A systematic review of interventions for neurocognitive dysfunctions in patients and survivors of a pediatric brain tumor.

Due 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 remains 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.

Associations between cancer-related distress and fatigue in childhood cancer survivors: A longitudinal study.

BACKGROUND AND AIMS: A chronic feeling of fatigue occurs in up to 85% of childhood cancer survivors (CCS). This phenomenon has a detrimental effect on quality of life, reintegration in daily life activities and psychosocial functioning of the patient. Therefore, it is important to elucidate potential individual risk and protective factors. METHODS: CCS who were treated in the University Hospital of Leuven, completed two annual questionnaires on cancer-related distress (fear of cancer recurrence and post-traumatic stress, resilience and fatigue). Associations between distress and fatigue levels were examined by performing cross-lagged panel analyses. Resilience was included as a potential moderator. These models included all within-time associations, stability paths, and cross-lagged paths. Gender and time since diagnosis were included as covariates. RESULTS: In total, 110 CCS participated in this study, aged 14-25 years (average time since diagnosis 12.2 years; 41.8% boys; diagnosed with leukemia/lymphoma [49%], solid tumor [15%], brain tumor [16%] or other [20%]). Fear of cancer recurrence and post-traumatic stress at baseline positively predicted fatigue 1 year later. Cross-lagged panel analyses showed that resilience did not buffer the effect of fear of cancer recurrence on fatigue, in contrary to our expectations. Stability coefficients were high for all study variables. CONCLUSION: This study indicates associations between cancer-related distress (fear of cancer recurrence and post-traumatic stress), resilience and cancer-related fatigue over time in CCS. Interventions to improve fatigue levels could be focusing on both tackling cancer-related distress, while improving resilience levels as well.

Effect of chemotherapy (with and without radiotherapy) on the intelligence of children and adolescents treated for acute lymphoblastic leukemia; a meta-analysis.

OBJECTIVE: This meta-analysis assesses cognitive functioning in children with acute lymphoblastic leukemia post-treatment who were treated with either chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). METHODS: The databases Pubmed and PsychInfo were searched between 1-1-2000 and 31-12-2021. Data were analyzed using Comprehensive Meta-Analysis (version 2). RESULTS: Mean weighted intelligence after treatment was 100.2 (number of studies n = 51, 95% CI: 98.8-101.5). For CT-only, it was 100.8 (95% CI: 99.5-102.2) and for CTRT 97.8 (95% CI: 95.9-100.2). Compared to recruited healthy controls, treated children had on average lower IQ scores (n = 23, mean difference -7.8, 95% CI: -10.7 to -5.0, p < 0.001). When looking only at studies using controls recruited from the patient's family, results remained significant (n = 5, mean difference -6.0, 95% CI: -8.6 to -3.5, p = 0.001). Meta-regressions aimed at identifying predictors of IQ after treatment failed to find an effect for sex or age. We could demonstrate an effect of time between diagnosis and IQ measurement for the CTRT treated patient (B = -0.26, 95% CI: -0.40 to -0.1, p = 0.002). CONCLUSIONS: IQ scores of patients treated with CT-only or CTRT treatment regimens did not differ from the normative population. However, compared to recruited control groups, patients showed lower mean IQ scores. The Flynn effect and/or selection effects may play a role in this discrepancy. Considering time since diagnosis may have a significant impact on IQ, at least in CTRT treated patients, long-term clinical follow-up of neurocognitive development may be prudent to detect possible (late) neurocognitive effects.

Identity Formation and General and Cancer-specific Functioning in Adolescent and Emerging Adult Survivors of Childhood Cancer: A Longitudinal Study into Directionality of Effects.

BACKGROUND: Adolescent and emerging adult survivors of childhood cancer generally adjust well psychologically similar to their peers. Nevertheless, some survivors are at greater risk for developing psychological and physical difficulties. To shed light on the psychosocial functioning of adolescent and emerging adult survivors of childhood cancer, personal identity formation and its interplay with general and cancer-specific functioning need to be investigated. PURPOSE: To examine the longitudinal associations linking identity formation to general and cancer-specific functioning in adolescent and emerging adult childhood cancer survivors using three-wave data over a 2-year period. METHODS: Dutch-speaking survivors (at baseline: n = 125; 53% female; age range: 14-25 years) treated at the pediatric oncology department of the University Hospitals Leuven (Belgium), completed self-report questionnaires at three annual timepoints. Directionality of effects and correlated changes were examined using cross-lagged structural equation modeling. RESULTS: Regarding general functioning, bidirectional effects occurred. Life satisfaction positively predicted identity synthesis and both life satisfaction and good physical functioning negatively predicted identity confusion over time. Identity synthesis, in turn, positively predicted life satisfaction and identity confusion negatively predicted good physical functioning over time. Regarding cancer-specific functioning, mainly unidirectional effects occurred. Post-traumatic stress symptoms negatively predicted identity synthesis and positively predicted identity confusion over time, whereas the reverse pattern of associations was found for benefit finding. Several correlated changes were found linking identity formation and psychosocial functioning as well. CONCLUSIONS: The present study uncovered clinically meaningful pathways linking identity formation to psychosocial functioning over time in adolescents and emerging adults who survived childhood cancer.

To shed light on the psychosocial functioning of adolescent and emerging adult survivors of childhood cancer, personal identity formation and its longitudinal interplay with general and cancer-specific functioning need to be investigated. Dutch-speaking survivors treated at the pediatric oncology department of the University Hospitals Leuven (Belgium), completed self-report questionnaires at three annual timepoints, resulting in three-wave data over a 2-year period. Regarding identity formation and general functioning, bidirectional effects occurred. Life satisfaction positively predicted identity synthesis and both life satisfaction and good physical functioning negatively predicted identity confusion over time. Identity synthesis, in turn, positively predicted life satisfaction and identity confusion negatively predicted good physical functioning over time. Regarding identity formation and cancer-specific functioning, mainly unidirectional effects occurred. Post-traumatic stress symptoms negatively predicted identity synthesis and positively predicted identity confusion over time, whereas the reverse pattern of associations was found for benefit finding. The present study uncovered meaningful pathways linking identity formation to psychosocial functioning over time in adolescents and emerging adults who survived childhood cancer. These longitudinal findings may provide important guidance for clinical practice, given that identity formation in today's western society has become particularly challenging.

Transatlantic progress in measurement of cognitive outcomes in paediatric oncology trials.

The importance of measuring quality of survival within paediatric oncology trials is increasingly recognised. However, capturing neuropsychological outcomes and other aspects of quality of survival in the context of large or multinational trials can be challenging. We provide examples of protocols designed to address this challenge recently employed in clinical trials in the USA and Europe. We discuss their respective strengths and challenges, obstacles encountered and future opportunities for transatlantic collaboration.

Recommendations for the surveillance of mental health problems in childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Survivors of childhood, adolescent, and young adult (diagnosed when <25 years of age) cancer are at risk of mental health problems. The aim of this clinical practice guideline is to harmonise international recommendations for mental health surveillance in survivors of childhood, adolescent, and young adult cancer. This guideline was developed by a multidisciplinary panel of experts under the sponsorship of the International Guideline Harmonization Group. We evaluated concordance among existing survivorship clinical practice guidelines and conducted a systematic review following evidence-based methods. Of 7249 studies identified, 76 articles from 12 countries met the inclusion criteria. Recommendations were formulated on the basis of identified evidence in combination with clinical considerations. This international clinical practice guideline strongly recommends mental health surveillance for all survivors of childhood, adolescent, and young adult cancers at every follow-up visit and prompt referral to mental health specialists when problems are identified. Overall, the recommendations reflect the necessity of mental health surveillance as part of comprehensive survivor-focused health care.

Worries and Benefit Finding in Cancer Survivors and Parents: A Longitudinal Study.

OBJECTIVE: The interplay and longitudinal associations between positive and negative illness-related experiences in childhood cancer survivors and their families remain unclear. Therefore, benefit finding, cancer-related worries, depressive symptoms, and life satisfaction were prospectively investigated in childhood cancer survivors and parents. Directionality of effects and interactions between benefit finding and cancer-related worries in predicting general well-being were examined. METHODS: Childhood cancer survivors (n = 125 at T1; aged 14-25), mothers (n = 133 at T1), and fathers (n = 91 at T1) completed two annual questionnaires on benefit finding, cancer-related worries, depressive symptoms, and life satisfaction. Cross-lagged panel analyses including benefit finding, cancer-related worries, their interaction, and depressive symptoms or life satisfaction were conducted in survivors, mothers, and fathers. RESULTS: Relatively high stability coefficients were found for all study variables. In survivors, cancer-related worries predicted relative increases in depressive symptoms and benefit finding over time. Benefit finding predicted relative increases in life satisfaction over time and buffered negative effects of cancer-related worries on life satisfaction. In mothers and fathers, positive correlated change at T2 (the correlation between residuals at T2) indicated that relative change in benefit finding over time was positively related to relative change in cancer-related worries. CONCLUSION: Benefit finding was related both to positive well-being and negative illness experiences, which calls for more research to unravel the different functions of benefit finding over time. Clinicians should be encouraged to attend to positive illness experiences along with more negative ones to obtain a more nuanced view on the illness experiences of survivors and their families.

Executive function mediates the link between externalizing behavior and HbA1c in children and adolescents with type 1 diabetes: A cross-national investigation.

OBJECTIVE: Externalizing behavior (i.e., conduct problems, hyperactivity) and executive function (EF) problems in children and adolescents with type 1 diabetes (T1D) have been associated with worse diabetes-related and psychosocial outcomes but have not been examined in relationship to each other. We aimed to examine whether externalizing behavior is associated with HbA1c and whether this relationship is mediated by EF problems, specifically metacognition (i.e., ability to initiate, plan, organize and monitor behavior) and behavioral regulation (i.e., impulse control, regulation of emotion and behavior). RESEARCH DESIGN AND METHODS: Cohorts of Belgian and Dutch parents of children and adolescents (6-18 years) with T1D filled out questionnaires on externalizing behavior (Strengths and Difficulties Questionnaire; SDQ) and EF (Behavior Rating Inventory of Executive Function; BRIEF) composite scales. Treating physicians collected HbA1c values. Mediation analyses were performed separately for the BRIEF composite Metacognition and Behavior Regulation scales, correcting for age, sex and diabetes duration. RESULTS: The 335 parents of children and adolescents with T1D (mean age 12.3 ± 2.8 SD; mean HbA1c 7.6% ± 1.1 SD [60 mmol/mol ± 12.0 SD]; mean diabetes duration 5.3 ± 3.6 SD; 49.6% female) participated. Analyses showed that the association between externalizing behavior and HbA1c is mediated by metacognition (ab path Point estimate = 0.05 BCa CI 95% 0.02-0.08), and not behavioral regulation. CONCLUSIONS: Results uncovered the influence externalizing behavior may have on EF problems in the metacognition domain, which in turn seem to influence HbA1c. Clinicians should be mindful of these EF problems when working with children and adolescents displaying externalizing behavior, and not only target behavioral but also cognitive processes.

Dissociating brain systems that respond to contingency and valence during monetary loss avoidance in adolescence.

Negative reinforcement processes allow individuals to avoid negative and/or harmful outcomes. They depend on the brain's ability to differentiate; (i) contingency from non-contingency, separately from (ii) judgements about positive and negative valence. Thirty-three males (8-18 years) performed a cued reaction-time task during fMRI scanning to differentiate the brain's responses to contingency and valence during loss avoidance. In two conditions, cues indicated no -contingency between participants' responses and monetary loss - (1) CERTAIN LOSS (negative valence) of €0.20, €1 or €5 or (2) CERTAIN LOSS AVOIDANCE (positive valence). In a third condition, cues indicated a contingency between short reaction times and avoidance of monetary loss. As expected participants had shorter reaction times in this latter condition where CONDITIONAL LOSS AVOIDANCE cues activated salience and motor-response-preparation brain networks - independent of the relative valence of the contrast (CERTAIN LOSS or CERTAIN LOSS AVOIDANCE). Effects of valence were seen toward the session's end where CERTAIN LOSS AVOIDANCE cues activated ventral striatum, medial-orbitofrontal cortex and medial-temporal areas more than CERTAIN LOSS. CONDITIONAL LOSS AVOIDANCE trials with feedback indicating "success" activated ventral striatum more than "failure feedback". The findings support the hypothesis that brain networks controlling contingency and valence processes during negative reinforcement are dissociable.

Task-related motivation and academic achievement in children and adolescents with ADHD.

Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which is likely to vary as a function of task characteristics. The current study employed a new questionnaire-the Child and Adolescent Motivational Profile (CHAMP)-to examine; (1) which task characteristic participants with ADHD perceive as most motivating relative to typically developing peers (TDP) and (2) whether these differences mediate academic functioning. 34 participants with ADHD and 435 TDP (8-16 years) completed the CHAMP. Academic achievement (grade point average) and self-reported positive/negative classroom experiences were recorded. No task characteristics were rated higher in terms of their motivational salience in the ADHD group than in the control sample. Marked/graded, Socially evaluated, Collaborative, Requiring focus and Cognitively challenging task characteristics were rated significantly lower by the ADHD group than controls. The lower rating of Socially evaluated was explained by comorbid ODD symptoms. Cognitively challenging was rated as particularly unmotivating by individuals with ADHD. ADHD was associated with a decreased GPA and a more negative classroom experience. The associations between ADHD and GPA/negative classroom experience were both partially mediated by scores on the Cognitively Challenging scale. For children and adolescents with ADHD tasks that are cognitively challenging were not particularly motivating. To increase task motivation, and improve academic performance of individuals with ADHD, it may be important to include rewarded task elements as they are appraised as particularly motivating by these individuals and this appraisal was similar to that of TDP.