Correlação da localização topográfica e do edema peritumoral em pacientes com glioma recidivo com a resposta terapêutica ao álcool perílico

Introdução: Gliomas são tumores cerebrais primários caracterizados pelo crescimento difuso e invasivo. Estudo biomatemático de proliferação e migração dos gliomas propõe que o crescimento de tumores na substância cinzenta profunda cerebral teria um intervalo de tempo maior comparado a lesões situadas na substância branca lobar, onde a invasão e migração seriam mais rápidas. Objetivo: Estabelecer uma correlação da topografia tumoral e edema peritumoral com a resposta terapêutica à administração intranasal do álcool perílico (AP) em pacientes com glioblastoma (GBM) recidivo após tratamento convencional. Métodos: A coorte incluiu o estudo retrospectivo de 119 pacientes com glioma recidivo, sendo 52 em tratamento paliativo de suporte (grupo controle não pareado) e 67 que foram incluídos no Estudo Fase I/II do álcool perílico e receberam administração pela via inalatória de 440 mg de AP diariamente durante o período de Janeiro 2005 a Dezembro 2009. Os parâmetros avaliados incluíram aspectos clínicos e de neuroimagem: topografia tumoral, volume tumoral, presença de desvio da linha média e extensão de edema peritumoral; análise dos dados demográficos, sintomas iniciais e sobrevida global. Análise estatística foi realizada usando testes log rank. A sobrevida global foi determinada pelo método de Kaplan-Meier, incluindo intervalos de confiança de 95%. Resultados: Pacientes do grupo controle apresentaram sobrevida reduzida (p 1 cm) foi estatisticamente significante como fator de risco para menor sobrevida (log rank test, p = 0,0062). Conclusões: Este estudo sugere que: (1) pacientes com tumor localizado na região profunda (tálamo) apresentaram sobrevida média maior do que pacientes com tumor localizado na região lobar; (2) edema peritumoral foi um fator determinante na sintomatologia, provavelmente implicado na morbidade podendo estar relacionado com a característica de invasividade do glioma maligno. Esses achados apóiam a teoria de que fatores presentes em diferentes microambientes do tecido cerebral (tálamo, córtex) possam contribuir para o processo de progressão tumoral, para o prognóstico clínico e a resposta terapêutica ao álcool perílico administrado pela vias inalatóriaIntroduction: Gliomas are primary brain tumors are characterized by diffuse and invasive growth. Study biomathematical proliferation and migration of gliomas suggests that the growth of tumors in deep brain gray matter would have a longer time interval compared with lesions in the lobar white matter, where the invasion and migration would be faster. Objective: To establish a correlation of peritumoral edema and tumor topography with the therapeutic response to intranasal administration of perillyl alcohol (PA) in patients with glioblastoma (GBM) relapsing after conventional treatment. Methods: The cohort included a retrospective study of 119 patients with relapsing glioma, 52 palliative care support (control group) and 67 that were included in the Study Phase I / II and received perillyl alcohol administration by inhalation of 440 mg AP daily during the period January 2005 to December 2009. The parameters evaluated included clinical and neuroimaging: topography tumor, tumor volume, presence of midline shift and extent of peritumoral edema, analysis of demographic data, initial symptoms and overall survival. Statistical analysis was performed using log rank tests. Overall survival was determined by Kaplan-Meier, including 95% confidence intervals. Glioma is a primary brain tumor characterized by diffuse growth and invasiveness. The pattern of differential tumor growth and invasiveness suggest that patients with tumoral lesion located in the lobar white matter region present lower survival rate than patients with lesion located in deep brain gray matter (thalamo). Objective: To establish a correlation between tumor topography and peritumoral edema with the therapeutic response to intranasal administration of perillyl alcohol (POH). Methods: This retrospective study analyzed 119 patients with recurrent glioma being 52 under supportive treatment (control group) and 67 included in the Phase I/II clinical trial that received intranasal administration of 440 mg daily AP from January 2005 to December 2009. The following parameters were analyzed: clinical assessment; demographic data, symptoms and overall survival, neuroimage analysis of topography including tumor volume, midline shift and extent of peritumoral edema. Statistical analysis was performed using log rank tests. The overall survival was determined by the Kaplan-Meier method, including 95% confidence intervals. Results: Patients from control group showed reduced overall survival (p 1 cm) was statistically significant as a risk factor for shorter survival (log rank test, p = 0062). Conclusions: This study indicates that: 1) patients with tumoral lesion in the deep region (thalamic) have longer overall survival than GBM patients with tumors in the lobar region; 2) presence of peritumoral edema contributes strongly to symptoms and is likely to influence morbidity and the invading potential of malignant glioma. These findings support the hypothesis that interaction between glioma cells and different brain microenvironment (thalamo, cortex) can influence the process of glioma progression, clinical prognosis and therapeutic response to intranasal delivery perillyl alcoho