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Seizure Feb 2018Gliomas, particularly low-grade gliomas (LGGs), are highly epileptogenic. Seizure is the most common presenting sign of LGG patients and significantly decreases their... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Gliomas, particularly low-grade gliomas (LGGs), are highly epileptogenic. Seizure is the most common presenting sign of LGG patients and significantly decreases their quality of life. Accordingly, there is a need for a better understanding of the mechanisms and risk factors of glioma-related epilepsy. The current study aimed to perform a comprehensive meta-analysis to investigate the correlation of isocitrate-dehydrogenase 1 (IDH1), an important molecular biomarker for glioma classification and prognosis, to preoperative seizure incidence in LGG.
METHODS
PUBMED, EMBASE, and Web of Science databases were searched for relevant studies. The odds ratio (OR) and corresponding 95% confidence interval (CI) were used as the primary measures to assess the correlation between IDH1 mutation and preoperative seizure incidence.
RESULTS
A total of 722 LGG patients, including 555 patients with IDH1 mutation and 167 patients with wild-type IDH1 were enrolled in the current meta-analysis. The pooled OR was 2.47 (95% CI 1.70-3.57, Z = 4.78, p < 0.01). No significant heterogeneity was observed among all included studies and no publication bias was identified.
CONCLUSION
The current meta-analysis identified that IDH1 mutation was correlated to a higher preoperative seizure incidence in LGG. This result would generate impetus for research on the mechanisms behind this correlation, and provide a new idea for the individualized treatment of glioma-related epilepsy.
Topics: Brain Neoplasms; Genetic Predisposition to Disease; Glioma; Humans; Incidence; Isocitrate Dehydrogenase; Seizures
PubMed: 29414139
DOI: 10.1016/j.seizure.2018.01.011 -
Frontiers in Immunology 2021Programmed cell death protein 1 (PD-1) can attenuate chimeric antigen receptor-T (CAR-T) cell-mediated anti-tumoral immune responses. In this regard, co-administration...
BACKGROUND
Programmed cell death protein 1 (PD-1) can attenuate chimeric antigen receptor-T (CAR-T) cell-mediated anti-tumoral immune responses. In this regard, co-administration of anti-PD-1 with CAR-T cells and PD-1 gene-editing of CAR-T cells have been suggested to disrupt this inhibitory axis. Herein, we aim to investigate the advantages and disadvantages of these two approaches and propose a novel strategy to ameliorate the prognosis of glioma patients.
METHODS
Scopus, Embase, and Web of Science were systematically searched to obtain relevant peer-reviewed studies published before March 7, 2021. Then, the current study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. The random-effect model was applied to evaluate the effect size of administrated agents on the survival of animal models bearing gliomas using RevMan version 5.4. The Cochran Q test and I were performed to assess the possible between-study heterogeneity. Egger's and Begg and Mazumdar's tests were performed to objectively assess potential asymmetry and publication bias using CMA version 2.
RESULTS
Anti-PD-1 can substantially increase the survival of animal models on second-generation CAR-T cells. Also, PD-1 knockdown can remarkably prolong the survival of animal models on third-generation CAR-T cells. Regardless of the CAR-T generations, PD-1 gene-edited CAR-T cells can considerably enhance the survival of animal-bearing gliomas compared to the conventional CAR-T cells.
CONCLUSIONS
The single-cell sequencing of tumoral cells and cells residing in the tumor microenvironment can provide valuable insights into the patient-derived neoantigens and the expression profile of inhibitory immune checkpoint molecules in tumor bulk. Thus, single-cell sequencing-guided fourth-generation CAR-T cells can cover patient-derived neoantigens expressed in various subpopulations of tumoral cells and inhibit related inhibitory immune checkpoint molecules. The proposed approach can improve anti-tumoral immune responses, decrease the risk of immune-related adverse events, reduce the risk of glioma relapse, and address the vast inter-and intra-heterogeneity of gliomas.
Topics: Animals; Brain Neoplasms; Gene Editing; Glioma; Humans; Immune Checkpoint Inhibitors; Immunotherapy, Adoptive; Mice; Precision Medicine; Programmed Cell Death 1 Receptor; Single-Cell Analysis
PubMed: 35126356
DOI: 10.3389/fimmu.2021.788211 -
Neurosurgery Aug 2022Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical utility, however, has not been standardized because the sensitivity and specificity of ctDNA remain undefined.
OBJECTIVE
To (1) review the primary literature about ctDNA in adults with glioma to compare the sensitivity and specificity of ctDNA in the cerebrospinal fluid vs the plasma and (2) to evaluate the effect of tumor grade on detection of ctDNA.
METHODS
PRISMA-guided systematic review and meta-analysis was performed using published studies that assessed ctDNA in either plasma or cerebrospinal fluid among adult patients with confirmed glioma. Summary receiver operating characteristic curves were generated using the Rücker-Schumacher method, and area under the curve (AUC) was calculated.
RESULTS
Meta-analysis revealed improved biomarker performance for CSF (AUC = 0.947) vs plasma (AUC = 0.741) ctDNA, although this did not reach statistical significance ( P = .141). Qualitative analysis revealed greater sensitivities among single-allele PCR and small, targeted next-generation sequencing panels compared with broader panels. It additionally demonstrated higher sensitivity of ctDNA detection in high-grade vs low-grade gliomas, although these analyses were limited by a lack of specificity reporting in many studies.
CONCLUSION
ctDNA seems to be a highly sensitive and specific noninvasive biomarker among adults with gliomas. To maximize its performance, CSF should be studied with targeted genetic analysis platforms, particularly in high-grade gliomas. Further studies on ctDNA are needed to define its clinical utility in diagnosis, prognostication, glioblastoma pseudoprogression, and other scenarios wherein neoadjuvant therapies may be considered.
Topics: Adult; Biomarkers, Tumor; Circulating Tumor DNA; Glioma; High-Throughput Nucleotide Sequencing; Humans; Mutation
PubMed: 35535984
DOI: 10.1227/neu.0000000000001982 -
Journal of Neurosurgery Jul 2023A cancer diagnosis is life altering and frequently associated with both acute and long-lasting psychosocial and behavioral distress for patients. The impact of a diffuse...
A cancer diagnosis is life altering and frequently associated with both acute and long-lasting psychosocial and behavioral distress for patients. The impact of a diffuse glioma diagnosis on mental health is an important aspect of the patient experience with their disease. This needs to be understood by neurosurgeons so these concerns can be appropriately addressed in a timely fashion and integrated into the multidisciplinary care of neuro-oncology patients. The relatively grave prognosis associated with diffuse gliomas, the morbidity associated with treatment, and the constant threat of developing a new neurological deficit all can negatively affect a patient's mental ability to cope and ultimately manifest in mental health disorders such as anxiety and depression. The objective of this systematic review was to describe the variety of behavioral health disorders patients may experience following a glioma diagnosis and discuss possible treatment options. The PubMed, Web of Science, Embase, and PsycINFO databases were searched through July 1, 2022, using broad search terms, which resulted in 5028 studies that were uploaded to Covidence systematic review software. Duplicates, non-English-language studies, and studies with irrelevant outcomes or incorrect design were removed (n = 3167). A total of 92 articles reporting behavioral health outcomes in brain tumor patients were categorized and extracted for associations with overall mental health, anxiety, depression, distress, stress, pharmacology, interventions, and mental health in caregivers. The authors identified numerous studies reporting the prevalence of mental health disorders and their negative influence in this population. However, there is a paucity of literature on therapeutic options for patients. Given the strong correlation between patient quality of life and mental well-being, there is a considerable need for early recognition and treatment of these behavioral health disorders to optimize everyday functioning for patients.
Topics: Humans; Quality of Life; Neurosurgeons; Mental Disorders; Mental Health; Glioma
PubMed: 36334288
DOI: 10.3171/2022.9.JNS221139 -
Genetics and Molecular Research : GMR Mar 2015Several studies have examined the association between excision repair cross-complementation group 1 (ERCC1) C8092A and ERCC2 Lys751Gln polymorphisms and glioma risk, but... (Meta-Analysis)
Meta-Analysis Review
Several studies have examined the association between excision repair cross-complementation group 1 (ERCC1) C8092A and ERCC2 Lys751Gln polymorphisms and glioma risk, but the results have been inconclusive. We conducted a meta-analysis of 12 studies to determine the association between ERCC1 rs3212986 and ERCC2 rs13181 genes and glioma susceptibility. We searched for relevant studies in both Chinese and English in PubMed, Web of Science, Cochrane Library, and EMBASE through January 1, 2014, and identified 3939 cases and 5407 controls. The results showed that individuals carrying the ERCC1 rs3212986 AA genotype had higher risk of glioma compared with the CC genotype, with a pooled odds ratio = 1.29, 95% confidence interval = 1.07-1.55. Subgroup analysis showed that the ERCC1 rs3212986 AA genotype was significantly associated with an increased risk of glioma in the Chinese population (odds ratio = 1.37, 95% confidence interval = 1.07-1.55), but no association in Caucasian Chinese. No significant association was observed between ERCC2 rs13181 polymorphisms and glioma risk. The results of our meta-analysis strongly suggested that the ERCC1 rs3212986 polymorphism was associated with a higher susceptibility to glioma, particularly in the Chinese population. Studies including a larger sample size and more specified information regarding pathological types of glioma are needed to confirm our results.
Topics: DNA-Binding Proteins; Endonucleases; Gene Frequency; Genetic Predisposition to Disease; Genotype; Glioma; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors; Xeroderma Pigmentosum Group D Protein
PubMed: 25867436
DOI: 10.4238/2015.March.31.17 -
Anticancer Research Oct 2016Historically, radiation oncologists have been cautious about re-irradiating brain tumors because of concerns about the risks of late central nervous system (CNS)... (Review)
Review
BACKGROUND
Historically, radiation oncologists have been cautious about re-irradiating brain tumors because of concerns about the risks of late central nervous system (CNS) toxicity, especially radionecrosis, that may occur several months to years following treatment. Today there are still limited prospective data addressing this approach.
MATERIALS AND METHODS
Systematic review of published trials reporting clinical results after re-irradiation of patients with different types of brain tumors was performed.
RESULTS
Data mainly related to glioblastoma, anaplastic glioma, medulloblastoma, ependymoma and meningioma have been published. Randomized studies are scarce. As in first-line scenarios, efficacy of radiotherapy is influenced by histology. Based on the reported outcomes, preliminary recommendations for dose/fractionation regimens can be given.
CONCLUSION
Re-irradiation of brain tumors is increasingly considered as our understanding of brain tolerance to radiation evolves and developments in radiation technology and imaging make highly accurate targeting of recurrent tumors possible. With developments in systemic therapy, further exploration of the role of re-irradiation on its own or in combination with novel agents is needed.
Topics: Animals; Brachytherapy; Brain Neoplasms; Central Nervous System; Combined Modality Therapy; Glioma; Humans; Meningioma; Neoplasm Recurrence, Local; Radiation Injuries; Re-Irradiation
PubMed: 27798857
DOI: 10.21873/anticanres.11067 -
Tumour Biology : the Journal of the... Jan 2014Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of glioma. However, the results from the studies... (Meta-Analysis)
Meta-Analysis Review
Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been suggested to be involved in the development of glioma. However, the results from the studies regarding the association between GSTP1 Ile105Val polymorphism and glioma risk have been inconsistent. Thus, we performed a meta-analysis to investigate this association. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using random or fixed effects model. Nine studies with 2,078 cases and 3,970 controls were finally included into this meta-analysis. The results suggested there was no association between GSTP1 Ile105Val polymorphism and glioma risk under recessive model (OR = 1.138, 95%CI = 0.966-1.341, Pheterogeneity = 0.088, P = 0.123). Subgroup analyses by ethnicity showed there was also no association between GSTP1 Ile105Val polymorphism and glioma risk in mixed populations under recessive model (OR = 1.199, 95%CI = 0.928-1.549, Pheterogeneity = 0.060, P = 0.166) and Caucasian populations (OR = 1.097, 95%CI = 0.885-1.360, Pheterogeneity = 0.186, P = 0.398). In conclusion, the meta-analysis suggests that there is no association between GSTP1 Ile105Val polymorphism and glioma risk. However, more well-designed and larger studies are needed to further assess this association.
Topics: Alleles; Amino Acid Substitution; Brain Neoplasms; Case-Control Studies; Genetic Association Studies; Genetic Predisposition to Disease; Glioma; Glutathione S-Transferase pi; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Publication Bias; Risk
PubMed: 23975366
DOI: 10.1007/s13277-013-1069-4 -
Association between Single Nucleotide Polymorphisms and Glioma Risk: A Systematic Literature Review.Cancer Investigation Mar 2020This study aimed to determine the main single nucleotide polymorphisms (SNPs) that are associated with an increased or decreased risk of glioma development in healthy...
This study aimed to determine the main single nucleotide polymorphisms (SNPs) that are associated with an increased or decreased risk of glioma development in healthy individuals. We conducted a systematic review of the articles published in English on the PUBMED database between January 2008 and December 2017. Our search resulted in a total of 743 articles; however, only 56 were included in this review. A total of 148 polymorphisms were found, which involved 64 different genes. The polymorphisms that were most associated with an increased risk of glioma development were polymorphic variants rs179782, rs13181, and rs3791679 of the genes XRCC1, ERCC2, and EFEMP1, respectively.
Topics: Brain Neoplasms; Extracellular Matrix Proteins; Genetic Association Studies; Genetic Predisposition to Disease; Glioma; Humans; Polymorphism, Single Nucleotide; X-ray Repair Cross Complementing Protein 1; Xeroderma Pigmentosum Group D Protein
PubMed: 31957502
DOI: 10.1080/07357907.2020.1719502 -
Cancer Aug 20165-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to... (Meta-Analysis)
Meta-Analysis Review
5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78. © 2016 American Cancer Society.
Topics: Aminolevulinic Acid; Brain Neoplasms; Glioma; Humans; Intraoperative Care; Magnetic Resonance Imaging; Neoplasm Grading; Neoplasm Recurrence, Local; Postoperative Care; Reproducibility of Results; Surgery, Computer-Assisted; Treatment Outcome
PubMed: 27183272
DOI: 10.1002/cncr.30088 -
Clinical Neurology and Neurosurgery Feb 2019The resection of insular gliomas remains a neurosurgical challenge due to the close proximity of functionally-important cortical, white matter tracts, and vasculature... (Meta-Analysis)
Meta-Analysis
The resection of insular gliomas remains a neurosurgical challenge due to the close proximity of functionally-important cortical, white matter tracts, and vasculature structures. More recently, the feasibility of resection has gained traction, however, there is a lack of consolidated neurological deficit metrics. Thus, the aim of this study was to determine the incidences of neurological deficits following insular glioma resection to better guide selection algorithms and resource allocations. Searches of seven electronic databases from inception to August 2018 were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted and pooled using meta-analysis of proportions. Meta-regression was used to identify potential sources of heterogeneity. Nineteen observational studies reported the neurological outcomes of 890 insular glioma patients. The pooled incidences of new temporary and permanent motor deficits were 11% (95% CI, 6-17%) and 4% (95% CI, 2-7%) respectively, and new temporary and permanent language deficits were 11% (95% CI, 6-17%) and 2% (95% CI, 0-4%) respectively. Single-surgeon series reported significantly lower incidences of both permanent motor (2% vs 7%; P < 0.001) and language (1% vs 3%; P = 0.03) deficits. The incidences of motor and language neurological deficits following insular glioma resection have been quantified, and will assist in determining the suitability and appropriateness of pursuing surgical resection for insular glioma. We note that permanent neurological deficits are lowest when reported by series describing outcomes of a single surgeon, indicating most optimal outcomes may be best achieved after intense training and/or greater experience.
Topics: Brain Neoplasms; Glioma; Humans; Incidence; Monitoring, Intraoperative; Neurosurgical Procedures; Postoperative Complications
PubMed: 30580067
DOI: 10.1016/j.clineuro.2018.12.013