RESUMEN
PURPOSE: FOLFOX (a combination of leucovorin, fluorouracil and oxaliplatin) has achieved substantial success in the treatment of colorectal cancer (CRC) patients. However, about half of all patients show resistance to this regimen and some develop adverse symptoms such as neurotoxicity. In order to select patients who would benefit most from this therapy, we aimed to build a predictor for the response to FOLFOX using microarray gene expression profiles of primary CRC samples. PATIENTS AND METHODS: Forty patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received modified FOLFOX6. Responders and nonresponders were determined according to the best observed response at the end of the first-line treatment. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. We identified discriminating genes whose expression differed significantly between responders and nonresponders and then carried out supervised class prediction using the k-nearest-neighbour method. RESULTS: We identified 27 probes that were differentially expressed between responders and nonresponders at significant levels. Based on the expression of these genes, we constructed a FOLFOX response predictor with an overall accuracy of 92.5%. The sensitivity, specificity, positive and negative predictive values were 78.6%, 100%, 100% and 89.7%, respectively. CONCLUSION: The present model suggests the possibility of selecting patients who would benefit from FOLFOX therapy both in the metastatic and the adjuvant setting. To our knowledge, this is the first study to establish a prediction model for the response to FOLFOX chemotherapy based on gene expression by microarray analysis.
Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/tratamiento farmacológico , Perfilación de la Expresión Génica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adenocarcinoma/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/genética , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
As complicacoes pulmonares sao causa de alta mortalidade no paciente idoso com cancer de esofago. O objetivo deste estudo foi analisar o valor de varios fatores de risco pre e peri-operatorio para prever complicacoes pulmonares no pos-operatorio. Com este objetivo, 47 casos de resseccao esofagiana em pacientes com mais de 70 anos de idade realizada em nosso Departamento, no periodo de 1977 a 1990, foram revistos. Vinte e dois fatores de risco pre e peri-operatorios foram estudados. Usando analise em variante unico, tres destes fatores foram considerados significantes (p<0,05)...