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The Cochrane Database of Systematic... Sep 2022Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of... (Review)
Review
BACKGROUND
Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.
OBJECTIVES
To assess the effectiveness and safety of pharmacological and non-pharmacological interventions for adults with PBT and clinically significant (or high levels) of fatigue.
SEARCH METHODS
For this updated review, we searched CENTRAL, MEDLINE and Embase, and checked the reference lists of included studies in April 2022. We also searched relevant conference proceedings, and ClinicalTrials.gov for ongoing trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that investigated any pharmacological or non-pharmacological intervention in adults with PBT and fatigue, where fatigue was the primary outcome measure. We restricted inclusion specifically to studies that enrolled only participants with clinically significant levels of fatigue to improve the clinical utility of the findings.
DATA COLLECTION AND ANALYSIS
Two review authors (JD, DC) independently evaluated search results for the updated search. Two review authors (JD, SYK) extracted data from selected studies, and carried out a risk of bias assessment. We extracted data on fatigue, mood, cognition, quality of life and adverse events outcomes.
MAIN RESULTS
The original review identified one study and this update identified a further two for inclusion. One study investigated the use of modafinil, one study the use of armodafinil and one study the use of dexamfetamine. We identified three ongoing studies. In the original review, the single eligible trial compared modafinil to placebo for 37 participants with a high- or low-grade PBT. One new study compared two doses of armodafinil (150 mg and 250 mg) to placebo for 297 people with a high-grade glioma. The second new study compared dexamfetamine sulfate to placebo for 46 participants with a low- or high-grade PBT. The evidence was uncertain for both modafinil and dexamfetamine regarding fatigue outcome measures, compared to controls, at study endpoint. Two trials did not reach the planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. These trials were at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation for one study because the investigators did not analyse the impact of imputation on the results and information regarding baseline characteristics and randomisation were not clear. The certainty of the evidence measured using GRADE was very low across all three studies. There was one identified study awaiting classification once data are available, which investigated the feasibility of 'health coaching' for people with a PBT experiencing fatigue. There were three ongoing studies that may be eligible for an update of this review, all investigating a non-pharmacological intervention for fatigue in people with PBT.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
Topics: Adult; Brain Neoplasms; Dextroamphetamine; Fatigue; Glioma; Humans; Modafinil
PubMed: 36094728
DOI: 10.1002/14651858.CD011376.pub3 -
Journal of the Neurological Sciences Nov 2022Esthesioneuroblastoma (ENB) is a rare malignant neoplasm of the olfactory epithelium with an estimated incidence of 0.4/million. It can directly extend along the... (Review)
Review
PURPOSE
Esthesioneuroblastoma (ENB) is a rare malignant neoplasm of the olfactory epithelium with an estimated incidence of 0.4/million. It can directly extend along the cribriform plate in order to metastasize to the central nervous system. However, non-contiguous intracranial involvement without recurrence at the primary site is extremely uncommon. In this report, the authors review the literature and present a case of non-contiguous intracranial metastasis of ENB without recurrence at the primary site. To the best of our knowledge, this case presents the longest disease-free interval reported in the literature.
METHODS
A systematic review of literature was conducted in accordance with the PRISMA guidelines. Additionally, the presentation, surgical management, and post-operative outcomes of an 82-year-old female with non-contiguous intracranial metastasis of ENB after 19 years of remission are described.
RESULTS
A total of 137 deduplicated works were identified after the search. Of these, 6 papers satisfied our inclusion criteria for our systematic review. Average age at presentation was 50.8 years (range: 26-66) and 52.6% of patients were female. A majority of cases achieved gross-total resection and received adjuvant radiotherapy for initial treatment. The median interval to intracranial metastasis was 6 years from the time of primary tumor presentation. The median overall survival from ENB recurrence with non-contiguous intracranial metastasis was 11.5 months.
CONCLUSIONS
ENB is a highly recurrent tumor and harbors the potential to involve the intracranial space even years after remission. Intracranial involvement entails poor overall survival. Lifetime radiographic follow-up should be considered in all patients with ENB.
Topics: Humans; Female; Aged, 80 and over; Male; Esthesioneuroblastoma, Olfactory; Nose Neoplasms; Nasal Cavity; Disease-Free Survival
PubMed: 36081302
DOI: 10.1016/j.jns.2022.120406 -
International Journal of Molecular... Aug 2022Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers... (Meta-Analysis)
Meta-Analysis Review
Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers to predict the response and outcome of current or newly designed therapies. While several molecular markers have been proposed as potential biomarkers for GBM, their uptake into clinical settings is slow and impeded by marker heterogeneity. Detailed assessment of prognostic and predictive value for biomarkers in well-defined clinical trial settings, if available, is scattered throughout the literature. Here we conducted a systematic review and meta-analysis to evaluate the prognostic and predictive significance of clinically relevant molecular biomarkers in GBM patients. Material and methods: A comprehensive literature search was conducted to retrieve publications from 3 databases (Pubmed, Cochrane and Embase) from January 2010 to December 2021, using specific terms. The combined hazard ratios (HR) and confidence intervals (95% CI) were used to evaluate the association of biomarkers with overall survival (OS) in GBM patients. Results: Twenty-six out of 1831 screened articles were included in this review. Nineteen articles were included in the meta-analyses, and 7 articles were quantitatively summarised. Fourteen studies with 1231 GBM patients showed a significant association of MGMT methylation with better OS with the pooled HR of 1.66 (95% CI 1.32−2.09, p < 0.0001, random effect). Five studies including 541 GBM patients analysed for the prognostic significance of IDH1 mutation showed significantly better OS in patients with IDH1 mutation with a pooled HR of 2.37 (95% CI 1.81−3.12; p < 0.00001]. Meta-analysis performed on 5 studies including 575 GBM patients presenting with either amplification or high expression of EGFR gene did not reveal any prognostic significance with a pooled HR of 1.31 (95% CI 0.96−1.79; p = 0.08). Conclusions: MGMT promoter methylation and IDH1 mutation are significantly associated with better OS in GBM patients. No significant associations were found between EGFR amplification or overexpression with OS.
Topics: Biomarkers; Biomarkers, Tumor; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Tumor Suppressor Proteins
PubMed: 36012105
DOI: 10.3390/ijms23168835 -
JAMA Network Open Aug 2022Pediatric patients with high-grade gliomas have a poor prognosis. The association among the extent of resection, tumor location, and survival in these patients remains... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Pediatric patients with high-grade gliomas have a poor prognosis. The association among the extent of resection, tumor location, and survival in these patients remains unclear.
OBJECTIVE
To ascertain whether gross total resection (GTR) in hemispheric, midline, or infratentorial pediatric high-grade gliomas (pHGGs) is independently associated with survival differences compared with subtotal resection (STR) and biopsy at 1 year and 2 years after tumor resection.
DATA SOURCES
PubMed, EBMR, Embase, and MEDLINE were systematically reviewed from inception to June 3, 2022, using the keywords high-grade glioma, pediatric, and surgery. No period or language restrictions were applied.
STUDY SELECTION
Randomized clinical trials and cohort studies of pHGGs that stratified patients by extent of resection and reported postoperative survival were included for study-level and individual patient data meta-analyses.
DATA EXTRACTION AND SYNTHESIS
Study characteristics and mortality rates were extracted from each article. Relative risk ratios (RRs) were pooled using random-effects models. Individual patient data were evaluated using multivariate mixed-effects Cox proportional hazards regression modeling. The PRISMA reporting guideline was followed, and the study was registered a priori.
MAIN OUTCOMES AND MEASURES
Hazard ratios (HRs) and RRs were extracted to indicate associations among extent of resection, 1-year and 2-year postoperative mortality, and overall survival.
RESULTS
A total of 37 studies with 1387 unique patients with pHGGs were included. In study-level meta-analysis, GTR had a lower mortality risk than STR at 1 year (RR, 0.69; 95% CI, 0.56-0.83; P < .001) and 2 years (RR, 0.74; 95% CI, 0.67-0.83; P < .001) after tumor resection. Subtotal resection was not associated with differential survival compared with biopsy at 1 year (RR, 0.82; 95% CI, 0.66-1.01; P = .07) but had decreased mortality risk at 2 years (RR, 0.89; 95% CI, 0.82-0.97; P = .01). The individual patient data meta-analysis of 27 articles included 427 patients (mean [SD] age at diagnosis, 9.3 [5.9] years), most of whom were boys (169 of 317 [53.3%]), had grade IV tumors (246 of 427 [57.7%]), and/or had tumors that were localized to either the cerebral hemispheres (133 of 349 [38.1%]) or midline structures (132 of 349 [37.8%]). In the multivariate Cox proportional hazards regression model, STR (HR, 1.91; 95% CI, 1.34-2.74; P < .001) and biopsy (HR, 2.10; 95% CI, 1.43-3.07; P < .001) had shortened overall survival compared with GTR but no survival differences between them (HR, 0.91; 95% CI, 0.67-1.24; P = .56). Gross total resection was associated with prolonged survival compared with STR for hemispheric (HR, 0.29; 95% CI, 0.15-0.54; P < .001) and infratentorial (HR, 0.44; 95% CI, 0.24-0.83; P = .01) tumors but not midline tumors (HR, 0.63; 95% CI, 0.34-1.19; P = .16).
CONCLUSIONS AND RELEVANCE
Results of this study show that, among patients with pHGG, GTR is independently associated with better overall survival compared with STR and biopsy, especially among patients with hemispheric and infratentorial tumors, and support the pursuit of maximal safe resection in the treatment of pHGGs.
Topics: Biopsy; Child; Cohort Studies; Female; Glioma; Humans; Male; Neurosurgical Procedures; Proportional Hazards Models
PubMed: 35972743
DOI: 10.1001/jamanetworkopen.2022.26551 -
Quality of Life Research : An... Mar 2023Low-grade glioma (LGG) patients may face health-related quality-of-life (HRQoL) impairments, due to the tumour, treatment and associated side-effects and prospects of... (Review)
Review
PURPOSE
Low-grade glioma (LGG) patients may face health-related quality-of-life (HRQoL) impairments, due to the tumour, treatment and associated side-effects and prospects of progression. We systematically identified quantitative studies assessing HRQoL in adult LGG patients, for: aspects of HRQoL impacted; comparisons with non-cancer controls (NCC) and other groups; temporal trends; and factors associated with HRQoL.
METHODS
MEDLINE, CINAHL, Embase, PubMed, and PsycINFO were systematically searched from inception to 14th September 2021. Following independent screening of titles and abstracts and full-texts, population and study characteristics, and HRQoL findings were abstracted from eligible papers, and quality appraised. Narrative synthesis was conducted.
RESULTS
Twenty-nine papers reporting 22 studies (cross-sectional, n = 13; longitudinal, n = 9) were identified. Papers were largely good quality, though many excluded patients with cognitive and communication impairments. Comparators included high-grade gliomas (HGG) (n = 7); NCCs (n = 6) and other patient groups (n = 3). Nineteen factors, primarily treatment (n = 8), were examined for association with HRQoL. There was substantial heterogeneity in HRQoL instruments used, factors and aspects of HRQoL assessed and measurement timepoints. HRQoL, primarily cognitive functioning and fatigue, in adult LGG patients is poor, and worse than in NCCs, though better than in HGG patients. Over time, HRQoL remained low, but stable. Epilepsy/seizure burden was most consistently associated with worse HRQoL.
CONCLUSION
LGG patients experience wide-ranging HRQoL impairments. HRQoL in those with cognitive and communication impairments requires further investigation. These findings may help clinicians recognise current supportive care needs and inform types and timings of support needed, as well as inform future interventions.
Topics: Humans; Adult; Cross-Sectional Studies; Quality of Life; Glioma; Cognition; Drug-Related Side Effects and Adverse Reactions
PubMed: 35931881
DOI: 10.1007/s11136-022-03207-x -
Scientific Reports Aug 2022High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However,... (Meta-Analysis)
Meta-Analysis
High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However, differentiating true tumour progression (TTP) from treatment-related effects or pseudoprogression (PsP), may critically influence subsequent management options. Structural MRI is routinely employed to evaluate treatment responses, but misdiagnosis of TTP or PsP may lead to continuation of ineffective or premature cessation of effective treatments, respectively. A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses method. Embase, MEDLINE, Web of Science and Google Scholar were searched for methods applied to differentiate PsP and TTP, and studies were selected using pre-specified eligibility criteria. The sensitivity and specificity of included studies were summarised. Three of the identified methods were compared in a separate subgroup meta-analysis. Thirty studies assessing seven distinct neuroimaging methods in 1372 patients were included in the systematic review. The highest performing methods in the subgroup analysis were DWI (AUC = 0.93 [0.91-0.95]) and DSC-MRI (AUC = 0.93 [0.90-0.95]), compared to DCE-MRI (AUC = 0.90 [0.87-0.93]). 18F-fluoroethyltyrosine PET (18F-FET PET) and amide proton transfer-weighted MRI (APTw-MRI) also showed high diagnostic accuracy, but results were based on few low-powered studies. Both DWI and DSC-MRI performed with high sensitivity and specificity for differentiating PsP from TTP. Considering the technical parameters and feasibility of each identified method, the authors suggested that, at present, DSC-MRI technique holds the most clinical potential.
Topics: Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging; Sensitivity and Specificity; Treatment Outcome
PubMed: 35918373
DOI: 10.1038/s41598-022-16726-x -
Neurotoxicology Sep 2022Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models... (Review)
Review
Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models including primary neuronal cultures and cell lines from rodents. The issues of species differences between humans and rodents, the animal ethical concerns and the time and cost required for neurotoxicity studies on in vivo animal models, do limit the use of animal-based models in neurotoxicology. In this context, human cell models appear relevant in elucidating cellular and molecular impacts of neurotoxicants and facilitating prioritization of in vivo testing. The SH-SY5Y human neuroblastoma cell line (ATCC® CRL-2266™) is one of the most used cell lines in neurosciences, either undifferentiated or differentiated into neuron-like cells. This review presents the characteristics of the SH-SY5Y cell line and proposes the results of a systematic review of literature on the use of this in vitro cell model for neurotoxicity research by focusing on organic environmental pollutants including pesticides, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), flame retardants, PFASs, parabens, bisphenols, phthalates, and PAHs. Organic environmental pollutants are widely present in the environment and increasingly known to cause clinical neurotoxic effects during fetal & child development and adulthood. Their effects on cultured SH-SY5Y cells include autophagy, cell death (apoptosis, pyroptosis, necroptosis, or necrosis), increased oxidative stress, mitochondrial dysfunction, disruption of neurotransmitter homeostasis, and alteration of neuritic length. Finally, the inherent advantages and limitations of the SH-SY5Y cell model are discussed in the context of chemical testing.
Topics: Adult; Animals; Cell Line, Tumor; Cell Survival; Child; Environmental Pollutants; Flame Retardants; Fluorocarbons; Humans; Neuroblastoma; Neurotoxicity Syndromes; Parabens; Pesticides; Polychlorinated Dibenzodioxins
PubMed: 35914637
DOI: 10.1016/j.neuro.2022.07.008 -
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 -
Neurosurgical Review Oct 2022The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the... (Review)
Review
The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the treatment spectrum of neuroendoscopy. This review aimed to present a systematic overview of the extent of resection, lesion characteristics, technical aspects, complications, and clinical outcomes related to using the NUA. Articles were identified by searching the PubMed/Medline, Embase, and Web of Science database through June 2022 with restriction to the last 20 years. We included case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews written in English. Studies reporting on endonasal approach or hematoma evacuation using the NUA were excluded. The references of the identified studies were reviewed as well. Nine full-text articles were included in the analysis, with a total of 40 patients who underwent surgery for a brain tumor using NUA. The most common underlying pathology treated by NUA was colloid cyst (17.5%), pilocytic astrocytoma (12.5%), subependymal giant cell astrocytoma (7.5%), subependymoma (7.5%), and craniopharyngioma (7.5%). Complete or near-total resection was achieved in 62.5%. The most frequently reported postoperative complication was secondary hydrocephalus (10%), meningitis/-encephalitis (7.5%), cognitive impairment (7.5%), and subdural hygroma (7.5%). In one case (2.5%), surgery-related death occurred due to a severe course of meningoencephalitis. According to the preliminary data, NUA seems to be a safe and efficient minimally invasive alternative to conventional microscopic resection of brain tumors. Further studies to investigate advantages and disadvantages of using the NUA are needed.
Topics: Astrocytoma; Brain; Brain Neoplasms; Colloid Cysts; Humans; Neuroendoscopy; Pituitary Neoplasms; Ultrasonics
PubMed: 35896917
DOI: 10.1007/s10143-022-01837-w -
Nutrients Jul 2022Glioblastoma (GBM), a highly lethal form of adult malignant gliomas with little clinical advancement, raises the need for alternative therapeutic approaches.... (Review)
Review
Glioblastoma (GBM), a highly lethal form of adult malignant gliomas with little clinical advancement, raises the need for alternative therapeutic approaches. Lipid-soluble vitamins have gained attention in malignant brain tumors owing to their pleiotropic properties and their anti-cancer potential have been reported in a number of human GBM cell lines. The aim of this paper is to systematically review and describe the roles of various biomarkers regulated by lipid-soluble vitamins, such as vitamins A, D, E, and K, in the pathophysiology of GBM. Briefly, research articles published between 2005 and 2021 were systematically searched and selected from five databases (Scopus, PubMed, Ovid MEDLINE, EMBASE via Ovid, and Web of Science) based on the study's inclusion and exclusion criteria. In addition, a number of hand-searched research articles identified from Google Scholar were also included for the analysis. A total of 40 differentially expressed biomarkers were identified from the 19 eligible studies. The results from the analysis suggest that retinoids activate cell differentiation and suppress the biomarkers responsible for stemness in human GBM cells. Vitamin D appears to preferentially modulate several cell cycle biomarkers, while vitamin E derivatives seem to predominantly modulate biomarkers related to apoptosis. However, vitamin K1 did not appear to induce any significant changes to the Raf/MEK/ERK signaling or apoptotic pathways in human GBM cell lines. From the systematic analysis, 12 biomarkers were identified that may be of interest for further studies, as these were modulated by one or two of these lipid-soluble vitamins.
Topics: Adult; Biomarkers; Brain Neoplasms; Glioblastoma; Humans; Lipids; Vitamins
PubMed: 35889829
DOI: 10.3390/nu14142873