Authors’ Contributions
Bullens Kristien: screening and review of articles, data analysis, data
interpretation, and writing of the manuscript; Sleurs Charlotte: design
of the review, screening and review of articles, data interpretation and
manuscript editing; Blommaert Jeroen: data interpretation and manuscript
editing; Lemiere Jurgen and Jacobs Sandra, conceptualization, design of
the review, data interpretation, and manuscript editing. All of the
authors approved the final version of the manuscript for submission.
FundingBullens Kristien is suported by “Kom op tegen Kanker” (grant:
KOTK/2018/11812/1) and Sleurs Charlotte (grant 12Y6122N) is supported by
Research Foundation Flanders (FWO). Funding organizations provide
financial resources to conduct research and do not review research
protocols.
Availability of data and materialsThe author confirms that all data generated or analyzed during this
study are included in this published article.
AbstractDue to a high burden of neurocognitive impairment on patients with a
pediatric brain tumor, interventions mitigating these symptoms are
highly needed. Currently, evidence on the efficacy and feasibility of
such interventions remain scarce. A systematic literature study was
performed based on four different databases (PubMed, Web of Science Core
Collection, Embase and PsycArticles). Resulting articles (n=2232) were
screened based on title and abstract, and full text. We included 28
articles, investigating cognitive effects of either a lifestyle
intervention (n=6), a cognitive training (n=15), or pharmacological
intervention (n=7). The most frequently studied interventions were the
Cogmed and methylphenidate. Most interventions showed short-term
efficacy. Fewer interventions also showed long-term maintenance of
positive results. Despite positive trends of these interventions,
results are heterogeneous, suggesting relatively limited efficacy of
existing interventions and more potential of more individualized as well
as multimodal approaches for future interventions.
Introduction
Over 40% of survivors of a pediatric brain tumor (PBT) experience
long-lasting neurocognitive impairment (NCI), which have a detrimental
impact on other psychosocial domains such as academic achievement,
marital status, and overall quality of life (QoL)1–3.
Hence, the medical field encounters major challenges in minimizing these
late effects during PBT survival3,4.
Complex interactions between tumor-, cancer therapy-, and patient-
related risk factors affect NCI4,5. Recently,
treatment protocols are being innovated towards a careful trade-off
between tumor treatment and sustaining neurocognitive and psychosocial
functions5. Patient-related risk factors, such as
access to healthcare, lifestyle, neurocognitive and social support, have
been associated with less NCI2,6. Targeting these risk
factors offer potential pathways to mitigate NCI and maintain
psychosocial well-being5. In addition to addressing
patient-specific risk factors, neurocognitive interventions aim to
directly target and improve neurocognitive functioning. Three general
categories of interventions can be distinguished, including: lifestyle-,
cognitive- and pharmacological interventions through neuro-protective
and restoring mechanisms. Physical exercise training has been shown to
improve neurocognition through mechanisms such as increased cerebral
blood flow, neurogenesis, and synaptic plasticity7,8.
Furthermore, cognitive rehabilitation can assist to engage brain
plasticity through retraining specific neurocognitive functions or by
teaching compensatory strategies. Finally, pharmacological compounds can
directly or indirectly ameliorate
neurotransmission4,8,9 7,8.
With this systematic review, we aim to provide a comprehensive overview
as well as an insight into the efficacy of all possible interventions
targeting NCI in patients with a PBT. In addition, a discussion of
clinical implications and necessary efforts for future research are
provided. Ultimately, these insights may facilitate evidence-based
guidelines for interventions targeting NCI, to preserve and improve
neurocognitive abilities of patients with a PBT.
Materials and Methods
2.1 Search Strategy
This review was conducted in accordance with the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses guidelines
(PRISMA)10. Comprehensive literature searches were
conducted within PubMed, Web of Science Core Collection, Embase and
PsycArticles databases, based on three main components: brain tumors,
neurocognitive intervention, and children. The detailed search strategy
is outlined in Supplementary Table 1.
2.2 Study Selection and data
collection
Title and abstract screening were conducted by two independent reviewers
(CS and KB) in Rayyan11. Interrater reliability
between the reviewers was calculated using the Cohen’s kappa coefficient
and any disagreements were resolved by discussion until
consensus12. The remaining articles were eligible for
inclusion after full text screening, if a study investigated the
efficacy of a neurocognitive intervention in patients with a PBT.
Studies were also required to fulfil following criteria: published in
English, sample size larger than 5, and at least 50% were patients with
cancer. Systematic screening was complemented by a manual search of
cited references from included articles.
Information was extracted from included studies using a predefined data
extraction sheet, capturing details such as information on the author,
publication year, type of intervention, study design, prescribed dose,
total number of inclusions, age at start of the intervention, age at
treatment/diagnosis, time since treatment/diagnosis, geographic
location, neurocognitive assessment battery, compliance, and key
results. Included articles were classified according to three
intervention categories: lifestyle, cognitive, and pharmacological.
Quality of individual studies were evaluated in accordance with the
PRISMA guidelines and risk of bias assessment is described in supporting
information10.