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The Neuroradiology Journal Apr 20232016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) has shown how molecular features can impact the classification of brain...
2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) has shown how molecular features can impact the classification of brain tumors. The continued combination of molecular features with histopathology has led to distinguish tumors with similar histopathologic features but distinct clinical prognosis. The 2021 revised 5. edition of the WHO classification further includes molecular features for CNS tumor categorization including altered diffuse astrocytoma which is a newly recognized type of low-grade pediatric-type brain tumor. We discuss imaging features of two pediatric-type low-grade gliomas with -mutation that encountered at our institution.
Topics: Humans; Child; Glioma; Brain Neoplasms; Central Nervous System Neoplasms; Astrocytoma; Prognosis; Mutation; Proto-Oncogene Proteins; Trans-Activators
PubMed: 36074655
DOI: 10.1177/19714009221126015 -
Neuro-oncology Jan 2018Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health...
BACKGROUND
Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health Organization (WHO) classification. Parameters derived from uptake dynamics of 18F-fluoro-ethyl-tyrosine PET (18F-FET-PET) such as minimal time-to-peak (TTPmin) allow discrimination between different prognostic glioma subgroups, too. The present study is aimed at exploring whether TTPmin analysis provides prognostic information beyond the WHO classification.
METHODS
Three hundred patients with newly diagnosed WHO 2007 grades II-IV gliomas with 18F-FET-PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut-1p/19q codel; IDH1/2 mut-1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and glioblastoma). Clinical and imaging factors such as age, Karnofsky performance score, treatment, TTPmin, and maximal tumor-to-brain ratio (TBRmax) were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis.
RESULTS
PFS and OS were longest in the IDH1/2 mut-1p/19q codel subgroup, followed by IDH1/2 mut-1p/19q non-codel, IDH1/2 wildtype, and GBM (P < 0.001). Further, outcome stratified by TTPmin with a cutoff of 17.5 minutes revealed significantly longer PFS and OS in patients with TTPmin >17.5 minutes (P < 0.001 for PFS and OS). Lower TBRmax values or the absence of 18F-FET uptake was also associated with favorable outcome in the entire group. In the subgroup analyses, longer median TTPmin was associated with improved outcome specifically in the IDH1/2 mut-1p/19q non-codel group.
CONCLUSION
18F-FET-PET-derived dynamic analysis defines prognostically distinct subgroups of IDH1/2 mutant-1p/19q non-codel gliomas which cannot be distinguished as yet by molecular marker analysis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Astrocytoma; Brain Neoplasms; Child; Chromosomes, Human, Pair 19; Female; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Positron-Emission Tomography; Prognosis; Time Factors; Tyrosine; Young Adult
PubMed: 29016996
DOI: 10.1093/neuonc/nox153 -
Neurologia Medico-chirurgica 2013World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the... (Comparative Study)
Comparative Study Review
World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the treatment outcome can still be improved. Review of previous clinical trials found the following: (1) GIIG increased in size by 3-5 mm per year when observed or treated with surgery alone; (2) after pathological diagnosis, the survival rate was increased by early aggressive tumor removal at an earlier stage compared to observation alone; (3) although the prognosis after total tumor removal was significantly better than that after partial tumor removal, half of the patients relapsed within 5 years; (4) comparing postoperative early radiotherapy (RT) and non-early RT after relapse, early RT prolonged progression-free survival (PFS) but did not affect overall survival (OS); (5) local RT of 45 to 64.8 Gy did not impact PFS or OS; (6) in patients with residual tumors, RT combined with chemotherapy (procarbazine plus lomustine plus vincristine) prolonged PFS compared with RT alone but did not affect OS; and (7) poor prognostic factors included astrocytoma, non-total tumor removal, age ≥40 years, largest tumor diameter ≥4-6 cm, tumor crossing the midline, and neurological deficit. To improve treatment outcomes, surgery with functional brain mapping or intraoperative magnetic resonance imaging or chemoradiotherapy with temozolomide is important. In this review, current knowledge regarding GIIG is described and treatment strategies are explored.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Cranial Irradiation; Craniotomy; Early Medical Intervention; Glioma; Humans; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Oligodendroglioma; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 23883553
DOI: 10.2176/nmc.53.429 -
The Journal of International Medical... Aug 2021A 57-year-old woman was diagnosed with IDH-wildtype (IDHwt) astrocytoma (World Health Organization grade II) with the molecular characteristics of glioblastoma. She...
Tumor treating fields combined with a poly (adenosine diphosphate-ribose) polymerase inhibitor during radiotherapy for rapidly progressing IDH-wildtype diffuse astrocytoma: a case report.
A 57-year-old woman was diagnosed with IDH-wildtype (IDHwt) astrocytoma (World Health Organization grade II) with the molecular characteristics of glioblastoma. She underwent concurrent radiotherapy and chemotherapy according to the Stupp protocol in combination with a multi-target antiangiogenic drug and additional intrathecal chemotherapy using methotrexate. During treatment, the patient's tumor showed rapid progression. The chemotherapy with temozolomide was stopped and replaced with radiotherapy combined with tumor treating fields (TTF), the poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor niraparib, and anlotinib. After the radiotherapy was completed, the symptoms of increased intracranial pressure and epilepsy were well controlled. Considering the patient's tolerance to the treatment, the combined therapy of TTF and anlotinib was continued, and osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor with good permeability of the blood-brain barrier, was added. The patient was regularly followed up and had no obvious adverse drug reactions. Head magnetic resonance imaging (plain scan + enhanced scan) suggested that the lesions were stable. For rapidly progressing glioblastomas or histological grade II/III IDHwt astrocytomas, the combination of TTF and a PARP inhibitor during radiotherapy may have a synergistic effect on tumor control and is well tolerated by patients.
Topics: Adenosine Diphosphate; Astrocytoma; Brain Neoplasms; Female; Glioblastoma; Humans; Middle Aged; Ribose
PubMed: 34407687
DOI: 10.1177/03000605211036847 -
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 -
Journal of Neuro-oncology Mar 2017In 2007, extraventricular neurocytoma was classified as a separate entity among glioneuronal tumors. However, extraventricular neurocytoma is not fully understood and...
In 2007, extraventricular neurocytoma was classified as a separate entity among glioneuronal tumors. However, extraventricular neurocytoma is not fully understood and may be misdiagnosed. Here, we describe the clinical and pathological features, prognoses, and treatments of 13 extraventricular neurocytoma cases, and compare their immunophenotypes with those of oligodendroglioma, diffuse astrocytoma, and ependymoma. Six typical and 7 atypical cases comprised the 13 extraventricular neurocytoma cases. Histological features included oligodendroglioma-like perinuclear halo, neuropil-like matrix, ganglion or ganglioid cells, perivascular pseudorosettes, vessel hyalinization, calcifications, and myxoid degeneration. Atypical histological features included increased mitotic figures, focal necrosis, endothelial cell proliferation, and/or a Ki-67 index of >2%. All lesions expressed synaptophysin and microtubule-associated protein-2, which distinguished them from other similar tumors. Two patients with atypical extraventricular neurocytoma had tumor recurrence, one of whom had cerebrospinal fluid dissemination, suggesting that atypical histological features might represent adverse prognostic factors. In conclusion, the present study identified morphological and immunohistochemical features that would aid the differential diagnosis of extraventricular neurocytoma. In addition, radiotherapy with subtotal resection could be considered an effective treatment for extraventricular neurocytoma, but because a pediatric patient died of intracranial hemorrhage during radiotherapy, radiotherapy-related side effects should be considered, especially when treating children. Additional cases with long-term follow-up are needed to develop optimal management protocols for extraventricular neurocytoma.
Topics: Adult; Astrocytoma; Brain Neoplasms; Child, Preschool; Ependymoma; Female; Humans; Male; Neurocytoma; Oligodendroglioma; Young Adult
PubMed: 27864704
DOI: 10.1007/s11060-016-2336-1 -
Biomedical Papers of the Medical... Sep 2017Astrocytoma is the most prevalent form of primary brain cancer categorized into four histological grades by the World Health Organization. Investigation into individual...
BACKGROUND
Astrocytoma is the most prevalent form of primary brain cancer categorized into four histological grades by the World Health Organization. Investigation into individual grades of astrocytoma by previous studies has provided some insight into dysregulation of regulatory networks associated with increasing astrocytoma grades. However, further understanding of key mechanisms that distinguish different astrocytoma grades is required to facilitate targeted therapies.
METHODS
In this study, we utilized a large cohort of publicly available RNA sequencing data from patients with diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), primary glioblastoma (grade IV), secondary glioblastoma (grade IV), recurrent glioblastoma (grade IV), and normal brain samples to identify genetic similarities and differences between these grades using bioinformatics applications.
RESULTS
Our analysis revealed a distinct gene expression pattern between grade II astrocytoma and grade IV glioblastoma (GBM). We also identified genes that were exclusively expressed in each of the astrocytoma grades. Furthermore, we identified known and novel genes involved in key pathways in our study. Gene set enrichment analysis revealed a distinct expression pattern of transcriptional regulators in primary GBM. Further investigation into molecular processes showed that the genes involved in cell proliferation and invasion were shared across all subtypes of astrocytoma. Also, the number of genes involved in metastasis, regulation of cell proliferation, and apoptosis increased with tumor grade.
CONCLUSIONS
We confirmed existing findings and shed light on some important genes and molecular processes that will improve our understanding of glioma biology.
Topics: Adult; Astrocytoma; Brain; Brain Neoplasms; Cell Proliferation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Male; Molecular Targeted Therapy; Neoplasm Grading; Sequence Analysis, RNA; Signal Transduction; Transcriptome
PubMed: 28452381
DOI: 10.5507/bp.2017.020 -
Acta Neurochirurgica Mar 2009Akt/Protein kinase B (PKB) is a common downstream molecule of Ras signaling essential for cell survival. In an attempt to find a novel prognostic marker of diffuse...
BACKGROUND
Akt/Protein kinase B (PKB) is a common downstream molecule of Ras signaling essential for cell survival. In an attempt to find a novel prognostic marker of diffuse astrocytoma, we performed an immunohistochemical analysis of Akt/PKB with regard to patient survival and regrowth patterns.
METHODS
Twenty-four adult patients with diffuse astrocytoma were similarly managed without early post-operative radiotherapy and followed up for a median period of 7.5 years. They were analysed by immunohistochemistry for Akt/PKB expression as well as p53 protein accumulation, epidermal growth factor receptor (EGFR) expression, and MIB-1 labeling index. The prognostic significance of each molecular covariate was tested by multivariate analysis using Cox's proportional hazard model including age, performance status, and extent of surgical resection.
FINDINGS
Akt/PKB overexpression significantly correlated with both shorter overall survival (OS) and progression-free survival (PFS) (p = 0.0110). All the Akt/PKB-positive patients with post-operative residual tumours experienced tumour recurrences, whereas only a small fraction of the Akt/PKB-negative individuals had recurrences (p = 0.0070). Invasive recurrence into surrounding brain occurred only in the Akt/PKB-overexpressed tumours. In contrast, MIB-1 labeling index correlated only with OS, while p53 protein accumulation correlated only with PFS. The Cox's proportional hazard model identified Akt/PKB overexpression as a significant prognostic factor for shorter PFS (p = 0.0117).
CONCLUSION
These results show that Akt/PKB overexpression would be suggestive of malignant progression and invasive regrowth of diffuse astrocytoma, and it can serve as a novel prognostic marker for this tumour.
Topics: Adult; Age Factors; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Disease Progression; ErbB Receptors; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins c-akt; Survival Rate; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases
PubMed: 19240976
DOI: 10.1007/s00701-009-0199-3 -
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 -
BMJ Case Reports Apr 2021A 34-year-old pregnant woman at 28 gestational weeks was diagnosed with a brain tumor after experiencing a generalised seizure. After completion of antenatal fetal lung...
A 34-year-old pregnant woman at 28 gestational weeks was diagnosed with a brain tumor after experiencing a generalised seizure. After completion of antenatal fetal lung maturation, she underwent an osteoplastic craniotomy parietal on the left side and a microsurgical partial tumor resection under general anaesthesia. With a histology of a diffuse astrocytoma and the postoperative stable amount of residual tumor on follow-up imaging, the pregnancy proceeded until 37 gestational weeks. A healthy baby boy was delivered by elective caesarean section. An awake craniotomy for removal of the residual tumor was planned two weeks later, followed by adjuvant treatment (combined radio-/chemotherapy). A multidisciplinary approach, combined with appropriate timing and a transparent and empathic communication, was able to create the most effective tailored management and optimise maternal and neonatal outcomes.
Topics: Adult; Astrocytoma; Brain Neoplasms; Cesarean Section; Craniotomy; Female; Glioblastoma; Humans; Infant, Newborn; Male; Pregnancy
PubMed: 33795261
DOI: 10.1136/bcr-2021-242135