Although pediatric midline-located gliomas (MGs) with H3K27 alteration have been widely known to have a poor prognosis, few researchers have assessed adult MGs with H3K27 alteration. We aimed to determine the effect of H3K27 alteration on the prognosis of adult MGs. And we tried to identify the factors affecting the prognosis of diffuse midline glioma (DMG). This is the first study to investigate the prognosis of adult DMGs according to histological grade and is the largest study to investigate the survival of adult patients with DMGs. We reviewed the charts of adult patients diagnosed with MG after undergoing resection or biopsy at our institution between 2010 and 2020. The Gehan–Breslow–Wilcoxon test was used for univariate survival analysis, and the Cox regression proportional hazard model was used for multivariate survival analysis. Among the 124 adult MGs identified, 44 (35.5

The role of adjuvant fractionated radiotherapy (aFRT) after gross total resection (GTR) of WHO-2 meningiomas remains unclear. We aimed to estimate the effect of aFRT on recurrence risk and survival following GTR and subtotal resection (STR). We analyzed 1452 patients with WHO-2 from our international, multicenter database (followed between 1989 and 2019). Outcomes were recurrence (10-year follow-up) and death (5-year follow-up). Risk estimates were obtained using competing risks and survival analysis. Average treatment effects were estimated by G-computation, adjusted for potential confounding by age, sex, Simpson grade, Ki-67 proliferation index, location, country group (universal healthcare or not), and year of treatment initiation. The robustness of findings was examined through sensitivity analyses. Overall, 276 of 1452 patients (19.0

Abstract Purpose The Ki-67 proliferation index (Ki-67 PI) has been associated with meningioma recurrence, yet its clinical utility remains debated. Whether Ki-67 PI provides prognostic information across subgroups defined by both WHO grade and extent of resection remains to be investigated. Methods We analyzed 5,050 patients with intracranial meningiomas from the international PERNS cohort (42 centers, diagnosed between 1989–2019) who underwent surgical resection without postoperative radiotherapy. Ki-67 PI prognostic accuracy was assessed up to 10 years postoperatively by using ROC analyses and estimating its association with the risk of recurrence. Results Results demonstrated that the prognostic value of Ki-67 PI differed by subgroups defined by WHO grade and Simpson grade. For patients with the same Simpson grade (1–3), the predictive accuracy of Ki-67 PI for 10-year recurrence risk was stronger in WHO-2 than in WHO-1. Within WHO-1 and WHO-2 meningiomas, the predictive accuracy of Ki-67 PI increased with higher Simpson grade (1–3). However, no predictive value was observed in Simpson grade 4 resections regardless of WHO grade. Conclusion These findings highlight that Ki-67 PI should be interpreted in the context of both WHO grade and extent of resection, and, if done so, may offer potential value to refine individualized surveillance strategies in meningioma patients with gross total resection in the initial 10-year postoperative timeframe. Findings cannot be extrapolated beyond 10 years, which may be particularly relevant for WHO-1 tumors with low Ki-67 PI and Simpson grade 1 resection.

Recurrence risk estimates underpin meningioma research, including molecular classification and clinical trial benchmarking, yet are often based on retrospective or historical data. The aim of this study was to assess the variation of recurrence risk estimates across calendar periods, WHO classification editions, geographical settings, and healthcare systems.thetermine We analyzed 4,111 patients with primary WHO-1/-2 meningiomas from 31 centers in 15 countries (1990–2019). Recurrence was defined according to local radiological assessment. The 5- and 10-year recurrence risks were estimated using regression standardization with inverse probability of censoring weights, adjusting for key clinical, surgical, and histopathological variables. Recurrence risk estimates varied across all domains examined. More recent calendar periods were associated with higher predicted recurrence risk, particularly for WHO-2 at 5 years (e.g., ≥ 2013 vs. ≤ 2007: RR 1.60, 95

Abstract Glioblastoma (GBM) remains lethal despite maximal therapy. The adult subventricular zone (SVZ), a neural stem-cell niche, has been implicated as a potential site of origin, yet the identity and functional properties of putative GBM origin-like cells (GBM-OCs) within the SVZ remain unclear. An SVZ-restricted somatic mutation mouse model (Cre-induced EGFRvIII expression with Trp53 and Pten disruption) was established and mouse SVZ-derived cells were prospectively isolated for functional and molecular profiling. Self-renewal, multipotency, invasive potential and tumour-initiating capacity were assessed relative to control SVZ cells and matched tumour-derived tumourspheres. Whole-genome and RNA sequencing defined genomic and transcriptional alterations during early progression. Mouse GBM-OCs exhibited self-renewal and multilineage differentiation and initiated tumours only after re-implantation into the SVZ (11/29, 38%), whereas direct striatal implantation failed (0/25, 0%), indicating context-dependent tumorigenic potential associated with the SVZ microenvironment. In contrast, tumour-derived tumourspheres retained tumorigenic capacity upon implantation into both the SVZ and the striatum. During progression from mouse GBM-OCs to tumours, whole-chromosome and arm-level aneuploidies accumulated. In patients with GBM, multi-region single-nucleus RNA sequencing of tumour-free SVZ, matched tumours and tumour-free cortex identified rare neural stem cell-like, astrocyte-like and oligodendrocyte precursor-like SVZ populations transcriptionally aligned with GBM programmes. These cells showed single-nucleus RNA-inferred chromosome 7 gain and/or chromosome 10 loss signals, with concordant low-frequency copy-number alterations in the SVZ detected by exome sequencing and enriched in matched tumours. Together, these findings support the presence of SVZ-resident stem or progenitor-like populations with early GBM-associated features, consistent with putative GBM-OCs, and highlight the SVZ niche as a potential target for early detection and niche-informed therapeutic strategies.

BACKGROUND IL-7 is a critical cytokine in T cell development, survival, and homeostasis. Previous preclinical and clinical studies reported that IL-7 treatment increased T cell counts, but its effect on peripheral blood T cells in cancer patients and molecular mechanisms have not been explored. METHODS We investigated effects of long-acting recombinant human IL-7 conjugated to a hybrid IgD/IgG4 Fc domain (rhIL-7-hyFc) on peripheral T cells in patients with advanced solid tumors. Peripheral blood samples were collected before and after treatment, followed by analysis through single-cell transcriptomics and flow cytometry. RESULTS We found that rhIL-7-hyFc induced marked expansion of proliferating T cells, and promoted transcriptional changes associated with immune activation, cell cycle progression, and antiapoptosis. Trajectory analysis revealed that posttreatment T cells had distinct transcriptional states enriched for cytokine- and TCR-mediated signaling pathways. Notably, a second dose administered after 3 weeks yielded diminished proliferation and minimal transcriptional changes, which were independent of antidrug antibody or CD127 downmodulation. Examination of elements of the IL-7 signaling pathway revealed intact proximal signaling (e.g., STAT5 phosphorylation) but downregulation of distal elements, including PIM-1 kinase and c-Myc. CONCLUSIONS Our results demonstrate that rhIL-7-hyFc induces robust peripheral T cell expansion and activation in patients with solid tumors, supporting its potential use for lymphopenic patients treated with cancer immunotherapy. TRIAL REGISTRATION ClinicalTrials.gov NCT03478995 and NCT03619239. FUNDING National Research Foundation of Korea (NRF-2022R1A2C3007292 and RS-2024-00439160), Ministry of Food and Drug Safety (RS-2025-02213409), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (RS-2025-25460003).

INTRODUCTION:The tumor control rate after stereotactic radiosurgery (SRS) for neurofibromatosis type 2-associated vestibular schwannomas (NF2-VSs) compared to sporadic vestibular schwannomas (S-VSs) remains unclear. This nationwide, multicenter, retrospective study (KGKRS-21-001) aimed to clarify this issue. METHODS:A total of 4718 patients treated with SRS for vestibular schwannomas were analyzed from 13 nationwide institutions in Korea. NF2-VS cases were propensity score-matched with S-VS cases at a ratio of 1:1, based on age, tumor volume, and marginal dose, resulting in 122 cases in each group. RESULTS:No significant differences in age, tumor volume, or marginal dose were observed between the matched cohorts. The overall tumor control rates at 1, 3, and 10 years after SRS were 93.3%, 87.7%, and 80.7%, respectively, with no significant difference between NF2-VS and S-VS groups (p = 0.63). Subgroup analysis showed that age ≤ 19 years was a significant negative prognostic factor for tumor control in NF2-VS patients (p < 0.001), whereas no such correlation was found in the S-VS cohort (p = 0.78). CONCLUSIONS:SRS provides comparable tumor control for NF2-VSs and S-VSs. However, among NF2-VS patients, younger age (≤ 19 years) was associated with poorer tumor control, suggesting that age may be a critical factor in treatment decisions.

Identifying the cell of origin that harbors an initial driver mutation is key to understanding tumor evolution and for the development of new treatments. For isocitrate dehydrogenase (IDH)-mutant gliomas, the most common malignant primary brain tumor in young adults, the cell of origin is currently poorly understood. We conducted deep sequencing on 142 tissues from 70 individuals comprising tumors, peritumoral cortex or subventricular zones, and blood. Low-level IDH mutations were found in the peritumoral cortex in 37.9% (11 of 29) of patients. Integrating cell-type-specific mutation analysis, the direction of clonal evolution, spatial transcriptomics from patient brains, and a cancer mouse model arising from mutant oligodendrocyte progenitor cell, we determined that glial progenitor cells harboring an initial IDH mutation were responsible for the development of IDH-mutant gliomas.

Extended reality (XR), encompassing virtual reality, augmented reality (AR), and mixed reality, has emerged as a transformative technology in neurosurgery. This narrative review examines the current applications of XR technologies across four major domains : surgical planning and visualization, intraoperative navigation, medical education and training, and patient/caregiver communication. The integration of artificial intelligence-based lesion segmentation with XR platforms has enabled precise three-dimensional visualization of complex intracranial pathologies. Modern AR navigation systems, utilizing both optical see-through and video see-through head-mounted displays, have demonstrated submillimeter accuracy in recent clinical studies. Educational applications of XR have shown significant improvements in anatomical understanding and surgical skill acquisition among neurosurgery trainees. Furthermore, XR-enhanced patient communication tools have improved comprehension of complex neurosurgical procedures and informed consent quality. Despite current limitations including hardware constraints, workflow integration challenges, and the need for larger validation studies, XR technologies hold substantial promise for advancing pediatric neurosurgical care. This review provides a critical analysis of current evidence, discusses the advantages and limitations of different XR modalities, and offers perspectives on future developments in this rapidly evolving field.

Abstract Meningioma is the most common primary intracranial tumour, yet its genetic origin and the temporal sequence of mutational events remain poorly defined. Here, we analysed 80 triple-matched tumour, histologically normal meninges, and blood samples from 22 patients. NF2 or TRAF7 driver mutations are detectable in phenotypically normal meninges in 81.8% of cases (95% CI: 59.7–94.8%; VAF ∼0.02%), corroborated by high-depth sequencing, single-cell cloning, and phylogenetic analysis. By distinguishing developmental mosaic mutations from postnatal tumour-private mutations, we revealed distinct mutational signatures and resolved the temporal sequence of meningioma evolution. The developmental origin was further underscored in patients with multiple meningiomas, where identical driver mutations were shared across genomically distinct tumours and meninges, and in intraventricular meningiomas (IVM), where driver mutations were detected in distant cranial dura. Reconstruction of mutational timing revealed lineage-specific trajectories, linking mosaicism to diverse disease presentations including solitary meningioma, IVM, meningiomatosis, and NF2 -related schwannomatosis. Together, these findings reveal an early origin of human meningioma, in which developmental mosaicism establishes a pre-neoplastic field within the meninges, providing a developmental framework for adult tumourigenesis.

BACKGROUND:To comprehensively investigate clinical, molecular, radiological, and surgical factors for prediction of progression-free survival (PFS) in patients with isocitrate dehydrogenase (IDH)-mutant astrocytomas. METHODS:A total of 210 patients with newly diagnosed World Health Organization (WHO) grade 2-4 IDH-mutant astrocytomas between 2005 and 2023 were included. Clinical, molecular, radiological, and surgical factors were evaluated. Total, contrast-enhancing, nonenhancing, and necrotic tumor volumes were quantified via automatic volumetric segmentation (cm3). Significant predictors of PFS were identified using univariable and multivariable Cox analyses. RESULTS:The median PFS was 106.8 months, with a 5-year PFS rate of 67.5%. On multivariable analysis, higher initial KPS (hazard ratio [HR] =0.76, P = .029) remained as a favorable predictor of PFS, while higher WHO grade (grade 3, HR = 1.01, P = .997; grade 4, HR = 2.91, P = .013; reference standard as grade 2, overall P = .032), larger total tumor volume (HR = 1.03, P = .013), and lesser extent of resection (EOR) (subtotal resection, HR = 1.80, P = .043; partial resection, HR = 2.14, P = .014; biopsy, HR = 3.79, P = .008; reference standard as gross total resection, overall P = .015) remained as unfavorable predictors of PFS. Age and O6-methylguanine-DNA methyltransferase promoter methylation were not significant predictors, while the adverse prognostic impact of WHO grade was primarily driven by WHO grade 4 tumors. CONCLUSIONS:Our work presents a detailed analysis of a large series of IDH-mutant astrocytomas, underscoring the prognostic importance of WHO grade 4, tumor volume, and EOR.

PURPOSE: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor, with a median survival of less than two years despite standard therapy. Transglutaminase 2 (TGM2) contributes to tumor progression and poor clinical outcomes. This study evaluated the therapeutic potential of combining streptonigrin (SN), a TGM2 inhibitor, with temozolomide (TMZ), the standard chemotherapeutic agent for GBM. METHODS: Two patient-derived GBM tumorspheres (TSs; TS15-88, proneural subtype; TS19-156, classical subtype) were treated with SN, TMZ, or their combination. Cell viability and ATP production were measured to assess cell proliferation, and synergy was quantified using the Bliss synergy score. Apoptosis was analyzed by flow cytometry. Stemness and invasiveness were evaluated using neurosphere formation and three-dimensional invasion assays. Protein and mRNA expression levels were assessed by western blotting and RNA sequencing. In vivo efficacy was evaluated using a mouse orthotopic xenograft model. RESULTS: The combination of SN and TMZ significantly reduced cell viability and ATP levels and induced apoptosis more effectively than either agent alone. Moreover, combination treatment effectively reduced stemness and invasiveness in GBM TSs, along with the expression of related proteins and mRNAs. In vivo, combination therapy prolonged survival in mice and reduced the expression of invasion-related proteins, as demonstrated by immunohistochemistry. CONCLUSION: These findings suggest that targeting TGM2 with SN enhances the therapeutic efficacy of TMZ in GBM. The combination of SN and TMZ may represent one potential therapeutic approach for GBM and warrants further mechanistic and translational investigation.

BACKGROUND AND PURPOSE:Intraoperative visual evoked potential (VEP) monitoring has been studied mainly in pituitary adenoma, while its role in nonpituitary suprasellar tumors has remained unclear. This study evaluated the predictive usefulness of intraoperative VEP monitoring during endoscopic endonasal surgery (EES) and aimed to identify optimal alarm criteria for visual outcomes. METHODS:We retrospectively analyzed a cohort of 87 patients who underwent EES with intraoperative VEP monitoring between April 2021 and September 2023. Visual outcomes were evaluated preoperatively and at short-term (≤3 months) and long-term (12 months) follow-ups, with visual deterioration at these time points defined as worsening of either visual acuity or the visual field. Reductions in the VEP amplitude were quantified using both the maximum intraoperative decrease and the final amplitude after recovery. Receiver operating characteristic (ROC) curve analyses were performed to identify the optimal alarm thresholds, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated for short-term and long-term visual deteriorations. RESULTS:Short-term and long-term visual deteriorations were detected in 12 (9.2%) and 5 (3.8%) of the 130 analyzed eyes, respectively. ROC curve analyses identified ≥40% and ≥30% reductions in the N75-P100 amplitude as optimal alarm criteria for short-term and long-term visual deteriorations, respectively. A 30% reduction without intraoperative recovery demonstrated markedly higher sensitivity than the conventional 50% alarm threshold for short-term (58.3% vs. 33.3%) and long-term (80.0% vs. 20.0%) outcomes, while maintaining acceptable specificity (82.2% and 80.8%, respectively). CONCLUSIONS:A 30% reduction in amplitude represents a more-sensitive and clinically relevant alarm threshold than a 50% reduction for intraoperative VEP monitoring during EES for nonpituitary suprasellar tumors. Incorporating both the magnitude and recovery pattern of VEP amplitude changes may improve the accuracy of predictions of long-term visual deterioration. However, the potential for false positives warrants cautious interpretation, and further studies are needed to validate the impact of intraoperative VEP monitoring on visual outcomes.

Background/Objectives: Hypofractionated stereotactic radiosurgery (hfSRS) is increasingly used for benign intracranial tumors that are large or located near critical neural structures to reduce treatment-related toxicity. However, the optimal interval between fractions remains poorly defined, particularly for slowly proliferating benign tumors. This study evaluated clinical outcomes and longitudinal volumetric response patterns following Gamma Knife hfSRS delivered at fixed two-week intervals, with particular attention to the biological relevance of fraction timing. Methods: We retrospectively analyzed 126 patients with benign intracranial tumors, including meningioma, non-functioning pituitary neuroendocrine tumor (PitNET), vestibular schwannoma, and craniopharyngioma, treated between 2016 and 2022. Treatment was delivered in 2-5 fractions at fixed two-week intervals using Gamma Knife radiosurgery. Radiological outcomes included tumor control rate and longitudinal volumetric changes, while clinical outcomes included visual, auditory, and endocrine function. Propensity score matching was performed in PitNET and vestibular schwannoma cohorts to compare hfSRS with single-fraction stereotactic radiosurgery while minimizing baseline imbalances. Results: The overall tumor control rate was 98.4%. Across the entire cohort, tumors demonstrated a median volume reduction of -0.64% per month. In the propensity score-matched PitNET cohort, tumor control was comparable between treatment groups, whereas hfSRS was associated with earlier and greater volumetric reduction over time compared with single-fraction treatment. In the matched vestibular schwannoma cohort, long-term tumor control was similar between groups; however, transient tumor enlargement occurred more frequently after hfSRS without adversely affecting long-term tumor control or functional hearing outcomes. Conclusions: Hypofractionated stereotactic radiosurgery delivered at fixed two-week intervals achieved excellent tumor control with acceptable toxicity in selected benign intracranial tumors. These findings support the clinical feasibility of a fixed two-week inter-fraction interval and suggest that fraction timing may represent a biologically relevant treatment parameter influencing early volumetric response patterns without compromising long-term outcomes.

Purpose:Neurofibromatosis type 2-related schwannomatosis (NF2-SWN) patients frequently present with intracranial meningiomatosis (multiple meningiomas), but optimal management remains unclear. We evaluated the safety and efficacy of wide dural radiation therapy (WDRT) in this population. Materials and Methods:Ten NF2-SWN patients treated with WDRT between March 2018 and December 2022 were reviewed. Endpoints included local control (LC) and progression-free survival (PFS) from the date of WDRT completion and acute toxicity. Progressive disease was defined as a >20% increase in tumor diameter or new lesion development. Results:Median age was 41 years (range 25-53) with a median follow-up of 45.8 months. All patients initiated WDRT for growing lesions or worsening symptoms. Median doses were 54 Gy to gross lesions and tumor bed and 48 Gy to the wide dural field (30 fractions). Ninety-one meningiomas with sizes greater than 5 mm received doses 48 Gy or higher with no infield progression. The 2-year LC rate was 100%, though follow-up remains limited for definitive long-term assessment. Three patients (30%) experienced outfield progression (median 31.3 months): two in intentionally untreated lesions (to be later treated with either surgery or radiosurgery) and one marginal recurrence at the edge of the supratentorial field. Two patients experienced acute grade 2 toxicity including nausea and headache. Conclusion:WDRT provides excellent local control and adequate safety profiles in NF2-SWN patients with meningiomatosis. Further prospective studies with a predefined target volume are warranted to validate our findings.

To evaluate the role of tumor oxygenation imaging parameters in predicting the overall survival (OS) of newly diagnosed isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients. This retrospective single-institution study included 236 patients with IDH-wildtype glioblastomas. ADC values were obtained from autosegmented tumor masks. The normalized relative cerebral blood volume (rCBV), relative cerebral metabolic rate of oxygen values (CMRO2), capillary transit time heterogeneity, and oxygen extraction fraction were also extracted from DSC imaging. Univariable and multivariable Cox analyses including age, sex, Karnofsky performance status (KPS), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, extent of resection (EOR), and quantitative imaging parameters were performed. On univariable analysis, older age, lower KPS, MGMT promoter unmethylation, lesser EOR, higher 10th percentile of rCBV, and higher 10th percentile of CMRO2 were significantly associated with poor OS. On multivariable analysis, older age (hazard ratio [HR] = 1.03, P < 0.001), MGMT promoter unmethylation (HR = 1.55, P < 0.001), lesser EOR (HR = 1.94, P < 0.001), and higher 10th percentile of CMRO2 (HR = 1.03, P = 0.045) were independently associated with poor OS. Higher 10th percentile of CMRO2 may predict dismal prognosis in IDH-wildtype glioblastoma patients independently of previously known clinical, molecular, and surgical prognostic factors.

The benefit of external beam radiotherapy (EBRT) over Gamma Knife surgery (GKS) for central neurocytoma (CN) remains unclear. The aim of this retrospective, multicenter study was to investigate the role of adjuvant radiotherapy (ART) after surgical removal of CN and compare the outcomes of these modalities. We included 128 patients with CN who underwent surgery during 2000–2020. Patients were categorized according to the extent of resection, Ki-67 labeling index, and ART modality. Progression-free survival (PFS) was assessed using Kaplan–Meier analysis and Cox proportional-hazards modeling. The median tumor size and follow-up duration were 5 cm and 66 months, respectively. ART was independently associated with an improved PFS (p = 0.005). Five-year PFS rates were higher among patients who received EBRT (n = 20, 95.0

We aimed to establish a robust vision-language model ("Glio-LLaMA-Vision") for molecular status prediction and radiology report generation (RRG) in adult-type diffuse gliomas. Multiparametric MRI data and paired radiology reports from 1001 patients with adult-type diffuse gliomas were included in the institutional training set. A vision-language model, Glio-LLaMA-Vision, was developed from LLaMA 3.1 pre-trained on 2.79 million biomedical image-text pairs from PubMed Central and further fine-tuned from the institutional training set. The performance was validated in 100 patients and 75 patients with paired MRI-radiology reports from an institutional validation set and another tertiary institution (AMC), and in 170 and 477 patients with MRI from TCGA and UCSF datasets, respectively. In terms of IDH mutation status prediction, Glio-LLaMA-Vision showed AUCs ranging from 0.85-0.95 in the internal validation and external datasets. In terms of RRG, the BLEU-1 and ROUGE-L scores were 0.50 and 0.49 in the internal validation, respectively, and 0.32 and 0.36 on the AMC dataset, respectively. Overall, 37.8% of generated reports were considered superior or equal to the original reports, while 91.0% of generated reports were considered clinically acceptable by neuroradiologists. In conclusion, Glio-LLaMA-Vision demonstrates promising performance in molecular status prediction and RRG in adult-type diffuse gliomas, showing potential for clinical assistance.

Among central nervous system (CNS) tumors, gliomas are the most prevalent type of tumor. Single nucleotide polymorphisms (SNPs) in telomerase reverse transcriptase (TERT) gene have been identified as risk loci for gliomas by previous genome-wide association studies (GWAS). We examined association between TERT variants and glioma risk in a Korean population. For a case-control study, a total of 32 TERT SNPs from 317 patients with glioma and 480 population-based controls were genotyped. Logistic regression was used for statistical analysis of the link between TERT SNPs and risk of glioma. In this study, eight TERT variants, including four glioma-associated variants reported in previous studies, showed significant association with the risk of glioma. Conditional and stepwise analyses were conducted to validate independent associations in the group of the eight variants. Both analyses identified an intronic variant (rs56345976) as the causal variant among the eight variants. Glioma subgroup analyses indicate that rs56345976 variant is associated with the risk of WHO grade 4, glioblastoma, isocitrate dehydrogenase (IDH) wild-type, and 1p/19q non-codeletion glioma. This study presents a profound comprehension of the relationship between TERT variants and the risk of glioma. Further studies of this variant are required to investigate its effect on glioma susceptibility.