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Journal of Neuro-oncology Aug 2023Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015 based on the randomized controlled EF-14 study. Subsequent approvals worldwide and increased adoption over time have raised the question of whether a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role.
METHODS
We conducted a literature search to identify clinical studies evaluating overall survival (OS) in TTFields-treated patients. Comparative and single-cohort studies were analyzed. Survival curves were pooled using a distribution-free random-effects method.
RESULTS
Among nine studies, seven (N = 1430 patients) compared the addition of TTFields therapy to standard of care (SOC) chemoradiotherapy versus SOC alone and were included in a pooled analysis for OS. Meta-analysis of comparative studies indicated a significant improvement in OS for patients receiving TTFields and SOC versus SOC alone (HR: 0.63; 95% CI 0.53-0.75; p < 0.001). Among real-world post-approval studies, the pooled median OS was 22.6 months (95% CI 17.6-41.2) for TTFields-treated patients, and 17.4 months (95% CI 14.4-21.6) for those not receiving TTFields. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, for patients included in studies reporting data on device usage (N = 1015), an average usage rate of ≥ 75% was consistently associated with prolonged survival (p < 0.001).
CONCLUSIONS
Meta-analysis of comparative TTFields studies suggests survival may be improved with the addition of TTFields to SOC for patients with newly diagnosed GBM.
Topics: Humans; Glioblastoma; Temozolomide; Electric Stimulation Therapy; Brain Neoplasms; Combined Modality Therapy
PubMed: 37493865
DOI: 10.1007/s11060-023-04348-w -
Frontiers in Immunology 2023Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival.
METHOD
Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356).
RESULTS
We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; = -2.00, = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; = -1.99, = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; = -3.53; = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; = -2.23; = 0.0256).
CONCLUSION
Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.
Topics: Humans; Standard of Care; Glioma; Brain Neoplasms; Progression-Free Survival; Immunotherapy
PubMed: 37483593
DOI: 10.3389/fimmu.2023.966696 -
International Journal of Molecular... Jun 2023Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state... (Review)
Review
Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy-namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories-clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets-and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.
Topics: Adult; Humans; Animals; Mice; Molecular Targeted Therapy; beta Catenin; Mutation; Glioma; Brain Neoplasms; Oligodendroglioma; Isocitrate Dehydrogenase
PubMed: 37445633
DOI: 10.3390/ijms241310456 -
Cancers Jul 2023Diffuse midline glioma (DMG), -altered are highly aggressive, incurable central nervous system (CNS) tumors. The current standard palliative treatment is radiotherapy,... (Review)
Review
Molecular Characterization and Treatment Approaches for Pediatric -Altered Diffuse Midline Glioma: Integrated Systematic Review of Individual Clinical Trial Participant Data.
Diffuse midline glioma (DMG), -altered are highly aggressive, incurable central nervous system (CNS) tumors. The current standard palliative treatment is radiotherapy, with most children succumbing to the disease in less than one year from the time of diagnosis. Over the past decade, there have been significant advancements in our understanding of these heterogeneous tumors at the molecular level. As a result, most of the newer clinical trials offered utilize more targeted approaches with information derived from the tumor biopsy. In this systematic review, we used individual participant data from seven recent clinical trials published over the past five years that met our inclusion and exclusion criteria to analyze factors that influence overall survival (OS). We found that the most prominent genetic alterations H3.3 () and were associated with worse OS and that ACVR had a protective effect. In addition, re-irradiation was the only statistically significant treatment modality that showed any survival benefit. Our findings highlight some important characteristics of DMG, -altered and their effects on OS along with the importance of continuing to review clinical trial data to improve our therapies for these fatal tumors.
PubMed: 37444588
DOI: 10.3390/cancers15133478 -
Brain and Behavior Aug 2023Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions. (Review)
Review
Tumoral parkinsonism-Parkinsonism secondary to brain tumors, paraneoplastic syndromes, intracranial malformations, or oncological intervention, and the effect of dopaminergic treatment.
INTRODUCTION
Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions.
OBJECTIVES
The first objective was to explore to what extent brain neoplasms, cavernomas, cysts, paraneoplastic syndromes (PNSs), and oncological treatment methods cause parkinsonism. The second objective was to investigate the effect of dopaminergic therapy on the symptomatology in patients with tumoral parkinsonism.
METHODS
A systematic literature review was conducted in the databases PubMed and Embase. Search terms like "secondary parkinsonism," "astrocytoma," and "cranial irradiation" were used. Articles fulfilling inclusion criteria were included in the review.
RESULTS
Out of 316 identified articles from the defined database search strategies, 56 were included in the detailed review. The studies, which were mostly case reports, provided research concerning tumoral parkinsonism and related conditions. It was found that various types of primary brain tumors, such as astrocytoma and meningioma, and more seldom brain metastases, can cause tumoral parkinsonism. Parkinsonism secondary to PNSs, cavernomas, cysts, as well as oncological treatments was reported. Twenty-five of the 56 included studies had tried initiating dopaminergic therapy, and of these 44% reported no, 48% low to moderate, and 8% excellent effect on motor symptomatology.
CONCLUSION
Brain neoplasms, PNSs, certain intracranial malformations, and oncological treatments can cause parkinsonism. Dopaminergic therapy has relatively benign side effects and may relieve motor and nonmotor symptomatology in patients with tumoral parkinsonism. Dopaminergic therapy, particularly levodopa, should therefore be considered in patients with tumoral parkinsonism.
Topics: Humans; Parkinsonian Disorders; Brain Neoplasms; Dopamine; Astrocytoma; Paraneoplastic Syndromes; Meningeal Neoplasms; Cysts
PubMed: 37433071
DOI: 10.1002/brb3.3151 -
Surgical Neurology International 2023Awake craniotomy (AC) aims to minimize postoperative neurological complications while allowing maximum safe resection. Intraoperative seizures (IOSs) have been a... (Review)
Review
BACKGROUND
Awake craniotomy (AC) aims to minimize postoperative neurological complications while allowing maximum safe resection. Intraoperative seizures (IOSs) have been a reported complication during AC; however, literature delving into the predictors of IOS remains limited. Therefore, we planned a systematic review and meta-analysis of existing literature to explore predictors of IOS during AC.
METHODS
From the inception until June 1, 2022, systematic searches of PubMed, Scopus, the Cochrane Library, CINAHL, and Cochrane's Central Register of Controlled Trials were conducted to look for published studies reporting IOS predictors during AC.
RESULTS
We found 83 different studies in total; included were six studies with a total of 1815 patients, and 8.4% of them experienced IOSs. The mean age of included patients was 45.3 years, and 38% of the sample was female. Glioma was the most common diagnosis among the patients. A pooled random effect odds ratio (OR) of frontal lobe lesions was 2.42 (95% confidence intervals [CI]: 1.10-5.33, = 0.03). Those with a pre-existing history of seizures had an OR of 1.80 (95% CI: 1.13-2.87, = 0.01), and patients on antiepileptic drugs (AEDs) had a pooled OR of 2.47 (95% CI: 1.59-3.85, < 0.001).
CONCLUSION
Patients with lesions of the frontal lobe, a prior history of seizures, and patients on AEDs are at higher risk of IOSs. These factors should be taken into consideration during the patient's preparation for an AC to avoid an intractable seizure and consequently a failed AC.
PubMed: 37404511
DOI: 10.25259/SNI_135_2023 -
Clinical & Translational Oncology :... Feb 2024Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal... (Review)
Review
Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords "glioblastoma," "xenotransplantation," and "zebrafish" for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50-100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32-33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials.
Topics: Animals; Humans; Glioblastoma; Transplantation, Heterologous; Zebrafish; Heterografts; Brain Neoplasms; Cell Line, Tumor; Xenograft Model Antitumor Assays; Disease Models, Animal
PubMed: 37400666
DOI: 10.1007/s12094-023-03258-7 -
Neurosurgical Review Jun 2023Maintaining the integrity of crucial fiber tracts allows functional preservation and improved recovery in patients with glioma resection. Diffusion tensor imaging (DTI)... (Meta-Analysis)
Meta-Analysis Review
Maintaining the integrity of crucial fiber tracts allows functional preservation and improved recovery in patients with glioma resection. Diffusion tensor imaging (DTI) and intraoperative subcortical mapping (ISM) are commonly required for pre- and intraoperative assessment of white matter fibers. This study investigated differences of clinical outcomes in glioma resection aided by DTI or ISM. A comprehensive literature retrieval of the PubMed and Embase databases identified several DTI or ISM studies in 2000-2022. Clinical data, including extent of resection (EOR) and postoperative neurological deficits, was collected and statistically analyzed. Heterogeneity was regressed by a random effect model and the Mann-Whitney U test was used to test statistical significance. Publication bias was assessed by Egger test. A total of 14 studies with a pooled cohort of 1837 patients were included. Patients undergoing DTI-navigated glioma surgery showed a higher rate of gross total resection (GTR) than ISM-assisted surgical resection (67.88%, [95% CI 0.55-0.79] vs. 45.73%, [95% CI 0.29-0.63], P = 0.032). The occurrence of early postoperative functional deficit (35.45%, [95% CI 0.13-0.61] vs. 35.60% [95% CI 0.20-0.53], P = 1.000), late postoperative functional deficit (6.00%, [95% CI 0.02-0.11] vs. 4.91% [95% CI 0.03-0.08], P = 1.000) and severe postoperative functional deficit (2.21%, [95% CI 0-0.08] vs. 5.93% [95% CI 0.01-0.16], P = 0.393) were similar between the DTI and ISM group, respectively. While DTI-navigation resulted in a higher rate of GTR, the occurrence of postoperative neurological deficits between DTI and ISM groups was comparable. Together, these data indicate that both techniques could safely facilitate glioma resection.
Topics: Humans; Diffusion Tensor Imaging; Databases, Factual; Glioma; Postoperative Period; White Matter
PubMed: 37380888
DOI: 10.1007/s10143-023-02058-5 -
International Journal of Molecular... Jun 2023The functions of cocaine- and amphetamine-regulated transcript (CART) neuropeptide encoded by the gene vary from modifying behavior and pain sensitivity to being an... (Review)
Review
The functions of cocaine- and amphetamine-regulated transcript (CART) neuropeptide encoded by the gene vary from modifying behavior and pain sensitivity to being an antioxidant. Putative CART peptide receptor GPR160 was implicated recently in the pathogenesis of cancer. However, the exact role of CART protein in the development of neoplasms remains unclear. This systematic review includes articles retrieved from the Scopus, PubMed, Web of Science and Medline Complete databases. Nineteen publications that met the inclusion criteria and describe the association of CART and cancer were analyzed. CART is expressed in various types of cancer, e.g., in breast cancer and neuroendocrine tumors (NETs). The role of CART as a potential biomarker in breast cancer, stomach adenocarcinoma, glioma and some types of NETs was suggested. In various cancer cell lines, acts an oncogene, enhancing cellular survival by the activation of the ERK pathway, the stimulation of other pro-survival molecules, the inhibition of apoptosis or the increase in cyclin D1 levels. In breast cancer, CART was reported to protect tumor cells from tamoxifen-mediated death. Taken together, these data support the role of CART activity in the pathogenesis of cancer, thus opening new diagnostic and therapeutic approaches in neoplastic disorders.
Topics: Humans; Female; Nerve Tissue Proteins; Neuroendocrine Tumors; Breast Neoplasms; Tamoxifen; Cocaine
PubMed: 37373130
DOI: 10.3390/ijms24129986 -
Frontiers in Pharmacology 2023To compare the efficacy and safety of treatments for patients with recurrent high-grade gliomas. Electronic databases including Pubmed, Embase, Cochrane Library and...
To compare the efficacy and safety of treatments for patients with recurrent high-grade gliomas. Electronic databases including Pubmed, Embase, Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials (RCT) related to high-grade gliomas. The inclusion of qualified literature and extraction of data were conducted by two independent reviewers. The primary clinical outcome measures of network meta-analysis were overall survival (OS) while progression-free survival (PFS), objective response rate (ORR) and adverse event of grade 3 or higher were secondary measures. 22 eligible trials were included in the systematic review, involving 3423 patients and 30 treatment regimens. Network meta-analysis included 11 treatments of 10 trials for OS and PFS, 10 treatments of 8 trials for ORR, and 8 treatments of 7 trials for adverse event grade 3 or higher. Regorafenib showed significant benefits in terms of OS in paired comparison with several treatments such as bevacizumab (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.21-0.73), bevacizumab plus carboplatin (HR, 0.33; 95%CI, 0.16-0.68), bevacizumab plus dasatinib (HR, 0.44; 95%CI, 0.21-0.93), bevacizumab plus irinotecan (HR, 0.4; 95%CI, 0.21-0.74), bevacizumab plus lomustine (90 mg/m) (HR, 0.53; 95%CI, 0.33-0.84), bevacizumab plus lomustine (110 mg/m) (HR, 0.21; 95%CI, 0.06-0.7), bevacizumab plus vorinostat (HR, 0.42; 95%CI, 0.18-0.99), lomustine (HR, 0.5; 95%CI, 0.33-0.76), and nivolumab (HR, 0.38; 95%CI, 0.19-0.73). For PFS, only the hazard ratio between bevacizumab plus vorinostat and bevacizumab plus lomustine (90 mg/m) was significant (HR,0.51; 95%CI, 0.27-0.95). Lomustine and nivolumab conferred worse ORR. Safety analysis showed fotemustine as the best and bevacizumab plus temozolomide as the worst. The results suggested that regorafenib and bevacizumab plus lomustine (90 mg/m) provide improvements in terms of survival but may have poor ORR in patients with recurrent high-grade glioma.
PubMed: 37324487
DOI: 10.3389/fphar.2023.1191480