Cognitive predictors of social adjustment in pediatric brain tumor survivors treated with photon versus proton radiation therapy.

BACKGROUND: Pediatric brain tumor survivors are at risk for poor social outcomes. It remains unknown whether cognitive sparing with proton radiotherapy (PRT) supports better social outcomes relative to photon radiotherapy (XRT). We hypothesized that survivors treated with PRT would outperform those treated with XRT on measures of cognitive and social outcomes. Further, we hypothesized that cognitive performance would predict survivor social outcomes. PROCEDURE: Survivors who underwent PRT (n = 38) or XRT (n = 20) participated in a neurocognitive evaluation >1 year post radiotherapy. Group differences in cognitive and social functioning were assessed using analysis of covariance (ANCOVA). Regression analyses examined predictors of peer relations and social skills. RESULTS: Age at evaluation, radiation dose, tumor diameter, and sex did not differ between groups (all p > .05). XRT participants were younger at diagnosis (XRT M = 5.0 years, PRT M = 7.6 years) and further out from radiotherapy (XRT M = 8.7 years, PRT M = 4.6 years). The XRT group performed worse than the PRT group on measures of processing speed (p = .01) and verbal memory (p < .01); however, social outcomes did not differ by radiation type. The proportion of survivors with impairment in peer relations and social skills exceeded expectation; χ2 (1) = 38.67, p < .001; χ2 (1) = 5.63, p < .05. Household poverty predicted peer relation difficulties (t = 2.18, p < .05), and verbal memory approached significance (t = -1.99, p = .05). Tumor diameter predicted social skills (t = -2.07, p < .05). CONCLUSIONS: Regardless of radiation modality, survivors are at risk for social challenges. Deficits in verbal memory may place survivors at particular risk. Results support monitoring of cognitive and social functioning throughout survivorship, as well as consideration of sociodemographic risk factors.

Treatment age and neurocognitive outcomes following proton beam radiotherapy for pediatric low- and intermediate-grade gliomas.

The relationship between age and neurocognitive functioning following proton beam radiotherapy (PRT) in low- and intermediate-grade gliomas (LIGG) has yet to be examined. Eighteen LIGG patients treated with PRT were prospectively enrolled and received annual neurocognitive evaluations of perceptual/verbal reasoning, working memory, and processing speed postradiotherapy. The median age at diagnosis was 8.2 years (range 1.0-14.7) and the median age at PRT was 9.9 years (range 4.2-17.0). Patients' neurocognitive performance did not change on any measure following PRT (p ≥ .142). We did not observe significant changes in cognitive function over time among a small group of LIGG patients treated with PRT.

Long-term cognitive and academic outcomes among pediatric brain tumor survivors treated with proton versus photon radiotherapy.

BACKGROUND: Proton radiotherapy (PRT) may be associated with less neurocognitive risk than photon RT (XRT) for pediatric brain tumor survivors. We compared neurocognitive and academic outcomes in long-term survivors treated with XRT versus PRT. METHODS: Survivors underwent neurocognitive evaluation >1 year after craniospinal (CSI) or focal PRT or XRT. Groups were compared using separate one-way analyses of covariance for the CSI and focal groups. RESULTS: PRT (n = 58) and XRT (n = 30) subgroups were similar on gender (66% male), age at RT (median = 6.5 years), age at follow-up (median = 14.6 years), and government assistance status (32%). PRT and XRT focal groups differed on follow-up interval, shunt history, and total RT dose (all p < .05), whereas PRT and XRT CSI groups differed on follow-up interval, baseline neurocognitive performance score, boost volume, and CSI dose (all p < .05). The PRT focal group outperformed the XRT focal group on inhibition/switching (p = .04). The PRT CSI group outperformed the XRT CSI group on inattention/impulsivity (both p < .05). Several clinical variables (i.e., RT dose, boost field, baseline performance) predicted neurocognitive outcomes (all p < .05). The PRT focal group performed comparably to population means on most neurocognitive measures, while both CSI groups performed below expectation on multiple measures. The XRT CSI group was most impaired. All groups fell below expectation on processing speed, fine motor, and academic fluency (most p < .01). CONCLUSIONS: Findings suggest generally favorable neurocognitive and academic long-term outcomes following focal PRT. Impairment was greatest following CSI regardless of modality. Dosimetry and baseline characteristics are important determinants of outcome alone or in combination with modality.

Effect of sensorineural hearing loss on neurocognitive and adaptive functioning in survivors of pediatric embryonal brain tumor.

PURPOSE: Survivors of pediatric embryonal brain tumors (BT) are at high risk for sensorineural hearing loss (SNHL) associated with neurocognitive decline. However, previous studies have not assessed the relationship between SNHL and adaptive functioning. We examined neurocognitive and adaptive functioning in patients with and without SNHL. METHODS: Participants included 36 patients treated for an embryonal BT with craniospinal irradiation (CSI) and cisplatin chemotherapy who were assessed 6.7 years post-treatment on average. The impact of SNHL on neurocognitive performance and parent-rated adaptive functioning was assessed in univariate and multivariate analyses. RESULTS: There were 17 cases with SNHL (mean age at evaluation = 14.4) and 19 cases with NH (mean age at evaluation = 13.8). After accounting for age at diagnosis and additional covariates in multivariable analyses, SNHL was associated with worse overall intellectual functioning (p = 0.027) and perceptual reasoning (p = 0.016) performance. There was no effect of SNHL on adaptive functioning in multivariable models. Age at diagnosis and sex were associated with performance on neurocognitive measures. CONCLUSIONS: SNHL in pediatric embryonal BT is associated with increased risk for neurocognitive deficits in conjunction with other demographic and treatment-related factors.

Premorbid functioning as a predictor of outcome in pediatric brain tumor: An initial examination of the normalcy assumption.

BACKGROUND: Research on neurodevelopmental outcome in survivors of pediatric brain tumor (BT) is often based on the assumption of normal development up to the onset of overt symptoms. We sought to verify the "normalcy assumption" and to investigate corollary issues including challenges inherent to the measurement of premorbid neurobehavioral functioning. PROCEDURE: The Brain Radiation Investigative Study Consortium (BRISC) is a prospective longitudinal multisite study of 58 children diagnosed with BT. Premorbid functioning was assessed via retrospective parent report on standardized rating scales and detailed questionnaires. Findings were examined for the sample as a whole and in patients grouped by tumor histology (embryonal and non-embryonal). RESULTS: Mean age at diagnosis was 9.84 years (range, 3-16). The overall sample showed low proportions of pre/postnatal risk factors and delays in development. The proportion of children with clinically significant premorbid attention (18%) problems based on the BASC-2 exceeded expectation of that in healthy children (6.68%). Similar findings were obtained for somatization (18%) and anxiety (14%). Delays in talking were significantly more common in children with embryonal than non-embryonal tumors (P = 0.02). The non-embryonal tumor group had significantly higher overall rates of premorbid psychosocial problems than the embryonal tumor group (P < 0.001). CONCLUSIONS: We describe a rigorous approach to estimating premorbid developmental status in pediatric BT. The findings suggest mixed support for the "normalcy assumption" and highlight the complexity of this concept and need for further investigation. Our results also suggest the need for further study of potential premorbid correlates with tumor histology.

Cognitive mediators of adaptive functioning outcomes in survivors of pediatric brain tumors treated with proton radiotherapy.

BACKGROUND: Cranial radiotherapy (RT) is associated with risk for cognitive and adaptive dysfunction. Proton RT (PRT) is a technique hypothesized to spare cognition by reducing exposure to nontarget brain tissue. However, little is known regarding functional outcomes in survivors of pediatric brain tumor (BT) treated with PRT. The present study examined the relationship between cognitive and adaptive outcomes in pediatric BT survivors post-PRT. METHODS: Survivors treated with either focal (n = 33) or craniospinal irradiation (CSI; n = 37) PRT completed neurocognitive evaluations approximately 5 years post-treatment. Results of intelligence testing and ratings of adaptive functioning are reported. Mediation models examined the relationship among radiation field, cognition, and adaptive functioning. RESULTS: The PRT CSI group demonstrated worse cognitive outcomes than the PRT Focal group across each cognitive index (Cohen's d = 0.56-0.70). Parent ratings of adaptive functioning were also worse in the PRT CSI group than the PRT Focal group (Global Adaptive Composite, d = 0.53; conceptual skills, d = 0.67). Cognitive performance fully mediated the relationship between radiation field and adaptive outcomes, while controlling for group differences in tumor histology and RT dose. CONCLUSIONS: Focal PRT survivors demonstrated generally positive outcomes with weaknesses in processing speed and aspects of adaptive functioning. CSI exposure was associated with more consistently poor cognitive and adaptive outcomes. The increased risk for adaptive dysfunction in the PRT CSI group appeared due to the effects of CSI on cognition. Efforts to reduce the volume of tissue exposure to RT remain important.

Neuropsychological and socioeconomic outcomes in adult survivors of pediatric low-grade glioma.

BACKGROUND: Current estimates suggest that 75% of children diagnosed with a central nervous system (CNS) tumor will become 5-year survivors. However, survivors of childhood CNS tumors are at increased risk for long-term morbidity. METHODS: To determine long-term neuropsychological and socioeconomic status (SES) outcomes, adult survivors of pediatric low-grade gliomas (n = 181) in the Childhood Cancer Survivor Study and a sibling comparison group that was frequency-matched by age and sex (n = 105) completed a comprehensive battery of standardized neuropsychological tests and an SES assessment. Multivariable regression models compared treatment-specific groups for neuropsychological and SES outcomes and evaluated associations with tumor location, age at diagnosis, sex, and age at evaluation. RESULTS: In adjusted models, survivors treated with surgery and radiotherapy (surgery+RT; median age at diagnosis, 7 years; median age at assessment, 41 years) scored lower on estimated IQ than survivors treated with surgery only, who scored lower than siblings (surgery+RT, 93.9; surgery only, 101.2; siblings, 108.5; all P values <.0001). Survivors diagnosed at younger ages had low scores for all outcomes (P < .05) except for attention/processing speed. For SES outcomes, survivors treated with surgery+RT had lower occupation scores (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1-5.9), lower income (OR, 2.6; 95% CI, 1.3-5.0), and less education (OR, 2.1; 95% CI, 1.1-4.0) than those treated with surgery only. CONCLUSIONS: Decades after treatment, survivors treated with radiotherapy and at younger ages had poorer neuropsychological and SES outcomes. Lifelong surveillance of survivors of pediatric low-grade gliomas may be warranted as life events, stages, and transitions (employment, family, and aging) present new challenges and risks.

Adaptive functioning in pediatric brain tumor survivors: An examination of ethnicity and socioeconomic status.

BACKGROUND: Survivors of pediatric brain tumor are at risk for adaptive difficulties. The present study examined adaptive functioning in a multiethnic sample of survivors accounting for socioeconomic status, and whether demographic, diagnostic, and/or treatment-related variables predict adaptive outcomes. METHOD: Participants included a multiethnic sample of survivors (58 Caucasian, 34 Hispanic, and 22 other non-Caucasian; M age = 14.05 years, SD = 4.33) who were approximately seven years post-treatment. Parents rated adaptive functioning and provided demographic information. Diagnostic and treatment-related information was abstracted from the electronic medical record. RESULTS: Parent ratings of adaptive functioning were similar across Caucasian, Hispanic, and other non-Caucasian survivors covarying for family income and primary caregiver education, both of which served as proxies for socioeconomic status. All ethnic groups were rated lower than the normative mean in overall adaptive functioning as well as the specific domains of conceptual, social, and practical skills. Demographic, diagnostic, and treatment-related variables were differentially associated with adaptive functioning in survivors of pediatric brain tumor, though socioeconomic status emerged as a strong significant predictor of adaptive functioning domains. CONCLUSIONS: Adaptive outcomes do not differ as a function of ethnicity after accounting for primary caregiver education and family income. Racial and ethnic minorities may be at increased risk for poorer outcomes given their overrepresentation at lower income levels. Assessing demographic and treatment-related variables early on may be helpful in identifying children likely to develop adaptive difficulties.

Predicting changes in adaptive functioning and behavioral adjustment following treatment for a pediatric brain tumor: A report from the Brain Radiation Investigative Study Consortium.

BACKGROUND: Children are at risk for behavioral and adaptive difficulties following pediatric brain tumor. This study explored whether familial/demographic, developmental, diagnostic, or treatment-related variables best predict posttreatment behavioral and adaptive functioning. METHODS: Participants included 40 children (mean age = 12.76 years, SD = 4.01) posttreatment (mean time since diagnosis = 1.99 years, SD = 0.21) for pediatric brain tumor. Parents rated children's behavioral adjustment and adaptive functioning and provided demographic and developmental histories. Diagnostic and treatment-related information was abstracted from medical records. RESULTS: Ratings of adaptive and behavioral functioning approximately 2 years postdiagnosis were within the average range, although the percentage of children exceeding clinical cutoffs for impairment in adaptive skills exceeded expectation, particularly practical skills. Premorbid behavior problems and tumor size predicted posttreatment adaptive functioning. After accounting for adaptive functioning near diagnosis, premorbid behavior problems predicted declines in adaptive functioning 2 years postdiagnosis. After accounting for adjustment near diagnosis, no variables predicted declines in behavioral adjustment. CONCLUSIONS: Children may be vulnerable to reduced adaptive functioning following pediatric brain tumor treatment, especially in practical skills. Assessing prediagnosis functioning and diagnostic and treatment-related variables may improve our ability to predict those at greatest risk, although those factors may be less helpful in identifying children likely to develop behavioral difficulties. Screening of these factors in tertiary care and long-term follow-up settings may improve identification of those at greatest need for support services.

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

BACKGROUND: Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. PROCEDURE: The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). RESULTS: Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. CONCLUSIONS: These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning.

Predictors of adaptive functioning and psychosocial adjustment in children with pediatric brain tumor: a report from the Brain Radiation Investigative Study Consortium.

BACKGROUND: Children are at risk for psychosocial and adaptive morbidities following diagnosis of and treatment for a pediatric brain tumor. This study examined whether familial/demographic, developmental, diagnostic, or treatment-related variables best predict the acute psychosocial adjustment and adaptive functioning of children soon after an initial diagnosis. PROCEDURE: Participants included 56 children (mean age = 10.72, SD = 4.02) newly diagnosed with a pediatric brain tumor. Parents completed background/demographic forms and completed ratings of children's behavioral and emotional symptoms, and adaptive behavior. Diagnostic and treatment-related information was abstracted from medical records. RESULTS: Parent ratings of behavioral symptoms and adaptive functioning were within normative expectation, although rates of clinical impairment in adaptive functioning exceeded expected rates. A combination of familial/demographic and diagnostic variables were associated with acute functioning. In multiple regressions, tumor size best predicted adaptive functioning after initial diagnosis, whereas tumor location best predicted variance in behavioral symptoms. CONCLUSIONS: Children may be more vulnerable to acute impairment in adaptive functioning following diagnosis of a pediatric brain tumor, but rates of behavioral symptoms were within expectation. Familial, sociodemographic, and diagnostic variables may help to identify those most at risk of impairment. Screening of these factors within tertiary care settings will be useful to identify those most in need of psychosocial care during the initial phases of treatment.

Oxandrolone for the treatment of bone marrow failure in Fanconi anemia.

BACKGROUND: A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization. PROCEDURE: A single arm, Phase I/II study was designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic response was noted at 16 weeks, a single dose escalation was offered. Subjects were regularly assessed for toxicity, including determinations of virilization, behavioral changes, and liver and kidney function. At 32 weeks, those who demonstrated hematologic response were allowed to continue study treatment, and those without improvement were deemed non-responsive. RESULTS: Nine subjects completed the study and were followed for a median of 99 weeks (46-136 weeks). Three (33.3%) subjects developed mild sub-clinical virilization and continued treatment with a dose reduction. None (0%) had adverse behavioral changes. Two (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven (77.8%) subjects had a hematologic response. CONCLUSION: Oxandrolone appears to be well-tolerated, has limited toxicities at the administered doses in FA with patients, and may be an alternative androgen for the treatment of BMF in FA.

Intellectual and academic outcome following two chemotherapy regimens and radiotherapy for average-risk medulloblastoma: COG A9961.

PURPOSE: Assess the intellectual and academic outcomes as well as risk factors associated with treatment for average-risk medulloblastoma in childhood using 23.4 Gy of craniospinal radiotherapy plus adjuvant chemotherapy. METHODS: From an overall sample of 379 enrolled in the parent study (COG A9961), 110 patients received a total of 192 assessments over more than 5 years with standardized IQ and academic achievement tests. Random coefficient models of the various outcomes were developed that incorporated covariates including chemotherapy regimen, age at diagnosis, sex, initial Full Scale IQ, and mutism. RESULTS: Participants in this study were found to be comparable to the overall sample in all demographic, disease, and treatment factors, except there were more gross total resections in the subsample undergoing intellectual and academic assessment. Major findings include significant decline in both intellectual and academic domains over time that were greater in children who were younger at diagnosis and had higher initial intelligence test scores. Children with mutism were at higher risk for initial effects on intelligence. No effects of sex were found. CONCLUSION: These results show progressive decline over several years post-treatment in standardized intellectual and academic scores. Despite recent improvements in therapies for these children, most notably a decrease dose of craniospinal radiation, they remain at risk. The pursuit of less toxic treatments, particularly for younger children, should continue. Neuropsychological surveillance should be routine at centers treating children with brain tumors.

The association between sleep disordered breathing, academic grades, and cognitive and behavioral functioning among overweight subjects during middle to late childhood.

STUDY OBJECTIVES: (1) to determine the associations of sleep disordered breathing (SDB) with behavioral functioning, cognitive test scores, and school grades during middle- to late-childhood, an under-researched developmental period in the SDB literature, and (2) to clarify whether associations between SDB and school grades are mediated by deficits in cognitive or behavioral functioning. DESIGN: cross-sectional correlative study. SETTING: Office/hospital, plus reported functioning at home and at school. PARTICIPANTS: 163 overweight subjects aged 10-16.9 years were divided into 4 groups based upon their obstructive apnea+hypopnea index (AHI) during overnight polysomnography and parent report of snoring: Moderate-Severe OSA (AHI > 5, n = 42), Mild OSA (AHI = 1-5, n = 58), Snorers (AHI < 1 + snoring, n = 26), and No SDB (AHI < 1 and nonsnoring, n = 37). MEASUREMENTS: inpatient overnight polysomnography, parent- and self-report of school grades and sleep, parent- and teacher-report of daytime behaviors, and office-based neuropsychological testing. RESULTS: The 4 groups significantly differed in academic grades and parent- and teacher-reported behaviors, particularly inattention and learning problems. These findings remained significant after adjusting for subject sex, race, socioeconomic status, and school night sleep duration. Associations with SDB were confined to reports of behavioral difficulties in real-world situations, and did not extend to office-based neuropsychological tests. Findings from secondary analyses were consistent with, but could not definitively confirm, a causal model in which SDB affects school grades via its impact on behavioral functioning. CONCLUSIONS: SDB during middle- to late-childhood is related to important aspects of behavioral functioning, especially inattention and learning difficulties, that may result in significant functional impairment at school.

[Formula: see text] Reliable change in pediatric brain tumor: A preliminary investigation.

Children treated for brain tumor show evidence of declines in general intellectual abilities (i.e., IQ). Group-level data indicate subtle declines over time on average, but no study has utilized a clinical criterion to identify and describe a reliable change in survivors of pediatric brain tumor (PBT). In this study, we discuss the utility of reliable change index (RCI) methodology to supplement group-level analysis (e.g., repeated measures ANOVA). This pilot sample consisted of 22 children (M age = 10.47 years) treated for PBT who completed initial and follow-up assessments (M interval = 23.58 months). Cognitive data included composite scores from the WISC-IV. An RCI z-score was calculated for each participant on each composite score based on two different test-retest reliability coefficients. As a group, survivors of PBT did not demonstrate a statistically significant change from initial to follow-up on any WISC-IV composite score. When RCI was calculated based on reliability coefficients with shorter test-retest intervals provided by the test publisher, 77% of survivors demonstrated a reliable change in performance on at least one measure. The frequency of RCI decreases in working memory was significantly higher than expected. In contrast, only 32% of survivors showed reliable changes on at least one measure when RCI was based on a reliability coefficient derived from a clinical sample with a longer retest interval. This study demonstrates that highly divergent results may be obtained with RCI and the importance of the source of reliability estimates.

Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma.

PURPOSE: Proton radiotherapy (PRT) may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy (XRT). We examined the change in intellectual scores over time in patients with pediatric medulloblastoma treated with craniospinal PRT versus XRT. METHODS: Intelligence test scores were obtained for a sample of pediatric patients treated between 2007 and 2018 on the same medulloblastoma protocols that differed only in radiotherapy modality (PRT v XRT). Growth curve analyses compared change in scores over time since diagnosis between groups. RESULTS: Longitudinal intelligence data from 79 patients (37 PRT, 42 XRT) were examined. Groups were similar on most demographic/clinical variables, including sex (67.1% male), age at diagnosis (mean, 8.6 years), craniospinal irradiation dose (median, 23.4 Gy), length of follow-up (mean, 4.3 years), and parental education (mean, 14.3 years). Boost dose (P < .001) and boost margin (P = .001) differed between groups. Adjusting for covariates, the PRT group exhibited superior long-term outcomes in global intelligence quotient (IQ), perceptual reasoning, and working memory compared with the XRT group (all P < .05). The XRT group exhibited a significant decline in global IQ, working memory, and processing speed (all P < .05). The PRT group exhibited stable scores over time in all domains with the exception of processing speed (P = .003). CONCLUSION: To our knowledge, this is the first study to compare intellectual trajectories between pediatric patients treated for medulloblastoma with PRT versus those treated with XRT on comparable, contemporary protocols. PRT was associated with more favorable intellectual outcomes in most domains compared with XRT, although processing speed emerged as a vulnerable domain for both groups. This study provides the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.

Processing speed in children treated for brain tumors: effects of radiation therapy and age.

The current study examined processing speed in children two years post-treatment for brain tumors (BT) with radiation therapy (RT) compared to those treated with without RT. Participants included 59 children (4-17 years) with BT assessed as part of the Brain Radiation Investigative Study Consortium (BRISC). Processing speed was assessed at two time points: Time1 (3-9 months post-surgery) for 26 children who received whole brain or focal RT (RT group) and 33 treated without RT (no-RT group), and again two years later (Time2) for 42 participants (17 RT, 25 no-RT). Linear mixed effects (LME) regression analyses examined differences in cognitive and motor speed between groups and across visits, with age at Time1 (age1) treated as a moderating variable, and sex and primary tumor size as covariates. No effects for treatment group or visit were found for motor speed (Pegboard) or mean reaction time (Attention Network Task). On the Wechsler Processing Speed Index (PSI), the no-RT group performed better than the RT group, with a group-by-age interaction such that across visits, the difference between the no-RT and RT groups was larger among children who were older at initial treatment (≥10 years) than among those who were younger (<10 years). Cumulative brain injury earlier in life (tumor, surgery, plus RT) may result in greater impact on more complex tasks of cognitive efficiency. Children receiving RT showed reduced processing speed over time, with a larger group difference among those who were over 10 years at treatment.

Interactions between visual working memory and visual attention among survivors of pediatric acute lymphoblastic leukemia (ALL) and their healthy peers.

Introduction: There is increasing concern for adverse cognitive late effects among survivors of pediatric acute lymphoblastic leukemia (ALL) given the widespread impact they have on academic achievement, particularly working memory and attention. We assessed performance among survivors and their healthy peers on a dual task paradigm measuring visual working memory (VWM) and visual attention independently and the dynamic relationship between the two. Assessing specific subsets within cognitive domains allows for understanding the distinct nature of cognitive impairments. Method: Participants were 34 survivors of ALL who have been off-treatment and disease free for 7.5 years; and 20 healthy controls, all between the ages of 10 and 18 years. We utilized behavioral single- and dual-task paradigms. In the dual tasks, participants maintained several items in VWM while performing a visual attention task (Eriksen Flanker Task) that required processing of a target stimulus while inhibiting the processing of distractor stimuli. The single tasks involved performing only the VWM task or only the visual attention task. Results: Results revealed survivors of ALL performed significantly worse than their healthy peers on the single visual attention task but not the single VWM task. Of particular interest, group differences were obtained on the dual VWM and visual attention tasks, such that the VWM and attention tasks reciprocally interfered with each other only among survivors and not their healthy peers. Conclusions: Our results highlight a core deficit in visual attention that is exacerbated by VWM demands among survivors of ALL. The implementation of tasks from cognitive neuroscience paradigms may be sensitive to cognitive impairments experienced by cancer survivors. Assessment and intervention practices among survivors of pediatric ALL are discussed.

Neuropsychological functioning following surgery for pediatric low-grade glioma: a prospective longitudinal study.

OBJECTIVE: High survival rates have led to an increased emphasis on the functional outcomes of children diagnosed with low-grade glioma. Most outcomes research has focused on risks associated with radiotherapy, but less is known about neuropsychological risks for patients treated with surgery alone. Here, the authors sought to examine the neuropsychological trajectories of children diagnosed with a low-grade glioma and monitored up to 6 years postsurgery. Secondarily, they explored demographic and clinical predictors of neuropsychological performance. METHODS: The neuropsychological functioning of 32 patients (median age at diagnosis 10.0 years) was prospectively assessed annually for up to 6 years after surgery (median days from surgery at baseline = 72). Tumor location was predominately supratentorial (65.6%). A combination of performance-based and parent-reported measures was used to assess intelligence, memory, executive functioning, and fine motor control in all patients. RESULTS: Binomial tests at the postoperative baseline revealed that the proportion of children falling below the average range (< 16th percentile) was significantly higher than the rate expected among healthy peers on measures of verbal memory, processing speed, executive functioning, and fine motor control (p < 0.05). Even so, linear mixed models indicated that neuropsychological functioning at the postoperative baseline did not significantly change over time for up to 6 years after surgery across all domains. A larger tumor size was associated with a slower reaction time (p < 0.01). A supratentorial tumor location and history of seizures were associated with more parent-reported executive difficulties (p < 0.01). CONCLUSIONS: While radiotherapy is a known risk factor for neuropsychological deficits in pediatric brain tumor patients, findings in this study indicate that children treated for low-grade glioma with surgery alone (without radiotherapy or chemotherapy) remain susceptible to difficulties with memory, executive functioning, and motor functioning that persist over time. Over half of the children in the study sample required school support services to address neuropsychological weaknesses. Although low-grade glioma is often conceptualized as a benign tumor, children treated for this lesion require ongoing monitoring and intervention to address neuropsychological weaknesses resulting from the tumor itself as well as the surgery.

Association of prenatal and childhood blood lead concentrations with criminal arrests in early adulthood.

BACKGROUND: Childhood lead exposure is a purported risk factor for antisocial behavior, but prior studies either relied on indirect measures of exposure or did not follow participants into adulthood to examine the relationship between lead exposure and criminal activity in young adults. The objective of this study was to determine if prenatal and childhood blood lead concentrations are associated with arrests for criminal offenses. METHODS AND FINDINGS: Pregnant women were recruited from four prenatal clinics in Cincinnati, Ohio if they resided in areas of the city with a high concentration of older, lead-contaminated housing. We studied 250 individuals, 19 to 24 y of age, out of 376 children who were recruited at birth between 1979 and 1984. Prenatal maternal blood lead concentrations were measured during the first or early second trimester of pregnancy. Childhood blood lead concentrations were measured on a quarterly and biannual basis through 6.5 y. Study participants were examined at an inner-city pediatric clinic and the Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio. Total arrests and arrests for offenses involving violence were collected from official Hamilton County, Ohio criminal justice records. Main outcomes were the covariate-adjusted rate ratios (RR) for total arrests and arrests for violent crimes associated with each 5 microg/dl (0.24 micromol/l) increase in blood lead concentration. Adjusted total arrest rates were greater for each 5 microg/dl (0.24 micromol/l) increase in blood lead concentration: RR = 1.40 (95% confidence interval [CI] 1.07-1.85) for prenatal blood lead, 1.07 (95% CI 0.88-1.29) for average childhood blood lead, and 1.27 (95% CI 1.03-1.57) for 6-year blood lead. Adjusted arrest rates for violent crimes were also greater for each 5 microg/dl increase in blood lead: RR = 1.34 (95% CI 0.88-2.03) for prenatal blood lead, 1.30 (95% CI 1.03-1.64) for average childhood blood lead, and 1.48 (95% CI 1.15-1.89) for 6-year blood lead. CONCLUSIONS: Prenatal and postnatal blood lead concentrations are associated with higher rates of total arrests and/or arrests for offenses involving violence. This is the first prospective study to demonstrate an association between developmental exposure to lead and adult criminal behavior.