Neuro-oncology最新文献

{"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}

{"title":"Clinical, molecular and radiological predictors of prognosis in newly diagnosed astrocytoma, IDH-mutant, WHO grade 4.","authors":"Aleksandra B Lasica, Zhou Lan, Julie J Miller, Albert Jiao, Ian Pan, Loai Aker, Prem Prabhakar, Julia Japo, Alyssa Russ, Catharina Westergaard, Elisa Aquilanti, Ugonma Chukwueke, L Nicolas Gonzalez Castro, J Ricardo McFaline Figueroa, Eudocia Quant Lee, Lakshmi Nayak, Rameen Beroukhim, Tracy T Batchelor, Daniel P Cahill, Vihang Nakhate, Tyler Lanman, Juan Pablo Ospina, Natalie Stec, Ruchit V Patel, David M Meredith, Wenya Linda Bi, David A Reardon, Keith L Ligon, Raymond Y Huang, Patrick Y Wen, Gilbert Youssef","doi":"10.1093/neuonc/noaf133","DOIUrl":"https://doi.org/10.1093/neuonc/noaf133","url":null,"abstract":"<p><strong>Background: </strong>Astrocytoma, isocitrate dehydrogenase-mutant, WHO grade 4 (Astro4), is a new tumor type in the 2021 WHO classification of central nervous system tumors that has been poorly characterized in the literature. This study evaluates predictors of prognosis in a large cohort of newly diagnosed Astro4.</p><p><strong>Methods: </strong>We retrospectively identified 128 consecutive adult patients who presented with an initial diagnosis of Astro4 at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2010 and 2021. Clinical, molecular, and radiological characteristics were recorded, and their associations with overall survival (OS) and progression-free survival (PFS) were measured by log-rank test and Cox proportional hazards model.</p><p><strong>Results: </strong>The median age at diagnosis was 37.1 years, and 61.7% were men. The median OS was 5.9 years (95% confidence interval, 4.4 - 7.3), while the median PFS was 2.7 years (1.8 - 3.6). Age ≥50 and homozygous CDKN2A/B deletion were independent negative prognosticators of OS on univariate and multivariate analyses [hazard ratio (HR), 2.21 (1.16 - 4.21), p=0.019; HR, 2.61 (1.27 - 5.38), p=0.013]. Maximal resection of enhancing disease was associated with longer PFS on univariate and multivariate analyses [HR, 0.48 (0.26 - 0.87), p=0.019]. There were no significant differences in OS or PFS based on MGMT promoter methylation status, T2/FLAIR extent of resection, T2/FLAIR mismatch, radiological pseudoprogression, or enhancement on the pre-operative scan.</p><p><strong>Conclusions: </strong>Our study comprehensively characterizes a large cohort of newly diagnosed patients with Astro4, emphasizing the prognostic value of CDKN2A/B deletion, age, and the extent of resection of enhancing disease in these patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181635","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":"Glioblastoma-enriched glycosphingolipids modulate the function of human iNKT cells.","authors":"Morgan J Coombs, Tyrone Dowdy, Md Masud Alam, Helena Muley Vilamú, Seketoulie Keretsu, Guzal Khayrullina, Orieta Celiku, Alexander Y Mitrophanov, Vibhuti Joshi, Jinkyu Jung, Ayaka Hara, Emily E Steffke, Laila Latifi, Hye Kim, Jo Spurgeon, Nargis Malik, John C Hancock, Byram H Ozer, Mark R Gilbert, Jenny Gumperz, Mioara Larion, Masaki Terabe","doi":"10.1093/neuonc/noaf135","DOIUrl":"https://doi.org/10.1093/neuonc/noaf135","url":null,"abstract":"<p><strong>Background: </strong>To develop effective therapies for glioblastoma (GBM), a deeper understanding of its underlying immunoregulatory mechanisms is needed. Invariant natural killer T (iNKT) cells are unconventional T cells that recognize lipid antigens and are known to regulate tumor immunity in other cancer types. Given the lipid-rich nature of the brain and the unique metabolic activity of GBM cells, we hypothesized that GBM-enriched lipids could direct iNKT cells to contribute to the immunosuppressive nature of the disease.</p><p><strong>Methods: </strong>Lipid levels of multiple human GBM stem-like cell (GSC) lines, low grade-glioma lines, and normal human astrocytes were determined using LC/MS. GSC-enriched lipids were tested in iNKT stimulation assays, with either human iNKT cell lines or PBMC samples from both healthy donors and GBM patients, to determine antigenicity and characterize the nature of iNKT activation.</p><p><strong>Results: </strong>Multiple lipid species were found to be uniquely enriched in GSCs. Many of these lipids, called sulfatides, were recognized by and activated iNKT cells in a dose-dependent manner when presented by CD1d. Pharmaceutical and genetic targeting of the sulfatide synthetic pathway within GSCs resulted in an altered ability to activate iNKT cells. However, one lipid, lyso-sulfatide, inhibited the activation of iNKT cells and suppressed activation induced by a cognate antigen, α-galactosylceramide.</p><p><strong>Conclusions: </strong>The modulation of iNKT cell functions by GSC-enriched glycosphingolipids may contribute to the immunosuppression of GBM and highlights sulfatide production as a potential therapeutic target for GBM treatment.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174250","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":"Expanding the Immunotherapeutic Toolbox in Glioblastoma: A Safe and Feasible Strategy at the Point of Surgery.","authors":"Ghazaleh Tabatabai","doi":"10.1093/neuonc/noaf124","DOIUrl":"https://doi.org/10.1093/neuonc/noaf124","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160472","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 Clinically Annotated Transcriptomic Atlas of Nervous System Tumors.","authors":"Chi H Le, Ajai K Nelson, Adam J Berrones, Janki R Naidugari, Robert P Naftel, Eyas M Hattab, Brian J Williams, Akshitkumar M Mistry","doi":"10.1093/neuonc/noaf130","DOIUrl":"https://doi.org/10.1093/neuonc/noaf130","url":null,"abstract":"<p><strong>Background: </strong>While DNA methylation signatures are distinct across nervous system neoplasms, it has not been comprehensively demonstrated whether transcriptomic signatures exhibit similar uniqueness. Additionally, no large-scale dataset for comparative gene expression analyses exists. This study addresses these knowledge and resource gaps.</p><p><strong>Methods: </strong>We compiled and harmonized raw transcriptomic and clinical data for neoplastic (n=5,402) and non-neoplastic (n=1,973) nervous system samples from publicly available sources, all profiled on the same microarray platform. After adjusting for surrogate variable effects ('batch effects'), machine learning methods were used to visualize, cluster, and reclassify samples with uncertain diagnoses (n=2,225).</p><p><strong>Results: </strong>We generated the largest clinically annotated transcriptomic atlas of nervous system tumors to date. Sample clustering was primarily driven by diagnosis. We show the utility of the atlas by refining the transcriptional subtypes of pheochromocytoma and paraganglioma (PH/PG), revealing six robust subtypes (Neuronal, Vascular, Metabolic, Steroidal, Developmental, Indeterminate), which were independently validated using TCGA RNA-seq data and that correlated with specific mutational signatures and clinical behaviors of these tumors.</p><p><strong>Conclusions: </strong>Like bulk DNA methylation, we demonstrate that bulk transcriptomic signatures are distinct across the diagnostic spectrum of nervous system neoplasms. Our atlas' broad coverage of diagnoses, including rarely studied entities, spans all ages and includes individuals from diverse geographical regions, enhancing its utility for comprehensive and robust comparative gene expression analyses, as exemplified by our PH/PG analyses. For access visit http://kdph.shinyapps.io/atlas/ or https://github.com/axitamm/BrainTumorAtlas.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151239","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":"Polyamine acetylation mediates crosstalk between cancer cells and myeloid cells to promote mesenchymal/plurimetabolic states in glioblastoma.","authors":"Ayush B Rana, Timothy M Horton, Vijay S Thakur, Dazhi Wang, Varsha Thakur, Molly Dalzell, Juliano T Freitas, Durga Prasad Gannamedi, Ifeanyichukwu Ogobuiro, Barbara Bedogni, Sakir H Gultekin, Timothy J Garrett, Alejandro V Villarino, Jun Lu, David B Lombard, Ashish H Shah, Scott M Welford","doi":"10.1093/neuonc/noaf128","DOIUrl":"https://doi.org/10.1093/neuonc/noaf128","url":null,"abstract":"<p><strong>Background: </strong>Metabolic reprogramming in glioblastoma (GBM) is a putative determinant of GBM subtype, malignant cell state and tumor-immune crosstalk. In the present study, we investigated how polyamine metabolic rewiring contributes to the malignant cell-intrinsic and microenvironment-dependent biological processes underpinning GBM subtype classification.</p><p><strong>Methods: </strong>Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was used for polyamine quantification in human and murine GBM tumors and cell lines. Through single-cell RNA sequencing, metabolic profiling and additional functional experiments, we dissect the malignant cell-intrinsic and paracrine signaling processes regulated by SAT1 (spermidine/spermine-N1-acetyltransferase1) and its product, N1-acetylspermidine.</p><p><strong>Results: </strong>We find that polyamine acetylation is elevated in human and murine GBM tumors and contributes to the classification of mesenchymal/plurimetabolic GBM through both regulation of tumor-cell intrinsic glucose metabolism and by facilitating metabolic crosstalk with tumor-associated macrophages/myeloid cells (TAMs). The impact of SAT1 on tumor cell metabolism is mediated, at least in part, by N1-acetylspermdine, the sole polyamine elevated in human and murine tumors. Furthermore, the relatively high levels of N1-acetylspermidine released by GBM is taken up by myeloid cells to promote intracellular polyamine flux, cellular respiration and migration. In vivo, both genetic disruption of polyamine acetylation and pharmacological inhibition of polyamine transport reduced myeloid cell infiltration and sensitized tumors to chemoradiation.</p><p><strong>Conclusions: </strong>Collectively, the findings highlight a previously unidentified role for SAT1 and its product, N1-acetylspermidine, in bridging the metabolic activity of tumor cells and tumor-associated macrophages/myeloid cells (TAMs), together promoting mesenchymal/plurimetabolic states and therapeutic resistance in GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160500","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":"Postoperative radiotherapy in subtotally-resected recurrent WHO grade 1 meningiomas with intermediate-/high-risk molecular profiles.","authors":"Maximilian Y Deng, Sybren L N Maas, Günes Anil, Philipp Sievers, Jonathan Lischalk, Eric Zhao, Sophie Rauh, Inga Jessen, Tanja Eichkorn, Sebastian Regnery, Lukas Bauer, Thomas Held, Philipp Hoegen-Sassmannshausen, Katharina Seidensaal, Juliane Hörner-Rieber, Stefan M Pfister, Antje Wick, Wolfgang Wick, Andreas von Deimling, Klaus Herfarth, Christine Jungk, Sandro M Krieg, Jürgen Debus, Felix Sahm, Laila König","doi":"10.1093/neuonc/noaf125","DOIUrl":"https://doi.org/10.1093/neuonc/noaf125","url":null,"abstract":"<p><strong>Background: </strong>Meningiomas represent the most common primary intracranial tumors in adults, with WHO grade 1 typically associated with favorable outcomes following gross total resection (GTR).</p><p><strong>Methods: </strong>This retrospective study included patients with CNS WHO grade 1 meningioma and available DNA methylation profiles (n=210). Clinical tumor characteristics and treatment course (e.g., surgical resection, extent of resection, radiotherapy) were evaluated. Integrated Scores (InS) were calculated based on methylation family using the DKFZ brain tumor classifier, CNS WHO grading, and chromosomal losses, categorized as low, intermediate, or high. Survival analyses employed Kaplan-Meier and Cox regression methods, with local progression-free survival defined as primary endpoint.</p><p><strong>Results: </strong>In newly diagnosed cases, GTR was associated with a 93.0% 3-year progression-free survival (PFS), compared to 69.3% following subtotal resection (STR). Stratification by IntS showed that patients in the IntS-low group had superior outcomes: 3-y PFS of 93.4 after GTR and 77.4% after STR. In contrast, patients with IntS-intermediate/high profiles showed significantly worse outcomes, with PFS of 85.9% after GTR and 40.0% after STR. Following tumor recurrence, particularly those with IntS-intermediate/high, postoperative radiotherapy (RT) after STR may improve 3-year PFS to 88.9%, compared to much lower PFS rates in newly diagnosed cases managed without adjuvant RT after STR (3-year PFS: 40.0%).</p><p><strong>Conclusion: </strong>Our findings highlight the combined impact of both the extent of resection (EoR) and molecular risk profile on prognosis in newly diagnosed cases. While conservative management is feasible in lower-risk primary cases, recurrent or higher-risk patients may benefit from early postoperative RT.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160504","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":"Deciphering neuron-tumor networks with rabies virus-based retrograde tracing.","authors":"Ekin Reyhan, Svenja K Tetzlaff, Varun Venkataramani","doi":"10.1093/neuonc/noaf066","DOIUrl":"https://doi.org/10.1093/neuonc/noaf066","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151242","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}