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Journal of Neurosurgery. Pediatrics Dec 2023Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for...
OBJECTIVE
Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for diagnostic and potentially therapeutic purposes. However, there is no consensus on the safety of biopsy or effect on survival. The authors aimed to characterize neurological risk associated with and the effect of stereotactic biopsy on survival among patients with DIPGs.
METHODS
A systematic review was performed in accordance with PRISMA guidelines to identify all studies examining pediatric patients with DIPG who underwent stereotactic biopsy. The search strategy was deployed in PubMed, Embase, and Scopus. The quality of studies was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system, and risk of bias was evaluated with the Cochrane Risk of Bias in Nonrandomized Studies-of Interventions tool. Bibliographic, demographic, clinical, and outcome data were extracted from studies meeting inclusion criteria.
RESULTS
Of 2634 resultant articles, 13 were included, representing 192 patients undergoing biopsy. The weighted mean age at diagnosis was 7.5 years (range 0.5-17 years). There was an overall neurosurgical complication rate of 13.02% (25/192). The most common neurosurgical complication was cranial nerve palsy (4.2%, 8/192), of which cranial nerve VII was the most common (37.5%, 3/8). The second most common complication was perioperative hemorrhage (3.6%, 7/192), followed by hemiparesis (2.1%, 4/192), speech disorders (1.6%, 3/192) such as dysarthria and dysphasia, and movement disorders (1.0%, 2/192). Hydrocephalus was less commonly reported (0.5%, 1/192), and there were no complications relating to wound infection/dehiscence (0%, 0/192) or CSF leak (0%, 0/192). No mortality was specifically attributed to biopsy. Diagnostic yield of biopsy revealed a weighted mean of 97.4% (range 91%-100%). Of the studies reporting survival data, 37.6% (32/85) of patients died within the study follow-up period (range 2 weeks-48 months). The mean overall survival in patients undergoing biopsy was 9.73 months (SD 0.68, median 10 months, range 6-13 months).
CONCLUSIONS
Children with DIPGs undergoing biopsy have mild to moderate rates of neurosurgical complications and no excessive morbidity. With reasonably acceptable surgical risk and high diagnostic yield, stereotactic biopsy of DIPGs can allow for characterization of patient-specific molecular and genetic features that may influence prognosis and the development of future therapeutic strategies.
Topics: Humans; Child; Infant; Child, Preschool; Adolescent; Glioma; Diffuse Intrinsic Pontine Glioma; Brain Stem Neoplasms; Biopsy
PubMed: 37724839
DOI: 10.3171/2023.7.PEDS22462 -
Cancer Control : Journal of the Moffitt... 2022Pediatric gliomas represent the most common brain tumor in children and its higher grades are associated with higher recurrence and low survival rate. All therapeutic...
INTRODUCTION
Pediatric gliomas represent the most common brain tumor in children and its higher grades are associated with higher recurrence and low survival rate. All therapeutic modalities are reported to be insufficient to achieve satisfactory result, with follow-up treatment such as adjuvant radiotherapy and chemotherapy recommended to increase survival and hinder tumor progression. Nimotuzumab is a monoclonal antibody that acts as an inhibitor of epidermal growth factor receptor found on the surface of glioma cells and had been studied for its usage in pediatric gliomas in recent years.
METHODS
A systematic review is performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A through literature search was conducted on PubMed, Scopus, Cochrane, and clinicaltrials.gov database. Articles were selected systematically based on the PRISMA protocol and reviewed completely. The relevant data were summarized and discussed. We measured overall survival, progression-free survival, and adverse Events (AE) for nimotuzumab usage as an adjunct therapy in pediatric glioma population.
RESULT
From 5 studies included for qualitative analysis, 151 patients are included with overall survival (OS) that vary from 3.2-22.8 mo, progression-free survival (PFS) from 1.7-21.6 mo, and relatively low serious adverse events (0-21) are recorded. Follow-up ranged from 2.4-66 mo with four studies reporting diffuse intrinsic pontine glioma (DIPG) patients and only one study reporting nimotuzumab usage in pediatric high-grade glioma (HGG) patients with better outcome in HGG patients than DIPG.
CONCLUSION
There are no significant differences in the PFS and OS of nimotuzumab as adjunct therapy for pediatric compared to result of standard therapy in majority of previous studies. There were also no differences in the AE of nimotuzumab for pediatric glioma between studies, and low event of serious adverse events indicating its safety. But still there is an evidence of possible benefit of nimotuzumab as adjuvant therapy in pediatric glioma. We recommend further studies with larger number of patients that may lead to possibly different results. There should also be more studies with better level of evidence to further validate the effect of nimozutumab on pediatric glioma.
Topics: Adolescent; Antibodies, Monoclonal, Humanized; Brain Neoplasms; Brain Stem Neoplasms; Child; Combined Modality Therapy; Glioma; Humans
PubMed: 35191733
DOI: 10.1177/10732748211053927 -
Acta Neurochirurgica Jan 2017Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In... (Review)
Review
BACKGROUND
Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma.
METHODS
We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events.
RESULTS
The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified.
CONCLUSIONS
5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.
Topics: Aminolevulinic Acid; Animals; Brain Neoplasms; Fluorescent Dyes; Glioma; Humans; Neurosurgical Procedures; Photosensitizing Agents
PubMed: 27878374
DOI: 10.1007/s00701-016-3028-5 -
World Neurosurgery Oct 2019Bevacizumab plus irinotecan is a new beneficial chemotherapy strategy for patients with malignant glioma. The purpose of this systematic review and meta-analysis was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bevacizumab plus irinotecan is a new beneficial chemotherapy strategy for patients with malignant glioma. The purpose of this systematic review and meta-analysis was to comprehensively assess the risk of adverse vascular events in adults with malignant glioma treated with bevacizumab plus irinotecan.
METHODS
The Cochrane Library, Embase and PubMed were searched, and relevant trials were identified up to June 2018. Two investigators screened all titles and abstracts for possible inclusion and extracted data independently. Six studies were included, and 5 of them in the control group using bevacizumab alone or bevacizumab with temozolomide. Three systems were used to assess the quality of evidence and the level of recommendation. The Oxford Centre for Evidence-Based Medicine Levels of Evidence (2009) system was used to classify the evidence into 5 levels (classes I-V). The star system from the Newcastle-Ottawa Scale was used to assess methodological quality. The GRADE profiler was used to evaluate the overall body of evidence.
RESULTS
Our data show that bevacizumab plus irinotecan therapy does not significantly affect the risk of systemic adverse events (odds ratio [OR], 1.17; 95% confidence interval [CI], 0.43-3.18). Patients treated with bevacizumab plus irinotecan had a similar risk of hematotoxicity (OR, 1.06; 95% CI, 0.26-4.38), thrombocytopenia (OR, 1.07; 95% CI, 0.25-4.63), and hypertension (OR, 1.34; 95% CI, 0.28-6.36) compared with the control group (those treated without irinotecan). Thrombosis occurred more frequently in patients treated with bevacizumab plus irinotecan compared with the control group (OR, 3.23; 95% CI, 1.47-7.12).
CONCLUSIONS
The risk of systemic adverse events was not significantly different between patients with malignant glioma treated with bevacizumab plus irinotecan and the control group. The risks of hematotoxicity, thrombocytopenia, and hypertension were similar in the 2 groups. The risk of thrombosis was higher in patients treated with bevacizumab plus irinotecan. Monitoring for thrombosis and administering anticoagulant therapy as necessary merit promotion for patients with malignant glioma receiving treatment with bevacizumab plus irinotecan.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Glioma; Humans; Intracranial Thrombosis; Irinotecan; Risk Factors; Topoisomerase I Inhibitors; Treatment Outcome
PubMed: 31203059
DOI: 10.1016/j.wneu.2019.06.043 -
Neurosurgical Review Jun 2023Glioblastoma (GBM) is the most common and aggressive glioma histological subtype, associated with high disability and poor survival. The etiology of this condition is... (Meta-Analysis)
Meta-Analysis Review
Glioblastoma (GBM) is the most common and aggressive glioma histological subtype, associated with high disability and poor survival. The etiology of this condition is still mostly unknown, and evidence about risk factors is elusive. The aim of this study is to identify modifiable risk factors for GBM. Electronic search was performed by two reviewers independently using the keywords and MeSH terms 'glioblastoma' OR 'glioma' OR 'brain tumor' AND 'risk factor'. The inclusion criteria were (1) observational studies or experimental studies on humans, (2) studies assessing the association between glioblastoma and exposure to modifiable conditions, and (3) studies published in English or Portuguese. Studies on the pediatric population or about exposure to ionizing radiation were excluded. A total of 12 studies were included. Seven were case-control studies, and five were cohort studies. The risk factors assessed included body mass index, alcohol consumption, exposure to magnetic fields, diabetes mellitus type 2 (DM2), and use of non-steroidal anti-inflammatory drugs (NSAID). No significant link was found between GBM incidence and DM2 or magnetic field exposure. On the other hand, higher BMI, alcohol consumption, and NSAID use demonstrated a protective effect on GMB risk. However, given the limited number of studies, it is not possible to obtain a behavioral recommendation; instead, these findings are relevant to guide future basic scientific studies on GBM oncogenesis.
Topics: Humans; Child; Glioblastoma; Risk Factors; Glioma; Brain Neoplasms; Diabetes Mellitus, Type 2; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37340151
DOI: 10.1007/s10143-023-02051-y -
Neurosurgical Review Sep 2019Epilepsy is a common manifestation of glioma patients and negatively impacts on quality of life and neurocognitive function. The risk of preoperative seizures in... (Meta-Analysis)
Meta-Analysis
Epilepsy is a common manifestation of glioma patients and negatively impacts on quality of life and neurocognitive function. The risk of preoperative seizures in patients with glioma is currently under discussion. We aimed to evaluate the relationship between tumor locations in the cerebrum and preoperative seizures in patients with glioma. PubMed, EMBASE, Web of Science, China Biology Medicine, and the Cochrane Library were systematically searched from inception to July 15, 2017, for original studies including reports of preoperative seizures in patients with gliomas in different brain regions. The pooled odds ratio (OR) and 95% confidence interval (CI) of the meta-analysis for preoperative seizure risk stratified by cerebrum regions were calculated. The quality of evidence was assessed per outcome, using the approach of the Grades of Recommendation, Assessment, Development and Evaluation. Overall, 4323 participants in 16 population-based studies were included in this meta-analysis. The meta-analysis indicated that gliomas in the frontal lobe (OR = 1.51, 95% CI = 1.09-2.09, P = 0.013) were associated with a higher risk for preoperative seizure compared to occipital lobe involved (OR = 0.53, 95% CI = 0.32-0.88, P = 0.014). Regarding the other three lobe involved gliomas, no difference was found between the incidence of preoperative seizures and tumor location. Current limited data suggest that frontal gliomas were associated with a higher risk of preoperative seizures, while gliomas in the occipital lobe were associated with a lower seizure risk. Further RCT studies recruiting larger sample sizes are required to validate these results and guide clinical practice.
Topics: Brain Neoplasms; Glioma; Humans; Incidence; Preoperative Period; Seizures
PubMed: 30073426
DOI: 10.1007/s10143-018-1014-5 -
Gene Aug 2018An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development of glioma. However, a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development of glioma. However, a systematic review and meta-analysis to evaluate the clinical value of lncRNA expression in glioma patients is lacking. We performed this study to assess the relationship between the expression of various lncRNAs and the clinicopathological features, diagnosis and prognosis of glioma.
MATERIALS AND METHODS
Eligible studies were identified through a comprehensive literature search. We conducted a subgroup analysis to assess the clinicopathological value of urothelial carcinoma associated 1 (UCA1). Pooled hazard ratios (HRs) of lncRNAs for survival were calculated to analyze the prognostic performance of lncRNAs.
RESULTS
In total, 40 studies, including 30 investigating clinicopathological features, 3 investigating diagnoses and 32 investigating prognoses, were analyzed in this study. UCA1 expression was positively associated with tumor size (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.06-4.15; P < 0.001) and World Health Organization (WHO) grade (OR, 3.84, [95% CI 1.84-8.01], P < 0.001). In the prognostic meta-analysis, high metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression could predict poor overall survival (OS) in patients with glioma, with a pooled HR of 2.32 (95% CI: 1.64-3.27, P < 0.001).
CONCLUSIONS
This systematic review and meta-analysis demonstrated that lncRNAs are associated with tumor size, WHO grade, and prognosis in glioma patients. lncRNAs could function as potential molecular biomarkers of the clinicopathology and prognosis of glioma.
Topics: Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Prognosis; RNA, Long Noncoding
PubMed: 29777909
DOI: 10.1016/j.gene.2018.05.054 -
The British Journal of Radiology Dec 2018The diversity of tumour characteristics among glioma patients, even within same tumour grade, is a big challenge for disease outcome prediction. A possible approach for... (Review)
Review
OBJECTIVE:
The diversity of tumour characteristics among glioma patients, even within same tumour grade, is a big challenge for disease outcome prediction. A possible approach for improved radiological imaging could come from combining information obtained at the molecular level. This review assembles recent evidence highlighting the value of using radiogenomic biomarkers to infer the underlying biology of gliomas and its correlation with imaging features.
METHODS:
A literature search was done for articles published between 2002 and 2017 on Medline electronic databases. Of 249 titles identified, 38 fulfilled the inclusion criteria, with 14 articles related to quantifiable imaging parameters (heterogeneity, vascularity, diffusion, cell density, infiltrations, perfusion, and metabolite changes) and 24 articles relevant to molecular biomarkers linked to imaging.
RESULTS:
Genes found to correlate with various imaging phenotypes were EGFR, MGMT, IDH1, VEGF, PDGF, TP53, and Ki-67. EGFR is the most studied gene related to imaging characteristics in the studies reviewed (41.7%), followed by MGMT (20.8%) and IDH1 (16.7%). A summary of the relationship amongst glioma morphology, gene expressions, imaging characteristics, prognosis and therapeutic response are presented.
CONCLUSION:
The use of radiogenomics can provide insights to understanding tumour biology and the underlying molecular pathways. Certain MRI characteristics that show strong correlations with EGFR, MGMT and IDH1 could be used as imaging biomarkers. Knowing the pathways involved in tumour progression and their associated imaging patterns may assist in diagnosis, prognosis and treatment management, while facilitating personalised medicine.
ADVANCES IN KNOWLEDGE:
Radiogenomics can offer clinicians better insight into diagnosis, prognosis, and prediction of therapeutic responses of glioma.
Topics: Biomarkers, Tumor; Brain; Brain Neoplasms; Gene Expression Profiling; Genetic Markers; Genomics; Glioma; Humans; Magnetic Resonance Imaging
PubMed: 29902076
DOI: 10.1259/bjr.20170930 -
Journal of Neuro-oncology Sep 2023This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This review compares reirradiation (reRT), systemic therapy and combination therapy (reRT & systemic therapy) with regards to overall survival (OS), progression-free survival (PFS), adverse effects (AEs) and quality of life (QoL) in patients with recurrent high-grade glioma (rHGG).
METHODS
A search was performed on PubMed, Scopus, Embase and CENTRAL. Studies reporting OS, PFS, AEs and/or QoL and encompassing the following groups were included; reirradiation vs systemic therapy, combination therapy vs systemic therapy, combination therapy vs reRT, and bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy. Meta-analyses were performed utilising a random effects model. Certainty of evidence was assessed using GRADE.
RESULTS
Thirty-one studies (three randomised, twenty-eight non-randomised) comprising 2084 participants were included. In the combination therapy vs systemic therapy group, combination therapy improved PFS (HR 0.57 (95% CI 0.41-0.79); low certainty) and OS (HR 0.73 (95% CI 0.56-0.95); low certainty) and there was no difference in grade 3 + AEs (RR 1.03 (95% CI 0.57-1.86); very low certainty). In the combination therapy vs reRT group, combination therapy improved PFS (HR 0.52 (95% CI 0.38-0.72); low certainty) and OS (HR 0.69 (95% CI 0.52-0.93); low certainty). In the bevacizumab-based combination therapy vs reRT with/without non-bevacizumab-based systemic therapy group, adding bevacizumab improved PFS (HR 0.46 (95% CI 0.27-0.77); low certainty) and OS (HR 0.42 (95% CI 0.24-0.72; low certainty) and reduced radionecrosis (RR 0.17 (95% CI 0.06-0.48); low certainty).
CONCLUSIONS
Combination therapy may improve OS and PFS with acceptable toxicities in patients with rHGG compared to reRT or systemic therapy alone. Particularly, combining bevacizumab with reRT prophylactically reduces radionecrosis.
REGISTRATION
CRD42022291741.
Topics: Humans; Bevacizumab; Quality of Life; Re-Irradiation; Neoplasm Recurrence, Local; Glioma; Randomized Controlled Trials as Topic
PubMed: 37733174
DOI: 10.1007/s11060-023-04441-0 -
Acta Neurochirurgica Feb 2020Fluorescence in the ventricular wall or the ependyma during fluorescence-guided resection (FGR) of malignant glioma is commonly observed when malignant gliomas...
BACKGROUND
Fluorescence in the ventricular wall or the ependyma during fluorescence-guided resection (FGR) of malignant glioma is commonly observed when malignant gliomas infiltrate the ventricles. However, the underlying pathophysiology and clinical importance are largely unknown but may play a role in deciding whether to continue resection into the ventricles or not. Here, we systematically review available data regarding ependymal fluorescence in FGR using five aminolevulinic acid (5-ALA) and sodium fluorescein (SF).
METHODS
A literature search on MEDLINE, EMBASE, and WEB OF SCIENCE was performed using the following headings and search operators: ependy* fluorescence AND (5-ALA OR five aminolevulinic acid), ventric* wall fluorescence AND (5-ALA OR five aminolevulinic acid), ependy* fluorescence AND fluorescein, and ventric* wall fluorescence AND fluorescein. Both authors analyzed abstracts independently. Included articles were further reviewed for prevalence of ependymal fluorescence, patterns of fluorescence, and histopathological characteristics of sampled tissues as well as radiological signs of ependymal fluorescence. Results are reported according to the PRISMA statement.
RESULTS
Of 202 records identified, 6 studies were included compiling a total number of 198 patients treated with FGR using 5-ALA. No study on ependymal fluorescence after administration of SF was found. Overall prevalence of ependymal fluorescence was 61.4%. A total of 54.5% of cases were found to be positive for tumor cells. A total of 25.5% of patients with ependymal fluorescence were related to contrast enhancement in ventricular walls.
CONCLUSIONS
The phenomenon of ventricular wall fluorescence in 5-ALA-derived fluorescence-guided resection of malignant glioma is poorly understood and not always may fluorescence represent tumor infiltration. A larger scale prospective sampling study with molecular analyses is currently ongoing and will hopefully provide further insight into pathophysiology and clinical implications of ependymal fluorescence.
Topics: Aminolevulinic Acid; Brain Neoplasms; Ependyma; Fluorescein; Fluorescence; Fluorescent Dyes; Glioma; Humans; Photosensitizing Agents; Surgery, Computer-Assisted
PubMed: 31754847
DOI: 10.1007/s00701-019-04144-4