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

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.

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

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.

scholarly journals Engrailed 1 overexpression as a potential prognostic marker in Lower Grade Glioma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7414
Author(s):  
Jin Zhu ◽  
Yu-Qi Zhang
Keyword(s):  
Survival Time ◽  
Prognostic Marker ◽  
Cox Regression ◽  
Bioinformatic Analysis ◽  
Idh1 Mutation ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Mutation Status ◽  
Lower Grade Glioma ◽  
Cancer Types

Background Engrailed 1 (EN1), as a member of homeobox-containing transcription factors, participates in the development of the brain. High expressions of EN1 exist in various tumors. However, the role of EN1 in lower grade glioma (LGG) is still unknown. Methods Coefficients of Cox regression were examined by data mining among 13 cancer types using OncoLnc to validate EN1 expressions in LGG patients from The Cancer Genome Atlas database (TCGA). Bioinformatic analysis was performed by using R2 and the UCSC Xena browser based on the data from 273 glioma cases in GSE16011 from GEO datasets and 530 cases of LGG patients in TCGA. Cases in GSE16011 were divided into two groups according to IDH1 mutation status. Cases in TCGA-LGG were classified to subtypes according to histopathological results, IDH1 mutation status and 1p19q status. The Kaplan–Meier survival curves were performed to analyze the relationship between EN1 expressions and clinicopathological characteristics and survival time respectively. Results Cox regression results showed that LGG was ranked statistically first among 13 different cancer types according to the false discovery rate (FDR) correction. Results from GSE16011 showed that: glioma, LGG and LGG with IDH1 mutation patients with high EN1 expressions had significantly shorter 5, 10, and 15-year overall survival time (OS) (p < 0.001). Similar results from TCGA-LGG showed that LGG patients with high EN1 expressions had significantly shorter 15-year OS, irrespective of IDH1 mutation and 1p19q co-deletion (p < 0.001). The astrocytoma subgroup showed highest levels of EN1 expression and shortest 5, 10 and 15-year OS compared with oligoastrocytoma and oligodendroglioma (p < 0.05). Conclusion EN1 can be used as a prognostic marker in LGG patients, combined with IDH1 mutation and 1p19q co-deletion.

scholarly journals Diagnostic value of PET/CT with 11C-methionine (MET) and 18F-fluorothymidine (FLT) in newly diagnosed glioma based on the 2016 WHO classification

2020 ◽  
Author(s):  
Tomoya Ogawa ◽  
Nobuyuki Kawai ◽  
Keisuke Miyake ◽  
Aya Shinomiya ◽  
Yuka Yamamoto ◽  
...  
Keyword(s):  
Who Classification ◽  
Idh1 Mutation ◽  
Histopathological Diagnosis ◽  
Newly Diagnosed ◽  
Mutation Status ◽  
Flt Pet ◽  
Molecular Features ◽  
Pet Ct ◽  
The Mean ◽  
Met Pet

Abstract Background The molecular features of isocitrate dehydrogenase ( IDH ) mutation and chromosome 1p and 19q (1p/19q) codeletion status have pivotal role for differentiating gliomas and have been integrated in the World Health Organization (WHO) classification in 2016. Positron emission tomography (PET) with 18 F-fluorothymidine (FLT) has been used to evaluate tumour grade and proliferative activity and compared with L-methyl- 11 C-methionine (MET) in glioma patients. Herein, we evaluated tracer uptakes of MET-PET/CT and FLT-PET/CT for differentiating glioma based on the 2016 WHO classification especially in relation to IDH1 mutation status. Methods In total, 81 patients with newly diagnosed supratentorial glioma were enrolled in this study. They underwent PET/CT studies with MET and FLT before surgery. The molecular features and histopathological diagnosis based on the 2016 WHO classification were determined using surgical specimens. The ratios of the maximum standardized uptake value (SUV) of the tumours to the mean SUV of the contralateral cortex (T/N ratios) were calculated on MET-PET/CT and FLT-PET/CT images. Results The mean T/N ratios of MET-PET/CT and FLT-PET/CT in IDH1 -wildtype tumours were significantly higher than those in IDH1 -mutant tumours ( P <0.001 and P <0.001, respectively). Receiver operating characteristic analysis for differentiating IDH1 mutation status showed that the area under the curve of the FLT T/N ratio was significantly larger than that of the MET T/N ratio ( P <0.01). The mean T/N ratio of FLT-PET/CT in IDH1 -wildtype tumours was significantly higher than that in IDH1 -mutant tumours among grade Ⅱ and Ⅲ gliomas ( P =0.005), but this was not the case for MET-PET/CT. Both MET-PET/CT and FLT-PET/CT were able to distinguish between grade Ⅱ and Ⅲ gliomas in IDH1 -mutant tumours ( P =0.002 and P <0.001, respectively), but only FLT-PET/CT was able to distinguish between grade Ⅲ and Ⅳ gliomas in IDH1 -wildtype tumours ( P =0.029). Conclusion This study showed that FLT-PET/CT can be used to determine the IDH1 mutation status and evaluate glioma grade more accurately than MET-PET/CT. FLT-PET/CT can improve glioma differentiation based on the 2016 WHO classification, but caution must be paid for tumours without contrast enhancement.

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 An independently validated survival nomogram for lower-grade glioma

2019 ◽  
Vol 22 (5) ◽  
pp. 665-674 ◽  
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.

scholarly journals Study of Histomolecular Classification of Glioma-Integrating Histology and Molecular Analysis in the Diagnosis of Brain Tumors

2018 ◽  
Vol 07 (02) ◽  
pp. 129-134
Author(s):  
Shameen Devi ◽  
Michelle De Padua ◽  
Iravathy Kalal
Keyword(s):  
Anaplastic Astrocytoma ◽  
Idh1 Mutation ◽  
Tumor Type ◽  
Diffuse Astrocytoma ◽  
Isocitrate Dehydrogenase 1 ◽  
Anaplastic Oligoastrocytoma ◽  
Diffuse Gliomas ◽  
Grade Ii ◽  
Classification Of Gliomas

Abstract Introduction The updated 2016 classification of gliomas incorporates well-established molecular parameters into the classification of diffuse gliomas, taking into account isocitrate dehydrogenase 1 (IDH1) mutation, α-thalassemia/mental retardation syndrome X-linked (ATRX) loss, and 1p/19q co-deletion. Aim and Objectives To study IDH1 and ATRX mutations in gliomas, 1p/19q co-deletion by fluorescent in situ hybridization (FISH) in oligodendroglioma, and to correlate IDH1, ATRX, and 1p/19q with tumor type and grade. Material and Methods Total 73 cases of gliomas were diagnosed on histology and graded as astrocytoma (grades 2–4), oligodendroglioma (grades 2–3), and oligoastrocytoma (grades 2–3) by two pathologists independently. IDH mutation and ATRX expression were analyzed using immunohistochemistry in all cases whereas 1p/19q co-deletion was studied using FISH in cases with oligodendroglioma and oligoastrocytoma morphology. Results Total 48 cases of astrocytoma, 9 cases of oligoastrocytoma, and 16 cases of oligodendroglioma were included. The maximum number of IDH1 mutation cases were seen in diffuse astrocytoma (7/10; 70%) as compared with anaplastic astrocytoma (5/15; 33.33%), glioblastoma multiforme (GBM) (3/23; 13.04%) grade II oligoastrocytoma (3/6; 50%), anaplastic oligoastrocytoma (2/3; 66.67%), and oligodendroglioma grade II (7/10; 70%). ATRX loss was seen in diffuse astrocytoma grade II (6/10; 60%), anaplastic astrocytoma (6/15; 40%), oligoastrocytoma grade II (2/6; 33.33%), and anaplastic oligoastrocytoma (1/3; 33.33%). 1p/19q co-deletion was seen in oligoastrocytoma (2/2; 100%), anaplastic oligoastrocytoma (1/2; 50%), oligodendroglioma (3/4; 75%), and anaplastic oligodendroglioma (1/3; 33.33%). Six of the seven cases with 1p/19q co-deletion also showed IDH1 mutation. One of seven 1p/19q co-deleted cases had loss of expression of ATRX. Conclusion Incorporation of IDH1 mutation, ATRX loss, and 1p/19q co-deletion molecular studies help in a more accurate diagnosis and classification of gliomas.

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.

scholarly journals Radiomics Features Predict CIC Mutation Status in Lower Grade Glioma

2020 ◽  
Vol 10 ◽  
Author(s):  
Luyuan Zhang ◽  
Felipe Giuste ◽  
Juan C. Vizcarra ◽  
Xuejun Li ◽  
David Gutman
Keyword(s):  
Lower Grade ◽  
Mutation Status ◽  
Lower Grade Glioma

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

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi161-vi161 ◽  
Author(s):  
Shumpei Onishi ◽  
Fumiyuki Yamasaki ◽  
Motoki Takano ◽  
Ushio Yonezawa ◽  
Akira Taguchi ◽  
...  
Keyword(s):  
Calculated Result ◽  
The Other ◽  
Dysembryoplastic Neuroepithelial Tumor ◽  
Specific Marker ◽  
Lower Grade ◽  
Diffuse Astrocytoma ◽  
Skull Bone ◽  
Rater Agreement ◽  
1P19q Codeletion ◽  
Lower Grade 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 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

scholarly journals MPC-18 CATEGORIZATION OF LOWER GRADE GLIOMA USING ONCOPANEL

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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