NIMG-47. METABOLIC CHARACTERIZATION OF IDH MUTANT LOWER GRADE GLIOMA USING SPECTROSCOPIC IMAGING OPTIMIZED FOR 2-HYDROXYGLUTARATE DETECTION

Abstract INTRODUCTION Mutations in isocitrate dehydrogenase (IDH1/2) genes are both diagnostic and prognostic biomarkers for lower grade gliomas, which can be noninvasively evaluated via MRS detection of 2-hydroxyglutarate (2HG). A high percentage of lower grade gliomas harbor IDH mutations that have a major impact on tumor biology. METHODS Forty IDH-mutant lower grade glioma patients were recruited and scanned using 2HG-optimized 97ms PRESS spectroscopy prior to surgical resection, whereupon image-guided tissue samples were acquired and analyzed via histopathology. Spectra were processed and quantified using LCModel. Wilcoxon ranksum tests were used to compare the difference in metabolic parameters between patient subgroups. Cox proportional hazard models were used to evaluate the influence of metabolic parameters on progression free survival (PFS). Pearson and Kendall Tau rank correlations were used for metabolites and histopathology parameters. RESULTS Levels of 2HG were quantifiable in 37/40 (92.5%) IDH+ patients, yielding a detection rate of 92.5%. A significant difference in myoinositol/total choline was found between astrocytoma and oligodendroglioma in the newly diagnosed grade II population (N=10/13, p=0.042) and also in the overall population (N=25/15, p=0.022). 2HG/creatine was the only significant prognostic indicator on PFS in newly diagnosed patients (p=0.036, HR=4.435; N=33), who had a median PFS of 1472 days [95%CI 994 1950 days] (15 censored). Significantly decreased glutamate/creatine and increased (2HG+GABA)/creatine (p< 0.0001) were found in the T2 lesion compared to those in the normal appearing white matter. At the location where the biopsy samples were taken, there was a significant relationship between 2HG/creatine and glycine/creatine (0.93±0.01; mean±SD Tau; p=0.0005) as well as 2HG/creatine and glutathione/creatine (0.96±0.02; mean±SD Tau; p=0.001) but no significance between the metabolites and pathology parameters were found. CONCLUSIONS The non-invasive detection of 2HG can provide clinically relevant information for patient management and our study demonstrated both the feasibility of 2HG detection and its relationship with PFS.

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Voxel-wise radiogenomic mapping of tumor location with key molecular alterations in patients with glioma

Neuro-Oncology ◽

10.1093/neuonc/noy134 ◽

2018 ◽

Vol 20 (11) ◽

pp. 1517-1524 ◽

Cited By ~ 13

Author(s):

Miguel Angel Tejada Neyra ◽

Ulf Neuberger ◽

Annekathrin Reinhardt ◽

Gianluca Brugnara ◽

David Bonekamp ◽

...

Keyword(s):

Tumor Location ◽

Molecular Characteristics ◽

Consecutive Series ◽

Lower Grade ◽

Newly Diagnosed ◽

Molecular Alterations ◽

Lateral Ventricles ◽

Lower Grade Glioma ◽

Idh Mutations ◽

The Impact

Abstract Background This study aims to evaluate the impact of tumor location on key molecular alterations on a single voxel level in patients with newly diagnosed glioma. Methods A consecutive series of n = 237 patients with newly diagnosed glioblastoma and n = 131 patients with lower-grade glioma was analyzed. Volumetric tumor segmentation was performed on preoperative MRI with a semi-automated approach and images were registered to the standard Montreal Neurological Institute 152 space. Using a voxel-based lesion symptom mapping (VLSM) analysis, we identified specific brain regions that were associated with tumor-specific molecular alterations. We assessed a predefined set of n = 17 molecular characteristics in the glioblastoma cohort and n = 2 molecular characteristics in the lower-grade glioma cohort. Permutation adjustment (n = 1000 iterations) was used to correct for multiple testing, and voxel t-values that were greater than the t-value in >95% of the permutations were retained in the VLSM results (α = 0.05, power > 0.8). Results Tumor location predilection for isocitrate dehydrogenase (IDH) mutant tumors was found in both glioblastoma and lower-grade glioma cohorts, each showing a concordant predominance in the frontal lobe adjacent to the rostral extension of the lateral ventricles (permutation-adjusted P = 0.021 for the glioblastoma and 0.013 for the lower-grade glioma cohort). Apart from that, the VLSM analysis did not reveal a significant association of the tumor location with any other key molecular alteration in both cohorts (permutation-adjusted P > 0.05 each). Conclusion Our study highlights the unique properties of IDH mutations and underpins the hypothesis that the rostral extension of the lateral ventricles is a potential location for the cell of origin in IDH-mutant gliomas.

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The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽

10.1093/neuros/nyab052 ◽

2021 ◽

Author(s):

Peng Wang ◽

Chen Luo ◽

Peng-jie Hong ◽

Wen-ting Rui ◽

Shuai Wu

Keyword(s):

Cox Regression ◽

Progression Free Survival ◽

Extent Of Resection ◽

Lower Grade ◽

Wild Type ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Lower Grade Glioma ◽

Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

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Evaluating the benefit of adaptive randomization in the CC-115 arm of the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A phase II randomized Bayesian adaptive platform trial in newly diagnosed MGMT unmethylated glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2006 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2006-2006

Author(s):

Rifaquat Rahman ◽

Lorenzo Trippa ◽

Geoffrey Fell ◽

Eudocia Quant Lee ◽

Isabel Arrillaga-Romany ◽

...

Keyword(s):

Mammalian Target Of Rapamycin ◽

Progression Free Survival ◽

Newly Diagnosed ◽

Adaptive Randomization ◽

Number Of Patients ◽

Significant Difference ◽

Enrollment Rates ◽

Dependent Protein ◽

The Impact ◽

Screening Trial

2006 Background: Adaptive randomization adjusts enrollment rates based upon early trial results, which can allow for decreased enrollment for therapies less likely to meet the primary endpoint of a trial. CC-115, a CNS-penetrant, oral inhibitor of mammalian target of rapamycin kinase (mTOR) and deoxyribonucleic acid-dependent protein kinase (DNA-PK), was evaluated in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. As CC-115 was discontinued due to concerns about toxicity and unfavorable risk-to-benefit ratio, we sought to investigate the impact of adaptive randomization in its testing. Methods: In INSIGhT, adults with newly diagnosed MGMT-unmethylated glioblastoma and available genomic data are adaptively randomized to an experimental arm or the control arm of standard radiotherapy with concurrent and adjuvant temozolomide. Patients randomized to CC-115 received it (10mg po BID) with radiotherapy and as adjuvant monotherapy, and a safety lead-in 3+3 design was used for this arm. By simulating the INSIGhT trial with standard uniform randomization, we estimated the reduction of enrollment rate and sample size of the CC-115 arm that was attributable to adaptive randomization. Results: Twelve patients were randomized to CC-115; 58% (n = 7) patients had possible treatment-related CTCAE grade > 3 toxicity. Compared to the control arm, there was no significant difference in progression-free survival (PFS, HR 0.66, 95% CI 0.32-1.36, p = 0.3) or overall survival (OS, HR 0.93, 95% CI 0.43-2.03, p = 0.8). Based on early PFS results, randomization probability to CC-115 decreased from 25% to 16%. At the time of the CC-115 arm closure, 14% of enrolled INSIGhT patients had been randomized to this arm. Compared to average expected enrollment by standard randomization, the use of adaptive randomization decreased the number of patients randomized to CC-115 by 50% (12 patients vs. 18 patients [95% CI 11-25 patients]). Conclusions: The INSIGhT trial, designed with adaptive randomization, facilitated more efficient testing of CC-115 and decreased the number of patients allocated to the CC-115 arm relative to a standard randomization design. Clinical trial information: NCT02977780.

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NIMG-13. RESPONSE ASSESSMENT IN GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL-BASED IMMUNOTHERAPY: A COMPARATIVE ANALYSIS OF MACDONALD, RANO, MRANO, IRANO AND VOLUMETRIC MEASUREMENTS

Neuro-Oncology ◽

10.1093/neuonc/noab196.513 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi130-vi130

Author(s):

Johanna Heugenhauser ◽

Malik Galijasevic ◽

Stephanie Mangesius ◽

Johanna Buchroithner ◽

Friedrich Erhart ◽

...

Keyword(s):

Dendritic Cell ◽

Progression Free Survival ◽

Response Assessment ◽

Assessment Tools ◽

Assessment Criteria ◽

Newly Diagnosed ◽

Significant Difference ◽

Different Response ◽

The Impact ◽

Spearman Test

Abstract INTRODUCTION Response assessment in the treatment of glioblastoma (GB) based on MR-imaging is still challenging, in particular for immunotherapeutic strategies. Several assessment tools have been proposed. In this post-hoc analysis we compared response assessment criteria (MacDonald, RANO, mRANO, Vol.-mRANO, iRANO) in newly diagnosed GB patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression free survival (PFS) and overall survival (OS). METHODS 76 patients with newly diagnosed GB enrolled in a multicenter randomized phase II trial receiving standard of care (SOC, n= 40) or SOC + Audencel vaccine (n= 36) were included. Tumor volumes were calculated by semiautomatic segmentation. To detect differences in PFS among the assessment criteria Kruskal-Wallis-test, for correlation analysis Spearman test was used. RESULTS There was a significant difference in median PFS based on the different assessments (mRANO 8.55 months [9.10-14.03], Vol.-mRANO 8.61 months [9.72-14.92] compared to MacDonald 4.04 months [5.21-8.75] and RANO 4.16 months [5.28-8.61]. For the vaccination arm only, median PFS by iRANO was 5.95 months [5.70-11.54]). There was no difference in PFS between SOC and SOC + Audencel using the different response criteria. The best correlation between PFS and OS was detected for mRANO (r= 0.65, p< 0.001) and Vol.-mRANO (r= 0.69, p< 0.001). At an 8-month landmark, the impact of progressive disease on median OS was best shown for mRANO (13.70 months [13.13-18.98], and Vol.-mRANO 12.03 months [12.51-17.94]) compared to MacDonald 17.97 months [15.45-20.92], RANO 17.97 months [15.92-20.95] and iRANO 17.34 months [14.99-22.73]. CONCLUSION When comparing different response assessments in GB patients treated with dendritic cell-based immunotherapy the best correlation between PFS and OS was observed for mRANO and Vol.-mRANO. Overall, no difference in PFS and OS was seen between the two treatment arms. iRANO was not superior for predicting OS in patients treated with Audencel.

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IMT-01 THERAPEUTIC EFFECT AGAINST LOWER GRADE GLIOMA INDUCED BY DENDRITIC CELL BASED IMMUNOTHERAPY

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.076 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii17-ii17

Author(s):

Yasuharu Akasaki ◽

Jun Takei ◽

Yuko Kamata ◽

Yohei Yamamoto ◽

Ryosuke Mori ◽

...

Keyword(s):

Glioma Cells ◽

Progression Free Survival ◽

Cervical Region ◽

Lower Grade ◽

Mri Findings ◽

Who Grade ◽

Lower Grade Glioma ◽

Major Interest ◽

Grade Ii

Abstract BACKGROUND This trial was designed to evaluate the safety and clinical responses to an immunotherapy with fusions of dendritic and glioma cells in patients with lower grade glioma (LGG; WHO grade II-III glioma). METHOD Autologous cultured glioma cells obtained from surgical specimens were fused with autologous dendritic cells (DC) using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region of subjects. Toxicity, progression-free survival (PFS), overall survival (OS), and MRI findings were evaluated. DNA for whole exome and RNA for whole transcriptome extracted from HLA-A*24:02 positive glioma cells were analyzed by next generation sequencer. Variant peptides showing strong binding affinity to HLA-A*24:02 but not the corresponding wild type peptides were selected as candidate of neo-antigens. RESULTS The number of subjects of this trial were 24 (initially diagnosed cases: 20, recurrence cases: 4). WHO grade III cases were 20, and grade II cases were 4. Male were 15, and female were 9. Mean of follow up periods were 53.0 months (the longest follow up period: 1322 months). The number of events on PFS and OS were 8 and 6, respectively. Mean of candidate of neo-antigen peptides in HLA-A*24:02 positive patients (n=8) was 34. Among these candidates, twelve types of common neo-antigen peptide were identified. Neo-antigen peptides specifically expressed in the glioma cells from the effective group were not identified. CONCLUSIONS These results indicate that the efficacy of FC-immunotherapy may not always depend on the number of gene mutations or the expression of the specific neo-antigens. FC-immunotherapy, as a means of producing specific immunity against neo-antigens may safely induce anti-tumor effects in patients with LGG. Analysis of prognostic factor in glioma immunotherapy may be the next area of major interest.

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Transcriptomic Analysis of Glioma Based on IDH Status Identifies ACAA2 as a Prognostic Factor in Lower Grade Glioma

BioMed Research International ◽

10.1155/2020/1086792 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Chenxing Wu ◽

Hongwang Song ◽

Xiaojun Fu ◽

Shouwei Li ◽

Tao Jiang

Keyword(s):

Prognostic Factor ◽

Network Analysis ◽

Targeted Therapies ◽

Correlation Network ◽

Lower Grade ◽

Gene Expressions ◽

Who Grade ◽

Lower Grade Glioma ◽

Idh Mutations ◽

Weighted Correlation

Background. Glioma is the most common and lethal tumor in the central nervous system (CNS). More than 70% of WHO grade II/III gliomas were found to harbor isocitrate dehydrogenase (IDH) mutations which generated targetable metabolic vulnerabilities. Focusing on the metabolic vulnerabilities, some targeted therapies, such as NAMPT, have shown significant effects in preclinical and clinical trials. Methods. We explored the TCGA as well as CGGA database and analyzed the RNA-seq data of lower grade gliomas (LGG) with the method of weighted correlation network analysis (WGCNA). Differential expressed genes were screened, and coexpression relationships were grouped together by performing average linkage hierarchical clustering on the topological overlap. Clinical data were used to conduct Kaplan–Meier analysis. Results. In this study, we identified ACAA2 as a prognostic factor in IDH mutation lower grade glioma with the method of weighted correlation network analysis (WGCNA). The difference of ACAA2 gene expressions between the IDH wild-type (IDH-WT) group and the IDH mutant (IDH-MUT) group suggested that there may be different potential targeted therapies based on the fatty acid metabolic vulnerabilities, which promoted the personalized treatment for LGG patients.

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An independently validated survival nomogram for lower-grade glioma

Neuro-Oncology ◽

10.1093/neuonc/noz191 ◽

2019 ◽

Vol 22 (5) ◽

pp. 665-674 ◽

Cited By ~ 12

Author(s):

Haley Gittleman ◽

Andrew E Sloan ◽

Jill S Barnholtz-Sloan

Keyword(s):

Health Care ◽

Brain Tumor ◽

Health Care Providers ◽

Molecular Subtype ◽

Lower Grade ◽

Newly Diagnosed ◽

Care Providers ◽

Lower Grade Glioma ◽

Grade Ii ◽

Online Software

Abstract Background Gliomas are the most common primary malignant brain tumor. Diffuse low-grade and intermediate-grade gliomas, which together compose the lower-grade gliomas (LGGs; World Health Organization [WHO] grades II and III), present a therapeutic challenge to physicians due to the heterogeneity of their clinical behavior. Nomograms are useful tools for individualized estimation of survival. This study aimed to develop and independently validate a survival nomogram for patients with newly diagnosed LGG. Methods Data were obtained for newly diagnosed LGG patients from The Cancer Genome Atlas (TCGA) and the Ohio Brain Tumor Study (OBTS) with the following variables: tumor grade (II or III), age at diagnosis, sex, Karnofsky performance status (KPS), and molecular subtype (IDH mutant with 1p/19q codeletion [IDHmut-codel], IDH mutant without 1p/19q codeletion, and IDH wild-type). Survival was assessed using Cox proportional hazards regression, random survival forests, and recursive partitioning analysis, with adjustment for known prognostic factors. The models were developed using TCGA data and independently validated using the OBTS data. Models were internally validated using 10-fold cross-validation and externally validated with calibration curves. Results A final nomogram was validated for newly diagnosed LGG. Factors that increased the probability of survival included grade II tumor, younger age at diagnosis, having a high KPS, and the IDHmut-codel molecular subtype. Conclusions A nomogram that calculates individualized survival probabilities for patients with newly diagnosed LGG could be useful to health care providers for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free online software for implementing this nomogram is provided: https://hgittleman.shinyapps.io/LGG_Nomogram_H_Gittleman/. Key Points 1. A survival nomogram for lower-grade glioma patients has been developed and externally validated. 2. Free online software for implementing this nomogram is provided allowing for ease of use by practicing health care providers.

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Cell cycle and apoptosis regulatory protein (CARP)-1 expression in neuroblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9578 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9578-9578

Author(s):

Santosh S. Hanmod ◽

Samantha Siegel ◽

James Hatfield ◽

Edi Levi ◽

Marwan Zidan ◽

...

Keyword(s):

Small Sample Size ◽

Regulatory Protein ◽

Tumor Biology ◽

Progression Free Survival ◽

Small Sample ◽

Immune Histochemistry ◽

Formalin Fixed Paraffin ◽

Number Of Patients ◽

Significant Difference ◽

Formalin Fixed Paraffin Embedded

9578 Background: Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. The prognosis for patients with high risk NB is still poor. Study of additional prognostic factors will enhance current understanding of the tumor biology and risk stratification. CARP-1 is a recently identified molecule mediating apoptosis signaling by agents like doxorubicin and etoposide. Since these agents are used in the front line treatment of NB, we tested whether CARP-1 expression could be another prognostic factor in NB. Methods: CARP-1 expression was examined by Western blot in a pair of NB cell lines, SK-N-SH and SK-N-SH Dox. We reviewed medical records of patients with NB at Children’s Hospital of Michigan from 2000-2009 and examined CARP-1 expression by immune-histochemistry in the archived, formalin fixed paraffin embedded NB tissues. CARP-1 expression was recorded as positive or negative. Correlation of CARP-1 expression and progression free survival (PFS) was calculated. Results: CARP-1 expression was detected in SK-N-SH but not SK-N-SH Dox, a doxorubicin-resistant derivative of SK-N-SH, suggesting that resistance to doxorubicin is associated with decreased level of CARP-1 expression in NB cells. Of the 30 cases studied, 53 % (16/30) expressed CARP-1. There was no significant difference in N-myc amplification status (13% vs.14%, p=0.3), or proportion of unfavorable Shimada histology (60% vs. 64%, p=0.5) between CARP-1 positive vs. negative groups. Twenty three percent (7/22) patients progressed or relapsed, including 2/16 (13%) in CARP-1 positive group vs. 5/14 (36%) in CARP-1 negative group (p=0.1). There was no significant difference in the PFS at 1 year (94% vs.79%, p=0.2) and 3 year (86% vs.71%, p=0.2) between CARP-1 positive vs. negative groups. Conclusions: CARP-1 expression was decreased in doxorubicin resistant NB cell line. CARP-1 expression was detected in approximately half (53%) of NB tumors. Patients with NB who expressed CARP-1 showed trend towards better 1- & 3-year PFS as compared to those who did not express CARP-1, however, the results are not statistically significant which could be due to the small sample size. Further study with a larger number of patients is warranted to clarify these findings.

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Histological evaluation of the intestine of broiler chickens: comparison of three sampling methods

Semina Ciências Agrárias ◽

10.5433/1679-0359.2021v42n6p3247 ◽

2021 ◽

Vol 42 (6) ◽

pp. 3247-3258

Author(s):

Marielen de Souza ◽

◽

Claudineia Emidio Cicero ◽

Maísa Fabiana Menck-Costa ◽

Larissa Justino ◽

...

Keyword(s):

Broiler Chickens ◽

Histological Analysis ◽

Relevant Information ◽

Histological Evaluation ◽

Standard Diet ◽

Sample Collection ◽

Tissue Samples ◽

Transversal Section ◽

Significant Difference ◽

Precise Diagnosis

After the growth-promoting antibiotics prohibition, intestinal health became an increasing concern worldwide in poultry farming. The intestinal histological evaluation is an inexpensive technique that brings relevant information, but in poultry, the immediate process of intestinal post-mortem autolysis interferes directly on the samples quality for histological analysis hindering a precise diagnosis. This study aimed to standardize a technique for broilers’ intestines sample collection and fixation for histological analysis. Seven broiler chickens received a standard diet until 23 days of age when they were euthanized. Fragments of duodenum, jejunum, and ileum were collected using three methods: intestine strips, transverse section, and Swiss roll and posteriorly fixed in 10% buffered formalin and bouin solution. Tissue samples were submitted for histological (number of villi and viable villi per field) and morphometrical (villi height, crypt depth and villi:crypt ratio) evaluations and the results analyzed statistically. A significant high number of villi and viable villi per field in all regions was observed in the Swiss roll method. In the duodenum (p= 0.0066) and jejunum (p= 0.0058) an interaction between the Swiss roll method and the fixative buffered formalin was observed in the viable and number of villi per field, respectively. Regarding the morphometrical analysis significant differences were observed, in the jejunum villi height sampling by the methods Swiss roll (1,157.66 ± 148.25 μm, p= 0.0015) that showed the highest mean. Deeper crypt depths were observed in the jejunum (156.59 ± 15.68 μm, p= 0.0002) and ileum (131.13 ± 15.01 μm, p= 0.0006) collect by the Swiss roll method. An interaction between the bouin fixative was also observed in the jejunum (p= 0.0223) for this variable. Duodenum sampling by transversal section (12.68 ± 1.45 μm, p= 0.0076) was the only segment that had a significant difference for villi:crypt ratio, showing the highest mean. It can be concluded that the Swiss roll technique was the best method for morphometrical evaluation of the chickens’ intestines, since the highest counts of villi per field and viable villi per field were obtained, while buffered formalin was considered as the best fixative.

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MPC-2 Clinical course and prognosis of lower-grade glioma, IDH wildtype and pTERT mutant

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab159.058 ◽

2021 ◽

Vol 3 (Supplement_6) ◽

pp. vi16-vi16

Author(s):

Yoshinobu Takahashi ◽

Hayato Takeuchi ◽

Seisuke Tanigawa ◽

Takanari Okamoto ◽

Naoya Hashimoto

Keyword(s):

Median Survival ◽

Lower Grade ◽

Diffuse Astrocytoma ◽

Who Grade ◽

Female Ratio ◽

Astrocytic Glioma ◽

Tert Promoter ◽

Lower Grade Glioma ◽

Idh Mutations ◽

Astrocytic Gliomas

Abstract Background and Purpose: In the cIMPACT-Now update 3, it was proposed that grade 2 astrocytic gliomas without IDH-mutations and grade 3 astrocytic gliomas with TERT promoter mutations should be designated as diffuse IDH wildtype astrocytic glioma with molecular features of WHO grade IV glioblastoma. Therefore, we investigated whether this group of tumors actually corresponds to grade IV prognostically in cases that we encountered ourselves. Cases and Methods: Among the 65 patients having primary astrocytic glioma who were operated in our hospital from January 2016 to March 2021, the prognostic values of seven patients with lower-grade glioma, IDH wildtype, and pTERT mutant were investigated. Results: Among the seven patients, the median age was 59 years (50–66 years). Four of them had anaplastic astrocytoma, two had diffuse astrocytoma, and no tumor lesion could be identified upon histological examination for one patient. The male-to-female ratio was 1:6. MGMT methylation was observed in two patients (29%). The median survival was 20 months, with a significantly worse prognosis when compared with lower-grade glioma without the TERT promoter mutation (13 patients: median survival 40 months), but a better prognosis when compared with glioblastoma (45 patients: median survival 13 months) (Log-rank p = 0.0051). Conclusion: Although EGFR amplification, combined whole chromosome 7 gain, and whole chromosome 10 loss were not examined, the prognostic value of lower-grade glioma, IDH wildtype, and pTERT mutant was not as poor as that of glioblastoma. Further investigation is required to confirm whether these groups of tumors should be treated in the same way as grade IV glioblastoma.

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