Survivors of paediatric leukaemia and brain tumour are at significantly increased risk for long-term cognitive impairments including executive function, memory, motor, visual-spatial and language deficits [1
]. Human neuroimaging studies as well as animal models suggest that these cancers may be associated with brain injury related to chemotherapy, radiation and/or surgery [4
]. In fact, neuroimaging studies of these children have revealed reduced brain volumes, impaired brain function and altered neurochemistry, even into adulthood [5
]. Increasing survival rates contribute to a large and growing cohort of cognitively affected children. The prospect of intervening to change this trajectory thus has tremendous significance—potentially affecting school services, family dynamics, vocational readiness and social services support.
Cognitive rehabilitation is a method of treatment for cognitive deficits that involves restoring impaired function and/or increased compensation for the area of deficit through strategy training and/or repeated skills practice [20
]. It has been implemented successfully in children with other forms of brain injury including traumatic brain injury (TBI) [21
] as well as other brain-based disorders such as attention-deficits [22
] and dyslexia [23
]. Butler et al. [24
] conducted a successful remediation program for attention deficits in young survivors of leukaemia and brain tumour involving multiple, in-person sessions. These results suggest that traditional, in-person cognitive rehabilitation is a promising treatment method for children with cancer; however, these programs tend to be costly, impractical and/or unavailable to the majority of patients and standardization across clinicians is difficult.
Children with leukaemia or brain tumour show deficits in executive function areas in addition to attention, including impairments in cognitive flexibility and working memory [25
]. Similar to attention, cognitive flexibility and working memory are executive function skills critical for goal-directed behaviour [27
]. Cognitive flexibility is the ability to generate alternate solutions to problems and fluidly shift between ideas and actions [28
]. Working memory refers to the manipulation of information in temporary storage [29
]. These skills are vulnerable to a variety of neuropsychiatric, developmental and medical conditions and tend to have diffuse effects on behaviour and quality-of-life, but are often the most difficult to assess and treat [27
]. Improving these skills can have positive downstream effects on other deficits including memory, social cognition, visual-spatial skills and expressive language [33
]. Thus, treatment for these skills may be the most likely means for having the greatest impact on cognitive outcome in paediatric cancer.
Computer-based cognitive intervention programs for children have become increasingly popular during the past several years [22
] and have many advantages over traditional approaches including immediate feedback, the ability to systematize delivery of the intervention and modifications to difficulty level, the ability to quantify progress and the provision of an entertaining and engaging interface. Studies of computer-based cognitive skills training programs demonstrate that they are at least equally effective as compared to traditional approaches [37
]. Computerized programs also allow for home practice, making them more accessible and practical for a wider range of participants. This may be particularly important for populations such as paediatric cancer patients whose condition may require isolation precautions during certain disease and treatment stages due to lowered immune function, for example.
However, the lack of direct clinician/researcher supervision may make home training more practical, but may also reduce motivation and compliance. These potential problems are increased in children and adolescents given that they often require more supervision and structure than adults. This may be particularly true of children and adolescents who have executive function impairments that reduce behavioural regulation. Children with executive functions who also have significant health problems may have even more difficulty with a home-based, computerized program. Paediatric cancer survivors tend to experience long-term fatigue, health issues and/or psychological difficulties [38
]. As a result, they may require more intensive clinical support and supervision during cognitive interventions. Therefore, one of the main goals of this pilot study was to determine the feasibility of implementing a computerized, home-based cognitive skills training program in a sample of children with cancer. This goal is important not only for evaluating executive function remediation specifically in paediatric cancer, but also to increase understanding regarding potential remediation alternatives for children in general.
A cognitive rehabilitation program for executive function was designed, including attention, cognitive flexibility and working memory skills remediation. A computer-based delivery of the intervention was chosen to significantly reduce participant and clinician burden and to provide a highly consistent intervention implementation. A one-armed, open, pilot trial of this program was conducted to test its feasibility and efficacy in children with paediatric cancer. Children with a history of either acute lymphoblastic leukaemia (ALL) or posterior fossa brain tumour were included as these are the diagnoses included in existing studies of cognitive and neurodevelopmental outcome in paediatric cancer. Additionally, these were the diagnostic categories included in previous paediatric cancer remediation studies [24
]. Furthermore, the authors did not want the results of the trial to be restricted to just one paediatric cancer type. While it was not feasible due to resource limitations to include every paediatric cancer in this trial, ALL and posterior fossa brain tumour are the most common paediatric cancers [41
] and thus it was believed that these categories would be the most representative of cancer-related brain injury in children for this initial, preliminary investigation.
Deficits in attention, cognitive flexibility and working memory, as well as other executive functions, tend to be associated with abnormalities in the prefrontal cortex in a variety of paediatric conditions [27
], including leukaemia and brain tumour [14
]. Functional MRI (fMRI) provides noninvasive, in vivo
assessment of cognitive rehabilitation treatment efficacy in terms of the intervention’s putative ability to result in neurobiologic changes that represent improved cognitive performance [42
]. Previous studies have shown significantly increased brain activation associated with various cognitive training programmes, irrespective of treatment length (some interventions as short as 30 minutes) [43
]. Thus, it was hypothesized that a cognitive rehabilitation program targeting executive function skills would be associated with increased prefrontal function.