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Neuro-oncology Mar 2018The use of contrast enhancement within the brain on CT or MRI has been the gold standard for diagnosis and therapeutic response assessment in malignant gliomas for... (Review)
Review
The use of contrast enhancement within the brain on CT or MRI has been the gold standard for diagnosis and therapeutic response assessment in malignant gliomas for decades. The use of contrast enhancing tumor size, however, remains controversial as a tool for accurately diagnosing and assessing treatment efficacy in malignant gliomas, particularly in the current, quickly evolving therapeutic landscape. The current article consolidates overwhelming evidence from hundreds of studies in the field of neuro-oncology, providing the necessary evidence base and specific contexts of use for consideration of contrast enhancing tumor size as an appropriate surrogate biomarker for disease burden and as a tool for measuring treatment response in malignant glioma, including glioblastoma.
Topics: Biomarkers; Brain Neoplasms; Contrast Media; Evidence-Based Medicine; Glioma; Humans; Neuroimaging
PubMed: 29040703
DOI: 10.1093/neuonc/nox193 -
Scientific Reports Dec 2019We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and...
We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and T2-weighted magnetic resonance images (T2WIs). We proposed a framework and applied it to CE-T1WIs and T2WIs (with tumor region data) acquired preoperatively from 157 patients with malignant glioma (grade III: 55, grade IV: 102) as the primary dataset and 67 patients with malignant glioma (grade III: 22, grade IV: 45) as the validation dataset. Radiomic features such as size/shape, intensity, histogram, and texture features were extracted from the tumor regions on the CE-T1WIs and T2WIs. The Wilcoxon-Mann-Whitney (WMW) test and least absolute shrinkage and selection operator logistic regression (LASSO-LR) were employed to select the radiomic features. Various machine learning (ML) algorithms were used to construct prediction models for the malignant glioma grades using the selected radiomic features. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the prediction models in the primary dataset. The selected radiomic features for all folds in the LOOCV of the primary dataset were used to perform an independent validation. As evaluation indices, accuracies, sensitivities, specificities, and values for the area under receiver operating characteristic curve (or simply the area under the curve (AUC)) for all prediction models were calculated. The mean AUC value for all prediction models constructed by the ML algorithms in the LOOCV of the primary dataset was 0.902 ± 0.024 (95% CI (confidence interval), 0.873-0.932). In the independent validation, the mean AUC value for all prediction models was 0.747 ± 0.034 (95% CI, 0.705-0.790). The results of this study suggest that the malignant glioma grades could be sufficiently and easily predicted by preparing the CE-T1WIs, T2WIs, and tumor delineations for each patient. Our proposed framework may be an effective tool for preoperatively grading malignant gliomas.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Area Under Curve; Brain Neoplasms; Child; Contrast Media; Databases as Topic; Female; Glioma; Humans; Machine Learning; Magnetic Resonance Imaging; Male; Middle Aged; ROC Curve; Reproducibility of Results; Young Adult
PubMed: 31857632
DOI: 10.1038/s41598-019-55922-0 -
Neuro-oncology Oct 2017Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and...
BACKGROUND
Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with cancer; however, little is known about PA or prognostic communication in MG. Moreover, research has yet to evaluate the impact of cognitive impairment on PA and preferred forms of communication.
METHODS
Fifty MG patients and 32 paired caregivers were evaluated in this exploratory study with a semi-structured PA assessment aimed to measure their awareness of MG incurability and LE. Full PA was defined as awareness of MG incurability and accurate estimate of LE. The assessment included a survey about preferences for prognostic communication (items from the Prognosis and Treatment Perceptions Questionnaire), neurocognitive assessment (Hopkins Verbal Learning Test-Revised, Trail Making Test Parts A and B, and the Controlled Oral Word Association Test), and measurements of mood (Hospital Anxiety and Depression Scale) and quality of life (Functional Assessment of Cancer Therapy-Brain [FACT-Br]).
RESULTS
Twenty (40%) patients and 22 (69%) caregivers had full PA. Thirty (60%) patients and 23 (72%) caregivers reported that prognostic information was extremely or very important, and 21 (42%) patients and 16 (50%) caregivers desired more prognostic information. Patients with memory impairment more frequently believed that prognostic information was important (P = 0.04, P = 0.03) and desired more information (P = 0.05, P = 0.003) as compared with those without impairment.
CONCLUSIONS
Most MG patients were unaware of their LE. Memory impairment may influence preferences for prognostic information.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Attitude to Health; Caregivers; Cognition; Communication; Female; Follow-Up Studies; Glioma; Health Knowledge, Attitudes, Practice; Humans; Life Expectancy; Male; Middle Aged; Prognosis; Prospective Studies; Quality of Life; Surveys and Questionnaires; Young Adult
PubMed: 28645200
DOI: 10.1093/neuonc/nox117 -
Journal of Cellular and Molecular... Aug 2019Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has... (Review)
Review
Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has become an important method of cancer treatment in addition to surgery, radiotherapy and chemotherapy. Although the performance of anti-angiogenic therapy in colorectal cancer is good, its performance in malignant glioma remains unsatisfactory. Several phase III clinical trials showed no overall survival benefits. To solve this problem, the division of patients into groups based on their molecular biomarkers is an important step. This paper provides current insights into anti-angiogenic drugs undergoing clinical trials and discusses the potential of molecular biomarkers to guide glioma diagnosis.
Topics: Angiogenesis Inhibitors; Bevacizumab; Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Indoles; Molecular Targeted Therapy; Prognosis; Snake Venoms
PubMed: 31210419
DOI: 10.1111/jcmm.14417 -
International Journal of Molecular... May 2021Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct... (Review)
Review
Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct tumor zones of this heterogeneous neoplasm develop their own microenvironment, in which subpopulations of cancer cells communicate. Adaptation to hypoxia in the center of the expanding tumor mass leads to the glycolytic and angiogenic switch, accompanied by upregulation of different glycolytic enzymes, transporters, and other metabolites. These processes render the tumor microenvironment more acidic, remodel the extracellular matrix, and create energy gradients for the metabolic communication between different cancer cells in distinct tumor zones. Escape mechanisms from hypoxia-induced cell death and energy deprivation are the result. The functional consequences are more aggressive and malignant behavior with enhanced proliferation and survival, migration and invasiveness, and the induction of angiogenesis. In this review, we go from the biochemical principles of aerobic and anaerobic glycolysis over the glycolytic switch, regulated by the key transcription factor hypoxia-inducible factor (HIF)-1α, to other important metabolic players like the monocarboxylate transporters (MCTs)1 and 4. We discuss the metabolic symbiosis model via lactate shuttling in the acidic tumor microenvironment and highlight the functional consequences of the glycolytic switch on glioma malignancy. Furthermore, we illustrate regulation by micro ribonucleic acids (miRNAs) and the connection between mutation status and glycolytic metabolism. Finally, we give an outlook about the diagnostic and therapeutic implications of the glycolytic switch and the relation to tumor immunity in malignant glioma.
Topics: Animals; Brain; Brain Chemistry; Brain Neoplasms; Carbonic Anhydrases; Glioma; Glycolysis; Humans; Hydrogen-Ion Concentration; Lactic Acid; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 34073734
DOI: 10.3390/ijms22115518 -
Diagnostic and Interventional Imaging Oct 2014Detecting a new area of contrast-enhancement at MRI after irradiation of malignant brain tumor arises the problem of differential diagnosis between tumor recurrence and...
Detecting a new area of contrast-enhancement at MRI after irradiation of malignant brain tumor arises the problem of differential diagnosis between tumor recurrence and radiation necrosis induced by the treatment. The challenge for imaging is to distinguish the two diagnoses given: the prognostic and therapeutic issues. Various criteria have been proposed in the literature based on morphological, functional or metabolic MRI. The purpose of this study was to perform an analysis of these tools to identify MRI best criteria to differentiate radiation necrosis lesions from malignant gliomas and brain metastases recurrence. For gliomas, the morphology of the contrast-enhancement cannot guide the diagnosis and the use of perfusion techniques and spectroscopy (multivoxels if possible) are necessary. In the follow-up of metastasis, a transient increase and moderate lesion volume is possible with a good prognosis. Morphological characteristics (volume ratio T2/T1Gd) and perfusion analysis provide valuable tools for approaching the diagnosis of radionecrosis.
Topics: Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging
PubMed: 25001364
DOI: 10.1016/j.diii.2014.06.013 -
Cancer Control : Journal of the Moffitt... 2004Despite advances in surgery, radiation therapy, and chemotherapy, only modest improvement has been achieved in the survival of patients with malignant gliomas. (Review)
Review
BACKGROUND
Despite advances in surgery, radiation therapy, and chemotherapy, only modest improvement has been achieved in the survival of patients with malignant gliomas.
METHODS
The authors review the immunologic aspects of gliomas, potential targets for therapy, and issues surrounding current immunotherapeutic strategies directed against malignant gliomas.
RESULTS
The blood-brain barrier and the purported immunological privilege of the brain are not necessarily insurmountable obstacles to effective immunotherapy for brain tumors. Preclinical studies suggest a number of potential therapeutic avenues. Translational studies offer the prospect of providing substantial new information about immunological trafficking in the nervous system and suggesting the most fruitful approaches to immunotherapy for malignant gliomas.
CONCLUSIONS
More effective adjuvant treatments for malignant gliomas are needed. The applicability of immunological approaches in the treatment of these tumors warrants continued study.
Topics: Animals; Antigens, Neoplasm; Blood-Brain Barrier; Brain; Cancer Vaccines; Clinical Trials as Topic; Dendritic Cells; Drug Delivery Systems; Genes, erbB-1; Glioma; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immune Tolerance; Immunotherapy; Interleukin-2; Mutation; Treatment Outcome
PubMed: 15153842
DOI: 10.1177/107327480401100306 -
Ultrasonics Sonochemistry Jul 2017Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include... (Review)
Review
Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include surgery, radiation therapy, and chemotherapy, although these approaches often failed to control tumor progression or improve patient survival. Sonodynamic therapy is a developing cancer treatment that uses ultrasound combined with a sonosensitizer to synergistically kill tumor cells, and has provided impressive results in both in vitro and in vivo studies. The ultrasound waves can penetrate deep tissues and reversibly open the blood-brain barrier to enhance drug delivery to the brain. Thus, sonodynamic therapy has a promising potential in glioma treatment. In this review, we summarize the studies that have confirmed the pre-clinical efficacy of sonodynamic therapy for glioma treatment, and discuss the future directions for this emerging treatment.
Topics: Animals; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Glioma; Humans; Ultrasonic Waves
PubMed: 28427672
DOI: 10.1016/j.ultsonch.2017.02.020 -
Cell Research Jun 2021Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis....
Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.
Topics: Carcinogenesis; Glioblastoma; Glioma; Humans; Neoplastic Stem Cells; Neural Stem Cells
PubMed: 33390587
DOI: 10.1038/s41422-020-00451-z -
Journal of Neuro-oncology Jun 2017Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided... (Review)
Review
Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided only modest improvements in overall survival and remain limited by inevitable local recurrence, necessitating exploration of novel therapies. Among approaches being investigated, one of the leading contenders is immunotherapy, which aims to modulate immune pathways to stimulate the selective destruction of malignant cells. Dendritic cells (DCs) are potent initiators of adaptive immune responses and therefore crucial players in the development and success of immunotherapy. Clinical trials of various DC-based vaccinations have demonstrated the induction of anti-tumor immune responses and prolonged survival in the setting of many cancers. In this review, we summarize current literature regarding DCs and their role in the tumor microenvironment, their application and current clinical use in immunotherapy, current challenges limiting their efficacy in anti-cancer therapy, and future avenues for developing successful anti-tumor DC-based vaccines.
Topics: Animals; Brain Neoplasms; Cancer Vaccines; Dendritic Cells; Glioma; Humans
PubMed: 28434112
DOI: 10.1007/s11060-017-2446-4