Pediatric Brain Tumor Survivors Research Articles

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.

Predictive factors for radiation-induced pituitary damage in pediatric patients with brain tumors

Background and purposeMultiple studies demonstrated hypothalamic–pituitary dysfunction in survivors of pediatric brain tumors. However, few studies investigated the trajectories of pituitary height in these patients and their associations with pituitary function. We aimed to evaluate longitudinal changes of pituitary height in children and adolescents with brain tumors, and their association with endocrine deficiencies. Materials and methodsWe conducted a retrospective analysis of 193 pediatric patients (54.9% male) diagnosed with brain tumors from 2002 to 2018, with a minimum of two years of radiological follow-up. Pituitary height was measured using MRI scans at diagnosis and at 2, 5, and 10 years post-diagnosis, with clinical data sourced from patient charts. ResultsAverage age at diagnosis was 7.6 ± 4.5 years, with a follow-up of 6.1 ± 3.4 years. 52.8% underwent radiotherapy and 37.8% experienced pituitary hormone deficiency. Radiation treatment was a significant predictor of decreased pituitary height at all observed time points (p = 0.016, p < 0.001, p = 0.008, respectively). Additionally, chemotherapy (p = 0.004) or radiotherapy (p = 0.022) history and pituitary height at 10 years (p = 0.047) were predictors of endocrine deficiencies. ANOVA revealed an expected increase in pituitary height over time in pediatric patients, but this growth was significantly impacted by radiation treatment and gender (p for interaction = 0.005 and 0.025, respectively). ConclusionCranial irradiation in pediatric patients is associated with impairment of the physiologic increase in pituitary size; in turn, decreased pituitary height is associated with endocrine dysfunction. We suggest that pituitary gland should be evaluated on surveillance imaging of pediatric brain tumor survivors, and if small for age, clinical endocrine evaluation should be pursued.

Video-based exergaming versus conventional rehabilitation on balance in pediatric brain tumor survivors: a randomized clinical trial

Balance problems are widely reported in Pediatric Brain Tumor Survivors (PBTS) due to tumor localization and the side effects of medical treatment. This study investigates the effects of conventional versus video-based games exercise training (exergaming) on balance in PBTS. The present study was a randomized controlled trial. The study included 23 PBTS who were randomized to a Video-Based balance exergaming Group (VBG) or Conventional balance exercise training Group (CG). In both groups, the interventions were targeted to the balance function and balance exercise training was administered twice a week for 8 weeks. VBG exercised using selected Nintendo Wii Fit Plus® balance games while CG received a specially designed balance training using conventional physiotherapy methods. The primary outcome was the balance tests (Timed Up and Go and Nintendo® Wii™ Center of Gravity: COG), and the secondary outcomes were the functional tests (10-m walking, 2-min walking, 5-step climb/descent/times), and disease effect test (PedsQL Brain Tumor Module). The outcomes were assessed before and after the intervention. At baseline, no significant clinical and outcome assessment differences existed between both groups except for COG (p = 0.0495). After training, overall scores for balance, functional, disease effect tests significantly improved in VBG (p < 0.05) while progress observed in CG was not significant (p > 0.05). Video-based balance exergaming was found effective and more so than conventional balance exercise training in PBTS. Greater effectiveness of exergaming is thought to be due to increased motivation and effort of the children who are more attracted to gaming than conventional exercising. Exergaming could be beneficial both in clinical and home settings with physiotherapist supervision and may reduce the costs of treatment while improving their health-related quality of life.

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

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. SPBT (N=54; ages 7-16) at least 2years 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. 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. 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.

Recurrence Patterns and Surveillance Imaging in Pediatric Brain Tumor Survivors.

Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in pediatric central nervous system (CNS) tumors. The frequency of neuroimaging surveillance varies without a standardized approach. A single-institutional retrospective cohort study evaluated the frequency of recurrences. This study included 476 patients with the majority diagnosed with low-grade glioma (LGG) (n=138, 29%), high-grade glioma (HGG) (n=77, 16%), ependymoma (n=70, 15%), or medulloblastoma (n=61, 13%). LGG, HGG, and ependymoma patients more commonly had multiply recurrent disease ( P =0.08), with ependymoma patients demonstrating ≥2 relapses in 47% of cases. Recurrent disease was identified by imaging more often than clinical symptoms (65% vs. 32%; P =<0.01). Patients diagnosed with meningioma demonstrated the longest mean time to first relapse (74.7mo) whereas those with atypical teratoid rhabdoid tumor and choroid plexus carcinoma tended to have the shortest time to relapse (8.9and 9mo, respectively). Overall, 22 patients sustained first relapse >10 years from initial diagnosis. With a higher tendency toward detection of tumor recurrence/progression on MRI surveillance in comparison to clinical progression, surveillance imaging is necessary in routine follow up of pediatric CNS tumor survivors. With some relapses >10 years from initial diagnosis, imaging beyond this time point may be useful in particular tumor types. While the study is limited in outcome analysis, earlier detection of recurrence would lead to earlier initiation of treatment and implementation of salvage treatment regimens which can impact survival and quality of life.

Key Questions on the Long-Term Utility of Methylphenidate in Paediatric Brain Tumour Survivorship: A Retrospective Clinical Case Series.

Methylphenidate has an established role in the management of attention-deficit hyperactivity disorder and attentional deficit secondary to brain injury. Increasingly, methylphenidate is considered for the attentional deficit in paediatric brain tumour survivors. A small number of studies have explored the benefit of methylphenidate in this population; however, studies are of short duration and do not address the impact of medium to long-term use of methylphenidate on intellectual function. We identified six patients who are survivors of a paediatric brain tumour aged 12-18 years with greater than three years of use of methylphenidate for inclusion in a clinical case series. We used this patient cohort to identify key questions to inform a future long-term cohort study. Linear mixed model and reliable change index analyses were performed on the data. Reliable change index analyses showed benefits to working memory (n = 3), processing speed (n = 2), and full-scale IQ (n = 4) performance for some patients. This exploratory case series suggests the potential medium to long-term benefit of methylphenidate in brain tumour survivorship, indicating the need for larger, appropriately powered studies. These patient data, alongside a discussion of learning points from our previously published studies, are used as a conduit for the identification of questions relating to the use of methylphenidate in a paediatric brain tumour.

Goal-directed therapeutic exercise for paediatric posterior fossa brain tumour survivors: a qualitative analysis of experiences

PurposeTo explore child and parent experiences of a 12-week goal-directed therapeutic exercise intervention in paediatric posterior fossa brain tumours survivors and to identify features of the program that influenced program adherence and acceptability.MethodsEleven interviews were conducted; five parent-child dyads (mothers = 83%) and one parent only (mean child age = 10.6 ± 3.0 years; 83% male). Posterior fossa brain tumour survivors, who participated in a weekly goal-directed exercise program for 12 weeks, completed semi-structured interviews to discuss their experience of the program. An inductive content analysis was undertaken. Interviews were transcribed, imported into NVivo and independently coded by two reviewers. Code and content categories were iteratively discussed and refined.ResultsFive content categories were generated: (1) perceived improvements, (2) program logistics, (3) activity selection, (4) connection with the therapist and (5) options for technology. All participants valued the tailored exercise program and described improvements in movement competence. Children and their parents discussed preferring home- and community-based locations and favoured face-to-face delivery. Occasionally, parents reported difficulty completing the home program due to low child motivation or family time restrictions. Multiple families suggested an interactive digital application would be an effective delivery channel for the supplemental home-based program.ConclusionA goal-directed exercise program delivered at home and in community-based locations was considered valuable and helpful for improving movement competence in paediatric survivors of posterior fossa brain tumour.Trial registrationACTRN12619000841178 June 12, 2019

Protocol for evaluation of the feasibility and preliminary efficacy of a targeted transition readiness workshop intervention for pediatric brain tumor survivors

BackgroundPediatric brain tumor survivors (PBTS) are at risk of physical, cognitive, and psychosocial challenges related to their diagnosis and treatment. Routine follow-up care as adults is therefore essential to their long-term health and quality of life. In order to successfully navigate to adult healthcare, it is recommended that youth develop transition readiness skills. Existing transition readiness interventions often focus on disease management. However, PBTS are also at risk of social competence and cognitive functioning challenges. In this paper, we describe the protocol of this pilot study and the methodology that will be used for the evaluation of the feasibility, acceptability, and preliminary efficacy testing of the first targeted transition intervention workshops specifically designed to meet the needs of PBTS and their caregivers.MethodsThis study will use a mixed method to evaluate three 1 ½-h workshops targeted for dyads (N = 40) of PBTS (14 years or older) and their parents. Dyads will be recruited via a community pediatric cancer organization and the long-term follow-up clinic of a large pediatric hospital. Participants will complete an online survey which includes the Transition Readiness Assessment Questionnaire (TRAQ) before and after the workshops.Each workshop will cover a specific topic related to PBTS transition readiness: disease management, social competence, and cognitive functioning. Workshops will follow the same structure: topic presentation, discussion by a post-transfer survivor or parent, teaching two strategies, and workshop evaluation. Workshops will be co-led by healthcare specialists and patient partners.Feasibility and acceptability will be assessed via recruitment, attendance, retention, and Likert scales, and they will be analyzed by describing and comparing rates. Satisfaction will be measured using satisfaction surveys and audio-recorded focus groups. Qualitative data will be described through thematic content analysis. In order to test the preliminary efficacy of this study, we will compare transition readiness skills pre- and post-workshops using paired samples T test and ANCOVA to examine the impact of workshop on TRAQ skills.DiscussionResults of the study will inform refinement and future broader implementation of targeted transition readiness workshops for the specific needs of pediatric brain tumor survivors.

Oxygen supplementation in anesthesia can block FLASH effect and anti-tumor immunity in conventional proton therapy

BackgroundRadiation-induced neurocognitive dysfunction is a major adverse effect of brain radiation therapy and has specific relevance in pediatric oncology, where serious cognitive deficits have been reported in survivors of pediatric brain tumors. Moreover, many pediatric patients receive proton therapy under general anesthesia or sedation to guarantee precise ballistics with a high oxygen content for safety. The present study addresses the relevant question of the potential effect of supplemental oxygen administered during anesthesia on normal tissue toxicity and investigates the anti-tumor immune response generated following conventional and FLASH proton therapy.MethodsRats (Fischer 344) were cranially irradiated with a single high dose of proton therapy (15 Gy or 25 Gy) using FLASH dose rate proton irradiation (257 ± 2 Gy/s) or conventional dose rate proton irradiation (4 ± 0.02 Gy/s), and the toxicities in the normal tissue were examined by histological, cytometric and behavioral analysis. Glioblastoma-bearing rats were irradiated in the same manner and tumor-infiltrating leukocytes were quantified by flow cytometry.ResultsOur findings indicate that supplemental oxygen has an adverse impact on both functional and anatomical evaluations of normal brain following conventional and FLASH proton therapy. In addition, oxygen supplementation in anesthesia is particularly detrimental for anti-tumor immune response by preventing a strong immune cell infiltration into tumoral tissues following conventional proton therapy.ConclusionsThese results demonstrate the need to further optimize anesthesia protocols used in radiotherapy with the goal of preserving normal tissues and achieving tumor control, specifically in combination with immunotherapy agents.

Barriers to Care and Perceived Need for Mental Health Services Among Adolescent and Emerging Adult Survivors of Pediatric Brain Tumors

Barriers to Care and Perceived Need for Mental Health Services Among Adolescent and Emerging Adult Survivors of Pediatric Brain Tumors

Higher order neurocognition in pediatric brain tumor survivors: What can we learn from white matter microstructure?

Pediatric brain tumor survivors (PBTS) experience neurocognitive late effects, including problems with working memory, processing speed, and other higher order skills. These skill domains are subserved by various white matter (WM) pathways, but not much is known about these brain-behavior links in PBTS. This study examined the anterior corona radiata (ACR), inferior fronto-occipital fasciculi (IFOF), and superior longitudinal fasciculi (SLF) by analyzing associations among diffusion metrics and neurocognition. Thirteen PBTS and 10 healthy controls (HC), aged 9-14years, completed performance-based measures of processing speed and executive function, and parents rated their child's day-to-day executive skills. Children underwent magnetic resonance imaging (MRI) with diffusion weighted imaging that yielded fractional anisotropy (FA) and mean diffusivity (MD) values. Independent samples t-tests assessed group differences on neurocognitive and imaging measures, and pooled within-group correlations examined relationships among measures across groups. PBTS performed more poorly than HC on measures of processing speed, divided attention, and shifting (d=-1.08 to -1.44). WM microstructure differences were significant in MD values for the bilateral SLF and ACR, with PBTS showing higher diffusivity (d=0.75 to 1.21). Better processing speed, divided attention, and shifting were associated with lower diffusivity in the IFOF, SLF, and ACR, but were not strongly correlated with FA. PBTS demonstrate poorer neurocognitive functioning that is linked to differences in WM microstructure, as evidenced by higher diffusivity in the ACR, SLF, and IFOF. These findings support the use of MD in understanding alterations in WM microstructure in PTBS and shed light on potential functions of these pathways.

Social participation of school-aged survivors of pediatric brain tumors: A daily diary report.

Difficulties with social functioning are common among survivors of pediatric brain tumors. Social participation is an understudied measure of social functioning that is associated with emotional health across the lifespan. This paper uses a diary method to assess the social participation of survivors of pediatric brain tumors in middle childhood. Survivors of pediatric brain tumors (N=47; age 10.6±1.4years; 51.1% male, 89.4% White) who were 5.3 (SD=2.4, range: 2-9.9) years post therapy completed a daily diary assessment of social interaction (5-7days) and an objective measure of facial affect recognition. The participant's caregiver completed the NIH Toolbox Emotion Measures and a background information questionnaire. Overall, frequency and quality of reported social interactions were low for survivors, with a large subset of survivors (n=16, 34%) endorsing fewer than 10 social interactions over the course of a typical school week, and almost half of parents (48.9%) reporting that their child participates in zero social activities outside of school during a typical week. Participants engaged in more positive social participation exhibited stronger social skills (facial affect recognition (F(2,44) =4.85, p<.05). School-aged survivors of pediatric brain tumors seemed to be infrequently engaged in social participation and quality interaction with peers. More specifically, the interactions most commonly reported on the diary assessment are not indicative of friendship development and maintenance. Survivors of pediatric brain tumors would likely benefit from interventions designed to increase quality time spent with peers.

6 Graph Analysis of Resting State Functional Brain Networks and Associations with Cognitive Outcomes in Survivors on Pediatric Brain Tumor

Objective:Adolescent and young adult survivors of pediatric brain tumors often live with long-term neuropsychological deficits, which have been found to be related to functional and structural brain changes related to the presence of the tumor itself as well as treatments such as radiation therapy. The importance of brain networks has become a central focus of research over recent decades across neurological populations. Graph theory is one way of analyzing network properties that can describe the integration, segregation, and other aspects of network organization. The existing literature using graph theory with survivors of brain tumor is small and inconsistent; therefore, more work is needed, particularly in survivors of pediatric brain tumors. The present study used graph theory to determine whether functional network properties in this population differ from healthy controls; whether graph metrics relate to core cognitive skills: attention, working memory, and processing speed; and whether they relate to a cumulative measure of neurological risk.Participants and Methods:31 survivors and 31 matched controls completed neuropsychological testing including measures of attention, working memory, and processing speed. They also underwent resting state functional magnetic resonance imaging. Resting state data were preprocessed and spatially constrained independent component analysis was completed to construct connectivity matrices. Finally, graph metrics were calculated utilizing an area under the curve method, including global efficiency, clustering coefficient, betweenness centrality, and small-worldness. Group differences and associations between graph metrics, cognitive outcomes, and neurological risk were analyzed using SPSS version 28.0.Results:Results revealed a significant difference such that brain tumor survivors exhibited less small-world properties in their functional brain networks. This was found to be related to working memory, such that less smallworldness in the network was related to poorer performance. There were no significant relationships with neurological risk, but there were nonsignificant correlations of small-moderate effect size such that lower global efficiency and clustering coefficient were associated with greater neurological risk. Comparisons to structural network analysis from a similar sample and additional post-hoc analyses are also discussed.Conclusions:These findings reveal that survivors of pediatric brain tumor indeed display significant differences in functional brain networks that are quantifiable by graph theory. It is also possible that, with further work, we might better understand how metrics such as smallworldness can be used to predict long-term cognitive outcomes and functional independence in adulthood.

4 Relationships Between Task-Switching Performance and Adaptive Behavior Outcomes in Survivors of Pediatric Brain Tumor

Objective:Survivors of pediatric brain tumor (BT) experience impaired executive function (EF) and adaptive behavior (i.e. the ability to complete daily living tasks independently). The literature hypothesizes that executive dysfunction contributes to suboptimal adaptive behavior outcomes in BT survivors; however, the aspects of EF that drive this relationship remain unexplored. Task-switching is an EF component that involves switching between concurrently presented tasks. This skill is critical for many day-to-day activities and may therefore contribute to observed adaptive functioning difficulties. This study investigates relationships between performance on two task-switching measures and adaptive behavior outcomes in BT survivors compared to healthy controls.Participants and Methods:86 survivors of pediatric BT (Mage(SD)= 23.42(4.24), 44 females) and 86 age- and sex-matched controls (Mage(SD) = 23.09(4.40), 44 females) from the Atlanta area completed the Delis-Kaplan Executive Function System Trail Making Test (TMT) and Verbal Fluency Test (VFT). Respectively, the Letter-Number Sequencing (LNS) and Category Switching (CS) conditions were isolated as measures of task-switching. Baseline conditions, representing the foundational skills needed to perform these timed task-switching measures rapidly (TMT: Letter Sequencing, Number Sequencing; VFT: Category Fluency), were included as covariates in all regressions. Informants familiar with the participants’ daily living were interviewed with the Scales of Independent Behavior-Revised (SIB-R) to measure adaptive behavior in four domains (Motor Skills, Social Communication, Personal Living, Community Living). Linear regressions and t-tests confirmed group differences on task-switching performance and on adaptive functioning outcomes, respectively. Then, linear regressions investigated relationships between performance on each task-switching measure (LNS, CS) and SIB-R scores for survivors. A group by task-switching interaction was added to directly explore group differences in these relationships. α=.0125 was used due to Bonferroni correction for the four SIB-R comparisons within each task-switching measure.Results:BT survivors were more impaired than controls on LNS, CS, and SIB-R scores (p&lt;.05, except Personal Living p=.058). For TMT, decreased performance on LNS predicted lower SIB-R scores in Social Communication (p=.001, r2semipartial=.14), Personal Living (p=.002, r2semipartial=.13), and Community Living (p=.003, r2semipartial =.11), but not Motor Skills (p=.184) in BT survivors. Strength of significant relationships was greater for survivors than controls (all p&lt;.002). For VFT, decreased performance on CS predicted lower SIB-R scores in Personal Living (p=.036, r2semipartial =.06) and Community Living (p=.04, r2semipartial =.05), but not in Motor Skills (p=.716) or Social Communication (p=.14) in BT survivors. Positive relationships between CS and SIB-R scores for all 4 domains were greater in survivors than controls (p&lt;.0125).Conclusions:These findings reveal a robust, positive relationship between task-switching performance and independent, daily behaviors that is specific to BT survivors. The relationship between LNS and Motor Skills may have been weakened by covariates involving baseline motor abilities; however, CS results suggest that task-switching is important for motor skills in survivors relative to controls. Community living skills were impaired in survivors and consistently related to task-switching performance. This work may inform interventions to target task-switching abilities and consequently, promote everyday living skills. Interventions aimed at vulnerabilities in adaptive behavior may help increase independence and quality-of-life as survivors transition to adulthood.

16 Superior Verbal Learning and Memory in Pediatric Brain Tumor Survivors Treated with Proton Versus Photon Radiotherapy

Objective:Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers less radiation to healthy brain tissue. PRT has been associated with improved long term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory outcomes.Participants and Methods:Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing &gt; 1 year following radiotherapy. XRT and PRT groups were similar with respect to sex, handedness, race, age at diagnosis, age at evaluation, tumor characteristics, and treatment history (i.e., craniospinal irradiation, craniotomy, shunting, chemotherapy, radiation dose). Verbal learning and memory were assessed using the age-appropriate version of the California Verbal Learning Test (CVLT-II/CVLT-C). Measures of intellectual functioning, executive functioning, attention and adaptive behavior were also collected. Performance on neuropsychological measures was compared between treatment groups (XRT vs. PRT) using analysis of covariance (ANCOVA). On the CVLT, each participant was classified as having an encoding deficit profile (i.e., impaired learning, recall, and recognition), retrieval deficit profile (i.e., impaired recall but intact recognition), intact profile, or other profile. Chi-squared tests of independence were used to compare the probability of each memory profile between treatment groups. Pearson correlation was used to examine associations between memory performance and strategy use, intellectual functioning, adaptive behavior, attention, and executive functioning.Results:Overall, patients receiving PRT demonstrated superior verbal learning (CVLT Trials 1-5; t(76) = 2.61, p = .011), recall (CVLT Long Delay Free; t(76) = 3.57, p = .001) and strategy use (CVLT Semantic Clustering; t(76) = 2.29, p = .025) compared to those treated with XRT. Intact performance was more likely in the PRT group than the XRT group (71% PRT, 38% XRT; X2 = 8.14, p = .004). Encoding and retrieval deficits were both more common in the XRT group, with encoding problems being most prevalent (Encoding Deficits: 31% XRT, 12% PRT, X2 = 4.51, p = .034; Retrieval Deficits: 17% XRT, 4% PRT, X2 = 4.11, p = .043). Across all participants, semantic clustering predicted better encoding (r = .28, p = .011) and retrieval (r = .26, p = .022). Better encoding predicted higher intellectual (r = .56, p &lt; .001) and adaptive functioning (r = .30, p = .011), and fewer parent-reported concerns about day-today attention (r = -.36, p = .002), and cognitive regulation (r = -.35, p = .002).Conclusions:Results suggest that PRT is associated with superior verbal memory outcomes compared to XRT, which may be driven by encoding skills and use of learning strategies. Moreover, encoding ability predicted general intellectual ability and day-to-day functioning. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline following radiotherapy, which will better inform treatment approaches for survivors of pediatric brain tumor.

3 Predicting Neuropsychological Late Effects in Pediatric Brain Tumor Survivors Using the Neurological Predictor Scale and the Pediatric Neuro-Oncology Rating of Treatment Intensity

Objective:Pediatric brain tumor survivors (PBTS) represent a growing group of childhood cancer survivors vulnerable to adverse neuropsychological outcomes following treatment. Although the identification of risk factors has motivated the efforts to reduce the incidence of neuropsychological late effects in PBTS, most of the prior research on late effects has examined these risk factors on an individually selective basis. Given that tumordirected treatments generally involve a multimodal approach, consisting of a combination of surgical resection, chemotherapy, and/or radiation, and that each patient may have varying degrees of neurological complications, research is needed that focuses on neurocognitive risk factors holistically. The Neurological Predictor Scale (NPS) measures neurological complications associated with neurocognitive risks (e.g., hydrocephalus) and the use of various tumordirected treatment modalities (e.g., craniospinal radiation). The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) measures the intensity of pediatric brain tumor treatments, but its association with neuropsychological late effects has not been well-established. The present study aims to 1) evaluate treatment intensity as a risk factor for the development of neuropsychological late effects; and 2) expand upon the validity and clinical utility of the NPS and PNORTI as predictive measures for the development of neuropsychological late effects in PBTS.Participants and Methods:A retrospective chart review was completed of PBTS (n = 167, Mage = 13.47, SD = 2.80) who were at least 2 years from the end of tumor-directed treatment (surgery, chemotherapy, and/or radiation therapy) and without a multi-system genetic disorder or severe developmental delay prior to brain tumor diagnosis. Neuropsychological outcomes of interest (IQ, processing speed, working memory, verbal comprehension, and perceptual reasoning) were analyzed in relation to the NPS and PNORTI.Results:NPS scores ranged from 1 to 11 (M = 5.58, SD = 2.28) and PNORTI scores ranged from 1 (n = 101; 62.7%) to 3 (n = 18; 11.2%). Survivors were on average approximately 6 years post-treatment (M = 6.13, SD = 3.39). Pearson bivariate correlations revealed that NPS scores were significantly correlated with IQ (r = -.20, p = .015) and processing speed (r = -.27, p = .015). Models examining the predictive utility of the NPS on neuropsychological outcomes showed that, when controlling for age at diagnosis and sex, NPS scores significantly predicted IQ [F(3, 147) = 10.83, p &lt; .001, R2 = .18, R2adjusted = .16] and processing speed [F(3,88) = 5.62, p = .001, R2 = .16, R2adjusted = .13]. A one-way ANOVA showed no significant differences on neuropsychological outcomes based on PNORTI scores.Conclusions:The findings suggest that the NPS has value in predicting IQ and processing speed above and beyond demographic variables. However, treatment intensity (PNORTI) was not associated with neuropsychological domains in our sample. Future longitudinal research should examine which specific neurological risk factors within the NPS account for the most variance in neuropsychological outcomes.

11 Social Determinants of Health in Pediatric Brain Tumor Survivors: Associations between Neighborhood Opportunity and Neurocognitive and Psychological Outcomes

Objective:A growing body of research demonstrates that social determinants of health (SDOH) are important predictors of neurocognitive and psychological outcomes in survivors of pediatric brain tumor (PBT). Existing research has focused primarily on individual level SDOH (e.g., family income, education, insurance status). Thus, more information is needed to understand community level factors which may contribute to health inequities in PBT survivors. This study aimed to examine the effects of specific aspects of neighborhood opportunity on cognitive and emotional/behavioral outcomes among PBT survivors.Participants and Methods:The sample included clinically-referred PBT survivors who completed a neuropsychological evaluation (N=199, Mage=11.63, SD= 4.63, 56.8% male, 71.8% White). Data included an age-appropriate Wechsler Scale and parent-report questionnaires (Behavior Rating Inventory of Executive Function, Child Behavior Checklist). Nationally-normed Child Opportunity Index (COI) scores were extracted for each participant from electronic medical records based on home address using Census tract geocoding. The COI measures neighborhood-level quality of environmental and social conditions that contribute to positive health. It includes three component scores assessing distinct aspects of opportunity, which include educational opportunity (e.g., educational quality, resources, and outcomes), health/environmental opportunity (e.g., access to healthy food, healthcare, and greenspace) and social/economic opportunity (e.g., income, employment, poverty). Stepwise linear regression models were examined to identify significant predictors of cognitive/psychological outcomes associated with PBT; the three COI indices were entered as predictors and retained in the model if they significantly contribute to variance in the outcome.Results:Lower educational opportunity was associated with lower processing speed performance (Wechsler Processing Speed Index: t = 2.47, p = 0.02) and increased parent-reported executive functioning problems (BRIEF GEC: t = -2.25, p = 0.03; BRIEF Working Memory: t = -2.45, p = 0.02) and externalizing problems (CBCL Externalizing: t = -2.19, p = 0.03). Lower social/economic opportunity was associated with lower working memory performance (Wechsler Working Memory Index: t = 2.63, p &lt; 0.01) and increased parent-reported internalizing problems (CBCL Internalizing: t = -2.38, p = 0.02). Health/environmental opportunity did not emerge as a primary predictor of any of the examined cognitive/psychological outcomes. Exploratory analyses examining the impact of age on associations between COI and cognitive/psychological outcomes found a significant moderation effect of age on the relationship between educational opportunity and processing speed (t = 2.35, p = 0.02) such that this association was stronger at older ages. There were no other moderation effects by age.Conclusions:Consistent with a growing body of literature demonstrating the impact of social and environmental contexts to health outcomes, these results show inequities in neurocognitive and psychosocial outcomes in PBT survivors related to neighborhood-level SDOH. Examination of specific neighborhood factors highlight educational and social/economic factors as particularly important contributors to neurocognitive/psychological risk for survivors. The identification of these specific and potentially modifiable risk factors is crucial to inform individual-level problem-prevention following oncological treatment, as well as community-level policy and advocacy efforts.

48 Longitudinal Language Outcomes in Pediatric Brain Tumor Patients Diagnosed in Early Childhood

Objective:Pediatric brain tumor (PBT) survivors are at risk for speech (e.g., articulation, prosody, fluency) and language (e.g., vocabulary, grammar, narratives, pragmatics) difficulties (Hodges et al., 2020). It is important to understand what treatment and/or demographic factors are associated with language functioning soon after diagnosis, and what factors are associated with language functioning years after treatment completion. This study characterizes longitudinal language functioning for clinically referred PBT survivors diagnosed in early childhood.Participants and Methods:Participants were 48 PBT patients (54% supratentorial, 6% disseminated), 21% with NF-1, who were diagnosed by age 6 (M = 43.2 months, SD 24.5) and received tumor-directed intervention including surgery (85%), chemotherapy (69%), and/or radiation therapy (50%). Hearing concerns existed for 29% of the patients. Age at first neuropsychological evaluation was 2-15 years (M=7.6, SD=3.63), age at second neuropsychological evaluation was 5-19 years (M=12.04, SD=3.86), with an average of 4.42 years (SD=2.37) between evaluations. Patients were 63% male, 77% White, 94% non-Hispanic, and fluent English speakers. Verbal IQ, working memory, fluencies, comprehension, memory, and parent-reported functional communication outcomes were assessed as part of comprehensive batteries. Rates of weak performance (1 SD&lt;Mean) were compared to the expected base rate of 16%.Results:Group means significantly diverged from age-expected performance by the second evaluation in all domains except semantic fluency. Weakness was identified on at least 1 verbal subtest for 79% of the sample at the first evaluation, and for 85% of the sample at the second evaluation. As a group, patients showed a significant increase in the number of weaknesses identified on performance-based measures from the first to second evaluation [t(47) = -3.60, p &lt;.001]. Over half of the sample showed an increase in the rate of verbal weaknesses identified (56.3%). Those with more weaknesses over time had lower IQ at the initial evaluation [t(36) =-2.61, p=.013]. An increase in the number of weaknesses from first to second evaluation was not associated with tumor type/location, treatment modality, or demographic variables.Conclusions:Brain tumor diagnosis in early childhood during rapid language development is associated with language impairments soon after diagnosis, and years after treatment completion. Causes for continued and increased impairment are multifactorial and risk cannot clearly be identified by demographic and treatment variables alone. Any early language weakness identification should signal need for intervention as the causes for difficulty are complex and these weaknesses are likely to persist and increase over time.

23 Developmental Outcomes and Educational Service Utilization for Pediatric Brain Tumor Survivors Treated with Proton Radiotherapy Prior to Four Years of Age

Objective:Pediatric brain tumor survivors treated with proton radiation therapy (PRT) prior to 4 years of age are at high risk for poor cognitive and developmental outcomes. This cross-sectional study examined developmental outcomes and educational service utilization at follow-up in a cohort of pediatric survivors treated with PRT before the age of 4 years.Participants and Methods:A total of 46 patients (58.7% female, 93.5% White) were assessed using age-appropriate measures for executive, behavioral, and adaptive functioning. Mean age at PRT was 2.4 years (SD=0.9, range 1.0-3.9 years); mean age at follow-up was 7.0 years (SD=4.8, range 2.0-18.6 years). Mean follow-up interval was 4.57 years (SD=4.52, range 0.9-16.2 years). Diagnoses included ependymoma (n=26, 54.2%), medulloblastoma (n=7, 14.6%), craniopharyngioma (n=4, 8.3%), and a few other tumor types. Infratentorial tumors were most common (69.6%). Treatment included prior surgical resection (93.5%) and chemotherapy (60.9%). Posterior fossa syndrome was present in 10.9% (n=5). PRT field consisted of focal (n=41, 89.1%) or craniospinal irradiation (CSI) (n=5, 10.9%). The impact of demographic, diagnostic, and treatment-related factors was examined, including age at PRT, gender, time interval since PRT, radiation field, and tumor location, on intelligence quotient (IQ), adaptive skills, and executive functioning. Rates of impairment (T-scores &gt;65) were calculated. The utilization of educational services was determined.Results:Mean IQ (SS = 97.6, SD=16.3), as well as mean global executive functioning (Mean T=53.4, SD=11.1) and adaptive skills (Mean SS = 92.5, SD=21.4), as assessed by parent rating scales (BRIEF; SIB), were in the average range. Despite mean scores being within the average range, a large proportion of patients demonstrated difficulties with social withdrawal (28.3%) and activities of daily living (28.3%) (BASC), and global executive dysfunction (17.4%) (BRIEF). Younger age at PRT was associated with lower global adaptive skills at follow-up (r=.39, p=.005), better activities of daily living (r=.53, p&lt;.001), lower social skills (r=.43, p=.002), and more hyperactivity (r=-.37, p=.008), but not aggression, anxiety, depression, somatization, atypical behaviors, withdrawal, or attention problems. Longer follow-up interval was correlated with better activities of daily living (r=.46, p&lt;.001), but more anxiety (r=.39, p=.006). Gender, SES, radiation field, history of hydrocephalus, and location of tumor were not significantly related to primary outcome variables. Posterior fossa syndrome was associated with lower adaptive skills (t=2.90, p=.003) and IQ (t=2.02, p=.026). Of those enrolled in school, 59% received special education services and/or accommodations (IEP n=18, Early Intervention n=6; 504 Plan n=3).Conclusions:Overall, PRT before age 4 years was associated with difficulties with withdrawal, adaptive skills, and executive functioning. Younger age at PRT was associated with lower adaptive functioning, lower social skills, and higher hyperactivity, but not with IQ, attention, mood, or anxiety. While a longer time interval since treatment was associated with improvement in activities of daily living, anxiety was increased, suggesting some late emotional effects. Furthermore, posterior fossa syndrome after surgery was related to lower adaptive skills and IQ. Attention problems were not indicated. Approximately half received school services/accommodations. Young children treated with PRT require proactive support and services to foster their developmental outcomes.

2 Cognitive Sparing in Proton Versus Photon Radiotherapy for Pediatric Brain Tumor Associated with White Matter Integrity

Objective:Radiotherapy for pediatric brain tumor is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to conventional photon radiotherapy (XRT), presumably due to sparing of healthy brain tissue. This study examined long-term white matter change and neuropsychological performance in pediatric brain tumor survivors treated with XRT vs. PRT.Participants and Methods:Pediatric brain tumor survivors treated with either XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging &gt; 7 years following radiotherapy. A healthy control group (n = 23) was also recruited. Groups had similar demographic characteristics, except for handedness (p = .01), mean years of age at testing (XRT = 21.7, PRT = 16.9, Control = 15.5; p = .01), and mean years since radiation (XRT =14.7, PRT = 8.9, p &lt; .001). Age and handedness were selected as covariates; analyses were not adjusted for time since radiation due to redundancy with treatment group (i.e., standard of care transitioned from XRT to PRT in 2007). Participants completed age-appropriate versions of the Weschler Intelligence Scales (WAISIV/WISC-IV/WISC-V) and the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI and Motor Coordination subtests). Tractography was conducted using automated fiber quantification (AFQ), and fractional anisotropy (FA) was extracted from 12 tracts of interest. Linear mixed models were used to summarize group differences in FA, with tracts nested within subjects. Neuropsychological performance and tract-level FA were compared between groups using analysis of covariance (ANCOVA). Pearson correlation was used to examine associations between cognitive functioning and tract-level FA.Results:Across all tracts, FA was significantly lower in the XRT group than the PRT group (t(514) = -2.58, p = .01), but did not differ between PRT and Control groups (t(514) = .65, p = .51). For individual tracts, FA differed significantly between treatment groups (XRT &lt; PRT) in the left inferior fronto-occipital fasciculus (IFOF), right IFOF, left inferior longitudinal fasciculus (ILF) and right uncinate (all t &lt; -2.05, all p &lt; .05). No significant differences in FA were found between PRT and Control participants for any tract. All neuropsychological scores were significantly lower for XRT than PRT patients (all p &lt; .03), while PRT and Control groups performed similarly on these measures (all p &gt;.19). Cognitive functioning was most consistently associated with FA of the corpus callosum major forceps (4/7 domains; all r &gt; .33, all p &lt; .04) and the left ILF (4/7 domains; all r &gt; .37, all p &lt;.02).Conclusions:Both white matter integrity and neuropsychological performance were generally reduced in patients with a history of XRT, but not in those who received PRT. The PRT group was similar to healthy control participants with respect to both FA and cognitive scores, suggesting improved long-term outcomes compared to patients receiving XRT. This exploratory study is the first to provide direct support for white matter integrity as a mechanism of cognitive sparing in PRT. Future work with larger samples is necessary to replicate these findings.