Neuro-oncology最新文献

{"title":"European Association of Neuro-Oncology guideline on molecular testing of meningiomas for targeted therapy selection.","authors":"Felix Sahm, Luca Bertero, Sebastian Brandner, David Capper, Roland Goldbrunner, Michael D Jenkinson, Michel Kalamarides, Katrin Lamszus, Nathalie L Albert, Maximilian J Mair, Anna S Berghoff, Christian Mawrin, Hans-Georg Wirsching, Sybren L N Maas, David R Raleigh, Guido Reifenberger, Leonille Schweizer, Abigail K Suwala, Ghazaleh Tabatabai, Emeline Tabouret, Susan Short, Patrick Y Wen, Michael Weller, Emilie Le Rhun, Pieter Wesseling, Martin van den Bent, Matthias Preusser","doi":"10.1093/neuonc/noae253","DOIUrl":"10.1093/neuonc/noae253","url":null,"abstract":"<p><p>Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to a lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy, or radioligand therapy. Here, we review the evidence for a predictive role of a wide range of molecular alterations and markers including NF2, AKT1, SMO, SMARCE1, PIK3CA, CDKN2A/B, CDK4/6, TERT, TRAF7, BAP1, KLF4,ARID1/2, SUFU, PD-L1, SSTR2A, PR/ER, mTOR, VEGF(R), PDGFR, as well as homologous recombination deficiency, genomic copy number variations, DNA methylation classes, and combined gene expression profiles. In our assessment based on the established ESMO ESCAT (European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets) evidence-level criteria, no molecular target reached ESCAT I (\"ready for clinical use\") classification, and only mTOR pathway activation and NF2 alterations reached ESCAT II (\"investigational\") classification, respectively. Our evaluations may guide targeted therapy selection in clinical practice and clinical trial efforts and highlight areas for which additional research is warranted.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"869-883"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693323","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}

{"title":"Using a pre-radiation window to identify potentially active cytotoxic agents in adults with newly diagnosed glioblastoma.","authors":"Danielle A Bazer, Antonio C Wolff, Stuart A Grossman","doi":"10.1093/neuonc/noae240","DOIUrl":"10.1093/neuonc/noae240","url":null,"abstract":"<p><p>Therapies shown to improve outcomes in patients with recurrent cancers are commonly used in the neoadjuvant setting to optimize surgery, reduce radiation fields, and treat micrometastatic disease. While the use of pre-radiation chemotherapy (PRC) has flourished in systemic cancers, it has not seen the same level of use in glioblastomas. This review documents these trajectories and highlights the potential of PRC to rapidly and safely screen cytotoxic drugs for efficacy in patients with newly diagnosed glioblastoma. Prospective trials of adults with newly diagnosed systemic and brain cancers treated with PRC published between 1980 and 2023 were identified in PubMed. The National Comprehensive Cancer Network guidelines were used to document the standard use of PRC in patients with systemic and brain cancers. Over 5000 prospective PRC trials in solid tumors were identified. These accrued  >1 million patients and resulted in neoadjuvant therapies being the standard of care in ~28 systemic cancers. Only 50 similar trials (2206 patients) were identified in high-grade gliomas. In 13 trials containing PRC temozolomide (n = 846), radiographic responses ranged from 6 to 53% with a median survival of ~13 months. Glioblastoma PRC trials were not associated with unexpected toxicities or major negative impacts on survival. Pre-radiation chemotherapy in patients with glioblastoma appears safe and feasible. The pre-radiation window is ideally suited to rapidly screen cytotoxic agents for efficacy. It permits radiographic response as a primary outcome, small sample sizes, and initiation of standard therapies a few months after diagnosis. Pre-radiation chemotherapy may be most appropriate for patients with glioblastoma who are unlikely to benefit from temozolomide.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"884-896"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625060","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}

{"title":"A field resource for the glioma cerebrospinal fluid proteome: Impacts of resection and location on biomarker discovery.","authors":"Cecile Riviere-Cazaux, Christopher J Graser, Arthur E Warrington, Matthew D Hoplin, Katherine M Andersen, Noor Malik, Elizabeth A Palmer, Lucas P Carlstrom, Surendra Dasari, Amanda Munoz-Casabella, Samar Ikram, Keyvan Ghadimi, Benjamin T Himes, Ignacio Jusue-Torres, Jann N Sarkaria, Fredric B Meyer, Jamie J Van Gompel, Sani H Kizilbash, Ugur Sener, Franziska Michor, Jian L Campian, Ian F Parney, Terry C Burns","doi":"10.1093/neuonc/noae277","DOIUrl":"10.1093/neuonc/noae277","url":null,"abstract":"<p><strong>Background: </strong>While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown.</p><p><strong>Methods: </strong>Aptamer-based proteomics was performed on 147 CSF samples from 74 patients; 71 of whom had grade 2-4 astrocytomas or grade 2-3 oligodendrogliomas. This included pre- versus post-resection intracranial CSF samples obtained at early (1-16 days; n = 20 patients) or delayed (86-153 days; n = 11 patients) time points for patients with glioma. Paired lumbar versus intracranial glioma CSF samples were also obtained (n = 14 patients).</p><p><strong>Results: </strong>Significant differences were identified in the CSF proteome between lumbar, subarachnoid, and ventricular CSF in patients with gliomas. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome, with distinct sets of proteins present at different time points since resection. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, such as bevacizumab and immunotherapies.</p><p><strong>Conclusions: </strong>The intracranial glioma CSF proteome serves as a rich and dynamic reservoir of potential biomarkers that can be used to evaluate the effects of resection and other therapies over time. All data within this study, including detailed individual clinical annotations, are shared as a resource for the neuro-oncology community to collectively address these unanswered questions and further understand glioma biology through CSF proteomics.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"948-962"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952454","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}

{"title":"VGLL fusions define a new class of intraparenchymal central nervous system schwannoma.","authors":"Simone Schmid, Kanish Mirchia, Anna Tietze, Ilon Liu, Christin Siewert, Jakob Nückles, Jens Schittenhelm, Felix Behling, Matija Snuderl, Christian Hartmann, Sebastian Brandner, Simon M L Paine, Andrey Korshunov, Martin Hasselblatt, Roland Coras, Sridhar Epari, Christine Stadelmann, Sabrina Zechel, Michèle Simon, Yelena Wilson, Francesca Gianno, Calixto-Hope G Lucas, Viktor Zherebitskiy, Vassil B Kaimaktchiev, Lorraina Robinson, Kenneth Aldape, Eelco W Hoving, Bastiaan B J Tops, Ashwyn Augustine Perera, Pauline Göller, Pablo Hernáiz Driever, Pieter Wesseling, Arend Koch, Arie Perry, Felix Sahm, David T W Jones, David Capper","doi":"10.1093/neuonc/noae269","DOIUrl":"10.1093/neuonc/noae269","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the central nervous system (CNS). They are not classified as a separate tumor type in the 2021 World Health Organization classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.</p><p><strong>Methods: </strong>We analyzed 20 tumor samples by histology, RNA next-generation sequencing, DNA-methylation profiling, copy number analyses, and single-nucleus RNA sequencing (snRNA-seq). Clinical data, including age, sex, and disease progression, were collected. Magnetic resonance imaging (MRI) series were included when available.</p><p><strong>Results: </strong>All cases with tissue available for histology review (n = 13) were morphologically consistent with intracerebral schwannoma, but differed in their extent of glial fibrillary acidic protein staining. All (n = 20) shared DNA-methylation profiles distinct from other CNS tumors, as well as from Vestigial-like family (VGLL)-altered peripheral nerve sheath tumors. Most cases (n = 14/17) harbored fusions of either Vestigial-like family member 3 (VGLL3) or Vestigial-like Family member 1 (VGLL1) (CHD7::VGLL3 [n = 9/17] and EWSR1::VGLL1 [n = 5/17]). In 2 cases, the presence of a VGLL3 fusion was also confirmed by copy number analyses (n = 2/17). MRI (n = 4) showed well-defined, nodular tumors with strong, homogeneous enhancement and no diffusion restriction. Tumors were located throughout the neuroaxis (supratentorial [n = 15], infratentorial [n = 4], and spinal [n = 1]). snRNA-seq of a VGLL1-fused tumor indicated VGLL1 upregulation in 28.6% of tumor cells (n = 1). During a median follow-up of 1.8 years (range 3 months-9 years), none of the tumors recurred (n = 10).</p><p><strong>Conclusions: </strong>We identify and define a new benign tumor class, designated VGLL-altered intraparenchymal CNS schwannomas. These tumors feature VGLL alterations and a specific DNA-methylation profile, with schwannoma-like histopathology and CNS localization, akin to previously classified intracerebral schwannomas.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1031-1045"},"PeriodicalIF":16.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877550","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}

{"title":"Decoding the Cancer Cell Proteome: A Delicate Equilibrium with the Genome and Epigenome.","authors":"Ryan J Duchatel, Javad Nazarian","doi":"10.1093/neuonc/noaf120","DOIUrl":"https://doi.org/10.1093/neuonc/noaf120","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012976","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":"Novel PET RANO BM 1.0 criteria: Regulatory perspectives on new endpoint definitions in brain metastases.","authors":"Francesco Pignatti, Ralf Herold, Pierre Demolis, Ulrich-Peter Rohr","doi":"10.1093/neuonc/noaf067","DOIUrl":"https://doi.org/10.1093/neuonc/noaf067","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034873","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":"Consortium trial demonstrates efficacy of Selumetinib in pediatric low-grade glioma.","authors":"Anirban Das","doi":"10.1093/neuonc/noaf119","DOIUrl":"https://doi.org/10.1093/neuonc/noaf119","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020751","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":"Multiomic profiling of glioblastoma metabolic lesions reveals complex intratumoral genomic evolution and dipeptidase-1-driven vascular proliferation.","authors":"Atul Anand, Jeanette Krogh Petersen, Lars van Brakel Andersen, Mark Burton, Clara Rosa Levina Oudenaarden, Martin Jakob Larsen, Philip Ahle Erichsen, Christian Bonde Pedersen, Frantz Rom Poulsen, Peter Grupe, Torben A Kruse, Mads Thomassen, Bjarne Winther Kristensen","doi":"10.1093/neuonc/noaf071","DOIUrl":"https://doi.org/10.1093/neuonc/noaf071","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma undergoes a complex and dynamic evolution involving genetic and epigenetic changes. Understanding the mechanisms underlying this evolution is vital for the development of efficient therapeutic strategies. Although treatment resistance is associated with intratumoral heterogeneity in glioblastoma, it remains uncertain whether hypometabolic and hypermetabolic lesions observed through clinical positron emission tomography (PET) imaging are influenced by spatial intratumoral genomic evolution.</p><p><strong>Methods: </strong>In this study, we precisely isolated autologous hypometabolic and hypermetabolic lesions from glioblastoma using advanced neurosurgical and brain tumor imaging technologies, followed by comprehensive whole-genome, exome, transcriptome, and imaging analyses.</p><p><strong>Results: </strong>Our findings unveil that hypermetabolic lesions, originating from hypometabolic lesions, exhibit strategic focal amplifications and deletions, and heightened APOBEC3 activity. Furthermore, we identify dipeptidase 1 as a novel vascular endothelial tip marker for hypermetabolic lesions in glioblastoma, facilitating angiogenesis and tumor metabolism by regulating transporter activities.</p><p><strong>Conclusions: </strong>Hypermetabolic lesions are associated with a higher frequency of genomic abnormalities and dipeptidase 1 emerges as a novel diagnostic and prognostic vascular marker for hypermetabolic lesions. This study underscores a spatial genomic evolution with diagnostic implications and elucidates challenges and opportunities crucial for the development of novel therapeutic strategies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030227","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":"Radiotherapy-Induced Neurocognitive Decline among Adult Intracranial Tumor Patients: A Voxel-Based approach.","authors":"Charlotte Sleurs, Catharina M L Zegers, Marvin F Ribeiro, Wouter van Elmpt, Jeanette Dijkstra, Alida A Postma, Laurien De Roeck, Karin Gehring, Wouter De Baene, Margriet M Sitskoorn, Maarten Lambrecht, Daniëlle B P Eekers","doi":"10.1093/neuonc/noaf114","DOIUrl":"https://doi.org/10.1093/neuonc/noaf114","url":null,"abstract":"<p><strong>Background: </strong>Cranial irradiation is a key component of neuro-oncological treatment, but can result in cognitive side effects. Preserving cognition from radiotherapy-(RT)-induced toxicity remains an ongoing debate. To spatially map radiotoxic effects in patients who underwent cranial RT, this study applied a voxel-based approach.</p><p><strong>Methods: </strong>Cognitive assessments (Controlled Word Association (COWA), Hopkins Verbal Learning (HVLT-R), and Trail Making Tests (TMT A,B)) were conducted prospectively before, 6months and 1year post-RT in 111 intracranial tumor patients (18-80years). Reliable change indices indicated cognitive changes across timepoints. CT and T1-weighted MRI scans acquired at diagnosis were co-registered, normalized to standard space, and smoothed. Voxel-wise permutation-based regression analyses examined the relationship between RT dose and cognitive decline (α<.05 at cluster level).</p><p><strong>Results: </strong>Images of 111 patients (Mdn age = 55.39 years; 47% male; lesions were gliomas (61%), meningiomas (18%), other (21%); in frontal (33%), temporal (25%), other location (42%)) were analyzed. Reliable decline was most pronounced at 6months, particularly on the TMT A (25.77%), TMT B (24.21%), and HVLT immediate recall (21%). At 1year, 20% of patients continued to show decline in TMT B. Higher RT doses to frontal gyri, temporal, occipital, and para-central regions were associated with declines in verbal fluency, memory, processing speed, and flexibility at both peak- and cluster-level.</p><p><strong>Conclusion: </strong>Differential voxel-wise RT dose effects at peak versus cluster level suggest local and network-based recruitment of diverse functional regions and vulnerability to cranial RT. These insights may help re-define key regions at risk from a network-based perspective, preserving cognition in future RT planning.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038444","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":"Response Assessment in Neuro-Oncology (RANO) 2009-2025: Broad Scope and Implementation - A Progress Report.","authors":"Martin J van den Bent, Michael A Vogelbaum, Tim Cloughesy, Norbert Galldiks, Nathalie L Albert, Joerg-Christian Tonn, Edward Avila, Jason Fangusaro, David Mirsky, Arjun Sahgal, Ricardo Soffietti, Philipp Karschnia, Minesh Mehta, Michelle M Kim, Florien Boele, Jason T Huse, Lakshmi Nayak, Mary Jane Lim-Fat, Emilie le Rhun, Annick Desjardins, Eudocia Q Lee, Ugonma Chukwueke, Johan A F Koekkoek, Tito Mendoza, Ashlee R Loughan, Joshua A Budhu, Spyridon Bakas, Raymond Y Huang, Javier E Villanueva-Meyer, Jose Pablo Leone, Hideho Okada, David A Reardon, Wenya L Bi, Patrick Y Wen, Susan M Chang","doi":"10.1093/neuonc/noaf118","DOIUrl":"https://doi.org/10.1093/neuonc/noaf118","url":null,"abstract":"<p><p>Since its first activities in 2008 and 2009, the Response Assessment in NeuroOncology (RANO) group has given guidance on response assessment, trial design and trial procedures in order to improve and standardize the way clinical trials in neurooncological studies are performed. To achieve its objectives, a variety of working groups have been initiated that cover many aspects of clinical trial design and outcome assessment in patients with tumors affecting the Central Nervous System. The RANO working groups are built on expertise without a formal structure, which makes rapid responses to new developments possible. RANO is aiming at evidence based guidelines and recommendations, but in the absence of evidence will provide consensus based guidance achieved by inviting recognized international experts. In its 15 year of existence, more than 60 RANO papers have been published mostly in high ranking journals, and its recommendations have been accepted by regulators and industry as guiding principes. RANO organizes two meetings per year, one in conjunction with the annual American Society for Clinical Oncology (ASCO) meeting, and one during the annual Society for Neuro-Oncology meeting. These meetings are open, as are the working groups of RANO. New initiatives are welcomed.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026390","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}