Measuring what gets done: Using goal attainment scaling in a vocational counseling program for survivors of childhood cancer.

BACKGROUND: Childhood cancer survivors face education and employment challenges due to physical, cognitive, and psychosocial effects of the disease and treatments, with few established programs to assist them. The objectives of this study were to describe the implementation of Goal Attainment Scaling (GAS) to evaluate an educational and vocational counseling program established for survivors of childhood cancer, and analyze patterns of program engagement and client outcomes, stratified by demographic and diagnostic characteristics. METHODS: A population-based retrospective cohort study of childhood cancer survivors who were engaged with the Pediatric Oncology Group of Ontario's School and Work Transitions Program (SWTP) between January 2015 and December 2018 was utilized. Survivors were followed from SWTP engagement until May 30, 2019 to capture goal attainment. Individual goals were summarized across various demographic, disease, and treatment strata. RESULTS: In total, 470 childhood cancer survivors (median age = 17.9, 58% male) set 4,208 goals in the SWTP during the study period. The mean length of observation was 130.8 weeks (SD = 56.9). Overall, 68% of the goals were achieved. Eighty-three percent of the goals related to further education. Clients diagnosed with a solid tumor set the most goals on average, followed by those with central nervous system tumors and leukemia/lymphoma. CONCLUSIONS: The SWTP assists childhood cancer survivors in realizing their academic and vocational goals. Application of GAS in this setting is a feasible way to evaluate program outcomes. From the volume and breadth of the GAS goals set and achieved, the overall success of the SWTP appears strong.

Quantitative MRI outcomes in child and adolescent leukemia survivors: Evidence for global alterations in gray and white matter.

INTRODUCTION: Cure rates for pediatric acute lymphoblastic leukemia (ALL) have reached an all-time high (>90%); however, neurocognitive difficulties continue to affect quality of life in at least a subset of survivors. There are relatively few quantitative neuroimaging studies in child and adolescent ALL survivors treated with chemotherapy only. Use of different outcome measures or limited sample sizes restrict our ability to make inferences about patterns of brain development following chemotherapy treatment. In this study, we used magnetic resonance imaging (MRI) to evaluate brain outcomes in ALL survivors, comparing against a group of typically developing, cancer free peers. MATERIALS AND METHODS: Participants included 71 ALL survivors, on average 8 years after diagnosis and 8-18 years of age, and 83 typically developing controls. Anatomical MRI was performed to evaluate brain structure; diffusion and magnetization transfer MRI were used to examine brain tissue microstructure. RESULTS: Successful MRI scans were acquired in 67 survivors (94%) and 82 controls (99%). Structurally, ALL survivors exhibited widespread reductions in brain volume, with 6% less white matter and 5% less gray matter than controls (p = 0.003 and 0.0006 respectively). Much of the brain appeared affected - 71 of 90 evaluated structures showed smaller volume - with the most notable exception being the occipital lobe, where no significant differences were observed. Average full-scale IQ in the survivor and control groups were 95 (CI 92-99) and 110 (CI 107-113), respectively. Using data from the NIH Pediatric MRI Data Repository, we evaluated the extent to which elevated IQ in the control group might affect the structural differences observed. We estimated that two thirds of the observed brain differences were attributable to ALL and its treatment. In addition to the structural changes, survivors showed, on average, globally lower white matter fractional anisotropy (-3%) and higher radial diffusivity (+5%) (p < 10-6), but no differences in magnetization transfer ratio. CONCLUSIONS: Neuroanatomical alterations in late childhood and adolescent ALL survivors treated with chemotherapy-only protocols are widespread, with white matter being somewhat more affected than gray matter. These MRI results indicate brain development is altered in ALL survivors and highlight the need to examine how these alterations emerge.

American Academy of Clinical Neuropsychology consensus conference statement on uniform labeling of performance test scores.

Objectives: Descriptive labels of performance test scores are a critical component of communicating outcomes of neuropsychological and psychological evaluations. Yet, no universally accepted system exists for assigning qualitative descriptors to scores in specific ranges. In addition, the definition and use of the term "impairment" lacks specificity and consensus. Consequently, test score labels and the denotation of impairment are inconsistently applied by clinicians, creating confusion among consumers of neuropsychological services, including referral sources, trainees, colleagues, and the judicial system. To reduce this confusion, experts in clinical and forensic neuropsychological and psychological assessment convened in a consensus conference at the 2018 Annual Meeting of the American Academy of Clinical Neuropsychology (AACN). The goals of the consensus conference were to recommend (1) a system of qualitative labels to describe results from performance-based tests with normal and non-normal distributions and (2) a definition of impairment and its application in individual case determinations. Results: The goals of the consensus conference were met resulting in specific recommendations for the application of uniform labels for performance tests and for the definition of impairment, which are described in this paper. In addition, included in this consensus statement is a description of the conference process and the rationales for these recommendations. Conclusions/Importance: This consensus conference is the first formal attempt by the professional neuropsychological community to make recommendations for uniform performance test score labels and to advance a consistent definition of impairment. Using uniform descriptors and terms will reduce confusion and enhance report comprehensibility by the consumers of our reports as well as our trainees and colleagues.

Brain Development and Heart Function after Systemic Single-Agent Chemotherapy in a Mouse Model of Childhood Leukemia Treatment.

PURPOSE: Chemotherapy for childhood acute lymphoblastic leukemia (ALL) can cause late-appearing side effects in survivors that affect multiple organs, including the heart and brain. However, the complex ALL treatment regimen makes it difficult to isolate the causes of these side effects and impossible to separate the contributions of individual chemotherapy agents by clinical observation. Using a mouse model, we therefore assessed each of eight representative, systemically-administered ALL chemotherapy agents for their impact on postnatal brain development and heart function. EXPERIMENTAL DESIGN: Mice were treated systemically with a single chemotherapy agent at an infant equivalent age, then allowed to age to early adulthood (9 weeks). Cardiac structure and function were assessed using in vivo high-frequency ultrasound, and brain anatomy was assessed using high-resolution volumetric ex vivo MRI. In addition, longitudinal in vivo MRI was used to determine the time course of developmental change after vincristine treatment. RESULTS: Vincristine, doxorubicin, and methotrexate were observed to produce the greatest deficiencies in brain development as determined by volumes measured on MRI, whereas doxorubicin, methotrexate, and l-asparaginase altered heart structure or function. Longitudinal studies of vincristine revealed widespread volume loss immediately following treatment and impaired growth over time in several brain regions. CONCLUSIONS: Multiple ALL chemotherapy agents can affect postnatal brain development or heart function. This study provides a ranking of agents based on potential toxicity, and thus highlights a subset likely to cause side effects in early adulthood for further study.

Characterizing neurocognitive late effects in childhood leukemia survivors using a combination of neuropsychological and cognitive neuroscience measures.

Knowledge about cognitive late effects in survivors of childhood acute lymphoblastic leukemia (ALL) is largely based on standardized neuropsychological measures and parent reports. To examine whether cognitive neuroscience paradigms provided additional insights into neurocognitive and behavioral late effects in ALL survivors, we assessed cognition and behavior using a selection of cognitive neuroscience tasks and standardized measures probing domains previously demonstrated to be affected by chemotherapy. 130 ALL survivors and 158 control subjects, between 8 and 18 years old at time of testing, completed the n-back (working memory) and stop-signal (response inhibition) tasks. ALL survivors also completed standardized measures of intelligence (Wechsler Intelligence Scales [WISC-IV]), motor skills (Grooved Pegboard), math abilities (WIAT-III), and executive functions (Delis-Kaplan Executive Function System). Parents completed behavioral measures of executive functions (Behavior Rating Inventory of Executive Function [BRIEF]) and attention (Conners-3). ALL survivors exhibited deficiencies in working memory and response inhibition compared with controls. ALL survivors also exhibited deficits on WISC-IV working memory and processing speed, Grooved Pegboard, WIAT-III addition and subtraction fluency, and numerical operations, as well as DKEFS number-letter switching. Parent reports suggested more attention deficits (Conners-3) and behavioral difficulties (BRIEF) in ALL survivors compared with referenced norms. Low correspondence between standardized and experimental measures of working memory and response inhibition was noted. The use of cognitive neuroscience paradigms complements our understanding of the cognitive deficits evident after treatment of ALL. These measures could further delineate cognitive processes involved in neurocognitive late effects, providing opportunities to explore their underlying mechanisms.

Brain structure, working memory and response inhibition in childhood leukemia survivors.

INTRODUCTION: Survival rates for children with acute lymphoblastic leukemia (ALL) approach 95%. At the same time, there is growing concern that chemotherapy causes alterations in brain development and cognitive abilities. We performed MRI measurements of white and gray matter volume to explore how variation in brain structure may be related to cognitive abilities in ALL survivors and healthy controls. METHODS: The sample included 24 male ALL survivors who had completed contemporary treatment 3-11 years prior, and 21 age- and sex-matched controls. Participants were between 8 and 18 years old. Working memory and motor response inhibition were measured with the N-Back and Stop Signal Tasks (SST), respectively. Participants underwent 3T structural MRI to assess white and gray matter volumes overall, lobe-wise, and in cortical and atlas-identified subcortical structures. Mental health was assessed with the Child Behavioral Checklist. RESULTS: ALL survivors performed more poorly on measures of working memory and response inhibition than controls. Frontal and parietal white matter, temporal and occipital gray matter volume, and volumes of subcortical white and gray matter structures were significantly reduced in ALL survivors compared with controls. Significant structure-function correlations were observed between working memory performance and volume of the amygdala, thalamus, striatum, and corpus callosum. Response inhibition was correlated with frontal white matter volume. No differences were found in psychopathology. CONCLUSIONS: Compared with controls, a reduction in volume across brain regions and tissue types, was detectable in ALL survivors years after completion of therapy. These structural alterations were correlated with neurocognitive performance, particularly in working memory. Confirming these observations in a larger, more representative sample of the population is necessary. Additionally, establishing the time course of these changes-and the treatment, genetic, and environmental factors that influence them-may provide opportunities to identify at-risk patients, inform the design of treatment modifications, and minimize adverse cognitive outcomes.

Pre-Morbid Developmental Vulnerabilities in Children With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL).

BACKGROUND: Not all children with acute lymphoblastic leukemia (ALL) were developing in a typical manner prior to diagnosis. Pre-existing developmental vulnerabilities (DV) may be related to long-term neuropsychological sequelae following ALL treatment, yet little is known about the prevalence or nature of prior DV in this population. PROCEDURE: Children with newly diagnosed ALL aged 2-18 years (n = 115) were screened for DV by asking parents about the child's prior developmental history and with the Developmental Profile-3 (DP-3). RESULTS: Twenty-six participants (23% of total sample) screened positive for prior DV, with one or more of the following: delayed early motor and/or language milestones that required intervention (n = 17), prior diagnosis of Down syndrome (n = 3), prior diagnosis of autism spectrum disorder (n = 1), prior diagnosis of attention-deficit/hyperactivity disorder and/or learning disability (n = 6), or prior neurological conditions (n = 5). CONCLUSIONS: A sizable proportion of children with newly diagnosed ALL have pre-morbid DV that could potentially make them more vulnerable to reduced educational opportunities during treatment and neurotoxic late effects following treatment. Identification of the subset of children with ALL and DV is essential to direct early interventions and to study their long-term outcomes.

Neuropsychological late effects of treatment for acute leukemia in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) have an elevated risk of developing acute leukemia, but little is known about treatment-related neuropsychological morbidity because they are systematically excluded from research in this area. The current study investigated neuropsychological outcomes in children with DS treated for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) compared to children with DS with no history of cancer. PROCEDURE: Participants were 4 to 17 years of age at testing and were administered measures of intelligence, academic achievement, language, visual-motor and fine-motor skills, and adaptive function. Patients had been off treatment for at least 2 years. RESULTS: The AML group (N = 12) had significantly lower verbal intelligence and receptive vocabulary compared to controls (N = 21). By contrast, the ALL group (N = 14) performed significantly worse than controls on measures of verbal intelligence, spelling, receptive and expressive vocabulary, visual-motor skills, and adaptive function. CONCLUSIONS: Patients with DS treated for AML may have specific post-treatment morbidity in verbal function, whereas those treated for ALL have broader morbidity affecting multiple neuropsychological domains and overall adaptive function. We hypothesize that the broader impairment profile of ALL survivors may be related to a combination of the longer duration of central nervous system-directed treatment for ALL compared to AML and the concomitant limited access to intervention opportunities during active treatment.

Functional plasticity in childhood brain disorders: when, what, how, and whom to assess.

At every point in the lifespan, the brain balances malleable processes representing neural plasticity that promote change with homeostatic processes that promote stability. Whether a child develops typically or with brain injury, his or her neural and behavioral outcome is constructed through transactions between plastic and homeostatic processes and the environment. In clinical research with children in whom the developing brain has been malformed or injured, behavioral outcomes provide an index of the result of plasticity, homeostasis, and environmental transactions. When should we assess outcome in relation to age at brain insult, time since brain insult, and age of the child at testing? What should we measure? Functions involving reacting to the past and predicting the future, as well as social-affective skills, are important. How should we assess outcome? Information from performance variability, direct measures and informants, overt and covert measures, and laboratory and ecological measures should be considered. In whom are we assessing outcome? Assessment should be cognizant of individual differences in gene, socio-economic status (SES), parenting, nutrition, and interpersonal supports, which are moderators that interact with other factors influencing functional outcome.

Impact of craniospinal dose, boost volume, and neurologic complications on intellectual outcome in patients with medulloblastoma.

PURPOSE: To examine the impact of radiation (ie, craniospinal irradiation [CSR] dose and boost volume) and complications (ie, hydrocephalus and other neurologic complications, including mutism) on patterns of change in intellectual functioning in medulloblastoma survivors. PATIENTS AND METHODS: We conducted a retrospective review of 113 patients treated for medulloblastoma between 1983 and 2011 who were seen for neuropsychological assessment, including longitudinal follow-up of intellectual function. Patients were treated with either standard-dose CSR with a posterior fossa (PF) boost (n=51), standard-dose CSR plus tumor bed (TB) boost (n=9), reduced-dose CSR plus PF boost (n=28), or reduced-dose CSR plus TB boost (n=23), with or without chemotherapy. A subset of patients developed hydrocephalus that required cerebrospinal fluid (CSF) diversion (n=54) and/or other neurologic complications (n=40), more than half of which were postoperative mutism (n=25). Growth curve analysis was used to determine stability or change in intelligence scores over time. RESULTS: Patients treated with reduced-dose CSR plus TB boost showed stable intellectual trajectories, whereas patients treated with higher doses and larger boost volumes experienced intellectual declines. Presence of complications was associated with worse intellectual outcome; however, hydrocephalus requiring CSF diversion and mutism differed in their pattern of decline. CONCLUSION: These results improve our understanding of factors that impair intellectual outcome in patients treated for medulloblastoma. Lower doses of CSR and smaller boost volumes seem to mitigate intellectual decline. Our findings validate the use of TB boost and suggest PF boost should be reconsidered.

Age, plasticity, and homeostasis in childhood brain disorders.

It has been widely accepted that the younger the age and/or immaturity of the organism, the greater the brain plasticity, the young age plasticity privilege. This paper examines the relation of a young age to plasticity, reviewing human pediatric brain disorders, as well as selected animal models, human developmental and adult brain disorder studies. As well, we review developmental and childhood acquired disorders that involve a failure of regulatory homeostasis. Our core arguments are as follows:

Long-term neurocognitive outcomes in young adult survivors of childhood acute lymphoblastic leukemia.

Five-year survival rates of childhood acute lymphoblastic leukemia (ALL) exceed 80% due to central nervous system-directed treatment including cranial radiation (CRT) and chemotherapy. However, these treatments are associated with neurocognitive compromise, the extent of which is correlated with higher dose and younger age at treatment. The aims of this study were to explore long-term neurocognitive outcomes in adult survivors of childhood ALL, and to identify measures sensitive to neurotoxicity in long-term survivors. We examined 24 adults who received 18 Gy CRT and chemotherapy for treatment of ALL between ages 2 and 15 years (median, 5.5). Time since diagnosis ranged from 6 to 26 years (median, 16.6). Younger age at diagnosis and longer time since diagnosis were associated with lower scores on a computerized battery that requires speed and accuracy across a number of domains (MicroCog), and other standardized neurocognitive tests. When compared with population norms, MicroCog indices were below average in survivors diagnosed with ALL before age 5, but only the reasoning/calculation index was below average in survivors diagnosed with ALL after age 5. In contrast, intelligence quotient (IQ) scores were average. In addition to confirming earlier studies showing that younger children are more vulnerable to treatment-related neurotoxicity, here we show that deficits exist many years post treatment even with a relatively lower dose of CRT, and that these deficits are especially evident on tasks involving rapid processing of information.

Longitudinal evaluation of neurocognitive function after treatment for central nervous system germ cell tumors in childhood.

BACKGROUND: Central nervous system germ cell tumors (CNS GCT) are typically localized to midline structures of the brain, including the pineal and suprasellar/pituitary regions. Management of these tumors depends on underlying histology (germinoma or nongerminomatous germ cell tumor). Knowledge about neurocognitive outcome in these patients is limited. Longitudinal neurocognitive outcome in CNS GCT patients seen for neuropsychological evaluation at a single institution was explored. METHODS: Thirty-five patients were seen for neurocognitive evaluation after diagnosis and treatment for a CNS GCT. Mean age at diagnosis was 11.66 years. Tumor location was suprasellar in 12 patients, pineal in 9, bifocal in 10, multifocal in 3, and thalamic in 1. Standardized cognitive tests of intelligence, receptive language, visual-motor ability, memory, and academic achievement were administered. Longitudinal and cross-sectional analyses were conducted. RESULTS: Intelligence, academic functioning, and receptive vocabulary were not significantly compromised in most patients treated for CNS GCT. Working memory, information processing speed, and visual memory declined significantly over time in all patients. Patients with pineal tumors showed early and stable deficits, whereas patients with suprasellar and bifocal tumors showed more protracted declines from initial average functioning. Patients treated with ventricular versus craniospinal radiation displayed better outcome. CONCLUSIONS: Although general cognitive abilities appeared stable and intact after treatment for most children with CNS GCT, a significant decline over time in working memory, processing speed, and visual memory was evident. Tumor location appeared to be important in understanding the trajectory of stability and decline in CNS GCT patients, as did radiation field.

Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes.

Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. While those diagnosed at younger ages are most vulnerable, little is known about the long-term neurocognitive, functional, and physical outcomes in survivors as they approach middle age. In this retrospective cohort study, we assessed 20 adults who were treated with surgery and radiotherapy for medulloblastoma during childhood (median age at assessment, 21.9 years [range, 18-47 years]; median time since diagnosis, 15.5 years [range, 6.5-42.2 years]). Nine patients also underwent chemotherapy. Cross-sectional analyses of current neurocognitive, functional, and physical status were conducted. Data from prior neuropsychological assessments were available for 18 subjects; longitudinal analyses were used to model individual change over time for those subjects. The group was well below average across multiple neurocognitive domains, and 90% had required accommodations at school for learning disorders. Longer time since diagnosis, but not age at diagnosis, was associated with continued decline in working memory, a common sign of aging. Younger age at diagnosis was associated with lower intelligence quotient and academic achievement scores, even many years after treatment had been completed. The most common health complications in survivors were hearing impairment, second cancers, diabetes, hypertension, and endocrine deficiencies. Adult survivors of childhood medulloblastoma exhibit signs of early aging regardless of how young they were at diagnosis. As survival rates for brain tumors continue to improve, these neurocognitive and physical sequelae may become evident in survivors diagnosed at different ages across the lifespan. It will become increasingly important to identify factors that contribute to risk and resilience in this growing population.

Neurodevelopmental sequelae of pediatric acute lymphoblastic leukemia and its treatment.

This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research. It is concluded that neurocognitive outcomes for the majority of children with standard-risk ALL treated according to current chemotherapy protocols is relatively good, but subgroups of children are more significantly compromised. As medical treatments advance and survival rates continue to improve, neurocognitive outcomes and other quality of life indicators will become increasingly important. Preventing or ameliorating treatment-related neuropsychological sequelae represents the next major challenge in pediatric ALL.

Adverse medical events associated with childhood cerebellar astrocytomas and medulloblastomas: natural history and relation to very long-term neurobehavioral outcome.

OBJECTIVES: The objectives of the study are to document the incidence of medical events in survivors of childhood posterior fossa astrocytoma or medulloblastoma in four time periods (diagnosis, perioperative, short-term survival, long-term survival), and to study whether medical events predict neurobehavioral outcome. MATERIALS AND METHODS: Twenty-nine astrocytoma and 29 medulloblastoma survivors were studied at least 5 years post-diagnosis. The incidence of medical events in each time period was compared in each group in relation to long-term intelligence, memory, functional independence, and health-related quality of life. As expected, medical and neurobehavioral outcome were poorer in the medulloblastoma group. In the astrocytoma group, poorer long-term neurobehavioral outcome was associated with more adverse medical events in the perioperative and short-term survival periods. CONCLUSIONS: Long-term neurobehavioral outcome is related to time-dependent medical events in astrocytoma survivors. The data confirm earlier reports of poorer outcome after medulloblastoma and add new information about clinical markers of poor neurobehavioral outcome in survivors of childhood astrocytoma.

Comparison of long-term neurocognitive outcomes in young children with acute lymphoblastic leukemia treated with cranial radiation or high-dose or very high-dose intravenous methotrexate.

PURPOSE: Cranial radiation therapy (CRT) is associated with neurocognitive morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). For most patients, CRT has been replaced with intensified systemic and intrathecal chemotherapy, often including methotrexate (MTX). The impact of chemotherapy-only protocols on neurocognitive outcomes is unclear, and the importance of systemic MTX dose has not been established. PATIENTS AND METHODS: Seventy nine of 120 eligible children diagnosed with high-risk ALL between the ages of 1.0 and 4.9 years participated in this retrospective cohort study. All patients were treated on a uniform chemotherapy protocol with one of three modalities of CNS prophylaxis, depending on their treatment era. In addition to intrathecal therapy, CNS-directed therapy consisted of CRT (18 Gy in 10 fractions) in 25 patients, high-dose intravenous (IV) MTX (8 g/m2 x 3 doses) in 32 patients and very high-dose IV MTX (33.6 g/m2 x 3 doses) in 22 patients. Participants completed tests of intelligence, academic achievement, attention, and memory. RESULTS: Neurocognitive assessment was conducted at least 5 years after diagnosis (mean, 10.5 years, standard deviation, 2.7 years). No difference was detected on any neurocognitive measure between children treated with high-dose or very high-dose IV MTX. The combined MTX groups scored near the population mean on 17/18 measures. Children treated with CRT performed more poorly than the MTX group on most measures. CONCLUSION: Treatment strategies for young children with ALL that avoid CRT are associated with good long-term neurocognitive outcomes. In this cohort, the dose of IV MTX did not influence these outcomes.

Long-term effects of transient cerebellar mutism after cerebellar astrocytoma or medulloblastoma tumor resection in childhood.

BACKGROUND: Following cerebellar tumor resection, some patients develop transient cerebellar mutism (TCM). Although the mutism resolves, it is not known whether there are long-term motor speech deficits in patients with TCM that are in excess of those in individuals with cerebellar tumors who had not developed postoperative TCM. METHODS: Long-term survivors of cerebellar tumors resected in childhood who developed TCM were matched to survivors without TCM and to controls. Speech samples were formally analyzed by two speech pathologists. RESULTS: Tumor survivors who had TCM had significantly more ataxic dysarthric speech and slower speech than either those without TCM or controls and were more dysfluent than controls. Tumor survivors without TCM did not differ from controls on ataxic dysarthria or speech rate. CONCLUSIONS: Survivors who had TCM showed more speech deficits than controls or survivors without TCM. The data suggest that speech deficits are chronic if not permanent sequelae of TCM.

Serial evaluation of academic and behavioral outcome after treatment with cranial radiation in childhood.

PURPOSE: To evaluate academic and behavioral outcome in radiated survivors of posterior fossa (PF) tumors. PATIENTS AND METHODS: Fifty-three patients (36 males) treated for malignant PF tumors were seen for evaluation of academics and/or behavioral functioning. Forty-six patients were treated for medulloblastoma, and seven patients were treated for ependymoma. Fourteen patients were treated with reduced-dose cranial radiation, and 34 patients were treated with standard-dose cranial radiation (dose was not available for four patients). All patients received an additional boost to the PF. One patient was treated with PF radiation only. Standardized achievement tests and behavioral questionnaires were administered at different times after diagnosis for each child. First, the influence of demographic and medical variables on outcome was examined. Second, the rate of change in scores was determined using mixed model regression for patients seen for serial assessment. RESULTS: The presence of hydrocephalus was related to poorer academics, but outcome was not related to radiation dose, extent of surgery, or treatment with chemotherapy. Younger age predicted poor reading ability and lower parent rating of academic achievement. Children's performance declined for spelling, mathematics, and reading. Significant declines were also evident in parent and teacher's ratings of academic ability. Behavioral functioning was generally not related to medical and demographic variables, and few clinically significant problems in externalizing behavior were evident. Increases in social and attention problems emerged over time. CONCLUSION: Cranial radiation is associated with declines in academic ability, social skills, and attention. However, neither psychological distress nor behavior problems were a significant concern for this sample.

Change in neurocognitive functioning after treatment with cranial radiation in childhood.

PURPOSE: To evaluate the pattern of stability and change over time across multiple domains of neurocognitive function in radiated survivors of posterior fossa (PF) tumors. PATIENTS AND METHODS: Thirty-four children (25 males) treated for malignant PF tumors were observed with serial clinical neuropsychologic assessments. Thirty patients were treated for medulloblastoma and four patients were treated for ependymoma. Twelve patients were treated with reduced-dose and 21 patients were treated with standard-dose cranial radiation. All patients received an additional boost to the PF. One patient was treated with PF radiation only. Standardized neuropsychologic tests were administered at different times after diagnosis for each child. The rate of change in scores was determined using a mixed model regression. RESULTS: Results showed a 2- to 4-point decline per year in intelligence scores. For our relatively young sample, intellectual function declined quickly in the first few years after treatment, and then more gradually. Significant declines in visual-motor integration, visual memory, verbal fluency, and executive functioning were also documented. No decline was evident for verbal memory and receptive vocabulary. CONCLUSION: Cranial radiation is associated with a decline in multiple neurocognitive domains, with a few notable exceptions. Our results must be interpreted in the context of common limitations of clinical research, including patient variability, changes in test versions, small sample size, and clinical referral bias.