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.