Pediatric Brain Tumor Survivors Research Articles

A - 140 The Association between Executive Functioning and Adaptive Outcomes in Pediatric Brain Tumor Survivors

Abstract Objective Pediatric brain tumor (PBT) survivors are at high risk for cognitive and adaptive challenges. We aimed to examine the relationship between executive functioning (EF) and adaptive functioning in PBT survivors to identify critical cognitive skills that are associated with functional impact to inform intervention and transition to adulthood. Method Retrospective neuropsychological data was collected for 95 clinically referred PBT survivors (8–24 years). A composite EF measure was created based on the average of selected EF subtest scores. The associations between EF skills, parent-report of child adaptive functioning, and full-scale IQ were analyzed using descriptive statistics, correlations, and multiple regression. Results Adaptive functioning was significantly related to parent (r = −0.701, p < 0.001) and teacher ratings (r = −0.372, p = 0.004) of EF, the testing composite measure of EF (r = 0.455, p = 0.033), as well as FSIQ (r = 0.386, p < 0.001), general cognitive ability (r = 0.328, p = 0.003), working memory (r = 0.279, p = 0.007), and processing speed (r = 0.425, p < 0.001). Parent reports of EF were not significantly related to the EF testing composite score, but both significantly predicted adaptive functioning (p < 0.001). Of parent-reported domains of EF, self-monitoring was most predictive of overall adaptive functioning (B = −0.415, p = 0.017). FSIQ and age did not impact the relationship between parent reports of EF and adaptive functioning. Conclusions Overall, EF on both parent reports and testing, especially self-monitoring, was predictive of adaptive functioning in PBT survivors, regardless of age and overall intellectual functioning. Future research should further examine the impact of individual and treatment factors.

Psychosocial and executive functioning late effects in pediatric brain tumor survivors after proton radiation.

Pediatric brain tumor survivors can experience detrimental effects from radiation treatment. This cross-sectional, large cohort study examined late psychosocial and executive functioning effects in pediatric patients treated ≥ 3years after proton radiation therapy (PRT). Parents of 101 pediatric brain tumor survivors completed the Behavior Assessment System for Children and the Behavior Rating Inventory of Executive Function. Standard scores were compared to published normative means, rates of impairment (T-score > 65) were calculated, and demographic and clinical characteristics were examined. Mean age at PRT was 8.12years and mean interval from PRT to assessment was 6.05years. Half were female (49.5%), 45.5% received craniospinal irradiation (CSI), and 58.4% were diagnosed with infratentorial tumors. All mean T-scores were within normal range. Mean T-scores were significantly elevated compared to the norm on the withdrawal, initiate, working memory, and plan/organize scales. Rates of impairment were notably high in working memory (24.8%), initiate (20.4%), withdrawal (18.1%), and plan/organize (17.0%). Greater withdrawal was significantly associated with CSI and also with chemotherapy and diagnosis of hearing loss. Mean T-scores were significantly lower than the norm on the hyperactivity, aggression, conduct problems, and inhibition scales. No significant problems were identified with social skills or depression. Interval since treatment was not correlated with any scale. Although psychosocial and executive functioning was within the normal range, on average, social withdrawal and metacognitive executive functioning (working memory, initiating, planning/organizing) were areas of concern. Targeted yearly screening and proactive executive skill and social interventions are needed for this population.

Evaluating Scholastic Achievement in Pediatric Brain Tumor Survivors Compared With Healthy Controls

BackgroundRadiotherapy (RT) causes cognitive deficits in pediatric brain tumor survivors (PBTS). Traditionally, this is measured using neuropsychological testing, which lack pre-diagnosis baseline and do not necessarily trigger action. This pilot project investigated a novel patient-centered outcome of scholastic performance using state-collected educational data. MethodsWe retrospectively analyzed scholastic achievements in children residing in Florida. Eligibility in the treatment group received brain-directed RT between 2007 – 2020 at our institution. Controls were matched at a 3:1 ratio by age, grade, district, and free or reduced lunch (FRL) eligibility. The Florida Department of Education provided educational records for both groups. Generalized linear mixed-effects models were used to predict scholastic outcomes with covariates age, time (binary value of pre- or post-RT), treatment group, and the primary independent variable as the interaction term between time and treatment. Scholastic data was matched with institutional clinical data. ResultsFifty PBTS and 150 matched controls were included for analysis. Median age of PBTS was 12, 12% identified as Black, and 18% as Hispanic. Fifty-two percent were FRL eligible. Forty percent received craniospinal irradiation, and 56% received chemotherapy. Post-RT PBTS had 21 times the odds of receiving accommodations (p=0.006), twice the odds of being retained (p=0.010), and 42% lower odds than controls receiving a passing mathematics score (p=0.068). ConclusionsTo our knowledge, this is the first American experience to successfully link individual scholastic and clinical data. Scholastic performance serves as a meaningful patient-centered outcome complementing the existing suite of neuropsychological testing.

Neighborhood resources are associated with neuropsychological outcomes among pediatric brain tumor survivors

Background: Cancer-related cognitive impairment in survivors of pediatric brain tumors is a public health concern, yet studies seldom explore the role of social determinants of health beyond treatment effects. We investigated the influence of neighborhood resources using the Child Opportunity Index (COI) on neuropsychological functioning in survivors. Methods: Intelligence (IQ) and untimed reading and math proficiency were assessed retrospectively in 190 survivors. Multiple regression analyses explored associations among the COI composite and indices (Education, Health-Environment, Social-Economic) and neuropsychological outcomes, controlling for cumulative neurological risk and treatment exposures (Neurological Predictor Scale; NPS) and parental education. Results: Performance was on average within normal limits: IQ (M = 94.08, SD = 15.85, d=.37) with 13.4% of scores below impairment thresholds; reading (M = 95.08, SD = 17.36, d=.28) and math calculation (M = 91.84, SD = 18.82, d=.43) with 16.92% and 20.63% of scores below impairment thresholds, respectively. Each COI domain predicted reading and IQ after controlling for NPS, parental education, and age at diagnosis; however, the Education domain was the only significant predictor of math outcomes. Conclusion: The COI domains significantly predicted IQ and untimed academic skills in survivors, revealing the critical role of neighborhood resources on cognition above and beyond parental education and treatment factors. This is among the first studies to illuminate the influence of neighborhood resources on cognition in survivors. Future research should examine neighborhood context, an understudied construct, with importance in the move toward precision medicine.

Social and Emotional Functioning of Pediatric Brain Tumor Survivors and Typically Developing Youth Following the Onset of the Pandemic.

Background: Social competence is a domain in which pediatric brain tumour survivors (PBTS) are at risk of challenges. To follow-up on our earlier work, in this study we assessed specific social interaction behaviors and emotional functioning in PBTS relative to typically developing youth (TD). The study coincided with the onset of the global pandemic. Methods: Sixteen PBTS and 16 typically developing youth (TD) between 8-16 years old participated in the study. Youth completed an assessment of social behavior and parents completed online surveys regarding child social and emotional adjustment. Results: PBTS experienced greater impairments in social interaction behaviors and on indices of social adjustment relative to TD. PBTS and TD experienced similar levels of emotional problems. Social behavior challenges were associated with indices of anxiety, rather than depression. Time since pandemic onset was not associated with social emotional outcomes. Conclusions: It will be important to monitor and support the social adjustment of populations such as PBTS, as well as the emotional adjustment across PBTS and TD youth, following the pandemic.

QOL-39. FATIGUE AS A RISK FACTOR FOR REDUCED SOCIAL CONNECTEDNESS IN PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract BACKGROUND Pediatric brain tumor survivors (PBTS) experience reduced social connectedness, including fewer friendships, less social acceptance, and greater isolation. Identifying modifiable factors contributing to social issues would yield treatment opportunities. Fatigue is common among PBTS and may relate to social challenges. This study evaluated fatigue among PBTS and its associations with various indices of social connectedness. METHODS Survivors (N = 34) of three types of brain tumors—medulloblastoma (N = 11), pilocytic astrocytoma (N = 15), and craniopharyngioma (N = 8)—completed self-reported measures of fatigue and social connectedness. Laboratory studies assessed thyroid function and growth hormone status. Caregivers completed measures of social functioning. Descriptive statistics summarized fatigue and endorsement of fatigue items. ANOVAs, t-tests, and Pearson correlations evaluated fatigue according to various medical factors, and Pearson correlations evaluated associations between self-reported fatigue and indices of social connectedness. RESULTS Over 20% of survivors reported elevated fatigue, with 53% and 35% indicating fatigue interfering with attention and socialization, respectively. We did not detect associations between self-reported fatigue and diagnosis, current age or age at diagnosis, time since end of treatment, or history of chemotherapy or cranial radiation therapy. We did not detect an association between BMI Z-score and collected hormones. Mean T scores on the self-reported peer relationships measure were below the reference mean (M = 45.8, SD = 11.9), with 22% of survivors endorsing concerns. Higher self-reported fatigue was significantly correlated with poorer self-reported peer relationships (r = -.62, p < 0.001) and more parent-reported social impairments (r =.61, p < 0.001). CONCLUSIONS Fatigue is common among PBTS and may interfere with peer relationships. Clinicians should screen for fatigue as a risk factor for reduced social connectedness. Further research is needed to identify predictors of fatigue and social difficulties and determine temporal associations between fatigue and social connectedness.

QOL-51. FEASIBILITY AND EASE OF USE OF A REMOTE ONLINE COGNITIVE BATTERY AMONG PEDIATRIC BRAIN TUMOR SURVIVORS

Abstract BACKGROUND Pediatric brain tumor survivors are at risk for cognitive deficits, including inattention, poor memory, and slow processing speed. Due to technology advances, computerized neuropsychological batteries were developed that can be completed via internet in the home. The primary aim of this study was to evaluate the rate of successful completion and ease of use of the Penn Computerized Neuropsychological Battery (CNB) among pediatric brain tumor survivors. METHODS Forty-eight pediatric brain tumor survivors completed the online remote administration version of the Penn CNB (10 subtests) assessing complex cognition, memory, executive control, processing speed, and motor speed. Participants were provided with an electronic link to the online cognitive battery as well as paper and electronic copies of an instruction guide and post-completion surveys to return via mail/email. RESULTS Patients (56.3% female) were diagnosed and treated for a brain tumor (54.2% received radiotherapy). All participants were at least 8 years of age (M=13.71, SD=3.82) and at least one-year post-diagnosis (M=4.76, SD=2.58 years). Eighty-eight percent of participants beginning the CNB completed all subtests. Sixty percent of participants completed and returned the post-assessment survey. Participants who returned post-assessment surveys were similar to those who did not on demographic and medical factors (all p-values >.05). Mean ratings suggest that survivors were “very interested” in the tasks and they were “somewhat easy” to complete. Younger children were more likely to have trouble understanding task instructions (r=.56, p <.01) and ask for help answering specific questions (r=.46, p <.05). CONCLUSIONS Remote administration of computerized batteries are feasible among pediatric brain tumor survivors and may assist with advancing both research and patient care. From a research standpoint, remote batteries may allow for participation and engagement in research with minimal survivor burden. Clinically, such batteries may offer alternatives for screening patients who will benefit from comprehensive services.

QOL-34. POST-TRAUMATIC GROWTH AND COPING STRATEGIES AMONG ADOLESCENTS AND YOUNG ADULTS SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Pediatric brain tumor survivors (PBTS) often report late psychosocial effects following the disease and the treatments. Recent studies have shown that PBTS can experience growth in their personal and interpersonal dimensions and develop coping strategies that allow them to deal with the stress caused by cancer diagnosis and subsequent therapies. This study aimed to describe post-traumatic growth (PTG) experiences and coping strategies among adolescents and young adults (AYA) survivors of pediatric brain tumors. METHODS AYA survivors were assessed using Post-Traumatic Growth Inventory (PTGI) and Coping Inventory for Stressful Situations (CISS) questionnaires. They received evaluation at a median age of 20.2 years (range 13.6-28.7), with a median of 92 months from diagnosis. RESULTS Among 22 AYA survivors (M =14; F=8), the diagnosed tumor types were: germ cell tumor (10/22), low-grade glioma (4/22), embryonal tumor (3/22), high-grade glioma (2/22), craniopharyngioma (2/22), and mesenchymal tumor of the meninges (1/22).The domains of PTG in which positive changes were most frequently reported were Personal Strength (25%), Appreciation for Life (25%), and New Possibilities (23%). The less impacted domain was Spiritual Growth (9%). As regards the most adopted coping style, 38% showed higher values in the Distraction scale, 31% in the Task-Oriented scale, 15% in the Avoidance scale, and 15% in the Social Diversion scale. CONCLUSIONS PTG and coping are important indicators of psychosocial adaptation to difficult or stressful events. To develop specific interventions that enhance PTG, it is essential to understand which factors influence growth in PBTS. Our preliminary data show that all AYA survivors report PTG after treatments, at least in some domains. Further analysis is needed to identify which coping styles may influence the development of PTG.

QOL-33. CANCER WORRY AND PSYCHOPATHOLOGICAL SYMPTOMS IN ADOLESCENTS AND YOUNG ADULTS SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Adolescent and young adult (AYA) survivors of pediatric brain tumors may experience cancer-related worries, defined as concerns about relapse and late effects of treatment. Late psychological effects include psychological distress, depression, immaturity, and poor development of social skills. Furthermore, pediatric brain tumor survivors (PBTS) are more vulnerable to developing long-term neurocognitive and psychosocial consequences compared both to the general population and survivors of other types of childhood cancer. The purpose of the study was to identify the presence of cancer worry and psychopathological symptoms in AYA survivors of pediatric brain tumors. METHODS AYA survivors were assessed using the Cancer Worry Scale and Child Behavior Checklist questionnaires. Neurocognitive evaluation was performed using the age-appropriate Wechsler Scale. RESULTS Among 22 AYA survivors (M =14; F=8), the diagnosed tumor types were: germ cell tumor (10/22), low-grade glioma (4/22), embryonal tumor (3/22), high-grade glioma (2/22), craniopharyngioma (2/22), and mesenchymal tumor of the meninges (1/22). Survivors received the assessment at a median age of 20.2 years (range 13.6-28.7), with a median of 92 months after diagnosis. Cancer worry was reported in 50% of patients. The psychological evaluation showed clinical levels of internalizing problems in 17% and externalizing problems in 8%. Depressive and anxiety problems were reported in 25% of our cohort. Neurocognitive assessment demonstrated an average tIQ of 104. CONCLUSIONS As reported in the literature, cancer worry can influence the psychosocial adjustment process, alter self-image, and influence lifestyle decisions in PBTS. These concerns can affect their life prospects and their ability to successfully complete developmental tasks. Therefore, these issues must be early identified to prevent, through targeted psychosocial interventions, the onset of troubles in having romantic relationships, finishing school, entering the job market, and obtaining a good quality of life.

QOL-14. EPILEPTIC SEIZURES, ANTI-SEIZURE MEDICATIONS, AND NEUROCOGNITION IN SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Younger age at diagnosis and cranial radiation therapy are associated with neurocognitive late complications in survivors of pediatric brain tumors (PBT). Less is known about the association between neurocognition and epileptic seizures, with the latter affecting 27% of 5-year survivors. This study aimed to explore whether epileptic seizures exacerbate neurocognitive late complications beyond treatment and demographic factors. METHODS Fifty-nine survivors of PBT who had experienced at least one epileptic seizure, and a control group of survivors matched on sex, age at diagnosis, and cancer treatment, all diagnosed at Skåne University Hospital, were included in the study. Demographic and clinical variables, along with neurocognitive measures of verbal and non-verbal reasoning, cognitive processing speed, working memory, and cognitive flexibility were collected from medical records. Neuropsychological scores, assessed on average 3.68 years after diagnosis, were transformed into z-scores employing age-adjusted norms (m=0, sd=1). Generalized linear models, controlling for increased intracranial pressure at diagnosis and tumor localization, were used to analyze the association between epileptic seizures, cumulative use of anti-seizure medications (ASM), and neurocognition. RESULTS Experiencing any type of epileptic seizures was associated with reduced processing speed (β = -0.91z, p<0.01) and cognitive flexibility (β =-1.05z, p<0.01). Treatment with one ASM was associated with reduced cognitive processing speed (β =-0.81z, p=0.03), and treatment with two or more ASM was associated with lower scores on measures of non-verbal reasoning (β =-0.81z, p<0.01), working memory (β =-0.77z, p=0.01), processing speed (β=-1.26z, p<0.01), and flexibility (β =-1.54z, p<0.01). CONCLUSIONS Epileptic seizures and treatment with ASM were both associated with neurocognitive late complications. Optimal seizure management presents a potential modifiable factor for reducing cognitive burden in survivors of PBT.

QOL-24. TREATMENT- AND TIME-RELATED IMPACT ON LONG-TERM NEUROCOGNITIVE OUTCOMES IN ADULT SURVIVORS OF A PEDIATRIC BRAIN TUMOR

Abstract Treatment for pediatric brain tumors has been associated with the risk of developing long-term neurocognitive impairment. However, it is not well understood which neurocognitive profiles exist within this population. We investigated neurocognitive functioning (NF) in survivors in early adulthood and aimed to assess the impact of radiotherapy dose (RTD) and time since treatment (TxT) on NF. Forty-six survivors of pediatric brain tumors (mean age 23.99±4.71, mean age at diagnosis 9.29±4.54) performed an extensive neurocognitive test battery resulting in intelligence (n=5), memory (n=2), and language (n=3) scores. NF in long-term survivors was compared to sex-, age-, and education-matched controls, and between the different treatment strategies (surgery-only n=19, chemotherapy n=8, radiotherapy n=11, or chemo-radiotherapy n=8). Furthermore, relation between max-RTD (range 40.28 – 61.61 Gy) as well as TxT and NF was assessed. Three ANCOVA models were tested, and false discovery rate (FDR) was applied. For all scales and domain scores, survivors scored lower compared to controls. Scores were significant lower on full scale intelligence (pfdr< 0.001), verbal comprehension (pfdr< 0.001), working memory (pfdr= 0.003), perceptual reasoning (pfdr< 0.001), processing speed (pfdr< 0.001), spoken word comprehension (pfdr= 0.001), and semantic word generation (pfdr= 0.036) compared to controls. NF was not significantly different between the different treatments, nor did the association with max-RTD reach significance. TxT was associated with verbal comprehension and spoken word comprehension; albeit significance was not retained after FDR correction. In this study, the overall survivor cohort scored lower on multiple cognitive outcomes. More detailed analysis of various risk factors might further elucidate the different neurocognitive profiles for this population. Furthermore, more detailed analysis of RTD distributions and affected brain structures may provide greater insight on the impact of radiotherapy on NF.

QOL-18. THE MODERATING ROLE OF SOCIAL VULNERABILITY IN THE RELATIONSHIP OF MATERNAL CAREGIVER CONDITION MANAGEMENT ABILITY AND TRANSITION READINESS OF THEIR YOUNG ADULT SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND The transition into adulthood is a particularly vulnerable time for young adult survivors of pediatric brain tumors (YAS) due to tumor/treatment-related late effects. Reduced supportive resource access and social determinants of health (SDH) can exacerbate challenges, impacting caregiver condition management ability (CMA) and YAS transition readiness. This study’s aim was to evaluate the relationship between YAS cognitive late effects, caregiver CMA, and YAS transition readiness, and the moderating role of SDH for YAS and caregivers with condition-focused family management. METHODS Fifty-three maternal caregivers (93% white, 98% non-Hispanic) of YAS (Mage=22) reporting low CMA completed the Transition Readiness Assessment Questionnaire (TRAQ; 5 subdomains) and rated YAS cognitive late effect severity. Medical experts scored 1) cognitive medical sequelae (0-6 scale), and 2) the Pediatric Neuro-Oncology Rating of Treatment Intensity. Social Vulnerability Index (SVI) measured cumulative SDH using 16 factors across US Census residential zip code data. Pearson correlations and moderated mediation analyses in Process Macro were used. RESULTS Caregiver ratings were associated with overall transition readiness (r=-.38, p=.005), cognitive medical sequelae (r=.53, p<.001), and treatment intensity (r=.28, p=.039). Expert ratings were not related to transition readiness (ps>.05); therefore, only caregiver ratings were used in moderated mediation models. For overall transition readiness, managing medications, appointment keeping, talking with providers, and managing daily activities, the direct effects of caregiver ratings (ps>.05) and indexes of moderated mediation via CMA (ps>.05) were not significant. For tracking health issues, the direct effect of caregiver ratings (p=.085) was not significant, but the index of moderated mediation was significant (95%CI=.026;.315). CONCLUSIONS Only caregiver cognitive late effect ratings were helpful in explaining YAS overall transition readiness. The role of social vulnerability in CMA and transition readiness warrants further exploration. Empirically based transition readiness YAS programs targeting access to resources for families with more social vulnerability are needed.

NURS-13. NEUROCOGNITIVE SIDE EFFECTS OF PEDIATRIC BRAIN TUMORS: A CONTINUING CHALLENGE

Abstract BACKGROUND Pediatric brain tumors pose a considerable challenge in clinical oncology, necessitating multimodal treatment approaches. Many of these have the potential to impact cognition on vulnerable, young brains. While advancements in therapies have improved survival rates, neurocognitive outcomes continue to be one of the most challenging late effects that affect quality of life for pediatric brain tumor survivors. METHODS We conducted a literature review to identify 1) current treatment approaches for pediatric brain tumors, 2) the neurocognitive effects that survivors of pediatric brain tumors experience, and 3) appropriate interventions that can be implemented to mitigate those neurocognitive effects. RESULTS Novel chemotherapeutic agents, such as molecularly targeted therapies, are increasingly implemented in a personalized approach to treatment. New approaches to radiation therapy, particularly proton therapy, have shown promise in minimizing cognitive decline compared to traditional photon therapy. Advances in neuroimaging techniques have enabled a more detailed understanding of structural and functional brain changes associated with treatment. While these newer treatment modalities are promising, their long-term side effects are mostly unknown and bear close monitoring over time. Because neurocognitive side effects continue to underscore the impact of pediatric brain tumor treatments, recent studies often specifically evaluate the cognitive side effects as well as attempt to personalize treatments to reduce cognitive damage. CONCLUSIONS Recent research findings reinforce the enduring concern of neurocognitive side effects in pediatric brain tumor survivors. The integration of advanced therapeutic modalities and targeted supportive care interventions may hold the key to optimizing treatment outcomes while minimizing cognitive morbidity. Continued research efforts are essential for refining treatment protocols and developing personalized strategies to safeguard neurocognitive function in this vulnerable population. Additionally, studies exploring the role of supportive care interventions, such as cognitive rehabilitation and neuroprotective strategies, demonstrate potential avenues for mitigating cognitive sequelae but require ongoing research.

QOL-48. NEUROPSYCHOLOGICAL INTERVENTION FOR PEDIATRIC BRAIN TUMOR PATIENTS AND SURVIVORS - A PRE-STUDY WITH A FOCUS ON PATIENT INVOLVEMENT

Abstract BACKGROUND Neuropsychological (i.e. cognitive, emotional and social) sequelae after pediatric brain tumors (PBT) can severely impair daily-life participation and consequently quality of life. Long-term access to appropriate interventions is therefore essential. Previous studies on effectiveness have recommended multi-component interventions tailored to the specific neuropsychological impairments and unique needs of the survivors. Hence, before conducting a new intervention study, we carried out a participative pre-study, in order to incorporate experienced needs of the group into a future concept. METHODS Known efficacy factors for neurocognitive interventions for PBT patients/survivors were analyzed in a systematic literature search (PubMed, PsychINFO and SCOPUS, 2000 -2024). In addition, a 3-part workshop (in total 4.5 days) was held with PBT survivors and carers (N=20) and Health-Care-Professionals (N=5). The “junior research academy” was designed to participatively run through the research process from the initial idea (how to improve interventions) to the study design. RESULTS After title and abstract screening only 27 studies remained for detailed analysis, with computerized/online cognitive training (mainly working memory), being the most frequently studied intervention, followed by exercise training. Single studies on the effect of medication, parent training, practice/strategy training and behavioral therapy, group training on social skills and neurofeedback were identified. Improvements in different domains have been shown, but recruitment often remains very difficult, as does the transfer to everyday life. Interestingly, the “junior research academy” developed in a slightly different direction: the winning projects (“family guide” or “everyday compass”) were primarily aimed at (1) providing quick and unbureaucratic information and support, (2) giving orientation in daily life, (3) helping to find appropriate interventions, and (4) providing emotional and organizational support. CONCLUSIONS A core group of the participating survivors and health-care-professionals will now finalize the development of an intervention with elements of both pillars and subsequently run a controlled trial.

QOL-23. POTENTIAL MYELIN REPAIR AFTER IRRADIATED PEDIATRIC BRAIN TUMOR: A MAGNETIZATION TRANSFER IMAGING ANALYSIS

Abstract BACKGROUND Exercise training and metformin treatment may improve cognition after cranial irradiation in pediatric brain tumors (PBT), but the neuronal mechanisms underlying the effect of these interventions remains unknown. Magnetization transfer imaging (MTI) is an imaging technique that may be sensitive to white matter microstructure – including myelin. METHODS In this work, we analyzed changes in magnetization transfer ratio (MTR) over a 12-week period in irradiated PBT survivors who participated in pilot clinical trials entailing 12 weeks of exercise training (exercise group, n=17), or metformin treatment (n=12). Pre- and post-intervention assessment included MRI scanning and neurocognitive tests. A no intervention control group, (n=7) was also included and seen before and after a 12 week period of time. We used a longitudinal Tract-Based Spatial Statistics (TBSS) approach to analyze differences in MTR across the 12 weeks in the three groups, using as covariates: age at baseline, sex, handedness, age at diagnosis and delay from diagnosis. Then we performed correlations between mean MTR changes and behavioral outcomes. RESULTS Clusters of significant increase in MTR were observed in the right temporal lobe in the exercise group after intervention and in the right minor forceps in the metformin group after treatment. These changes respectively correlated with higher performance in free recall score in exercise group and with higher performances in inhibitory control and attention in metformin group. There was no difference in MTR changes between groups nor within the control group. DISCUSSION This exploratory work suggests either a 12-week period of exercise training or metformin may promote myelination in PBT survivors in brain regions. These changes appear to be associated with improved memory and executive function, two core domains of neurocognitive deficit in this population.

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

ObjectiveSurvivors 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.MethodsDiffusion 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.ResultsSPBT 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.ConclusionsMicrostructural 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.

Risk factors for domain-specific neurocognitive outcome in pediatric survivors of a brain tumor in the posterior fossa - Results of the HIT 2000 trial.

Neurocognition can be severely affected in pediatric brain tumor survivors. We analyzed the association of cognitive functioning with radiotherapy dose, postoperative cerebellar mutism syndrome (pCMS), hydrocephalus, intraventricular methotrexate (MTX) application, tumor localization and biology in pediatric survivors of a posterior fossa tumor. Subdomain-specific neurocognitive outcome data from 279 relapse-free survivors of the HIT-2000 trial (241 medulloblastoma and 38 infratentorial ependymoma) using the Neuropsychological Basic Diagnostic (NBD) tool based on Cattell-Horn-Carroll's model for intelligence were analyzed. Cognitive performance 5.14 years (mean; range=1.52-13.02) after diagnosis was significantly below normal for all subtests. Processing speed and psychomotor abilities were most affected. Influencing factors were domain-specific: CSI-dose had strong impact on most subtests. pCMS was associated with psychomotor abilities (β=-0.25 to -0.16) and processing speed (β=-0.32). Postoperative hydrocephalus correlated with crystallized intelligence (β=-0.20) and short-term memory (β=-0.15), age with crystallized intelligence (β=0.15) and psychomotor abilities (β=-0.16 and β=-0.17). Scores for fluid intelligence (β=-0.23), short-term memory (β=-0.17) and visual processing (β=-0.25) declined, and scores for selective attention improved (β=0.29) with time after diagnosis. Dose of CSI was strongly associated with neurocognitive outcome. Low psychomotor abilities and processing speed both in patients treated with and without CSI suggest a strong contribution of the tumor and its surgery on these functions. Future research therefore should analyze strategies to both reduce CSI-dose and toxicity caused by other treatment modalities.

Evaluating scholastic achievement in pediatric brain tumor survivors compared to healthy controls.

10065 Background: Radiotherapy (RT) causes cognitive deficits in pediatric brain tumor survivors (PBTS). This has traditionally been measured using exams such as serial IQ tests administered after diagnosis. Scholastic data provides pre-diagnostic measurements and is practical for patients and families. In our state, testing in reading and mathematics is mandated annually for grades 3-11. We sought to evaluate scholastic achievement in PBTS pre- and post-RT treatment. Methods: With IRB approval, we retrospectively analyzed scholastic achievement in children (<21) with primary brain tumors treated with RT at our institution. Eligible children all resided within the state of the institution and were treated 2007-2020. The state’s Department of Education (DOE) provided test scores, school grades, and accommodations, which were matched to institutional clinical data. The other scholastic outcome of interest was Achievement Level (range 1-5 where 5 reflects highest achievement) from state-mandated standardized assessments in Mathematics and Reading, tested annually in grades 3-11. The DOE also provided scholastic data on healthy children matched 3:1 to treated patients by year, district, age, and whether the child was eligible for free or reduced lunch. A general linear mixed-effects model was performed with the above dependent variables and independent variables grade, time (a binary value being pre- or post-time of RT), and treatment (a child being treated or healthy). The interaction term of time*treatment was the outcome of interest, with α=0.1 for this pilot. Odds ratios (ORs) are reported. Results: A total of 200 students were available for analysis: 50 recruited patients and 150 matched controls identified by the DOE with median age 11.6 years at treatment and 7 years median follow-up. Fifty-two percent were eligible for free or reduced lunch. Fifty-six percent received craniospinal irradiation. Thirty-seven (60%) children had post-treatment scholastic data with 179 annual observations available. Of those, there were 10 (6%) physical education waivers, 32 (18%) testing accommodations, and 6 (3%) academic retentions. Compared to matched controls, treated patients were significantly more likely to receive accommodations (OR=31; p=0.001) and significantly less likely to receive a standard grade promotion (OR=0.57; p=0.005) or passing Mathematics scores (OR=0.47; p=0.05). Conclusions: We present the first reporting of scholastic data for United States PBTS. We demonstrate a novel method using existing state mandated school performance testing to evaluate academic performance in PBTS receiving RT. Compared to matched healthy children, we noted significantly increased needs and worse scholastic performance for PBTS. Evaluating scholastic success is an unmet need for PBTS, and we demonstrate the feasibility of using school performance as a novel patient-centered metric.

Relationships between cognitive flexibility performance and adaptive behavior outcomes in survivors of pediatric brain tumor

Objective: Survivors of pediatric brain tumors are at increased risk of executive function (EF) and adaptive behavior difficulties. While previous research suggests that executive dysfunction impacts suboptimal adaptive outcomes, the specific elements of EF influencing this relationship remain unexplored. This study examines the relationship between cognitive flexibility and adaptive behavior in survivors compared to healthy controls. Methods: 86 survivors (M age(SD)=23.41(4.24), 44 females) and 86 controls (M age(SD)=23.09(4.50), 44 females) completed the Delis-Kaplan Executive Function System Trail Making Test (TMT) and Verbal Fluency Test (VFT). The Letter-Number Sequencing (LNS) and Category Switching (CS) conditions were isolated as measures of cognitive flexibility. Informants provided responses to obtain adaptive behavior ratings using the Scales of Independent Behavior-Revised (SIB-R). Linear regressions explored relationships between cognitive flexibility and SIB-R scores in survivors compared to controls. Results: For both TMT and VFT, the relationship between cognitive flexibility and adaptive behavior was significantly different between survivors and controls for SIB-R scores in Social Communication, Community Living, and Personal Living Skills (p<.0125). Survivors’ better LNS performance predicted greater SIB-R scores across the same 3 domains (all p= <.001, r 2semipartial=.08). Similarly, survivors’ better CS performance predicted greater SIB-R scores across the same 3 domains (p = 0.002 to .02, r 2semipartial =.03 to .04). No significant relationships were found in controls (all p >.05). After adjusting for working memory and inhibitory control, most relationships remained significant in survivors (p= <.001 to .046, r 2semipartial=.02 to .08). Conclusion: These findings reveal a robust, positive relationship between cognitive flexibility performance and adaptive behaviors specific to survivors.

Quality of life for rural and Appalachian pediatric brain tumor survivors in Ohio and Kentucky.

Quality of life for rural and Appalachian pediatric brain tumor survivors in Ohio and Kentucky.