Neuro-oncology最新文献

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Identifying appropriate external control datasets in support of future glioblastoma clinical trials leveraging external data. 确定适当的外部对照数据集,以支持未来利用外部数据的胶质母细胞瘤临床试验。
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf031
Rifaquat Rahman, Steffen Ventz, Robert Redd, Geoffrey Fell, Yujue Tan, Peter Orio, Kirk Tanner, Patrick Y Wen, Lorenzo Trippa
{"title":"Identifying appropriate external control datasets in support of future glioblastoma clinical trials leveraging external data.","authors":"Rifaquat Rahman, Steffen Ventz, Robert Redd, Geoffrey Fell, Yujue Tan, Peter Orio, Kirk Tanner, Patrick Y Wen, Lorenzo Trippa","doi":"10.1093/neuonc/noaf031","DOIUrl":"10.1093/neuonc/noaf031","url":null,"abstract":"<p><strong>Background: </strong>Recent interest in leveraging external data for clinical trial design and analysis in glioblastoma has raised questions on the identification of appropriate data to use as external controls for future trials. We perform a comprehensive analysis assessing candidate sources of external data and comparing clinical trial and real-world datasets in newly diagnosed glioblastoma.</p><p><strong>Methods: </strong>Individual patient-level data (PLD) from several clinical trials, a large academic institutional database and a registry (National Cancer Database) were used for analysis of patients receiving standard of care radiation with concurrent and adjuvant temozolomide. Data summaries from randomized trials 2012-2022 were analyzed to account for trials without available PLD. Multivariable modeling was employed to compare survival across datasets.</p><p><strong>Results: </strong>In total, 8 datasets with PLD for 3061 patients with newly diagnosed glioblastoma treated with standard chemoradiation were analyzed. Patients on trials were younger (age < 60:64% vs. 48%, p < 0.001) and had higher KPS (KPS≥90:58% vs. 48%, P < .001) compared to non-trial patients. Patients in clinical trials exhibited inferior survival relative to non-trial patients (HR 1.30,95%CI 1.13-1.48, P < .001) after adjustment for age, sex, KPS, extent of resection and MGMT methylation status. In assessment of data summaries of 19 randomized trials, there was no detectable time-trend toward improved outcomes 2012-2022.</p><p><strong>Conclusions: </strong>In newly diagnosed glioblastoma patients treated with standard of care chemoradiation, there were significant differences between trial datasets and real-world datasets but no evidence of a trial effect benefit from trial participation. After adjustment of relevant covariates, there was no evidence of temporal drift of improved survival over the last decade.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1507-1518"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mind over microbes: targeting the gut-brain axis to improve treatment of pediatric low-grade glioma. 微生物之上的思想:瞄准肠-脑轴改善小儿低级别胶质瘤的治疗。
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf094
Vijay Ramaswamy, Uri Tabori
{"title":"Mind over microbes: targeting the gut-brain axis to improve treatment of pediatric low-grade glioma.","authors":"Vijay Ramaswamy, Uri Tabori","doi":"10.1093/neuonc/noaf094","DOIUrl":"10.1093/neuonc/noaf094","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1594-1596"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline Rapid Recommendation Update. 成人弥漫性星形细胞和少突胶质肿瘤的治疗:ASCO-SNO指南快速推荐更新
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf072
Jaishri Blakeley, Nimish A Mohile, Hans Messersmith, Andrew B Lassman, David Schiff
{"title":"Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline Rapid Recommendation Update.","authors":"Jaishri Blakeley, Nimish A Mohile, Hans Messersmith, Andrew B Lassman, David Schiff","doi":"10.1093/neuonc/noaf072","DOIUrl":"10.1093/neuonc/noaf072","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1412-1418"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glioma-Associated Microglia Potentiate Neuronal Hyper-Excitability in the Glioma Environment. 胶质瘤相关的小胶质细胞在胶质瘤环境中增强神经元的高兴奋性。
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf181
Jaeseung Yei, Na Kyeong Lee, Seungmin Ryu, Seong-Eun Ryu, Juheon Lee, Taeyoung Park, Yoonyi Jeong, Rian Kang, Ho-Keun Kwon, Seong-Gi Kim, Jong-Chan Park, Chun Gwon Park, Minah Suh
{"title":"Glioma-Associated Microglia Potentiate Neuronal Hyper-Excitability in the Glioma Environment.","authors":"Jaeseung Yei, Na Kyeong Lee, Seungmin Ryu, Seong-Eun Ryu, Juheon Lee, Taeyoung Park, Yoonyi Jeong, Rian Kang, Ho-Keun Kwon, Seong-Gi Kim, Jong-Chan Park, Chun Gwon Park, Minah Suh","doi":"10.1093/neuonc/noaf181","DOIUrl":"https://doi.org/10.1093/neuonc/noaf181","url":null,"abstract":"<p><strong>Background: </strong>Hyper-excitable neurons are observed in the glioma brain, contributing to the notorious nature of glioma. It is well established that microglia can modulate neuronal excitability through crosstalk via P2RY12. However, the role of microglia in glioma environments remains poorly understood. Thus, this study aimed to investigate whether loss of microglial P2RY12 could contribute to hyper-excitable neurons within the glioma environment.</p><p><strong>Methods: </strong>Using two distinct tumor models and normal Thy1-GCaMP6f mice, spontaneous neuronal activity was imaged in the peritumor region with an in vivo 2-photon microscope. Neuronal calcium activity was then compared to expression level of microglial P2RY12. Neuronal activity was further quantified after administering a microglial blocker and compared across different tumor models and cortical regions of a glioma mouse model.</p><p><strong>Results: </strong>Our findings revealed that hyper-excitable neurons were exclusively observed in cortical regions surrounding glioma tissues. In the glioma environment, microglia exhibited significantly reduced expression of P2RY12, a receptor known to modulate neuronal activity via negative feedback control. In contrast, neuronal excitability and microglial P2RY12 expression relatively remained same to the control in environments of a brain metastasis model. Furthermore, blocking microglial P2RY12 enhanced spontaneous neuronal activity in both the brain metastasis model and distal regions of glioma tumors, effectively replicating the functional loss of P2RY12 observed in glioma conditions.</p><p><strong>Conclusions: </strong>Results of this study support that neuronal hyper-excitability is a unique observation within a peri-glioma environment driven by loss of microglial P2RY12.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753909","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}
引用次数: 0
Intrathecal sintilimab for leptomeningeal metastases of non-small cell lung cancer failed from targeted therapy and intrathecal chemotherapy (LMIS study). 鞘内辛替单抗治疗靶向治疗和鞘内化疗失败的非小细胞肺癌轻脑膜转移(LMIS研究)。
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf025
Chengjuan Fan, Yuanyuan Hu, Chong Teng, Yanju Lv, Xiaowei Song, Weixi Shen, Qiuying Jiang, Dayong Huang, Lina Du, Guohua Wang, Yang Du, Siqi Man, Zhichao Zhang, Jing Zhang, Li Li, Tao Xin
{"title":"Intrathecal sintilimab for leptomeningeal metastases of non-small cell lung cancer failed from targeted therapy and intrathecal chemotherapy (LMIS study).","authors":"Chengjuan Fan, Yuanyuan Hu, Chong Teng, Yanju Lv, Xiaowei Song, Weixi Shen, Qiuying Jiang, Dayong Huang, Lina Du, Guohua Wang, Yang Du, Siqi Man, Zhichao Zhang, Jing Zhang, Li Li, Tao Xin","doi":"10.1093/neuonc/noaf025","DOIUrl":"10.1093/neuonc/noaf025","url":null,"abstract":"<p><strong>Background: </strong>Leptomeningeal metastases (LMs) are serious complications of non-small cell lung cancer (NSCLC). This study aimed to investigate the safety and efficacy of intrathecal immune checkpoint inhibitors (ICIs) in treating NSCLC-LM.</p><p><strong>Methods: </strong>We conducted this prospective phase 1 study (ChiCTR2200062245) using a traditional \"3+3\" design with intrathecal sintilimab (dose escalation 10, 20, 30, and 40 mg) for NSCLC-LM patients who had progressed from targeted therapy and intrathecal pemetrexed. The primary study endpoints were safety and recommended dose, and the secondary endpoints included clinical response rate, progression-free survival (PFS), intracranial progression-free survival (iPFS), and overall survival (OS).</p><p><strong>Results: </strong>No dose-limiting toxicity was found at 10, 20, 30, and 40 mg for intrathecal sintilimab. Therefore, sintilimab 40 mg was recommended for intrathecal injection. A total of 19 patients were enrolled in this study. The median age at diagnosis of LM was 53 years. The overall incidence of adverse events (AEs) was 68.4%, and rash (n = 4, 21.1%) was the most common AEs, which returned to normal after symptomatic treatment. As 1 patient was lost to follow-up and 18 patients could be evaluated for efficacy, the clinical response rate was 38.9% (7/18). Median PFS was 3.5 months (95% CI: 2.7-4.2 months), median iPFS was 3.5 months (95% CI: 1.3-5.6 months), and median OS was 11.5 months (95% CI: 0.0-25.4 months).</p><p><strong>Conclusions: </strong>Intrathecal ICIs for NSCLC-LM patients are safe, and the recommended dose of sintilimab is 40 mg. Intrathecal sintilimab for NSCLC-LM failed from multi-line therapies, showed potential effectiveness in some patients, and is worthy of further study.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1559-1566"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling spatial heterogeneity in medulloblastoma: A multi-omics analysis of cellular state and geographical organization. 揭示髓母细胞瘤的空间异质性:细胞状态和地理组织的多组学分析。
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf020
Jiankang Li, Hailong Liu, Ziwei Wang, Jiao Zhang, Xuan Chen, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Hiromichi Suzuki, Pasqualino De Antonellis, Alexandra Rasnitsyn, Winnie Ong, Evan Y Wang, Liam D Hendrikse, Yu Su, Yu Tian, Dongming Han, Ruohan Wang, Jialin Mo, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yifei Jiang, Yanong Li, Yuting Ma, Zijia Liu, Meiyu Li, Peiyi Tian, Yanfeng Shi, Yong Jiang, Tao Yang, Shouwei Li, Jianfeng Liang, Jingchuan Wu, Ying Wang, Wanjing Zou, Yina Jiang, Lusheng Wang, Fang Chen, Xin Jin, Shuaicheng Li, Xiaoguang Qiu, Chunde Li, Ya Gao, Yujie Tang, Michael D Taylor, Tao Jiang
{"title":"Unveiling spatial heterogeneity in medulloblastoma: A multi-omics analysis of cellular state and geographical organization.","authors":"Jiankang Li, Hailong Liu, Ziwei Wang, Jiao Zhang, Xuan Chen, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Hiromichi Suzuki, Pasqualino De Antonellis, Alexandra Rasnitsyn, Winnie Ong, Evan Y Wang, Liam D Hendrikse, Yu Su, Yu Tian, Dongming Han, Ruohan Wang, Jialin Mo, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yifei Jiang, Yanong Li, Yuting Ma, Zijia Liu, Meiyu Li, Peiyi Tian, Yanfeng Shi, Yong Jiang, Tao Yang, Shouwei Li, Jianfeng Liang, Jingchuan Wu, Ying Wang, Wanjing Zou, Yina Jiang, Lusheng Wang, Fang Chen, Xin Jin, Shuaicheng Li, Xiaoguang Qiu, Chunde Li, Ya Gao, Yujie Tang, Michael D Taylor, Tao Jiang","doi":"10.1093/neuonc/noaf020","DOIUrl":"10.1093/neuonc/noaf020","url":null,"abstract":"<p><strong>Background: </strong>Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.</p><p><strong>Methods: </strong>We analyze single-nucleus and spatial transcriptomes and chromatin accessibility from human MB spanning four subgroups, to identify malignant cell populations and describe the spatial evolutionary trajectories. The spatial copy number variations (CNVs) patterns and niches were analyzed to investigate the cellular interactions.</p><p><strong>Results: </strong>Three main malignant cell populations were identified, including progenitor-like, cycling, and differentiated populations. Gene signatures of cell populations strongly correlate to clinical outcomes. These tumor cell populations are geographically organized as stem-like and mature regions, highlighting their spatially heterogeneous nature. Progenitor-like and cycling cells are mainly concentrated in stem-like regions, whereas various differentiated populations are primarily distributed in mature regions. By analyzing chromosomal alterations, we find that stem-like regions typically harbor a single pattern of CNVs, reflecting high originality and uniformity, which is in stark contrast to mature regions exhibiting multiple patterns with a broader range of biological functions. Projecting cellular state programs onto spatial sections fully illustrates the evolution from stem-like regions to various functional zones in mature regions, which is correlated to microenvironmental components along the paths to maintain stemness or promote differentiation.</p><p><strong>Conclusions: </strong>This multi-omics database comprehensively facilitates the understanding of MB spatial evolutionary organization.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1611-1627"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433137","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}
引用次数: 0
Local tumor control and neurological outcomes after surgery for spinal hemangioblastomas in sporadic and von Hippel-Lindau disease: A multicenter study. 散发性和Von-Hippel-Lindau病脊柱血管母细胞瘤手术后局部肿瘤控制和神经预后:一项多中心研究
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf041
Johannes Wach, Alim Emre Basaran, Martin Vychopen, Tarik Tihan, Maria Wostrack, Vicki M Butenschoen, Bernhard Meyer, Sebastian Siller, Nils Ole Schmidt, Julia Onken, Peter Vajkoczy, Alejandro N Santos, Laurèl Rauschenbach, Philipp Dammann, Ulrich Sure, Jan-Helge Klingler, Roberto Doria-Medina, Jürgen Beck, Bianca-Ioana Blaß, Christine Julia Gizaw, Romina Hohenhaus, Sandro Krieg, Obada T Alhalabi, Lukas Klein, Claudius Thomé, Nikolaus Kögl, Przemyslaw Kunert, Tomasz Czernicki, Tobias Pantel, Maximilian Middelkamp, Sven Oliver Eicker, Ahed H Kattaa, David J Park, Steven D Chang, Fatma Kilinc, Marcus Czabanka, Erdem Güresir
{"title":"Local tumor control and neurological outcomes after surgery for spinal hemangioblastomas in sporadic and von Hippel-Lindau disease: A multicenter study.","authors":"Johannes Wach, Alim Emre Basaran, Martin Vychopen, Tarik Tihan, Maria Wostrack, Vicki M Butenschoen, Bernhard Meyer, Sebastian Siller, Nils Ole Schmidt, Julia Onken, Peter Vajkoczy, Alejandro N Santos, Laurèl Rauschenbach, Philipp Dammann, Ulrich Sure, Jan-Helge Klingler, Roberto Doria-Medina, Jürgen Beck, Bianca-Ioana Blaß, Christine Julia Gizaw, Romina Hohenhaus, Sandro Krieg, Obada T Alhalabi, Lukas Klein, Claudius Thomé, Nikolaus Kögl, Przemyslaw Kunert, Tomasz Czernicki, Tobias Pantel, Maximilian Middelkamp, Sven Oliver Eicker, Ahed H Kattaa, David J Park, Steven D Chang, Fatma Kilinc, Marcus Czabanka, Erdem Güresir","doi":"10.1093/neuonc/noaf041","DOIUrl":"10.1093/neuonc/noaf041","url":null,"abstract":"<p><strong>Background: </strong>Spinal hemangioblastomas (sHBs) are rare vascular tumors with significant neurological implications. Their management, particularly in von Hippel-Lindau (VHL) disease, remains challenging due to recurrence and functional decline. Timely identification and intervention are critical for optimal outcomes.</p><p><strong>Methods: </strong>This international, multicenter retrospective cohort study included 357 patients (199 VHL-associated, 158 sporadic) from 13 neuro-oncological centers. Clinical and imaging data were analyzed to assess progression-free survival (PFS) and functional outcomes using the modified McCormick Scale (mMCS) at 12 months. Secondary analyses identified factors associated with VHL disease in sHBs.</p><p><strong>Results: </strong>Complete resection was achieved in 87.7% of cases, leading to significantly improved PFS at 72 months (sporadic: 95.1%, VHL-associated: 91.1%; hazard ratio: 0.18, 95% CI: 0.08-0.4). Multivariable analysis identified predictors of unfavorable outcomes at 12 months: preoperative mMCS ≥2 (odds ratio [OR]: 5.17, P = .008), intramedullary tumor location (OR: 9.48, P = .01), and preoperative bleeding (OR: 31.12, P = .02). Factors independently associated with VHL disease in sHBs included non-cervical tumor location (OR: 2.08, P = .004), intramedullary growth (OR: 2.39, P < .001), and age <43 years (OR: 3.24, P < .001). Functional improvements were observed in most patients, particularly those with sporadic sHBs.</p><p><strong>Conclusions: </strong>Complete surgical resection is essential for long-term tumor control and favorable functional outcomes in both sporadic and VHL-associated sHBs. Early intervention, particularly in mild symptomatic and progressive cases, before neurological deterioration or hemorrhage, optimizes recovery. This study, the largest of its kind in a multicentric international setting, provides robust evidence to guide the management of both sporadic and VHL-associated sHBs.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1567-1578"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intestinal Bacteroides drives glioma progression by regulating CD8+ T cell tumor infiltration. 肠道乳杆菌通过调节 CD8+ T 细胞的肿瘤浸润来推动胶质瘤的发展。
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf024
Jit Chatterjee, Xuanhe Qi, Rui Mu, Xuanwei Li, Talia Eligator, Megan Ouyang, Stephanie L Bozeman, Rachel Rodgers, Somya Aggarwal, Danielle E Campbell, Lawrence A Schriefer, Megan T Baldridge, David H Gutmann
{"title":"Intestinal Bacteroides drives glioma progression by regulating CD8+ T cell tumor infiltration.","authors":"Jit Chatterjee, Xuanhe Qi, Rui Mu, Xuanwei Li, Talia Eligator, Megan Ouyang, Stephanie L Bozeman, Rachel Rodgers, Somya Aggarwal, Danielle E Campbell, Lawrence A Schriefer, Megan T Baldridge, David H Gutmann","doi":"10.1093/neuonc/noaf024","DOIUrl":"10.1093/neuonc/noaf024","url":null,"abstract":"<p><strong>Background: </strong>The intestinal microbiota regulates normal brain physiology and the pathogenesis of several neurological disorders. While prior studies suggested that this operates through immune cells, the underlying mechanisms remain unclear. Leveraging 2 well-characterized murine models of low-grade glioma occurring in the setting of the neurofibromatosis type 1 (NF1) cancer predisposition syndrome, we sought to determine the impact of the gut microbiome on optic glioma progression.</p><p><strong>Methods: </strong>Neurofibromatosis type 1 (Nf1)-mutant mice genetically engineered to develop optic pathway gliomas (Nf1OPG mice) by 3 months of age were reared under germ-free (GF) conditions, treated with specific cocktails of antibiotics, or given fecal matter transplants (FMTs). Intestinal microbial species were identified by 16S genotyping. Neutralizing transforming growth factor-beta (TGFβ) antibodies were delivered systemically, while in vitro experiments used isolated murine microglia and T cells. Single-cell RNA sequencing analysis was performed using established methods.</p><p><strong>Results: </strong>Nf1 OPG mice raised in a GF environment or postnatally treated with vancomycin did not harbor optic gliomas or exhibit OPG-induced retinal nerve fiber layer thinning, which was reversed following conventionally raised mouse FMT or colonization with Bacteroides species. Moreover, this intestinal microbiota-regulated gliomagenesis was mediated by circulating TGFβ, such that systemic TGFβ neutralization reduced Nf1-OPG growth. TGFβ was shown to act on tumor-associated monocytes to induce Ccl3 expression and recruit CD8+ T cells necessary for glioma growth.</p><p><strong>Conclusions: </strong>Taken together, these findings establish, for the first time, a mechanistic relationship between Bacteroides in the intestinal microbiome and NF1-LGG pathobiology, suggesting both future predictive risk assessment strategies and therapeutic opportunities.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1579-1593"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phase II trial of brain MRI surveillance in stage IV breast cancer. 脑MRI监测IV期乳腺癌的II期试验。
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf018
Kamran A Ahmed, Youngchul Kim, Avan J Armaghani, John A Arrington, Ricardo L Costa, Brian J Czerniecki, Roberto Diaz, Robin A Dowell, Martine Extermann, Peter A Forsyth, Kimberley T Lee, Loretta Loftus, Matthew N Mills, Vania H Phuoc, Marilin Rosa, Hatem H Soliman, Christine S Sam, Iman R Washington, Aixa E Soyano, Hyo S Han
{"title":"Phase II trial of brain MRI surveillance in stage IV breast cancer.","authors":"Kamran A Ahmed, Youngchul Kim, Avan J Armaghani, John A Arrington, Ricardo L Costa, Brian J Czerniecki, Roberto Diaz, Robin A Dowell, Martine Extermann, Peter A Forsyth, Kimberley T Lee, Loretta Loftus, Matthew N Mills, Vania H Phuoc, Marilin Rosa, Hatem H Soliman, Christine S Sam, Iman R Washington, Aixa E Soyano, Hyo S Han","doi":"10.1093/neuonc/noaf018","DOIUrl":"10.1093/neuonc/noaf018","url":null,"abstract":"<p><strong>Background: </strong>Screening of asymptomatic stage IV breast cancer with brain MRIs is currently not recommended by National Comprehensive Cancer Network Guidelines. The incidence of asymptomatic brain metastasis is not well documented.</p><p><strong>Methods: </strong>The study is designed as a single-arm, phase II trial, with the goal of investigating surveillance brain MRIs in neurologically asymptomatic patients with metastatic breast cancer. Breast cancer patients were classified into triple-negative (TN), HER2+, and hormone receptor (HR)+/HER2-. Patients underwent a surveillance brain MRI and a second brain MRI at 6 months if the baseline MRI was negative. Asymptomatic, stage IV breast cancer patients, ECOG ≤ 2, and life expectancy ≥ 6 months were eligible. The primary objective was to determine the frequency of asymptomatic brain metastasis in metastatic breast cancer. Clinical trial information: NCT05115474.</p><p><strong>Results: </strong>A total of 101 patients completed the surveillance brain MRI including 40 HR+/HER2-, 33 HER2+, and 28 TN patients. The overall frequency of brain metastasis on initial surveillance brain MRI was 14% (n = 14) with rates of 18%, 15%, and 10% in TN, HER2+, and HR+/HER2- patients, respectively. Following the 6-month MRI, the cumulative rates of brain metastasis increased to 25% in TN, 24% in HER2+, and 23% in HR+/HER2- patients.</p><p><strong>Conclusions: </strong>The highest frequency of brain metastases at baseline was in TN and HER2+ breast cancer. Following the 6-month MRI, the cumulative frequency was approximately a quarter across all subtypes. These results warrant confirmatory trials to refine brain MRI surveillance recommendations for neurologically asymptomatic stage IV breast cancer.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1550-1558"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular-based decision-making in glioblastoma surgery: When to aim for supramaximal resection. 胶质母细胞瘤手术中基于分子的决策:何时瞄准最大切除。
IF 13.4 1区 医学
Neuro-oncology Pub Date : 2025-07-30 DOI: 10.1093/neuonc/noaf062
Richard Drexler, Michael Lim, Shawn L Hervey-Jumper
{"title":"Molecular-based decision-making in glioblastoma surgery: When to aim for supramaximal resection.","authors":"Richard Drexler, Michael Lim, Shawn L Hervey-Jumper","doi":"10.1093/neuonc/noaf062","DOIUrl":"10.1093/neuonc/noaf062","url":null,"abstract":"<p><p>The advent of molecular techniques has enhanced our understanding of the biology of malignancies over the past decade. Multi-omics has facilitated an in-depth characterization of glioblastomas at the cellular level, revealing intricate details about tumor cell states and their compositions. This advancement has substantially enriched our comprehension of tumor cell interactions with the surrounding microenvironment-such as neurons and immune cells-shedding light on patterns of tumor growth, infiltration, and therapeutic resistance. Despite the introduction of immunotherapies and molecularly guided chemotherapeutic treatments, surgical resection remains a cornerstone of the glioblastoma therapeutic regimen. While maximal resection is universally considered to improve patient outcomes, integrating molecular data and insights into tumor cell interactions suggests a role for molecular-based surgical decision-making. Herein, we review how the molecular characterization of glioblastoma subtypes and their interactions can predict the benefits of surgical resection. We discuss how these insights could refine neurosurgical management in the future. Integrating multi-omics-preferably in real-time during surgery-promises to guide patient selection and optimize neurosurgical decision-making. Although these developments are promising for enhancing surgical strategies and improving patient outcomes, further validation in prospective studies involving larger cohorts and the development of workflows for clinical practice is needed.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1434-1442"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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