scholarly journals Preferential Tumor Localization in Relation to 18F-FDOPA Uptake for Lower-Grade Gliomas

2021 ◽  
Author(s):  
Hiroyuki Tatekawa ◽  
Hiroyuki Uetani ◽  
Akifumi Hagiwara ◽  
Jingwen Yao ◽  
Talia C. Oughourlian ◽  
...  
Keyword(s):  
Frontal Lobe ◽  
Standardized Uptake Value ◽  
Tumor Segmentation ◽  
Tumor Localization ◽  
Lower Grade ◽  
Wild Type ◽  
Who Grade ◽  
Positron Emission ◽  
Grade Ii ◽  
Differential Involvement

Abstract PurposeAlthough tumor localization and 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine (FDOPA) uptake may have an association, preferential tumor localization in relation to FDOPA uptake is yet to be investigated in lower-grade gliomas (LGGs). This study aimed to identify differences in the frequency of tumor localization between FDOPA hypometabolic and hypermetabolic LGGs using a probabilistic radiographic atlas.MethodsFifty-one patients with newly diagnosed LGG (WHO grade II, 29; III, 22; isocitrate dehydrogenase wild-type, 21; mutant 1p19q non-codeleted ,16; mutant codeleted, 14) who underwent FDOPA positron emission tomography (PET) were retrospectively selected. Semiautomated tumor segmentation on FLAIR was performed. Patients with LGGs were separated into two groups (FDOPA hypometabolic and hypermetabolic LGGs) according to the normalized maximum standardized uptake value of FDOPA PET (a threshold of the uptake in the striatum) within the segmented regions. Spatial normalization procedures to build a 3D MRI-based atlas using each segmented region were validated by an analysis of differential involvement statistical mapping.ResultsSuperimposition of regions of interest showed a high number of hypometabolic LGGs localized in the frontal lobe, while a high number of hypermetabolic LGGs was localized in the insula, putamen, and temporal lobe. The statistical mapping revealed that hypometabolic LGGs occurred more frequently in the superior frontal gyrus (close to the supplementary motor area), while hypermetabolic LGGs occurred more frequently in the insula. ConclusionRadiographic atlases revealed preferential frontal lobe localization for FDOPA hypometabolic LGGs, which may be associated with relatively early detection.

scholarly journals IDH mutation status is associated with distinct vascular gene expression signatures in lower-grade gliomas

2018 ◽  
Vol 20 (11) ◽  
pp. 1505-1516 ◽  
Author(s):  
Lei Zhang ◽  
Liqun He ◽  
Roberta Lugano ◽  
Kenney Roodakker ◽  
Michael Bergqvist ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Lower Grade ◽  
Idh Mutation ◽  
Wild Type ◽  
Who Grade ◽  
Mutation Status ◽  
Grade Ii ◽  
Grade Ii Glioma

Abstract Background Vascular gene expression patterns in lower-grade gliomas (LGGs; diffuse World Health Organization [WHO] grades II–III gliomas) have not been thoroughly investigated. The aim of this study was to molecularly characterize LGG vessels and determine if tumor isocitrate dehydrogenase (IDH) mutation status affects vascular phenotype. Methods Gene expression was analyzed using an in-house dataset derived from microdissected vessels and total tumor samples from human glioma in combination with expression data from 289 LGG samples available in the database of The Cancer Genome Atlas. Vascular protein expression was examined by immunohistochemistry in human brain tumor tissue microarrays (TMAs) representing WHO grades II–IV gliomas and nonmalignant brain samples. Regulation of gene expression was examined in primary endothelial cells in vitro. Results Gene expression analysis of WHO grade II glioma indicated an intermediate stage of vascular abnormality, less severe than that of glioblastoma vessels but distinct from normal vessels. Enhanced expression of laminin subunit alpha 4 (LAMA4) and angiopoietin 2 (ANGPT2) in WHO grade II glioma was confirmed by staining of human TMAs. IDH wild-type LGGs displayed a specific angiogenic gene expression signature, including upregulation of ANGPT2 and serpin family H (SERPINH1), connected to enhanced endothelial cell migration and matrix remodeling. Transcription factor analysis indicated increased transforming growth factor beta (TGFβ) and hypoxia signaling in IDH wild-type LGGs. A subset of genes specifically induced in IDH wild-type LGG vessels was upregulated by stimulation of endothelial cells with TGFβ2, vascular endothelial growth factor, or cobalt chloride in vitro. Conclusion IDH wild-type LGG vessels are molecularly distinct from the vasculature of IDH-mutated LGGs. TGFβ and hypoxia-related signaling pathways may be potential targets for anti-angiogenic therapy of IDH wild-type LGG.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

scholarly journals The Expression of Progesterone Receptors in Meningiomas of Different Grades

2019 ◽  
Vol 8 (2) ◽  
pp. 65-69
Author(s):  
Mohammad Tahir ◽  
Tehreem Atif ◽  
Summaya Sohail ◽  
Arfa Nawazish ◽  
Huma Mushtaq
Keyword(s):  
Progesterone Receptor ◽  
Treatment Options ◽  
Progesterone Receptors ◽  
Lower Grade ◽  
Immunoperoxidase Method ◽  
Nuclear Staining ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Background: Meningiomas are slow growing intracranial and intraspinal neoplasms with a tendency to recur locally. WHO grades them as I (benign), II (atypical) and III (anaplastic) in order of their increasing aggressiveness, based on histological parameters and brain parenchymal invasion. Progesterone receptors (PR) are more prevalent amongst the lower grade meningiomas. The objective of this study was to determine the immunohistochemical expression of progesterone receptors in meningiomas of different grades.Material and Methods: A total of 100 cases were selected over a period of 2.5 years. Three to five microns’ thick sections stained with Hematoxylin and Eosin were examined microscopically by a team of two Histopathologists and graded into grades I, II and III, according to 2016 WHO classification criteria. Another section of the original tumor was stained with progesterone receptor antibody using the conventional immunoperoxidase method. Stained slides were than examined by the same team of Histopathologists and declared positive (if nuclear staining was observed in more than 10% of tumor cells) or negative. Statistical analysis was done using SPSS version 21.Results: Out of a total of 100 cases of meningioma, there were 79 cases of benign/typical WHO grade I, 15 cases of atypical/ WHO grade II and 6 cases of anaplastic/ WHO grade III tumor. PR status was positive in 89.8 % (71/79) of grade I meningiomas and 46.6 % (7/15) of grade II/Atypical meningiomas. The 06 cases of Anaplastic/WHO grade III tumors were negative for PR. There was a higher prevalence of Progesterone receptors in female patients (89.8%; 53/59) as compared to male meningioma patients (60.9%; 25/41).Conclusion: We observed a decreased expression of progesterone receptor in higher grades of meningioma in this study. It is an effort to explore conservative treatment options for inoperable lesions, as anti-progesterone therapy may hold a promise as a new treatment option in the near future.

scholarly journals Huge heterogeneity in survival in a subset of adult patients with resected, wild-type isocitrate dehydrogenase status, WHO grade II astrocytomas

2019 ◽  
Vol 130 (4) ◽  
pp. 1289-1298 ◽  
Author(s):  
Gaëtan Poulen ◽  
Catherine Gozé ◽  
Valérie Rigau ◽  
Hugues Duffau
Keyword(s):  
Radiation Therapy ◽  
Malignant Transformation ◽  
Isocitrate Dehydrogenase ◽  
Adult Patients ◽  
World Health ◽  
Wild Type ◽  
Who Grade ◽  
Grade Ii ◽  
The Individual

OBJECTIVEWorld Health Organization grade II gliomas are infiltrating tumors that inexorably progress to a higher grade of malignancy. However, the time to malignant transformation is quite unpredictable at the individual patient level. A wild-type isocitrate dehydrogenase (IDH-wt) molecular profile has been reported as a poor prognostic factor, with more rapid progression and a shorter survival compared with IDH-mutant tumors. Here, the oncological outcomes of a series of adult patients with IDH-wt, diffuse, WHO grade II astrocytomas (AII) who underwent resection without early adjuvant therapy were investigated.METHODSA retrospective review of patients extracted from a prospective database who underwent resection between 2007 and 2013 for histopathologically confirmed, IDH-wt, non–1p19q codeleted AII was performed. All patients had a minimum follow-up period of 2 years. Information regarding clinical, radiographic, and surgical results and survival were collected and analyzed.RESULTSThirty-one consecutive patients (18 men and 13 women, median age 39.6 years) were included in this study. The preoperative median tumor volume was 54 cm3 (range 3.5–180 cm3). The median growth rate, measured as the velocity of diametric expansion, was 2.45 mm/year. The median residual volume after surgery was 4.2 cm3 (range 0–30 cm3) with a median volumetric extent of resection of 93.97% (8 patients had a total or supratotal resection). No patient experienced permanent neurological deficits after surgery, and all patients resumed a normal life. No immediate postoperative chemotherapy or radiation therapy was given. The median clinical follow-up duration from diagnosis was 74 months (range 27–157 months). In this follow-up period, 18 patients received delayed chemotherapy and/or radiotherapy for tumor progression. Five patients (16%) died at a median time from radiological diagnosis of 3.5 years (range 2.6–4.5 years). Survival from diagnosis was 77.27% at 5 years. None of the 21 patients with a long-term follow-up greater than 5 years have died. There were no significant differences between the clinical, radiological, or molecular characteristics of the survivors relative to the patients who died.CONCLUSIONSHuge heterogeneity in the survival data for a subset of 31 patients with resected IDH-wt AII tumors was observed. These findings suggest that IDH mutation status alone is not sufficient to predict risk of malignant transformation and survival at the individual level. Therefore, the therapeutic management of AII tumors, in particular the decision to administer early adjuvant chemotherapy and/or radiation therapy following surgery, should not solely rely on routine molecular markers.

scholarly journals The Relationship Between IDH1 Mutation Status and Metabolic Imaging in Nonenhancing Supratentorial Diffuse Gliomas: A 11C-MET PET Study

2019 ◽  
Vol 18 ◽  
pp. 153601211989408
Author(s):  
Nijiati Kudulaiti ◽  
Huiwei Zhang ◽  
Tianming Qiu ◽  
Junfeng Lu ◽  
Abudumijiti Aibaidula ◽  
...  
Keyword(s):  
Standardized Uptake Value ◽  
Idh1 Mutation ◽  
Metabolic Imaging ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Mutation Status ◽  
Positron Emission ◽  
Diffuse Gliomas ◽  
The Relationship ◽  
Met Pet

Purpose: We evaluated the relationship between isocitrate dehydrogenase 1 (IDH1) mutation status and metabolic imaging in patients with nonenhancing supratentorial diffuse gliomas using 11C-methionine positron emission tomography (11C-MET PET). Materials and Methods: Between June 2012 and November 2017, we enrolled 86 (38 women and 48 men; mean age, 41.9 ± 13.1 years [range, 8-67 years]) patients with newly diagnosed supratentorial diffuse gliomas. All patients underwent preoperative 11C-MET PET. Tumor samples were obtained and immunohistochemically analyzed for IDH1 mutation status. Results: The mutant and wild-type IDH1 diffuse gliomas had significantly different mean maximum standardized uptake value values (2.73 [95% confidence interval, CI: 2.32-3.16] vs 3.85 [95% CI: 3.22-4.51], respectively; P = .004) and mean tumor-to-background ratio (1.90 [95% CI: 1.65-2.16] vs 2.59 [95% CI: 2.17-3.04], respectively; P = .007). Conclusions: 11C-methionine PET can noninvasively evaluate the IDH1 mutation status of patients with nonenhancing supratentorial diffuse gliomas.

scholarly journals P14.95 Is the pathological-grade relevant in “IDH-wild type, TERT-mutant” diffuse-gliomas? An analysis in 147 patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii90-iii90
Author(s):  
A E Danyeli ◽  
C B Akyerli ◽  
A Dinçer ◽  
E Coşgun ◽  
U Abacıoğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Lower Grade ◽  
Wild Type ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Tert Promoter ◽  
Diffuse Gliomas

Abstract BACKGROUND Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics. MATERIAL AND METHODS 147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival. RESULTS Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007). CONCLUSION Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.

scholarly journals NIMG-12. 18F-FLUORETHYLTYROSINE POSITRON EMISSION TOMOGRAPHY VERSUS MAGNETIC RESONANCE SPECTROSCOPY IN PREOPERATIVE DETECTION OF NEWLY DIAGNOSED GLIOMAS BY USING MACHINE LEARNING

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii149-ii149
Author(s):  
Lazaros Lazaridis ◽  
Sied Kebir ◽  
Manuel Weber ◽  
Teresa Schmidt ◽  
Kathy Keyvani ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Emission Tomography ◽  
Resonance Spectroscopy ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Fet Pet ◽  
Positron Emission ◽  
Grade Ii

Abstract BACKGROUND Advanced imaging techniques entered the field of neurooncology. In this analysis we compare the diagnostic potential of 18F-fluorethyltyrosine (FET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) in their potential to preoperatively predict certain glioma subtypes. AIMS Goal of this analysis ist the evaluation of FET PET and MRS regarding the preoperative prediction of glioma subtypes. METHODS We analyzed 33 patients with histopathologically confirmed newly diagnosed glioma. The patients received FET PET and MRS during one single preoperative diagnostic session. According to the molecular portfolio patients were subdivided in IDH wildtype glioblastoma patients (GBM), IDH wildtype WHO grade II/III glioma patients (Astro_IDHwt), IDH mutant WHO grade II/III glioma patients without 1p/19q codeletion (Astro_IDHmut) and with 1p/19q codeletion (ODG). Mean and maximum tumor-to-brain ratio (TBRmean and TBRmax), N-acetylaspartate, choline and creatine peaks were correlated with postoperative tumor diagnosis. To gain generalizable implications we subdivided the study cohort into a development and validation subcohort. A support vector machine model was fitted to the development subcohort and evaluated on the validation subcohort. Receiver operating characteristic curve served to assess model performance. RESULTS GBM patients had highest TBRmax and TBRmean values (mean: 3.5 and 3.8) and the ODG patients showed the second highest TBRmax and TBRmean values (mean: 2.6 and 3). The distribution of MRS markers exhibited to clear trend. The performance of glioma subtyping was comparatively low for the TBR values (AUC: 0.68) and even lower for the MRS markers (AUC: 0.60). These results are in line with preliminary investigations performed by our institute for the comparison of 11C-methionine PET with MRS in preoperative glioma subtyping. CONCLUSIONS FET PET and MRS bear limited potential in glioma subgrouping. However, FET PET appears to be slightly superior. Investigation in a larger cohort is required to draw definite conclusions.

Clinical, histopathological, and molecular analyses of IDH-wild-type WHO grade II–III gliomas to establish genetic predictors of poor prognosis

2019 ◽  
Vol 36 (4) ◽  
pp. 135-143 ◽  
Author(s):  
Kiyonori Kuwahara ◽  
Shigeo Ohba ◽  
Shunsuke Nakae ◽  
Natsuki Hattori ◽  
Eriel Sandika Pareira ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Wild Type ◽  
Who Grade ◽  
Molecular Analyses ◽  
Genetic Predictors ◽  
Grade Ii

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

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.

scholarly journals OS10.1 Survival analysis of IDH wildtype astrocytomas with molecular features of glioblastoma, WHO grade IV

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii20-iii20 ◽  
Author(s):  
C M S Tesileanu ◽  
J A F Koekkoek ◽  
L Dirven ◽  
H J Dubbink ◽  
J M Kros ◽  
...  
Keyword(s):  
Molecular Data ◽  
Lower Grade ◽  
Who Grade ◽  
Historical Cohort ◽  
Molecular Features ◽  
Tert Promoter ◽  
Significant Difference ◽  
Tert Promoter Mutations ◽  
Grade Ii ◽  
Promoter Mutations

Abstract BACKGROUND Recently, isocitrate dehydrogenase wildtype (IDHwt) lower grade gliomas (LGGs) that have a telomerase reverse transcriptase (TERT) promoter mutation and/or gain of chromosome 7 combined with loss of chromosome 10 and/or epidermal growth factor receptor amplification have been reclassified as IDHwt astrocytomas with molecular features of glioblastoma, WHO grade IV (‘astrocytomas IDHwt, WHO IV’). Survival of these tumors meeting the criteria of these tumors is less well studied. The objective of this study is to compare the overall survival (OS) between the IDHwt astrocytomas, WHO IV and histological glioblastomas (GBMs). MATERIAL AND METHODS In this retrospective multicenter cohort study, all adult patients with a newly diagnosed IDHwt LGG (histologically WHO grade II or III) and with molecular data available were selected from the Erasmus MC and the LUMC from October 2002 to April 2019. LGG patients showing contrast enhancement with necrosis on the MRI at the time of histological diagnosis were excluded. Molecular data were determined using a diagnostic NGS panel. A historical cohort of 195 patients with IDHwt GBMs with molecular data available was used to compare OS. OS was measured from the date of the first diagnostic MR scan. RESULTS 79 IDHwt LGG patients were identified of which 62 patients had molecular features of glioblastoma (‘astrocytomas IDHwt, WHO IV’), 11 patients did not have these molecular features (‘astrocytomas IDHwt, WHO II & III’). In the remaining 6 patients the molecular data were not conclusive (astrocytomas IDHwt, WHO NOS). Patients with astrocytomas IDHwt, WHO IV were slightly older at diagnosis (median age = 57 years) than patients with GBMs IDHwt in the reference cohort or astrocytomas IDHwt, WHO II & III (respectively: median age 55 years, p=0.032 and 47 years, p=0.035). The relatively young age of our GBM IDHwt cohort reflects more extensive molecular testing in younger patients and histologically lower grade tumors. The median OS of astrocytomas IDHwt, WHO IV (23.8 months) was similar to the median OS of GBMs (19.2 months, log-rank test p=0.37). The median OS in 19 patients with only TERT promoter mutations was 16.8 months, similar to GBMs (p=0.94). CONCLUSION There is no statistically significant difference between the OS of IDHwt astrocytomas with molecular features of glioblastoma and the OS of true glioblastomas. Grade II and III IDHwt astrocytoma with molecular features of glioblastoma should be designated WHO grade IV. The presence of TERT promoter mutations alone in this histological context also qualifies for this designation.

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