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Stereotactic Brachytherapy Iodine-125 (SBT I-125) has been investigated by some studies for the treatment of lowgrade gliomas. We performed a meta-analysis to assess the efficacy and safety of SBT I-125 Brachytherapy for treatment of patients with Low-Grade Gliomas. PubMed, Cochrane, Web of Science, and EMBASE databases were searched for randomized and observational studies. This systematic review and meta-analysis was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. We used relative risk (RR) with 95% confidence intervals and random effects model to compare the effects of I-125 SBT treatment on the interest outcomes. We evaluated heterogeneity using I2 statistics; we considered heterogeneity to be significant if the p-value was less than 0.05 and I2 was higher than 35%. We performed statistical analysis using the software R (version 4.2.3). A total of 20 studies with a cohort of 988 patients with low grade gliomas who received SBT I-125 as a treatment option. The pooled analysis evidenced: (1) Complication rate of 10% (95% CI: 7–12%; I² = 60%); (2) 5-year PFS of 66% (99% CI: 45-86%; I²= 98%); (3) 10-year PFS was 66% (99% CI: 45-86%; I²= 98%); (4) Malignant transformation rate of 26% (95% CI: 8–45%; I²=0); (5) Mortality of 33% (95% CI: 15–51%; I² = 0%). Our systematic review and meta-analysis of SBT I-125 for low-grade gliomas have revealed significant concerns regarding its safety and efficacy. Despite a proportion of patients remaining progression-free, elevated rates of complications and mortality cast doubt on the intervention's reliability. Future research should prioritize long-term follow-up studies, standardized protocols, and comparative effectiveness research. [ABSTRACT FROM AUTHOR]

Background: Family with sequence similarity 109, member B (FAM109B) is involved in endocytic transport and affects genetic variation in brain methylation. It is one of the important genes related to immune cell-associated diseases. In the tumor immune system, methylation can regulate tumor immunity and influence the maturation and functional response of immune cells. Whether FAM109B is involved in tumor progression and its correlation with the tumor immune microenvironment has not yet been disclosed. Methods: A comprehensive pan-cancer analysis of FAM109B expression, prognosis, immunity, and TMB was conducted. The expression, clinical features, and prognostic value of FAM109B in low-grade gliomas (LGG) were evaluated using TCGA, CGGA, and Gravendeel databases. The expression of FAM109B was validated by qRT-PCR, immunohistochemistry (IHC), and Western blotting (WB). The relationship between FAM109B and methylation, Copy Number Variation (CNV), prognosis, immune checkpoints (ICs), and common chemotherapy drug sensitivity in LGG was explored through Cox regression, Kaplan–Meier curves, and Spearman correlation analysis. FAM109B levels and their distribution were studied using the TIMER database and single-cell analysis. The potential role of FAM109B in gliomas was further investigated through in vitro and in vivo experiments. Results: FAM109B was significantly elevated in various tumor types and was associated with poor prognosis. Its expression was related to aggressive progression and poor prognosis in low-grade glioma patients, serving as an independent prognostic marker for LGG. Glioma grade was negatively correlated with FAM109B DNA promoter methylation. Immune infiltration and single-cell analysis showed significant expression of FAM109B in tumor-associated macrophages (TAMs). The expression of FAM109B was closely related to gene mutations, immune checkpoints (ICs), and chemotherapy drugs in LGG. In vitro studies showed increased FAM109B expression in LGG, closely related to cell proliferation. In vivo studies showed that mice in the sh-FAM109B group had slower tumor growth, slower weight loss, and longer survival times. Conclusions: FAM109B, as a novel prognostic biomarker for low-grade gliomas, exhibits specific overexpression in TAMs and may be a potential therapeutic target for LGG patients. [ABSTRACT FROM AUTHOR]

Whether N6‐Methyladenosine (m6A)‐ and ferroptosis‐related genes act on immune responses to regulate glioma progression remains unanswered. Data of glioma and corresponding normal brain tissues were fetched from the TCGA database and GTEx. Differentially expressed genes (DEGs) were identified for GO and KEGG enrichment analyses. The FerrDb database was based to yield ferroptosis‐related DEGs. Hub genes were then screened out using the cytoHubba database and validated in clinical samples. Immune cells infiltrating into the glioma tissues were analysed using the CIBERSORT R script. The association of gene signature underlying the m6A‐related ferroptosis with tumour‐infiltrating immune cells and immune checkpoints in low‐grade gliomas was analysed. Of 6298 DEGs enriched in mRNA modifications, 144 were ferroptosis‐related; NFE2L2 and METTL16 showed the strongest positive correlation. METTL16 knockdown inhibited the migrative and invasive abilities of glioma cells and induced ferroptosis in vitro. NFE2L2 was enriched in the anti‐m6A antibody. Moreover, METTL16 knockdown reduced the mRNA stability and level of NFE2L2 (both p < 0.05). Proportions of CD8+ T lymphocytes, activated mast cells and M2 macrophages differed between low‐grade gliomas and normal tissues. METTL16 expression was negatively correlated with CD8+ T lymphocytes, while that of NFE2L2 was positively correlated with M2 macrophages and immune checkpoints in low‐grade gliomas. Gene signatures involved in the m6A‐related ferroptosis in gliomas were identified via bioinformatic analyses. NFE2L2 interacted with METTL16 to regulate the immune response in low‐grade gliomas, and both molecules may be novel therapeutic targets for gliomas. [ABSTRACT FROM AUTHOR]

Abstract Background Family with sequence similarity 109, member B (FAM109B) is involved in endocytic transport and affects genetic variation in brain methylation. It is one of the important genes related to immune cell-associated diseases. In the tumor immune system, methylation can regulate tumor immunity and influence the maturation and functional response of immune cells. Whether FAM109B is involved in tumor progression and its correlation with the tumor immune microenvironment has not yet been disclosed. Methods A comprehensive pan-cancer analysis of FAM109B expression, prognosis, immunity, and TMB was conducted. The expression, clinical features, and prognostic value of FAM109B in low-grade gliomas (LGG) were evaluated using TCGA, CGGA, and Gravendeel databases. The expression of FAM109B was validated by qRT-PCR, immunohistochemistry (IHC), and Western blotting (WB). The relationship between FAM109B and methylation, Copy Number Variation (CNV), prognosis, immune checkpoints (ICs), and common chemotherapy drug sensitivity in LGG was explored through Cox regression, Kaplan–Meier curves, and Spearman correlation analysis. FAM109B levels and their distribution were studied using the TIMER database and single-cell analysis. The potential role of FAM109B in gliomas was further investigated through in vitro and in vivo experiments. Results FAM109B was significantly elevated in various tumor types and was associated with poor prognosis. Its expression was related to aggressive progression and poor prognosis in low-grade glioma patients, serving as an independent prognostic marker for LGG. Glioma grade was negatively correlated with FAM109B DNA promoter methylation. Immune infiltration and single-cell analysis showed significant expression of FAM109B in tumor-associated macrophages (TAMs). The expression of FAM109B was closely related to gene mutations, immune checkpoints (ICs), and chemotherapy drugs in LGG. In vitro studies showed increased FAM109B expression in LGG, closely related to cell proliferation. In vivo studies showed that mice in the sh-FAM109B group had slower tumor growth, slower weight loss, and longer survival times. Conclusions FAM109B, as a novel prognostic biomarker for low-grade gliomas, exhibits specific overexpression in TAMs and may be a potential therapeutic target for LGG patients.

Background: Diffuse astrocytomas preferentially infiltrate eloquent areas affecting the outcome. A preoperative understanding of isocitrate dehydrogenase (IDH) status may offer opportunities for specific targeted therapies impacting treatment management. The aim of this study was to analyze clinical, topographical, radiological in WHO 2 astrocytomas with different IDH status and the long-term patient’s outcome. Methods: A series of confirmed WHO 2 astrocytoma patients (between 2005 and 2015) were retrospectively analyzed. MRI sequences (FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations into the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was used as an overlay for infiltration analysis of each tumor. Long-term follow-up was used to perform a survival analysis. Results: Forty patients with confirmed IDH status (26 IDH-mutant, IDHm/14 IDH-wild type, IDHwt) according to WHO 2021 classification were included with a mean follow-up of 7.8 years. IDHm astrocytomas displayed a lower number of BG-voxels (P < 0.05) and were preferentially located in the anterior insular region. IDHwt group displayed a posterior insular and peritrigonal location. IDHwt group displayed a shorter OS compared with IDHm (P < 0.05), with the infiltration of 7 or more BG-voxels as an independent factor predicting a shorter OS. Conclusions: IDHm and IDHwt astrocytomas differed in preferential location, number of BG-voxels and OS at long follow-up time. The number of BG-voxels affected the OS in IDHwt was possibly reflecting higher tumor invasiveness. We encourage the systematic use of alternative observational tools, such as gradient maps and the Brain-Grid analysis, to better detect differences of tumor invasiveness in diffuse low-grade gliomas subtypes.

Mutations in isocitrate dehydrogenase (IDH) genes have important prognostic signifi cance for patients with glial neoplasms of the brain. Proton MR spectroscopy provides non-invasive determination of the metabolic properties of tumor tissue at the preoperative stage. The aim of the present work was to investigate the feasibility of determining isocitrate dehydrogenase (IDH) mutation status using magnetic resonance spectroscopy (MRS) to detect the presence of 2-hydroxyglutarate (2HG), the metabolic product of the enzyme IDH. We examined 33 patients with glial brain tumors with different degrees of malignancy (grades 2–4), with subsequent identifi cation of IDH mutations. IDH mutations found by proton MRS were confi rmed immunohistochemically in 20 cases. In 13 cases, the 2HG peak was not detected on the MR spectrum and analysis of IDH did not reveal mutations. The use of proton MRS has demonstrated that this method has high sensitivity in predicting the mutation status of glial brain tumors, which makes this method an important tool in preoperative diagnosis. [ABSTRACT FROM AUTHOR]

Dissemination in pediatric low-grade gliomamay occur in about 4%-10% of patients according to retrospective cohort studies. Due to its low incidence, there is no consensus on treatment for these patients. According to the constitutional activation of the MAPK/ERK pathway in these tumors, MEK inhibitors such as trametinib have been used successfully in the relapsed setting. Skin toxicity is frequent in patients receiving trametinib, normally mild to moderate, but sometimes severe, needing to discontinue the drug, limiting the efficacy in the tumor. There is notmuch information in the literature regarding whether reducing the dose of trametinib is able to maintain efficacy while, at the same time, decreasing toxicity. Here, we present an adolescent, with severe skin toxicity, whose trametinib dose was reduced by 50% and efficacy on the tumor continued while skin toxicity significantly decreased. [ABSTRACT FROM AUTHOR]

AbstractThis study is part of a longitudinal research program, in which patients diagnosed with low-grade gliomas (LGG: n = 13), as well as healthy controls (n = 13), were consecutively recruited and neuropsychologically followed for 7 years. The patients are followed up regardless of variations in treatment. A composite score is used (Global Deficit Score: GDS) included cognitive measures where at least five patients had a negative change: information processing speed, speed of naming, construction ability, verbal fluency, non-verbal thinking, and immediate non-verbal memory. The most important finding in this 7-year follow-up study is that two-thirds of the patients developed cognitive impairment. The remaining third of the patients showed stability in their cognitive ability and were still alive 17 years after diagnosis. Younger patients with tumors in the right frontal or posterior regions showed a more favorable development. Patients with frontal tumors and a declined GDS show also significant changes in executive functions. Given the limited number, no firm conclusions can be drawn regarding the impact of tumor localization. The impact of LGG on cognition and the survival time after diagnosis varies considerably between patients. However, most of the patients (69%) showed cognitive impairment during the seven years we followed them. [ABSTRACT FROM AUTHOR]

The main treatment of low-grade glioma (LGG) is still surgical resection followed by radiotherapy and/or chemotherapy, which has certain limitations, including side effects and drug resistance. Immunotherapy is a promising treatment for LGG, but it is generally hindered by the tumor microenvironment with the limited expression of tumor antigens. We integrated RNA sequencing data sets and clinical information and conducted consistent cluster analysis to explore the most suitable patients for immune checkpoint therapy. Gene set enrichment analysis, UMAP analysis, mutation correlation analysis, TIMER analysis, and TIDE analysis were used to identify the immune characteristics of 3 immune subtypes and the feasibility of 5 antigens as immune checkpoint markers. We analyzed the isolation and mutation of homologous recombination repair genes (HRR) of the 3 immune subtypes, and the HRR genes of the 3 subtypes were obviously segregated. Among them, the IS2 subtype has a large number of HRR gene mutations, which increases the immunogenicity of tumors—this is consistent with the results of tumor mutation load analysis of 3 immune subtypes. Then we evaluated the immune cell infiltration of immune subtypes and found that IS2 and IS3 subtypes were rich in immune cells. It is worth noting that there are many Treg cells and NK cells in the IS1 subtype. In addition, when analyzing the immune checkpoint gene expression of the 3 subtypes, we found that they were upregulated most in IS2 subtypes compared with other subtypes. Then when we further confirmed the role of immune-related genes in LGG; through TIDE analysis and TISIDB analysis, we obtained 5 markers that can predict the efficacy of ICB in patients with LGG. In addition, we confirmed that they were associated with poor prognosis through survival analysis. We obtained 3 reliable immune subtypes, and patients with the IS2 subtype are suitable for immunotherapy, in which NAMPT, SLC11A1, TNC, VIM, and SPP1 are predictive panel markers for ICB in the LGG group. Our findings provide a rationale for immunotherapy selection and prediction of patient prognosis in LGG patients. [ABSTRACT FROM AUTHOR]

Low grade gliomas (LGGs) of pineal region are usually difficult to remove and they frequently relapse or progress after front line chemotherapy. Bevacizumab-Irinotecan (BEVIRI) combination has been successfully attempted in children with recurrent LGGs, in most cases not previously irradiated. The efficacy of bevacizumab has also been described in radiation necrosis. Considering the possible overlapping of radiation treatment effect and disease progression and difficulty in differentiating, we report on the use of BEVIRI in a case of a recurrent relapsing low-grade glioma of the pineal region, subjected to multiple neurosurgical interventions, also treated with a carboplatin-etoposide regimen and a radiation course, at present at one-year follow-up showing a stable response, with no adverse events. [ABSTRACT FROM AUTHOR]

Objectives: The location of the brain tumor in the frontal or temporal lobes has been reported as a predictor for seizure occurrence in patients with a brain tumor but the predictive value of other locations is uncertain. We aimed to ascertain the pooled prevalence of pre-operative seizures in relation to the brain tumor locations, by employing a systematic review and meta-analysis. Methods: The search was conducted up to 1st May 2023, in Pubmed, Embase, and Web of Science and references were exported and managed using EndNote 20. Articles were included if they reported a prevalence or incidence of the seizure at the tumor location. MetaXL by Epigear was used to generate the meta-analysis. Results: The pooled prevalence for preoperative seizures in gliomas was 51–63% in most locations (frontal, temporal, parietal, and insula) but lowest in the occipital lobe (28%). Subgroup analysis on low-grade gliomas showed a high pre-operative seizure prevalence in all locations: frontal lobe [75% (95% CI: 68–81%)], temporal lobe [73% (95% CI: 63–82%)], parietal lobe [79% (95% CI: 57–82%)], occipital lobe [46% (95% CI: 0–95%)], and insular [76% (95% CI: 65–77%)]. In the astrocytoma and meningioma subanalysis, the pooled prevalence is ≥ 40% in most cortical location. In brain metastases, the pooled prevalence was similar in most locations (18–39%), lowest in the temporal lobe. Conclusion: Tumor location is not the main influencing factor for pre-operative seizure independent from tumor type. Extensive seizure screening should be considered irrespective of tumor location, especially in those with low-grade gliomas.

Dissemination in pediatric low-grade glioma may occur in about 4%–10% of patients according to retrospective cohort studies. Due to its low incidence, there is no consensus on treatment for these patients. According to the constitutional activation of the MAPK/ERK pathway in these tumors, MEK inhibitors such as trametinib have been used successfully in the relapsed setting. Skin toxicity is frequent in patients receiving trametinib, normally mild to moderate, but sometimes severe, needing to discontinue the drug, limiting the efficacy in the tumor. There is not much information in the literature regarding whether reducing the dose of trametinib is able to maintain efficacy while, at the same time, decreasing toxicity. Here, we present an adolescent, with severe skin toxicity, whose trametinib dose was reduced by 50% and efficacy on the tumor continued while skin toxicity significantly decreased.

Abstract Background Due to the heterogeneity of low‐grade gliomas (LGGs), the lack of randomized control trials, and strong clinical evidence, the effect of the extent of resection (EOR) is currently controversial. Aim To determine the best choice between subtotal resection (STR) and gross‐total resection (GTR) for individual patients and to identify features that are potentially relevant to treatment heterogeneity. Methods Patients were enrolled from the SEER database. We used a novel DL approach to make treatment recommendations for patients with LGG. We also made causal inference of the average treatment effect (ATE) of GTR compared with STR. Results The patients were divided into the Consis. and In‐consis. groups based on whether their actual treatment and model recommendations were consistent. Better brain cancer‐specific survival (BCSS) outcomes in the Consis. group was observed. Overall, we also identified two subgroups that showed strong heterogeneity in response to GTR. By interpreting the models, we identified numerous variables that may be related to treatment heterogeneity. Conclusions This is the first study to infer the individual treatment effect, make treatment recommendation, and guide surgical options through deep learning approach in LGG research. Through causal inference, we found that heterogeneous responses to STR and GTR exist in patients with LGG. Visualization of the model yielded several factors that contribute to treatment heterogeneity, which are worthy of further discussion.

BackgroundSince IDH-mutant (mIDH) low-grade gliomas (LGGs) progress slowly and have a relatively long survival, there is a significant need for earlier measurements of clinical benefit. Guidance using the LGG RANO criteria recommends serial bidirectional (2D) measurements on a single slice; however, questions remain as to whether volumetric (3D) measurements are better, since they would allow for more accurate measurements in irregular shaped lesions and allow readers to better assess areas of subtle change.MethodsTwenty-one (out of 24) non-enhancing, recurrent mIDH1 LGGs were enrolled in a phase I, multicenter, open-label study of oral ivosidenib (NCT02073994), and with imaging pre- and post-treatment as part of this exploratory ad hoc analysis. 2D and 3D measurements on T2-weighted FLAIR images were centrally evaluated at an imaging contract research organization using a paired read and forced adjudication paradigm. The effects of 2D vs 3D measurements on progression-free survival (PFS), growth rate measurement variability, and reader concordance and adjudication rates were quantified.Results3D volumetric measurements showed significantly longer estimated PFS (P = .0181), more stable (P = .0063) and considerably slower measures of tumor growth rate (P = .0037), the highest inter-reader agreement (weighted kappa = 0.7057), and significantly lower reader discordance rates (P = .0002) with 2D LGG RANO.Conclusion3D volumetric measurements are better for determining response assessment in LGGs due to more stable measures of tumor growth rates (ie, less "yo-yo-ing" of measurements over time), highest inter-reader agreement, and lowest reader discordance rates. Continued evaluation in future studies is warranted to determine whether these measurements reflect clinical benefit.

Objective: Epithelial-mesenchymal transition (EMT) is a tightly regulated and dynamic process occurring in both embryonic development and tumor progression. Our study aimed to comprehensively explore the molecular subtypes, immune landscape, and prognostic signature based on EMT-related genes in low-grade gliomas (LGG) in order to facilitate treatment decision-making and drug discovery. Methods: We curated EMT-related genes and performed molecular subtyping with consensus clustering algorithm to determine EMT expression patterns in LGG. The infiltration level of diverse immune cell subsets was evaluated by implementing the single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms. The distinctions in clinical characteristics, mutation landscape, and immune tumor microenvironment (TME) among the subtypes were subjected to further investigation. Gene Set Variation Analysis (GSVA) was performed to explore the biological pathways that were involved in subtypes. The chemo drug sensitivity and immunotherapy of subtypes were estimated through GDSC database and NTP algorithm. To detect EMT subtype-related prognostic gene modules, the analysis of weighted gene co-expression network (WGCNA) was performed. The LASSO algorithm was utilized to construct a prognostic risk model, and its efficacy was verified through an independent CGGA dataset. Finally, the expression of the hub genes from the prognostic model was evaluated through the single-cell dataset and in-vitro experiment. Results: The TCGA-LGG dataset revealed the creation of two molecular subtypes that presented different prognoses, clinical implications, TME, mutation landscapes, chemotherapy, and immunotherapy. A three-gene signature (SLC39A1, CTSA and CLIC1) based on EMT expression pattern were established through WGCNA analysis. Low-risk patients showed a positive outlook, increased immune cell presence, and higher expression of immune checkpoint proteins. In addition, several promising drugs, including birinapant, fluvastatin, clofarabine, dasatinib, tanespimycin, TAK-733, GDC-0152, AZD8330, trametinib and ingenol-mebutate had great potential to the treatment of high risk patients. Finally, CTSA and CLIC1 were highly expressed in monocyte cell through single-cell RNA sequencing analysis. Conclusion: Our research revealed non-negligible role of EMT in theTME diversity and complexity of LGG. A prognostic signature may contribute to the personalized treatment and prognostic determination. [ABSTRACT FROM AUTHOR]

Low-Grade Gliomas (LGGs) represent a diverse group of brain tumors originating from glial cells, characterized by their unique histopathological and molecular features. This article offers a comprehensive exploration of LGGs, shedding light on their subtypes, histological and molecular aspects. By delving into the World Health Organization's grading system, 5th edition, various specificities were added due to an in-depth understanding of emerging laboratory techniques, especially genomic analysis. Moreover, treatment modalities are extensively discussed. The degree of surgical resection should always be considered according to postoperative quality of life and cognitive status. Adjuvant therapies focused on chemotherapy and radiotherapy depend on tumor grading and invasiveness. In the current literature, emerging targeted molecular therapies are well discussed due to their succinctly therapeutic effect; in our article, those therapies are summarized based on posttreatment results and possible adverse effects. This review serves as a valuable resource for clinicians, researchers, and medical professionals aiming to deepen their knowledge on LGGs and enhance patient care. [ABSTRACT FROM AUTHOR]

Introduction: Despite advances in comprehending cancer biology, malignant gliomas remain incurable. The present work conducted a multi-omics analysis for investigating the significance of chloride intracellular channel 1 (CLIC1) in gliomas. Methods: Multi-omics data of glioma covering transcriptomics, genomics, DNA methylation and single-cell transcriptomics from multiple public cohorts were enrolled for analyzing CLIC1. In vitro experiments were conducted to measure apoptosis and cell mobility in U251 and U373 glioma cells following transfection of CLIC1 siRNAs. Results: Elevated CLIC1 expression was proven to stably and independently estimate worse survival outcomes. CLIC1 expression was higher in more advanced stage, wild-type IDH and unmethylated MGMT samples. Tumorigenic and anticancer immunity pathways were remarkably enriched in CLIC1-up-regulated tumors. Additionally, CLIC1 was positively linked with cancer-immunity cycle, stromal activation, DNA damage repair and cell cycle. Suppressing CLIC1 resulted in apoptosis and attenuated cell motility of glioma cells. More frequent genomic alterations were found in CLIC1-up-regulated tumors. CLIC1 expression presented a remarkably negative connection to DNA methylation. High CLIC1 expression samples were more sensitive to camptothecin, cisplatin, doxorubicin, erlotinib, paclitaxel, rapamycin, clofarabine, tanespimycin, methotrexate, everolimus, TAK-733, trametinib and AZD8330. Tumors with upregulated CLIC1 presented abundant immune cell infiltration, higher expression of immune-checkpoints and -modulators and similar transcriptome profiling, indicative of well response to immune-checkpoint blockade (ICB). Nevertheless, due to elevated TIDE score, tumors with CLIC1 upregulation appeared to be resistant to ICB. Singlecell analysis unveiled that CLIC1 was expressed ubiquitously in tumor cells and tumor microenvironment. Conclusions: Overall, CLIC1 was a promising treatment vulnerability in glioma. [ABSTRACT FROM AUTHOR]

Background: Due to the heterogeneity of low‐grade gliomas (LGGs), the lack of randomized control trials, and strong clinical evidence, the effect of the extent of resection (EOR) is currently controversial. Aim: To determine the best choice between subtotal resection (STR) and gross‐total resection (GTR) for individual patients and to identify features that are potentially relevant to treatment heterogeneity. Methods: Patients were enrolled from the SEER database. We used a novel DL approach to make treatment recommendations for patients with LGG. We also made causal inference of the average treatment effect (ATE) of GTR compared with STR. Results: The patients were divided into the Consis. and In‐consis. groups based on whether their actual treatment and model recommendations were consistent. Better brain cancer‐specific survival (BCSS) outcomes in the Consis. group was observed. Overall, we also identified two subgroups that showed strong heterogeneity in response to GTR. By interpreting the models, we identified numerous variables that may be related to treatment heterogeneity. Conclusions: This is the first study to infer the individual treatment effect, make treatment recommendation, and guide surgical options through deep learning approach in LGG research. Through causal inference, we found that heterogeneous responses to STR and GTR exist in patients with LGG. Visualization of the model yielded several factors that contribute to treatment heterogeneity, which are worthy of further discussion. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effectiveness and safety of various adjuvant regimens in patients with low-grade gliomas and to further explore the optimal adjuvant treatment for patients with low-grade gliomas and the differences in the efficacy of each treatment regimens in different tumor types. A comprehensive search of the PubMed, Cochrane Library, Ovid, Embase, and Web of Science databases was conducted to screen randomized and nonrandomized controlled trials related to adjuvant therapy in patients with low-grade gliomas. The Cochrane quality assessment method and the Newcastle-Ottawa Scale were used to assess the quality of the included randomized and nonrandomized controlled trials, respectively. The data from previous studies were extracted using Excel and GetData Graph Digitizer 2.26 software, and network meta-analysis was performed using RevMan 5.3 and Stata 16.0 statistical software. The specific ranking of 5-year progression-free survival (5-year PFS) for each treatment regimen from the best to the worst in patients with low-grade gliomas was surgery (S) combined with procarbazine, lomustine, and vincristine (S + PCV); surgery combined with standard radiotherapy and PCV multidrug chemotherapy (S + RT + PCV); surgery combined with standard radiotherapy and temozolomide monotherapy (S + RT + TMZ); surgery combined with enhanced radiotherapy (S + H-RT); surgery combined with standard radiotherapy (S + RT); surgery combined with TMZ (S + TMZ); and S. The 5-year overall survival (OS) ranking was S + RT + TMZ, S + RT + PCV, surgery combined with enhanced radiotherapy and TMZ monotherapy (S + H-RT + TMZ), S + H-RT, S + RT, and S. The 2-year progression-free survival ranking was S + RT + TMZ, S + PCV, S + RT, S + RT + PCV, S + TMZ, S + H-RT, and S. The 2-year overall survival ranking was S + RT + TMZ, S + H-RT + TMZ, S + RT, S + RT + PCV, S + H-RT, and S. The incidence of adverse events (≥3) was ranked from highest to lowest as follows: S + RT + PCV, S + RT + TMZ, S + PCV, S + H-RT, S + TMZ, and S + RT. In the isocitrate dehydrogenase 1/2 mutation nonchromosome 1p and 19q chromosome whole arm codeletion (IDHmt/noncoder) group, the S + RT + PCV and S + H-RT regimens had better 5-year PFS and 5-year OS. In the isocitrate dehydrogenase 1/2 mutation and chromosome 1p and 19q chromosome whole arm codeletion (IDHmt/coder) group, the 5-year PFS of each treatment regimen ranked from the best to the worst was S + RT + TMZ, S + RT + PCV, S + H-RT, S + RT, S + TMZ, and S. The order of 5-year OS from the best to the worst was S + H-RT, S + RT + TMZ, S + RT + PCV, S + RT, and S. In the isocitrate dehydrogenase 1/2 wild-type (IDHwt) group, the S + H-RT and S + TMZ regimens had better 5-year PFS. This study revealed that both the S + RT + TMZ and S + RT + PCV regimens might be effective therapies for treating patients with low-grade gliomas. Among these, the S + RT + TMZ regimen seemed to be safer but might lead to tumor deterioration. In the IDHmt/coder type, the S + RT + TMZ scheme might have a significant advantage. In the IDHmt/noncoder type, the S + RT + PCV scheme might be more dominant, while in the IDHwt type, the S + H-RT and S + TMZ schemes also might be good treatment options. [ABSTRACT FROM AUTHOR]

Background. Pyroptosis, a lytic form of programmed cell death initiated by inflammasomes, has been reported to be closely associated with tumor proliferation, invasion and metastasis. However, the roles of pyroptosis genes (PGs) in low-grade glioma (LGG) remain unclear. Methods. We obtained information for 1,681 samples, including the mRNA expression profiles of LGGs and normal brain tissues and the relevant corresponding clinical information from two public datasets, TCGA and GTEx, and identified 45 differentially expressed pyroptosis genes (DEPGs). Among these DEPGs, nine hub pyroptosis genes (HPGs) were identified and used to construct a genetic risk scoring model. A total of 476 patients, selected as the training group, were divided into low-risk and high-risk groups according to the risk score. The area under the curve (AUC) values of the receiver operating characteristic (ROC) curves verified the accuracy of the model, and a nomogram combining the risk score and clinicopathological characteristics was used to predict the overall survival (OS) of LGG patients. In addition, a cohort from the Gene Expression Omnibus (GEO) database was selected as a validation group to verify the stability of the model. qRT-PCR was used to analyze the gene expression levels of nine HPGs in paracancerous and tumor tissues from 10 LGG patients. Results. Survival analysis showed that, compared with patients in the low-risk group, patients in the high-risk group had a poorer prognosis. A risk score model combining PG expression levels with clinical features was considered an independent risk factor. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that immune-related genes were enriched among the DEPGs and that immune activity was increased in the high-risk group. Conclusion. In summary, we successfully constructed a model to predict the prognosis of LGG patients, which will help to promote individualized treatment and provide potential new targets for immunotherapy. [ABSTRACT FROM AUTHOR]

The POFUT1 gene, known to be up-regulated in various tumor tissues and associated with tumor biology, has yet to be explored for its potential role in immune response regulation and tumor immune microenvironment. The normalized pan-cancer dataset (TCGA Pan-Cancer) was downloaded from the UCSC database, followed by analysis of POFUT1 expression in various tumors and functional enrichment analysis. The correlation between POFUT1 expression levels and patient prognosis was assessed. GSEA of POFUT1 based on low-grade glioma (LGG) samples and immune infiltration analyses of LGG and glioblastoma (GBM) were conducted. The correlation between POFUT1 expression levels and infiltration levels of 22 immune cells in LGG and GBM was examined, as well as the correlation between immune cell infiltration levels and LGG patient prognosis. Additionally, the relationship between POFUT1 expression levels and characteristic gene expression of identified immune cells was evaluated. Lastly, external dataset validation was performed using the integrated CGGA dataset. Significant differences were observed in POFUT1 expression levels across 20 tumor types. High POFUT1 expression correlated with poor prognosis in GBMLGG, and LGG patients. Enrichment analysis and GSEA of POFUT1 in LGG demonstrated involvement in tumor-related and immune-related pathways. A positive correlation was identified between POFUT1 expression levels and infiltration levels of resting memory CD4+ T cells, as well as M2 macrophages or M2-like TAMs in the LGG immune microenvironment, potentially contributing to poor prognosis. External dataset validation revealed a positive correlation between M2 macrophages or M2-like TAMs and POFUT1 expression levels in LGG, and a negative correlation with LGG patient prognosis. POFUT1's negative impact on LGG prognosis may result from its influence on M2 macrophage and M2-like TAM infiltration levels within the immune microenvironment. This suggests its potential as a prognostic predictor and therapeutic target for LGG.

Low-grade gliomas (LGG) are the most common primary tumours in the central nervous system in children. Histologically, they are a heterogeneous group of brain tumours. The most common of them is pilocytic astrocytoma. The signalling pathway of mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of these tumours, so the search for effective targeted drugs with few side effects is the subject of current research. This article presents a clinical case of a boy with inoperable LGG, which was poorly responsive to established systemic treatment, so he received targeted treatment with an MEK inhibitor.

Background: The determination of area tumor presents the chief challenge in brain tumor therapy and assessment. Without ionizing radiation, the medical Magnetic Resonance Imaging (MRI) tool has appeared as an essential diagnostic technique for brain cancers. Using 2D MRI images, manual segmentation of brain tumor size is a slow, error-prone task which the performance is extremely depends on operator's experience. In that respect, a consistent totally automated segmentation approach for the brain tumor detection is effectively needed to get a proficient dimension of the tumor size. Results: In this paper, an effusively computerized scheme for brain tumor detection is proposed by the use of deep convolutional networks. The proposed method was appraised on Brain Tumor Image Segmentation (BRATS 2020) datasets, including 1352 affected by brain tumor. Conclusion: Cross-validation technique has revealed that our process can attain talented segmentation competently reaching higher accuracy compared to other previous studies.

Low grade gliomas (LGGs) of pineal region are usually difficult to remove and they frequently relapse or progress after front line chemotherapy. BevacizumabIrinotecan (BEVIRI) combination has been successfully attempted in children with recurrent LGGs, in most cases not previously irradiated. The efficacy of bevacizumab has also been described in radiation necrosis. Considering the possible overlapping of radiation treatment effect and disease progression and difficulty in differentiating, we report on the use of BEVIRI in a case of a recurrent relapsing low-grade glioma of the pineal region, subjected to multiple neurosurgical interventions, also treated with a carboplatin-etoposide regimen and a radiation course, at present at one-year follow-up showing a stable response, with no adverse events. [ABSTRACT FROM AUTHOR]

Fusions involving CRAF (RAF1) are infrequent oncogenic drivers in pediatric low‐grade gliomas, rarely identified in tumors bearing features of pilocytic astrocytoma, and involving a limited number of known fusion partners. We describe recurrent TRAK1::RAF1 fusions, previously unreported in brain tumors, in three pediatric patients with low‐grade glial‐glioneuronal tumors. We present the associated clinical, histopathologic and molecular features. Patients were all female, aged 8 years, 15 months, and 10 months at diagnosis. All tumors were located in the cerebral hemispheres and predominantly cortical, with leptomeningeal involvement in 2/3 patients. Similar to previously described activating RAF1 fusions, the breakpoints in RAF1 all occurred 5′ of the kinase domain, while the breakpoints in the 3′ partner preserved the N‐terminal kinesin‐interacting domain and coiled‐coil motifs of TRAK1. Two of the three cases demonstrated methylation profiles (v12.5) compatible with desmoplastic infantile ganglioglioma (DIG)/desmoplastic infantile astrocytoma (DIA) and have remained clinically stable and without disease progression/recurrence after resection. The remaining tumor was non‐classifiable; with focal recurrence 14 months after initial resection; the patient remains symptom free and without further recurrence/progression (5 months post re‐resection and 19 months from initial diagnosis). Our report expands the landscape of oncogenic RAF1 fusions in pediatric gliomas, which will help to further refine tumor classification and guide management of patients with these alterations. [ABSTRACT FROM AUTHOR]

Malignant transformation (MT) of low‐grade gliomas (LGGs) to a higher‐grade variant seems inevitable, yet it remains unclear which LGG patients will progress to grade 3 or even directly to grade 4 after receiving a long course of treatment. To elucidate this, we conducted a retrospective cohort study based on 229 adults with recurrent LGG. Our study aimed to disclose the characteristics of different MT patterns and to build predictive models for patients with LGG. Patients were allocated into group 2–2 (n = 81, 35.4%), group 2–3 (n = 91, 39.7%), and group 2–4 (n = 57, 24.9%), based on their MT patterns. Patients who underwent MT showed lower Karnofsky performance scale (KPS) scores, larger tumor sizes, smaller extents of resection (EOR), higher Ki‐67 indices, lower rates of 1p/19q codeletion, but higher rates of subventricular involvement, radiotherapy, chemotherapy, astrocytoma, and post‐progression enhancement (PPE) compared with those in group 2–2 (p < 0.01). On multivariate logistic regression, 1p/19q codeletion, Ki‐67 index, radiotherapy, EOR, and KPS score were independently associated with MT (p < 0.05). Survival analyses demonstrated that patients in group 2–2 had the longest survival, followed by group 2–3 and then group 2–4 (p < 0.0001). Based on these independent parameters, we constructed a nomogram model that exhibited superior potential (sensitivity: 0.864, specificity: 0.814, and accuracy: 0.843) compared with PPE in early prediction of MT. Combining the factors of 1p/19q codeletion, Ki‐67 index, radiotherapy, EOR, and KPS score that were presented at initial diagnosis could precisely forecast the subsequent MT patterns of patients with LGG. [ABSTRACT FROM AUTHOR]

Purpose: Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival. Methods: All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival. Results: 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0–19.6). Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02–1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02–1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70–11.78, p = 0.002). In our material, surgical strategy was not associated with survival. Conclusion: Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival. [ABSTRACT FROM AUTHOR]

The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; p = 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; p = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; p = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered.

Low grade gliomas (LGGs) of pineal region are usually difficult to remove and they frequently relapse or progress after front line chemotherapy. Bevacizumab-Irinotecan (BEVIRI) combination has been successfully attempted in children with recurrent LGGs, in most cases not previously irradiated. The efficacy of bevacizumab has also been described in radiation necrosis. Considering the possible overlapping of radiation treatment effect and disease progression and difficulty in differentiating, we report on the use of BEVIRI in a case of a recurrent relapsing low-grade glioma of the pineal region, subjected to multiple neurosurgical interventions, also treated with a carboplatin-etoposide regimen and a radiation course, at present at one-year follow-up showing a stable response, with no adverse events.

Recently, studies have shown that immune checkpoint-related genes (ICGs) are instrumental in maintaining immune homeostasis and can be regarded as potential therapeutic targets. However, the prognostic applications of ICGs require further elucidation in low-grade glioma (LGG) cases. In the present study, a unique prognostic gene signature in LGG has been identified and validated as well based on ICGs as a means of facilitating clinical decision-making. The RNA-seq data as well as corresponding clinical data of LGG samples have been retrieved utilizing the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ICG-defined non-negative matrix factorization (NMF) clustering was performed to categorize patients with LGG into two molecular subtypes with different prognoses, clinical traits, and immune microenvironments. In the TCGA database, a signature integrating 8 genes has been developed utilizing the LASSO Cox method and validated in the GEO database. The signature developed is superior to other well-recognized signatures in terms of predicting the survival probability of patients with LGG. This 8-gene signature was then subsequently applied to categorize patients into high- and low-risk groups, and differences between them in terms of gene alteration frequency were observed. There were remarkable variations in IDH1 (91% and 64%) across low-as well as high-risk groups. Additionally, various analyses like function enrichment, tumor immune microenvironment, and chemotherapy drug sensitivity revealed significant variations across high- and low-risk populations. Overall, this 8-gene signature may function as a useful tool for prognosis and immunotherapy outcome predictions among LGG patients.

Simple Summary: Low-grade gliomas (LGGs) are relatively slow-growing primary brain tumors where the clinical criteria for tumor diagnosis and progression assessment include both qualitative and quantitative analytics. The Response Assessment in Neuro-Oncology (RANO) criteria for LGGs define tumor progression as ≥25% change in the T2/FLAIR signal area based on an operator's discretion of the perpendicular diameter of the largest tumor cross-section. However, sources of error exist, including the limitation of 2D quantification, operator selection of both the tumor cross-section and perpendicular diameters, and the inability to quantify satellite tumor components. The aim of this retrospective study was to assess the accuracy and reproducibility of RANO in LGGs. In a heterogeneous population of 63 participants with different subtypes of LGGs, we showed that the accuracy of RANO compared to visual and volumetric gold standards was, at best, 67% and 57%, respectively. Reproducibility varied widely, even between board-certified neuroradiologists. Our results suggest that advanced approaches, such as computer-assisted tumor segmentation and annotation tools, are necessary to accurately assess LGG progression by reducing human variability. Purpose: The Response Assessment in Neuro-Oncology (RANO) criteria for lower-grade gliomas (LGGs) define tumor progression as ≥25% change in the T2/FLAIR signal area based on an operator's discretion of the perpendicular diameter of the largest tumor cross-section. Potential sources of error include acquisition inconsistency of 2D slices, operator selection variabilities in both representative tumor cross-section and measurement line locations, and the inability to quantify infiltrative tumor margins and satellite lesions. Our goal was to assess the accuracy and reproducibility of RANO in LG. Materials and Methods: A total of 651 FLAIR MRIs from 63 participants with LGGs were retrospectively analyzed by three blinded attending physicians and three blinded resident trainees using RANO criteria, 2D visual assessment, and computer-assisted 3D volumetric assessment. Results: RANO product measurements had poor-to-moderate inter-operator reproducibility (r2 = 0.28–0.82; coefficient of variance (CV) = 44–110%; mean percent difference (diff) = 0.4–46.8%) and moderate-to-excellent intra-operator reproducibility (r2 = 0.71–0.88; CV = 31–58%; diff = 0.3–23.9%). When compared to 2D visual ground truth, the accuracy of RANO compared to previous and baseline scans was 66.7% and 65.1%, with an area under the ROC curve (AUC) of 0.67 and 0.66, respectively. When comparing to volumetric ground truth, the accuracy of RANO compared to previous and baseline scans was 21.0% and 56.5%, with an AUC of 0.39 and 0.55, respectively. The median time delay at diagnosis was greater for false negative cases than for false positive cases for the RANO assessment compared to previous (2.05 > 0.50 years, p = 0.003) and baseline scans (1.08 > 0.50 years, p = 0.02). Conclusion: RANO-based assessment of LGGs has moderate reproducibility and poor accuracy when compared to either visual or volumetric ground truths. [ABSTRACT FROM AUTHOR]

Introduction: MR-tractography is increasingly used in neurosurgical practice to evaluate the anatomical relationships between glioma and nearby subcortical tracts. In some patients, the subcortical tracts seem displaced by the glioma, while in other patients, the subcortical tracts seem infiltrated without displacement. At this point, it is unknown whether these different patterns are related to tumor type. The aim of this exploratory study was to investigate whether tumor type is related to the spatial tractography pattern of the frontal aslant tract (FAT) in low-grade gliomas (LGGs). Methods: In 64 IDH-mutated LGG patients, the FAT was generated using a pipeline for automatic tractography. In 41 patients, the glioma adjoined the FAT, and four blinded reviewers independently assessed the following two dichotomous categories (yes/no): (i) glioma displaces the tract, and (ii) glioma infiltrates the tract. Results: Fisher's exact tests demonstrated strong and significant positive associations between displacement and astrocytomas (p =.002, φ =.497) and infiltration and oligodendrogliomas (p =.004, φ =.484). The interobserver agreement was good for both categories: (i) κ = 0.76 and (ii) κ = 0.71. Conclusion: High sensitivity but low specificity for displacement in astrocytomas demonstrates that in the case of an astrocytoma, the tract is most likely displaced, but that displacement in itself is not necessarily predictive for astrocytomas, as oligodendrogliomas may both infiltrate and displace a tract. Overall, these results demonstrate that oligodendrogliomas tend to infiltrate the nearby subcortical tract, whereas astrocytomas only tend to displace it. [ABSTRACT FROM AUTHOR]

Background. The T2-FLAIR (fluid-attenuated inversion recovery) mismatch sign has been defined over the last few years as an important novel radiogenomic marker highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q noncodeleted gliomas (astrocytomas). Existing studies have demonstrated that this has good specificity but limited sensitivity for IDH-mut astrocytomas. The new 2021 WHO Classification of Tumors of the Central Nervous System (WHO CNS5) has introduced a layered grading system in which all IDH mutant diffuse astrocytic tumours are considered a single type (Astrocytoma, IDH-mutant) and are graded as CNS WHO grade 2, 3, or 4. Because of the growing importance of molecular information in CNS tumour classification, diagnoses and diagnostic reports need to combine different data types into a single diagnosis. Whether the T2FLAIR mismatch sign is of clinical relevance for the management of low-grade gliomas still needs to be further determined. Methods. We included histologically verified supratentorial low-grade gliomas (LGG) WHO grade 2-3 retrospectively during the period 2013-2018 (n=18). For the period 2019-2023 (n=27), patients with a radiological presumptive diagnosis of low-grade glioma were prospectively included, and we took into consideration the fact that in this group we could encounter other diagnoses thanglioma. Clinical, radiological and histology data were collected. We aimed to examine the association of the T2-FLAIR mismatch sign (where identified) with clinical factors and outcomes. We evaluated the diagnostic reliability of the mismatch sign and its relation to the definitive histological diagnosis, the co-existence of an MR spectroscopy signature; we have also tried to determine whether the identification of the radiogenomic marker had any impact on the clinical outcome through the decision-making in neurosurgical management. Results. Out of 45 patients with radiological suspected glioma, 30 had a definitive diagnosis of diffuse astrocytoma grade 2 and 3 (Astrocytoma, IDH-mutant according to WHOCNS5). 6 patients had a diagnosis of glioblastoma (Glioblastoma, IDHwildtype according to WHOCNS5). 8 patients have been diagnosed with oligodendroglioma (Oligodendroglioma, IDHmutant, and 1p/19q-codeleted according to WHOCNS5) and 1 case had a definitive histology of cerebral abscess. Out of the 30 patients with IDH-mut astrocytoma, 6 (20.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut astrocytoma detection were 20% and 98.6%, respectively. There were no differences between patients with an IDH-mut astrocytoma with or without T2FLAIR mismatch sign when grouped according to this with related to baseline characteristics, clinical outcome and presenting symptoms. MR spectroscopy sequences were analyzed where available for the retrospective and prospective cohort. There were 7 cases where MR spectroscopy was performed and, for the IDH-mut astrocytoma cases (n=4) it showed a persistent high Cho/NAA ratio without any difference between the patients with or without the T2FLAIR mismatch sign. Conclusion. In our relatively small retrospective and prospective cohorts, the T2-FLAIR mismatch sign, where identified, was not correlated with clinical features at presentation, prognosis or outcome. Until recently, the grading of CNS tumours has been focusing mainly on histology characteristics, but specific molecular markers can now be used for valuable prognostic information. For this reason, molecular-specific information has been added as an essential feature in grading and it is considered very useful for further estimation of prognosis within variable tumor types. We could not determine if the IDH-mut astrocytomas with mismatch sign represent a specific subgroup. Our study has confirmed that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas. [ABSTRACT FROM AUTHOR]

Purpose: Low-grade gliomas compose 30% of pediatric central nervous system tumors and outcomes of disease-free progression, and survival is directly correlated to the extent of resection. The use of sodium fluorescein (Na-Fl) is an intraoperative method in the localization of tumor cells in adult patients to optimize resection. Our purpose is to describe the use of Na-Fl in pediatric low-grade gliomas and its outcomes. Methods: Patients under 18 years of age with low-grade gliomas at the author's institution underwent resection with the use of Na-Fl, with review of preoperative imaging findings, intraoperative results, and follow-up. Then, a comprehensive, narrative literature review of the use of Na-Fl in pediatric low-grade glioma was performed. Results: Our single-institution use of Na-Fl in pediatric patients with suspected low-grade glioma demonstrated excellent results of intraoperative enhancement of tumor cells as well as gross total resection. The literature demonstrated 84% Na-Fl staining and 59.2% of gross total resection in pediatric low-grade gliomas with few small case studies, a range of reported findings, and few side effects. Conclusion: Na-Fl has a promising use in low-grade glioma resection in the pediatric patient population. Further research is warranted, such as randomized controlled studies, to assess Na-Fl as a potential tool in improving resection and long-term favorable outcomes. [ABSTRACT FROM AUTHOR]

Background: Sodium fluorescein (SF) is routinely used in several centers as a valid intraoperative adjunct in adult oncological neurosurgery. Its use in pediatric neurosurgery is increasing, although its role is not yet well-defined in children. We reviewed the current literature in order to evaluate the use of SF in children with CNS and PNS lesions. Methods: For this systematic review, we searched PubMed, Scopus, and Embase databases, and forward and backward citations for studies published between database inception and July 31st, 2022. We included any article type or congress abstract adding at least a new case, without restrictions of language or publication status, concerning the use of SF in neurosurgical procedures in patients under 18 years of age. We excluded studies concerning purely vascular cases and cerebrospinal fluid leaks. Results: Of 4094 records identified, 19 articles were eligible and included for further analysis. As per July 31st, 2022, at least 119 patients aged from 11 months to 17.9 years underwent surgery with SF. No serious adverse events were reported. A large variety of tumor types was operated, in most cases resected under the specific YELLOW 560 nm filter after a low-dose SF injection (2–5 mg/kg) at the end of anesthesia induction. SF was reported particularly useful in gangliogliomas and pilocytic astrocytomas. Discussion/conclusion: Given its easy-to-use profile, low cost, and safety, SF seems to be a feasible and valid adjunct in the pediatric population when aiming at individuating a biopsy target or maximizing extent of resection, particularly in some tumor types. Further studies are required to strengthen the evidence on its impact on outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Diffuse low-grade gliomas (DLGGs) are low-malignancy brain tumors originating from the glial cells of the brain growing continuously and infiltratively along the neural axons and infiltrating the surrounding brain tissue. DLGGs usually transform into higher malignancy, causing progressive disability and premature death. MRI scans are valuable when assessing soft tissue abnormalities, but, due to the infiltrative properties of DLGGs, delineating the tumor borders is a challenging task. Therefore, the aim of this study was to explore the difference in gross tumor volume (GTV) of DLGGs delineated from 7 Tesla and 3 Tesla MRI scans. Method: Patients were recruited at the department of neurosurgery and were scanned in both a 7T and a 3T MRI scanner prior to the operation. Two observers delineated the tumors using semi-automatic delineation software. The results from each observer were blinded to the other observer's delineation. Results: Comparing GTVs from 7T and 3T, the percentage difference varied up to 40.4% on the T2-weighted images. The percentage difference in GTV varied up to 15.3% on the fluid-attenuated inversion recovery (FLAIR) images. On the T2-weighted images, most cases varied by approximately 15%; on the FLAIR sequence, half of the cases varied by approximately 5% and the other half by approximately 15%. The overall inter-observer agreement was near perfect, with an intraclass correlation of 0.969. The intraclass correlation was better on the FLAIR sequence than on the T2 sequence. Conclusion: Overall, the GTVs delineated from 7T images were smaller. The increase in field strength improved the inter-observer agreement only on the FLAIR sequence. [ABSTRACT FROM AUTHOR]

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Purpose: To investigate the feasibility and dosimetric characteristics of dose painting for non-enhancing low-grade gliomas (NE-LGGs) guided by three-dimensional arterial spin labeling (3D-ASL). Materials and methods: Eighteen patients with NE-LGGs were enrolled. 3D-ASL, T2 fluid-attenuated inversion recovery (T2 Flair) and contrast-enhanced T1-weighted magnetic resonance images were obtained. The gross tumor volume (GTV) was delineated on the T2 Flair. The hyper-perfusion region of the GTV (GTV-ASL) was determined by 3D-ASL, and the GTV-SUB was obtained by subtracting the GTV-ASL from the GTV. The clinical target volume (CTV) was created by iso-tropically expanding the GTV by 1 cm. The planning target volume (PTV), PTV-ASL were obtained by expanding the external margins of the CTV, GTV-ASL, respectively. PTV-SUB was generated by subtracting PTV-ASL from PTV. Three plans were generated for each patient: a conventional plan (plan 1) without dose escalation delivering 95–110% of 45–60 Gy in 1.8–2 Gy fractions to the PTV and two dose-painting plans (plan 2 and plan 3) with dose escalating by 10–20% (range, 50–72 Gy) to the PTV-ASL based on plan 1. The plan 3 was obtained from plan 2 without the maximum dose constraint. The dosimetric differences among the three plans were compared. Results: The volume ratio of the PTV-ASL to the PTV was (23.49 ± 11.94)% (Z = − 3.724, P = 0.000). Compared with plan 1, D2%, D98% and Dmean of PTV-ASL increased by 14.67%,16.17% and 14.31% in plan2 and 19.84%,15.52% and 14.27% in plan3, respectively (P < 0.05); the D2% of the PTV and PTV-SUB increased by 11.89% and 8.34% in plan 2, 15.89% and 8.49% in plan 3, respectively (P < 0.05). The PTV coverages were comparable among the three plans (P > 0.05). In plan 2 and plan 3, the conformity indexes decreased by 18.60% and 12.79%; while the homogeneity index increased by 1.43 and 2 times (P < 0.05). Compared with plan 1, the D0.1 cc of brain stem and Dmax of optic chiasma were slightly increased in plan 2 and plan 3, and the absolute doses met the dose constraint. The doses of the other organs at risk (OARs) were similar among the three plans (P > 0.05). Conclusion: The dose delivered to hyper-perfusion volume derived from 3D-ASL can increased by 10–20% while respecting the constraints to the OARs for NE-LGGs, which provides a basis for future individualized and precise radiotherapy, especially if the contrast agent cannot be injected or when contrast enhancement is uncertain. [ABSTRACT FROM AUTHOR]

Low-grade gliomas (LGG) are central nervous system Grade I tumors, and as they progress they are becoming one of the deadliest brain tumors. There is still great need for timely and accurate diagnosis and prognosis of LGG. Herein, we aimed to identify diagnostic and prognostic biomarkers associated with LGG, by employing diverse computational approaches. For this purpose, differential gene expression analysis on high-throughput transcriptomics data of LGG versus corresponding healthy brain tissue, derived from TCGA and GTEx, respectively, was performed. Weighted gene co-expression network analysis of the detected differentially expressed genes was carried out in order to identify modules of co-expressed genes significantly correlated with LGG clinical traits. The genes comprising these modules were further used to construct gene co-expression and protein-protein interaction networks. Based on the network analyses, we derived a consensus of eighteen hub genes, namely, CD74, CD86, CDC25A, CYBB, HLA-DMA, ITGB2, KIF11, KIFC1, LAPTM5, LMNB1, MKI67, NCKAP1L, NUSAP1, SLC7A7, TBXAS1, TOP2A, TYROBP, and WDFY4. All detected hub genes were up-regulated in LGG, and were also associated with unfavorable prognosis in LGG patients. The findings of this study could be applicable in the clinical setting for diagnosing and monitoring LGG. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioneuronal and neuronal tumours are rare and mostly found in young adults and children, representing less than 5% of primary central nervous system (CNS) tumours. Accurate diagnosis is often difficult, requiring a significant body of evidence (clinical, radiological, pathology and molecular). The aim of this paper is to describe the main entities reported in the 2021 World Health Organization (WHO) classification, including, on the one hand, their histomolecular and imaging features and, on the other hand, their therapeutic management. Gross total resection is the cornerstone of the treatment of these tumours when achievable. MAPK pathway abnormalities could represent an interesting target for novel drugs. Rare glial, neuronal and glioneuronal tumours in adults form a heterogeneous group of rare, primary central nervous system tumours. These tumours, with a glial and/or neuronal component, are challenging in terms of diagnosis and therapeutic management. The novel classification of primary brain tumours published by the WHO in 2021 has significantly improved the diagnostic criteria of these entities. Indeed, diagnostic criteria are nowadays multimodal, including histological, immunohistochemical and molecular (i.e., genetic and methylomic). These integrated parameters have allowed the specification of already known tumours but also the identification of novel tumours for a better diagnosis. [ABSTRACT FROM AUTHOR]

Background. The T2-FLAIR (fluid-attenuated inversion recovery) mismatch sign has been defined over the last few years as an important novel radiogenomic marker highly suggestive of isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted gliomas (astrocytomas). Existing studies have demonstrated that this has good specificity but limited sensitivity for IDH-mut astrocytomas. The new 2021 WHO Classification of Tumors of the Central Nervous System (WHO CNS5) has introduced a layered grading system in which all IDH mutant diffuse astrocytic tumours are considered a single type (Astrocytoma, IDH-mutant) and are graded as CNS WHO grade 2, 3, or 4. Because of the growing importance of molecular information in CNS tumour classification, diagnoses and diagnostic reports need to combine different data types into a single diagnosis. Whether the T2FLAIR mismatch sign is of clinical relevance for the management of low-grade gliomas still needs to be further determined. Methods. We included histologically verified supratentorial low-grade gliomas (LGG) WHO grade 2-3 retrospectively during the period 2013–2018 (n=18). For the period 2019–2023 (n=27), patients with a radiological presumptive diagnosis of low-grade glioma were prospectively included, and we took into consideration the fact that in this group we could encounter other diagnoses than glioma. Clinical, radiological and histology data were collected. We aimed to examine the association of the T2-FLAIR mismatch sign (where identified) with clinical factors and outcomes. We evaluated the diagnostic reliability of the mismatch sign and its relation to the definitive histological diagnosis, the co-existence of an MR spectroscopy signature; we have also tried to determine whether the identification of the radiogenomic marker had any impact on the clinical outcome through the decision-making in neurosurgical management. Results. Out of 45 patients with radiological suspected glioma, 30 had a definitive diagnosis of diffuse astrocytoma grade 2 and 3 (Astrocytoma, IDH-mutant according to WHOCNS5). 6 patients had a diagnosis of glioblastoma (Glioblastoma, IDH-wildtype according to WHOCNS5). 8 patients have been diagnosed with oligodendroglioma (Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted according to WHOCNS5) and 1 case had a definitive histology of cerebral abscess. Out of the 30 patients with IDH-mut astrocytoma, 6 (20.0%) showed a mismatch sign. The sensitivity and specificity of the mismatch sign for IDH-mut astrocytoma detection were 20% and 98.6%, respectively. There were no differences between patients with an IDH-mut astrocytoma with or without T2FLAIR mismatch sign when grouped according to this with related to baseline characteristics, clinical outcome and presenting symptoms. MR spectroscopy sequences were analyzed where available for the retrospective and prospective cohort. There were 7 cases where MR spectroscopy was performed and, for the IDH-mut astrocytoma cases (n=4) it showed a persistent high Cho/NAA ratio without any difference between the patients with or without the T2FLAIR mismatch sign. Conclusion. In our relatively small retrospective and prospective cohorts, the T2-FLAIR mismatch sign, where identified, was not correlated with clinical features at presentation, prognosis or outcome. Until recently, the grading of CNS tumours has been focusing mainly on histology characteristics, but specific molecular markers can now be used for valuable prognostic information. For this reason, molecular-specific information has been added as an essential feature in grading and it is considered very useful for further estimation of prognosis within variable tumor types. We could not determine if the IDH-mut astrocytomas with mismatch sign represent a specific subgroup. Our study has confirmed that the T2-FLAIR mismatch sign is a reliable and specific marker of IDH-mut astrocytomas.

Low-Grade Gliomas (LGGs) represent a diverse group of brain tumors originating from glial cells, characterized by their unique histopathological and molecular features. This article offers a comprehensive exploration of LGGs, shedding light on their subtypes, histological and molecular aspects. By delving into the World Health Organization’s grading system, 5th edition, various specificities were added due to an in-depth understanding of emerging laboratory techniques, especially genomic analysis. Moreover, treatment modalities are extensively discussed. The degree of surgical resection should always be considered according to postoperative quality of life and cognitive status. Adjuvant therapies focused on chemotherapy and radiotherapy depend on tumor grading and invasiveness. In the current literature, emerging targeted molecular therapies are well discussed due to their succinctly therapeutic effect; in our article, those therapies are summarized based on posttreatment results and possible adverse effects. This review serves as a valuable resource for clinicians, researchers, and medical professionals aiming to deepen their knowledge on LGGs and enhance patient care.

Abstract Background Low-grade gliomas (LGG) are WHO grade II tumors presenting as the most common primary malignant brain tumors in adults. Currently, LGG treatment involves either or a combination of surgery, radiation therapy, and chemotherapy. Despite the knowledge of constitutive genetic risk factors contributing to gliomas, the role of single genes as diagnostic and prognostic biomarkers is limited. The aim of the current study is to discover the predictive and prognostic genetic markers for LGG. Methods Transcriptome data and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We first performed the tumor microenvironment (TME) survival analysis using the Kaplan-Meier method. An analysis was undertaken to screen for differentially expressed genes. The function of these genes was studied by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Following which a protein-protein interaction network (PPI) was constructed and visualized. Univariate and multivariate COX analyses were performed to obtain the probable prognostic genes. The key genes were selected by an intersection of core and prognostic genes. A clinical correlation analysis of single-gene expression was undertaken. GSEA enrichment analysis was performed to identify the function of key genes. Finally, a single gene-related correlation analysis was performed to identify the core immune cells involved in the development of LGG. Results A total of 529 transcriptome data and 515 clinical samples were obtained from the TCGA. Immune cells and stromal cells were found to be significantly increased in the LGG microenvironment. The top five core genes intersected with the top 38 prognostically relevant genes and two key genes were identified. Our analysis revealed that a high expression of HLA-DRA was associated with a poor prognosis of LGG. Correlation analysis of immune cells showed that HLA-DRA expression level was related to immune infiltration, positively related to macrophage M1 phenotype, and negatively related to activation of NK cells. Conclusions HLA-DRA may be an independent prognostic indicator and an important biomarker for diagnosing and predicting survival in LGG patients. It may also be associated with the immune infiltration phenotype in LGG.

Low-grade gliomas (LGG) are central nervous system Grade I tumors, and as they progress they are becoming one of the deadliest brain tumors. There is still great need for timely and accurate diagnosis and prognosis of LGG. Herein, we aimed to identify diagnostic and prognostic biomarkers associated with LGG, by employing diverse computational approaches. For this purpose, differential gene expression analysis on high-throughput transcriptomics data of LGG versus corresponding healthy brain tissue, derived from TCGA and GTEx, respectively, was performed. Weighted gene co-expression network analysis of the detected differentially expressed genes was carried out in order to identify modules of co-expressed genes significantly correlated with LGG clinical traits. The genes comprising these modules were further used to construct gene co-expression and protein-protein interaction networks. Based on the network analyses, we derived a consensus of eighteen hub genes, namely, CD74, CD86, CDC25A, CYBB, HLA-DMA, ITGB2, KIF11, KIFC1, LAPTM5, LMNB1, MKI67, NCKAP1L, NUSAP1, SLC7A7, TBXAS1, TOP2A, TYROBP, and WDFY4. All detected hub genes were up-regulated in LGG, and were also associated with unfavorable prognosis in LGG patients. The findings of this study could be applicable in the clinical setting for diagnosing and monitoring LGG.

Low-grade gliomas are among the most common CNS lesions in pediatrics and surgery is often the first-line treatment. Intraoperative tools have been developed to maximize the results of surgery, and in particular dyes such as sodium fluorescein (SF) have been investigated in high-grade adult lesions. The use of SF in pediatric low-grade gliomas is still unclear. We retrospectively reviewed 22 pediatric CNS low-grade gliomas operated on with SF from September 2021 to October 2022. A total of 86% of lesions showed SF uptake, which was helpful intraoperatively (confirmation of initial localization of the tumor, or identification of tumor remnants) in 74% of them. The intraoperative fluorescence seems associated with gadolinium enhancement at the preoperative MRI. Interestingly, the extemporaneous pathological sampling (EPS) was informative in every case showing SF uptake, whereas in cases without SF uptake, the EPS was non-informative, although the tissue was later confirmed as pathological. These findings highlight the interest of SF for perioperative diagnosis of tumor tissue and may suggest in which cases the differentiation of tumor–healthy tissue could be especially blurred, posing difficulties for the pathologist. [ABSTRACT FROM AUTHOR]

In 2016, the World Health Organization (WHO) updated the glioma classification by incorporating molecular biology parameters, including low‐grade glioma (LGG). In the new scheme, LGGs have three molecular subtypes: isocitrate dehydrogenase (IDH)‐mutated 1p/19q‐codeleted, IDH‐mutated 1p/19q‐noncodeleted, and IDH‐wild type 1p/19q‐noncodeleted entities. This work proposes a model prediction of LGG molecular subtypes using magnetic resonance imaging (MRI). MR images were segmented and converted into radiomics features, thereby providing predictive information about the brain tumor classification. With 726 raw features obtained from the feature extraction procedure, we developed a hybrid machine learning‐based radiomics by incorporating a genetic algorithm and eXtreme Gradient Boosting (XGBoost) classifier, to ascertain 12 optimal features for tumor classification. To resolve imbalanced data, the synthetic minority oversampling technique (SMOTE) was applied in our study. The XGBoost algorithm outperformed the other algorithms on the training dataset by an accuracy value of 0.885. We continued evaluating the XGBoost model, then achieved an overall accuracy of 0.6905 for the three‐subtype classification of LGGs on an external validation dataset. Our model is among just a few to have resolved the three‐subtype LGG classification challenge with high accuracy compared with previous studies performing similar work. [ABSTRACT FROM AUTHOR]