Neuro-oncology最新文献

{"title":"Health-Related Quality of Life in Glioma Subtypes: A Pooled Analysis of 16 Randomized Trials from the CODAGLIO 2.0 project.","authors":"Ogechukwu A Asogwa, Linda Dirven, Martin J van den Bent, Neil K Aaronson, Brigitta G Baumert, Alba A Brandes, Paul M Clement, Corneel Coens, Thierry Gorlia, Ulrich Herrlinger, Caroline Hertler, Florence Keime-Guibert, Emilie Le Rhun, Luigi Lim, Annika Malmström, Christine Marosi, Francesca Martinelli, Matthijs van der Meulen, Kathy Oliver, Andrea Pace, Claudia Panciroli, Jaap C Reijneveld, Mirjam Renovanz, Patrick Roth, Clemens Seidel, Roger Stupp, Wolfgang Wick, Michael Weller, Martin J B Taphoorn, Johan A F Koekkoek","doi":"10.1093/neuonc/noag231","DOIUrl":"https://doi.org/10.1093/neuonc/noag231","url":null,"abstract":"<p><strong>Background: </strong>It is unclear whether glioma subtypes differ in health-related quality of life (HRQoL) over time.</p><p><strong>Methods: </strong>We analyzed data from the CODAGLIO 2.0 database, comprising 16 randomized controlled trials with HRQoL assessed using the EORTC QLQ-C30 and QLQ-BN20 questionnaires. Differences in mean HRQoL at baseline (before postoperative treatments) and 3 months were compared across glioma subtypes. Linear mixed models (LMMs) were used to identify factors independently associated with HRQoL, and anchor-based minimally important differences determined clinical relevance.</p><p><strong>Results: </strong>A total of 4,301 patients had baseline HRQoL data; 75% completed follow-up. In stratified analyses, at 3 months, physical, social, role, and cognitive functioning were statistically and clinically significantly worse in glioblastoma than in astrocytoma or oligodendroglioma. In adjusted LMMs, compared with glioblastoma, patients with astrocytoma had worse physical (-2.78, 95% CI -4.68 to -1.01) and cognitive functioning (-3.63, -6.18 to -1.05), more pain (2.74, 0.41-4.95), communication deficits (5.03, 2.44-7.66), and seizures (4.49, 2.55-6.72). Patients with oligodendroglioma had worse social functioning (-5.39, -10.57 to -0.11), communication deficits (7.40, 1.63-12.81), and seizures (8.61, 4.17-14.26). None of these differences exceeded clinical relevance thresholds. Performance status was the only variable associated with clinically meaningful HRQoL changes across most scales.</p><p><strong>Conclusions: </strong>At 3 months, patients with glioblastoma show clinically worse HRQoL than IDH-mutant glioma patients in unadjusted analyses. However, after adjusting for clinical variables, glioblastoma patients exhibit statistically but not clinically better HRQoL in several domains. Performance status emerges as the key factor independently associated with HRQoL and should play a central role in clinical decision-making.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112699","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":"Breaking barriers in leptomeningeal disease: A Society for Neuro-Oncology and The American Society of Clinical Oncology consensus review on clinical trial design and basic science integration.","authors":"Yolanda Piña, Maxine Umeh Garcia, Adrienne Boire, Andrew Brenner, David Ross Camidge, Susan Chang, Peter A Forsyth, Melanie Hayden Gephart, David Olayinka Kamson, Priya Kumthekar, Eudocia Quant Lee, Emilie Le Rhun, Barbara O'Brien, Elena Pentsova, David Piccioni, Jan Remsik, Inna Smalley, Jeffrey Wefel, Michael Weller, Jessica Wilcox, Jonathan T Yang, Seema Nagpal, Isabella Claudia Glitza Oliva","doi":"10.1093/neuonc/noag126","DOIUrl":"10.1093/neuonc/noag126","url":null,"abstract":"<p><p>Leptomeningeal disease (LMD) is a devastating complication of cancer, and its incidence is rising. The inaugural LMD Think Tank Meeting took place in 2023 during the Society for Neuro-Oncology (SNO) and American Society of Clinical Oncology (ASCO) Central Nervous System (CNS) annual meeting, convening an international group of clinicians and scientists dedicated to understanding and treating LMD in a multidisciplinary fashion. While this meeting laid the foundation for a SNO/ASCO consensus review on the clinical management of LMD, the frequent exclusion of LMD patients from trials was identified as a clear and pervasive challenge. To address this gap, a follow-up assembly convened in 2024 with a goal of developing an SNO/ASCO consensus on best practices for clinical research; this included addressing the role of industry and basic scientists in clinical trials, providing guidance for improved clinical trial design, and accelerating the enrollment of LMD patients into clinical trials. Academic-industry partnerships and multi-institutional collaborations are crucial to advance our understanding of LMD, expand treatment access, and ultimately, improve survival and quality of life for our patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2299-2312"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programmable microfluidic modeling of the glioblastoma immune microenvironment recapitulates temporally regulated tumor-immune signaling.","authors":"Seokgyu Han, Yona Kim, Sein Kim, Chanyang Lee, Jaehyun Lee, Min-Hyeok Kim, Hyo Eun Moon, Sarnai Amartumur, Chaejeong Heo, Sun Ha Paek, Sungsu Park","doi":"10.1093/neuonc/noag151","DOIUrl":"10.1093/neuonc/noag151","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) progression is driven by intricate interactions between neoplastic cells and immune populations within the tumor microenvironment (TME), yet the temporal organization of these processes remains insufficiently defined. While tumor-associated macrophages (TAMs), composed of microglia and monocyte-derived macrophages, constitute a major immune population in GBM, microglia play a prominent role in shaping local immunosuppressive niches, thereby limiting cytotoxic lymphocyte infiltration. However, static co-culture models constrain interrogation of dynamic tumor-immune signaling.</p><p><strong>Methods: </strong>We utilized a programmable multi-inlet microfluidic platform that allows sequential, order-specific introduction of immune cells into GBM constructs, enabling controlled interrogation of MG- and natural killer (NK)-mediated interactions under defined temporal conditions. Bulk transcriptomic profiling and single-cell analyses were used to characterize tumor- and immune-associated pathways elicited by distinct temporal configurations.</p><p><strong>Results: </strong>In triculture constructs containing identical populations of GBM cells, microglia, and NK cells, MG-first delivery preferentially activated STAT3-associated immunoregulatory transcriptional programs, whereas NK-first delivery induced cytotoxic and interferon-related gene expression profiles. IL12A expression was selectively increased under NK-first conditions and correlated with immune-active GBM states in patient datasets. STAT3 inhibition reduced MG-associated suppression, increased IL12A expression, and enhanced the response to temozolomide.</p><p><strong>Conclusions: </strong>This programmable spheroid platform not only recapitulates hallmark features of the GBM immune microenvironment but also uncovers temporally regulated pathways arising from sequential cellular interactions. By enabling controlled reconstruction of dynamic tumor-immune signaling, this system offers a versatile strategy for mechanistic investigation and provides a foundation for evaluating immune-modulatory approaches and microenvironment-targeted interventions in GBM and other malignancies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2352-2368"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating androgen signaling tumor dependency with host neuroendocrine immunity for glioblastoma therapies.","authors":"Iris Lavon, Alexander Lossos, Nima Sharifi, Justin D Lathia","doi":"10.1093/neuonc/noag156","DOIUrl":"10.1093/neuonc/noag156","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2296-2298"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective histone deacetylase inhibition as a therapeutically relevant strategy in H3K27M-glioma.","authors":"Andrew Groves, Orville O Kirkland, Costanza Lo Cascio, Xiuqi Wang, Caleb Heaslip, Joana Graca Marques, Chen Song, Rebecca Poetschke, Tingjian Wang, Diana H Chin, Yaw Asante, Qi Liu, Hyunmin Kim, Shanqing Gu, Maria Trissal, Jenna Labelle, Gustavo Alencastro Veiga Cruzeiro, Kristen L Jones, Amy B Cameron, Louise M Clark, Brittaney Leeper, Quang-De Nguyen, Berkley E Gryder, Mariella G Filbin, Jun Qi","doi":"10.1093/neuonc/noag142","DOIUrl":"10.1093/neuonc/noag142","url":null,"abstract":"<p><strong>Background: </strong>Diffuse midline glioma (DMG) is a lethal pediatric brain tumor, driven by profound epigenetic dysregulation, raising the possibility that targeting epigenetic regulators such as histone deacetylases (HDACs) could provide a therapeutic benefit. However, despite preclinical activity, currently available HDAC inhibitors have shown limited clinical translation due to poor central nervous system (CNS) penetration and a lack of HDAC isoform selectivity.</p><p><strong>Methods: </strong>We combined CRISPR/Cas9 screening and pharmacologic HDAC inhibition to identify isoform-specific dependencies in DMG cell lines. Mechanistic studies were performed using bulk RNA-seq and HiChIP, and therapeutic efficacy was evaluated in orthotopic patient-derived xenograft mouse models.</p><p><strong>Results: </strong>We identify that the nuclear-localized Class I HDAC isoforms are dependencies in DMG and demonstrate that HDAC2 represents a selective dependency that is highly expressed in patient tumors. We further identify a CNS-penetrant HDAC inhibitor, Compound 26, with preferential HDAC1/2 isoform selectivity. Transcriptomic and chromatin conformation analyses reveal that Compound 26 induces rapid transcriptional reprogramming, restores physiologic pontine histone patterns, and induces cell cycle arrest through chromatin reorganization. Consistent with these effects, Compound 26 slows DMG growth in vitro and in orthotopic in vivo models.</p><p><strong>Conclusions: </strong>Our findings establish HDAC2 as a critical and therapeutically actionable dependency in DMG. Genetic or pharmacological targeting of HDAC2 disrupts DMG chromatin architecture and induces cell cycle arrest. The HDAC1/2-selective inhibitor Compound 26 exhibits favorable CNS-penetration, tolerability, and antitumor activity in disease-relevant patient-derived xenograft models. Collectively, these data support isoform-selective HDAC inhibition as a rational strategy to overcome the translational limitations of pan-HDAC inhibitors in DMG.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2485-2499"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148331696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAPK-driven glioma progression and reprogramming of the tumor-associated immune response.","authors":"Elaheh Hashemi, Ravishkumar Lakshmi Akshaya, Lin Wang, Spencer Bergland, Hadeesha Piyadasa, Jolene S Ranek, Viva Voong, Aditya Kshirsagar, Anny Shai, Benjamin Oberlton, Anupam Kumar, Mitchel S Berger, Edward F Chang, Michael C Oldham, Robert M Prins, Sean C Bendall, Michael Angelo, Shawn L Hervey-Jumper, Hideho Okada, Aaron Diaz, Joanna J Phillips","doi":"10.1093/neuonc/noag147","DOIUrl":"10.1093/neuonc/noag147","url":null,"abstract":"<p><strong>Background: </strong>In brain tumors, the immunosuppressive microenvironment leads to tumor aggressiveness and immunotherapy resistance. To identify factors that regulate the glioma-immune landscape, we took advantage of the disease trajectory of the MAPK-driven glioma, pleomorphic xanthoastrocytoma (PXA), which evolves from an immune-rich low-grade tumor to an aggressive glioma.</p><p><strong>Methods: </strong>Using a multiomics approach that included single-nucleus RNA sequencing, spatial transcriptomics, and spatial proteomics, a cohort of 38 tumors, including 10 longitudinal pairs, was profiled.</p><p><strong>Results: </strong>Tumor progression was associated with transition to a more proliferative progenitor state and increased hypoxia. Hypoxic reprogramming of the immune landscape included increased TGF-β signaling and altered chemokine signaling, including decreased CXC-chemokine ligand 14 (CXCL14) and CXCL16-CXCR6 signaling important in immune cell recruitment and activation. The resulting immune landscape was spatially reorganized with reduced HLA class II expression, reduced CD8+ and CD4+ T cells, and dominated by immunosuppressive myeloid cells.</p><p><strong>Conclusions: </strong>Hypoxia and chemokine signaling emerged as key components of the glioma-immune landscape that evolve with tumor progression. These findings identify potential therapeutic opportunities in PXA, and they argue that optimal immunomodulatory strategies in glioma will differ along the disease trajectory.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2384-2400"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-associated epilepsy at diagnosis in glioblastoma patients reveals an inflammatory molecular signature and is associated with better overall survival.","authors":"Lilyana Dimova, Jenny Stritzelberger, Diyan Dimov, Jonas Ort, Hussam Aldin Hamou, Hans Clusmann, Oliver Schnell, Hajo Hamer, Florian Putz, Stefanie Corradini, Ludwig Singer, Arnd Dörfler, Franz Ricklefs, Richard Drexler, Matthias Simon, Dieter Henrik Heiland, Daniel Delev","doi":"10.1093/neuonc/noag134","DOIUrl":"10.1093/neuonc/noag134","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GB) is the most aggressive primary brain tumor in adults. Tumor-associated epilepsy (TAE) at diagnosis is common, yet its prognostic significance remains unclear.</p><p><strong>Methods: </strong>We analyzed a retrospective multicenter test cohort of 855 GB patients (Aachen, Hamburg, Bielefeld) and validated findings in a prospectively collected cohort of 344 patients (Erlangen). Survival was assessed using multivariable Cox regression, propensity score matching, and interaction modeling of TAE and extent of resection (EOR). Molecular profiling included methylation-based classification, epigenetic deconvolution, and spatial transcriptomics.</p><p><strong>Results: </strong>Tumor-associated epilepsy was independently associated with improved survival (hazard ratio [HR] 0.81, 95% CI 0.69-0.99, P = .036, absolute survival advantage ∼4-5 months). This effect was validated in the independent cohort (C-index 0.68, 95% CI 0.62-0.74) and persisted in propensity-matched analyses (HR 0.74, 95% CI 0.56-0.96, P = .027). Interaction modeling revealed that gross total resection (GTR) improved survival in both groups but particularly in patients with TAE (EOR interaction HR 0.69, 95% CI 0.49-0.99, P = .041). In this subgroup, partial resection provided no significant advantage over biopsy, whereas patients without seizures benefited incrementally from both partial resection and GTR. Molecular analysis demonstrated enrichment of the RTK II subtype, differentiated cell states, and an inflammatory microenvironment in GB with TAE; tumors without seizures displayed neuronal and stem-like features. Functional validation using electrogenomics showed that GB cortical slices with increased inflammatory score exhibited synchronization of action potentials characteristic for seizure-like epileptiform activity.</p><p><strong>Conclusions: </strong>Tumor-associated epilepsy at diagnosis is a favorable prognostic marker in GB, defining a biologically distinct subgroup. Seizure status modifies the prognostic effect of surgical resection, underscoring the importance of GTR particularly in patients presenting with TAE.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2461-2471"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Amide proton transfer-weighted (APTw) CEST MRI in clinical routine for single time point diagnosis of pseudoprogression in IDH-wildtype glioblastoma.","authors":"","doi":"10.1093/neuonc/noag176","DOIUrl":"10.1093/neuonc/noag176","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"e34"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic value of CDKN2A/CDKN2B hemizygous deletion in meningioma remains uncertain.","authors":"Junpeng Ma, Wei Chen, Yaqiang Hong, Dake Zhang, Liang Wang","doi":"10.1093/neuonc/noag158","DOIUrl":"10.1093/neuonc/noag158","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2514-2515"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Investigator-led clinical trial of boron neutron capture therapy system for recurrent high-grade meningiomas after radiation therapy: Randomized phase II study.","authors":"","doi":"10.1093/neuonc/noag230","DOIUrl":"https://doi.org/10.1093/neuonc/noag230","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112625","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}