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Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions. • Multi-omic data consensus clustering reveals four molecular subtypes of PCNSL with prognostic relevance. • RNA-seq data alone and a publicly accessible algorithm can be used to assign the multi-omic defined PCNSL subtypes. • PCNSL molecular subtyping can improve future clinical stratification and suggest rational subtype-based targeted therapies. [ABSTRACT FROM AUTHOR]

Résumé Les métastases cérébrales ont un impact sur la survie des patients mais également sur leur qualité de vie. L’objectif de la prise en charge est donc double. Actuellement, en raison des progrès thérapeutiques, les survies des patients tendent à s’allonger, en particulier pour certains sous-types tumoraux. Au cours de l’évolution de la maladie, différents signes et symptômes neurologiques peuvent être rencontrés en fonction de la localisation, du nombre et du volume des lésions métastatiques. La perte d’autonomie et les troubles cognitifs sont particulièrement redoutés par les patients et leur entourage. Un dialogue permanent, tout au long de la maladie, est nécessaire afin d’adapter la prise en charge aux objectifs fixés avec le patient, en fonction des taux de réponse objectifs aux traitements oncologiques et du retentissement de la maladie et de sa prise charge dans le quotidien du patient. Les traitements ayant une pertinence clinique seront ceux considérés comme les plus appropriés au regard de leur impact sur la survie globale, de leur capacité à préserver l’indépendance fonctionnelle et à maintenir la qualité de vie, de leur capacité à contrôler et à prévenir l’apparition de nouveaux symptômes et signes neurologiques et de leurs effets secondaires. Les traitements et soins de support, la cognition et la qualité de vie doivent ainsi être régulièrement évalués et adaptés à la prise en charge des patients atteints de métastases cérébrales. Les différentes approches sont décrites dans cet article. Brain metastases impact on the survival of the patients, but on their quality of life as well. The objective of the management of these patients is then double. Currently, due to medical advances, survivals tend to improve, especially for some tumor subtypes. During the course of the disease, different neurological signs and symptoms can be observed according to the location, the number and the volume of the metastase(s). Patients and caregivers are especially worried about the loss of autonomy and cognitive impairments. A permanent dialogue, during the course of the disease, is mandatory, in order to adapt the management to the objectives determined by the patients and the medical team. These objectives may vary according to the objective response rates of the disease to anticancer therapies, according to the impact of the disease and its management in daily living. Anticancer therapies and supportive care must be appreciated according to their impact on the survival, on the preservation of the functional independence and the quality of life of the patient, on their abilities to preserve the neurological status and delay the apparition of new neurological signs and symptoms, and their adverse events. Supportive care, cognition and quality of life should be regularly evaluated and adapted according to the objectives of the management of brain metastases patients. Different approaches are described in this paper. [ABSTRACT FROM AUTHOR]

This randomised phase II study (120 patients) evaluated BEV and IRI as neo-adjuvant and adjuvant treatment in combination with temozolomide-based chemoradiation versus chemoradiation alone for patients with unresectable glioblastoma (RPA class V). Median Progression Free Survival was 7.1 months in the experimental arm versus 5.2 months in the control arm. However, median overall survival was not different between the two arms (11.1 months).Background Prognosis of unresectable glioblastoma (GB) remains poor, despite temozolomide (TMZ)-based chemoradiation. Activity of bevacizumab (BEV) and irinotecan (IRI) has been reported in recurrent disease. We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for unresectable GB. Patients and methods Patients with unresectable GB, age 18–70, IK ≥50 were eligible. The experimental arm (BEV/IRI) consisted of neo-adjuvant intravenous BEV, 10 mg/kg, and IRI, 125 mg/m2, every 2 weeks for four cycles before radiotherapy (RT) (60 Gy), concomitant oral TMZ, 75 mg/m2/day, and BEV, 10 mg/kg every 2 weeks. Adjuvant BEV and IRI were given every 2 weeks for 6 months. The control arm consisted of concomitant oral TMZ, 75 mg/m2/day during RT, and 150–200 mg/m2 for 5 days every 28 days for 6 months. The use of BEV was allowed at progression in the control arm. Results Patients (120) were included from April 2009 to January 2011. The working hypothesis was that treatment would increase the progression-free survival at 6 month (PFS-6) from 50% to 66%. The primary objective was not achieved, and only 30 out of 60 patients were alive without progression at 6 months (50.0% [IC95% (36.8; 63.1)] in the BEV/IRI arm when 37 out of 60 patients were required according to the Fleming decision rules. PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm. The median overall survival was not different between the two arms (11.1 months). Main toxicities were three fatal intracranial bleedings, three bile duct or digestive perforations/infections (1 fatal), and six thrombotic episodes in the BEV/IRI arm, whereas there was one intracranial bleeding, two bile duct or digestive perforations/infections (1 fatal), and one thrombotic episode in the control arm. Conclusions Neo-adjuvant and adjuvant BEV/IRI, combined with TMZ-radiation, is not recommended for further evaluation in the first-line treatment of unresectable GB. Clinical trial registration Clinical trial registered under EUDRACT number 2008-002775-28 (NCT01022918). [ABSTRACT FROM AUTHOR]

Introduction/Background Gliomas are the most common primary brain tumors in adults. Physical activity is proposed as an associated care in multiple cancers with proven benefits but has not been often and specifically evaluated for gliomas. The main objective of our study was to assess the feasibility and the potential effectiveness of exercise training in patients with high and low-grade gliomas. Material and method Twenty-eight patients (mean age 49 years, 16 high grades and 12 low-grades, minimal Karnofksy Performance Status at 70%) were addressed by the neuro-oncology for fatigue complaint. They were first screened by a physiatrist and then included a program of individual exercise training. A Six-Minute-Walking-Test was realized before and after the training. Results On the 17 patients included, 14 finished the program (7 high grade and 7 low-grade gliomas). Only 2 patients were excluded for a clinical degradation and only 1 patient did not finish it for a reason linked to his tumor. Mean number of sessions was 8; no major sides effects were reported. After the program, a statistically significant increase of the 6-Minute-Test was found ( P = 0.0007). Conclusion In this population, this kind of program seems to be feasible and efficient. However, our results cannot be extended to all gliomas patients due to the good general state of our population and the inner limits of the Six-Minute-Walking-Test. Further studies are needed to assess the possible benefits in larger sample. [ABSTRACT FROM AUTHOR]

Objective Exercise behavior has shown its interest in cancers and may have a prognosis value in brain tumors [1] . The aim of this prospective study is to show the effectiveness of a guided personalized rehabilitation-reconditioning program in brain tumors. Patients Inclusion criteria: patients over 18; complain of fatigue and decrease or interruption of a physical activity; histological diagnosis of brain tumor; Karnofsky Performance Status > 60. Exclusion criteria: major neurological or cognitive impairment; cardiac or pulmonary contraindication; high risk of tumor progression. Methods Patients underwent an incremental, physician-supervised cardiopulmonary exercise test (CPET) before including the personalized rehabilitation reconditioning program. The program included 5 to 10 individualized sessions, supervised by a physiotherapist; from 30 to 45 minutes per session; 1 to 2 times per week; altered or continuous on walking treadmill or bicycle. The endurance phase was calculated depending on results of the CPET. The objectives of the sessions were personalized; the physical therapist gave the patient therapeutic advices to continue physical activity after the reconditioning program, with a written notebook of follow-up for self- sessions provided at home. The primary outcome was a 6-minute walk test (6MWT) [2] . Results Nineteen patients, mean aged of 53 years old (standard deviation 14.2) were proposed by the neurologist to follow the program; 11 had high-grade glioma and 8 of them low-grade glioma. Fourteen patients were included; 9 completed the program, 3 are currently following it. At follow up, all patients who had completed the program increased their walking speed from 1.68 m/sec (6 km/h) to 1.92 m/sec (6.9 km/h) ( p = 0.022). Discussion Brain tumor survivors can improve walking function after a personalized and guided rehabilitation reconditioning program. This study is a preliminary study before a controlled study measuring the effects of such a program on quality of life and survey in glioblastoma. [ABSTRACT FROM AUTHOR]