Quality of Life in Paediatric Survivors of Medulloblastoma.

Medulloblastoma (MB) is among the most common malignant paediatric brain tumours usually arising in the cerebellum. The treatment is surgical resection followed by craniospinal radiation with or without chemotherapy. We assessed the current literature on survivors of MB and their quality of life (QoL). The QoL of MB survivors is significantly compromised in terms of decreased neurocognitive functions, Intelligence Quotient (IQ), and social functioning. These also lead to a compromised overall performance, school performance, lack of employment, social isolation, and caregiver burden. The survivors often self-reported better performances as compared to objective performance and that rated by the caregivers. The predictors of worse QoL include earlier age at diagnosis, hydrocephalus, shunt placement, altered mental status at diagnosis, incomplete/subtotal resection of the tumour, and metastatic disease.

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 Profile in Children with Posterior Fossa Tumors with or Without Postoperative Cerebellar Mutism Syndrome (CMS).

Cerebellar mutism syndrome (CMS) is a common surgical sequela in children following posterior fossa tumor (PFT) resection. Here, we analyze the neuropsychological features associated with PFT in children, focusing particularly on the differential profiles associated with the presence or absence of CMS after surgery. We further examine the effect of post-resection treatments, tumor type, and presence/absence of hydrocephalus on surgical outcome. Thirty-six patients diagnosed with PFT (19 with and 17 without CMS) and 34 age- and gender-matched healthy controls (HCs) were recruited. A comprehensive neuropsychological evaluation was conducted in all patients postoperatively and in HCs, including an assessment of general cognitive ability, motor skills, perception, language, memory, attention, executive functions, and academic competence. CMS was found to be a clinical marker of lower neuropsychological profile scores across all cognitive domains except auditory-verbal processing and visual memory tasks. PFT patients not presenting CMS exhibited milder impairment in intellectual functioning, motor tasks, reasoning, language, verbal learning and recall, attention, cognitive executive functions, and academic competence. High-grade tumors were associated with slower processing speed and verbal delayed recall as well as alterations in selective and sustained attention. Hydrocephalus was detrimental to motor functioning and nonverbal reasoning. Patients who had undergone surgery, chemotherapy, and radiotherapy presented impaired processing speed, verbal learning, and reading. In addition to the deleterious effects of PFT, post-resection PFT treatments have a negative cognitive impact. These undesired consequences and the associated tumor-related damage can be assessed using standardized, long-term neuropsychological evaluation when planning rehabilitation.

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.

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.

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.

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.

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.

Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood.

UNLABELLED: Abstract Purpose: A number of studies report neurological and cognitive deficits and behavioural disorders in children after surgical treatment for a benign cerebellar tumour. The present study explores functional outcome in adolescents and adults treated for a low-grade cerebellar astrocytoma in childhood. MATERIALS AND METHODS: Participants were 18 adolescents and 46 adults treated for low-grade astrocytoma in childhood. Academic achievement, professional status and neurological, cognitive and behavioural disturbances were collected using self-completed and parental questionnaires for adolescents and phone interview for adults. For the adolescent group, a control group filled in the same questionnaires. RESULTS: Mean time lapse from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to post-operative complications, post-operative mutism and/or brain stem involvement. All the other participants presented close-to-normal academic achievement and normal autonomy, despite a high rate of reported cognitive difficulties and difficulties related to mild neurological sequelae (fine motor skills, balance). CONCLUSION: The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brain stem involvement. No major impact of neurological deficits, cognitive problems and emotional disorders on academic achievement and independent functioning was observed.

[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.

Working memory abilities among children treated for medulloblastoma: parent report and child performance.

OBJECTIVE: We investigated the 5-year postsurgical developmental trajectory of working memory (WM) in children with medulloblastoma using parent and performance-based measures. METHOD: This study included 167 patients treated for medulloblastoma. Serial assessments of WM occurred at predetermined time points for 5 years. RESULTS: There was a subtle, statistically significant increase in parental concern about WM, coupled with a statistically significant decrease in age-standardized scores on performance-based measures. However, whole-group mean scores on both parent and performance-based measures remained in the age-expected range. Posterior fossa syndrome was consistently associated with poorer WM. Younger age at treatment and higher treatment intensity were associated with greater negative change in WM performance only. CONCLUSIONS: Most children treated for medulloblastoma display WM within the age-appropriate range according to parent report and performance. However, the subtle negative changes over time and identified subgroups at increased risk highlight the need for ongoing monitoring of this population.

Conceptions of time in children treated for malignant cerebellar tumours.

PRIMARY OBJECTIVE: Conceptions of time in children having survived malignant cerebellar tumours (CT) and healthy children matched for chronological age (HCCA) were compared, knowing that the cerebellum has been involved in time perception. METHODS AND PROCEDURE: Study participants included 20 children with CT (13 boys) and 20 HCCA (10 boys) aged 6-12 years. All children with CT were at least 1 year after the end of treatment without relapse. A time questionnaire (TQ) exploring duration of daily activities, time units, planning and diachronic thinking was used, as well as a video animation (VA) displaying cyclic and linear time. MAIN OUTCOMES AND RESULTS: Children with CT obtained similar results as HCCA for time units, planning and diachronic thinking, but showed more difficulties than controls in estimating the duration of daily activities and understanding linear and cyclic time concepts (VA). CONCLUSIONS: These findings are not in favour of impaired time conceptions in children with CT and are probably linked to the specific life experience among children treated for a malignant pathology, rather than to the role of the cerebellum in time processing.

Adaptive, behavioral, and emotional outcomes following postoperative pediatric cerebellar mutism syndrome in survivors treated for medulloblastoma.

OBJECTIVE: Patients who experience postoperative pediatric cerebellar mutism syndrome (CMS) during treatment for medulloblastoma have long-term deficits in neurocognitive functioning; however, the consequences on functional or adaptive outcomes are unknown. The purpose of the present study was to compare adaptive, behavioral, and emotional functioning between survivors with and those without a history of CMS. METHODS: The authors examined outcomes in 45 survivors (15 with CMS and 30 without CMS). Comprehensive neuropsychological evaluations, which included parent-report measures of adaptive, behavioral, and emotional functioning, were completed at a median of 2.90 years following craniospinal irradiation. RESULTS: Adaptive functioning was significantly worse in the CMS group for practical and general adaptive skills compared with the group without CMS. Rates of impairment in practical, conceptual, and general adaptive skills in the CMS group exceeded expected rates in the general population. Despite having lower overall intellectual functioning, working memory, and processing speed, IQ and related cognitive processes were uncorrelated with adaptive outcomes in the CMS group. No significant group differences or increased rates of impairment were observed for behavioral and emotional outcomes. CONCLUSIONS: Survivors with CMS, compared with those without CMS, are rated as having significant deficits in overall or general adaptive functioning, with specific weakness in practical skills several years posttreatment. Findings from this study demonstrate the high risk for ongoing functional deficits despite acute recovery from symptoms of CMS, highlighting the need for intervention to mitigate such risk.

Memory disorders in patients with cerebral tumors.

In patients with cerebral tumors, deficits in declarative episodic memory typically result from damage to structures of the Papez circuit. These deficits can arise directly from the action of the tumor mass or indirectly from the surgical intervention. Memory deficits are also frequently seen in patients who show no direct involvement of the Papez circuit. In these patients, the memory impairment probably results from disruption of frontal lobe functioning (caused by localization of the tumor at this level or disconnection from subcortical afferents). Here, I review the neuropsychological tools used to differentiate amnesic syndromes resulting from lack of consolidation of new memory traces (as a consequence of damage to the Papez circuit) from amnesias resulting from reduced efficiency of elaborative encoding and/or strategic retrieval processes (as a consequence of frontal lobe damage). The clinical and rehabilitative implications of this distinction are briefly discussed.

Glioblastoma occurring at the site of a previous medulloblastoma following a 5-year remission period.

We describe a case of a 14-year-old boy who developed a cerebellar and brainstem glioblastoma 5 years after treatment for a medulloblastoma. The patient first presented in 2003 with 9 months of vomiting and a 9-kg weight loss. A head MRI showed a heterogeneously enhancing posterior fossa mass with hydrocephalus. Gross total resection was performed and the tumor was consistent with a classic medulloblastoma. Postoperative chemotherapy and craniospinal radiation was administered. The patient remained tumor-free until 2008, at which time he presented with right-sided weakness and numbness, left eye pain, vomiting and weight loss. Imaging showed abnormalities within the posterior pons, medulla, inferior cerebellar peduncles, cerebellar hemispheres and cervicomedullary junction with expansion of the medulla and cervical spinal cord. Due to the location of the lesion, biopsy was felt to be too risky and was avoided. Despite receiving chemotherapy, his symptoms continued to worsen and he died 4 months later. Post mortem examination limited to the brain and spinal cord confirmed the radiographic extent of the tumor. Microscopic examination showed a highly cellular infiltrative glial neoplasm with extensive palisading necrosis. A diagnosis of glioblastoma was rendered. The question of whether the first and second tumors were related is of potential clinical and academic interest. The first tumor was synaptophysin-positive and GFAP-negative, consistent with medulloblastoma. The second tumor was synaptophysin-negative and focally GFAP-positive, consistent with glioblastoma. The glioblastoma displayed EGF receptor amplification, and interestingly, it also displayed MYCN amplification; both tumors showed low level PTEN deletion. The medulloblastoma displayed a signal pattern consistent with an isochromosome 17q, while the glioblastoma showed some cells with an isochromosome 17q signal pattern amid a background of cells with abundant chromosomal instability. The relationship between these two tumors, particularly with regard to various molecular events, is discussed.

Teachers' report of learning and behavioural difficulties in children treated for cerebellar tumours.

PRIMARY OBJECTIVE: The aim of the study was the validation of the Deasy-Spinetta Questionnaire (DSQ) in 6-11 year olds with attention to the verification of three factors (learning difficulties, socialization and emotionality) and its application in children treated for cerebellar tumour. METHODS AND PROCEDURES: Twenty-nine children aged between 6-11 years were compared with 609 classmates. Teachers completed the DSQ. Patients were evaluated according to Wechsler Scales, the Purdue Pegboard and the International Cooperative Ataxia Rating scale. MAIN OUTCOMES AND RESULTS: In classmates, the DSQ factorial analysis showed three factors: learning, socialization difficulties and disturbing behaviour. Teachers reported more learning difficulties in patients than in classmates. Learning difficulties in patients were greater for mathematics and reasoning than for reading. Patients were described as less active, without evidence of autistic-like behaviour or irritability. The teachers' report of learning difficulties was significantly correlated with IQ scores, but not with neurological deficits. CONCLUSIONS: The proposed DSQ scores are interesting for the assessment of learning and behavioural difficulties in children treated for cerebellar tumours, as they provide complementary ecological information to that given by clinical and neuropsychological testing.

Intellectual impairment after treatment for medulloblastoma and astrocytoma in childhood: the Brazilian experience.

BACKGROUND: This study investigated the impact of posterior fossa tumors and their respective treatments, and the impact of clinical and sociodemographic variables, on the intelligence quotient (IQ) of Brazilian children. METHODS: Twenty patients took part in the study, of which 13 were diagnosed with astrocytoma (average age at evaluation 10.2 y) and 7 with medulloblastoma (average age at evaluation 9.2 y). The first subgroup was submitted exclusively to tumor resection surgery and the second subgroup underwent surgery, chemotherapy (Vincristine, Cisplatine, and Carmustine), and radiotherapy (total dose of 54 Gy). The Wechsler Intelligence Scale for Children (WISCIII) was used. RESULTS: The following statistically significant effects were identified: treatment modality on performance intelligence quotient scores (P=0.02) and processing speed index (PSI) (P=0.01); presence of hydrocephalus at diagnosis on verbal intelligence quotient (P=0.04); tumor localization on perceptual organization index (P=0.03); time interval between diagnosis and neuropsychological evaluation on PSI (P=0.05) and freedom from distraction index (P=0.03); and level of parental formal education on full scale IQ (P=0.02). CONCLUSIONS: Exposure to radiotherapy has a significant effect on processing speed and consequently on global intellectual capacity. The impact on intelligence of clinical and sociodemographic variables such as tumor localization, time interval between diagnosis and cognitive evaluation, and parental level of formal education is confirmed in the specific setting of a developing country.