Neuro-oncology最新文献

{"title":"Beyond the hippocampus: Limbic white matter injury implicated in post-radiation memory performance in primary brain tumor patients.","authors":"Alexander S Qian, Roshan Karunamuni, Soumya Unnikrishnan, Mia A Salans, Austin Hopper, Suma Gudipati, Justin Yu, Michael Connor, Kathryn R Tringale, Michelle D Tibbs, Anny Reyes, Jiwandeep S Kohli, Alena Stasenko, Carrie R McDonald, Jona A Hattangadi-Gluth","doi":"10.1093/neuonc/noaf144","DOIUrl":"https://doi.org/10.1093/neuonc/noaf144","url":null,"abstract":"<p><strong>Background: </strong>Limbic white matter (WM) of the Papez circuit, including the fornix, dorsal cingulum, and parahippocampal cingulum (PHC), interplay with the hippocampus as key components of the memory network. We analyzed biomarkers of injury to these pathways to understand their impact on post-radiation therapy (RT) memory performance.</p><p><strong>Methods: </strong>Primary brain tumor patients on a prospective trial receiving fractionated brain RT (n=57) underwent volumetric MRI, diffusion tensor imaging, and memory assessments (Hopkins Verbal Learning Test-Revised [HVLT-R] Total and Delayed Recall and Brief Visuospatial Memory Test -Revised [BVMT-R] Total and Delayed Recall) at baseline and 3, 6, and 12 months post-RT. MRI biomarkers included volume, fractional anisotropy (FA), and mean diffusivity (MD). Linear mixed-effects models assessed associations between biomarkers and memory performance over time.</p><p><strong>Results: </strong>Smaller volumes in the right fornix was associated with lower BVMT-R-Total scores (p=0.019) and left PHC volume loss was associated with worse performance on BVMT-R-Delayed (p=0.039). Lower FA in the left (p=0.010) and right (p=0.019) fornix was associated with lower BVMT-R-Total performance. Lower FA in the left dorsal cingulum (p=0.038) and right PHC (p=0.039) were associated with lower HVLT-R-Total and HVLT-R-Delayed scores, respectively. Higher MD in bilateral fornix (p=0.01) and right PHC (p=0.011) correlated with lower BVMT-R-Total scores; higher MD in the right PHC (p=0.046) also correlated with lower HVLT-R-Total scores. Hippocampal volume was not associated with memory scores.</p><p><strong>Conclusion: </strong>Poorer microstructural integrity in limbic WM tracts of the Papez circuit predicted worse memory performance, while hippocampal injury did not. Dose avoidance in these tracts may preserve memory outcomes.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285831","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":"Novel GABAAR antagonists target networked gene hubs at the leading-edge in high-grade gliomas.","authors":"Chloe Shard, Anya C Jones, Anahita Fouladzadeh, Helen M Palethorpe, Abbie Francis, Yasmin Boyle, Rebecca J Ormsby, Brittany Dewdney, Yen Yeow, Ishika Mahajan, Matthew Barker, Irina Kuznetsova, Matthew E Jones, Ashwini Patil, Sara Rezaeiravesh, Zi Ying Ng, Santosh I Poonnoose, Anthony Bosco, Santosh Valvi, Alistair R R Forrest, Terrance G Johns, Guillermo A Gomez, Emily V Fletcher","doi":"10.1093/neuonc/noaf143","DOIUrl":"https://doi.org/10.1093/neuonc/noaf143","url":null,"abstract":"<p><strong>Background: </strong>Ion channel activity underlying biological processes that drive high-grade gliomas (HGG) is largely unknown. We aimed to determine the networking of ion channel genes and validate their expression within HGG patient tumors, to identify ion channel-targeting drugs that would inhibit tumor-promoting processes.</p><p><strong>Methods: </strong>We used weighted gene co-expression network analysis (WGCNA) of RNAseq data to identify ion channel gene hubs in diffuse midline glioma (DMG) and glioblastoma. Using scRNA-seq, spatial transcriptomics, and immunohistochemistry, we characterized the expression of identified hubs within patient tumors, validating their role by testing the efficacy of ion channel inhibitors alone or in combination with radiation and temozolomide on the growth and invasion of patient-derived glioblastoma explant organoids (GBOs).</p><p><strong>Results: </strong>Network analysis revealed a preserved HGG \"neuronal regulation\" module, containing the greatest number of ion channels, with its corresponding genes concentrated at the tumor's leading-edge. Hubs within this module included γ-Aminobutyric-acid type A receptor (GABAAR) genes GABRA1 (α1) and GABRG2 (γ2), which immunohistochemically colocalized with GABAergic synaptic markers at the leading-edge. GBOs failed to retain this synaptic architecture but expressed a glioblastoma hub GABRA5 (α5), a component of extrasynaptic GABAARs. S44819, an α5-GABAAR antagonist strongly inhibited GBO invasion, with GABA(A)-compound 1b, a partial antagonist of GABAARs, robustly inhibiting GBO proliferation and invasion. Moreover, combined with standard of care (SOC) regimens, the anti-invasive properties of both compounds were enhanced in GBOs.</p><p><strong>Conclusions: </strong>Our co-expression network analysis identified key ion channels at the leading-edge in HGGs, which can be targeted by GABAAR-acting drugs to disrupt tumor progression.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266919","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":"Phase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group.","authors":"Claire Mazewski, Sarah E S Leary, Guolian Kang, Bryan K Li, Stewart Kellie, Laura Hayes, Dennis Shaw, Ben Ho, Alyssa Reddy, Jeffrey Gossett, Peter C Burger, Alexander R Judkins, Paul Aridgides, J Russell Geyer, Amar Gajjar, Ian F Pollack, Maryam Fouladi, Annie Huang","doi":"10.1093/neuonc/noaf132","DOIUrl":"10.1093/neuonc/noaf132","url":null,"abstract":"<p><strong>Background: </strong>Embryonal brain tumors are the leading cause of cancer death in young children.</p><p><strong>Methods: </strong>ACNS0334 was a phase 3 randomized study evaluating high-dose methotrexate in young children < 36 months old with newly diagnosed high-risk embryonal brain tumors. Treatment included three cycles of induction chemotherapy with or without methotrexate followed by three cycles of high-dose consolidation chemotherapy with hematopoietic stem cell infusion. Primary endpoint was complete response (CR) at end of therapy. Secondary endpoints included comparison of event-free survival (EFS) between arms and to historical controls. Molecular characterization was conducted retrospectively. Tests of significance were one-sided.</p><p><strong>Results: </strong>Of 77 eligible patients, 59 with detectable disease were evaluable for response and 28 (47.5%) achieved CR, 15/30 (50%) treated with methotrexate compared to 13/29 (45%) without methotrexate (p=0.35). For MB, CR was 12/19 (63%) with methotrexate compared to 6/20 (30%) without methotrexate (p=0.039). Considering molecular diagnosis, all SHH MB (n=11) were survivors. Five-year EFS was 70% [90% CI:39.6-87.2] for 10 Group 3 MB with methotrexate versus 33.3% [90% CI:15.0-52.9] for 15 without (p=0.037). In other embryonal tumors, CR was 3/11 (27%) with methotrexate compared to 7/9 (78%) without (p=0.99). No benefit with methotrexate was observed for Embryonal Tumor with Multilayered Rosettes (n=14, EFS 20.0% [90% CI:1.8-52.5] with methotrexate versus 33.3% [90% CI:10.8-58.1] without, p=0.58), or pineoblastoma (n=9, EFS 16.7% [90% CI:1.6-46.1] with methotrexate versus 0% without, p=0.52).</p><p><strong>Conclusions: </strong>The addition of methotrexate to intensive chemotherapy improved CR and EFS for young children with high-risk Group 3 MB, but not other diagnoses.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248888","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":"Erratum to: Phase 1 dose-escalation trial using convection-enhanced delivery of radio-immunotheranostic 124I-Omburtamab for diffuse intrinsic pontine glioma.","authors":"","doi":"10.1093/neuonc/noaf138","DOIUrl":"https://doi.org/10.1093/neuonc/noaf138","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258629","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":"Nuclear cholesterol regulates nuclear size and DNA damage responses in cancer stem cells.","authors":"Tingting Duan, Suchet Taori, Shruti Bhargava, Sisi Lai, Cuiqing Zhong, Shira Yomtoubian, Huairui Yuan, Xujia Wu, Po Zhang, Tengfei Huang, Donghai Wang, Fanen Yuan, Daqi Li, Huan Li, Hailong Mi, Weichi Wu, Rui Wang, Ahmed Habib, Farrukh Hammed, Frank P Vendetti, Pascal O Zinn, Christopher J Bakkenist, Marlies Meisel, Qiulian Wu, Jeremy N Rich","doi":"10.1093/neuonc/noaf110","DOIUrl":"https://doi.org/10.1093/neuonc/noaf110","url":null,"abstract":"<p><strong>Background: </strong>Nuclear atypia is associated with increased malignancy in numerous cancers, including glioblastoma (GBM). Here, we found that GBM stem cells display small nuclear size, prompting investigation of mechanisms underlying nuclear size regulation in the tumor hierarchy.</p><p><strong>Methods: </strong>We performed comparative gene expression and proteomics in GBM stem cells (GSCs) and neural stem cells (NSCs) to discover potential regulators of nuclear size. Through transcriptomic analysis, mass spectrometry, and pharmacologic inhibition, we interrogated the functional significance of nuclear size regulation.</p><p><strong>Results: </strong>GSCs were enriched for a nuclear sterol reductase, Lamin B Receptor (LBR). Targeting LBR increased nuclear size and decreased GSC viability and tumor initiation. Regulation of nuclear cholesterol synthesis underlaid LBR-dependency in GSCs. Loss of LBR or reduction of cholesterol levels induced double-strand DNA breaks (DSBs), activating P53-dependent DNA damage responses (DDR). The GSC proteomic LBR interactome revealed DDR mediators, including DEAD-box RNA helicase DDX5 that resolves R-loops at DSBs. Genetic targeting of LBR reduced the DDX5-R loop interaction, leading to increased R-loop formation rescued by cholesterol supplementation. Pharmacological sterol reductase inhibition mirrored genetic LBR targeting by reducing the DDX5-R loop interaction and increasing R-loops and DSBs. Targeting LBR genetically and pharmacologically inhibits GSC growth in vivo and synergizes with irradiation.</p><p><strong>Conclusions: </strong>Stem-like GBM cells display reduced nuclear size, driven by nuclear cholesterol synthesis to regulate radiation responses, revealing a novel therapeutic paradigm.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248887","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":"TUXEDO-3: A phase 2 trial of patritumab deruxtecan for patients with leptomeningeal metastasis.","authors":"Emilie Le Rhun, Enrico Franceschi, Michael Weller","doi":"10.1093/neuonc/noaf122","DOIUrl":"https://doi.org/10.1093/neuonc/noaf122","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216422","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":"Radiogenomics and Radiomics of Skull Base Chordoma: Classification of Novel Radiomic Subgroups and Prediction of Genetic Signatures and Clinical Outcomes.","authors":"Zachary C Gersey, Serafettin Zenkin, Priyadarshini Mamindla, Mohammadreza Amjadzadeh, Murat Ak, Tritan Plute, Vishal Peddagangireddy, Hussein Abdallah, Nallammai Muthiah, Eric W Wang, Carl Snyderman, Paul A Gardner, Rivka R Colen, Georgios A Zenonos","doi":"10.1093/neuonc/noaf131","DOIUrl":"https://doi.org/10.1093/neuonc/noaf131","url":null,"abstract":"<p><strong>Background: </strong>Chordomas are rare, aggressive tumors of notochordal origin, commonly affecting the spine and skull base. Skull Base Chordomas (SBCs) comprise approximately 39% of cases, with an incidence of less than 1 per million annually in the U.S. Prognosis remains poor due to resistance to chemotherapy, often requiring extensive surgical resection and adjuvant radiotherapy. Current classification methods based on chromosomal deletions are invasive and costly, presenting a need for alternative diagnostic tools. Radiomics allows for non-invasive SBC diagnosis and treatment planning.</p><p><strong>Methods: </strong>We developed and validated radiomic-based models using MRI data to predict Overall Survival (OS) and Progression-Free Survival following Surgery (PFSS) in SBC patients. Machine learning classifiers, including eXtreme Gradient Boosting (XGBoost), were employed along with feature selection techniques. Unsupervised clustering identified radiomic-based subgroups, which were correlated with chromosomal deletions and clinical outcomes.</p><p><strong>Results: </strong>Our XGBoost model demonstrated superior predictive performance, achieving an area under the curve (AUC) of 83.33% for OS and 80.36% for PFSS, outperforming other classifiers. Radiomic clustering revealed two SBC groups with differing survival and molecular characteristics, strongly correlating with chromosomal deletion profiles. These findings indicate that radiomics can non-invasively characterize SBC phenotypes and stratify patients by prognosis.</p><p><strong>Conclusions: </strong>Radiomics shows promise as a reliable, non-invasive tool for the prognostication and classification of SBCs, minimizing the need for invasive genetic testing and supporting personalized treatment strategies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199659","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":"Renaming low-grade MPNST: look before we leap.","authors":"Xuan Yu, Jingxuan Huang, Zhichao Wang","doi":"10.1093/neuonc/noaf074","DOIUrl":"https://doi.org/10.1093/neuonc/noaf074","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192057","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":"Impact of corticosteroid administration on contrast-enhancing volume and diffusion MRI in treatment naïve glioblastoma.","authors":"Francesco Sanvito, Asher Kim, Catalina Raymond, Ashley Teraishi, Richard G Everson, Phioanh L Nghiemphu, Albert Lai, Robert A Chong, David A Nathanson, Noriko Salamon, Timothy F Cloughesy, Jingwen Yao, Benjamin M Ellingson","doi":"10.1093/neuonc/noaf136","DOIUrl":"https://doi.org/10.1093/neuonc/noaf136","url":null,"abstract":"<p><strong>Background: </strong>Corticosteroids impact the radiographic interpretation of glioblastoma, including artificial reduction in contrast-enhancing tumor volume and intensity (i.e., a \"pseudoresponse\") and in the apparent coefficient diffusion (ADC). This study aimed to estimate the influence of corticosteroids on these measurements in treatment naïve glioblastoma before surgery.</p><p><strong>Methods: </strong>57 pairs of MRI scans from 54 patients with pre-surgical treatment-naïve glioblastoma were retrospectively grouped as increased (n=29, all corticosteroid-free at baseline), stable (n=25), or decreased (n=3) corticosteroid dose between scans (median interval: 15 days). Tumor size and ADC changes between timepoints were compared between lesions with increased and stable corticosteroids. Volumetric changes ascribable to increased corticosteroid dose was modeled, adjusting for the time between scans.</p><p><strong>Results: </strong>Increased corticosteroid dose showed an observed volumetric shrinkage of the contrast-enhancing tumor (median: -23.7%) and reduction in estimated growth rates (median: -2.48% per day), significantly different (p<0.0001) from the control group receiving a stable dose (median: +36.0% volume; +2.08% growth rate). When adjusting for the time interval between scans, the estimated corticosteroid-induced volumetric shrinkage was 44.0% (p<0.0001, 95%C.I. 25.7-62.2%). Increased corticosteroid dose also decreased ADC in the contrast-enhancing tumor (median: 180, IQR=39-281×10-6 mm2/s, p=0.0005).</p><p><strong>Conclusion: </strong>Corticosteroid administration can induce a significant \"pseudoresponse\" in glioblastoma, with an observed reduction in contrast-enhancing tumor volume of 23.7% and a time interval adjusted reduction of 44.0% (25.7-62.2%), and an ADC drop of 180×10-6 mm2/s (14.2%). These data confirm that radiographic measurements are impacted by corticosteroids and provide benchmarks for development of adjusted response criteria accounting for corticosteroid use.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181118","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":"Unraveling the Effects of Radiotherapy on the Blood Brain Barrier: Fact or Fiction?","authors":"Rupesh Kotecha, Minesh P Mehta","doi":"10.1093/neuonc/noaf137","DOIUrl":"https://doi.org/10.1093/neuonc/noaf137","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187391","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}