Neuro-oncology最新文献

{"title":"Biomarker-guided treatment strategies for patients with gliomas in clinical practice.","authors":"Emilie Le Rhun, Ingo K Mellinghoff, Tobias Weiss, Marian C Neidert, Wolfgang Wick, Michael Weller","doi":"10.1093/neuonc/noag238","DOIUrl":"https://doi.org/10.1093/neuonc/noag238","url":null,"abstract":"<p><p>Targeted therapy has made important contributions to improving outcomes for patients with many solid tumors, but has had only limited activity so far in patients with gliomas, notably glioblastoma. Failure of targeted therapy in glioblastoma is likely due to redundance of oncogenic pathway activation and so far the inability to identify suitable targets and apply biomarker-based enrichment strategies in clinical trial designs. In contrast, in non-glioblastoma tumors, there are promising developments which have already changed clinical practice: inhibition of mutant isocitrate dehydrogenase (IDH) exemplified by vorasidenib, the first approved drug specifically for IDH-mutant gliomas, has changed the landscape for targeted therapy of WHO grade 2 gliomas. Furthermore, dordaviprone, an antagonist of dopamine receptor D2/3 (DRD2/3) and an allosteric agonist of the mitochondrial protease caseinolytic mitochondrial matrix peptidase proteolytic subunit (ClpP), emerges as a potentially active agent in patients with recurrent K27M-mutant diffuse midline gliomas. Finally, BRAF mutations, neurotrophic tyrosine receptor kinase ( r fibroblast growth factor receptor (FGFR) gene fusions continue to raise interest as therapeutic targets at least for subsets of patients with gliomas. Almost no targeted therapy approaches for ependymomas have emerged. Improved clinical trial designs including shared control arms early on and using pharmacodynamic endpoints ideally in enriched patient populations are the path forward towards the identification of further active treatments for patients with gliomas.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Homeobox A3 and KDM6A cooperate in transcriptional control of aerobic glycolysis and glioblastoma progression.","authors":"","doi":"10.1093/neuonc/noag242","DOIUrl":"https://doi.org/10.1093/neuonc/noag242","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-Based Machine Learning to Differentiate True Progression from Pseudoprogression in Glioblastoma: An Updated Systematic Review and Meta-Analysis.","authors":"Xin Zhang, Xiaopeng Guo, Yu Wang, Konrad Wagstyl, Thomas C Booth","doi":"10.1093/neuonc/noag259","DOIUrl":"https://doi.org/10.1093/neuonc/noag259","url":null,"abstract":"<p><strong>Background: </strong>Differentiating true progression (TP) from pseudoprogression (PsP) after chemoradiation for glioblastoma remains clinically difficult. We evaluated externally validated diagnostic performance of magnetic resonance imaging (MRI)-based machine learning models and appraised study quality and transparency.</p><p><strong>Methods: </strong>PubMed, Embase, MEDLINE, and Cochrane Library were searched through October 1, 2025 (PROSPERO registration CRD420251144894). Eligible adult glioblastoma studies used MRI-based machine learning to distinguish TP from PsP against histopathology and/or clinicoradiologic follow-up. The primary meta-analysis included external test cohorts with extractable 2 × 2 data; internal and combined internal and external test analyses were secondary. Diagnostic accuracy was synthesized with bivariate random-effects models.</p><p><strong>Results: </strong>Thirty-one studies including 2,344 patients undergoing imaging assessment were included. Seven external test cohorts, including 219 patient observations, entered the primary meta-analysis. Pooled sensitivity was 0.78 (95% confidence interval [CI], 0.63-0.88), specificity was 0.75 (95% CI, 0.63-0.84), and summary area under the receiver operating characteristic curve (AUC) was 0.81 (bootstrap 95% CI, 0.69-0.91). Internal test cohorts showed higher apparent performance than external cohorts (AUC, 0.91 vs 0.81), but the difference was not statistically significant (difference, -0.09; 95% CI, -0.22 to 0.02; P = 0.12). Risk of bias was frequently high or unclear, and reporting transparency was heterogeneous.</p><p><strong>Conclusions: </strong>MRI-based machine learning showed moderate-to-good external validation performance for TP-versus-PsP discrimination, but evidence remains limited by small external test cohorts, bias, and incomplete reporting. Larger transparent multicenter validations are needed before routine clinical implementation.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuning CAR-T Cell Fitness Through Tonic Signaling in Diffuse Midline Glioma.","authors":"S Z Winson Ho, Rongze Olivia Lu","doi":"10.1093/neuonc/noag250","DOIUrl":"https://doi.org/10.1093/neuonc/noag250","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Trifecta of Combining innate and adaptive checkpoint blockade.","authors":"David S Beltran-Cardona, Siddhartha S Mitra","doi":"10.1093/neuonc/noag264","DOIUrl":"https://doi.org/10.1093/neuonc/noag264","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finding a new strategy to defeat an old foe: Overcoming radioresistance in glioblastoma.","authors":"Monica Venere","doi":"10.1093/neuonc/noag263","DOIUrl":"https://doi.org/10.1093/neuonc/noag263","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Significance of Contrast Enhancement in Newly Diagnosed Grade 2 IDH-mutant Glioma.","authors":"Vihang Nakhate, Aleksandra B Lasica, Loai Aker, Julie J Miller, Ian Pan, Jason Lauer, Julien Rousseau, Elisa Aquilanti, Isabel Arrillaga-Romany, Tamar R Berger, Tracy T Batchelor, Rameen Beroukhim, Ugonma N Chukwueke, Jorg Dietrich, Deborah A Forst, Elizabeth R Gerstner, L Nicolas Gonzalez Castro, Eudocia Q Lee, Lakshmi Nayak, Scott R Plotkin, John Y Rhee, Nancy Wang, David A Reardon, Raymond Y Huang, Gilbert Youssef, Patrick Y Wen","doi":"10.1093/neuonc/noag262","DOIUrl":"https://doi.org/10.1093/neuonc/noag262","url":null,"abstract":"<p><strong>Background: </strong>Contrast enhancement is generally considered an adverse prognostic feature in adult glioma. However, its significance in newly diagnosed grade 2 IDH-mutant glioma remains uncertain, with important implications for use of the mutant IDH inhibitor vorasidenib. We evaluated survival outcomes associated with preoperative enhancement in this population.</p><p><strong>Methods: </strong>We retrospectively evaluated consecutive patients with grade 2 IDH-mutant glioma treated at two institutions between 2010 and 2021. Preoperative MRIs were assessed for intratumoral enhancement by two independent readers with third-reader adjudication. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier analysis, univariate and multivariable Cox regression.</p><p><strong>Results: </strong>Among 325 evaluable patients, median age was 37 years, 47% had 1p/19q-codeletion, and 35% had gross-total resection. Median follow-up was 10.5 years. Preoperative enhancement was observed in 53 (16%) patients, most commonly nonmeasurable (72%) or ill-defined (62%); most (87%) had no residual postoperative enhancement. Preoperative enhancement was not associated with OS or PFS in either univariate analyses (OS HR 1.16 [0.67-2.01], p = 0.591; PFS HR 1.25 [0.88-1.80], p = 0.216) or multivariable analyses adjusting for established prognostic factors (OS HR 0.86 [0.46-1.61], p = 0.633; PFS HR 1.29 [0.86-1.92], p = 0.219). Enhancement characteristics (measurable size, well-defined morphology) were not associated with OS.</p><p><strong>Conclusion: </strong>In grade 2 IDH-mutant glioma, preoperative enhancement was not associated with OS or PFS. These findings suggest that preoperative enhancement does not identify a higher-risk subgroup in this population, and that its presence alone should not preclude consideration of vorasidenib in eligible patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Routing to the seizure in postoperative human glioma cortex: spatio-temporal uncoupling between slow and fast extracellular neuronal activities.","authors":"Belén Díaz-Fernández, David Henao-Herreno, Elena Dossi, Adrien Le Marchand, Alesya Evstratova, Johan Pallud, Laurent Capelle, Jan Pyrzowski, Nathalie Rouach, Sandrine Katsahian, Michel Le Van Quyen, Gilles Huberfeld","doi":"10.1093/neuonc/noag258","DOIUrl":"https://doi.org/10.1093/neuonc/noag258","url":null,"abstract":"<p><strong>Background: </strong>Diffuse gliomas are frequently associated with epilepsy, particularly in low-grade variants. Seizures are key events to be considered in glioma management, including during surgery. Optimizing resection of epileptic areas may affect not only postoperative epilepsy but also glioma prognosis in the context of interactions between glioma growth and neuronal activities. As for glioma tissue resection, surgery of epileptic networks requires a deeper understanding of their organization and reliable biomarkers.</p><p><strong>Methods: </strong>We investigated the spatiotemporal dynamics of the transition from interictal to ictal-like events (ILEs) using ex vivo human peritumoral tissue from glioma patients. Slices were recorded with multi-electrode arrays during the transition from the spontaneous interictal state to pharmacologically induced seizures considering the dynamics of slow versus fast oscillatory neuronal activities.</p><p><strong>Results: </strong>Transition to seizure was characterized by the emergence of preictal discharges (PIDs), allowing subdivision of the preictal phase into build-up, steady-state, and trigger periods. PIDs progressively increased in amplitude, duration, and slope with significant changes during the trigger phase. Concurrently, high-frequency activity (180-550 Hz) and high-frequency oscillations (HFOs) increased across the transition period, particularly during the trigger phase. In addition to such preictal recruitment, the reinforcement of HFOs was accompanied by a spatial organization in additive microdomains, peaking at seizure onset and encompassing slow field potential dynamics.</p><p><strong>Conclusions: </strong>In the periglioma human cortex, seizures arise from progressively recruited neuronal assemblies sculpted together with HFOs, providing new insights into the microphysiological processes of glioma-related ictogenesis and requiring consideration of the preictal fast and focal neuronal activity.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unilateral vs Bilateral Hippocampal Avoidance During WBRT With Memantine for Brain Metastases: A Randomized Single-Blind Phase 2 Clinical Trial.","authors":"Wen-Chi Yang, Ya-Fang Chen, Chi-Cheng Yang, Szu-Huai Lu, Shao-Lun Lu, Ming-Che Kuo, Chin-Hao Chang, Feng-Ming Hsu","doi":"10.1093/neuonc/noag261","DOIUrl":"https://doi.org/10.1093/neuonc/noag261","url":null,"abstract":"<p><strong>Background: </strong>Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) with memantine reduces, but does not eliminate, cognitive decline. Left hippocampal dose may be more closely associated with cognitive outcomes. We investigated whether unilateral (left) HA-WBRT is equivalent to bilateral HA-WBRT for neurocognitive function.</p><p><strong>Methods: </strong>In this randomized, single-blind, phase 2 equivalence trial, patients with brain metastases were assigned 1:1 to unilateral (left) or bilateral HA-WBRT (30 Gy in 10 fractions) with concurrent memantine. The primary endpoint was relative decline in Hopkins Verbal Learning Test-Revised (HVLT-R) memory score from baseline to 6 months; equivalence required the 90% CI for the between-arm difference to fall within ±15 percentage points.</p><p><strong>Results: </strong>Among 73 patients (unilateral, n = 36; bilateral, n = 37; median follow-up, 13.2 months), mean 6-month relative HVLT-R decline was 4.75% versus 5.05% (difference, -0.31%; 90% CI, -12.02% to 11.40%; TOST P = .02), meeting the equivalence criterion. Brain progression-free survival (10.3 vs 10.8 months; P = .96), overall survival (17.8 vs 12.8 months; P = .94), acute toxicity (≥ grade 2, 44.4% vs 35.1%; P = .43), and 6-month neurocognitive failure (61.1% vs 56.8%; Gray test P = .78) were similar. Global health status appeared more stable with unilateral HA-WBRT (interaction, P < .001). Exploratory plasma BDNF trajectories varied by neurocognitive failure status (FDR q = .09).</p><p><strong>Conclusions: </strong>Unilateral (left) HA-WBRT with memantine met the prespecified equivalence criterion for verbal memory, with comparable oncologic outcomes and safety; non-verbal memory was not assessed. These findings warrant validation, particularly when bilateral avoidance is challenging.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of inactivating NOTCH1 mutations in an IDH-mutant astrocytoma with clinical resistance to vorasidenib treatment.","authors":"Tomoyuki Nakano, Nicholas A Jessop, Charlotte I Wang, Maria Martinez-Lage, Itay Tirosh, Mario L Suva, Hiroaki Wakimoto, Daniel P Cahill, Christine Lu-Emerson, Julie J Miller","doi":"10.1093/neuonc/noag174","DOIUrl":"https://doi.org/10.1093/neuonc/noag174","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}