Radiotherapy for newly diagnosed primary central nervous system lymphoma: role and perspective

Whole brain radiotherapy (WBRT) has long been a key treatment of newly diagnosed primary central nervous system lymphoma (PCNSL). In the 1990s, the addition of high dose Methotrexate-based induction chemotherapy (HD MTX-based CT) has enabled a drastic improvement in PCNSL patients outcome. However, combined treatment has led to radiation-induced delayed neurotoxicity, especially in older patients. Alternative treatment strategies have been assessed to improve the efficacy and neurotoxicity ratio. Nowadays, in the elderly patients WBRT is widely omitted or deferred, and in younger patients WBRT is challenged by high dose chemotherapy with autologous stem cell transplant (HCT-ASCT) for consolidation treatment after HD MTX-based CT. In this setting, this review is addressed to clinicians with the aim to summarize the role of WBRT in the treatment of newly diagnosed PCNSL and its perspectives

Who Is In Charge, and Who Should Be? The Disciplinary Role of the Commander in Military Justice Systems

BackgroundStandard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma. MethodsWe randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival. ResultsA total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P=0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P=0.049) and 33.9% and 30.1% at 2 years (P=0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%). ConclusionsThe addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo.

Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

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Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

International audienceThe management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients

Tracking the Genetic Susceptibility Background of B-Cell Non-Hodgkin's Lymphomas from Genome-Wide Association Studies

International audienceB-cell non-Hodgkin's lymphoma (NHL) risk associations had been mainly attributed to family history of the disease, inflammation, and immune components including human leukocyte antigen (HLA) genetic variations. Nevertheless, a broad range of genome-wide association studies (GWAS) have shed light into the identification of several genetic variants presumptively associated with B-cell NHL etiologies, survival or shared genetic risk with other diseases. The present review aims to overview HLA structure and diversity and summarize the evidence of genetic variations, by GWAS, on five NHL subtypes (diffuse large B-cell lymphoma DLBCL, follicular lymphoma FL, chronic lymphocytic leukemia CLL, marginal zone lymphoma MZL, and primary central nervous system lymphoma PCNSL). Evidence indicates that the HLA zygosity status in B-cell NHL might promote immune escape and that genome-wide significance variants can give biological insight but also potential therapeutic markers such as WEE1 in DLBCL. However, additional studies are needed, especially for non-DLBCL, to replicate the associations found to date

Treatment of Primary Central Nervous System Lymphoma in Immunocompetent Patients

International audiencePURPOSE OF REVIEW: This review focuses on the findings of recent randomized prospective trials evaluating new therapeutic options for primary central nervous system lymphoma (PCNSL) in first-line treatment and on the most promising novel agents.RECENT FINDINGS: The current standard treatment of newly diagnosed PCNSL has long been depending on high-dose methotrexate (HD-MTX)-based polychemotherapy followed by whole-brain radiotherapy (WBRT). Recent randomized trials have provided evidence that high-dose chemotherapy with autologous stem cell transplantation (ASCT) is a valuable alternative option to WBRT as consolidation after induction HD-MTX-based chemotherapy. For the elderly, cumulative studies confirm that chemotherapy alone as initial treatment is the best approach in this frail population in order to reduce chemoradiation neurotoxicity. If the role of rituximab needs to be further investigated, novel agents such as imids and ibrutinib have shown to be promising drugs to be incorporated in innovative combination treatment. The role of WBRT, at least at conventional dose, is declining in first-line treatment in favor of intensive consolidation chemotherapy with or without ASCT and possibly maintenance chemotherapy in the elderly. Despite their rarity, it has been shown that ambitious randomized trials in PCNSL are feasible thanks to collaborative networks.Summary: The role of WBRT, at least at conventional dose, is declining in first-line treatment in favor of intensive consolidation chemotherapy with or without ASCT and possibly maintenance chemotherapy in the elderly. Despite their rarity, it has been shown that ambitious randomized trials in PCNSL are feasible thanks to collaborative networks

Targeting mutants of PTEN reveal distinct subsets of tumour suppressor functions

Au xixe siècle, les lycées éprouvent à l’égard des villes qui les abritent des sentiments ambivalents, entre attraction et rejet. En contrepartie des multiples ressources qu’elles procurent, les villes occasionnent en effet des nuisances qui menacent sans cesse la santé, la sécurité et la moralité des élèves ainsi que la bonne marche de leurs études. Pendant longtemps, les établissements peinent à faire entendre leurs revendications et doivent donc s’adapter seuls au contexte urbain. Mais, peu à peu, ces rapports conflictuels s’apaisent : à la fin du siècle, après que le gouvernement a échoué dans sa tentative de transporter à la campagne les établissements d’internes, la ville est devenue un véritable partenaire avec lequel les lycées n’hésitent plus à multiplier les échanges. Par son exemplarité, le cas des lycées parisiens illustre cette lente évolution.In the 19th century, lycées experienced ambivalent feelings towards the cities that harboured them, ranging from attraction to rejection. Cities offered many ressources to schools, on the other hand they caused threatening damage to the health, safety and moral standards of the pupils, as well as to the course of their studies. For a long time, schools struggled to put forward their claims and had therefore to adapt alone to the urban context. However, these conflictual relationships gradually died down. Towards the end of the century, after the government’s failure to set up boarding schools outside the cities, lycées and cities became real partners with an increasing number of contacts between the two. Because of its exemplary nature, the case of the lycées in Paris illustrates this slow evolution.Im 19. Jahrhundert standen die Gymnasien den städtischen Zentren, innerhalb derer sie angesiedelt waren, mit eher gemischten Gefühlen gegenüber, denn trotz der unverzichtbaren Ressourcen, die die Städte zu bieten hatten, wirkten sie sich auf den Gesundheitszustand, die Sicherheit und das Benehmen der Schüler natürlich immer wieder negativ aus und störten so deren schulische Ausbildung. Dennoch gelang es den schulischen Einrichtungen zumeist nicht, ihren Forderungen Gehör zu verschaffen; sie kamen deshalb nicht umhin, sich ihrerseits ihrer Umgebung so weit wie möglich anzupassen. Erst gegen Ende des Jahrhunderts, nachdem man von Regierungsseite vergeblich versucht hatte, die Internatsschulen in eine ländliche Umgebung zu verlegen, lösten sich diese Konflikte allmählich auf. Erst zu diesem Zeitpunkt wurden die Städte zu regelrechten Partnern der Gymnasien, mit denen ein Austausch auf den unterschiedlichsten Ebenen stattfinden konnte. Diese langsam fortschreitende Entwicklung wird am Beispiel der Pariser Gymnasien exemplarisch aufgezeigt