L'état fonctionnel autonome comme critère de jugement principal chez les patients atteints de glioblastome inopérable : analyse exploratoire rétrospective monocentrique

Introduction : l’objectif principal de notre étude était de définir et de déterminer la durée de l’état fonctionnel autonome chez des patients atteints de glioblastome (GBM) inopérable. En effet, nous considérons que l’autonomie de ces patients est un véritable critère de qualité de vie à prendre en compte dans les essais thérapeutiques en neuro-oncologie. Ce paramètre pourrait être utilisé dans l’évaluation de nouveaux traitements.Méthode : Pour cette étude monocentrique, nous avons recueilli des données cliniques, d’imagerie, histologiques et thérapeutiques chez des patients atteints de glioblastome inopérable. Les 139 patients ont été recrutés de façon rétrospective dans le service de neuro-oncologie du CHU La Timone à Marseille, entre 2014 et 2017. Nous avons décrit l’évolution de cette population au cours du suivi : traitements oncologiques reçus, leurs complications, la meilleure réponse selon les critères radio-cliniques RANO (Response Assessment in Neuro-Oncology) en première ligne de traitement. L’état fonctionnel a été évalué par l’indice de Karnofsky (IK). Nous avons testé un nouveau paramètre pour évaluer l’autonomie des patients : la durée avec un IK ≥70, qui correspond à la durée d’autonomie. Puis nous avons rapporté cette durée à la survie de chaque patient. Nous avons étudié les caractéristiques des patients traités par radiochimiothérapie (RCT) d’emblée, et celles des patients traités par chimiothérapie néoadjuvante (CT néoadjuvante). Résultats : Nous avons trouvé que l’âge au diagnostic, la surface de la lésion et la survie étaient corrélés à la préservation de l’autonomie. On note que, pour 50% des patients, la durée avec un IK≥70 est inférieure à 2 semaines. Dans cette population de glioblastome inopérable, où le standard de traitement n’est pas clairement établi, les patients ont été traités soit par RCT, soit par CT néoadjuvante. La plupart des patients qui ont débuté la RCT arrivent à la terminer. En revanche, lorsque la RCT n’est pas débutée d’emblée, sa réalisation est rarement appliquée. Nous avons pu individualiser deux profils de patients différents. Les patients qui ont été traités par RCT avaient un meilleur pronostic et une préservation plus longue de l’autonomie. Les patients traités par chimiothérapie néoadjuvante avaient un pronostic plus sombre et une autonomie moins longtemps préservée. Dans le groupe traité par RCT, la durée d’autonomie est influencée par l’IK lors de la consultation d’annonce et par la latéralisation (unilatéral versus bilatéral) de la tumeur. Dans le groupe traité par CT néoadjuvante, la durée d’autonomie semble influencée par l’IK à la consultation d’annonce et par la topographie (envahissement de la ligne médiane) de la tumeur, qui est un nouveau paramètre de classification de l’imagerie que nous avons mis au point.Conclusion : L’autonomie est un critère qui doit être pris en compte dans les essais thérapeutiques en neuro-oncologie, notamment pour les patients atteints de glioblastome inopérable. Cette étude pourrait permettre de déterminer des paramètres décisionnels pour la prise en charge thérapeutique des patients atteints de glioblastomes inopérables

Primary central nervous system lymphoma (PCNSL) in older patients

Introduction Primary central nervous system lymphoma (PCNSL) is a rare, chemo and radio-sensitive tumor limited to the central nervous system. The incidence of PCSNL increases notably in the elderly population which represented approximately half of the patients. The limit of ‘elderly’ population remained debated and nonuniform, including 60 years as a cutoff for brain radiotherapy, 65 years for autologous stem-cell transplantation, and 70 years for the last clinical trials. Current therapeutic options include first line treatment based on high-dose methotrexate based polychemotherapy, consolidation chemotherapy, and adapted autologous stem cell transplantation for highly selected patients. At relapse, single agent targeted therapies or salvage chemotherapy followed by intensive consolidation are promising therapeutic options. Nevertheless, improving management of elderly patients is an urgent medical need that currently remains unresolved. Objective We will focus on elderly patients with PCNSL and their specificities including clinical presentations, available therapeutic options and adaptations to be made. Conclusion To improve survival, it will be necessary to personalized and adapt the treatments, to each patient and his comorbidities, to increase their effectiveness and limit their toxicity in this frail population. Finally, inclusion of these patients in clinical trials is one of the major challenges to significantly change PCNSL elderly patient prognosis

Prognostic value of Beta 2-Microglobulinin in cerebrospinal fluid in primary central nervous system lymphoma.

International audienc

Association of inoperable glioblastoma with a heterogeneous functional and survival outcome.

International audiencee14036 Background: “Biopsy only” GBM patients is an understudied group of patients associated to a poor outcome, which has been reported to represent 21% of histologically confirmed GBM in the US National Cancer Data Base. Pattern of care included radiotherapy-temozolomide (RT-TMZ) standard regimen completed in 15% of patients, any other form of oncologic treatment in 60%, and supportive care alone in 25% of patients (Kole, Cancer 2016). Our objective was to explore heterogeneity of inoperable GBM patients group, both for patients characteristics, pattern of care planned and completed, functional and survival outcome. Methods: Patients with inoperable GBM included in a prospective regional glioma cohort initiated in 2014 were retrospectively reviewed for patients characteristics, MRI finding, treatment allocation and delivery. Functional independency analyzed as a cumulative time of KPS≥70, PFS and OS were analyzed. Results: Of 535 patients referred to our center, 449 patients were included at initial surgery, of which 158 patients (35%) underwent biopsy only. 18 patients were excluded for missing data leaving 139 patients for the present analysis. 54 (39%) were referred to RT-TMZ (50 patients completed concomitant treatment), 68 (49%) considered unfitted for RT received chemotherapy upfront (CT-UF) (of which 3 were subsequently referred to RT), 17 (12%) referred to palliative care only (PC). Groups differed at baseline for age (mean 60, 68, 69y for RT-TMZ, CT-UF, PC respectively); for KPS (70, 60, 50 for RT-TMZ, CT-UF, PC respectively); for mean tumor surface (793, 1420, 1412 cm2 for RT-TMZ, CT-UF, PC); for tumor extension (bilateral in 6.4% and 29.3% for RT-CT and CT-UF respectively); for steroid intake (45, 60, 100 mg daily respectively). Median OS was 14 months (95% CI, 9.65-18.71), 8 months (95% CI, 4.62-7.67), 2 months (95% CI, 0.67-3.33) for RT-TMZ, CT-UF, PC respectively. Of importance, mean duration of functional independence was of 8.3 months, 2.1 months, and 0.1 month for RT-TMZ, CT-UF, and PC respectively; 33/139 (24%) of the patients experienced functional independency for more than 40% of their life time. Conclusions: Inoperable GBM constitute a large and heterogeneous population in which more than 1/3 of the patients are amenable to standard of care, with survival outcome similar to the one of patients who underwent surgery. Patients considered unfit for RT-CT at diagnosis fail to be referred subsequently to RT after CT and exhibit a poor survival outcome that deserve new effective treatments. Cumulative duration of functional independence is limited and should be considered as part of treatment evaluation

REVOLUMAB: A phase II trial of Nivolumab in recurrent IDH mutant high-grade gliomas

International audienceBackground: Novel effective treatments are needed for recurrent IDH mutant high-grade gliomas (IDHm HGGs). The aim of the multicentric, single-arm, phase II REVOLUMAB trial (NCT03925246) was to assess the efficacy and safety of the anti-PD1 Nivolumab in patients with recurrent IDHm HGGs.Patients and methods: Adult patients with IDHm WHO grade 3-4 gliomas recurring after radiotherapy and ≥ 1 line of alkylating chemotherapy were treated with intravenous Nivolumab until end of treatment (12 months), progression, unacceptable toxicity, or death. The primary endpoint was the 24-week progression-free survival rate (24w-PFS) according to RANO criteria.Results: From July 2019 to June 2020, 39 patients with recurrent IDHm HGGs (twenty-one grade 3, thirteen grade 4, five grade 2 with radiological evidence of anaplastic transformation; 39% 1p/19q codeleted) were enrolled. Median time since diagnosis was 5.7 years, and the median number of previous systemic treatments was two. The 24w-PFS was 28.2% (11/39, CI95% 15-44.9%). Median PFS and OS were 1.84 (CI95% 1.81-5.89) and 14.7 months (CI95% 9.18-NR), respectively. Four patients (10.3%) achieved partial response according to RANO criteria. There were no significant differences in clinical or histomolecular features between responders and non-responders. The safety profile of Nivolumab was consistent with prior studies.Conclusions: We report the results of the first trial of immune checkpoint inhibitors in IDHm gliomas. Nivolumab failed to achieve its primary endpoint. However, treatment was well tolerated, and long-lasting responses were observed in a subset of patients, supporting further evaluation in combination with other agents (e.g. IDH inhibitors)

Immunosuppression in patients with grade 3 acute‐on‐chronic liver failure at transplantation: A practice analysis study

Transplantation for patients with acute-on-chronic liver failure grade 3 (ACLF3) has encouraging results with 1-year-survival of 80-90%. These patients with multiple organ failure meet the conditions for serious alterations of drug metabolism and increased toxicity. The goal of this study was to identify immunosuppression-dependent factors that affect survival. This retrospective monocentric study was conducted in patients with ACLF3 consecutively transplanted between 2007 and 2019. The primary endpoint was 1-year survival. Secondary endpoints were overall survival, treated rejection, and surgical complications. Immunosuppression was evaluated as to type of immunosuppression, post-transplant introduction timing, trough levels, and trough level intra-patient variability (IPV). One hundred patients were included. Tacrolimus IPV < 40% (P = .019), absence of early tacrolimus overdose (P = .033), use of anti-IL2-receptor antibodies (P = .034), and early mycophenolic acid introduction (P = .038) predicted 1-year survival. Treated rejection was an independent predictor of survival (P = .001; HR 4.2 (CI 95%: 1.13-15.6)). Early everolimus introduction was neither associated with higher rejection rates nor with more surgical complications. Management of immunosuppression in ACLF3 critically ill patients undergoing liver transplantation is challenging. Occurrence and treatment of rejection impacts on survival. Early introduction of mTOR inhibitor seems safe and efficient in this situation. Keywords: basilliximab; critically ill patients; everolimus; mycophenolic acid; rejection