj tumors) or childhood malignancy or (childhood adj malignancies) or childhood neoplasm$).mp.
8. ((pediatric adj malignancy) or (pediatric adj malignancies) or (paediatric adj malignancy) or (paediatric adj malignancies)).mp.
9. ((brain adj tumor$) or (brain adj tumour$) or (brain adj neoplasms) or (brain adj cancer$) or brain neoplasm$).mp.
10. (central nervous system tumor$ or central nervous system neoplasm or central nervous system neoplasms or central nervous system tumour$).mp.
11. intracranial neoplasm$.mp.
12. LEUKEMIA/ or LYMPHOMA/ or brain tumor/ or central nervous system tumor/ or teratoma/ or sarcoma/ or osteosarcoma/
13. nephroblastoma/ or neuroblastoma/ or rhabdomyosarcoma/ or hepatoblastoma/ or medulloblastoma/ or neuroectodermal tumor/ or retinoblastoma/ or meningioma/ or glioma/ or childhood cancer/
14. or/1-13

3. Forcancer the following Emtree terms and text words were used:

1. (cancer or cancers or cancer$).mp.
2. (oncology or oncolog$).mp. or exp oncology/
3. (neoplasm or neoplasms or neoplasm$).mp. or exp neoplasm/
4. (carcinoma or carcinom$).mp. or exp carcinoma/
5. (tumor or tumour or tumor$ or tumour$ or tumors or tumours).mp. or exp tumor/
6. (malignan$ or malignant).mp.
7. (hematooncological or hemato oncological or hemato-oncological or hematologic neoplasms or hematolo$).mp. or exp hematologic malignancy/
8. or/1-7

4. For physical excercise training therapy the following Emtree terms and text words were used:

1. (exercise or exercises or exercis$).mp.
2. exp exercise/
3. (physical exercise or physical exercises).mp.
4. exp isometric exercise/
5. (isometric exercise or isometric exercises).mp.
6. (warm up exercise or warm up exercises or warm-up exercise or warm-up exercises).mp.
7. exp aerobic exercise/
8. (aerobic exercise or aerobic exercises).mp.
9. exp kinesiotherapy/
10. (exercise therapy or exercise therapies).mp.
11. (physical therapy modality or physical therapy modalities).mp.
12. exp pediatric physiotherapy/ or exp physiotherapy/
13. (physiotherapy or physiotherapies).mp.
14. (physical therapy technique or physical therapy techniques or physical therapy or physical therapies).mp.
15. exp exercise test/
16. (exercise test or exercise tests).mp.
17. exp stretching exercise/
18. (muscle stretching exercise or muscle stretching exercises).mp.
19. (strengthen$ or stretch$).mp.
20. exp muscle exercise/ or stability training.mp. or exp muscle training/
21. training$.mp.
22. (exercise movement technique or exercise movement techniques).mp.
23. (exercise movement technic or exercise movement technics).mp.
24. (pilates-based exercise or pilates based exercise or pilates-based exercises or pilates based exercises).mp.
25. pilates.mp. or exp pilates/
26. physical exercise.mp.
27. (gymnastic or gymnastics or gymnastic$).mp.
28. exp swimming/ or swimming.mp.
29. exp locomotion/
30. (locomotion or locomotions or locomotion$).mp.
31. exp treadmill/ or exp treadmill exercise/
32. treadmill.mp.
33. walking.mp. or exp walking/
34. exp running/ or running.mp.
35. cycling.mp. or exp cycling/
36. jogging.mp. or exp jogging/
37. (aerobic or aerobics or aerobic$).mp.
38. exertion.mp.
39. disability of function.mp.
40. exp occupational therapy/
41. (occupational therapy or occupational therapies).mp.
42. (functional therapy or functional therapies).mp.
43. training program.mp.
44. (physical education and training).mp.
45. physical education.mp. or exp physical education/
46. fitness.mp. or exp fitness/
47. cardio training.mp.
48. weight lifting.mp. or exp weight lifting/
49. power training.mp.
50. muscle training.mp.
51. rowing.mp. or exp rowing/
52. sports.mp. or exp sport/
53. exp jumping/ or (jump or jumping).mp.
54. or/1-53

5. For outcome the following Emtree terms and text words were used:

1. exp "quality of life"/
2. (quality of life or QoL).mp.
3. general condition improvement/
4. condition$.mp.
5. physical fitness.mp. or exp fitness/
6. (human physical conditioning or human physical conditionings).mp.
7. physical effort.mp.
8. physical skill.mp.
9. physical activity.mp. or exp physical activity/
10. (muscle strength or muscular strength).mp. or exp muscle strength/
11. lung function.mp. or exp lung function/
12. pulmonary function.mp.
13. vital capacity.mp. or exp vital capacity/
14. depression.mp. or exp depression/
15. depressive disorder.mp.
16. involutional depression.mp. or exp involutional depression/
17. fear.mp. or exp fear/
18. recovery of function.mp. or exp convalescence/
19. physical endurance.mp. or exp endurance/
20. range of motion.mp. or exp "range of motion"/
21. (VO2 or VO2peak).mp.
22. (VO adj 2peak).mp.
23. ventilatory threshold.mp.
24. heart rate.mp. or exp heart rate/
25. exp endurance/ or endurance.mp.
26. exp energy expenditure/ or activity energy expenditure.mp.
27. exp dual energy X ray absorptiometry/ or DXA scan.mp.
28. activity participation.mp.
29. mets score.mp.
30. (mets or DeltaMetS).mp.
31. Wingate anaerobic test.mp.
32. exp Steep Ramp Test/ or steep ramp test.mp.
33. dynamometer.mp. or exp dynamometer/
34. (Six Minute Walk Distance or 6MWD).mp.
35. lateral step up.mp.
36. Sit-to-Stand.mp.
37. ten repetition maximum.mp.
38. minimum chair height.mp.
39. muscle power.mp.
40. (gross motor function or GMFCS or GMFM).mp.
41. incremental shuttle walking.mp.
42. sit-and-reach.mp.
43. or/1-42

6. For RCTs and CCTs the following Emtree terms and text words were used:

1. Randomized Controlled Trial/
2. Controlled Clinical Trial/
3. randomized.ti,ab.
4. placebo.ti,ab.
5. randomly.ti,ab.
6. trial.ti,ab.
7. groups.ti,ab.
8. drug therapy.sh.
9. or/1-8
10. Human/
11. 9 and 10

Final search

1 and (2 or 3) and 4 and 5 and 6

[mp]=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name
[ti,ab]=title, abstract
[sh]=subject heading
[/]=Emtree term
[$]=1+more characters
[RCT]= randomised controlled trial
[CCT]= controlled clinical trial

 

Appendix 3. Search strategy for Central Register of Controlled Trials (CENTRAL)

1. For children the following text words were used for searching Title, Abstract, or Keywords:

infant OR infan* OR newborn OR newborn* OR new-born* OR baby OR baby* OR babies OR neonat* OR perinat* OR postnat* OR child OR child* OR schoolchild* OR schoolchild OR school child OR school child* OR kid OR kids OR toddler* OR adolescent OR adoles* OR teen* OR boy* OR girl* OR minors OR minors* OR underag* OR under ag* OR juvenil* OR youth* OR kindergar* OR puberty OR puber* OR pubescen* OR prepubescen* OR prepuberty* OR pediatrics OR pediatric* OR paediatric* OR peadiatric* OR schools OR nursery school* OR preschool* OR pre school* OR primary school* OR secondary school* OR elementary school* OR elementary school OR high school* OR highschool* OR school age OR schoolage OR school age* OR schoolage* OR infancy

2. For childhood cancer the following text words were used for searching Title, Abstract, or Keywords:

(leukemia OR leukemi* OR leukaemi* OR (childhood ALL) OR AML OR lymphoma OR lymphom* OR hodgkin* OR T-cell OR B-cell OR non-hodgkin OR sarcoma OR sarcom* OR Ewing* OR osteosarcoma OR osteosarcom* OR wilms tumor OR wilms* OR nephroblastom* OR neuroblastoma OR neuroblastom* OR rhabdomyosarcoma OR rhabdomyosarcom* OR teratoma OR teratom* OR hepatoma OR hepatom* OR hepatoblastoma OR hepatoblastom* OR PNET OR medulloblastoma OR medulloblastom* OR PNET* OR neuroectodermal tumors, primitive OR retinoblastoma OR retinoblastom* OR meningioma OR meningiom* OR glioma OR gliom* OR pediatric oncology OR paediatric oncology OR childhood cancer OR childhood tumor OR childhood tumors OR cancer or neoplasms or tumor or cancers or neoplasm or tumors)

3. For cancer the following text words were used for searching Title, Abstract, or Keywords:

cancer OR oncology OR oncolog* OR neoplasms OR neoplas* OR carcinoma OR carcinom* OR tumor OR tumour OR tumor* OR tumour* OR cancer* OR malignan* OR hematooncological OR hemato oncological OR hemato-oncological OR hematologic neoplasms OR hematolo* OR bone marrow transplantation OR bone marrow transplant* OR leukaemia OR lymphoma

4. For physical excercise training therapy the following text words were used for searching Title, Abstract, or Keywords:

exercise OR exercises OR exercis* OR Physical Exercise OR Physical Exercises OR Isometric Exercises OR Isometric Exercise OR Warm-Up Exercise OR Warm Up Exercise OR Warm-Up Exercises OR Aerobic Exercises OR Aerobic Exercise OR exercise therapy OR Exercise Therapies OR physical therapy modalities OR Physical Therapy Modality OR Physiotherapy (Techniques) OR Physiotherapies (Techniques) OR Physical Therapy Techniques OR Physical Therapy Technique OR exercise test OR exercise tests OR muscle stretching exercise OR muscle stretching exercises OR physical therapy OR physical therapies OR strengthen* OR stretch* OR physiotherapy OR physiotherap* OR stability training OR training* OR exercise movement technique OR exercise movement techniques OR exercise movement technic OR Exercise Movement Technics OR pilates based exercise OR pilates-based exercise OR Pilates Based Exercises OR Pilates-Based Exercises OR pilates OR physical exercise OR gymnastics OR gymnastic OR gymnastic* OR swimming OR locomotion OR locomotions OR locomotion* OR treadmill OR walking OR running OR aerobic OR aerobics OR aerobic* OR cycling OR jogging OR Exertion OR disability of function OR occupational therapy OR occupational therapies OR functional therapy OR functional therapies OR training program OR physical education and training OR Physical Education OR fitness OR cardio training OR weight lifting OR power training OR muscle training OR rowing OR sports OR jump OR jumping

5. For outcome the following text words were used for searching Title, Abstract, or Keywords:

quality of life OR Qol OR condition* OR physical fitness OR Human Physical Conditioning OR Human Physical Conditionings OR physical effort OR physical skill OR physical activity OR muscle strength OR muscular strength OR lung function OR pulmonary function OR vital capacity OR Depression OR Depressive Disorder OR involutional depression OR fear OR recovery of function OR physical endurance OR range of motion OR VO2 OR VO(2peak) OR ventilatory threshold OR heart rate OR endurance OR activity energy expenditure OR DXA scan OR activity participation OR mets score OR DeltaMetS OR Wingate anaerobic test OR steep ramp test OR dynamometer OR Six Minute Walk Distance OR 6MWD OR lateral step up OR Sit-to-Stand OR ten repetition maximum OR minimum chair height OR muscle power OR gross motor function OR GMFCS OR GMFM OR incremental shuttle walking OR sit-and-reach

Final search:

1 and (2 or 3) and 4 and 5

[*]=1+ more characters

 

Appendix 4. Search strategy for CINAHL

1. For children the following the following MeSH headings (MH) and text words were used for searching Title, Abstract, or Keywords:

"schoolage" OR (MH "Schools+") OR "peadiatric" OR "paediatric" OR "pediatric" OR (MH "Puberty+") OR "juvenile" OR "underage" OR "under age" OR ("teenager") or (MH "Adolescence+") OR "adolescent" OR "kids" OR "kid" OR "schoolchild" OR ("child*") or (MH "Child") ("newborn") or (MH "Infant, Newborn+") OR ("infant") or (MH "Infant+")

2. For cancer and childhood cancer the following the following MeSH headings (MH) and text words were used for searching Title, Abstract, or Keywords:

(MH "Central Nervous System Neoplasms+") OR "childhood tumour" OR "childhood tumor" "childhood cancer" OR (MH "Meningioma") OR (MH "Retinoblastoma") OR (MH "Neuroectodermal Tumors+") OR (MH "Ameloblastoma") OR (MH "Teratoma") OR (MH "Rhabdomyosarcoma") OR (MH "Neuroblastoma") OR (MH "Nephroblastoma") OR (MH "Osteosarcoma+") OR (MH "Sarcoma, Ewing's") OR (MH "Sarcoma+") or (MH "Osteosarcoma") OR (MH "Lymphoma+") OR (MH "Leukemia+") OR (MH "Bone Marrow Transplantation+") or (MH "Bone Marrow Neoplasms") OR "hemato oncological" OR ("malignancy") or (MH "Hematologic Neoplasms+") OR "tumour" OR "tumor" OR (MH "Carcinoma+") OR (MH "Neoplasms+") OR ("oncology") or (MH "Oncology+") or (MH "Pediatric Oncology Nursing") or (MH "Oncologic Care") OR ("cancer") or (MH "Neoplasms")

3. For physical exercise training therapy the following the following MeSH headings (MH) and text words were used for searching Title, Abstract, or Keywords:

("sports") or (MH "Sports+") or (MH "Amateur Sports") or (MH "Aquatic Sports") (MH "Rowing") or (MH "Ergometry") OR ("muscle training") or (MH "Muscle Strengthening") OR "power training" OR (MH "Weight Lifting") OR ("cardio training") or (MH "Athletic Training") or (MH "Athletic Training Programs") OR ("fitness") or (MH "Physical Fitness") OR (MH "Physical Education and Training+") OR "training program" "functional therapies" OR "functional therapy" OR (MH "Occupational Therapy+") or (MH "Pediatric Occupational Therapy") OR "disability of function" OR (MH "Exertion") OR (MH "Cycling") or (MH "Ergometry") OR (MH "Running") or (MH "Running, Distance") OR (MH "Walking") or (MH "Sports") OR (MH "Treadmills") OR (MH "Locomotion") or (MH "Movement") OR (MH "Swimming") OR (MH "Gymnastics") OR ("pilates") or (MH "Pilates") OR (MH "Therapeutic Exercise+") or (MH "Aerobic Exercises") or (MH "Arm Exercises") or (MH "Back Exercises") OR (MH "Stretching") OR (MH "Exercise Test+") or (MH "Exercise Test, Cardiopulmonary") or (MH "Exercise Test, Muscular+") OR "physiotherapy" OR ("exercise therapy") or (MH "Therapeutic Exercise+") or (MH "Exercise Therapy: Ambulation (Iowa NIC)") or (MH "Exercise Therapy: Balance (Iowa NIC)") or (MH "Exercise Therapy: Joint Mobility (Iowa NIC)") or (MH "Exercise Therapy: Muscle Control (Iowa NIC)") OR ("physical therapy") or (MH "Physical Therapy+") or (MH "Pediatric Physical Therapy") or (MH "Physical Therapy Practice, Evidence-Based") or (MH "Physical Therapy Practice, Research-Based") OR "therapies" OR (MH "Aerobic Exercises+") or (MH "Therapeutic Exercise+") OR (MH "Warm-Up Exercise") (MH "Isometric Contraction") or (MH "Isometric Exercises") OR ("physical") or (MH "Education, Physical Therapy") or (MH "Home Physical Therapy") or (MH "Pediatric Physical Therapy") or (MH "Physical Activity") OR ("exercise") or (MH "Exercise+") or (MH "Abdominal Exercises") or (MH "Aerobic Exercises+") or (MH "Anaerobic Exercises") or (MH "Aquatic Exercises") or (MH "Arm Exercises") or (MH "Back Exercises")

4. For outcome the following the following MeSH headings (MH) and text words were used for searching Title, Abstract, or Keywords:

"shuttle walking test" or ("repetition maximum") or (MH "Anaerobic Threshold") (MH "Rising") OR("lateral step up") or (MH "Step") OR ("six minute walking distance") or (MH "Running, Distance") or (MH "Walking+") OR(MH "Dynamometry") OR "steep ramp test" OR ("anaerobic test") or (MH "Achievement Tests") OR "wingate" OR (MH "Basal Metabolism") or (MH "Glucose Metabolism Disorders") OR (MH "Leisure Participation (Iowa NOC)") or (MH "Play Participation (Iowa NOC)") OR ("DXA scan") or (MH "Biometrics") OR (MH "Energy Metabolism+") or (MH "Activities of Daily Living+") or (MH "Human Activities+") OR ("endurance") OR (MH "Heart Rate+") or (MH "Heart Rate Variability") OR (MH "Respiratory Muscles") OR "VO2" OR "Vo2 peak" OR (MH "Range of Motion") or (MH "Range of Motion (Saba CCC)") or (MH "Motion Therapy, Continuous Passive") or (MH "Motion") OR (MH "Physical Endurance+") OR (MH "Recovery") or (MH "Functional Assessment") OR (MH "Fear+") OR (MH "Depression+") OR ("lung function") or (MH "Respiratory Function Tests+") or (MH "Functional Status") OR ("muscle strength") or (MH "Muscle Strength+") or (MH "Muscle Strengthening+") or (MH "Exercise Test, Muscular+") OR ("physical skill") or (MH "Exercise Test") or (MH "Motor Skills") or (MH "Social Skills") or (MH "Social Skills Training") OR (MH "Exertion") or (MH "Education, Physical Therapy") or (MH "Home Physical Therapy") OR (MH "Physical Fitness+") or (MH "Fitness Centers") OR (MH "Conditioning (Psychology)") or (MH "Conditioning, Cardiopulmonary") OR (MH "Quality of Life+") or (MH "Health and Life Quality (Iowa NOC) (Non-Cinahl)+")

5. For RCTs and CCTs the following MeSH headings and text words were used: (MH "randomized controlled trial") or (MH "controlled clinical trial") or (MH "randomized") or (MH "placebo") or ("drug therapy") or (MH "randomly+") or (MH "trial") or (MH "groups+") and (MH "human")

 Final search

1 and 2 and 3 and 4 and 5

[MH] = MeSH headings: exploding retrieves all documents containing any of the subject terms below the term selected.

[+] = related terms are also taken into the search: In case of a plus sign (+) next to a narrower or related term, there are narrow terms below the term.

[RCT]= randomised controlled trial
[CCT]= controlled clinical trial

 

Appendix 5. Search strategy for PEDro

1. For children the textword "paediatrics" was used in <Subdiscipline> field

2. For cancer and childhood cancer the textwords "cancer" OR "oncolog" OR "neoplasm" OR "carcinom" or "tumor" OR "malignan" were used in the <Abstract & Title> field

3. For physical exercise training therapy the textword "exercise" was used in the <Abstract & Title> field and combined (with OR) with the textwords "fitness training" OR "hydrotherapy, balneotherapy" OR "neurodevelopmental therapy, neurofacilitation" OR "skill training" OR "strength training" in the <Therapy> field

4. For RCTs and CCTs the textword "clinical trial" was used in the <Method> field

Final search

1 and 2 and 3 and 4

For outcome no search terms were defined

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Last assessed as up-to-date: 5 March 2012.


DateEventDescription

28 August 2013AmendedAs part of an audit of reviews by the Cochrane Editorial Unit some comments were received via email; these comments have been incorporated into the discussion and the Summary of Findings table sections of the review.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

KB and PT where the principle authors of this Cochrane review and all other authors contributed to the writing of the review. ED and MV were involved in the overall content and quality of the review while TT also was the third-party arbitrator in case of discrepancies or no consensus and the expert on childhood physiology discussions. GJK is head of the paediatric oncology/haematology department of VU University Medical Center. He was responsible for the medical and oncological background of the review protocol.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms
 

Internal sources

  • Pediatric oncology hematology, VU University Medical Center, Amsterdam, Netherlands.
  • Child Development & Exercise Center, Wilhelmina Children's Hospital/University Medical Center Utrecht, Netherlands.
  • Dutch Cochrane Center (DCC), Netherlands.
    systematic review course

 

External sources

  • Alphe d'HuZes/Dutch Cancer Society, Netherlands.
  • Roparun, Netherlands.
  • VONK, Netherlands.
    VUmc Onderzoek Naar Kinderkanker; a single-centre research fund for paediatric oncology research programmes

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

The review differed from the protocol on a number of aspects.

Instead of using the Cochrane Childhood Cancer Group module for the risk of bias, we used the latest update, which was described in the Cochrane Handbook for Systematic Reviews of Interventions of March 2011 to assess the risk of bias of the included studies (Higgins 2011).

The study of Hartman 2009 included children at diagnosis who were aged one to 18 years. In the protocol we reported our intention to include studies with participants older than three years of age. We opted to change this because some of the studies introduced a tailored exercise programme that could be adjusted for the child's age. To see changes in outcomes a child needs to be trainable, co-operative, and testable. For intensive training, which we had in mind when writing the protocol, children aged less than three years will not be able to complete the exercises. However, the study of Hartman 2009 did not assess the effect of a structured intensive training programme, but included physiotherapy sessions with exercises that were appropriate for all ages.

We added possible tests that could have been used to assess the primary outcome.

Finally, we added the clinical trial database as resource for the search of ongoing trials (www.clinicaltrials.gov). We also searched the clinical trial database for missed studies.

 

Index terms

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Index terms

Medical Subject Headings (MeSH)

*Exercise; *Physical Fitness; Antineoplastic Agents [therapeutic use]; Body Mass Index; Bone Density; Controlled Clinical Trials as Topic; Muscle Strength [physiology]; Muscle, Skeletal [physiology]; Neoplasms [therapy]; Physical Endurance [physiology]; Precursor Cell Lymphoblastic Leukemia-Lymphoma [*drug therapy]; Quality of Life; Randomized Controlled Trials as Topic; Range of Motion, Articular [physiology]

MeSH check words

Adolescent; Child; Female; Humans; Male

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Hartman 2009 {published and unpublished data}
  • Hartman A, Te Winkel ML, Van Beek RD, De Muinck Keizer-Schrama SM, Kemper HC, Hop WC, et al. A randomized trial investigating an exercise program to prevent reduction of bone mineral density and impairment of motor performance during treatment for childhood acute lymphoblastic leukemia. Pediatric Blood and Cancer 2009;53(1):64-71.
Macedo 2010 {published data only}
  • De Macedo TMF, Oliveira KMC, Melo JBDC, De Medeiros MG, De Medeiros Filho WC, Ferreira GMH, et al. Inspiratory muscle training in patients with acute leukemia: preliminary results. Revista Paulista de Pediatria 2010;28:352-8.
Marchese 2004 {published data only}
Moyer-Mileur 2009 {published data only}
  • Moyer-Mileur LJ, Ransdell L, Bruggers CS. Fitness of children with standard-risk acute lymphoblastic leukemia during maintenance therapy: response to a home-based exercise and nutrition program. Journal of Pediatric Hematology/Oncology 2009;31(4):259-66.
Yeh 2011 {published data only}
  • Yeh CH, Man Wai JP, Lin US, Chiang YC. A pilot study to examine the feasibility and effects of a home-based aerobic program on reducing fatigue in children with acute lymphoblastic leukemia. Cancer Nursing 2011;34:3-12.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Chamorro-Vina 2010 {published data only}
  • Chamorro-Vina C, Ruiz JR, Santana-Sosa E, Gonzalez Vicent M, Madero L, Perez M, et al. Exercise during hematopoietic stem cell transplant hospitalization in children. Medicine and Science in Sports and Exercise 2010;42(6):1045-53.
Hinds 2007 {published data only}
  • Hinds PS, Hockenberry M, Rai SN, Zhang L, Razzouk BI, Cremer L, et al. Clinical field testing of an enhanced-activity intervention in hospitalized children with cancer. Journal of Pain and Symptom Management 2007;33(6):686-97.
Speyer 2010 {published data only}
Te Winkel 2008 {published data only}
  • Winkel Te M, Beek Van R, Muinck Keizer De-Schrama S, Hop W, Heuvel Van den M, Pieters R. A randomised trial investigating an exercise program to prevent osteoporosis and motor problems during treatment for childhood acute lymphoblastic leukemia. Pediatric Blood and Cancer 2008;50(5 Suppl):121.

References to ongoing studies

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Braam 2011 {published data only}
  • Braam KI, Van Dijk EM, Veening MA, Van Dulmen-den Broeder E, Huisman J, TakkenT, et al. Quality of life in motion: a combined physical exercise and psychosocial training program to improve physical fitness in children with cancer. www.trialregister.nl/trialreg/admin/rctview.asp?TC=1531 (accessed 6 March 2013).
Cox 2011 {published data only}
  • Cox CL. Physical activity to modify sequelae and quality of life in childhood acute lymphoblastic leukemia (PAQOL). clinicaltrials.gov/ct2/show/NCT00902213 (accessed 6 March 2013).

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
ACSM 2010
  • American College of Sports Medicine. ACSM's Guidelines for Exercise Testing and Prescription. 8th Edition. Philadelphia, PA: Lippincott Williams & Wilkins, 2010.
Arroyave 2008
  • Arroyave WD, Clipp EC, Miller PE, Jones LW, Ward DS, Bonner MJ, et al. Childhood cancer survivors' perceived barriers to improving exercise and dietary behaviors. Oncology Nursing Forum 2008;35(1):121-30.
Aznar 2006
  • Aznar S, Webster AL, San Juan AF, Chamorro-Viña C, Maté-Muñoz JL, Moral S, et al. Physical activity during treatment in children with leukemia: a pilot study. Applied Physiology, Nutrition, and Metabolism 2006;31(4):407-13.
Cancer Research UK 2011
  • Cancer Research UK. Childhood cancer incidences. www.cancerresearchuk.org/cancer-info/cancerstats/childhoodcancer/incidence/ (accessed 8 March 2013).
Cox 2008
Cramp 2008
De Caro 2006
  • De Caro E, Fioredda F, Calevo MG, Smeraldi A, Saitta M, Hanau G, et al. Exercise capacity in apparently healthy survivors of cancer. Archives of Disease in Childhood 2006;91(1):47-51.
Dimeo 2001
Faigenbaum 2010
  • Faigenbaum AD, Myer GD. Pediatric resistance training: benefits, concerns, and program design considerations. Current Sports Medicine Reports 2010;9(3):161-8.
Ganley 2011
  • Ganley KJ, Paterno MV, Miles C, Stout J, Brawner L, Girolami G, et al. Health-related fitness in children and adolescents. Pediatric Physical Therapy 2011;23(3):208-20.
Geenen 2007
  • Geenen MM, Cardous-Ubbink MC, Kremer LC, van den Bos C, van der Pal HJ, Heinen RC, et al. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. Journal of American Medical Association 2007;297(24):2705-15.
Guyatt 2008
  • Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. British Medical Journal 2008;336(7650):924-6.
Guyatt 2008a
Hartman 2008
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Hovi 1993
Huang 2011
  • Huang TT, Ness KK. Exercise interventions in children with cancer: a review. International Journal of Pediatrics 2011;2011:461512. [DOI: 10.1155/2011/461512]
National Cancer Institute 2012
  • American Cancer Society. Cancer Facts & Figures 2012. www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-031941.pdf (accessed 6 March 2013).
Ness 2005
  • Ness KK, Mertens AC, Hudson MM, Wall MM, Leisenring WM, Oeffinger KC, et al. Limitations on physical performance and daily activities among long-term survivors of childhood cancer. Annals of Internal Medicine 2005;143(9):639-47.
Ness 2009
Oldervoll 2004
  • Oldervoll LM, Kaasa S, Hjermstad MJ, Lund JA, Loge JH. Physical exercise results in the improved subjective well-being of a few or is effective rehabilitation for all cancer patients?. European Journal of Cancer 2004;40(7):951-62.
RevMan 2011
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
San Juan 2008
  • San Juan AF, Chamorro-Viña C, Maté-Muñoz JL, Fernández del Valle M, Cardona C, Hernández M, et al. Functional capacity of children with leukemia. International Journal of Sports Medicine 2008;29(2):163-7.
Schmitz 2005
  • Schmitz KH, Holtzman J, Courneya KS, Mâsse LC, Duval S, Kane R. Controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. Cancer Epidemiology, Biomarkers & Prevention 2005;14(7):1588-95.
Schneider 2007
  • Schneider CM, Hsieh CC, Sprod LK, Carter SD, Hayward R. Cancer treatment-induced alterations in muscular fitness and quality of life: the role of exercise training. Annals of Oncology 2007;18(12):1957-62.
Van Brussel 2006
  • Van Brussel M, Takken T, Van der Net J, Engelbert RH, Bierings M, Schoenmakers MA, et al. Physical function and fitness in long-term survivors of childhood leukaemia. Pediatric Rehabilitation 2006;9(3):267-74.
Van Brussel 2011
  • van Brussel M, van der Net J, Hulzebos E, Helders PJM, Takken T. The Utrecht approach to exercise in chronic childhood conditions: the decade in review. Pediatric Physical Therapy 2011;23:2-14.
Warner 1998
Warner 2008
Watson 2004
Winter 2009
Winter 2010
  • Winter C, Müller C, Hoffmann C, Boos J, Rosenbaum D. Review, physical activity and childhood cancer. Pediatric Blood and Cancer 2010;54:501-10.
Wright 1998
Wright 2005
  • Wright MJ, Galea V, Barr RD. Proficiency of balance in children and youth who have had acute lymphoblastic leukemia. Physical Therapy 2005;85(8):782-90.