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Journal of Neuropathology and... Jun 2018The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas...
The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Astrocytoma; Brain Neoplasms; DNA Methylation; Disease Progression; Female; Glioblastoma; Humans; Immunohistochemistry; Isocitrate Dehydrogenase; Male; Middle Aged; Molecular Diagnostic Techniques; Mutation; Young Adult
PubMed: 29444314
DOI: 10.1093/jnen/nly012 -
Surgical Pathology Clinics Jun 2020Well-circumscribed intra-axial CNS tumors encompass a wide variety of gliomas and glioneuronal tumors, usually corresponding to WHO grades I and II. Nonetheless,... (Review)
Review
Well-circumscribed intra-axial CNS tumors encompass a wide variety of gliomas and glioneuronal tumors, usually corresponding to WHO grades I and II. Nonetheless, sometimes high-grade 'diffuse' gliomas such as gliosarcoma and giant cell glioblastoma can be relatively circumscribed but are often found to have foci of diffuse infiltration on careful examination, harboring distinct molecular alterations. These tumors are excluded from the discussion in this chapter with the current review emphasizing on lower-grade entities to include a brief description of their histology and associated molecular findings. Like elsewhere in brain biopsy evaluation, imaging is crucial and acts as a surrogate to gross examination. Given the circumscribed nature of these tumors, surgery alone is the mainstay treatment in most entities.
Topics: Astrocytoma; Central Nervous System Neoplasms; Glioma; Humans
PubMed: 32389265
DOI: 10.1016/j.path.2020.02.004 -
Journal of Clinical Neuroscience :... Sep 2017This study aims to review the literature and identify key molecular markers affecting the prognosis of Gliomatosis cerebri (2) to evaluate the level of evidence and... (Review)
Review
This study aims to review the literature and identify key molecular markers affecting the prognosis of Gliomatosis cerebri (2) to evaluate the level of evidence and identify outstanding markers requiring further study. A literature search was conducted across 5 major databases using the key terms: "Molecular markers" AND "Gliomatosis cerebri" OR "diffuse astrocytoma." Critical appraisal and data presentation was performed inline with the PRISMA guidelines. Following search strategy implementation, 11 studies were included in the final review process. Our data demonstrates significant prognostic value associated with IDH1 mutation and variable evidence surrounding the role of INA expression, MGMT promoter methylation and other factors. However, there are significant limitations in the level of evidence obtained. As the genetic basis for the pathogenesis of Gliomatosis cerebri continues to widen, there is little data on markers aside from IDH1 mutation available. IDH1 mutation has been demonstrated to have significant effect on survival, particularly in patients with Gliomatosis cerebri type 2.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Humans; Neoplasms, Neuroepithelial; Prognosis
PubMed: 28539209
DOI: 10.1016/j.jocn.2017.04.043 -
CNS Oncology Nov 2019Pleomorphic xanthoastrocytoma (PXA) is a rare primary CNS tumor. Recent advances in the molecular characterization are helping to define subtypes of tumor. The discovery... (Review)
Review
Pleomorphic xanthoastrocytoma (PXA) is a rare primary CNS tumor. Recent advances in the molecular characterization are helping to define subtypes of tumor. The discovery of mutations within a substantial percentage of PXA fosters a clearer understanding of the pathophysiology of these tumors with clear prognostic and therapeutic implications. These findings are expected to provide insight into the spectrum of clinical behavior observed in PXA, ranging from cure with surgery to diffuse dissemination throughout the neuraxis. This review details the clinical presentation including radiographic appearance of PXA. Pathology, including molecular pathology is discussed. Therapeutic management including surgical resection, radiotherapy and systemic therapies are reviewed.
Topics: Astrocytoma; Brain Neoplasms; Combined Modality Therapy; Humans; Prognosis
PubMed: 31535562
DOI: 10.2217/cns-2019-0009 -
Journal of Neuro-oncology Jan 2021The aim of this study was to understand the use of chemotherapy (CMT) and radiotherapy (RT) in pilocytic astrocytoma (PA) and their impact on overall survival (OS). (Review)
Review
PURPOSE
The aim of this study was to understand the use of chemotherapy (CMT) and radiotherapy (RT) in pilocytic astrocytoma (PA) and their impact on overall survival (OS).
METHODS
Data from the National Cancer Database (NCDB) for patients with non-metastatic WHO grade I PA from 2004 to 2014 were analyzed. Pearson's chi-squared test and multivariate logistic regression analyses were performed to assess the distribution of demographic, clinical, and treatment factors. Inverse probability of treatment weighting (IPTW) was used to account for differences in baseline characteristics. Kaplan-Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling were used to analyze OS.
RESULTS
Of 3865 patients analyzed, 294 received CMT (7.6%), 233 received RT (6.0%), and 42 (1.1%) received both. On multivariate analyses, decreasing extent of surgical resection was associated with receipt of both CMT and RT. Brainstem tumors were associated with RT, optic nerve tumors were associated with CMT. Cerebellar tumors were inversely associated with both CMT and RT. Younger age was associated with receipt of CMT; conversely, older age was associated with receipt of RT. After IPTW, receipt of CMT and/or RT were associated with an OS decrement compared with matched patients treated with surgery alone or observation (HR 3.29, p < 0.01).
CONCLUSIONS
This is the largest study to date to examine patterns of care and resultant OS outcomes in PA. We identified patient characteristics associated with receipt of CMT and RT. After propensity score matching, receipt of CMT and/or RT was associated with decreased OS.
Topics: Adult; Astrocytoma; Chemoradiotherapy; Child; Humans; Prognosis
PubMed: 33131004
DOI: 10.1007/s11060-020-03653-y -
Journal of Neuro-oncology Aug 2023To synthesize the evidence on the impact on progression-free survival (PFS) and overall survival (OS) of supramaximal resection (SMR) over gross total resection (GTR) in... (Meta-Analysis)
Meta-Analysis Review
Supramaximal versus gross total resection in Glioblastoma, IDH wild-type and Astrocytoma, IDH-mutant, grade 4, effect on overall and progression free survival: systematic review and meta-analysis.
PURPOSE
To synthesize the evidence on the impact on progression-free survival (PFS) and overall survival (OS) of supramaximal resection (SMR) over gross total resection (GTR) in Glioblastoma, IDH wild-type and Astrocytoma, IDH-mutant, grade 4 (Glioblastoma).
METHODS
The PubMed, Scopus, Web of Science, Ovid and Cochrane databases were systematically searched (up to November 30, 2022). Studies reporting OS and PFS on adult humans with a suspected Glioblastoma, treated either with a SMR or GTR were included. Hazard ratios were estimated for each study and treatment effects were calculated through DerSimonian and Laird random effects models.
RESULTS
The literature search yielded 14 studies published between 2013 and 2022, enrolling a total of 6779 patients. Analysis of the included studies reveals significantly better clinical outcomes favoring SMR over GTR in terms of PFS (HR 0.67; p = 0.0007), and OS (HR 0.7; p = 0.0001).
CONCLUSION
Glioblastoma, IDH wild-type and Astrocytoma, IDH-mutant, grade 4, are aggressive tumors with a very short long-term OS. SMR is an effective therapeutic approach contributing to increased PFS and OS in patients with this catastrophic disease.
Topics: Adult; Humans; Astrocytoma; Brain Neoplasms; Disease-Free Survival; Glioblastoma; Progression-Free Survival; Retrospective Studies
PubMed: 37561356
DOI: 10.1007/s11060-023-04409-0 -
Current Treatment Options in Oncology Oct 2018The treatment paradigm for anaplastic glioma has shifted, owing to new diagnostic criteria and new phase III clinical trial evidence. In 2016, the WHO classification of... (Review)
Review
The treatment paradigm for anaplastic glioma has shifted, owing to new diagnostic criteria and new phase III clinical trial evidence. In 2016, the WHO classification of brain tumors including diffuse gliomas was redefined to include molecular criteria, often supplanting the morphological appearance of the tumor cells. This was necessary as prognosis is more closely associated with molecular diagnosis than with morphology and grade. Recently, the benefit of adjuvant chemotherapy in addition to radiotherapy has been demonstrated in both anaplastic oligodendroglioma and anaplastic astrocytoma, as well as lower grade gliomas with the most marked benefit evident in IDH-mutated (astrocytoma) and 1p/19q co-deleted (oligodendroglial) tumors. The defining principle of recent breakthroughs has been the benefit of combinatorial therapy (chemo-radiation) as opposed to treatment in series or treatment of either modality after a period of observation upon evidence of progression.
Topics: Astrocytoma; Brain Neoplasms; Chemoradiotherapy; Chemotherapy, Adjuvant; Humans; Isocitrate Dehydrogenase; Oligodendroglioma; Pathology, Molecular
PubMed: 30361986
DOI: 10.1007/s11864-018-0579-0 -
Pediatric Neurosurgery 2019Pilomyxoid astrocytoma (PMA) is a rare brain tumour generally located in the chiasmatic-hypothalamic region. In comparison to pilocytic astrocytoma, PMA has distinct...
Pilomyxoid astrocytoma (PMA) is a rare brain tumour generally located in the chiasmatic-hypothalamic region. In comparison to pilocytic astrocytoma, PMA has distinct histopathological features, aggressive clinical behaviour, a high recurrence rate, and early cerebrospinal fluid dissemination. Only 14 cases of PMA have been reported in the spinal cord since its pathological description in 1999. Here, we report the 15th case in a 3-year-old girl who was treated with chemoradiotherapy and followed up for 5 years. In this report, we also present a review of spinal PMA including treatment options and prognosis.
Topics: Astrocytoma; Chemoradiotherapy, Adjuvant; Child, Preschool; Dose Fractionation, Radiation; Female; Humans; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Salvage Therapy; Spinal Cord Neoplasms
PubMed: 31593949
DOI: 10.1159/000502615 -
Neuro-oncology Apr 2023
Topics: Humans; Senotherapeutics; Astrocytoma; Brain
PubMed: 36702510
DOI: 10.1093/neuonc/noad016 -
No Shinkei Geka. Neurological Surgery Sep 2023The Central Nervous System Tumours: WHO Classification of Tumours, 5 ed.(WHO CNS5)incorporates molecular pathogenesis with histopathology to classify brain tumors into...
The Central Nervous System Tumours: WHO Classification of Tumours, 5 ed.(WHO CNS5)incorporates molecular pathogenesis with histopathology to classify brain tumors into more biologically and narrowly defined entities. According to this approach, adult-type diffuse gliomas are classified into three tumor types: astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and glioblastoma, IDH-wildtype. Astrocytoma and oligodendroglioma are clearly defined as IDH-mutant tumors, and glioblastoma as an IDH-wildtype tumor. WHO CNS5 provides clear diagnostic criteria framed as "essential and desirable diagnostic criteria," including histopathological and molecular features. In this article, we summarized the diagnostic and grading criteria of adult-type diffuse gliomas, which include histopathological and molecular features. Further, we presented a clinical diagnostic workflow based on the immunohistopathological studies, molecular tests and their surrogate assays, and histopathological features to establish the diagnosis of adult-type diffuse gliomas. We also discussed the limitations of the clinical diagnostic workflow; for instance, some tumors may not fit within this classification provided by this diagnostic flow. Despite these limitations, we are required to utilize the diagnostic criteria and determine optimal treatment in the clinical setting.
Topics: Adult; Humans; Glioblastoma; Oligodendroglioma; Glioma; Astrocytoma; Brain Neoplasms
PubMed: 37743327
DOI: 10.11477/mf.1436204816