scholarly journals Diffuse Midline Glioma (H3K27M mutant) in Adult: A Diagnostic Challenge

2020 ◽  
Vol 7 (10) ◽  
pp. C123-127
Author(s):  
Sonal Paul ◽  
Nitin M Gadgil ◽  
Chetan Chaudhari
Keyword(s):  
Memory Loss ◽  
High Grade Glioma ◽  
Low Grade ◽  
Diagnostic Challenge ◽  
Microvascular Proliferation ◽  
Astrocytic Differentiation ◽  
Infiltrative Growth Pattern ◽  
Quadrigeminal Plate ◽  
Pineal Neoplasm ◽  
Diffuse Midline Glioma

Introduction: Diffuse midline glioma (DMG), H3K27M mutant is an infiltrative midline high grade glioma with predominantly astrocytic differentiation and K27M mutation in either H3F3A or HIST1H3B/C. Case Report:  A 45-year-old female presented with complaints of headache and memory loss for 3 months. MRI was suggestive of an infiltrative mass lesion in the quadrigeminal plate cistern suggestive of pineal neoplasm. Squash and histomorphology showed a low-grade astrocytic tumour with infiltrative growth pattern. Microvascular proliferation and necrosis were absent. Immunohistochemistry showed loss of ATRX protein, focal positivity for p53 proteinand IDH1R132H negativity. On molecular analysis, H3K27M mutation was noted and the case was labelled as DMG H3K27Mmutant (WHO IV) Conclusion: DMG (H3K27M) is a newly added entity in the WHO 4th revised editionof 2016. It presents with a diagnostic challenge as it has varied histomorphology, not requiring atypia, mitosis, endothelial hyperplasia and necrosis for diagnosis as Grade IV.

scholarly journals Advanced imaging in adult diffusely infiltrating low-grade gliomas

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nail Bulakbaşı ◽  
Yahya Paksoy
Keyword(s):  
Mr Imaging ◽  
Mr Spectroscopy ◽  
Capillary Permeability ◽  
Meta Analysis ◽  
High Grade Glioma ◽  
Low Grade ◽  
Imaging Data ◽  
Low Grade Gliomas ◽  
Microvascular Proliferation ◽  
Slow Growing

AbstractThe adult diffusely infiltrating low-grade gliomas (LGGs) are typically IDH mutant and slow-growing gliomas having moderately increased cellularity generally without mitosis, necrosis, and microvascular proliferation. Supra-total resection of LGG significantly increases the overall survival by delaying malignant transformation compared with a simple debulking so accurate MR diagnosis is crucial for treatment planning. Data from meta-analysis support the addition of diffusion and perfusion-weighted MR imaging and MR spectroscopy in the diagnosis of suspected LGG. Typically, LGG has lower cellularity (ADCmin), angiogenesis (rCBVmax), capillary permeability (Ktrans), and mitotic activity (Cho/Cr ratio) compared to high-grade glioma. The identification of 2-hydroxyglutarate by MR spectroscopy can reflect the IDH status of the tumor. The initial low ADCmin, high rCBVmax, and Ktrans values are consistent with the poor prognosis. The gradual increase in intratumoral Cho/Cr ratio and rCBVmax values are well correlated with tumor progression. Besides MR-based technical artifacts, which are minimized by the voxel-based assessment of data obtained by histogram analysis, the problems derived from the diversity and the analysis of imaging data should be solved by using artificial intelligence techniques. The quantitative multiparametric MR imaging of LGG can either improve the diagnostic accuracy of their differential diagnosis or assess their prognosis.

An Overview of High-grade Glioma: Current and Emerging Treatment Approaches

2020 ◽  
Vol 16 ◽  
Author(s):  
Kavya S.G. ◽  
Remya Reghu
Keyword(s):  
Radiation Therapy ◽  
Tumour Progression ◽  
Memory Loss ◽  
High Grade Glioma ◽  
Clonic Seizure ◽  
Severe Form ◽  
High Grade ◽  
Environmental Carcinogens ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Anatomic Structure

: High grade glioma is one among the severe form of tumour that progresses in the glial cells of the brain and spinal cord. Age, gender, exposure to infections, race, ethnicity, viruses and allergens, environmental carcinogens, diet, head injury or trauma and ionizing radiation may report with increased glioma risk. Headache, seizure mainly generalized tonic-clonic seizure, memory loss and altered sensorium are considered as common symptoms of glioma. Magnetic Resonance Imaging (MRI), CT scans, neurological examinations and biopsy are considered as the diagnostic option for glioma. Treatment for glioma mainly depended upon the tumour progression, malignancy, cell type, age, location of tumour growth and its anatomic structure. The standard treatment includes surgery, radiation therapy and chemotherapy. Temozolomide is usually prescribed at a dosage of 75 mg/m2 and began in combination with radiation therapy and continued daily. The primary indicator of hepatotoxicity is the elevation of the liver profiles, i.e. the changes in any of the liver panels may be considered to be hepatotoxic. Serum glutamic oxaloacetic transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), Alkaline phosphatase (ALP) are rising panels of the liver which are elevated during toxicity. In some patients, albumin and globulin levels may show variations. Treatment for glioma associated symptoms like seizures, depression anxiety etc. are also mentioned along with supportive care for glioma. New trends in the treatment for glioma are RINTEGA, an experimental immunotherapeutic agent and bevazizumab a recombinant monoclonal, humanized antibody against the VEGF ligand [VEGF-A (vascular endothelial growth factor)] in tumor cells.

scholarly journals Height in Adolescence as a Risk Factor for Glioma Subtypes: a Nationwide Retrospective Cohort Study of 2.2 Million Subjects

2021 ◽  
Author(s):  
Roi Tschernichovsky ◽  
Lior H Katz ◽  
Estela Derazne ◽  
Matan Ben-Zion Berliner ◽  
Maya Simchoni ◽  
...  
Keyword(s):  
Risk Factor ◽  
Statistical Significance ◽  
Positive Association ◽  
High Grade Glioma ◽  
Low Grade ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Glioma Risk ◽  
Incident Cases

Abstract Background Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. Methods The cohort included 2,223,168 adolescents between the ages of 16-19. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47,635,745 person-years. Cox proportional hazard models were used to estimate the hazard ratio for glioma and glioma subtypes according to height, body mass index (BMI) and sex. Results 1,195 patients were diagnosed with glioma during the study period. Mean(SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10cm increase) was positively associated with the risk for glioma of any type (HR 1.15; p=0.002). The association was retained in subgroup analyses for low-grade glioma (HR 1.17; p=0.031), high-grade glioma (HR 1.15; p=0.025), oligodendroglioma (HR 1.31; p=0.015), astrocytoma (HR 1.12; p=0.049), and a category of presumed IDH-mutated glioma (HR 1.17; p=0.013). There was a trend towards a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; p=0.07). After stratification of the cohort by sex, height remained a risk factor for men, but not for women. Conclusions The previously - established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype.

scholarly journals PATH-17. NOVEL DUAL HISTONE 3 K27M AND G34R POINT MUTATIONS IN A MIDLINE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii167-ii167
Author(s):  
Peter Pan ◽  
Tejus Bale ◽  
Alexandra Miller ◽  
Marc Ladanyi ◽  
Marc Rosenblum ◽  
...  
Keyword(s):  
Point Mutations ◽  
Histone 3 ◽  
First Case ◽  
Microvascular Proliferation ◽  
Motor Neuron Facial Nerve ◽  
Methylguanine Methyltransferase ◽  
Mitotic Figures ◽  
In Cis ◽  
Generation Sequencing ◽  
Diffuse Midline Glioma

Abstract BACKGROUND Histone H3 alterations due to mutations on H3F3A and HIST1H3B genes, have in recent years been associated with distinct entities and tumor locations within the context of infiltrative gliomas. H3K27M is associated with a midline location and is included in the WHO 2016 as the diffuse midline glioma H3K27M-mutant, a specific diagnostic entity. H3G34R, thought to be a mutually exclusive alteration, is less common but has been associated with a cerebral hemispheric location. We report the first case to our knowledge with both of these alterations in the same tumor. METHODS Clinical and pathologic records of the patient were reviewed and presented. RESULTS A 39-year-old man presented with acute right face, arm, and leg numbness and mild weakness; examination was notable for right lower motor neuron facial nerve palsy and numbness, along with numbness and subtle slowing of rapid alternating movements in the left arm and leg. A non-enhancing left thalamic mass was identified and stereotactically biopsied. Infiltrative glial neoplasm with moderately-increased cellularity was seen, with ovoid cells, enlarged nuclei, apoptotic bodies, and mitotic figures. No necrosis or microvascular proliferation seen. Immunostain was positive for H3K27M. O6-methylguanine-methyltransferase (MGMT) promoter was not methylated. Next-generation sequencing showed dual in cis H3 point mutations in K27M (HIST1H3B c.83A >T) and G34R (HIST1H3B c.103G >C). Additional alterations were noted in NF1, PIK3CA, ATRX, FGFR3, and NSD1. Isocitrate dehydrogenase (IDH1/2) mutations were not identified. CONCLUSION This case of a young man with a midline glioma is novel for carrying both H3K27M and H3G34R alterations and indicates these alterations are not mutually exclusive. The interaction seen here suggests H3K27M dominance for a midline phenotype.

scholarly journals Radiation necrosis after a combination of external beam radiotherapy and iodine-125 brachytherapy in gliomas

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Indrawati Hadi ◽  
Daniel Reitz ◽  
Raphael Bodensohn ◽  
Olarn Roengvoraphoj ◽  
Stefanie Lietke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Radiation Necrosis ◽  
Irradiation Time ◽  
External Beam Radiotherapy ◽  
High Grade Glioma ◽  
Metabolic Imaging ◽  
Time Interval ◽  
Low Grade ◽  
External Beam ◽  
Iodine 125

Abstract Purpose Frequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown. Methods Patients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models. Results Eighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence. Conclusion The combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.

scholarly journals Deep Learning Can Differentiate IDH-Mutant from IDH-Wild GBM

2021 ◽  
Vol 11 (4) ◽  
pp. 290
Author(s):  
Luca Pasquini ◽  
Antonio Napolitano ◽  
Emanuela Tagliente ◽  
Francesco Dellepiane ◽  
Martina Lucignani ◽  
...  
Keyword(s):  
Deep Learning ◽  
Hypoxia Inducible Factor ◽  
Model Performance ◽  
High Grade Glioma ◽  
Learning Model ◽  
Dense Layer ◽  
Idh Mutation ◽  
Diagnostic Challenge ◽  
Who Grade ◽  
Deep Learning Model

Isocitrate dehydrogenase (IDH) mutant and wildtype glioblastoma multiforme (GBM) often show overlapping features on magnetic resonance imaging (MRI), representing a diagnostic challenge. Deep learning showed promising results for IDH identification in mixed low/high grade glioma populations; however, a GBM-specific model is still lacking in the literature. Our aim was to develop a GBM-tailored deep-learning model for IDH prediction by applying convoluted neural networks (CNN) on multiparametric MRI. We selected 100 adult patients with pathologically demonstrated WHO grade IV gliomas and IDH testing. MRI sequences included: MPRAGE, T1, T2, FLAIR, rCBV and ADC. The model consisted of a 4-block 2D CNN, applied to each MRI sequence. Probability of IDH mutation was obtained from the last dense layer of a softmax activation function. Model performance was evaluated in the test cohort considering categorical cross-entropy loss (CCEL) and accuracy. Calculated performance was: rCBV (accuracy 83%, CCEL 0.64), T1 (accuracy 77%, CCEL 1.4), FLAIR (accuracy 77%, CCEL 1.98), T2 (accuracy 67%, CCEL 2.41), MPRAGE (accuracy 66%, CCEL 2.55). Lower performance was achieved on ADC maps. We present a GBM-specific deep-learning model for IDH mutation prediction, with a maximal accuracy of 83% on rCBV maps. Highest predictivity achieved on perfusion images possibly reflects the known link between IDH and neoangiogenesis through the hypoxia inducible factor.

scholarly journals DIPG-19. TARGETING ATM MUTATION IN METASTATIC DIFFUSE MIDLINE GLIOMA – A CASE OF SUSTAINED RESPONSE USING PARP INHIBITOR

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii290-iii291
Author(s):  
Karen Tsui ◽  
Andrew Law ◽  
Michael K Watson
Keyword(s):  
Parp Inhibitor ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Radiological Criteria ◽  
Metastatic Recurrence ◽  
Curative Therapy ◽  
First Case ◽  
Metastatic Relapse ◽  
Diffuse Midline Glioma

Abstract Diffuse midline glioma (DMG) with H3.3K27M mutation is associated with an extremely poor prognosis, with a median survival of 10 to 12 months. Radiation remains the standard of care however there is no established curative therapy available. We describe a patient diagnosed with a diffuse intrinsic pontine glioma at 5 years of age by clinical and radiological criteria. He was treated with focal radiation 59Gy which resulted in reduction in size of the tumour, and partial improvement of T2 changes on MRI. At 18 months post diagnosis, the patient developed metastatic recurrence at the anterior fornix. This was biopsied and histopathology demonstrated a high grade glioma. Next generation sequencing revealed a H3F3A K27M mutation, and an ATM R3008H mutation. He received whole ventricular radiation 36Gy and boost to the lesion to 45Gy, followed by Olaparib 135mg/m2/day twice daily. He remains in radiological remission 20 months post metastatic relapse and has no organ toxicity to Olaparib. CONCLUSION: H3.3K27M and ATM co-segregating mutations are described in DMG. This is the first case report of targeting ATM mutation with a PARP inhibitor which resulted in prolonged remission of metastatic DMG. Olaparib was well tolerated.

scholarly journals NI-01 Usefulness of preoperative evaluation of glioma elasticity by the magnetic resonance elastography

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii12-ii13
Author(s):  
Shinichiro Koizumi ◽  
Kazuhiko Kurozumi
Keyword(s):  
Elastic Modulus ◽  
Magnetic Resonance ◽  
Preoperative Evaluation ◽  
Tumor Resection ◽  
High Grade Glioma ◽  
Magnetic Resonance Elastography ◽  
Low Grade ◽  
Intracranial Tumors ◽  
Grade 3 ◽  
Malignant Grade

Abstract Introduction: The elasticity of intracranial tumors is difficult to assess non-invasively because the lesion is surrounded by the skull. Therefore, intracranial tumors have not been verified before surgery in terms of elastic modulus. Magnetic resonance elastography (MRE) is an epoch-making method capable of non-invasively imaging the elasticity of internal organs. We have examined the elasticity of meningiomas and pituitary adenomas and reported their usefulness. This time, we measured the glioma elasticity and verified usefulness of MRE. Method: Twenty-four gliomas (mean age 51.8±15.7 years, male: female = 17: 7) who underwent tumor resection after MRE imaging from July 2017 to May 2020 were targeted. The average elasticity was measured as an evaluation of tumor elastic modulus by MRE. Gliomas were divided into a low-grade glioma group (LGG: Grade 1, 2) and a high-grade glioma group (HGG: Grade 3, 4). Then, a comparative statistical study was conducted. Results: The average values of the average elasticity of LGG group (9 cases) and HGG group (15 cases) were 1.8±0.8 kPa and 2.5±0.8 kPa, respectively. The average elasticity was significantly higher in the HGG group (p=0.023). In the ROC analysis, the cutoff value was 2.1 kPa (sensitivity 70%, specificity 70%). Therefore, it was suggested that the tumor is likely to be HGG when the average elasticity is 2.1 kPa or more. Discussion: The glioma elasticity by preoperative MRE was significantly higher in the HGG group. Based on actual surgical experience, the tumor seems to be hard in the HGG group, and it was judged to be consistent with this our MRE research. The preoperative evaluation of glioma elasticity by MRE was considered useful, and it might help in planning a surgical strategy considering malignant grade.

scholarly journals IMG-14. DEVELOPING A PREDICTIVE GRADING MODEL FOR CHILDREN WITH GLIOMAS BASED ON DIFFUSION KURTOSIS IMAGING METRICS: ACCURACY AND CLINICAL CORRELATIONS WITH SURVIVAL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii357-iii358
Author(s):  
Ioan Paul Voicu ◽  
Antonio Napolitano ◽  
Alessia Carboni ◽  
Lorenzo Lattavo ◽  
Andrea Carai ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
High Grade Glioma ◽  
Diffusion Kurtosis Imaging ◽  
Low Grade ◽  
Free Survival ◽  
Kaplan Meier ◽  
Model Predictions ◽  
Probability Prediction ◽  
Grading Model ◽  
Diffusion Kurtosis

Abstract PURPOSE To develop a predictive grading model based on diffusion kurtosis imaging (DKI) metrics in children affected by gliomas, and to investigate the clinical impact of the model via correlations with overall survival and progression-free survival. MATERIALS AND METHODS We retrospectively studied 59 children (33M, 26F, median age 7.2 years) affected by gliomas on a 3T magnet. Patients with tumor locations other than infratentorial midline were included. Conventional and DKI sequences were obtained. Mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were obtained. Whole tumor volumes (VOIs) were segmented semiautomatically. Mean DKI values were calculated for each metric. The quantitative values from DKI-derived metrics were used to develop a predictive grading model with penalized logistic regression (glmnet package, R). Elasticnet regularization was used to avoid model overfitting. Fitted model coefficients from each metric were used to develop a probability prediction of a high-grade glioma (HGG). Grading accuracy of the resulting probabilities was tested with ROC analysis. Finally, model predictions were correlated to progression-free survival (PFS) with a Kaplan-Meier analysis. RESULTS The cohort included 46 patients with low-grade gliomas (LGG) and 13 patients with HGG. The developed model predictions yielded an AUC of 0.946 (95%CI: 0.890–1). Model predictions were significantly correlated with PFS (23.1 months for HGG vs 34.7 months for LGG, p<0.004). CONCLUSION In our cohort, a DKI-based predictive model was highly accurate for pediatric glioma grading. DKI-based model predictions were significantly correlated with progression-free survival.

scholarly journals Convection Enhanced Delivery in the Setting of High-Grade Gliomas

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 561
Author(s):  
Chibueze D. Nwagwu ◽  
Amanda V. Immidisetti ◽  
Michael Y. Jiang ◽  
Oluwasegun Adeagbo ◽  
David C. Adamson ◽  
...  
Keyword(s):  
Rapid Development ◽  
Systemic Exposure ◽  
Therapeutic Index ◽  
High Grade Glioma ◽  
High Grade ◽  
Clinical Experiences ◽  
Convection Enhanced Delivery ◽  
Drug Concentrations ◽  
Infiltrative Growth Pattern ◽  
High Grade Gliomas

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood–brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

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