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Cancer Control : Journal of the Moffitt... 2022Glioblastoma multiforme (GBM) makes 60-70% of gliomas and 15% of primary brain tumors. Despite the availability of standard multimodal therapy, 2 years, 3 years, and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Glioblastoma multiforme (GBM) makes 60-70% of gliomas and 15% of primary brain tumors. Despite the availability of standard multimodal therapy, 2 years, 3 years, and 5 years survival rate of GBM are still low. Active immunotherapy is a relatively new treatment option for GBM that seems promising.
METHODS
An electronic database search on PubMed, Cochrane, Scopus, and clinicaltrials.gov was performed to include all relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Reported parameters are OS, PFS, AEs, post treatment KPS, and 2 year mortality.
RESULTS
Active immunotherapy provided better OS (HR = .85; 95% CI = .71-1.01; = .06) and PFS (HS = .83; 95% CI= .66 - 1.03; = .11) side albeit not statistically significant. Active immunotherapy reduces the risk of 2 year mortality as much as 2.5% compared to control group (NNT and RRR was 56.7078 and 0,0258, respectively).
CONCLUSION
Active immunotherapy might be beneficial in terms of survival rate in patients with GBM although not statistically significant. It could be a treatment option for GBM in the future.
Topics: Humans; Glioblastoma; Brain Neoplasms; Glioma; Combined Modality Therapy; Immunotherapy, Active; Immunotherapy
PubMed: 36748348
DOI: 10.1177/10732748221079474 -
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 -
European Review For Medical and... Nov 2021The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent glioblastoma (GBM). We conducted a systematic review and meta-analysis to assess the efficacy of bevacizumab in recurrent GBM patients.
MATERIALS AND METHODS
We searched electronic databases (Medline, Embase, and Web of Science) contrasting the bevacizumab with standard treatments up to May 2021. For the continuous outcomes of median progression-free survival (PFS) and median overall survival (OS), we summarized the mean difference (MD) as the effective index. We used relative risk (RR) to estimate the data with a random-effects model to get the outcomes of objective response rate (ORR), 12-month OS, 6-month PFS, and any mentioned adverse events.
RESULTS
A total of 807 patients in 5 RCTs included into our systematic review and meta-analysis. The results showed bevacizumab could provide benefits of the ORR (RR, 2.67; 95% CI: 1.14-6.26, p = 0.02), median PFS (MD, 1.12 months; 95% CI: 0.35-1.90 months, p = 0.005), but not the median OS (MD, -0.19 months; 95% CI: -1.37-0.99 months, p = 0.75). Whereas the rates of the secondary outcomes of interest were similar between the bevacizumab group and control group, including 6 month-PFS (RR, 1.23; 95% CI, 0.82-1.84, p = 0.32) and 12 month-OS (RR, 0.93; 95% CI, 0.79-1.09, p = 0.36). As for adverse events, patients with bevacizumab showed higher rates of grade 3/4 and any grade hypertension compared with those with standard treatments (RR, 3.71; 95% CI: 1.17-11.76, p = 0.03; RR, 2.68; 95% CI: 1.26-5.76, p = 0.01, respectively).
CONCLUSIONS
This study provides clear proof of the beneficial effects of bevacizumab treatment in recurrent GBM patients. The only observed adverse event was grade 3/4 or any grade hypertension.
Topics: Angiogenesis Inhibitors; Bevacizumab; Brain Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34787852
DOI: 10.26355/eurrev_202111_27092 -
Journal of Cancer Research and... 2016Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood neuroblastoma. A meta-analysis was performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood neuroblastoma. A meta-analysis was performed statistically surmising all available observational studies on this topic in order to evaluate the potential correlation of maternal smoking during pregnancy and risk of childhood neuroblastoma.
METHODS
Published literature was obtained from PubMed, Embase, ISI Web of Science, and Cochrane library, and all studies were inclusive until July 2014. Data from epidemiological studies were combined using a general variance-based meta-analytic method employing 95% confidence intervals. The outcome of interest was shown as odds ratio (OR) reflecting the risk of neuroblastoma development associated with smoking while pregnant. Newcastle-Ottawa Scale was used to assess the quality of studies.
RESULTS
Seven case-control studies meeting protocol specified inclusion criteria were obtained through a comprehensive literature search. These studies enrolled a total of 1909 patients and 15,683 controls. Analysis for homogeneity demonstrated that the data were heterogeneous (P < 0.05) and could be statistically combined with randomized effect model. Combining all seven reports yielded an OR of 1.28 (1.01-1.62), a statistically significant result suggesting possible association between maternal smoking during pregnancy and risk of childhood neuroblastoma development (P = 0.005). There was no association between the dosage of maternal smoking during pregnancy and risk of neuroblastoma.
CONCLUSION
The available epidemiological data support a possible association between maternal smoking during pregnancy and pediatric neuroblastoma development.
Topics: Case-Control Studies; Child; Female; Humans; Maternal Exposure; Neuroblastoma; Odds Ratio; Pregnancy; Prenatal Exposure Delayed Effects; Publication Bias; Risk Factors; Smoking
PubMed: 27461688
DOI: 10.4103/0973-1482.171367 -
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 -
Translational Stroke Research Dec 2018Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic... (Meta-Analysis)
Meta-Analysis Review
Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers. Oxygen-glucose deprivation, HO, hypoxia, glucose-deprivation and glutamate excitotoxicity yielded - 58, - 61, - 29, - 45 and - 49% injury, respectively, with a dose-response relationship found only for HO injury (R = 29.29%, p < 0.002). Heterogeneity (I = 99.36%, df = 132, p < 0.0001) was largely attributable to the methods used to detect injury (R = 44.77%, p < 0.000) with cell death assays detecting greater injury than survival assays (- 71 vs - 47%, R = 28.64%, p < 0.000). Seventy-four percent of publications provided no description of differentiation status, but in the 26% that did, undifferentiated cells were susceptible to greater injury (R = 4.13%, p < 0.047). One hundred and sixty-nine interventions improved average survival by 34.67% (p < 0.0001). Eighty-eight comparisons using oxygen-glucose deprivation found both benefit and harm, but studies using glutamate and HO injury reported only improvement. In studies using glucose deprivation, intervention generally worsened outcome. There was insufficient data to rank individual interventions, but of the studies reporting greatest improvement (> 90% effect size), 7/13 were of herbal medicine constituents (24.85% of the intervention dataset). We conclude that surprisingly little is known of the human neuronal response to ischaemic injury, and that the large impact of methodology on outcome indicates that further model validation is required. Lack of evidence for randomisation, blinding or power analysis suggests that the intervention data is at substantial risk of bias.
Topics: Databases, Bibliographic; Humans; Ischemia; Neuroblastoma
PubMed: 29572690
DOI: 10.1007/s12975-018-0620-4 -
Neuro-oncology Feb 2019Emerging evidence suggests survival benefit from resection beyond all MRI abnormalities present on T1-enhanced and T2‒fluid attenuated inversion recovery (FLAIR)...
BACKGROUND
Emerging evidence suggests survival benefit from resection beyond all MRI abnormalities present on T1-enhanced and T2‒fluid attenuated inversion recovery (FLAIR) modalities in glioma (supratotal resection); however, the quality of evidence is unclear. We addressed this question via systematic review of the literature.
METHODS
EMBASE, MEDLINE, Scopus, and Web of Science databases were queried. Case studies, reviews or editorials, non-English, abstract-only, brain metastases, and descriptive works were excluded. All others were included.
RESULTS
Three hundred and nine unique references yielded 41 studies for full-text review, with 7 included in the final analysis. Studies were mostly of Oxford Center for Evidence-Based Medicine Level 4 quality. A total of 88 patients underwent supratotal resection in a combined cohort of 492 patients (214 males and 278 females, age 18 to 82 years). Fifty-one supratotal resections were conducted on high-grade gliomas, and 37 on low-grade gliomas. Karnofsky performance status, overall survival, progression-free survival, neurological deficits postoperatively, and anaplastic transformation were the main measured outcomes. No randomized controlled trials were identified. Preliminary low-quality support was found for supratotal resection in increasing overall survival and progression-free survival for both low-grade and high-grade glioma.
CONCLUSION
The literature suggests insufficient evidence for carte blanche application of supratotal resection, particularly in lower-grade gliomas where neurological deficits can result in long-term disability. While the preliminary studies discussed here, containing data from only a few centers, have reported increased progression-free and overall survival, these claims require validation in prospective research studies involving larger patient populations with clearly defined appropriate outcome metrics in order to reduce potential bias.
Topics: Brain Neoplasms; Glioma; Humans; Meta-Analysis as Topic; Neurosurgical Procedures; Prognosis
PubMed: 30321384
DOI: 10.1093/neuonc/noy166 -
Journal of Experimental & Clinical... May 2015CD133 and Nestin, as the markers of cancer stem cells, have recently been reported frequently in the pathogenesis and development of human gliomas. However, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
CD133 and Nestin, as the markers of cancer stem cells, have recently been reported frequently in the pathogenesis and development of human gliomas. However, the prognostic role of CD133 and Nestin in gliomas still remains controversial. In this study, we aimed to evaluate the association between the expression of CD133 and Nestin and the outcome of glioma patients by conducting a systematic review and meta-analysis.
METHODS
We performed systematically electronic and manual searches through the database of Pubmed and embase (until to December 25, 2014) for titles and abstracts which investigated the relationships between CD133 and Nestin expression and outcome of glioma patients. A systematic review and meta-analysis was executed to generate Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS).
RESULTS
A total of 1,490 patients from 32 studies (13 articles) were included in the analysis. 19 studies and 13 studies investigated correlation between CD133 expression or Nestin and survival in gliomas, respectively. Our results showed that high CD133 expression in patients with glioma was associated with poor prognosis in terms of OS (HR 1.69; 95 % CI, 1.16-2.47; P =0.0060) and PFS (HR, 1.64; 95 % CI, 1.12-2.39; P = 0.010). In addition, high Nestin expression were associated with worse OS (HR 1.751; 95 % CI, 1.19-2.58, p = 0.004) but has no significant association with PFS (HR 1.55; 95 % CI, 0.96-2.51, p = 0.074). Even more important, the results of the subgroup meta-analyses show that that high CD133 expression was associated with worse prognosis in terms of OS and PFS in patients with WHO IV glioma but not WHO II-III. On the other hand, Nestin high expression was associated with worse prognosis in terms of OS and PFS in patients with WHO II-III glioma but not WHO IV.
CONCLUSION
High level of CD133 expression trends to correlate with a worse OS and PFS in glioma patients, especially WHO IV gliomas and Nestin high expression trends to correlate with a worse OS in glioma patients especially WHO II-III, revealing both the markers of cancer stem cells may as the potential pathological prognostic markers for glioma patients.
Topics: AC133 Antigen; Antigens, CD; Biomarkers, Tumor; Female; Gene Expression; Glioma; Glycoproteins; Humans; Male; Neoplastic Stem Cells; Nestin; Peptides; Prognosis; Proportional Hazards Models; Publication Bias; Survival Analysis
PubMed: 25967234
DOI: 10.1186/s13046-015-0163-4 -
Neuro-oncology Mar 2023This systematic review provides updated insights, from the published literature in the past 5 years, based on the 2017 European Association of Neuro-Oncology (EANO)...
BACKGROUND
This systematic review provides updated insights, from the published literature in the past 5 years, based on the 2017 European Association of Neuro-Oncology (EANO) guidelines for palliative care in adults with malignant brain tumors. It provides an overview of palliative care options, including during the end-of-life phase for patients with malignant brain tumors.
METHODS
A systematic literature search was conducted from 2016 to 2021 focusing on four main topics: (1) symptom management, (2) caregiver needs, (3) early palliative care, and (4) care in the end-of-life phase. An international panel of palliative care experts in neuro-oncology synthesized the literature and reported the most relevant updates. A total of 140 articles were included.
RESULTS
New insights include that: Hippocampal avoidance and stereotactic radiosurgery results in a lower risk of neurocognitive decline in patients with brain metastases; levetiracetam is more efficacious in reducing seizures than valproic acid as first-line monotherapy antiseizure drug (ASD) in glioma patients; lacosamide and perampanel seem well-tolerated and efficacious add-on ASDs; and a comprehensive framework of palliative and supportive care for high-grade glioma patients and their caregivers was proposed. No pharmacological agents have been shown in randomized controlled trials to significantly improve fatigue or neurocognition.
CONCLUSIONS
Since the 2017 EANO palliative care guidelines, new insights have been reported regarding symptom management and end-of-life care, however, most recommendations remain unchanged. Early palliative care interventions are essential to define goals of care and minimize symptom burden in a timely fashion. Interventional studies that address pain, fatigue, and psychiatric symptoms as well as (the timing of) early palliative care are urgently needed.
Topics: Humans; Adult; Terminal Care; Brain Neoplasms; Glioma; Death; Fatigue
PubMed: 36271873
DOI: 10.1093/neuonc/noac216 -
Cancer Metastasis Reviews Mar 2022Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine... (Review)
Review
BACKGROUND
Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis.
METHODS
Statistical correlations for all RTK family members' expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal ( http://depmap.org )). Finally, we provide a detailed literature review for highly ranked candidates.
RESULTS
Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets.
CONCLUSIONS
Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.
Topics: Carcinogenesis; Cell Line, Tumor; Child; Humans; Neuroblastoma; Receptor Protein-Tyrosine Kinases; Signal Transduction
PubMed: 34716856
DOI: 10.1007/s10555-021-10001-7