Clinical, radiologic & prognostic profile of IDH wild type diffuse astrocytic glioma with molecular features of glioblastoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2557-2557
Author(s):  
Oluwatosin Akintola ◽  
Wesley Samore ◽  
Maria Martinez-Lage Alvarez ◽  
Elizabeth Robins Gerstner
Keyword(s):  
Clinical Trials ◽  
Methylation Status ◽  
Diffuse Astrocytoma ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Who Grade ◽  
Egfr Amplification ◽  
Astrocytic Glioma ◽  
Molecular Features ◽  
Tert Promoter

2557 Background: In 2018, The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) recommended that IDH-wildtype diffuse astrocytic glioma Grade II/III with either EGFR amplification, combined whole chromosome 7 gain and whole chromosome 10 loss (+7/−10), or TERT promoter mutation should receive an integrated histological and molecular grade classification: Diffuse astrocytic glioma, IDH-wildtype with molecular features of glioblastoma, WHO grade IV. The natural history, radiologic characteristics and standard management for these patients has not been well described. They are typically excluded from clinical trials for WHO Grade IV gliomas. Methods: Adults diagnosed at Massachusetts General Hospital with IDH wildtype diffuse astrocytoma and EGFR amplification or TERT promoter mutation from 2011-2019 were identified. Demographics, functional status, radiologic features, MGMT promoter methylation status, time to progression, and overall survival were collected retrospectively. Qualitative MRI data was analyzed using the VASARI feature set. Response assessment was performed using the RANO criteria. Results: 50 patients were identified (table). 37/50 patients received standard Stupp protocol, 2/50 received hypofractionated radiotherapy with temozolomide, 6/50 received radiotherapy alone, and 1 patient received a MEK inhibitor. None were enrolled in clinical trials at diagnosis. mPFS was 10 months in the 47/50 with confirmed progression and mOS in the patients with confirmed deaths (40/50) was 17.5 months (4-47). 9/50 patients are alive with survival ranging 6-52 months. Conclusions: Outcomes for patients with molecularly defined GBM were variable. Analysis of the cohort to characterize factors that led to the observed variability is in progress. More studies on molecularly defined glioblastomas are required to better understand their behavior and to provide guidance for their inclusion or exclusion in clinical trials. [Table: see text]

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

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.

PATH-19. TERT PROMOTER MUTATION, NOT H3K27M MUTATION IS A PROGNOSTIC FACTOR FOR ADULT THALAMIC GLIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi118-vi119
Author(s):  
Masayuki Nitta ◽  
Yoshihiro Muragaki ◽  
Takashi Komori ◽  
kenta Masui ◽  
Taiichi Saito ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Tumor Resection ◽  
Pathological Diagnosis ◽  
Diffuse Glioma ◽  
Idh Mutation ◽  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Who Grade ◽  
Tert Promoter ◽  
H3k27m Mutation

Abstract Purpose Thalamic diffuse glioma is classified as WHO grade 4 as Diffuse midline glioma, H3K27M mutation if H3K27M mutation was found regardless of its histological findings, but the significance of H3K27M mutation is not clear compared with pediatric cases. We aimed to find genetic prognostic factors in adult thalamic diffuse gliomas. METHODS Pathological diagnosis, genetic abnormalities, and clinical course of adult newly diagnosed thalamic gliomas diagnosed and treated at our institution from July 2007 to March 2020 were retrospectively analyzed. RESULTS The number of cases was 41 (24 males, 17 females), median age was 47 years (20-75 years). Tumor localization was 20 cases on the left, 14 cases on the right, and 7 cases on both sides. The pathological diagnosis was GBM 15 cases, DMG 15 cases, AA-IDH WT 7 cases, DA-IDH WT 4 cases, all of which were IDH wild type, and none of them had IDH mutation and 1p/19q co-deletion. H3K27M mutations were found in 15 cases and TERT promoter mutations were found in 12 cases, both of which were completely mutually exclusive. Tumor resection and biopsy was performed in 33 and 8 cases, respectively, and the median removal rate was 95% for those who underwent tumor resection. The median PFS and OS of all cases were 14.3 months and 38 months, respectively, and the median OS by pathological diagnosis was GBM 12.4 months, DMG 47.4 months, AA-IDH WT 37.3 months, DA-IDH WT not reached. The median OS in the H3K27M mutant group (47.4 months) was significantly better (p=0.02) than that in the TERT promoter mutation group (13.5 months). CONCLUSION There was no IDH mutation in adult thalamic gliomas, the H3K27M mutation and the TERT promoter mutation were mutually exclusive. The H3K27M mutation was not a prognostic factor, but the TERT promoter mutation was the strongest prognostic factor.

TERT promoter mutation is associated with worse prognosis in WHO grade II and III meningiomas

2018 ◽  
Vol 139 (3) ◽  
pp. 671-678 ◽  
Author(s):  
Annamaria Biczok ◽  
Theo Kraus ◽  
Bogdana Suchorska ◽  
Nicole A. Terpolilli ◽  
Jun Thorsteinsdottir ◽  
...  
Keyword(s):  
Tert Promoter Mutation ◽  
Promoter Mutation ◽  
Who Grade ◽  
Tert Promoter ◽  
Grade Ii ◽  
Worse Prognosis

scholarly journals TB-06 Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii7-ii7
Author(s):  
Tomoyuki Nakano ◽  
Kenji Fujimoto ◽  
Takamune Achiha ◽  
Hideyuki Arita ◽  
Mami Yasukawa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Intraperitoneal Administration ◽  
Tert Promoter Mutation ◽  
Malignant Meningioma ◽  
Promoter Mutation ◽  
Who Grade ◽  
Orthotopic Xenograft ◽  
Tert Promoter ◽  
Meningioma Cell

Abstract Meningioma is the most common intracranial tumor, and its prognosis is typically favorable. However, patients of malignant meningioma (WHO grade III) most often experience recurrence, undergo multiple surgical treatments, and have poor prognosis. No effective therapy for malignant meningioma has been established yet. We recently reported an efficacy of eribulin (Haraven®) for glioblastoma. Eribulin is considered to target TERT, which is frequently mutated in its promoter. Since TERT promoter mutation is also found in malignant meningioma, this study aims at investigating the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo. Two meningioma cell lines IOMM-Lee and HKBMM were used in this study. In the viability assay and the flow cytometry, eribulin strongly inhibited cell proliferation by cell cycle arrest. Apoptotic cell death in malignant meningioma cell lines was confirmed by vital dye assay and immunoblotting. Moreover, wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. To assess the effect of eribulin in vivo, orthotopic xenograft mouse models of both malignant meningioma cell lines were constructed. The intraperitoneal administration of eribulin significantly prolonged the survival of meningioma cell lines implanted in the brain (p<0.0001). Furthermore, apoptosis was histologically observed in brain tumor tissue by immunohistochemistry. Thus, this study suggests that eribulin is a potential therapeutic agent for treating malignant meningioma.

scholarly journals TB-04 TERT PROMOTER MUTATION AS A SUSCEPTIBLE MOLECULAR MARKER OF BCNU LOCAL THERAPY

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii10-ii11
Author(s):  
Shigeta Miyake ◽  
Kensuke Tateishi ◽  
Joe Sasame ◽  
Yohei Miyake ◽  
Shinichirou Matsuyama ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Methylation Status ◽  
Malignant Gliomas ◽  
Local Therapy ◽  
Tert Promoter Mutation ◽  
Mgmt Methylation ◽  
Promoter Mutation ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Abstract INTRODUCTION Alkylating agents, including Temozolomide (TMZ) and CCNU (ACNU) have been widely accepted as a standard treatment in malignant gliomas. Several studies also demonstrated that BCNU wafer placement extended survival in glioblastoma patients. However, little study demonstrated gene-specific efficacy of BCNU local therapy in malignant gliomas. Herein, we investigated BCNU sensitivity for patient-derived primary cultured glioma cells. MATERIALS AND METHODS From January 2017 to July 2019, 58 gliomas (grade III, IV) were tested genomic analysis and ATP-based cell viability after BCNU treatment. IDH1/2 mutation and TERT promoter mutation status was determined by Sanger sequencing. MGMT methylation status were evaluated by methylation specific PCR. RESULTS Of 58 cases,10 cases (17.2%) and 32 (55.2%) cases harbored IDH1/2 mutation and TERT mutation (C228T, C250T), respectively. Among them, co-mutation was identified in 5/58 cases (8.6%). MGMT was methylated in 17/58 cases (29.3%). Interestingly, the presence of TERT promoter mutation was positively correlated with BCNU sensitivity, particularly in IDH1/2 wild-type tumors (p<0.05). In contrast, there was no significant relationship between TMZ sensitivity and IDH mutation/MGMT methylation status. CONCLUSION Although sample size is small, our results imply TERT promoter mutations might be a predictive molecular marker for BCNU sensitivity in malignant gliomas. Since TERT mutations are located at two hot spot loci (C228T and C250T), vast majority of TERT promoter mutations can be evaluated during surgery, which may contribute tailored therapeutic strategy in malignant gliomas.

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