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Frontiers in Endocrinology 2023Elderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict...
Development and external validation of dual online tools for prognostic assessment in elderly patients with high-grade glioma: a comprehensive study using SEER and Chinese cohorts.
BACKGROUND
Elderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict overall survival (OS) and cancer-specific survival (CSS), assisting clinical decision-making.
METHODS
We scrutinized data from the SEER database on 5,245 elderly patients diagnosed with high-grade glioma between 2000-2020, segmenting them into training (3,672) and validation (1,573) subsets. An additional external validation cohort was obtained from our institution. Prognostic determinants were pinpointed using Cox regression analyses, which facilitated the construction of the nomogram. The nomogram's predictive precision for OS and CSS was gauged using calibration and ROC curves, the C-index, and decision curve analysis (DCA). Based on risk scores, patients were stratified into high or low-risk categories, and survival disparities were explored.
RESULTS
Using multivariate Cox regression, we identified several prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with high-grade gliomas, including age, tumor location, size, surgical technique, and therapies. Two digital nomograms were formulated anchored on these determinants. For OS, the C-index values in the training, internal, and external validation cohorts were 0.734, 0.729, and 0.701, respectively. We also derived AUC values for 3-, 6-, and 12-month periods. For CSS, the C-index values for the training and validation groups were 0.733 and 0.727, with analogous AUC metrics. The efficacy and clinical relevance of the nomograms were corroborated via ROC curves, calibration plots, and DCA for both cohorts.
CONCLUSION
Our investigation pinpointed pivotal risk factors in elderly glioma patients, leading to the development of an instrumental prognostic nomogram for OS and CSS. This instrument offers invaluable insights to optimize treatment strategies.
Topics: Aged; Humans; Prognosis; Nomograms; Glioma; Asian People; China
PubMed: 38075045
DOI: 10.3389/fendo.2023.1307256 -
International Journal of Oncology Jun 2022As the most common primary tumour of the central nervous system, gliomas have a high recurrence rate after surgical resection and are resistant to chemotherapy,... (Review)
Review
As the most common primary tumour of the central nervous system, gliomas have a high recurrence rate after surgical resection and are resistant to chemotherapy, particularly high‑grade gliomas dominated by glioblastoma multiforme (GBM). The prognosis of GBM remains poor despite improvements in treatment modalities, posing a serious threat to human health. At present, although drugs such as temozolomide, cisplatin and bevacizumab, are effective in improving the overall survival of patients with GBM, most patients eventually develop drug resistance, leading to poor clinical prognosis. The development of multidrug resistance has therefore become a major obstacle to improving the effectiveness of chemotherapy for GBM. The ability to fully understand the underlying mechanisms of chemotherapy resistance and to develop novel therapeutic targets to overcome resistance is critical to improving the prognosis of patients with GBM. Of note, growing evidence indicates that a large number of abnormally expressed noncoding RNAs (ncRNAs) have a central role in glioma chemoresistance and may target various mechanisms to modulate chemosensitivity. In the present review, the roles and molecular mechanisms of ncRNAs in glioma drug resistance were systematically summarized, the potential of ncRNAs as drug resistance markers and novel therapeutic targets of glioma were discussed and prospects for glioma treatment were outlined. ncRNAs are a research direction for tumor drug resistance mechanisms and targeted therapies, which not only provides novel perspectives for reversing glioma drug resistance but may also promote the development of precision medicine for clinical diagnosis and treatment.
Topics: Drug Resistance, Neoplasm; Glioblastoma; Glioma; Humans; RNA, Untranslated; Temozolomide
PubMed: 35506469
DOI: 10.3892/ijo.2022.5366 -
Revue Neurologique Jun 2023This paper reviews 30 years of developments in the area of low-grade gliomas. This includes the changes in diagnostics with the incorporation of 1p/19q and IDH mutations... (Review)
Review
This paper reviews 30 years of developments in the area of low-grade gliomas. This includes the changes in diagnostics with the incorporation of 1p/19q and IDH mutations in the diagnostic classifier, the improved surgical techniques, improved delivery of radiotherapy and chemotherapy. More recently, the better understanding of the altered cellular processes has lead to the development of novel drugs that may alter completely alter the management of patients early in the course of their disease.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Mutation; Glioma; Astrocytoma
PubMed: 37029057
DOI: 10.1016/j.neurol.2023.03.001 -
Journal of Child Neurology Nov 2009Pediatric low-grade gliomas encompass a heterogeneous set of tumors of different histologies. Cerebellar pilocytic astrocytomas occur most frequently followed by... (Review)
Review
Pediatric low-grade gliomas encompass a heterogeneous set of tumors of different histologies. Cerebellar pilocytic astrocytomas occur most frequently followed by supratentorial diffuse fibrillary astrocytomas. Recent research has implicated activation of the RAS/RAF/MEK pathway in tumorigenesis of these tumors. Surgery is the mainstay of therapy. Overall survival rates for patients whose tumors are completely resected are 90% or greater, 10 years from diagnosis. Conversely, most optic pathway/hypothalamic, deep midline, and brain stem gliomas have minimal potential for resection; these tumors can be difficult to treat and deserve special attention. Combination chemotherapy is currently recommended as front-line adjuvant treatment for progressive or recurrent tumors. Second-line radiotherapy can also improve overall survival but is associated with more frequent and significant neurocognitive, endocrine, and other long-term toxicities.
Topics: Brain Neoplasms; Child; Glioma; Humans; Models, Neurological; Neoplasm Staging
PubMed: 19841428
DOI: 10.1177/0883073809342005 -
The Cochrane Database of Systematic... 2002Trials on the effect of systemic chemotherapy on survival and recurrence in adults with high-grade glioma have had inconclusive results. We undertook a systematic review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Trials on the effect of systemic chemotherapy on survival and recurrence in adults with high-grade glioma have had inconclusive results. We undertook a systematic review and meta-analysis to assess the effects of such treatment on survival and recurrence.
OBJECTIVES
To compare radiotherapy plus chemotherapy with radiotherapy alone in completely resected adults with high-grade glioma. To investigate whether or not pre-defined patient subgroups benefit more or less from chemotherapy.
SEARCH STRATEGY
MEDLINE and CancerLit searches were supplemented with information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists and organisations. These searches were carried out in June 1997, June 1999 and December 2000.
SELECTION CRITERIA
Trials comparing radiotherapy versus radiotherapy + chemotherapy were eligible for inclusion provided that they randomized adult patients using a method which precluded prior knowledge of treatment assignment.
DATA COLLECTION AND ANALYSIS
A quantitative meta-analysis using updated information from individual patients from all available randomized trials was carried out. Data from all patients randomized in all eligible trials were sought directly from those responsible. Updated information on survival and date of follow-up were obtained, as were details of treatment allocation, date of randomization, age, sex, histological cell type, stage and performance status. To avoid potential bias, information was requested for all randomized patients including those who had been excluded from the investigators' original analyses. All analyses were done on an intention to treat basis on the endpoint of survival. For trials using cisplatin-based regimens, subgroup analyses by age, sex, histological cell type, tumour stage and performance status were also done.
MAIN RESULTS
Data from 12 randomized trials and 3004 patients were included. The results show a significant prolongation of survival associated with chemotherapy, with a hazard ratio of 0.85 (95% CI 0.78-0.91, p=0.00004) or 15% relative decrease in the risk of death. This is equivalent to an absolute increase in one year survival rate of 6% (95% confidence interval 3% to 9%) from 40% to 46% and a two-month increase in median survival time (95% confidence interval one month to three months). There was no evidence that the effect of chemotherapy was different in any group of patients defined by age, sex, histology, performance status or extent of resection.
REVIEWER'S CONCLUSIONS
This small but clear improvement in survival from chemotherapy encourages further study of drug treatment of these tumours
Topics: Combined Modality Therapy; Glioma; Humans; Randomized Controlled Trials as Topic
PubMed: 12519620
DOI: 10.1002/14651858.CD003913 -
FEBS Open Bio Feb 2021Glioma is a common primary malignant tumor that has a poor prognosis and often develops drug resistance. The coumarin derivative osthole has previously been reported to...
Glioma is a common primary malignant tumor that has a poor prognosis and often develops drug resistance. The coumarin derivative osthole has previously been reported to induce cancer cell apoptosis. Recently, we found that it could also trigger glioma cell necroptosis, a type of cell death that is usually accompanied with reactive oxygen species (ROS) production. However, the relationship between ROS production and necroptosis induced by osthole has not been fully elucidated. In this study, we found that osthole could induce necroptosis of glioma cell lines U87 and C6; such cell death was distinct from apoptosis induced by MG-132. Expression of necroptosis inhibitor caspase-8 was decreased, and levels of necroptosis proteins receptor-interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein were increased in U87 and C6 cells after treatment with osthole, whereas levels of apoptosis-related proteins caspase-3, caspase-7, and caspase-9 were not increased. Lactate dehydrogenase release and flow cytometry assays confirmed that cell death induced by osthole was primarily necrosis. In addition, necroptosis induced by osthole was accompanied by excessive production of ROS, as observed for other necroptosis-inducing reagents. Pretreatment with the RIP1 inhibitor necrostatin-1 attenuated both osthole-induced necroptosis and the production of ROS in U87 cells. Furthermore, the ROS inhibitor N-acetylcysteine decreased osthole-induced necroptosis and growth inhibition. Overall, these findings suggest that osthole induces necroptosis of glioma cells via ROS production and thus may have potential for development into a therapeutic drug for glioma therapy.
Topics: Apoptosis; Brain Neoplasms; Cell Line, Tumor; Coumarins; Drug Screening Assays, Antitumor; Glioma; Humans; Leupeptins; Membrane Potential, Mitochondrial; Mitochondria; Necroptosis; Reactive Oxygen Species
PubMed: 33350608
DOI: 10.1002/2211-5463.13069 -
Scientific Reports Jun 2023Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific...
Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate.
Topics: Humans; Deep Learning; Precision Medicine; Retrospective Studies; Glioma; Judgment
PubMed: 37302994
DOI: 10.1038/s41598-023-36298-8 -
Analytical Cellular Pathology... 2021Glioma is the most common malignant tumor in adult brain characteristic with poor prognosis and low survival rate. Despite the application of advanced surgery,...
Glioma is the most common malignant tumor in adult brain characteristic with poor prognosis and low survival rate. Despite the application of advanced surgery, chemotherapy, and radiotherapy, the patients with glioma suffer poor treatment effects due to the complex molecular mechanisms of pathological process. In this paper, we conducted the experiments to prove the critical roles TET1 played in glioma and explored the downstream targets of TET1 in order to provide a novel theoretical basis for clinical glioma therapy. RT-qPCR was adopted to detect the RNA level of TET1 and -catenin; Western blot was taken to determine the expression of proteins. CCK8 assay was used to detect the proliferation of glioma cells. Flow cytometry was used to test cell apoptosis and distribution of cell cycle. To detect the migration and invasion of glioma cells, wound healing assay and Transwell were performed. It was found that downregulation of TET1 could promote the proliferation migration and invasion of glioma cells and the concomitant upregulation of -catenin, and its downstream targets like cyclinD1 and c-myc were observed. The further rescue experiments were performed, wherein downregulation of -catenin markedly decreases glioma cell proliferation in vitro and in vivo. This study confirmed the tumor suppressive function of TET1 and illustrated the underlying molecular mechanisms regulated by TET1 in glioma.
Topics: Animals; Apoptosis; Brain Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Down-Regulation; Gene Expression Regulation, Neoplastic; Glioma; Humans; Male; Mice, Inbred BALB C; Mice, Nude; Mixed Function Oxygenases; Neoplasm Invasiveness; Proto-Oncogene Proteins; RNAi Therapeutics; Wnt Signaling Pathway; Xenograft Model Antitumor Assays; beta Catenin; Mice
PubMed: 34926132
DOI: 10.1155/2021/8980711 -
Communications Biology Sep 2022Tumefactive demyelinating lesion (TDL) is an immune-mediated disease which can be misdiagnosed as glioma. At present, there is no study comparing difference between the...
Tumefactive demyelinating lesion (TDL) is an immune-mediated disease which can be misdiagnosed as glioma. At present, there is no study comparing difference between the two disorders at the cellular level. Here, we perform integrative and comparative single-cell RNA sequencing (ScRNA-seq) transcriptomic analysis on TDL and glioma lesions. At single-cell resolution, TDL is comprised primarily of immune cells, which is completely different from glioma. The integrated analysis reveals a TDL-specific microglial subset involving in B cell activation and proliferation. Comparative analysis highlights remyelination function of glial cells and demyelination function of T cells in TDL. Subclustering and pseudotime trajectory analysis of T cells in TDL reveal their heterogeneity and diverse functions involving in TDL pathogenesis and recovery process. Our study identifies substantial differences between TDL and glioma at single-cell resolution. The observed heterogeneity and potentially diverse functions of cells in TDL may be critical in disease progression.
Topics: Gene Expression Profiling; Glioma; Humans; Neuroglia; Single-Cell Analysis; Transcriptome
PubMed: 36085357
DOI: 10.1038/s42003-022-03900-0 -
CNS Oncology Mar 2014In the last few decades, we have seen significant advances in brain imaging, which have resulted in more detailed anatomic and functional localization of gliomas in... (Review)
Review
In the last few decades, we have seen significant advances in brain imaging, which have resulted in more detailed anatomic and functional localization of gliomas in relation to the eloquent cortex, as well as improvements in microsurgical techniques and enhanced delivery of adjuvant stereotactic radiation. While these advancements have led to a relatively modest improvement in clinical outcomes for patients with malignant gliomas, much more work remains to be done. As with other types of cancer, we are now rapidly moving past the era of histopathology dictating treatment for brain tumors and into the realm of molecular diagnostics and associated targeted therapies, specifically based on the genomic architecture of individual gliomas. In this review, we discuss the current era of molecular glioma characterization and how these profiles will allow for individualized, patient-specific targeted treatments.
Topics: Animals; Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Precision Medicine
PubMed: 25055018
DOI: 10.2217/cns.14.7