Discussion
In this systematic review 28 articles were identified investigating the
potential impact of an intervention on cognitive functioning in
pediatric brain tumor patients. The included articles described a
variety of lifestyle, cognitive, and pharmacological possibilities.
First, exercise training had a beneficial impact on processing speed and
long-term memory, and on anxiety and emotional
control13,40. However, none of the lifestyle
interventions reported on effect size. The positive effects of a
exercise intervention were greater if the activities occurred in a group
setting, whereas they were not amplified by adding attentional tasks to
the exercise training13,34. For in-group training, it
is unclear whether the social stimulation caused additional improvement
of neurocognition or rather it had led to more intensive physical
training35,40. Overall, the included studies
consolidated the idea that exercise training is easily accessible, safe,
and that it can be initiated at any moment after
diagnosis13,35,40. The benefits for patients with a
PBT are likely to be even more evident if exercise training is
integrated into a sustainable healthy lifestyle, rather than being used
as a short-term intervention34. Incorporating exercise
training in a healthy lifestyle may be crucial, not only for its
potential neurocognitive benefits but also for many other health-related
factors that may be compromised in patients with a
PBT2,35,40–42.
In contrast to the low number of physical exercise studies, most of the
existing studies focused on cognitive interventions. These approaches
either aim to target and improve one specific neurocognitive domain, or
they are designed to teach compensatory strategies. Based on the
reported effect sizes most promising outcomes were found for Cogmed in
the domains of WM, executive functioning and symbolic WM; for CRP in the
domains of learning strategies, inattention, and attention and
hyperactivity symptoms; and for CRC in the domains of processing speed
and visual memory 17,26–28,30,37,38. Other cognitive
interventions also showed a positive impact on neurocognition however,
their effect sizes were moderate or small, or they were not
reported43. Except for neurofeedback training, this
showed no effect on neurocognition16. It is important
to critically reflect on how cognitive impact is measured after a
cognitive intervention. If the intervention efficacy is assessed using
cognitive tests that overlap with the content of the training exercises,
the training effect can be limited to the specific tool-specific skill,
rather than a generalizable effect44,45. Therefore, to
increase ecological validity of the intervention results, it is
essential to incorporate a more broadened neurocognitive assessment
battery as well as patient- or parent-reported outcomes in daily
life46.
Regarding pharmacological possibilities, the current literature
described two pharmacological compounds for their potential mitigation
of NCI, namely MPH and donepezil. MPH showed to improve attention in
pediatric cancer patients with attentional problems. Nevertheless,
reported effect sizes are moderate to small and one study did not
confirm the improvement of attention21. Other domains
such as academic achievement and processing speed appeared to improve as
well, these results were inconsistent across different studies as well.
Disparities in study outcomes may be attributable to different
neurocognitive assessment batteries. Furthermore, results may not be
generalizable to patients with a PBT that have a NCI in domains other
than attention, and long-term safety and duration of effects is still
uncertain20,22,47. Donepezil was found to be effective
in irradiated patients with a PBT for both performance and
proxy-reported measures of executive functioning. However, similar to
MPH, there is no indication whether long-term safety can be guaranteed
and what neurocognitive effects would be39.
Notwithstanding the promising results found for the abovementioned
psychostimulants, multiple side effects were reported. By contrast,
cognitive interventions did not report specific side effects and only
one fall was reported in the lifestyle intervention studies, and
therefore provide initial good alternatives with limited potential side
effects.
Based on the results of the included studies, it may be concluded that a
tendency towards positive effects of neurocognitive interventions on NCI
in patients with a PBT exists. Nevertheless, some limitations must be
considered. A large methodological variability exists across included
studies, decreasing comparability and generalizability of the results to
the entire population of patients with a PBT. Also, study populations
were relatively small and effect size was not always reported.
Measurement of long-term effects in the studies is limited and the
impact of the intervention on lifestyle and daily-life functioning
should be considered. Additionally, each type of intervention comes with
their own advantages and disadvantages. For instance, digital
interventions are increasingly accessible, hence they are susceptible
for technical and ethical problems, and more parental involvement is
required48. Conversely, therapist-delivered
interventions are time-, labor- and
cost-intensive30,35. Though, in therapist-delivered
interventions, a therapist can better estimate how the patient is doing
and their progress, in order to adapt the intervention in time. Also,
personal contact is highly important in efficacy. Furthermore, even
though implementing cognitive interventions during treatment may be
particularly challenging for the pediatric patient during this stressful
period, early mitigation might yield larger effect sizes than
post-treatment interventions38,49–51.
Altogether, the heterogeneity of intervention results and the inherent
variability among patients with a PBT may suggest that a
one-size-fits-all cognitive intervention may not be achievable. A
patient-tailored implementation of neurocognitive interventions may be
more beneficial4,49. Therefore, it is advised that
these interventions should be contextualized alongside the
prevention-based neurocognitive follow-up model2. Such
model was proposed by Jacola et al. (2021), in which a primary
intervention level is intended for all patients with a PBT. This level
can encompass interventions like lifestyle- and behavioral
interventions, psychoeducation, social engagement, improving school
attendance and school engagement2,4,41. A second and a
third intervention level can target patients with more specific
neurocognitive risk factors and with more severe NCI. These patients may
need more intense and targeted support, based on individual
neurocognitive strengths and weaknesses as well as the patients’
resilience, fatigue and mental capacity2.
Interventions such as school-based accommodations, teaching
organizational strategies, time management, planning, cognitive
remediation and problem-solving training, may be appropriate for these
patients2,4,6,25.
This systematic review comprehensively reviewed the existing
intervention studies in pediatric brain tumors. Still, some limitations
need to be noted. First, articles were included if PBTs participated,
also if other diagnoses were included. This methodological choice
increases the extent of literature regarding possible interventions in
patients with a PBT. However, it could also contribute to a more
heterogeneous outcome and could complicate generalizability to the PBT
population in specific (vs. pediatric oncology patients). Furthermore,
we were unable to perform a meta-analysis given the large heterogeneity
of different study designs and neurocognitive assessment instruments. A
consensus on the neurocognitive assessment instruments and the optimal
timing of assessments would facilitate comparison between different
intervention methods and different studies 2. Finally,
by manual reference tracking, one additional study was identified, We
cannot exclude the possibility there may be other remaining articles
which were not detected.