Tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology and treatment

2052 Background: Immune modulating therapies have been a long withstanding treatment approach in glioma. However, gliomas are characterized by a particular absence of tumor infiltrating lymphocytes in the local tumor microenvironment. We aimed to gain insight on the distinct patterns of inflammation associated with survival prognosis in glioma. Methods: Patients were recruited at time of glioma diagnosis or progression in the prospective observational Vienna Cancer and Thrombosis Study (CATS). A single blood draw was performed at study inclusion. PD-L1 expression in the tumor tissue was investigated via immunohistochemistry. Optimal cut-off according to ROC curve was used to assess cut off values for survival analysis. Results: 193 patients with glioma (75.6% glioblastoma (WHO grade IV), 19.7% anaplastic glioma (WHO grade III), and 4.7% diffuse glioma (WHO grade II)) were included. 40/193 (20.7%) glioma had an IDH1 mutation. Membranous PDL1 expression in the tumor tissue was observed in 20/193 (10.4%) patients. 1/20 patient presented with PD-L1 expression and IDH1 mutation ( p = 0.082). PD-L1 significantly correlated with increased monocyte count (median: 0.657 vs. 0.450 [G/L], p = 0.008), higher C-reactive protein (CRP) (0.43 vs. 0.1 [mg/dL], p = 0.005) and higher fibrinogen (379 vs. 303 [mg/dL], p = 0.001). Presence of IDH1 mutation significantly correlated with increased platelet count (303 vs. 232 [G/L], p = 0.001) and lower Neutrophil/Lymphocyte (N/L) ratio (3.34 vs. 5.13, p = 0.016). Higher lymphocyte count ( > 1.484 [G/L], log-rank: p = 0.011), higher platelet count ( > 245.5 [G/L], p = 0.0001), as well as decreased N/L ratio ( < 5.13, p = 0.001) were significantly associated with increased survival prognosis. Conclusions: PD-L1 expression in tumor tissue was associated with markers of systemic inflammation in glioma patients. Systemic inflammation markers furthermore predicted improved survival. Immune modulating therapy approaches might be a promising approach in subgroups of glioma associated with increased baseline interaction of immune system and glioma.

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New-Onset Postoperative Seizures in Patients With Diffuse Gliomas: A Risk Assessment Analysis

Frontiers in Neurology ◽

10.3389/fneur.2021.682535 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lianwang Li ◽

Guanzhang Li ◽

Shengyu Fang ◽

Kenan Zhang ◽

Ruoyu Huang ◽

...

Keyword(s):

Risk Factors ◽

Prognostic Value ◽

Independent Predictor ◽

Idh1 Mutation ◽

Categorical Variables ◽

Binary Logistic Regression Analysis ◽

Low Grade ◽

Diffuse Glioma ◽

Ki 67 ◽

New Onset

Background: Glioma-related epilepsy (GRE) is the most common presenting sign of patients with diffuse glioma. According to clinical experience, new-onset postoperative seizures can be observed even in patients without preoperative GRE. The current study mainly aimed to explore the risk factors of new-onset postoperative seizures in those patients. In addition, the prognostic value of new-onset postoperative seizures was also discussed.Methods: Data of 313 patients without GRE were retrospectively reviewed. Chi-square test or Fisher's exact test were first performed to compare categorical variables between patients with new-onset postoperative seizures and those without. Subsequently, binary logistic regression analysis was conduct to further assess risk factors of new-onset postoperative seizures. Kaplan-Meier and Cox analysis were used to investigate the prognostic value of new-onset postoperative seizures for progression-free survival (PFS) and overall survival (OS).Results: Patients with low-grade tumors (p = 0.006), isocitrate dehydrogenase 1 (IDH1) mutation (p = 0.040) or low Ki-67 expression (p = 0.005) showed a higher incidence of new-onset postoperative seizures. IDH1 mutation was identified as the only independent predictor for new-onset postoperative seizures (OR, 2.075; 95% CI, 1.051–4.098; p = 0.035). Additionally, new-onset postoperative seizure occurrence was demonstrated as an independent predicter of prolonged OS (OR, 0.574; 95% CI, 0.335–0.983; p = 0.043), while younger age, gross total resection, low-grade and IDH1 mutation were independently correlated with prolonged OS and PFS.Conclusions: IDH1 mutation is an independent predictor for new-onset postoperative seizures in patients without preoperative GRE. Moreover, new-onset postoperative seizures can independently predict prolonged OS in those patients. The results of the current study can contribute to improving the individualized management of diffuse glioma.

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New-onset postoperative seizures in patients with diffuse gliomas: a risk assessment analysis

10.21203/rs.3.rs-137298/v1 ◽

2021 ◽

Author(s):

Lianwang Li ◽

Guanzhang Li ◽

Shengyu Fang ◽

Kenan Zhang ◽

Ruoyu Huang ◽

...

Keyword(s):

Risk Factors ◽

Prognostic Value ◽

Independent Predictor ◽

Idh1 Mutation ◽

Categorical Variables ◽

Binary Logistic Regression Analysis ◽

Low Grade ◽

Diffuse Glioma ◽

Ki 67 ◽

New Onset

Abstract Background Glioma-related epilepsy (GRE) is the most common presenting sign of patients with diffuse glioma. According to clinical experience, new-onset postoperative seizures can be observed even in patients without preoperative GRE. The current study mainly aimed to explore the risk factors of new-onset postoperative seizures in those patients. In addition, the prognostic value of new-onset postoperative seizures was also discussed. Methods Data of 313 patients without GRE were retrospectively reviewed. Chi-square test or Fisher’s exact test were first performed to compare categorical variables between patients with new-onset postoperative seizures and those without. Subsequently, binary logistic regression analysis was conduct to further assess risk factors of new-onset postoperative seizures. Kaplan-Meier and Cox analysis were used to investigate the prognostic value of new-onset postoperative seizures for progression-free survival (PFS) and overall survival (OS). Results Patients with low-grade tumors (p = 0.006), isocitrate dehydrogenase 1 (IDH1) mutation (p = 0.040) or low Ki-67 expression (p = 0.005) showed a higher incidence of new-onset postoperative seizures. IDH1 mutation was identified as the only independent predictor for new-onset postoperative seizures (OR, 2.075; 95% CI, 1.051–4.098; p = 0.035). Additionally, new-onset postoperative seizure occurrence was demonstrated as an independent predicter of prolonged OS (OR, 0.574; 95% CI, 0.335–0.983; p = 0.043). Conclusions IDH1 mutation is an independent predictor for new-onset postoperative seizures in patients without preoperative GRE. Moreover, new-onset postoperative seizures can independently predict prolonged OS in those patients. The results of the current study can contribute to improving the individualized management of diffuse glioma.

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Radiosensitization and a Less Aggressive Phenotype of Human Malignant Glioma Cells Expressing Isocitrate Dehydrogenase 1 (IDH1) Mutant Protein: Dissecting the Mechanisms

Cancers ◽

10.3390/cancers11060889 ◽

2019 ◽

Vol 11 (6) ◽

pp. 889 ◽

Cited By ~ 3

Author(s):

Jacqueline Kessler ◽

Tim Hohmann ◽

Antje Güttler ◽

Marina Petrenko ◽

Christian Ostheimer ◽

...

Keyword(s):

Malignant Glioma ◽

Isocitrate Dehydrogenase ◽

Idh1 Mutation ◽

Cell Stiffness ◽

Diffuse Glioma ◽

Isocitrate Dehydrogenase 1 ◽

Aggressive Phenotype ◽

Γh2ax Foci ◽

Mutant Idh1

The presence of an isocitrate dehydrogenase 1 (IDH1) mutation is associated with a less aggressive phenotype, increased sensitivity to radiation, and increased overall survival in patients with diffuse glioma. Based on in vitro experimentations in malignant glioma cell lines, the consequences on cellular processes of IDH1R132H expression were analyzed. The results revealed that IDH1R132H expression enhanced the radiation induced accumulation of residual γH2AX foci and decreased the amount of glutathione (GSH) independent of the oxygen status. In addition, expression of the mutant IDH1 caused a significant increase of cell stiffness and induced an altered organization of the cytoskeleton, which has been shown to reinforce cell stiffness. Furthermore, IDH1R132H expression decreased the expression of vimentin, an important component of the cytoskeleton and regulator of the cell stiffness. The results emphasize the important role of mutant IDH1 in treatment of patients with diffuse gliomas especially in response to radiation. Hence, detection of the genetic status of IDH1 before therapy massively expands the utility of immunohistochemistry to accurately distinguish patients with a less aggressive and radiosensitive IDH1-mutant diffuse glioma suitable for radiotherapy from those with a more aggressive IDH1-wildtype diffuse glioma who might benefit from an individually intensified therapy comprising radiotherapy and alternative medical treatments.

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