Search Results for: Glioma

Messo a punto da Int per il glioma diffuso della linea mediana

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
Neurosurgery is a risk factor for postoperative delirium. Dexmedetomidine has a potential effect on reducing postoperative delirium. We aim to test the primary hypothesis that perioperative administration of dexmedetomidine reduces the incidence of postoperative delirium in patients undergoing neurosurgical resections of temporal glioma.

Methods
This is a single-centre, randomised, blinded and parallel-group controlled trial. A total of 366 patients will be randomised to either dexmedetomidine group (n=183) or placebo group (n=183). Subjects assigned to dexmedetomidine group will be given a continuous infusion at 0.4 µg/kg/h after anaesthesia induction until dural closure and then immediately receive an infusion of dexmedetomidine at 0.08 µg/kg/h by intravenous analgesia pump during the first 48 hours postoperatively. Patients in the placebo group will be given comparable volumes of normal saline, and intravenous analgesia pumps contain equal amounts of sufentanil and antiemetics, but no dexmedetomidine. The primary outcome is the incidence of postoperative delirium, which will be assessed with the Confusion Assessment Method two times per day during the first five postoperative days.

Ethics and dissemination
The protocol (V.1.1) has been approved by the medical ethics committee of Beijing Tiantan Hospital, Capital Medical University (KY2023-186-02). The findings of this study will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals.

Trial registration number
NCT06164314.

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
A greater extent of resection of the contrast-enhancing (CE) tumour part has been associated with improved outcomes in glioblastoma. Recent results suggest that resection of the non-contrast-enhancing (NCE) part might yield even better survival outcomes (supramaximal resection, SMR). Therefore, this study evaluates the efficacy and safety of SMR with and without mapping techniques in high-grade glioma (HGG) patients in terms of survival, functional, neurological, cognitive and quality of life outcomes. Furthermore, it evaluates which patients benefit the most from SMR, and how they could be identified preoperatively.

Methods and analysis
This study is an international, multicentre, prospective, two-arm cohort study of observational nature. Consecutive glioblastoma patients will be operated with SMR or maximal resection at a 1:1 ratio. Primary endpoints are (1) overall survival and (2) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months postoperatively. Secondary endpoints are (1) residual CE and NCE tumour volume on postoperative T1-contrast and FLAIR (Fluid-attenuated inversion recovery) MRI scans; (2) progression-free survival; (3) receipt of adjuvant therapy with chemotherapy and radiotherapy; and (4) quality of life at 6 weeks, 3 months and 6 months postoperatively. The total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

Ethics and dissemination
The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

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

Objectives
This study aimed to systematically elucidate the prognostic significance of cyclin-dependent kinase subunit 2 (CKS2) expression in various cancers and its correlation with their clinicopathological characteristics.

Design
In this meta-analysis and bioinformatic analysis, articles were identified through searches of multiple databases and meta-analysed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. Data from The Cancer Genome Atlas were examined using UCSC Xena tools to further confirm the prognostic effect of CKS2.

Data sources
The PubMed, Embase, Web of Science and Cochrane Library databases were searched for articles published from their inception to 1 January 2023, using a combination of subject terms and free words, including ‘CKS2’, ‘cancer’, ‘tumor’, ‘neoplasm’, ‘carcinoma’, ‘malignancy’ and ‘prognosis’.

Eligibility criteria
The analysis included cohort or case–control studies, reported in English, with malignancy diagnoses confirmed by pathological methods, available HRs and 95% CIs for overall survival (OS) or extractable Kaplan-Meier curves, and a sample size of ≥20 patients. Reviews, commentaries, letters, conference reports, case reports, in vitro and animal studies, studies of CKS2 gene variants, studies with sample cases from public databases and studies with unavailable survival or duplicated data were excluded.

Data extraction and synthesis
Two researchers independently screened the articles, extracted the data and evaluated the quality of included studies using the Newcastle-Ottawa Scale. Meta-analysis and bioinformatic analyses were performed using the STATA and R software, respectively.

Results
The analysis included 13 retrospective studies encompassing 1348 cases across 10 cancer types. Nine studies involving 1124 patients examined the correlation between CKS2 expression levels and OS. A fixed-effects model analysis revealed a significant association between high CKS2 expression and reduced OS (HR=2.27, 95% CI=1.87 to 2.77, p

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.

To the Editor In their cohort study recently published in JAMA Oncology, Kinslow et al reached a compelling conclusion that the presence of O6-methylguanine-DNA methyltransferase promoter methylation (mMGMT) holds a significant association with the response to chemotherapy for low-grade and anaplastic gliomas. Consequently, they propose that mMGMT status could serve as a crucial stratification factor for patients with isocitrate dehydrogenase (IDH)–wild-type and IDH-mutant gliomas. Personally, such findings are highly innovative, as they shed light on the association between mMGMT and lower-grade glioma (LGG, grade 2 and 3), which remains a subject of controversy. While this study contributes valuable evidence on the matter, there are still some concerns that warrant consideration.

Introduction
Despite their recent FDA(Food and Drug Administration) approval, tumour treatment fields (TTFields) have not seen acceptance as part of standard of care (SOC) for the treatment of high-grade gliomas (HGGs). Few studies have reported the clinical effect of simultaneous or sequential use of TTFields with the current SOC. However, whether TTFields are beneficial over the standard treatment remains to be established with a meta-analysis. Therefore, we here performed a systematic review and meta-analysis to understand the benefit of TTFields for patients with HGGs.

Methods and analysis
We registered this systematic review with the PROSPERO network (registration number: CRD42023398972) and aimed to follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in the study. All articles related to TTFields in glioma will be systematically searched for in the following databases since their inception until November 2023: the China National Knowledge Infrastructure, Embase, Cochrane Library, Wanfang Database, China Science Journal Database, China Biomedical Documentation Database, VIP database, Web of Science and PubMed. Article screening and data extraction will be done independently by the authors and cross-checked by two of the authors on completion. The Cochrane risk of bias assessment tool will be used for quality assessment of the included studies. Review Manager V.5.3 (Cochrane Collaboration) will be used to perform the meta-analysis.

Ethics and dissemination
Ethical approval is not required because the data used will be obtained from published studies, and there will be no concerns about privacy. The results of this study will be published in a peer-reviewed journal.

PROSPERO registration number
CRD42023398972.

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.

In Reply In response to our recent Review, Dr Wang raises several interesting points regarding the use of prophylaxis against P jirovecii pneumonia in patients with glioma, but conflates 2 different clinical scenarios. The first is P jirovecii pneumonia prophylaxis in the setting of long-term steroid use ( >4 weeks), as discussed in our Review. The second scenario is empirical P jirovecii pneumonia prophylaxis in the setting of chemoradiation, which is the scenario addressed in the article cited by Wang.

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