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Neurology India 2022Different variant of GBM has been reported viz. Epithelioid Glioblastoma (GBM-E), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro...
OBJECTIVES
Different variant of GBM has been reported viz. Epithelioid Glioblastoma (GBM-E), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro ectodermal differentiation (GBM-PNET) with unknown behavior.
MATERIALS
We conducted a systematic review and individual patient data analysis of these rare GBM variants. We searched PubMed, google search, and Cochrane library for eligible studies till July 1 2016 published in English language and collected data regarding age, sex, subtype and treatment received, Progression Free Survival (PFS), Overall Survival (OS). Statistical Package for social sciences (SPSS) v16 software was used for all statistical analysis.
RESULTS
We retrieved data of 196 patients with rare GBM subtypes. Among these GBM-GC is commonest (51%), followed by GBM-R (19%), GBM-PNET (13%), GBM-SC (9%) and GBM-E (8%). Median age at diagnosis was 38, 40, 43.5, 69.5 and 18 years, respectively. Male: female ratio was 2:1 for GBM-E, and 1:3 for GBM-SC. Maximal safe resection followed by adjuvant local radiation was used for most of the patients. However, 6 patients with GBM-PNET, 3 each of GBM-E, GBM-SC received adjuvant craniospinal radiation. Out of 88 patients who received chemotherapy, 64 received Temozolomide alone or combination chemotherapy containing Temozolomide. Median PFS and OS for the entire cohort were 9 and 16 months. In univariate analysis, patient with a Gross Total Resection had significantly better PFS and OS compared to those with a Sub Total Resection [23 vs. 13 months (p-0.01)]. Median OS for GBM PNET, GBM-GC, GBM-SC, GBM-R and GBM-E were 32, 18.3, 11, 12 and 7.7 months, respectively (P = 0.001). Interestingly, 31.3%, 37.8% of patients with GBM-E, GBM-R had CSF dissemination.
CONCLUSION
Overall cohort of rarer GBM variant has equivalent survival compared to GBM not otherwise specified. However, epithelioid and Rhabdoid GBM has worst survival and one third shows CSF dissemination.
Topics: Humans; Male; Female; Glioblastoma; Temozolomide; Data Analysis; Brain Neoplasms; Retrospective Studies; Neuroectodermal Tumors, Primitive; Antineoplastic Agents, Alkylating
PubMed: 36352613
DOI: 10.4103/0028-3886.359222 -
Neurosurgical Review Dec 2022Glioblastoma is the most common primary malignant brain tumor in the adult population. It causes the patient to incur a great deal of malady. Even with the advances in... (Meta-Analysis)
Meta-Analysis Review
Glioblastoma is the most common primary malignant brain tumor in the adult population. It causes the patient to incur a great deal of malady. Even with the advances in management and the Stupp protocol in place, the prognosis remains grim. There are various parameters to evaluate patients' performance status and frailty pre-operatively, but these are mostly subjective and thus suffer from inter-observer variability. Assessment of sarcopenia serves as an objective parameter to assess the patient's performance status pre-operatively. Temporalis muscle thickness serves as a surrogate to assess sarcopenia in patients with glioblastoma. We conducted a literature review and meta-analysis to determine the prognostic implications of temporalis muscle thickness in 3283 patients with primary glioblastoma. The pooled overall survival hazard's ratio of thick versus thin TMT was 0.54. The pooled progression-free survival hazard's ratio of thick versus thin TMT was 0.38. Thus, the main finding of this study is that thicker temporal muscle is associated with better OS and PFS as compared to thinner temporal muscle. We thus conclude that TMT is a viable surrogate for predicting sarcopenia and survival in primary glioblastoma. TMT measurement is extremely easy and can be incorporated as a part of the routine neurosurgical workflow in these patients. Survival prediction will help inform treatment decisions in glioblastoma patients having poor prognosis, at the initial diagnosis itself.
Topics: Adult; Humans; Glioblastoma; Prognosis; Temporal Muscle; Brain Neoplasms; Sarcopenia
PubMed: 36350492
DOI: 10.1007/s10143-022-01892-3 -
Frontiers in Surgery 2022Survival amongst posterior fossa tumour (PFT) patients is improving. Clinical endpoints such as overall survival fail to depict QoL. There is yet to be a review of... (Review)
Review
INTRODUCTION
Survival amongst posterior fossa tumour (PFT) patients is improving. Clinical endpoints such as overall survival fail to depict QoL. There is yet to be a review of current QoL instruments used for adult PFTs. Aim of this review is to outline the QoL reporting in the management of PFTs and measure participation level.
METHODS
This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis. A search strategy to identify adult patients with PFTs who took part in QoL metrics was conducted. Observational and experimental studies published from 1990 to date were included. Studies with a sample size less than 10 and performance measures such as Karnofsky Performance Status were not considered.
RESULTS
A total of 116 studies were included in the final analysis. Vestibular schwannomas were the most common tumour pathology ( = 23,886, 92.6%) followed by pilocytic astrocytomas ( = 657, 2.5%) and meningiomas ( = 437, 1.7%) Twenty-five different QoL measures were used in the study pool. SF-36 was the most common ( = 55, 17 47.4%) QoL metric in the whole study pool, followed by the Penn Acoustic Neuroma QoL scale ( = 24, 20.7%) and Dizziness Handicap Inventory ( = 16, 13.8%). Seventy-two studies reported less-than 100% participation in QoL evaluation. The commonest reason for non-participation was a lack of response ( = 1,718, 60.8%), incomplete questionnaires ( = 268, 9.4%) and cognitive dysfunction ( = 258, 9.1%).
CONCLUSION
Informed clinical decision-making in PFT patients requires the development of specific QoL outcomes. Core outcome sets, and minimal clinically important differences (MCID) are essential for these metrics to show clinically significant improvements in patient QoL.
PubMed: 36303860
DOI: 10.3389/fsurg.2022.970889 -
Current Issues in Molecular Biology Oct 2022Both (isocitrate dehydrogenase 1) and (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular...
Both (isocitrate dehydrogenase 1) and (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular metabolic processes. Here we describe a case of a patient with an IDH-mutant astrocytoma, in which both and mutations were detected within the same tumour. The patient remains disease-free, nine and a half years after her initial diagnosis. Interrogation of cancer genomic databases and a systematic review was undertaken, demonstrating the rarity of the co-occurrence of and mutations in a variety of cancer types, and in glioma specifically. Due to the favourable outcome observed in this patient, the potential effect of concurrent and mutations on survival was also investigated.
PubMed: 36286062
DOI: 10.3390/cimb44100348 -
Brain & Spine 2022Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income... (Review)
Review
BACKGROUND
Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income countries (LMIC) remains low despite advances in neurosurgical care and diagnostics over the past decades. The aim of this systematic review was to investigate the surgical outcomes for PBT in Sub-Saharan Africa, and the distribution of PBT types.
METHODS
A systematic review was conducted on PubMed, for all available literature on the surgical outcomes of PBT in Sub-Saharan Africa, published before May 3, 2022. Two reviewers performed abstract, full text screening and data collection independently, resolving any conflicts by consensus.
RESULTS
The search yielded 256 studies, of which 22 met the inclusion criteria, amounting to a total of 243 patients. Nigeria was the country with most data. Only subgroups of patients could be extracted from 12 studies, and variables of interest in 6 studies had inconsistent sample sizes. The age centered around 9 years, and there were approximately equal number of girls and boys. The most common tumor was medulloblastoma, followed by craniopharyngioma and astrocytoma. There was large heterogeneity in the reporting of outcomes, and a trend was difficult to discern, considering the large number of different tumor types and different extents of resection.
DISCUSSION AND CONCLUSION
Data is insufficient and inconsistent, precluding statistical conclusions. There is a need for more studies in the field.
PubMed: 36248098
DOI: 10.1016/j.bas.2022.100912 -
European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
Chinese Clinical Oncology Aug 2022Glioma is the most common intracranial primary malignant tumor, and half of it is glioblastoma. Despite receiving the standard treatment, the prognosis of glioblastoma...
BACKGROUND AND OBJECTIVE
Glioma is the most common intracranial primary malignant tumor, and half of it is glioblastoma. Despite receiving the standard treatment, the prognosis of glioblastoma is still poor and its 5-year survival rate in China is only 9%. In addition, new targeted and immunotherapy therapy and tumor treating fields also have certain curative effects on glioblastoma. To help clinicians and patients make appropriate treatment based on current evidences, we summarize the Chinese guidelines on the management of glioma and review the recent management of glioblastoma.
METHODS
We systematically searched PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang databases to retrieve guidelines on glioma in China published from the establishment of the database to 24 January 2022. We performed a narrative review of current clinical study related to the management of glioblastoma, especially in the surgical, targeted and immunotherapy therapy and tumor treating fields.
KEY CONTENT AND FINDINGS
In this review, 19 guidelines were included, including 8 subclassified as the guideline, 8 subclassified as the consensus and 3 subclassified as the standard. Two guidelines reported the contents of the system search, 4 guidelines are updated, and 9 guidelines reported the source of funding. At present, most clinical trials on the immune and targeted therapy of glioblastoma are ongoing in China.
CONCLUSIONS
China's guidelines still need to be improved in terms of preciseness, applicability and editorial independence. In addition, the cooperation in clinical research of glioblastoma in multiple centers needs to be strengthened in China.
Topics: Brain Neoplasms; China; Databases, Factual; Glioblastoma; Glioma; Humans
PubMed: 36098100
DOI: 10.21037/cco-22-18 -
Neurosurgical Review Oct 2022Little is known about the survivorship of glioblastoma (GBM) patients in low- and middle-income countries (LMICs). We hypothesize that this would be lower than published... (Meta-Analysis)
Meta-Analysis
Little is known about the survivorship of glioblastoma (GBM) patients in low- and middle-income countries (LMICs). We hypothesize that this would be lower than published figures for high-income countries due to cancer health disparities. We performed a systematic review and meta-analysis to estimate the median overall survival (OS) of GBM in LMICs and determine factors affecting OS. A systematic review of 12 electronic databases was conducted according to PRISMA guidelines to identify studies of newly diagnosed adult GBM patients done in countries classified as LMIC by the World Bank (WB) from inception to December 2020. Random effects meta-analysis of collected median overall survival data was done. Subgroup analysis and meta-regression were done to determine if WB income classification (WBIC), start year of recruitment (pre- or post-popularization of the standard Stupp protocol), and treatment modality affected OS. The 24 articles (n = 2,552) that met the inclusion criteria were from 8 low-middle income and upper-middle income countries, with 0 articles from low-income countries. Random effects analysis of 24 studies showed a pooled median OS of 14.17 months (95% CI 12.90-15.43, I = 79). Subgroup analysis showed a significant difference (p < 0.05) in the pooled median OS of studies predating Stupp protocol (12.54 mo, 95% CI 11.13-13.96, I = 80%; n = 1027) and studies postdating Stupp protocol (15.64 mo, 95% CI 13.58-17.69, I = 77; n = 1412). Subgroup analysis of WBIC and treatment modalities did not show significant differences. Published data on the survivorship of GBM patients in LMICs is sparse, highlighting the need for good quality pragmatic studies from LMICs. The limited evidence suggests improving survivorship after introduction of the Stupp protocol.
Topics: Adult; Developing Countries; Glioblastoma; Humans; Income
PubMed: 36044130
DOI: 10.1007/s10143-022-01844-x -
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 -
World Journal of Transplantation Jun 2022Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria. The risk assessment of tumor transmission organ transplant...
BACKGROUND
Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria. The risk assessment of tumor transmission organ transplant in primary brain tumors is primarily based on the assessment of tumor histotype and grade. Previous surgeries, chemo-/radiotherapy, and ventriculo-peritoneal shunt placement can lead to a disruption of the blood-brain barrier, concurring to an increase in the transmission risk.
AIM
To investigate the role of tumor transmission risk factors in donors with oligodendrogliomas and astrocytomas.
METHODS
We searched PubMed and EMBASE databases for studies reporting extraneural spreading of oligodendrogliomas and astrocytomas and extracted clinical-pathological data on the primary tumor histotype and grade, the elapsed time from the diagnosis to the onset of metastases, sites and number of metastases, prior surgeries, prior radiotherapy and/or chemotherapy, ventriculo-atrial or ventriculo-peritoneal shunt placement, and the presence of isocitrate dehydrogenase 1/2 mutation and 1p/19q codeletion. Statistical analysis was performed using R software. Statistical correlation between chemotherapy or radiotherapy and the presence of multiple extra-central nervous system metastases was analyzed using and Fischer exact test. The Kaplan-Meier method was used to evaluate the presence of a correlation between the metastasis-free time and: (1) Localization of metastases; (2) The occurrence of intracranial recurrences; and (3) The occurrence of multiple metastases.
RESULTS
Data on a total of 157 patients were retrieved. The time from the initial diagnosis to metastatic spread ranged from 0 to 325 mo in patients with oligodendrogliomas and 0 to 267 mo in those with astrocytomas. Respectively, 19% and 39% of patients with oligodendroglioma and astrocytoma did not receive any adjuvant therapy. The most frequent metastatic sites were bone, bone marrow, and lymph nodes. The lungs and the liver were the most commonly involved visceral sites. There was no significant correlation between the occurrence of multiple metastases and the administration of adjuvant chemo-/radiotherapy. Patients who developed intracranial recurrences/metastases had a significantly longer extraneural metastasis-free time compared to those who developed extraneural metastases in the absence of any intra- central nervous system spread.
CONCLUSION
A long follow-up time does not exclude the presence of extraneural metastases. Therefore, targeted imaging of bones and cervical lymph nodes may improve safety in the management of these donors.
PubMed: 35979537
DOI: 10.5500/wjt.v12.i6.131