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Chinese Clinical Oncology Apr 2024The role of adjuvant radiotherapy (RT) after gross total resection (GTR) of the World Health Organization (WHO) grade II ependymoma is controversial. Therefore, we aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of adjuvant radiotherapy (RT) after gross total resection (GTR) of the World Health Organization (WHO) grade II ependymoma is controversial. Therefore, we aimed to compare the outcomes of adjuvant RT against observation after GTR of WHO grade II ependymoma. We also compared the outcomes of adjuvant RT against observation after subtotal resection (STR) of WHO grade II ependymoma and performed further subgroup analysis by age and tumor location.
METHODS
PubMed and Embase were systematically reviewed for studies published up till 25 November 2022. Studies that reported individual-participant data on patients who underwent surgery followed by adjuvant RT/observation for WHO grade II ependymoma were included. The exposure was whether adjuvant RT was administered, and the outcomes were recurrence and overall survival (OS). Subgroup analyses were performed by the extent of resection (GTR or STR), tumor location (supratentorial or infratentorial), and age at the first surgery (<18 or ≥18 years old).
RESULTS
Of the 4,647 studies screened, three studies reporting a total of 37 patients were included in the analysis. Of these 37 patients, 67.6% (25 patients) underwent GTR, and 51.4% (19 patients) underwent adjuvant RT. Adjuvant RT after GTR was not significantly associated with both recurrence (odds ratio =5.50; 95% confidence interval: 0.64-60.80; P=0.12) and OS (P=0.16). Adjuvant RT was also not significantly associated with both recurrence and OS when the cohort was analyzed as a whole and on subgroup analysis by age and tumor location. However, adjuvant RT was associated with significantly longer OS after STR (P=0.03) with the median OS being 6.33 years, as compared to 0.40 years for patients who underwent STR followed by observation.
CONCLUSIONS
Based on our meta-analysis of 37 patients, administration of adjuvant RT after GTR was not significantly associated with improvement in OS or recurrence in patients with WHO grade II ependymoma. However, due to the small number of patients included in the analysis, further prospective controlled studies are warranted.
Topics: Humans; Ependymoma; Radiotherapy, Adjuvant; Female; Male; Neoplasm Grading; World Health Organization
PubMed: 38644544
DOI: 10.21037/cco-23-136 -
Frontiers in Neurology 2024This study aimed to explore the prevalence and risk factors of early postoperative seizures in patients with glioma through meta-analysis.
OBJECTIVE
This study aimed to explore the prevalence and risk factors of early postoperative seizures in patients with glioma through meta-analysis.
METHODS
Case-control studies and cohort studies on the prevalence and risk factors of early postoperative seizures in glioma patients were retrieved from various databases including CNKI, Wanfang, VIP, PubMed, Embase, Cochrane Library, and Web of Science, and the retrieval deadline for the data was 1 April 2023. Stata15.0 was used to analyze the data.
RESULTS
This review included 11 studies consisting of 488 patients with early postoperative seizures and 2,051 patients without early postoperative seizures. The research findings suggest that the prevalence of glioma is complicated by seizures (ES = 19%, 95% confidence interval [CI] [14%-25%]). The results also indicated a history of seizures (RR = 1.94, 95% CI [1.76, 2.14], = 0.001), preoperative dyskinesia (RR = 3.13, 95% CI [1.20, 8.15], = 0.02), frontal lobe tumor (RR = 1.45, 95% CI [1.16, 1.83], = 0.001), pathological grade ≤2 (RR = 1.74, 95% CI [1.13, 2.67], = 0.012), tumor≥ 3 cm (RR = 1.70, 95% CI [1.18, 2.45], = 0.005), tumor resection (RR = 1.60, 95% CI [1.36, 1.88], = 0.001), tumor edema ≥ 2 cm (RR = 1.77, 95% CI [1.40, 2.25], = 0.001), and glioma cavity hemorrhage (RR=3.15, 95% CI [1.85, 5.37], = 0.001). The multivariate analysis results showed that a history of seizures, dyskinesia, tumor ≥3 cm, peritumoral edema ≥2 cm, and glioma cavity hemorrhage were indicated as risk factors for glioma complicated with early postoperative seizures.
SIGNIFICANCE
Based on the existing evidence, seizure history, dyskinesia, frontal lobe tumor, pathological grade ≤2, tumor ≥3 cm, partial tumor resection, edema around tumor ≥2 cm, and glioma cavity hemorrhage are indicated as risk factors for glioma complicated with early postoperative seizures.
PubMed: 38572493
DOI: 10.3389/fneur.2024.1356715 -
Frontiers in Surgery 2024Recently, non-technical skills (NTS) and teamwork in particular have been demonstrated to be essential in many jobs, in business as well as in medical specialties,...
BACKGROUND
Recently, non-technical skills (NTS) and teamwork in particular have been demonstrated to be essential in many jobs, in business as well as in medical specialties, including plastic, orthopedic, and general surgery. However, NTS and teamwork in neurosurgery have not yet been fully studied. We reviewed the relevant literature and designed a mock surgery to be used as a team-building activity specifically designed for scrub nurses and neurosurgeons.
METHODS
We conducted a systematic review by searching PubMed (Medline) and CINAHL, including relevant articles in English published until 15 July 2023. Then, we proposed a pilot study consisting of a single-session, hands-on, and cadaver-free activity, based on role play. Scrub nurses were administered the SPLINTS (Scrub Practitioners' List of Intraoperative Non-Technical Skills) rating form as a self-evaluation at baseline and 20-30 days after the simulation. During the experiment, surgeons and scrub nurses role-played as each other, doing exercises including a simulated glioma resection surgery performed on an advanced model of a cerebral tumor (Tumor Box, UpSurgeOn®) under an exoscope. At the end, every participant completed an evaluation questionnaire.
RESULTS
A limited number of articles are available on the topic. This study reports one of the first neurosurgical team-building activities in the literature. All the participating scrub nurses and neurosurgeons positively evaluated the simulation developed on a roleplay. The use of a physical simulator seems an added value, as the tactile feedback given by the model further helps to understand the actual surgical job, more than only observing and assisting. The SPLINTS showed a statistically significant improvement not only in "Communication and Teamwork" ( = 0.048) but also in "Situation Awareness" ( = 0.031).
CONCLUSION
Our study suggests that team-building activities may play a role in improving interprofessional teamwork and other NTS in neurosurgery.
PubMed: 38558881
DOI: 10.3389/fsurg.2024.1386887 -
BMC Neurology Mar 2024MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT...
BACKGROUND
MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.
METHODS
To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.
RESULTS
We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.
CONCLUSION
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Topics: Humans; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Glioma; Prognosis; Tumor Suppressor Proteins
PubMed: 38521933
DOI: 10.1186/s12883-024-03605-3 -
Frontiers in Neurology 2024Brain neoplasms and central nervous system (CNS) disorders, particularly gliomas, have shown a notable increase in incidence over the last three decades, posing...
INTRODUCTION
Brain neoplasms and central nervous system (CNS) disorders, particularly gliomas, have shown a notable increase in incidence over the last three decades, posing significant diagnostic and therapeutic challenges. MicroRNAs (miRNAs) have emerged as promising biomarkers due to their regulatory role in gene expression, offering potential enhancements in glioma diagnosis and prognosis.
METHODS
This systematic review and meta-analysis, adhering to PRISMA guidelines, included 25 studies for diagnostic accuracy and 99 for prognostic analysis, published until August 27th, 2023. Studies were identified through comprehensive searches of PubMed, Web of Science, and Scopus databases. Inclusion criteria encompassed peer-reviewed original research providing sensitivity, specificity, and area under the curve (AUC) for miRNAs in glioma diagnosis, as well as survival outcomes with hazard ratios (HRs) or mean survival.
RESULTS AND DISCUSSION
Meta-analysis demonstrated miRNAs' high diagnostic accuracy, with a pooled sensitivity of 0.821 (95% CI: 0.781-0.855) and specificity of 0.831 (95% CI: 0.792-0.865), yielding an AUC of 0.893. Subgroup analysis by specimen type revealed consistent accuracy across blood, cerebrospinal fluid (CSF), and tissue samples. Our results also showed miRNAs can be potential prognostic biomarkers. miRNAs showed significant associations with overall survival (OS) (pooled HR: 2.0221; 95% CI: 1.8497-2.2105), progression-free survival (PFS) (pooled HR: 2.4248; 95% CI: 1.8888-3.1128), and disease-free survival (DFS) (pooled HR: 1.8973; 95% CI: 1.1637-3.0933) in tissue specimens. These findings underscore miRNAs' potential as valuable biomarkers for improving glioma diagnosis and prognosis, offering insights for enhancing clinical decision-making and patient outcomes.
PubMed: 38487328
DOI: 10.3389/fneur.2024.1357321 -
Radiation Oncology (London, England) Mar 2024Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival...
PURPOSE/OBJECTIVE(S)
Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival outcomes. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemotherapy and radiation therapy (RT).
MATERIALS/METHODS
Following PRISMA guidelines, a systematic literature review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. A pooled analysis was performed using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS.
RESULTS
Ten of 104 identified studies met inclusion criteria, representing 1,718 patients. The lymphopenia cutoff value varied (400-1100 cells/uL) and as well as the timing of its onset. Studies were grouped as time-point (i.e., lymphopenia at approximately 2-months post-RT) or time-range (any lymphopenia occurrence from treatment-start to approximately 2-months post-RT. The mean overall pooled incidence of lymphopenia for all studies was 31.8%, and 11.8% vs. 39.9% for time-point vs. time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI 1.46-2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI 1.24-1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies.
CONCLUSION
These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between lymphopenia with OS in GBM patients, highlighting lymphopenia as a poor prognostic factor.
Topics: Humans; Glioblastoma; Temozolomide; Brain Neoplasms; Lymphopenia
PubMed: 38481255
DOI: 10.1186/s13014-023-02393-3 -
International Journal of Molecular... Mar 2024Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular... (Review)
Review
Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular pathogenesis and biology of this tumor in the past decade, the prognosis for GBM patients remains poor. GBM is characterized by aggressive biological behavior and high degrees of inter-tumor and intra-tumor heterogeneity. Increased understanding of the molecular and cellular heterogeneity of GBM may not only help more accurately define specific subgroups for precise diagnosis but also lay the groundwork for the successful implementation of targeted therapy. Herein, we systematically review the key achievements in the understanding of GBM molecular pathogenesis, mechanisms, and biomarkers in the past decade. We discuss the advances in the molecular pathology of GBM, including genetics, epigenetics, transcriptomics, and signaling pathways. We also review the molecular biomarkers that have potential clinical roles. Finally, new strategies, current challenges, and future directions for discovering new biomarkers and therapeutic targets for GBM will be discussed.
Topics: Humans; Glioblastoma; Pathology, Molecular; Brain Neoplasms; Biomarkers; Gene Expression Profiling; Biomarkers, Tumor
PubMed: 38474286
DOI: 10.3390/ijms25053040 -
Neuro-oncology Advances 2024The effect of exogenous hormone replacement therapy (HRT) and oral contraceptive pills (OCPs) on glioma risk in females is unclear despite numerous studies; hence, we...
BACKGROUND
The effect of exogenous hormone replacement therapy (HRT) and oral contraceptive pills (OCPs) on glioma risk in females is unclear despite numerous studies; hence, we conducted a meta-analysis to evaluate this relationship.
METHODS
Studies investigating the impact of exogenous female hormones on glioma risk were retrieved by searching 4 databases from inception until September 2022. Articles of any design, such as case-control and cohort studies, proving the relative risk (RR), odds ratio (OR), or hazard ratio were included. Summary OR values were calculated using a random effects model.
RESULTS
Both HRT and OCP use of any duration decreased the risk of developing glioma [HRT OR = 0.78, 95% CI 0.66-0.91, = .00; OCP: OR = 0.80, 95% CI 0.67-0.96, = .02]. When stratified by duration of use, HRT use >1 year significantly reduced glioma risk (<1 year: OR = 0.82, 95% CI 0.63-1.07, = 0.15; 1-5 years: OR = 0.79, 95% CI 0.67-0.92, = .00; 5-10 years: OR = 0.80, 95% CI 0.66-0.97, = .02; >10 years: OR = 0.69, 95% CI 0.54-0.88, = .00). In contrast, only OCP use for >10 years significantly reduced glioma risk (<1 year: OR = 0.72, 95% CI 0.49-1.05, = .09; 1-5 years: OR = 0.88, 95% CI 0.72-1.02, = .09; 5-10 years: OR = 0.85, 95% CI 0.65-1.1, = 0.21; >10 years: OR = 0.58, 95% CI 0.45-0.74, = .00).
CONCLUSIONS
Our pooled results strongly suggest that sustained HRT and OCP use is associated with reduced risk of glioma development.
PubMed: 38405204
DOI: 10.1093/noajnl/vdad167 -
Biomedicines Jan 2024Gliomas are aggressive brain tumors with poor prognosis even after surgical removal and radio-chemotherapy, stressing the urgency to find alternative therapies. Several... (Review)
Review
Gliomas are aggressive brain tumors with poor prognosis even after surgical removal and radio-chemotherapy, stressing the urgency to find alternative therapies. Several preclinical studies evaluating the anticancer effect of curcumin in animal models of glioma are reported, but a systematic review with meta-analysis of these studies, considering the different experimental conditions used, has not been made up to this date. A search in different databases (Pubmed, Web of Science, Scopus, and SciELO) following the PRISMA statement was conducted during November 2023 to systematically identify articles assessing the effect of curcumin in murine xenograft models of glioma and identified 15 articles, which were subdivided into 24 studies. Tumor volume before and after treatment with curcumin or vehicle was extracted and the efficacy of curcumin was evaluated by performing a random effects meta-analysis of the data. Publication bias and the impact of different experimental conditions on curcumin efficacy were assessed. Treatment with curcumin decreased tumor volume. Comparing curcumin with control groups, the overall weighted standardized difference in means was -2.079 (95% CI: -2.816 to -1.341; -value < 0.001). The curcumin effect was observed for different animal models, types of glioma cells, administration routes, and curcumin formulations. Publication bias was identified but does not invalidate curcumin's effectiveness. The findings suggest the potential therapeutic efficacy of curcumin against glioma.
PubMed: 38397870
DOI: 10.3390/biomedicines12020268 -
Medicine Feb 2024Deep learning techniques explain the enormous potential of medical image analysis, particularly in digital pathology. Concurrently, molecular markers have gained...
BACKGROUND
Deep learning techniques explain the enormous potential of medical image analysis, particularly in digital pathology. Concurrently, molecular markers have gained increasing significance over the past decade in the context of glioma patients, providing novel insights into diagnosis and more personalized treatment options. Deep learning combined with imaging and molecular analysis enables more accurate prognostication of patients, more accurate treatment plan proposals, and accurate biomarker (IDH) prediction for gliomas. This systematic study examines the development of deep learning techniques for IDH prediction using histopathology images, spanning the period from 2019 to 2023.
METHOD
The study adhered to the PRISMA reporting requirements, and databases including PubMed, Google Scholar, Google Search, and preprint repositories (such as arXiv) were systematically queried for pertinent literature spanning the period from 2019 to the 30th of 2023. Search phrases related to deep learning, digital pathology, glioma, and IDH were collaboratively utilized.
RESULTS
Fifteen papers meeting the inclusion criteria were included in the analysis. These criteria specifically encompassed studies utilizing deep learning for the analysis of hematoxylin and eosin images to determine the IDH status in patients with gliomas.
CONCLUSIONS
When predicting the status of IDH, the classifier built on digital pathological images demonstrates exceptional performance. The study's predictive effectiveness is enhanced with the utilization of the appropriate deep learning model. However, external verification is necessary to showcase their resilience and universality. Larger sample sizes and multicenter samples are necessary for more comprehensive research to evaluate performance and confirm clinical advantages.
Topics: Humans; Brain Neoplasms; Deep Learning; Glioma; Biomarkers; Isocitrate Dehydrogenase; Mutation; Magnetic Resonance Imaging; Multicenter Studies as Topic
PubMed: 38363910
DOI: 10.1097/MD.0000000000037150