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diffuse_glioma

Diffuse glioma

The World Health Organization Classification of Tumors of the Central Nervous System 2016 is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas.

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).

Epidemiology

Diffuse infiltrative gliomas are by far the most common primary brain tumors in adults, esp. its most malignant form, glioblastoma multiforme (GBM) 2).

Diffuse gliomas are the second most common central nervous system tumors, behind meningiomas, and account for roughly 80% of primary malignant brain tumors 3) 4) 5).

Classification

Based on the resemblance of the tumor cells with non-neoplastic glial cells, most diffuse gliomas are histopathologically typed as astrocytic, oligodendroglial, or oligoastrocytic 6).

Diffuse gliomas are classified as grades II-IV on the basis of histologic features, with prognosis determined mainly by clinical factors and histologic grade supported by molecular markers.

Diffuse gliomas consist of both low- and high-grade varieties, each with distinct morphological and biological features. The often extended periods of relative indolence exhibited by low grade gliomas (LGG; WHO grade II) differ sharply from the aggressive, rapidly fatal clinical course of primary glioblastoma (GBM; WHO grade IV). Nevertheless, until recently, the molecular foundations underlying this stark biological contrast between glioma variants remained largely unknown. The discoveries of distinctive and highly recurrent genomic and epigenomic abnormalities in LGG have both informed a more accurate classification scheme and pointed to viable avenues for therapeutic development. As such, the field of neurooncology now seems poised to capitalize on these gains to achieve significant benefit for LGG patients 7).

Diagnosis

Apparent diffusion coefficient (ADC) values had a better correlation with overall survival than relative cerebral blood flow (CBV) values. A preoperative prognostic model based on patient age, relative cerebral blood volume, and ADC values predicted overall survival of patients with diffuse gliomas independent of pathology 8).

Treatment

Diffuse glioma patients are far from being cured by conventional therapies, and there is an urgent need for other therapeutic approaches 9).

The management of diffuse gliomas has undergone many changes since 2000s, with novel approaches to surgery, radiation, and chemotherapy improving survival and quality of life for patients 10).

With regard to surgery, a more extensive surgical resection has been associated with longer life expectancy for both low- and high-grade newly diagnosed gliomas 11).

Case series

In a paper, Loit et al. propose to build a distribution map of small deep infarcts in glioma surgery, and to analyze patients' cognitive outcome in relation to stroke occurrence.

They retrospectively studied a consecutive series of patients operated on for a diffuse glioma between June 2011and June 2017. Patients with lower-grade glioma were cognitively assessed, both before and 4 months after surgery. Areas of decreased apparent diffusion coefficient (ADC) on the immediate postoperative MRI were segmented. All images were registered in the MNI reference by ANTS algorithm, allowing to build a distribution map of the strokes. Stroke occurrence was correlated with the postoperative changes in semantic fluency score in the lower-grade glioma cohort.

One hundred fifteen patients were included. Areas of reduced ADC were observed in 27 out of 54 (50%) patients with a lower-grade glioma, and 25 out of 61 (41%) patients with a glioblastoma. Median volume was 1.6 cc. The distribution map revealed five clusters of deep strokes, corresponding respectively to callosal, prefrontal, insulo-opercular, parietal, and temporal tumor locations. No motor nor speech long-term deficits were caused by these strokes. Cognitive evaluations at 4 months showed that the presence of small infarcts correlated with a slight decrease of semantic fluency scores.

Deep small infarcts are commonly found after glioma surgery, but their actual impact in terms of patients' quality of life remains to be demonstrated. Further studies are needed to better evaluate the cognitive consequences-if any-for each of the described hotspots and to identify risk factors other than the surgery-induced damage of microvessels 12).

2017

In a retrospective study. Patients with grades II-IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included. The primary outcome was seizure frequency over the first 12 postoperative months: Group A - postoperative seizure freedom; Group B - 1-11 seizures over 12months (less than one seizure per month); and Group C - greater than one seizure per month. Rates of IDH1-R132H mutation were compared between the three outcome groups in univariate and multivariate analyses. Subgroup analysis was performed in 64 patients with IDH1/2 pyrosequencing data.

One hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III, and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12months, compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and 70.0% (14/20) of Group C patients (p=0.001). On multivariate analysis, after controlling for preoperative seizure, grade, and temporal tumor location, IDH1-R132H was associated with Group C when compared with both Group A (RR 4.75, p=0.032) and Group B (RR 9.70, p=0.012). In the subgroup with IDH1/2 molecular data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of Group C, and 87.5% (14/16) of Group C patients (p=0.004).

In patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated with a more severe phenotype of postoperative epilepsy. These findings support further research into IDH mutations, and the potential for an antiepileptic therapeutic effect of their inhibitors, in patients with glioma-associated epilepsy 13).

1)
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2)
CBTRUS (2006) CBTRUS statistical report. Primary brain tumors in the United States, 1998–2002. Central Brain Tumor Registry of the United States. http://www.cbtrus.org
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4) , 10)
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5)
Theeler BJ, Yung WK, Fuller GN, et al. Moving toward molecular classification of diffuse gliomas in adults. Neurology 2012;79:1917–26
6)
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7)
Huse JT, Wallace M, Aldape KD, Berger MS, Bettegowda C, Brat DJ, Cahill DP, Cloughesy T, Haas-Kogan DA, Marra M, Miller CR, Nelson SJ, Salama SR, Soffietti R, Wen PY, Yip S, Yen K, Costello JF, Chang S. Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) Low-grade Glioma Research Workshop. Neuro Oncol. 2013 Dec 4. [Epub ahead of print] PubMed PMID:24305708.
8)
Hilario A, Sepulveda JM, Perez-Nuñez A, Salvador E, Millan JM, Hernandez-Lain A, Rodriguez-Gonzalez V, Lagares A, Ramos A. A Prognostic Model Based on Preoperative MRI Predicts Overall Survival in Patients with Diffuse Gliomas. AJNR Am J Neuroradiol. 2014 Jan 23. [Epub ahead of print] PubMed PMID: 24457819.
9)
Reardon DA, Rich JN, Friedman HS, Bigner DD (2006) Recent advances in the treatment of malignant astrocytoma. J Clin Oncol 24:1253–1265
11)
Hardesty DA, Sanai N. The value of glioma extent of resection in the modern neurosurgical era. Front Neurol 2012;3:140–47
12)
Loit MP, Rheault F, Gayat E, Poisson I, Froelich S, Zhi N, Velut S, Mandonnet E. Hotspots of small strokes in glioma surgery: an overlooked risk? Acta Neurochir (Wien). 2018 Nov 10. doi: 10.1007/s00701-018-3717-3. [Epub ahead of print] PubMed PMID: 30415385.
13)
Neal A, Kwan P, O'Brien TJ, Buckland ME, Gonzales M, Morokoff A. IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy. Epilepsy Behav. 2017 Nov 21;78:30-36. doi: 10.1016/j.yebeh.2017.10.027. [Epub ahead of print] PubMed PMID: 29172136.
diffuse_glioma.txt · Last modified: 2019/05/09 12:18 by administrador