Background Glioblastoma multiforme (GBM) is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecula...Background Glioblastoma multiforme (GBM) is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecular and treatment factors that influence clinical outcomes of patients with GBM. Methods A total of 116 patients with GBM who received surgery and radiation between January 2006 and December 2007 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patients' progression free survival (PFS) time and overall survival (OS) time. Results Age, preoperative Karnofsky Performance Scale (KPS) score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 expression level and adjuvant chemotherapy were statistically significant factors (P 〈0.05) for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age 〈50 years, preoperative KPS score 〉80, KPS score change after operation 〉0, involvement of single frontal lobe, non-eloquent area or deep structure involvement, low Ki-67 expression and adjuvant chemotherapy were independent favorable factors (P 〈0.05) for patients' clinical outcomes. Conclusions Age at diagnosis, preoperative KPS score, KPS score change at 2 weeks postoperation, involvement of brain lobe, involvement of eloquent cortex or deep structure, Ki-67 expression level and adjuvant chemotherapy correlate significantly with the prognosis of patients with GBM.展开更多
Background Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown promising activity in recurrent malignant gliomas. We reported the treatment response for the combination o...Background Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown promising activity in recurrent malignant gliomas. We reported the treatment response for the combination of bevacizumab and chemotherapy in a series of six patients with recurrent malignant glioma and investigated the molecular alterations in cancer pathways using the surgical biopsies from these patients. Methods Standard therapy with primary resection followed by adjuvant chemoradiotherapy had failed in all patients. Bevacizumab was administered at a dose of 10 mg/kg every 2 weeks. Concomitantly, four patients received temozolomide (50 mg·m^-2·d^-1), one patient irinotecan (125 mg/m^2 every 2 weeks) and one patient topotecan (1.2 mg·m^-2·d^-1). Response to therapy was mainly determined by magnetic resonance imaging. The expression of Ras, phosphorylated mitogen activated protein kinase (p-MAPK), phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were semiquantitatively assessed by immunohistochemistry using surgical biopsies before the initial treatment. Results Five of the six patients had a radiographic response. Three were complete response, and two were partial response. Only one patient had progressive disease. The 6-month progession-free survival (PFS) was 33% and the median PFS was 15 weeks, with a range of 6 to more than 60 weeks. Of the three core pathways analyzed in this study, the Ras/MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR pathways were more likely to be associated with the treatment response to bevacizumab. In two younger patients (ages 〈50) with complete response, simultaneous overexpression of p-MAPK, p-AKT and p-mTOR might be the crucial feature. Conclusions Bevacizumab in combination with chemotherapeutic agents may be an effective strategy for patients with recurrent malignant glioma. Activated MAPK and AKT might be possible biomarkers for selecting suitable patients for this targeted therapy.展开更多
Gliomatosis cerebri (GC) is a diffuse glial tumor that infiltrates the brain extensively. The optimaltherapeutic strategy for this tumor has not yet been established. Radiotherapy, temozolomide and other chemotherap...Gliomatosis cerebri (GC) is a diffuse glial tumor that infiltrates the brain extensively. The optimaltherapeutic strategy for this tumor has not yet been established. Radiotherapy, temozolomide and other chemotherapeutic modalities have been used to treat GC.2 Despite aggressive and often multimodal therapeutic intervention, survival rates for adult and pediatric patients with GC are extremely poor. Here we report two cases of GC in which we initially explored a new therapeutic strategy for this disease.展开更多
基金This study was supported by grants from National Key Project of Science and Technology Supporting Programs of China (No. 2007BAI05B08), National Natural Science Foundation of China (No. 30772238) and Key Project of National Natural Science Foundation of China (No. 30730035).
文摘Background Glioblastoma multiforme (GBM) is the most malignant kind of astrocytic tumors and is associated with a poor prognosis. In this retrospective study, we assessed the clinical, radiological, genetic molecular and treatment factors that influence clinical outcomes of patients with GBM. Methods A total of 116 patients with GBM who received surgery and radiation between January 2006 and December 2007 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to find the factors independently influencing patients' progression free survival (PFS) time and overall survival (OS) time. Results Age, preoperative Karnofsky Performance Scale (KPS) score, KPS score change at 2 weeks after operation, neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortex or deep structure, involvement of brain lobe, Ki-67 expression level and adjuvant chemotherapy were statistically significant factors (P 〈0.05) for both PFS and OS in the univariate analysis. Cox proportional hazards modeling revealed that age 〈50 years, preoperative KPS score 〉80, KPS score change after operation 〉0, involvement of single frontal lobe, non-eloquent area or deep structure involvement, low Ki-67 expression and adjuvant chemotherapy were independent favorable factors (P 〈0.05) for patients' clinical outcomes. Conclusions Age at diagnosis, preoperative KPS score, KPS score change at 2 weeks postoperation, involvement of brain lobe, involvement of eloquent cortex or deep structure, Ki-67 expression level and adjuvant chemotherapy correlate significantly with the prognosis of patients with GBM.
基金This work was supported by grants from National Key Technology R&D Program of China during the llth Five-Year Plan Period (No. 2007BAI05B08) and National Natural Science Foundation of China (No. 30772238).
文摘Background Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown promising activity in recurrent malignant gliomas. We reported the treatment response for the combination of bevacizumab and chemotherapy in a series of six patients with recurrent malignant glioma and investigated the molecular alterations in cancer pathways using the surgical biopsies from these patients. Methods Standard therapy with primary resection followed by adjuvant chemoradiotherapy had failed in all patients. Bevacizumab was administered at a dose of 10 mg/kg every 2 weeks. Concomitantly, four patients received temozolomide (50 mg·m^-2·d^-1), one patient irinotecan (125 mg/m^2 every 2 weeks) and one patient topotecan (1.2 mg·m^-2·d^-1). Response to therapy was mainly determined by magnetic resonance imaging. The expression of Ras, phosphorylated mitogen activated protein kinase (p-MAPK), phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were semiquantitatively assessed by immunohistochemistry using surgical biopsies before the initial treatment. Results Five of the six patients had a radiographic response. Three were complete response, and two were partial response. Only one patient had progressive disease. The 6-month progession-free survival (PFS) was 33% and the median PFS was 15 weeks, with a range of 6 to more than 60 weeks. Of the three core pathways analyzed in this study, the Ras/MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR pathways were more likely to be associated with the treatment response to bevacizumab. In two younger patients (ages 〈50) with complete response, simultaneous overexpression of p-MAPK, p-AKT and p-mTOR might be the crucial feature. Conclusions Bevacizumab in combination with chemotherapeutic agents may be an effective strategy for patients with recurrent malignant glioma. Activated MAPK and AKT might be possible biomarkers for selecting suitable patients for this targeted therapy.
文摘Gliomatosis cerebri (GC) is a diffuse glial tumor that infiltrates the brain extensively. The optimaltherapeutic strategy for this tumor has not yet been established. Radiotherapy, temozolomide and other chemotherapeutic modalities have been used to treat GC.2 Despite aggressive and often multimodal therapeutic intervention, survival rates for adult and pediatric patients with GC are extremely poor. Here we report two cases of GC in which we initially explored a new therapeutic strategy for this disease.