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glioma

Glioma

Studies on gliomas suggested that the microenvironment of human gliomas contains both glioma stem cells (GSCs) and glioma associated (GA)-mesenchymal stem cells (MSCs; (GA-MSCs). Also, studies have suggested that nano- sized vesicles, termed exosomes, have been recently observed to contribute towards intercellular communication within the tumor niche 1).

Classification

Gliomas originate from glial cells and comprise a heterogeneous group of benign and malignant neoplasms.

With the advance of genomics research, there have been a new breakthrough in the molecular classification of gliomas. Glioblastoma (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesochymal according to the mRNA expression. Low grade gliomas (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p/19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and TERTp (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas. Genotype and phenotype were integrated to diagnose gliomas. In the meantime, precision treatment for gliomas has also been vigorously developed 2).

With the advance of genomics research, there have been a new breakthrough in the molecular classification of gliomas. Glioblastoma (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesenchymal according to the mRNA expression. Low grade gliomas (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and TERTp (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas. Genotype and phenotype were integrated to diagnose gliomas. In the meantime, precision treatment for gliomas has also been vigorously developed 3).

Epidemiology

Glioma is the most frequent central nervous system tumor in adults.

The annual incidence for glioma is six per 100,000.

The are more frequent among males 4).

Classification

Etiology

Clinical Features

Many gliomas become symptomatic with either seizures or focal neurological deficits and are subsequently detected via MRI.

Diagnosis

The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection.

Imaging

Glioma imaging, used for diagnostics, treatment planning, and follow-up, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal.

Gadolinium-enhanced T1-weighted (T1-Gad) MR images often underestimate the true extent of the tumor, while T2-weighted images preferentially highlight peritumoral edema.

Lesions supposed to be diffuse gliomas on MR imaging, FET-PET and MR spectroscopy analyses markedly improved the diagnostic efficacy of targeted biopsies 5).

A combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone 6).

Although MRI can predict a glioma with high accuracy, a definite diagnosis must be obtained by means of histological analysis.

Diffusion weighted imaging (DWI) is considered the most sensitive for early pathological changes and therefore can potentially be useful in evaluating the features of gliomas 7).

To overcome a limitation of DWI, which is that perfusion can substantially confound diffusion measurements because of the incoherent motion of blood, intravoxel incoherent motion (IVIM) based on DWI is proposed 8) 9).

The ADC value can potentially reveal the differences in cellularity and nuclear atypia of gliomas 10).

Theoretically, high cellularity in advanced gliomas may impede free water diffusion and thus lead to a decreased ADC value. In a study by Higano et al., the minimum ADC varied significantly between WHO grade III 11). Another study also revealed a significantly higher frequency of low ADC values in high- compared with low-grade gliomas 12). In addition, parameter D was shown to be inversely correlated with cell density 13).

Previous studies have suggested that the relative cerebral blood volume (rCBV) value is correlated with the grade and vascularity in gliomas 14) 15).

Usually, low-grade gliomas show no increase in tumor rCBV, whereas high-grade gliomas demonstrate high rCBV that in some cases even extends outside the contrast-enhancing portions of the tumor 16).

Pulsed arterial spin labeling, DTI, and MR spectroscopy are useful for predicting glioma grade. Additionally, the parameters obtained on DTI and MR spectroscopy closely correlated with the proliferative potential of gliomas 17).

Treatment

Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway. Furthermore, recent advances in targeting immunotherapy and stem cell therapy also brought numerous strategies to glioma treatment 18).


Treatment options depend on the type of glioma, and patient-specific factors such as location and size of the glioma, patient age, symptoms and neurological status. In addition, three molecular markers – 1p/19q co-deletion, O6-methylguanine methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) 1/2 mutations – are known to have important diagnostic, prognostic and predictive (for treatment efficacy) roles in glioma treatment (for reviews see Tabatabai et al. 2010 19) and Leu et al. 20).


The therapeutic management and prognosis of cerebral gliomas depend on tumor type and grade, and on exact definition of boundary 21) 22) 23).

In glioma patients, a presumed eloquent location has been identified as a key variable influencing the treatment strategy 24) 25).

Surgery

Outcome

Human gliomas are related to high rates of morbidity and mortality.

Gliomas are a heterogeneous group of tumours varying in prognosis, treatment approach, and overall survival.

Novel biomarkers have been identified which are linked to patient prognosis and therapeutic response. Especially the mutation of the enzyme isocitrate dehydrogenase 1 or isocitrate dehydrogenase 2 (IDH1/2) gene and the O6 methylguanine DNA methyltransferase (MGMT) promoter methylation status seem to be the most important predictors of survival.

Infiltrative gliomas invade the brain, relentlessly recur, transform into higher-grade gliomas, and are invariably lethal 26) 27) 28). , mostly due to the poor prognosis of glioblastoma multiforme (Grade IV glioma).

Gliomas are considered incurable due to recurrence as demonstrated in a series of five patients who underwent hemispherectomies in 1928 29).

The prognosis improves as the amount of glioma removed increases 30) 31) 32) 33) 34).

Books

Gliomas, Volume 134 (Handbook of Clinical Neurology)

Gliomas provides a thorough overview of the evolving fields of tumor biology and clinical medicine as they relate to our understanding of brain tumors.

Gliomas reviews the current paradigms that underlie these fields, beginning with the molecular epidemiology of glioma susceptibility and prognosis through population-based science and genome-wide association studies. The book’s discussion of imaging modalities extends beyond advances in anatomical imaging to include metabolic and physiological studies. This work provides thorough discussion of the clinical view of tumors, ranging from the presentation of the patient to surgical management, and covers all therapeutic options for patient care, including chemotherapy, targeted molecular therapies, immunotherapies, and even personalized approaches to impact the set of lesions. Additionally, the book discusses radiotherapy with regard to the many options available to treat patients using myriad fractionated techniques with various sources. Finally, Gliomas reviews issues specific to the quality of life for patients, and techniques for maximizing the effect of caregivers.

464 pages

Case series

2016

From 2012 to 2015, 94 Czech patients with primary brain tumors were enrolled into the study. The IDH1/2 mutation was detected by denaturing capillary electrophores. The methylation status of the MGMT gene and other 46 genes was revealed by MS-MLPA. In all 94 patients, the clinical data were correlated with molecular markers by Kaplan Meier analyses and Cox regression model. The MGMT promoter methylation status was established and compared to clinical data. In our study eight different probes were used to elucidate the MGMT methylation status; hypermethylation was proclaimed if four and more probes were positive. This 3 : 5 ratio was tested and confirmed by Kaplan-Meier and Cox analyses. The study confirmed the importance of the IDH1/2 mutation and hypermethylation of the MGMT gene promoter being present in tumour tissue. Both markers are independent positive survival predictors; in the Cox model the IDH hazard ratio was 0.10 and in the case of MGMT methylation it reached 0.32. The methylation analysis of the panel of additional 46 genes did not reveal any other significant epigenetic markers; none of the candidate genes have been confirmed in the Cox regression analyses as an independent prognostic factor 35).

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glioma.txt · Last modified: 2017/08/15 22:29 by administrador