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Primary central nervous system lymphomas (PCNSLs) classically remain confined within the CNS throughout their evolution for unknown reasons. Our objective was to analyse the rare extracerebral relapses of PCNSL in a nationwide population-based study. We retrospectively selected PCNSL patients who experienced extracerebral relapse during their follow-up from the French LOC database. Of the 1968 PCNSL included in the database from 2011, 30 (1.5%, median age 71 years, median KPS 70) presented an extracerebral relapse, either pure (n = 20) or mixed (both extracerebral and in the CNS) (n = 10), with a histological confirmation in 20 cases. The median delay between initial diagnosis and systemic relapse was 15.5 months [2-121 months]. We found visceral (n = 23, 77%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n = 12, 40%), and peripheral nervous system (PNS) (n = 7, 23%) involvement. Twenty-seven patients were treated with chemotherapy, either with only systemic targets (n = 7) or mixed systemic and CNS targets (n = 20), 4 were consolidated by HCT-ASCT. After systemic relapse, the median progression-free survival and overall survival (OS) were 7 and 12 months, respectively. KPS > 70 and pure systemic relapses were significantly associated with higher OS. Extracerebral PCNSL relapses are rare, mainly extranodal, and frequently involve the testis, breast, and PNS. The prognosis was worse in mixed relapses. Early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic workup that should systematically include a PET-CT. Paired tumour analysis at diagnosis/relapse would provide a better understanding of the underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

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]

Background: The prognosis of recurrent glioblastoma (GBM) is poor, with limited options of palliative localized or systemic treatments. Survival can be improved by a second localized treatment; however, it is not currently possible to identify which patients would benefit from this approach. This study aims to evaluate which factors lead to a lower Karnofsky performance status (KPS) score after fractionated stereotactic RT (fSRT). Methods: We retrospectively collected data from patients treated with fSRT for recurrent GBM at the Institut de Cancérologie de Lorraine between October 2010 and November 2017 and analyzed which factors were associated with a lower KPS score. Results: 59 patients received a dose of 25 Gy in 5 sessions spread over 5–7 days (80% isodose). The median time from the end of primary radiotherapy to the initiation of fSRT was 10.7 months. The median follow-up after fSRT initiation was 8.8 months. The incidence of KPS and ADL impairment in all patients were 51.9% and 37.8% respectively with an adverse impact of PTV size on KPS (HR = 1.57 [95% CI 1.19–2.08], p = 0.028). Only two patients showed early grade 3 toxicity and none showed grade 4 or late toxicity. The median overall survival time, median overall survival time after fSRT, median progression-free survival and institutionalization-free survival times were 25.8, 8.8, 3.9 and 7.7 months, respectively. Initial surgery was associated with better progression-free survival (Hazard ratio (HR) = 0.48 [95% CI 0.27–0.86], p = 0.013). Conclusions: A larger PTV should predicts lower KPS in the treatment of recurrent GBM using fSRT. [ABSTRACT FROM AUTHOR]

Isolated tumefactive demyelinating lesion (TDL) is a rare disease and a challenging entity especially for the differential diagnosis, biopsy indications, and therapeutic decisions. Long-term evolution is not well known. The objective of the study is to describe clinical and MRI characteristics and long-term follow-up of patients with isolated TDL. We performed a retrospective study including patients (1) with one TDL radiologically defined by a ≥20 mm FLAIR hyperintensity involving the white matter associated with T1 hypointensity that enhanced after gadolinium injection and (2) without any other MS lesion on the first MRI. Tumor, abscess, or other inflammatory diseases (ADEM, Baló's concentric sclerosis, systemic disease) were excluded. Sixteen patients (11 females/5 males) were included. The mean age of onset was 35.7 years (range 20-65). MRI disclosed supratentorial lesions with a mean size of 39.4 mm and usually mild edema/mass effect. Peripheral (mainly open-ring pattern) and central (mainly heterogeneous) enhancement were respectively seen in 9/16 and 11/16 patients. CSF study ( n = 15) found oligoclonal bands (OCB) in seven. A cerebral biopsy was performed in 11 cases showing acute inflammatory demyelination. Thirteen patients were treated by pulse steroids with marked improvement in ten. At last clinical follow-up (mean 65.8 months, range 6-181), diagnosis was MS in 5 (31 %), isolated TDL in 10 (63 %) and one patient had a second TDL (6 %). Isolated tumefactive demyelinating lesions are a rare diagnostic entity. After a mean follow-up of 5 years, almost one-third became MS whereas most of the patients had no further event. [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]

Objectives: Here we present a model aiming to provide an estimate of time from tumour genesis, for grade II gliomas. The model is based on a differential equation describing the diffusion-proliferation process. We have applied our model to situations where tumour diameter was shown to increase linearly with time, with characteristic diametric velocity. Materials and methods: We have performed numerical simulations to analyse data, on patients with grade II gliomas and to extract information concerning time of tumour biological onset, as well as radiology and distribution of model parameters. Results and conclusions: We show that the estimate of tumour onset obtained from extrapolation using a constant velocity assumption, always underestimates biological tumour age, and that the correction one should add to this estimate is given roughly by 20/ v (year), where v is the diametric velocity of expansion of the tumour (expressed in mm/year). Within the assumptions of the model, we have identified two types of tumour: the first corresponds to very slowly growing tumours that appear during adolescence, and the second type corresponds to slowly growing tumours that appear later, during early adulthood. That all these tumours become detectable around a mean patient age of 30 years could be interesting for formulation of strategies for early detection of tumours. [ABSTRACT FROM AUTHOR]

An abstract of the article "A neuroimmunological aproach to CNS neoplastic disease: the way to immunotherapy," by R. Tanasescu and colleagues is presented.

Purpose: Few studies have evaluated the health-related quality of life (HRQoL) of patients with diffuse low-grade glioma (LGG) during a clinical and radiological monitoring period. We report a cross sectional cohort study of HRQoL in patients with LGG and compare the results with normative population data. We then explore factors associated with HRQoL., Methods: We used the European Organisation for Research and Treatment of Cancer QLQ-C30, BN-20 and the Hospital Anxiety and Depression Scale (HADS) to evaluate HRQoL. Averaged QLQC30 and HADS scores were compared with scores of a normative population. A general linear model multivariate analysis of variance was used to investigate the association between HRQoL and independent factors., Results: A total of 62 patients with LGG completed HRQoL questionnaires. Compared with a normative population, LGG patients reported statistical and clinically significant lower cognitive, emotional, role and social functioning. Fatigue, anxiety, depression and sleep disturbances were frequently reported. Awake surgery and preserved high Karnofsky Performance Status were found to be independent prognostic factors for better global HRQoL, while radiotherapy was associated with worsened HRQoL., Conclusion: Despite a non-therapeutic and progression free phase, LGG patients report noticeable limitations in several HRQoL subscales. Our study highlights the importance of HRQoL assessment not only at diagnosis or during active therapeutic stage. Further studies are needed to develop better adapted tools of HRQoL assessment., Competing Interests: Declarations. Ethical approval: Ethical approval was waived by the local Ethics Committee of the Nancy University Hospital. Consent to participate: Written informed consent was obtained from the parents. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Diffuse low-grade gliomas are rare brain tumors transforming to higher grade even with surgery, chemotherapy, and radiotherapy. Their preferential infiltration of white matter tracts, beyond tumor boundaries on fluid-attenuated inversion recovery (FLAIR), make difficult to plan focal treatment such as surgery or radiotherapy and monitor response to chemotherapy. Diffusion tensor imaging (DTI) might reflect this infiltration of white matter tracts. The aim of our study is to assess how DTI signal in the peritumoral zone might be modified before FLAIR tumor progression appears at 1-year follow-up., Methods: The study retrospectively enrolled 5 patients who met inclusion criteria: DTI with 25 directions, T1 and FLAIR at initial imaging; FLAIR at one-year follow-up. Patients with surgery, radiotherapy, and chemotherapy completed less than 2 years before initial imaging were excluded. FLAIR tumor progression, named progression mask, was assessed by subtracting tumor masks between initial imaging and one-year follow-up. Initial DTI signal was analyzed within this progression mask and compared with the healthy contralateral side., Results: Tumor progression was confirmed for the 5 patients at 1 year. All patients showed pre-existing DTI signal abnormalities within the progression mask. Mean fractional anisotropy (P = 0.03) was lower in the progression mask, whereas mean diffusivity, axial diffusivity, and radial diffusivity mean (P = 0.03) was higher in the progression mask, compared with the healthy side., Conclusions: This study shows pre-existing DTI signal abnormalities in regions with tumor progression at 1 year. Such abnormalities could correspond to a tumor infiltration not yet visible on FLAIR. This might be helpful to predict tumor progression and allow to adapt the therapeutic strategy., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)