RESUMO
A DPD deficiency should be considered in case of severe toxicity even in the absence of common risk variants in DPYD.
Assuntos
Antimetabólitos Antineoplásicos , Capecitabina , Deficiência da Di-Hidropirimidina Desidrogenase , Di-Hidrouracila Desidrogenase (NADP) , Humanos , Deficiência da Di-Hidropirimidina Desidrogenase/genética , Capecitabina/efeitos adversos , Di-Hidrouracila Desidrogenase (NADP)/genética , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Masculino , Feminino , Evolução Fatal , Pessoa de Meia-IdadeRESUMO
SCN1A is the most clinically relevant epilepsy gene and is associated with generalized epilepsy and febrile seizure plus (GEFS+) and Dravet syndrome. We postulated that earlier onset of febrile seizures in the febrile seizure (FS) and febrile seizure plus (FS+) phenotypes may occur in the presence of a SCN1A mutation. This was because of the age-related onset of Dravet syndrome, which typically begins in the first year of life. We found that patients with FS and FS+ with SCN1A mutations had earlier median onset of febrile seizures compared to the population median. Patients with GABRG2 mutations had a similar early onset in contrast to patients with SCN1B mutations where onset was later. This study is the first to demonstrate that a specific genetic abnormality directly influences the FS and FS+ phenotype in terms of age of onset.
Assuntos
Epilepsia Generalizada/genética , Saúde da Família , Mutação/genética , Proteínas do Tecido Nervoso/genética , Convulsões Febris/genética , Canais de Sódio/genética , Idade de Início , Criança , Pré-Escolar , Intervalos de Confiança , Análise Mutacional de DNA/métodos , Eletroencefalografia/métodos , Epilepsia Generalizada/complicações , Feminino , Humanos , Lactente , Masculino , Canal de Sódio Disparado por Voltagem NAV1.1 , Receptores de GABA-A/genética , Convulsões Febris/complicações , Estatísticas não ParamétricasRESUMO
INTRODUCTION: Elderly patients have glioblastomas (GBM) that are aggressive and poorly responsive to treatment. They are also prone to the side effects of treatment of GBM. METHODS: To shed light on the treatment of elderly patients with GBM, we reviewed the treatment toxicities and survival of patients 65 years of age or older who were treated with chemoradiotherapy, which is the new standard of care for GBM in younger patients. RESULTS: Thirty-nine patients at a single cancer center in Canada met the eligibility criteria for this retrospective study. Nineteen patients were treated initially with TMZ and radiotherapy and 20 others were treated with radiotherapy alone (only two had TMZ subsequently). Eight patients in the chemoradiotherapy group (42%) experienced Grade III or IV toxicity versus none in the radiotherapy group. The median overall survival in the chemoradiotherapy group was 8.5 months (range, 2.0-24.7 months) versus 5.2 months (range, 1.5-14.2 months) in the radiotherapy group, an apparent benefit which may have been due to an imbalance in age at diagnosis, extent of resection and performance status. In this series of GBM cases, methylation of the MGMT gene promoter was not associated with longer survival, either overall, or within the chemoradiotherapy treated subset. CONCLUSIONS: Elderly patients with GBM treated with chemoradiotherapy can be expected to experience significant toxicity. Large randomized trials will be necessary to determine whether chemoradiotherapy prolongs the survival of elderly patients and whether MGMT promoter status predicts benefit from temozolomide in this subset of patients.
