Neuroimaging Biomarkers and Neurocognitive Outcomes in Pediatric Medulloblastoma Patients: a Systematic Review.

Medulloblastoma is a malign posterior fossa brain tumor, mostly occurring in childhood. The CNS-directed chemoradiotherapy treatment can be very harmful to the developing brain and functional outcomes of these patients. However, what the underlying neurotoxic mechanisms are remain inconclusive. Hence, this review summarizes the existing literature on the association between advanced neuroimaging and neurocognitive changes in patients that were treated for pediatric medulloblastoma. The PubMed/Medline database was extensively screened for studies investigating the link between cognitive outcomes and multimodal magnetic resonance (MR) imaging in childhood medulloblastoma survivors. A behavioral meta-analysis was performed on the available IQ scores. A total of 649 studies were screened, of which 22 studies were included. Based on this literature review, we conclude medulloblastoma patients to be at risk for white matter volume loss, more frequent white matter lesions, and changes in white matter microstructure. Such microstructural alterations were associated with lower IQ, which reached the clinical cut-off in survivors across studies. Using functional MR scans, changes in activity were observed in cerebellar areas, associated with working memory and processing speed. Finally, cerebral microbleeds were encountered more often, but these were not associated with cognitive outcomes. Regarding intervention studies, computerized cognitive training was associated with changes in prefrontal and cerebellar activation and physical training might result in microstructural and cortical alterations. Hence, to better define the neural targets for interventions in pediatric medulloblastoma patients, this review suggests working towards neuroimaging-based predictions of cognitive outcomes. To reach this goal, large multimodal prospective imaging studies are highly recommended.

Neuropsychological consequences of childhood medulloblastoma and possible interventions: A review.

BACKGROUND: Children who have been treated for a medulloblastoma often suffer long-term cognitive impairments that often negatively affect their academic performance and quality of life. In this article, we will review the neuropsychological consequences of childhood medulloblastoma and discuss the risk factors known to influence the presence and severity of these cognitive impairments and possible interventions to improve their quality of life. METHODS: This narrative review was based on electronic searches of PubMed to identify all relevant studies. RESULTS: Although many types of cognitive impairments often emerge during a child's subsequent development, the core cognitive domains that are most often affected in children treated for a medulloblastoma are processing speed, attention and working memory. The emergence and magnitude of these deficits varies greatly among patients. They are influenced by demographic (age at diagnosis, parental education), medical and treatment-related factors (perioperative complications, including posterior fossa syndrome, radiation therapy dose, etc.), and the quality of interventions such as school adaptations provided to the child or rehabilitation programs that focus on cognitive skills, behavior and psychosocial functioning. CONCLUSION: These patients require specialized and coordinated multidisciplinary rehabilitation follow-up that provides timely and adapted assessments and culminates in personalized intervention goals being set with the patient and the family. Follow-up should be continued until referral to adult services.

Neurocognitive functioning and health-related quality of life in adult medulloblastoma patients: long-term outcomes of the NOA-07 study.

BACKGROUND: Combined radiochemotherapy followed by maintenance chemotherapy with cisplatin, lomustine and vincristine within the NOA-07 study resulted in considerable short-term toxicity in adult medulloblastoma patients. Here we investigated the long-term impact of this treatment, focusing on neurocognitive functioning and health-related quality of life (HRQoL). METHODS: Neurocognitive functioning and HRQoL scores over time were determined, and differences between the post-treatment and follow-up assessments were calculated up to 18 months for neurocognition and 60 months for HRQoL. RESULTS: 28/30 patients were analyzed. The three preselected HRQoL scales (role, social and cognitive functioning) showed improved scores, to a clinically relevant extent (≥ 10 points), compared to post-treatment levels up to 30 months, but decreased afterwards. Z-scores for verbal working memory were worse during follow-up compared to post-treatment scores and remained impaired during 18 months follow-up (i.e. z-score below - 1 standard deviation). Attention was impaired post-treatment, and remained impaired to a clinically relevant extent during follow-up. Coordination/processing speed and lexical verbal fluency improved compared to post-treatment scores, and remained within the normal range thereafter. Other tests of verbal fluency were stable over time, with z-scores within the normal range. CONCLUSIONS: This long-term follow-up study showed that the NOA-07 treatment regimen was not associated with a deterioration in HRQoL in the post-treatment period. Verbal working memory deteriorated, while other neurocognitive domains did not seem to be impacted negatively by the treatment.

Treatment of children under 4 years of age with medulloblastoma and ependymoma in the HIT2000/HIT-REZ 2005 trials: Neuropsychological outcome 5 years after treatment.

Young children with brain tumours are at high risk of developing treatment-related sequelae. We aimed to assess neuropsychological outcomes 5 years after treatment. This cross-sectional study included children under 4 years of age with medulloblastoma (MB) or ependymoma (EP) enrolled in the German brain tumour trials HIT2000 and HIT-REZ2005. Testing was performed using the validated Wuerzburg Intelligence Diagnostics (WUEP-D), which includes Kaufman-Assessment-Battery, Coloured Progressive Matrices, Visual-Motor Integration, finger tapping "Speed", and the Continuous Performance Test. Of 104 patients in 47 centres, 72 were eligible for analyses. We assessed whether IQ was impacted by disease extent, disease location, patient age, gender, age at surgery, and treatment (chemotherapy with our without craniospinal irradiation [CSI] or local radiotherapy [LRT]). Median age at surgery was 2.3 years. Testing was performed at a median of 4.9 years after surgery. Patients with infratentorial EPs (treated with LRT) scored highest in fluid intelligence (CPM 100.9±16.9, mean±SD); second best scores were achieved by patients with MB without metastasis treated with chemotherapy alone (CPM 93.9±13.2), followed by patients with supratentorial EPs treated with LRT. In contrast, lowest scores were achieved by patients that received chemotherapy and CSI, which included children with metastasised MB and those with relapsed MB M0 (CPM 71.7±8.0 and 73.2±21.8, respectively). Fine motor skills were reduced in all groups. Multivariable analysis revealed that type of treatment had an impact on IQ, but essentially not age at surgery, time since surgery or gender. Our results confirm previous reports on the detrimental effects of CSI in a larger cohort of children. Comparable IQ scores in children with MB treated only with chemotherapy and in children with EP suggest that this treatment strategy represents an attractive option for children who have a high chance to avoid application of CSI. Longitudinal follow-up examinations are warranted to assess long-term neuropsychological outcomes.

Anatomo-functional study of the cerebellum in working memory in children treated for medulloblastoma.

INTRODUCTION: Medulloblastoma is the most common malignant cerebral tumor during childhood, arising in the posterior fossa. Children treated for medulloblastoma often experience working memory (WM) deficits, affecting their quality of life and school performance. The aim of the present study undertaken to describe the cerebellar involvement in WM deficits observed in these children. MATERIAL AND METHODS: 23 healthy children and 11 children treated for medulloblastoma were included into study. All subjects performed a detailed neuropsychological examination, an anatomical and functional MRI. Stimuli were presented to the participants with alternating sensory modality and nature of communication in a block design during functional magnetic resonance imaging acquisitions. Non-parametric tests were used for analyzing neuropsychological and behavioral data. SPM8 and SUIT (Spatially Unbiased Atlas Template) were used for anatomical and functional MRI data analyses. RESULTS: Patients had cerebellar resections mainly located in the left posterior lobe. Patients had significantly reduced intelligence quotient, central executive and visuospatial WM. In healthy children group, fMRI showed activations for non-verbal and visuospatial WM in the left posterior cerebellar lobe. CONCLUSION: This study provides further evidence that left posterior cerebellar lobe plays a critical role in WM. Indeed, lesions of left posterior cerebellar lobe were associated with WM impairment in children treated for cerebellar medulloblastoma. Additionally, fMRI using WM tasks showed activation in the left posterior cerebellar lobe in healthy children. Taken together, these findings may help for improving treatment and rehabilitation of children referred for cerebellar tumor.

PPAR and GST polymorphisms may predict changes in intellectual functioning in medulloblastoma survivors.

PURPOSE: Advances in the treatment of pediatric medulloblastoma have led to improved survival rates, though treatment-related toxicity leaves children with significant long-term deficits. There is significant variability in the cognitive outcome of medulloblastoma survivors, and it has been suggested that this variability may be attributable to genetic factors. The aim of this study was to explore the contributions of single nucleotide polymorphisms (SNPs) in two genes, peroxisome proliferator activated receptor (PPAR) and glutathione-S-transferase (GST), to changes in general intellectual functioning in medulloblastoma survivors. METHODS: Patients (n = 44, meanage = 6.71 years, 61.3% males) were selected on the basis of available tissue samples and neurocognitive measures. Patients received surgical tumor resection, craniospinal radiation, radiation boost to the tumor site, and multiagent chemotherapy. Genotyping analyses were completed using the Illumina Human Omni2.5 BeadChip, and 41 single nucleotide polymorphisms (SNPs) were assessed across both genes. We used a machine learning algorithm to identify polymorphisms that were significantly associated with declines in general intellectual functioning following treatment for medulloblastoma. RESULTS: We identified age at diagnosis, radiation therapy, chemotherapy, and eight SNPs associated with PPARs as predictors of general intellectual functioning. Of the eight SNPs identified, PPARα (rs6008197), PPARγ (rs13306747), and PPARδ (rs3734254) were most significantly associated with long-term changes in general intellectual functioning in medulloblastoma survivors. CONCLUSIONS: PPAR polymorphisms may predict intellectual outcome changes in children treated for medulloblastoma. Importantly, emerging evidence suggests that PPAR agonists may provide an opportunity to minimize the effects of treatment-related cognitive sequelae in these children.

Computerized assessment of cognitive impairment among children undergoing radiation therapy for medulloblastoma.

PURPOSE: Advantages to computerized cognitive assessment include increased precision of response time measurement and greater availability of alternate forms. Cogstate is a computerized cognitive battery developed to monitor attention, memory, and processing speed. Although the literature suggests the domains assessed by Cogstate are areas of deficit in children undergoing treatment for medulloblastoma, the validity of Cogstate in this population has not been previously investigated. METHODS: Children participating in an ongoing prospective trial of risk-adapted therapy for newly diagnosed medulloblastoma (n = 73; mean age at baseline = 12.1 years) were administered Cogstate at baseline (after surgery, prior to adjuvant therapy) and 3 months later (6 weeks after completion of radiation therapy). Gold-standard neuropsychological measures of similar functions were administered at baseline. RESULTS: Linear mixed models revealed performance within age expectations at baseline across Cogstate tasks. Following radiation therapy, there was a decline in performance on Cogstate measures of reaction time (Identification and One Back). Females exhibited slower reaction time on One Back and Detection tasks at baseline. Higher-dose radiation therapy and younger age were associated with greater declines in performance. Pearson correlations revealed small-to-moderate correlations between Cogstate reaction time and working memory tasks with well-validated neuropsychological measures. CONCLUSIONS: Cogstate is sensitive to acute cognitive effects experienced by some children with medulloblastoma and demonstrates associations with clinical predictors established in the literature. Correlations with neuropsychological measures of similar constructs offer additional evidence of validity. The findings provide support for the utility of Cogstate in monitoring acute cognitive effects in pediatric cancer.

Cognitive deficits and psychopathological symptoms among children with medulloblastoma.

Children with medulloblastoma (MB) are predisposed for negative cognitive sequela, which has been widely identified in this population. The purpose of the present study was to explore cognitive deficits and psychopathological symptoms and analyse their relation among MB survivors. The Wechsler Intelligence Scale for Children and the Mini International Neuropsychiatric Interview (MINI-KID) was administered to 34 MB survivors to measure cognitive functioning and psychopathological symptoms. The MB survivors had lower global IQ (86.41 [79.70-93.13]) compared with the control population mean. We found impaired functioning in all IQ subscales in the MB survivors group, of which processing speed (84.15 [77.71-90.58]) was the most affected. Higher radiation dose and high-dose chemotherapy with stem cell rescue were significantly associated factors for lowered global IQ, while age at diagnosis, sex and time period from diagnosis were not significantly associated. Compulsive disorder, generalised anxiety, separation anxiety and posttraumatic stress disorder were significantly more prevalent in the MB survivor group than a group of 46 control participants. No correlation was found between the cognitive deficits and the psychopathological symptoms. Our results identify that MB survivors suffer from cognitive and psychopathological impairments, and these could exist independently from each other.

Impaired Recent, but Preserved Remote, Autobiographical Memory in Pediatric Brain Tumor Patients.

Medulloblastomas, the most common malignant brain tumor in children, are typically treated with radiotherapy. Refinement of this treatment has greatly improved survival rates in this patient population. However, radiotherapy also profoundly affects the developing brain and is associated with reduced hippocampal volume and blunted hippocampal neurogenesis. Such hippocampal (as well as extrahippocampal) abnormalities likely contribute to cognitive impairments in this population. While several aspects of memory have been examined in this population, the impact of radiotherapy on autobiographical memory has not previously been evaluated. Here we evaluated autobiographical memory in male and female patients who received radiotherapy for posterior fossa tumors (PFTs), including medulloblastoma, during childhood. Using the Children's Autobiographical Interview, we retrospectively assessed episodic and nonepisodic details for events that either preceded (i.e., remote) or followed (i.e., recent) treatment. For post-treatment events, PFT patients reported fewer episodic details compared with control subjects. For pretreatment events, PFT patients reported equivalent episodic details compared with control subjects. In a range of conditions associated with reduced hippocampal volume (including medial temporal lobe amnesia, mild cognitive impairment, Alzheimer's disease, temporal lobe epilepsy, transient epileptic amnesia, frontal temporal dementia, traumatic brain injury, encephalitis, and aging), loss of episodic details (even in remote memories) accompanies hippocampal volume loss. It is therefore surprising that pretreatment episodic memories in PFT patients with reduced hippocampal volume are retained. We discuss these findings in light of the anterograde and retrograde impact on memory of experimentally suppressing hippocampal neurogenesis in rodents.SIGNIFICANCE STATEMENT Pediatric medulloblastoma survivors develop cognitive dysfunction following cranial radiotherapy treatment. We report that radiotherapy treatment impairs the ability to form new autobiographical memories, but spares preoperatively acquired autobiographical memories. Reductions in hippocampal volume and cortical volume in regions of the recollection network appear to contribute to this pattern of preserved preoperative, but impaired postoperative, memory. These findings have significant implications for understanding disrupted mnemonic processing in the medial temporal lobe memory system and in the broader recollection network, which are inadvertently affected by standard treatment methods for medulloblastoma tumors in children.

Impact of attention on social functioning in pediatric medulloblastoma survivors.

BACKGROUND: Parent-reported attention problems have been associated with social functioning in a broad sample of pediatric cancer survivors. OBJECTIVE: The present study focused on a more homogeneous sample (pediatric medulloblastoma survivors), with the novel inclusion of self-reported attention ratings. PARTICIPANTS/METHODS: Thirty-three pediatric medulloblastoma survivors, ages 7-18 years, completed a brief IQ measure and self-report of attentional and social functioning. Parents rated patients' attentional and social functioning. RESULTS: Mean attention ratings were average based on both parent- and self-report, though parent ratings were significantly discrepant from normative means. No significant demographic or treatment-related predictors of self-reported attention problems were identified, whereas female gender was associated with greater parent-reported attention problems. Canonical correlation analysis revealed a significant association between parent-reported attention difficulties and social functioning in pediatric medulloblastoma survivors, but there was no association between self-reported attention problems and measures of social functioning. CONCLUSIONS: Consistent with existing literature in broader samples of pediatric cancer survivors, the present study further affirms attention deficits as an underlying contributor to social deficits in pediatric medulloblastoma survivors while also finding little relationship between self-reports of attention and social performance. Notably, present findings provide additional support suggesting that attention functioning is a more significant contributor to social outcomes for pediatric medulloblastoma survivors than the level of cognitive ability.

Do we still need IQ-scores? Misleading interpretations of neurocognitive outcome in pediatric patients with medulloblastoma: a retrospective study.

Over the past decades, many studies used global outcome measures like the IQ when reporting cognitive outcome of pediatric brain tumor patients, assuming that intelligence is a singular and homogeneous construct. In contrast, especially in clinical neuropsychology, the assessment and interpretation of distinct neurocognitive domains emerged as standard. By definition, the full scale IQ (FIQ) is a score attempting to measure intelligence. It is established by calculating the average performance of a number of subtests. Therefore, FIQ depends on the subtests that are used and the influence neurocognitive functions have on these performances. Consequently, the present study investigated the impact of neuropsychological domains on the singular "g-factor" concept and analysed the consequences for interpretation of clinical outcome. The sample consisted of 37 pediatric patients with medulloblastoma, assessed 0-3 years after diagnosis with the Wechsler Intelligence Scales. Information processing speed and visuomotor function were measured by the Trailmaking Test, Form A. Our findings indicate that FIQ was considerably impacted by processing speed and visuomotor coordination, which leaded to an underestimation of the general cognitive performance of many patients. One year after diagnosis, when patients showed the largest norm-deviation, this effect seemed to be at its peak. As already recommended in international guidelines, a comprehensive neuropsychological test battery is necessary to fully understand cognitive outcome. If IQ-tests are used, a detailed subtest analysis with respect to the impact of processing speed seems essential. Otherwise patients may be at risk for wrong decision making, especially in educational guidance.

Smaller hippocampal subfield volumes predict verbal associative memory in pediatric brain tumor survivors.

The developing hippocampus is highly sensitive to chemotherapy and cranial radiation treatments for pediatric cancers, yet little is known about the effects that cancer treatents have on specific hippocampal subfields. Here, we examined hippocampal subfield volumes in 29 pediatric brain tumor survivors treated with cranial radiation and chemotherapy, and 30 healthy developing children and adolescents. We also examined associations between hippocampal subfield volumes and short-term verbal memory. Hippocampal subfields (Cornus Ammonis (CA) 1, CA2-3, dentate gyrus (DG)-CA4, stratum radiatum-lacunosum-moleculare, and subiculum) were segmented using the Multiple Automatically Generated Templates for Different Brains automated segmentation algorithm. Neuropsychological assessment of short-term verbal associative memory was performed in a subset of brain tumor survivors (N = 11) and typically developing children (N = 16), using the Children's Memory Scale or Wechsler's Memory Scale-third edition. Repeated measures analysis of variance showed that pediatric brain tumor survivors had significantly smaller DG-CA4, CA1, CA2-3, and stratum radiatum-lacunosum-moleculare volumes compared with typically developing children. Verbal memory performance was positively related to DG-CA4, CA1, and stratum radiatum-lacunosum-moleculare volumes in pediatric brain tumor survivors. Unlike the brain tumor survivors, there were no associations between subfield volumes and memory in typically developing children and adolescents. These data suggest that specific subfields of the hippocampus may be vulnerable to brain cancer treatments, and may contribute to impaired episodic memory following brain cancer treatment in childhood.

Long-term neuropsychological follow-up of young children with medulloblastoma treated with sequential high-dose chemotherapy and irradiation sparing approach.

High-dose chemotherapy (HDC) strategies were developed in brain tumor protocols for young children to prevent neuropsychological (NP) impairments associated with radiotherapy. However, comprehensive NP evaluations of these children treated with such strategies remain limited. We examined the long-term neurocognitive outcomes of young children (<6 years) with medulloblastoma, treated similarly, with a HDC strategy "according to" the chemotherapy regimen of the protocol CCG 99703. This retrospective study included young children less than 6 years of age at diagnosis of medulloblastoma treated from 1998 to 2011 at 7 North American institutions. Twenty-four patients who had at least one NP assessment post-treatment are the focus of the current study. Of 24 patients in this review, 15 (63%) were male and the mean age at diagnosis was 29.4 months (SD = 13.5). Posterior fossa syndrome (PFs) was reported in five patients (21%). Nine (37.5%) received radiotherapy (5 focal, 4 craniospinal). On average, children were assessed 3.5 years (SD = 1.8) post-diagnosis, and full-scale intellectual quotient (FSIQ) scores ranged from 56 to 119 ([Formula: see text]= 92; SD = 16.8). The majority of children (74%) had low-average to average NP functioning. Very young children treated with radiotherapy, who needed hearing support or with PFs had worse neurocognitive outcomes. Clinically significant deficits (<10th percentile) in at least one area of NP functioning were found in 25% of the children. NP data obtained from this sample of survivors of medulloblastoma in early childhood, all treated with sequential HDC and 1/3 with radiotherapy, describe NP functioning within average normal limits overall. However, almost 25% of children had significant deficits in specific domains.

Posterior fossa syndrome: Review of the behavioral and emotional aspects in pediatric cancer patients.

Medulloblastoma, the most common malignant brain tumor of childhood, occurs in the posterior fossa, the part of the intracranial cavity that contains the brainstem and the cerebellum. The cerebellum is involved in many complex aspects of human behavior and function, and when it is disrupted or insulted, this can lead to significant sequelae in children with posterior fossa tumors. A constellation of impairing and distressing symptoms, including mutism, ataxia/hypotonia, and emotional lability, develops in approximately 25% of children after the surgical resection of posterior fossa tumors. These symptoms may impede treatment and frequently require intervention in order for children to be able to participate in their care. The eventual recovery of speech occurs for most, but with slowly improving dysarthria over many months. Behavioral changes and emotional lability also occur. This phenomenon has been classified differently by different investigators over the past 35 years. For the purposes of this article, the term posterior fossa syndrome is used to refer to the neuropsychiatric and behavioral features that compose this condition. The current review summarizes the development of the clinical understanding of this phenomenon with a focus on near- and long-term psychosocial and psychiatric implications. Also, clinical examples of the presentation, management, and lasting implications of this syndrome are provided. This review is intended to be a resource for clinicians who treat affected children. Cancer 2017;123:551-559. © 2016 American Cancer Society.

Clinical characteristics and late effects in CNS tumours of childhood: Do not forget long term follow-up of the low grade tumours.

AIM: To investigate clinical characteristics and late effects of CNS tumours in childhood with a special focus on low-grade tumours, especially low-grade astrocytoma and glioneuronal tumours. METHODS: A retrospective population based study was performed at Uppsala University Children's Hospital, a tertiary referral centre for children with CNS tumours. Patients were identified from the National Brain Tumour Registry and the National Epilepsy Surgery Registry. Hospital medical records were analysed for patients with a follow up of ≥5 years after diagnosis. A re-evaluation of the neuro-pathological diagnosis was performed. RESULTS: A total of 193 patients (age 0-17.99 years) during a twelve-year period (1995-2006) were included; 149 survived ≥5 years. Three larger subgroups could be identified: astrocytic, embryonal and glioneuronal tumours. A supratentorial location was found in 52%. Medical late effects were mainly neurological and endocrinological, affecting 81% and 26% of surviving patients. Cognitive late effects were a frequent finding in the whole group but also in low-grade astrocytoma and glioneuronal tumours (53% and 67%). Thirty per cent had some kind of pedagogic support in school. CONCLUSION: Late effects are common in long-term survivors of CNS tumours in childhood. Low-grade astrocytoma and glioneuronal tumours are no exception, and the findings support the need for long-term follow up.

Effect of motivation on academic fluency performance in survivors of pediatric medulloblastoma.

It has been proposed previously that extrinsic motivation may enable survivors of childhood medulloblastoma to significantly improve aspects of neurocognitive performance. In healthy populations, enhanced motivation has been shown to promote academic fluency, a domain likely more relevant to the educational outcomes of pediatric medulloblastoma survivors than academic skill development. The present study investigates the effect of enhanced extrinsic motivation on fluent (i.e., accurate and efficient) academic performance in pediatric medulloblastoma survivors. Participants were 36 children, ages 7-18, who had completed treatment for medulloblastoma. Participants completed a neuropsychological battery that included administration of equivalent tasks on Forms A and B of the Woodcock-Johnson III Tests of Achievement. Half were randomly assigned to an incentive condition prior to the administration of Form B. Provision of a performance-based incentive resulted in statistically significant improvement, but not normalization of function, in performance on measures of academic fluency. No demographic, treatment-related, academic, neuropsychological, or self-perception variables predicted response to incentive. Findings suggest that academic performance of survivors may significantly improve under highly motivating conditions. In addition to implications for educational services, this finding raises the novel possibility that decreased motivation represents an inherent neuropsychological deficit in this population and provides a rationale for further investigation of factors affecting individual differences in motivational processes. Further, by examining effort in a context where effort is not inherently suspect, present findings also significantly contribute to the debate regarding the effects of effort and motivation on neuropsychological performance.

[Play as a care strategy for children with cancer]. / O lúdico como estratégia no cuidado à criança com cancer.

OBJECTIVE: To understand the influence of play in the care process as perceived by children with cancer. METHOD: A descriptive, exploratory and qualitative study conducted in a children's cancer unit in Natal, Rio Grande do Norte, Brazil. Data were collected between October 2013 and January 2014 by means of photographic records and semi-structured interviews with eight children, and content analysis with emphasis on two categories: Auxiliary instruments during play; and The influence of play in the process of care. RESULTS: Recreational activities involve watching television, using computers, games and toys, drawing, the playroom and the clown, which provide fun, feelings of joy, distraction and interaction with other people. CONCLUSION: There are several activities at the hospital that are considered play-related and, for the children, they all benefit their care process.

Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy.

PURPOSE: In the European HIT-SIOP PNET4 randomized controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated radiation therapy (HFRT arm, including a partially focused boost) or standard radiation therapy (STRT arm), followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that the HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children <8 years of age at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms. METHODS AND MATERIALS: Neuropsychological data were collected prospectively in 137 patients. Using the Wechsler Intelligence Scales, Kaufman Assessment Battery for Children, and Raven's Progressive Matrices, we estimated full-scale intelligence quotient (FSIQ) and, when available, verbal IQ (VIQ), performance IQ (PIQ), working memory index (WMI), and processing speed index (PSI). RESULTS: Among the 137 participants (HFRT arm n=71, STRT arm n=66, 63.5% males), mean (±SD) ages at diagnosis and assessment respectively were 9.3 (±3.2) years of age (40.8% < 8 years of age at diagnosis) and 14.6 (±4.3) years of age. Mean (±SD) FSIQ was 88 (±19), and mean intergroup difference was 3.88 (95% confidence interval: -2.66 to 10.42, P=.24). No significant differences were found in children >8 years of age at diagnosis. In children <8 years of age at diagnosis, a marginally significant trend toward higher VIQ was found in those treated in the HFRT arm; a similar trend was found for PSI but not for PIQ, WMI, or FSIQ (mean intergroup differences were: 12.02 for VIQ [95% CI: 2.37-21.67; P=.02]; 3.77 for PIQ [95% CI: -5.19 to 12.74; P>.10]; 5.20 for WMI [95% CI: -2.07 to 12.47; P>.10]; 10.90 for PSI [95% CI: -1.54 to 23.36; P=.08]; and 5.28 for FSIQ [95% CI: -4.23 to 14.79; P>.10]). CONCLUSIONS: HFRT was associated with marginally higher VIQ in children <8 years of age at diagnosis, consistent with a previous report using questionnaire-based data. However, overall cognitive ability was not significantly different.

Play as a care strategy for children with cancer / Lo lúdico como estrategia en cuidado de niños con cáncer / O lúdico como estratégia no cuidado à criança com câncer

OBJECTIVE: To understand the influence of play in the care process as perceived by children with cancer. METHOD: A descriptive, exploratory and qualitative study conducted in a children's cancer unit in Natal, Rio Grande do Norte, Brazil. Data were collected between October 2013 and January 2014 by means of photographic records and semi-structured interviews with eight children, and content analysis with emphasis on two categories: Auxiliary instruments during play; and The influence of play in the process of care. RESULTS: Recreational activities involve watching television, using computers, games and toys, drawing, the playroom and the clown, which provide fun, feelings of joy, distraction and interaction with other people. CONCLUSION: There are several activities at the hospital that are considered play-related and, for the children, they all benefit their care process. .

OBJETIVO: Comprender la influencia de lo lúdico en el proceso de atención, en la percepción de los niños con cáncer. MÉTODO: Estudio cualitativo, exploratorio descriptivo, realizado en un sector de oncología pediátrica en Natal, Rio Grande do Norte, Brasil. Los datos fueron recogidos entre los meses de octubre de 2013 y enero de 2014, a través de los registros fotográficos y entrevistas semiestructuradas con ocho hijos, y analizados según el análisis de contenido, destacando dos categorías de discusión: Los instrumentos auxiliares en la alegría; La influencia de lo lúdico en el proceso de atención. RESULTADOS: Las actividades recreativas implican ver televisión, usar computadoras, juegos y juguetes, la realización de dibujos y el payaso, que proporcionan diversión, sentimientos de alegría, distracción y la interacción con los demás. CONCLUSIÓN: Hay varias actividades, en el hospital, entendido como lúdico y que, para el niño, todos proporcionan beneficios para su proceso de atención. .

OBJETIVOS: Compreender a influência do lúdico para o processo de cuidar, na percepção de crianças com câncer. MÉTODO: Estudo qualitativo, exploratório descritivo, realizado em um setor de oncopediatria em Natal, Rio Grande do Norte, Brasil. Os dados foram coletados entre os meses de outubro de 2013 e janeiro de 2014, por meio de registros fotográficos e entrevista semiestruturada, com oito crianças, e analisados conforme a Análise de Conteúdo, destacando-se duas categorias de discussão: Os instrumentos auxiliares na ludicidade; e A influência do lúdico no processo de cuidar. RESULTADOS: As atividades lúdicas envolvem o assistir à televisão, o uso de computadores, os jogos e os brinquedos, a realização de desenhos, a brinquedoteca e o palhaço, os quais proporcionam diversão, sentimentos de alegria, distração e interação com outras pessoas. CONCLUSÃO: Existem diversas atividades, no hospital, entendidas como lúdicas, todas as quais, para a criança, proporcionam benefícios para o seu processo de cuidar. .