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CNS Oncology 2015Radiotherapy has been a longstanding treatment option for low-grade glioma. Improvements in tumor control and radiation-related toxicity may be attributed to advances in... (Review)
Review
Radiotherapy has been a longstanding treatment option for low-grade glioma. Improvements in tumor control and radiation-related toxicity may be attributed to advances in neuroimaging as well as radiotherapy planning and delivery. The discovery of various molecular prognostic factors have aided in patient selection for radiotherapy. These prognostic and predictive factors may also play a key role in determining which patients are likely to benefit most from combined systemic therapy and radiation.
Topics: Brain Neoplasms; Combined Modality Therapy; Humans; Neuroimaging; Oligodendroglioma; Radiotherapy Dosage; Radiotherapy, Computer-Assisted
PubMed: 26477980
DOI: 10.2217/cns.15.25 -
Current Opinion in Oncology Nov 2015Genetic, epigenetic, and expression analyses have refined the traditional, histopathology-based classification of diffusely infiltrating gliomas. This review summarizes... (Review)
Review
PURPOSE OF REVIEW
Genetic, epigenetic, and expression analyses have refined the traditional, histopathology-based classification of diffusely infiltrating gliomas. This review summarizes these trends and implications for elderly patients.
RECENT FINDINGS
The vast majority of diffusely infiltrating gliomas in elderly patients share an unfavorable molecular phenotype, that is, telomerase reverse transcriptase promoter mutation in the absence of isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. Histopathologically, these are mostly astrocytic tumors and treatment is guided by the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter. 1p/19q codeletion indicates oligodendroglial histology and benefit from the addition of procarbazine, chlorethyl-cyclohexyl-nitroso-urea/lomustine, and vincristine polychemotherapy to radiotherapy. These tumors are almost exclusively associated with IDH mutations, but their molecular profile is rare in elderly patients. Two large phase III trials, RTOG 0825 and AVAglio, failed to demonstrate an overall survival benefit from antiangiogenic therapy with bevacizumab added to combined chemoradiotherapy (TMZ) in patients with newly diagnosed glioblastoma, but a trend toward improved survival with increasing age can be noted. Ongoing clinical trials in elderly patients with diffusely infiltrating glioma will clarify the role of combined chemoradiotherapy, and of bevacizumab or other antiangiogenic agents as an adjunct to radiotherapy.
SUMMARY
The choice of first-line therapy in elderly patients with diffusely infiltrating glioma is between postoperative hypofractionated radiotherapy and chemotherapy, guided by MGMT methylation in most patients.
Topics: Aged; Angiogenesis Inhibitors; Antineoplastic Agents; Central Nervous System Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; DNA Methylation; DNA Modification Methylases; Epigenomics; Gene Expression Regulation, Neoplastic; Glioma; Humans; Isocitrate Dehydrogenase; Molecular Targeted Therapy; Telomerase
PubMed: 26397765
DOI: 10.1097/CCO.0000000000000236 -
AJNR. American Journal of Neuroradiology Nov 2022Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI...
BACKGROUND AND PURPOSE
Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI can be used to distinguish astrocytomas and oligodendrogliomas and whether malignant grading of gliomas is possible.
MATERIALS AND METHODS
7T SWI was performed on 21 patients with gliomas before surgery with optimization for sharp visualization of the corticomedullary junction. Scoring for cortical thickening and displacement of medullary vessels, characteristic of oligodendroglial tumors, and cortical tapering, characteristic of astrocytic tumors, was performed. Additionally, characteristics of malignancy, including thickening of the medullary veins, the presence of microbleeds, and/or necrosis were scored.
RESULTS
Scoring for oligodendroglial (highest possible score, +3) and astrocytic (lowest score possible, -3) characteristics yielded a significant difference between astrocytomas and oligodendrogliomas (mean, -1.93 versus +1.71, < .01). Scoring for malignancy was significantly different among the World Health Organization grade II ( = 10), grade III ( = 4), and grade IV ( = 7) tumors (mean, 0.20 versus 1.38 versus 2.79). Cortical thickening was observed significantly more frequently in oligodendrogliomas ( < .02), with a sensitivity of 71.4% and specificity of 85.7%; observation of tapering of the cortex was higher in astrocytomas ( < .01) with a sensitivity of 85.7% and specificity of 100%.
CONCLUSIONS
Visualization of the corticomedullary junction by 7T SWI was useful in distinguishing astrocytomas and oligodendrogliomas. Observation of tapering of the cortex was most sensitive and specific for diagnosing astrocytomas. Reliably predicting malignant grade was also possible by 7T SWI.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Astrocytoma; Glioma; Magnetic Resonance Imaging
PubMed: 36229164
DOI: 10.3174/ajnr.A7666 -
CNS Oncology 2015Several morphology- and polymerase chain reaction (PCR)-based methods for chromosome 1p 19q deletion status assessment are available. Important prerequisites for all... (Review)
Review
Several morphology- and polymerase chain reaction (PCR)-based methods for chromosome 1p 19q deletion status assessment are available. Important prerequisites for all molecular techniques concern tissue quality and selection of regions of interest. The most common methods for diagnostic 1p 19q assessment are fluorescence in situ hybridization and PCR-based microsatellite analysis. While the latter requires the use of autologous blood samples, more advanced techniques such as array comparative genomic hybridization, multiplex ligation-dependent probe amplification or real-time PCR are independent from autologous DNA samples. However, due to high technical demand and experience required their applicability as diagnostic tests remains to be shown. On the other hand, chromogenic in situ hybridization evolves as attractive alternative to FISH. Herein, the available test methods are reviewed and outlined, their advantages and drawbacks being discussed in detail.
Topics: Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 9; Glioma; Humans; In Situ Hybridization, Fluorescence; Pathology, Molecular
PubMed: 26545171
DOI: 10.2217/cns.15.28 -
Current Opinion in Neurology Dec 2013The purpose of this review is to describe the recent knowledge gathered from the identification of seven genomic regions that have been linked to the risk of developing... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to describe the recent knowledge gathered from the identification of seven genomic regions that have been linked to the risk of developing malignant glioma.
RECENT FINDINGS
The recent novel discoveries in fine mapping and genotype-phenotype studies will be highlighted. Through imputation and next-generation sequencing a novel genetic variant, rs55705857, with a strong association at 8q24 has been discovered and validated in two studies. This locus is specifically associated with IDH1-mutated and IDH2-mutated tumors and oligodendroglial tumors, albeit the specific mechanism of tumor development is not understood. The genetic variants associated with the risk of glioma in the EGFR gene have also been associated with specific somatic aberrations, including loss at the CDKN2A/B locus and allele specific loss of EGFR in the tumors. A specific TP53 low frequency variant has also been associated with glioma risk and validated in a separate data set. The genetic risk in the telomere regulating genes TERT and RTEL appear to be associated with higher grade tumors without IDH mutations.
SUMMARY
The link of genetic loci to specific tumor subtypes may have relevance for understanding glioma biology, and for developing new diagnostic tools and targeted therapy for glioma.
Topics: Biomarkers, Tumor; Brain Neoplasms; Genetic Predisposition to Disease; Genome-Wide Association Study; Glioma; Humans
PubMed: 24184969
DOI: 10.1097/WCO.0000000000000033 -
Folia Neuropathologica 2021This study has assessed the diagnostic ability of oligodendrocyte-2 (Olig2), CD99, and epithelial membrane antigen (EMA) immunohistochemical stains to diagnose...
INTRODUCTION
This study has assessed the diagnostic ability of oligodendrocyte-2 (Olig2), CD99, and epithelial membrane antigen (EMA) immunohistochemical stains to diagnose oligodendroglial-like neoplasms as central neurocytoma, ependymoma, or oligodendroglioma.
MATERIAL AND METHODS
An immunohistochemistry (IHC) panel of Olig2, EMA, and CD99 was performed on 18 central neurocytomas, 46 ependymomas, and 28 oligodendrogliomas. A quantitative labelling index of stained tumor cells was assessed using a scoring system, and its diagnostic predictability was evaluated with multinomial logistic regression.
RESULTS
Significant differences in IHC expression patterns were observed between all tumor groups (p < 0.001). The labeling indices of the histochemical expression of Olig2, EMA, and CD99 were related to diagnostic predictability. Olig2 was unlikely to differentiate ependymoma from central neurocytoma (p = 0.154), while EMA and CD99 were significant in diagnosing these two tumors (p < 0.05). Olig2 was a specific marker of oligodendroglioma, differentiating it from ependymoma and central neurocytoma (p 0.05), but CD99 significantly differentiated ependymoma from oligodendroglioma (p = 0.022). These labelling indices were used to re-assess the diagnostic accuracy, regardless of tumor location and histology, and yielded significantly different tumor diagnoses.
CONCLUSIONS
The IHC panel of Olig2, EMA, and CD99 should be used to differentiate oligodendroglial-like neoplasms. Olig2 is a specific IHC marker to diagnose oligodendroglioma and differentiate it from ependymoma and central neurocytoma. Lack of Olig2 expression rules out oligodendroglioma and suggests the diagnosis of ependymoma rather than central neurocytoma if the EMA labelling index shows diffuse/partial expression. CD99 is considered a sensitive marker for ependymoma but not central neurocytoma.
Topics: 12E7 Antigen; Biomarkers, Tumor; Brain Neoplasms; Ependymoma; Humans; Mucin-1; Neurocytoma; Oligodendrocyte Transcription Factor 2; Oligodendroglia; Oligodendroglioma
PubMed: 34628794
DOI: 10.5114/fn.2021.108526 -
Neuro-oncology Nov 2019We identify cognitive impairment and MRI structural brain changes in long-term oligodendroglial tumor survivors treated with radiation therapy (RT) alone (21%) or with...
BACKGROUND
We identify cognitive impairment and MRI structural brain changes in long-term oligodendroglial tumor survivors treated with radiation therapy (RT) alone (21%) or with chemotherapy (CT) (79%).
METHODS
Oligodendroglial tumor patients (based on the World Health Organization [WHO] 2007 classification) who completed RT ± CT at least 2 years before the study initiation, were classified into 3 groups according to the time treatment was completed: Group 1 = 2-5 years (n = 22), Group 2 = 6-10 years (n = 13), and Group 3 >10 years (n = 13). All patients had a cross-sectional neuropsychological evaluation (n = 48) and a longitudinal volumetric analysis (gray matter [GM; n = 34]) between postsurgical and last follow-up MRI. White matter (WM) changes on MRI were assessed using a qualitative scale.
RESULTS
There were no differences regarding tumor or treatment-related characteristics between groups. Six of 22 patients (27.3%) in Group 1; 5/13 (38.5%) in Group 2; and 9/13 (69.2%) in Group 3 had cognitive impairment that was considered severe in 3/22 patients (13.6%) in Group 1; 4/13 (30.8%) in Group 2; and 6/13 (46.2%) in Group 3. Patients in Groups 2 and 3 showed significant GM atrophy and more leukoencephalopathy than Group 1. Cognitive deficits were associated with brain atrophy and WM changes.
CONCLUSIONS
Long-term oligodendroglial tumor survivors who underwent standard RT ± CT treatment, mainly >5 years of its completion, present cognitive impairment, especially on memory and executive functions, associated with late GM and WM damage, thus highlighting the need of developing future strategies in patients with oligodendroglial tumor and long expected survival.
Topics: Adult; Aged; Cancer Survivors; Chemoradiotherapy; Cognition Disorders; Cross-Sectional Studies; Female; Follow-Up Studies; Gray Matter; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Oligodendroglioma; Prognosis; Retrospective Studies; Survival Rate; White Matter; Young Adult
PubMed: 31549152
DOI: 10.1093/neuonc/noz130 -
Ideggyogyaszati Szemle Sep 2021Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to...
BACKGROUND AND PURPOSE
Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes.
METHODS
Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested for the expression of p53 and ATRX by immunohistochemistry, and codeletion of 1p19q by fluorescent in situ hybridization. Expression levels of the non-canonical Wnt5a and Fzd2, and the canonical Wnt3a and beta-catenin Wnt pathway markers were determined by immunohistochemistry, and compared between subgroups stratified according to grade, lineage and the presence or absence of IDH1 R132H/C mutations.
RESULTS
In the normal brain - grade II-IV glioma comparisons, a gradual increase was observed for the expressions of Wnt5a, Wnt3a, Fzd2 and beta-catenin. In the astroglial and oligodendroglial lineages of grade II and III gliomas, only the Wnt5a expression was significantly higher in the astroglial subgroup. Stratification according to the IDH1 status resulted in a significant increase of the Wnt3 expression in the wild type grade II-IV gliomas.
CONCLUSION
These data extend previous observations and show a correlation of Wnt pathway activity with glioma grade. Further investigations of the Wnt marker expression regulation according to glioma lineage or IDH gene mutational status are in progress by using more exact molecular approaches.
Topics: Brain Neoplasms; Glioma; Humans; In Situ Hybridization, Fluorescence; Isocitrate Dehydrogenase; Wnt Signaling Pathway
PubMed: 34657400
DOI: 10.18071/isz.74.0349 -
Veterinary Pathology Sep 2021Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain...
Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed. Tumors were diagnosed as astrocytic, oligodendroglial, or undefined glioma using Comparative Brain Tumor Consortium criteria. Putative features of malignancy were evaluated, namely, mitotic counts, glomeruloid vascularization, and necrosis. For biopsies, dogs with astrocytic tumors lived longer than those with oligodendroglial or undefined tumor types (median survival 743, 205, and 144 days, respectively). Dogs with low-grade gliomas lived longer than those with high-grade gliomas (median survival 734 and 194 days, respectively). Based on analysis of tumor biopsies, low mitotic counts, absence of glomeruloid vascularization, and absence of necrosis correlated with increased survival (median 293, 223, and 220 days, respectively), whereas high mitotic counts, glomeruloid vascularization, and necrosis correlated with poor survival (median 190, 170, and 154 days, respectively). Mitotic count was the only histological feature in biopsy samples that significantly correlated with survival ( < .05). Whole-brain analyses for those same histologic features had similar and more robust correlations, and were statistically significant for all features ( < .05). The small size of biopsy samples may explain differences between biopsy and whole-brain tumor data. These findings will allow more accurate prognosis for gliomas.
Topics: Animals; Astrocytoma; Brain Neoplasms; Dog Diseases; Dogs; Glioma; Prognosis; Retrospective Studies
PubMed: 34219560
DOI: 10.1177/03009858211025795 -
Archives of Pathology & Laboratory... Sep 2014Astrocytomas arising within the eye display 2 distinct histologies: one comprises interlacing bundles of spindle-shaped cells mixed with a minority of polygonal cells,... (Review)
Review
Astrocytomas arising within the eye display 2 distinct histologies: one comprises interlacing bundles of spindle-shaped cells mixed with a minority of polygonal cells, and the other consists of large cells with abundant glassy cytoplasm (gemistocytic astrocytes) indistinguishable from cells found in subependymal giant cell astrocytoma. Both histologic patterns express glial fibrillary acid protein diffusely, are biologically benign, and are frequently associated with dysgenic syndromes, particularly tuberous sclerosis complex. Tumors with gemistocytes, however, demonstrate a greater propensity for invasive growth. The clinical history may provide information to guide the pathologist in distinguishing intraocular astrocytoma from reactive astrocytosis, conditions that are histologically similar. It remains to be determined if other types of primary intraocular glioma exist or whether some degree of ependymal or oligodendroglial differentiation can accompany reactive astrocytosis.
Topics: Astrocytoma; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Humans; Optic Nerve; Optic Nerve Glioma; Optic Nerve Neoplasms; Retina; Retinal Neoplasms; Retinoblastoma; S100 Proteins
PubMed: 25171711
DOI: 10.5858/arpa.2013-0448-RS