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1.
Oncologist ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31346129

RESUMO

BACKGROUND: Astroblastoma (ABM) is a rare glial brain tumor. Recurrent meningioma 1 (MN1) alterations have been recently identified in most pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined. MATERIALS AND METHODS: We performed clinical and molecular characterization of a retrospective cohort of 14 adult and 1 adolescent ABM. RESULTS: Strikingly, we found that MN1 fusions are a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA)-like or high-grade glioma (HGG)-like. PXA-like ABM show BRAF mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific alterations of diffuse midline glioma (2/5) or glioblastoma (GBM; 3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival (p = .021). Mitogen-activated protein kinase pathway alterations (including FGFR fusion, BRAF and NF1 mutations) were present in 10 of 15 patients and overrepresented in the HGG-like group (3/5) compared with previously reported prevalence of these alterations in GBM and diffuse midline glioma. CONCLUSION: We suggest that gliomas with astroblastic features include a variety of molecularly sharply defined entities. Adult ABM harboring molecular features of PXA and HGG should be reclassified. Central nervous system high-grade neuroepithelial tumors with MN1 alterations and histology of ABM appear to be uncommon in adults. Astroblastic morphology in adults should thus prompt thorough molecular investigation aiming at a clear histomolecular diagnosis and identifying actionable drug targets, especially in the mitogen-activated protein kinase pathway. IMPLICATIONS FOR PRACTICE: Astroblastoma (ABM) remains a poorly defined and controversial entity. Although meningioma 1 alterations seem to define a large subset of pediatric cases, adult cases remain molecularly poorly defined. This comprehensive molecular characterization of 1 adolescent and 14 adult ABM revealed that adult ABM histology comprises several molecularly defined entities, which explains clinical diversity and identifies actionable targets. Namely, pleomorphic xanthoastrocytoma-like ABM cases show a favorable prognosis whereas high-grade glioma (glioblastoma and diffuse midline gliome)-like ABM show significantly worse clinical courses. These results call for in-depth molecular analysis of adult gliomas with astroblastic features for diagnostic and therapeutic purposes.

2.
J Clin Oncol ; 37(10): 823-833, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785830

RESUMO

PURPOSE: To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS: Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION: WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

3.
Br J Haematol ; 183(4): 608-617, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30421536

RESUMO

Neurodegenerative (ND) complications in Langerhans cell histiocytosis (LCH) are a late-onset but dramatic sequelae for which incidence and risk factors are not well defined. Based on a national prospective registry of paediatric LCH patients, we determined the incidence rate of clinical ND LCH (cND-LCH) and analysed risk factors, taking into account disease extent and molecular characteristics. Among 1897 LCH patients, 36 (1·9%) were diagnosed with a cND-LCH. The 10-year cumulative incidence of cND-LCH was 4·1%. cND-LCH typically affected patients previously treated for a multisystem, risk organ-negative LCH, represented in 69·4% of cND-LCH cases. Pituitary gland, skin and base skull/orbit bone lesions were more frequent (P < 0·001) in cND-LCH patients compared to those without cND-LCH (respectively 86·1% vs. 12·2%, 75·0% vs. 34·2%, and 63·9% vs. 28·4%). The 'cND susceptible patients' (n = 671) i.e., children who had experienced LCH disease with pituitary or skull base or orbit bone involvement, had a 10-year cND risk of 7·8% vs. 0% for patients who did not meet these criteria. Finally, BRAFV 600E status added important information among these cND susceptible patients, with the 10-year cND risk of 33·1% if a BRAFV 600E mutation was present compared to 2·9% if it was absent (P = 0·002).

4.
J Neurooncol ; 133(2): 315-320, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28432587

RESUMO

Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m2 D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m2 D1-2). Addition of rituximab (375 mg/m2 D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Citarabina/uso terapêutico , Feminino , Seguimentos , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Procarbazina/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
5.
Neuro Oncol ; 19(3): 422-429, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27994065

RESUMO

Background: Our aim was to review MRI characteristics of patients with primary CNS lymphoma (PCNSL) enrolled in a randomized phase II trial and to evaluate their potential prognostic value and patterns of relapse, including T2 fluid attenuated inversion recovery (FLAIR) MRI abnormalities. Methods: Neuroimaging findings in 85 patients with PCNSL enrolled in a prospective trial were reviewed blinded to outcomes. MRI characteristics and responses according to International PCNSL Collaborative Group (IPCG) criteria were correlated with progression-free survival (PFS) and overall survival (OS). Results: Multivariate analysis showed that objective response at 2 months (P < .001) and at end of treatment (P = .015) were predictors of prolonged OS. Infratentorial location (P = .008) and large (>11.4 cm3) enhancing tumor volume (P = .006) were associated with poor OS and PFS, respectively. Ratio of change in product of largest diameters at early MRI evaluation but not timing of complete response achievement (early vs delayed) was prognostic for OS. Sixty-nine patients relapsed. Relapse in the brain (n = 52) involved an initial enhancing site, a different site, or both in 46%, 40%, and 14% of patients, respectively. At baseline, non-enhancing T2-FLAIR hypersignal lesions distant from the enhancing tumor site were detected in 18 patients. These lesions markedly decreased (>50%) in 16 patients after chemotherapy, supporting their neoplastic nature. Of these patients, 10/18 relapsed, half (n = 5) in the initially non-enhancing T2-FLAIR lesions. Conclusions: Baseline tumor size and infratentorial localization are of prognostic value in PCNSL. Our findings provide evidence that non-enhancing FLAIR abnormalities may add to overall tumor burden, suggesting that response criteria should be refined to incorporate evaluation of T2-weighted/FLAIR sequences.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/patologia , Linfoma não Hodgkin/patologia , Imagem por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/metabolismo , Seguimentos , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
6.
Presse Med ; 46(1): 79-84, 2017 Jan.
Artigo em Francês | MEDLINE | ID: mdl-27816346

RESUMO

Langerhans cell histiocytosis (LCH) is a rare multisystemic disease. LCH is characterized by proliferation of myeloid progenitors with altered differentiation program and similar phenotypic features to epidermal dendritic cells termed Langerhans cell. LCH cells express CD1a+ and langerin and exhibit BRAF V600E mutation in ∼50% of cases. Neurological involvement or neuro-LCH is observed in 5 to 10% of cases. Three subtypes of neuro-LCH are individualized. The tumor type, accounting for 45% of neuro-LCH, affect mainly young adults. Tumor neuro-LCH is characterized by space occupying lesion(s) with contrast enhancement on MRI. Clinical symptoms are due to tumor brain location(s). Pathological examination of tumor neuro-LCH lesions reveals typical features of LCH. Treatment relies on surgical resection with/without chemotherapy. Degenerative neuro-LCH, accounting for 45% of cases, is usually revealed, mostly in children, by: (i) a cerebellar syndrome, (ii) a pyramidal syndrome, (iii) a pseubulbar palsy, and/or (iv) cognitive disorders. On MRI, several signs may coexist: (i) cortex atrophy, (ii) white matter T2 hyperintensities, and (iii) deep gray matter T1 hyperintensities. Pathological analysis of degenerative neuro-LCH lesions have been rarely performed and have never detected CD1a+ histiocytes but unspecific lesions (i.e. gliosis, neuronal loss and/or demyelination). Treatment of degenerative neuro-LCH patients is poorly standardized and poorly efficient. Functional rehabilitation and socio-educational care of these young patients are crucial. The mixed subtype of neuro-LCH combines clinico-radio-pathological characteristics of the first two first forms in the same patient, and represents 10% of neuro-HL. Neuro-HL, therefore, includes three very distinct entities with epidemiological, clinical, radiological and histological specific features requiring specific medical management.


Assuntos
Encefalopatias , Histiocitose de Células de Langerhans , Adulto , Idade de Início , Encefalopatias/epidemiologia , Encefalopatias/etiologia , Encefalopatias/patologia , Criança , Pré-Escolar , Histiocitose de Células de Langerhans/classificação , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/epidemiologia , Histiocitose de Células de Langerhans/patologia , Humanos , Degeneração Neural/complicações , Degeneração Neural/epidemiologia , Degeneração Neural/patologia , Adulto Jovem
7.
Nat Commun ; 7: 11263, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27090007

RESUMO

Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished on the basis of the IDH mutation and 1p/19q co-deletion. Here we present an integrated analysis of the transcriptome, genome and methylome of 156 OT. Not only does our multi-omics classification match the current classification but also reveals three subgroups within 1p/19q co-deleted tumours, associated with specific expression patterns of nervous system cell types: oligodendrocyte, oligodendrocyte precursor cell (OPC) and neuronal lineage. We confirm the validity of these three subgroups using public datasets. Importantly, the OPC-like group is associated with more aggressive clinical and molecular patterns, including MYC activation. We show that the MYC activation occurs through various alterations, including MYC genomic gain, MAX genomic loss, MYC hypomethylation and microRNA-34b/c down-regulation. In the lower grade glioma TCGA dataset, the OPC-like group is associated with a poorer outcome independently of histological grade. Our study reveals previously unrecognized heterogeneity among 1p/19q co-deleted tumours.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 1/genética , Metilação de DNA , Genômica , Oligodendroglioma/genética , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica/métodos , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Oligodendroglia/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Transdução de Sinais/genética , Células-Tronco/metabolismo , Análise de Sobrevida , Adulto Jovem
10.
J Neurooncol ; 120(3): 581-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25139026

RESUMO

Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is usually considered to be the standard treatment. However, the role of chemotherapy in treating relapses after RT is unclear, and this study aimed to assess the use of temozolomide (TMZ) in this situation. We conducted a retrospective analysis of patients from our database with "low grade" adult diffuse infiltrating brainstem glioma who received TMZ at relapse after failing RT. The patients were diagnosed by histology or MRI criteria compatible with a low-grade glioma. The tumors were localized in the pons, medulla oblongata or midbrain, excluding supratentorial or infratentorial tumors that had infiltrated the brainstem secondarily. The patients' clinical and radiological responses were assessed, and their progression free survival (PFS) and overall survival (OS) time were estimated. Fifteen adult patients (median age 34 years) fulfilled the inclusion criteria. Histological analysis was available in 5 cases and showed grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), and grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment and had a median PFS of 34.2 months (95 % CI 24.1-44.2). The median KPS at the time of relapse was 80. TMZ was administered orally at 150-200 mg/m(2) for 5 days, every 28 days. Clinical improvement after TMZ was observed in 9 cases (60 %), whereas radiological assessment detected responses in 6/15 cases, including 4 partial and 2 minor responses. The estimated median PFS after TMZ was 9.5 months (95 % CI 7.9-11), and the median OS was 14.4 months (95 % CI 10.5-18.2). Grade 3 thrombopenia was observed in 26 % of cases. TMZ could be useful after RT failure in adult patients with recurrent diffuse "low grade" brainstem glioma.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Neoplasias do Tronco Encefálico/radioterapia , Dacarbazina/análogos & derivados , Glioma/tratamento farmacológico , Glioma/radioterapia , Adulto , Idoso , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/patologia , Tronco Encefálico/efeitos da radiação , Neoplasias do Tronco Encefálico/patologia , Terapia Combinada , Dacarbazina/uso terapêutico , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Glioma/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Estudos Retrospectivos , Temozolomida , Resultado do Tratamento , Adulto Jovem
11.
Eur J Radiol ; 83(10): 1828-42, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25043984

RESUMO

PURPOSE: The radiologist plays a critical role at all steps of the management of patients with fibrous dysplasia (FD) and McCune-Albright syndrome (MAS). The development of a standardized approach to the management of FD/MAS is crucial given the low incidence and multiple clinical presentations of these conditions. Our aim was to develop recommendations for bone imaging in FD/MAS management. MATERIALS AND METHODS: The establishment of National Reference Centers in France as part of a Health Ministry program for orphan diseases has triggered the development of recommendations for the clinical management of FD/MAS. We used a well-established robust methodological approach involving an extensive literature review by a multidisciplinary working group (20 healthcare professionals) and scoring by a peer-review group (20 healthcare professionals different from the 20 previous ones). There were four phases: a systematic literature review, drafting of initial recommendations, peer-review of this initial draft, and drafting of the final recommendations. RESULTS: Fifty-seven specific recommendations are provided as key points for the diagnosis, prognosis, and follow-up of patients with FD/MAS. Issues of special interest are highlighted in the discussion, and areas in which future research is needed are identified. CONCLUSION: We believe the dissemination of these recommendations within the radiology community may facilitate communication between radiologists and other healthcare providers, thereby substantially improving the management of patients with these rare but potentially disabling conditions.


Assuntos
Diagnóstico por Imagem , Displasia Fibrosa Poliostótica/diagnóstico , Biópsia , Diagnóstico Diferencial , França , Humanos , Guias de Prática Clínica como Assunto , Prognóstico
12.
J Neurol ; 261(8): 1537-43, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24848633

RESUMO

Clinical spectrum of cognitive troubles complicating neurodegenerative Langerhans cell histiocytosis (ND-LCH) is poorly known. The aim of this study is to evaluate cognitive functions in ND-LCH. The cognitive functions of a series of eight adult patients (7 males and 1 female; mean age 26 years IQ 25-75; range 20-33) suffering from clinical and/or radiological ND-LCH were evaluated using the following tests: (1) forward/backward digit and spatial span tasks of the WAIS-R scale and the Corsi block task, (2) the French version of the free and cued selective reminding test, (3) verbal fluency tests, (4) the Frontal Assessment Battery (FAB), (5) backward measurement of the verbal and visuospatial memories of the WAIS-R scale, (6) the Rey complex figure test, (7) the trail making tests A and B, (8) digit symbol and symbol search of the WAIS-IV scale, and (9) the Stroop test. Episodic (i.e. autobiographical or personal) memory free recall, categorical verbal fluency, phonological verbal fluency, visuospatial processing skills, attention, speed of processing, and sensitivity to interference were impaired in ND-LCH patients. In contrast, verbal and visuospatial short-term memories (i.e. immediate memories or forward span tasks) were preserved in all patients. Adult ND-LCH patients suffer from a severe but dissociated dysexecutive syndrome, mostly affecting executive strategies and relatively sparing short-term memory. Our study supports the need of assessing executive functions using comprehensive cognitive evaluation in ND-LCH patients for early diagnosis.


Assuntos
Transtornos Cognitivos/etiologia , Histiocitose de Células de Langerhans/complicações , Doenças Neurodegenerativas/complicações , Adulto , Atenção/fisiologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Estudos Retrospectivos , Percepção Espacial/fisiologia , Aprendizagem Verbal/fisiologia , Adulto Jovem
13.
Neuro Oncol ; 16(5): 662-70, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24353325

RESUMO

BACKGROUND: The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. RESULTS: Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. CONCLUSION: In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.


Assuntos
Neoplasias Encefálicas/patologia , Deleção Cromossômica , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 1/genética , Imagem por Ressonância Magnética , Oligodendroglioma/patologia , Adulto , Idoso , Neoplasias Encefálicas/genética , Cromossomos Humanos Par 9 , Feminino , Expressão Gênica , Instabilidade Genômica , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Mutação , Neovascularização Patológica/genética , Oligodendroglioma/genética , Polimorfismo de Nucleotídeo Único , Adulto Jovem
14.
Oncologist ; 17(3): 388-97, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22382458

RESUMO

Brainstem gliomas are uncommon in adults and account for only 1%-2% of intracranial gliomas. They represent a heterogeneous group of tumors that differ from those found in their pediatric counterparts. In adults, a low-grade phenotype predominates, which is a feature that likely explains their better prognosis compared to that in children. Because biopsies are rarely performed, classifications based on the radiological aspect of magnetic resonance imaging results have been proposed to establish treatment strategies and to determine outcomes: (a) diffuse intrinsic low-grade, (b) enhancing malignant glioma, (c) focal tectal gliomas, and (d) exophytic gliomas. Despite significant advances in neuroradiology techniques, a purely radiological classification remains imperfect in the absence of a histological diagnosis. Whereas a biopsy may often be reasonably avoided in the diffuse nonenhancing forms, obtaining histological proof seems necessary in many contrast-enhanced brainstem lesions because of the wide variety of differential diagnoses in adults. Conventional radiotherapy is the standard treatment for diffuse intrinsic low-grade brainstem gliomas in adults (the median survival is 5 years). In malignant brainstem gliomas, radiotherapy is the standard treatment. However, the possible benefit of combined radiotherapy and chemotherapy (temozolomide or other agents) has not been thoroughly evaluated in adults. The role of anti-angiogenic therapies in brainstem gliomas remains to be defined. A better understanding of the biology of these tumors is of primary importance for identifying homogeneous subgroups and for improving therapy options and outcomes.


Assuntos
Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/terapia , Glioma/patologia , Glioma/terapia , Adulto , Idade de Início , Neoplasias do Tronco Encefálico/classificação , Neoplasias do Tronco Encefálico/epidemiologia , Seguimentos , Glioma/classificação , Glioma/epidemiologia , Humanos , Imagem por Ressonância Magnética/métodos , Estadiamento de Neoplasias , Prognóstico
16.
Orphanet J Rare Dis ; 6: 83, 2011 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-22151964

RESUMO

BACKGROUND: Vinblastine (VBL) is the standard treatment for systemic Langerhans cell histiocytosis (LCH), but little is known about its efficacy in central nervous system (CNS) mass lesions. METHODS: A retrospective chart review was conducted. Twenty patients from the French LCH Study Group register met the inclusion criteria. In brief, they had CNS mass lesions, had been treated with VBL, and were evaluable for radiologic response. RESULTS: The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m2 was given in a 6-week induction treatment, followed by a maintenance treatment. The median total duration was 12 months (range: 3-30). Eleven patients received steroids concomitantly. Fifteen patients achieved an objective response; five had a complete response (CR: 25%), ten had a partial response (PR: 50%), four had stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four out of the six patients who received VBL without concomitant steroids achieved an objective response. With a median follow-up of 6.8 years, the 5-year event-free and overall survival was 61% and 84%, respectively. VBL was well-tolerated and there were no patient withdrawals due to adverse events. CONCLUSION: VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Sistema Nervoso Central/patologia , Histiocitose de Células de Langerhans/tratamento farmacológico , Vimblastina/uso terapêutico , Adolescente , Adulto , Sistema Nervoso Central/efeitos dos fármacos , Doenças do Sistema Nervoso Central/mortalidade , Criança , Pré-Escolar , Feminino , Histiocitose de Células de Langerhans/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esteroides/uso terapêutico , Resultado do Tratamento , Adulto Jovem
17.
J Neurol ; 255(4): 575-80, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18227990

RESUMO

INTRODUCTION: The so called "neurodegenerative Langerhans cell histiocytosis" (ND-LCH) is a rare and severe complication of LCH presenting as a progressive cerebellar ataxia associated with pyramidal tract signs, and cognitive impairment. MRI is the gold standard to investigate CNS lesions of ND-LCH but little is known about functional changes observed in this disease. OBJECTIVES: To search for CNS metabolic changes in NDLCH. METHODS: Seven patients suffering from ND-LCH were investigated by 18F-FDG PET in this prospective study and compared with 21 healthy controls. RESULTS: ND-LCH patients demonstrated recurrent abnormalities including bilateral hypometabolism in the cerebellum, the basal ganglia (caudate nuclei), frontal cortex and, bilateral, a relatively increased metabolism in the amygdalae (p < 0.001). Functional changes in these anatomical regions may be detected in the absence of any apparent lesion on MRI. CONCLUSIONS: ND-LCH demonstrates a recurrent 18F-FDG PET metabolic signature. Our results suggest that 18F-FDG PET might be a useful tool for an early diagnosis of ND-LCH before neuroradiologic abnormalities appear.


Assuntos
Histiocitose de Células de Langerhans/complicações , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/fisiopatologia , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/etiologia , Ataxia Cerebelar/fisiopatologia , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/diagnóstico por imagem , Doença dos Neurônios Motores/etiologia , Doença dos Neurônios Motores/fisiopatologia , Doenças Neurodegenerativas/etiologia , Tomografia por Emissão de Pósitrons/normas , Valor Preditivo dos Testes , Prognóstico
18.
Neuro Oncol ; 8(1): 60-6, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16443949

RESUMO

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong immunostimulating activity and drive the immune response toward the Th1 (T helper type 1) phenotype. These ODNs have shown promising efficacy in preclinical studies when injected locally in several cancer models. We conducted a phase 1 trial to define the safety profile of CpG-28, a phosphorothioate CpG ODN, administered intratumorally by convection-enhanced delivery in patients with recurrent glioblastoma. Cohorts of three to six patients were treated with escalating doses of CpG-28 (0.5-20 mg), and patients were observed for at least four months. Twenty-four patients entered the trial. All patients had previously been treated with radiotherapy, and most patients had received one or several types of chemotherapy. Median age was 58 years (range, 25-73) and median KPS was 80% (range, 60%-100%). Adverse effects possibly or probably related to the studied drug were moderate and consisted mainly in worsening of neurological conditions (four patients), fever above 38 degrees C that disappeared within a few days (five patients), and reversible grade 3 lymphopenia (seven patients). Only one patient experienced a dose-limiting toxicity. Preliminary evidence of activity was suggested by a minor response observed in two patients and an overall median survival of 7.2 months. In conclusion, CpG-28 was well tolerated at doses up to 20 mg per injection in patients with recurrent glioblastoma. Main side effects were limited to transient worsening of neurological condition and fever.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/terapia , Oligodesoxirribonucleotídeos/efeitos adversos , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Relação Dose-Resposta a Droga , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Injeções Intraventriculares , Imagem por Ressonância Magnética , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Oligodesoxirribonucleotídeos/administração & dosagem , Análise de Sobrevida
19.
Rev Prat ; 56(16): 1757-67, 2006 Oct 31.
Artigo em Francês | MEDLINE | ID: mdl-17315501

RESUMO

Magnetic resonance imaging became the gold standard examination of pretherapeutic planning and post-treatment follow-up of cerebral tumours, even if computed tomography remains useful. During the last years, many new modalities of magnetic resonance examination arose, thus leading to increase its specificity. Then, spectroscopy allows better understanding of tumoural metabolism, whereas perfusion weighted imaging provides informations on its neovascularisation. Functional cortical activation imaging and diffusion tensor imaging allows delineation of tumoural extension towards eloquent areas and fiber bundles. Last, peroperative magnetic resonance imaging may lead to better control tumour resection during operation. However, while numerous and increasing the specificity of magnetic resonance examination, confrontation to pathology data remains necessary.


Assuntos
Neoplasias Encefálicas/diagnóstico , Imagem por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Tomografia Computadorizada por Raios X , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Circulação Cerebrovascular , Diagnóstico Diferencial , Humanos , Sensibilidade e Especificidade
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