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Journal of Neuro-oncology Oct 2017Diagnosis of a pediatric high grade brain stem glioma is devastating with dismal outcomes. This systematic review and meta-analysis was undertaken to determine the... (Meta-Analysis)
Meta-Analysis Review
Diagnosis of a pediatric high grade brain stem glioma is devastating with dismal outcomes. This systematic review and meta-analysis was undertaken to determine the survival rates and assess potential prognostic factors including selected interventions. Studies included involved pediatric participants with high grade brain stem gliomas diagnosed by magnetic resonance imaging or biopsy reporting overall survival rates. Meta-analysis was undertaken using a binomial random effects model. Sixty-five studies (2336 participants) were included. Meta-analysis showed 1 year overall survival (OS) of 41% (95% confidence interval (CI) 38-44%, I-sq 52%, 2083 participants), 2 year OS of 15.3% (95% confidence interval 12-20%, I-sq 73.1%, 1329 participants) and 3 year OS of 7.3% (95% confidence interval 5.2-10%, I-sq 26%, 584 participants). Meta-analyses of median overall survival results was not possible due to the lack of reported measures of variance. Subgroup analysis comparing date of study, classification of tumor, use of temozolomide, non-standard interventions or phase 1/2 versus other studies demonstrated no difference in survival outcomes. There was insufficient data to undertake subgroup meta-analysis of patient age, duration of symptoms, K27M histone mutations and AVCR1 mutations. Survival outcomes of high grade brain stem gliomas have remained very poor, and do not clearly vary according to classification, phase of study or use of different therapeutic interventions. Future studies should harmonize outcome and prognostic variable reporting to enable accurate meta-analysis and better exploration of prognosis.
Topics: Brain Stem Neoplasms; Child; Glioma; Humans; Neoplasm Grading; Prognosis; Survival Rate
PubMed: 28681244
DOI: 10.1007/s11060-017-2546-1 -
Journal of Controlled Release :... Sep 2022Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated... (Review)
Review
Gliomas are the deadliest of all primary brain tumors, and they constitute a serious global health problem. MicroRNAs (miRNAs) are gene expression regulators associated with glioma pathogenesis. Thus, miRNAs represent potential therapeutic agents for treating gliomas. However, miRNAs have not been established as part of the regular clinical armamentarium. This systemic review evaluates current molecular and pre-clinical studies with the aim of defining the most appealing supramolecular platform for administering therapeutic miRNA to patients with gliomas. An integrated analysis suggested that cationic lipid nanoparticles, functionalized with octa-arginine peptides, represent a potentially specific, practical, non-invasive intervention for treating gliomas. This supramolecular platform allows loading both hydrophilic (miRNA) and hydrophobic (anti-tumor drugs, like temozolomide) molecules. This systemic review is the first to describe miRNA delivery systems targeted to gliomas that integrate several types of molecules as active ingredients. Further experimental validation is warranted to confirm the practical value of miRNA delivery systems.
Topics: Arginine; Brain Neoplasms; Glioma; Humans; Liposomes; MicroRNAs; Nanoparticles; Peptides; Temozolomide
PubMed: 35905783
DOI: 10.1016/j.jconrel.2022.07.027 -
Brain Sciences May 2022: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between... (Review)
Review
: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A "seed and soil" approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile "soil" and interact with the "seed" (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). An online literature search was launched on PubMed Medline and Scopus using the following research string: "((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))". The last search for articles pertinent to the topic was conducted in February 2022. The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile 'soil' for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia-glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments.
PubMed: 35741603
DOI: 10.3390/brainsci12060718 -
Cureus Aug 2022As oncology practice is rapidly shifting away from toxic chemotherapy, gene therapy provides a highly specific therapeutic approach for brain tumors. In this systematic... (Review)
Review
As oncology practice is rapidly shifting away from toxic chemotherapy, gene therapy provides a highly specific therapeutic approach for brain tumors. In this systematic review, we investigate gene therapy's status in pediatric brain tumors and future recommendations. The search was conducted systematically using PubMed, Cochrane, Google Scholar, and ClinicalTrials.gov databases. The field search used in the process was selected based on the keywords and Medical Subject Headings (MeSH), depending on the database used. We included cases of neurofibromatosis type 1 (NF1) brain tumors in all age groups with the additional inclusion of English language, free full text, articles published within the last 20 years, randomized controlled trials (RCTs), observational studies, systematic reviews, and meta-analyses. We excluded case reports, case studies, and editorials. The search identified a total of 1,213 articles from the databases. We included 19 studies with 16 narrative reviews, one systematic review, and two randomized clinical trials with 43 patients. After reviewing all data in the articles, we found that gene therapy can improve standard treatment efficacy when used as adjuvant therapy. It can be used to overcome barriers such as chemotherapy resistance by downregulating resistance genes. It is associated with mild toxicity when compared with other available treatment options, but given the overall poor prognosis in pediatric brain tumors, further studies are warranted.
PubMed: 36120213
DOI: 10.7759/cureus.27963 -
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 -
Neuro-oncology May 2024H3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a...
H3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a distinct form of grade IV glioma. Despite recognition as an important prognostic and diagnostic feature in diffuse glioma, radiation remains the sole standard of care and no effective systemic therapies are available for H3K27M mutant tumors. This review will detail treatment interventions applied to diffuse midline glioma and diffuse intrinsic pontine glioma (DIPG) prior to the identification of the H3 K27M mutation, the current standard-of-care for H3 K27M-mutant diffuse glioma treatment, and ongoing clinical trials listed on www.clinicaltrials.gov evaluating novel therapeutics in this population. Current clinical trials were identified using clinicaltrials.gov, and studies qualifying for this analysis were active or ongoing interventional trials that evaluated a therapy in at least 1 treatment arm or cohort comprised exclusively of patients with DIPG and H3 K27M-mutant glioma. Forty-one studies met these criteria, including trials evaluating H3 K27M vaccination, chimeric antigen receptor T-cell therapy, and small molecule inhibitors. Ongoing evaluation of novel therapeutics is necessary to identify safe and effective interventions in this underserved patient population.
Topics: Humans; Brain Stem Neoplasms; Diffuse Intrinsic Pontine Glioma; Glioma; Mutation; Histones; Prognosis; Brain Neoplasms
PubMed: 38102230
DOI: 10.1093/neuonc/noad220 -
International Journal of Molecular... Nov 2017The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years,... (Review)
Review
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.
Topics: Adult; Brain Neoplasms; Cell Movement; Disease Progression; GTP-Binding Proteins; Glioblastoma; Humans; Lysophospholipids; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Receptors, Lysosphingolipid; Sphingosine
PubMed: 29149079
DOI: 10.3390/ijms18112448 -
Glia Aug 2019Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and...
Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and treatment strategies. Although recent developments in the molecular biology of glioma have improved diagnosis, classical histological methods and biomarkers are still being used. The glial fibrillary acidic protein (GFAP) is a classical marker of astrocytoma, both in clinical and experimental settings. GFAP is used to determine glial differentiation, which is associated with a less malignant tumor. However, since GFAP is not only expressed by mature astrocytes but also by radial glia during development and neural stem cells in the adult brain, we hypothesized that GFAP expression in astrocytoma might not be a direct indication of glial differentiation and a less malignant phenotype. Therefore, we here review all existing literature from 1972 up to 2018 on GFAP expression in astrocytoma patient material to revisit GFAP as a marker of lower grade, more differentiated astrocytoma. We conclude that GFAP is heterogeneously expressed in astrocytoma, which most likely masks a consistent correlation of GFAP expression to astrocytoma malignancy grade. The GFAP positive cell population contains cells with differences in morphology, function, and differentiation state showing that GFAP is not merely a marker of less malignant and more differentiated astrocytoma. We suggest that discriminating between the GFAP isoforms GFAPδ and GFAPα will improve the accuracy of assessing the differentiation state of astrocytoma in clinical and experimental settings and will benefit glioma classification.
Topics: Animals; Astrocytoma; Biomarkers, Tumor; Central Nervous System Neoplasms; Glial Fibrillary Acidic Protein; Humans; Protein Isoforms
PubMed: 30667110
DOI: 10.1002/glia.23594 -
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 -
Medicine Oct 2020The standard treatment for diffuse intrinsic pontine glioma (DIPG) is radiotherapy, although conventional fractionated radiotherapy (CFRT) may not be in the best... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The standard treatment for diffuse intrinsic pontine glioma (DIPG) is radiotherapy, although conventional fractionated radiotherapy (CFRT) may not be in the best interest of the patient. Instead, hypofractionated radiotherapy (HFRT) may shorten the treatment period and reduce related costs for this treatment, which is typically palliative in nature.
METHODS
This systematic review and meta-analysis evaluated survival outcomes among patients who received HFRT or CFRT for DIPG. The PubMed, Medline, EMBASE, Cochrane Central Register, and Scopus databases were searched to identify relevant studies. Overall survival was the primary outcome of interest and progression-free survival was the secondary outcome of interest.
RESULTS
The search identified a total of 2376 reports, although only 4 reports were ultimately included in the meta-analysis. The studies included 88 patients who underwent HFRT and 96 patients who underwent CFRT. Relative to CFRT, HFRT provided comparable outcomes in terms of overall survival (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 0.77-1.47) and progression-free survival (HR: 1.04, 95% CI: 0.75-1.45).
CONCLUSIONS
The results of this meta-analysis suggest that CFRT and HFRT provide similar survival outcomes for patients with DIPG.
Topics: Brain Stem Neoplasms; Diffuse Intrinsic Pontine Glioma; Humans; Radiation Dose Hypofractionation
PubMed: 33080729
DOI: 10.1097/MD.0000000000022721