NIMG-01. T2WI-FLAIR MISMATCH SIGN IN LOWER GRADE GLIOMA AND DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR

Abstract BACKGROUND T2-FLAIR mismatch sign was reported as a specific imaging marker for diffuse astrocytoma with IDH-mutant and 1p/19q non-codeletion. However, most of the previous studies for T2-FLAIR mismatch were confirmed only among lower grade glioma (LGG). The purpose of this study is to explore the T2-FLAIR mismatch sing in supratentorial non-enhancing tumor including LGG and dysembryoplastic neuroepithelial tumor (DNET) and to unveil the exception rules of the sign. METHODS Forty-four patients of non-enhancing LGG and DNET were included in this study. LGG（diffuse astrocytoma with IDH mutant (IDHmut-Noncodel), oligodendroglioma with IDH-mutant and 1p19q codeletion (IDHmut-Codel), diffuse astrocytoma with IDH wildtype (IDHwt)）and DNET were diagnosed based on WHO 2016 classification. The tumors were evaluated MRI by 2 independent reviewers to assess presence or absence of T2-FLAIR mismatch sign. CT was also performed to evaluate the localized thinning of the skull bone. Inter-reviewer agreement with Cohen’s kappa (κ) was calculated. RESULT: Ten out of 18 cases (55.6%) of IDHmut-Noncodel presented T2-FLAIR mismatch sign. None of the other LGG (IDHmut-Codel and IDHwt) presented T2-FLAIR mismatch. Eight out of 11 cases (72.7%) of DNET also present the T2-FLAIR mismatch. The overlying part of the skull bone thinning was observed in 5 cases of DNET, but none of LGG presented the localized skull bone thinning. The inter-rater agreement for the T2-FLAIR mismatch and the localized thinning of the skull bone were excellent (κ= 1.00). CONCLUSION The T2-FLAIR mismatch sign was specific marker for IDHmut-Noncodel among LGG. However, DNET also presented the T2-FLAIR mismatch sign. The localized skull bone thinning could be useful for differentiating between IDHmut-Noncodel and DNET

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NI-17 T2-FLAIR MISMATCH SIGN IN DIFFUSE GLIOMA AND DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.128 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii28-ii28

Author(s):

Shumpei Onishi ◽

Fumiyuki Yamasaki ◽

Motoki Takano ◽

Ushio Yonezawa ◽

Kazuhiko Sugiyama ◽

...

Keyword(s):

Low Grade Glioma ◽

The Other ◽

Dysembryoplastic Neuroepithelial Tumor ◽

Specific Marker ◽

Low Grade ◽

Diffuse Glioma ◽

Diffuse Astrocytoma ◽

Predictive Values ◽

1P19q Codeletion ◽

Diffuse Midline Glioma

Abstract BACKGROUND T2-FLAIR mismatch sign was reported as a specific imaging marker for diffuse astrocytoma with IDH-mutant and 1p/19q non-codeletion. However, most of the previous studies for T2-FLAIR mismatch were confirmed only among low grade glioma. The purpose of this study is to assess the T2-FLAIR mismatch sign in supratentorial diffuse glioma, diffuse midline glioma and dysembryoplastic neuroepithelial tumor (DNT) to unveil the exception rules of the sign. METHODS In total, 51 patients were included in this study; 33 supratentorial diffuse glioma (18 diffuse astrocytoma with IDH mutant (IDHmut-Noncodel), 12 oligodendroglioma with IDH-mutant and 1p19q codeletion (IDHmut-Codel), 3 diffuse astrocytoma with IDH wildtype (IDHwt)), 18 diffuse midline glioma and 11 DNT. The tumors were evaluated by 2 independent reviewers to assess presence or absence of T2-FLAIR mismatch sign. RESULT Ten out of 18 cases of IDHmut-Noncodel presented T2-FLAIR mismatch sign. None of the other supratentorial diffuse glioma (IDHmut-Codel and IDHwt) presented T2-FLAIR mismatch. The T2-FLAIR mismatch sign for IDHmut-Noncodel presented 100% positive predictive values among supratentorial diffuse glioma. However, 8 out of 18 cases of diffuse midline glioma and 8 out of 11 cases of DNT also presented the T2-FLAIR mismatch. CONCLUSION The T2-FLAIR mismatch sign was specific marker for IDHmut-NonCodel among supratentorial diffuse glioma. Physicians need to be aware that diffuse midline glioma and DNT could present the T2-FLAIR mismatch sign.

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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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NI-13 Prediction of outcome at the time of discontinuing TMZ-adjuvant therapy in IDH-mutant lower grade glioma using 11C-methinine PET

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab159.075 ◽

2021 ◽

Vol 3 (Supplement_6) ◽

pp. vi20-vi20

Author(s):

Takaaki Beppu ◽

Yuichi Sato ◽

Toshiaki Sasaki ◽

Kazunori Terasaki ◽

Takeshi Iwaya ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Univariate Analysis ◽

Methylation Status ◽

Normal Brain ◽

Lower Grade ◽

Diffuse Astrocytoma ◽

Cox Regression Analysis ◽

Cutoff Values ◽

Lower Grade Glioma ◽

Met Pet

Abstract Purpose: This study aimed to clarify whether positron emission tomography with 11C-methyl-L-methionine (11C-met PET) can predict consequential outcomes at the time of discontinuing temozolomide (TMZ)-adjuvant chemotherapy in patients with residual isocitrate dehydrogenase gene (IDH)-mutant lower-grade glioma.Methods: In 30 patients showing residual lesions of IDH-mutant lower grade glioma (16 with diffuse astrocytoma and 14 with anaplastic astrocytoma), we performed 11C-met PET, and calculated the tumor-to-normal brain tissue ratio of standardized uptake values (SUVT/N) at the time of discontinuing TMZ-adjuvant chemotherapy. We determined cutoff values to predict tumor relapse using the receiver operating characteristic curve for various prognostic factors including age, Karnofsky performance scale, number of courses of therapy, residual tumor size, and SUVT/N. The promotor methylation status of O6-methylguanine-DNA methyl-transferase gene (MGMT) was assessed using methylation-specific polymerase chain reaction. Progression-free survival (PFS) was compared between groups divided by cutoff values. Uni- and multivariate analyses were conducted using log-rank testing and Cox regression analysis, respectively.Results: Univariate analysis identified MGMT methylation status (p = 0.04) and an SUVT/N of 1.27 (p = 0.02) as predictors of PFS after TMZ discontinuation. In multivariate analysis, both unmethylated MGMT and SUVT/N ≥ 1.27 remained as strong predictors of unfavorable outcome. Conclusion: The present study suggested that 11C-met PET allows prediction of outcomes comparable to MGMT promotor methylation status at the time of discontinuing TMZ-adjuvant chemotherapy in patients with residual IDH-mutant lower-grade glioma.

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Fractal analysis of 11C-methionine PET in patients with newly diagnosed glioma

EJNMMI Physics ◽

10.1186/s40658-021-00418-y ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Yukito Maeda ◽

Yuka Yamamoto ◽

Takashi Norikane ◽

Katsuya Mitamura ◽

Tetsuhiro Hatakeyama ◽

...

Keyword(s):

Fractal Dimension ◽

Fractal Analysis ◽

Anaplastic Astrocytoma ◽

Idh1 Mutation ◽

Lower Grade ◽

Diffuse Astrocytoma ◽

Newly Diagnosed ◽

Mutation Status ◽

Lower Grade Glioma ◽

Met Pet

Abstract Background The present study tested the possible utility of fractal analysis from l-[methyl-11C]-methionine (MET) uptake in patients with newly diagnosed gliomas for differentiating glioma, especially in relation to isocitrate dehydrogenase 1 (IDH1) mutation status, and as compared with the conventional standardized uptake value (SUV) parameters. Methods Investigations of MET PET/CT were performed retrospectively in 47 patients with newly diagnosed glioma. Tumors were divided into three groups: lower grade glioma (IDH1-mutant diffuse astrocytoma and IDH1-mutant anaplastic astrocytoma), higher grade glioma (IDH1-wildtype diffuse astrocytoma and IDH1-wildtype anaplastic astrocytoma), and glioblastoma. The fractal dimension for tumor, maximum SUV (SUVmax) for tumor (T) and mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) and total lesion MET uptake (TLMU) were also measured. Results There were significant differences in SUVmax (p = 0.006) and T/N ratio (p = 0.02) between lower grade glioma and glioblastoma. There were no significant differences among any of the three groups in MTV or TLMU. Significant differences were obtained in the fractal dimension between lower grade glioma and higher grade glioma (p = 0.006) and glioblastoma (p < 0.001). Conclusions The results of this preliminary study in a small patient population suggest that the fractal dimension using MET PET in patients with newly diagnosed gliomas is useful for differentiating glioma, especially in relation to IDH1 mutation status, which has not been possible with SUV parameters.

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MPC-18 CATEGORIZATION OF LOWER GRADE GLIOMA USING ONCOPANEL

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.113 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii25-ii25

Author(s):

Hiroyuki Uchida ◽

Toshiaki Akahane ◽

Nayuta Higa ◽

Mari Kirishima ◽

Tsubasa Hiraki ◽

...

Keyword(s):

Genetic Alterations ◽

Lower Grade ◽

Diffuse Glioma ◽

Diffuse Astrocytoma ◽

Idh Mutation ◽

Who Grade ◽

Egfr Amplification ◽

Integrated Diagnosis ◽

Lower Grade Glioma ◽

Tert Mutation

Abstract PURPOSE We are developing a 48-gene OncoPanel (Kagoshima Brain Tumor 48 OncoPanel) specializing in glioma diagnosis. Clinical application of genetic diagnosis derived from genetic alterations detected by OncoPanel, including IDH mutation, 1p/19q-codeletion, and other gene mutations in lower-grade glioma was verified. METHODS The 48 genes consist of 24 genes related to glioma and 24 genes on chromosomes 1 and 19. DNA was extracted from tumor FFPE samples and blood samples, and then single nucleotide variants and copy number variants were detected using next-generation sequencer. RESULTS Among the 99 diffuse glioma cases that had undergone OncoPanel analysis by July 2019, 40 cases diagnosed histologically as WHO grade 2 or 3 diffuse glioma were included. The integrated diagnosis by conventional gene analysis were Diffuse astrocytoma 10 cases, anaplastic astrocytoma 11 cases, oligodendroglioma 10 cases, anaplastic oligodendroglioma 9 cases. IDH1 mutation was detected in 30 cases, of which in 19 cases 1p/19q-codeletion was detected, all with TERT mutation. Among 11 cases with 1p/19q-non-codeletion, ATRX mutation was detected in 10 cases and was almost mutually exclusive with TERT mutation. In 10 cases without IDH mutation, EGFR amplification or mutation was detected in 6 cases, of which 4 cases were accompanied by TERT mutation. DISCUSSION KBT48 can detect TERT and ATRX mutations in a mutually exclusive manner and can improve the classification accuracy of oligodendroglioma and astrocytoma. Groups with gene profiles similar to glioblastoma with EGFR amplification/mutation and TERT mutation can also be classified. CONCLUSIONS In the diagnostic classification of lower-grade glioma, KBT48 can well classify into oligodendroglioma group, astrocytoma group and glioblastoma-like group, and is considered to be applicable in clinical practice.

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RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma

Scientific Reports ◽

10.1038/s41598-021-91382-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Haiwei Wang ◽

Xinrui Wang ◽

Liangpu Xu ◽

Ji Zhang ◽

Hua Cao

Keyword(s):

Transcription Factor ◽

Low Frequency ◽

Tumor Grade ◽

The Cancer Genome Atlas ◽

Lower Grade ◽

Wild Type ◽

Lower Grade Glioma ◽

Cancer Genome Atlas ◽

Worse Prognosis ◽

Genome Atlas

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.

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QOLP-37. QUALITATIVE RESEARCH IN LOWER GRADE GLIOMA: UNDERSTANDING SIGNS, SYMPTOMS, AND DISEASE IMPACTS DURING EXPECTANT MANAGEMENT

Neuro-Oncology ◽

10.1093/neuonc/noz175.857 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi206-vi206

Author(s):

Audra Boscoe ◽

Ted Wells ◽

Christina Graham ◽

Caitlin Pohl ◽

Brooke Witherspoon ◽

...

Keyword(s):

Treatment Options ◽

Expectant Management ◽

Signs And Symptoms ◽

Molecular Therapy ◽

Patient Specific ◽

Lower Grade ◽

Concept Elicitation ◽

Post Surgery ◽

Lower Grade Glioma ◽

Isocitrate Dehydrogenase Mutation

Abstract BACKGROUND Patients with lower grade glioma (LGG) (i.e., grade II or III) have limited treatment options. After surgical resection of their tumor, patients will undergo either a period of expectant management (watch and wait) or treatment with adjuvant chemotherapy and/or radiotherapy. Approximately 80% of patients with LGG have an isocitrate dehydrogenase mutation, which is a viable target for molecular therapy. This offers a therapeutic intervention that could potentially delay the need for chemotherapy and/or radiotherapy in select patients. Several prognostic and patient-specific factors contribute to the decision to recommend expectant management, including concerns about the side effects of chemotherapy and radiotherapy. The aim of this project was to understand patients’ signs and symptoms during the expectant management period and how LGG impacts their lives. METHODS Concept elicitation interviews were conducted in the US with patients with LGG as well as key opinion leaders (KOLs) with experience treating patients with LGG. Interview data were analyzed using Atlas.ti, and patient data were reviewed against KOL data. RESULTS Seven patients with ≥ 3 months of expectant management experience and three KOLs were interviewed. During their expectant management periods, patients reported 12 signs/symptoms, mostly related to deficits in cognition. Patients reported 16 impacts across four categories, with a substantial proportion of the impacts identified as negatively affecting emotional function. The signs/symptoms and impacts reported by patients were generally also reported by KOLs. During expectant management, patients typically resume their original quality of life post-surgery, but may also experience anxiety. Patients and KOLs indicated a preference for expectant management and delaying chemotherapy or radiotherapy. CONCLUSIONS Patient and KOL interviews characterized the LGG experience and indicated a preference for expectant management, which may be supported by therapies that delay the initiation of chemotherapy and/or radiotherapy.

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Identification and Validation of an Individualized Prognostic Signature of Lower-Grade Glioma Based on Nine Immune Related Long Non-coding RNA

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2020.106464 ◽

2021 ◽

pp. 106464

Author(s):

Aierpati Maimaiti ◽

Lei Jiang ◽

Xixian Wang ◽

Xin Shi ◽

Yinan Pei ◽

...

Keyword(s):

Lower Grade ◽

Prognostic Signature ◽

Non Coding Rna ◽

Lower Grade Glioma ◽

Long Non Coding Rna

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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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