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Frontiers in Immunology 2023Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival.
METHOD
Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356).
RESULTS
We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; = -2.00, = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; = -1.99, = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; = -3.53; = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; = -2.23; = 0.0256).
CONCLUSION
Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.
Topics: Humans; Standard of Care; Glioma; Brain Neoplasms; Progression-Free Survival; Immunotherapy
PubMed: 37483593
DOI: 10.3389/fimmu.2023.966696 -
The Journal of International Medical... Aug 2020We investigated the association between the consumption of fresh and processed fish and glioma risk using a meta-analysis approach. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We investigated the association between the consumption of fresh and processed fish and glioma risk using a meta-analysis approach.
METHODS
We selected and analyzed observational studies that discussed the relationships between fresh and processed fish intake on glioma risk from PubMed, Web of Science, Embase, and the SinoMed and Wanfang databases from inception to 31 March 2020. Studies were selected according to pre-established eligibility criteria and data were extracted separately by two researchers. A meta-analysis was conducted based on a random-effects model to provide pooled odds ratios (OR) and 95% confidence intervals (CIs).
RESULTS
Eight studies considered the relationship between fish intake (seven fresh and seven processed fish) and glioma risk and were included in this meta-analysis. The OR effect size for fresh fish intake and glioma risk was 0.72 (95%CI 0.53-0.97) and the overall OR effect size for processed fish intake and glioma risk was 1.88 (95%CI 1.06-3.34).
CONCLUSION
Dietary intake of fresh fish may reduce the risk of glioma, but consumption of processed fish may increase the risk of glioma. This study had some limitations, and further studies are therefore required to clarify the associations between fish intake and glioma risk.
Topics: Animals; Fishes; Glioma; Humans; Odds Ratio; Risk Factors
PubMed: 32840400
DOI: 10.1177/0300060520939695 -
Clinical Neurology and Neurosurgery Aug 2023A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically... (Review)
Review
BACKGROUND
A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically reviewed clinical outcomes in glioma patients treated with one or more nutritional adjunct and/or an antimetabolite drug.
METHODOLOGY
A systematic review of the literature following PRISMA guidelines was performed using Pubmed from inception till February 2023. In total, 22 manuscripts on nutrition representing 828 patients were included in the review. Statistical analyses were performed to compare the outcomes of various adjuncts.
RESULTS
The median overall survival (OS) increased for newly diagnosed (21 months) and recurrent cases (10 months) when compared to historical data. For newly diagnosed cases, a ketogenic diet had the highest median OS of all the adjuncts (42.6 months) while in recurrent cases, a low copper diet coupled with 1 g penicillamine had the highest median OS (18.5 months). However, no statistically significant difference was observed in OS or progression-free survival (PFS) of newly diagnosed or recurrent gliomas.
CONCLUSION
While nutritional adjuncts may offer a therapeutic benefit in the treatment of glioma, more human subject research is needed to derive meaningful conclusions.
Topics: Humans; Neoplasm Recurrence, Local; Glioma; Progression-Free Survival; Brain Neoplasms
PubMed: 37390567
DOI: 10.1016/j.clineuro.2023.107853 -
Quality of Life Research : An... Mar 2023Low-grade glioma (LGG) patients may face health-related quality-of-life (HRQoL) impairments, due to the tumour, treatment and associated side-effects and prospects of... (Review)
Review
PURPOSE
Low-grade glioma (LGG) patients may face health-related quality-of-life (HRQoL) impairments, due to the tumour, treatment and associated side-effects and prospects of progression. We systematically identified quantitative studies assessing HRQoL in adult LGG patients, for: aspects of HRQoL impacted; comparisons with non-cancer controls (NCC) and other groups; temporal trends; and factors associated with HRQoL.
METHODS
MEDLINE, CINAHL, Embase, PubMed, and PsycINFO were systematically searched from inception to 14th September 2021. Following independent screening of titles and abstracts and full-texts, population and study characteristics, and HRQoL findings were abstracted from eligible papers, and quality appraised. Narrative synthesis was conducted.
RESULTS
Twenty-nine papers reporting 22 studies (cross-sectional, n = 13; longitudinal, n = 9) were identified. Papers were largely good quality, though many excluded patients with cognitive and communication impairments. Comparators included high-grade gliomas (HGG) (n = 7); NCCs (n = 6) and other patient groups (n = 3). Nineteen factors, primarily treatment (n = 8), were examined for association with HRQoL. There was substantial heterogeneity in HRQoL instruments used, factors and aspects of HRQoL assessed and measurement timepoints. HRQoL, primarily cognitive functioning and fatigue, in adult LGG patients is poor, and worse than in NCCs, though better than in HGG patients. Over time, HRQoL remained low, but stable. Epilepsy/seizure burden was most consistently associated with worse HRQoL.
CONCLUSION
LGG patients experience wide-ranging HRQoL impairments. HRQoL in those with cognitive and communication impairments requires further investigation. These findings may help clinicians recognise current supportive care needs and inform types and timings of support needed, as well as inform future interventions.
Topics: Humans; Adult; Cross-Sectional Studies; Quality of Life; Glioma; Cognition; Drug-Related Side Effects and Adverse Reactions
PubMed: 35931881
DOI: 10.1007/s11136-022-03207-x -
Journal of Experimental & Clinical... May 2015CD133 and Nestin, as the markers of cancer stem cells, have recently been reported frequently in the pathogenesis and development of human gliomas. However, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
CD133 and Nestin, as the markers of cancer stem cells, have recently been reported frequently in the pathogenesis and development of human gliomas. However, the prognostic role of CD133 and Nestin in gliomas still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and Nestin and the outcome of glioma patients by conducting a systematic review and meta-analysis.
METHODS
We performed systematically electronic and manual searches through the database of Pubmed and embase (until to December 25, 2014) for titles and abstracts which investigated the relationships between CD133 and Nestin expression and outcome of glioma patients. A systematic review and meta-analysis was executed to generate Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS).
RESULTS
A total of 1,490 patients from 32 studies (13 articles) were included in the analysis. 19 studies and 13 studies investigated correlation between CD133 expression or Nestin and survival in gliomas, respectively. Our results showed that high CD133 expression in patients with glioma was associated with poor prognosis in terms of OS (HR 1.69; 95 % CI, 1.16-2.47; P =0.0060) and PFS (HR, 1.64; 95 % CI, 1.12-2.39; P = 0.010). In addition, high Nestin expression were associated with worse OS (HR 1.751; 95 % CI, 1.19-2.58, p = 0.004) but has no significant association with PFS (HR 1.55; 95 % CI, 0.96-2.51, p = 0.074). Even more important, the results of the subgroup meta-analyses show that that high CD133 expression was associated with worse prognosis in terms of OS and PFS in patients with WHO IV glioma but not WHO II-III. On the other hand, Nestin high expression was associated with worse prognosis in terms of OS and PFS in patients with WHO II-III glioma but not WHO IV.
CONCLUSION
High level of CD133 expression trends to correlate with a worse OS and PFS in glioma patients, especially WHO IV gliomas and Nestin high expression trends to correlate with a worse OS in glioma patients especially WHO II-III, revealing both the markers of cancer stem cells may as the potential pathological prognostic markers for glioma patients.
Topics: AC133 Antigen; Antigens, CD; Biomarkers, Tumor; Female; Gene Expression; Glioma; Glycoproteins; Humans; Male; Neoplastic Stem Cells; Nestin; Peptides; Prognosis; Proportional Hazards Models; Publication Bias; Survival Analysis
PubMed: 25967234
DOI: 10.1186/s13046-015-0163-4 -
Critical Reviews in Oncology/hematology Apr 2017Coined as the "Warburg effect" and a recognized hallmark of cancer, energy metabolism is aberrantly geared towards aerobic glycolysis in most human cancers, including... (Review)
Review
BACKGROUND
Coined as the "Warburg effect" and a recognized hallmark of cancer, energy metabolism is aberrantly geared towards aerobic glycolysis in most human cancers, including malignant glioma. Ketogenic metabolic therapy (KMT), i.e. nutritional intervention with ketogenic or low-glycemic diets, has been proposed as an anti-neoplastic strategy in glioma patients.
MATERIALS AND METHODS
We here review the rationale and existing data investigating KMT in management of patients with malignant glioma and discuss the promise and potential challenges of this novel strategy. Results from published clinical studies and ongoing clinical trials on the topic are systematically reviewed, including 6 published original articles and 10 ongoing clinical trials. Search criteria for this review entailed the databases MEDLINE, EMBASE, Cochrane CENTRAL, and Google Scholar, as well as ICTRP (WHO) and ClinicalTrials.gov (NIH) registries.
RESULTS
A substantial amount of preclinical literature demonstrates KMT efficacy and safety in model systems of malignant glioma. Clinical literature indicates KMT safety and feasibility; 2 clinical studies suggest KMT-associated anti-neoplastic efficacy and clinical benefit. Ongoing clinical trials address KMT safety and metabolic impact, patient compliance, and patient clinical/survival benefit.
CONCLUSIONS
While clinical evidence is still limited in this evolving field, increasing numbers of ongoing clinical trials suggest that KMT is emerging as a potential therapeutic option and might be combinable with existing anti-neoplastic treatments for malignant glioma. Emerging clinical data will help answer questions concerning safety and efficacy of KMT, and are aiming to identify the most promising KMT regimen, compatibility with other anti-cancer treatments, ethical aspects, and impact on quality of life of cancer patients.
Topics: Animals; Diet, Ketogenic; Glioma; Humans
PubMed: 28325264
DOI: 10.1016/j.critrevonc.2017.02.016 -
World Neurosurgery Jun 2022Isocitrate dehydrogenase (IDH) mutations are present in 70% of World Health Organization grade II and III gliomas. IDH mutation induces accumulation of the... (Review)
Review
BACKGROUND
Isocitrate dehydrogenase (IDH) mutations are present in 70% of World Health Organization grade II and III gliomas. IDH mutation induces accumulation of the oncometabolite 2-hydroxyglutarate. Therefore, therapies targeting reversal of epigenetic dysregulation in gliomas have been suggested. However, the utility of epigenetic treatments in gliomas remains unclear. Here, we present the first clinical systematic review of epigenetic therapies in treatment of IDH-mutant gliomas and highlight their safety and efficacy.
METHODS
We conducted a systematic search of electronic databases from 2000 to January 2021 following PRISMA guidelines. Articles were screened to include clinical usage of epigenetic therapies in case reports, prospective case series, or clinical trials. Primary and secondary outcomes included safety/tolerability of epigenetic therapies and progression-free survival/overall survival, respectively.
RESULTS
A total of 133 patients across 8 clinical studies were included in our analysis. IDH inhibitors appear to have the best safety profile, with an overall grade 3/grade 4 adverse event rate of 9%. Response rates to IDH-mutant inhibitors were highest in nonenhancing gliomas (stable disease achieved in 55% of patients). In contrast, histone deacetylase inhibitors demonstrate a lower safety profile with single-study adverse events as high as 28%.
CONCLUSION
IDH inhibitors appear promising given their benign toxicity profile and ease of monitoring. Histone deacetylase inhibitors appear to have a narrow therapeutic index, as lower concentrations do not appear effective, while increased doses can produce severe immunosuppressive effects. Preliminary data suggest that epigenetic therapies are generally well tolerated and may control disease in certain patient groups, such as those with nonenhancing lesions.
Topics: Brain Neoplasms; Epigenesis, Genetic; Glioma; Histone Deacetylase Inhibitors; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 35314408
DOI: 10.1016/j.wneu.2022.03.051 -
Journal of Neuro-oncology Jan 2023To provide a summary of the diagnostic performance of F-FET-PET in the management of patients with high-grade brain gliomas or metastases from extracranial primary... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To provide a summary of the diagnostic performance of F-FET-PET in the management of patients with high-grade brain gliomas or metastases from extracranial primary malignancies.
METHODS
MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases were searched for studies that reported on diagnostic test parameters in radiotherapy planning, response assessment, and tumour recurrence/treatment-related changes differentiation. Radiomic studies were excluded. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool and the GRADE approach. A bivariate, random-effects model was used to produce summary estimates of sensitivity and specificity.
RESULTS
Twenty-six studies with a total of 1206 patients/lesions were included in the analysis. For radiotherapy planning of glioma, the pooled proportion of patients from 3 studies with F-FET uptake extending beyond the 20 mm margin from the gadolinium enhancement on standard MRI was 39% (95% CI, 10-73%). In 3 studies, F-FET-PET was also shown to be predictive of early responders to treatment, whereas MRI failed to show any prognostic value. For the differentiation of glioma recurrence from treatment-related changes, the pooled sensitivity and specificity of TBR 1.9-2.3 from 6 studies were 91% (95% CI, 74-97%) and 84% (95% CI, 69-93%), respectively. The respective values for brain metastases from 4 studies were 82% (95% CI, 74-88%) and 82% (95% CI, 74-88%) using TBR 2.15-3.11.
CONCLUSION
While F-FET shows promise as a complementary modality to standard-of-care MRI for the management of primary and metastatic brain malignancies, further validation with standardized image interpretation methods in well-designed prospective studies are warranted.
Topics: Humans; Contrast Media; Neoplasm Recurrence, Local; Gadolinium; Brain Neoplasms; Glioma; Positron-Emission Tomography; Magnetic Resonance Imaging; Tyrosine
PubMed: 36502457
DOI: 10.1007/s11060-022-04201-6 -
Nitric Oxide : Biology and Chemistry Sep 2023Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and... (Review)
Review
INTRODUCTION
Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and treatment strategies, median survival remains disappointingly low. Inflammatory processes involving nitric oxide (NO), critically contribute to glioma formation. The inducible isoform of NO synthase (iNOS) is highly overexpressed in gliomas and has been linked to resistance against temozolomide (TMZ) treatment, neoplastic transformation, and modulation of immune response. While both in vitro and in vivo studies showed the potential of iNOS inhibitors as effective treatments for gliomas, no clinical trials on gliomas have been published. This review aims to summarize the available evidence regarding iNOS as a target for glioma treatment, focusing on clinically relevant data.
METHODS
Following PRISMA guidelines, we conducted a systematic review by searching PubMed/Medline, and Embase databases in May 2023. We included studies that investigated the impact of NOS inhibitors on glioma cells using L-NMMA, CM544, PBN, 1400W or l-NAME either alone or combined with TMZ. We extracted data on the NOS inhibitor used, subtype, study setting, animal model or cell lines employed, obtained results, and safety profile. Our inclusion criteria encompassed original articles in English or Spanish, studies with an untreated control group, and a primary outcome focused on the biological effects on glioma cells.
RESULTS
Out of 871 articles screened from the aforementioned databases, 37 reports were assessed for eligibility. After excluding studies that did not utilize glioma cells or address the designated outcome, 11 original articles satisfied the inclusion and exclusion criteria. Although no NOS inhibitor has been tested in a published clinical trial, three inhibitors have been evaluated using in vivo models of intracranial gliomas. l-NAME, 1400W, and CM544 were tested in vitro. Co-administration of l-NAME, or CM544 with TMZ showed superior results in vitro compared to individual agent testing.
CONCLUSION
Glioblastomas remain a challenging therapeutic target. iNOS inhibitors exhibit substantial potential as treatment options for oncologic lesions, and they have demonstrated a safe toxicity profile in humans for other pathological conditions. Research endeavors should be focused on investigating their potential effects on brain tumors.
Topics: Animals; Humans; Glioblastoma; NG-Nitroarginine Methyl Ester; Glioma; Temozolomide; Brain Neoplasms; Enzyme Inhibitors; Nitric Oxide Synthase; Nitric Oxide
PubMed: 37279819
DOI: 10.1016/j.niox.2023.06.002 -
Neurological Sciences : Official... Jun 2024High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years,... (Review)
Review
High-grade gliomas (HGGs) constitute the most common malignant primary brain tumor with a poor prognosis despite the standard multimodal therapy. In recent years, immunotherapy has changed the prognosis of many cancers, increasing the hope for HGG therapy. We conducted a comprehensive search on PubMed, Scopus, Embase, and Web of Science databases to include relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Fifty-two papers were finally included (44 phase II and eight phase III clinical trials) and further divided into four different subgroups: 14 peptide vaccine trials, 15 dendritic cell vaccination (DCV) trials, six immune checkpoint inhibitor (ICI) trials, and 17 miscellaneous group trials that included both "active" and "passive" immunotherapies. In the last decade, immunotherapy created great hope to increase the survival of patients affected by HGGs; however, it has yielded mostly dismal results in the setting of phase III clinical trials. An in-depth analysis of these clinical results provides clues about common patterns that have led to failures at the clinical level and helps shape the perspective for the next generation of immunotherapies in neuro-oncology.
Topics: Humans; Glioma; Immunotherapy; Brain Neoplasms; Immune Checkpoint Inhibitors
PubMed: 38308708
DOI: 10.1007/s10072-024-07350-w