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PURPOSE: We describe the results of a risk-adapted, response-based therapeutic approach from the Brazilian GCT-99 study on germ cell tumors. PATIENTS AND METHODS: From May 1999 to October 2009, 579 participants were enrolled in the Brazilian GCT-99 study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk-group assignment at diagnosis with consideration for stage and primary tumor site. Patients at low risk received no chemotherapy. Patients at intermediate risk (IR) with a good response (GR) received four cycles of platinum and etoposide (PE), for total doses of platinum 420 mg/m(2) and etoposide 2,040 mg/m(2). Patients at IR with a partial response (PR) received three cycles of PE plus three cycles of ifosfamide, vinblastine, and bleomycin. Patients at high risk (HR) with a GR received four cycles of PE and ifosfamide (PEI) at total doses of platinum 420 mg/m(2), etoposide 1,200 mg/m(2), and ifosfamide 30 g/m(2). Patients at HR with a PR received six cycles of PEI. RESULTS: The risk-group distribution was 213 LR, 138 IR, and 129 HR for 480 evaluable patients. Overall survival (OS) and event-free survival (EFS) rates at 10 years were, respectively, 90% and 88.6% in the IR-GR group (n = 126) and 74.1% and 74.1% in the IR-PR group (n = 12). Ten-year rates for the HR-GR group (n = 86) were an OS of 66.8% and an EFS of 62.5%. The HR-PR group (n = 43) had an OS of 74.8% and an EFS of 73.4%. In univariable and multivariable analysis, increased serum lactate dehydrogenase level and histology for a metastatic immature teratoma were prognostic of a worsened outcome. CONCLUSION: Reduction of therapy to two drugs did not compromise survival outcomes for patients in the IR-GR group, and escalation of therapy with PEI did not significantly improve OS and EFS in patients at HR.

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Objetivos: analisar a sobrevida de pacientes com diagnóstico de tumores do sistema nervoso central (SNC) em um serviço de referência em Oncologia Pediátrica, sua apresentação clínica, evolução e influência de fatores prognósticos. Métodos: estudo de coorte histórica. Foram estudados pacientes menores de 19 anos, no período de março de 2003 a dezembro de 2009. O método de Kaplan-Meier foi utilizado para estimar a probabilidade de sobrevida global (SGLO). O teste de log rank e o modelo de regressão de Cox foram usados nas análises univariada e multivariada. Resultados: foram incluídos 159 pacientes, com mediana de tempo de seguimento de 13 meses. O intervalo entre o início dos sintomas e o diagnóstico teve mediana de 1,9 mês; 52% eram do gênero masculino. A mediana de idade ao diagnóstico foi de 7,2 anos. Os diagnósticos histológicos mais frequentes foram glioma de baixo grau (27%), meduloblastoma (19,5%) e tumor de tronco encefálico (17,6%). Cefaleia foi o sintoma mais frequente ao diagnóstico. A localização primária mais comum dos tumores foi a infratentorial (55,3%). A SGLO aos cinco anos foi de 42% (IC 95, 33 a 53%). Na análise univariada, foi observada associação significativa entre tempo de surgimento dos sintomas e o diagnóstico (p=0,046) e diagnóstico histológico (p<0,001). Na análise multivariada, esses fatores mantiveram-se e foram acrescidos da localização primária do tumor. Discussão: a SGLO observada neste estudo foi claramente inferior às descritas na literatura internacional, porém semelhante à de dois outros centros de referência nacionais. Estudos multicêntricos em nível nacional são necessários para confirmação desses resultados.

Objetives: To evaluate outcome of patients with the diagnosis of Central Nervous System tumors at a local reference pediatric oncology service, their clinical presentation, evolution and influence of prognostic factors. Methods: Patients enrolled in this retrospective study between March,2003 and December,2009, were less than nineteen years old at the time of the diagnosis. Kaplan-Meier method was used to estimate the overall survival (OS). Log rank test and Cox?s method were used in the statistical analysis. Results: Study population consisted of 159 patients with median follow up period of 13 months. Median of the time between onset of symptoms and diagnosis was 1,9 months. Boys comprised 52% of the studied population. Median age at diagnosis was 7,2 years. Most common diagnostic subtypes were low grade glioma (27%), medulloblastoma (19,5%) and brain stem tumors (17,6%). Headache was the most frequent symptom (57%) and infratentorial tumors correspond to 55,3% of the cases. An estimated OS of 42% (CI 95%, 33% to 53%) was observed for the role group. An association between outcome and the following variables was observed: interval between the time of onset of symptoms and diagnosis (p=0,046)and histological classification of the tumors (p<0,001). In the multivariate analysis, these variables were sustained, added of the primary location of the tumor in the Central Nervous System. Discussion: Overall survival detected in this study was clearly worse when compared with international centers rates, although were similar to other Brazilian studies. It?s important to develop multicentric studies to confirm data showed in this study

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OBJECTIVE: To detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia. METHODS: Fifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis. RESULTS: Immunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%). For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%), then TCRG (61.4%), and TCRD and IgK (47.7%); for T-acute lymphocytic leukemia, TCRG (80.0%), and TCRD and Sil-Tal deletion (20.0%) were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 10(9)/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7). CONCLUSION: Immunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.

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OBJECTIVE To detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia. METHODS Fifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis. RESULTS Immunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%). For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%), then TCRG (61.4%), and TCRD and IgK (47.7%); for T-acute lymphocytic leukemia, TCRG (80.0%), and TCRD and Sil-Tal deletion (20.0%) were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 109/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7). CONCLUSION Immunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.

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O câncer infanto-juvenil é uma doença relativamente rara, sendo responsável por 0,5-3% do total de casos de câncer. Entretanto, ainda é causa de grande morbimortalidade em pacientes nessa faixa etária em nosso meio. Diagnóstico precoce e tratamento em centros especializados são essenciais para aumento da sobrevida em longo prazo. Objetivo: alertar o pediatra a respeito da importância do reconhecimento precoce das principais neoplasias malignas da infância e adolescência, dando ênfance à epedemiologia e apresentação clínica dos tumores sólidos. Métodos: foram selecionados 26 referências bibliográficas em pesquisa realizada nas base de dados Medline e no LILACS, em português, espanhol e inglês, utilizando-se as palavras-chave câncer infanto-juvenil, apresentação clínica, sobrevida.

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