Efficacy of Cognitive and Physical Trainings in Pediatric Cancer Survivors

2016-04-25 19:38:21 | BioPortfolio


Cancer survival comes at a price: pediatric cancer survivors have a high risk for a wide range of cognitive difficulties, particularly survivors of cancer involving the central nervous system (CNS, e.g., brain tumors [BT]) are prone to neurocognitive impairments in areas such as executive functions, working memory, attention, memory, visuospatial and motor skills, processing speed as well as language. The aim of this interdisciplinary longitudinal study is to extend empirical knowledge on training and transfer effects in children with a history of cancer. It is hypothesized that early cognitive and physical interventions affect the remediation of pediatric cancer survivors in terms of cognitive functions. These changes are further hypothesized to be associated with white matter changes.


Aims and Hypotheses:

The overall purpose of this study is threefold: first, this study aims to deepen the knowledge about particular patterns of long-term cognitive impairment in pediatric cancer survivors. Understanding the nature of cognitive deficits in this population will be helpful for developing tailored therapeutic strategies. Second, the availability of well-designed child-friendly evidence-based training is of major clinical relevance to prevent school problems and further decline of cognitive functions. Third, the detection of training-induced neuronal changes in white-matter structure will give insight into the functional plasticity of the child's brain. In addition, training-induced changes in white matter would build strong evidence for the effect of the particular intervention.

The following hypotheses will be assessed in particular in the present study:

1. Children with history of brain tumors (BT) show particular problems in memory and attention, resulting in a general deficit in several cognitive areas. Children with a history of cancer without involvement of the CNS show fewer problems than children with a history of cancer with BT in the same cognitive domains but more problems than healthy control children.

2. Standardized working memory training leads to improvement of working memory performance. Transfer of the training effect especially to the areas of executive functions, memory and attention is expected.

3. Physical training leads to improvement of coordination, endurance and motor strength. A transfer to several cognitive areas (i.e. executive functions) and physical self-concept is expected.

4. After working memory training and physical training, the white matter structure of the patients will show significant changes in fractional anisotropy. There will also be changes in functional connectivity.

5. Neuropsychological effects of training will still be present after 6 months post training for both experimental groups.

All comparisons will be carried out on an individual level (intra-individual level, primary objective) as well as on an inter-individual level (between-groups comparisons, secondary objective). The level of significance is set to α = 0.05.


Cancer Survivors: Researchers will include 180 children and adolescents aged 7-16 years who received an initial diagnosis of cancer with / without CNS (central nervous system) involvement in the past 7 years and terminated their treatment (surgery, radiation, and / or chemotherapy) at least 12 months prior to their participation in the study. Cancer survivors will be recruited at two different specialized pediatric units in Switzerland. In order to minimize the heterogeneity of the sample, children with a history of cancer without CNS involvement and only surgical removal of the tumor without subsequent radiation and / or chemotherapy will be excluded from the study. Because of the increased likelihood of drop-out of children with a history of cancer in a longitudinal study, more than the statistically required quantity of participants (> 27 children per group) will be recruited to reach sufficient statistical power.

Healthy Controls: 40 healthy children and adolescents (matched for age and gender) will be included in the first assessment and serve as a healthy control sample. They will be recruited mainly via their siblings, who are included in the cancer survivor group and also from personal acquaintances among hospital staff and the study collaborators.


The present study is designed as a randomized stratified controlled trial including two intervention groups, one waiting group (children with a history of cancer [both CNS+ (with involvement of the CNS) and CNS- (without involvement of the CNS] and a healthy control group (matched for age and gender). All cancer survivors will be assigned to either intervention group A (cognitive training) or intervention group B (physical training). However, some children of the patient group will be allocated to a waiting-control group (group C) to determine the training effects and their training starts later on. Stratification will be applied by etiology (CNS- vs. CNS+) and age (younger vs. older children). Children with physical restraints (e.g. remaining paresis after surgery) who are not able to perform physical activities will be assigned to group A. As this assignment breaks the randomization, these children will be excluded from between-groups comparisons and only exploratively analyzed within a separate observation group. However, their performances on the intra-individual level (performance before and after the training) will be analyzed within group A.

Neuropsychological assessment will be carried out before the intervention / training and re-performed with all participants at the end of the memory training or physical training and at 6 months post training. Structural and functional imaging will be performed prior and shortly after working memory training and physical training. A 3 Tesla whole body MRI system will be used. Anatomical imaging will be obtained using a sequence for T1 weighted structural brain imaging with whole brain coverage. Structural connectivity images will be acquired by using a q-ball sequence, functional connectivity will be measured by using a multiband echo planar imaging sequence (MB EPI). Pre- and post-processing of the structural data will be performed using statistical software.


All 180 participants with a history of cancer will be randomly but in a stratified manner as described above assigned to one of three groups (group A, B and C). Written informed consent will be obtained of all participants and / or their parents / legal guardians.

Group A (n1= 30 CNS+, n2 = 30 CNS-) will undergo a working memory training program (Training A). The children will receive individual memory training based on the computer program "Cogmed RM" and will be supervised by trained neuropsychologists. Its efficacy in the use with children with cancer has been recently published. The children will undergo 30 - 35 training sessions "online"; each session takes about 45 minutes and consists of a selection of various tasks that target the different aspects of working memory. The difficulty level of the training is always adjusted based on the user's performance. The children will perform the memory training program at home over a period of 10 weeks. The child and a licensed Cogmed RM coach (neuropsychologist) will review and monitor the results of each day's training online. In an initial session at the Hospital (Zurich or Bern) the Cogmed RM coach plans and structures the training together with the child and the parents. The coach will provide weekly supervision and feedback on the child's performance and progress via phone call to the child's home. In the closing session with the child and the parents, the training experience will be reviewed .

Group B (n1= 30 CNS+, n2 = 30 CNS-) will receive a physical training that can be executed at home (Training B). The training will be based on xbox Kinect games and comprise games and activities such as jump'n'run games, physical training, and dance activities. All material will be provided by the University Hospital Bern. One training session will last approximately 45 minutes and will be performed 4 days a week over a period of 10 weeks.

Group C (n1= 30 CNS+, n2 = 30 CNS-) will serve as a waiting control group and will receive either the physical or the working memory training program after completion of the Neuropsychological Assessment II.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Pediatric Cancer


Working Memory Training, Physical Training


Not yet recruiting


University Hospital Inselspital, Berne

Results (where available)

View Results


Published on BioPortfolio: 2016-04-25T19:38:21-0400

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