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Background: Glioblastoma are highly malignant type of primary brain tumors. Treatment for glioblastoma multiforme (GBM) generally involves surgery combined with chemotherapy and radiotherapy. However, the development of tumoral chemo- and radioresistance induces complexities in clinical practice. Multiple signaling pathways are known to be involved in radiation-induced cell survival. However, the role of alpha-thalassemia X-linked mutant retardation syndrome (ATRX), a chromatin remodeling protein, in GBM radioresistance remains unclear. Methods: In the present study, the ATRX mutation rate in patients with glioma was obtained from The Cancer Genome Atlas, while its expression analyzed using bioinformatics. Datasets were also obtained from the Gene Expression Omnibus, and ATRX expression levels following irradiation of GBM were determined. The effects of ATRX on radiosensitivity were investigated using a knockdown assays. Results: The present study demonstrated that the ATRX mutation rate in patients with GBM was significantly lower than that in patients with low-grade glioma, and that patients harboring an ATRX mutation exhibited a prolonged survival, compared with to those harboring the wild-type gene. Single-cell RNA sequencing demonstrated that ATRX counts increased 2 days after irradiation, with ATRX expression levels also increasing in U-251MG radioresistant cells. Moreover, the results of in vitro irradiation assays revealed that ATRX expression was increased in U-251MG cells, while ATRX knockdown was associated with increased levels of radiosensitivity. Conclusions: High ATRX expression levels in primary GBM may contribute to high levels of radioresistance. Thus ATRX is a potential target for overcoming the radioresistance in GBM. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The classification of patients based on pathology and molecular features is important for improving WHO grade II glioma patient prognosis, especially for the initially diagnosed patients. Less invasive and more convenient methods for the prediction of the pathological type and gene status are desired.Materials and Methods: This study investigates the ability to use conventional magnetic resonance imaging (MRI) and computed tomography (CT) features for determining the Isocitrate Dehydrogenase (IDH)-mutant and 1p/19q-codeletion status, through a retrospective review of information obtained from 189 WHO grade II glioma patients. Diffuse astrocytoma (IDH-mutant), Diffuse astrocytoma (IDH- wildtype) and Oligodendroglioma (IDH-mutant and 1p/19q co-deletion) were included in this cohort. All patients were divided into IDH-mutant group and IDH-wildtype group according to the IDH R132H mutation status. Moreover, all patients were divided into 1p/19q co-deletion group and 1p/19q non-codeletion group according to the 1p and 19q chromosome status. Patients underwent pre-operative CT and MRI scans, followed by operation and histopathological analyses, including immunohistochemistry and polymerase chain reaction analysis for IDH mutants, and fluorescence capillary electrophoresis analysis for the 1p/19q co-deletion. The χ2 test, logistical regression and receiver operating characteristic curve analysis were conducted for statistical analysis.Results: IDH-mutant group patients exhibited a higher calcification frequency (25.2% vs 2.4%, p = 0.006) and lower frequency of T1 enhancement (20.4% vs 38.1%, p = 0.028) comparing patients in IDH-wildtype group, while 1p/19q co-deletion group patients exhibited a higher calcification frequency (46.67% vs 2.6%, p < 0.001) and lower homogenous signal frequency in T2WI (12.0% vs 31.6%, p = 0.014), sharp lesion margins (14.7% vs 43.0%, p = 0.010), T2/fluid attenuated inversion recovery mismatch signs (22.7% vs 50.9%, p = 0.001), and subventricular zone involvement (64.0% vs 15.8%, p = 0.021) comparing patients in 1p/19q non-codeletion group. According to the results of receiver operating characteristic analysis, these features were observed to have certain diagnostic abilities, especially with regard to combination parameters, which had a high diagnostic capability, with an area under the curve of 0.848.Conclusion: Conventional MRI and CT features, which still represent the most convenient and widely used predictive method, might be a promising noninvasive predictor for differentiating between varied WHO grade II gliomas. Patients with calcification and T1 nonenhancement are more likely to be IDH-mutant. Moreover, patients with noncalcification, homogenous signal, sharp lesion margins, subventricular zone involvement on T2 and T2/fluid attenuated inversion recovery mismatch signs are more likely to be 1p/19q non-codeletion. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Different histology and gene status of gliomas results in different natural history, treatment, and prognosis in different subgroups. Low-grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutant and 1p/19q-codeleted are kind of gliomas with the most favorable outcome, reflecting operational strategy. Less invasive method for prediction of pathological type-even gene status-is desired.Materials and Methods: This study investigates the potential ability of methionine-positron emission tomography (MET-PET) to determine LGGs with IDH-mutant and 1p/19q-codeleted through a retrospective review of information of 70 glioma patients. Patients underwent preoperative MET-PET, followed by operation and histopathological analysis including Immunohistochemistry and polymerase chain reaction analysis for IDH-mutant and fluorescence capillary electrophoresis analysis for 1p/19q codeletion. Texture analysis was performed for further data mining. The t-test and receiver operating characteristic curve analysis were conducted for statistical analysis.Results: In the whole cohort analysis, SUVmax, SUVmean and texture features (SD and median) of oligodendroglioma, IDH-mutant and 1p/19q-codeleted patients were lower than these values of other patients. In WHO grade II subgroup analysis, no statistical difference of conventional features was observed between groups. Texture analysis displayed higher diffEntropy, diffVariance, and entropy in oligodendroglioma, IDH-mutant and 1p/19q-codeleted patients. Receiver operating characteristic analysis suggested AUCs of some conventional features and texture features ranged from 0.722 to 0.892 that are effective for diagnosis, determining LGGs with IDH-mutant and 1p/19q-codeleted in this cohort and WHO II grade glioma subgroup analysis respectively.Conclusion: 11C-Methionine integrated PET/MRI based texture analysis and conventional features may be a promising noninvasive predictor for differentiating the varied gliomas. [ABSTRACT FROM AUTHOR]

It is always a great challenge to distinguish high-grade glioma (HGG) from primary central nervous system lymphoma (PCNSL). We conducted a meta-analysis to assess the performance of MR perfusion-weighted imaging (PWI) in differentiating HGG from PCNSL. The heterogeneity and threshold effect were evaluated, and the sensitivity (SEN), specificity (SPE) and areas under summary receiver operating characteristic curve (SROC) were calculated. Fourteen studies with a total of 598 participants were included in this meta-analysis. The results indicated that PWI had a high level of accuracy (area under the curve (AUC) = 0.9415) for differentiating HGG from PCNSL by using the best parameter from each study. The dynamic susceptibility-contrast (DSC) technique might be an optimal index for distinguishing HGGs from PCNSLs (AUC = 0.9812). Furthermore, the DSC had the best sensitivity 0.963 (95%CI: 0.924, 0.986), whereas the arterial spin-labeling (ASL) displayed the best specificity 0.896 (95% CI: 0.781, 0.963) among those techniques. However, the variability of the optimal thresholds from the included studies suggests that further evaluation and standardization are needed before the techniques can be extensively clinically used. [ABSTRACT FROM AUTHOR]

Objective: Magnetic resonance spectroscopy (MRS) is a powerful tool for preoperative grading of gliomas. We performed a meta-analysis to evaluate the diagnostic performance of MRS in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs).Methods: PubMed and Embase databases were systematically searched for relevant studies of glioma grading assessed by MRS through 27 March 2015. Based on the data from eligible studies, pooled sensitivity, specificity, diagnostic odds ratio and areas under summary receiver operating characteristic curve (SROC) of different metabolite ratios were obtained.Results: Thirty articles comprising a total sample size of 1228 patients were included in our meta-analysis. Quantitative synthesis of studies showed that the pooled sensitivity/specificity of Cho/Cr, Cho/NAA and NAA/Cr ratios was 0.75/0.60, 0.80/0.76 and 0.71/0.70, respectively. The area under the curve (AUC) of the SROC was 0.83, 0.87 and 0.78, respectively.Conclusions: MRS demonstrated moderate diagnostic performance in distinguishing HGGs from LGGs using tumoural metabolite ratios including Cho/Cr, Cho/NAA and NAA/Cr. Although there was no significant difference in AUC between Cho/Cr and Cho/NAA groups, Cho/NAA ratio showed higher sensitivity and specificity than Cho/Cr ratio and NAA/Cr ratio. We suggest that MRS should combine other advanced imaging techniques to improve diagnostic accuracy in differentiating HGGs from LGGs.Key Points: • MRS has moderate diagnostic performance in distinguishing HGGs from LGGs. • There is no significant difference in AUC between Cho/Cr and Cho/NAA ratios. • Cho/NAA ratio is superior to NAA/Cr ratio. • Cho/NAA ratio shows higher sensitivity and specificity than Cho/Cr and NAA/Cr ratios. • MRS should combine other advanced imaging techniques to improve diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Balancing the benefit of extensive tumor resection with the consequence of potential postoperative language deficits remains a challenge in glioma surgery involving language areas. This study is designed to evaluate the impact of intraoperative magnetic resonance imaging (iMRI) and functional neuronavigation on surgical outcome in patients with gliomas involving language areas. Two hundred seventeen patients were prospectively enrolled, 124 in the study group underwent iMRI and functional neuronavigation-guided microsurgery and 93 in the control group underwent conventional navigation-guided microsurgery. Extent of tumor volume resection (EoR) and rate of gross total resection (rGTR) were calculated perioperatively. Aphasia quotient (AQ) was assessed to evaluate the change of language function perioperatively and at 6-month follow-up. Survival outcome for glioblastoma, including progression-free survival (PFS) and overall survival (OS), were recorded. In 198 glioma patients (112 in the study group and 86 in the control group), EoR (95.50 versus 89.85 %, p < 0.001) and rGTR (69.60 versus 47.70 %, p = 0.002) were significantly higher in the study group, and language functions were also better at 6-month follow-up in the study group (87.47 versus 78.73, p = 0.001). Furthermore, postoperative new aphasia occurred in 34.8 % of the control group, whereas it occurred only in 2.3 % of the study group ( p < 0.001). In addition, PFS (12.5 versus 6.6 m, p = 0.003) and OS (19.6 versus 13.0 m, p < 0.001) for patients with glioblastomas were dramatically prolonged in the study group than in the control group. These results indicated that iMRI and functional neuronavigation may help maximize tumor resection, minimize language deficits in patients with gliomas involving language areas, and improve survival time for patients with glioblastomas. [ABSTRACT FROM AUTHOR]