Nádia Trompieri

Potential Role for Valproate in the Treatment of High-Risk Brain Tumors of Childhood—Results from a Retrospective Observational Cohort Study

Although substantial progress has been made in pediatric brain tumor management, patients with brainstem tumors and high-grade gliomas, as well as patients less than 3 years of age with high-risk malignant tumors, have a poorer prognosis. The authors have been treating these patients with radiotherapy and standard carboplatin and vincristine chemotherapy. Since January 2007 the authors have been using valproate as anticonvulsant for prophylaxis. The authors performed a retrospective cohort analysis of pediatric patients with high-risk brain tumors treated with chemotherapy, radiotherapy, and valproate prophylaxis, comparing this group with a historical control. The 2007–2008 group was comprised of 22 patients, 15 with brainstem tumors (7 diffuse intrinsic pontine glioma [DIPG], 3 focal, the remaining infiltrating with a solid portion), 4 with diencephalic tumors (2 thalamic), and 3 with supratentorial high-grade tumors (1 glioblastoma, 1 recurrent grade III ependymoma, 1 with gliomatosis). There were 15 patients alive (68%) after a mean follow-up time of 19 months. Survival function comparison by log rank test was highly significant (P = .004) with a hazard ratio of 0.31 (0.14–0.70). Radiological response showed 3 complete responses (14%), 8 partial responses (36%), 5 stable diseases (23%), and 5 progresssive diseases (23%). The authors hypothesize that valproate may have potentiated the antiangiogenic effect of vincristine, diminished expression of resistance to carboplatin, and sensitized tumor cells to radiotherapy. The authors suggest that clinical trials of carboplatin and vincristine associated with oral continuous low-dose valproate are indicated for pediatric patients with high-risk brain tumor.

Pediatric acute promyelocytic leukemia: all-transretinoic acid therapy in a Brazilian pediatric hospital.

Acute promyelocytic leukemia (APL) is an uncommon form of pediatric acute nonlymphocytic leukemia. It is characterized by clinical (refractory coagulopathy), morphologic (promyelocytic differentiation arrest), and cytogenetic t(15;17) hallmarks. The introduction of all-transretinoic acid (ATRA) or tretinoin, a biologic response modifier, in its therapy was followed by dramatic improvement in its outcome. To show the results of APL treatment in our hospital, we reviewed the information about 15 patients less than 18 years old, newly diagnosed with APL between November 2002 and November 2006. The diagnosis was made upon examination of bone marrow aspirates. The clinical charts were searched for data regarding clinical presentation, diagnosis, initial response with induction therapy, toxicity of ATRA, and antracyclic drug (daunorubicin). The median age was 10 years; the male-to-female ratio was 2:1. Fourteen patients received induction chemotherapy. Thirteen achieved complete remission. Six patients showed signs of coagulopathy. Only 1 patient was diagnosed with ATRA syndrome. There was a death owing to sepsis before the beginning of the therapy and 2 relapses with death associated with the therapy discontinuation. Preliminary results are encouraging and confirm that ATRA is safe and efficacious as first choice therapy for APL.

Analysis of survival and prognostic factors of pediatric patients with brain tumor

OBJECTIVES To estimate survival and evaluate prognostic factors of pediatric patients with central nervous system (CNS) tumors treated in a single center. METHODS Retrospective analysis of survival of 103 children with primary brain tumors diagnosed consecutively from January 2000 to December 2006. Cox regression was used for multivariate analysis of factors that affect overall survival to define possible prognostic factors. RESULTS Median and mean ages were 7.2 and 7.6 years. There was a male predominance (1.22:1). Most patients had medulloblastomas or primitive neuroectodermal tumors (PNET, 38%), or low-grade astrocytomas (18%). The anatomic site of most tumors was the cerebellum (49%) and the brain stem (21%). Five-year survival after diagnosis was 84% for low-grade astrocytomas and 51% for medulloblastomas and PNET. Prognostic factors for overall survival were histopathological type (high-grade astrocytomas and ependymomas; hazard ratio = 3.7 to 3.9), surgery (hazard ratio of 0.5 for completely resected tumors) and radiotherapy (hazard ratio of 0.5 for patients who underwent radiotherapy). CONCLUSIONS Overall survival of pediatric patients with brain tumors in this study was similar to that found in populations of the United States and Europe. The prognostic factors defined for overall survival are also similar to those published in previous studies.

Treatment of children and adolescents with hemangioma using propranolol: preliminary results from a retrospective study

CONTEXT AND OBJECTIVE Hemangiomas are the commonest vascular tumors during childhood. In 2008, the effect of propranolol for treating capillary hemangiomas was demonstrated. Other similar results followed, showing that it rapidly reduces lesion volume. The objective here was to evaluate children and adolescents with hemangiomas that were treated with propranolol. DESIGN AND SETTING Retrospective study, conducted in a childrens hospital. METHODS Patients aged 0-19 years with or without previous treatment, who were treated between January 2009 and December 2010, were included. The response was assessed by comparing the lesion appearance between the start of treatment and the last consultation. We considered partial or complete responses as the response to treatment. RESULTS Sixty-nine patients with a median follow-up of 11 months (mean age: 31 months) were included. Of these, 58 patients were recently diagnosed and 11 had had previous treatment. A response (partial or complete) was seen in 60 patients (87%). Among the capillary hemangioma cases, responses were seen in 50 out of 53 (94%), while in other lesion types, it was 10 out of 16 (63%) (P = 0.3; chi-square). Responses in patients less than one year of age were seen in 37 out of 38 (97%), whereas in those over one year of age, in 23 out of 31 (74%) (P = 0.4; chi-square). Side effects were uncommon and mild. CONCLUSIONS Propranolol seemed to be effective for treatment of hemangiomas in children and adolescents, and not just in the proliferative stage, with responses in almost all the patients.

Análise de sobrevida e fatores prognósticos de pacientes pediátricos com tumores cerebrais

OBJETIVOS: Realizar analise de sobrevida e avaliar, atraves de analise multivariada, a influencia de diversas variaveis na sobrevida, definindo fatores prognosticos de pacientes pediatricos com tumores do sistema nervoso central (SNC) tratados em um unico centro. METODOS: Analisamos, retrospectivamente, a sobrevida de 103 criancas portadoras de tumores cerebrais primarios, diagnosticadas consecutivamente no periodo entre janeiro de 2000 e dezembro de 2006. Analise multivariada de fatores influenciando a sobrevida global por regressao de Cox foi usada para definir possiveis fatores prognosticos. RESULTADOS: A mediana e a media de idade foram de 7,2 e 7,6 anos. Houve predominância do sexo masculino (relacao 1,22:1). A maioria dos pacientes tinha meduloblastoma ou tumores neuroectodermicos primitivos (PNET, 38%) ou astrocitomas de baixo grau (18%). As topografias mais comuns foram cerebelar (49%) e tronco cerebral (21%). A sobrevida, 5 anos apos o diagnostico, foi de 84% para astrocitomas de baixo grau e 51% para meduloblastomas e PNET. Fatores prognosticos para a sobrevida global foram histopatologico (astrocitomas de alto grau e ependimomas, razao de risco entre 3,7 e 3,9), cirurgia (razao de risco 0,5 para tumores completamente ressecados) e radioterapia (razao de risco 0,5 para pacientes que receberam radioterapia). CONCLUSOES: A sobrevida global de pacientes pediatricos com tumores cerebrais neste estudo e comparavel aquela dos registros populacionais dos Estados Unidos e Europa. Os fatores de prognostico definidos para sobrevida global tambem se assemelham aqueles previamente publicados.