Neuro-oncology advances最新文献

Background: Central nervous system tumors present significant diagnostic and therapeutic challenges, as WHO histomolecular prognostic criteria are not always optimal. Decision-making increasingly relies on multidisciplinary team meetings (MDTs), which require highly qualified specialists. We aimed to assess available human resources and propose a framework for subregional collaboration through a West African neuro-oncology MDT.

Methodology: A multicenter descriptive study was conducted via an online questionnaire from April 13 to June 15, 2025, involving 35 healthcare professionals from nine West African countries.

Results: Participants included 45.7% neurosurgeons, over 57% with <3 years' experience. Most managed <100 patients/year, and 90% performed <100 tumor excisions. Awake surgery and stereotactic biopsy were rare. Access to chemotherapy, pathology, immunohistochemistry, and molecular biology was reported by 83%, 80%, 51%, and 14% of respondents, respectively. Median turnaround time was about 3 weeks for histopathology and about 1 month for immunohistochemistry. Clinical trial access was available to 26%. Neurosurgeon density was <1 per million inhabitants, peaking in Senegal (1 per 700,000). Only 34% reported functional MDTs. Nearly all participants (95%) supported establishing a subregional network with regular online MDTs (monthly or bimonthly) and a specialized interuniversity degree.

Conclusion: MDTs are essential in neuro-oncology, enabling individualized therapeutic planning. Given critical workforce shortages in West Africa, a subregional collaborative MDT network could optimize patient care, enhance resource sharing, and standardize management across the region.

Background: Bevacizumab (BVZ) is widely used in patients with central nervous system (CNS) tumors. Due to its potential to impair wound healing, a minimum interval of 28 days between BVZ administration and surgery - both before and after the procedure - is generally recommended. However, strict adherence to this interval is often challenging in clinical practice, particularly when urgent oncologic treatment or time-sensitive surgical interventions are required.

Methods: Pediatric patients with a CNS tumor receiving intravenous BVZ from January 2005 to December 2022 treated at the Medical University of Vienna were retrospectively analyzed for surgical complications.

Results: One hundred and nineteen patients had 344 surgeries with BVZ therapy before and or after surgery. 11 wound complications (3.20%) of any grade (n=1 CTCAE grade I; n=10 CTCAE grade III) occurred in 11 children (9.24%). Group comparison of BVZ exposure intervals (BVZ ≤28/>28 days and ≤14/>14 days) revealed no statistically significant differences in wound complication rates, with odds ratios of 3.91 (≤28/>28 d; P = .55) and 1.15 (≤14/>14 d; P=1.00) before surgery as well as 1.93 (≤28/>28 d; P = .46) and 3.16 (≤14/>14 d; P = .11) after surgery.

Conclusion: BVZ can be administered within ≤ 28 days before or after surgery when postponing the procedure is not feasible or when immediate (re)initiation of therapy is required, provided that non-absorbable sutures are used, and close wound-monitoring is ensured.

Introduction: A novel dopamine-receptor small molecule inhibitor, ONC201, was observed to elicit a treatment response in patients with H3K27M-altered diffuse midline gliomas (DMG). Given restricted access to this therapy, an alternative formulation from Germany (GsONC201) was made available by compassionate means. We describe the treatment outcomes of these patients and our experience with GsONC201.

Methods: This was a multicenter retrospective study of adult Chinese patients with histologically confirmed H3K727M-altered DMG. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, the observed response rate (ORR) at 3 months after radiotherapy and GsONC201-associated adverse effects.

Results: Twenty-seven patients, median age of 40 years (range: 31-52), were identified. Fifty-two percent (14/27) of tumors arose from the thalamus followed by the pons (22%, 6). Eighty-five percent (23/27) of patients received standard-of-care (SOC) fractionated radiotherapy. Thirty-seven percent (10/27) of patients received GsONC201 of which 80% (8/10) started it as first-line monotherapy after SOC. The mOS of the entire cohort was 17.4 months (IQR: 12.1-30.0). GsONC201 + SOC patients (8) had a mOS of 18.9 months (IQR: 11.3-54.4) compared to 16.0 months (IQR: 12.5-27.6) for SOC-alone patients (13, P value: .57). The ORR was 33% (7/21) and 63% of GsONC201 + SOC patients had a treatment response compared to 15% of SOC-alone patients (P value: .01). No GsONC201-associated adverse effects were observed.

Conclusion: This is the first real-world study to review the outcomes of first-line imipridone-class agent therapy in adult Chinese DMG patients. GsONC201 was well-tolerated, but its effect on OS remains unknown.

Childhood brain tumors are the leading cause of cancer-related morbidity and mortality in children worldwide. Delayed diagnosis and inadequate diagnostic and treatment infrastructure are significant barriers to an optimal outcome in low- and middle-income countries (LMICs), where 80% of children with cancer live. Pediatric neuro-oncology has undergone a transformation with recent developments in molecular diagnostics and the emergence of targeted therapies. However, the implementation of precision medicine in LMICs is challenging in view of high costs, lack of trained personnel, and restricted access to essential medications. Targeted therapies such as MEK, BRAF & NTRK inhibitors have demonstrated promising efficacy with improved toxicity profiles in pediatric brain tumors with actionable mutations. Despite their potential, availability in LMICs is largely restricted to compassionate use programs and select clinical trials. Encouraging results, albeit from few institutions in LMICs, have demonstrated that targeted therapies have a significant impact on quality of life (QOL), in addition to comparable efficacy. Sustainable integration of precision medicine in LMICs requires improved access to affordable molecular diagnostics, inclusion of more targeted drugs in the WHO Essential Medicines List, and participation in international clinical trials. Collaborative models-such as twinning programs, telemedicine, regional reference laboratories, and capacity-building initiatives-can support implementation. Global programs like the WHO Global Initiative for Childhood Cancer and the ATOM Coalition play a vital role in improving drug access and policy advocacy. Enabling precision medicine in LMICs calls for a coordinated multi-stakeholder approach, including integration into the national cancer care policy, and is critical to bridging the survival gap and ensuring equitable outcomes for children with brain tumors globally.

Background: Delta-like ligand 3 (DLL3), an inhibitory Notch ligand, is now explored as a therapeutic target in recurrent diffuse glioma. Since clinical trials may select patients with recurrent glioma based on DLL3 expression in the primary tumor, this study aims to determine whether initial DLL3 expression in glioma is retained at recurrence.

Methods: 198 formalin fixed, paraffin-embedded (FFPE) samples of paired primary and recurrent gliomas were retrieved from the biobank in the Erasmus MC, Rotterdam, the Netherlands. The cohort included oligodendroglioma, isocitrate dehydrogenase mutant (IDHmt) and 1p/19q co-deleted (n = 36), astrocytoma IDHmt (n = 38) and glioblastoma IDH wildtype (IDHwt) (n = 124). DLL3 protein expression was assessed by immunohistochemistry, and samples were categorized as DLL3-negative (0%), DLL3-low (>0-10%), DLL3-medium (10%-50%) and DLL3-high (>50%) based on the estimated percentage of DLL3-positive cells within vital tumor tissue.

Results: DLL3 expression was detected in the majority of glioma samples (86%, 164/190). Expression levels were highest in oligodendroglioma (94% medium or high) and astrocytoma (78.4% medium or high), and lowest in glioblastoma (42% medium or high). 26/190 samples were DLL3-negative. In most patients, DLL3 expression stayed in the same category or increased at recurrence (oligodendroglioma 87.6%, astrocytoma 66.6%, glioblastoma 77.2%). Loss of initial DLL3-positivity at recurrence occurred in only 7/91 patients (7.7%).

Conclusion: DLL3 expression level is retained or increased in the majority of recurrent gliomas. Inclusion in trials with DLL3-targeting agents in recurrent glioma based on primary tumor material is justified, depending on the required level of DLL3 positivity for inclusion.

Background: There is increasing interest in the glioma-to-neuro communication at the brain-tumor interface (BTI). In vitro studies indicate that gliomas with a mutation of the isocitrate dehydrogenase (IDH) increase neuronal excitability of the peritumoral cortex, contributing to epileptogenesis in these patients. However, in vivo evidence is missing. This study evaluates the electric characteristics of the BTI relative to the IDH mutation status.

Methods: To investigate peritumoral cortical excitability (CE), we applied 5258 pulses of transcranial magnetic stimulation (TMS) at the BTI of IDH-mutant (IDH-mt) and IDH-wildtype (IDH-wt) glial tumors in 39 patients. Cortical excitability was assessed by the resting motor threshold (RMT) and the synchronized electromyographic (EMG) activity (ie, event-related spectral perturbation, ERSP) after TMS. The ERSP values were related to the IDH status, tumor grading, antiepileptic drug (AED) intake, and the spatial relationship to the tumor borders.

Results: Within our sample, there was no significant group difference in RMT. The TMS to the BTI triggered an EMG synchronization decreasing linearly with the distance to the functional hotspot. In contrast, IDH-mt gliomas demonstrated an increased cortical output of the peritumoral brain tissue compared with IDH-wt gliomas. This effect was not attributable to AED intake or other histological and molecular characteristics. Notably, cortical hyperexcitability was detectable well beyond the tumor border.

Conclusions: This study provides in vivo evidence of cortical hyperexcitability at the BTI of IDH-mt gliomas. The data demonstrate how molecular glioma characteristics affect peritumoral neuronal circuits. Modulating interactions at the BTI might pave the way for novel therapies.

Background: Preoperative survival prediction in newly diagnosed glioblastoma (nGBM) remains challenging due to limited robustness and standardization across radiomic approaches. We aimed to validate a machine learning-based prognostic model using preoperative MR images and assess its generalizability.

Methods: Two independent cohorts were analyzed: the Kansai Molecular Diagnosis Network for CNS Tumors (KNBTG) and The Cancer Genome Atlas (TCGA). All cases with available preoperative MR images (T1WI, T2WI, and Gd-T1WI) were included. The KNBTG cohort was divided into a training dataset (TD, n = 137) and an internal test dataset (ITD, n = 141), while the TCGA cohort served as the external test dataset (ETD, n = 105). A total of 489 texture features were extracted. Overall survival (OS) was dichotomized at the median, and predictive modeling was performed using least absolute shrinkage and selection operator regularization. The trained model was validated on ITD and ETD.

Results: Radiomic high-risk status was associated with significantly shorter OS in both ITD and ETD (log-rank P < .05) and remained independently prognostic in multivariate Cox analysis. Time-dependent area under the receiver operating characteristic curves was consistently higher in models incorporating radiomic-based risk. Of the 13 selected features, "T2_core_GLCMhomogeniety_3_SD" was the only consistent predictor across cohorts and showed strong prognostic stratification, particularly between low- and high-risk groups (cutoff range: 0.0145-0.0180).

Conclusions: Radiomics-based modeling provides reproducible prognostic value in nGBM. The feature "T2_core_GLCMhomogeniety_3_SD" may serve as a reliable imaging biomarker for preoperative risk stratification and individualized treatment planning.

Background: Leptomeningeal disease (LMD) is characterized by the spread of cancer to the leptomeninges and cerebrospinal fluid (CSF) and is associated with poor survival. Diagnosing LMD is challenging, as traditional methods such as MRI and CSF cell cytology demonstrate variable sensitivity. This study aims to explore the diagnostic potential of CSF circulating tumor cell (CTC) quantification for LMD in conjunction with current standards.

Methods: This retrospective case series includes 12 patients with suspected LMD who underwent CSF analysis with the CNSide assay for CTC quantification and next-generation sequencing (NGS), alongside MRI and CSF cytology. Relying on a composite definition of LMD-positive, the diagnostic performance of CTC quantification was assessed.

Results: Of 12 patients evaluated for LMD with CNSide, 11 were found to have brain metastases (BM). Lung carcinoma was the most common primary cancer (4/12). Nine patients were deemed LMD-positive based on clinical criteria: 7/9 had a preceding brain metastasis diagnosis, while 2/9 co-presented with LMD and BM. CNSide detected CTCs in 7/12 patients (7/9 of those with LMD) and influenced clinical decision-making by guiding chemotherapy selection and prompting proton craniospinal irradiation. Of the three patients deemed LMD-negative with clinical criteria, all three had negative results on the CNSide assay. The CNSide assay demonstrated a sensitivity of 77.8%, specificity of 100%, and overall accuracy of 83.3%.

Conclusion: The integration of CTC quantification with next-generation sequencing (NGS) can be a valuable adjunct to cell cytology in diagnosing leptomeningeal disease. CSF liquid biopsy may provide earlier detection and inform treatment decisions, ultimately improving patient outcomes.

Background: Current understanding of transporter protein expression and localization within the neurovascular unit (NVU) of the human normal brain cortex and glioblastoma (GBM) remains largely qualitative and lacks cellular resolution. This study aimed to provide a quantitative characterization of transporter protein expression and cell-specific localization in the NVU of normal brain cortex and GBM.

Methods: Protein expression of major ATP-binding cassette transporters and solute carrier transporters was quantified in microvessels isolated from distinct regions of the human normal brain cortex and GBM using LC-MS/MS-based targeted proteomics. NVU structure and cell-specific transporter localization were visualized and quantitatively assessed by high-resolution confocal immunofluorescence microscopy.

Results: Targeted proteomics revealed marked alterations in transporter protein abundance in microvessels isolated from both non-enhancing and enhancing regions of GBM, compared with normal brain cortex. ATP-binding cassette (ABC) efflux transporters (ABCB1, ABCG2) were largely preserved. Ion and nutrient transporters (Na⁺/K⁺-ATPase, GLUT3, EAAT1, EAAT2, SNAT2) were significantly reduced (ANOVA, P < .05). GLUT1 appeared downregulated while not reaching statistical significance. LAT1 and SNAT3 protein abundance was significantly increased (ANOVA, P < .05). Confocal immunofluorescence microscopy demonstrated a well-organized NVU architecture in normal brain cortex and a markedly disorganized structure in GBM. Quantitative co-localization analyses identified distinct, cell-type specific transporter distribution patterns in the normal NVU, contrasted by diffuse and mislocalized transporter expression in GBM NVU.

Conclusions: GBM drives profound NVU remodeling at both molecular and structural levels. Disruption of transporter protein expression and cell-specific localization likely contributes to pharmacokinetic heterogeneity, metabolic plasticity, and invasive phenotype of GBM.

Background: Pediatric ependymomas (EPNs) frequently develop in the cerebellum and are treated with non-targeted therapies, partly due to limited understanding of their pathobiology. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis but remain mostly unexplored in pediatric EPNs. This study aimed to identify novel oncogenic drivers and prognostic biomarkers in posterior fossa (PF) EPN by profiling the genome-wide lncRNA expression landscape.

Methods: We used RNA sequencing data from 13 samples (3 controls and 10 PF EPNs) to profile the lncRNA expression landscape. Perturbation and functional assays in EPN cell lines were used to investigate putative oncogenic drivers, while large public datasets were used to explore associations with prognosis.

Results: We identified several aberrantly expressed lncRNAs, including IGF2-AS, CD44-DT, and HOTAIRM1 and lncRNAs associated with poor prognosis such as DELEC1, H19, and CD44-AS1. We focused on H19 and IGF2-AS, which reside in the same imprinted locus together with IGF2, a gene encoding a growth factor. Knockdown of H19 reduced expression of cell cycle-related genes, decreased cell viability, and increased apoptosis and cell cycle arrest. In contrast, IGF2-AS knockdown upregulated H19 and the expression of cell cycle-related genes. Finally, public data showed that H19 is more abundant in the EPN PF subgroup A, and that methylation of its imprinting control region (ICR) correlates strongly with better prognosis in EPN PF subgroup B (PFB).

Conclusion: These findings suggest that H19 plays an oncogenic role in EPN and that the methylation status of its ICR may serve as a prognostic biomarker in PFB.