Neuro-oncology最新文献

{"title":"Window of opportunity evaluation of blood-brain barrier permeability heterogeneity within and across high-grade glioma patients.","authors":"Ju-Hee Oh, Sarah K Reed, Cecile Riviere-Cazaux, Minjee Kim, Ann C Mladek, Silvia M Illamola, Wenjuan Zhang, Rachael A Vaubel, Alissa Caron, Michael S Regan, Angela K Birnbaum, Afroz Mohammad, Wenqiu Zhang, Jesse G Dixon, Timothy J Kaufmann, Leland S Hu, Daniel J Ma, Sani Kizilbash, Nathalie Y R Agar, Caterina Giannini, Susan M Geyer, Ian F Parney, Evanthia Galanis, Terry C Burns, William F Elmquist, Jann N Sarkaria","doi":"10.1093/neuonc/noaf204","DOIUrl":"https://doi.org/10.1093/neuonc/noaf204","url":null,"abstract":"<p><strong>Background: </strong>Disruption of the blood-brain barrier (BBB) in high-grade brain tumors is characterized by contrast accumulation on diagnostic imaging. This window of opportunity study correlates contrast imaging features with the tumor distribution of BBB-permeable (levetiracetam) and -impermeable (cefazolin) drugs.</p><p><strong>Methods: </strong>Patients with a clinical diagnosis of a high-grade brain tumor underwent MRI for surgical planning. Cefazolin and levetiracetam were administered prior to skin incision, and serial plasma and image-registered tumor samples were collected during the operation. Drug levels were measured by LC-MS/MS, tissue drug levels were corrected for residual blood, and tumor-to-plasma concentration ratios were calculated. Intraoperative microdialysis was performed in a subset of patients to measure the same two drugs.</p><p><strong>Results: </strong>Tumor (n=125) and plasma (n=261) samples were available for analysis from 42 operative cases. Across all samples, the tumor-to-plasma ratio was significantly lower for cefazolin (marginal mean (MM): 0.15, 95% CI: 0.11-0.19) as compared to levetiracetam (MM: 0.70, 95% CI: 0.64-0.75; p<0.001). When compared between contrast-enhancing and non-enhancing regions, tumor-to-plasma ratios for cefazolin varied by 4.4-fold (0.27, 95% CI: 0.20-0.35 vs. 0.06, 95% CI: 0.04-0.08, respectively; p<0.001), and varied for levetiracetam by 1.4-fold (0.88, 95% CI: 0.78-0.97 vs. 0.61, 95% CI: 0.55-0.66, respectively; p<0.001). These results were confirmed with the intra-operative microdialysis and a population pharmacokinetic analysis.</p><p><strong>Conclusions: </strong>This study demonstrates significant inter- and intra-tumoral heterogeneity in drug delivery for both levetiracetam and cefazolin within high-grade brain tumors that is not necessarily predicted by clinical MR-imaging and may reflect tumor-induced changes in both perfusion and BBB integrity.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015969","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":"Preoperative embolization improves local control and modulates gene expression in atypical WHO grade 2 meningioma.","authors":"Alexander F Haddad, Rithvik Ramesh, Naomi Zakimi, Jia-Shu Chen, Daniel Quintana, Eugene Gil, Aymen S Kabir, Youssef E Sibih, Blanca Morales Lugo, Shubhang Bhalla, William C Chen, Javier E Villanueva-Meyer, Kazim H Narsinh, Stephen T Magill, Ramin A Morshed, Ethan Winkler, Philip V Theodosopoulos, Michael W McDermott, Manish K Aghi, David R Raleigh","doi":"10.1093/neuonc/noaf203","DOIUrl":"https://doi.org/10.1093/neuonc/noaf203","url":null,"abstract":"<p><strong>Background: </strong>Preoperative embolization is hypothesized to reduce blood loss and operative time for meningioma resection, but the impact of preoperative embolization on long-term oncological outcomes and molecular features of meningiomas is incompletely understood. Here we investigate how preoperative embolization influences perioperative and long-term outcomes and molecular features of atypical WHO grade 2 meningiomas.</p><p><strong>Methods: </strong>Patients who underwent resection of WHO grade 2 meningiomas from 1997 to 2021 were retrospectively identified from an institutional database. Univariate and multivariate Cox proportional hazards modeling and propensity matching were used for clinical analyses. Available DNA methylation profiling, bulk RNA sequencing, and targeted gene expression profiling data were used to elucidate how preoperative embolization influences the molecular architecture of atypical WHO grade 2 meningiomas.</p><p><strong>Results: </strong>A total of 319 patients with atypical WHO grade 2 meningiomas were identified, of which 106 (33.2%) underwent preoperative embolization without significant changes in perioperative outcomes, such as blood loss or operative time, in comparison to patients who did not undergo preoperative embolization. In propensity matched multivariate analyses, preoperative embolization was independently associated with longer recurrence free survival (RFS, HR 0.55, 95% CI 0.31-0.96, p=0.037), particularly in patients with subtotal resection (median RFS 16.2 years versus 5.9 years, p=0.045; HR 0.32, 95% CI 0.14-0.70, p=0.005). Bioinformatic analyses demonstrated that preoperative embolization led to enrichment of pathways linked to cellular differentiation and hypoxia, and suppression of pathways implicated in mitosis and cell cycle progression, suggesting that improved long-term oncological outcomes may occur through inhibition of the cell cycle in atypical WHO grade 2 meningiomas.</p><p><strong>Conclusions: </strong>Preoperative embolization improves local control and modulates gene expression in atypical WHO grade 2 meningiomas, a subgroup of meningiomas that have intermediate clinical outcomes with standard interventions.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016005","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":"Spatial profiling of longitudinal glioblastoma reveals consistent changes in cellular architecture, post-treatment.","authors":"Shoaib Ajaib, Joshua Winter-Luke, Richard J Digby, Steven Pollock, Gemma Hemmings, Arief Gusnanto, Aruna Chakrabarty, Azzam Ismail, Erica Wilson, Bethany Hunter, Andrew Filby, David McDonald, Asa A Brockman, Rebecca A Ihrie, Lucy F Stead","doi":"10.1093/neuonc/noaf190","DOIUrl":"10.1093/neuonc/noaf190","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM), the most aggressive adult brain cancer, comprises a complex tumour microenvironment (TME) with diverse cellular interactions that drive progression and pathobiology. The aim of this study was to understand how these spatial patterns and interactions evolve with treatment.</p><p><strong>Methods: </strong>To explore these relationships, we employed imaging mass cytometry to measure the expression of 34 protein markers, enabling the identification of GBM-specific cell types and their interactions at single-cell protein level in paired primary (pre-treatment) and recurrent (post-treatment) GBM samples from five patients.</p><p><strong>Results: </strong>We find a significant post-treatment increase in normal brain cells alongside a reduction in vascular cells. Moreover, despite minimal overall change in cellular diversity, interactions among astrocytes, oligodendrocytes, and vascular cells increase post-treatment, suggesting reorganisation of the TME. The GBM TME cells form spatially organized layers driven by hypoxia pre-treatment, but this influence diminishes post-treatment, giving way to less organised layers with organisation driven by reactive astrocytes and lymphocytes.</p><p><strong>Conclusions: </strong>These findings provide insight into treatment-induced shifts in GBM's cellular landscape, highlighting aspects of the evolving TME that appear to facilitate recurrence and are, therefore, potential therapeutic targets.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963262","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":"Preanalytical variables and analytes in liquid biopsy approach for brain tumors: A comprehensive review and recommendations from the RANO Group and the Brain Liquid Biopsy Consortium.","authors":"Chetan Bettegowda, Houtan Noushmehr, Alessandra Affinito, Manmeet S Ahluwalia, Olaf Ansorge, Katayoun Ayasoufi, Stephen Bagley, Jill Barnholtz-Sloan, Myron Best, Dieta Brandsma, Chaya Brodie, Anke Brüning-Richardson, Ana Valeria Castro, Susan M Chang, Gerolama Condorelli, Ahmad Daher, Vineet Datta, John de Groot, Pim French, Evanthia Galanis, Anna Golebiewska, Petra Hamerlik, C Oliver Hanemann, Matthias Holdhoff, Jason Huse, Mustafa Khasraw, Suzanne LeBlang, Beatrice Melin, Florent Mouliere, Claire O'Leary, Janusz Rak, Amitava Ray, Stephen Robinson, Ola Rominiyi, Federico Roncaroli, Roberta Rudà, Joan Seoane, Nik Sol, Martin J van den Bent, Michael A Vogelbaum, Tobias Walbert, Colin Watts, Tobias Weiss, Michael Weller, Patrick Y Wen, Victoria Wykes, Stephen Yip, Susan C Short, Riccardo Soffietti","doi":"10.1093/neuonc/noaf140","DOIUrl":"https://doi.org/10.1093/neuonc/noaf140","url":null,"abstract":"<p><p>This review explores the pivotal role of preanalytical variables in bringing liquid biopsy approaches into the clinic for brain tumors. Preanalytical variables encompass a range of critical issues, from blood sample collection and handling to the impact of tumor heterogeneity and patient-specific factors. These variables introduce challenges such as false positives, false negatives, and variability in the analysis of tumor signals, which can hinder the diagnostic and prognostic utility of liquid biopsies. Understanding the nuances of preanalytical variables is essential for the successful implementation of liquid biopsy in clinical settings. This paper delves into strategies aimed at mitigating the influence of preanalytical variables by emphasizing the importance of standardized sample collection protocols, optimized sample processing and storage, quality control measures, and the integration of multiple liquid biopsy modalities.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963249","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":"Phase IB Study of Avelumab and Whole Brain Radiotherapy (WBRT) in Patients with Leptomeningeal Disease (LMD) from Solid Tumors: Results and Molecular Analyses.","authors":"Yolanda Piña, Vincent Law, Solmaz Sahebjam, Nam Tran, Navya Siddarajappa, Jiannong Li, Qianxing Mo, Manali S Phadke, John Arrington, Robert Macaulay, Sepideh Mokhtari, Brittany Evernden, Kamran A Ahmed, Inna Smalley, Michael Yu, Keiran S M Smalley, Peter A Forsyth","doi":"10.1093/neuonc/noaf183","DOIUrl":"https://doi.org/10.1093/neuonc/noaf183","url":null,"abstract":"<p><strong>Background: </strong>Leptomeningeal disease (LMD) from solid tumors has a dismal prognosis, even following treatment with anti-PD-1 therapy. We performed a phase IB study evaluating the safety of Avelumab with whole brain radiotherapy (WBRT) in LMD (NCT03719768).</p><p><strong>Methods: </strong>Fifteen patients were enrolled with LMD from breast, lung, nasopharyngeal, ovary, and pancreatic tumors. Patients were treated with Avelumab with WBRT, with first infusion of Avelumab starting 14 days pre-WBRT and continuing during and post-WBRT for up to 5 cycles. Primary endpoints were safety and 3-month OS (OS3). Secondary endpoints included assessment of immune cells in the cerebrospinal fluid (CSF) using single cell RNA-sequencing (scRNA-Seq) pre- and post-last treatment of Avelumab.</p><p><strong>Results: </strong>DLTs occurred in 2 patients, i.e., adrenal insufficiency, hypothyroidism, and pneumonitis. Treatment-related toxicities happened in 5 patients with grade 1/2 and 5 patients with grade 3/4. Immune-related adverse events occurred in 5 patients with grade 1/2 and 3 patients with grade 3/4. The OS3 was 67% (10 of 15; 95% CI: 38 - 84%). Median-OS was 3.85 months (95%CI: 0.9-34.4 months) and median-PFS 3.85months (95%CI: 0.9-12.1 months). scRNA-Seq analysis of CSF pre- and post-last-treatment showed Avelumab+WBRT stimulated an adaptive immune response associated with decrease regulatory T cells (Tregs), among other changes in the expression of immune checkpoints on CD8+ T cells and macrophages.</p><p><strong>Conclusion: </strong>The combination of Avelumab and WBRT is safe and demonstrates activity in patients with LMD. The identification of high levels of Tregs and macrophages in the CSF of LMD patients offers future avenues for therapeutic development.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963313","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 Tumor Microtubes and Brain Fatty Acid-binding Protein: Path to Directional Infiltration.","authors":"Won-Shik Choi, Pureunsol Jeon, Seth Peyton, Mansi Garg, John Maringa Githaka, Rong-Zong Liu, Darryl D Glubrecht, Amirali B Bukhari, Daniel McGinn, Lubna Yasmin, Caitlin Mak, Xia Xu, Matthew P Larocque, Xuejun Sun, Frank K H van Landeghem, Karolyn Au, Ing Swie Goping, Roseline Godbout","doi":"10.1093/neuonc/noaf200","DOIUrl":"https://doi.org/10.1093/neuonc/noaf200","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a deadly brain cancer with a dismal prognosis. There is evidence that infiltration and therapy resistance in GBM are driven by tumor microtubes (TMs), ultra-long membrane-enclosed protrusions that serve as intercellular communication channels. The aims of this study were to investigate the role of TMs and identify the molecular drivers involved in TM formation.</p><p><strong>Methods: </strong>We used patient-derived GBM neurosphere cultures that produce TMs to investigate TM dynamics, the proteins and pathways involved in TM formation, and the effect of targeting brain fatty acid-binding protein (FABP7) on mouse survival using an orthotopic model of GBM.</p><p><strong>Results: </strong>The radial glial cell marker, FABP7, is highly expressed in TMs. Like GAP43, FABP7 is critically important for the formation of TMs in GBM neurosphere cultures. We show that GBM cells use TMs as a fiber network for rapid and directional migration. Our results indicate that GAP43 phosphorylation is required for TM formation, with GAP43 phosphorylation facilitated by FABP7 expression. We also show that depletion or inhibition of protein kinase C (PKC), the kinase responsible for GAP43 phosphorylation, decreases TM formation. Targeting FABP7 in an orthotopic mouse model of TM-forming GBM cells increases survival but does not sensitize tumors to radiation.</p><p><strong>Conclusions: </strong>We found that the FABP7-PKC-pGAP43 axis is key to GBM TM formation, with TMs serving as networks for efficient long-distance cell migration. Our results indicate that TM formation can be mitigated by FABP7 inhibition with the potential of improving clinical outcomes in GBM patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963320","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":"AI-driven WHO 2021 classification of gliomas based only on H&E-stained slides.","authors":"Shubham Innani, W Robert Bell, MacLean P Nasrallah, Bhakti Baheti, Spyridon Bakas","doi":"10.1093/neuonc/noaf189","DOIUrl":"https://doi.org/10.1093/neuonc/noaf189","url":null,"abstract":"<p><strong>Background: </strong>The WHO 2021 classification criteria for adult diffuse glioma integrate histology with molecular profiling for conclusive diagnosis. Since molecular profiling can be expensive and time-consuming, often necessitating outsourcing or leading to the 'not otherwise specified (NOS) label', this study develops an AI-driven WHO 2021 classification of gliomas solely from H&E whole-slide images (WSIs).</p><p><strong>Methods: </strong>Our pipeline is based on a multi-institutional dataset reclassified per WHO 2021 guidelines. This dataset includes a) Primarily US based TCGA-GBM/TCGA-LGG (n=1,320) for model training, independently evaluated on two hold-out sets, b) Austria-based EBRAINS (n= 794) c) India-based IPD-Brain (n=304). Each WSI undergoes pre-processing followed by quantitative benchmarking across i) eight pathology foundation models, ii) nine aggregation methods, and (iii) 15 combinations of magnification levels through a late fusion approach. Model interpretability conducted through heatmaps highlights distinct, identifiable morphology features.</p><p><strong>Results: </strong>Our best-performing combination of FM, AM, and multi-magnification achieved an AUC of 97.95% on the training cohort, 96.30% on EBRAINS (set 1), and 92.61% on IPD (set 2). The results yield the following key insights: (1) domain-specific FMs outperform ImageNet-based models, (2) AMs while theoretically promising yield larger performance improvements when used with ImageNet based feature extractor rather than FMs, and (3) Fusion of multiple magnifications adds value in performance.</p><p><strong>Conclusion: </strong>Determining glioma diagnosis directly from H&E slides can obviate the need for molecular profiling, expedite conclusive diagnosis, and, hence, clinical decision-making. These findings motivate the development of advanced domain-relevant foundation models and the design of more adaptable slide-level aggregation techniques.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963162","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":"Perfusion, diffusion, and anatomical MRI characteristics of pathologically-confirmed malignant transformation in IDH-mutant gliomas.","authors":"Nicholas S Cho, Viên Lam Le, Ashley Teraishi, Vicki Liu, Francesco Sanvito, Donatello Telesca, Masanori Nakajo, Chencai Wang, Sonoko Oshima, Blaine S C Eldred, Jingwen Yao, Phioanh L Nghiemphu, Noriko Salamon, Timothy F Cloughesy, Albert Lai, Benjamin M Ellingson","doi":"10.1093/neuonc/noaf171","DOIUrl":"https://doi.org/10.1093/neuonc/noaf171","url":null,"abstract":"<p><strong>Background: </strong>This study explored MRI characteristics at the time of tumor progression to study pathologically-confirmed MT in IDHm 1p/19q-intact astrocytomas (IDHm-A) and IDHm 1p/19q-co-deleted oligodendrogliomas (IDHm-O).</p><p><strong>Methods: </strong>N=64 patients with initial pathological grade 2 IDH-mutant glioma diagnosis who underwent repeated tissue sampling and were classified as pathologically-confirmed MT (n=35) or non-MT (n=29) with available pre-surgical anatomical (n=64), diffusion-weighted (n=61), and dynamic susceptibility contrast perfusion MRI (n=53) were retrospectively studied. Measurable contrast enhancement (>1000mm3), tumor volume, tumor growth rate, sphericity, median apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) were compared between MT vs. non-MT IDHm-A and IDHm-O.</p><p><strong>Results: </strong>81% of contrast-enhancing IDHm-A and 100% of contrast-enhancing IDHm-O demonstrated MT, while 41% of IDHm-A and 62% IDHm-O exhibited both non-enhancing tumor progression and MT. Tumor volumes were significantly larger in patients with MT compared to non-MT groups for IDHm-A (P=0.02) and IDHm-O (P=0.04). T2/FLAIR tumor volume growth rate was significantly higher (P=0.003), nrCBV was significantly higher (P=0.002), and ADC trended lower (P=0.06) in MT vs. non-MT IDHm-A. There were no significant differences in growth rate, ADC, nrCBV, or sphericity when comparing MT vs. non-MT IDHm-O (P>0.05).</p><p><strong>Conclusions: </strong>Many MT IDHm gliomas remain non-enhancing. Growth rate, diffusion, and perfusion MRI show differences between MT and non-MT in IDHm-A but not IDHm-O, which may reflect the different tumor biology of these IDHm molecular subtypes and their need for separate imaging biomarkers. Tumor volumes can help determine MT for both IDHm-A and IDHm-O.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963344","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":"Genomics correlates of brain metastasis and progression in colorectal cancer.","authors":"Chengcheng Gui, Henry S Walch, Kirin D Mueller, Lillian A Boe, Anna Skakodub, Emily Miao, Ishaani Khatri, Rahul Kumar, Michel Padilla Mazzeo, Junchao Shen, Claire Cooper, Mitchell Parker, Audree Hsu, Roshal R Patel, A Turan Ilica, Joseph N Stember, Jordan E Eichholz, Rabih Bou Nassif, Kenny K H Yu, Jessica A Wilcox, Paolo Manca, Yao Yu, Yoshiya Yamada, Brandon S Imber, Steven B Maron, Michael B Foote, Walid K Chatila, Rona Yaeger, Nikolaus Schultz, Luke R G Pike","doi":"10.1093/neuonc/noaf198","DOIUrl":"https://doi.org/10.1093/neuonc/noaf198","url":null,"abstract":"<p><strong>Background: </strong>Brain metastasis (BM) in colorectal cancer (CRC) is a rare event that undermines longevity and neurocognitive function. However, the molecular basis of BM in CRC is poorly understood. We analyzed next-generation sequencing (NGS) from patients with CRC to identify genomic features associated with BM and intracranial progression (IP).</p><p><strong>Methods: </strong>Patients with CRC who had NGS between 2014 and 2024 were included. Sequenced tumor specimens were classified by the anatomic site of biopsy as primary tumors (PT), extracranial metastases (EM), or BM. Sequenced PT specimens were compared to identify genomic differences between patients who did and did not develop BM. Among patients with BM, sequenced tumor specimens were compared to identify genomic differences by anatomic site. Sequenced BM samples were compared to identify genomic differences between patients who and did not experience IP after BM-directed local therapy.</p><p><strong>Results: </strong>This analysis included 5526 with NGS of CRC, including 269 patients with BM. PT of patients who developed BM more frequently contained alterations in the KRAS, BRAF, and SMAD4, compared with PT of patients without BM. Among patients with BM, resected BM specimens had greater tumor mutation burden, fraction of genome altered, and frequency of TP53, SMAD4, and MYC alterations, compared with extracranial tumor specimens. Patients with BM carrying SMAD4 or PI3K pathway alterations showed a trend toward earlier IP after BM-directed therapy.</p><p><strong>Conclusions: </strong>This study identifies novel genomic associations with intracranial metastasis and progression in CRC, suggesting a potential basis for personalized clinical management.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963167","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":"Distinct and Reproducible Neurocognitive Profiles in Stable Diffuse Glioma: A Data-Driven Approach to Understanding Cognitive Heterogeneity.","authors":"Maxine Gorter, Jantine G Röttgering, Vera Belgers, Marike R van Lingen, Philip C De Witt Hamer, Linda Douw, Martin Klein","doi":"10.1093/neuonc/noaf197","DOIUrl":"https://doi.org/10.1093/neuonc/noaf197","url":null,"abstract":"<p><strong>Background: </strong>Glioma patients often exhibit neurocognitive deficits across multiple domains, yet studies typically assess these impairments separately. This study explores aggregated neurocognitive functioning (NCF), identifying distinct profiles and their clinical correlates.</p><p><strong>Methods: </strong>NCF in glioma patients with stable disease (≥ 2 months after treatment without clinical or radiological progression) was assessed across five domains: attention, information processing speed, verbal memory, working memory, and flexibility. We used hierarchical cluster analysis to distinguish neurocognitive profiles and replicated these profiles in an independent glioma cohort. Associations between neurocognitive profiles and clinical characteristics were examined using multinomial logistic regression.</p><p><strong>Results: </strong>Four distinct neurocognitive profiles were identified in both the study (N = 108) and the validation cohort (N = 185): a preserved, memory, processing/attention, and multi-domain profile. In both cohorts, 40% of patients exhibited impaired NCF, with deficits in at least one domain observed in 44% in the study cohort and 38% in the validation cohort. In the study cohort, tumor hemisphere and prior treatment with radiotherapy or combined radio- and chemotherapy were associated with processing/attention and multi-domain profiles. In both the cohorts, the multi-domain profile showed a weak association with self-perceived NCF. No other significant associations with patient, tumor, or treatment characteristics were observed.</p><p><strong>Conclusions: </strong>NCF in glioma patients can be classified in four reproducible neurocognitive profiles. Importantly, concurrent problems in NCF are highly prevalent. Neurocognitive profiles are associated with tumor laterality, previous oncological treatment, and self-perceived NCF, but not with other clinical characteristics.</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":"144963222","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}