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

• Ano de defesa: 2010
• Autor(a) principal: Silva, Júlio César Thomé de Souza
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/87559/00130000085t3
• Idioma: por
• Instituição de defesa: Programa de Pós-graduação em Ciências Médicas; Ciências Médicas
• Palavras-chave em Português: Tumor cerebral; Glioma; Alcool perílico; Topografia; Cerebral tumor; Perillyl alcohol; Topography; CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA
• Link de acesso: https://app.uff.br/riuff/handle/1/17358

Introduction: 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 < 0,0001) in comparison with patients included in the Phase I/II that received treatment with perillyl alcohol. Among 67 GBM patients, 14 (21%) had tumoral lesion in the thalamic region and 53 (79%) in the lobar region. Patients with thalamic tumor survived significantly longer than those with tumor located in the lobar region (log rank test, p = 0.0003). Patients with tumor regression with reduction of peritumoral edema had positive clinical response, whereas poor prognosis was observed in those with tumor regression but without reduction of peritumoral edema. Presence of midline shift (> 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 alcohol.