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CNS Oncology 2015Oligodendroglioma (WHO Grade 2) and anaplastic oligodendroglioma (WHO Grade 3) are glial tumors composed of neoplastic cellular elements that resemble oligodendrocytes.... (Review)
Review
Oligodendroglioma (WHO Grade 2) and anaplastic oligodendroglioma (WHO Grade 3) are glial tumors composed of neoplastic cellular elements that resemble oligodendrocytes. The treatment of recurrent, alkylator refractory oligodendroglial tumors is challenging given the paucity of effective treatment and lack of randomized controlled trials on which to base therapy. Notwithstanding the lack of prospective, randomized data, treatment of oligodendroglial tumors with bevacizumab can be recommended tentatively recognizing that preliminary studies suggest efficacy. Somatic mutations of the isocitrate dehydrogenase enzymes (IDH1 and IDH2) appear to play a critical role in the pathogenesis of most oligodendroglial tumors and agents that target these mutations are a potential therapeutic option. Additionally, reversal of CpG island hypermethylated phenotype status through inhibition of DNA methyltransferase with an inhibitor such as decitabine may provide a target for future studies.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Humans; Isocitrate Dehydrogenase; Neoplasm Recurrence, Local; Oligodendroglioma; Vascular Endothelial Growth Factor A
PubMed: 26509217
DOI: 10.2217/cns.15.27 -
Seizure Apr 2012Carbamazepine is used to control seizures. Its common side effects are sleep disorders, anorexia, nausea, vomiting, polydipsia, irritability, ataxia, and diplopia....
Carbamazepine is used to control seizures. Its common side effects are sleep disorders, anorexia, nausea, vomiting, polydipsia, irritability, ataxia, and diplopia. Involvement of the immune system is rare, and few cases of decreased immunoglobulin levels have been reported. We describe a patient with low immunoglobulin levels due to carbamazepine use who presented with recurrent urinary tract infection. Intravenous immunoglobulin was administered, and immunoglobulin levels increased to safer levels after discontinuation of carbamazepine. Previous reports describe severe infection after carbamazepine-induced hypogammaglobulinemia. Therefore, in patients using antiepileptics, particularly carbamazepine, serum immunoglobulin levels should be checked in those with recurrent infections.
Topics: Adult; Agammaglobulinemia; Anticonvulsants; Brain Neoplasms; Carbamazepine; Humans; Male; Oligodendroglioma; Seizures; Urinary Tract Infections
PubMed: 22251925
DOI: 10.1016/j.seizure.2011.12.013 -
Folia Histochemica Et Cytobiologica 2008Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination...
Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with tumour histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP) and microvessel density (MVD). Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following antibodies were used Ki-67 and PCNA (DAKO). Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO). The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Proliferation; Endothelial Cells; Female; Glioma; Humans; Immunohistochemistry; Male; Middle Aged; Neovascularization, Pathologic; Oligodendroglioma
PubMed: 18296266
DOI: 10.2478/v10042-008-0009-4 -
Scientific Reports Nov 2020The aim of this study was to evaluate prognostic factors including surgical, radiographic, and histopathologic analyses in anaplastic oligodendroglioma (AO) patients. We...
The aim of this study was to evaluate prognostic factors including surgical, radiographic, and histopathologic analyses in anaplastic oligodendroglioma (AO) patients. We reviewed the electronic records of 95 patients who underwent surgery and were diagnosed with AO for 20 years. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariable analyses included clinical, histopathological, and radiographic prognostic factors. Subgroup analysis was performed in isocitrate dehydrogenase (IDH1/2)-mutant and 1p/19q-codeleted patients. The median PFS and OS were 24.7 months and 50.8 months, respectively. The 1-, 3-, 5-, and 10-year PFS were 75.8%, 42.9%, 32.4%, and 16.4%, respectively. Furthermore, the 1-, 3-, 5-, and 10-year OS were 98.9%, 76.9%, 42.9%, and 29.7%, respectively. The median PFS and OS of the IDH1/2-mutant and 1p/19q-codeleted patients were 54.2 and 57.8 months, respectively. In univariate analyses, young age, frontal lobe, weak enhancement, gross total resection (GTR), low Ki-67 index, 1p/19q codeletion, and IDH1/2 mutations were associated with a favorable outcome. In multivariable analyses, IDH1/2 mutation was related to better PFS and OS. In subgroup analysis, GTR was associated with favorable outcomes.
Topics: Adult; Aged; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Chromosome Deletion; Chromosomes, Human, Pair 1; Disease-Free Survival; Female; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Oligodendroglioma; Prognosis; Young Adult
PubMed: 33214617
DOI: 10.1038/s41598-020-77228-2 -
Journal of Neuro-oncology May 2023Astrocytomas and oligodendrogliomas are mainly diffuse primary brain tumors harboring a diagnostic and prognostically favorable isocitrate dehydrogenase mutation. They... (Review)
Review
PURPOSE
Astrocytomas and oligodendrogliomas are mainly diffuse primary brain tumors harboring a diagnostic and prognostically favorable isocitrate dehydrogenase mutation. They are still incurable besides growing molecular knowledge and therapy options. Circumscribed astrocytomas are also discussed here, although they represent a separate entity despite similarities in the nomenclature.
METHODS
We reviewed clinical trials, preclinical approaches as well as guideline recommendations form the major scientific Neuro-Oncology organizations for astrocytomas and oligodendrogliomas according to PRISMA guidelines.
RESULTS
After histopathological diagnosis and eventually a maximal safe resection, patients with good prognostic factors may be followed by magnetic resonance imaging (MRI). If further treatment is necessary, either after diagnosis or at progression, diffuse astrocytomas and oligodendrogliomas are mainly treated with combined radiochemotherapy or maximal safe resection followed by combined radiochemotherapy according to current guidelines based on randomized trials. Circumscribed gliomas like pilocytic astrocytomas, CNS WHO grade 1, or pleomorphic xanthoastrocytomas, CNS WHO grade 2, are often treated with surgery alone. Current approaches for therapy optimization include decision of the best chemotherapy regimen. The IDH mutation presents a rational target for small molecule inhibition and immune therapy in diffuse astrocytomas and oligodendrogliomas, while the BRAF pathway is frequently mutated and treatable in circumscribed gliomas.
CONCLUSION
Despite establishment of standard treatment approaches for gliomas that include resection, radio- and chemotherapy, there is a lack of effective treatments for progressive disease. Immune- and targeted therapies are currently investigated.
Topics: Humans; Oligodendroglioma; Astrocytoma; Glioma; Magnetic Resonance Imaging; Mutation
PubMed: 36566461
DOI: 10.1007/s11060-022-04216-z -
Brain Pathology (Zurich, Switzerland) Jan 2024The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion in addition to...
The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion in addition to codeletion of 1p/19q to characterize IDH-mutant gliomas. Here, we demonstrated the use of a nanopore-based copy-number variation sequencing (nCNV-seq) approach to simultaneously identify deletions of CDKN2A/B and 1p/19q. The nCNV-seq approach was initially evaluated on three distinct glioma cell lines and then applied to 19 IDH-mutant gliomas (8 astrocytomas and 11 oligodendrogliomas) from patients. The whole-arm 1p/19q codeletion was detected in all oligodendrogliomas with high concordance among nCNV-seq, FISH, DNA methylation profiling, and whole-genome sequencing. For the CDKN2A/B deletion, nCNV-seq detected the loss in both astrocytoma and oligodendroglioma, with strong correlation with the CNV profiles derived from whole-genome sequencing (Pearson correlation (r) = 0.95, P < 2.2 × 10 to r = 0.99, P < 2.2 × 10 ) and methylome profiling. Furthermore, nCNV-seq can differentiate between homozygous and hemizygous deletions of CDKN2A/B. Taken together, nCNV-seq holds promise as a new, alternative approach for a rapid and simultaneous detection of the molecular signatures of IDH-mutant gliomas without capital expenditure for a sequencer.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Nanopore Sequencing; Mutation; Glioma; Astrocytoma; Isocitrate Dehydrogenase; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19
PubMed: 37574201
DOI: 10.1111/bpa.13203 -
International Journal of Molecular... Oct 2023The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2...
The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2 oligodendroglioma. Targeted alpha therapy (TAT), using the modified peptide vector [Bi]Bi/[Ac]Ac-DOTA-substance P, has been developed to treat glioblastoma (GBM), a prevalent malignant brain tumor. In order to assess the risk of late neurotoxicity, assuming that reduced tumor cell proliferation and invasion should directly translate into good responses in low-grade gliomas (LGGs), a limited number of patients with diffuse invasive astrocytoma (n = 8) and oligodendroglioma (n = 3) were offered TAT. In two oligodendroglioma patients, TAT was applied as a second-line treatment for tumor progression, 10 years after targeted beta therapy using [Y]Y-DOTA-substance P. The radiopharmaceutical was locally injected directly into the tumor via a stereotactic insertion of a capsule-catheter system. The activity used for radiolabeling was 2-2.5 GBq of Bismuth-213 and 17 to 35 MBq of Actinium-225, mostly applied in a single fraction. The recurrence-free survival times were in the range of 2 to 16 years (median 11 years) in low-grade astrocytoma (n = 8), in which TAT was administered following a biopsy or tumor debulking. Regarding oligodendroglioma, the recurrence-free survival time was 24 years in the first case treated, and 4 and 5 years in the two second-line cases. In conclusion, TAT leads to long-term tumor control in the majority of patients with LGG, and recurrence has so far not manifested in patients with low-grade (grade 2) astrocytomas who received TAT as a first-line therapy. We conclude that targeted alpha therapy has the potential to become a new treatment paradigm in LGG.
Topics: Humans; Oligodendroglioma; Substance P; Glioma; Astrocytoma; Glioblastoma; Brain Neoplasms
PubMed: 37958683
DOI: 10.3390/ijms242115701 -
Cancer Medicine Aug 2023Oligodendroglioma is known for its relatively better prognosis and responsiveness to radiotherapy and chemotherapy. However, little is known about the evolution of...
BACKGROUND
Oligodendroglioma is known for its relatively better prognosis and responsiveness to radiotherapy and chemotherapy. However, little is known about the evolution of genetic changes as oligodendroglioma progresses.
METHODS
In this study, we evaluated gene evolution invivo during tumor progression based on deep whole-genome sequencing data (ctDNA). We analyzed longitudinal genomic data from six patients during tumor evolution, of which five patients developed distant recurrence.
RESULTS
Whole-exome sequencing demonstrated that the rate of shared mutations between the primary and recurrent samples was relatively low. In two cases, even well-known major driver mutations in CIC and FUBP1 that were detected in primary tumors were not detected in the relapse samples. Among these cases, two patients had a conversion from the IDH mutation in the originating state to the IDH1 wild state during the process of gene evolution under chemotherapy treatment, indicating that the cell phenotype and genetic characteristics of oligodendroglioma may change during tumor evolution. Two patients received long-term temozolomide (TMZ) treatment before the operation, and we found that recurrence tumors harbored mutations in the PI3K/AKT and Sonic hedgehog (SHh) signaling pathways. Hypermutation occurred with mutations in MMR genes in one patient, contributing to the rapid progression of the tumor.
CONCLUSION
Oligodendroglioma displayed great spatial and temporal heterogeneity during tumor evolution. The PI3K/AKT and SHh signaling pathways may play an important role in promoting treatment resistance and distant relapse during oligodendroglioma evolution. In addition, there was a tendency to increase the degree of tumor malignancy during evolution. Distant recurrence may be a later event duringoligodendroglioma progression.
CLINICALTRIALS
gov, Identifier: NCT05512325.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Hedgehog Proteins; Neoplasm Recurrence, Local; Mutation; Genomics; Isocitrate Dehydrogenase; DNA-Binding Proteins; RNA-Binding Proteins
PubMed: 37533228
DOI: 10.1002/cam4.6327 -
Neurologia Medico-chirurgica Feb 1990A 32-year-old male was hospitalized with headache and disturbance of consciousness. Computed tomography (CT) revealed a tumor and an intracranial hematoma in the right... (Review)
Review
A 32-year-old male was hospitalized with headache and disturbance of consciousness. Computed tomography (CT) revealed a tumor and an intracranial hematoma in the right frontal lobe. The tumor was totally removed, and postoperative radiation therapy was administrated locally at 50 Gy. Five years later, he experienced sudden onset of headache and vertigo. CT demonstrated a mass lesion with a hematoma in the cerebellar vermis. The tumor was subtotally removed and he underwent postoperative local irradiation at 50 Gy as well as ventriculoperitoneal shunting. Four years later, he complained of visual and gait disturbances, and CT disclosed a tumor in the suprasellar region. Following partial removal of the tumor, local brain irradiation was given at 40 Gy. Histological examination proved all three tumors to be oligodendrogliomas with no evidence of malignant change.
Topics: Adult; Brain Neoplasms; Cerebral Hemorrhage; Humans; Male; Neoplasms, Multiple Primary; Oligodendroglioma
PubMed: 1695334
DOI: 10.2176/nmc.30.127 -
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