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1.
Oncologist ; 26(8): 647-e1304, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33783067

RESUMO

LESSONS LEARNED: Treatment with temozolomide and BCNU was associated with substantial response and survival rates for patients with unresectable anaplastic glioma, suggesting potential therapeutic alternative for these patients. The optimal treatment for unresectable large anaplastic gliomas remains debated. BACKGROUND: The optimal treatment for unresectable large anaplastic gliomas remains debated. METHODS: Adult patients with histologically proven unresectable anaplastic oligodendroglioma or mixed gliomas (World Health Organization [WHO] 2007) were eligible. Treatment consisted of BCNU (150 mg/m2 ) and temozolomide (110 mg/m2 for 5 days) every 6 weeks for six cycles before radiotherapy. RESULTS: Between December 2005 and December 2009, 55 patients (median age of 53.1 years; range, 20.5-70.2) were included. Forty percent of patients presented with wild-type IDH1 gliomas, and 30% presented with methylated MGMT promoter. Median progression-free survival (PFS), centralized PFS, and overall survival (OS) were 16.6 (95% confidence interval [CI], 12.8-20.3), 15.4 (95% CI, 10.0-20.8), and 25.4 (95% CI, 17.5-33.2) months, respectively. Complete and partial responses under chemotherapy were observed for 28.3% and 17% of patients, respectively. Radiotherapy completion was achieved for 75% of patients. Preservation of functional status and self-care capability (Karnofsky performance status [KPS] ≥70) were preserved until disease progression for 69% of patients. Grade ≥ 3 toxicities were reported for 52% of patients, and three deaths were related to treatment. By multivariate analyses including age and KPS, IDH mutation was associated with better prognostic for both PFS and OS, whereas MGMT promoter methylation was associated with better OS. CONCLUSION: The association of BCNU and temozolomide upfront is active for patients with unresectable anaplastic gliomas, but toxicity limits its use.


Assuntos
Neoplasias Encefálicas , Glioma , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Dacarbazina/uso terapêutico , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Adulto Jovem
2.
Oncologist ; 23(5): 524-e44, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29472310

RESUMO

LESSONS LEARNED: Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate, survival, performance, quality of life, and cognition in elderly patients with glioblastoma multiforme with poor performance status.Whether this combination is superior to temozolomide alone remains to be demonstrated by a randomized study. BACKGROUND: The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is not established. This clinical trial evaluated the efficacy and safety of upfront temozolomide (TMZ) and bevacizumab (Bev) in patients aged ≥70 years and a KPS <70. MATERIALS AND METHODS: Patients aged ≥70 years with a KPS <70 and biopsy-proven GBM were eligible for this multicenter, prospective, nonrandomized, phase II trial of older patients with impaired performance status. Treatment consisted of TMZ administered at 130-150 mg/m2 per day for 5 days every 4 weeks plus Bev administered at 10 mg/kg every 2 weeks. RESULTS: The trial included 66 patients (median age of 76 years; median KPS of 60). The median overall survival (OS) was 23.9 weeks (95% confidence interval [CI], 19-27.6), and the median progression-free survival (PFS) was 15.3 weeks (95% CI, 12.9-19.3). Twenty-two (33%) patients became transiently capable of self-care (i.e., KPS >70). Cognition and quality of life significantly improved over time during treatment. Grade ≥3 hematological adverse events occurred in 13 (20%) patients, high blood pressure in 16 (24%), venous thromboembolism in 3 (4.5%), cerebral hemorrhage in 2 (3%), and intestinal perforation in 2 (3%). CONCLUSION: This study suggests that TMZ + Bev treatment is active in elderly patients with GBM with low KPS and has an acceptable tolerance level.


Assuntos
Bevacizumab/uso terapêutico , Glioblastoma/tratamento farmacológico , Temozolomida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/farmacologia , Feminino , Humanos , Masculino , Temozolomida/farmacologia
3.
J Neurosurg ; 128(1): 3-13, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28298039

RESUMO

OBJECTIVE The goal of this study was to provide insight into the influence of gliomas on gestational outcomes, the impact of pregnancy on gliomas, and the identification of patients at risk. METHODS In this multiinstitutional retrospective study, the authors identified 52 pregnancies in 50 women diagnosed with a glioma. RESULTS For gliomas known prior to pregnancy (n = 24), we found the following: 1) An increase in the quantified imaging growth rates occurred during pregnancy in 87% of cases. 2) Clinical deterioration occurred in 38% of cases, with seizures alone resolving after delivery in 57.2% of cases. 3) Oncological treatments were immediately performed after delivery in 25% of cases. For gliomas diagnosed during pregnancy (n = 28), we demonstrated the following: 1) The tumor was discovered during the second and third trimesters in 29% and 54% of cases, respectively, with seizures being the presenting symptom in 68% of cases. 2) The quantified imaging growth rates did not significantly decrease after delivery and before oncological treatment. 3) Clinical deterioration resolved after delivery in 21.4% of cases. 4) Oncological treatments were immediately performed after delivery in 70% of cases. Gliomas with a high grade of malignancy, negative immunoexpression of alpha-internexin, or positive immunoexpression for p53 were more likely to be associated with tumor progression during pregnancy. Deliveries were all uneventful (cesarean section in 54.5% of cases and vaginal delivery in 45.5%), and the infants were developmentally normal. CONCLUSIONS When a woman harboring a glioma envisions a pregnancy, or when a glioma is discovered in a pregnant patient, the authors suggest informing her and her partner that pregnancy may impact the evolution of the glioma clinically and radiologically. They strongly advise a multidisciplinary approach to management. ■ CLASSIFICATION OF EVIDENCE Type of question: association; study design: case series; evidence: Class IV.


Assuntos
Neoplasias Encefálicas/epidemiologia , Glioma/epidemiologia , Complicações Neoplásicas na Gravidez/epidemiologia , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Progressão da Doença , Feminino , Seguimentos , Glioma/diagnóstico , Glioma/terapia , Humanos , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/terapia , Resultado da Gravidez , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
4.
Acta Neuropathol Commun ; 4: 31, 2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-27036230

RESUMO

IDH mutations are found in the majority of adult, diffuse, low-grade and anaplastic gliomas and are also frequently found in cartilaginous tumors. Ollier disease and Maffucci syndrome are two enchondromatosis syndromes characterized by the development of multiple benign cartilaginous tumors due to post-zygotic acquisition of IDH mutations. In addition to skeletal tumors, enchondromatosis patients sometimes develop gliomas. The aim of the present study was to determine whether gliomas in enchondromatosis patients might also result from somatic IDH mosaicism and whether their characteristics are similar to those of sporadic IDH-mutated gliomas. For this purpose, we analyzed the characteristics of 6 newly diagnosed and 32 previously reported cases of enchondromatosis patients who developed gliomas and compared them to those of a consecutive series of 159 patients with sporadic IDH-mutated gliomas. As was the case with sporadic IDH mutated gliomas, enchondromatosis gliomas were frequently located in the frontal lobe (54 %) and consisted of diffuse low-grade (73 %) or anaplastic gliomas (21 %). However, they were diagnosed at an earlier age (25.6 years versus 44 years, p < 0.001) and were more frequently multicentric (32 % versus 1 %, p < 0.001) and more frequently located within the brainstem than sporadic IDH mutated gliomas (21 % versus 1 %, p < 0.001). Their molecular profile was characterized by IDH mutations and loss of ATRX expression. In two patients, the same IDH mutation was demonstrated in the glioma and in a cartilaginous tumor. In contrast to sporadic IDH mutated gliomas, no enchondromatosis glioma harbored a 1p/19q co-deletion (0/6 versus 59/123, p = 0.03). The characteristics of gliomas in patients with enchondromatosis suggest that these tumors, as cartilaginous tumors, result from somatic IDH mosaicism and that the timing of IDH mutation acquisition might affect the location and molecular characteristics of gliomas. Early acquisition of IDH mutations could shift gliomagenesis towards the brainstem thereby mimicking the regional preference of histone mutated gliomas.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Mosaicismo , Mutação/genética , Adulto , Neoplasias Encefálicas/patologia , Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Feminino , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos
5.
Neuro Oncol ; 17(11): 1497-503, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26014047

RESUMO

BACKGROUND: The diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL. METHODS: We retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion. RESULTS: CSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P < .001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P < .001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P < .001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively. CONCLUSION: Assessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these results.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Linfoma/diagnóstico , Neopterina/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Linfoma/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
6.
Clin Cancer Res ; 18(18): 5071-80, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22761472

RESUMO

PURPOSE: To develop a tumor growth inhibition model for adult diffuse low-grade gliomas (LGG) able to describe tumor size evolution in patients treated with chemotherapy or radiotherapy. EXPERIMENTAL DESIGN: Using longitudinal mean tumor diameter (MTD) data from 21 patients treated with first-line procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine (PCV) chemotherapy, we formulated a model consisting of a system of differential equations, incorporating tumor-specific and treatment-related parameters that reflect the response of proliferative and quiescent tumor tissue to treatment. The model was then applied to the analysis of longitudinal tumor size data in 24 patients treated with first-line temozolomide (TMZ) chemotherapy and in 25 patients treated with first-line radiotherapy. RESULTS: The model successfully described the MTD dynamics of LGG before, during, and after PCV chemotherapy. Using the same model structure, we were also able to successfully describe the MTD dynamics in LGG patients treated with TMZ chemotherapy or radiotherapy. Tumor-specific parameters were found to be consistent across the three treatment modalities. The model is robust to sensitivity analysis, and preliminary results suggest that it can predict treatment response on the basis of pretreatment tumor size data. CONCLUSIONS: Using MTD data, we propose a tumor growth inhibition model able to describe LGG tumor size evolution in patients treated with chemotherapy or radiotherapy. In the future, this model might be used to predict treatment efficacy in LGG patients and could constitute a rational tool to conceive more effective chemotherapy schedules.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioma/terapia , Modelos Biológicos , Adolescente , Algoritmos , Criança , Pré-Escolar , Feminino , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Masculino , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Carga Tumoral , Adulto Jovem
7.
Neuro Oncol ; 13(7): 775-82, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21727213

RESUMO

Recent advances in the treatment of malignant gliomas have highlighted the fact that the appearance of new contrast-enhancing lesions on magnetic resonance imaging (MRI) is not always indicative of tumor recurrence. It has been suggested that transient seizure-related MRI changes could mimic disease progression (peri-ictal pseudoprogression [PIPG]). However, the clinical and MRI features associated with this situation have not been well described. Here, we consulted the databases of 6 institutions to identify patients with brain tumor who presented during the follow-up period transient MRI lesions wrongly suggesting tumor progression in a context of epileptic seizures. Ten patients were identified. All patients but 1 were long-term survivors who had initially been treated with radiotherapy. The PIPG episode occurred after a median interval of 11 years after radiotherapy. MRI features were highly similar across patients and consisted of transient focal cortical and/or leptomeningeal enhancing lesions that erroneously suggested tumor progression. All patients improved after adjustment of their antiepileptic drugs and transient oral corticosteroids, and MRI findings were normalized 3 months after the PIPG episode. Two patients demonstrated several seizure relapses with the same clinicoradiological pattern. After a median follow-up period of 3.5 years after the initial PIPG episode, only 1 patient presented with a tumor recurrence. In conclusion, in patients with brain tumor, especially in long-term survivors of radiotherapy, the appearance of new cortical and/or leptomeningeal contrast-enhancing lesions in a context of frequent seizures should raise the suspicion of PIPG. This phenomenon is important to recognize in order to avoid futile therapeutic escalation.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Sobreviventes , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Progressão da Doença , Feminino , Glioma/mortalidade , Glioma/radioterapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Convulsões/etiologia , Taxa de Sobrevida , Resultado do Tratamento
8.
J Clin Oncol ; 29(22): 3050-5, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21709196

RESUMO

PURPOSE: The management of glioblastoma multiforme (GBM) in elderly patients with poor performance status is not well established. A trial evaluating the efficacy and safety of temozolomide alone in this population was undertaken. PATIENTS AND METHODS: Patients age 70 years or older with newly diagnosed GBM and postoperative Karnofsky performance score (KPS) less than 70 were eligible for this nonrandomized phase II trial. Treatment consisted of 150 to 200 mg/m(2)/d temozolomide for 5 days every 4 weeks until disease progression. Radiotherapy was not administered. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), safety, quality of life, and cognition. RESULTS: Seventy patients (median age, 77 years; median KPS, 60) were enrolled between July 2007 and February 2009. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 13% and 14% of patients, respectively. Median PFS was 16 weeks (95% CI, 10 to 20 weeks), and median OS was 25 weeks (95% CI, 19 to 28 weeks), comparing favorably with a 12- to 16-week OS expected from a purely supportive approach. Twenty-three patients (33%) improved their KPS by 10 or more points, and 18 (26%) became capable of self-care (KPS ≥ 70). Overall quality of life and cognition improved over time before disease progression. In the 31 tumors evaluated for O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, a methylated status indicated longer PFS (26 v 11 weeks; P = .03) and OS (31 v 19 weeks; P = .03). CONCLUSION: Temozolomide has an acceptable tolerance in elderly patients with GBM and KPS less than 70. It is associated with improvement of functional status in 33% of patients and appears to increase survival compared with supportive care alone, especially in patients with methylated MGMT promoter.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Cognição , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Feminino , França/epidemiologia , Glioblastoma/diagnóstico , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Masculino , Reação em Cadeia da Polimerase , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Temozolomida , Resultado do Tratamento , Proteínas Supressoras de Tumor/metabolismo
10.
Neuro Oncol ; 12(10): 1078-82, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20488959

RESUMO

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8-7.7) after PCV onset and 2.7 years (range, 0-7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Lomustina/administração & dosagem , Lomustina/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Procarbazina/administração & dosagem , Procarbazina/uso terapêutico , Estudos Retrospectivos , Vincristina/administração & dosagem , Vincristina/uso terapêutico
11.
Ann Neurol ; 67(3): 398-404, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20373352

RESUMO

Twelve pregnancies in 11 adult women harboring World Health Organization (WHO) grade II gliomas (GIIGs) prior to pregnancy were reviewed to address whether pregnancy affects tumor growth using a quantitative approach of the radiological velocity of diametric expansion (VDE) on successive magnetic resonance images. VDE was significantly increased during pregnancy as compared to prepregnancy (p < 0.001) and to postdelivery (p = 0.012) periods. Pregnancy increases the radiological growth rates of GIIGs. An increase in seizure frequency was observed concomitantly in 40% of cases and further oncological treatment was started after delivery in 25% of cases.


Assuntos
Neoplasias Encefálicas/patologia , Encéfalo/patologia , Glioma/patologia , Invasividade Neoplásica/patologia , Complicações Neoplásicas na Gravidez/patologia , Adulto , Astrocitoma/patologia , Astrocitoma/fisiopatologia , Encéfalo/fisiopatologia , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/fisiopatologia , Proliferação de Células , Progressão da Doença , Feminino , Glioma/classificação , Glioma/fisiopatologia , Hormônios Esteroides Gonadais/metabolismo , Hormônio do Crescimento/metabolismo , Humanos , Imageamento por Ressonância Magnética , Oligodendroglioma/patologia , Oligodendroglioma/fisiopatologia , Placenta/metabolismo , Gravidez , Complicações Neoplásicas na Gravidez/fisiopatologia , Convulsões/etiologia , Convulsões/fisiopatologia , Organização Mundial da Saúde , Adulto Jovem
12.
J Stroke Cerebrovasc Dis ; 19(1): 75-6, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20123231

RESUMO

Occasionally, patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) present atypical features such as confusion, coma, or nonconvulsive status epilepticus. Acute focal neuropsychological syndrome revealing the disease has been poorly documented. We report the atypical presentation of two patients in whom CADASIL was revealed by an episode of headache followed by focal neuropsychological impairment.


Assuntos
CADASIL/diagnóstico , Cefaleia/etiologia , Doenças do Sistema Nervoso/etiologia , Doença Aguda , Adulto , CADASIL/complicações , CADASIL/genética , CADASIL/psicologia , Análise Mutacional de DNA , Imagem de Difusão por Ressonância Magnética , Cefaleia/genética , Cefaleia/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/psicologia , Testes Neuropsicológicos , Receptor Notch3 , Receptores Notch/genética
13.
J Neurooncol ; 99(1): 89-94, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20058048

RESUMO

Upfront temozolomide (TMZ) is often proposed for elderly patients with malignant gliomas as an alternative to radiotherapy (RT). A recent randomized trial showed that RT provides a survival benefit in elderly glioblastoma patients (>or=70 years) with good performance status (KPS >or= 70) compared with supportive care alone (median survival (MS) = 29.1 vs. 16.9 weeks). We retrospectively analyzed all patients who were eligible for this trial, but who refused to participate and were finally treated with TMZ alone. Thirty-nine eligible patients (median age: 75 years (range 70-83), median KPS: 70 (range 70-80), histologically proven glioblastomas) were treated up-front with oral TMZ for 1-12 cycles (mean = 5). One complete response and 10 partial responses were observed. Overall median survival (MS) was 36 weeks and median progression-free survival (PFS) was 20 weeks for the whole group. MS was 27.4 weeks and PFS was 19.5 weeks for the 27 patients that did not receive second-line treatment at progression. Eight grade III/IV toxicities (seven hematologic, one gastro-intestinal) were seen, but no treatment-related deaths were observed. These preliminary results support further randomized studies comparing TMZ with RT.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Geriatria , Glioblastoma/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Dacarbazina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Análise de Sobrevida , Temozolomida , Resultado do Tratamento , Proteínas Supressoras de Tumor/metabolismo
14.
Psychol Neuropsychiatr Vieil ; 6(3): 209-18, 2008 Sep.
Artigo em Francês | MEDLINE | ID: mdl-18786880

RESUMO

Patients with limbic encephalitis (LE) display various disorders including anterograde amnesia, mood disturbances (irritability, agitation or pseudo-depressive symptoms) and epilepsy, often partial but sometimes generalized, and rapidely progressive course. On account of the variability of the initial symptoms, limbic encephalitis is clearly under-diagnosed and often misdiagnosed as viral encephalitis. From a pathophysiological point of view, two types of LE can be identified. First, LE associated with antibodies directed against an intracellular neuronal antigen. They correspond to the traditional paraneoplastic LE, and are characterized by a weak response to treatment even when the causal tumor is treated. Second, LE associated with antibodies directed against antigens present on cellular membranes. These LE can be paraneoplastic or idiopathic, and present a better response to immunological treatments.


Assuntos
Encefalite Límbica/diagnóstico , Doenças Autoimunes/imunologia , Diagnóstico Diferencial , Humanos , Encefalite Límbica/imunologia
15.
N Engl J Med ; 356(15): 1527-35, 2007 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-17429084

RESUMO

BACKGROUND: There is no community standard for the treatment of glioblastoma in patients 70 years of age or older. We conducted a randomized trial that compared radiotherapy and supportive care with supportive care alone in such patients. METHODS: Patients 70 years of age or older with a newly diagnosed anaplastic astrocytoma or glioblastoma and a Karnofsky performance score of 70 or higher were randomly assigned to receive supportive care only or supportive care plus radiotherapy (focal radiation in daily fractions of 1.8 Gy given 5 days per week, for a total dose of 50 Gy). The primary end point was overall survival; secondary end points were progression-free survival, tolerance of radiotherapy, health-related quality of life, and cognition. RESULTS: We randomly assigned 85 patients from 10 centers to receive either radiotherapy and supportive care or supportive care alone. The trial was discontinued at the first interim analysis, which showed that with a preset boundary of efficacy, radiotherapy and supportive care were superior to supportive care alone. A final analysis was carried out for the 81 patients with glioblastoma (median age, 73 years; range, 70 to 85). At a median follow-up of 21 weeks, the median survival for the 39 patients who received radiotherapy plus supportive care was 29.1 weeks, as compared with 16.9 weeks for the 42 patients who received supportive care alone. The hazard ratio for death in the radiotherapy group was 0.47 (95% confidence interval, 0.29 to 0.76; P=0.002). There were no severe adverse events related to radiotherapy. The results of quality-of-life and cognitive evaluations over time did not differ significantly between the treatment groups. CONCLUSIONS: Radiotherapy results in a modest improvement in survival, without reducing the quality of life or cognition, in elderly patients with glioblastoma. (ClinicalTrials.gov number, NCT00430911 [ClinicalTrials.gov].).


Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/mortalidade , Astrocitoma/radioterapia , Astrocitoma/terapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Cognição/efeitos da radiação , Feminino , Glioblastoma/mortalidade , Glioblastoma/terapia , Humanos , Masculino , Modelos de Riscos Proporcionais , Qualidade de Vida , Dosagem Radioterapêutica , Análise de Sobrevida
16.
J Neurooncol ; 76(2): 201-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16200347

RESUMO

Gliomatosis cerebri (GC) is a rare disease, defined as a diffuse neoplastic glial cell infiltration of the brain. Diagnosis and management of GC are difficult. This study analyzed 296 individual cases (90 patients followed through the ANOCEF network, and 206 cases from the literature), aged 1 month to 85 years (median 42), sex ratio=1.31. Median survival was 14.5 months. It was higher for patients younger than 42 years (17 months vs. 13 months), with performance status>or=80 (27 months vs. 9 months), low grade gliomatosis (grade 2=20 months, grade 3=11.5 months, grade 4=8.5 months), oligodendroglial subtype (36 months compared to 14 months for mixed GC and 11 months for astrocytic GC). Male population was younger (median 39 years vs. 45), had a higher incidence of oligodendroglial GC (22% vs. 13%), which may explain their better prognosis (median survival 17 months vs. 11.5 months) than female population. Despite a high rate of stabilization, the impact on survival of whole brain radiotherapy, which carries the risk of severe toxicity, is still unclear. Up-front chemotherapy benefit to some patients and may be preferred to whole brain radiotherapy. However, the many bias of such retrospective heterogeneous data claim for multicentric clinical trials in this rare disease.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Neuroepiteliomatosas/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Terapia Combinada , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Lactente , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/epidemiologia , Neoplasias Neuroepiteliomatosas/terapia , Prognóstico , Sistema de Registros , Fatores Sexuais , Análise de Sobrevida , Tomografia Computadorizada por Raios X
17.
Curr Opin Oncol ; 16(6): 614-20, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15627026

RESUMO

PURPOSE OF REVIEW: To describe specificities and new advances in paraneoplastic neurologic syndromes (PNSs). RECENT FINDINGS: Paraneoplastic neurologic syndromes are defined as neurologic syndromes of unknown cause that often antedate the diagnosis of an underlying, usually not clinically evident, cancer. In the last 2 decades, the discovery that many PNSs are associated with antibodies against neural antigens expressed by the tumor has suggested that some PNSs are immune-mediated. PNSs are rare and occur in less than 1% of patients with cancer. However, the diagnosis and treatment are important because the disability caused by the PNS is often severe, and the correct diagnosis usually leads to the discover of a small tumor with high chances of being cured. SUMMARY: There is increasing recognition of an extensive variety of PNSs and of several paraneoplastic antibodies as clinical markers of these disorders. Basic immunologic studies support the pathogenic role of some of these antibodies, and basic molecular studies support the role of some antigens in neuronal degeneration and tumoral growth.


Assuntos
Síndromes Paraneoplásicas do Sistema Nervoso/fisiopatologia , Humanos , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/terapia
18.
Medicine (Baltimore) ; 82(3): 216-23, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12792307

RESUMO

We conducted the current review of the paraneoplastic neurologic syndromes (PNSs) associated with gynecologic and breast carcinomas to describe their clinical and immunologic characteristics and their relative frequency. We retrospectively reviewed 92 patients whose serum was sent to our laboratories to detect onconeural antibodies and who were diagnosed as having PNSs associated with breast or gynecologic tumors. PNSs were defined as "definitive" and "possible" (atypical PNS, no onconeural antibodies, and no improvement after tumor treatment). Forty-nine patients had breast and 43 had gynecologic cancer. Sixty-three patients had onconeural antibodies (50 Yo-ab, 5 Hu-ab, 5 Ri-ab, and 3 amphiphysin-ab). Cerebellar ataxia represented 57 (62%) of all PNSs and was associated with anti-Yo in 88%. All Yo-abnegative patients had breast cancer; 4 of them had a mild cerebellar syndrome that improved after tumor treatment. Sensorypredominant neuropathies were present in 17 (18%) patients. Seven of them had Hu-ab (5) or amphiphysin-ab (2). Other PNSs were opsoclonus-myoclonus syndrome (4 cases, Ri-ab in 2), sensorimotor neuropathy (4 cases), paraneoplastic encephalomyelitis (4 cases, Ri-ab in 3), paraneoplastic retinopathy (2 cases), amyotrophic lateral sclerosis (2 cases), stiff-person syndrome (1 with amphiphysin-ab), and limbic encephalitis (1 case). All patients with gynecologic cancer presented definitive PNS, and onconeural antibodies were diagnosed in 93% of them. In contrast, 20% of PNSs associated with breast cancer were defined as possible and the incidence of onconeural antibodies was 51%, excluding the 2 patients with paraneoplastic retinopathy in whom antiretinal antibodies were not analyzed. In patients with possible PNS, a coincidental association between the tumor and the neurologic disorder cannot be excluded.


Assuntos
Neoplasias da Mama/complicações , Neoplasias dos Genitais Femininos/complicações , Polineuropatia Paraneoplásica/complicações , Idoso , Anticorpos Antineoplásicos/imunologia , Antígenos de Neoplasias/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Polineuropatia Paraneoplásica/imunologia , Estudos Retrospectivos
19.
Curr Neurol Neurosci Rep ; 3(3): 223-8, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12691627

RESUMO

Oligodendrogliomas have been the focus of considerable interest over the past decade, ever since they were recognized as chemosensitive tumors. They were once believed to represent less than 5% of gliomas, but by using expanded criteria, they may well represent up to one third. In fact, morphologic criteria are vague and highly subjective and the histologic diagnosis, therefore, remains highly controversial and unsatisfactory. New oligodendrocytic lineage markers, such as OLIG1/2 gene, will probably help to define the real spectrum of oligodendroglial tumors, which may include a wide variety of tumors with very different prognoses. Recently, genetic markers, and particularly loss of 1p and 19q chromosomes, have been shown to predict both prognosis and response to treatment. There is little doubt that these emerging techniques will be very helpful in clinical practice for refining both classification and therapeutic indications of oligodendroglial tumors.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica/genética , Oligodendroglioma/genética , Animais , Biomarcadores Tumorais/análise , Pesquisa Biomédica , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/terapia , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 19 , Humanos , Perda de Heterozigosidade/genética , Oligodendroglioma/classificação , Oligodendroglioma/terapia
20.
Rev Prat ; 53(19): 2147-52, 2003 Dec 15.
Artigo em Francês | MEDLINE | ID: mdl-15008471

RESUMO

Neurological complications of cancer are common, and some of them are true emergency. Rapid diagnosis and treatment can preserve neurologic functions and sometimes save a life. Raised intracranial pressure, epilepsy, spinal cord compression, cerebral vascular complication and infectious meningitis are the most common neurologic emergencies in cancer patient.


Assuntos
Neoplasias/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/terapia , Epilepsia/etiologia , Epilepsia/terapia , Humanos , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/terapia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/terapia
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