Risultati per: Glioma

Introduction
All grade 2/3 gliomas are incurable and at the time of inevitable relapse, patients have significant unmet needs with few effective treatments. This study aims to improve outcomes by molecular profiling of patients at relapse, then matching them with the best available drug based on their molecular profile, maximising the chances of patient benefit while simultaneously testing multiple novel drugs.

Methods and analysis
Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2) will be an international, phase 2, multicentre, open-label, biomarker-directed, umbrella clinical trial for recurrent isocitrate dehydrogenase mutant, histologically grade 2/3 gliomas. Investigational treatment will be assigned based on molecular profiling of contemporaneous tissue obtained at disease relapse using next-generation sequencing. LUMOS-2 will begin with three therapeutic treatment arms: paxalisib, cadonilimab and selinexor. Patient molecular profiles will be assessed by an expert, multidisciplinary Molecular Tumour Advisory Panel. Patients whose molecular profile is considered suitable for a targeted agent like paxalisib will be allocated to that arm, others will be randomised to the available arms of the trial. The primary endpoint is progression-free survival at 6 months. Secondary objectives include assessment of overall survival, response rate, safety and quality of life measures. Two additional therapeutic arms are currently in development.

Ethics and dissemination
Central ethics approval was obtained from the Sydney Local Health District Ethics Review Committee, Royal Prince Alfred Hospital Zone, Sydney, Australia (Approval: 2022/ETH02230). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. A report describing the results of the study will be submitted to international meetings and peer-reviewed journals.

Trial registration number
ACTRN12623000096651.

Stroke, Volume 56, Issue Suppl_1, Page ATP312-ATP312, February 1, 2025. Background/Objectives:Perioperative stroke is a significant cause of morbidity and mortality in patients undergoing cardiac, vascular, and neurosurgical procedures. We assessed the rate, characteristics, risk factors and survival outcomes of perioperative stroke following surgical resection of glioma.Design:This is a retrospective chart review of a single quaternary care center of patients with glioma between 2005-2021 who underwent resection. Stroke within 30 days of surgical resection was identified based on the radiology read of MRI brain for ischemic stroke and CT brain for hemorrhagic stroke that was obtained as part of clinical care. This was then confirmed retrospectively by a neurologist who reviewed imaging and medical records, excluding expected post-operative changes. Descriptive analysis and logistic regression were conducted. Overall survival was estimated with Kaplan-Meier methods from the date of surgery to death and compared with the log rank test.Results:Out of 738 patients who underwent surgical resection of their glioma and underwent brain MRI or CT head, 20 (2.71%) had radiographic evidence of strokes, with the mean (SD) time from surgery to stroke 5.4 (16.2) days. Of these, 13 (65%) had ischemic strokes, 7 (35%) had hemorrhagic strokes. Out of all perioperative strokes, 9 (45%) were symptomatic (total incidence of 1.2%), and 11 (55%) were asymptomatic. Patients who had a stroke were older [mean (SD); 60.4 (13.7) vs. 52.8 (15.0) years; p=0.026], had a higher rate of atrial fibrillation (p= 0.002), and had comorbid hyperlipidemia (p=0.039) and hypertension (p=0.047). Descriptive analysis of this cohort is summarized in Table 1. Older age, carrying a diagnosis of atrial fibrillation, and having hyperlipidemia were associated with higher odds of having a perioperative stroke (Table 2). In an attempt to generate a multivariate logistic model, stepwise selection yielded no significant results likely due to the low number of strokes in this cohort. The median survival for patients with stroke was 24.6 months (95% CI:21.8-32.1), which was lower than for patients who did not suffer a stroke (29.3 months, 95% CI: 25.6-32.9) (p=0.052).Conclusion:Older age, atrial fibrillation, hyperlipidemia, and hypertension were associated with perioperative stroke risk after glioma resection. Future studies should evaluate underlying mechanisms and stroke etiologies to better identify high risk patients.

Introduction
High-grade glioma patients and their caregivers often suffer from distress and a lower quality of life. Results from studies with patients with mixed cancer entities suggest that yoga can be an effective support. However, it is unclear whether this also applies to high-grade glioma patients and their caregivers. This study aims to investigate the effects of mindfulness-based online yoga for patients and their caregivers on emotional distress, quality of life and stress-associated physiological parameters compared with a waiting control group (WCG).

Methods & analysis
The study is designed as a multicentre randomised controlled trial. Adult glioma patients (central nervous system WHO grades 3 and 4) and their caregivers will be recruited. Examined yoga instructors deliver the intervention (1 hour per week) in a synchronous format over 8 weeks via video conferencing. The WCG will receive standard care during the 8-week waiting period. Data will be collected before and after the end of the intervention and another 3 months later using questionnaires as well as blood serum and hair samples to evaluate biochemical stress parameters. Primary outcome is self-reported generalised anxiety and secondary outcomes are self-reported fear of progression, depression and quality of life as well as brain-derived neurotrophic factor (BDNF), dehydroepiandrosterone (DHEA)/dehydroepiandrosterone sulfate (DHEAS), ferritin and hair cortisol. We hypothesise better outcomes in the intervention group compared with the WCG at all measurement points. 70 patients and 70 caregivers will be recruited consecutively. Primary endpoints are significant effect detections in the Generalised Anxiety Disorder scale-7 of patients and caregivers at the end of the intervention. Analyses of covariance will be performed to analyse the treatment effects.

Ethics and dissemination
The Ethics Committee of the University of Würzburg approved the YINOTA-O (Yoga-Intervention bei Neuroonkologischen Tumorpatienten und deren Angehörigen – Online) study on 26 October 2021 (No.185/18-me). Results will be presented at conferences and published in peer-reviewed journals.

Trial registration number
German Clinical Trials Register No. DRKS00029554.

Introduction
Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms’ tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG.

Methods and analysis
10 paediatric patients with newly diagnosed or pretreated HGG or DIPG were treated according to the trial protocol. The trial protocol consists of leukapheresis of mononuclear cells, the manufacturing of autologous WT1/DC vaccines and the combination of WT1/DC-vaccine immunotherapy with conventional antiglioma treatment. In newly diagnosed patients, this comprises chemoradiation (oral temozolomide 90 mg/m2 daily+radiotherapy 54 Gy in 1.8 Gy fractions) followed by three induction WT1/DC vaccines (8–10×106 cells/vaccine) given on a weekly basis and a chemoimmunotherapy booster phase consisting of six 28-day cycles of oral temozolomide (150–200 mg/m2 on days 1–5) and a WT1/DC vaccine on day 21. In pretreated patients, the induction and booster phase are combined with best possible antiglioma treatment at hand. Primary objectives are to assess the feasibility of the production of mRNA-electroporated WT1/DC vaccines in this patient population and to assess the safety and feasibility of combining conventional antiglioma treatment with the proposed immunotherapy. Secondary objectives are to investigate in vivo immunogenicity of WT1/DC vaccination and to assess disease-specific and general quality of life.

Ethics and dissemination
The ethics committee of the Antwerp University Hospital and the University of Antwerp granted ethics approval. Results of the clinical trial will be shared through publication in a peer-reviewed journal and presentations at conferences.

Trial registration number
NCT04911621

Introduction
Glial brain tumours are highly mortal and are noted as major neurosurgical challenges due to frequent recurrence or progression. Despite standard-of-care treatment for gliomas, the prognosis of patients with higher-grade glial tumours is still poor, and hence empowering antitumour immunity against glioma is a potential future oncological prospect. This review is designed to improve our understanding of the efficacy of cell-based immunotherapies for glioma.

Methods and analysis
This systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of main electronic databases: PubMed/MEDLINE, Scopus, ISI Web of Science EMBASE and ProQuest will be done on original articles, followed by a manual review of review articles. Only records in English and only clinical trials will be encountered for full-text review. All the appropriate studies that encountered the inclusion criteria will be screened, selected and then will undergo data extraction step by two independent authors. For meta-analyses, data heterogeneity for each parameter will be first evaluated by Cochran’s Q and I2 statistics. In case of possible heterogeneity, a random-effects meta-analysis will be performed and for homogenous data, fixed-effects models will be selected for reporting the results of the proportional meta-analysis. Bias risk will be assessed through Begg’s and Egger’s tests and will also be visualised by Funnel plots.

Ethics and dissemination
As this study will be a systematic review without human participants’ involvement, no ethical registration is required and meta-analysis will be presented at a peer-reviewed journal.

PROSPERO registration number
CRD42022373297

Objectives
To use a nomogram to predict the risk of mortality and estimate the impact of current treatment on the prognosis of glioma patients.

Methods
A total of 3798 cases were obtained from the Surveillance Epidemiology and End Results database according to the selection criteria. A nomogram was built on the independent clinical factors screened by the variance inflation factor, univariate analyses and a multivariate Cox regression model. Then, categorising the overall population into high-risk, medium-risk and low-risk groups using nomogram-derived risk scores, to study the impact of treatment on different subgroups’ survival outcomes. Furthermore, based on the postmatch cohorts, the influences of treatment on survival outcomes were assessed by the log-rank test.

Result
Age, race, stage of disease, histological type, histological grade, surgery, radiotherapy and chemotherapy were identified as the independent prognostic factors. A nomogram with good discrimination and consistency was built. Generally, the patients who underwent surgery, radiotherapy and chemotherapy were more likely to achieve better prognosis than those who did not, except for those who received radiotherapy in the low-risk cohort and those who underwent surgery in the high-risk cohort. Furthermore, the isocitrate dehydrogenase 1/2 (IDH1/2) wild-type patients with surgery, radiotherapy or chemotherapy tended to have higher survival probabilities, while some inconsistent results were observed in the IDH mutant-type cohort.

Conclusion
Surgery, radiotherapy and chemotherapy improved the prognosis, while appropriate selection of topical treatment for the low-risk or high-risk patients deserves further consideration. IDH status gene might be a reliable indicator of therapeutic effectiveness.

New England Journal of Medicine, Volume 389, Issue 12, Page 1108-1120, September 2023.

New England Journal of Medicine, Volume 389, Issue 7, Page 655-659, August 2023.

This cohort study evaluates the association of MGMT promoter methylation for low-grade and anaplastic gliomas with chemotherapy response.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Volume 388, Issue 14, Page 1332-1334, April 2023.

Objective
The purpose of this study was to evaluate the diagnostic accuracy of 6 different imaging modalities for differentiating glioma recurrence from postradiotherapy changes by performing a network meta-analysis (NMA) using direct comparison studies with 2 or more imaging techniques.

Data sources
PubMed, Scopus, EMBASE, the Web of Science and the Cochrane Library were searched from inception to August 2021. The Confidence In Network Meta-Analysis (CINeMA) tool was used to evaluate the quality of the included studies with the criterion for study inclusion being direct comparison using 2 or more imaging modalities.

Data extraction and synthesis
The consistency was evaluated by examining the agreement between direct and indirect effects. NMA was performed and the surface under the the cumulative ranking curve (SUCRA) values was obtained to calculate the probability of each imaging modality being the most effective diagnostic method. The CINeMA tool was used to evaluate the quality of the included studies.

Main outcomes and measures
Direct comparison, inconsistency test, NMA and SUCRA values.

Results
A total of 8853 potentially relevant articles were retrieved and 15 articles met the inclusion criteria. 18F-FET showed the highest SUCRA values for sensitivity, specificity, positive predictive value and accuracy, followed by 18F-FDOPA. The quality of the included evidence is classified as moderate.

Conclusion and relevance
This review indicates that 18F-FET and 18F-FDOPA may have greater diagnostic value for glioma recurrence relative to other imaging modalities (Grading of Recommendations, Assessment, Development and Evaluations B).

PROSPERO registration number
CRD42021293075.

Gerritsen JKW, Dirven CMF, De Vleeschouwer S, et al. The PROGRAM study: awake mapping versus asleep mapping versus no mapping for high-grade glioma resections: study protocol for an international multicenter prospective three-arm cohort study. BMJ Open 2021;11:e047306. doi: 10.1136/bmjopen-2020-047306 The authors want to notify the readers on the updates done in the published version. We have added two authors to the author list: neuro-linguistic expert Dr Djaina D Satoer (Department of Neurosurgery, Erasmus MC, Rotterdam, The Netherlands), who has been of tremendous in developing the neuro-linguistic test battery for the PROGRAM study; and neurosurgeon and neurophysiologist Dr Kathleen Seidel (Department of Neurosurgery, Inselspital Universitätsspital Bern, Bern, Switzerland), who has co-developed the Bern protocol for asleep motor mapping. This specific mapping protocol for the Bern location has been added to the revised manuscript. Moreover, we have added “Object Naming” to the neuro-linguistic test battery and more extensive quality of life…

Stroke, Volume 53, Issue Suppl_1, Page AWP15-AWP15, February 1, 2022. Introduction:Glioma is the most common malignant type of brain tumours. Glioma patients are at higher risk for cerebrovascular mortality compared to the general population and other cancer types. Whether the risk differs by the grade, a marker of aggressiveness in gliomas, remains unclear.Methods:Using the US National Cancer Institute’s Surveillance Epidemiology and End Results program, we identified adult patients with a primary diagnosis of malignant gliomas in 2000 to 2018 (N=72,252). Age-, sex-, and calendar-year- adjusted standardized mortality ratios (SMRs) were calculated for cerebrovascular mortality comparing glioma patients with the general population. Gliomas were classified into four grades based on WHO definition in which increasing grade indicates the higher degrees of invasiveness. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox regression model to examine cerebrovascular mortality in patients with different grades of gliomas.Results:Over 80% of patients were diagnosed with high grade gliomas (Grade 3 & 4). Patients with gliomas in all grades had excess cerebrovascular mortality compared with the general population (SMRs 2.64-4.18, p