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World Neurosurgery Feb 2022Hemangioblastomas (HBs) are well-vascularized, benign central nervous system tumors and the third most common primary spinal cord tumor after astrocytoma/ependymoma,... (Review)
Review
BACKGROUND
Hemangioblastomas (HBs) are well-vascularized, benign central nervous system tumors and the third most common primary spinal cord tumor after astrocytoma/ependymoma, occurring sporadically or as a part of autosomal dominant von Hippel-Lindau disease, in which tumors are often multiple and prone to relapse. Spinal HBs are commonly located in the cervical cord and associated with a syrinx formation. Owing to location and growth trends, they may cause significant neurological deficit, impairing quality of life. We conducted a systematic review to understand better clinical insights into spinal HB in adults and compare spinal HB versus posterior cranial fossa HB.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting systematic reviews, we reviewed the English-language literature on adult spinal HB in the MEDLINE/PubMed database over the last 40 years.
RESULTS
We reviewed 237 articles on adult spinal HB and analyzed national and continental distribution, clinical symptoms, tumor location and presence of syringomyelia, treatment strategies and postoperative complications, histology and immunochemistry, and treatment outcomes. We compared individual characteristics in sporadic and von Hippel-Lindau disease spinal HBs. Finally, we compared features of posterior cranial fossa and spinal HBs.
CONCLUSIONS
Spinal cord HBs most commonly have a dorsal intramedullary location. Total surgical tumor resection is the first treatment option; preoperative embolization may be performed to reduce intraoperative bleeding and surgical time. HBs located in the spine have decreased mortality and rate of infection, but increased rates of cardiopulmonary complications compared with HBs in the posterior cranial fossa.
Topics: Adult; Hemangioblastoma; Humans; Neoplasm Recurrence, Local; Quality of Life; Spinal Cord Neoplasms; Syringomyelia; von Hippel-Lindau Disease
PubMed: 34687932
DOI: 10.1016/j.wneu.2021.10.105 -
Journal of Neuro-oncology Nov 2021Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature.
METHODS
A systematic literature review from 1970 to 2020 was performed, and individualized clinical data for patients diagnosed with DIA/DIG were extracted. Aggregated data were excluded from collection. Outcome measures of interest were mortality and tumor recurrence/progression, as well as time-to-event (TTE) for each of these. Participants without information on these outcome measures were excluded. Cox regression survival analyses were performed to determine predictors of mortality and tumor recurrence / progression.
RESULTS
We identified 98 articles and extracted individual patient data from 188 patients. The cohort consisted of 58.9% males with a median age of 7 months. The majority (68.1%) were DIGs, while 24.5% were DIAs and 7.5% were non-specific desmoplastic infantile tumors; DIAs presented more commonly in deep locations (p = 0.001), with leptomeningeal metastasis (p = 0.001), and was associated with decreased probability of gross total resection (GTR; p = 0.001). Gender, age, and tumor pathology were not statistically significant predictors of either mortality or tumor recurrence/progression. On multivariate survival analysis, GTR was a predictor of survival (HR = 0.058; p = 0.007) while leptomeningeal metastasis at presentation was a predictor of mortality (HR = 3.27; p = 0.025). Deep tumor location (HR = 2.93; p = 0.001) and chemotherapy administration (HR = 2.02; p = 0.017) were associated with tumor recurrence/progression.
CONCLUSION
Our IPDMA of DIA/DIG cases reported in the literature revealed that GTR was a predictor of survival while leptomeningeal metastasis at presentation was associated with mortality. Deep tumor location and chemotherapy were associated with tumor recurrence / progression.
Topics: Astrocytoma; Brain Neoplasms; Female; Ganglioglioma; Humans; Infant; Male; Meningeal Carcinomatosis; Neoplasm Recurrence, Local
PubMed: 34613581
DOI: 10.1007/s11060-021-03860-1 -
Progres En Urologie : Journal de... Feb 2014A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the... (Review)
Review
INTRODUCTION
A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers.
MATERIAL AND METHOD
We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting.
RESULTS
Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers.
CONCLUSION
Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings.
Topics: Humans; Renin-Angiotensin System; Urologic Neoplasms
PubMed: 24485075
DOI: 10.1016/j.purol.2013.09.010 -
Journal of Ethnopharmacology May 2024Paeoniae Radix Rubra (PRR) is the dried root of Paeonia lactiflora Pall, which has been widely used to anti-thrombotic, lipid-lowering, anti-spasmodic, antioxidant,... (Meta-Analysis)
Meta-Analysis Review
ETHNOPHARMACOLOGICAL RELEVANCE
Paeoniae Radix Rubra (PRR) is the dried root of Paeonia lactiflora Pall, which has been widely used to anti-thrombotic, lipid-lowering, anti-spasmodic, antioxidant, antibacterial, hepatoprotective, and anti-tumor in Chinese clinical practice. Recent research has demonstrated that PRR plays a significant anti-tumor role in animal models of tumor-bearing.
AIM OF THE STUDY
There has not been the evaluation of the anti-tumor effects of PRR. This study conducts a meta-analysis to assess the anti-tumor efficacy of PRR on animal models, providing scientific evidence for clinical application of PRR in the adjuvant therapy of tumors.
MATERIALS AND METHODS
English databases (PubMed, The Cochrane Library, Embase, and Web of Science) and Chinese databases (CNKI, WanFang, SinoMed, CTSJ-VIP) were used to search all pertinent animal studies investigating the anti-tumor effects of PRR and its extracts. The quality of the included studies was evaluated using the SYRCLE animal experiment risk assessment tool, and statistical analysis was carried out using Revman 5.3 software. Egger's test and funnel plots were used to assess potential publication bias in the studies.
RESULTS
The initial search produced a total of 3905 potentially pertinent studies, and 24 studies met the inclusion criteria. These studies included animal tumor models of hepatocellular carcinoma, lung cancer, sarcoma, bladder cancer, leukemia, colon cancer, glioblastoma, and pancreatic cancer. The meta-analysis findings demonstrated that both PRR and its extracts significantly inhibited tumor growth in animals. Compared with the control group, PRR substantively inhibited tumor volume (SMD, -3.09; 95% CI, [-4.05, -2.13]; P < 0.0001), reduced tumor weight (SMD, -1.08; 95% CI, [-1.37, -0.78]; P < 0.0001), decreased tumor number (SMD, -2.16; 95% CI, [-3.45, -0.86]; P = 0.001), and prolonged the survival duration time (SMD, 0.97; 95% CI, [0.23, 1.71]; P = 0.01) on the experimental animals.
CONCLUSIONS
PRR displayed a potential therapeutic efficacy on eight tumors in animal models including hepatocellular carcinoma, lung cancer, sarcoma, bladder cancer, leukemia, colon cancer, glioblastoma, and pancreatic cancer. However, the quality and quantity of included studies may affect the accuracy of positive results. In the future, more high-quality randomized controlled animal experiments are need for meta-analysis.
Topics: Animals; Carcinoma, Hepatocellular; Glioblastoma; Lung Neoplasms; Models, Animal; Liver Neoplasms; Sarcoma; Leukemia; Colonic Neoplasms; Pancreatic Neoplasms; Urinary Bladder Neoplasms; Drugs, Chinese Herbal; Plant Extracts; Paeonia
PubMed: 38423407
DOI: 10.1016/j.jep.2024.117987 -
Child's Nervous System : ChNS :... Sep 2020Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and... (Review)
Review
INTRODUCTION
Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order to identify trends in current research and provide an overview to guide future research efforts.
METHODS
This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Cochrane Controlled Register of Trials (CENTRAL) and ClinicalTrials.gov were searched. Inclusion and exclusion criteria were applied and final results were reviewed.
RESULTS
501 clinical trials were identified with the search strategy. All were screened and eligible studies extracted and reviewed. This yielded 36 ongoing clinical trials, 27 of which were pharmacological agents in phase I-III. The remaining trials were a mixture of biological agents, radiation optimisation, diagnostic imaging, surgical intervention, and a social function analysis.
CONCLUSION
OPG is a complex multifaceted disease, and advances in care require ongoing research efforts across a spectrum of different research fields. This review provides an update on the current state of research in OPG and summarises ongoing trials.
Topics: Astrocytoma; Humans; Neurofibromatosis 1; Optic Nerve Glioma
PubMed: 32556546
DOI: 10.1007/s00381-020-04724-1 -
Cellular and Molecular Neurobiology Nov 2023Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for... (Review)
Review
Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for diagnosis, follow- up and treatment. We propose a clinical utility score (CUS) for biomarkers in LGG that mirrors their clinical usefulness. We conducted a PRISMA review. We examined each biomarker classifying them by CUS and Level of Evidence (LOE). We identified four classes of biomarkers: (1). Circulating protein-(a) vitronectin discriminates LGG from HGG (Sn:98%, Sp:91%, CUS: 3, LOE: III), (b) CTLA-4 discriminates LGG from HGG, (cutoff: 220.43 pg/ml, Sn: 82%, Sp: 78%, CUS:3, LOE:III), (c) pre-operative TGF b1 predict astrocytoma (cutoff: 2.52 ng/ml, Sn: 94.9%, Sp: 100%, CUS:3, LOE:VI). (2). micro-RNA (miR)-(a) miR-16 discriminates between WHO IV and WHO II and III groups (AUC = 0.98, CUS:3, LOE: III), (b) miR-454-3p is higher in HGG than in LGG (p = 0.013, CUS:3, LOE: III), (c) miR-210 expression is related to WHO grades (Sn 83.2%, Sp 94.3%, CUS: 3, LOE: III). (3). Circulating DNA-(a) IDH1R132H mutation detected in plasma by combined COLD and digital PCR (Sn: 60%, Sp: 100%, CUS: 3, LOE: III). 4. Exosomes-(a) SDC1 serum levels could discriminate GBM from LGG (Sn: 71%, Sp: 91%, CUS: 2C, LOE: VI). Our investigation showed that miRs appear to have the highest clinical utility. The LOE of the studies assessed is generally low. A combined approach between different biomarkers and traditional diagnostics may be considered. We identified four main classes of biomarkers produced by LGG. We examined each biomarker, classifying them by clinical utility score (CUS) and level of evidence (LOE). Micro-RNA (miRs) appears to have the highest CUS and LOE.
Topics: Humans; Glioma; Brain Neoplasms; Biomarkers, Tumor; Liquid Biopsy; MicroRNAs; Neoplasm Grading
PubMed: 37704931
DOI: 10.1007/s10571-023-01406-9 -
The Cochrane Database of Systematic... Apr 2013High grade glioma (HGG) is an aggressive form of brain cancer. Treatment of HGG usually entails biopsy, or resection if safe, followed by radiotherapy. Temozolomide is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High grade glioma (HGG) is an aggressive form of brain cancer. Treatment of HGG usually entails biopsy, or resection if safe, followed by radiotherapy. Temozolomide is a novel oral chemotherapy drug that penetrates into the brain and purportedly has a low incidence of adverse events.
OBJECTIVES
To assess whether temozolomide has any advantage for treating HGG in either primary or recurrent disease settings.
SEARCH METHODS
The following databases were searched: CENTRAL (Issue 10, 2012), MEDLINE, EMBASE, Science Citation Index, Physician Data Query and the Meta-Register of Controlled Trials in October, 2012. Reference lists of identified studies were searched. The Journal of Neuro-Oncology and Neuro-oncology were handsearched from 1999 to 2012 including conference abstracts. We contacted neuro-oncologists regarding ongoing and unpublished trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) where the interventions were the use of temozolomide during primary therapy or for recurrent disease. Comparisons included no chemotherapy, non-temozolomide chemotherapy or different dosing schedules of temozolomide. Patients included those of all ages with histologically proven HGG.
DATA COLLECTION AND ANALYSIS
Two review authors undertook the quality assessment and data extraction. Outcome measures included: overall survival (OS); progression-free survival (PFS); quality of life (QoL); and adverse events.
MAIN RESULTS
For primary therapy three RCTs were identified, enrolling a total of 745 patients, that investigated temozolomide in combination with radiotherapy versus radiotherapy alone for glioblastoma multiforme (GBM). Temozolomide increased OS (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.46 to 0.79, P value 0.0003) and increased PFS (HR 0.63, 95% CI 0.43 to 0.92, P value 0.02), when compared with radiotherapy alone, although these benefits only appear to emerge when therapy is given in both concomitant and adjuvant phases of treatment. A single RCT found that temozolomide did not have a statistically significant effect on QoL. Risk of haematological complications, fatigue and infections were increased with temozolomide.In recurrent HGG, two RCTs enrolling 672 patients in total found that temozolomide did not increase OS compared to standard chemotherapy (HR 0.9, 95% CI 0.76 to 1.06, P value 0.2) but it did increase PFS in a subgroup analysis of grade IV GBM tumours (HR 0.68, 95% CI 0.51 to 0.90, P value 0.008). Adverse events were similar between arms.In the elderly, 2 RCTs of 664 patients found OS and PFS was similar with temozolomide alone versus radiotherapy alone. QoL did not appear to differ between arms in a single trial but certain adverse events were significantly more common with temozolomide.
AUTHORS' CONCLUSIONS
Temozolomide when given in both concomitant and adjuvant phases is an effective primary therapy in GBM compared to radiotherapy alone. It prolongs survival and delays progression without impacting on QoL but it does increase early adverse events. In recurrent GBM, temozolomide compared with standard chemotherapy improves time-to-progression (TTP) and may have benefits on QoL without increasing adverse events but it does not improve overall. In the elderly, temozolomide alone appears comparable to radiotherapy in terms of OS and PFS but with a higher instance of adverse events.
Topics: Age Factors; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Glioblastoma; Humans; Neoplasm Grading; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Survival Analysis; Temozolomide
PubMed: 23633341
DOI: 10.1002/14651858.CD007415.pub2 -
Journal of Neuro-oncology Dec 2015Adult patients (age ≥18 years) who have suspected low-grade diffuse glioma.
TARGET POPULATION
Adult patients (age ≥18 years) who have suspected low-grade diffuse glioma.
QUESTION
What are the optimal neuropathological techniques to diagnose low-grade diffuse glioma in the adult?
RECOMMENDATION
LEVEL I: Histopathological analysis of a representative surgical sample of the lesion should be used to provide the diagnosis of low-grade diffuse glioma.
LEVEL III
Both frozen section and cytopathologic/smear evaluation should be used to aid the intra-operative assessment of low-grade diffuse glioma diagnosis. A resection specimen is preferred over a biopsy specimen, to minimize the potential for sampling error issues.
TARGET POPULATION
Patients with histologically-proven WHO grade II diffuse glioma.
QUESTION
In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is testing for IDH1 mutation (R132H and/or others) warranted? If so, is there a preferred method?
LEVEL II
IDH gene mutation assessment, via IDH1 R132H antibody and/or IDH1/2 mutation hotspot sequencing, is highly-specific for low-grade diffuse glioma, and is recommended as an additional test for classification and prognosis.
TARGET POPULATION
Patients with histologically-proven WHO grade II diffuse glioma.
QUESTION
In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is testing for 1p/19q loss warranted? If so, is there a preferred method?
LEVEL III
1p/19q loss-of-heterozygosity testing, by FISH, array-CGH or PCR, is recommended as an additional test in oligodendroglial cases for prognosis and potential treatment planning.
TARGET POPULATION
Patients with histologically-proven WHO grade II diffuse glioma.
QUESTION
In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is MGMT promoter methylation testing warranted? If so, is there a preferred method?
RECOMMENDATION
There is insufficient evidence to recommend methyl-guanine methyl-transferase (MGMT) promoter methylation testing as a routine for low-grade diffuse gliomas. It is recommended that patients be enrolled in properly designed clinical trials to assess the value of this and related markers for this target population.
TARGET POPULATION
Patients with histologically-proven WHO grade II diffuse glioma.
QUESTION
In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is Ki-67/MIB1 immunohistochemistry warranted? If so, is there a preferred method to quantitate results?
LEVEL III
Ki67/MIB1 immunohistochemistry is recommended as an option for prognostic assessment.
Topics: Humans; Brain; Brain Neoplasms; Disease Management; Evidence-Based Medicine; Glioma; Neoplasm Grading
PubMed: 26530263
DOI: 10.1007/s11060-015-1909-8 -
Frontiers in Immunology 2022Glioblastoma (GBM) is the most common malignant brain tumor in adults, and immunotherapies and genetic therapies for GBM have evolved dramatically over the past decade,... (Review)
Review
Glioblastoma (GBM) is the most common malignant brain tumor in adults, and immunotherapies and genetic therapies for GBM have evolved dramatically over the past decade, but GBM therapy is still facing a dilemma due to the high recurrence rate. The inflammatory microenvironment is a general signature of tumors that accelerates epigenetic changes in GBM and helps tumors avoid immunological surveillance. GBM tumor cells and glioma-associated microglia/macrophages are the primary contributors to the inflammatory condition, meanwhile the modification of epigenetic events including DNA methylation, non-coding RNAs, and histone methylation and deacetylases involved in this pathological process of GBM, finally result in exacerbating the proliferation, invasion, and migration of GBM. On the other hand, histone deacetylase inhibitors, DNA methyltransferases inhibitors, and RNA interference could reverse the inflammatory landscapes and inhibit GBM growth and invasion. Here, we systematically review the inflammatory-associated epigenetic changes and regulations in the microenvironment of GBM, aiming to provide a comprehensive epigenetic profile underlying the recognition of inflammation in GBM.
Topics: Brain Neoplasms; Epigenesis, Genetic; Glioblastoma; Humans; Inflammation; Tumor Microenvironment
PubMed: 35572545
DOI: 10.3389/fimmu.2022.869307 -
European Journal of Cancer (Oxford,... Apr 2017The aetiology of primary central nervous system (CNS) tumours remains largely unknown, but their childhood peak points to perinatal parameters as tentative risk factors.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aetiology of primary central nervous system (CNS) tumours remains largely unknown, but their childhood peak points to perinatal parameters as tentative risk factors. In this meta-analysis, we opted to quantitatively synthesise published evidence on the association between birth anthropometrics and risk of primary CNS tumour.
METHODS
Eligible studies were identified via systematic literature review; random-effects meta-analyses were conducted for the effect of birth weight and size-for-gestational-age on childhood and adult primary CNS tumours; subgroup, sensitivity, meta-regression and dose-response by birth weight category analyses were also performed.
RESULTS
Forty-one articles, encompassing 53,167 CNS tumour cases, were eligible. Birth weight >4000 g was associated with increased risk of childhood CNS tumour (OR: 1.14, [1.08-1.20]; 22,330 cases). The risk was higher for astrocytoma (OR: 1.22, [1.13-1.31]; 7456 cases) and embryonal tumour (OR: 1.16, [1.04-1.29]; 3574 cases) and non-significant for ependymoma (OR: 1.12, [0.94-1.34]; 1374 cases). Increased odds for a CNS tumour were also noted among large-for-gestational-age children (OR: 1.12, [1.03-1.22]; 10,339 cases), whereas insufficient data for synthesis were identified for other birth anthropometrics. The findings remained robust across subgroup and sensitivity analyses controlling for several sources of bias, whereas no significant heterogeneity or publication bias were documented. The limited available evidence on adults (4 studies) did not reveal significant associations between increasing birth weight (500-g increment) and overall risk CNS tumour (OR: 0.99, [0.98-1.00]; 1091 cases) or glioma (OR: 1.03, [0.98-1.07]; 2052 cases).
CONCLUSIONS
This meta-analysis confirms a sizeable association of high birth weight, with childhood CNS tumour risk, particularly astrocytoma and embryonal tumour, which seems to be independent of gestational age. Further research is needed to explore underlying mechanisms, especially modifiable determinants of infant macrosomia, such as gestational diabetes.
Topics: Adolescent; Adult; Anthropometry; Astrocytoma; Birth Weight; Central Nervous System Neoplasms; Child; Child, Preschool; Gestational Age; Humans; Infant; Infant, Newborn; Neoplasms, Germ Cell and Embryonal; Observational Studies as Topic; Risk Factors; Young Adult
PubMed: 28219020
DOI: 10.1016/j.ejca.2016.12.033