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Clinical Neurology and Neurosurgery Sep 2018There is currently a lack of a well-formed consensus regarding the effects of depression on the survival of glioma patients. A more thorough understanding of such... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
There is currently a lack of a well-formed consensus regarding the effects of depression on the survival of glioma patients. A more thorough understanding of such effects may better highlight the importance of recognizing depressive symptoms in this patient population and guide treatment plans in the future.
OBJECTIVE
The aim of this meta-analysis was to study the effect of depression on glioma patients' survival.
METHODS
A meta-analysis was conducted according to the PRISMA guidelines. PubMed, Embase, and Cochrane databases were searched for studies that reported depression and survival among glioma patients through 11/06/2016. Both random-effects (RE) and fixed-effect (FE) models were used to compare survival outcomes in glioma patients with and without depression.
RESULTS
Out of 619 identified articles, six were selected for the meta-analysis. Using RE model, the various measures for survival outcomes displayed worsened outcomes for both high and low-grade glioma patients with depression compared to those without depression. For binary survival outcomes, the overall pooled risk ratio for survival was 0.70 (95% CI: 0.47, 1.04; 6 studies; I = 54.9%, P-heterogeneity = 0.05) for high grade gliomas (HGG) and 0.28 (95% CI: 0.04, 1.78; I = 0%, P-heterogeneity = 1.00; one study) for low grade gliomas (LGG) was. A sub-group analysis in the HGG group by depression timing (pre- versus post-operative) revealed no differences between depression and survival outcomes (P-interaction = 0.47). For continuous survival outcomes, no statistically significant difference was found among the high and low-grade glioma groups (P-interaction = 0.31). The standardized mean difference (SMD) in survival outcomes was -0.56 months (95%CI: -1.13, 0.02; 4 studies, I = 89.4%, P-heterogeneity < 0.01) for HGG and -1.69 months (95%CI: -3.26, -0.13; one study; I = 0%, P-heterogeneity = 1.00) for LGG. In patients with HGG, the pooled HR of death also showed a borderline significant increased risk of death among depressive patients (HR 1.42, 95% CI: 1.00, 2.01). Results using the FE model were not materially different.
CONCLUSIONS
Depression was associated with significantly worsened survival regardless of time of diagnosis, especially among patients with high-grade glioma.
Topics: Brain Neoplasms; Depression; Glioma; Humans; Neoplasm Grading; Patient Selection; Risk Factors
PubMed: 29957299
DOI: 10.1016/j.clineuro.2018.06.016 -
Cancer Science Sep 2018Glioma is the most common central nervous system tumor and associated with poor prognosis. Identifying effective diagnostic biomarkers for glioma is particularly... (Meta-Analysis)
Meta-Analysis Review
Glioma is the most common central nervous system tumor and associated with poor prognosis. Identifying effective diagnostic biomarkers for glioma is particularly important in order to guide optimizing treatment. MicroRNAs (miRNAs) have drawn much attention because of their diagnostic value in diverse cancers, including glioma. We summarized studies to identify the potential diagnostic values of miRNAs in glioma patients. We included articles reporting miRNAs for differentiation of glioma patients from controls. We calculated sensitivities, specificities, and area under the curves (AUC) of individual miRNA and miRNA panels. We found that overall sensitivity, specificity, and AUC of miRNAs in diagnosis of glioma were 85% (95% confidence interval [CI]: 0.81-0.89), 90% (95% CI 0.85-0.93), and 93% (95% CI 0.91-0.95), respectively. Meta-regression analysis showed that the detection of miRNAs expression in cerebrospinal fluid (CSF) and brain tissue largely improved the diagnostic accuracy. Likewise, panels of multiple miRNAs could enhance the pooled sensitivity. Moreover, AUC of miR-21 was 0.88, with 86% sensitivity and 94% specificity. This study demonstrated that miRNAs could function as potential diagnosis markers in glioma. Detection of miRNAs in CSF and brain tissue displays high accuracy in the diagnosis of glioma.
Topics: Biomarkers, Tumor; Brain; Brain Neoplasms; Glioma; Humans; MicroRNAs; Sensitivity and Specificity
PubMed: 29949235
DOI: 10.1111/cas.13714 -
Neuro-oncology Advances 2022A comprehensive review and description of the clinical features that impact prognosis for patients with diffuse hemispheric glioma, H3 G34-mutant (G34-DHG) is needed....
BACKGROUND
A comprehensive review and description of the clinical features that impact prognosis for patients with diffuse hemispheric glioma, H3 G34-mutant (G34-DHG) is needed. Understanding survival and prognostic features is paramount for clinical advancements and patient care.
METHODS
PubMed, Embase, and Google Scholar were searched for English articles published between January 1, 2012 and June 30, 2021. Eligible studies included patient(s) of any age diagnosed with an H3 G34-mutant brain tumor with at least one measure of survival or progression. Patient-level data were pooled for analyses. This study was prospectively registered in PROSPERO (CRD42021267764) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
RESULTS
Twenty-seven studies met the criteria with a total of 135 patients included. Median age at diagnosis was 15.8 years (interquartile range [IQR]: 13.3-22.0) with 90% having localized disease. Co-occurring alterations included mutation in 93%, mutation in 88%, and promoter methylation in 70%. Median time-to-progression was 10.0 months (IQR: 6.0-18.0) and median overall survival was 17.3 months (95% CI: 15.0 to 22.9). The median time from progression to death was 5.0 months (IQR: 3.0-11.7). Factors associated with survival duration were age, as patients ≥18 y/o demonstrated longer survival (hazard ratio [HR] =2.05, 95% CI: 1.16 to 3.62), and degree of upfront resection, as near or gross-total resection demonstrated longer survival compared to those with less than near-total resection (HR = 3.75, 95% CI: 2.11 to 6.62).
CONCLUSION
This systematic review highlights available clinical data for G34-DHG demonstrating poor outcomes and important prognostic features, while serving as a baseline for future research and clinical trials.
PubMed: 36105387
DOI: 10.1093/noajnl/vdac133 -
Frontiers in Surgery 2022Hemorrhage into optic pathway-hypothalamic glioma (OPHG) is rare. Variable clinical presentations and outcomes are associated with such pathology. We aim to present two... (Review)
Review
BACKGROUND
Hemorrhage into optic pathway-hypothalamic glioma (OPHG) is rare. Variable clinical presentations and outcomes are associated with such pathology. We aim to present two infants presented with OPHG and a systematic review of the literature.
METHODS
We describe two cases of infants presenting with sudden decreased vision, poor feeding, and irritability due to OPHG. Both patients underwent urgent craniotomy and subtotal resection followed by chemotherapy. We systematically reviewed the literature using PubMed, Google Scholar, and Embase. In addition, we included all English published reports for all ages discussing the optic pathway (optic nerve and optic chiasm) or hypothalamic glioma associated with hemorrhage from the year of the first reported case (1970) to January 2022.
RESULTS
Of 17,949, 44 articles met the inclusion criteria of this review. A total of 56 cases were described with a mean of 21.35 years (0.5-70), with the male gender 52% and the female gender 45%. The hemorrhage location was sellar/suprasellar in 43% cases. Histopathology of included cases was pilocytic astrocytoma in 41%, followed by pilomyxoid astrocytoma in 16% cases. The outcome was unfavorable; 37.5% cases showed improvement, whereas 18% cases resulted in death.
CONCLUSION
Apoplexy of the OPHG can be fatal and associated with poor outcomes. A systematic review of the literature has shown that younger age, pilocytic or pilomexyoid astrocytoma histopathology, and chiasmal/hypothalamic locations are associated with a higher risk of intertumoral hemorrhage and poor prognosis. Further genetic studies for OPHG may provide information for high-risk patients.
PubMed: 35733436
DOI: 10.3389/fsurg.2022.891556 -
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 -
International Journal of Molecular... Jun 2023Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state... (Review)
Review
Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy-namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories-clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets-and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.
Topics: Adult; Humans; Animals; Mice; Molecular Targeted Therapy; beta Catenin; Mutation; Glioma; Brain Neoplasms; Oligodendroglioma; Isocitrate Dehydrogenase
PubMed: 37445633
DOI: 10.3390/ijms241310456 -
Cellular and Molecular Neurobiology Nov 2023Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for... (Review)
Review
Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for diagnosis, follow- up and treatment. We propose a clinical utility score (CUS) for biomarkers in LGG that mirrors their clinical usefulness. We conducted a PRISMA review. We examined each biomarker classifying them by CUS and Level of Evidence (LOE). We identified four classes of biomarkers: (1). Circulating protein-(a) vitronectin discriminates LGG from HGG (Sn:98%, Sp:91%, CUS: 3, LOE: III), (b) CTLA-4 discriminates LGG from HGG, (cutoff: 220.43 pg/ml, Sn: 82%, Sp: 78%, CUS:3, LOE:III), (c) pre-operative TGF b1 predict astrocytoma (cutoff: 2.52 ng/ml, Sn: 94.9%, Sp: 100%, CUS:3, LOE:VI). (2). micro-RNA (miR)-(a) miR-16 discriminates between WHO IV and WHO II and III groups (AUC = 0.98, CUS:3, LOE: III), (b) miR-454-3p is higher in HGG than in LGG (p = 0.013, CUS:3, LOE: III), (c) miR-210 expression is related to WHO grades (Sn 83.2%, Sp 94.3%, CUS: 3, LOE: III). (3). Circulating DNA-(a) IDH1R132H mutation detected in plasma by combined COLD and digital PCR (Sn: 60%, Sp: 100%, CUS: 3, LOE: III). 4. Exosomes-(a) SDC1 serum levels could discriminate GBM from LGG (Sn: 71%, Sp: 91%, CUS: 2C, LOE: VI). Our investigation showed that miRs appear to have the highest clinical utility. The LOE of the studies assessed is generally low. A combined approach between different biomarkers and traditional diagnostics may be considered. We identified four main classes of biomarkers produced by LGG. We examined each biomarker, classifying them by clinical utility score (CUS) and level of evidence (LOE). Micro-RNA (miRs) appears to have the highest CUS and LOE.
Topics: Humans; Glioma; Brain Neoplasms; Biomarkers, Tumor; Liquid Biopsy; MicroRNAs; Neoplasm Grading
PubMed: 37704931
DOI: 10.1007/s10571-023-01406-9 -
Insights Into Imaging Jun 2022Molecular characterization plays a crucial role in glioma classification which impacts treatment strategy and patient outcome. Dynamic susceptibility contrast (DSC) and... (Review)
Review
BACKGROUND
Molecular characterization plays a crucial role in glioma classification which impacts treatment strategy and patient outcome. Dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) perfusion imaging have been suggested as methods to help characterize glioma in a non-invasive fashion. This study set out to review and meta-analyze the evidence on the accuracy of DSC and/or DCE perfusion MRI in predicting IDH genotype and 1p/19q integrity status.
METHODS
After systematic literature search on Medline, EMBASE, Web of Science and the Cochrane Library, a qualitative meta-synthesis and quantitative meta-analysis were conducted. Meta-analysis was carried out on aggregated AUC data for different perfusion metrics.
RESULTS
Of 680 papers, twelve were included for the qualitative meta-synthesis, totaling 1384 patients. It was observed that CBV, ktrans, Ve and Vp values were, in general, significantly higher in IDH wildtype compared to IDH mutated glioma. Meta-analysis comprising of five papers (totaling 316 patients) showed that the AUC of CBV, ktrans, Ve and Vp were 0.85 (95%-CI 0.75-0.93), 0.81 (95%-CI 0.74-0.89), 0.84 (95%-CI 0.71-0.97) and 0.76 (95%-CI 0.61-0.90), respectively. No conclusive data on the prediction of 1p/19q integrity was available from these studies.
CONCLUSIONS
Future research should aim to predict 1p/19q integrity based on perfusion MRI data. Additionally, correlations with other clinically relevant outcomes should be further investigated, including patient stratification for treatment and overall survival.
PubMed: 35670981
DOI: 10.1186/s13244-022-01230-7 -
Neuro-oncology Practice Feb 2023Histone deacetylase inhibitors (HDACi) including valproic acid (VPA) have the potential to improve radiotherapy (RT) efficacy and reduce treatment adverse events (AE)...
BACKGROUND
Histone deacetylase inhibitors (HDACi) including valproic acid (VPA) have the potential to improve radiotherapy (RT) efficacy and reduce treatment adverse events (AE) via epigenetic modification and radio-sensitization of neoplastic cells. This systematic review and meta-analysis aimed to assess the efficacy and AE associated with HDACi used as radio-sensitizers in adult solid organ malignancy patients.
METHODS
A systematic review utilized electronic searches of MEDLINE(Ovid), Embase(Ovid), The Cochrane Library, and the International Clinical Trials Registry Platform to identify studies examining the efficacy and AEs associated with HDACi treatment in solid organ malignancy patients undergoing RT. Meta-analysis was performed with overall survival (OS) reported as hazard ratios (HR) as the primary outcome measure. OS reported as median survival difference, and AEs were secondary outcome measures.
RESULTS
Ten studies reporting on the efficacy and/or AEs of HDACi in RT-treated solid organ malignancy patients met inclusion criteria. All included studies focused on HDACi valproic acid (VPA) in high-grade glioma patients, of which 9 studies ( = 6138) evaluated OS and 5 studies ( = 1055) examined AEs. The addition of VPA to RT treatment protocols resulted in improved OS (HR = 0.80, 95% CI 0.67-0.96). No studies focusing on non-glioma solid organ malignancy patients, or non-VPA HDACi met the inclusion criteria for this review.
CONCLUSIONS
This review suggests that glioma patients undergoing RT may experience prolonged survival due to HDACi VPA administration. Further randomized controlled trials are required to validate these findings. Additionally, more research into the use of HDACi radio-adjuvant treatment in non-glioma solid organ malignancies is warranted.
PubMed: 36659976
DOI: 10.1093/nop/npac078 -
Journal of Controlled Release :... Sep 2022Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated... (Review)
Review
Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated with glioma pathogenesis. Thus, miRNAs represent potential therapeutic agents for treating gliomas. However, miRNAs have not been established as part of the regular clinical armamentarium. This systemic review evaluates current molecular and pre-clinical studies with the aim of defining the most appealing supramolecular platform for administering therapeutic miRNA to patients with gliomas. An integrated analysis suggested that cationic lipid nanoparticles, functionalized with octa-arginine peptides, represent a potentially specific, practical, non-invasive intervention for treating gliomas. This supramolecular platform allows loading both hydrophilic (miRNA) and hydrophobic (anti-tumor drugs, like temozolomide) molecules. This systemic review is the first to describe miRNA delivery systems targeted to gliomas that integrate several types of molecules as active ingredients. Further experimental validation is warranted to confirm the practical value of miRNA delivery systems.
Topics: Arginine; Brain Neoplasms; Glioma; Humans; Liposomes; MicroRNAs; Nanoparticles; Peptides; Temozolomide
PubMed: 35905783
DOI: 10.1016/j.jconrel.2022.07.027