The study highlights that diffuse glioma, a prevalent type of brain tumor, affect approximately 100,000 individuals worldwide each year. IDH-mutant astrocytoma and oligodendrogliomas typically have a more favorable prognosis compared to IDH-wildtype glioblastomas. However, many IDH-mutant astrocytoma has the potential to progress to grade 4 glioblastomas, leading to a less favorable prognosis. In a recent investigation, Shumpei Onishi et al. examined the T2-FLAIR mismatch sign as a possible imaging biomarker for assessing CDKN2A status in non-enhancing IDH-mutant astrocytoma. The findings indicate that the T2-FLAIR mismatch sign is linked to CDKN2A-intact astrocytoma, providing a valuable tool for diagnostic and prognostic purposes. Additionally, the use of Indocyanine Green (ICG) for real-time visualization during neurosurgical procedures demonstrates potential, though it may have limitations in specificity. While these advancements offer promise in glioma management, there remains a critical need for larger, standardized studies to validate these findings and further improve treatment outcomes.

UNASSIGNED: The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM).
UNASSIGNED: This study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification.
UNASSIGNED: We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes.
UNASSIGNED: 163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM.
UNASSIGNED: Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

BACKGROUND: Grade 2-3 diffuse gliomas (DGs) show extensive infiltration through white matter (WM) tracts. Along-tract analysis of WM tracts based on diffusion tensor tractography (DTI) can been performed to assess the microstructural integrity of WM tracts. The clinical implication of these DTI-related findings is still under debate, especially in tumor patients. The aim of this study was to analyze and compare diffusion-based parameters along WM tracts and variables specific to WM -tumor interactions in DGs and correlate them with preoperative neuropsychological assessment.
METHODS: Fourteen patients with IDH-mutated grade 2-3 DGs were included. Tumor volumes were manually segmented on 3D-FLAIR images after spatial normalisation to MNI space. DTI was acquired using a single-shot echo-planar sequence on a 3T with 48 sampling directions. DTI data were reconstructed within the MNI space using q-space diffeomorphic reconstruction (QSDR) in DSI studio. Five bilateral sets of WM tracts were reconstructed based on the HCP-1065 template. All WM tracts were stretched to the same length of 100 indices, and for each index diffusion-based parameters fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), mean diffusivity (MD) and quantitative anisotropy (QA) were sampled. Tumor-related parameters (TRP); tumor volume (Tv), maximum tumor presence (MTP) and the number of sequential indices in which a tumor is present (Te) were derived based on the along-tract analysis. Normal data were constructed by calculating the average and standard deviations of contralateral and not-affected WM tracts for each diffusion-based parameter, respectively. Affected WM tracts were individually compared to normal data using a z-test. Preoperative neuropsychological assessment was performed in all subjects and correlated to results from the along-tract analysis using correlation and logistic regression models.
RESULTS: Abnormalities in diffusion-based parameters were detected in WM tracts. Topographical and quantitative information were presented within the same graph. AD and MD displayed the highest linear correlation with the TRPs. Abnormal QA showed a linear correlation with Tv per WM tract. Neuropsychological impairment was correlated with all the TRPs and with abnormal FA (p < 0.05) and abnormal QA (p < 0.01). Abnormal QA was the only independent variable able to predict the presence of neuropsychological impairment in the patients based on the linear regression analysis.
CONCLUSIONS: Graphical presentation of the along-tract analysis presented in this study shows that it may be a sensitive and robust method to acquire and display topographical and qualitative information regarding WM tracts in close proximity to DGs. Further studies and refinements to the methods presented herein may advance current clinical methods for evaluating displacement and infiltrations and further aid the efforts of pre-planning surgical interventions with the goal to maximise EOR and tailor oncological treatment.

In diffuse glioma patients, Lys-27-Met mutations in histone 3 genes (H3K27M) are associated with an aggravated prognosis and further decreased overall survival. By using frequency importance analysis on chemical exchange saturation transfer (CEST) MRI, this study aimed to assess the predictability of the H3K27M status in diffuse glioma patients.
Twenty-two patients diagnosed with diffuse glioma, with a known H3K27M status, were included in the present study. All patients underwent CEST MRI scans. The previously proposed frequency importance analysis was performed to determine the relative contribution of the amide and aliphatic protons for the differentiation between normal tissues and tumors. For this comparison, the conventional MTRasym analysis of amide protons at 3.5 ppm, i.e., the amide proton transfer-weighted (APTw) signal, was employed. Statistical analysis was performed using the Mann-Whitney U test, and the receiver operating characteristic (ROC) and area under the curve (AUC) analyses.
The mean and 90th percentile of the ΔAPTw intensities, amide and aliphatic frequency importance values revealed statistically significant differences between the wildtype and the H3K27M-altered patient groups (p < 0.05). For the prediction of the H3K27M status, amide frequency importance achieved highest AUCs of 0.97, with a specificity of 0.93. In contrast, the ΔAPTw intensities and aliphatic frequency importance showed relatively lower AUCs (<0.35) in predicting the H3K27M status.
Amide frequency importance exhibited satisfactory performance in the prediction of the H3K27M status. As such, it may be considered as a non-invasive MRI biomarker for the diagnosis of diffuse gliomas.

By generating protein diversity, alternative splicing provides an important oncogenic pathway. Isocitrate dehydrogenase (IDH) 1 and 2 mutations and 1p/19q co-deletion have become crucial for the novel molecular classification of diffuse gliomas, which also incorporates DNA methylation profiling. In this study, we have carried out a bioinformatics analysis to examine the impact of the IDH mutation, as well as the 1p/19q co-deletion and the glioma CpG island methylator phenotype (G-CIMP) status on alternative splicing in a cohort of 662 diffuse gliomas from The Cancer Genome Atlas (TCGA). We identify the biological processes and molecular functions affected by alternative splicing in the various glioma subgroups and provide evidence supporting the important contribution of alternative splicing in modulating epigenetic regulation in diffuse gliomas. Targeting the genes and pathways affected by alternative splicing might provide novel therapeutic opportunities against gliomas.

Diffuse gliomas are the most common primary malignant brain tumors in adults. Advancements in the molecular profiling of diffuse gliomas in recent years have led to a far better understanding of their biology and clinical outcomes. The fifth edition of the World Health Organization Classification of Central Nervous System Tumors, published in 2021, incorporates this genomic information to a much greater degree than prior editions. It is important for radiologists to understand the new glioma classification system and the characteristic neuroimaging features associated with each entity. This review aims to provide an overview of the diffuse gliomas that can present in adults, with an emphasis on their molecular features and associated imaging findings.

In 2021, the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) underwent significant restructuring to incorporate additional molecular diagnostics, several newly recognized tumor types, and new grading schemes for existing tumor types. The 2021 CNS WHO classification further elaborates and integrates histopathologic and molecular diagnostic criteria to improve diagnostic classification. Furthermore, it is the hope that identification of molecular alterations in pediatric and adult tumors facilitates improved prognostic information and development of novel targeted therapies for adults and children with CNS tumors. In one of the largest changes in the new WHO classification, diffuse gliomas are divided into pediatric-type and adult-type gliomas to highlight our expanding knowledge of their different molecular drivers and prognostic associations. Several new pediatric-type diffuse low-grade gliomas are defined including (I) diffuse astrocytoma, MYB- or MYBL1-altered, (II) polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and (III) diffuse low-grade glioma, MAPK-pathway altered. In addition, several new pediatric-type diffuse high-grade gliomas are recognized including (I) diffuse hemispheric glioma, H3 G34R-mutant (II) diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, and (III) infant-type hemispheric glioma. These new tumor types have associated clinical, genetic and epigenetic features that are distinct from adult-type diffuse gliomas. This review provides an overview of updates in the 2021 CNS WHO classification specific to diffuse gliomas, with a particular focus on the histopathology and molecular findings of the newly described pediatric-type low-grade and high-grade gliomas.

For decades, diffuse glioma (DG) studies mostly focused on oncological considerations, whereas functional outcomes received less attention. Currently, because overall survival has increased in DG, especially in low-grade glioma (overall survival > 15 years), quality of life including neurocognitive and behavioral aspects should be assessed and preserved more systematically, particularly regarding surgery. Indeed, early maximal tumor removal results in greater survival in both high-grade and low-grade gliomas, leading to propose \"supra-marginal\" resection, with excision of the peritumoral zone in diffuse neoplasms. To minimize functional risks while maximizing the extent of resection, traditional \"tumor-mass resection\" is replaced by \"connectome-guided resection\" conducted under awake mapping, taking into account inter-individual brain anatomo-functional variability. A better understanding of the dynamic interplay between DG progression and reactional neuroplastic mechanisms is critical to adapt a personalized multistage therapeutic strategy, with integration of functional neurooncological (re)operation(s) in a multimodal management scheme including repeated medical therapies. Because the therapeutic armamentarium remains limited, the aims of this paradigmatic shift are to predict one/several step(s) ahead glioma behavior, its modifications, and compensatory neural networks reconfiguration over time in order to optimize the onco-functional benefit of each treatment - either in isolation or in combination with others - in human beings bearing a chronic tumoral disease while enjoying an active familial and socio-professional life as close as possible to their expectations. Thus, new ecological endpoints such as return to work should be incorporated into future DG trials. \"Preventive neurooncology\" might also be envisioned, by proposing a screening policy to discover and treat incidental glioma earlier.

Diffuse gliomas of the spine (DGS)-consisting of intradural intramedullary glioblastoma, astrocytoma, and oligodendroglioma-are exceedingly rare tumors that account for about 2% of primary spinal cord tumors. Much is unknown about their optimal treatment regimen due to a relative lack of clinical outcome data.
To provide an updated analysis on treatment and outcomes in DGS.
Observational cohort study using The National Cancer Database (NCDB), a multicenter prospectively collected oncology outcomes database. A systematic literature review was also performed to compare the resulting data to previous series.
Patients with histologically confirmed DGS from 2004 to 2018.
Long-term overall survival and short-term 30/90-day postsurgical mortality, 30-day readmission, and prolonged hospital length of stay.
Impact of extent of resection and adjuvant therapy on overall survival was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression. Univariate and multivariate logistic regression was used to analyze covariables and their prognostic impact on short-term surgical outcomes.
Of the 747 cases that met inclusion criteria, there were 439 astrocytomas, 14 oligodendrogliomas, and 208 glioblastomas. Sixty percent (n=442) of patients received radiation, and 45% (n=324) received chemotherapy. Tumor histology significantly impacted survival; glioblastoma had the poorest survival (median survival time [MS]: 12.3 months), followed by astrocytoma (MS: 70.8 months) and oligodendroglioma (MS: 71.6 months) (p<.001). Gross total resection (GTR) independently conferred a survival benefit in patients with glioblastoma (hazard ratio [HR]: 0.194, p<0.001) and other WHO grade four tumors (HR: 0.223, p=.003). Adjuvant chemotherapy also improved survival in patients with glioblastoma (HR: 0.244, p=.007) and WHO grade four tumors (HR: 0.252, p<.001). Systematic literature review identified 14 prior studies with a combined DGS mortality rate of 1.3%, which is lower than the 4% real-world outcomes calculated from the NCDB. This difference may be explained by selection biases in previously published literature in which only centers with favorable outcomes publish their results.
There remains a paucity of data regarding treatment paradigms and outcomes for DGS. Our analysis, the largest to date, demonstrates that GTR and adjuvant therapy independently improve survival for certain high-grade subgroups of DGS. This best-available data informs optimal management for such patients.

UNASSIGNED: Gliomas distribute unevenly in the supratentorial brain space. Many factors were linked to tumor locations. This study aims to describe a more detailed distributing pattern of these tumors with age and pathological factors concerned.
UNASSIGNED: A consecutive series of 990 adult patients with newly-diagnosed supratentorial diffuse gliomas who underwent resection in Beijing Tiantan Hospital between January 2013 and January 2017 were retrospectively reviewed. For each patient, the anatomic locations were identified by the preoperative MRI, and the pathological subtypes were reviewed for histological grade and molecular status (if any) from his medical record. The MNI template was manually segmented to measure each anatomic location\'s volume, and its invaded ratio was then adjusted by the volume to calculate the frequency density. Factors of age and pathological subtypes were also compared among locations.
UNASSIGNED: The insulae, hippocampi, and corpus callosum were locations of the densest frequencies. The frequency density decreased from the anterior to posterior (frontal - motor region - sensory region - parietal - occipital), while the grade (p < 0.0001) and the proportion of IDH-wt (p < 0.0001) increased. More tumors invading the right basal ganglion were MGMT-mt (p = 0.0007), and more of those invading the left frontal were TERT-wt (p = 0.0256). Age varied among locations and pathological subtypes.
UNASSIGNED: This study demonstrated more detailed spatial disproportions of supratentorial gliomas. There are potential interactions among age, pathological subtypes, and tumor locations.