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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 -
Cancer Imaging : the Official... Nov 2022Advances in molecular diagnostics accomplished the discovery of two malignant glioma entities harboring alterations in the H3 histone: diffuse midline glioma, H3... (Review)
Review
BACKGROUND
Advances in molecular diagnostics accomplished the discovery of two malignant glioma entities harboring alterations in the H3 histone: diffuse midline glioma, H3 K27-altered and diffuse hemispheric glioma, H3 G34-mutant. Radiogenomics research, which aims to correlate tumor imaging features with genotypes, has not comprehensively examined histone-altered gliomas (HAG). The aim of this research was to synthesize the current published data on imaging features associated with HAG.
METHODS
A systematic search was performed in March 2022 using PubMed and the Cochrane Library, identifying studies on the imaging features associated with H3 K27-altered and/or H3 G34-mutant gliomas.
RESULTS
Forty-seven studies fulfilled the inclusion criteria, the majority on H3 K27-altered gliomas. Just under half (21/47) were case reports or short series, the remainder being diagnostic accuracy studies. Despite heterogeneous methodology, some themes emerged. In particular, enhancement of H3 K27M-altered gliomas is variable and can be less than expected given their highly malignant behavior. Low apparent diffusion coefficient values have been suggested as a biomarker of H3 K27-alteration, but high values do not exclude this genotype. Promising correlations between high relative cerebral blood volume values and H3 K27-alteration require further validation. Limited data on H3 G34-mutant gliomas suggest some morphologic overlap with 1p/19q-codeleted oligodendrogliomas.
CONCLUSIONS
The existing data are limited, especially for H3 G34-mutant gliomas and artificial intelligence techniques. Current evidence indicates that imaging-based predictions of HAG are insufficient to replace histological assessment. In particular, H3 K27-altered gliomas should be considered when occurring in typical midline locations irrespective of enhancement characteristics.
Topics: Humans; Artificial Intelligence; Brain Neoplasms; Glioma; Histones; Mutation
PubMed: 36397143
DOI: 10.1186/s40644-022-00500-3 -
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 -
Brain and Behavior Oct 2020We aim to review the literature to collate and describe features of encephalitides arising from autoantibodies against leucine-rich glioma-inactivated 1 (LGI1), gamma... (Review)
Review
AIM
We aim to review the literature to collate and describe features of encephalitides arising from autoantibodies against leucine-rich glioma-inactivated 1 (LGI1), gamma aminobutyric acid receptor (GABABR), and contactin-associated protein-like 2 (CASPR2) in Asian populations and compare them with findings of Western studies.
METHODS
Peer-reviewed articles published till 24 May 2020 were searched, and original, full-text studies from Asia with serum/CSF antibody-based diagnosis and at least 2 patients were selected. Twenty-four studies with 263 patients (139 anti-LGI1, 114 anti-GAGABR, and 10 anti-CASPR2) were included. Data were pooled to produce descriptive information on demographics, clinical characteristics, diagnostics, treatments, and outcome.
RESULTS
The mean age was 54.2 (anti-LGI1), 55.2 (anti-GABABR), and 47.7 years (anti-CASPR2), with an overall male predominance of 62.0%. Commonest clinical features across all types were seizures (87.5%), memory deficits (80.7%), psychiatric disturbances (75.9%), and altered consciousness (52.9%). Four anti-LGI1, 40 anti-GABABR, and 1 anti-CASPR2 patients had tumors. CSF, MRI, and EEG were abnormal in 33.3%, 54.1%, and 75% patients in anti-LGI1; 60.0%, 49.6%, and 85.7% in anti-GABABR; and 50%, 44.4%, and 100% in anti-CASPR2 patients, respectively. 95.6% patients received first-line therapy alone (steroids/IVIG/Plasma therapy), and 4.4% received second-line therapy (rituximab/cyclophosphamide). 91.7%, 63.6%, and 70% of patients had favorable outcomes (modified Rankin Score 0-2) with mortality rates at 2.5%, 23.2%, and 0% in the three types, respectively.
CONCLUSION
Our findings suggest that these disorders present in Asian patients at a relatively young age often with features of seizures, memory deficits, and psychiatric disturbances and usually demonstrate a favorable clinical outcome.
Topics: Asia; Glioma; Humans; Intracellular Signaling Peptides and Proteins; Leucine; Male; Middle Aged; Receptors, GABA
PubMed: 32783406
DOI: 10.1002/brb3.1793 -
Neuro-oncology Practice Oct 2021Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic... (Review)
Review
BACKGROUND
Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.
METHODS
Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) ≥50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months.
RESULTS
A total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning ≥50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of ≥6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid.
CONCLUSION
Given the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied.
PubMed: 34589231
DOI: 10.1093/nop/npab030 -
Diagnostics (Basel, Switzerland) May 2023Our aim was to provide a comprehensive overview of the existing literature concerning the clinical applications of positron emission computed tomography (PET) with... (Review)
Review
Our aim was to provide a comprehensive overview of the existing literature concerning the clinical applications of positron emission computed tomography (PET) with radiopharmaceuticals targeting the translocator protein (TSPO) in gliomas. A literature search for studies about TSPO PET in the last 10 years (from 2013 to February 2023) was carried out on PubMed, Scopus, and Web of Science using the following keywords: "PET" AND "Gliomas" AND "TSPO". The Critical Appraisal Skills Program checklist for diagnostic test studies was used for testing the quality of selected papers. Ten articles were selected, encompassing 314 glioma patients submitted to PET/CT (9/10) or PET/MRI (1/10) with TSPO ligands. Among the various available TSPO tracers, the most frequently used was the third-generation ligand, [F]-GE-180. TSPO PET results were useful to identify anaplastic transformation in gliomas and for the prognostic stratification of patients bearing homogeneous genetic alterations. When compared to amino-acid PET, TSPO PET with [F]-GE-180 presented superior image quality and provided larger and only partially overlapping PET-based volumes. Although biased by some issues (i.e., small sample size, most of the studies coming from the same country), preliminary applications of TSPO PET were encouraging. Further studies are needed to define implications in clinical practice and shape the role of TSPO PET for patients' selection for potential TSPO-targeted molecular therapies.
PubMed: 37238297
DOI: 10.3390/diagnostics13101813 -
Journal of Neurosurgery May 2023Gliomas arising from the insular cortex can be epileptogenic, with a significant proportion of patients having medically refractory epilepsy. The impact of surgery on... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Gliomas arising from the insular cortex can be epileptogenic, with a significant proportion of patients having medically refractory epilepsy. The impact of surgery on seizure control for such tumors is not well established. In this study, the authors aimed to investigate seizure outcomes after resection of insular gliomas using a meta-analysis and institutional experience.
METHODS
Three databases (Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) were systematically searched for published studies of seizure outcomes after insular glioma resection from database inception to March 27, 2021. In addition, data were retrospectively collected on all adults (age > 17 years) who had undergone insular glioma resection between June 1997 and June 2015 at the authors' institution. Primary outcome measures were seizure freedom rates at 1 year and the last follow-up. Secondary outcome measures consisted of persistent postoperative neurological deficit beyond 90 days, mortality, and tumor progression or recurrence.
RESULTS
Eight studies reporting on 453 patients who had undergone 460 operations were included in the meta-analysis. The pooled mean age of the patients was 42 years. The pooled percentages of patients with extents of resection (EORs) ≥ 90%, 70%-89%, and < 70% were 55%, 33%, and 11%, respectively. The pooled seizure freedom rate at 1 year was 73% for Engel class IA and 78% for Engel class I. The pooled seizure freedom rate at the last follow-up was 60% for Engel class IA and 79% for Engel class I. The pooled percentage of persistent neurological deficit beyond 90 days was 3%. At the authors' institution, 109 patients had undergone resection of insular glioma. A greater EOR was the only significant independent predictor of seizure freedom after surgery (HR 0.290, p = 0.017). The optimal threshold for seizure freedom corresponded to an EOR of 81%. Patients with an EOR > 81% had a significantly higher seizure freedom rate (OR 2.16, p = 0.048).
CONCLUSIONS
Maximal safe resection can be performed with minimal surgical morbidity to achieve favorable seizure freedom rates in both the short and long term. When gross-total resection is not possible, an EOR > 81% confers the greatest sensitivity and specificity for achieving seizure freedom. Systematic review registration no.: CRD42021249404 (https://www.crd.york.ac.uk/prospero/).
Topics: Adult; Humans; Adolescent; Brain Neoplasms; Retrospective Studies; Treatment Outcome; Glioma; Seizures
PubMed: 36242570
DOI: 10.3171/2022.8.JNS221067 -
Biomedicines Jan 2022Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined... (Review)
Review
BACKGROUND
Glioblastoma is the most frequent malignant primitive brain tumor in adults. The treatment includes surgery, radiotherapy, and chemotherapy. During follow-up, combined chemoradiotherapy can induce treatment-related changes mimicking tumor progression on medical imaging, such as pseudoprogression (PsP). Differentiating PsP from true progression (TP) remains a challenge for radiologists and oncologists, who need to promptly start a second-line treatment in the case of TP. Advanced magnetic resonance imaging (MRI) techniques such as diffusion-weighted imaging, perfusion MRI, and proton magnetic resonance spectroscopic imaging are more efficient than conventional MRI in differentiating PsP from TP. None of these techniques are fully effective, but current advances in computer science and the advent of artificial intelligence are opening up new possibilities in the imaging field with radiomics (i.e., extraction of a large number of quantitative MRI features describing tumor density, texture, and geometry). These features are used to build predictive models for diagnosis, prognosis, and therapeutic response.
METHOD
Out of 7350 records for MR spectroscopy, GBM, glioma, recurrence, diffusion, perfusion, pseudoprogression, radiomics, and advanced imaging, we screened 574 papers. A total of 228 were eligible, and we analyzed 72 of them, in order to establish the role of each imaging modality and the usefulness and limitations of radiomics analysis.
PubMed: 35203493
DOI: 10.3390/biomedicines10020285 -
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 -
PloS One 2022The XRCC3 p.Thr241Met (rs861539) polymorphism has been extensively studied for its association with glioma risk, but results remain conflicting. Therefore, we performed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The XRCC3 p.Thr241Met (rs861539) polymorphism has been extensively studied for its association with glioma risk, but results remain conflicting. Therefore, we performed a systematic review and meta-analysis to resolve this inconsistency.
METHODS
Studies published up to June 10, 2022, were searched in PubMed, Web of Science, Scopus, VIP, Wanfang, and China National Knowledge Infrastructure databases and screened for eligibility. Then, the combined odds ratio (OR) of the included studies was estimated based on five genetic models, i.e., homozygous (Met/Met vs. Thr/Thr), heterozygous (Thr/Met vs. Thr/Thr), dominant (Thr/Met + Met/Met vs. Thr/Thr), recessive (Met/Met vs. Thr/Thr + Thr/Met) and allele (Met vs. Thr). The study protocol was preregistered at PROSPERO (registration number: CRD42021235704).
RESULTS
Overall, our meta-analysis of 14 eligible studies involving 12,905 subjects showed that the p.Thr241Met polymorphism was significantly associated with increased glioma risk in both homozygous and recessive models (homozygous, OR = 1.381, 95% CI = 1.081-1.764, P = 0.010; recessive, OR = 1.305, 95% CI = 1.140-1.493, P<0.001). Subgroup analyses by ethnicity also revealed a statistically significant association under the two aforementioned genetic models, but only in the Asian population and not in Caucasians (P>0.05).
CONCLUSION
We demonstrated that the XRCC3 p.Thr241Met polymorphism is associated with an increased risk of glioma only in the homozygous and recessive models.
Topics: Case-Control Studies; Genetic Predisposition to Disease; Glioma; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 36264998
DOI: 10.1371/journal.pone.0276313