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glioma

Glioma

Tumor that originates from glial cells.

Glial tumor is a general term for numerous tumors of the central nervous system, including astrocytomas, ependymal tumors, glioblastoma multiforme, and primitive neuroectodermal tumors.

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 1).


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 2).

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 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 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 4).

Epidemiology

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.

Approximately 89,000 new primary brain tumors are diagnosed in the United States each year, for which 27% are gliomas and 32.8% are malignant gliomas 5).

The are more frequent among males 6).

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.

MRI

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 7).


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 8) and Leu et al. 9).


The therapeutic management and prognosis of cerebral gliomas depend on tumor type and grade, and on exact definition of boundary 10) 11) 12).

In glioma patients, a presumed eloquent location has been identified as a key variable influencing the treatment strategy 13) 14).

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 15) 16) 17). , 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 18).

The prognosis improves as the amount of glioma removed increases 19) 20) 21) 22) 23).

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 24).

1)
Siegal T. Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas. Adv Tech Stand Neurosurg. 2016;43:91-108. doi: 10.1007/978-3-319-21359-0_4. PubMed PMID: 26508407.
2)
Xu H, Zhang K, Zong H, Shang M, Li K, He X. Exosomal communication in glioma - a review. J BUON. 2016 Nov-Dec;21(6):1368-1373. PubMed PMID: 28039693.
3) , 4)
Hua W, Mao Y. [Advance of molecular subtyping and precise treatment for gliomas]. Zhonghua Wai Ke Za Zhi. 2017 Jan 1;55(1):63-66. doi: 10.3760/cma.j.issn.0529-5815.2017.01.016. Chinese. PubMed PMID: 28056258.
5)
Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012. Neuro Oncol. 2015 Oct;17 Suppl 4:iv1-iv62. doi: 10.1093/neuonc/nov189. Epub 2015 Oct 27. PubMed PMID: 26511214; PubMed Central PMCID: PMC4623240.
6)
Ohgaki H and Kleihues P (2005) Epidemiology and etiology of gliomas. Acta Neuropathol 109: 93–108.
7)
Lin L, Cai J, Jiang C. Recent advances in targeted therapy for glioma. Curr Med Chem. 2016 Dec 23. [Epub ahead of print] PubMed PMID: 28019637.
8)
Tabatabai G, Stupp R, van den Bent MJ, Hegi ME, Tonn JC, Wick W, et al. Molecular diagnostics of gliomas: the clinical perspective. Acta Neuropathol. 2010;120(5):585–92.
9)
Leu S, von Felten S, Frank S, Vassella E, Vajtai I, Taylor E, et al. IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival. Neuro Oncol. 2013;15(4):469–79. doi: 10.1093/neuonc/nos317.
10)
Behin A, Hoang-Xuan K, Carpentier AF, Delattre J-Y (2003) Primary brain tumours in adults. Lancet 361:323–331
11)
Grant R (2004) Overview: brain tumour diagnosis and management/Royal College of Physicians guidelines. J Neurol Neurosurg Psychiatry 75 [Suppl 2]:II18–II23
12)
Schneider JP, Trantakis C, Rubach M, et al (2005) Intraoperative MRI to guide the resection of primary supratentorial glioblastoma multiforme – a quantitative radiological analysis. Neuroradiology 47:489–500
13)
Jakola AS, Unsgård G,Myrmel KS, et al. Low grade gliomas in eloquent locations - implications for surgical strategy, survival and long term quality of life. PLoS One 2012;7(12):e51450.
14)
Seiz M, Freyschlag CF, Schenkel S, et al. Management of patients with low-grade gliomas - a survey among German neurosurgical departments. Cen Eur Neurosurg 2011;72(4):186-191.
15)
DeAngelis LM (2001) Brain tumors. N Engl J Med 344:114–123.
16)
Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507.
17)
Behin A, Hoang-Xuan K, Carpentier AF, et al.(2003) Primary brain tumours in adults. Lancet 361:323–331.
18)
Dandy WE. Removal of right cerebral hemisphere for certain tumors with hemiplegia: preliminary report. JAMA. 1928;90:823–825.
19)
Chan-Seng E, Moritz-Gasser S, Duffau H. Awake mapping for low-grade gliomas involving the left sagittal stratum: Anatomofunctional and surgical considerations. J Neurosurg. 2014;120:1069–1077. doi: 10.3171/2014.1.JNS132015.
20)
Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. Neurosurgery. 2008;62:753–764. doi: 10.1227/01.neu.0000318159.21731.cf.
21)
Han SJ, Sughrue ME. The rise and fall of ‘biopsy and radiate’: A history of surgical nihilism in glioma treatment. Neurosurg Clin N Am. 2012;23:207–214. doi: 10.1016/j.nec.2012.02.002.
22)
Giussani C, Roux FE, Ojemann J, Sganzerla EP, Pirillo D, Papagno C. Is preoperative functional magnetic resonance imaging reliable for language areas mapping in brain tumor surgery? Review of language functional magnetic resonance imaging and direct cortical stimulation correlation studies. Neurosurgery. 2010;66:113–120. doi: 10.1227/01.NEU.0000360392.15450.C9.
23)
Choi BD, Mehta AI, Batich KA, Friedman AH, Sampson JH. The use of motor mapping to aid resection of eloquent gliomas. Neurosurg Clin N Am. 2012;23:215–225. doi: 10.1016/j.nec.2012.01.013.
24)
Kramář F, Minárik M, Benešová L, Halková T, Netuka D, Bradáč O, Beneš V. IDH1/2 Mutation and MGMT Promoter Methylation - the Relevant Survival Predictors in Czech Patients with Brain Gliomas. Folia Biol (Praha). 2016;62(5):194-202. PubMed PMID: 27978414.
glioma.txt · Last modified: 2017/10/19 12:48 by administrador