Service de Neurologie Mazarin

Paris, France

Service de Neurologie Mazarin

Paris, France
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Dhermain F.,Institute Gustave Roussy | Dhermain F.,French Institute of Health and Medical Research | Saliou G.,CHU Bicetre | Parker F.,CHU Bicetre | And 5 more authors.
Journal of Neuro-Oncology | Year: 2010

Perfusion estimates and microvascular leakage (MVL) were recently correlated with glioma angiogenesis and aggressiveness, but their role in predicting outcome of patients (pts) with unfavorable low-grade gliomas (ULGG) is unclear. Their prognostic value was then investigated, versus conventional factors such as age, neurological status, tumor size, and contrast enhancement (CE). Clinical and anatomical magnetic resonance imaging (MRI) criteria of a cohort of ULGG pts were prospectively evaluated. A dynamic T2*-weighted MR sequence was included to detect high-perfusion areas, using the maximal value of the relative cerebral blood volume (rCBV) estimate, and MVL. Conventional and microvascular characteristics were correlated with progression-free survival (PFS). Among the 46 pts included, the following features were present in 61%, 26%, 67%, and 26%, respectively: age <40 years, neurological deficits, tumor size <6 cm, and CE. High perfusion value was noted in 30% of cases and MVL in 52%. With median follow-up of 22 months (range 4-46 months), median PFS was 32 months [95% confidence interval (CI) 17-45 months]. On univariate analysis, CE, rCBV, and MVL were significantly correlated with PFS. On multivariate analysis, only CE and MVL were unfavorable factors, with hazard ratio of 3.0 and 7.3 and P value of 0.04 and 0.02, respectively. Different prognostic subgroups were identified, with 2-year PFS of 86%, 57%, and 19% for pts with no MVL, MVL without CE, and MVL with CE, respectively. MVL and CE seem to predict short-term outcome in ULGG pts. © 2009 Springer Science+Business Media, LLC.

PubMed | groupe hospitalier Pellegrin, The Saints, Institute for Radiological Protection and Nuclear Safety, Ecole Normale Superieure de Cachan and 3 more.
Type: | Journal: BMC neurology | Year: 2015

Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations.The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement.With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors.NCT02544178.

Laigle-Donadey F.,Service de neurologie Mazarin | Reyes-Botero G.,Service de neurologie Mazarin | Ricard D.,Service de neurologie
NPG Neurologie - Psychiatrie - Geriatrie | Year: 2012

The growing incidence of malignant gliomas in the elderly population encourages developing specific schedules of treatment for this population. Increasing age is one of the most important negative prognostic factors in gliomas, justifying until recently a " nihilistic" approach in this population. However, this approach is progressively changing towards more active strategies, because prospective randomized studies have recently established the benefit of radiotherapy in older patients suffering from malignant gliomas. The benefits of chemotherapy and surgery are still under evaluation in this population. Initial performance status, quality of life, concomitant pathologies, as well as the willingness of the patient and his/her caregivers will also obviously be the key to the therapeutic decision. © 2011 Elsevier Masson SAS.

Alberti P.,University of Milan Bicocca | Rossi E.,University of Milan Bicocca | Cornblath D.R.,Johns Hopkins University | Merkies I.S.J.,Spaarne Hospital | And 25 more authors.
Annals of Oncology | Year: 2014

Background: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. Patients and methods: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute- Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc©), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). Results: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Laigle-Donadey F.,Service de Neurologie Mazarin | Figarella-Branger D.,Service dAnatomo Pathologie | Chinot O.,Service dOncologie | Taillandier L.,Service de Neurologie | And 5 more authors.
Journal of Neuro-Oncology | Year: 2010

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 (≥70 years) with good performance status (KPS ≥ 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. © 2010 Springer Science+Business Media, LLC.

Laigle-Donadey F.,Service de Neurologie Mazarin | Delattre J.-Y.,Service de Neurologie Mazarin
Geriatrie et Psychologie Neuropsychiatrie du Vieillissement | Year: 2011

The incidence of malignant gliomas is growing in the elderly population. Unfortunately, increasing age is one of the most important negative prognostic factors for gliomas, and the optimal management of this population remains largely unsettled because older patients are often excluded from clinical trials. However, the former nihilistic approach is progressively changing towards more active strategies. Indeed prospective randomized studies have recently established the benefit of radiotherapy and the validity of an accelerated course of irradiation in older patients suffering from malignant gliomas. The interest of debulking surgery remains still unknown in this population, and the interest of chemotherapy, alone or concomitant with radiotherapy is still under evaluation. Symptomatic treatments such as corticosteroids and antiepileptic drugs may be less tolerated in the elderly compared to younger patients and should be used only if requered. Initial performance status, quality of life and concomitant pathologies are obviously important factors to consider before treatment onset. The willingness of the patient and his caregivers will also be a key for the therapeutic decision. In the future, specific schedules of treatment in the elderly should be developed, and prospective randomized clinical trials are needed to improve the pattern of care of malignant gliomas in this population.

Delattre J.-Y.,Service de Neurologie Mazarin
Revue Neurologique | Year: 2011

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. © 2011 Elsevier Masson SAS. All rights reserved.

Laigle-Donadey F.,Service de Neurologie Mazarin | Doz F.,University of Paris Descartes | Delattre J.-Y.,Service de Neurologie Mazarin
Handbook of Clinical Neurology | Year: 2012

Diffuse brainstem glioma is the most common subtype of brainstem tumor and remains a devastating malignancy, particularly in children. Recent advances in radiological diagnostic techniques may improve the classification of these heterogeneous tumors and contribute to differential diagnosis. However, biopsy remains indicated in many contrast-enhancing brainstem masses in adults because of the great variety of differential diagnoses. New magnetic resonance imaging techniques can also help neurosurgeons in removing resectable brainstem tumors. Conventional radiotherapy is the standard of care. Classical chemotherapy drugs have been disappointing to date, suggesting that a better understanding of the biology of this tumor may be the key to more targeted therapy. Improvement in the pattern of care of brainstem gliomas is strongly needed. © 2012 Elsevier B.V.

Poisson M.,Service de Neurologie Mazarin
Pratique Neurologique - FMC | Year: 2011

Medical practice involves two approaches, one ethical and one practical, with different means and finalities. The ethical approach focuses on recognition and respect of the humanity of each individual patient while, in reality, the second attempts to achieve the best result possible. Neuro-oncology provides an illustrative example of the need to associate these two approaches to patient management. © 2011 Publié par Elsevier Masson SAS.

Franceschi E.,Bellaria Maggiore Hospital | Stupp R.,University of Lausanne | Van Den Bent M.J.,Erasmus Medical Center | Van Herpen C.,Radboud University Nijmegen | And 8 more authors.
Neuro-Oncology | Year: 2012

The treatment of patients with recurrent glioblastoma remains a major oncologic problem, with median survival after progression of 7-9 months. To determine the maximum tolerated dose and dose-limiting toxicity (DLT), the combination of dasatinib and cyclonexyl-chloroethyl-nitrosourea (CCNU) was investigated in this setting. The study was designed as multicenter, randomized phase II trial, preceded by a lead-in safety phase. The safety component reported here, which also investigated pharmacokinetics and preliminary clinical activity, required expansion and is therefore considered a phase I part to establish a recommended dosing regimen of the combination of CCNU (90-110 mg/m2) and dasatinib (100-200 mg daily). Overall, 28 patients were screened, and 26 patients were enrolled. Five dose levels were explored. DLTs, mainly myelosuppression, occurred in 10 patients. Grade 3 or 4 neutropenia was recorded in 7 patients (26.9) and thrombocytopenia in 11 patients (42.3). No significant effect of CCNU coadministration on dasatinib pharmacokinetics was found. Median progression-free survival (PFS) was 1.35 months (95 confidence interval: 1.2-1.4) and 6-month PFS was 7.7. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents. © 2012 The Author(s).

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