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.

Chimeric antigen receptor (CAR) T-cell therapy is a novel treatment approach for refractory hematological malignancies. Risk factors for cognitive changes have been identified with CAR-T cell therapy, including severe cognitive problems due to neurotoxicity. Given the novelty of this treatment, research on this topic remains limited. Only one known study has examined cognitive performance following CAR T-cell therapy among patients diagnosed with non-Hodgkin’s lymphoma and observed a pattern of initial decline in executive functioning and visuospatial skills with improvement towards baseline one year following treatment. Additional research is needed to understand cognitive functioning in the context of CAR T-cell therapy. Our study presents preliminary descriptive longitudinal cognitive data among a small cohort of patients with mixed cancers undergoing CART cell therapy.

Adult patients undergoing CAR T-cell therapy (N=16) completed the NIH-Toolbox core cognitive battery prior to treatment, and at 100-, 180-, and one-year post-treatment. Subtests of the Weschler Abbreviated Scale of Intelligence (WASI-II; block design, vocabulary) and the Wide Range Achievement Test (WRAT-5; word reading, math computation) were administered at baseline and one year follow up. Mean age of participants was 51.6 (SD = 14.4). Most patients had completed high school or more education (89.7%) identified as male (56.3%) and were white (75%). Diagnoses included lymphoblastic leukemia (n=2), diffuse large B-cell lymphoma (n=7), follicular lymphoma (n=3), mantle cell lymphoma (n=1), metastatic sarcoma (n=1), myxoid liposarcoma (n=1), and synovial sarcoma (n=1).

Mean cognitive scores (adjusted for age) were calculated. At baseline, mean cognitive performance was average across domains, except for inhibitory control, which was in the low average range. At day 100, mean cognitive performance showed the same pattern as baseline. At day 180, mean scores in all domains were within the average range. At one year, all scores were within the average range or higher, although only two participants have completed the one-year follow-up, as data collection is ongoing. One participant died due to neurotoxicity following treatment, thus did not complete follow-up evaluations.

Overall, cognitive performances were broadly within normal limits in the sample and demonstrated relatively stable performance over time. Interestingly, baseline and day 100 mean inhibitory control was an area of relative weakness across participants, which is consistent with prior research. CAR T-cell therapy is reserved for refractory malignancies; thus, patients may have executive functioning deficits at baseline due to prior treatments. One patient died due to neurotoxicity. Overall, although severe cognitive changes and neurotoxicity have been observed as a risk of CAR T-cell therapy, this may be a distinct adverse event rather than the norm, as surviving patients in our sample remained cognitively stable following treatment. Although a unique and important population of study, our sample is limited due to its size. Results should be considered preliminary, and data collection is ongoing.

The Functional Assessment of Cancer Therapy-Cognitive scale (FACT-Cog) is one of the most frequently used patient-reported outcome (PRO) measures of cancer-related cognitive impairment (CRCI) and of CRCI-related impact on quality of life (QOL). Previous studies using the FACT-Cog found that >75% of women with breast cancer (BCa) experience CRCI. Distress tolerance (DT) is a complex construct that encompasses both the perceived capacity (i.e., cognitive appraisal) and the behavioral act of withstanding uncomfortable/aversive/negative emotional or physical experiences. Low DT is associated with psychopathology and executive dysfunction. We previously found that women with BCa with better DT skills reported less CRCI on the FACT-Cog. However, this relationship has not been tested using a performance-based cognitive measure. Therefore, the aims of this study were to: (1) assess the relationship between the FACT-Cog and the Telephone Interview for Cognitive Status (TICS), a performance-based cognitive measure; and (2) test whether the association between DT and CRCI (using the FACT-Cog) was replicated with the TICS.

Participants completed the Distress Tolerance Scale (DTS), the FACT-Cog, and the TICS after undergoing BCa surgery and prior to starting adjuvant therapy [101 women, age >50 years, M(SD)= 61.15(7.76), 43% White Non-Hispanic, 34.4% White Hispanic, 10.8% Black, with nonmetastatic BCa, 55.4% lumpectomy, 36.6% mastectomy; median 29 days post-surgery].

Although there was a significant correlation between the TICS total score and the FACT-CogQOL subscale (r = 0.347, p < 0.001), the TICS total score was not correlated with scores on the FACT-Cog perceived cognitive impairment (CogPCI), perceived cognitive abilities (CogPCA), or comments from others (CogOth) subscales. However, the TICS memory item, a 10-word list immediate recall task, had a weak statistically significant correlation with CogPCI (r = 0.237, p < 0.032), CogOth (r = 0.223, p < 0.044), and CogPCA (r = 0.233, p < 0.036). Next, the sample was divided based on the participant’s score on TICS memory item (i.e., < vs. > sample mean of 5.09). Results of independent samples t-tests demonstrated significant differences in mean scores for CogPCI, f(80) = -2.09, p = 0.04, Mdt = -7.65, Cohen’s d = 0.483, and CogQOL, f(80) = -2.57, p = 0.01, Mditt = -2.38, Cohen’s d = 0.593. A hierarchical linear regression found that DTS subscale and total scores did not significantly predict performance on the TICS. However, DTS continued to be a significant predictor of poorer FACT-Cog PCI scores while controlling for TICS scores.

We found a weak relationship between self-reported cognitive impairment and objective cognitive performance (TICS). However, greater self-reported PCI and its impact on QOL was found in participants who scored below the sample mean on a recall task from the TICS. Although perceived ability to tolerate distress continued to predict self-reported PCI on the FACT-Cog, it did not predict overall performance on the TICS. Therefore, responses on the FACT-Cog may be more representative of an individual’s ability to tolerate distress related to perceived CRCI than actual overall cognitive ability or impairment.

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.

Erdheim-Chester disease (ECD) is a rare disorder characterized by excessive production and accumulation of histiocytes within multiple tissues and organs. ECD primarily affects adults, and symptoms vary depending upon the specific location and severity. Etiology is not always known, but some patients with ECD may have a non-inherited genetic change that allows histiocytes to reproduce uncontrollably. Currently, the cognitive outcomes of ECD are not well understood, and there are no previous neuropsychological findings in the literature. Thus, the objective of this case study was to describe the neuropsychological presentation and findings of an ECD case to inform diagnosis and treatment better.

The patient was a 64-year-old white, non-Hispanic, right-handed man diagnosed with ECD in 2017. ECD accounted for a constellation of medical problems, including diabetes insipidus, hypogonadism, and interstitial lung disease. A brain MRI in 2018 revealed orbital nodularities and pituitary infiltration thought to be consistent with ECD. The patient first noticed cognitive functioning difficulties in 2020 primarily related to short-term memory. Approximately two years later, he noted significant cognitive changes, including difficulties recalling recent events, dates, and conversations, problem-solving, and planning. He had difficulty driving and had two recent car accidents when leaving his driveway. Physically, he reported increased fatigue, unsteadiness, and occasional falls. In 2022, he had a brain MRI that demonstrated a progression of multiple diffuse cerebral, cerebellum, and brainstem lesions and cerebral volume loss compared to prior imaging. He was referred for a neuropsychological assessment to rule out a neurodegenerative disorder.

Neuropsychological data demonstrated moderate-to-severe deficits on tests of basic spatial working memory, visually based processing speed, visual memory, letter verbal fluency, and semantic verbal fluency. He demonstrated mild-to-moderate deficits on tests of basic auditory attention, verbal memory, higher-level visuospatial processing, abstract nonverbal reasoning, multistep, organization and planning, self-monitoring of performance quality, and fine hand and motor dexterity. He demonstrated variable initial learning of new information across modalities, although he did benefit from structured verbal material. Recognition was variable, with difficulty demonstrated in discriminating visual information presented, from similar competing information, along with availability recalling visual information. He showed average auditory-based divided attention, confrontational object naming, and abstract verbal reasoning. Regarding his emotional functioning, he reported mild depressive and anxiety symptoms.

To the best of our knowledge, this is the first report documenting detailed neuropsychological data on this rare disease. The case study documents widespread cognitive deficits with greater difficulty with visually based abilities than verbal abilities. Specifically, patients with ECD may present with cognitive difficulties in visual learning and memory, processing speed, visuospatial processing, select areas of executive/frontal systems, letter and semantic verbal fluency, and fine motor dexterity.

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.

Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.

Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores >1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.

The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p < 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p < 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p < 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p < 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p<.001) and semantic fluency (ß=7.59, p=.007).

These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.

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.

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.

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.

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.

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.

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 purpose of this study using archival data was to examine processing speed (PS) and its relation with academic fluencies in children who were diagnosed with, and treated with chemotherapy for, acute lymphoblastic leukemia (ALL) before vs. after five years of age. Chemotherapy is the first-line treatment for childhood leukemias, and the impact of cancer treatment on academic and global functioning may include a steady decline in functions over time (Baron & Rey-Casserly, 2013). Specifically, this research initiative examined age and gender factors in PS and academic fluencies in this population.

Sixty-eight participants (39 M, 29 F; mean age 10.6 years) diagnosed with ALL and who were previously treated with chemotherapy were included. Thirty-seven participants (23 M, 14 F) were <5 years of age at the time of diagnosis and onset of chemotherapy, while 31 participants (16M, 15 F) were >5 years of age at diagnosis and treatment. Participants ranged in age from 6 to 17 years at the time of their neuropsychological evaluation. Participants were given the WISC-V (PS subtests) and WJ-IV academic fluencies (math and reading). To evaluate research questions and hypotheses, correlational tests, independent samples t-tests, and analyses of variance (ANOVA) were used. Results at the p< .05 level are reported.

There were significant correlations between PS and WJ math fluency (r=.510) and reading fluency (r=.392). Independent samples t-test analyses revealed that children who scored below 85 (standard score) on PS composite score demonstrated poorer performance on WJ math fluency (t(60)=-3.971, p=.000, d=1.065) and reading fluency (t(56)=-3.041, p=.004, d=0.896) compared to children whose PS scores were > 85. For children whose PS scores were <85, mean scores were in the low average range for WJ-IV math fluency (M=81.05) and reading fluency (M=84.50). No significant differences were found for age or gender in relation to PS and academic fluencies.

Findings are important in highlighting the need for school accommodations in pediatric survivors of ALL. Processing speed is one of the most vulnerable functions impacted by cancer therapies and was positively correlated with reading and math fluencies in this study. Mean scores for math and reading fluencies were low average for age. In terms of academic accommodations, due to the slow processing speed of these boys and girls, regardless of their age at diagnosis and onset of chemotherapy, the provision for extra time for ALL survivors is recommended to ensure they are given the opportunity to maximize their learning potential and demonstrate their true academic abilities. Parents are encouraged to practice basic fluencies at home as early as possible. Inhospital and home-bound schooling supports are recommended to maintain educational progress. For children at higher risk for late effects and neurocognitive decline, rehabilitation similar to that which TBI survivors receive can be effective, as well. Future prospective research, including longitudinal tracking, with more homogeneous samples of pediatric survivors of ALL is expected to extend and refine findings of the present study.

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.

This study examines the clinical validity of the NIH Toolbox Cognition Battery measures in patients with oncological diagnoses and tumor predisposition syndromes, including Neurofibromatosis, Type 1 (NF1).

Participants included 158 patients (61% male, 67% White) ages 3 to 25 years (M = 8.38, SD = 4.32) who underwent neuropsychological evaluation between 2019 and 2022. Patients with brain tumors (n = 50) and leukemias (n = 49) accounted for 2/3 of the sample. The remainder had solid tumors, lymphomas, or cancer predisposition syndrome. Forty-eight had a diagnosis of NF1. Performance-based measures of attention, executive functioning, and processing speed were administered as part of neuropsychological evaluations. Patients were administered between 1 to 4 NIH Toolbox Cognition measures, including Flanker Inhibitory Control and Attention Test (Flanker), Dimensional Change Card Sort Test (DCCS), Pattern Comparison Processing Speed Test (PCCS), and List Sorting Test. Parent-reported measures of attention and EF were also obtained. Z-scores were used to compare performance across measures that assessed equivalent constructs. The rates of weak performance (>1 SD below the mean) using Toolbox measures were compared to rates of weak performance on traditional neuropsychological measures (e.g., Digit Span), and rates of functional impairment (e.g., parent-reported concerns, ADHD diagnosis).

FSIQ, Coding, and NEPSY Inhibition correlated with all 4 Toolbox measures, while Digit Span correlated with List Sorting, DCCS, and Flanker. DCCS and PCCS correlated with verbal fluency measures. NF1 patients scored lower than non-NF1 patients on Flanker, F(1,126) = 13.01, p<.001 and DCCS, F(1,150) = 6.85, p = .01. Toolbox performance did not differ significantly by age group. Rates of identified weakness were relatively similar on Toolbox measures, some traditional measures, and parent-reported attention problems. In identifying those with and without weakness, the agreement between Flanker and other measures ranged from 52% (Auditory Attention) to 66% (Coding). Agreement between DCCS and traditional measures ranged from 47% (Letter Fluency) to 80% (Switching). For PCCS, concordance ranged from 45% (Semantic Fluency) to 69% (Switching). List Sorting had 80% agreement with Digit Span and Coding.

List Sorting had the highest agreement with parent-reported attention problems (76%), EF problems (72%), and ADHD diagnosis (79%). There was relatively high concurrence between DCCS and ADHD diagnosis (69%) and parent-reported attention problems (60%) and EF problems (65%) and between Flanker and ADHD diagnosis (67%). PCCS had less agreement with functional outcomes, ranging from 49% for EF problems to 58% for attention problems and ADHD diagnosis. In comparison, Digit Span had 64% agreement for EF problems, 70% for attention problems, and 73% for ADHD diagnosis.

The NIH Toolbox Cognition Battery can be used to identify neurocognitive weaknesses in pediatric oncology patients and provide clinically meaningful data. Evaluation of the Toolbox measures’ sensitivity to change over time is warranted, as monitoring the progression of cognitive late effects is particularly salient in cancer survivorship.