RESUMO
BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Adulto , Humanos , Idoso , Glioblastoma/terapia , Glioblastoma/tratamento farmacológico , Temozolomida/uso terapêutico , Dacarbazina/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Estudos Retrospectivos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , PrognósticoRESUMO
BACKGROUND: In glioma, TERT promoter mutation and loss of ATRX (ATRX loss) are associated with reactivation of telomerase or alternative lengthening of telomeres (ALT), respectively, i.e. the two telomere maintenance mechanisms (TMM). Strangely, 25% of gliomas have been reported to display neither or both of these alterations. MATERIALS AND METHODS: The C-circle (CC) assay was adapted to tumor (formalin-fixed paraffin-embedded and frozen) and blood samples to investigate the TMM. RESULTS: We constructed a CC-based algorithm able to identify the TMM and reported a sensitivity of 100% and a specificity of 97.3% (n = 284 gliomas). By combining the TMM, the mutational status of the isocitrate dehydrogenase 1/2 (IDH) gene (IDHmt), and the histological grading, we propose a new classification tool: TeloDIAG. This classification defined five subtypes: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low-grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma (GBM), respectively; the last class gathers ALT+ IDHwt gliomas that tend to be related to longer survival (21.2 months) than tGBM (16.5 months). The TeloDIAG was 99% concordant with the World Health Organization classification (n = 312), and further modified the classification of 55 of 144 (38%) gliomas with atypical molecular characteristics. As an example, 14 of 69 (20%) of TERTwt, ATRXwt, and IDHwt GBM were actually tAIV. Outstandingly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 97% (n = 206 gliomas and 30 healthy donors). CONCLUSION: The TeloDIAG is a new, simple, and effective tool helping in glioma diagnosis and a promising option for liquid biopsy.
Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Biópsia Líquida , Telômero/genética , Proteína Nuclear Ligada ao X/genéticaAssuntos
Neoplasias do Sistema Nervoso/patologia , Oligodendroglioma/patologia , Biomarcadores Tumorais , França/epidemiologia , Deleção de Genes , Humanos , Neoplasias do Sistema Nervoso/epidemiologia , Neoplasias do Sistema Nervoso/genética , Oligodendroglioma/epidemiologia , Oligodendroglioma/genéticaRESUMO
OBJECTIVE: The combination of irinotecan-bevacizumab is effective in patients with glioblastoma relapse but fatigue is a commonly reported side effect. The objective of this study was to evaluate the level and evolution of fatigue in a series of patients treated with therapeutic combination. PATIENTS AND METHODS: We used two self-evaluation tools to quantify the physical and emotional aspects of this fatigue. The Norris Visual Analog Scale (VAS Norris) and the Multidimensional Fatigue Inventory-20 (MFI) tools were undertaken by 39 patients with glioblastoma relapse treated with irinotecan-bevacizumab, initially before the first cycle and thereafter with each cycle up until tumor progression. RESULTS: Analysis of the results of the VAS Norris scale did not demonstrate an increase in emotional fatigue but did show an increase in physical fatigue that did not reach statistical significance. With regards to the MFI 20 tool, analysis of the results demonstrated a significant increase in general (P=0.0260) as well as physical (P=0.0141) fatigue but there was no difference in the other indices. CONCLUSION: This study demonstrated a progressive increase in physical fatigue in patients with glioblastoma relapse treated with irinotecan-bevacizumab. We suspect that this is as a direct consequence of the treatment. There are however other confounding factors: insidious tumour progression not detected on follow-up imaging or delayed side effects of the initial radiotherapy-chemotherapy.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Camptotecina/análogos & derivados , Fadiga/diagnóstico , Glioblastoma/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Autoavaliação Diagnóstica , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Glioblastoma/epidemiologia , Glioblastoma/patologia , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Recidiva , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Low-grade gliomas (LGG) are thought to be very rare in elderly patients (>60 years) and have not been thoroughly studied. METHODS: A series of 62 elderly (>or=60 years of age) LGG patients were identified in a department database collecting information on pathologically identified adult supratentorial LGG. The clinical, radiologic, pathologic, and therapeutic data of these patients were analyzed and compared to those of 704 younger LGG patients (<60 years). RESULTS: Comparisons between older and younger groups showed that elderly patients more often presented with a clinical deficit (p < 0.0001), a lower Karnofsky performance status (p = 0.0002), a larger tumor on MRI (p = 0.03), and a lower rate of tumor resection (p < 0.0001). Chemotherapy was more often used as first line treatment (p = 0.001). Among the patients who died of progressive disease, 55% of the elderly patients had not received radiotherapy compared to 11% in the younger group (p < 0.0001). Survival was shorter in older patients (p < 0.0001), with a 5-year survival rate of 40%. An astrocytic phenotype (p = 0.0097), increasing age (p = 0.0049), and a tumor crossing the midline (p = 0.028) were negative prognostic factors in the older group. CONCLUSION: We found that 8% of low-grade gliomas (LGG) occur in older patients (>or=60 years of age). The clinical-radiologic picture of LGG in the elderly population differs from younger patients. Although long-term survival occurs, the course is generally more severe because elderly patients accumulate negative prognostic factors and because they are probably undertreated.
Assuntos
Glioma/fisiopatologia , Glioma/terapia , Neoplasias Supratentoriais/fisiopatologia , Neoplasias Supratentoriais/terapia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Glioma/diagnóstico , Glioma/epidemiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Prognóstico , Radioterapia/estatística & dados numéricos , Índice de Gravidade de Doença , Neoplasias Supratentoriais/diagnóstico , Neoplasias Supratentoriais/epidemiologia , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Treatment with a regimen of bevacizumab-irinotecan has been shown to be effective in recurrent grade 3 and 4 gliomas, but the effect of this regimen against recurrent oligodendroglial tumors has not been specifically studied. METHODS: The bevacizumab-irinotecan regimen was retrospectively evaluated in a consecutive series of 25 patients with recurrent oligodendroglial tumors. All patients had not responded to previous treatment with radiation therapy and at least one line of temozolomide chemotherapy. Bevacizumab (10 mg/kg) and irinotecan (125 or 340 mg/m(2) according to the antiepileptic regimen) were administered every 14 days. Response was measured clinically and on monthly MRI. RESULTS: The objective response rate was 72% (20% complete response, 52% partial response). After a median follow up of 202 days, the median progression-free survival was 140 days (95% confidence interval [CI] 116-infinity), and overall survival had not been reached. The 6-month progression-free survival was 42% (95% CI 26%-67%). Among the 17 patients in whom the status of the main molecular alterations of gliomas could be evaluated (search for deletions of chromosomes 1p, 19q, 9p, and 10q and amplification of epidermal growth factor receptor, mouse double-minute gene, and cyclin-dependent kinase 4 gene), no relation could be found between the response rate and the type of genetic change (including 1p-19q codeletion). The profile of tolerance was fair, with treatment discontinuation in 20% of patients. Intratumoral hemorrhages occurred in 6 patients (24%), but the treatment had to be discontinued because of symptomatic bleeding in only 1 patient (4%). CONCLUSIONS: This regimen is effective in recurrent oligodendrogliomas, and the overall tolerance is acceptable.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Camptotecina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Oligodendroglioma/tratamento farmacológico , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Bevacizumab , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Hemorragia Cerebral/epidemiologia , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença/genética , Testes Genéticos , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Oligodendroglioma/patologia , Oligodendroglioma/fisiopatologia , Cooperação do Paciente , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Despite recent and significant progress, the prognosis of glioblastoma remains extremely poor. Concomitant chemoradiotherapy with temozolomide is now the standard of care for newly diagnosed glioblastoma. This treatment is well-tolerated and results in improvement of overall survival and dramatic increase of long term survivor rate, especially in good performance status patients. Besides, this benefit is particularly marked in patients with MGMT (methylguanine methyltransferase) methylated tumor, suggesting a growing place of molecular markers in pattern of care of such patients. At recurrence, the combination of bevacizumab (anti-VEGF) with irinotecan has shown surprising high response rates in a phase II trial for recurrent malignant gliomas. Many other targeted therapies are currently under investigation, alone or in association, at recurrence or up-front and during radiotherapy. For this reason, in the future a more precise understanding of gliomagenesis is needed for a better molecular stratification of patients.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos Alquilantes/uso terapêutico , Bevacizumab , Neoplasias Encefálicas/irrigação sanguínea , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Terapia Combinada/métodos , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Glioblastoma/irrigação sanguínea , Humanos , Irinotecano , Neovascularização Patológica/tratamento farmacológico , Temozolomida , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
BACKGROUND: alpha-Internexin (INA) is a proneural gene encoding a neurofilament interacting protein that is upregulated in some gliomas, particularly oligodendrogliomas. METHODS: INA expression was evaluated by immunohistochemistry in a series of 122 gliomas, and correlated to the 1p19q codeletion, a favorable prognostic marker of oligodendroglial tumors. RESULTS: INA expression was strong (>10% positive cells) in 22 cases (22 oligodendroglial tumors and 0 astrocytic tumors), weak (<10% cells) in 14 cases (12 oligodendroglial tumors, 2 glioblastoma with an oligodendroglial component, and 0 astrocytic tumors), and negative in 86 cases (49 oligodendroglial tumors, 9 glioblastoma with an oligodendroglial component, and 28 astrocytic tumors). Among the 27 tumors exhibiting the 1p19q codeletion (all with an oligodendroglial phenotype), INA was detected in 96% (26/27, 18 strong, 8 weak) as compared to 11% (10/95, 4 strong, 6 weak) in the tumors without 1p19q codeletion (with an oligodendroglial or an astrocytic phenotype) (p < 0.001). In oligodendroglial tumors, INA expression specificity for 1p19q codeletion was 86%, sensitivity 96%, positive predictive value 76%, and negative predictive value was 98%. The prognostic impact of INA expression could be evaluated in grade III oligodendroglial tumors. Similar to 1p19q deletion, positive INA expression was correlated with better progression-free survival (52.6 vs 8.7 months [p = 0.001]) and overall survival (121.1 vs 31.4 months [p = 0.0001]). CONCLUSION: alpha-Internexin (INA) expression appears to be a simple, reliable prognostic marker and a surrogate marker of 1p19q codeletion.
Assuntos
Neoplasias Encefálicas/genética , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 1/genética , Predisposição Genética para Doença/genética , Glioma/genética , Proteínas de Filamentos Intermediários/genética , Neoplasias Encefálicas/diagnóstico , Análise Mutacional de DNA , Progressão da Doença , Deleção de Genes , Genes , Testes Genéticos , Genótipo , Glioma/diagnóstico , Humanos , Mutação/genética , Oligodendroglioma/diagnóstico , Oligodendroglioma/genética , Valor Preditivo dos Testes , PrognósticoRESUMO
The incidence of primary CNS lymphoma (PCNSL), which has considerably increased these last years, remains stable in the immunocompetent population, while it is steadily decreasing in the immunosuppressed population. The addition of high dose methotrexate (MTX) based chemotherapy (CT) before whole brain radiotherapy (WBRT) has clearly improved the prognosis of PCNSL with a median survival of three to four years. About 30% of the patients may hope to have a long survival and to be cured. In the elderly (age over 60 years) CT alone (without RT) is recommended as initial treatment. This approach seems useful to avoid RT and to reduce the risk of delayed neurotoxicity due to the combined treatment. In the young population (age less than 60 years), intensive chemotherapy followed by hematopoietic stem cell rescue (ICH) appears as a promising approach in recurrent tumors and potentially as an alternative option to RT as consolidation treatment in newly diagnosed patients. A prospective trial will be activated in France soon randomizing ICH and RT in the initial treatment of PCNSL.
Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Terapia Combinada , Humanos , Imunocompetência , Linfoma/tratamento farmacológico , Linfoma/radioterapia , PrognósticoRESUMO
We report the case of a patient presenting a sudden bilateral hearing loss. Four years before, a bladder carcinoma was resected and a chemotherapy was started. Gadolinium-enhanced magnetic resonance images revealed enhancement of both acoustic nerves. Cerebrospinal fluid analysis showed malignant cells consistent with the initial bladder cancer. Meningeal metastases from bladder carcinoma are extremely rare. Systemic chemotherapy and its low meningeal diffusion may enhance the incidence of this complication. Bilateral hearing loss is a rare initial manifestation of meningeal carcinomatosis.