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Tomography (Ann Arbor, Mich.) Aug 2023Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the... (Meta-Analysis)
Meta-Analysis Review
Intraoperative Fluorophores: An Update on 5-Aminolevulinic Acid and Sodium Fluorescein in Resection of Tumors of the Central Nervous System and Metastatic Lesions-A Systematic Review and Meta-Analysis.
INTRODUCTION
Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the morbidity and mortality of the surgery. One area of recent interest has been the use of intraoperative fluorophores for tumor visualization such as 5-aminolevulinic acid (5-ala) and sodium fluorescein. We performed a systematic review and meta-analysis on the utility of fluorophore administration and EOR with each fluorophore to update the current literature.
METHODS
We conducted a systematic review and meta-analysis on the use of intraoperative 5-ala or fluorescein between 2021 and 2023 using the PubMed, SCOPUS, and WOS databases. The initial search yielded 8688 results. After inclusion and exclusion criteria were met, 44 studies remained for review. A meta-analysis was performed to compare the EOR between studies for each fluorophore and to compare the presence of intraoperative fluorescence by tumor type. Odds ratios (OR) were calculated for gross total resection (GTR), and two-way ANOVA tests were performed to compare rates of intraoperative fluorescence by fluorophore and tumor type.
RESULTS
In all groups except low-grade glioma, fluorescence was present after 5-ala administration; fluorescence was present for all groups after fluorescein administration. Two-way ANOVA analysis for both fluorophores demonstrated no statistically significant difference in presence of fluorescence between type of tumor resected. Meta-analysis of EOR did show a higher, but not significant, rate of GTR in the 5-ala group compared to controls (OR = 1.29, 95% CI = 0.49; 3.37). In the fluorescein group, there were statistically significant higher odds of GTR compared to the control group (OR = 2.10, 95% CI = 1.43; 3.10, I = 0%).
CONCLUSIONS
Both 5-ala and sodium fluorescein demonstrated intraoperative fluorescence among various tumor types in both cranial and spinal tumors, as well as efficacy in improving EOR. Both fluorophores merit further investigation for use in surgery of CNS tumors.
Topics: Humans; Fluorescein; Aminolevulinic Acid; Levulinic Acids; Glioma
PubMed: 37736977
DOI: 10.3390/tomography9050124 -
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 -
Reviews in the Neurosciences Feb 2021Vascular endothelial growth factor (VEGF) has a crucial role in the angiogenesis of various tumors, including glioma. As the levels of VEGF would change in patients with... (Meta-Analysis)
Meta-Analysis Review
Vascular endothelial growth factor (VEGF) has a crucial role in the angiogenesis of various tumors, including glioma. As the levels of VEGF would change in patients with glioma, we conducted the current systematic review and meta-analysis to more clearly determine the VEGF level alterations in different grades of glioma. PubMed and Scopus databases were sensitively searched for all the possible keywords addressing glioma and VEGF. Case-control and cohort studies on human subjects, which measured VEGF levels were eligible to be included in the study. Out of a total number of 3,612 studies, 22 studies were included and 12 studies entered the meta-analysis. This review revealed that serum levels of VEGF in glioma patients were 1.56 pg/dL higher compared to healthy controls ( = 0.05). Besides, immunohistochemistry (IHC) measurement of VEGF in surgical biopsies indicated significant difference in these two groups as well ( = 0.02). Yet, there was not a significant difference between patients with low-grade gliomas (World Health Organization (WHO) grades I-II, LGG) and those with high-grade gliomas (WHO grades III-IV, HGG) ( = 0.43). The results of this systematic review and meta-analysis demonstrate that VEGF levels would significantly increase in glioma, and therefore, could be potentially considered as a biomarker for this cancer.
Topics: Brain Neoplasms; Glioma; Humans; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 33125340
DOI: 10.1515/revneuro-2020-0062 -
Cells Apr 2022Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival.... (Review)
Review
Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival. These tumors are highly heterogeneous, having complex interactions among different cells within the tumor and with the tumor microenvironment. One of the main challenges in the neuro-oncology field is achieving optimal conditions to evaluate a tumor's molecular genotype and phenotype. In this respect, the zebrafish biological model is becoming an excellent alternative for studying carcinogenic processes and discovering new treatments. This review aimed to describe the results of xenotransplantation of patient-derived CNS tumors in zebrafish models. The reviewed studies show that it is possible to maintain glioblastoma and neuroblastoma primary cell cultures and transplant the cells into zebrafish embryos. The zebrafish is a suitable biological model for understanding tumor progression and the effects of different treatments. This model offers new perspectives in providing personalized care and improving outcomes for patients living with central nervous system tumors.
Topics: Animals; Central Nervous System Neoplasms; Glioblastoma; Humans; Neuroblastoma; Tumor Microenvironment; Zebrafish
PubMed: 35406768
DOI: 10.3390/cells11071204 -
Oncology (Williston Park, N.Y.) Mar 2023Glioblastoma is the most common primary neoplasm of the central nervous system. Standard treatment includes surgery with maximum safe resection and radiotherapy plus...
BACKGROUND
Glioblastoma is the most common primary neoplasm of the central nervous system. Standard treatment includes surgery with maximum safe resection and radiotherapy plus concomitant and adjuvant chemotherapy; however, almost invariably, tumor relapse occurs. We aimed to describe signaling pathways and molecular mechanisms present in tumor relapse of glioblastoma.
METHODS
This systematic review followed the PRISMA guidelines. We searched the PubMed, EMBASE and Web of Science databases. We included studies that enrolled patients 15 years or older with a diagnosis of glioblastoma according to Louis criteria and focused on signaling pathways and molecular mechanisms present in tumor relapse of glioblastoma. The outcome of interest was progression-free survival.
RESULTS
We identified 1470 articles; 31 met the inclusion criteria. From each publication, we obtained the associated markers O-6-methylguanine-DNA methyltransferase, isocitrate dehydrogenase, mRNA, epidermal growth factor receptor (EGFR), p53, and others. All publications were evaluated with the Q-Genie checklist tool for quality assessment.
CONCLUSIONS
We identified a wide variety of signaling pathways and molecular processes that are involved in glioblastoma relapse. This diversity would explain intra- and intertumor heterogeneity, treatment evasion, and relapse. However, only a few molecular processes have robust evidence for clinical utility.
Topics: Humans; Glioblastoma; Brain Neoplasms; Chemotherapy, Adjuvant; Recurrence; Signal Transduction
PubMed: 36961958
DOI: 10.46883/2023.25920986 -
World Neurosurgery Mar 2023Laser interstitial thermal therapy (LITT) is a minimally invasive treatment option for intracranial tumors that are challenging to treat via traditional methods;... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Laser interstitial thermal therapy (LITT) is a minimally invasive treatment option for intracranial tumors that are challenging to treat via traditional methods; however, its safety and efficacy are not yet well validated in the literature. The objectives of the study were to assess the available evidence of the indications and adverse events (AEs) of LITT and 1-year progression-free survival and 1-year overall survival in the treatment of primary and secondary brain tumors.
METHODS
A comprehensive literature search was conducted through the databases PubMed, Embase, and the Cochrane Library until October 2021. Comparative and descriptive studies, except for case reports, were included in the meta-analysis. Separate analyses by tumor type (high-grade gliomas, including World Health Organization grade 4 astrocytomas [which include glioblastomas] as a specific subgroup; low-grade gliomas; and brain metastases) were conducted. Pooled effect sizes and their 95% confidence intervals (CI) were generated via random-effects models.
RESULTS
Forty-five studies met the inclusion criteria, yielding 826 patients for meta-analysis. There were 829 lesions in total, of which 361 were classified as high-grade gliomas, 116 as low-grade gliomas, 337 as metastatic brain tumors, and 15 as nonglial tumors. Indications for offering LITT included deep/inaccessible tumor (12 studies), salvage therapy after failed radiosurgery (9), failures of ≥2 treatment options (3), in pediatric patients (4), patient preference (1); indications were nonspecific in 12 studies. Pooled incidence of all (minor or major) procedure-related AEs was 30% (95% CI, 27%-40%) for all tumors. Pooled incidence of neurologic deficits (minor or major) was 16% (12%-22%); postprocedural edema 14% (8%-22%); seizure 6% (4%-9%); hematoma 20% (14%-29%); deep vein thrombosis 19% (11%-30%); hydrocephalus 8% (5%-12%); and wound infection 5% (3%-7%). One-year progression-free survival was 18.6% (11.3%-29.0%) in high-grade gliomas, 16.9% (11.6%-24.0%) among the grade 4 astrocytomas; and 51.2% (36.7%-65.5%) in brain metastases. One-year overall survival was 43.0% (36.0%-50.0%) in high-grade glioma, 45.9% (95% CI, 37.9%-54%) in grade 4 astrocytomas; 93.0% (42.3%-100%) in low-grade gliomas, and 56.3% (47.0%-65.3%) in brain metastases.
CONCLUSIONS
New neurologic deficits and postprocedural edema were the most reported AEs after LITT, albeit mostly transient. This meta-analysis provides the best statistical estimates of progression and survival outcomes based on the available information. LITT is generally a safe procedure for selected patients, and future well-designed comparative studies on its outcomes versus the current standard of care should be performed.
Topics: Humans; Child; Laser Therapy; Brain Neoplasms; Glioma; Glioblastoma; Lasers
PubMed: 36549438
DOI: 10.1016/j.wneu.2022.12.079 -
Critical Reviews in Oncogenesis 2019Epstein-Barr virus (EBV) is an established pathogen linked to a wide range of lymphoproliferative disorders and solid tumors. Astrocytoma is one of the most frequent...
Epstein-Barr virus (EBV) is an established pathogen linked to a wide range of lymphoproliferative disorders and solid tumors. Astrocytoma is one of the most frequent brain tumors in children, adolescents, and young adults. Astrocyte proliferation usually occurs after brain tissue aggression, which may be of different types, including viral infection. In particular, it has been suggested that EBV may play a role in astrocytoma pathogenesis. This article presents the summarized results of a systematic review of the literature on the relationship between EBV infection and astrocytoma pathophysiology. Although most studies detect the presence of EBV DNA in subsets of astrocytoma tumors, our conclusion is that currently, except for rare cases, there is no clear evidence that EBV plays a role in the development of astrocytoma.
Topics: Astrocytoma; Brain Neoplasms; Carcinogenesis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders
PubMed: 32421989
DOI: 10.1615/CritRevOncog.2020032954 -
Photodiagnosis and Photodynamic Therapy Dec 2014The present systematic review and meta-analysis was to analyze of the advantages of intraoperative fluorescence-guided resection of high-grade gliomas. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The present systematic review and meta-analysis was to analyze of the advantages of intraoperative fluorescence-guided resection of high-grade gliomas.
METHODS
Systematic computerized searches of the PubMed and Web of Knowledge were performed. The outcomes included diagnostic value for identification of tumor tissue, gross total resection, and prognosis. The summary receiver operating characteristic curves (SROC), the pooled sensitivities, the pooled specificities, the pooled odd ratio (OR) and the pooled hazard ratio (HR) were estimated by meta-analysis.
RESULTS
Twelve studies were included. The pooled sensitivity and the pooled specificity for identification of tumor tissue was 0.84 (95% CI: 0.81-0.87), and 0.91 (95% CI: 0.87-0.94), respectively. And the overall weighted AUC of the SROC curve was 0.9520 ± 0.0116. The summary OR of the gross total resection rate in patients with fluorescein-guided resection compared with patients with no fluorescein was 4.372 (95% CI 2.937-6.508). Fluorescein-guided resection was associated with a reduced risk of progression-free survival compared with no fluorescein, with HR 0.73 (95% CI 0.57-0.94, P = 0.01). The pooled HR of overall survival was 1.000 (95% CI 0.960-1.040) between two groups. No significant publication bias was found.
CONCLUSION
Fluorescence-guided resection of high-grade gliomas is effective for diagnosing tumor margins, increasing gross total resection, and reducing the risk of progression-free survival. But this conclusion should be confirmed by large sample randomized controlled clinical trials.
Topics: Brain Neoplasms; Fluorescent Dyes; Glioma; Humans; Microscopy, Fluorescence; Neoplasm Grading; Prevalence; Risk Factors; Surgery, Computer-Assisted; Survival Rate; Treatment Outcome
PubMed: 25131747
DOI: 10.1016/j.pdpdt.2014.08.001 -
Journal of Cancer Research and... 2016Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood neuroblastoma. A meta-analysis was performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood neuroblastoma. A meta-analysis was performed statistically surmising all available observational studies on this topic in order to evaluate the potential correlation of maternal smoking during pregnancy and risk of childhood neuroblastoma.
METHODS
Published literature was obtained from PubMed, Embase, ISI Web of Science, and Cochrane library, and all studies were inclusive until July 2014. Data from epidemiological studies were combined using a general variance-based meta-analytic method employing 95% confidence intervals. The outcome of interest was shown as odds ratio (OR) reflecting the risk of neuroblastoma development associated with smoking while pregnant. Newcastle-Ottawa Scale was used to assess the quality of studies.
RESULTS
Seven case-control studies meeting protocol specified inclusion criteria were obtained through a comprehensive literature search. These studies enrolled a total of 1909 patients and 15,683 controls. Analysis for homogeneity demonstrated that the data were heterogeneous (P < 0.05) and could be statistically combined with randomized effect model. Combining all seven reports yielded an OR of 1.28 (1.01-1.62), a statistically significant result suggesting possible association between maternal smoking during pregnancy and risk of childhood neuroblastoma development (P = 0.005). There was no association between the dosage of maternal smoking during pregnancy and risk of neuroblastoma.
CONCLUSION
The available epidemiological data support a possible association between maternal smoking during pregnancy and pediatric neuroblastoma development.
Topics: Case-Control Studies; Child; Female; Humans; Maternal Exposure; Neuroblastoma; Odds Ratio; Pregnancy; Prenatal Exposure Delayed Effects; Publication Bias; Risk Factors; Smoking
PubMed: 27461688
DOI: 10.4103/0973-1482.171367 -
Current Oncology (Toronto, Ont.) Nov 2023The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and... (Meta-Analysis)
Meta-Analysis Review
The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and biopsy. MEDLINE, EMBASE and Cochrane Library were screened to conduct a systematic review of the literature, according to the PRISMA statement. Analysis was limited to articles including patients older than 18 years of age and those published from 1990 to September 2022. Case reports, review articles, meta-analyses, abstracts, reports of aggregated data, and reports on multimodal therapy where surgery was not the primary treatment were excluded. The ROBINS-I tool was applied to evaluate the risk of bias. Six studies were ultimately considered for the meta-analysis. The resective group was composed of 213 subjects and the bioptic group comprised 125. The analysis demonstrated a survival benefit in those patients in which an extensive resection was possible (STR HR 0.59 (95% CI 0.42, 0.82)) (GTR HR 0.63 (95% CI 0.43, 0.92)). Although surgical resection is associated with increased survival, the significantly higher complication rate makes it difficult to recommend surgery instead of biopsy for BSGs. Future investigations combining volumetric data and molecular profiles could add important data to better define the proper indication between resection and biopsy.
Topics: Humans; Adult; Brain Neoplasms; Glioma; Biopsy; Combined Modality Therapy; Brain Stem
PubMed: 37999129
DOI: 10.3390/curroncol30110709