Epidemiological characteristics and survival outcomes of children with medulloblastoma treated at the National Cancer Institute (INCA) in Rio de Janeiro, Brazil.

BACKGROUND: Medulloblastoma (MB),the most common malignant brain tumor of childhood has survival outcomes exceeding 80% for standard-risk and 60% for high-risk patients in high-income countries (HICs). These results have not been replicated in low- and middle-income countries (LMICs), where 80% of children with cancer live. METHODS: This is a retrospective review of 114 children aged 3-18 years diagnosed with MB from 1997 to 2016 at National Cancer Institute (INCA). Sociodemographic, clinical, and treatment data were extracted from the medical records and summarized descriptively. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: The male-to-female ratio was 1.32 and the median age at diagnosis was 8.2 years. Headache (83%) and nausea/vomiting (78%) were the most common presenting symptoms. Five-year OS was 59.1% and PFS was 58.4%. The OS for standard-risk and high-risk patients was 69% and 53%, respectively. The median time to diagnosis interval was 50.5 days and the median time from surgery to radiation therapy initiation was 50.4 days. Patients who lived >40 km from INCA fared better (OS = 68.2% vs. 51.1%, p = .032). Almost 20% of families lived below the Brazilian minimum wage. Forty-five patients (35%) had metastatic disease at admission. Gross total resection was achieved in 57% of the patitents. CONCLUSIONS: Although there are considerable barriers to deliver effective MB treatment in countries like Brazil, the OS seen in the present study demonstrates that good outcomes are not only feasible but can and should be increased with appropriate interventions.

Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma Subgroup.

Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MBSHH, MBWNT, MBGRP3, or MBGRP4). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology. In this study, formalin-fixed, paraffin-embedded samples from 164 Brazilian medulloblastomas were evaluated, applying the 22-gene panel, and subclassified into the low and high expression of nine key medulloblastoma-related genes. In addition, TP53 mutation status was assessed using TruSight Tumor 15 Panel, and its correlation with expression and prognostic impact was evaluated. Samples from 149 of 164 patients (90%) were classified into MBSHH (47.7%), MBWNT (16.1%), MBGRP3 (15.4%), and MBGRP4 (20.8%). GNAS presented the highest expression levels, with higher expression in MBSHH. TP53, MYCN, SOX2, and MET were also up-regulated in MBSHH, whereas PTEN was up-regulated in MBGRP4. GNAS, TP53, and PTEN low expression was associated with the unfavorable patient outcome only for MBSHH (P = 0.04, P = 0.01, and P = 0.02, respectively). TP53 mutations were detected in 28.57% of MBSHH cases and exhibited association with lower expression and worse clinical outcome, although not statistically significant. The 22-gene panel for molecular classification of medulloblastoma associated with the expression of GNAS, TP53, and PTEN improves the patient prognostication in MBSHH subgroup and can be easily incorporated in the 22-gene panel without any additional costs.

OTX1 and OTX2 Genes in Medulloblastoma.

OBJECTIVE: To study the prevalence of OTX1 and OTX2 gene expression in 60 medulloblastoma specimen samples and to establish correlations between gene expression and clinical and histopathological aspects. METHODS: We performed a retrospective analysis of 60 patients with a diagnosis of medulloblastoma at the Clinicas Hospital of the School of Medicine, University of São Paulo, and the Cancer Hospital of Barretos. We created a database of the 60 patients containing information on the gene expression of OTX1 and OTX2 (obtained using real-time polymerase chain reaction) and clinical and epidemiological data. Statistical tests were performed to verify potential correlations of clinicopathological data and follow-up aspects with gene expression. RESULTS: The OTX1 gene was expressed in 52% of the study population. Expression varied with age (higher in adults), location (predominantly by hemisphere), and histological type (desmoplastic). The OTX2 gene was expressed in 62% of the study population. Expression varied with age (higher in younger age groups), location (predominantly vermis), and histological type (classic and anaplastic). A statistical correlation between OTX2 gene expression and the development of leptomeningeal metastases was observed. CONCLUSIONS: The relative expression of OTX1 and OTX2 was dependent on patient age, tumor location, and histological variant. In addition, OTX2 expression might be a predictive factor for leptomeningeal metastases of medulloblastoma. The OTX pathway should be consider as an important venue for medulloblastomas development.

Pediatric central nervous system tumors: a single-center experience from 1989 to 2009.

The objective of this study was to determine the epidemiology of primary tumors of the central nervous system (CNS) in pediatric patients from a Brazilian oncology institute. We retrospectively analyzed 741 charts (415 males and 326 females) of patients under 21 years of age who were diagnosed with a CNS tumor. The analysis included patients from 1989 to 2009 and was performed using the World Health Organization criteria. We evaluated the distribution of age, sex, topography, clinical symptoms, symptom intervals, and classification of the tumors. Patients with clinical/radiologic diagnoses were included. Seven hundred forty-one patients with tumors in the CNS were reviewed, and 83% of the patients presented a histologic diagnosis. Males (56%) were more prevalent than females. In children under the age of 1 year, the supratentorial compartment was the predominant region involved (62.0%). Astrocytoma was the most frequent tumor type (37.0%), followed by medulloblastoma (13.6%), craniopharyngioma (10.5%), and ependymoma (6.8%). Headaches were the most common symptom, and the symptom intervals varied from 1 to 5010 days. Approximately 4% of the patients had associated genetic syndromes. Although it was not a population study and selection bias may have occurred, this study supplies important epidemiologic data from an emerging country in which population studies are rare.

Meduloblastoma: correlação entre ressonância magnética convencional, difusão e espectroscopia de prótons / Medulloblastoma: correlation among findings of conventional magnetic resonance imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy", "_i": "en

OBJETIVO: Correlacionar os achados de ressonância magnética convencional, difusão e espectroscopia de prótons nos meduloblastomas, e compará-los aos dados da literatura. MATERIAIS E MÉTODOS: Análise retrospectivade exames de ressonância magnética pré-operatórios de nove pacientes na faixa pediátrica com diagnóstico histológico de meduloblastoma (oito desmoplásicos e um de células gigantes). Foram considerados dados demográficos e características do tumor como localização, característica morfológica, intensidade de sinal, realce, disseminação e achados na difusão e espectroscopia. RESULTADOS: Na maioria dos casos os tumores apresentaram epicentro no vermis cerebelar (77,8%), sendo predominantemente sólido (88,9%), com hipossinal nas seqüências ponderadas em T1 e iso/hipersinal nas seqüências ponderadas em T2 e FLAIR, realce heterogêneo (100%), sinais de disseminação/extensão tumoral (77,8%) e restrição à movimentação das moléculas de água (100%). A espectroscopia de prótons pela técnica STEAM (n = 6) demonstrou redução da relação Naa/Cr (83,3%) e aumento de Co/Cr (100%) e mI/Cr (66,7%), e pela técnica PRESS (n = 7) evidenciou pico de lactato (57,1%). CONCLUSÃO: O conjunto dos achados macroscópicosobtidos pela ressonância magnética, somado às características bioquímicas dos meduloblastomas, têm sido úteis na tentativa de diferenciação entre os principais tumores da fossa posterior.

OBJECTIVE: To correlate imaging findings of medulloblastomas at conventional magnetic resonance imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy, comparing them with data in the literature. MATERIALS AND METHODS: Preoperative magnetic resonance imaging studies of nine pediatric patients with histologically confirmed medulloblastomas (eight desmoplastic medulloblastoma, and one giant cell medulloblastoma) were retrospectively reviewed, considering demographics as well as tumorscharacteristics such as localization, morphology, signal intensity, contrast-enhancement, dissemination, anddiffusion-weighted imaging and spectroscopy findings. RESULTS: In most of cases the tumors were centeredin the cerebellar vermis (77.8%), predominantly solid (88.9%), hypointense on T1-weighted images andintermediate/hyperintense on T2-FLAIR-weighted images, with heterogeneous enhancement (100%), tumor dissemination/extension (77.8%) and limited water molecule mobility (100%). Proton spectroscopy acquiredwith STEAM technique (n = 6) demonstrated decreased Naa/Cr ratio (83.3%) and increased Co/Cr (100%)and mI/Cr (66.7%) ratios; and with PRESS technique (n = 7) demonstrated lactate peak (57.1%). CONCLUSION: Macroscopic magnetic resonance imaging findings in association with biochemical features of medulloblastomas have been useful in the differentiation among the most frequent posterior fossa tumors. Keywords: Medulloblastoma; Infratentorial neoplasms; Pediatric brain tumors; Magnetic resonance imaging;Diffusion-weighted magnetic resonance imaging; Magnetic resonance spectroscopy.

Neurological evaluation of children and adolescents with brain tumor, based on ambulatory-oriented follow-up.

Taken as proved that brain tumors are the second most frequent childhood neoplasm - only outnumbered by leukemias - we have undertaken a clinical perspective study with seventy brain tumor patients ranging from one to fifteen years of age, throughout a four-year period (1993-1997), based on ambulatory-oriented follow-up. Forty-one male and twenty-nine female patients were analyzed, in that a slightly higher number of infratentorial tumors was observed (thirty-eight cases), compared to those supratentorially located (thirty-two cases). The most repeatedly observed during the study was the medulloblastoma (twenty-one patients), followed by the astrocytoma (fifteen patients) and the germinoma (eleven patients). It should be pointed out that during the ambulatory follow-up 75,5% of patients developed neurological sequels. A tumor recurrence was noticed in 34,3% of them, while 21,4% eventually died.

[Medulloblastomas: clinical, epidemiological and pathological findings in 28 cases]. / Meduloblastomas: achados clínicos, epidemiológicos e anátomo-patológicos de 28 casos.

We report the clinical, epidemiological and pathological findings of 28 patients with medulloblastoma: 22 were male; age ranged from 1 to 50 years, with a mean of 15 years. The most frequent symptoms and signs were headache (64%) and vomiting (64%). Only one patient showed a desmoplastic medulloblastoma variant, the others showed classical medulloblastomas. Regarding treatment, most patients were submitted to total resection (n=10) or partial tumorectomy (n=7). A low rate of tumoral recurrence was observed, occurring in 21% of the patients (n=6) after 4 years of follow-up. Chemotherapy seemed to contribute to a lower recurrence rate amongst our patients. Our findings are similar to those reported in literature, thus helping to understand the biological behavior of this type of tumor.

Meduloblastomas: achados clínicos, epidemiológicos e anátomo-patológicos de 28 casos / Medulloblastomas: clinical, epidemiological and pathological findings of 28 cases

Relatamos os achados clínicos, epidemiológicos e anátomo-patológicos de 28 casos de meduloblastomas. Dos 28 pacientes analisados, 22 eram do sexo masculino e seis do sexo feminino. As idades variaram de 1 a 50 anos, com média de 15 anos. Os sinais e sintomas de maior frequência foram cefaléia (64 por cento) e vômitos (64 por cento). Em relação ao tratamento, a maioria dos pacientes foi submetida a ressecção cirúrgica total (n=10) ou a exérese parcial (n=7). Com a exceção de um paciente que apresentava meduloblastoma desmoplásico, os demais apresentavam a forma clássica do meduloblastoma. Foi evidenciada uma taxa de recidiva tumoral total de 21 por cento (n=6) em 4 anos de seguimento clínico. A quimioterapia adjuvante parece contribuir para melhor evolução clínica dos pacientes. Estes achados aproximam-se dos encontrados na literatura, contribuindo para a compreensão do comportamento biológico deste tumor.

[Primary pediatric tumours of the central nervous system. Anatomopathological study of 623 cases]. / Tumores pediátricos primários do sistema nervoso central. Estudio anatomopatológico de 623 casos.

Tumours of central nervous system (CNS) represent the second most frequent malignancy in children under 15 years of age but are the commonest cause of death. The authors present the epidemiologic and histopathologic analysis of 623 primary tumours of CNS occurring during the period 1990 to 1996 in paediatric patients. In this period 3318 biopsies of CNS were analyzed. In this total were included 623 paediatric tumours (18 7%). The age of patients ranged from 5 months to 15 years, 325 tumours occurred in males and 298 in females. The majority affected the posterior fossa. The majority of paediatric neoplasias were of glial origin (n = 277). The most frequent tumours were: astrocytoma (27.9%), medulloblastoma (9.95%), craniopharyngioma (5.93%), ependymoma (4.97%) and glioblastoma (3.37%).

Brain tumors in the first two years of life: a review of forty cases.

From 1962 to 1989, 40 infants with brain tumors and less than 2 years old were treated at the Department of Neurology of the Clinical Hospital of the University of São Paulo Medical School. The clinical and neuropathological findings were reviewed as to histological diagnosis, age, sex, signs and symptoms, therapy and outcome. Medulloblastoma was the most common histological type (n = 11), followed by ependymoma (n = 9), choroid plexus tumor (n = 6), astrocytoma (n = 3) and primitive neuroectodermal tumor (n = 2). The tumor was infratentorial in 21 infants, supratentorial in 18 and disseminated in 1.

Avances en neuropediatria / Advances in neuropediatry

Diagnósticos prenatales de patología neuropediátrica. Embarazo y epilepsia, medicación, efectos sobre el recien nacido. Convulsiones neonatales, febriles, afebriles, epilepsias: diagnóstico y tratamiento. Benzodiazepinas: farmacología. Absorción del diazepan por vía sublingual versus oral. Niveles sanguineos con dosis únicas y múltiples. Electromiografias, resonancia magnética y mapeo cerebral en neuropediatría. Actualización en tumores de fosa posterior: meduloblastoma

Avances en neuropediatria / Advances in neuropediatry

Diagnósticos prenatales de patología neuropediátrica. Embarazo y epilepsia, medicación, efectos sobre el recien nacido. Convulsiones neonatales, febriles, afebriles, epilepsias: diagnóstico y tratamiento. Benzodiazepinas: farmacología. Absorción del diazepan por vía sublingual versus oral. Niveles sanguineos con dosis únicas y múltiples. Electromiografias, resonancia magnética y mapeo cerebral en neuropediatría. Actualización en tumores de fosa posterior: meduloblastoma

Meduloblastoma / Meduloblastoma

Se revisan todos los casos de Meduloblastoma diagnosticados y comprobados con Biopsia, en el Instituto de Anatomia Patologica del Hospital Universitario de San Vicente de Paul, desde el 1 de Enero de 1975, al 1 de Enero de 1980. Se encuentran 11 casos, todos suceptibles de seguimiento. Hay predominancia en hombres, en relacion de 1.75 a 1. El promedio de edad es de 8.6 anos, y el 64 X 100 de los pacientes son menores de 10 anos. La incidencia parece ir en aumento, a juzgar por el numero de pacientes que se han tabulado luego de la fecha del corte, y con miras a un informe posterior. La cefalea, el vomito y la ataxia, fueron los sintomas predominantes para la consulta. Una gran mayoria (mas del 90 X 100) de los tumores, son del vermis, y el resto del hemisferio, (tumor de adulto). Todos los pacientes fueron operados, la mayoria con reseccion macroscopicamente completa del tumor y 9 recibieron un regimen completo de terapia ionizante post-operatoria. De estos ultimos, la supervivencia es de 55.55 X 100 y la supervivencia global, es de 45.45 X 100. El tiempo entre cirugia y radioterapia fue en promedio 24 dias. La causa de muerte, es, casi siempre, la recidiva en fosa posterior