Neuro-oncology最新文献

{"title":"Final Report on NCCTG N0877 (Alliance): A Phase II Randomized, Placebo-Controlled Trial of Chemoradiotherapy with or without Dasatinib for Glioblastoma.","authors":"William G Breen, J G Dixon, S K Anderson, J N Sarkaria, P D Brown, E S Yan, S Kizilbash, E Galanis, Daniel Anderson, David Tran, Miroslaw Mazurczak, Derek R Johnson, F J Geoffroy, Clinton Leinweber, N N Laack","doi":"10.1093/neuonc/noaf156","DOIUrl":"https://doi.org/10.1093/neuonc/noaf156","url":null,"abstract":"<p><strong>Background: </strong>Dasatinib is an oral inhibitor of the Src kinase family, with preclinical data indicating impact on gliomagenesis, tumor invasion, and radiosensitivity.</p><p><strong>Methods: </strong>NCCTG N0877 is a phase 1 dose escalation and phase II randomized study evaluating the maximum tolerated dose (MTD), safety, and efficacy of dasatinib with radiation and temozolomide (TMZ) for glioblastoma. Following identification of the MTD, adult patients with a histologic diagnosis of glioblastoma were randomized 2:1 between dasatinib given with standard concurrent and adjuvant TMZ, versus placebo with standard concurrent and adjuvant TMZ. Radiation dose was 60 Gy in 30 fractions. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), toxicity, and quality of life.</p><p><strong>Results: </strong>Thirteen patients were enrolled on the phase I component and established the MTD and phase II dose of 150 mg given daily. A total of 204 patients were enrolled on the phase II component. OS was not different between arms (median OS 15.6 months for dasatinib compared to 19.3 months for placebo, hazard ratio:1.21 favoring placebo, 95% CI: 0.88-1.65, logrank p-value: 0.238). Similarly, PFS was not significantly different between dasatinib and placebo arms. There was significantly increased anemia, nausea, and creatinine elevation with dasatinib, but significantly more grade 3 lymphopenia with placebo.</p><p><strong>Conclusions: </strong>The addition of dasatinib to standard chemoradiation did not improve outcomes for patients with glioblastoma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529079","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":"CAF-derived LRRC15 orchestrates macrophage polarization and limits PD-1 immunotherapy efficacy in glioblastoma.","authors":"Feifei Luo, Yan Mei, Yanwen Li, Jiahao Yang, Shaoyan Xi, Endong Cao, Cong Shen, Dexiang Zhou, Peng Wang, Dong Zhou, Haiping Cai","doi":"10.1093/neuonc/noaf157","DOIUrl":"https://doi.org/10.1093/neuonc/noaf157","url":null,"abstract":"<p><strong>Background: </strong>The effectiveness of PD-1/PD-L1 immune checkpoint blockade therapy in glioblastoma (GBM) is limited due to the tumor immunosuppressive microenvironment (TIME). Therefore, strategies of reprogramming TIME to a proinflammatory state offers a promising therapeutic approach.</p><p><strong>Methods: </strong>We applied bioinformatics analysis of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (stRNA-seq) to identify a significant accumulation of a cancer-associated fibroblasts (CAFs) subcluster with elevated LRRC15 expression in the nonresponders to anti-PD-1 therapy. Molecular mechanism of LRRC15 were functionally validated in vitro and in vivo.</p><p><strong>Results: </strong>These CAFs subcluster drive the infiltration of macrophages (Mφ) into the tumor microenvironment and promote their polarization toward the M2 phenotype. Deletion of Lrrc15 in CAFs significantly restrained tumor growth and prolonged survival in mouse models. Mechanistically, LRRC15 in CAFs promotes IL8 expression by activating the downstream FAK/SRC/NF-κB pathways, leading to Mφ migration and M2-like polarization. In turn, M2-like Mφs secrete TGF-β, which induces LRRC15 expression in CAFs via SMAD2-dependent transcriptional activation. Targeting CAFs subcluster with elevated LRRC15 expression in combination with anti-PD-1 treatment enhanced antitumor efficacy.</p><p><strong>Conclusions: </strong>Our findings suggest that targeting LRRC15 may provide a novel strategy to augment anti-PD-1 therapy and overcome immunotherapy resistance in GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497561","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":"Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.","authors":"Shoma Tsubota, Daniel R Carter, Janith A Seneviratne, Haruka Hirose, Teppei Shimamura, Yukie Kashima, Yutaka Suzuki, Koji Tsuda, Glenn M Marshall, Kenji Kadomatsu","doi":"10.1093/neuonc/noaf129","DOIUrl":"https://doi.org/10.1093/neuonc/noaf129","url":null,"abstract":"<p><strong>Background: </strong>Understanding the factors that determine the spontaneous regression of pre-cancerous lesions is critical to advancing cancer prevention. Neuroblastoma, a pediatric cancer, undergoes spontaneous regression more frequently than other types of cancer.</p><p><strong>Methods: </strong>Here, we analyzed the transcriptomic features of spontaneous regression in pre-cancerous neuroblasts using Th-MYCN mice, an animal model that closely resembles human neuroblastoma. Single-cell transcriptomic analysis of ganglion tissues from Th-MYCN mice was conducted to elucidate the cellular and molecular underpinnings.</p><p><strong>Results: </strong>Trajectory analysis of pre-cancerous neuroblasts revealed a distinct subtype we designated as \"uncommitted\" cells, characterized by the expression of neuronal genes, indicative of a semi-differentiated state. Samples with predicted failed tumorigenesis had a greater proportion of these uncommitted cells, hinting at their association with spontaneous regression. In clinical specimens, heightened uncommitted gene expression corresponded with favorable neuroblastomas and an improved prognosis.</p><p><strong>Conclusion: </strong>Collectively, the identification of this novel neuroblastoma-related cell subtype and its transcriptomic signature not only enhances our understanding of spontaneous regression mechanisms but also holds potential for therapeutic advancements in treating neuroblastomas.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529082","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":"Practical and statistical aspects of subgroup analyses in surgical neuro-oncology: A comprehensive review from the PIONEER consortium.","authors":"Jasper K W Gerritsen, Philipp Karschnia, Jacob S Young, Martin J van den Bent, Susan M Chang, Timothy R Smith, Brian V Nahed, Jordina Rincon-Torroella, Chetan Bettegowda, Nader Sanai, Sandro M Krieg, Takashi Maruyama, Philippe Schucht, Marike L D Broekman, Joerg-Christian Tonn, Patrick Y Wen, Steven De Vleeschouwer, Arnaud J P E Vincent, Shawn Hervey-Jumper, Mitchel S Berger, Rania A Mekary, Annette M Molinaro","doi":"10.1093/neuonc/noae261","DOIUrl":"10.1093/neuonc/noae261","url":null,"abstract":"<p><p>Subgroup analyses are essential to generate new hypotheses or to estimate treatment effects in clinically meaningful subgroups of patients. They play an important role in taking the next step toward personalized surgical treatment for brain tumor patients. However, subgroup analyses must be used with consideration and care because they have significant potential risks. Although some recommendations are available on the pearls and pitfalls of these analyses, a comprehensive guide is lacking, especially one focused on surgical neuro-oncology patients. This paper, therefore, reviews and summarizes for the first time comprehensively the practical and statistical considerations that are critical to this field. First, we evaluate the considerations when choosing a study design for surgical neuro-oncology studies and examine those unique to this field. Second, we give an overview of the relevant aspects to interpret subgroup analyses adequately. Third, we discuss the practical and statistical elements necessary to appropriately design and use subgroup analyses. The paper aims to provide an in-depth and complete guide to better understand risk modeling and assist the reader with practical examples of designing, using, and interpreting subgroup analyses.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1149-1164"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807659","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":"Autophagy modulates glioblastoma cell sensitivity to Selinexor-mediated XPO1 inhibition.","authors":"Yongjian Tang, Lisa Sprinzen, Yukinori Terada, Karrie M Kiang, Chuntao Li, Yu Zeng, Fangkun Liu, Hongshu Zhou, Xisong Liang, Jianzhong Zhang, Russell O Pieper, Bo Chen, Liyang Zhang","doi":"10.1093/neuonc/noae280","DOIUrl":"10.1093/neuonc/noae280","url":null,"abstract":"<p><strong>Background: </strong>Selinexor is a selective inhibitor of exportin-1 (XPO1), a key mediator of the nucleocytoplasmic transport for molecules critical to tumor cell survival. Selinexor's lethality is generally associated with the induction of apoptosis, and in some cases, with autophagy-induced apoptosis. We performed this study to determine Selinexor's action in glioblastoma (GBM) cells, which are notoriously resistant to apoptosis.</p><p><strong>Methods: </strong>Patient-derived GBM cells were treated with Selinexor, and drug response and autophagy levels were monitored. Homozygous C528S XPO1 mutant GBM43 cells were generated by CRISPR/Cas9 editing. Single Selinexor or combination treatment with autophagy inhibitors was evaluated. In addition, bulk-tissue, single-cell, and spatial transcriptome were analyzed, and molecular docking was performed.</p><p><strong>Results: </strong>Although all cell lines exhibited a dose- and time-dependent reduction of cell viability, the most profound molecular response to Selinexor was induction of autophagy instead of apoptosis. Selinexor-induced autophagy was an on-target consequence of XPO1 inhibition, and could be mitigated by expression of a mutant, Selinexor-resistant form of XPO1, and Selinexor-induced autophagy was related at least in part to nuclear trapping of the transcription factor TFEB. Furthermore, genetic or pharmacologic suppression of autophagy sensitized the cells to Selinexor-induced toxicity in association with the induction of apoptosis. Finally, in intracranial PDX studies, the combination of Selinexor with the autophagy inhibitor chloroquine significantly impeded tumor growth and extended mouse survival relative to single-agent treatment.</p><p><strong>Conclusion: </strong>These results suggest that activation of autophagy confers a protective mechanism against Selinexor in GBM cells, and that the combination of Selinexor with autophagy inhibitors may serve as a viable means to enhance Selinexor-induced cell death.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1210-1226"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896331","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":"Development and validation of a molecular classifier of meningiomas.","authors":"Alexander P Landry, Justin Z Wang, Jeff Liu, Vikas Patil, Chloe Gui, Zeel Patel, Andrew Ajisebutu, Yosef Ellenbogen, Qingxia Wei, Olivia Singh, Julio Sosa, Sheila Mansouri, Christopher Wilson, Aaron A Cohen-Gadol, Mohamed A Zaazoue, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Jill S Barnholtz-Sloan, Andrew E Sloan, Silky Chotai, Lola B Chambless, Alexander D Rebchuk, Serge Makarenko, Stephen Yip, Alireza Mansouri, Derek S Tsang, Kenneth Aldape, Andrew Gao, Farshad Nassiri, Gelareh Zadeh","doi":"10.1093/neuonc/noae242","DOIUrl":"10.1093/neuonc/noae242","url":null,"abstract":"<p><strong>Background: </strong>Meningiomas exhibit considerable clinical and biological heterogeneity. We previously identified 4 distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, and proliferative) that address much of this heterogeneity. Despite the utility of these groups, the stochasticity of clustering methods and the use of multi-omics data for discovery limits the potential for classifying prospective cases. We sought to address this with a dedicated classifier.</p><p><strong>Methods: </strong>Using an international cohort of 1698 meningiomas, we constructed and rigorously validated a machine learning-based molecular classifier using only DNA methylation data as input. Original and newly predicted molecular groups were compared using DNA methylation, RNA sequencing, copy number profiles, whole-exome sequencing, and clinical outcomes.</p><p><strong>Results: </strong>We show that group-specific outcomes in the validation cohort are nearly identical to those originally described, with median progression-free survival (PFS) of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Tumors classified as NF2-wildtype had no NF2 mutations, and 51.4% had canonical mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group, and cell cycle programs in the proliferative group. Bulk deconvolution similarly revealed the enrichment of macrophages in immunogenic tumors and neoplastic cells in hypermetabolic and proliferative tumors with similar proportions to those originally described.</p><p><strong>Conclusions: </strong>Our DNA methylation-based classifier, which is publicly available for immediate clinical use, recapitulates the biology and outcomes of the original molecular groups as assessed using multiple metrics/platforms that were not used in its training.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1258-1269"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952456","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":"Therapeutic effect of novel drug candidate, PRG-N-01, on NF2 syndrome-related tumor.","authors":"Yeon-Ho Chung, Soyoung Park, Moonyoung Lee, Jongwon Lee, Yeongseon Ji, Yi Jin Song, Tae-Gyun Woo, Eunbyeol Shin, Songyoung Baek, Young Jun Hwang, Yuju Kim, Minju Kim, Jin Han, Hong-Rae Kim, Jungmin Choi, Bae-Hoon Kim, Bum-Joon Park","doi":"10.1093/neuonc/noae282","DOIUrl":"10.1093/neuonc/noae282","url":null,"abstract":"<p><strong>Background: </strong>NF2-related schwannomatosis (NF2-SWN) is associated with multiple benign tumors in the nervous system. NF2-SWN, caused by mutations in the NF2 gene, has developed into intracranial and spinal schwannomas. Because of the high surgical risk and frequent recurrence of multiple tumors, targeted therapy is necessary. However, there are no approved drugs.</p><p><strong>Methods: </strong>We examined the action mechanism of PRG-N-01, a candidate molecule for NF2-SWN, through the direct binding assay and mass spectrometry. For in vitro anti-proliferative experiments, primary cells derived from the NF2 mouse model and patient tumors were treated with PRG-N-01. The in vivo therapeutic and preventive efficacy was validated via intraperitoneal and oral administration in the NF2 mouse model (Postn-Cre; Nf2f/f). Gene expression profile in the DRG of the mouse model was explored by RNA sequencing. The pharmacological properties of PRG-N-01 were analyzed through the preclinical study.</p><p><strong>Results: </strong>PRG-N-01 binds to the N-terminal extremity of TGFβR1 (TβR1) kinase domain, where TβR1 and RKIP interact, inhibiting the binding and preventing degradation of RKIP. In vivo administration in the mouse model suppressed schwannoma progression in the DRG. Early oral administration of the PRG-N-01 also demonstrated preventive effects on NF2-SWN. PRG-N-01 treatment suppressed tumor growth genes while upregulating genes related to for normal cell metabolism and Schwann cell differentiation in DRG. PRG-N-01 showed druggable properties through the preclinical study, including ADME, pharmacodynamics, pharmacokinetics, and toxicology.</p><p><strong>Conclusions: </strong>Together, our study provides the rationale and critical data for a prospective clinical trial of PRG-N-01 in NF2-SWN patients indicating PRG-N-01 as a promising candidate for the treatment.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1241-1255"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896324","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":"Molecular subtypes of adamantinomatous craniopharyngiomas.","authors":"Wenhao An, Shouwei Li, Yihua An, Zhixiong Lin","doi":"10.1093/neuonc/noaf030","DOIUrl":"10.1093/neuonc/noaf030","url":null,"abstract":"<p><p>Adamantinomatous craniopharyngioma (ACP) is the most common benign tumor in the sellar region of children and originates from embryonic remnants. Owing to its unique location and frequent tight adhesion to and invasion of surrounding structures, the ACP poses significant challenges for neurosurgical treatment. Traditionally, the core treatment for ACPs has been surgical resection supplemented with radiotherapy in cases of residual or recurrent tumors. As a result, ACP classification has been based primarily on the tumor's relationship with surrounding anatomical and histological structures, guiding the selection of surgical approaches and the prevention of complications. Moreover, efforts to explore pharmacological treatments for ACP have yielded varying results across different cases, creating confusion among researchers. This variability also suggests the possibility of different molecular subtypes within ACPs, despite being driven by a single-gene mutation. With advancements in molecular biological studies, such as ACP RNA sequencing, whole-exome sequencing, and methylation analysis, along with the discovery of interactions between different molecular pathways within ACP, researchers have been continuously exploring the molecular subtyping of ACP and predicting the efficacy of targeted therapies on the basis of these subtypes. This review focuses on summarizing and synthesizing the molecular mechanisms and potential subtypes of ACP, aiming to provide theoretical support for future research on the molecular subtyping of ACP.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1180-1192"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080841","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":"When machines start examining tissue specimens on their own.","authors":"Manabu Kinoshita, Yoshiko Okita, Haruhiko Kishima","doi":"10.1093/neuonc/noaf021","DOIUrl":"10.1093/neuonc/noaf021","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1311-1312"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046521","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":"Fast intraoperative detection of primary central nervous system lymphoma and differentiation from common central nervous system tumors using stimulated Raman histology and deep learning.","authors":"David Reinecke, Nader Maarouf, Andrew Smith, Daniel Alber, John Markert, Nicolas K Goff, Todd C Hollon, Asadur Chowdury, Cheng Jiang, Xinhai Hou, Anna-Katharina Meissner, Gina Fürtjes, Maximilian I Ruge, Daniel Ruess, Thomas Stehle, Abdulkader Al-Shughri, Lisa I Körner, Georg Widhalm, Thomas Roetzer-Pejrimovsky, John G Golfinos, Matija Snuderl, Volker Neuschmelting, Daniel A Orringer","doi":"10.1093/neuonc/noae270","DOIUrl":"10.1093/neuonc/noae270","url":null,"abstract":"<p><strong>Background: </strong>Accurate intraoperative diagnosis is crucial for differentiating between primary central nervous system (CNS) lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge.</p><p><strong>Methods: </strong>We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&E-like images within <3 min. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and 2 additional independent test cohorts. We trained on 54 000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS neoplastic/nonneoplastic lesions. Training and test data were collected from 4 tertiary international medical centers. The final histopathological diagnosis served as ground truth.</p><p><strong>Results: </strong>In the prospective test cohort of PCNSL and non-PCNSL entities (n = 160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ± 0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 77.77%). The additional test cohorts (n = 420, n = 59) reached balanced accuracy rates of 95.44% ± 0.74 and 95.57% ± 2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma's capabilities to detect class-specific histomorphological key features.</p><p><strong>Conclusions: </strong>RapidLymphoma proves reliable and valid for intraoperative PCNSL detection and differentiation from other CNS entities. It provides visual feedback within 3 min, enabling fast clinical decision-making and subsequent treatment strategy planning.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"1297-1310"},"PeriodicalIF":16.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824461","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}