Neuro-oncology advances最新文献

{"title":"Plasma ctDNA liquid biopsy of IDH1, TERTp, and EGFRvIII mutations in glioma.","authors":"Jordan J Jones, Hong Nguyen, Stephen Q Wong, James Whittle, Josie Iaria, Stanley Stylli, James Towner, Thomas Pieters, Frank Gaillard, Andrew H Kaye, Katharine J Drummond, Andrew P Morokoff","doi":"10.1093/noajnl/vdae027","DOIUrl":"https://doi.org/10.1093/noajnl/vdae027","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor DNA has emerging clinical applications in several cancers; however, previous studies have shown low sensitivity in glioma. We investigated if 3 key glioma gene mutations <i>IDH1</i>, <i>TERTp</i>, and <i>EGFRvIII</i> could be reliably detected in plasma by droplet digital polymerase chain reaction (ddPCR) thereby demonstrating the potential of this technique for glioma liquid biopsy.</p><p><strong>Methods: </strong>We analyzed 110 glioma patients from our biobank with a total of 359 plasma samples (median 4 samples per patient). DNA was isolated from plasma and analyzed for <i>IDH1</i>, <i>TERTp</i>, and <i>EGFRvIII</i> mutations using ddPCR.</p><p><strong>Results: </strong>Total cfDNA was significantly associated with tumor grade, tumor volume, and both overall and progression-free survival for all gliomas as well as the grade 4 glioblastoma subgroup, but was not reliably associated with changes in tumor volume/progression during the patients' postoperative time course. <i>IDH1</i> mutation was detected with 84% overall sensitivity across all plasma samples and 77% in the preoperative samples alone; however, <i>IDH1</i> mutation plasma levels were not associated with tumor progression or survival. <i>IDH1m</i> plasma levels were not associated with pre- or postsurgery progression or survival. The <i>TERTp C228T</i> mutation was detected in the plasma ctDNA in 88% but the <i>C250T</i> variant in only 49% of samples. The <i>EGFRvIII</i> mutation was detected in plasma in 5 out of 7 patients (71%) with tissue <i>EGFRvIII</i> mutations in tumor tissue.</p><p><strong>Conclusions: </strong>Plasma ctDNA mutations detected with ddPCR provide excellent diagnostic sensitivity for <i>IDH1</i>, <i>TERTp-C228T</i>, and <i>EGFRvIII</i> mutations in glioma patients. Total cfDNA may also assist with prognostic information. Further studies are needed to validate these findings and the clinical role of ctDNA in glioma.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae027"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10989869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in chimeric antigen receptor-expressing T-cell therapy for glioblastoma multiforme: Literature review and future directions.","authors":"Michael Goutnik, Alexandria Iakovidis, Megan E H Still, Rachel S F Moor, Kaitlyn Melnick, Sandra Yan, Muhammad Abbas, Jianping Huang, Ashley P Ghiaseddin","doi":"10.1093/noajnl/vdae025","DOIUrl":"10.1093/noajnl/vdae025","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is an aggressive cancer that has been difficult to treat and often requires multimodal therapy consisting of surgery, radiotherapy, and chemotherapy. Chimeric antigen receptor-expressing (CAR-T) cells have been efficacious in treating hematological malignancies, resulting in several FDA-approved therapies. CAR-T cells have been more recently studied for the treatment of GBM, with some promising preclinical and clinical results. The purpose of this literature review is to highlight the commonly targeted antigens, results of clinical trials, novel modifications, and potential solutions for challenges that exist for CAR-T cells to become more widely implemented and effective in eradicating GBM.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae025"},"PeriodicalIF":3.7,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10939440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation landscapes in DIPG reveal methylome variability that can be modified pharmacologically.","authors":"Ashley R Tetens, Allison M Martin, Antje Arnold, Orlandi V Novak, Adrian Idrizi, Rakel Tryggvadottir, Jordyn Craig-Schwartz, Athanasia Liapodimitri, Kayleigh Lunsford, Michael I Barbato, Charles G Eberhart, Adam C Resnick, Eric H Raabe, Michael A Koldobskiy","doi":"10.1093/noajnl/vdae023","DOIUrl":"10.1093/noajnl/vdae023","url":null,"abstract":"<p><strong>Background: </strong>Diffuse intrinsic pontine glioma (DIPG) is a uniformly lethal brainstem tumor of childhood, driven by histone H3 K27M mutation and resultant epigenetic dysregulation. Epigenomic analyses of DIPG have shown global loss of repressive chromatin marks accompanied by DNA hypomethylation. However, studies providing a static view of the epigenome do not adequately capture the regulatory underpinnings of DIPG cellular heterogeneity and plasticity.</p><p><strong>Methods: </strong>To address this, we performed whole-genome bisulfite sequencing on a large panel of primary DIPG specimens and applied a novel framework for analysis of DNA methylation variability, permitting the derivation of comprehensive genome-wide DNA methylation potential energy landscapes that capture intrinsic epigenetic variation.</p><p><strong>Results: </strong>We show that DIPG has a markedly disordered epigenome with increasingly stochastic DNA methylation at genes regulating pluripotency and developmental identity, potentially enabling cells to sample diverse transcriptional programs and differentiation states. The DIPG epigenetic landscape was responsive to treatment with the hypomethylating agent decitabine, which produced genome-wide demethylation and reduced the stochasticity of DNA methylation at active enhancers and bivalent promoters. Decitabine treatment elicited changes in gene expression, including upregulation of immune signaling such as the interferon response, STING, and MHC class I expression, and sensitized cells to the effects of histone deacetylase inhibition.</p><p><strong>Conclusions: </strong>This study provides a resource for understanding the epigenetic instability that underlies DIPG heterogeneity. It suggests the application of epigenetic therapies to constrain the range of epigenetic states available to DIPG cells, as well as the use of decitabine in priming for immune-based therapies.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae023"},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10926944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specifics of spinal neuropathology in the molecular age.","authors":"Catena Kresbach, Karoline Hack, Franz Ricklefs, Ulrich Schüller","doi":"10.1093/noajnl/vdad127","DOIUrl":"10.1093/noajnl/vdad127","url":null,"abstract":"<p><p>Tumors located in the spinal cord and its coverings can be diagnostically challenging and require special consideration regarding treatment options. During the last decade, important advances regarding the molecular characterization of central and peripheral nervous system tumors were achieved, resulting in improved diagnostic precision, and understanding of the tumor spectrum of this compartment. In particular, array-based global DNA methylation profiling has emerged as a valuable tool to delineate biologically and clinically relevant tumor subgroups and has been incorporated in the current WHO classification for central nervous system tumors of 2021. In addition, several genetic drivers have been described, which may also help to define distinct tumor types and subtypes. Importantly, the current molecular understanding not only sharpens diagnostic precision but also provides the opportunity to investigate both targeted therapies as well as risk-adapted changes in treatment intensity. Here, we discuss the current knowledge and the clinical relevance of molecular neuropathology in spinal tumor entities.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 Suppl 3","pages":"iii3-iii12"},"PeriodicalIF":3.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Separation surgery for metastatic spine tumors: How less became more.","authors":"Xiaoran Zhang, Alexandra Giantini Larsen, Natasha Kharas, Mark H Bilsky, William Christopher Newman","doi":"10.1093/noajnl/vdae017","DOIUrl":"10.1093/noajnl/vdae017","url":null,"abstract":"<p><p>Metastatic epidural spinal cord compression (MESCC) is an increasingly common clinical entity in cancer patients and is associated with significant morbidity and neurologic sequalae. Management of MESCC has undergone many significant paradigms shifts over the past 50 years and was at times managed exclusively with either surgery or radiation. Historically, aggressive surgical techniques to achieve en bloc or intralesional gross tumor resections were pursued but were associated with significant morbidity and poor tumor control rates when combined with conventional external beam radiation. However, improvements in radiation treatment delivery in the form of stereotactic body radiation therapy have allowed for the safe delivery of high-dose conformal photon beam radiation providing histology-independent ablative responses. This shifted the goals of surgery away from maximal tumor resection toward simple spinal cord decompression with reconstitution of the thecal to create a tumor target volume capable of being irradiated within the constraints of spinal cord tolerance. This new approach of creating space between the thecal sac and the tumor was termed separation surgery and when combined with postoperative SBRT, it is referred to as hybrid therapy. Herein, we will describe the evolution of the management of MESCC, the technique of separation surgery and its outcomes, and finish with an illustrative case example.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 Suppl 3","pages":"iii94-iii100"},"PeriodicalIF":3.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal ependymal tumors.","authors":"Manfred Westphal, Malte Mohme","doi":"10.1093/noajnl/vdad138","DOIUrl":"10.1093/noajnl/vdad138","url":null,"abstract":"<p><p>Spinal ependymomas are strictly to be subdivided into intramedullary lesions and extramedullary lesions as they are histologically and genetically distinct. Whereas the intramedullary lesions (SPE) are assigned to the WHO grade 2 and very rarely grade 3, the extramedullary lesions or myxopapilary tumors (MPE) are only as recently also assigned to WHO grade 2. The major difference is that in general, an intramedullary lesion of grade 2 remains confined to the local site of origin, even when rarely recurring after complete resection. In contrast, the MPEs have the capacity to spread throughout the cerebrospinal fluid compartment but can also be controlled by cautious complete resection. We here review the clinical features of spinal ependymomas, contrasting the entities, and describe the treatment found best from the literature to manage these lesions including interdisciplinary approaches.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 Suppl 3","pages":"iii57-iii65"},"PeriodicalIF":3.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fractionated radiotherapy for spinal tumors: A literature review regarding spinal glioma, ependymoma, and meningioma.","authors":"Raphael Bodensohn, Erik Haehl, Claus Belka, Maximilian Niyazi","doi":"10.1093/noajnl/vdad158","DOIUrl":"10.1093/noajnl/vdad158","url":null,"abstract":"<p><p>Radiation therapy plays a vital role in the management of primary spinal tumors in adults. However, due to the rarity of these tumor types, the literature on optimal treatment indications and radiation doses is limited. Many treatment recommendations are extrapolated from their cranial counterparts, where more data are available. Despite the absence of prospective data, numerous retrospective studies have provided valuable insights to guide treatment decisions until more comprehensive data become available. This review provides an overview of the most relevant literature, with a specific focus on spinal gliomas, ependymomas, and meningiomas, in the context of the role of radiation therapy.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 Suppl 3","pages":"iii101-iii109"},"PeriodicalIF":3.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal cord hemangioblastomas in von Hippel-Lindau disease.","authors":"Daniel C Kreatsoulas, Russell R Lonser","doi":"10.1093/noajnl/vdad153","DOIUrl":"10.1093/noajnl/vdad153","url":null,"abstract":"<p><strong>Background: </strong>von Hippel-Lindau disease (VHL) is an autosomal dominant familial neoplasia syndrome. The most common manifestation of VHL is central nervous system hemangioblastomas. VHL patients will often develop multiple hemangioblastomas along their craniospinal axis over their lifetime. Spinal cord hemangioblastomas account for nearly half of all nervous system hemangioblastomas in VHL.</p><p><strong>Methods: </strong>The authors conducted a literature review and summation of available articles on spinal cord hemangioblastomas associated with VHL.</p><p><strong>Results: </strong>The embryological origins, epidemiology, natural history, surgical outcomes, nonsurgical treatments, and future directions in spinal cord hemangioblastomas are discussed.</p><p><strong>Conclusions: </strong>Hemangioblastomas in VHL are optimally managed with a multidisciplinary approach that includes surgical resection of symptomatic lesions. Novel treatments are gaining traction, but must be studied further for efficacy and safety.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 Suppl 3","pages":"iii66-iii72"},"PeriodicalIF":3.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Surgery versus radiosurgery for vestibular schwannoma: Shared decision making in a multidisciplinary clinic.","authors":"","doi":"10.1093/noajnl/vdae011","DOIUrl":"https://doi.org/10.1093/noajnl/vdae011","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/noajnl/vdad089.].</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae011"},"PeriodicalIF":0.0,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10838117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-nucleus expression characterization of non-enhancing region of recurrent high-grade glioma.","authors":"Kunal S Patel, Kaleab K Tessema, Riki Kawaguchi, Lindsey Dudley, Alvaro G Alvarado, Sree Deepthi Muthukrishnan, Travis Perryman, Akifumi Hagiwara, Vivek Swarup, Linda M Liau, Anthony C Wang, William Yong, Daniel H Geschwind, Ichiro Nakano, Steven A Goldman, Richard G Everson, Benjamin M Ellingson, Harley I Kornblum","doi":"10.1093/noajnl/vdae005","DOIUrl":"10.1093/noajnl/vdae005","url":null,"abstract":"<p><strong>Background: </strong>Non-enhancing (NE) infiltrating tumor cells beyond the contrast-enhancing (CE) bulk of tumor are potential propagators of recurrence after gross total resection of high-grade glioma.</p><p><strong>Methods: </strong>We leveraged single-nucleus RNA sequencing on 15 specimens from recurrent high-grade gliomas (<i>n</i> = 5) to compare prospectively identified biopsy specimens acquired from CE and NE regions. Additionally, 24 CE and 22 NE biopsies had immunohistochemical staining to validate RNA findings.</p><p><strong>Results: </strong>Tumor cells in NE regions are enriched in neural progenitor cell-like cellular states, while CE regions are enriched in mesenchymal-like states. NE glioma cells have similar proportions of proliferative and putative glioma stem cells relative to CE regions, without significant differences in % Ki-67 staining. Tumor cells in NE regions exhibit upregulation of genes previously associated with lower grade gliomas. Our findings in recurrent GBM paralleled some of the findings in a re-analysis of a dataset from primary GBM. Cell-, gene-, and pathway-level analyses of the tumor microenvironment in the NE region reveal relative downregulation of tumor-mediated neovascularization and cell-mediated immune response, but increased glioma-to-nonpathological cell interactions.</p><p><strong>Conclusions: </strong>This comprehensive analysis illustrates differing tumor and nontumor landscapes of CE and NE regions in high-grade gliomas, highlighting the NE region as an area harboring likely initiators of recurrence in a pro-tumor microenvironment and identifying possible targets for future design of NE-specific adjuvant therapy. These findings also support the aggressive approach to resection of tumor-bearing NE regions.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae005"},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11012612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}