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Expert Reviews in Molecular Medicine Mar 2023Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18... (Review)
Review
Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in and settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.
Topics: Adult; Humans; Telomerase; Glioma; Brain Neoplasms; Glioblastoma; Genetic Therapy
PubMed: 36919343
DOI: 10.1017/erm.2023.6 -
Patient Education and Counseling May 2013Patients diagnosed with primary malignant glioma (PMG) face substantial challenges with poor prognosis, high symptom burden and care needs. This study aims to collate... (Review)
Review
OBJECTIVE
Patients diagnosed with primary malignant glioma (PMG) face substantial challenges with poor prognosis, high symptom burden and care needs. This study aims to collate current literature detailing the supportive and palliative care needs of patients with PMG and their carers, and to subject it to a novel approach of formal evaluation.
METHODS
Medline, EMBASE, CINAHL, PsychInfo were searched with core concepts: (1) glioma, (2) high-grade disease, and (3) palliative and supportive care needs. A narrative synthesis approach was undertaken including a quality appraisal of the 21 included studies.
RESULTS
Key themes related to the need for consistent well-delivered information around disease sequelae, treatment, and resources available; health service needs including a key professional identified to coordinate care; the need for psychological and social supports, and clear avenues of communication with treating professionals.
CONCLUSION
The literature remains limited in the number and quality of evidence with two level I, eight level II, and eleven level III studies. The findings call for improved information, communication and support practices to address the complexity and breadth of needs.
PRACTICE IMPLICATIONS
Specialised and individually tailored information, attention to clear, consistent communication and support practices should be incorporated into a future needs-based model of care.
Topics: Central Nervous System Neoplasms; Glioma; Health Services Needs and Demand; Humans; Palliative Care; Social Support
PubMed: 23218925
DOI: 10.1016/j.pec.2012.11.002 -
Neuro-oncology Mar 2023This systematic review provides updated insights, from the published literature in the past 5 years, based on the 2017 European Association of Neuro-Oncology (EANO)...
BACKGROUND
This systematic review provides updated insights, from the published literature in the past 5 years, based on the 2017 European Association of Neuro-Oncology (EANO) guidelines for palliative care in adults with malignant brain tumors. It provides an overview of palliative care options, including during the end-of-life phase for patients with malignant brain tumors.
METHODS
A systematic literature search was conducted from 2016 to 2021 focusing on four main topics: (1) symptom management, (2) caregiver needs, (3) early palliative care, and (4) care in the end-of-life phase. An international panel of palliative care experts in neuro-oncology synthesized the literature and reported the most relevant updates. A total of 140 articles were included.
RESULTS
New insights include that: Hippocampal avoidance and stereotactic radiosurgery results in a lower risk of neurocognitive decline in patients with brain metastases; levetiracetam is more efficacious in reducing seizures than valproic acid as first-line monotherapy antiseizure drug (ASD) in glioma patients; lacosamide and perampanel seem well-tolerated and efficacious add-on ASDs; and a comprehensive framework of palliative and supportive care for high-grade glioma patients and their caregivers was proposed. No pharmacological agents have been shown in randomized controlled trials to significantly improve fatigue or neurocognition.
CONCLUSIONS
Since the 2017 EANO palliative care guidelines, new insights have been reported regarding symptom management and end-of-life care, however, most recommendations remain unchanged. Early palliative care interventions are essential to define goals of care and minimize symptom burden in a timely fashion. Interventional studies that address pain, fatigue, and psychiatric symptoms as well as (the timing of) early palliative care are urgently needed.
Topics: Humans; Adult; Terminal Care; Brain Neoplasms; Glioma; Death; Fatigue
PubMed: 36271873
DOI: 10.1093/neuonc/noac216 -
Oncotarget Feb 2018Malignant glioma is a devastating disease affecting both adults and children with limited treatment strategies. Pre-clinical animal studies are critical to the...
Malignant glioma is a devastating disease affecting both adults and children with limited treatment strategies. Pre-clinical animal studies are critical to the development and planning of novel treatment designs for human clinical trials. Topoisomerases has been a target of interest in the treatment of high grade gliomas, such as glioblastoma, in the past years. Here we assess pre-clinical glioma literature with the aim to identify predictive variables that favour treatment outcomes from topoisomerase inhibition. Data was extracted from 90 experimental comparisons, this was divided based on available survival ( = 61) and tumor volume ( = 29) data. The meta-analysis revealed that the overall effect of topoisomerase inhibition prolonged survival by a factor of 1.33 (95% CI: 1.23-1.43) and reduced tumor growth by a factor of 3.21 (95% CI: 1.99-5.88), with considerable between-study heterogeneity. Multivariable meta-regression identified glioma model, type of control, route of drug administration and drug of choice to be predictive of improved survival outcome. Publication bias assessment by contour-enhanced funnel plots, Egger's regression test and trim and fill analysis showed evidence of publication bias in all studies. This study identified multiple study design factors that should be taken into consideration to improve the translation of pre-clinical investigation of topoisomerase inhibition into clinical use.
PubMed: 29541421
DOI: 10.18632/oncotarget.24334 -
Thrombosis Research Nov 2022Patients with malignancies including malignant gliomas have a relatively high risk for venous thromboembolism (VTE). Recent evidence has linked isocitrate dehydrogenase... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with malignancies including malignant gliomas have a relatively high risk for venous thromboembolism (VTE). Recent evidence has linked isocitrate dehydrogenase (IDH) mutation with reduced VTE risk in malignant glioma. This meta-analysis aims to quantify the association of IDH mutation status with risks of VTE in patients with glioma.
METHODS
We searched PubMed, Google Scholar, Medline OVID, Cochrane library, Cumulative Index to Nursing and Allied Health Literature databases to identify relevant studies. The overall odd ratio (OR) was pooled using the random-effects model. We evaluated the statistical heterogeneity using Cochran's Q statistics and I tests. We performed subgroup analyses according to age, tumor, study design, and study quality.
RESULTS
A total of 2600 patients from 8 studies were included in the meta-analysis. Patients with IDH mutant-type gliomas had a significantly lower risk of VTE (OR: 0.21, 95 % confidence interval [CI]: 0.09-0.46, I2 = 34 %) compared to patients with IDH wild-type gliomas. Among high-grade (III and IV) glioma, VTE events in IDH-mutant gliomas occurred with an OR of 0.28 (95 % CI: 0.14-0.53). No statistically significant decrease in the VTE risk was observed in grade II gliomas with IDH mutation compared to IDH wild-type gliomas, as indicated by the OR of 0.60 (95 % CI: 0.17-2.11).
CONCLUSION
IDH mutation is significantly associated with 79 % lower risk of VTE among patients with high-grade glioma compared to IDH wild-type. Our findings suggest the potential utility of IDH mutation status regarding thromboprophylaxis, and the need for further studies to elucidate the mechanism of the association.
Topics: Anticoagulants; Brain Neoplasms; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Venous Thromboembolism
PubMed: 36088710
DOI: 10.1016/j.thromres.2022.08.029 -
BioMed Research International 2019Different microRNAs (miRs) have been demonstrated to relate with the outcome of glioma patients, while the conclusions are inconsistent. We perform a meta-analysis to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Different microRNAs (miRs) have been demonstrated to relate with the outcome of glioma patients, while the conclusions are inconsistent. We perform a meta-analysis to clarify the relationship between different miRs and prognosis of glioma.
METHODS
Related studies were retrieved from PubMed, Embase, and Cochrane Library. Pooled hazard ratios (HRs) of different miRs expression for survival and 95% confidence intervals (CIs) were calculated using random-effects model.
RESULTS
A total of 15 miRs with 4708 glioma patients were ultimately included. Increased expression of miR-15b (HR, 1.584; 95% CI, 1.199-2.092), 21 (HR, 1.591; 95% CI, 1.278-1.981), 148a (HR, 1.122; 95% CI, 1.023-1.231), 196 (HR, 1.877; 95% CI, 1.033-3.411), 210 (HR, 1.251; 95% CI, 1.010-1.550), and 221 (HR, 1.269; 95% CI, 1.054-1.527) or decreased expression of miR-106a (HR, 0.809; 95% CI, 0.655-0.998) and 124 (HR, 0.833; 95% CI, 0.729-0.952) was correlated with poor outcome of glioma patients.
CONCLUSIONS
miR-15b, 21, 148a, 196, 210, 221, 106a, and 124 are valuable biomarkers for the prognosis of glioma which might be used in clinical settings.
Topics: Biomarkers, Tumor; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Glioma; Humans; MicroRNAs; Prognosis; Survival Analysis
PubMed: 31032345
DOI: 10.1155/2019/4015969 -
Neuro-oncology Jul 2015There is growing evidence that antitumor treatment contributes to better seizure control in low-grade glioma patients. We performed a systematic review of the current... (Review)
Review
There is growing evidence that antitumor treatment contributes to better seizure control in low-grade glioma patients. We performed a systematic review of the current literature on seizure outcome after radiotherapy and chemotherapy and evaluated the association between seizure outcome and radiological response. Twenty-four studies were available, of which 10 described seizure outcome after radiotherapy and 14 after chemotherapy. All studies demonstrated improvements in seizure outcome after antitumor treatment. Eight studies reporting on imaging response in relation to seizure outcome showed a seizure reduction in a substantial part of patients with stable disease on MRI. Seizure reduction may therefore be the only noticeable effect of antitumor treatment. Our findings demonstrate the clinical relevance of monitoring seizure outcome after radiotherapy and chemotherapy, as well as the potential role of seizure reduction as a complementary marker of tumor response in low-grade glioma patients.
Topics: Brain Neoplasms; Glioma; Humans; Seizures; Treatment Outcome
PubMed: 25813469
DOI: 10.1093/neuonc/nov032 -
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 -
Neurosurgery Jan 2024Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions.
METHODS
MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day).
RESULTS
Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD] = MD = 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30).
CONCLUSION
Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.
Topics: Humans; Brain Neoplasms; Wakefulness; Retrospective Studies; Glioma; Craniotomy; Seizures
PubMed: 37489887
DOI: 10.1227/neu.0000000000002612 -
Journal of Clinical Neuroscience :... Jul 2021Glioma is the most common primary intraparenchymal tumor of the brain and the 5-year survival rate of high-grade glioma is poor. Magnetic resonance imaging (MRI) is...
Glioma is the most common primary intraparenchymal tumor of the brain and the 5-year survival rate of high-grade glioma is poor. Magnetic resonance imaging (MRI) is essential for detecting, characterizing and monitoring brain tumors but definitive diagnosis still relies on surgical pathology. Machine learning has been applied to the analysis of MRI data in glioma research and has the potential to change clinical practice and improve patient outcomes. This systematic review synthesizes and analyzes the current state of machine learning applications to glioma MRI data and explores the use of machine learning for systematic review automation. Various datapoints were extracted from the 153 studies that met inclusion criteria and analyzed. Natural language processing (NLP) analysis involved keyword extraction, topic modeling and document classification. Machine learning has been applied to tumor grading and diagnosis, tumor segmentation, non-invasive genomic biomarker identification, detection of progression and patient survival prediction. Model performance was generally strong (AUC = 0.87 ± 0.09; sensitivity = 0.87 ± 0.10; specificity = 0.0.86 ± 0.10; precision = 0.88 ± 0.11). Convolutional neural network, support vector machine and random forest algorithms were top performers. Deep learning document classifiers yielded acceptable performance (mean 5-fold cross-validation AUC = 0.71). Machine learning tools and data resources were synthesized and summarized to facilitate future research. Machine learning has been widely applied to the processing of MRI data in glioma research and has demonstrated substantial utility. NLP and transfer learning resources enabled the successful development of a replicable method for automating the systematic review article screening process, which has potential for shortening the time from discovery to clinical application in medicine.
Topics: Algorithms; Artificial Intelligence; Brain Neoplasms; Glioma; Humans; Machine Learning; Magnetic Resonance Imaging; Neural Networks, Computer; Neuroimaging; Neurosurgical Procedures; Support Vector Machine
PubMed: 34119265
DOI: 10.1016/j.jocn.2021.04.043