Neuro-oncology最新文献

{"title":"DNA damage response profile distinguishes poor-acting gliomas with shared methylome signatures.","authors":"Nalin Leelatian, Charu Singh, Richard Bouffard, Ranjini K Sundaram, Kirsten E Diggins, William Sullivan, Sateja Paradkar, Zeynep Erson Omay, Bret C Mobley, Susan E Gueble, Juan C Vasquez, Ranjit S Bindra","doi":"10.1093/neuonc/noaf199","DOIUrl":"https://doi.org/10.1093/neuonc/noaf199","url":null,"abstract":"<p><strong>Background: </strong>Therapies for diffuse glioma induce DNA damage response (DDR), and strategies to exploit DDR defects are active areas of investigation. While global DNA methylation profiling effectively classifies gliomas into subtypes, the epigenetic and gene expression patterns of DDR genes, and their contribution to tumor classification and outcomes, have yet to be fully elucidated. Thus, dissecting the DDR epigenetics, gene expression, and single-cell heterogeneity may reveal key molecular characteristics, refine prognosis, and identify novel treatment strategies and resistance mechanisms.</p><p><strong>Methods: </strong>We characterized DDR epigenetics and gene expression of TCGA glioblastomas (GBM) and low-grade gliomas (LGG). Single-cell protein analysis by imaging mass cytometry (IMC) was performed on a separate cohort of 118 diffuse gliomas.</p><p><strong>Results: </strong>Analysis of TCGA cohorts revealed two DDR methylation groups that correlated with IDH mutation status and previously reported molecular groups. DDR transcription profiling further classified tumors into four groups. Those with high DDR transcription across pathways were linked to poor survival independent of IDH or MGMT status, and potentially improved prognostication beyond established biomarkers. Single-cell characterization of a separate cohort revealed intratumoral DDR diversity and identified proliferative tumor cells with high DDR protein expression across pathways that are associated with unfavorable grade and survival.</p><p><strong>Conclusions: </strong>Tumor-level epigenetic and transcriptional DDR signatures alone can distinguish molecular-defined diagnosis and outcomes of gliomas beyond established biomarkers. A higher abundance of glioma cells with high DDR effector expression across pathways is associated with poor survival. Thus, clinical assessment of pan-DDR expression may inform prognosis and identify potential therapeutic targets.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting TGFβ docking receptor Glycoprotein A Repetitions Predominant (GARP) via novel chimeric antigen receptor (CAR)-T cell platform to treat glioblastoma.","authors":"Bill Xingjun Wu, Daniel Kreatsoulas, Hakan Cam, Chelsea Bolyard, Yuzhou Chang, Jay Mandula, Parker W Welsh, Ziyu Wang, Anqi Li, Payton Weltge, J Bradley Elder, Pierre Giglio, Jose J Otero, Prajwal Rajappa, Damien Gerald, Dongjun Chung, Qin Ma, Maria Velegraki, Zihai Li I","doi":"10.1093/neuonc/noaf195","DOIUrl":"https://doi.org/10.1093/neuonc/noaf195","url":null,"abstract":"<p><strong>Background: </strong>Glycoprotein A-repetitions predominant (GARP) is a cell surface non-signaling receptor for docking and activating latent transforming growth factor beta (LTGFβ) expressed by regulatory T cells, platelets and tumor cells. In lung and breast cancers, its expression correlates with advanced stage and poor prognosis - suggesting that GARP could act as a therapeutic target. This study examines the therapeutic impact of targeting GARP in glioblastoma (GBM) via a novel anti-GARP chimeric antigen receptor-expressing T cell (CAR-T) modality in murine models of GBM.</p><p><strong>Methods: </strong>We examined multiple human glioma databases to correlate the expression of GARP with clinical outcomes. We then performed multi-plex imaging of human GBM samples to understand the impact of GARP expression on the tumor microenvironment (TME). Importantly, we developed a novel anti-GARP CAR-T cell strategy to treat GBM. We examine if this therapy is efficacious against orthotopic models of GBM, in both immunocompetent syngeneic and immunodeficient mice.</p><p><strong>Results: </strong>We demonstrate that elevated GARP expression in human GBM correlates with poor overall survival, mesenchymal subtype, and gene signatures associated with angiogenesis and immune exclusion in the TME. Our novel anti-GARP CAR-T is efficacious in vitro and in vivo, against multiple preclinical models of GBM including patient-derived xenograft (PDX) models without significant toxicity.</p><p><strong>Conclusions: </strong>GARP-LTGFβ plays a key role in the development and prognostics of GBM and GARP-targeted CAR-T therapy shows promising efficacy and safety in murine orthotopic GBM models. A first-in-human phase I clinical trial for patients with recurrent GBM began to enroll patients in May 2025 (NCT06964737).</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Intraoperative Genetic Analysis of Adult-type Diffuse Gliomas Using a Microfluidic Real-Time Polymerase Chain Reaction Device.","authors":"Sachi Maeda, Yotaro Kitano, Fumiharu Ohka, Kazuya Motomura, Kosuke Aoki, Shoichi Deguchi, Yoshiki Shiba, Masafumi Seki, Yuma Ikeda, Hiroki Shimizu, Kenichiro Iwami, Kazuhito Takeuchi, Yuichi Nagata, Junya Yamaguchi, Keisuke Kimura, Yuhei Takido, Ryo Yamamoto, Akihiro Nakamura, Shohei Ito, Keiko Shinjo, Yutaka Kondo, Shohei Miyagi, Kennosuke Karube, Ryuta Saito","doi":"10.1093/neuonc/noaf188","DOIUrl":"https://doi.org/10.1093/neuonc/noaf188","url":null,"abstract":"<p><strong>Background: </strong>The 5th edition of the World Health Organization Classification of Tumors of the Central Nervous System introduced a subclassification of tumors based on key molecular markers. In adult-type diffuse gliomas, isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter mutations play pivotal roles in the molecular classification. This study developed a rapid genotyping system using GeneSoC®, a real-time polymerase chain reaction (PCR) platform with microfluidic thermal cycling capable of completing 50 cycles of PCR within 20 min.</p><p><strong>Methods: </strong>To establish optimal analytical conditions, frozen tumor tissues from 67 patients and artificial DNA vectors were analyzed using this system. This system demonstrated a detection limit of at least 5% variant allele frequency for the IDH1 R132H and TERT promoter C228T/C250T mutations. Subsequently, intraoperative testing was performed in 120 cases using this system.</p><p><strong>Results: </strong>The sensitivity and specificity of IDH1 R132H mutation were 0.985 and 0.982, respectively, whereas those of TERT promoter C228T/C250T mutation were 1.000 and 1.000, respectively. These mutations were detected intraoperatively within approximately 25 min after tumor tissue collection. Furthermore, this assay identified tumor boundaries in an IDH-mutated glioma case, where IDH1 R132H mutations could not be detected.</p><p><strong>Conclusions: </strong>The GeneSoC®-based rapid genotyping system may be effective not only for intraoperative diagnosis of diffuse glioma but also for detecting tumor boundaries.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic stratification of newly diagnosed IDH-mutant gliomas by [18F]fluoroethyltyrosine and [11C]methionine PET - a retrospective, bicentric cohort study.","authors":"Maximilian J Mair, Jan-Michael Werner, Jonathan Weller, Enio Barci, Sophie Katzendobler, Jera Isakaj, Luzia Berchtold, Thedora Aras, Roman Stürzl, Juliane Hennenberg, Jonas Reis, Hannah C Puhr, Thomas Schabhüttl, Barbara Kiesel, Georg Widhalm, Adelheid Wöhrer, Thomas Nakuz, Marcus Hacker, Julia Furtner, Stephan Schönecker, Patrick N Harter, Louisa von Baumgarten, Anna S Berghoff, Niklas Thon, Matthias Preusser, Nathalie L Albert","doi":"10.1093/neuonc/noaf196","DOIUrl":"https://doi.org/10.1093/neuonc/noaf196","url":null,"abstract":"<p><strong>Background: </strong>Improved prognostic stratification including imaging-based parameters is needed to guide treatment decisions in IDH-mutant glioma.</p><p><strong>Methods: </strong>In this bicentric retrospective study, 457 patients with IDH-mutant glioma and [18F]fluoroethyltyrosine or [11C]methionine positron emission tomography (PET) prior to radiotherapy or systemic treatment were included. Associations of maximum and mean tumor-to-background ratios (TBRmax/TBRmean) and PET-positive volume (PET volume) with time to next intervention (TTNI) and overall survival (OS) were analyzed.</p><p><strong>Results: </strong>Overall, 251 (54.9%) patients with astrocytoma and 206 (45.1%) with oligodendroglioma were included. In patients with astrocytoma who underwent PET before resection, measurable disease according to PET RANO 1.0 criteria was associated with shorter TTNI compared to no/non-measurable disease (median 46.0 vs. 67.9 months; p=0.004). Univariable analysis showed an association of TTNI with TBRmax, TBRmean and PET volume in astrocytoma and PET volume in oligodendroglioma. Multivariable analyses including age, WHO grade, extent of resection, postoperative treatment and magnetic resonance imaging (MRI)-based tumor extent indicated an association of TTNI with TBRmax (HR 1.48 [95%CI: 1.09-2.01]) and TBRmean (HR 1.93 [95%CI: 1.14-3.27]) in astrocytoma and PET volume (HR [10 ml increase]: 1.18 [95%CI: 1.03-1.36]) in oligodendroglioma. In astrocytoma, also OS was related to TBRmax (HR: 1.40 [95%CI: 1.13-1.74]), TBRmean (HR: 1.97 [95%CI: 1.21-3.22]), and PET volume (HR: 1.23 [95%CI: 1.10-1.37]) in univariable analysis. Further analyses considering timepoint of PET showed consistent results.</p><p><strong>Conclusions: </strong>In this retrospective study, amino acid PET parameters were associated with outcome in newly diagnosed IDH-mutant glioma. Future clinical trials should include PET imaging to define imaging-based prognostic signatures.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, Radiological, and Molecular Insights into Extracranial Metastases from Adult Gliomas.","authors":"Julie Jacobsen, Alessio Locallo, Colm J O'Rourke, Jonathan F Carlsen, Jonathan Cohen, Jesper D Ewald, David Scheie, Kirsten Grunnet, Ane Y Schmidt, Linea C Melchior, Vibeke A Larsen, Jesper B Andersen, Hans S Poulsen, Joachim Weischenfeldt, Helle Broholm, Signe R Michaelsen, Bjarne W Kristensen","doi":"10.1093/neuonc/noaf178","DOIUrl":"https://doi.org/10.1093/neuonc/noaf178","url":null,"abstract":"<p><strong>Background: </strong>Extracranial metastases from adult gliomas cause diagnostic and therapeutic challenges and are generally poorly investigated. The aim of this study was to provide clinical and molecular insights into glioma metastasis.</p><p><strong>Methods: </strong>Our cohort consisted of tumor tissue from 16 glioma patients with metastasis (14 glioblastomas and 2 lower-grade gliomas). Paired primary tumors, recurrences, and metastases were investigated by DNA sequencing, genome-wide DNA methylation profiling, RNA sequencing, immunohistochemistry, and MRI examinations.</p><p><strong>Results: </strong>The metastases were distributed across scalp/upper neck (8), lymph nodes (5), bone (2), and liver (1). Six out of 14 glioblastomas displayed significant sarcomatous differentiation, consistent with the otherwise rare histological subtype gliosarcoma. A majority of the scalp lesions were connected to the intracranial brain tumor via tumor extension through craniotomy burr holes, proposing that surgery is a contributing factor to tumor spread. Next-generation sequencing-based mutational analysis revealed that the true metastases originated from the primary tumors and not later recurrences. We observed tumor plasticity as the tumors progressed to metastasis, demonstrated by changes in epigenetic methylation classes and transcriptional subtypes. Despite different locations of metastases in the cohort, the immune cell composition in the tumor microenvironment remained overall stable during tumor progression.</p><p><strong>Conclusion: </strong>Metastases from adult gliomas originates from the primary brain tumors and not later recurrences. While RNA sequencing and methylation profiling revealed tumor plasticity during progression to metastasis, the immune cell composition remained overall stable.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicenter basket trial for Central Nervous System tumors identifies activity of the CDK4/6 inhibitor abemaciclib in recurrent meningioma.","authors":"Thomas J Kaley, Christian Grommes, Elizabeth Coffee, Robert J Young, Tara Morrison, Ahmad Daher, Lauren R Schaff, Yufei Deng, Subhiksha Nandakumar, Eli L Diamond, Lisa M DeAngelis, Katherine S Panageas, Igor Gavrilovic, Andrew Lin, Elena Pentsova, Jacqueline Stone, Bianca D Santomasso, Anna F Piotrowski, Suresh Nair, Nikolaus Schultz, Anne S Reiner, Ingo K Mellinghoff","doi":"10.1093/neuonc/noaf184","DOIUrl":"https://doi.org/10.1093/neuonc/noaf184","url":null,"abstract":"<p><strong>Background: </strong>Central nervous system (CNS) tumors are associated with considerable morbidity and high mortality. Cyclin-dependent kinases (CDKs) regulate cell division in cancer, and CDK4/6 inhibitors are used for the treatment of breast cancer, representing an attractive therapy for different tumor types.</p><p><strong>Methods: </strong>Here, we report mature results of a multicenter basket trial exploring the CDK4/6 inhibitor abemaciclib in patients with recurrent CNS tumors, including patients with glioma, primary CNS lymphoma, meningioma, and ependymoma. We expanded our cohort of meningioma patients based on preliminary evidence for activity. Patients were treated with 200mg oral abemaciclib twice daily for days 1-28, following FDA recommendations for breast cancer. Primary outcomes included radiographic response rates and progression free survival (PFS) at 6 months post-treatment. We also evaluated overall survival (OS) and toxicity. Exploratory outcomes included next-generation sequencing of tumor biopsies.</p><p><strong>Results: </strong>Most cohorts did not demonstrate activity with the exception of the cohort of patients with recurrent meningioma, including patients with grade 2 or 3 disease (19/22 meningioma patients). In that group, the median PFS was 15 months (95% CI: 6.5, not reached) and median OS was 32.9 months (95% CI: 10.7, not reached), the 6-month PFS was 68.2% (95% CI: 51.3%, 90.7%). All 22 patients were evaluable for radiographic response, showing stable disease in 16/22 (73%) and progressive disease in 6/22 patients (27%).</p><p><strong>Conclusion: </strong>Our data suggests that abemaciclib improves PFS and OS in patients with advanced meningioma. The 6-month PFS with abemaciclib in this study (68.2%) exceeded RANO proposed benchmarks for activity (49%).Trial registration: NCT03220646.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting an old therapy for new, promising combinations: biology and perspectives of lomustine in glioma treatment.","authors":"Charlotte Bellamy, Cynthia Hajal, Keith L Ligon, Mehdi Touat","doi":"10.1093/neuonc/noaf192","DOIUrl":"10.1093/neuonc/noaf192","url":null,"abstract":"<p><p>The alkylating agents temozolomide (TMZ) and lomustine (CCNU) are the most effective systemic agents for malignant gliomas. However, resistance - whether intrinsic or acquired - inevitably develops in all patients, and these tumors remain incurable. Although CCNU has demonstrated clinical benefit, its clinical use has been relatively limited due to a less favorable safety profile compared to TMZ. Recently, interest in CCNU and other nitrosoureas has been renewed in light of positive clinical trials in both adult and pediatric gliomas. Despite this renewed attention, critical questions remain unaddressed regarding the use of nitrosoureas. While resistance and response to temozolomide have been associated with the status of both MGMT and the mismatch repair DNA repair pathway, our understanding of the unique mechanisms of resistance to nitrosoureas beyond MGMT remains limited. Recent advances in molecular biology, preclinical models and the use of longitudinal analyses of treated samples offer new insights, offering opportunities to refine the clinical and develop novel strategies. In this review, we explore the current role of nitrosoureas in glioma treatment, examine known and emerging mechanisms of sensitivity and resistance to these agents, and explore potential for combination approaches to enhance their efficacy.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioblastoma in Adults: A Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) Consensus Review on Current Management and Future Directions.","authors":"Patrick Y Wen, Michael Weller, Eudocia Q Lee, Mehdi Touat, Mustafa Khasraw, Rifaquat Rahman, Michael Platten, Michael Lim, Frank Winkler, Craig Horbinski, Roel G W Verhaak, Raymond Y Huang, Manmeet S Ahluwalia, Nathalie L Albert, Joerg-Christian Tonn, David Schiff, Jill S Barnholtz-Sloan, Quinn Ostrom, Kenneth D Aldape, Tracy T Batchelor, Ranjit S Bindra, E Antonio Chiocca, Timothy F Cloughesy, John F DeGroot, Pim French, Evanthia Galanis, Norbert Galldiks, Mark R Gilbert, Monika E Hegi, Andrew B Lassman, Emilie Le Rhun, Minesh P Mehta, Ingo K Mellinghoff, Giuseppe Minniti, Patrick Roth, Marc Sanson, Martin J B Taphoorn, Andreas von Deimling, Tobias Weiss, Wolfgang Wick, Gelareh Zadeh, David A Reardon, Susan M Chang, Susan C Short, Martin J van den Bent, Matthias Preusser","doi":"10.1093/neuonc/noaf177","DOIUrl":"10.1093/neuonc/noaf177","url":null,"abstract":"<p><p>Glioblastoma is the most common type of malignant primary brain tumor and a major cause of morbidity and mortality. In 2021 the World Health Organization updated the classification of Central Nervous System (CNS) tumors to restrict glioblastomas to isocitrate dehydrogenase-wildtype (IDHwt) tumors, improving understanding of the prognosis and optimal therapy for these tumors. This revision also enables more homogeneous populations of patients to be enrolled into clinical trials, facilitating the evaluation of novel therapies. In this updated consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of patients with glioblastoma is discussed. In addition, novel therapies such as immunotherapies, viral therapies, targeted molecular therapies, theranostics and antibody-drug conjugates will be reviewed, as well as the current challenges and future directions for research.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT3 expression in brain metastases from breast cancer is correlated with molecular subtype and impacts clinical outcome.","authors":"Alessia Pellerino, Neibla Priego, Luca Bertero, Alessia Andrea Ricci, Luca Mangherini, Francesco Bruno, Alessandra Beano, Gloria Mittica, Marinella Mistrangelo, Diego Garbossa, Joaquim Bosch-Barrera, Paola Cassoni, Renacer, Manuel Valiente, Riccardo Soffietti, Roberta Rudà","doi":"10.1093/neuonc/noaf187","DOIUrl":"https://doi.org/10.1093/neuonc/noaf187","url":null,"abstract":"<p><strong>Background: </strong>A high pSTAT3 expression in reactive astrocytes surrounding brain metastases (BrM) promotes tumor growth in preclinical models. The impact of STAT3 expression on outcome of patients with BrM from breast cancer is unknown.</p><p><strong>Methods: </strong>The expression of pSTAT3 in reactive astrocytes of 100 resected BrM from breast cancer was investigated by immunohistochemistry and correlated with molecular subtypes, risk of intracranial recurrence and progression-free survival. To explore whether clinical findings could be replicated in preclinical models, we used two human BrM cell lines (triple-negative MDA-231 and HER2-positive HCC1954-), and evaluated pSTAT3 expression on established BrM.</p><p><strong>Results: </strong>High pSTAT3 expression in reactive astrocytes was detected in 57% of BrM, and prevailed in triple-negative (80.9%) over HER2-positive (43.2%) and luminal (33.3%) metastases (p=0.002). A different pSTAT3 expression was confirmed in animal models: as it was detected in 50% of reactive astrocytes in triple negative MDA-231 BrM lesions compared with 13% in HER2-positive HCC1954 - BrM lesions (p=0.0001). Patients with high pSTAT3 expression in BrM displayed higher intracranial recurrence rate (66.7 vs 33.3%) (p=0.0353), and shorter intracranial PFS (9 months vs 28 months) (p=0.0002), and this finding was significant for triple-negative patients only (p=0.0008).</p><p><strong>Conclusions: </strong>This study indicates that STAT3 expression prevails in reactive astrocytes surrounding triple-negative BrM in comparison to HER2-positive and luminal BrM, and these findings mirror those observed in animal models. A high STAT3 expression correlates with higher risk of intracranial recurrence and shorter progression-free survival, particularly in patients with triple-negative BrM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Radiotherapy in MPNST and the Impact of NF1 Status on Outcomes: Insights From A Multicenter Cohort Study.","authors":"Christianne Y M N Jansma, Dirk J Grünhagen, Uta E Flucke, Willem-Bart M Slooff, Thijs van Dalen, Lukas B Been, Han J Bonenkamp, Monique H M E Anten, Martinus P G Broen, Marc H A Bemelmans, Jos A M Bramer, Gerard R Schaap, Arthur J Kievit, Winan J van Houdt, Jos van der Hage, Michiel A J van de Sande, Courtney Pendleton, Robert J Spinner, J Henk Coert, Cornelis Verhoef, Walter Taal, Enrico Martin","doi":"10.1093/neuonc/noaf186","DOIUrl":"https://doi.org/10.1093/neuonc/noaf186","url":null,"abstract":"<p><strong>Background: </strong>Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare, aggressive sarcomas, with 40% associated with neurofibromatosis type 1 (NF1). Surgical excision is the main treatment for localized disease, however, local recurrence (LR) remains high. Radiotherapy (RTx) is increasingly used to enhance local control in STS, but its use remains controversial due to the potential for increased major wound complications and an increased risk of secondary malignancies in NF1 patients. This study investigated the use and impact of RTx on local control in MPNSTs, particularly in the NF1 setting.</p><p><strong>Methods: </strong>Surgically treated primary MPNSTs from 1988 to 2019 in the MONACO multicenter cohort were included. Differences in demographics, treatment, and RTx use between NF1 and non-NF1 cases were examined. Factors influencing RTx administration and LR were assessed via multivariable analyses.</p><p><strong>Results: </strong>Among 499 patients (33.1% NF1), 143 (28.7%) experienced LRs. Radiotherapy was administered to 56.3% of patients (57.0% in the NF1 group), with 27.3% receiving neoadjuvant and 72.7% adjuvant RTx. RTx was administered significantly more often to high-grade and extremity tumors. While RTx did not affect overall survival, it reduced LR risk in sporadic cases (HR 0.530; 95% CI 0.354-0.793) but not in the NF1 subgroup (HR 1.00; 95% CI 0.545-1.85). In NF1 patients, a microscopically positive margin (R1) was the only risk factor for LR development (HR 2.1; 95% CI, 1.19-3.79).</p><p><strong>Conclusions: </strong>RTx is frequently used in the treatment of MPNSTs, regardless of NF1 status. While it may affect LR rate in sporadic cases, its impact in NF1 patients is less clear.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835885","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}