Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas(LGGs) facilitates the understanding of LGG response to radiotherapy.In this study,we used immunohistochemistry to analyze the exp...Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas(LGGs) facilitates the understanding of LGG response to radiotherapy.In this study,we used immunohistochemistry to analyze the expression of Ki-67,tumor protein P53(TP53),P21,and P27 in 8 paired WHO grade II astrocytoma samples.The interval between radiotherapy(RT) and the second surgery was more than 3 months in all cases.The average Ki-67 labeling index(LI) was 5.3% in pre-RT samples and 11.54% in post-RT samples.Ki-67 LI was higher in the primary tumors that underwent malignant transformation observed at the second surgery after radiation.Post-RT Ki-67 LI decreased in 2 cases with an interval of less than 12 months between RT and the second surgery.TP53 expression was found in 3 out of 4 pre-RT samples with malignant transformation and in 1 out of 4 pre-RT samples without malignant transformation.Post-RT TP53 increased in 2 cases in which increased expression of P21 or P27 was also observed.Our study suggests that radiotherapy can inhibit WHO grade II astrocytoma proliferation as reflected by Ki-67 LI,but the effect attenuates with time.In addition,there is a tendency of malignant transformation for WHO grade II astrocytomas with a high Ki-67 level or TP53 expression in initial samples.展开更多
Nonresectable Low-Grade Astrocytomas (LGA) can compromise function and threaten life. For the majority of patients, the most appropriate strategy is initial chemotherapy followed by Radiation Therapy (RT). Since curat...Nonresectable Low-Grade Astrocytomas (LGA) can compromise function and threaten life. For the majority of patients, the most appropriate strategy is initial chemotherapy followed by Radiation Therapy (RT). Since curative treatment is not available for most of these patients, it is reasonable to conduct clinical studies to evaluate new agents. This Phase II study evaluates efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in LGA. Sixteen children diagnosed with LGA were treated. They included 12 males and 4 females, ages 1.6 - 17.4 years (median 10.6). Efficacy was evaluated in 16 patients. The majority of patients were previously treated, but 1 patient had stereotactic biopsy only. Out of the remaining 15 patients, 6 patients received chemotherapy, and 7 patients had surgery, and 2 patients received RT and chemotherapy after surgery. The patients received treatment with ANP administered daily every 4 hours (median dose of A10 was 7.71 g/kg/d and AS2-1 was 0.26 g/kg/d) until objective response or stable disease was documented and for 8 months thereafter. The duration of ANP IV ranged from 1.4 to 286 weeks with a median of 83 weeks. A complete response was documented in 25.0%, partial response in 12.5%, and stable disease in 37.5%. Overall survival was 67.7% at 5 years, and 54.2% at 10 and 15 years. Progression-free survival was 48.1%, 34.4% and 34.4% at 5, 10, and 15 years respectively. The treatment was associated with grade 3 or grade 4 Adverse Drug Experiences (ADE) in 6 patients. There were two hypernatremias of grade 4 (12%). Grade 3 ADE included urinary frequency (6%), fatigue (6%) and hypernatremia (6%). There were no chronic toxicities, and there was a high quality of survival. ANP shows efficacy with a very good toxicity profile in this cohort of children with low-grade astrocytoma.展开更多
Introduction: Meningiomas are tumors formed by arachnoid cells, typically attached to the inner surface of the dura mater. Malignant forms are rare and no case has been reported in the Malagasy literature. The objecti...Introduction: Meningiomas are tumors formed by arachnoid cells, typically attached to the inner surface of the dura mater. Malignant forms are rare and no case has been reported in the Malagasy literature. The objective of our study is to report two Malagasy cases of malignant meningioma and to discuss the epidemiological and anatomical-clinical particularities of this tumor. Observation: The first patient, a 41-year-old woman, presented with a rapidly progressive intracranial hypertension syndrome. The patient had undergone surgery two years earlier for a grade II meningioma and had no family history of meningioma, neurofibromatosis, or personal history of brain irradiation or head trauma. Her brain scan showed a heterogeneous polylobed left parieto-occipital mass with a meningeal implantation base. The anatomopathological examination of the samples revealed a malignant meningioma. The second patient was a 33-year-old man, operated for grade I meningioma eleven months before admission, with no other personal or family history. The patient was hospitalized for tumor recurrence with signs of intracranial hypertension. The brain computed tomography (CT) scan showed a heterogeneous extra-axial tumor in right temporo-parietal lobe. Surgical excision was performed. On histological examination, a proliferation of tumor cells of meningothelial appearance with papillary architecture was observed, leading to the diagnosis of malignant meningioma. Conclusion: Malignant meningioma is a rare and serious entity. The clinical manifestations are nonspecific and imaging may mimic a low-grade meningioma. The diagnosis of certainty is histological and is based on essentially morphological criteria. The latter condition the overall survival of the patient and the therapeutic conduct.展开更多
Grade II oligodendrogliomas are rare and slow growing tumors, making long-term follow up difficult, but necessary for better understanding. In this retrospective study a review of all grade II oligodendrogliomas encou...Grade II oligodendrogliomas are rare and slow growing tumors, making long-term follow up difficult, but necessary for better understanding. In this retrospective study a review of all grade II oligodendrogliomas encountered in the last 20 years at one institution, was undertaken to determine if specific tumor location and immunohistochemical analysis had any impact on recurrence rate, progression free survival, or life expectancy. Eighty-nine grade II oligodendroglioms cases were reviewed (38 females and 51 males;mean age was 40.3 ± 13.8 years). Tumor location was: frontal lobe (44, 49.4%) and superior frontal gyrus (30, 33.7%). 1p19q data were available in 49 patients. Twenty-nine cases were co-deleted (59.2%). There was no significant difference in the incidence of 1p19q co-deletion between superior frontal gyrus tumors vs. other frontal tumors or extra-frontal tumors (p?= 0.45). Follow up of at least 3 months after diagnosis was available in 79 patients (mean follow up: 93.2 months). In recurrence analysis, recurrence by 1p19q status and recurrence by location revealed no significant differences. In analysis of progression, progression by 1p19q status and progression by location revealed no significant differences. An analysis of deaths for the sample, deaths by 1p19q status and deaths by location revealed no significant differences. There was a higher death rate among patients >50 years of age, however this, too, was not significant.?There did not appear to be any advantage in recurrence rate, progression free survival, or life expectancy for tumors located in the frontal lobe or superior frontal gyrus. 1p19q co-deletion did not appear to confer an advantage as measured by time to recurrence, time to progression, or overall survival. Other than age, eloquent location, Karnofsky status, and overall tumor size as reported by others, tumor location and 1p19q status in low grade oligodendrogliomas are not currently predictive of survival.展开更多
Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, B...Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, BT-06, which was transferred from the National Institutes of Health (NIH). Protocol BT-09 was designed for different types of primary brain tumors in adults that were not curable by standard treatment. The study was designed as a single arm, two-stage, phase II trial of ANP as a monotherapy in a high-risk, poor-prognosis population. The total number of registered subjects was 40. The majority of patients were diagnosed with high-grade tumors (N = 33). In this group, 12 patients carried diagnosis of anaplastic astrocytoma (AA) and 11 patients of glioblastoma. In the group of low-grade tumors (N = 7), there were 6 cases of low-grade glioma, and 1 neurocytoma grade 2. A group of 12 patients did not receive any prior treatment, 12 patients had surgical resection only, 5 patients received radiation therapy (RT) only, and 11 patients received both RT and chemotherapy. The median duration of ANP was 16.6 weeks. The median dosage of A10 was 7.16 g/kg/d and AS2-1 was 0.27 g/kg/d. Responses were accessed by gadolinium-enhanced magnetic resonance imaging (MRI). Objective responses (OR) in all patients were 22.5% and in the AA group were 41.7% of patients. The median progression-free survival (PFS) in the AA group was 5.4 months. The median overall survival (OS) was 12.7 months and OS at 1 and 2 years was 54.5% and 45.5% correspondingly. The treatment was well-tolerated with reversible grade 3 and 4 toxicities in 35% of all patients (N = 40). In conclusion, the study reached efficacy endpoint and ANP was well-tolerated and compared favorably to the current treatment of AA.展开更多
文摘Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas(LGGs) facilitates the understanding of LGG response to radiotherapy.In this study,we used immunohistochemistry to analyze the expression of Ki-67,tumor protein P53(TP53),P21,and P27 in 8 paired WHO grade II astrocytoma samples.The interval between radiotherapy(RT) and the second surgery was more than 3 months in all cases.The average Ki-67 labeling index(LI) was 5.3% in pre-RT samples and 11.54% in post-RT samples.Ki-67 LI was higher in the primary tumors that underwent malignant transformation observed at the second surgery after radiation.Post-RT Ki-67 LI decreased in 2 cases with an interval of less than 12 months between RT and the second surgery.TP53 expression was found in 3 out of 4 pre-RT samples with malignant transformation and in 1 out of 4 pre-RT samples without malignant transformation.Post-RT TP53 increased in 2 cases in which increased expression of P21 or P27 was also observed.Our study suggests that radiotherapy can inhibit WHO grade II astrocytoma proliferation as reflected by Ki-67 LI,but the effect attenuates with time.In addition,there is a tendency of malignant transformation for WHO grade II astrocytomas with a high Ki-67 level or TP53 expression in initial samples.
文摘Nonresectable Low-Grade Astrocytomas (LGA) can compromise function and threaten life. For the majority of patients, the most appropriate strategy is initial chemotherapy followed by Radiation Therapy (RT). Since curative treatment is not available for most of these patients, it is reasonable to conduct clinical studies to evaluate new agents. This Phase II study evaluates efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in LGA. Sixteen children diagnosed with LGA were treated. They included 12 males and 4 females, ages 1.6 - 17.4 years (median 10.6). Efficacy was evaluated in 16 patients. The majority of patients were previously treated, but 1 patient had stereotactic biopsy only. Out of the remaining 15 patients, 6 patients received chemotherapy, and 7 patients had surgery, and 2 patients received RT and chemotherapy after surgery. The patients received treatment with ANP administered daily every 4 hours (median dose of A10 was 7.71 g/kg/d and AS2-1 was 0.26 g/kg/d) until objective response or stable disease was documented and for 8 months thereafter. The duration of ANP IV ranged from 1.4 to 286 weeks with a median of 83 weeks. A complete response was documented in 25.0%, partial response in 12.5%, and stable disease in 37.5%. Overall survival was 67.7% at 5 years, and 54.2% at 10 and 15 years. Progression-free survival was 48.1%, 34.4% and 34.4% at 5, 10, and 15 years respectively. The treatment was associated with grade 3 or grade 4 Adverse Drug Experiences (ADE) in 6 patients. There were two hypernatremias of grade 4 (12%). Grade 3 ADE included urinary frequency (6%), fatigue (6%) and hypernatremia (6%). There were no chronic toxicities, and there was a high quality of survival. ANP shows efficacy with a very good toxicity profile in this cohort of children with low-grade astrocytoma.
文摘Introduction: Meningiomas are tumors formed by arachnoid cells, typically attached to the inner surface of the dura mater. Malignant forms are rare and no case has been reported in the Malagasy literature. The objective of our study is to report two Malagasy cases of malignant meningioma and to discuss the epidemiological and anatomical-clinical particularities of this tumor. Observation: The first patient, a 41-year-old woman, presented with a rapidly progressive intracranial hypertension syndrome. The patient had undergone surgery two years earlier for a grade II meningioma and had no family history of meningioma, neurofibromatosis, or personal history of brain irradiation or head trauma. Her brain scan showed a heterogeneous polylobed left parieto-occipital mass with a meningeal implantation base. The anatomopathological examination of the samples revealed a malignant meningioma. The second patient was a 33-year-old man, operated for grade I meningioma eleven months before admission, with no other personal or family history. The patient was hospitalized for tumor recurrence with signs of intracranial hypertension. The brain computed tomography (CT) scan showed a heterogeneous extra-axial tumor in right temporo-parietal lobe. Surgical excision was performed. On histological examination, a proliferation of tumor cells of meningothelial appearance with papillary architecture was observed, leading to the diagnosis of malignant meningioma. Conclusion: Malignant meningioma is a rare and serious entity. The clinical manifestations are nonspecific and imaging may mimic a low-grade meningioma. The diagnosis of certainty is histological and is based on essentially morphological criteria. The latter condition the overall survival of the patient and the therapeutic conduct.
文摘Grade II oligodendrogliomas are rare and slow growing tumors, making long-term follow up difficult, but necessary for better understanding. In this retrospective study a review of all grade II oligodendrogliomas encountered in the last 20 years at one institution, was undertaken to determine if specific tumor location and immunohistochemical analysis had any impact on recurrence rate, progression free survival, or life expectancy. Eighty-nine grade II oligodendroglioms cases were reviewed (38 females and 51 males;mean age was 40.3 ± 13.8 years). Tumor location was: frontal lobe (44, 49.4%) and superior frontal gyrus (30, 33.7%). 1p19q data were available in 49 patients. Twenty-nine cases were co-deleted (59.2%). There was no significant difference in the incidence of 1p19q co-deletion between superior frontal gyrus tumors vs. other frontal tumors or extra-frontal tumors (p?= 0.45). Follow up of at least 3 months after diagnosis was available in 79 patients (mean follow up: 93.2 months). In recurrence analysis, recurrence by 1p19q status and recurrence by location revealed no significant differences. In analysis of progression, progression by 1p19q status and progression by location revealed no significant differences. An analysis of deaths for the sample, deaths by 1p19q status and deaths by location revealed no significant differences. There was a higher death rate among patients >50 years of age, however this, too, was not significant.?There did not appear to be any advantage in recurrence rate, progression free survival, or life expectancy for tumors located in the frontal lobe or superior frontal gyrus. 1p19q co-deletion did not appear to confer an advantage as measured by time to recurrence, time to progression, or overall survival. Other than age, eloquent location, Karnofsky status, and overall tumor size as reported by others, tumor location and 1p19q status in low grade oligodendrogliomas are not currently predictive of survival.
文摘Antineoplastons A10 and AS2-1 (ANP) are synthetic derivatives of glutamine, isoglutamine, and phenylacetic acid. In 1993, a phase II clinical trial program began according to protocols based on the initial protocol, BT-06, which was transferred from the National Institutes of Health (NIH). Protocol BT-09 was designed for different types of primary brain tumors in adults that were not curable by standard treatment. The study was designed as a single arm, two-stage, phase II trial of ANP as a monotherapy in a high-risk, poor-prognosis population. The total number of registered subjects was 40. The majority of patients were diagnosed with high-grade tumors (N = 33). In this group, 12 patients carried diagnosis of anaplastic astrocytoma (AA) and 11 patients of glioblastoma. In the group of low-grade tumors (N = 7), there were 6 cases of low-grade glioma, and 1 neurocytoma grade 2. A group of 12 patients did not receive any prior treatment, 12 patients had surgical resection only, 5 patients received radiation therapy (RT) only, and 11 patients received both RT and chemotherapy. The median duration of ANP was 16.6 weeks. The median dosage of A10 was 7.16 g/kg/d and AS2-1 was 0.27 g/kg/d. Responses were accessed by gadolinium-enhanced magnetic resonance imaging (MRI). Objective responses (OR) in all patients were 22.5% and in the AA group were 41.7% of patients. The median progression-free survival (PFS) in the AA group was 5.4 months. The median overall survival (OS) was 12.7 months and OS at 1 and 2 years was 54.5% and 45.5% correspondingly. The treatment was well-tolerated with reversible grade 3 and 4 toxicities in 35% of all patients (N = 40). In conclusion, the study reached efficacy endpoint and ANP was well-tolerated and compared favorably to the current treatment of AA.
