White matter connectivity and social functioning in survivors of pediatric brain tumor.

OBJECTIVE: Survivors of pediatric brain tumors (SPBT) are at risk for social deficits, fewer friendships, and poor peer relations. SPBT also experience reduced brain connectivity via microstructural disruptions to white matter from neurological insults. Research with other populations implicates white matter connectivity as a key contributor to poor social functioning. This case-controlled diffusion-weighted imaging study evaluated structural connectivity in SPBT and typically developing controls (TDC) and associations between metrics of connectivity and social functioning. METHODS: Diffusion weighted-imaging results from 19 SPBT and 19 TDC were analyzed using probabilistic white matter tractography. Survivors were at least 5 years post-diagnosis and 2 years off treatment. Graph theory statistics measured group differences across several connectivity metrics, including average strength, global efficiency, assortativity, clustering coefficient, modularity, and betweenness centrality. Analyses also evaluated the effects of neurological risk on connectivity among SPBT. Correlational analyses evaluated associations between connectivity and indices of social behavior. RESULTS: SPBT demonstrated reduced global connectivity compared to TDC. Several medical factors (e.g., chemotherapy, recurrence, multimodal therapy) were related to decreased connectivity across metrics of integration (e.g., average strength, global efficiency) in SPBT. Connectivity metrics were related to peer relationship quality and social challenges in the SPBT group and to social challenges in the total sample. CONCLUSIONS: Microstructural white matter connectivity is diminished in SPBT and related to neurological risk and peer relationship quality. Additional neuroimaging research is needed to evaluate associations between brain connectivity metrics and social functioning in SPBT.

The interaction of family functioning and disease- and treatment-related factors on quality of life for children after cancer.

PURPOSE: Children with cancer experience low quality of life (QOL), yet heterogeneity underscores a need to understand how risk and resilience factors interact. This study evaluated if family functioning relates to QOL differentially depending on diagnosis and treatment intensity. METHODS: Participants included children (ages 8-14) who completed treatment within six months for either brain tumor (BT; n = 42) or non-central nervous system solid tumor (ST; n = 29). Caregivers and children rated QOL and family functioning. Treatment intensity was categorized as low, moderate, or high. Cross-informant moderation models tested hypothesized interactions. RESULTS: Child-reported family functioning significantly interacted with diagnosis and treatment intensity in models of caregiver-reported QOL. More maladaptive family functioning was associated with reduced QOL for children with BT and moderately-intense treatments. CONCLUSIONS: Children with BT and moderate treatment intensities are sensitive to family functioning, highlighting an at-risk group to target for family-level intervention. Future work should evaluate these associations longitudinally.

Social impairment in survivors of pediatric brain tumors via reduced social attention and emotion-specific facial expression recognition.

BACKGROUND/OBJECTIVES: Survivors of pediatric brain tumors (SPBT) experience significant social challenges, including fewer friends and greater isolation than peers. Difficulties in face processing and visual social attention have been implicated in these outcomes. This study evaluated facial expression recognition (FER), social attention, and their associations with social impairments in SPBT. METHODS: SPBT (N = 54; ages 7-16) at least 2 years post treatment completed a measure of FER, while parents completed measures of social impairment. A subset (N = 30) completed a social attention assessment that recorded eye gaze patterns while watching videos depicting pairs of children engaged in joint play. Social Prioritization scores were calculated, with higher scores indicating more face looking. Correlations and regression analyses evaluated associations between variables, while a path analysis modeling tool (PROCESS) evaluated the indirect effects of Social Prioritization on social impairments through emotion-specific FER. RESULTS: Poorer recognition of angry and sad facial expressions was significantly correlated with greater social impairment. Social Prioritization was positively correlated with angry FER but no other emotions. Social Prioritization had significant indirect effects on social impairments through angry FER. CONCLUSION: Findings suggest interventions aimed at improving recognition of specific emotions may mitigate social impairments in SPBT. Further, reduced social attention (i.e., diminished face looking) could be a factor in reduced face processing ability, which may result in social impairments. Longitudinal research is needed to elucidate temporal associations between social attention, face processing, and social impairments.

Predicting neuropsychological late effects in pediatric brain tumor survivors using the Neurological Predictor Scale and the Pediatric Neuro-Oncology Rating of Treatment Intensity.

OBJECTIVE: The Neurological Predictor Scale (NPS) quantifies cumulative exposure to tumor- and treatment-related neurological risks. The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) measures the intensity of different treatment modalities, but research is needed to establish whether it is associated with late effects. This study evaluated the predictive validity of the NPS and PNORTI for neuropsychological outcomes in pediatric brain tumor survivors. METHOD: A retrospective chart review was completed of pediatric brain tumor survivors (PBTS) (n = 161, Mage = 13.47, SD = 2.80) who were at least 2 years from the end of tumor-directed treatment. Attention, intellectual functioning, perceptual reasoning, processing speed, verbal reasoning, and working memory were analyzed in relation to the NPS and PNORTI. RESULTS: NPS scores ranged from 1 to 11 (M = 5.57, SD = 2.27) and PNORTI scores ranged from 1 (n = 101; 62.7%) to 3 (n = 18; 11.2%). When controlling for age, sex, SES factors, and time since treatment, NPS scores significantly predicted intellectual functioning [F(7,149) = 12.86, p < .001, R2 = .38] and processing speed [F(7,84) = 5.28, p < .001, R2 = .31]. PNORTI scores did not significantly predict neuropsychological outcomes. CONCLUSIONS: The findings suggest that the NPS has value in predicting IF and processing speed above-and-beyond demographic variables. The PNORTI was not associated with neuropsychological outcomes. Future research should consider establishing clinical cutoff scores for the NPS to help determine which survivors are most at risk for neuropsychological late effects and warrant additional assessment.

Radiotherapy-Induced Neurocognitive Impairment Is Driven by Heightened Apoptotic Priming in Early Life and Prevented by Blocking BAX.

Although external beam radiotherapy (xRT) is commonly used to treat central nervous system (CNS) tumors in patients of all ages, young children treated with xRT frequently experience life-altering and dose-limiting neurocognitive impairment (NI) while adults do not. The lack of understanding of mechanisms responsible for these differences has impeded the development of neuroprotective treatments. Using a newly developed mouse model of xRT-induced NI, we found that neurocognitive function is impaired by ionizing radiation in a dose- and age-dependent manner, with the youngest animals being most affected. Histologic analysis revealed xRT-driven neuronal degeneration and cell death in neurogenic brain regions in young animals but not adults. BH3 profiling showed that neural stem and progenitor cells, neurons, and astrocytes in young mice are highly primed for apoptosis, rendering them hypersensitive to genotoxic damage. Analysis of single-cell RNA sequencing data revealed that neural cell vulnerability stems from heightened expression of proapoptotic genes including BAX, which is associated with developmental and mitogenic signaling by MYC. xRT induced apoptosis in primed neural cells by triggering a p53- and PUMA-initiated, proapoptotic feedback loop requiring cleavage of BID and culminating in BAX oligomerization and caspase activation. Notably, loss of BAX protected against apoptosis induced by proapoptotic signaling in vitro and prevented xRT-induced apoptosis in neural cells in vivo as well as neurocognitive sequelae. On the basis of these findings, preventing xRT-induced apoptosis specifically in immature neural cells by blocking BAX, BIM, or BID via direct or upstream mechanisms is expected to ameliorate NI in pediatric patients with CNS tumor. SIGNIFICANCE: Age- and differentiation-dependent apoptotic priming plays a pivotal role in driving radiotherapy-induced neurocognitive impairment and can be targeted for neuroprotection in pediatric patients.

A Pilot Randomized Clinical Trial of Intranasal Oxytocin to Promote Weight Loss in Individuals With Hypothalamic Obesity.

Context: Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective: To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity. Methods: This randomized, double-blind, placebo-controlled, crossover pilot trial (NCT02849743), conducted at an outpatient academic medical center, included patients aged 10 to 35 years with hypothalamic obesity from hypothalamic/pituitary tumors. Participants received intranasal OXT (Syntocinon, 40 USP units/mL, 4 IU/spray) vs excipient-matched placebo, 16 to 24 IU 3 times daily at mealtimes. Weight loss attributable to OXT vs placebo and safety (adverse events) were assessed. Results: Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3 years, IQR 13.3-20.6), 10 completed the entire study. We observed a nonsignificant within-subject weight change of -0.6 kg (95% CI: -2.7, 1.5) attributable to OXT vs placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed. Conclusion: In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was well-tolerated, so future larger studies could examine different dosing, combination therapies, and potential psychosocial benefits.

A Survey of Patient-Relevant Outcomes in Pediatric Craniopharyngioma: Focus on Hypothalamic Obesity.

Context: Individuals treated for pediatric craniopharyngioma, a rare, grade 1 brain tumor, frequently develop hypothalamic obesity, a complication often recalcitrant to intervention. Although hypothalamic obesity is known to adversely impact quality of life, less is known about how caregivers and patients experience this condition. Objective: Our goal was to examine the approaches that families take towards weight management and the impact on social function in individuals with craniopharyngioma and obesity. Individuals with craniopharyngioma without obesity were included as a comparison. Subjects and Methods: Adult caregivers of children <18y with craniopharyngioma completed a web-based survey posted by a patient advocacy organization between February and July 2020. Questions related to the child's diagnosis, medications, lifestyle modifications, and social function along with research priorities. Descriptive statistics were generated. Linear regression was used to assess the independent effects of obesity and other covariates on social function. Results: Of 106 respondents, 60 (57%) reported their child had obesity at the time of survey completion. In contrast, only 6 (5.7%) had obesity prior to craniopharyngioma diagnosis. A majority (92%) of those with obesity had tried limiting calories or carbohydrates; 31% and 69% found these helpful, respectively. Thirty-eight percent had tried weight loss medications (stimulants, metformin, GLP1R-agonists, and topiramate) and 48% found at least one helpful. Both stimulant and anti-depressant use were reported more frequently with obesity. An index (T-score) reflecting social function was lower in the cohort than a population reference, 41 (SD 11) vs. 50 (SD 10), p<0.001. In a linear model, both older age and obesity were independently associated with greater social impairment. Ninety-four percent of respondents caring for a child with obesity (and 79% of all respondents) identified "improving treatments and prevention for hypothalamic obesity" as a key research priority. Conclusions: Only a minority of individuals with hypothalamic obesity had trialed medication, even though many reported that lifestyle modification was inadequate. Furthermore, social function was significantly impaired overall in survivors compared to a reference cohort, and even more so in individuals with obesity. These findings highlight the opportunity to improve social functioning as an additional potential benefit of improved treatments for hypothalamic obesity.

A prospective study of social competence in survivors of pediatric brain and solid tumors.

BACKGROUND/OBJECTIVES: Survivors of pediatric brain tumors are at increased risk for difficulties with social competence, including poor social information processing (SIP) and peer relationships. Improved survival rates heighten the need to better understand these challenges and if they are specific to survivors of pediatric brain tumors versus survivors of other childhood cancers. METHODS: Fifty-one survivors of pediatric brain tumors and 34 survivors of pediatric solid tumors completed evaluations of SIP and peer relationship quality within six months of completing treatment and one year later. Caregivers completed a measure of social skills. Linear mixed models evaluated differences between survivors of pediatric brain and solid tumors on SIP and social skills and how indices of SIP were associated with peer relationships over time. RESULTS: The two groups did not differ on indices of SIP or social skills over time. A three-way interaction between measures of SIP, group, and time predicted peer relationships. Survivors of pediatric solid tumors showed a positive association between baseline social skills and theory of mind and peer relationships over time, whereas survivors of pediatric brain tumors showed an inverse association between baseline social skills and theory of mind and peer relationships over time. CONCLUSION: Findings revealed unanticipated associations between baseline SIP and social skills and peer relationships over time among survivors of pediatric brain tumors. Additional research is needed to elucidate the factors most influential on peer relationships in this group to inform interventions.

Reduced Fusiform Gyrus Activation During Face Processing in Pediatric Brain Tumor Survivors.

OBJECTIVE: The neural mechanisms contributing to the social problems of pediatric brain tumor survivors (PBTS) are unknown. Face processing is important to social communication, social behavior, and peer acceptance. Research with other populations with social difficulties, namely autism spectrum disorder, suggests atypical brain activation in areas important for face processing. This case-controlled functional magnetic resonance imaging (fMRI) study compared brain activation during face processing in PBTS and typically developing (TD) youth. METHODS: Participants included 36 age-, gender-, and IQ-matched youth (N = 18 per group). PBTS were at least 5 years from diagnosis and 2 years from the completion of tumor therapy. fMRI data were acquired during a face identity task and a control condition. Groups were compared on activation magnitude within the fusiform gyrus for the faces condition compared to the control condition. Correlational analyses evaluated associations between neuroimaging metrics and indices of social behavior for PBTS participants. RESULTS: Both groups demonstrated face-specific activation within the social brain for the faces condition compared to the control condition. PBTS showed significantly decreased activation for faces in the medial portions of the fusiform gyrus bilaterally compared to TD youth, ps ≤ .004. Higher peak activity in the left fusiform gyrus was associated with better socialization (r = .53, p < .05). CONCLUSIONS: This study offers initial evidence of atypical activation in a key face processing area in PBTS. Such atypical activation may underlie some of the social difficulties of PBTS. Social cognitive neuroscience methodologies may elucidate the neurobiological bases for PBTS social behavior.

Face Processing and Social Functioning in Pediatric Brain Tumor Survivors.

OBJECTIVE: Pediatric brain tumor survivors (PBTS) experience deficits in social functioning. Facial expression and identity recognition are key components of social information processing and are widely studied as an index of social difficulties in youth with autism spectrum disorder (ASD) and other neurodevelopmental conditions. This study evaluated facial expression and identity recognition among PBTS, youth with ASD, and typically developing (TD) youth, and the associations between these face processing skills and social impairments. METHODS: PBTS (N = 54; ages 7-16) who completed treatment at least 2 years prior were matched with TD (N = 43) youth and youth with ASD (N = 55) based on sex and IQ. Parents completed a measure of social impairments and youth completed a measure of facial expression and identity recognition. RESULTS: Groups significantly differed on social impairments (p < .001), with youth with ASD scoring highest followed by PBTS and lastly TD youth. Youth with ASD performed significantly worse on the two measures of facial processing, while TD youth and PBTS were not statistically different. The association of facial expression recognition and social impairments was moderated by group, such that PBTS with higher levels of social impairment performed worse on the expression task compared to TD and ASD groups (p < .01, η2 = 0.07). CONCLUSIONS: Variability in face processing may be uniquely important to the social challenges of PBTS compared to other neurodevelopmental populations. Future directions include prospectively examining associations between facial expression recognition and social difficulties in PBTS and face processing training as an intervention for PBTS.

Patterns of family relationships in pediatric oncology: implications for children's adjustment upon treatment completion.

OBJECTIVE: Family characteristics influence children's adaptation following a cancer diagnosis. Little is known about the importance of family relationships on children's social and emotional health immediately after treatment completion. In this study, we identify subtypes of family relationships and evaluate how these profiles relate to child adjustment upon treatment completion. METHODS: Youth (N = 77; ages 7-14) who completed cancer treatment within the past 7 months provided their perceptions of their relationships with their caregivers and siblings. Caregivers and teachers rated participants' internalizing and externalizing symptoms, while participants and caregivers reported on child social and overall functioning. Latent profile analyses identified patterns of family relationships, and we examined associations between these patterns and youth outcomes. RESULTS: A four-profile solution best characterized families as (1) low closeness/high sibling-only discord (12.4%); (2) low closeness/high discord (6.6%); (3) high closeness/low discord (47.6%); and (4) moderate closeness/moderate discord (33.4%). Family relationship profiles were differentially associated with self, caregiver, and teacher ratings of adaptation. Participants from families characterized by low closeness/high discord reported more difficulties with peer interactions than participants with high closeness/low discord in their families. Caregivers and teachers reported significantly higher externalizing symptoms for participants from low closeness/high discord and low closeness/high sibling discord families in comparison to participants with high closeness/low discord in their family. CONCLUSIONS: Findings underscore the importance of assessing children's perceptions of family relationships in pediatric oncology and providing support to the family during and after treatment. Future directions include assessing how these profiles predict outcomes over time.

Family factors and health-related quality of life within 6 months of completion of childhood cancer treatment.

OBJECTIVE: The transition from active cancer treatment to survivorship represents a period of uncertainty for youth and their families, but factors associated with adaptation during this period are understudied. We evaluated associations among cancer and treatment-related variables, family factors (family functioning, caregiver health-related quality of life [HRQL], and caregiver distress), and patient HRQL after treatment completion. We assessed the indirect effects of neurocognitive difficulties on youth HRQL through family factors. METHODS: One hundred fifty-four caregivers (of patients' ages 0-18 years) and 52 youth (ages 7-18 years) completed questionnaires assessing family factors, neurocognitive difficulties, and HRQL for patients within 6 months following treatment completion. Electronic health records were reviewed for cancer and treatment-related information. Bootstrapping analyses assessed whether neurocognitive function had indirect effects on HRQL through family factors. RESULTS: Family factors were associated with self- and caregiver reports of children's HRQL. Controlling for demographic, cancer, and treatment covariates, caregiver reports of their child's neurocognitive difficulties had an indirect effect on their reports of child physical HRQL through family functioning. Caregiver reports of their child's neurocognitive difficulties indirectly related to caregiver reports of child psychosocial HRQL through family functioning and caregiver HRQL. Indirect effects for self-reported neurocognitive difficulties and HRQL were not supported. CONCLUSIONS: Findings highlight the need for routine psychosocial screening for youth and caregiver reports of family adjustment and HRQL during the transition off treatment. Providers are encouraged to offer interventions matched to specific needs for families at risk for poor family functioning to improve patient outcomes as they transition off treatment.

Pain in long-term survivors of childhood cancer: A systematic review of the current state of knowledge and a call to action from the Children's Oncology Group.

Survivors of childhood cancer may be at risk of experiencing pain, and a systematic review would advance our understanding of pain in this population. The objective of this study was to describe: 1) the prevalence of pain in survivors of childhood cancer, 2) methods of pain measurement, 3) associations between pain and biopsychosocial factors, and 4) recommendations for future research. Data sources for the study were articles published from January 1990 to August 2019 identified in the PubMed, PsycINFO, EMBASE, and Web of Science data bases. Eligible studies included: 1) original research, 2) quantitative assessments of pain, 3) articles published in English, 4) cancers diagnosed between birth and age 21 years, 5) survivors at 5 years from diagnosis and/or at 2 years after therapy completion, and 6) a sample size >20. Seventy-three articles were included in the final review. Risk of bias was considered using the Cochrane risk of bias tool. The quality of evidence was evaluated according to Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria. Common measures of pain were items created by the authors for the purpose of the study (45.2%) or health-related quality-of-life/health status questionnaires (42.5%). Pain was present in from 4.3% to 75% of survivors across studies. Three studies investigated chronic pain according the definition in the International Classification of Diseases. The findings indicated that survivors of childhood cancer are at higher risk of experiencing pain compared with controls. Fatigue was consistently associated with pain, females reported more pain than males, and other factors related to pain will require stronger evidence. Theoretically grounded, multidimensional measurements of pain are absent from the literature.

Diminished social attention in pediatric brain tumor survivors: Using eye tracking technology during naturalistic social perception.

OBJECTIVE: The etiology of pediatric brain tumor survivor (PBTSs) social difficulties is not well understood. A model of social competence for youth with brain disorder and evidence from youth with autism spectrum disorder (ASD) suggests that diminished social attention may underlie social deficits in PBTSs. This study used eye tracking technology to compare visual social attention in PBTSs, youth with ASD, and typically developing (TD) youth. METHODS: Participants included 90 age-, gender-, and IQ-matched youth (N = 30 per group). PBTSs were at least 5 years from diagnosis and 2 years from the completion of tumor-directed therapy. Participants' eye gaze patterns were recorded while watching an established social play paradigm that presented videos of children engaging in either interactive or parallel play. Group differences in proportional gaze duration toward social versus nonsocial areas of interest were compared. Medical correlates of social attention in PBTSs were evaluated. RESULTS: Groups significantly differed in gaze preference across conditions, with PBTSs looking less at social areas of interest than TD youth and in a manner comparable to youth with ASD. Among PBTSs, multimodal tumor-directed therapy was associated with reduced gaze preference for faces. CONCLUSIONS: This study provides the first evidence of disrupted social attention in PBTSs, with parallels to the social attention deficits observed in ASD. Findings offer a new way to conceptualize the social difficulties of PBTSs and could guide interventions aimed at improving PBTS social adjustment by increasing visual attention to socially relevant information during social interactions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Friendships in Pediatric Brain Tumor Survivors and Non-Central Nervous System Tumor Survivors.

OBJECTIVE: Brain tumors during childhood may disrupt the development and maintenance of friendships due to the impact of disease- and treatment-related factors on functioning. The goal of this study was to determine if children treated for either a brain tumor or a non-central nervous system (CNS) solid tumor could name a friend and to evaluate the social information processes associated with the ability to name a friend. METHOD: Youth (ages 7-14) treated for either a brain tumor (n = 47; mean age = 10.51 years) or a non-CNS solid tumor (n = 34; mean age = 11.29) completed an assessment within 6 months of the conclusion of treatment that included asking participants to name a friend and completing measures of social information processing (SIP). Rates of self-reported friendship were compared between groups and correlates of being able to name a friend were evaluated. RESULTS: Youth treated for a brain tumor (61.7%) were significantly less likely to name a friend compared with youth treated for a non-CNS solid tumor (85.3%). Diagnosis type (brain vs. non-CNS), relapse status, attribution style, and facial affect recognition were significant predictors of being able to name a friend or not in a logistic regression model. CONCLUSIONS: Youth treated for a brain tumor and those who experienced a disease relapse are at risk for impairments in friendships; difficulties with SIP may increase this risk. Targeted screening and intervention efforts for children diagnosed with brain tumors and those who have relapsed could address difficulties with peers.

Social attainment in survivors of pediatric central nervous system tumors: a systematic review and meta-analysis from the Children's Oncology Group.

PURPOSE: Improved therapies for pediatric central nervous system (CNS) tumors have increased survival rates; however, many survivors experience significant long-term functional limitations. Survivors of pediatric CNS tumors can experience deficits in social attainment. The aim of this review was to systematically amalgamate findings pertaining to social attainment (i.e., educational attainment, marriage, employment outcomes) in survivors of pediatric CNS tumors. METHODS: PubMed (web-based), PsycINFO (EBSCO), EMBASE (Ovid), and Web of Science (Thomson Reuters) were used to identify articles published between January 2011 and September 2018. Eligible studies reported outcomes for survivors of pediatric CNS tumors diagnosed before age 21 years and > 5 years from diagnosis and/or > 2 years off therapy. All data were independently abstracted by two reviewers. Random-effects meta-analyses were performed using Review Manager 5.0. RESULTS: The search yielded 7021 unique publications. Forty-six were included in the current review. Meta-analyses revealed survivors of CNS tumors were significantly more likely to have completed compulsory education only (OR = 1.87, 95% CI = 1.66, 2.12, p < 0.00001), less likely to be married (OR = 4.70, 95% CI = 3.89, 5.68, p < 0.00001), and more likely to be unemployed (OR = 2.84, 95% CI = 2.62, 3.08, p < 0.00001) compared to non-cancer controls. Cranial radiation therapy, neurocognitive deficits, and younger age at diagnosis were associated with poorer outcomes. Hearing loss and bilateral blindness were also related to poorer outcomes. Sex did not impact social attainment outcomes. CONCLUSIONS: Survivors of pediatric CNS tumors are at elevated risk for poor attainment of key adult social outcomes. IMPLICATIONS FOR CANCER SURVIVORS: There is a critical need to develop interventions to support survivors in becoming independent and productive adults.

Clinical diagnosis of attention-deficit/hyperactivity disorder in survivors of pediatric brain tumors.

PURPOSE: Survivors of pediatric brain tumors often have neurodevelopmental late effects, such as inattention. Symptoms may mirror those of attention-deficit/hyperactivity disorder (ADHD), which affects ~ 5-8% of the general population. This retrospective study of survivors followed at a large tertiary care center examined the prevalence of a clinical diagnosis of ADHD, and risk factors associated with ADHD diagnosis and ADHD-related medication use. METHODS: A retrospective chart review of brain tumor survivors (n = 528), diagnosed between 2000 and 2015, who were at least 6 years old and 2 years from the end of tumor-directed therapy or from diagnosis, if no interventions were received. Clinical and demographic data were extracted from the medical record. RESULTS: Survivors were 55.7% male with mean age 8.15 ± 4.4 (0.0-16.0) years at brain tumor diagnosis. The most common diagnoses were low-grade glioma, medulloblastoma, and craniopharyngioma, with 52.5% of tumors supratentorial. Of the survivors, 81.3% received surgery, 40.0% radiation therapy, and 36.6% chemotherapy. Sixty-nine survivors (13.1%) had ADHD diagnoses, 105 (19.9%) had symptoms of ADHD without diagnoses, and 64 (12.1%) had ADHD medication use. ADHD diagnosis was associated with younger age at tumor diagnosis (p = 0.05) and supratentorial tumor location (p = 0.001). ADHD diagnosis was not associated with gender, tumor type, or treatment type. CONCLUSIONS: Survivors of brain tumors are at increased risk of ADHD and related symptoms. The greatest increase in risk occurs for survivors with diagnoses at younger ages and supratentorial tumors. Additional research is warranted, as select survivors may benefit from behavioral or pharmacologic ADHD treatments to optimize functioning.

Acceptability and Feasibility in a Pilot Randomized Clinical Trial of Computerized Working Memory Training and Parental Problem-Solving Training With Pediatric Brain Tumor Survivors.

OBJECTIVE: To evaluate the feasibility and acceptability of computerized working memory training in pediatric brain tumor survivors (PBTS) with cognitive deficits, as well as computerized working memory training that is enhanced with parental problem-solving skills training (PSST). METHODS: Twenty-seven PBTS (ages 7-16) recruited from a large, tertiary academic medical center were randomly assigned to computerized working memory training (Standard; n = 14) or computerized working memory training plus PSST (Combined; n = 13). PBTS completed a baseline assessment and parents completed acceptability surveys. Primary outcomes included number of intervention sessions completed and acceptability ratings. RESULTS: Fourteen of the 27 participants completed at least 20 sessions of the computerized training with average sessions lasting over an hour (M = 68.42 min, SD = 14.63). Completers had significantly better baseline auditory attention abilities than noncompleters. Parents reported both frustration and satisfaction related to the interventions and identified barriers to completing intervention sessions. CONCLUSIONS: This pilot randomized clinical trial raises significant questions related to the feasibility of computerized working memory training in PBTS with cognitive deficits. Findings also offer considerations for integrating family-based treatment approaches into cognitive remediation interventions for PBTS.

PROMIS Peer Relationships Short Form: How Well Does Self-Report Correlate With Data From Peers?

Objective: To examine the psychometric properties of the Patient-Reported Outcomes Measurement Information System (PROMIS®) peer relationships short form (PR-SF), including association with peer-reported friendships, likeability, and social reputation. Method: 203 children (Mage = 10.12 years, SD = 2.37, range = 6-14) in Grades 1-8 completed the 8-item PR-SF and friendship nominations, like ratings, and social reputation measures about their peers during 2 classroom visits approximately 4 months apart, as part of a larger study. A confirmatory factor analysis, followed by an exploratory factor analysis, was conducted to examine the factor structure of the PR-SF. Spearman correlations between the PR-SF and peer-reported outcomes evaluated construct validity. Results: For the PR-SF, a 2-factor solution demonstrated better fit than a 1-factor solution. The 2 factors appear to assess friendship quality (3 items) and peer acceptance (5 items). Reliability was marginal for the friendship quality factor (.66) but adequate for the acceptance factor (.85); stability was .34 for the PR-SF over 4 months. The PR-SF (8 items) and acceptance factor (5 items) both had modest but significant correlations with measures of friendship (rs = .25-.27), likeability (rs = .21-.22), and social reputation (rs = .29-.44). Conclusions: The PR-SF appears to be measuring two distinct aspects of social functioning. The 5-item peer acceptance scale is modestly associated with peer-reported friendship, likeability, and social reputation. Although not a replacement for peer-reported outcomes, the PR-SF is a promising patient-reported outcome for peer relationships in youth.