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Clinical Neurology and Neurosurgery Jun 2023The clinical benefit and the safety of fractionated stereotactic re-irradiation in treating patients with recurrent glioblastoma are still disputed. Thus, we conducted a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The clinical benefit and the safety of fractionated stereotactic re-irradiation in treating patients with recurrent glioblastoma are still disputed. Thus, we conducted a meta-analysis to explore the clinical benefit and the safety of fractionated stereotactic re-irradiation for patients with recurrent glioblastoma.
MATERIALS AND METHODS
We retrieved the eligible papers published up to Nov. 2022 through PubMed, Embase, Cochrane, Web of Science, and Clinical Trials. Gov, and other biomedical databases and evaluated the quality of the studies by Newcastle-Ottawa Scale. The random effect model was used to pool 12-month overall survival rates, 12-month progression-free survival rates, and radiational necrosis risk, and an interaction test was used to compare defined subgroups.
RESULTS
We identified eight eligible studies, including 307 patients. The overall survival rate of 12 months was 33.1 % (95 % CI 26.0 %-40.9 %), and the progression-free survival rate of 12 months was 13.4 % (95 % CI 8.0 %-21.3 %). Radiation necrosis was low in incidence in the included studies. Additionally, the subgroup analysis demonstrated that factors such as age, time interval (from the first radiation to the re-irradiation), total dose, and single dose, impacted the survival rate.
CONCLUSION
Fractionated stereotactic re-irradiation produces relative clinical benefit and safety for patients with recurrent glioblastoma.
Topics: Humans; Glioblastoma; Re-Irradiation; Brain Neoplasms; Neoplasm Recurrence, Local; Radiosurgery; Necrosis
PubMed: 37105068
DOI: 10.1016/j.clineuro.2023.107728 -
Oncology (Williston Park, N.Y.) Mar 2023Glioblastoma is the most common primary neoplasm of the central nervous system. Standard treatment includes surgery with maximum safe resection and radiotherapy plus...
BACKGROUND
Glioblastoma is the most common primary neoplasm of the central nervous system. Standard treatment includes surgery with maximum safe resection and radiotherapy plus concomitant and adjuvant chemotherapy; however, almost invariably, tumor relapse occurs. We aimed to describe signaling pathways and molecular mechanisms present in tumor relapse of glioblastoma.
METHODS
This systematic review followed the PRISMA guidelines. We searched the PubMed, EMBASE and Web of Science databases. We included studies that enrolled patients 15 years or older with a diagnosis of glioblastoma according to Louis criteria and focused on signaling pathways and molecular mechanisms present in tumor relapse of glioblastoma. The outcome of interest was progression-free survival.
RESULTS
We identified 1470 articles; 31 met the inclusion criteria. From each publication, we obtained the associated markers O-6-methylguanine-DNA methyltransferase, isocitrate dehydrogenase, mRNA, epidermal growth factor receptor (EGFR), p53, and others. All publications were evaluated with the Q-Genie checklist tool for quality assessment.
CONCLUSIONS
We identified a wide variety of signaling pathways and molecular processes that are involved in glioblastoma relapse. This diversity would explain intra- and intertumor heterogeneity, treatment evasion, and relapse. However, only a few molecular processes have robust evidence for clinical utility.
Topics: Humans; Glioblastoma; Brain Neoplasms; Chemotherapy, Adjuvant; Recurrence; Signal Transduction
PubMed: 36961958
DOI: 10.46883/2023.25920986 -
Scientific Reports Mar 2023Glioblastomas presenting topographically at the cerebellopontine angle (CPA) are exceedingly rare. Given the specific anatomical considerations and their rarity, overall...
Glioblastomas presenting topographically at the cerebellopontine angle (CPA) are exceedingly rare. Given the specific anatomical considerations and their rarity, overall survival (OS) and management are not discussed in detail. The authors performed an integrative survival analysis of CPA glioblastomas. A literature search of PubMed, Scopus, and Web of Science databases was performed per PRISMA guidelines. Patient data including demographics, clinical features, neuroimaging, management, follow-up, and OS were extracted. The mean age was 39 ± 26.2 years. The mean OS was 8.9 months. Kaplan-Meier log-rank test and univariate Cox proportional-hazards model identified hydrocephalus (log-rank, p = 0.034; HR 0.34; 95% CI 0.12-0.94; p = 0.038), chemotherapy (log-rank, p < 0.005; HR 5.66; 95% CI 1.53-20.88; p = 0.009), and radiotherapy (log-rank, p < 0.0001; HR 12.01; 95% CI 3.44-41.89; p < 0.001) as factors influencing OS. Hydrocephalus (HR 3.57; 95% CI 1.07-11.1; p = 0.038) and no adjuvant radiotherapy (HR 0.12; 95% CI 0.02-0.59; p < 0.01) remained prognostic on multivariable analysis with fourfold and twofold higher risk for the time-related onset of death, respectively. This should be considered when assessing the risk-to-benefit ratio for patients undergoing surgery for CPA glioblastoma.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Glioblastoma; Cerebellopontine Angle; Survival Analysis; Prognosis; Proportional Hazards Models; Kaplan-Meier Estimate; Retrospective Studies
PubMed: 36932101
DOI: 10.1038/s41598-023-30677-x -
World Neurosurgery Jul 2023Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes while minimizing morbidity and complications....
BACKGROUND
Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes while minimizing morbidity and complications. Conversely, staged surgery for primary intraparenchymal neoplasms is less commonly performed and has not been reported as extensively within the literature. As such, we performed a systematic review to examine the unique surgical indications for staging, timing between stages, specific surgical approaches utilized, and postoperative complications of staged surgery for primary intra-axial neoplasms.
METHODS
A literature search was conducted in August 2021 using PubMed, Web of Science, and Cochrane databases using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Titles and abstracts were evaluated independently by 2 authors, after which articles were selected for final analysis based on application of strict inclusion criteria during full text screen. Each included article was then qualitatively assessed and relevant variables-including operative approaches, timing, and outcomes-were extracted for synthesis.
RESULTS
Of 115 results, 7 articles were included for final analysis and consisted of 17 pediatric and 4 adult patients. Staged approaches were more commonly utilized in the pediatric patient population for resection of astrocytoma and glioma. Pediatric patients had a timing of surgeries ranging from 5-10 days between operations, compared with 18 days to 4 months in adult patients. Complications in pediatric patients were most commonly hemiparesis, hydrocephalus, cranial nerve VI and VII palsies, truncal ataxia, and cerebellar mutism, while complications in adult patients included language and abstract thinking deficits, respiratory failure, and motor weakness.
CONCLUSIONS
This study reports the first comprehensive review of staged surgical procedures for primary, intra-axial cranial neoplasms. There exists a large degree of heterogeneity in complications resulting from staged surgeries for intra-axial neoplasms, which are similar to complications associated with single-stage surgery for intraparenchymal lesions as well as multi-stage surgeries for skull base lesions.
Topics: Adult; Humans; Child; Skull Base; Glioma; Astrocytoma; Postoperative Complications
PubMed: 36924887
DOI: 10.1016/j.wneu.2023.03.046 -
Expert Opinion on Drug Delivery Apr 2023Glioblastoma (GB) is one of the most challenging central nervous system (CNS) tumors in treatment options and response, urging the development of novel management...
INTRODUCTION
Glioblastoma (GB) is one of the most challenging central nervous system (CNS) tumors in treatment options and response, urging the development of novel management strategies. The anti-alcoholism drug, disulfiram (DS), has a potential anticancer activity, and its complex mechanism of action is assumed to be well exploited against the heterogeneous GB.
AREA COVERED
Through a systematic literature review about repositioning DS to GB treatment, an evaluation of the clinical, pharmacological, and formulation strategies is provided to specify the challenges of drug delivery and thus to advance its clinical translation. From six databases, 35 articles were selected, including case report (1); clinical trials (3); original articles mainly representing in vitro and preclinical pharmacological data, and 10 dealing with technological approaches.
EXPERT OPINION
The repositioning of DS in GB treatment is facing drug and tumor-associated limitations due to the oral drug's low bioavailability, unwanted metabolism, and inefficient delivery to brain-tumor tissue. Development strategies using molecular encapsulation of DS and the parenteral dosage forms improve the anticancer pharmacology of the drug. The development of optimized drug delivery systems (DDS) shows promise for the clinical translation of DS into GB adjuvant therapy.
Topics: Humans; Disulfiram; Glioblastoma; Brain Neoplasms; Brain; Drug Delivery Systems
PubMed: 36922013
DOI: 10.1080/17425247.2023.2190581 -
Expert Reviews in Molecular Medicine Mar 2023Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18... (Review)
Review
Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in and settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.
Topics: Adult; Humans; Telomerase; Glioma; Brain Neoplasms; Glioblastoma; Genetic Therapy
PubMed: 36919343
DOI: 10.1017/erm.2023.6 -
Cureus Feb 2023Subependymal giant cell astrocytoma (SEGA) is the most common intracranial tumor in tuberous sclerosis (TS) patients. The tumor generally localizes in the proximity of...
Subependymal giant cell astrocytoma (SEGA) is the most common intracranial tumor in tuberous sclerosis (TS) patients. The tumor generally localizes in the proximity of Monro's foramen; as it grows, it subsequently causes hydrocephalus and increases intracranial pressure (ICP). However, acute symptoms of increased ICP due to intratumoral bleeding rarely manifest in SEGA patients. We present a 27-year-old male with TS who presented due to hemorrhagic complications of SEGA with intratumoral bleeding and vitreous orbital hemorrhage. We then conducted a systematic review with four databases (PubMed, Web of Science, Google Scholar, and Cochrane) to identify similar cases using the following keywords: "Subependymal giant cell astrocytoma," "Hemorrhage," "Haemorrhage," and "Bleeding." Our review identified 12 articles reporting 14 cases of hemorrhagic complications of SEGA in addition to our case report. The median age of diagnosis was 21 (range 5-79) years with unequal gender distribution (M:F ratio, 11:4). Headache was the most presented symptom, followed by hemiparesis, seizure, altered mental status, visual deterioration, and headache accompanied by seizure. TS was seen in most of the cases (80%). Gross total resection (GTR) was achieved in 53.5% of the patients. Regarding the clinical outcome, 66.7% had a good outcome, 20% died, and 13.3% had no report of their outcomes. No tumor recurrence was seen in the cases with a reported duration of follow-up. Catastrophic presentation of SEGA apoplexy is a rare occurrence. We present a case report with a systematic review and discuss SEGA apoplexy's possible pathophysiology and outcome.
PubMed: 36915840
DOI: 10.7759/cureus.34784 -
BMC Cancer Feb 2023Glioblastoma, the most common primary malignant brain tumour in adults, is a highly vascular tumour characterised by abnormal angiogenesis. Additional mechanisms of...
BACKGROUND
Glioblastoma, the most common primary malignant brain tumour in adults, is a highly vascular tumour characterised by abnormal angiogenesis. Additional mechanisms of tumour vascularisation have also been reported in glioblastoma, including the formation of tumour cell-derived vessels by vasculogenic mimicry (VM) or the transdifferentiation of tumour cells to endothelial cells. VM and endothelial transdifferentiation have frequently been reported as distinct processes, however, the use of both terms to describe a single process of vascularisation also occurs. Some overlapping characteristics have also been reported when identifying each process. We therefore aimed to determine the markers consistently attributed to VM and endothelial transdifferentiation in the glioblastoma literature.
METHODS
Ovid MEDLINE and Ovid Embase were searched for studies published between January 1999 and July 2021 that assessed VM or tumour to endothelial transdifferentiation in human glioblastoma. The online systematic review tool Covidence was used for screening and data extraction. Extracted data included type of tumour-derived vasculature reported, methods and techniques used, and markers investigated. Studies were grouped based on type of vasculature reported for further assessment.
RESULTS
One hundred and thirteen of the 419 unique records identified were included for analysis. VM was reported in 64/113 studies, while tumour to endothelial transdifferentiation was reported in 16/113 studies. The remaining studies used both terms to describe a single process, did not define the process that occurred, or concluded that neither VM nor endothelial transdifferentiation occurred. Absence of CD34 and/or CD31 in vascular structures was the most common indicator of VM, while expression of CD34 and/or CD31, in addition to various other endothelial, stem cell or tumour cell markers, indicated tumour to endothelial transdifferentiation.
CONCLUSION
Cells derived from tumour to endothelial transdifferentiation express typical endothelial markers including CD34 and CD31, while tumour cells contributing to VM lack CD34 and CD31 expression. Additional tumour markers are required to identify transdifferentiation in glioblastoma tissue, and this process requires further characterisation.
Topics: Adult; Humans; Glioblastoma; Endothelial Cells; Cell Transdifferentiation; Neovascularization, Pathologic; Cell Differentiation; Biomarkers, Tumor
PubMed: 36823554
DOI: 10.1186/s12885-023-10659-y -
The Spine Journal : Official Journal of... Jul 2023Diffuse gliomas of the spine (DGS)-consisting of intradural intramedullary glioblastoma, astrocytoma, and oligodendroglioma-are exceedingly rare tumors that account for...
BACKGROUND CONTENT
Diffuse gliomas of the spine (DGS)-consisting of intradural intramedullary glioblastoma, astrocytoma, and oligodendroglioma-are exceedingly rare tumors that account for about 2% of primary spinal cord tumors. Much is unknown about their optimal treatment regimen due to a relative lack of clinical outcome data.
PURPOSE
To provide an updated analysis on treatment and outcomes in DGS.
STUDY DESIGN/SETTING
Observational cohort study using The National Cancer Database (NCDB), a multicenter prospectively collected oncology outcomes database. A systematic literature review was also performed to compare the resulting data to previous series.
PATIENT SAMPLE
Patients with histologically confirmed DGS from 2004 to 2018.
OUTCOME MEASURES
Long-term overall survival and short-term 30/90-day postsurgical mortality, 30-day readmission, and prolonged hospital length of stay.
METHODS
Impact of extent of resection and adjuvant therapy on overall survival was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression. Univariate and multivariate logistic regression was used to analyze covariables and their prognostic impact on short-term surgical outcomes.
RESULTS
Of the 747 cases that met inclusion criteria, there were 439 astrocytomas, 14 oligodendrogliomas, and 208 glioblastomas. Sixty percent (n=442) of patients received radiation, and 45% (n=324) received chemotherapy. Tumor histology significantly impacted survival; glioblastoma had the poorest survival (median survival time [MS]: 12.3 months), followed by astrocytoma (MS: 70.8 months) and oligodendroglioma (MS: 71.6 months) (p<.001). Gross total resection (GTR) independently conferred a survival benefit in patients with glioblastoma (hazard ratio [HR]: 0.194, p<0.001) and other WHO grade four tumors (HR: 0.223, p=.003). Adjuvant chemotherapy also improved survival in patients with glioblastoma (HR: 0.244, p=.007) and WHO grade four tumors (HR: 0.252, p<.001). Systematic literature review identified 14 prior studies with a combined DGS mortality rate of 1.3%, which is lower than the 4% real-world outcomes calculated from the NCDB. This difference may be explained by selection biases in previously published literature in which only centers with favorable outcomes publish their results.
CONCLUSIONS
There remains a paucity of data regarding treatment paradigms and outcomes for DGS. Our analysis, the largest to date, demonstrates that GTR and adjuvant therapy independently improve survival for certain high-grade subgroups of DGS. This best-available data informs optimal management for such patients.
Topics: Humans; Glioblastoma; Oligodendroglioma; Neurosurgical Procedures; Astrocytoma; Prognosis; Retrospective Studies; Observational Studies as Topic; Multicenter Studies as Topic
PubMed: 36804437
DOI: 10.1016/j.spinee.2023.02.010 -
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