RESUMO
OBJECT: Adult brainstem gliomas are a rare group of heterogeneous brain tumors. Classical clinical presentation includes progressive impairment of cranial nerves associated with long tract signs. The prognosis and response to treatment are poor; nevertheless, some patients do have a long survival. The objective of this study was to describe a series of patients with an isolated persistent hemifacial spasm and/or facial nerve palsy as the presenting symptom of a brainstem glioma. METHODS: Fourteen patients from 3 French hospitals (Paris, Caen, Lille) were included. Clinical and radiological features and overall survival were retrospectively analyzed. A review of the literature of similar cases was performed. RESULTS: Mean age at diagnosis was 35 years (range 19-57 years). Mean duration of facial nerve involvement before diagnosis was 17 months (range 1-48 months). Tumors were characterized on MRI by a lateralized location in the pons, a T1-weighted hyposignal, a T2-weighted hypersignal and no contrast enhancement after Gadolinium injection except for 2 cases. Biopsies were performed in 10 cases and showed 8 low-grade and 2 high-grade gliomas. All the patients were initially treated with radiotherapy and 6 patients with chemotherapy after progression. Eleven patients died from tumor progression. Median survival time was 90 months. CONCLUSIONS: Adult brainstem gliomas revealed by a progressive isolated involvement of the facial nerve seem to have particular clinico-radiological features of slow progressive tumors and may be associated with long patient survival.
Assuntos
Glioma , Espasmo Hemifacial , Adulto , Nervo Facial , Glioma/diagnóstico , Glioma/diagnóstico por imagem , Espasmo Hemifacial/diagnóstico por imagem , Espasmo Hemifacial/etiologia , Humanos , Pessoa de Meia-Idade , Paralisia , Ponte , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE/BACKGROUND: Posterior fossa (PF) recurrences of supratentorial (ST) World Health Organization (WHO) grade II and III gliomas are thought to be rare and to have grim prognoses. METHODS: This study entailed searching through our database and reviewing the records of patients with grade II and III ST gliomas who developed PF recurrence with no overt secondary gliomatosis or leptomeningeal spread. RESULTS: Of 2266 grade II and III gliomas, 14 fulfilled the inclusion criteria: 5 oligodendrogliomas (O; 1 OII, 4 OIII); 7 astrocytomas (A; 4 AII, 3 AIII); and 2 oligoastrocytomas (OA; both OAIII). The male/female gender ratio was 10/4, and median age at recurrence was 43 years. Two groups were identified. In one group (n=8; 1 AII, 3 AIII, 2 OAIII, 2 OIII), a rapidly growing contrast-enhancing PF mass (6/8) was associated with ST progression, and median survival time after detection was only 6.5 months despite radiotherapy and/or chemotherapy. In the second group (n=6; 3 AII, 1 OII, and 2 OIII), a non-contrast-enhancing (5/6), asymptomatic (5/6), slow-growing PF mass remained isolated, and treatment with radio- or chemotherapy produced objective responses in three patients and durable stabilization in the remaining three. After a median follow-up of 63months, only one patient died due to delayed recurrence of the ST lesion, while the remaining five patients are still alive. CONCLUSION: Non-contiguous PF relapses of ST grade II and III gliomas are rare. A high-grade ST tumor that is concomitantly progressing appears to be a predictor of poor survival. Conversely, the tumor course may be indolent if the ST lesion is low-grade and non-progressive at the time of PF involvement. The possible mechanism(s) behind this tropism are also discussed.
Assuntos
Glioma/patologia , Neoplasias Infratentoriais/secundário , Neoplasias Supratentoriais/patologia , Adulto , Feminino , Glioma/diagnóstico , Glioma/mortalidade , Glioma/terapia , Humanos , Neoplasias Infratentoriais/diagnóstico , Neoplasias Infratentoriais/mortalidade , Neoplasias Infratentoriais/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Neoplasias Supratentoriais/diagnóstico , Neoplasias Supratentoriais/mortalidade , Neoplasias Supratentoriais/terapia , Análise de Sobrevida , Organização Mundial da Saúde , Adulto JovemRESUMO
Although upfront temozolomide (TMZ) has been widely-used to treat 1p/19q-codeleted diffuse low-grade gliomas (LGG), its long-term impact on the growth kinetics of these tumors has not been determined. Based on serial magnetic resonance images we retrospectively evaluated the evolution of the mean tumor diameter (MTD) in 36 progressive 1p/19q-codeleted LGG treated with upfront TMZ. After TMZ onset, all but two patients (94.4%) presented a progressive MTD decrease that lasted for a median duration of 23 months (range 3-114). In 10 patients (27%) MTD regrowth occurred during TMZ treatment and in 22 patients (66%) after TMZ discontinuation. In these patients, median time to MTD regrowth after TMZ discontinuation was 12 months (range 1-88). The rate of MTD regrowth at 3 and 5 years after TMZ onset was 77 and 94%, respectively. Time to tumor progression (TTP) based on volumetric analysis was shorter than TTP based on Response Assessment in Neuro-Oncology (RANO) bidimensional criteria (23 vs. 35 months, p = 0.05) and shorter than time to next oncological treatment (23 vs. 46 months, p = 0.001). In 10 patients (27%), absence of volumetric analysis led to continue TMZ for a median of 10 cycles after MTD had started to regrow. Volumetric analysis is important to precisely assess chemotherapy efficacy in 1p/19q-codeleted LGG, identify early tumor progression and avoid futile chemotherapy continuation. In the present series, although some long-lasting volumetric responses were observed, most tumors resumed their growth within 3 years after TMZ onset.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Glioma/tratamento farmacológico , Glioma/genética , Temozolomida/uso terapêutico , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Deleção Cromossômica , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 19 , Progressão da Doença , Feminino , Glioma/diagnóstico por imagem , Glioma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare complication of cerebral radiation therapy that usually presents>10 years after treatment as reversible paroxysmal episodes of neurological dysfunction associated with headaches. CASES: We report here on two cases of SMART syndrome in long-term survivors of high-grade glioma for whom neuropathological data were available. The course of the disease was unfavorable. Although the clinico-radiological picture of SMART syndrome clearly differs from classic cerebral radionecrosis, the gross neuropathological lesions observed in our two patients appeared to be similar to those described in focal radionecrosis. CONCLUSION: SMART syndrome may progress from a benign reversible form to a severe and eventually irreversible form. This severe course may also be confused with tumor progression, and lead to permanent disability and inadequate antitumor treatment. Clinicians should be aware of this latter atypical presentation.
Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Cefaleia/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Lesões por Radiação/complicações , Acidente Vascular Cerebral/etiologia , Adulto , Evolução Fatal , Feminino , Cefaleia/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Acidente Vascular Cerebral/diagnósticoAssuntos
Neurologia/organização & administração , Sociedades Científicas/organização & administração , História do Século XXI , Humanos , Oncologia/organização & administração , Oncologia/tendências , Neurologia/normas , Neurologia/tendências , Psicologia/organização & administração , Psicologia/normas , Psicologia/tendências , Sociedades Científicas/normas , Recursos HumanosRESUMO
Both molecular profiling of tumors and longitudinal tumor size data modeling are relevant strategies to predict cancer patients' response to treatment. Herein we propose a model of tumor growth inhibition integrating a tumor's genetic characteristics (p53 mutation and 1p/19q codeletion) that successfully describes the time course of tumor size in patients with low-grade gliomas treated with first-line temozolomide chemotherapy. The model captures potential tumor progression under chemotherapy by accounting for the emergence of tissue resistance to treatment following prolonged exposure to temozolomide. Using information on individual tumors' genetic characteristics, in addition to early tumor size measurements, the model was able to predict the duration and magnitude of response, especially in those patients in whom repeated assessment of tumor response was obtained during the first 3 months of treatment. Combining longitudinal tumor size quantitative modeling with a tumor''s genetic characterization appears as a promising strategy to personalize treatments in patients with low-grade gliomas.
Assuntos
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
BACKGROUND: The role of telomerase reverse transcriptase (TERT) in gliomagenesis has been recently further strengthened by the frequent occurrence of TERT promoter mutations (TERTp-mut) in gliomas and evidence that the TERT SNP genetic rs2736100 influences glioma risk. TERTp-mut creates a binding site for Ets/TCF transcription factors, whereas the common rs2853669 polymorphism disrupts another Ets/TCF site on TERT promoter. METHODS: We sequenced for TERTp-mut in 807 glioma DNAs and in 235 blood DNAs and analysed TERT expression by RT-PCR in 151 samples. TERTp-mut status and TERTp polymorphism rs2853669 were correlated with histology, genomic profile, TERT mRNA expression, clinical outcome and rs2736100 genotype. RESULTS: TERTp-mut identified in 60.8% of gliomas (491 out of 807) was globally associated with poorer outcome (Hazard ratio (HR)=1.50). We defined, based on TERTp-mut and IDH mutation status, four prognostic groups: (1) TERTp-mut and IDH-mut associated with 1p19q codeletion, overall survival (OS)>17 years; (2) TERTp-wt and IDH-mut, associated with TP53 mutation, OS=97.5 months; (3) TERTp-wt and IDH-wt, with no specific association, OS=31.6 months; (4) TERTp-mut and IDH-wt, associated with EGFR amplification, OS=15.4 months. TERTp-mut was associated with higher TERT mRNA expression, whereas the rs2853669 variant was associated with lower TERT mRNA expression. The mutation of CIC (a repressor of ETV1-5 belonging to the Ets/TCF family) was also associated with TERT mRNA upregulation. CONCLUSIONS: In addition to IDH mutation status, defining the TERTp-mut status of glial tumours should afford enhanced prognostic stratification of patients with glioma. We also show that TERTp-mut, rs2853669 variant and CIC mutation influence Tert expression. This effect could be mediated by Ets/TCF transcription factors.
Assuntos
Biomarcadores Tumorais/genética , Glioma/genética , Glioma/patologia , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Telomerase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Glioma/mortalidade , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Reação em Cadeia da Polimerase , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: To describe the characteristics of patients presenting a paraneoplastic cerebellar degeneration without classical onconeural antibodies (seronegative PCD). METHODS: Thirty-nine seronegative PCD patients from the Paraneoplastic Neurological Syndrome Euronetwork were retrospectively analyzed and compared with 180 patients with PCD associated with classical onconeural antibodies (seropositive PCD). RESULTS: No patient had anti-CASPR2 or anti-mGluR1 antibodies. No significant difference between the clinical characteristics of seronegative and seropositive PCD patients was observed. Yet the frequency of associated tumors was different. Lymphoma was more frequent in seronegative than in seropositive women (24% vs. 2%, P = 0.002) whilst gynecological cancer were less frequent (38% vs. 74%, P = 0.002). In comparison with seropositive men, seronegative men more frequently had a non-small-cell lung cancer (27% vs. 6%, P = 0.08) or a genitourinary cancer (22% vs. 0%, P = 0.04) but less frequently a small-cell lung cancer (23% vs. 74%, P = 0.002). Seronegative and seropositive PCD patients with similar tumors had a similar overall survival. CONCLUSION: The clinical characteristics of seronegative and seropositive PCD are similar but the spectrum of associated tumors is different. The immunological scenario of seronegative PCD seems to be different from that of limbic encephalitis with only few patients harboring anti-neuropile antibodies.
Assuntos
Anticorpos/sangue , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Degeneração Paraneoplásica Cerebelar/sangue , Degeneração Paraneoplásica Cerebelar/imunologia , Receptores de AMPA/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente)/epidemiologia , Feminino , Humanos , Linfoma/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Adulto JovemRESUMO
Gliomas represent the most frequent form of primary brain tumors in adults, the prognosis of which remains extremely poor. Inactivating mutations on the tumor suppressor TP53 were proposed as a key etiological trigger of glioma development. p53 has been recently identified as a transcriptional target of parkin. Interestingly, somatic mutations on parkin have also been linked to glioma genesis. We examined the possibility that a disruption of a functional interaction between p53 and parkin could contribute to glioma development in samples devoid of somatic parkin mutations or genetic allele deletion. We show here that parkin levels inversely correlate to brain tumor grade and p53 levels in oligodendrogliomas, mixed gliomas and glioblastomas. We demonstrate that p53 levels negatively and positively correlate to bax and Bcl2 respectively, underlying a loss of p53 transcriptional activity in all types of glial tumors. Using various cell models lacking p53 or harboring either transcriptionally inactive or dominant negative p53, as well as in p53 knockout mice brain, we establish that p53 controls parkin promoter transactivation, mRNA and protein levels. Furthermore, we document an increase of parkin expression in mice brain after p53-bearing viral infection. Finally, both cancer-related p53 inactivating mutations and deletion of a consensus p53 binding sequence located on parkin promoter abolish p53-mediated control of parkin transcription, demonstrating that p53 regulates parkin transcription via its DNA binding properties. In conclusion, our work delineates a functional interplay between mutated p53 and parkin in glioma genesis that is disrupted by cancer-linked pathogenic mutations. It also allows envisioning parkin as a novel biomarker of glioma biopsies enabling to follow the progression of this type of cancers.
Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias/metabolismo , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/fisiologia , Alelos , Animais , Sítios de Ligação , Encéfalo/metabolismo , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Análise Mutacional de DNA , Feminino , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Camundongos , Mutação , Neoplasias/genética , Oligodendroglioma/genética , Oligodendroglioma/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ativação Transcricional , Proteína X Associada a bcl-2/metabolismoRESUMO
High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy.
Assuntos
Encéfalo/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade , Procedimentos Neurocirúrgicos , Crânio/cirurgia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Humanos , Cirurgia Assistida por Computador/métodosRESUMO
INTRODUCTION: Nutritional status is a major clinical parameter in multiple cancers. Indeed, nutritional status is a prognostic factor and a predictor of response and toxicity to treatments in breast and lung cancers for instance. To our knowledge, in patients suffering from malignant primary brain tumors, nutritional status has been poorly investigated. METHODS: Nutritional status of 26 glioblastoma patients relapsing after a first line of treatment was studied. The body mass index (BMI), the prognostic inflammatory and nutritional index (PINI) and the instant nutritional score (INS) were assessed. RESULTS: The BMI was abnormal in 12 patients, two were malnourished while 10 were overweight. The BMI was not correlated to age of patients. Overweight status did not impact patient survival but it was associated with reduced performance status. The PINI was abnormal in three patients. Finally, the INS was abnormal in 24 patients, noted 2 (n=22) or 4 (n=4). CONCLUSIONS/DISCUSSION: Our results were not in favor of systematic nutritional support in patients with recurrent glioblastoma after a first line of treatment. Being overweight does not influence prognosis but may influence performance status. Steroid therapy and chemotherapy (inducing sodium and water retention and lymphopenia) weaken the relevance of BMI and INS for nutritional assessment in patients with recurrent glioblastoma. Further studies using additional nutritional tests in larger, independent and prospective cohorts of patients are warranted to obtain more details.
Assuntos
Neoplasias Encefálicas/fisiopatologia , Glioblastoma/fisiopatologia , Recidiva Local de Neoplasia/fisiopatologia , Estado Nutricional/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/cirurgia , Estudos de Coortes , Terapia Combinada , Progressão da Doença , Feminino , Glioblastoma/epidemiologia , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Distúrbios Nutricionais/epidemiologiaRESUMO
BACKGROUND: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma. METHODS: To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls. RESULTS: The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10(-24), minor allele frequency ~0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown. CONCLUSION: Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3'-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma.
Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Penetrância , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Neoplasias Encefálicas/epidemiologia , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Glioma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/fisiologia , Processamento de Terminações 3' de RNA/genética , Proteína Supressora de Tumor p53/fisiologia , Estados Unidos/epidemiologiaRESUMO
Isolated case reports suggest that breast tumors from patients with paraneoplastic cerebellar degeneration (PCD) and Yo antibodies overexpress human epidermal growth factor receptor 2 (HER2). HER2 overexpression is present in 15%-25% of breast cancers and is associated with poor prognosis. We retrospectively analyzed the status of HER2 in breast tumors of 27 patients with anti-Yo-associated PCD to evaluate whether HER2 overexpression in this group of patients is higher than expected. In addition, we analyzed HER2 status of 19 breast tumors from patients with paraneoplastic neurological syndromes and Ri antibodies to see whether HER2 was specifically related to anti-Yo-associated PCD. We also assessed cdr2 expression (the onconeural antigen recognized by Yo antibodies) in 21 HER2-positive breast tumors from patients without paraneoplastic neurological syndromes. HER2 was overexpressed in 26 patients (96.3%) with anti-Yo-associated PCD but only in 2 patients (10.5%) with paraneoplastic neurological syndromes associated with Ri antibodies (P< .0001). Only 5 (23.8%) of the 21 HER2-positive breast tumors showed cdr2 immunoreactivity. This study shows a very high frequency of HER2 overexpression in breast cancers in patients with anti-Yo-associated PCD but not in those from patients with Ri antibodies. Although the expression of cdr2 onconeural antigen is not high in HER2-positive breast cancers, HER2 overexpression seems to be an important requirement to develop an anti-Yo-associated PCD.
Assuntos
Neoplasias da Mama/metabolismo , Degeneração Paraneoplásica Cerebelar/metabolismo , Receptor ErbB-2/metabolismo , Adulto , Idoso , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/metabolismo , Antígeno Neuro-Oncológico Ventral , Degeneração Paraneoplásica Cerebelar/genética , Degeneração Paraneoplásica Cerebelar/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/genética , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/metabolismo , Proteínas de Ligação a RNA/imunologia , Receptor ErbB-2/genética , Estudos RetrospectivosRESUMO
The incidence of malignant gliomas in the aging population of industrialized countries is increasing. This observation justifies an important ongoing clinical research effort specifically dedicated to this population. The first results of prospective studies have showed the interest of radiotherapy and chemotherapy with temozolomide. The effect of combined concomitant and adjuvant chemotherapy with radiotherapy is currently being evaluated in a phase III study. The likely beneficial effect of surgical resection needs to be formally demonstrated in this fragile population. Initial functional status, quality of life and concomitant systemic pathologies are important factors to tailor the treatment according to patients status.
Assuntos
Idoso/estatística & dados numéricos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Glioblastoma/epidemiologia , Glioblastoma/terapia , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Quimiorradioterapia Adjuvante , Terapia Combinada , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Países Desenvolvidos , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , TemozolomidaRESUMO
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
OBJECTIVES: Recent studies have shown that IDH1 and IDH2 mutations occur frequently in gliomas, including low-grade gliomas. However, their impact on the prognosis and chemosensitivity of low-grade gliomas remains unclear. METHODS: Search for IDH1 and IDH2 mutations, loss of heterozygosity on chromosomes 1p and 19q, MGMT promoter methylation, and p53 expression was performed in a series of 271 low-grade gliomas and correlated with overall survival. A subgroup of 84 patients treated up-front with temozolomide was individualized. Response to temozolomide was evaluated by progression-free survival, as well as by tumor size on successive MRI scans, and then correlated with molecular alterations. RESULTS: IDH (IDH1 or IDH2) mutations were found in 132/189 patients (70%). IDH mutation and 1p-19q codeletion were associated with prolonged overall survival in univariate (p = 0.002 and p = 0.0001) and multivariate analysis (p = 0.003 and p = 0.004). 1p-19q codeletion, MGMT promoter methylation, and IDH mutation (p = 0.01) were correlated with a higher rate of response to temozolomide. Further analysis of the course of the disease prior to any treatment except for surgery (untreated subgroup) showed that 1p-19q codeletion was associated with prolonged progression-free survival in univariate analysis, whereas IDH mutation was not. CONCLUSION: IDH mutation appears to be a significant marker of positive prognosis and chemosensitivity in low-grade gliomas, independently of 1p-19q codeletion, whereas its impact on the course of untreated tumors seems to be limited.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas , Dacarbazina/análogos & derivados , Glioma , Isocitrato Desidrogenase/genética , Mutação/genética , Farmacogenética , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Distribuição de Qui-Quadrado , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Análise Mutacional de DNA , Enzimas Reparadoras do DNA/genética , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Feminino , Glioma/tratamento farmacológico , Glioma/genética , Glioma/mortalidade , Humanos , Perda de Heterozigosidade/genética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Estatística como Assunto , Temozolomida , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
BACKGROUND: Recently, the gene encoding the human cytosolic NADPH-dependent isocitrate dehydrogenase (IDH1) was reported frequently mutated in gliomas. Rare mutations were also found in the sequence of the mitochondrial isoform IDH2. METHODS: In a series of 764 gliomas genome-wide characterized, we determined the presence of mutations in the sequences of both IDH1 and IDH2 genes by direct sequencing. RESULTS: We found that all tumors with complete 1p19q codeletion (n = 128) were mutated in the IDH1 (118) or IDH2 (10) gene. This 100% mutation rate contrasted strikingly with other gliomas exhibiting either variable 1p and 19q alterations (n = 159, IDH1/IDH2 mutation rate of 33%) or no 1p19q alteration (n = 477, IDH1/IDH2 mutation rate 32%). Our data also confirm the prognostic impact of IDH1/IDH2 mutation in gliomas whatever grade considered: patients harboring mutations of IDH1/IDH2 have an improved median overall survival. Moreover, in WHO grade II and III gliomas, 3 groups with significantly different outcomes were identified according to their 1p19q and IDH1/IDH2 statuses. Tumors carrying both alterations had longer overall survival than their nonmutated counterpart. CONCLUSIONS: This exclusive association suggests a new mechanism of tumorigenesis. Perhaps the IDH1/IDH2 mutation is a prerequisite for the occurrence of the t(1;19) translocation, or it is required for the 1p19q codeleted cells to acquire a tumor phenotype.
Assuntos
Neoplasias Encefálicas/genética , Cromossomos Humanos Par 1/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Mutação/genética , Neoplasias Encefálicas/mortalidade , Seguimentos , Estudo de Associação Genômica Ampla/métodos , Glioma/mortalidade , Humanos , Análise de SobrevidaRESUMO
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.