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Journal of Cancer Research and Clinical... Jan 2024Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive... (Review)
Review
BACKGROUND
Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive biomarker associated with improved overall survival (OS). In response to the clinical need, recent studies have focused on the development of non-invasive artificial intelligence (AI)-based methods for MGMT estimation. In this systematic review, we not only delve into the technical aspects of these AI-driven MGMT estimation methods but also emphasize their profound clinical implications. Specifically, we explore the potential impact of accurate non-invasive MGMT estimation on GBM patient care and treatment decisions.
METHODS
Employing a PRISMA search strategy, we identified 33 relevant studies from reputable databases, including PubMed, ScienceDirect, Google Scholar, and IEEE Explore. These studies were comprehensively assessed using 21 diverse attributes, encompassing factors such as types of imaging modalities, machine learning (ML) methods, and cohort sizes, with clear rationales for attribute scoring. Subsequently, we ranked these studies and established a cutoff value to categorize them into low-bias and high-bias groups.
RESULTS
By analyzing the 'cumulative plot of mean score' and the 'frequency plot curve' of the studies, we determined a cutoff value of 6.00. A higher mean score indicated a lower risk of bias, with studies scoring above the cutoff mark categorized as low-bias (73%), while 27% fell into the high-bias category.
CONCLUSION
Our findings underscore the immense potential of AI-based machine learning (ML) and deep learning (DL) methods in non-invasively determining MGMT promoter methylation status. Importantly, the clinical significance of these AI-driven advancements lies in their capacity to transform GBM patient care by providing accurate and timely information for treatment decisions. However, the translation of these technical advancements into clinical practice presents challenges, including the need for large multi-institutional cohorts and the integration of diverse data types. Addressing these challenges will be critical in realizing the full potential of AI in improving the reliability and accessibility of MGMT estimation while lowering the risk of bias in clinical decision-making.
Topics: Humans; Glioblastoma; Artificial Intelligence; Reproducibility of Results; DNA Methylation; Brain Neoplasms; DNA Modification Methylases; DNA Repair Enzymes; DNA; Tumor Suppressor Proteins
PubMed: 38291266
DOI: 10.1007/s00432-023-05566-5 -
BMC Cancer Jan 2024Central nervous system (CNS) tumors are the most common solid tumors in children and the leading cause of cancer-related death in the latter. Currently, the incidence...
BACKGROUND
Central nervous system (CNS) tumors are the most common solid tumors in children and the leading cause of cancer-related death in the latter. Currently, the incidence rate exceeds that of leukemia and ranks first in the incidence of malignant tumors in children.
METHODS
The epidemiological data on childhood CNS tumors were collected from the Chinese Cancer Registry Annual Report. The annual percent change (APC) of incidence and mortality-rate changes were estimated via Joinpoint regression. Due to a lack of pertinent data, we performed a system review on the clinical-pathological characteristics in Chinese publications.
RESULTS
There was no significant increase in the incidence rate (APC: -0.1, 95% CI: -1.5 to 1.3), but there was a significant increase in the mortality rate (APC: 1.8, 95% CI: 0.3 to 3.4) for childhood CNS tumors. In the subgroup analysis, there were significant increases in both the incidence and mortality rates in rural areas (APC in the incidence: 6.2, 95% CI: 2.4 to 10.2; APC in mortality: 4.4, 95% CI: 0.4 to 8.4). The most common location and type of childhood CNS were, respectively, the cerebral hemisphere (25.5%, 95% CI: 21.7% to 29.4%) and astrocytomas (26.8%, 95% CI: 23.9% to 29.6%).
CONCLUSIONS
The epidemiological trends, and the relevant prediction, highlighted the need to pay continual attention to childhood CNS tumors, and the clinicopathology evinced its own distinctive characteristics. Timely detection and effective treatment must be further promoted regarding childhood CNS tumors with a view to decreasing the disease burden, especially in rural areas.
Topics: Child; Humans; Central Nervous System Neoplasms; China; Incidence; Leukemia; Registries
PubMed: 38281032
DOI: 10.1186/s12885-024-11883-w -
Radiology. Artificial Intelligence Jan 2024Purpose To perform a systematic review and meta-analysis assessing the predictive accuracy of radiomics in the noninvasive determination of isocitrate dehydrogenase )... (Meta-Analysis)
Meta-Analysis
Purpose To perform a systematic review and meta-analysis assessing the predictive accuracy of radiomics in the noninvasive determination of isocitrate dehydrogenase ) status in grade 4 and lower-grade diffuse gliomas. Materials and Methods A systematic search was performed in the PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases for relevant articles published between January 1, 2010, and July 7, 2021. Pooled sensitivity and specificity across studies were estimated. Risk of bias was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2, and methods were evaluated using the radiomics quality score (RQS). Additional subgroup analyses were performed according to tumor grade, RQS, and number of sequences used (PROSPERO ID: CRD42021268958). Results Twenty-six studies that included 3280 patients were included for analysis. The pooled sensitivity and specificity of radiomics for the detection of mutation were 79% (95% CI: 76, 83) and 80% (95% CI: 76, 83), respectively. Low RQS scores were found overall for the included works. Subgroup analyses showed lower false-positive rates in very low RQS studies (RQS < 6) (meta-regression, = -1.9; = .02) compared with adequate RQS studies. No substantial differences were found in pooled sensitivity and specificity for the pure grade 4 gliomas group compared with the all-grade gliomas group (81% and 86% vs 79% and 79%, respectively) and for studies using single versus multiple sequences (80% and 77% vs 79% and 82%, respectively). Conclusion The pooled data showed that radiomics achieved good accuracy performance in distinguishing mutation status in patients with grade 4 and lower-grade diffuse gliomas. The overall methodologic quality (RQS) was low and introduced potential bias. Neuro-Oncology, Radiomics, Integration, Application Domain, Glioblastoma, IDH Mutation, Radiomics Quality Scoring Published under a CC BY 4.0 license.
Topics: Humans; Isocitrate Dehydrogenase; Radiomics; Glioma; Glioblastoma; Mutation
PubMed: 38231039
DOI: 10.1148/ryai.220257 -
World Neurosurgery Mar 2024Glioblastoma (GBM) is an aggressive tumor known for its poor prognosis. Despite extensive research into its molecular and clinical aspects, the current management... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glioblastoma (GBM) is an aggressive tumor known for its poor prognosis. Despite extensive research into its molecular and clinical aspects, the current management strategies have shown limited efficacy in improving survival rate. Despite some preclinical studies exploring the combination of temozolomide (TMZ) with biguanides such as metformin (MET) and others, the potential benefits of this combination remain uncertain. The aim of this study is to evaluate the overall survival (OS) in GBM murine-models treated with a combination of TMZ + biguanide compared to those treated with TMZ alone.
METHODS
We systematically searched Medline, Embase, and Lilacs databases for studies comparing TMZ + biguanide versus TMZ alone in GBM models and reporting OS data. The mean difference (MD) with 95% confidence interval and random-effects model was adopted.
RESULTS
Nine studies were included in this systematic review. The meta-analysis comprised 6 studies involving 85 rat-models, with 45 subjects undergoing combined-treatment. GBM-murine models treated with TMZ + biguanide exhibited notably superior OS rates compared to those who received TMZ alone, showing an MD of 21.0 days (6.9-35.0). Within the subgroup of orthotopic models, the OS was also significantly better in combination-therapy with an MD of 23.7 days (6.5-40.9). Similarly, in the subgroup where MET was used as biguanide therapy, TMZ + MET demonstrated a significant increase in OS, with an MD of 27.4 days (6.0-48.8). In immunocompromised models, the combination-therapy also exhibited higher survival rates, with an MD of 13 days (9.4-16.6).
CONCLUSIONS
This systematic review and meta-analysis provide compelling evidence regarding the beneficial effects of TMZ + biguanide in GBM models compared with TMZ alone, resulting in a significant improvement in OS.
Topics: Humans; Mice; Rats; Animals; Temozolomide; Glioblastoma; Antineoplastic Agents, Alkylating; Brain Neoplasms; Metformin
PubMed: 38184227
DOI: 10.1016/j.wneu.2024.01.006 -
Journal of Neuro-oncology Jan 2024Glioblastomas, the most common primary malignant brain tumors in adults, still hold poor prognosis. Corticosteroids, such as dexamethasone, are usually prescribed to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Glioblastomas, the most common primary malignant brain tumors in adults, still hold poor prognosis. Corticosteroids, such as dexamethasone, are usually prescribed to reduce peritumoral edema and limit neurological symptoms, although potential detrimental effects of these drugs have been described. The present meta-analysis aimed to explore the association of dexamethasone with overall survival (OS) and progression free survival (PFS) in patients with newly diagnosed glioblastoma.
METHODS
PubMed, Cochrane Library, Embase, and ClinicalTrials.gov were searched for pertinent studies following the Preferred Reporting Items of Systematic Review and Meta-Analysis checklist. Pooled multivariable-adjusted hazard ratios (HR) for OS and PFS and their associated 95% confidence intervals (CIs) were calculated using the random-effects model and the heterogeneity among studies was assessed using I. The quality of evidence was assessed using the GRADE criteria.
RESULTS
Seven studies were included, pooling data of 1,257 patients, with age varying from 11 to 81 years. Glioblastoma patients on pre- or peri-operative dexamethasone were associated with a significantly poorer overall survival (HR: 1.33, 95% CI: 1.15, 1.55; 7 studies; I: 59.9%) and progression free survival (HR: 1.77, 95% CI: 1.05, 2.97; 3 studies; I: 71.1%) compared to patients not on dexamethasone. The quality of evidence was moderate for overall survival and low for progression free survival.
CONCLUSION
Dexamethasone appeared to be associated with poor survival outcomes of glioblastoma patients.
Topics: Adult; Humans; Child; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Glioblastoma; Progression-Free Survival; Dexamethasone; Disease-Free Survival
PubMed: 38151699
DOI: 10.1007/s11060-023-04549-3 -
Brain Sciences Dec 2023(1) Background: Glioblastoma (GBM) is categorized as a grade IV astrocytoma by the World Health Organization (WHO), representing the most aggressive and prevalent form... (Review)
Review
(1) Background: Glioblastoma (GBM) is categorized as a grade IV astrocytoma by the World Health Organization (WHO), representing the most aggressive and prevalent form of glioma. It presents a significant clinical challenge, with limited treatment options and poor prognosis. This systematic review evaluates the efficacy and safety of various nanotherapy approaches for GBM and explores future directions in tumor management. Nanomedicine, which involves nanoparticles in the 1-100 nm range, shows promise in improving drug delivery and targeting tumor cells. (2) Methods: Following PRISMA guidelines, a systematic search of databases including Google Scholar, NCBI PubMed, Cochrane Library, and ClinicalTrials.gov was conducted to identify clinical trials on GBM and nanomedicine. The primary outcome measures were median overall survival, progression-free survival, and quality of life assessed through Karnofsky performance scores. The safety profile was assessed by adverse events. (3) Results: The analysis included 225 GBM patients, divided into primary and recurrent sub-populations. Primary GBM patients had a median overall survival of 6.75 months, while recurrent GBM patients had a median overall survival of 9.7 months. The mean PFS period was 2.3 months and 3.92 months in primary GBM and recurrent GBM patients, respectively. Nanotherapy showed an improvement in quality of life, with KPS scores increasing after treatment in recurrent GBM patients. Adverse events were observed in 14.2% of patients. Notably, Bevacizumab therapy exhibited better survival outcomes but with a higher incidence of adverse events. (4) Conclusions: Nanotherapy offers a modest increase in survival with fewer severe side effects. It shows promise in improving the quality of life, especially in recurrent GBM patients. However, it falls short in terms of overall survival compared to Bevacizumab. The heterogeneous nature of treatment protocols and reporting methods highlights the need for standardized multicenter trials to further evaluate the potential of nanomedicine in GBM management.
PubMed: 38137175
DOI: 10.3390/brainsci13121727 -
Journal of Neuro-oncology Dec 2023Surgical resection of glioblastoma (GBM) remains a cornerstone in the current treatment paradigm. The postoperative evolution of hydrocephalus necessitating... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgical resection of glioblastoma (GBM) remains a cornerstone in the current treatment paradigm. The postoperative evolution of hydrocephalus necessitating ventriculoperitoneal shunting (VPS) continues to be defined. Correspondingly the objective of this study was to aggregate pertinent metadata to better define the clinical course of VPS for hydrocephalus following glioblastoma surgery in light of contemporary management.
METHODS
Searches of multiple electronic databases from inception to November 2023 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. Outcomes were pooled by random-effects meta-analyses where possible.
RESULTS
A total of 12 cohort studies satisfied all selection criteria, describing a total of 6,098 glioblastoma patients after surgery with a total of 261 (4%) of patients requiring postoperative VPS for hydrocephalus. Meta-analysis demonstrated the estimated pooled rate of symptomatic improvement following VPS was 78% (95% CI 66-88), and the estimated pooled rate of VPS revision was 24% (95% CI 16-33). Pooled time from index glioblastoma surgery to VPS surgery was 4.1 months (95% CI 2.8-5.3), and pooled survival time for index VPS surgery was 7.3 months (95% CI 5.4-9.4). Certainty of these outcomes were limited by the heterogenous and palliative nature of postoperative glioblastoma management.
CONCLUSIONS
Of the limited proportion of glioblastoma patients requiring VPS surgery for hydrocephalus after index surgery, 78% patients are expected to show symptom improvement, and 24% can expect to undergo revision surgery. An individualized approach to each patient is required to optimize both index glioblastoma and VPS surgeries to account for anatomy and goals of care given the poor prognosis of this tumor overall.
Topics: Humans; Glioblastoma; Hydrocephalus; Ventriculoperitoneal Shunt; Cohort Studies; Disease Progression; Retrospective Studies; Treatment Outcome
PubMed: 38112893
DOI: 10.1007/s11060-023-04538-6 -
Neurosurgical Review Dec 2023Intradural spinal tumors present significant challenges due to involvement of critical motor and sensory tracts. Achieving maximal resection while preserving functional... (Meta-Analysis)
Meta-Analysis Review
Intradural spinal tumors present significant challenges due to involvement of critical motor and sensory tracts. Achieving maximal resection while preserving functional tissue is therefore crucial. Fluorescence-guided surgery aims to improve resection accuracy and is well studied for brain tumors, but its efficacy has not been fully assessed for spinal tumors. This meta-analysis aims to delineate the efficacy of fluorescence guidance in intradural spinal tumor resection. The authors performed a systematic review in four databases. We included studies that have utilized fluorescence agents, 5-aminolevulinic acid (5-ALA) or sodium fluorescein, for the resection of intradural spinal tumors. A meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 12 studies involving 552 patients undergoing fluorescence-guided intradural spinal tumor resection were included. Meningiomas demonstrated a 98% fluorescence rate and were associated with a homogenous florescence pattern; however, astrocytomas had variable fluorescence rate with pooled proportion of 70%. There was no significant difference in gross total resection (GTR) rates between fluorescein and 5-ALA (94% vs 84%, p = .22). Pre-operative contrast enhancement was significantly associated with intraoperative fluorescence with fluorescein. Intramedullary tumors with positive intraoperative fluorescence were significantly associated with higher GTR rates (96% vs 73%, p = .03). Utilizing fluorescence guidance during intradural spinal tumor resection holds promise of improving intraoperative visualization for specific intradural spinal tumors. Meningiomas and ependymomas have the highest fluorescence rates especially with sodium fluorescein; on the other hand, astrocytomas have variable fluorescence rates with no superiority of either agent. Positive fluorescence of intramedullary tumors is associated with a higher degree of resection.
Topics: Humans; Spinal Neoplasms; Fluorescein; Fluorescence; Meningioma; Spinal Cord Neoplasms; Astrocytoma; Aminolevulinic Acid; Meningeal Neoplasms
PubMed: 38085385
DOI: 10.1007/s10143-023-02230-x -
World Neurosurgery Feb 2024Currently, arterial spin labeling (ASL) and amide proton transfer (APT) imaging have shown potential for distinguishing glioblastoma from brain metastases. Thus, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, arterial spin labeling (ASL) and amide proton transfer (APT) imaging have shown potential for distinguishing glioblastoma from brain metastases. Thus, a meta-analysis was conducted to investigate this further.
METHODS
An extensive and comprehensive search was conducted in 6 English and Chinese databases according to predefined inclusion and exclusion criteria, encompassing data up to July 2023. Data from eligible literature were extracted, and bivariate models were employed to calculate pooled sensitivities, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve.
RESULTS
The meta-analysis included 11 articles. For ASL, the pooled sensitivity was 0.77 (95% confidence interval [CI], 0.63-0.87), and the pooled specificity was 0.87 (95% CI, 0.77-0.93). The pooled PLR was 5.89 (95% CI, 2.97-11.69), the pooled NLR was 0.26 (95% CI, 0.15-0.47), the pooled DOR was 22.33 (95% CI, 6.89-72.34), and AUC was 0.90 (95% CI, 0.87-0.92). For APT imaging, the pooled sensitivity was 0.78 (95% CI, 0.70-0.85), and the pooled specificity was 0.86 (95% CI, 0.77-0.92). The pooled PLR was 5.51 (95% CI, 3.24-9.37), the pooled NLR was 0.25 (95% CI, 0.17-0.37), the pooled DOR was 21.99 (95% CI, 10.28-47.03), and the AUC was 0.90 (95% CI, 0.87-0.92).
CONCLUSIONS
This meta-analysis suggest that both ASL and APT imaging exhibit high accuracy in distinguishing between glioblastoma and brain metastasis.
Topics: Humans; Glioblastoma; Protons; Spin Labels; Brain Neoplasms; ROC Curve; Sensitivity and Specificity
PubMed: 38072160
DOI: 10.1016/j.wneu.2023.12.023 -
Journal of Clinical Neuroscience :... Jan 2024Primary brain tumors have the potential to present a substantial health hazard, ultimately resulting in unforeseen fatalities. Despite the enhanced comprehension of many... (Review)
Review
OBJECTIVE
Primary brain tumors have the potential to present a substantial health hazard, ultimately resulting in unforeseen fatalities. Despite the enhanced comprehension of many diseases, the precise prediction of disease progression continues to pose a significant challenge. The objective of this study is to investigate cases of unexpected mortality resulting from primary brain tumors and analyze the variables that contribute to such occurrences.
METHODS
This systematic review explores research on individuals diagnosed with primary brain tumors who experienced unexpected deaths. It uses PRISMA standards and searches PubMed, Google Scholar, and Scopus. Variables considered include age, gender, symptoms, tumor type, WHO grade, postmortem findings, time of death - time taken from first medical presentation or hospital admission to death, comorbidity, and risk factors.
RESULTS
This study examined 46 studies to analyze patient-level data from 76 individuals with unexpected deaths attributed to intracranial lesions, deliberately excluding colloid cysts. The cohort's age distribution showed an average age of 37 years, with no significant gender preference. Headache was the most common initial symptom. Astrocytomas, meningiomas, and glioblastoma were the most common lesions, while the frontal lobe, temporal lobe, and cerebellum were common locations. Meningiomas and astrocytomas showed faster deaths within the first hour of hospital admission.
CONCLUSION
The etiology of unforeseen fatalities resulting from cerebral tumors elucidates an intricate and varied phenomenon. Although unexpected deaths account for a very tiny proportion of total fatalities, it is probable that their actual occurrence is underestimated as a result of underreporting and misdiagnosis.
Topics: Humans; Adult; Colloid Cysts; Meningioma; Death, Sudden; Glioblastoma; Meningeal Neoplasms; Brain Neoplasms
PubMed: 38029695
DOI: 10.1016/j.jocn.2023.11.022