Principles and Practices of Returning Individual Research Results to Participants in Large Studies of Pregnancy and Childhood.

Investigators conducting human subject research have typically conveyed only clinically actionable results back to individual participants. Shifting scientific culture around viewing participants as partners in research, however, is prompting investigators to consider returning as much data or results as the participant would like, even if they are not clearly actionable. Expanding return of individual results may add value for individual participants and their communities, refine future research questions and methods, build trust, and enhance retention of participants. Yet, gaps remain in understanding the implications of these changes for groups of 'vulnerable' participants, including pregnant and pediatric participants. We present the findings of a National Institutes of Health workshop on returning individual research results, particularly as applicable to pregnant and pediatric participants. Research participants who were panelists at the workshop agreed that they desire to receive their results. Workshop findings and current literature indicate that participants have differing preferences for what results they receive. One way to address the limits of current practice is to develop flexible digital platforms that convey individual results along with researchers' availability to answer questions, and to provide as much information as possible about actionable steps to control environmental exposures associated with disease risk.

Impact of Propofol Exposure on Neurocognitive Outcomes in Children With High-Risk B ALL: A Children's Oncology Group Study.

PURPOSE: Many children treated for ALL develop long-term neurocognitive impairments. Increased risk of these impairments is associated with treatment and demographic factors. Exposure to anesthesia is an additional possible risk factor. This study evaluated the impact of cumulative exposure to anesthesia on neurocognitive outcomes among a multicenter cohort of children with ALL. METHODS: This study was embedded in AALL1131, a Children's Oncology Group phase III trial for patients with high-risk B-ALL. In consenting patients age 6-12 years, prospective uniform assessments of neurocognitive function were performed during and at 1 year after completion of therapy. Exposure to all episodes of anesthetic agents was abstracted. Multivariable linear regression models determined associations of cumulative anesthetic agents with the primary neurocognitive outcome reaction time/processing speed (age-normed) at 1 year off therapy, adjusting for baseline neurocognitive score, age, sex, race/ethnicity, insurance status (as a proxy for socioeconomic status), and leukemia risk group. RESULTS: One hundred and forty-four children, 76 (52.8%) males, mean age of 9.1 (min-max, 6.0-12.0) years at diagnosis, underwent a median of 27 anesthetic episodes (min-max, 1-37). Almost all patients were exposed to propofol (140/144, 97.2%), with a mean cumulative dose of 112.3 mg/kg. One year after therapy, the proportion of children with impairment (Z-score ≤-1.5) was significantly higher compared with a normative sample. In covariate-adjusted multivariable analysis, cumulative exposure to propofol was associated with a 0.05 Z-score decrease in reaction time/processing speed per each 10 mg/kg propofol exposure (P = .03). CONCLUSION: In a multicenter and uniformly treated cohort of children with B-ALL, cumulative exposure to propofol was an independent risk factor for impairment in reaction time/processing speed 1 year after therapy. Anesthesia exposure is a modifiable risk, and opportunities to minimize propofol use should be considered.

Reaching "The Other Half": Teacher Referral Increases Inclusivity in Intervention Research for Neurodivergent School-Age Children.

OBJECTIVE: Researchers employed two recruitment strategies in a school-based comparative effectiveness trial for students with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism. This study assessed the: 1) effectiveness of school-based referrals for identifying students meeting diagnostic criteria and 2) impact of eliminating requirements for existing diagnoses on recruitment, sample characteristics, and intervention response. METHOD: Autistic students and students with ADHD in schools serving underresourced communities were recruited for an executive functioning (EF) intervention trial over 2 years. In Year 1, school staff nominated students with previous diagnoses. In Year 2, school staff nominated students demonstrating EF challenges associated with ADHD or autism; previous diagnosis was not required. Study staff then confirmed diagnoses. RESULTS: More students were included in Year 2 (N = 106) than Year 1 (N = 37). In Year 2, 96% of students referred by school staff met diagnostic criteria for ADHD or autism, 53% of whom were not previously diagnosed. Newly identified students were less likely than previously diagnosed students to be receiving services and, for those with ADHD, were more likely to speak primarily Spanish at home. Previously diagnosed and newly identified students did not differ on other demographic variables or intervention response. Caregivers of previously diagnosed students reported more symptoms than caregivers of newly identified students for both diagnostic groups. Previously diagnosed students with ADHD had more researcher-rated symptoms than newly identified students. CONCLUSIONS: Recruitment for an intervention study using behavior-based referrals from school staff enhanced enrollment without compromising the sample's diagnostic integrity and engaged children who otherwise would have been excluded.

Impaired neurocognitive functioning 3 months following diagnosis of high-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer diagnosis. Cognitive late effects develop in 20%-40% of ALL survivors, but the course of declines is unclear. The aim of this paper is to characterize cognitive functioning, and its association with patient-reported outcomes, early in treatment. PATIENTS AND METHODS: A total of 483 children with high-risk ALL, aged 6-12 years at diagnosis, consented to the neurocognitive study embedded in a prospective therapeutic trial, Children's Oncology Group (COG) AALL1131. A computerized neurocognitive battery (Cogstate) was administered 3 months post diagnosis assessing reaction time, visual attention, working memory, visual learning, and executive functioning. Parent-reported executive functioning and patient-reported physical symptoms were also collected. RESULTS: Data from 390 participants (mean age at diagnosis = 9.2 years, 55.4% male) were obtained. Relatively few patients reported pain (16.0%) or nausea (22.6%), but a majority (68.5%) reported feeling at least some fatigue at testing. Mean Cogstate Z-scores were within normal limits across tasks; however, rates of impairment (Z-scores ≤ -1.5) for reaction time, working memory, visual learning, and visual attention were all higher than expected compared to the standardization sample. Patients reporting fatigue were significantly more likely to have impaired reaction time and visual attention compared to those reporting no fatigue. CONCLUSION: Findings support feasibility of computerized cognitive assessments and suggest higher-than-expected rates of impaired cognitive performance early during treatment for pediatric ALL, notably within 3 months of diagnosis, suggesting intervention efforts may be indicated. These results also highlight acute factors that may impact reliability of "baseline" assessments conducted soon after diagnosis.

Transatlantic progress in measurement of cognitive outcomes in paediatric oncology trials.

The importance of measuring quality of survival within paediatric oncology trials is increasingly recognised. However, capturing neuropsychological outcomes and other aspects of quality of survival in the context of large or multinational trials can be challenging. We provide examples of protocols designed to address this challenge recently employed in clinical trials in the USA and Europe. We discuss their respective strengths and challenges, obstacles encountered and future opportunities for transatlantic collaboration.

Design and methods of a randomized web-based physical activity intervention among children with cancer: A report from the Children's Oncology Group.

BACKGROUND: Promoting physical activity soon after treatment for childhood cancer may benefit health because sedentary lifestyle during curative therapy may perpetuate physical and emotional complications. The primary goals of this study are to evaluate the effects of a 6-month web-based, rewards-based physical activity intervention on fitness, biomarkers of cardiometabolic health, inflammation, adipokine status, quality of life and school attendance, and determine if effect of intervention on markers of cardiometabolic health is mediated by changes in fitness. The primary outcome of interest is fitness (physiological cost index, six-minute walk test) measured at end of intervention. METHODS: This ongoing study is a two-arm, prospective, randomized design with accrual goals of 192 children for intervention and control groups. Children ≥8 years and < 16 years of age, not meeting recommended levels of physical activity, who completed therapy within the past 12 months are eligible. Both groups receive: 1) educational materials encouraging physical activity, 2) activity monitor, 3) access to web-based interface designed to motivate physical activity, 4) rewards based on physical activity levels, and 5) access to their activity data on the web-interface. Those randomized to intervention: 1) can view others' activity and interact with other participants, and 2) receive rewards based on physical activity levels throughout the intervention (vs. at the end of the intervention for control group). CONCLUSION: Unique, scalable, and portable physical activity interventions that motivate young survivors are needed. This study will inform future web-based physical activity interventions for children with cancer by demonstrating effects of rewards and social interaction. CLINICAL TRIALS: ClinicalTrials.gov Identifier: NCT03223753; COG Identifier: ALTE1631.

Sluggish Cognitive Tempo in Pediatric Sickle Cell Disease.

Background: Sickle cell disease (SCD) imparts risk for a range of neurodevelopmental and neurocognitive disorders. Sluggish cognitive tempo (SCT) is a distinct syndrome that often co-occurs with attention-deficit/hyperactivity disorder (ADHD) but has not been described in SCD. We investigated the reliability and validity of a SCT measure in SCD and examined associations with biopsychosocial risk factors and functional outcomes. Materials and Methods: Caregivers (n = 85) of children with SCD ages 7-16 reported on socio-demographics and the Kiddie-Sluggish Cognitive Tempo (K-SCT) measure, Behavior Rating Inventory of Executive Function, and Conners 3. Disease-related characteristics were extracted from health records. Results: The K-SCT demonstrated excellent internal consistency (α = 0.92) and test-retest reliability (r = 0.82, p < 0.001). K-SCT scores were correlated with ADHD-Inattention (r = 0.64, p < 0.001) and ADHD-Hyperactive/Impulsive (r = 0.46, p < 0.001) scores, as well as functional outcomes, including learning problems (r = 0.69, p < 0.001). In multivariate analyses controlling for ADHD symptoms, SCT accounted for unique variance in learning (b = 9.67, p < 0.01) and executive functioning (b = 5.93, p < 0.01). Nearly all participants (93%) with elevated levels of co-occurring SCT and ADHD-Inattention symptoms had significant learning problems. Conclusion: The K-SCT is a reliable and valid measure of SCT in SCD. SCT symptoms are associated with learning difficulties even after controlling for ADHD symptoms. Further research is needed to understand the biopsychosocial factors that lead to SCT symptoms in SCD and examine long-term implications of SCT.

Parents matter: Parent acceptance of school-based executive functions interventions relates to improved child outcomes.

OBJECTIVES: School-based interventions with parent-training components might improve access among lower-income families to effective help for children with neurodevelopmental disorders. This potential might be realized, however, only if parents perceive the interventions as acceptable and therefore engage with treatment. METHODS: Parents (N = 124) of 3rd-5th grade students diagnosed with Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder rated the acceptability of their child's treatment (one of two culturally responsive behavioral interventions). Parent engagement was measured through attendance at parent training sessions and the extent to which they read a corresponding workbook. RESULTS: Education and income correlated inversely with parent perceptions of treatment acceptability. Acceptability correlated positively with engagement, more strongly among lower-income families. Acceptability had an indirect effect on treatment outcome, mediated by parent engagement. CONCLUSIONS: Treatment providers should focus on strategies to increase parent acceptability, with particular attention to improving access for lower-income families.

Adding the missing voice: How self-report of autistic youth self-report on an executive functioning rating scale compares to parent report and that of youth with attention deficit hyperactivity disorder or neurotypical development.

LAY ABSTRACT: Executive functions are often impaired in autistic people and relate to important outcomes such as mental health, success in school and work, and quality of life. Evaluating executive functions helps autistic people, clinicians, and families identify targets for external supports and skill building. Youth self-report of executive function has not been studied, yet we know that self-report from autistic youth is key to understanding other cognitive/behavioral phenomena in autism such as anxiety, obsessions/compulsions, sensory sensitivities, and repetitive behaviors. We investigated self- and parent-report of executive function problems in 197 autistic youth without intellectual disability (ages 11-18 years), including the magnitude and profiles of executive function problems autistic youth report across subdomains of executive function. We compared autistic self-report with that of 114 youth with attention deficit hyperactivity disorder without intellectual disability and 197 neurotypical youth. We found that autistic youth report significant executive function problems compared to neurotypical youth and a distinctive profile of challenges in comparison to attention deficit hyperactivity disorder youth. Parents and their autistic children diverged regarding the magnitude of the youth's executive function difficulties, but both identify inflexibility as the most impaired executive function subdomain. Autistic youth and their parents were somewhat more concordant in their report of executive function problems than youth with attention deficit hyperactivity disorder and their parents, but only showed moderate concordance at best. These findings elevate the importance of asking autistic youth directly about their executive functioning when engaging them in assessment and intervention, or researching executive functions in autism.

Assessment of Arsenic Trioxide and All-trans Retinoic Acid for the Treatment of Pediatric Acute Promyelocytic Leukemia: A Report From the Children's Oncology Group AAML1331 Trial.

IMPORTANCE: All-trans retinoic acid (ATRA) and arsenic trioxide therapy without the use of maintenance therapy has been found to be beneficial for the treatment of adults with standard-risk acute promyelocytic leukemia (APL). However, it is unclear whether similar regimens are safe and beneficial for the treatment of high-risk APL or pediatric patients with standard-risk APL. OBJECTIVE: To assess whether treatment with an ATRA and arsenic trioxide-based regimen is safe and allows for the elimination or substantial reduction of chemotherapy use among pediatric patients with standard-risk or high-risk APL, respectively. DESIGN, SETTING, AND PARTICIPANTS: The Children's Oncology Group AAML1331 study is a nonrandomized, noninferiority trial that examined survival outcomes among 154 pediatric patients with APL compared with a historical control group of patients with APL from the AAML0631 study. Patients aged 1 to 21 years were enrolled at 85 pediatric oncology centers (members of the Children's Oncology Group) in Australia, Canada, and the US from June 29, 2015, to May 7, 2019, with follow-up until October 31, 2020. All patients had newly diagnosed APL and were stratified into standard-risk APL (white blood cell count <10 000/µL) and high-risk APL (white blood cell count ≥10 000/µL) cohorts. INTERVENTIONS: All patients received ATRA and arsenic trioxide continuously during induction therapy and intermittently during 4 consolidation cycles. Patients with high-risk APL received 4 doses of idarubicin during induction therapy only. The duration of therapy was approximately 9 months, and no maintenance therapy was administered. MAIN OUTCOMES AND MEASURES: Event-free survival (EFS) at 2 years after diagnosis. RESULTS: Among 154 patients (median age, 14.4 years [range, 1.1-21.7 years]; 81 male participants [52.6%]) included in the analysis, 98 patients (63.6%) had standard-risk APL, and 56 patients (36.4%) had high-risk APL. The median follow-up duration was 24.7 months (range, 0-49.5 months) for patients with standard-risk APL and 22.8 months (range, 0-47.7 months) for patients with high-risk APL. Patients with standard-risk APL had a 2-year EFS rate of 98.0% and an overall survival rate of 99.0%; adverse events included 1 early death during induction therapy and 1 relapse. Patients with high-risk APL had a 2-year EFS rate of 96.4% and an overall survival rate of 100%; adverse events included 2 relapses and 0 deaths. These outcomes met predefined noninferiority criteria (noninferiority margin of 10% among those with standard-risk APL and 14.5% among those with high-risk APL). CONCLUSIONS AND RELEVANCE: In this nonrandomized, noninferiority trial, pediatric patients with standard-risk APL who received treatment with a chemotherapy-free ATRA and arsenic trioxide regimen experienced positive outcomes. Patients with high-risk APL also had positive outcomes when treated with a novel ATRA and arsenic trioxide-based regimen that included 4 doses of idarubicin during induction therapy only and no maintenance therapy. The 2-year EFS estimates were noninferior to the historical comparator group, and advantages of the regimen included shorter treatment duration, lower exposure to anthracycline and intrathecal chemotherapy, and fewer days hospitalized. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02339740.

Suicidal ideation and executive functioning in pediatric cancer.

OBJECTIVE: Neurocognitive impairments and psychological distress are among the most common difficulties experienced by children treated for cancer. Elevated rates of suicidal ideation (SI) are documented among cancer survivors, and a link between neurocognitive deficits and SI is evident, yet the relationship between SI and pediatric cancer-related neurocognitive effects has not yet been studied. PARTICIPANTS AND METHODS: Participants were 166 pediatric cancer patients (57.8% Brain Tumor, 31.3% leukemia, 10.8% other cancers) aged 6-23 (M = 11.57, SD = 3.82; 45.8% female) referred for neuropsychological surveillance. SI prevalence was measured by parent, teacher, or patient endorsement of self-harm related items on informant-report measures (e.g., the Child Behavior Checklist). Executive functioning (Behavior Rating Inventory of Executive Function), ADHD symptoms (ADHD Rating Scale), and performance-based measures were compared between those with SI and those without. RESULTS: 17.5% of pediatric cancer patients experienced SI, of which 44.7% had self-endorsement only, 58.5% parent-endorsement only, 20.6% teacher-endorsement only, and 24.1% had two endorsements. Those with SI had significantly greater impairments in global executive composite scores by both parent- and teacher-report (ps < 0.05). Parents of children with SI endorsed significantly more inattention symptoms (M = 6.10, SD = 15.48) than those without SI (M = 50.56, SD = 8.70; p < 0.01), but hyperactivity symptoms did not differ. Intellectual and executive function performance did not differ between those with and without SI (ps > 0.1). CONCLUSIONS: An elevated number of children treated for cancer experience SI and related neurocognitive problems. Screening for SI and further assessment of the connection between executive functioning and SI in pediatric cancer populations is needed.

Computerized Working Memory Training for Children With Neurofibromatosis Type 1 (NF1): A Pilot Study.

INTRODUCTION: The present study aimed to evaluate the feasibility and efficacy of CogmedRM, a computerized, home-based working memory (WM) training program, in children with NF1. METHOD: A pre-post design was used to evaluate changes in performance-based measures of attention and WM, and parent-completed ratings of executive functioning. Children meeting eligibility criteria completed CogmedRM over 9 weeks. Primary outcomes included compliance statistics and change in attention and WM scores. RESULTS: Thirty-one children (52% male; M age = 10.97 ± 2.51), aged 8-15, were screened for participation; 27 children (87%) evidenced WM difficulties and participated in CogmedRM training. On average, participants completed 19.7 out of 25 prescribed sessions, with an adherence rate of 69%. Participants demonstrated improvements in short-term memory, attention, and executive functioning (all Ps < .05). CONCLUSION: Results suggest that computerized, home-based WM training programs may be both feasible and efficacious for children with NF1 and cognitive deficits.

Recommendations for Social Skills End Points for Clinical Trials in Neurofibromatosis Type 1.

OBJECTIVE: To review parent-report social skills measures to identify and recommend consensus outcomes for use in clinical trials of social deficit in children and adolescents (ages 6-18 years) with neurofibromatosis type 1 (NF1). METHODS: Searches were conducted via PubMed and ClinicalTrials.gov to identity social skills outcome measures with English language versions used in clinical trials in the past 5 years with populations with known social skills deficits, including attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD). Measures were rated by the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Neurocognitive Committee on patient characteristics, use in published studies, domains assessed, availability of standard scores, psychometric properties, and feasibility to determine their appropriateness for use in NF1 clinical trials. RESULTS: Two measures were ultimately recommended by the committee: the Social Responsiveness Scale-2 (SRS-2) and the Social Skills Improvement System-Rating Scale (SSIS-RS). CONCLUSIONS: Each of the 2 measures assesses different aspects of social functioning. The SSIS-RS is appropriate for studies focused on broader social functioning; the SRS-2 is best for studies targeting problematic social behaviors associated with ASD. Researchers will need to consider the goals of their study when choosing a measure, and specific recommendations for their use are provided.

Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma.

PURPOSE: Children with average-risk medulloblastoma (MB) experience survival rates of ≥ 80% at the expense of adverse consequences of treatment. Efforts to mitigate these effects include deintensification of craniospinal irradiation (CSI) dose and volume. METHODS: ACNS0331 (ClinicalTrials.gov identifier: NCT00085735) randomly assigned patients age 3-21 years with average-risk MB to receive posterior fossa radiation therapy (PFRT) or involved field radiation therapy (IFRT) following CSI. Young children (3-7 years) were also randomly assigned to receive standard-dose CSI (SDCSI; 23.4 Gy) or low-dose CSI (LDCSI; 18 Gy). Post hoc molecular classification and mutational analysis contextualized outcomes according to known biologic subgroups (Wingless, Sonic Hedgehog, group 3, and group 4) and genetic biomarkers. Neurocognitive changes and ototoxicity were monitored over time. RESULTS: Five hundred forty-nine patients were enrolled on study, of which 464 were eligible and evaluable to compare PFRT versus IFRT and 226 for SDCSI versus LDCSI. The five-year event-free survival (EFS) was 82.5% (95% CI, 77.2 to 87.8) and 80.5% (95% CI, 75.2 to 85.8) for the IFRT and PFRT regimens, respectively, and 71.4% (95% CI, 62.8 to 80) and 82.9% (95% CI, 75.6 to 90.2) for the LDCSI and SDCSI regimens, respectively. IFRT was not inferior to PFRT (hazard ratio, 0.97; 94% upper CI, 1.32). LDCSI was inferior to SDCSI (hazard ratio, 1.67%; 80% upper CI, 2.10). Improved EFS was observed in patients with Sonic Hedgehog MB who were randomly assigned to the IFRT arm (P = .018). Patients with group 4 MB receiving LDCSI exhibited inferior EFS (P = .047). Children receiving SDCSI exhibited greater late declines in IQ (estimate = 5.87; P = .021). CONCLUSION: Reducing the radiation boost volume in average-risk MB is safe and does not compromise survival. Reducing CSI dose in young children with average-risk MB results in inferior outcomes, possibly in a subgroup-dependent manner, but is associated with better neurocognitive outcome. Molecularly informed patient selection warrants further exploration for children with MB to be considered for late-effect sparing approaches.

A Randomized Controlled Trial of Working Memory Training in Pediatric Sickle Cell Disease.

OBJECTIVE: Youth with sickle cell disease (SCD) are at risk for neurocognitive deficits including problems with working memory (WM), but few interventions to improve functioning exist. This study sought to determine the feasibility and efficacy of home-based, digital WM training on short-term memory and WM, behavioral outcomes, and academic fluency using a parallel group randomized controlled trial design. METHODS: 47 children (7-16 years) with SCD and short-term memory or WM difficulties were randomized to Cogmed Working Memory Training at home on a tablet device (N = 24) or to a standard care Waitlist group (N = 23) that used Cogmed after the waiting period. Primary outcomes assessed in clinic included performance on verbal and nonverbal short-term memory and WM tasks. Secondary outcomes included parent-rated executive functioning and tests of math and reading fluency. RESULTS: In the evaluable sample, the Cogmed group (N = 21) showed greater improvement in visual WM compared with the Waitlist group (N = 22; p = .03, d = 0.70 [CI95 = 0.08, 1.31]). When examining a combined sample of participants, those who completed ≥10 training sessions exhibited significant improvements in verbal short-term memory, visual WM, and math fluency. Adherence to Cogmed was lower than expected (M = 9.07 sessions, SD = 7.77), with 19 participants (41%) completing at least 10 sessions. Conclusions: Visual WM, an ability commonly affected by SCD, is modifiable with cognitive training. Benefits extended to verbal short-term memory and math fluency when patients completed a sufficient training dose. Additional research is needed to identify ideal candidates for training and determine whether training gains are sustainable and generalize to real-world outcomes.

Assessing neuropsychological phenotypes of pediatric brain tumor survivors.

INTRODUCTION: Pediatric brain tumor survivors (PBTS) are at risk for both neurocognitive impairments and psychological difficulties, yet these two domains have historically been discretely examined, with assessment of psychosocial outcomes rarely included in studies of cognitive outcomes. Taking a person-centered approach, the current study aimed to more comprehensively evaluate PBTS late effect profiles, including both neurocognitive and psychological sequelae, and predictors of these profiles. METHOD: PBTS (N = 89) were assessed in a pediatric neuropsychological clinic between May 2009 and May 2018, diagnosed at least 1 year prior, and off-treatment for at least 3 months (Mage  = 6.57 years, SD = 4.53; 46.1% female). Parent- and teacher-report of psychological symptoms, and performance-based measures of neurocognitive functioning were examined using latent profile analysis. The R3STEP procedure identified predictors of class membership. RESULTS: The optimal model identified four classes characterized by: (1) average functioning across all measures ("Average," n = 47), (2) average psychosocial functioning and impaired neurocognitive functioning ("Cognitive Deficit," n = 25), (3) elevated social problems and significant neurocognitive impairments ("Social/Cognitive Deficit," n = 9), and (4) impaired visual planning and problem-solving and elevated parent-reported psychosocial problems, but average processing speed, working memory, and teacher-reported psychosocial outcomes ("Discrepant," n = 8). Ethnicity, race, radiation treatment, and diagnoses of neurofibromatosis 1, hydrocephalus, and cerebellar mutism syndrome were significant predictors of class membership (ps < 0.05). CONCLUSION: The present study identified distinct phenotypes with unique patterns of relations among neurocognitive and psychological domains. These findings are a vital first step toward identifying those at highest risk for poor outcomes and informing interventions that effectively address interrelated treatment targets for specific groups.