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Neurology India 2022Seizures often herald the clinical appearance of glioma. Temozolomide (TMZ) is the first-line chemotherapeutic agent that has been used to treat glioma. (Review)
Review
BACKGROUND
Seizures often herald the clinical appearance of glioma. Temozolomide (TMZ) is the first-line chemotherapeutic agent that has been used to treat glioma.
OBJECTIVE
We conducted a systematic review to determine seizure outcomes in glioma patients treated with TMZ.
METHODS AND MATERIAL
We searched EMBASE and PubMed databases (January 1, 2003-August 26, 2021) by using search terms closely related to glioma, seizure, and temozolomide. Titles, abstracts, and full texts were screened and selected using previously established inclusion and exclusion criteria. The research team members reviewed potential articles and reached a consensus on the final articles to be included.
RESULTS
Nine studies containing data from three continents met our inclusion criteria. From several descriptive studies on low-grade gliomas (LGGs), the percentage of patients with partial seizure control after TMZ treatment ranged from 29% to 89.7%, and the percentage of patients with complete seizure control after TMZ ranged from 19.4% to 72%. In a retrospective cohort study of patients with LGGs, there was a marked difference in decreased seizure frequency between patients receiving TMZ and those who did not receive TMZ. In a randomized trial, TMZ seemed to have little effect on seizure control in elderly patients with glioblastoma.
CONCLUSIONS
At present, there are few high-quality and well-designed clinical studies on TMZ for gliomas-related seizures. In terms of the literature included in this review, TMZ has an inhibitory effect on epilepsy. More randomized controlled trials are needed to elucidate the clinical benefits of TMZ in the treatment of gliomas-related seizures.
Topics: Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Glioma; Humans; Randomized Controlled Trials as Topic; Retrospective Studies; Seizures; Temozolomide
PubMed: 35864610
DOI: 10.4103/0028-3886.349588 -
CNS Neuroscience & Therapeutics Oct 2022Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM immunotherapy prognosis and investigate the potential predictors.
METHODS
A quantitative meta-analysis was conducted using the random-effects model. Several potential factors were also reviewed qualitatively.
RESULTS
A total of 39 clinical trials were included after screening 1317 papers. Patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation [hazard ratio (HR) for overall survival (OS) = 2.30, p < 0.0001; HR for progression-free survival (PFS) = 2.10, p < 0.0001], gross total resection (HR for OS = 0.70, p = 0.02; HR for PFS = 0.56, p = 0.004), and no baseline steroid use (HR for OS = 0.52, p = 0.0002; HR for PFS = 0.61, p = 0.02) had a relatively significant favorable OS and PFS following immunotherapy. Patients with a Karnofsky Performance Status score < 80 (HR = 1.73, p = 0.0007) and undergoing two prior relapses (HR = 2.08, p = 0.003) were associated with worse OS. Age, gender, tumor programmed death-ligand 1 expression, and history of chemotherapy were not associated with survival outcomes. Notably, immunotherapy significantly improved the OS among patients undergoing two prior recurrences (HR = 0.40, p = 0.008) but not among patients in any other subgroups, as opposed to non-immunotherapy.
CONCLUSION
Several factors were associated with prognostic outcomes of GBM patients receiving immunotherapy; multiple recurrences might be a candidate predictor. More marker-driven prospective studies are warranted.
Topics: Brain Neoplasms; DNA Methylation; DNA Modification Methylases; Glioblastoma; Humans; Immunotherapy; Neoplasm Recurrence, Local; Prognosis
PubMed: 35822692
DOI: 10.1111/cns.13915 -
Clinical Neurology and Neurosurgery Aug 2022High-grade gliomas cause cognitive impairment in those who suffer from them. However, there is a lack of precise data describing the cognitive deficit that occurs in... (Review)
Review
INTRODUCTION
High-grade gliomas cause cognitive impairment in those who suffer from them. However, there is a lack of precise data describing the cognitive deficit that occurs in this population, which would allow to better focus neuropsychological evaluations and make better clinical decisions in favor of the patient's recovery and quality of life. For this purpose, a systematic review of the literature was carried out to search for studies on neurocognitive alterations in patients with malignant brain tumors.
MATERIALS AND METHODS
The systematic review was conducted under the criteria of the PRISMA guideline for reporting systematic review and meta-analysis reports, with a search of the PubMed database (MEDLINE). Descriptive and analytical observational studies between 2015 and 2020 were considered.
RESULTS
506 articles were identified, of which 16 met the inclusion criteria and were selected in the qualitative synthesis and described in the manuscript.
CONCLUSIONS
High-grade gliomas cause significant alterations in cognitive domains such as language, attention, memory, empathy and executive functions. However, more studies focused on describing the neuropsychological alterations in this population are needed in order to make better clinical treatment and rehabilitation decisions.
Topics: Adult; Brain Neoplasms; Cognition; Cognitive Dysfunction; Glioma; Humans; Observational Studies as Topic; Quality of Life
PubMed: 35662053
DOI: 10.1016/j.clineuro.2022.107296 -
Contrast Media & Molecular Imaging 2022Meningioma, glioma, and metastases are the most common intracranial tumors in clinical practice. In order to improve the prognosis of patients, timely diagnosis and... (Meta-Analysis)
Meta-Analysis
Meningioma, glioma, and metastases are the most common intracranial tumors in clinical practice. In order to improve the prognosis of patients, timely diagnosis and early treatment are crucial. Hydrogen proton magnetic resonance spectroscopy (1H-MRS) imaging can noninvasively display the biochemical information of tissues and has been applied to identify and diagnose intracranial tumors. We want to comprehensively evaluate 1H-MRS identify and diagnose intracranial tumors by meta-analysis. Some databases such as PubMed and Cochrane Library were used to systematically search articles that were about identifying and diagnosing intracranial tumors with 1H-MRS. Then, weighted mean difference (WMD) was used as an effect size to conduct meta-analysis. There are altogether nine articles, including 533 patients. Results of meta-analysis: The Cho/Cr and Cho/NAA ratios in the LGG group were significantly lower than those in the HGG group (WMD = -0.69, 95% CI (-0.92, -0.45), < 0.001, WMD = -0.76, 95% CI (-1.03, -0.48), < 0.001). The Cho/Cr ratio of tumor and peritumor in the HGG group was significantly different from that in the metastasis group (0.68, 95% CI (-1.27, 2.62), < 0.001, WMD = 0.94, 95% CI (0.41, 1.47), < 0.001). There was no significant difference in the tumor and peritumor NAA/Cr ratio between the HGG group and metastasis group (WMD = -0.64, 95% CI (-1.63, 0.34), =0.31, WMD = -0.22, 95% CI (-0.59, 0.15), =0.24). 1H-MRS can provide metabolic information of different intracranial tumors and can effectively diagnose and differentiate glioma and metastasis. 1H-MRS can also provide a reliable basis for the classification of glioma, and has certain clinical application value.
Topics: Brain Neoplasms; Diagnosis, Differential; Glioma; Humans; Hydrogen; Meningeal Neoplasms; Proton Magnetic Resonance Spectroscopy
PubMed: 35655732
DOI: 10.1155/2022/7242192 -
Journal of Medical Imaging and... Sep 2022Chemotherapy and radiotherapy can produce treatment-related effects, which may mimic tumour progression. Advances in Artificial Intelligence (AI) offer the potential to... (Meta-Analysis)
Meta-Analysis Review
Machine learning imaging applications in the differentiation of true tumour progression from treatment-related effects in brain tumours: A systematic review and meta-analysis.
INTRODUCTION
Chemotherapy and radiotherapy can produce treatment-related effects, which may mimic tumour progression. Advances in Artificial Intelligence (AI) offer the potential to provide a more consistent approach of diagnosis with improved accuracy. The aim of this study was to determine the efficacy of machine learning models to differentiate treatment-related effects (TRE), consisting of pseudoprogression (PsP) and radiation necrosis (RN), and true tumour progression (TTP).
METHODS
The systematic review was conducted in accordance with PRISMA-DTA guidelines. Searches were performed on PubMed, Scopus, Embase, Medline (Ovid) and ProQuest databases. Quality was assessed according to the PROBAST and CLAIM criteria. There were 25 original full-text journal articles eligible for inclusion.
RESULTS
For gliomas: PsP versus TTP (16 studies, highest AUC = 0.98), RN versus TTP (4 studies, highest AUC = 0.9988) and TRE versus TTP (3 studies, highest AUC = 0.94). For metastasis: RN vs. TTP (2 studies, highest AUC = 0.81). A meta-analysis was performed on 9 studies in the gliomas PsP versus TTP group using STATA. The meta-analysis reported a high sensitivity of 95.2% (95%CI: 86.6-98.4%) and specificity of 82.4% (95%CI: 67.0-91.6%).
CONCLUSION
TRE can be distinguished from TTP with good performance using machine learning-based imaging models. There remain issues with the quality of articles and the integration of models into clinical practice. Future studies should focus on the external validation of models and utilize standardized criteria such as CLAIM to allow for consistency in reporting.
Topics: Artificial Intelligence; Brain Neoplasms; Diagnostic Imaging; Glioma; Humans; Machine Learning
PubMed: 35599360
DOI: 10.1111/1754-9485.13436 -
Frontiers in Immunology 2022Glioblastoma (GBM) is the most common malignant brain tumor in adults, and immunotherapies and genetic therapies for GBM have evolved dramatically over the past decade,... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor in adults, and immunotherapies and genetic therapies for GBM have evolved dramatically over the past decade, but GBM therapy is still facing a dilemma due to the high recurrence rate. The inflammatory microenvironment is a general signature of tumors that accelerates epigenetic changes in GBM and helps tumors avoid immunological surveillance. GBM tumor cells and glioma-associated microglia/macrophages are the primary contributors to the inflammatory condition, meanwhile the modification of epigenetic events including DNA methylation, non-coding RNAs, and histone methylation and deacetylases involved in this pathological process of GBM, finally result in exacerbating the proliferation, invasion, and migration of GBM. On the other hand, histone deacetylase inhibitors, DNA methyltransferases inhibitors, and RNA interference could reverse the inflammatory landscapes and inhibit GBM growth and invasion. Here, we systematically review the inflammatory-associated epigenetic changes and regulations in the microenvironment of GBM, aiming to provide a comprehensive epigenetic profile underlying the recognition of inflammation in GBM.
Topics: Brain Neoplasms; Epigenesis, Genetic; Glioblastoma; Humans; Inflammation; Tumor Microenvironment
PubMed: 35572545
DOI: 10.3389/fimmu.2022.869307 -
World Journal of Surgical Oncology May 2022Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of...
BACKGROUND
Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM, and for this purpose, it focuses primarily on developmental gliogenic processes. It also focuses on the impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons.
METHODS
Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, and astrocytogenic genes.
RESULTS
The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate-specific genes to keep the cells differentiated in their specific cell types such as p300, BMP, HOPX, and NRSF/REST. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, and hey1. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300, and then GFAP, leading to upregulation of nestin, SHH, NF-κB, and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression.
CONCLUSION
Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, and TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, and ASCL1. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR, and others.
Topics: Brain Neoplasms; Carcinogenesis; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Janus Kinases; NF-kappa B; Neoplastic Stem Cells; Neurogenesis; SOXC Transcription Factors; STAT Transcription Factors; Signal Transduction
PubMed: 35538578
DOI: 10.1186/s12957-022-02602-5 -
European Radiology Oct 2022Radiomics is a promising avenue in non-invasive characterisation of diffuse glioma. Clinical translation is hampered by lack of reproducibility across centres and...
OBJECTIVES
Radiomics is a promising avenue in non-invasive characterisation of diffuse glioma. Clinical translation is hampered by lack of reproducibility across centres and difficulty in standardising image intensity in MRI datasets. The study aim was to perform a systematic review of different methods of MRI intensity standardisation prior to radiomic feature extraction.
METHODS
MEDLINE, EMBASE, and SCOPUS were searched for articles meeting the following eligibility criteria: MRI radiomic studies where one method of intensity normalisation was compared with another or no normalisation, and original research concerning patients diagnosed with diffuse gliomas. Using PRISMA criteria, data were extracted from short-listed studies including number of patients, MRI sequences, validation status, radiomics software, method of segmentation, and intensity standardisation. QUADAS-2 was used for quality appraisal.
RESULTS
After duplicate removal, 741 results were returned from database and reference searches and, from these, 12 papers were eligible. Due to a lack of common pre-processing and different analyses, a narrative synthesis was sought. Three different intensity standardisation techniques have been studied: histogram matching (5/12), limiting or rescaling signal intensity (8/12), and deep learning (1/12)-only two papers compared different methods. From these studies, histogram matching produced the more reliable features compared to other methods of altering MRI signal intensity.
CONCLUSION
Multiple methods of intensity standardisation have been described in the literature without clear consensus. Further research that directly compares different methods of intensity standardisation on glioma MRI datasets is required.
KEY POINTS
• Intensity standardisation is a key pre-processing step in the development of robust radiomic signatures to evaluate diffuse glioma. • A minority of studies compared the impact of two or more methods. • Further research is required to directly compare multiple methods of MRI intensity standardisation on glioma datasets.
Topics: Artificial Intelligence; Glioma; Humans; Magnetic Resonance Imaging; Reference Standards; Reproducibility of Results
PubMed: 35486171
DOI: 10.1007/s00330-022-08807-2 -
World Neurosurgery Aug 2022Atypical teratoid/rhabdoid tumor (ATRT) is a rare malignant neoplasm in the pediatric population. ATRT is characterized by rhabdoid cells combined with the loss of... (Review)
Review
The Impact of Surgical Resection and Adjuvant Therapy on Survival in Pediatric Patients with Atypical Teratoid/Rhabdoid Tumor: Systematic Review and Pooled Survival Analysis.
BACKGROUND
Atypical teratoid/rhabdoid tumor (ATRT) is a rare malignant neoplasm in the pediatric population. ATRT is characterized by rhabdoid cells combined with the loss of either the INI1 (integrase interactor 1) or BRG1 (Brahma-related gene-1) protein.
OBJECTIVE
To systematically review and analyze patient and tumor characteristics, prognosis, and impact of treatment on survival in pediatric patients with ATRT confirmed by alterations in INI1 or BRG1. This systematic review is the first to include only pediatric cases of ATRT confirmed with either INI1 or BRG1 alterations.
METHODS
MEDLINE was searched using the terms "atypical teratoid/rhabdoid tumor" AND "paediatric/pediatric." Cases were included if confirmed by loss of INI1 or BRG1. The extracted dataset was analyzed using descriptive statistics, log-rank test, and Kaplan-Meier survival analysis via SPSS.
RESULTS
A total of 38 articles were included in this study. The average age at diagnosis was 3 years. The most common locations reported are the supratentorial region and cerebral hemispheres. Ninety-three patients were reported to show evidence of dissemination. The average overall survival was 29 months. A significant difference in survival was noted between the tumor location groups, particularly worse outcomes for patients with spinal ATRT (P < 0.001). Extent of resection and adjuvant therapy were significant for survival (χ = 10.107, P = 0.018 and χ = 20.38, P < 0.0001, respectively).
CONCLUSIONS
ATRT of the central nervous system in pediatric populations is a rare neoplasm associated with a poor prognosis in most patients. Future studies should be directed to find a standardized treatment protocol.
Topics: Central Nervous System Neoplasms; Child; Humans; Neoplasms, Neuroepithelial; Rhabdoid Tumor; Survival Analysis; Teratoma
PubMed: 35470083
DOI: 10.1016/j.wneu.2022.04.073 -
International Journal of Molecular... Apr 2022Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular... (Review)
Review
Despite the multidisciplinary management in the treatment of glioblastomas, the average survival of GBM patients is still 15 months. In recent years, molecular biomarkers have gained more and more importance both in the diagnosis and therapy of glial tumors. At the same time, it has become clear that non neoplastic cells, which constitute about 30% of glioma mass, dramatically influence tumor growth, spread, and recurrence. This is the main reason why, in recent years, scientific research has been focused on understanding the function and the composition of tumor microenvironment and its role in gliomagenesis and recurrence. The aim of this review is to summarize the most recent discovery about resident microglia, tumor-associated macrophages, lymphocytes, and the role of extracellular vesicles and their bijective interaction with glioma cells. Moreover, we reported the most recent updates about new therapeutic strategies targeting immune system receptors and soluble factors. Understanding how glioma cells interact with non-neoplastic cells in tumor microenvironment is an essential step to comprehend mechanisms at the base of disease progression and to find new therapeutic strategies for GBM patients. However, no significant results have yet been obtained in studies targeting single molecules/pathways; considering the complex microenvironment, it is likely that only by using multiple therapeutic agents acting on multiple molecular targets can significant results be achieved.
Topics: Brain Neoplasms; Glioblastoma; Glioma; Humans; Macrophages; Microglia; Tumor Microenvironment
PubMed: 35456984
DOI: 10.3390/ijms23084166