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Le Touquet – Paris-Plage, France

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.

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.

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).

Ricard D.,Service de Neurologie | Ricard D.,University Pierre and Marie Curie | Soussain C.,University Pierre and Marie Curie | Soussain C.,Hopital Rene Huguenin Institute Curie | Psimaras D.,Service de Neurologie Mazarin
Revue Neurologique | Year: 2011

Treatment-induced CNS toxicity remains a major cause of morbidity in patients with cancer. Real advances in the design of safer radiation procedures have been counterbalanced by a wider use of combined radiotherapy (RT)-chemotherapy regimens, the development of radiosurgery, and the increasing number of long-term survivors. While classic radionecrosis or chemonecrosis have become less common, more subtle changes such as progressive cognitive dysfunction are increasingly reported after RT (radiation-induced leukoencephalopathy) or chemotherapy (administered alone or in combination). The most important and controversial complications of RT, chemotherapy and combined treatments in the CNS are reviewed here, including new diagnostic tools, practical management and prevention that will influence the future management of cancer patients. © 2011 Elsevier Masson SAS. All rights reserved.

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