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Journal of Veterinary Diagnostic... Jul 2024Most canine gliomas occur in adult and aged dogs, and reports in puppies < 12-mo-old are exceedingly rare. Here we describe the occurrence of gliomas in 5 dogs...
Most canine gliomas occur in adult and aged dogs, and reports in puppies < 12-mo-old are exceedingly rare. Here we describe the occurrence of gliomas in 5 dogs ≤ 12-mo-old. The affected patients (4 males, 1 female) were 3-12-mo-old (x̄ = 6.6-mo-old). None of the dogs were brachycephalic. Clinical signs consisted of dullness (2 cases), seizures (2 cases), vestibular signs, and deafness (1 case each). All patients were euthanized. Grossly, neoplasms were pale-tan or red, soft masses in the telencephalon (4 cases) or gelatinous leptomeningeal thickening in the brain and spinal cord (1 case). Neoplasms were classified as astrocytomas (3 cases) and oligodendrogliomas (2 cases) based on histology or histology and IHC. Our findings confirm that, while exceptionally rare, canine gliomas occur in the first year of life, and are clinically, morphologically, and immunohistochemically similar to gliomas in adult and aged dogs.
Topics: Dogs; Animals; Dog Diseases; Female; Male; Glioma; Brain Neoplasms
PubMed: 38561905
DOI: 10.1177/10406387241242733 -
Translational Oncology Jun 2024The KCa3.1 channel (KCNN4) is extensively investigated as an oncogene in human cancers. The current study aimed to explore the clinicopathological significance of KCNN4...
BACKGROUND
The KCa3.1 channel (KCNN4) is extensively investigated as an oncogene in human cancers. The current study aimed to explore the clinicopathological significance of KCNN4 expression in patients with primary adult-type diffuse gliomas.
METHODS
Demographic, RNA-seq, and follow-up data of 477 patients were retrospectively reviewed. Patients were divided into the experimental and validation groups (278 and 199). KCNN4-related genes were determined by Pearson correlation analysis, and enrichment analyses and tumor-infiltrating immune cell assessments were applied to explore the potential mechanisms of KCNN4 involving glioma progression. The Kaplan-Meier method and the Cox regression analysis were used to evaluate the prognostic value of KCNN4 expression.
RESULTS
KCNN4 showed significantly higher expression level in glioblastoma, IDH-wildtype, followed by astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (p < 0.001). Enrichment analyses and tumor-infiltrating immune cell assessments suggested that KCNN4 could involve glioma progression through extracellular regulation, affecting immune response, and modulating subcellular trafficking. At last, the Kaplan-Meier analysis showed that high KCNN4 expression was significantly correlated with poor progression-free and overall survival (p < 0.001 for both). While multivariate Cox regression analysis obtained an insignificant result.
CONCLUSIONS
KCNN4 was identified to be overexpressed in glioma cells and its expression level is positively related to tumor malignancy. It potentially participates in glioma biology by affecting extracellular regulation, subcellular trafficking, and immune escape. Additionally, high KCNN4 expression was correlated with poor survival outcomes of patients. The results can shed new light on the mechanisms of glioma progression, and provide a potential therapeutic target for treating gliomas.
PubMed: 38555740
DOI: 10.1016/j.tranon.2024.101947 -
Clinical Oncology (Royal College of... Jun 2024Despite relatively favourable outcomes associated with IDH-mutant grade 3 gliomas, many patients present with diffuse non-enhancing disease involving multiple brain...
AIMS
Despite relatively favourable outcomes associated with IDH-mutant grade 3 gliomas, many patients present with diffuse non-enhancing disease involving multiple brain regions, prompting concern over both durable disease control and the morbidity associated with large volume radiation therapy. This study audits volumetric response, survival and functional outcomes in this 'large volume' subgroup that undergoes intensity modulated radiation therapy (IMRT).
MATERIALS AND METHODS
From a prospective database of 187 patients with IDH-mutant grade 3 gliomas managed with IMRT between 2008 and 2020, recorded PTV was divided into quartiles. The top quartile, termed the 'large volume cohort' (LVC), was identified. IMRT involved FET-FDG guided integrated boost (59.4/54Gy in 33 fractions). Manual volumetric segmentation of baseline, four months and 13 months post-IMRT tumour were performed for T1, T2 and T1gd MRI sequences. The primary endpoint was volumetric reduction on the T1 and T2 sequences at 13 months and analysed with relapse-free survival (RFS) and overall survival (OS). Morbidity endpoints were assessed at year four post-IMRT and included performance status (ECOG PS) and employment outcomes.
RESULTS
The fourth quartile (LVC) identified 44 patients for whom volumetric analysis was available. The LVC had median PTV of 320cm compared to 186.2cm for the total group. Anaplastic astrocytoma and oligodendroglioma were equally distributed and tumour sites were frontal (54%), temporal (18%) and parietal lobes (16%). Median follow-up for survivors was 71.5 months. Projected 10-year RFS and OS in LVC was 40% and 62%, compared to 53% and 62% respectively in the overall cohort. The RFS (p = 0.06) and OS (p = 0.65) of the LVC was not significantly different to other PTV quartiles; however the impact of PTV volume reached significance when analysed as a continuous variable (RFS p < 0.01; OS p = 0.02). Median T1 volumes were 26.1cm, 8.0cm and 5.3cm at months +0, +3 and +12, respectively. The corresponding T2 volumes were 120.8cm 29.1cm and 26.3cm. The median T1 and T2 volume reductions were 77% (q1-3: 57-92%) and 78% (q1-3: 60-85%) at 13 months post-IMRT. Initial T2 volume was associated with worse RFS (p = 0.04) but not OS (p = 0.96). There was no association between median T2 volume reduction and RFS (p = 0.77). For patients assessable at year 4 post-IMRT, no late CTCAE Grade 3/4 toxicity events were recognised. 92% of patients were ECOG PS 0-1, 45% were employed at prior capacity and 28% were working with impairment.
CONCLUSION
Patients with large volume IDH-mutant Grade 3 glioma demonstrated significant tumour reduction post-IMRT, and good long-term outcomes with respect to survival and functional status. Although larger IMRT volumes were associated with poorer RFS, this was also associated with the initial volume of non-enhancing tumour.
Topics: Humans; Male; Female; Radiotherapy, Intensity-Modulated; Middle Aged; Brain Neoplasms; Glioma; Isocitrate Dehydrogenase; Adult; Fluorodeoxyglucose F18; Aged; Mutation; Prospective Studies; Radiopharmaceuticals; Neoplasm Grading
PubMed: 38553362
DOI: 10.1016/j.clon.2024.03.002 -
European Radiology Mar 2024
PubMed: 38530428
DOI: 10.1007/s00330-024-10711-w -
European Radiology Mar 2024To distinguish isocitrate dehydrogenase (IDH) genotypes and tumor subtypes of adult-type diffuse gliomas based on the fifth edition of the World Health Organization...
OBJECTIVES
To distinguish isocitrate dehydrogenase (IDH) genotypes and tumor subtypes of adult-type diffuse gliomas based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) in 2021 using standard, high, and ultra-high b-value diffusion-weighted imaging (DWI).
MATERIALS AND METHODS
This prospective study enrolled 70 patients with adult-type diffuse gliomas who underwent multiple b-value DWI. Apparent diffusion coefficient (ADC) values including ADC, ADC, ADC, ADC, ADC, ADC, and ADC in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The ADC ratios of TP/NAWM were assessed for correlations with IDH genotypes, tumor subtypes, and Ki-67 status; diagnostic performances were compared.
RESULTS
All ADCs were significantly higher in IDH mutant gliomas than in IDH wild-type gliomas (p < 0.01 for all); ADC had the highest area under the curve (AUC) of 0.866. All ADCs were significantly lower in glioblastoma than in astrocytoma (p < 0.01 for all). ADCs other than ADC were significantly lower in glioblastoma than in oligodendroglioma (p < 0.05 for all). ADC and ADC were significantly higher in oligodendroglioma than in astrocytoma (p = 0.034 and 0.023). The highest AUCs were 0.818 for ADC when distinguishing glioblastoma from astrocytoma, 0.979 for ADC and ADC when distinguishing glioblastoma from oligodendroglioma, and 0.773 for ADC when distinguishing astrocytoma from oligodendroglioma. Additionally, all ADCs were negatively correlated with Ki-67 status (p < 0.05 for all).
CONCLUSION
Ultra-high b-value DWI can reliably separate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using WHO CNS5 criteria.
CLINICAL RELEVANCE STATEMENT
Ultra-high b-value diffusion-weighted imaging can accurately distinguish isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas, which may facilitate personalized treatment and prognostic assessment for patients with glioma.
KEY POINTS
• Ultra-high b-value diffusion-weighted imaging can accurately distinguish subtle differences in water diffusion among biological tissues. • Ultra-high b-value diffusion-weighted imaging can reliably separate isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas. • Compared with standard b-value diffusion-weighted imaging, high and ultra-high b-value diffusion-weighted imaging demonstrate better diagnostic performances.
PubMed: 38528135
DOI: 10.1007/s00330-024-10708-5 -
Neuro-oncology Practice Apr 2024Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes...
BACKGROUND
Isocitrate dehydrogenase (IDH) is commonly mutated (mIDH) in gliomas, and this mutant enzyme produces the oncometabolite 2-hydroxyglutarate (2HG). 2HG promotes gliomagenesis and is implicated in epileptogenesis. Ivosidenib (IVO), a small molecule oral mIDH1 inhibitor, is FDA-approved for mIDH1 newly diagnosed and relapsed/refractory acute myeloid leukemia. Moreover, IVO has efficacy in clinical trials for recurrent mIDH1 gliomas. Given the lack of targeted treatments for gliomas, we initiated off-label IVO for mIDH glioma patients in October 2020.
METHODS
Retrospectively, we sought to assess early outcomes in our patients and describe their experience on IVO from October 2020 through February 2022. Our objective was to report on the following variables of off-label use of IVO: radiographic response, seizure control, tolerability, and access to the medication. All patients initially received single-agent IVO dosed at 500 mg orally once daily.
RESULTS
The cohort age range was 21-74 years. Tumor types included astrocytoma ( = 14) and oligodendroglioma ( = 16), with most being grade 2 ( = 21). The best radiographic response in nonenhancing disease ( = 22) was 12 stable diseases, 5 minor responses, 3 partial responses, and 2 progressive diseases. Seizure frequency was stable to improved for most patients (70%, = 21). IVO was well-tolerated, with the most common toxicities being diarrhea, elevated creatine kinase, and QTc interval prolongation. Most patients (66.7%, = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%.
CONCLUSIONS
Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes.
PubMed: 38496920
DOI: 10.1093/nop/npad068 -
World Neurosurgery May 2024Oligosarcoma is a rare central nervous system (CNS) neoplasm that may arise following oligodendroglioma resection, which demonstrates a unique genetic profile and...
BACKGROUND
Oligosarcoma is a rare central nervous system (CNS) neoplasm that may arise following oligodendroglioma resection, which demonstrates a unique genetic profile and aggressive clinical phenotype. We present a systematic review and illustrative case example emphasizing the clinical and prognostic features of this unusual and unfavorable neuro-oncologic disease.
METHODS
Systematic literature review and illustrative case report.
RESULTS
A 41-year-old man who had undergone 2 neurosurgical resections for a World Health Organization grade II oligodendroglioma (Ki-67 = 5-10%, 1p/19q codeleted, IDH2 mutated), without adjuvant chemoradiation, presented with seizures seven years after resection. An extra-axial mass was identified adjacent to the resection cavity, in which gross total resection was achieved. Pathology confirmed World Health Organization grade IV oligosarcoma (Ki-67 = 20%). Adjuvant chemoradiation was initiated, with disease control observed over 6 months of follow-up. Seven publications met inclusion criteria. Oligosarcoma has been confirmed in 36 lesions, arising in 35 patients; 5 were primary oligosarcoma, while 31 occurred in the setting of prior resected oligodendroglioma or oligoastrocytoma. Features shared by these lesions include regain of H3K27me3 expression, 1p/19q codeletion, homozygous deletion of CDKN2A/B, loss of 6q, loss of NF1 and YAP1, and attenuation of CpG island methylator. Median survival after oligosarcoma diagnosis was 1.3 years (range, 0-5.2; n = 35).
CONCLUSIONS
Oligosarcoma is a prognostically unfavorable CNS neoplasm with characteristic imaging and pathologic features, and a strong association with previously resected oligodendroglioma. Aggressive treatment is recommended, including gross total resection and adjuvant chemoradiation. Further study is required to define optimal treatment protocol for this CNS malignancy.
Topics: Humans; Oligodendroglioma; Adult; Male; Brain Neoplasms; YAP-Signaling Proteins; Adaptor Proteins, Signal Transducing; Chemoradiotherapy, Adjuvant
PubMed: 38490447
DOI: 10.1016/j.wneu.2024.03.028 -
World Journal of Clinical Oncology Feb 2024Gliomas are primary brain tumors derived from glial cells of the central nervous system, afflicting both adults and children with distinct characteristics and... (Review)
Review
Gliomas are primary brain tumors derived from glial cells of the central nervous system, afflicting both adults and children with distinct characteristics and therapeutic challenges. Recent developments have ushered in novel clinical and molecular prognostic factors, reshaping treatment paradigms based on classification and grading, determined by histological attributes and cellular lineage. This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023. For adults, the therapeutic triad typically consists of surgical resection, chemotherapy, and radiotherapy. In contrast, pediatric gliomas, due to their diversity, require a more tailored approach. Although complete tumor excision can be curative based on the location and grade of the glioma, certain non-resectable cases demand a chemotherapy approach usually involving, vincristine and carboplatin. Additionally, if surgery or chemotherapy strategies are unsuccessful, Vinblastine can be used. Despite recent advancements in treatment methodologies, there remains a need of exploration in the literature, particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts. This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.
PubMed: 38455131
DOI: 10.5306/wjco.v15.i2.178 -
Frontiers in Immunology 2024In 2021, the World Health Organization published a new classification system for central nervous system tumors. This study reclassified the adult diffuse glioma (ADG)...
INTRODUCTION
In 2021, the World Health Organization published a new classification system for central nervous system tumors. This study reclassified the adult diffuse glioma (ADG) into astrocytoma, oligodendroglioma, and glioblastoma (GBM) according to the new tumor classification.
METHODS
The association of TERT promoter (pTERT) mutation, MGMT methylation, and CD47/TIGIT expression with patient prognosis was investigated.
RESULTS
Immunohistochemical analysis showed that the expression levels of CD47 and TIGIT in tumor tissues were significantly higher than those in normal brain tissues. CD47 levels were higher in GBM and grade 4 astrocytoma tissues. TIGIT expression was also higher in patients with GBM. The high expressions of CD47, TIGIT, and CD47/TIGIT were positively correlated with unmethylation but not p mutation. Moreover, unmethylation was associated with poor overall survival in astrocytoma. High CD47, TIGIT, and CD47/TIGIT levels were associated with significantly reduced survival in ADG and GBM. GBM, unmethylation, and high CD47 expression were independent prognostic factors for overall survival in ADG.
DISCUSSION
Collectively, these results showed that the unmethylation and high levels of CD47 and TIGIT are associated with a poor prognosis in ADG. Patients with high CD47 and TIGIT expression may benefit from anti-CD47 and TIGIT immunotherapy.
Topics: Adult; Humans; Brain Neoplasms; CD47 Antigen; Glioma; Glioblastoma; Astrocytoma; Prognosis; DNA Modification Methylases; Tumor Suppressor Proteins; DNA Repair Enzymes; Receptors, Immunologic
PubMed: 38404571
DOI: 10.3389/fimmu.2024.1323307 -
Case Reports in Oncology 2024Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting...
INTRODUCTION
Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting with disseminated leptomeningeal enhancement and an occasional intraparenchymal mass. Diagnosis is often impeded by infectious/immunological differentials, necessitating a biopsy to confirm the diagnosis. We report an adult male with DLGNT without hydrocephalus, which is rare in patients with cerebellar masses.
CASE PRESENTATION
A 56-year-old man presented with headaches, vertigo, diplopia, impaired hearing, and gait imbalance over 6 months. Magnetic resonance imaging showed a cystic right cerebellar mass with its leptomeningeal dissemination but without hydrocephalus. Cerebrospinal fluid analysis revealed elevated proteins with CD56-positive tumor cells. Cerebellar lesion biopsy verified the diagnosis of DLGNT (WHO Grade 3) with fusion and 1p deletion. Radiotherapy was prematurely aborted due to clinical deterioration. The patient was subsequently discharged to palliative home care and lost to follow-up.
CONCLUSION
We conducted the first review of all 34 adult DLGNT cases, including ours (one of the oldest), hitherto published in the literature. The majority presented with signs and symptoms of increased intracranial pressure. 52.0% of adult DLGNT patients were alive at follow-up. DLGNT should be considered in the differential diagnoses of diffuse leptomeningeal enhancement in imaging. Further studies comparing pediatric and adult subgroups of DLGNT are needed to evaluate histopathological prognosticators and standardize therapy for both subpopulations.
PubMed: 38404404
DOI: 10.1159/000536400