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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 -
Nitric Oxide : Biology and Chemistry Sep 2023Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and... (Review)
Review
INTRODUCTION
Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and treatment strategies, median survival remains disappointingly low. Inflammatory processes involving nitric oxide (NO), critically contribute to glioma formation. The inducible isoform of NO synthase (iNOS) is highly overexpressed in gliomas and has been linked to resistance against temozolomide (TMZ) treatment, neoplastic transformation, and modulation of immune response. While both in vitro and in vivo studies showed the potential of iNOS inhibitors as effective treatments for gliomas, no clinical trials on gliomas have been published. This review aims to summarize the available evidence regarding iNOS as a target for glioma treatment, focusing on clinically relevant data.
METHODS
Following PRISMA guidelines, we conducted a systematic review by searching PubMed/Medline, and Embase databases in May 2023. We included studies that investigated the impact of NOS inhibitors on glioma cells using L-NMMA, CM544, PBN, 1400W or l-NAME either alone or combined with TMZ. We extracted data on the NOS inhibitor used, subtype, study setting, animal model or cell lines employed, obtained results, and safety profile. Our inclusion criteria encompassed original articles in English or Spanish, studies with an untreated control group, and a primary outcome focused on the biological effects on glioma cells.
RESULTS
Out of 871 articles screened from the aforementioned databases, 37 reports were assessed for eligibility. After excluding studies that did not utilize glioma cells or address the designated outcome, 11 original articles satisfied the inclusion and exclusion criteria. Although no NOS inhibitor has been tested in a published clinical trial, three inhibitors have been evaluated using in vivo models of intracranial gliomas. l-NAME, 1400W, and CM544 were tested in vitro. Co-administration of l-NAME, or CM544 with TMZ showed superior results in vitro compared to individual agent testing.
CONCLUSION
Glioblastomas remain a challenging therapeutic target. iNOS inhibitors exhibit substantial potential as treatment options for oncologic lesions, and they have demonstrated a safe toxicity profile in humans for other pathological conditions. Research endeavors should be focused on investigating their potential effects on brain tumors.
Topics: Animals; Humans; Glioblastoma; NG-Nitroarginine Methyl Ester; Glioma; Temozolomide; Brain Neoplasms; Enzyme Inhibitors; Nitric Oxide Synthase; Nitric Oxide
PubMed: 37279819
DOI: 10.1016/j.niox.2023.06.002 -
Journal of Neuro-oncology Aug 2018This review aims to summarize challenges in clinical management of concomitant gliomas and pregnancy and provides suggestions for this management based on current...
INTRODUCTION
This review aims to summarize challenges in clinical management of concomitant gliomas and pregnancy and provides suggestions for this management based on current literature.
METHODS
PubMed and Embase databases were systematically searched for studies on glioma and pregnancy. Observational studies and articles describing expert opinions on clinical management were included. The strength of evidence was categorized as arguments from observational studies, consensus in expert opinions, or single expert opinions. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS).
RESULTS
27 studies were selected, including 316 patients with newly diagnosed (n = 202) and known (n = 114) gliomas during pregnancy. The median sample size was 6 (range 1-65, interquartile range 1-9). Few recommendations originated from observational studies; the remaining arguments originated from consensus in expert opinions.
CONCLUSION
Findings from observational studies of adequate quality include (1) There is no known effect of pregnancy on survival in low-grade glioma patients; (2) Pregnancy can provoke clinical deterioration and tumor growth on MRI; (3) In stable women at term, there is no benefit of cesarean section over vaginal delivery, with respect to adverse events in mother or child. Unanswered questions include when pregnancy should be discouraged, what best monitoring schedule is for both mother and fetus, and if and how chemo- and radiation therapy can be safely administered during pregnancy. A multicenter individual patient level meta-analysis collecting granular information on clinical management and related outcomes is needed to provide scientific evidence for clinical decision-making in pregnant glioma patients.
Topics: Brain Neoplasms; Female; Glioma; Humans; Observational Studies as Topic; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 29623596
DOI: 10.1007/s11060-018-2851-3 -
Neurology India 2022Seizures often herald the clinical appearance of glioma. Temozolomide (TMZ) is the first-line chemotherapeutic agent that has been used to treat glioma. (Review)
Review
BACKGROUND
Seizures often herald the clinical appearance of glioma. Temozolomide (TMZ) is the first-line chemotherapeutic agent that has been used to treat glioma.
OBJECTIVE
We conducted a systematic review to determine seizure outcomes in glioma patients treated with TMZ.
METHODS AND MATERIAL
We searched EMBASE and PubMed databases (January 1, 2003-August 26, 2021) by using search terms closely related to glioma, seizure, and temozolomide. Titles, abstracts, and full texts were screened and selected using previously established inclusion and exclusion criteria. The research team members reviewed potential articles and reached a consensus on the final articles to be included.
RESULTS
Nine studies containing data from three continents met our inclusion criteria. From several descriptive studies on low-grade gliomas (LGGs), the percentage of patients with partial seizure control after TMZ treatment ranged from 29% to 89.7%, and the percentage of patients with complete seizure control after TMZ ranged from 19.4% to 72%. In a retrospective cohort study of patients with LGGs, there was a marked difference in decreased seizure frequency between patients receiving TMZ and those who did not receive TMZ. In a randomized trial, TMZ seemed to have little effect on seizure control in elderly patients with glioblastoma.
CONCLUSIONS
At present, there are few high-quality and well-designed clinical studies on TMZ for gliomas-related seizures. In terms of the literature included in this review, TMZ has an inhibitory effect on epilepsy. More randomized controlled trials are needed to elucidate the clinical benefits of TMZ in the treatment of gliomas-related seizures.
Topics: Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Glioma; Humans; Randomized Controlled Trials as Topic; Retrospective Studies; Seizures; Temozolomide
PubMed: 35864610
DOI: 10.4103/0028-3886.349588 -
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 -
Neurology Oct 2015Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these associations in detail.
METHODS
We conducted a systematic review and meta-analysis of adiposity and physical activity in relation to meningioma and glioma using cohort and case-control studies published through February 2015. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
We identified 12 eligible studies of body mass index (BMI) and 6 studies of physical activity, comprising up to 2,982 meningioma cases and 3,057 glioma cases. Using normal weight as the reference group, overweight (summary relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.01-1.43) and obesity (RR = 1.54, 95% CI = 1.32-1.79) were associated with increased risk of meningioma. In contrast, overweight (RR = 1.06, 95% CI = 0.94-1.20) and obesity (RR = 1.11, 95% CI = 0.98-1.27) were unrelated to glioma. Similarly, dose-response meta-analyses revealed a statistically significant positive association of BMI with meningioma, but not glioma. High vs low physical activity levels showed a modest inverse relation to meningioma (RR = 0.73, 95% CI = 0.61-0.88) and a weak inverse association with glioma (RR = 0.86, 95% CI = 0.76-0.97). Relations persisted when the data were restricted to prospective studies, except for the association between physical activity and glioma, which was rendered statistically nonsignificant (RR = 0.91, 95% CI = 0.77-1.07).
CONCLUSIONS
Adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma.
Topics: Body Mass Index; Brain Neoplasms; Case-Control Studies; Exercise; Glioma; Humans; Meningeal Neoplasms; Meningioma; Motor Activity; Obesity; Prospective Studies; Risk Factors
PubMed: 26377253
DOI: 10.1212/WNL.0000000000002020 -
European Journal of Clinical... May 2024Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents.
METHODS
PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models.
RESULTS
Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35-65%) for low-grade gliomas (LGG) and 40% (95% CI: 29-51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36-54%) for both glioma grades. The complete response rate was 13% (95% CI: 05-27%) for HGG and 5% (95% CI: 1-10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58-98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34-79%). Grade 1-4 adverse events occurred in 100% of LGG and 63% of HGG patients.
CONCLUSIONS
Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes.
Topics: Humans; Imidazoles; Glioma; Oximes; Pyridones; Mutation; Antineoplastic Combined Chemotherapy Protocols; Pyrimidinones
PubMed: 38345637
DOI: 10.1007/s00228-024-03635-3 -
Brain Tumor Pathology Jul 2023The WHO 2021 classification defines IDH wild type (IDHw) histologically lower-grade glioma (hLGG) as molecular glioblastoma (mGBM) if TERT promoter mutation (pTERTm),... (Meta-Analysis)
Meta-Analysis Review
The WHO 2021 classification defines IDH wild type (IDHw) histologically lower-grade glioma (hLGG) as molecular glioblastoma (mGBM) if TERT promoter mutation (pTERTm), EGFR amplification or chromosome seven gain and ten loss aberrations are indicated. We systematically reviewed articles of IDHw hLGGs studies (49 studies, N = 3748) and meta-analyzed mGBM prevalence and overall survival (OS) according to the PRISMA statement. mGBM rates in IDHw hLGG were significantly lower in Asian regions (43.7%, 95% confidence interval [CI: 35.8-52.0]) when compared to non-Asian regions (65.0%, [CI: 52.9-75.4]) (P = 0.005) and were significantly lower in fresh-frozen specimen when compared to formalin-fixed paraffin-embedded samples (P = 0.015). IDHw hLGGs without pTERTm rarely expressed other molecular markers in Asian studies when compared to non-Asian studies. Patients with mGBM had significantly longer OS times when compared to histological GBM (hGBM) (pooled hazard ratio (pHR) 0.824, [CI: 0.694-0.98], P = 0.03)). In patients with mGBM, histological grade was a significant prognostic factor (pHR 1.633, [CI: 1.09-2.447], P = 0.018), as was age (P = 0.001) and surgical extent (P = 0.018). Although bias risk across studies was moderate, mGBM with grade II histology showed better OS rates when compared to hGBM.
Topics: Humans; Glioblastoma; Brain Neoplasms; Mutation; Isocitrate Dehydrogenase; Telomerase; Glioma; Prognosis
PubMed: 37212969
DOI: 10.1007/s10014-023-00463-8 -
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 -
Clinical Neurology and Neurosurgery Aug 2023A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically... (Review)
Review
BACKGROUND
A variety of dietary adjuncts are known to affect the pathophysiology of glioma, making them a potential therapeutic adjunct to standard of care. We systematically reviewed clinical outcomes in glioma patients treated with one or more nutritional adjunct and/or an antimetabolite drug.
METHODOLOGY
A systematic review of the literature following PRISMA guidelines was performed using Pubmed from inception till February 2023. In total, 22 manuscripts on nutrition representing 828 patients were included in the review. Statistical analyses were performed to compare the outcomes of various adjuncts.
RESULTS
The median overall survival (OS) increased for newly diagnosed (21 months) and recurrent cases (10 months) when compared to historical data. For newly diagnosed cases, a ketogenic diet had the highest median OS of all the adjuncts (42.6 months) while in recurrent cases, a low copper diet coupled with 1 g penicillamine had the highest median OS (18.5 months). However, no statistically significant difference was observed in OS or progression-free survival (PFS) of newly diagnosed or recurrent gliomas.
CONCLUSION
While nutritional adjuncts may offer a therapeutic benefit in the treatment of glioma, more human subject research is needed to derive meaningful conclusions.
Topics: Humans; Neoplasm Recurrence, Local; Glioma; Progression-Free Survival; Brain Neoplasms
PubMed: 37390567
DOI: 10.1016/j.clineuro.2023.107853