Journal of Neuro-Oncology最新文献

{"title":"[¹⁸F]FET uptake in diffuse lower-grade IDH-mutant glioma correlates with glioma-related epilepsy.","authors":"Zeynep Özdemir, Wolfgang Roll, Walter Stummer, Stjepana Kovac, Michael Müther","doi":"10.1007/s11060-026-05815-w","DOIUrl":"https://doi.org/10.1007/s11060-026-05815-w","url":null,"abstract":"<p><strong>Purpose: </strong>Diffuse lower-grade glioma (DLGG), i.e. WHO grade 2 and 3 tumors, frequently manifests with epileptic seizures, significantly affecting quality of life. While [¹⁸F]FET PET is routinely used to assess glioma metabolism, differences between patients with and without glioma-related epilepsy have not yet been assessed systematically. The objective of this study was to assess whether preoperative [¹⁸F]FET PET uptake is associated with epileptic seizures at initial presentation in patients with DLGG.</p><p><strong>Methods: </strong>This retrospective study included 121 patients with DLGG with preoperative [¹⁸F]FET PET (2015-2025). [¹⁸F]FET uptake parameters were determined in patients with measurable disease according to PET RANO 1.0 criteria. Seizure status was assessed exclusively for seizures occurring before surgery. Statistical analyses included Fisher's exact test, Mann-Whitney U test, and multivariable logistic regression.</p><p><strong>Results: </strong>Seventy-eight patients (64%) demonstrated measurable disease in [¹⁸F]FET, of whom 57 (73%) presented with epileptic seizures compared to 17 (40%) in the no-uptake group (p < 0.001). In the measurable disease group, those with seizures exhibited significantly higher median TBR_max (3.02; IQR 2.35-4.00) and TBR_mean (2.2; IQR 1.8-2.5) values than those without seizures (TBR_max 2.4; IQR 2.00-3.16, TBR_mean 1.9; IQR 1.7-2.2). The tumor location did not account for the observed association between [¹⁸F]FET uptake and seizures (p > 0.05). In multivariable analyses, [¹⁸F]FET uptake remained independently associated with preoperative seizures (adjusted OR 2.86, 95% CI 1.18-7.07; p = 0.020).</p><p><strong>Conclusion: </strong>These findings demonstrate an association between [¹⁸F]FET uptake and glioma-related epilepsy in DLGG. Further research on amino acid transporter expression and glutamatergic pathways may elucidate underlying mechanisms.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"180 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel minimally invasive diagnostic approach of various brain malignancies based on differential miRNA expression.","authors":"Dmitry Yu Gvaldin, Natalia A Petrusenko, Ekaterina P Omelchuk, Natalya N Timoshkina, Moez Eid, Dema Alset, Eduard E Rostorguev, Sergey E Kavitskiy, Oleg I Kit","doi":"10.1007/s11060-026-05810-1","DOIUrl":"10.1007/s11060-026-05810-1","url":null,"abstract":"<p><strong>Background: </strong>Brain tumors are typically diagnosed after symptoms appear and requires definitive analysis of biopsy which takes a long time. Therefore, it is important to find markers for early diagnosis of different brain tumors. We aimed to validate and construct miRNA-based diagnostic panel for minimally-invasive differential diagnosis of brain tumors using plasma samples.</p><p><strong>Methods: </strong>Circulating miRNAs were isolated from 67patients with glioblastoma, 33 with astrocytoma; 6 with oligodendroglioma; 33 with meningioma; 14 with lung cancer brain metastases and 25 with breast cancer brain metastases. Targeted and references miRNAs genetic expression was studied with RT-qPCR. Bioinformatics tools were used to develop diagnostic models and then functional enrichment for target genes and signalling pathways was conducted using KEGG, Reactome and WikiPathways databases.</p><p><strong>Results: </strong>Based on genetic expression of 10-miRNAs, validated models for differential diagnosis of each studied brain tumor were constructed. It was found that CASP3, EIF2S2, FYN, GNAQ, ITPR1, KPNB1, KREMEN1, MTOR, SREBF1, TYMS, VPS4B, and WASL were the most significant target genes of these miRNAs.</p><p><strong>Conclusion: </strong>This study is among the first to include the three types of malignant brain tumors in addition to the benign brain tumor and also two types of secondary brain tumors. Results could be used as a minimally-invasive approach for early detection and monitoring recurrence of primary and metastatic brain lesions.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A patient-derived organoid platform for predominantly posterior fossa adult ependymoma: histopathologic preservation, culture-associated transcriptomic remodeling, and in vivo tumorigenicity.","authors":"Rong Zhang, Shenglan Li, Yingfan Sun, Sihan Ma, Can Wang, Zhuang Kang, Xue Yang, Botao Zhang, Ning Xu, Anchen Guo, Zhen Wu, Feng Chen, Wenbin Li","doi":"10.1007/s11060-026-05814-x","DOIUrl":"10.1007/s11060-026-05814-x","url":null,"abstract":"<p><strong>Purpose: </strong>Well-characterized patient-derived models of adult ependymoma (EPN) remain limited. We established a patient-derived organoid (PDO) platform from adult EPN and evaluated its histopathologic and immunophenotypic characteristics, transcriptomic relationship to parental tumors, and in vivo tumorigenicity.</p><p><strong>Methods: </strong>Fresh surgical specimens from 22 adult patients with EPN were processed for PDO establishment. Tumor-PDO fidelity was assessed by histology and immunofluorescence. Three matched tumor-PDO pairs underwent RNA sequencing followed by paired differential-expression, gene-set enrichment, microenvironmental signature, and ESTIMATE analyses. Selected PDO models were further evaluated by subcutaneous and intracranial xenografting.</p><p><strong>Results: </strong>PDOs were successfully established from 20 of 22 specimens (90.9%). Established PDOs broadly retained parental tumor morphology and expression of major ependymoma-associated and neural/progenitor markers. Selected morphologic and immunophenotypic features remained detectable during prolonged culture. Transcriptomic profiling of three matched tumor-PDO pairs demonstrated high global expression similarity (Pearson r = 0.84-0.88) together with substantial culture-associated remodeling. Endothelial signatures and ESTIMATE-derived stromal scores were reduced in all three PDOs, whereas other immune and stromal signatures showed patient-specific changes. Paired transcriptomic analysis further identified enrichment of ribosome/translation and oxidative-phosphorylation programs in PDOs, accompanied by reduced cilia- and axoneme-associated programs. Selected PDO-derived models demonstrated tumorigenic capacity in subcutaneous and intracranial settings.</p><p><strong>Conclusion: </strong>Adult EPN can be propagated efficiently as PDOs that retain selected tumor-associated features while undergoing measurable transcriptional and microenvironment-associated adaptation to ex vivo culture. Selected models also retained tumorigenic capacity in vivo. These models provide a complementary experimental platform for studying adult EPN biology.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning and computational approaches to model therapeutic response and resistance in diffuse midline glioma.","authors":"Océane A Dubois, Olive E L Loughnan, Yuanhao Jiang, Bella Petraello, Alicia M Douglas, Tabitha McLachlan, Izac J Findlay, Tuan Vo, Clara Savary, Matthew D Dun","doi":"10.1007/s11060-026-05817-8","DOIUrl":"10.1007/s11060-026-05817-8","url":null,"abstract":"<p><strong>Purpose: </strong>Diffuse midline glioma (DMG) remains one of the most lethal cancers affecting children, adolescents and young adults and is near-universally resistant to treatment. Histone H3-alterations establish a profoundly dysregulated epigenetic landscape that promotes extensive intratumoral heterogeneity and cellular plasticity, key drivers of therapeutic resistance and treatment failure. Although single-cell RNA sequencing and spatial transcriptomics have transformed the study of tumor evolution, the mechanisms underpinning treatment resistance in DMG remain poorly understood. This Review examines how computational and machine learning-based approaches can be leveraged to study tumor adaptation under therapeutic pressure.</p><p><strong>Methods: </strong>We provide an overview of computational frameworks developed for the analysis of single-cell and spatial transcriptomic datasets to model four major axes of tumor evolution: i) compositional shifts, ii) functional state remodeling, iii) tumor plasticity, and iv) intercellular communication; while highlighting how these approaches provided novel insights into DMG biology and the mechanisms underlying treatment adaptation.</p><p><strong>Results: </strong>Computational and machine learning-based frameworks provide powerful tools for modeling the spatiotemporal dynamics of tumor evolution in high-dimensional transcriptomic data. Across the four dimensions examined, these approaches identify resistant cellular populations, characterize adaptive transcriptional programs, reconstitute cell-state transitions, and map tumor-microenvironment interactions, revealing mechanisms of therapeutic resistance and treatment adaptation.</p><p><strong>Conclusion: </strong>Computational approaches developed to model tumor evolution under therapeutic pressure using single-cell and spatial transcriptomic data are rapidly advancing. As increasingly large and multimodal DMG datasets become available, the application of these approaches may help uncover resistance mechanisms, therapeutic vulnerabilities, and biomarkers that inform more precise and patient-specific treatment strategies.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter pathlength maps from diffusion-weighted MRI tractography for radiotherapy target planning in glioblastoma.","authors":"Michael Wahl, Christopher H Chapman, Olivier Morin, Kesshi Jordan, Roland G Henry, Susan M Chang, Javier E Villanueva-Meyer, Pratik Mukherjee, Philip Theodosopoulos, Michael W McDermott, Mitchel S Berger, Penny Sneed, Steve E Braunstein, Janine M Lupo","doi":"10.1007/s11060-026-05789-9","DOIUrl":"10.1007/s11060-026-05789-9","url":null,"abstract":"<p><strong>Purpose: </strong>Conventional radiotherapy target delineation for glioblastoma (GBM) includes an isotropic expansion from gross tumor visible on anatomic MRI to an empirically defined clinical target volume (CTV) for coverage of microscopic infiltrative disease. GBM spreads preferentially along white matter tracts, but this information has not previously been systematically incorporated into radiotherapy planning. We investigated using white matter tractography from diffusion-weighted MRI (dwMRI) to inform target delineation.</p><p><strong>Methods: </strong>Thirteen patients with GBM underwent 55-directional dwMRI at the time of post-operative radiation planning MRI. Whole-brain tractography was performed, and streamlines passing within 5 mm of gross disease were used to generate maps representing white matter path length from gross disease. Clinical target volumes were generated using tractography (CTV_tract) and conventional isotropic expansion (CTV_isotropic). MRI at time of GBM recurrence was registered to the radiation planning MRI, and coverage of the recurrence volume was compared between CTV_tract and CTV_isotropic.</p><p><strong>Results: </strong>CTV_tract demonstrated non-isotropic expansion of the primary tumor along regional white matter tracts while respecting natural anatomic boundaries. CTV_tract volumes using a 2 cm path-length were a median of 67 cc smaller (-19%) than the paired 2 cm CTV_isotropic volumes (p = 0.003). 10/13 recurrence volumes were included in CTV_isotropic, while 12/13 recurrence volumes were included in CTV_tract.</p><p><strong>Conclusion: </strong>Tractography can be used to define CTV that may provide superior coverage of areas at risk of recurrence while simultaneously reducing target volume.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic impact of blood group O in MGMT-methylated glioblastoma patients receiving radiochemotherapy with temozolomide and lomustine.","authors":"Julia Scheuble, Thomas Zeyen, Matthias Schneider, Anna-Laura Potthoff, Niklas Schäfer, Lea Lex, Lea L Friker, Alexander Radbruch, Julian P Layer, Eleni Gkika, Hartmut Vatter, Ulrich Herrlinger, Johannes Weller","doi":"10.1007/s11060-026-05813-y","DOIUrl":"10.1007/s11060-026-05813-y","url":null,"abstract":"<p><strong>Purpose: </strong>Blood group O has recently been associated with improved survival in patients with MGMT-methylated glioblastoma. However, whether this association persists in patients treated with intensified first-line radiochemotherapy according to the CeTeG/NOA-09 regimen remains unclear. We aimed to validate the prognostic impact of ABO blood group in an independent cohort of patients with MGMT-methylated, IDH-wildtype glioblastoma uniformly treated with CCNU/temozolomide (CCNU/TMZ).</p><p><strong>Methods: </strong>We performed a retrospective single-center cohort study including adult patients with newly diagnosed MGMT-methylated, IDH-wildtype glioblastoma treated according to the CeTeG/NOA-09 protocol between 2008 and 2023. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier estimates, log-rank tests, and multivariable Cox proportional hazards models adjusted for age, extent of resection, and Karnofsky Performance Status.</p><p><strong>Results: </strong>Sixty-one patients were included, of whom 24 (39.3%) had blood group O and 37 (60.7%) had non-O blood groups. Blood group O was associated with longer OS (median 42.1 vs. 23.7 months; log-rank p = 0.04) and a trend toward longer PFS (median 21.8 vs. 17.5 months; log-rank p = 0.10). After multivariable adjustment, non-O blood groups remained independently associated with shorter PFS (HR 1.86, 95% CI 1.04-3.34; p = 0.037) and OS (HR 2.29, 95% CI 1.16-4.52; p = 0.017).</p><p><strong>Conclusion: </strong>Blood group O remained associated with improved progression-free and overall survival in patients with MGMT-methylated, IDH-wildtype glioblastoma treated according to the CeTeG/NOA-09 regimen. These findings support an association between blood group O and improved survival outcomes and warrant further investigation of its biological and clinical relevance in glioblastoma.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-operative day one discharge following craniotomy for tumour resection.","authors":"Krishmila Yogeswaran, Frederick Ewbank, Rebecca Khoo, Daniel O'flaherty, Md Islam, Antony Kaldas, Arif Zafar, Andrew Durnford, Paul Grundy, Joy Roach","doi":"10.1007/s11060-026-05790-2","DOIUrl":"10.1007/s11060-026-05790-2","url":null,"abstract":"<p><strong>Purpose: </strong>Post-operative admission following craniotomy for tumour resection (CTR) remains standard practice. To improve efficiency, optimise patient flow, and reduce length of stay (LOS), a post-operative day one (POD1) discharge pathway was implemented. This study evaluated the feasibility of POD1 discharge and identified factors associated with delayed discharge and 30-day unplanned readmission.</p><p><strong>Methods: </strong>A retrospective analysis of 263 consecutive patients undergoing CTR between November 2022 and December 2023 was performed. Baseline demographic, clinical, tumour-related, operative, and post-operative variables were collected. The primary outcome was POD1 discharge. Secondary outcomes included 30-day unplanned readmission and factors associated with discharge and readmission. Univariable logistic regression and Fisher's exact test were used.</p><p><strong>Results: </strong>POD1 discharge was achieved in 146 patients (55.5%). The overall 30-day unplanned readmission rate was 8.0%, including 7.5% among patients discharged on POD1. Mean cumulative 30-day hospital days were 1.0 days among patients discharged on POD1 compared with 7.0 days among patients requiring prolonged admission. POD1 discharge was not associated with increased odds of readmission (OR 0.87, 95% CI 0.35-2.17, p = 0.760). Diabetes mellitus (OR 0.41, 95% CI 0.17-0.96, p = 0.044), post-operative adverse events (OR 0.18, 95% CI 0.06-0.47, p = 0.001), and post-operative neurological deficits (OR 0.05, 95% CI 0.01-0.17, p < 0.001) were associated with reduced odds of POD1 discharge. Eloquent tumour location was associated with increased odds of readmission (OR 3.35, 95% CI 1.36-8.78, p = 0.010).</p><p><strong>Conclusion: </strong>POD1 discharge following CTR was feasible in more than half of patients and was not associated with increased 30-day readmission. These findings support structured POD1 discharge pathways in appropriately selected patients.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplementary motor area syndrome in intracranial gliomas is not associated with worse survival.","authors":"Dragan Jankovic, Sophie Rosenke, Jens Blobner, Andrea Szelényi, Veit Stöcklein, Santhosh G Thavarajasingam, Andreas Kramer, Philipp Karschnia, Nico Teske, Florian Ringel, Darius Kalasauskas","doi":"10.1007/s11060-026-05805-y","DOIUrl":"10.1007/s11060-026-05805-y","url":null,"abstract":"<p><strong>Purpose: </strong>Resection of gliomas involving the supplementary motor area (SMA) carries a substantial risk of postoperative functional deficits, which may affect patients' ability to undergo adjuvant therapy. This study evaluated whether postoperative SMA syndrome is associated with delayed initiation of adjuvant therapy and with progression-free survival (PFS) and overall survival (OS).</p><p><strong>Methods: </strong>We performed a retrospective single-center study of patients undergoing resection of gliomas involving, adjacent to, or approached through the SMA between 2015 and 2024. SMA syndrome was defined as new-onset motor deficits and/or language impairment without corresponding intraoperative neuromonitoring changes and without involvement of the primary motor cortex or corticospinal tract. Logistic and Cox regression analyses were performed.</p><p><strong>Results: </strong>Seventy-four patients were included, of whom 37 (50%) developed postoperative SMA syndrome. In univariate logistic regression, RANO class 2 A and class 2B resections were associated with higher odds of postoperative SMA syndrome compared with RANO class 1 resections (p = 0.048 and p = 0.035, respectively). In the pairwise multivariable model, grouped RANO class 2 resections remained associated with higher odds of postoperative SMA syndrome compared with class 1 resections (OR 5.05, 95% CI 1.24-20.57; p = 0.024). Postoperative SMA syndrome was not associated with delayed initiation of adjuvant therapy (HR 0.86, 95% CI 0.49-1.53; p = 0.617), PFS (HR 1.21, 95% CI 0.63-2.32; p = 0.573), or OS (HR 1.21, 95% CI 0.49-2.95; p = 0.681). Postoperative functional decline (≥ 20-point KPS decrease) was independently associated with receipt of modified or reduced-intensity adjuvant therapy (adjusted OR 13.91, 95% CI 2.21-87.64; p = 0.005), whereas SMA syndrome itself was not associated with treatment modification.</p><p><strong>Conclusions: </strong>Postoperative SMA syndrome was not associated with delayed adjuvant therapy or worse survival. Functional status, rather than SMA syndrome, influenced treatment intensity, supporting maximal safe resection in the SMA region.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"nTMS-determined cortical excitability is associated with overall survival in patients with motor-eloquent glioblastoma.","authors":"José Pedro Lavrador, Ana Mirallave-Pescador, Sabina Patel, Qusai Al-Banna, Feras Fayez, Vindhya Prasad, Asfand Baig Mirza, Filippo Andrea Sinosi, Sankhya Prakashvel, Kapil Rajwani, Nida Kalyal, Yasir A Chowdhury, Francesco Marchi, Ali Elhag, Laura Ferrari, Alba Diaz Baamonde, Jose Sadio Mosquera, Keyoumars Ashkan, Ranjeev Bhangoo, Francesco Vergani","doi":"10.1007/s11060-026-05806-x","DOIUrl":"10.1007/s11060-026-05806-x","url":null,"abstract":"<p><strong>Background: </strong>Preoperative prognostication in glioblastoma remains challenging despite advances in histomolecular classification. Navigated transcranial magnetic stimulation (nTMS) enables non-invasive assessment of cortical excitability, but its role as a survival biomarker remains unclear.</p><p><strong>Objective: </strong>To determine whether preoperative nTMS-derived cortical excitability metrics independently predict overall survival (OS) in patients with WHO grade 4 IDH-wildtype glioblastoma.</p><p><strong>Methods: </strong>This single-centre retrospective cohort study included patients undergoing resection for motor-eloquent WHO grade 4 IDH-wildtype glioblastoma between 2018 and 2024. Preoperative nTMS mapping was used to derive the IntraM1 Excitability Score (IMES) and Cortical Excitability Score (CES). Cox regression adjusted for age, sex, neurological deficit, MGMT methylation, and extent of resection.</p><p><strong>Results: </strong>Seventy-seven patients were included (mean age 55.4 ± 16.0 years; 41 males; mean OS 20.5 months). Lower IMES and higher CES were associated with worse OS on univariate analysis and remained independently prognostic on multivariate analysis: IMES (HR 0.16, p = 0.003) and CES (HR 2.63, p = 0.034). Bilateral nTMS improved 12-month survival prediction over unilateral mapping.</p><p><strong>Conclusions: </strong>Preoperative nTMS-derived cortical excitability metrics independently predict OS after adjustment for established prognostic factors, supporting excitability profiling as a clinically actionable prognostic tool in glioblastoma.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-derived tissue cultures complement neurospheres for preclinical evaluation of AAV-mediated gene delivery in glioblastoma.","authors":"Franziska Köhler, Katharina Hess, Cindy Koloske, Frank Gaunitz, Steffen K Rosahl, Rüdiger Gerlach, Sonja Kallendrusch","doi":"10.1007/s11060-026-05807-w","DOIUrl":"10.1007/s11060-026-05807-w","url":null,"abstract":"<p><p>Glioblastoma (GBM) is characterized by extensive intratumoral heterogeneity and a complex tumor microenvironment that complicate the preclinical evaluation of gene therapy vectors. We investigated how culture model, epidermal growth factor (EGF) supplementation, and adeno-associated virus (AAV) serotype influence vector-mediated gene delivery in patient-derived GBM models. Patient-derived neurospheres (PDNS) and patient-derived tissue slice cultures (PDTC) were transduced with AAV2 or AAV6 vectors encoding green fluorescent protein (GFP). Transduction was evaluated by live confocal imaging, quantitative PCR, flow cytometry, and immunofluorescence under EGF-containing and EGF-free culture conditions. In PDNS, AAV6 produced significantly greater GFP expression than AAV2 and demonstrated a dose-dependent increase in transduction at both 2 and 5 days after vector exposure. EGF supplementation altered transduction patterns and was associated with changes in PDNS growth and marker-defined stem-like cell populations. In contrast, PDTC preserved tissue architecture and stromal, vascular, and immune-associated compartments while revealing substantial interpatient variability in AAV-mediated transduction. AAV-mediated gene delivery in GBM is influenced by culture model, growth factor conditions, and capsid serotype. Patient-derived tissue slice cultures complement neurosphere models by preserving features of the native tumor microenvironment and may improve the preclinical evaluation of gene therapy vectors for GBM.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}