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Swiss Medical Weekly 2011Glioblastomas (World Health Organisation (WHO) grade IV) and anaplastic gliomas (astrocytomas, oligoastrocytomas, oligodendrogliomas) (WHO grade III) are collectively... (Review)
Review
Glioblastomas (World Health Organisation (WHO) grade IV) and anaplastic gliomas (astrocytomas, oligoastrocytomas, oligodendrogliomas) (WHO grade III) are collectively referred to as malignant gliomas. The diagnosis of malignant glioma may be suspected based on clinical history and neuroimaging findings, but histological confirmation remains the diagnostic "gold standard". Molecular markers such as 1p/19q codeletion and isocitrate dehydrogenase (IDH) mutation provide important diagnostic and prognostic information. O-methylguanylmethyltransferase (MGMT) promoter methylation is another favourable prognostic marker and predicts benefit from alkylating agent chemotherapy in glioblastoma. Additionally, the extent of neurosurgical resection is a prognostic factor. Radiotherapy of the involved brain region or chemotherapy using the alkylating agent, temozolomide, are common therapeutic options for patients with anaplastic glioma. In contrast, temozolomide plus radiotherapy is the standard of care for most patients with glioblastoma. The increasing population of elderly patients with glioblastoma represents a particular challenge, with surgery followed by radiotherapy as the standard of care. Contemporary clinical studies focus on the role of angiogenesis. Specifically, pivotal phase III studies exploring the antibody to vascular endothelial growth factor (VEGF), bevacizumab, and the αvβ3/5 antagonist, cilengitide, in the management of newly diagnosed glioblastoma have completed enrolment. Moreover, a broad spectrum of other experimental treatment approaches, including immunotherapy with vaccines against glioma-associated antigens, are currently being explored in phase I/II clinical trials.
Topics: Biomarkers, Tumor; Central Nervous System Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Oligodendroglioma
PubMed: 21607882
DOI: 10.4414/smw.2011.13210 -
Arquivos de Neuro-psiquiatria Dec 2023Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or...
Long-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma or altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.
Topics: Adolescent; Young Adult; Humans; Child; Epilepsy; Glioma; Brain Neoplasms; Ganglioglioma; Astrocytoma; Neoplasms, Neuroepithelial
PubMed: 38157880
DOI: 10.1055/s-0043-1777730 -
Cell Reports. Medicine Jan 2023High-grade adult-type diffuse gliomas are malignant neuroepithelial tumors with poor survival rates in combined chemoradiotherapy. The current WHO classification is...
High-grade adult-type diffuse gliomas are malignant neuroepithelial tumors with poor survival rates in combined chemoradiotherapy. The current WHO classification is based on IDH1/2 mutational and 1p/19q codeletion status. Glioma proteome alterations remain undercharacterized despite their promise for a better molecular patient stratification and therapeutic target identification. Here, we use mass spectrometry to characterize 42 formalin-fixed, paraffin-embedded (FFPE) samples from IDH-wild-type (IDHwt) gliomas, IDH-mutant (IDHmut) gliomas with and without 1p/19q codeletion, and non-neoplastic controls. Based on more than 5,500 quantified proteins and 5,000 phosphosites, gliomas separate by IDH1/2 mutational status but not by 1p/19q status. Instead, IDHmut gliomas split into two proteomic subtypes with widespread perturbations, including aerobic/anaerobic energy metabolism. Validations with three independent glioma proteome datasets confirm these subgroups and link the IDHmut subtypes to the established proneural and classic/mesenchymal subtypes in IDHwt glioma. This demonstrates common phenotypic subtypes across the IDH status with potential therapeutic implications for patients with IDHmut gliomas.
Topics: Adult; Humans; Brain Neoplasms; Glioma; Mutation; Proteome; Proteomics; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19
PubMed: 36584682
DOI: 10.1016/j.xcrm.2022.100877 -
The Oncologist Dec 2019Astroblastoma (ABM) is a rare glial brain tumor. Recurrent meningioma 1 (MN1) alterations have been recently identified in most pediatric cases. Adolescent and adult...
BACKGROUND
Astroblastoma (ABM) is a rare glial brain tumor. Recurrent meningioma 1 (MN1) alterations have been recently identified in most pediatric cases. Adolescent and adult cases, however, remain molecularly poorly defined.
MATERIALS AND METHODS
We performed clinical and molecular characterization of a retrospective cohort of 14 adult and 1 adolescent ABM.
RESULTS
Strikingly, we found that MN1 fusions are a rare event in this age group (1/15). Using methylation profiling and targeted sequencing, most cases were reclassified as either pleomorphic xanthoastrocytomas (PXA)-like or high-grade glioma (HGG)-like. PXA-like ABM show mutation (6/7 with V600E mutation and 1/7 with G466E mutation) and CD34 expression. Conversely, HGG-like ABM harbored specific alterations of diffuse midline glioma (2/5) or glioblastoma (GBM; 3/5). These latter patients showed an unfavorable clinical course with significantly shorter overall survival ( = .021). Mitogen-activated protein kinase pathway alterations (including fusion, and mutations) were present in 10 of 15 patients and overrepresented in the HGG-like group (3/5) compared with previously reported prevalence of these alterations in GBM and diffuse midline glioma.
CONCLUSION
We suggest that gliomas with astroblastic features include a variety of molecularly sharply defined entities. Adult ABM harboring molecular features of PXA and HGG should be reclassified. Central nervous system high-grade neuroepithelial tumors with alterations and histology of ABM appear to be uncommon in adults. Astroblastic morphology in adults should thus prompt thorough molecular investigation aiming at a clear histomolecular diagnosis and identifying actionable drug targets, especially in the mitogen-activated protein kinase pathway.
IMPLICATIONS FOR PRACTICE
Astroblastoma (ABM) remains a poorly defined and controversial entity. Although meningioma 1 alterations seem to define a large subset of pediatric cases, adult cases remain molecularly poorly defined. This comprehensive molecular characterization of 1 adolescent and 14 adult ABM revealed that adult ABM histology comprises several molecularly defined entities, which explains clinical diversity and identifies actionable targets. Namely, pleomorphic xanthoastrocytoma-like ABM cases show a favorable prognosis whereas high-grade glioma (glioblastoma and diffuse midline gliome)-like ABM show significantly worse clinical courses. These results call for in-depth molecular analysis of adult gliomas with astroblastic features for diagnostic and therapeutic purposes.
Topics: Adult; Aged; Brain Neoplasms; Female; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinases; Neoplasms, Neuroepithelial; Young Adult
PubMed: 31346129
DOI: 10.1634/theoncologist.2019-0223 -
Medicina (Kaunas, Lithuania) Nov 2022: Survival estimation for patients diagnosed with Glioblastoma (GBM) is an important information to consider in patient management and communication. Despite some known... (Review)
Review
: Survival estimation for patients diagnosed with Glioblastoma (GBM) is an important information to consider in patient management and communication. Despite some known risk factors, survival estimation remains a major challenge. Novel non-invasive technologies such as radiomics and artificial intelligence (AI) have been implemented to increase the accuracy of these predictions. In this article, we reviewed and discussed the most significant available research on survival estimation for GBM through advanced non-invasive methods. : PubMed database was queried for articles reporting on survival prognosis for GBM through advanced image and data management methods. Articles including in their title or abstract the following terms were initially screened: ((glioma) AND (survival)) AND ((artificial intelligence) OR (radiomics)). Exclusively English full-text articles, reporting on humans, published as of 1 September 2022 were considered. Articles not reporting on overall survival, evaluating the effects of new therapies or including other tumors were excluded. Research with a radiomics-based methodology were evaluated using the radiomics quality score (RQS). : 382 articles were identified. After applying the inclusion criteria, 46 articles remained for further analysis. These articles were thoroughly assessed, summarized and discussed. The results of the RQS revealed some of the limitations of current radiomics investigation on this field. Limitations of analyzed studies included data availability, patient selection and heterogeneity of methodologies. Future challenges on this field are increasing data availability, improving the general understanding of how AI handles data and establishing solid correlations between image features and tumor's biology. : Radiomics and AI methods of data processing offer a new paradigm of possibilities to tackle the question of survival prognosis in GBM.
Topics: Humans; Glioblastoma; Artificial Intelligence; Glioma; Forecasting; Prognosis
PubMed: 36556948
DOI: 10.3390/medicina58121746 -
Brain Pathology (Zurich, Switzerland) Sep 2023Recent epigenomic analyses have revealed the existence of a new DNA methylation class (MC) of infant-type hemispheric glioma (IHG). Like desmoplastic infantile...
A comprehensive analysis of infantile central nervous system tumors to improve distinctive criteria for infant-type hemispheric glioma versus desmoplastic infantile ganglioglioma/astrocytoma.
Recent epigenomic analyses have revealed the existence of a new DNA methylation class (MC) of infant-type hemispheric glioma (IHG). Like desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA), these tumors mainly affect infants and are supratentorial. While DIG/DIA is characterized by BRAF or RAF1 alterations, IHG has been shown to have receptor tyrosine kinase (RTK) gene fusions (ALK, ROS1, NTRK1/2/3, and MET). However, in this rapidly evolving field, a more comprehensive analysis of infantile glial/glioneuronal tumors including clinical, radiological, histopathological, and molecular data is needed. Here, we retrospectively investigated data from 30 infantile glial/glioneuronal tumors, consecutively compiled from our center. They were analyzed by two experienced pediatric neuroradiologists in consensus, without former knowledge of the molecular data. We also performed a comprehensive clinical, and histopathological examination (including molecular evaluation by next-generation sequencing, RNA sequencing, and fluorescence in situ hybridization [FISH] analyses), as well as DNA methylation profiling for the samples having sufficient material available. The integrative histopathological, genetic, and epigenetic analyses, including t-distributed stochastic neighbor embedding (t-SNE) analyses segregated tumors into 10 DIG/DIA (33.3%), six IHG (20.0%), three gangliogliomas (10.0%), two pleomorphic xanthoastrocytomas (6.7%), two pilocytic astrocytomas (6.7%), two supratentorial ependymomas, ZFTA fusion-positive (6.7%), two supratentorial ependymomas, YAP1 fusion-positive (6.7%), two embryonal tumors with PLAGL2-family amplification (6.7%), and one diffuse low-grade glioma, MAPK-pathway altered. This study highlights the significant differential features, in terms of histopathology (leptomeningeal infiltration, intense desmoplasia and ganglion cells in DIG/DIA and necrosis, microvascular proliferation, and siderophages in IHG), and radiology between DIG/DIA and IHG. Moreover, these results are consistent with the literature data concerning the molecular dichotomy (BRAF/RAF1 alterations vs. RTK genes' fusions) between DIG/DIA and IHG. This study characterized histopathologically and radiologically two additional cases of the novel embryonal tumor characterized by PLAGL2 gene amplification.
Topics: Humans; Ganglioglioma; Brain Neoplasms; Proto-Oncogene Proteins B-raf; Retrospective Studies; In Situ Hybridization, Fluorescence; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Astrocytoma; Central Nervous System Neoplasms; Neoplasms, Neuroepithelial; Ependymoma; DNA-Binding Proteins; Transcription Factors; RNA-Binding Proteins
PubMed: 37349135
DOI: 10.1111/bpa.13182 -
Neuropathology and Applied Neurobiology Dec 2022Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of...
AIMS
Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS WHO) does not list anaplastic ganglioglioma as a distinct diagnosis due to lack of molecular data in previous publications. We retrospectively compiled a cohort of 54 histologically diagnosed anaplastic gangliogliomas to explore whether the molecular profiles of these tumours represent a separate type or resolve into other entities.
METHODS
Samples were subjected to histological review, desoxyribonucleic acid (DNA) methylation profiling and next-generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis.
RESULTS
The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric-type high-grade glioma, H3 wild type and IDH wild type (11 and 2/54), followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis, and common molecular profiles pointing to a separate entity were not evident.
CONCLUSIONS
In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.
Topics: Child; Humans; Ganglioglioma; Retrospective Studies; Glioma; Astrocytoma; Brain Neoplasms; Central Nervous System Neoplasms; Isocitrate Dehydrogenase
PubMed: 35977725
DOI: 10.1111/nan.12847 -
CNS Oncology Apr 2018To evaluate the use of chemotherapy and radiation, and their outcomes for patients with astroblastoma.
AIM
To evaluate the use of chemotherapy and radiation, and their outcomes for patients with astroblastoma.
PATIENTS & METHODS
This is a retrospective review of patients extracted from the National Cancer Database. We investigated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards models were used to correlate OS with risk variables and treatments.
RESULTS
OS at 5 years was 79.5%. Patients with high-grade tumors were more likely to receive chemotherapy and radiation. Patients with high-grade astroblastoma who did not receive adjuvant radiation had poor survival.
CONCLUSION
Patients with astroblastoma should be treated with curative intent. Radiation is likely beneficial in high-grade astroblastoma. The exact role of radiation and chemotherapy following surgical resection warrant further investigation.
Topics: Adolescent; Adult; Brain Neoplasms; Child; Child, Preschool; Follow-Up Studies; Humans; Infant; Infant, Newborn; Neoplasm Grading; Neoplasms, Neuroepithelial; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 29708401
DOI: 10.2217/cns-2017-0038 -
Expert Review of Anticancer Therapy Jun 2015The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes mutate frequently in gliomas, and it has become increasingly apparent that IDH mutation status accounts for...
The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes mutate frequently in gliomas, and it has become increasingly apparent that IDH mutation status accounts for much of the prognostic information previously rendered by histological grading. Most glioblastomas (90-95%) are IDH wild-type and most lower-grade diffuse gliomas (80%) are IDH-mutant. We examine here how IDH mutation status interacts with treatments known to influence survival (surgery, chemotherapy and radiotherapy) in patients with gliomas, and the impact of the IDH mutations on patients' survival after such treatments. IDH mutations is associated with more complete surgical resection of enhancing disease, and with a better response to RT. In addition, there is increasing clinical evidence that, in certain contexts, IDH mutations predict chemotherapeutic sensitivity. Mutations in IDH and other genes are beginning to drive decisions on therapy for diffuse gliomas and will likely allow tailoring of treatment by molecular profile in the future.
Topics: Animals; Glioblastoma; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Survival
PubMed: 25980633
DOI: 10.1586/14737140.2015.1047351 -
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