Immunologic treatment options are uncommon in low-grade gliomas, although such therapies might be beneficial for inoperable and aggressive cases. Knowledge of the immune and stromal cells in low-grade gliomas is highly relevant for such approaches but still needs to be improved. Published gene-expression data from 400 low-grade gliomas and 193 high-grade gliomas were gathered to quantify 10 microenvironment cell populations with a deconvolution method designed explicitly for brain tumors. First, we investigated general differences in the microenvironment of low- and high-grade gliomas. Lower-grade and high-grade tumors cluster together, respectively, and show a general similarity within and distinct differences between these groups, the main difference being a higher infiltration of fibroblasts and T cells in high-grade gliomas. Among the analyzed entities, gangliogliomas and pleomorphic xanthoastrocytomas presented the highest overall immune cell infiltration. Further analyses of the low-grade gliomas presented three distinct microenvironmental signatures of immune cell infiltration, which can be divided into T-cell/dendritic/natural killer cell-, neutrophilic/B lineage/natural killer cell-, and monocytic/vascular/stromal-cell-dominated immune clusters. These clusters correlated with tumor location, age, and histological diagnosis but not with sex or progression-free survival. A survival analysis showed that the prognosis can be predicted from gene expression, clinical data, and a combination of both with a support vector machine and revealed the negative prognostic relevance of vascular markers. Overall, our work shows that low- and high-grade gliomas can be characterized and differentiated by their immune cell infiltration. Low-grade gliomas cluster into three distinct immunologic tumor microenvironments, which may be of further interest for upcoming immunotherapeutic research.

OBJECTIVE: Unresectable pediatric low-grade gliomas (LGG) usually need adjuvant therapy, and carboplatin hypersensitivity reaction (HR) commonly leads to premature treatment cessation of a standard chemotherapy regimen. In the molecular era, advances in understanding tumor genetic characteristics allowed the development of targeted therapies for this group of tumors; however, cost-effectiveness assessment of treatments, especially in low-income countries, is crucial. The aim is to describe the results of carboplatin desensitization protocol in a single center in a middle-income country.
METHODS: Prospective analysis of children with LGG submitted to carboplatin desensitization from December 2017 to June 2020 with follow-up until April 2024.
RESULTS: Nine patients were included. The mean age was 11 years. Five patients were male. Seven had optic pathway and two cervicomedullary location. Six had histologic diagnosis and four molecular analyses. The incidence of carboplatin reactions during the study period was 39.1%. Six patients underwent skin prick test, three with positive results. The first HR occurred, on average, around the 9th cycle of treatment. All patients had cutaneous symptoms, and five out of nine had anaphylaxis as the first reaction. 77.7% of the patients completed the protocol, and the clinical benefit rate (stable disease and partial response) was 88.8%. Six patients further required other lines of therapy. Monthly, the total cost for carboplatin was $409.09, and for target therapies (dabrafenib plus trametinib), $4929.28 to $5548.57.
CONCLUSIONS: Our study presented an interesting and cost-effective option where desensitization allowed children with HR to be treated with first-line therapy, avoiding the discontinuation of an effective treatment.

UNASSIGNED: Radiological follow-up of diffuse low-grade gliomas (LGGs) growth is challenging. Approximative visual assessment still predominates over objective quantification due to the complexity of the pathology. The infiltrating character, diffuse borders and presence of surgical cavities demand LGG-based linear measurement rules to efficiently and precisely assess LGG evolution over time.
UNASSIGNED: We compared optimized 1D, 2D, and 3D linear measurements with manual volume segmentation as a reference to assess LGG tumor growth in 36 patients with LGG (340 magnetic resonance imaging scans), using the clinically important mean tumor diameter (MTD) and the velocity diameter expansion (VDE). LGG-specific progression thresholds were established using the high-grade gliomas-based RECIST, Macdonald, and RANO criteria, comparing the sensitivity to identify progression/non-progression for each linear method compared to the ground truth established by the manual segmentation.
UNASSIGNED: 3D linear volume approximation correlated strongly with manually segmented volume. It also showed the highest sensitivity for progression detection. The MTD showed a comparable result, whereas the VDE highlighted that caution is warranted in the case of small tumors with multiple residues. Novel LGG-specific progression thresholds, or the critical change in estimated tumor volume, were increased for the 3D (from 40% to 52%) and 2D methods (from 25% to 33%) and decreased for the 1D method (from 20% to 16%). Using the 3D method allowed a ~5-minute time gain.
UNASSIGNED: While manual volumetric assessment remains the gold standard for calculating growth rate, the 3D linear method is the best time-efficient standardized alternative for radiological evaluation of LGGs in routine use.

BACKGROUND: The transcallosal retroforniceal transchoroidal approach represents an advanced neurosurgical technique that allows access to lesions located within the posterior third ventricle and mesencephalon. It relies on a comprehensive understanding of microsurgical anatomy and embryology, integrating modern neurosurgical operative techniques to minimize retraction and injury to the normal neuronal structures.
METHODS: We report the cases of 2 patients undergoing treatment via this approach, one presenting with a thalamic cavernoma and the other with cystic low-grade glioma of the midbrain.
RESULTS: In these 2 cases, the decision to use the transcallosal approach was mainly due to improved trajectory, gravitational retraction of the hemisphere, and improved delivery of the lesion into the operative field by gravity alone.
CONCLUSIONS: Through a detailed description of the surgical approach and anatomy, we illustrate the feasibility of the transcallosal retroforniceal transchoroidal approach for accessing lesions located deeply in the brain.

UNASSIGNED: Low-grade gliomas (LGG) are a variety of brain tumors that show different clinical outcomes. The methylation of the GSTM5 gene has been noted in the development of LGG, however, its prognostic importance remains uncertain.
UNASSIGNED: The objective of this study was to examine the correlation between GSTM5 DNA methylation and clinical outcomes in individuals diagnosed with LGG.
UNASSIGNED: Analysis of GSTM5 methylation levels in LGG samples was conducted using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The overall survival based on GSTM5 methylation status was evaluated using Kaplan-Meier curves. The DNA methylation heatmap for particular CpG sites in the GSTM5 gene was visualized using the \"pheatmap\" R package.
UNASSIGNED: The study analyzed that LGG tumors had higher levels of GSTM5 methylation than normal tissues. There was an inverse relationship discovered between GSTM5 expression and methylation. LGG patients with hypermethylation of GSTM5 promoter experienced a positive outcome. Age, grade, and GSTM5 methylation were determined as independent prognostic factors in LGG through both univariate and multivariate Cox regression analyses.
UNASSIGNED: Methylation of GSTM5 DNA, specifically at certain CpG sites, is linked to a positive outlook in patients with LGG. Utilizing the \"pheatmap\" R package to visualize GSTM5 methylation patterns offers important information for identifying prognostic markers and therapeutic targets in low-grade gliomas.

Low-grade glioma (LGG) is a grade II-III glioma accompanied by distinct clinical and molecular characteristics and the studies related to its prognosis are still unclear. The objective of this study is to explore the involvement of mitochondrial-related genes SLBP, COMMD7, LSM4, TOMM34, RPP40, FKBP1A, ARPC1A, and TBCA for the prognosis of LGG. We detected differences in the expression of some of the genes by analyzing the bioinformatics dataset and combining it with RT-PCR experiments. Subsequently, a nomogram was constructed and validated for the clinical relevance of risk factors such as age, WHO grade, IDH mutation status, Ch.1p19q co-deletion status, and high and low expression of ARPC1A to predict the 1-, 3-, 5-year overall survival and prognostic relevance of ARPC1A. Gene set enrichment analysis was performed for the relevant datasets pertinent to the expression of ARPC1A to elucidate the cancer-promoting pathways involved in the LGG through KEGG and GO analysis. Transfection assays, CCK-8 assays, and flow cytometry were used to determine the proliferation rate, and apoptosis rate of the HS683 and SW1783 cell lines respectively. Western blotting was used to examine the involvement of the cancer-promoting activity of ARPC1A through MAPK signaling. In this study, the prognostic value of ARPC1A in LGG was found by bioinformatics analysis combined with experimental approach analysis and may be a significant independent risk factor. ARPC1A fosters a higher LGG proliferation rate that may control the MAP kinase signaling and could be a prominent biomarker for LGG. Future studies are warranted to explore its clinical implications.

Tumors may contain billions of cells, including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that are consistently expressed by astrocytoma truncal clones, including AKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors.

UNASSIGNED: The Neurological Assessment for Neuro-Oncology (NANO) scale was elaborated to assess neurologic function in integration with radiological criteria to evaluate neuro-oncological patients in clinical setting and enable the standardization of neurological assessment in clinical trials. The objective of this study is the translation to Brazilian Portuguese and transcultural adaptation of NANO scale in patients with the diagnosis of glioblastoma, brain metastasis and low-grade glioma.
UNASSIGNED: Patients with diagnosis of glioblastoma, brain metastasis, and low-grade glioma were prospectively evaluated between July 2019 and July 2021. The process of translating and cross-culturally adapting the NANO scale included: translation from English to Portuguese, synthesis and initial revision by an expert committee, back-translation from Portuguese to English, a second revision by the expert committee, and the application of the NANO scale. Regarding the reliability of the NANO scale, Cronbach\'s alpha was employed to measure the internal consistency of all scale items and assess the impact of item deletion. Additionally, Spearman\'s correlation test was used to evaluate the convergent validity between the NANO scale and Karnofsky Performance Scale (KPS).
UNASSIGNED: One hundred and seventy-four patients were evaluated. A statistically significant inverse relation (p < 0.001) between KPS and NANO scale was founded. The Cronbach\'s alpha values founded for NANO scale were 0.803 for glioblastoma, 0.643 for brain metastasis, and 0.482 for low grade glioma.
UNASSIGNED: The NANO scale Brazilian Portuguese version proves to be reproducible and valid to evaluate neuro-oncological patients with glioblastoma and brain metastasis, presenting a strong correlation with KPS scale. Further studies are warranted to assess the validity and reliability of the scale in patients diagnosed with low-grade glioma.

OBJECTIVE: To review the literature on second-look surgery in pediatric low-grade gliomas (LGG) with a view to presenting both sides of the picture of re-exploration.
METHODS: Collection of material from recent literature on pediatric LGG. This was a retrospective review of these publications.
RESULTS: There are a number of publications recommending second-look surgery in selected cases, provided morbidity of the second surgery is minimum, and indeed some in which there is improvement in the neurodeficit after the second resection.
CONCLUSIONS: There seems a fair balance of articles recommending and dissuading the practice of second-look surgery, but in our limited experience we have found it useful in selected patients.

Glioma is the most common primary malignant tumor in the brain, characterizing by high disability rate and high recurrence rate. Although low-grade glioma (LGG) has a relative benign biological behavior, the prognosis of LGG patients still varies greatly. Glioma stem cells (GSCs) are considered as the chief offenders of glioma cell proliferation, invasion and resistance to therapies. Our study screened a series of glioma stem cell-related genes (GSCRG) based on mDNAsi and WCGNA, and finally established a reliable single-gene prognostic model through 101 combinations of 10 machine learning methods. Our result suggested that the expression level of TNFAIP6 is negatively correlated with the prognosis of LGG patients, which may be the result of pro-cancer signaling pathways activation and immunosuppression. In general, this study revealed that TNFAIP6 is a robust and valuable prognostic factor in LGG, and may be a new target for LGG treatment.