Journal of Neuro-Oncology最新文献

{"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}

{"title":"Malignant transformation of lower-grade glioma: contrast enhancement, extent of resection, and the natural history under interval-censored analysis.","authors":"Baran Atli, Maximilian Wartha, Matthias Gmeiner, Martin Aichholzer, Serge Weis, Dominik Vorhauer, Helga Wagner, Tanja Hauer, Carlo Serra, Petra Böhm, Michael Sonnberger, Nico Stroh-Holly, Stefan Aspalter, Kathrin Aufschnaiter, Tobias Rossmann, Maria Gollwitzer, Jawed Ziai, Annette Leibetseder, Josef Pichler, Wolfgang Thomae, Christian Dorfer, Andreas Gruber, Harald Stefanits, Philip Rauch","doi":"10.1007/s11060-026-05803-0","DOIUrl":"10.1007/s11060-026-05803-0","url":null,"abstract":"<p><strong>Purpose: </strong>Malignant transformation (MT) is the principal driver of mortality in lower-grade glioma (LGG), yet its preoperative determinants and timing remain poorly defined. We quantified imaging elements of MT and its timing, correcting for bias in dating transformation.</p><p><strong>Methods: </strong>We evaluated contrast enhancement (CE), tumour volume and 99 radiomic features in 155 patients with WHO grade 2-3 LGG, radiologically low-grade at diagnosis with at most minimal enhancement (77 transformations; median surveillance among non-transformers 4.8 years). Because MT is ascertainable only between scans, timing was modelled as interval-censored across four complementary models, with extent of resection (EOR) time-varying.</p><p><strong>Results: </strong>CE at diagnosis was the strongest predictor of MT, exceeding tumour volume and a co-modelled 99-feature radiomic panel (Bayesian HR 22.1, 95% CrI 10.5-53.2); conditioned on transformation-free survival to six months, HR 5.65 (95% CI 2.23-14.31). No radiomic feature survived shrinkage or native interval-censoring. Initial enhancement predicted post-surgical transformation independently of grade, IDH status and EOR, even after gross-total resection (GTR), itself associated with a two-thirds lower hazard (HR 0.32, 95% CI 0.13-0.77). Interval censoring proved material: conventional dating overstated the hazard four-fold.</p><p><strong>Conclusion: </strong>CE at diagnosis predicted transformation risk and timing. It remained predictive after GTR removed the enhancing tissue, a postoperative role not previously recognised. The signal was present in each integrated tumour type and survived adjustment for grade, IDH status and EOR, may reflect intrinsic tumour biology and could refine postoperative risk estimation. GTR was the only modifiable determinant. These are the first interval-censored estimates of MT timing.</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/PMC13597587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025124","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":"Radiation-induced cranial meningiomas are associated with earlier relapse: a propensity score-matched cohort study.","authors":"Leon Schmidt, Dragan Jankovic, Santhosh Thavarajasingam, Reem Fakak, Michael Kosterhon, Alice Dauth, Marc Brockmann, Clemens Sommer, Florian Ringel, Darius Kalasauskas","doi":"10.1007/s11060-026-05809-8","DOIUrl":"10.1007/s11060-026-05809-8","url":null,"abstract":"<p><strong>Background: </strong>Intracranial meningiomas may be induced after radiation exposure, for example following radiotherapy for CNS malignancies. However, data on their clinical characteristics and risk factors for recurrence remain limited. This study aimed to evaluate clinical features and independent predictors of progression-free survival in radiation-induced meningiomas compared to sporadic tumors.</p><p><strong>Methods: </strong>All cases of radiation-induced (RI) intracranial meningiomas that underwent tumor resection at our institution between 2007 and 2023 were identified. Patients were matched to non-radiation-induced controls by propensity score using age, WHO grade, and Simpson grade as covariates (1:5 ratio). Demographics, tumor characteristics, and outcomes were compared. Survival was analyzed using Kaplan-Meier curves and Cox regression.</p><p><strong>Results: </strong>A total of 39 RI meningioma cases were matched to 195 non-exposed controls. After matching, there were no significant differences in age, WHO grade, or Simpson grade between groups, confirming adequate baseline balance. Prior cranial surgery was more frequent in the RI group (38.5% vs. 4.1%; p < 0.001), and adjuvant radiotherapy was more commonly administered (33.3% vs. 11.3%; p < 0.001). Relapse rate was significantly higher in RI tumors (28% vs. 17%; p = 0.001). In multivariate Cox regression, RI tumor status (HR 2.1; 95% CI 1.02-434; p = 0.04) and complete resection (HR 0.29; 95% CI 0.15-0.54; p < 0.001) were independent predictors of progression-free survival.</p><p><strong>Conclusion: </strong>Radiation-induced meningioma status was associated with shorter progression-free survival following propensity score matching and multivariable adjustment. Complete resection was associated with improved PFS, supporting maximal safe resection when clinically feasible. However, residual measured and unmeasured confounding cannot be excluded, and the present findings should not be interpreted as evidence of intrinsically more aggressive tumor biology.</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/PMC13597638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025117","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":"BK_Ca channel deletion modulates the DNA damage response to electron ultra-high dose rate irradiation in glioblastoma cells.","authors":"Kamila Maliszewska-Olejniczak, Michał Fryc, Agata Kustra, Katarzyna Wiktorska, Aleksandra Lenartowicz-Gasik, Wojciech Soroka, Jacek Rzadkiewicz, Monika Żochowska, Bogusz Kulawiak, Piotr Bednarczyk","doi":"10.1007/s11060-026-05804-z","DOIUrl":"10.1007/s11060-026-05804-z","url":null,"abstract":"<p><strong>Purpose: </strong>Large-conductance Ca^{2 +}-activated potassium (BK_Ca) channels have been implicated in glioblastoma progression and oxidative stress; however, their contribution to the cellular response to ionizing radiation remains poorly understood. Potassium channels represent attractive therapeutic targets because their activity can be modulated pharmacologically using selective inhibitors or genetically by gene silencing (siRNA) or gene knockout (CRISPR/Cas9). Here, we investigated whether genetic inhibition of BK_Ca modulates the DNA damage response of human glioblastoma cells following electron ultra-high dose rate (UHDR) irradiation.</p><p><strong>Methods: </strong>Human U87MG glioblastoma cells and BK_Ca-knockout cells (U87MG ΔαBK_Ca) were exposed to an electron UHDR-9 MeV beam with an average dose rate of 150 Gy/s. Clonogenic survival, reactive oxygen species levels, cell-cycle distribution, apoptosis, DNA-DSBs, DNA repair, and expression of selected genes encoding DDR pathways were analyzed.</p><p><strong>Results: </strong>BK_Ca deletion did not significantly alter clonogenic survival following UHDR irradiation. Cells lacking the BK_Ca channel exhibited elevated ROS levels, altered cell cycle distribution with G0/G1 accumulation, and enhanced apoptosis. UHDR induced lower γH2AX accumulation and reduced 53BP1 foci formation in U87MG ΔαBK_Ca cells, suggesting impaired DNA damage recognition and repair complex assembly. Gene expression analysis revealed a shift toward upregulation of DSBR pathways and downregulation of PARP-dependent SSBR mechanisms.</p><p><strong>Conclusion: </strong>In conclusion, these findings identify BK_Ca as a regulator of the early molecular response of glioblastoma cells to electron UHDR irradiation and provide a basis for further studies investigating BK_Ca-dependent radiation responses as a target for therapeutic modulation.</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/PMC13597620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025160","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":"Posterior fossa ependymoma: a comprehensive review of molecular classification, management guidelines, and clinical outcomes (Part I of ependymomas across compartments).","authors":"George W Koutsouras, Francisco Rivera, Anthony M Price, Derek S Tsang, Adam Esbenshade, Vijay Ramaswamy, Peter B Dirks, Michael C Dewan","doi":"10.1007/s11060-026-05808-9","DOIUrl":"10.1007/s11060-026-05808-9","url":null,"abstract":"<p><strong>Purpose: </strong>To review the clinical, molecular, and imaging landscape of posterior fossa (PF) ependymoma and outline current management principles guiding surgical and adjuvant treatment decisions.</p><p><strong>Methods: </strong>We performed a narrative review of the contemporary literature on molecular classification, imaging characteristics, and treatment outcomes of PF ependymoma, focusing on distinctions between posterior fossa group A (PFA) and group B (PFB) tumors.</p><p><strong>Results: </strong>PFA and PFB ependymomas are molecularly and clinically distinct. PFA tumors predominate in younger children, follow a more aggressive course, and show loss of H3K27me3, EZHIP overexpression, Moreover, in PFA tumors 1q gain and/or 6q loss defines a very high-risk group with increased recurrence and metastasis. PFB tumors arise more often in older patients, generally retain H3K27me3, harbor numerous arm-level chromosomal gains/losses, and carry more favorable outcomes. On MRI, PFA tumors more frequently show larger volume, hydrocephalus, lateral extension, skull base involvement, and lower apparent diffusion coefficient values. Gross total resection remains the most important prognostic factor and should be pursued whenever safe. Focal postoperative radiotherapy may be standard for localized disease, while chemotherapy has only a limited adjunctive role. Recurrence, especially among PFA tumors, is managed with early detection, repeat resection, and selective re-irradiation; 1q gain and 6q loss are enriched at relapse.</p><p><strong>Conclusions: </strong>PF ependymoma comprises two biologically and clinically distinct entities. Maximal safe resection and focal radiotherapy remain the backbone of treatment, but integrating molecular subgrouping, imaging biomarkers, and modern radiotherapeutic techniques into surgical and adjuvant planning offers the clearest path to improved outcomes, particularly for high-risk PFA tumors.</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/PMC13597556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025137","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":"Intracranial germ cell tumors: an underrecognized diagnostic consideration in adults with sellar/suprasellar lesions.","authors":"Shirui Wang, Yining Zhen, Yong Yao, Lian Duan, Xin Lian, Linjie Wang, Shi Chen, Hui Pan, Lin Lu, Fengying Gong, Kan Deng, Yi Zhang, Bing Xing, Hui You, Feng Feng, Xinxin Mao, Xiaoyuan Li, Huijuan Zhu","doi":"10.1007/s11060-026-05737-7","DOIUrl":"10.1007/s11060-026-05737-7","url":null,"abstract":"<p><strong>Purpose: </strong>Sellar/suprasellar intracranial germ cell tumors (iGCTs) predominantly occur in children and adolescents, while adult-onset cases are rare and poorly characterized. We aimed to characterize adult-onset iGCTs and improve their differential diagnosis.</p><p><strong>Methods: </strong>Patients with iGCTs and onset age ≥ 18 years were enrolled in a single center. Adult-onset LYH patients served as comparison. iGCT and LYH were diagnosed using predefined pathological or clinical criteria incorporating characteristic clinical presentations, laboratory findings, MRI features, and treatment response. A nomogram was developed to distinguish iGCTs from LYH and was internally validated using 1,000 bootstrap resamples.</p><p><strong>Results: </strong>Forty-eight adult patients with iGCTs were enrolled, including 36 with germinoma and 12 with nongerminomatous germ cell tumors. The median age at onset was 23.4 years (range 18.1-53.5), and 87.5% were male. Forty-six patients with LYH were included for comparison. CSF β-hCG accurately diagnosed iGCTs from LYH (AUC 0.897, 95% CI 0.821-0.973). The optimal cutoff was 2.52 U/L, yielding a sensitivity of 78.6% and a specificity of 95.5%. The nomogram incorporating sex, log-transformed serum β-hCG, hyperprolactinemia, and pituitary stalk thickening differentiated iGCTs from LYH with an AUC of 0.939 (95% CI 0.875-1.000). Among patients with documented treatment regimens, 17 (53.1%) underwent radiotherapy, and 15 (46.9%) received chemoradiotherapy. During a median follow-up of 1.7 years (range 0.2-13.5), four patients developed progression or recurrence.</p><p><strong>Conclusions: </strong>iGCT represents a rare yet possible etiology of suprasellar/sellar lesions in adults. CSF β-hCG and the proposed nomogram may aid differential diagnosis, although external validation in independent cohorts is still required.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016926","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":"Single-stage tumor resection and immediate CAD/CAM-assisted cranio-orbital reconstruction for spheno-orbital meningiomas: a standardized surgical workflow and outcome analysis.","authors":"Panagiotis Fistouris, Elisa Ventura, Ahmad Abdullah Altayyar, Ali Alanesi, Manou Overstijns, Roland Roelz, Benjamin Brokinkel, Uta Schick","doi":"10.1007/s11060-026-05811-0","DOIUrl":"10.1007/s11060-026-05811-0","url":null,"abstract":"<p><strong>Background: </strong>Spheno-orbital meningiomas (SOMs) are surgically challenging lesions characterized by tumor infiltration and hyperostosis of the sphenoid wing and orbit. Surgical treatment requires tumor resection, drilling of hyperostotic bone, orbital decompression and skull base reconstruction. Traditionally, reconstruction has been performed either free hand or as a delayed second-stage procedure, often resulting in suboptimal skull and facial symmetry. Single-stage resection with immediate CAD/CAM-assisted reconstruction offers a feasible alternative but requires meticulous preoperative planning and a standardized surgical workflow.</p><p><strong>Methods: </strong>In this retrospective study of 34 patients with SOMs, we present our institutional standardized protocol for preoperative CAD/CAM planning and single-stage tumor resection with immediate skull reconstruction technique. Clinical, functional and radiological outcomes were also assessed.</p><p><strong>Results: </strong>Exopthalmos was the predominant presenting symptom. Gross-total resection was achieved in 73.5% of cases, resulting in a reduction of exophthalmos in 85% of patients and improvement of visual acuity in approximately 70%. However, postoperative amaurosis occurred in 8.8% and transient diplopia in 55.9%. CAD/CAM implants demonstrated appropriate intraoperative fit without major implant-related complications and with preservation of orbital and facial symmetry.</p><p><strong>Conclusion: </strong>Single-stage resection with immediate CAD/CAM-assisted skull reconstruction for SOMs is feasible, safe and reproducible. The standardized workflow by combining tumor resection and patient-specific reconstruction within a single-stage procedure may offer practical advantages in the overall surgical pathway.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008719","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":"Characterizing intradural spinal metastasis in the metastatic cascade: clinical course, dissemination timing, and molecular features in 69 patients.","authors":"Yuanxuan Xia, Lansaol Yang, Anthony Davidson, Taha Khalilullah, Connor Liu, Shuodan Zhang, Eric Christenson, Nicholas Theodore, Timothy F Witham, Ali Bydon, Jon D Weingart, Chetan Bettegowda, David O Kamson, Daniel Lubelski","doi":"10.1007/s11060-026-05794-y","DOIUrl":"10.1007/s11060-026-05794-y","url":null,"abstract":"<p><strong>Introduction: </strong>Metastatic cancers to the central nervous system (CNS) usually affect the brain, but a small and clinically significant portion also affect the intradural spinal space. Here, we characterize the molecular features of metastatic intradural spinal disease and describe the metastatic chronology and timeline such cancers go through to reach this space.</p><p><strong>Methods: </strong>All patients with MRI spine findings of intramedullary or leptomeningeal lesions from 2020-2025 at a tertiary academic center were screened. Patients with primary CNS cancer or non-cancer diagnoses were excluded. Demographic information, imaging findings, dates of primary cancer and metastasis detection, and molecular data across disease sites were collected. The primary outcome of interest was overall survival (OS) after primary diagnosis.</p><p><strong>Results: </strong>69 patients met inclusion criteria out of 1401 patients screened. The most common primary pathologies were lung (33.3%) and breast (31.9%). 11.6% of patients underwent surgery for intradural disease. The distribution of intradural spine disease on initial detection was 55.1% cervical, 65.2% thoracic, and 76.8% lumbar. The mortality rate was 87.0% within a median follow-up of 42.0 (IQR 20.6-72.9) months after primary cancer diagnosis. The median time to any metastasis was 0.5 (0-6.7), to the brain was 14.9 (0.6-42.7), to the osseous spine was 19.4 (0.7-38.9), and to the intradural spine was 29.5 (14.0-52.6) months. Targetable mutations were noted in 46.4% of primary lesions and such patients trended towards improved OS (51.7 months, 31.2-105.2) compared to patients without (30.1 months, 12.6-58.9, p = 0.072). This difference was driven by patients with such biomarkers qualifying for targeted therapies, which demonstrated improved OS (56.2 vs 31.2 months, p = 0.029).</p><p><strong>Conclusion: </strong>Targetable biomarkers are present in nearly 50% of primary lesions for patients who develop spinal intradural disease, and regular molecular characterization and sequencing of this space (e.g. CSF liquid biopsy) could have a clinically meaningful impact on these patients.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990437","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":"Metabolic modulation of glioblastoma by dietary intervention: a systematic review.","authors":"Maged T Ghoche, Kenji Miki, Fanen Yuan, Megan Mantica, Sameer Agnihotri, Samuel K McBrayer, Kalil G Abdullah","doi":"10.1007/s11060-026-05779-x","DOIUrl":"10.1007/s11060-026-05779-x","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate and critically synthesize preclinical and clinical evidence on the efficacy, safety, mechanistic rationale, and interpretive limitations of ketogenic diet (KD) and methionine restriction (MR) in glioma treatment.</p><p><strong>Methods: </strong>We systematically searched PubMed and Embase from inception through August 19, 2026, for in vivo preclinical and clinical studies evaluating KD or MR in glioma Clinical studies were eligible with or without a non-diet comparator because most available studies were early-phase, single-arm feasibility investigations. We extracted intervention, comparator, concurrent oncologic treatment, metabolic, safety, feasibility, and outcome data; assessed risk of bias using design-appropriate tools; and conducted narrative and structured direction-of-effect syntheses.</p><p><strong>Results: </strong>A total of 43 eligible reports were included: 14 preclinical and 18 clinical KD reports and 9 preclinical and 2 clinical studies of MR. Preclinical effects were heterogeneous: several diet-only experiments reduced growth or prolonged survival, whereas others showed limited activity; selected combinations with radiation, antiangiogenic therapy, glutamine targeting, or immune modulation produced greater effects. Clinical evidence primarily supported feasibility and metabolic activity, not independent efficacy, because most studies were small, uncontrolled, and confounded by concurrent or prior treatment. MR showed preclinical activity, but clinical evidence remained limited to two small chemotherapy-combination trials.</p><p><strong>Conclusion: </strong>KD and MR have biologic rationale and can alter systemic or intratumoral metabolism, but current clinical data do not establish an independent survival benefit. Their effects cannot be separated reliably from surgery, radiotherapy, chemotherapy, bevacizumab, corticosteroids, and other co-interventions in most studies. Randomized trials with intention-to-treat analysis, standardized glucose-ketone index reporting, treatment and corticosteroid documentation, and longitudinal nutritional assessment are required before these diets can be recommended as effective glioma therapy.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001534","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":"Reirradiation outcomes following salvage conventionally fractionated Gamma Knife stereotactic radiotherapy (SFGK) to recurrent primary non-glial brain tumors.","authors":"Cristian Udovicich, Chia-Lin Tseng, Jay Detsky, Hanbo Chen, Deepak Dinakaran, Hany Soliman, K Liang Zeng, Mark Ruschin, Collins Yeboah, Lori Holden, Eshetu G Atenafu, Arjun Sahgal","doi":"10.1007/s11060-026-05757-3","DOIUrl":"10.1007/s11060-026-05757-3","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the efficacy and safety of salvage conventionally fractionated Gamma Knife stereotactic radiotherapy (SFGK) reirradiation for recurrent, previously irradiated primary non-glial brain tumours.</p><p><strong>Methods: </strong>Consecutive patients underwent SFGK from 2019 to 2024 for progressive, previously definitively irradiated primary intracranial tumours. The primary endpoint was local progression-free survival (LPFS). Secondary endpoints were overall survival (OS) and safety.</p><p><strong>Results: </strong>Twenty-six patients (44 tumours) were treated. There were 34 meningiomas (77%), of which 28 were WHO Grade 2. The median time from prior radiotherapy was 50.4 months (IQR 19.7-86.8). The SFGK prescription dose was 50.4 Gy in 28 fractions in 37 tumors (84%). The median cumulative prescription EQD2 was 102.7 Gy (IQR 99.6-114.6) for those with one prior radiotherapy course. The median normal brain EQD2 was 99.2 Gy (97.9-117.5) for those with one prior radiotherapy course. The median follow-up was 18.1 months (IQR 10.5-28.2). Overall LPFS at 12 and 24 months was 91.0% (95% CI 73.6-97.2%) and 75.1% (95% CI 51.0-88.6%), respectively. OS at 12 and 24 months was 96.2% (95% CI 75.7-99.4%) and 83.2% (95% CI 54.8-94.6%), respectively. For the meningioma cohort, 12- and 24-month LPFS was 90.6% (95% CI 65.7-97.7%) and 74.1% (95% CI 42.7-90.0%), respectively. Grade 3 radionecrosis occurred in two patients (6.9%), one case of Grade 3 progressive intracranial hemorrhage (3.4%), and no Grade 4 or 5 events were observed.</p><p><strong>Conclusions: </strong>SFGK re-irradiation is feasible and well tolerated, achieving durable local control in recurrent non-glial brain tumours with few serious adverse events despite high cumulative doses.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":"179 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001706","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}