Cognitive difficulties among diffuse glioma survivors are common in survivorship due to cancer treatment effects (i.e., surgery, chemotherapy, and/or radiation therapy), which can diminish quality of life. Routine monitoring of cognitive symptoms in survivorship is recommended and can help address patient needs and inform clinical interventions (e.g., cognitive rehabilitation). While several patient-reported outcome (PRO) measures have been used in brain tumor populations, there has been few studies comparing the performance of these PROs in patients with diffuse glioma. In order to better understand the value of different PROs, we conducted preliminary analyses associating cognitive PROs with neuropsychological impairment in a well-characterized sample of patients with diffuse glioma.

23 glioma patients (mean aged 44.26 ± 12.24), six or more months after completing cancer treatment, underwent comprehensive psychosocial and neuropsychological assessments. The neuropsychological battery included the Hopkins Verbal Learning Test - Revised, Brief Visuospatial Memory Test - Revised, Wechsler Adult Intelligence Scale-IV tests of Coding and Digit Span, Trail-Making Test, Stroop Test, FAS, Animals, Boston Naming Test, and Rey-Osterrieth Complex Figure (copy). Completed cognitive PROs included the Functional Assessment of Cancer - Cognitive Function and Brain questionnaires (FACT-Cog; FACT-Br), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire for Brain Neoplasms (EORTC QLQ-BN20), and the Multidimensional Fatigue Symptom Inventory, short form (MFSI-SF) Mental subscale. Based on published norms, we divided the sample into cognitively impaired and non-impaired groups (two or more primary neuropsychological test scores <= -2 z-score). We compared PRO scores between impaired and non-impaired groups using Mann-Whitney U tests. Higher medians equate to better cognitive functioning for all PROs, except for the MSFI-SF.

We found significantly worse scores in the impaired group compared to non-impaired group on the FACT-Cog subscales of perceived cognitive ability (PCA), [Non-Impaired (Mdn = 21, n = 11), Impaired (Mdn = 10, n = 12), U = 22.5, z = -2.68, = 0.007], perceived cognitive impairment (PCI), [Non-Impaired (Mdn = 59, n = 11), Impaired (Mdn = 44, n = 12), U = 32.5, z = -2.06, p=0.039]. The impaired group also trended towards worse scores on the FACT-Br additional concerns subscale [Non-Impaired (Mdn = 79.5, n = 10), Impaired (Mdn = 61, n = 12), U = 32.5, z = -1.81, p=0.07]. Group differences were not observed on the MSFI-SF [Non-Impaired (Mdn = 5, n = 11), Impaired (Mdn = 7, n = 12), U = 40.5, z = -1.57, p=0.12], or EORTC Cognitive Functioning subscale [Non-Impaired (Mdn = 83.33, n = 10), Impaired (Mdn = 75, n = 12), U = 42, z = -1.23, p=0.218].

The preliminary findings suggest that the FACT-Cog, especially the PCA and PCI correspond with neuropsychological impairment among diffuse glioma survivors better than other cognitive PROs. The FACT-Br subscale was somewhat effective. The MFSI-SF Mental and EORTC Cognitive Functioning subscales did not correspond to impairment status. The FACT-Cog is a promising instrument and future work is needed to better determine relative utility of cognitive PROs in this population.

Glioblastomas, Grade 4 astrocytomas, comprise about 60% of all astrocytomas and have a median survival rate between 14 and 16 months. The extent of resection impacts the prognosis, with an eloquent balance of preserving the patient's functional status. As preoperative imaging and intraoperative techniques improve to maximize safe operative resection, thorough neuropsychological evaluation can aid in assessing cognitive decline and quality of life pre- and post-treatment. In light of the tumors' progressive nature and potential presence in precarious brain locations, it is imperative that the functional burden of the various presentations of glioblastomas be understood. Given the limited data on cognitive presentations of glioblastomas, we present a case study describing a neuropsychological and neuroradiologic profile of a Grade 4 astrocytoma in a patient with a left temporal glioblastoma.

The patient signed consent for clinical evaluation and research. At the time of evaluation, he was 68 years old with a master's degree and was working at multiple start-up companies. He began noticing subtle cognitive functioning changes approximately two months prior with difficulty understanding information. His challenges progressed to difficulty composing emails, word-finding issues, and some slurring and mispronunciations. He was diagnosed with a brain tumor after an emergency MRI was performed. He participated in a neuropsychological evaluation just prior to surgery. The evaluation included a battery of neuropsychological tests examining attention, processing speed, executive functioning, learning and memory, language functioning, visuospatial functioning, motor functioning, and mood.

The imaging results revealed a non-enhancing intra-axial mass in the left superior temporal lobe with surrounding edema. Also noted were rare scattered nonspecific T2 hyperintensities. The scores showed variable motor functioning and deficits within attention for complex information, executive functioning abilities (i.e., motor planning and sequencing, phonemic fluency), language functioning, visuospatial functioning, and learning and memory of information relative to his premorbid level of functioning, indicating total brain involvement consistent with imaging findings of edema.

Taken together, the results of the evaluation and imaging were suggestive of a level of cognitive decline that is more than expected with normal aging. Moreover, there was a lack of evidence representative of a lateralized profile. Notably, the evaluation was conducted before resection surgery, and therefore, the patient continued to experience significant brain edema due to the tumor. Although medication may have contributed to dysfunction, particularly with motor and cognitive slowing, it is not likely that it explained his presentation entirely. As such, the evaluation results were suggestive of neurocognitive dysfunction, which was partially attributable to the tumor and edema displacing neuronal tissue. Given the potential for improvement following tumor resection and secondary decline resulting from recurrence or treatment, it is crucial to have a baseline and the ability to map out higher order functioning, including frontal and temporal lobe functioning. Ultimately, as the field continues to look toward long-term survival for patients with currently lethal brain tumors, the goal is to achieve maximum resection with minimal neurocognitive loss.

Survivors of childhood brain tumor are historically thought to perform worse on measures of executive functioning, including cognitive flexibility (CF; e.g., set-shifting), when compared to their peers. Commonly utilized measures, such as subtests from the Delis-Kaplan Executive Function System (D-KEFS), have baseline conditions that attempt to measure performances independent of but critical for CF tasks (e.g., motor speed on trail making, letter fluency on verbal fluency). However, in research, conditions measuring CF are often included in analyses without accounting for these important baseline conditions. The aim of the current study is to explore differences in CF performance between survivors and their healthy peers when controlling for baseline conditions. The variance explained by each baseline condition on CF condition performance in survivors is also explored.

A sample of 107 long-term survivors of childhood brain tumor (Mage=21.81, SD=5.99, 50.5% female) and 142 healthy controls (Mage= 23.25, SD=6.61, 61.3% female) were administered the Trail Making Test (TMT), Color-Word Interference (CWI), and Verbal Fluency (VF) subtests from the D-KEFS. For the TMT, baseline conditions include visually scanning for a target, motor speed, and letter and number sequencing. For the CWI subtest, baseline conditions include rapid color naming, word reading, and reading words in a different colored ink. On the VF subtest, baseline conditions include rapidly naming words with a specific letter and from a specific category. An analysis of covariance was conducted for each subtest to determine if groups differed in performance on the CF condition (i.e., Number-Letter Switching, Inhibition/Switching, Category Switching Accuracy) when controlling for baseline conditions. In survivors only, linear regressions investigated the amount of variance explained by each baseline condition on the CF conditions of each subtest.

Groups did not differ in CF performance of each subtest when controlling for baseline conditions (ps>.10). Across subtests, baseline conditions significantly predicted CF performance in survivors. On the TMT, Letter Sequencing (p=.003, unique-R2=.05), but not Visual Scanning, Number Sequencing, or Motor Speed, was a significant predictor of Number-Letter Sequencing performance (p<.001, R2=.50). On the CWI subtest, Word Reading (p<.001, unique-R2=.09) and Inhibition (p<.001, unique-R2=.05), but not Color Naming, were significant predictors of Inhibition/Switching performance (p<.001, R2=.67). On the VF subtest, Letter Fluency (p=.009, unique-R2=.06) and Category Fluency (p<.001, unique-R2=.08) were significant predictors of Category Switching Accuracy performance (p<.001, R2=.37).

Findings suggest that CF may not differ between survivors and their healthy peers, but that other factors of executive functioning, such as processing speed, drive performance differences on measures of CF. As these tasks rely heavily on speed, survivors may be slower than their healthy counterparts, but may not perform worse on set-shifting. In addition, these results highlight the importance of controlling for lower-order processes in analyses to help isolate CF performance and more accurately characterize potential differences between groups. While replication of findings in survivors and other clinical groups (e.g., congenital heart disease, traumatic brain injury) is still needed, this work can help inform which processes are most important to account for, which is not yet established.

Children who suffer from brain insults (i.e., traumatic brain injury (TBI), chemotherapy and radiation treatment for brain tumors) are susceptible to late-emerging cognitive sequelae. Even with similar neurological risk variables, variability in long-term cognitive outcomes remains an area of investigation for researchers of acquired brain injury. Given the potential for genetic factors to influence response to chemoradiation, researchers have examined associations between germline, inherited, single nucleotide polymorphisms (SNPs), and neurocognitive outcomes for cancer survivors. Children who sustain an uncomplicated mild TBI generally recover without long-term neuropsychological consequences. However, TBI survivors have overlapping mechanism categories with cancer survivors through secondary injury variables that can be influenced by genomic variation (e.g., oxidative stress and neuroinflammation). Furthermore, the study of genomic vulnerability is limited in heterogenous groups of pediatric TBI survivors. This study aims to identify associations between genotype and long-term neurocognitive outcomes for acquired brain injury survivors by utilizing machine learning to uncover pathophysiological similarities and differences between groups.

Fourteen brain tumor survivors, 139 traumatic brain injury survivors, and 63 healthy, age-matched controls completed the Letter N-back task to obtain performances on core neurocognitive skills (attention, working memory, and processing speed). Ten targeted genotypes were examined across five pathophysiological pathways (neurotransmission, oxidative stress, neuroinflammation, plasticity, growth and repair, and folate metabolism). Data were trained and tested utilizing three regression machine learning models. Mean estimated error and R2 were generated for each neurocognitive outcome. A feature importance score for models with positive variance was generated to determine how predictive a given SNP is for neurocognitive outcomes.

Genotype only accounted for a small amount of variance in cognitive outcomes when all clinical groups were combined. The mean absolute error for the best-fitting models from analyses where all groups were combined decreased when groups were examined separately; however, the differences in model R2 values were not significant. The relationship between brain tumor survivors and processing speed performance depended on genotype. Two SNPs had positive feature importance at the interaction level (rs58225473 and rs1801394). These SNPs are located on the CACNB2 and MTR genes and have functional consequences for neurotransmission and folate metabolism. Models of traumatic brain injury survivors did not explain positive variance and could not be examined for feature importance. Additionally, even when removing the only mechanism of action that should not be relevant for TBI survivors (folate metabolism polymorphisms), the TBI models still did not explain positive variance.

Findings of the importance of two key SNPs on MTR and CACNB2 genes align with recent systematic reviews, which found associations between these polymorphisms and neuropsychological outcomes in more than one group or cohort of pediatric cancer survivors. Models for TBI survivors were limited by the heterogeneity of the group and ceiling effects on performance. An understanding of genetic vulnerabilities influenced by treatment and injury-related factors in acquired brain injury will inform our understanding of the developing and recovering childhood brain. The current study is an initial contribution to this goal and highlights the utility of machine learning methodology for future studies that examine the influence of genetic heterogeneity in pediatric acquired brain injury.

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.

Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing > 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.

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 < .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).

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.

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.

Pediatric brain tumor survivors treated with either XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging > 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 < .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.

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 < PRT) in the left inferior fronto-occipital fasciculus (IFOF), right IFOF, left inferior longitudinal fasciculus (ILF) and right uncinate (all t < -2.05, all p < .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 < .03), while PRT and Control groups performed similarly on these measures (all p >.19). Cognitive functioning was most consistently associated with FA of the corpus callosum major forceps (4/7 domains; all r > .33, all p < .04) and the left ILF (4/7 domains; all r > .37, all p <.02).

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.

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.

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.

BT survivors were more impaired than controls on LNS, CS, and SIB-R scores (p<.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<.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<.0125).

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.

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.

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 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.

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.

High-grade gliomas are aggressive and infiltrate surrounding brain parenchyma, making gross total resection difficult, and despite aggressive treatment, its recurrence is inevitable (Zhou et al., 2016). Repeated tumor resections have been shown to increase survival (Chaichana et al., 2013) but the cost of doing so on quality of life (QoL) and functioning is not known. To address this gap, we compared changes in QoL using the Functional Assessment of Cancer Therapy-Brain questionnaire (FACT-Br; Weitzner et al., 1995) in high-grade glioma patients undergoing first versus repeat surgical resection.

Thirty-three patients with high-grade gliomas (mean age=52, 54.5% female) that underwent tumor resection and completed comprehensive neuropsychological evaluations that included FACT-Br pre-operative and at 2-week follow up were included in this study. FACT-Br assesses four QoL domains: physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), and functional well-being (FWB). A subscale total score was computed for each domain, and these subscale scores were summed to compute a total score for overall QoL. Difference scores were computed for each subscale score and total score by subtracting patients’ pre-operative rating from post-operative rating. More positive scores indicate lesser perceived changes of QoL post-operatively. One-way MANOVA analysis was run to compare the difference scores between patients that underwent first resection and those that underwent repeated resection.

There was no significant difference in perceived changes of overall QoL between the two groups of patients. However, patients with previous resection reported larger decline in perceived physical well-being compared to patients without previous resection (F(1,30)=99.93, p<.05,partial n2=.16). There were no significant differences in other QoL domains between the two groups.

We showed no differences in perceived changes across most QoL domains in patients undergoing repeat versus first surgical resection for treatment of high-grade glioma, suggesting that repeated resections may be a viable strategy in managing tumor recurrences. Specifically, there were no group differences in social, emotional, and functional well-being pre-to postoperatively. However, patients with previous resection reported significantly larger decline in their perceived physical well-being than those without any previous resection. A possible explanation is that patients with previous resection underwent adjuvant therapies (e.g., radiation therapy, chemotherapy) and experienced tumor progression necessitating reoperation, which could have made them more vulnerable to the physical impacts of surgery. Our findings are encouraging and may provide useful insight to guide treatment strategies and patient’s decision making to optimize both surgical and functional outcomes.

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.

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 >65) were calculated. The utilization of educational services was determined.

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<.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<.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).

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.

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.

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.

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 < .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.

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.

Adaptive functioning, most notably practical skills, are impacted in pediatric brain tumor survivors. This study aimed to examine the individual components of practical adaptive functions that are most impacted in pediatric brain tumor survivors, and to identify specific medical and socio-demographic factors that contribute to weaknesses in this domain.

The sample consisted of 117 pediatric brain tumor patients seen for a clinical neuropsychological evaluation. Inclusion criteria included participants <18 years at time of brain tumor diagnosis, and whose parents were administered the Adaptive Behavior Assessment System, Second (ABAS-II) or Third Edition (ABAS-3) as a measure of adaptive functioning. Medical and socio-demographic variables were gathered from the patient’s medical record. Medical variables examined were age at diagnosis, age at evaluation, time since diagnosis, tumor location (supratentorial or infratentorial), and history of treatment and associated complications as measured by the Neurologic Predictor Scale (NPS). Socio-demographic factors examined included sex, race, insurance type, parental education, and Area Deprivation Index (ADI) as a measure of neighborhood deprivation/access to community resources. One sample t-tests compared the brain tumor sample to population normative means. Correlations examined associations between practical skills and medical and socio-demographic variables. To determine predictors of practical skills, significant correlations were entered into separate linear regressions for each of the four practical subscales (Community Use, Home Living, Health & Safety, Self-Care).

Participants were diagnosed around 7 years and were approximately 5 years from diagnosis at the time of neuropsychological evaluation. Practical skills were clinically and statistically significantly below the normative mean (Standard Score=85.5, p<.001). Additionally, all practical subscales were statistically significantly below the normative mean (p<.001), with both Community Use (Scale Score=7.6, p<.001) and Home Living (Scaled Score=6.9, p<.001) being clinically significant. Community Use was positively correlated with age at diagnosis (r=.27, p=.004) and negatively correlated with Neurologic Predictor Scale (r=-.33, p<.001), time since diagnosis (r=-.24, p=.01), and ADI (r=-.23, p=.02). Health and Safety was positively correlated with age at diagnosis (r=.21, p=.024). Self-Care was positively correlated with age at diagnosis (r=.202, p=.029) and parental education (r=.203, p=.037); Home Living was not correlated with any of the variables examined. Predictors of Community Use included NPS score (p=.002); ADI approached significance (p=.07). Age at diagnosis predicted Health & Safety practical skills (p=.024), and parental education predicted Self-Care skills (p=.004).

Pediatric brain tumor survivors demonstrate clinically significant weakness in practical skills. While specific medical and socio-demographic factors contribute to lower practical adaptive functioning (e.g., younger age at diagnosis, higher NPS score suggestive of greater treatment burden, longer time since diagnosis, lower ADI score suggestive of greater neighborhood deprivation, and lower parental education), medical and socio-demographic factors do not equally impact practical adaptive functions, but rather individual factors predict specific practical skills. While there is appreciation for the contribution of medical factors in pediatric oncology, few studies have examined socio-demographic factors in this population. This study highlights the importance of considering the role of family and environmental factors on neuropsychological functioning in pediatric oncology in addition to medical factors.

Medulloblastoma is the most common pediatric malignant brain tumor. Approximately 29% of medulloblastoma patients experience postoperative posterior fossa syndrome (PFS) characterized by impairments in speech, motor, and mood. An interdisciplinary rehabilitation approach is associated with greater rehabilitation gains than a single discipline approach for brain injury patients with significant rehabilitation needs. However, literature regarding the feasibility and utility of this approach within a tertiary care pediatric hematology/oncology setting is lacking. The Acute Neurological Injury (ANI) service was developed to coordinate care for neurologically complex hematology/oncology patients receiving active cancer treatment, including those with PFS. ANI care coordination includes bimonthly interdisciplinary team meetings, interdisciplinary goal implementation for each patient, parent psychoeducation about applicable brain-behavior relationships (including PFS) at treatment initiation, neuropsychological assessment at transition times throughout treatment, cognitive remediation, and coordinated end of treatment transition planning. We gathered caregiver perspective on this approach within a tertiary care pediatric hematology/oncology setting.

Parents of children and young adults (ages 4-20) with PFS after medulloblastoma resection who received coordinated care as part of the ANI program (n=20) were interviewed at least 4 months following completion of cancer treatment. 75% experienced postoperative mutism while the remainder experienced significantly decreased speech without mutism. All received cranial-spinal irradiation and focal boosts to tumor sites followed by chemotherapy per multi-institutional treatment protocol. Caregivers were interviewed regarding perceived feasibility and utility of ANI program components including parent psychoeducation, neuropsychological assessment, cognitive remediation, and interdisciplinary team coordination/goal setting, as well as parental supports. Yes/no responses were gathered as well as responses regarding the perceived utility of aspects of the interdisciplinary ANI program approach via a five-point Likert scale.

Surveys were completed by 66% of families contacted. Mean age at first contact with neuropsychology as part of the ANI program was 9.45 years (SD=4.4 years). Mean time between end of treatment and parent interview was 3.20 years (SD=2.01 years). Most parents reported that initial psychoeducation about PFS helped to decrease their concerns (81%) and increased their understanding of their child’s functioning in the context of PFS (88%). They reported benefit from neuropsychological assessment reports prior to initiating adjuvant treatment (92%), at end of treatment (90%), and one year following initiation of cancer treatment (100%), though they perceived less benefit from assessments intended to inform provider interventions during treatment (81% and 66%). Reports were shared most often with schools (75%), behavioral therapists (50%), physicians (50%), and rehabilitation specialists (25%). Parents indicated that the interdisciplinary ANI program approach was helpful (94%) and the coordinated interdisciplinary goal was beneficial (92%). Most parents favored the weekly frequency of cognitive remediation sessions (83%). Much interest was voiced in establishing a formal mentoring program to offer peer support by parents whose children have previously experienced PFS to those acutely managing a new PFS diagnosis (95%). Of note, all participants indicated that they would be willing to serve in a peer mentor role (100%).

The interdisciplinary ANI program approach is feasible with perceived benefits to families managing new PFS and medulloblastoma diagnoses and receiving active cancer treatment.

Children with pediatric brain tumors (PBT) are at increased risk of psychosocial challenges (e.g., emotional distress, social difficulties), which in turn can result in functional impairment, or problems engaging appropriately across settings. These concerns have been shown to be especially pronounced in patients with lower socioeconomic status (SES), which tends to be overrepresented among ethnic minorities, such as Latino populations. On the other hand, resilience (the ability to utilize resources to alleviate stress and overcome adversity) can act as a protective factor against functional impairment. While resilience has been found to be lower among Latino survivors of pediatric cancer, little is known about the potential role of resilience in mitigating functional impairment among Latino patients with PBT. The authors hypothesized poorer resilience and increased functional impairment among Latino patients with PBT compared to normative expectations, in an attempt to explore need for additional support within this population.

42 Latino patients with PBT ages 2-20 (x=11.08 years, SD=5.24) completed neuropsychological evaluation between 2018 and 2022. The sample was split relatively equally in terms of sex (47.6% male, 52.4% female), tumor location (45.2% infratentorial, 54.8% supratentorial), and household language (47.6% predominantly English, 52.4% predominantly Spanish). Outcome variables included Resiliency and Functional Impairment content scales from the Behavior Assessment Scale for Children – Third Edition: Parent Rating Scales (BASC-3: PRS). Standardized T-scores (x=50; SD=10) were derived using age-appropriate normative data, with higher T-scores indicating better resiliency, yet poorer functional impairment. Median household income for specific neighborhoods was used as a proxy for SES.

The sample as a whole did not deviate from age expectations in terms of resiliency [t(41)=-.469, p=.642] or functional impairment [t(38)=.118, p=.907]. However, when separated by household language, participants from English speaking households demonstrated lower resiliency and increased functional impairment as compared to both normative expectations [t(19)=-2.748, p=.006; t(18)=1.882, p=.038, respectively] and participants from Spanish speaking households [t(40)=-3.327, p=.002; t(37)=2.717, p=.010, respectively]. In contrast, participants from Spanish speaking households performed similarly to same-aged peers in terms of both resiliency [t(21)=1.931, p=.067] and functional impairment [t(19)=-1.969, p=.064]. Furthermore, household language predicted both resiliency [F(2, 39)=8.639, p=.0008] and functional impairment [F(2, 36)=6.203, p=.005] above and beyond SES, explaining an additional 29.4% (p=.0002) and 24.3% (p=.002) of the variation in these variables, respectively.

Latino patients with PBT from Spanish speaking households had better reported resiliency and lower functional impairment than their counterparts from English speaking households. Given the subjective nature of parent reported outcomes and the importance of appropriately supporting patients and families from underserved populations, the roles of culturally-ingrained protective factors and cultural/linguistic differences in perceiving or articulating distress need further exploration. Future research, including comparison of parent report with objective measurement of impairment, is needed to better understand relationships between home language and these important variables. Additionally, examination of diagnostic and treatment-related factors will be beneficial to determine the best approaches to interventions and resources within this population.

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 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<Mean) were compared to the expected base rate of 16%.

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 <.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.

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.

Neurocognitive decline is prevalent in patients with metastatic cancers, attributed to various disease, treatment, and individual factors. Whether the presence of brain metastases (BrMets) contributes to neurocognitive decline is unclear. Aims of this study are to examine neurocognitive performance in BrMets patients and compare findings to patients with advanced metastatic cancer without BrMets. Here, we present baseline findings from an ongoing, prospective longitudinal study.

English-speaking adults with advanced metastatic cancers were recruited from the brain metastases and lung clinics at the Princess Margaret Cancer Centre. Participants completed standardized tests (WTAR, HVLT-R, BVMT-R, COWAT, Trailmaking test, WAIS-IV Digit Span) and questionnaires (FACT-Cog v3, EORTC-QLQ C30 and BN20, PROMIS Depression(8a) and Anxiety(6a)) prior to cranial radiotherapy for those who required it. Test scores were converted to z-scores based on published normative data and averaged to create a composite neurocognitive performance score and domain scores for memory, attention/working memory, processing speed and executive function. Neurocognitive impairment was defined according to International Cancer and Cognition Task Force criteria. Univariate and multivariate regressions were used to identify individual, disease and treatment variables that predict cognitive performance.

76 patients (mean (SD) age: 63.2 (11.7) years; 53% male) with BrMets were included. 61% experienced neurocognitive impairment overall; impairment rates varied across domains (38% memory, 39% executive functioning, 13% attention/working memory, 8% processing speed). BrMets quantity, volume, and location were not associated with neurocognitive performance. Better performance status (ECOG; ß[95%CI];-0.38[-0.70,-0.05], p=0.021), higher premorbid IQ (0.34[0.10,0.58], p=0.005) and greater cognitive concerns (0.02[-3.9e-04,0.04], p=0.051) were associated with better neurocognitive performance in univariate analyses. Only premorbid IQ (0.37[0.14,0.60], p=0.003) and cognitive concerns (0.02[0.0004, 0.03], p=0.05) remained significant in multivariate analysis. We also recruited 31 patients with metastatic non-small cell lung cancer (mNSCLC) with no known BrMets (age: 67.5 (8.3); 32% male) and compared them to the subgroup of BrMets patients in our sample with mNSCLC (N=32; age: 67.8 (11.7); 53% male). We found no differences in impairment rates (BrMets/non-BrMets: Cognitive Composite, 59%/55%; Memory, 31%/32%; Executive Functioning, 35%/29%; Attention/working memory, 16%/13%; Processing speed, 7%/6%; Wilcoxon rank-sum test, all p-value’s > 0.5). The presence or absence of BrMets did not predict neurocognitive performance. Among patients with mNSCLC, higher education (0.11[0.03,0.18], p=0.004) and premorbid IQ (0.36[0.12,0.61], p=0.003), fewer days since primary diagnosis (0.00290[-0.0052,-0.0005], p=0.015) fewer pack-years smoking history (0.01[0.02,-0.001], p=0.027) and greater cognitive concerns (0.02[7e-5,0.04], p=0.045) were associated with better neurocognitive performance in univariate analyses; only premorbid IQ (0.26[0.02,0.51], p=0.04) and cognitive concerns (0.02[0.01,0.04], p=0.02) remained significant in multivariate analysis.

Cognitive impairment is prevalent in patients with advanced metastatic cancers, particularly affecting memory and executive functioning. However, 39% of patients in our sample were not impaired in any domain. We found no associations between the presence of BrMets and neurocognitive function in patients with advanced cancers prior to cranial radiation. Premorbid IQ, a proxy for cognitive reserve, was associated with cognitive outcomes in our sample. Our longitudinal study will allow us to identify risk and resilience factors associated with neurocognitive changes in patients with metastatic cancers to better inform therapeutic interventions in this population.

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.

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.

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 < 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.

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.

Phonemic fluency, an important cognitive skill for everyday functioning, has been shown to decline in comparison to same-aged peers following pediatric cancer diagnosis and treatment, despite intact semantic fluency. More generally, socioeconomic status (SES) has recently been shown to be one of the strongest predictors of neuropsychological outcomes among pediatric oncology patients, with lower SES predicting worse intellectual and academic functioning. However, the association between SES and phonemic fluency within this population has yet to be explored. The main objective of this project was to determine whether SES (specifically estimated household income) significantly predicts phonemic fluency performance among patients with PBT, and it was hypothesized that higher SES would be associated with better phonemic fluency outcomes.

136 participants with PBT ages 7-20 (x=14.15 years, SD=3.87), were administered phonemic fluency trials (either from the NEPSY - Second Edition or Delis-Kaplan Executive Function System, with no significant differences in performance between measures). The sample was 58.8% male and half Latino (50.0%), followed by Caucasian (30.1%), Asian American (7.4%), Black (6.6%), and Other (5.9%) ethnicity. All patients identified English as their primary and preferred language regardless of predominant household language, reducing the potential confounding impact of language. Given documented associations between PBT and lower intelligence following diagnosis and treatment, estimated intellectual functioning was included in the first block of hierarchical regression to isolate and further elucidate the potential contributing influence of SES on phonemic fluency. Median household income for specific neighborhoods was used as a proxy for SES, while Wechsler Matrix Reasoning (MR) was used as an estimate of general intellectual functioning given the high correlation between MR and full scale IQ.

Consistent with prior literature, phonemic fluency was lower than normative age expectations [t(135)=-3.653, p=.0002], though still within the average range clinically (x=8.93). As hypothesized, SES was positively correlated with phonemic fluency [r(136)=.219, p=.005]. Furthermore, SES significantly predicted phonemic fluency performance above and beyond estimated intelligence, accounting for a significant increase in variance (p=.020). Post-hoc analyses also revealed poorer phonemic fluency among participants with infratentorial brain tumors as compared to supratentorial brain tumors after controlling for SES, t(108)=-1.748, p=.042.

Consistent with the known impact of SES on neuropsychological late effects among patients with pediatric cancer, phonemic fluency was positively correlated with SES among participants with PBT above and beyond estimated intelligence, suggesting the distinct role of SES on rapid verbal retrieval within this population. This has important implications for identifying patients at higher risk, helping to ensure timely provision of services and supports. Poorer phonemic fluency was also noted among patients with infratentorial (vs. supratentorial) brain tumors after controlling for SES, which may influence studies combining tumor location as the vast majority of PBTs are infratentorial. This supports prior literature demonstrating the need for increased cerebellar activation during phonemic (vs. semantic) retrieval. Additional research is needed to further explore these findings.

Treatment for pediatric brain tumors (PBTs) is associated with neurocognitive risk, including declines in IQ, executive function, and visual motor processing. Low grade tumors require less intensive treatment (i.e., focal radiotherapy (RT) or surgical resection alone), and have been associated with more favorable cognitive outcomes. However, these patients remain at risk of cognitive problems, which may present differently depending on tumor location. Executive functioning (EF), in particular, has been broadly associated with both frontal-subcortical networks (supratentorial) and the cerebellum (infratentorial). The current study examined intellectual functioning, executive functioning (set-shifting and inhibition), and visual motor skills in patients who were treated for low-grade tumors located in either the supratentorial or infratentorial region.

Participants were survivors (age 8-18) previously treated with focal proton RT or surgery alone for infratentorial (n=21) or supratentorial (n=34) low grade glioma (83.6%) or low grade glioneuronal tumors (16.4%). Survivors >2.5 years post-treatment completed cognitive testing (WISC-IV/WAIS-IV; D-KEFS Verbal Fluency (VF), Color-Word Interference (CW), Trail Making Test (TM); Beery Visual-Motor Integration). We compared outcomes between infratentorial and supratentorial groups using analysis of covariance (ANCOVA). Demographic and clinical variables were compared using Welch’s t-tests. ANCOVAs were adjusted for age at evaluation, age at treatment, and history of posterior fossa syndrome due to significant or marginally significant differences between groups.

Tumor groups did not significantly differ with respect to sex (49.0% male), length of follow-up (M 4.4 years), or treatment type (74.5% surgery alone, 25.5% proton RT). Marginally significant group differences were found for age at evaluation (infratentorial M = 12.4y, supratentorial M = 14.1y, p = .054) and age at treatment (infratentorial M = 7.9y, supratentorial M = 9.7y, p =.074). Posterior fossa syndrome only occurred with infratentorial tumors (n=5, p = .003). Adjusting for covariates, the supratentorial group exhibited significantly superior performance on a measure of inhibition and set-shifting (CW Switching Time (t(32) = -2.05, p=.048, n2 =.11). There was a marginal group difference in the same direction on CW Inhibition Time (t(32 = -1.77, p = .086, n2 =.08). On the other hand, the supratentorial group showed significantly lower working memory than the infratentorial group (t(50) = 2.45, p = .018, n2 = .11), and trends toward lower verbal reasoning (t(50)=1.96, p = .056, n2 = .07) and full-scale IQ (t(50)=1.73, p = .090, n2 = .055). No other group differences were identified across intellectual, EF, and visualmotor measures.

Infratentorial tumor location was associated with weaker switching and inhibition performance, while supratentorial tumor location was associated with lower performance on intellectual measures, particularly working memory. These findings suggest that even with relatively conservative treatment (i.e., focal proton RT or surgery alone), there remains neurocognitive risk in children treated for low-grade brain tumors. Moreover, tumor location may predict distinct patterns of long-term neurocognitive outcomes, depending on which brain networks are involved.

The goal of the current study is to compare QoL between tumor grade levels (i.e., low vs high) as well as the relationship between QoL, cognition, and tumor grade.

Participants were 156 individuals diagnosed with a brain tumor who completed neuropsychological evaluation within an interdisciplinary brain tumor clinic (mean age=51.67; SD=15.0; mean education=13.98; SD=2.6; 59% male). Independent samples T-Test was utilized to review participants’ reported overall quality of life (QoL) on the FACT-Br in relation to tumor grade level (i.e., high vs low). Linear regression analysis was utilized to determine which cognitive variable may be most predictive of QoL.

Results of the Independent T-test demonstrated that low and high tumor grade level groups did not significantly differ in total or individual sub-domain QoL. With regard to the regression analysis, cognitive variables as measured by TMT B, HVLT delayed recall, and FAS accounted for significant variance in quality of life in both low grade and high grade tumor groups (low tumor grade level effect size R2 =0.21; high tumor grade level effect size R2 = 0.19). However, TMT B emerged as a significant predictor of QoL in only the low grade group, while cognitive performance within these same tasks did not significantly predict QoL for the high tumor grade level group.

Our findings did not significantly differ in the overall impact tumor grade level (i.e., low vs., high) has on QoL. Notably, cognitive performance on TMT B significantly predicts QoL for the low but not high tumor grade level group.