Gliomas are the most frequent intrinsic tumours of the central nervous system and encompass two principle subgroups: diffuse gliomas and gliomas showing a more circumscribed growth pattern ('non-diffuse gliomas'). In the revised 4th edition of the World Health Organization Classification of Tumors of the Central Nervous System published in 2016, classification of especially diffuse gliomas has fundamentally changed: for the first time a large subset of these tumours is now defined based on presence/absence of IDH mutation and 1p/19q codeletion. Following this approach, the diagnosis of (anaplastic) oligoastrocytoma can be expected to largely disappear 1).
Sorting and grading of glial tumors by the WHO grade classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular biomarkers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neurooncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in elderly glioblastoma 2).
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 3).
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 4).
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 5).
Gliomas are the second most common primary brain tumors, with an incidence of 4–5/100 000 individuals. Gliomas are the second leading cause of cancer mortality in adults under the age of 35, the fourth leading cause in those under the age of 54, and result in death in approximately 13 770 individuals per year in the United States.
The are more frequent among males 7).
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.
see MRI for glioma.
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 8).
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 9) and Leu et al. 10).
see Glioma surgery
see Glioma outcome.
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.
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 16).