Chongshun Zhao, Bo Liang, Xiaopeng Li, Peiheng Ma, Yiming Li, Zenghui Qian, Zhong Zhang, Tao Jiang, Wei Zhang
{"title":"Anatomical distribution and prognostic heterogeneity in glioma: unique clinical features of occipital glioblastoma.","authors":"Chongshun Zhao, Bo Liang, Xiaopeng Li, Peiheng Ma, Yiming Li, Zenghui Qian, Zhong Zhang, Tao Jiang, Wei Zhang","doi":"10.1007/s11060-025-05144-4","DOIUrl":"10.1007/s11060-025-05144-4","url":null,"abstract":"<p><strong>Background: </strong>Adult-type diffuse gliomas, particularly IDH-wildtype glioblastoma, exhibit significant differences in incidence across brain regions, with the occipital lobe being the rarest location. However, whether occipital glioblastoma differs from tumour in other regions in terms of prognosis and biological characteristics remains poorly understood.</p><p><strong>Methods: </strong>This study included a total of 7,583 adult-type diffuse glioma patients from the SEER database, two public glioma datasets (UCSF-PDGM and UPENN-GBM), and a private dataset (Beijing Tiantan Hospital). For imaging data, Tumour location was classified using the USCLobes atlas, and white matter Tract Density Index (TDI) was computed to assess structural infiltration. Survival analyses employed Cox models and propensity score matching (PSM), adjusting for age, resection extent, and other confounders.</p><p><strong>Results: </strong>The occipital lobe was the least common location for adult-type diffuse glioma (p < 0.001). Multivariable analysis adjusting for extent of resection and other confounders demonstrated that occipital tumours retained a significant survival advantage (adjusted HR = 0.82, 95% CI: 0.69-0.97, p = 0.019), corroborated in PSM cohorts (median OS 14 vs. 13 months, p = 0.012) and validated across independent datasets (HR = 0.73, 95% CI: 0.55-0.97, p = 0.027). Occipital glioblastoma exhibited lower TDI (p < 0.001).</p><p><strong>Conclusion: </strong>Occipital glioblastoma represents a distinct clinical entity associated with improved survival outcomes. This survival advantage may be attributed to reduced white matter tract infiltration. Future research should focus on the differences in biological characteristics and treatment strategies of gliomas at different locations.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"525-537"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540561","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}
Jose Torres, Bethany E Bundrant, Antonio Dono, Pavel S Pichardo-Rojas, Sigmund Hsu, Mark Amsbaugh, Jay-Jiguang Zhu, Angel I Blanco, Roy F Riascos, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi
{"title":"Cystic glioblastoma IDH-wildtype: genetic alterations and outcomes.","authors":"Jose Torres, Bethany E Bundrant, Antonio Dono, Pavel S Pichardo-Rojas, Sigmund Hsu, Mark Amsbaugh, Jay-Jiguang Zhu, Angel I Blanco, Roy F Riascos, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi","doi":"10.1007/s11060-025-05143-5","DOIUrl":"10.1007/s11060-025-05143-5","url":null,"abstract":"<p><strong>Purpose: </strong>In the past decade, studies have reclassified infiltrating glioblastomas (GBM) IDH-wildtype utilizing molecular and phenotypic features. Cystic GBMs are one such phenotypic subtype whose genetic and clinical characteristics remain incompletely understood. The goal of this study was to genetically characterize cystic GBMs and examine patient outcomes as compared to non-cystic GBMs.</p><p><strong>Methods: </strong>Retrospective analysis of GBM IDH-wildtype with pre-operative and post-operative MRI and comprehensive next-generation sequencing were performed with evaluation of 205 genes. Tumors were evaluated by their cystic characteristics. Benjamini-Hochberg's false discovery rate (BH-FDR) was performed for multiple comparison adjustments. Univariable and multivariable analysis for survival was performed.</p><p><strong>Results: </strong>176 GBM IDH-WT patients met the inclusion criteria. Of these, 17 patients were identified as having a cystic component. Compared to non-cystic GBMs, cystic GBMs had a higher incidence of mutation in PDGFRA (41.2% vs. 16.4%, p = 0.021), RB1 (35.3% vs 11.9%, p = 0.019), and KIT (35.3% vs 10.7%, p = 0.012), and a lower incidence of mutation in CDKN2A/B (41.2% vs 69.2%, p = 0.029). No difference in progression-free survival (6.87 vs 7.83 months. p = 0.541) or overall survival (19.5 vs 18.2 months, p = 0.243) was identified between patients with cystic versus non-cystic GBM.</p><p><strong>Conclusions: </strong>Cystic GBMs were found to have lower frequencies of CDKN2A/B alterations and higher frequencies of PDGFRA, KIT, and RB1 alterations as compared to non-cystic GBMs. No statistically significant differences in PFS or OS were identified.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"515-523"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560421","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}
Tyler A Lanman, Hana Gross, Caylin M Faria, Julie J Miller, Daniel P Cahill, Helen A Shih, Giuliana V Zarrella, Jorg Dietrich, Michael W Parsons
{"title":"Factors associated with cognitive impairment in long-term IDH-mutant glioma survivors.","authors":"Tyler A Lanman, Hana Gross, Caylin M Faria, Julie J Miller, Daniel P Cahill, Helen A Shih, Giuliana V Zarrella, Jorg Dietrich, Michael W Parsons","doi":"10.1007/s11060-025-05155-1","DOIUrl":"10.1007/s11060-025-05155-1","url":null,"abstract":"<p><strong>Purpose: </strong>Cognition is a critical patient-relevant outcome in IDH-mutant (IDHm) glioma; however, there is a limited understanding of long-term neurocognition in this population and its implications for quality of life (QoL), especially in the modern era of molecular classification. We sought to evaluate long-term neurocognitive outcomes in patients with IDHm glioma.</p><p><strong>Methods: </strong>We identified a cohort of adult patients with molecularly defined IDHm glioma treated at Massachusetts General Hospital who underwent neuropsychological assessment 3 + years from initial diagnosis.</p><p><strong>Results: </strong>This cohort included 63 patients with pathologically proven IDH-mutant gliomas (46% female, median age 45, median 16 years of education, and underwent testing a median 7 years from diagnosis). 40% had oligodendroglioma, and 60% had astrocytoma, with 44, 49, and 6% WHO grade 2, 3, and 4 tumors, respectively. Cognitive impairment (defined as z-score ≤ -1.5 on at least 2 tests in different cognitive domains) was present in 30 patients (48%) and was associated with higher grade (p = 0.03 for grade 3 vs. 2), L-sided laterality (p = 0.02), female sex (p = 0.04), less education (p = 0.02), older age at testing (p = 0.03), longer disease duration (p = 0.01), prior chemotherapy (p = 0.03), and prior radiotherapy (p = 0.03). Cognitive impairment predicted lower scores on a cognitive-focused QoL measure (p < 0.001). This cohort was more impaired compared to a previously reported cohort who were tested at disease onset.</p><p><strong>Conclusion: </strong>In this population of long-term survivors of IDHm glioma, neurocognitive deficits were common, occurred more frequently than in a comparable newly diagnosed cohort, related to QoL, and associated with clinical and demographic factors. These findings emphasize the need for future research on interventions to support these patients' neurocognitive abilities and QoL.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"611-619"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690556","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}
Zhenwei Du, Yi Luo, Jinju Sun, He Long, Jianping You, Xin Li, Lunshan Xu, Weiguo Zhang, Xiao Chen
{"title":"<sup>18</sup>F-NOTA-NFB PET/MRI in glioma recurrence: comparison with <sup>11</sup>C-methionine PET/MRI and contrast-enhanced MRI.","authors":"Zhenwei Du, Yi Luo, Jinju Sun, He Long, Jianping You, Xin Li, Lunshan Xu, Weiguo Zhang, Xiao Chen","doi":"10.1007/s11060-025-05159-x","DOIUrl":"10.1007/s11060-025-05159-x","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the clinical utility of <sup>18</sup>F-NOTA-NFB PET/MRI relative to <sup>11</sup>C-methionine (<sup>11</sup>C-MET) PET/MRI and contrast-enhanced MRI (CE-MRI) for glioma recurrence detection.</p><p><strong>Methods: </strong>Patients with suspected recurrence of glioma were prospectively enrolled. All patients underwent paired <sup>18</sup>F-NOTA-NFB and <sup>11</sup>C-MET PET/MRI. Diagnostic efficiency of glioma recurrence detection by different imaging methods were assessed and compared. The suspected lesions showed via <sup>18</sup>F-NOTA-NFB and <sup>11</sup>C-MET PET/MRI were compared by SUVmax and tumor-to-background ratio (TBR). The diagnostic performance of <sup>18</sup>F-NOTA-NFB and <sup>11</sup>C-MET SUVmax/TBR was tested by receiver operating characteristic curve.</p><p><strong>Results: </strong>Thirty-eight patients with suspected recurrent glioma were included, with 28 positive for recurrent gliomas and 10 negative for recurrence which were confirmed by the pathology or clinical follow-up. For visual assessment, the accuracy and specificity of <sup>18</sup>F-NOTA-NFB PET were equivalent to <sup>11</sup>C-MET PET (accuracy: 92.11% vs. 94.74%, P = 1.00; specificity: 70.00% vs. 80.00%, P = 1.00) and higher than CE-MRI (accuracy: 92.11% vs. 76.32%, P = 0.031; specificity: 70.00% vs. 10.00%, P = 0.031). For quantitative analysis, in recurrent gliomas, <sup>18</sup>F-NOTA-NFB PET revealed higher SUVmax (P = 0.007) and TBR (P = 0.002) than treatment-related effects, with higher TBR for recurrence than that of <sup>11</sup>C-MET (P < 0.001). Although <sup>11</sup>C-MET SUVmax had the highest AUC of 0.911 for detecting glioma recurrence, but with no significant difference relative to <sup>11</sup>C-MET TBR (AUC = 0.889, P = 0.75), <sup>18</sup>F-NOTA-NFB SUVmax (AUC = 0.793, P = 0.32), and <sup>18</sup>F-NOTA-NFB TBR (AUC = 0.829, P = 0.42).</p><p><strong>Conclusion: </strong>The diagnostic efficacy of <sup>18</sup>F-NOTA-NFB PET or PET/MRI performed equivalent to <sup>11</sup>C-MET PET or PET/MRI, and better than CE-MRI for diagnosis of recurrent gliomas. Compared to <sup>11</sup>C-MET, <sup>18</sup>F-NOTA-NFB PET/MRI exhibited higher TBR, giving advantages in glioma delineation that might provide valuable information for making treatment strategy.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"647-656"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675005","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":"Tunneling nanotubes between glioblastoma cells and T cells and hijack of mitochondria.","authors":"Yanamandra Venkataratnam, Victor Mukherjee, Nikhil Rai, Mahesh Mahalingaswamy, Diksha Shandilya, Subhas Konar, Nandeesh Bevinahalli Nanjegowda, Girish Waghmare, Nandakumar Dalavaikodihalli Nanjaiah","doi":"10.1007/s11060-025-05150-6","DOIUrl":"10.1007/s11060-025-05150-6","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastoma is a highly aggressive and invasive brain tumor that can interact dynamically with its surrounding tumor microenvironment, including resident and infiltrating-immune cells. These interactions largely govern glioblastoma progression and resistance to therapy. Glioblastoma cells can actively modulate immune cell functions, either by inhibiting immune responses or reprogramming immune cells. This study explores the dynamic interaction between glioblastoma cells and T cells.</p><p><strong>Methods: </strong>The connections between glioblastoma cells and T cells were analyzed by immunohistochemistry, immunofluorescence and scanning electron microscopy. Inhibition of tunneling nanotubes (TNTs) between glioblastoma cells and T cells was performed using carbenoxolone. Fluorogenic probes were used for mitochondrial membrane potential and reactive oxygen species (ROS) in mitochondria, glioblastoma cells and T cells after co-culture. Viability and LAG-3 levels were analyzed in T cells.</p><p><strong>Results: </strong>Glioblastoma cells show connections between themselves and forms physical connections with T cells through TNTs. Glioblastoma cells hijack mitochondria from T cells through these connections and effect was reversed on using carbenoxolone. Glioblastoma cells show increased mitochondrial membrane potential and decreased mitochondrial ROS after co-culture, while ROS was increased in glioblastoma cells and decreased in T cells.</p><p><strong>Conclusion: </strong>We show for the first time that glioblastoma cells and T cells physically connect through TNTs. Most importantly, glioblastoma cells hijack the mitochondria of T cells for its own advantage. By focusing on these complex tumor-immune cell interactions, this study aims to uncover a novel mode of physical communication in glioblastoma microenvironment.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"571-583"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674913","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}
Maria Neu, Ehab Shiban, Philipp Krauss, Björn Sommer, Zoha Roushan, Susanne Gutser, Christoph J Maurer, Tilman Janzen, Georg Stüben, Klaus-Henning Kahl
{"title":"Comparing intraoperative radiotherapy (IORT) and hypofractionated stereotactic radiotherapy (HSRT) after brain metastasis surgery: impact on oncological outcome and radionecrosis.","authors":"Maria Neu, Ehab Shiban, Philipp Krauss, Björn Sommer, Zoha Roushan, Susanne Gutser, Christoph J Maurer, Tilman Janzen, Georg Stüben, Klaus-Henning Kahl","doi":"10.1007/s11060-025-05152-4","DOIUrl":"10.1007/s11060-025-05152-4","url":null,"abstract":"<p><strong>Purpose: </strong>Due to significantly lower neurocognitive toxicity, whole-brain irradiation (WBI) has largely been replaced by focal irradiation of the resection cavity following brain metastasis surgery. However, the optimal treatment modality and fractionation scheme remain controversial. This study conducts a comparative analysis of hypofractionated stereotactic radiotherapy (HSRT) and intraoperative radiotherapy (IORT), focusing on clinical outcomes and toxicity profiles.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted, analyzing 129 patients (HSRT: 72, IORT: 57) with 137 treated cavities (HSRT: 75, IORT: 62) at the University Hospital of Augsburg (UKA) between 2013 and 2021. Baseline characteristics, oncological outcomes, incidence of radionecrosis (RN), and time to further treatment were compared.</p><p><strong>Results: </strong>Radionecrosis occurred significantly less frequently in the IORT group compared to HSRT, with 1-year RN rates of 3.7% (95% CI: 0.5-23.5%) and 21.8% (95% CI: 11.7-39.2%), respectively (p = 0.00025). At two years, the RN rate remained substantially lower after IORT (8.5% vs. 53.2%). Notably, in patients without prior cerebral irradiation, no symptomatic RN (sRN) occurred following IORT, whereas the 2-year sRN rate in the HSRT group reached 35.5% (p = 0.0036). Oncological outcomes, including overall survival (OS), local control (LC), intracranial disease control, leptomeningeal dissemination (LMD), and WBI avoidance, were comparable between the two groups. However, distant brain control (DBC) at one year was higher in the HSRT group. While HSRT was initiated after a median delay of 29 days (range: 14-71), IORT was delivered intraoperatively, enabling immediate continuation of systemic therapy.</p><p><strong>Conclusion: </strong>In this retrospective single-center analysis, IORT demonstrated comparable oncological efficacy to HSRT while significantly reducing the risk of RN. Given its intraoperative delivery and the ability to promptly resume systemic therapy, and the precise application directly at the resection cavity, IORT may represent a practical and effective alternative in selected patients.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"845-856"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835354","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}
Catherine R Garcia, Kaitlin Highsmith, Stephanie Knight, Ivan Pradilla Andrade, Cheuk Hong Leung, Vinay Puduvalli, Carlos Kamiya-Matsuoka
{"title":"Single center experience of IDH inhibitors in recurrent high-grade gliomas.","authors":"Catherine R Garcia, Kaitlin Highsmith, Stephanie Knight, Ivan Pradilla Andrade, Cheuk Hong Leung, Vinay Puduvalli, Carlos Kamiya-Matsuoka","doi":"10.1007/s11060-025-05183-x","DOIUrl":"10.1007/s11060-025-05183-x","url":null,"abstract":"<p><strong>Purpose: </strong>The role of IDH inhibitors in recurrent high-grade gliomas (HGG) is not well described. We present the outcomes of patients with HGG that were treated with these agents at our institution.</p><p><strong>Methods: </strong>We reviewed patients with recurrent IDH-mutant HGG treated with FDA approved IDH inhibitors (ivosidenib, enasidenib, and vorasidenib) from December 2019 to December 2024 at the University of Texas MD Anderson Cancer Center.</p><p><strong>Results: </strong>23 patients were identified of which 65.2% were male. Tumors included astrocytoma (n = 14, 60.9%) and WHO grade 3 oligodendroglioma (n = 9, 39.1%), with four patients having a WHO grade 4 astrocytoma and 10 a WHO grade 3 astrocytoma. Twenty patients had enhancing disease at the time an IDH inhibitor was recommended. One patient was treated with enasidenib, 17 with ivosidenib, and 5 with vorasidenib. Of those initially treated with ivosidenib, 9 were switched to vorasidenib. Two patients discontinued the drugs due to side effects, that included elevated liver enzymes (n = 1), and diarrhea (n = 1). All patients had received prior surgery, radiation, and chemotherapy before starting an IDH inhibitor. Median overall survival (OS) was not reached. OS after IDH inhibitor was 20.7 months and was longer in patients that had not received initial chemotherapy (p = 0.032). Median progression-free survival (PFS) was 6.8 months and was not different between tumor type, sex, or number of recurrences, but was longer in patients that did not receive initial chemotherapy (p = 0.041).</p><p><strong>Conclusion: </strong>IDH inhibitors were well tolerated in patients with IDH-mutant HGG previously treated with DNA-damaging agents. A median PFS longer than 6 months is encouraging in this patient population and may be due to antitumor activity of IDH inhibitors in recurrent HGG.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"837-844"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760357","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":"SIN1 facilitates glioma progression and is associated with the KRAS/ERK pathway.","authors":"Haowei Cao, Zhihan Yan, Mengwei Li, Jing Wang, Haihan Zhang, Yu Cheng, Jinmin Sun, Jing Ren, Dejun Yang","doi":"10.1007/s11060-025-05166-y","DOIUrl":"10.1007/s11060-025-05166-y","url":null,"abstract":"<p><strong>Purpose: </strong>Glioma is the most common primary brain and spinal cord tumor, with effective treatments still lacking. Stress-activated protein kinase-interacting protein 1 (SIN1) has been reported to be upregulated in various tumor types, contributing to tumorigenesis. However, its specific role in glioma remains unclear. This study aimed to investigate SIN1's expression, clinical significance, biological functions, and underlying molecular mechanisms in glioma.</p><p><strong>Methods: </strong>SIN1 expression and its association with clinicopathological features and prognosis were analyzed using data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). SIN1 levels were quantified in glioma tissues and cell lines. The functional roles of SIN1 were evaluated by silencing or overexpressing it in glioma cells. RNA sequencing was used to identify downstream pathways, which were further validated through in vitro experiments. Additionally, the relationship between SIN1 and immune cell infiltration was investigated.</p><p><strong>Results: </strong>SIN1 is aberrantly upregulated in glioma, significantly correlating with adverse clinicopathological features and poor patient prognosis. Functional studies reveal that SIN1 upregulation enhances glioma cell proliferation and migration while suppressing apoptosis. Mechanistically, SIN1 exerts its oncogenic effects might be through the KRAS4A/ERK pathway. Furthermore, SIN1 expression is associated with altered immune cell infiltration within the tumor microenvironment.</p><p><strong>Conclusion: </strong>This study identifies SIN1 as a critical oncoprotein in glioma, upregulated in tumors and associated with aggressive features and poor survival. It drives tumor progression by enhancing proliferation/migration and suppressing apoptosis might via the KRAS4A/ERK pathway, while potentially modulating immune infiltration. These findings highlight SIN1's promise as a novel therapeutic target.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"697-711"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674911","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}
Jens Blobner, Viktoria Ruf, Jonathan Weller, Nico Teske, Robert Forbrig, Niklas Thon, Nathalie L Albert, Louisa von Baumgarten, Stephan Schoenecker, Joerg-Christian Tonn, Florian Ringel, Patrick N Harter, Philipp Karschnia
{"title":"Clinical and neuropathological criteria for distinguishing between IDH-mutant astrocytomas of WHO grade 2 and 3.","authors":"Jens Blobner, Viktoria Ruf, Jonathan Weller, Nico Teske, Robert Forbrig, Niklas Thon, Nathalie L Albert, Louisa von Baumgarten, Stephan Schoenecker, Joerg-Christian Tonn, Florian Ringel, Patrick N Harter, Philipp Karschnia","doi":"10.1007/s11060-025-05173-z","DOIUrl":"10.1007/s11060-025-05173-z","url":null,"abstract":"<p><strong>Background: </strong>The 2021 WHO classification of CNS tumors allows flexibility in the grading of IDH-mutant astrocytic gliomas, leading to some ambiguity. Following the approval of vorasidenib for WHO grade 2 astrocytomas and oligodendrogliomas based on the positive Phase III INDIGO trial, identifying prognostic criteria to differentiate between grade 2 and grade 3 tumors has become increasingly important.</p><p><strong>Methods: </strong>We retrospectively searched our institutional database for patients meeting the diagnostic criteria for IDH-mutant astrocytomas (grade 2 and 3) according to the WHO 2021 classification. Clinical, radiological and molecular data were collected; outcome was compared using log-rank analysis and prognostic markers were subsequently forwarded in a multivariate model.</p><p><strong>Results: </strong>We identified 91 patients with IDH-mutant astrocytomas with available neuropathological and clinical data, including 61 WHO grade 2 (67.0%) and 30 WHO grade 3 (33.0%) tumors. At a median follow-up of 89 months, median progression-free survival was 67 months for WHO grade 2 and 53 months for WHO grade 3 tumors. Median overall survival was 216 months for WHO grade 3 tumors, while it was not reached for WHO grade 2 tumors. Univariate analysis showed that higher WHO grade, increased mitotic count, elevated Ki67 indices and preoperative contrast enhancement were associated with poorer outcomes; however, only contrast enhancement retained prognostic significance on multivariate analysis (p = 0.03 for overall survival, p = 0.02 for progression-free survival).</p><p><strong>Conclusion: </strong>While our findings await confirmation in larger prospective cohorts, neuropathological grading criteria might need to be accompanied by clinical information including contrast enhancement to prognostically distinguish grade 2 from grade 3 tumors.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"763-774"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698795","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}