Neuro-oncology advances最新文献

{"title":"Differential gene expression underlying epileptogenicity in patients with gliomas.","authors":"Armin Mortazavi, Anas U Khan, Edwin Nieblas-Bedolla, Ujwal Boddeti, Muzna Bachani, Alexander Ksendzovsky, Kory Johnson, Kareem A Zaghloul","doi":"10.1093/noajnl/vdae103","DOIUrl":"10.1093/noajnl/vdae103","url":null,"abstract":"<p><strong>Background: </strong>Seizures are a common sequela for patients suffering from gliomas. Molecular properties are known to influence the initiation of seizures that may influence tumor growth. Different levels of gene expression with seizures related to gliomas remain unclear. We analyzed RNA sequencing of gliomas to further probe these differences.</p><p><strong>Methods: </strong>Total RNA sequencing was obtained from The Cancer Genome Atlas-Lower-Grade Glioma project, comprised of 2021 World Health Organization classification low-grade gliomas, including IDH-mutant and IDH-wild type, to distinguish differential expression in patients who did and did not experience seizures. Utilizing QIAGEN Ingenuity Pathways Analysis, we identified canonical and functional pathways to characterize differential expression.</p><p><strong>Results: </strong>Of 289 patients with gliomas, 83 (28.7%) had available information regarding seizure occurrence prior to intervention and other pertinent variables of interest. Of these, 50 (60.2%) were allocated to the seizure group. When comparing the level of RNA expression from these tumors between the seizure and non-seizure groups, 52 genes that were significantly differentially regulated were identified. We found canonical pathways that were altered, most significantly RhoGDI and semaphorin neuronal repulsive signaling. Functional gene analysis revealed tumors that promoted seizures had significantly increased functional gene sets involving neuronal differentiation and synaptogenesis.</p><p><strong>Conclusions: </strong>In the setting of gliomas, differences in tumor gene expression exist between individuals with and without seizures, despite similarities in patient demographics and other tumor characteristics. There are significant differences in gene expression associated with neuron development and synaptogenesis, ultimately suggesting a mechanistic role of a tumor-neuron synapse in seizure initiation.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636356","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":"Glioblastoma vulnerability to neddylation inhibition is dependent on PTEN status, and dysregulation of the cell cycle and DNA replication.","authors":"Brett Taylor, Nanyun Tang, Yue Hao, Matthew Lee, Sen Peng, Rita Bybee, Lauren Hartman, Krystine Garcia-Mansfield, Ritin Sharma, Patrick Pirrotte, Jianhui Ma, Alison D Parisian, Frank Furnari, Harshil D Dhruv, Michael E Berens","doi":"10.1093/noajnl/vdae104","DOIUrl":"10.1093/noajnl/vdae104","url":null,"abstract":"<p><strong>Background: </strong>Neddylation (NAE) inhibition, affecting posttranslational protein function and turnover, is a promising therapeutic approach to cancer. We report the cytotoxic vulnerability to NAE inhibitors in a subset of glioblastoma (GBM) preclinical models and identify genetic alterations and biological processes underlying differential response.</p><p><strong>Methods: </strong>GBM DNA sequencing and transcriptomic data were queried for genes associated with response to NAE inhibition; candidates were validated by molecular techniques. Multi-omics and functional assays revealed processes implicated in NAE inhibition response.</p><p><strong>Results: </strong>Transcriptomics and shotgun proteomics depict PTEN signaling, DNA replication, and DNA repair pathways as significant differentiators between sensitive and resistant models. Vulnerability to MLN4924, a NAE inhibitor, is associated with elevated S-phase populations, DNA re-replication, and DNA damage. In a panel of GBM models, loss of WT <i>PTEN</i> is associated with resistance to different NAE inhibitors. A NAE inhibition response gene set could segregate the GBM cell lines that are most resistant to MLN4924.</p><p><strong>Conclusions: </strong>Loss of WT <i>PTEN</i> is associated with non-sensitivity to 3 different compounds that inhibit NAE in GBM. A NAE inhibition response gene set largely consisting of DNA replication genes could segregate GBM cell lines most resistant to NAEi and may be the basis for future development of NAE inhibition signatures of vulnerability and clinical trial enrollment within a precision medicine paradigm.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908749","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":"An update on central nervous system tumors in germline replication-repair deficiency syndromes.","authors":"Anirban Das, Ayse Bahar Ercan, Uri Tabori","doi":"10.1093/noajnl/vdae102","DOIUrl":"10.1093/noajnl/vdae102","url":null,"abstract":"<p><p>DNA replication-repair deficiency (RRD) arises from pathogenic variants in the mismatch repair and/or polymerase-proofreading genes. Multiple germline cancer predisposition syndromes in children and young adults, including constitutional mismatch repair deficiency (CMMRD), Lynch, polymerase-proofreading deficiency, and rare digenic syndromes can lead to RRD cancers. The most frequent brain tumors in these children are high-grade gliomas. Embryonal tumors like medulloblastoma have also been described. Lower-grade tumors are reported from cancer surveillance initiatives. The latter has an extremely high rate of malignant transformation. Novel functional assays quantifying the genomic microsatellite indel load have been demonstrated to be highly sensitive and specific for the diagnosis of RRD cancers and children with germline CMMRD. Importantly, RRD brain tumors uniformly harbor high mutation and microsatellite burden. High T-cell infiltration makes these aggressive cancers amenable to immune checkpoint inhibition, irrespective of their germline genetic background. Synergistic combinations are reported to be successful in patients failing checkpoint inhibitor monotherapy. Future directions include the development of innovative approaches to improve immune surveillance for RRD brain cancers. Additionally, the use of novel tools including circulating tumor DNA and quantifying microsatellite indel load over time can be useful to monitor disease burden and treatment responses in patients.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636355","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":"Germline susceptibility from broad genomic profiling of pediatric brain cancers","authors":"Elaine R. Mardis, Samara L Potter, K. Schieffer, Elizabeth A. Varga, Mariam T Mathew, Heather M Costello, G. Wheeler, B. Kelly, Katherine E Miller, Elizabeth A R Garfinkle, Richard K. Wilson, C. Cottrell","doi":"10.1093/noajnl/vdae099","DOIUrl":"https://doi.org/10.1093/noajnl/vdae099","url":null,"abstract":"\u0000 \u0000 \u0000 Identifying germline predisposition in CNS malignancies is of increasing clinical importance, as it contributes to diagnosis and prognosis, and determines aspects of treatment. Inclusion of germline testing has historically been limited due to challenges surrounding access to genetic counseling, complexity in acquiring a germline comparator specimen, concerns about the impact of findings, or cost considerations. These limitations were further defined by the breadth and scope of clinical testing to precisely identify complex variants as well as concerns regarding the clinical interpretation of variants including those of uncertain significance.\u0000 \u0000 \u0000 \u0000 In the course of conducting an IRB approved protocol that performed genomic, transcriptomic and methylation-based characterization of pediatric CNS malignancies, we catalogued germline predisposition to cancer based on paired exome capture sequencing, coupled with computational analyses to identify variants in known cancer predisposition genes and to interpret them relative to established clinical guidelines.\u0000 \u0000 \u0000 \u0000 In certain cases, these findings refined diagnosis or prognosis, or provided important information for treatment planning.\u0000 \u0000 \u0000 \u0000 We outline our aggregate findings on cancer predisposition within this cohort which identified 16% of individuals (27 of 168) harboring a variant predicting cancer susceptibility and contextualize the impact of these results in terms of treatment-related aspects of precision oncology.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141336667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase I and Pharmacodynamic Study of Arsenic Trioxide plus Radiotherapy in Patients with Newly Diagnosed Glioblastoma","authors":"Samuel Ryu, Xiaobu Ye, Jeffrey J. Olson, T. Mikkelsen, Lev Bangiyev, Glenn J Lesser, T. Batchelor, B. Nabors, S. Desideri, T. Walbert, S. Grossman","doi":"10.1093/noajnl/vdae089","DOIUrl":"https://doi.org/10.1093/noajnl/vdae089","url":null,"abstract":"\u0000 \u0000 \u0000 When Arsenic trioxide (ATO) was combined with radiation for treatment of transplanted murine gliomas in the brain, tumor response improved with disrupted tumor blood flow and survival was significantly prolonged.\u0000 \u0000 \u0000 \u0000 Total of 31 patients with newly diagnosed glioblastoma were accrued to a multi-institutional, NCI-funded, Phase I study to determine the maximum tolerated dose (MTD) of ATO administered with radiation. Secondary objectives were survival and pharmacodynamic changes in perfusion on magnetic resonance imaging (MRI). Patients (unknown MGMT and IDH status) received ATO either once or twice weekly during radiation without concurrent or adjuvant temozolomide.\u0000 \u0000 \u0000 \u0000 Median age: 54.9 years, male: 68%, KPS >90: 77%, debulking surgery: 77%. Treatments were well-tolerated: 81% of patients received all the planned ATO doses. Dose-limiting toxicities included elevated liver function tests, hypokalemia, and edema. The MTD on the weekly schedule was 0.4mg/kg and on the biweekly was 0.3mg/kg. The median survival (mOS) for all patients was 17.7 months. Survival on the biweekly schedule (22.8 months) was longer than on the weekly schedule (12.1 months) (P=0.039) as was progression free survival (p=0.004). Similarly, cerebral blood flow was significantly reduced in patients treated on the biweekly schedule (p=0.007).\u0000 \u0000 \u0000 \u0000 ATO with standard radiation is well tolerated in patients with newly diagnosed glioblastoma. Even without temozolomide or adjuvant therapy, the overall survival of all patients (17.7 months) and especially patients who received biweekly ATO (22.8 months) is surprising and accompanied by pharmacodynamic changes on MRI. Further studies of this regimen are warranted.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141348781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of normal tissue neurovascular unit damage following brain irradiation – factors affecting damage severity and timing of effects","authors":"Annet Nakkazi, Duncan Forster, Gillian A Whitfield, Douglas P Dyer, Ben R Dickie","doi":"10.1093/noajnl/vdae098","DOIUrl":"https://doi.org/10.1093/noajnl/vdae098","url":null,"abstract":"\u0000 \u0000 \u0000 Radiotherapy is key in the treatment of primary and secondary brain tumours. However, normal tissue is inevitably irradiated, causing toxicity and contributing to cognitive dysfunction. The relative importance of vascular damage to cognitive decline is poorly understood. Here, we systematically review the evidence for radiation-induced damage to the entire neurovascular unit (NVU), particularly focusing on establishing the factors that influence damage severity, and timing and duration of vascular effects relative to effects on neural tissue.\u0000 \u0000 \u0000 \u0000 Using PubMed and Web of Science, we searched preclinical and clinical literature published between 1st January 1970 and 1st December 2022 and evaluated factors influencing NVU damage severity and timing of NVU effects resulting from ionising radiation.\u0000 \u0000 \u0000 \u0000 Seventy-two rodent, four canine, one rabbit, and five human studies met inclusion criteria. Radiation increased blood-brain-barrier (BBB) permeability, reduced endothelial cell number and extracellular matrix proteoglycans, reduced tight junction proteins, upregulated cellular adhesion molecule expression, reduced activity of glucose and BBB efflux transporters and activated glial cells. In the brain parenchyma, increased metalloproteinases 2 and 9 levels, demyelination, cell death, and inhibited differentiation were observed. Effects on the vasculature and neural compartment were observed across acute, delayed, and late timepoints, and damage extent was higher with low linear energy transfer (LET) radiation, higher doses, lower dose-rates, broader beams, and in the presence of a tumour.\u0000 \u0000 \u0000 \u0000 Irradiation of normal brain tissue leads to widespread and varied impacts on the NVU. Data indicates that vascular damage is in most cases an early effect that does not quickly resolve. More studies are needed to confirm sequence of damages, and mechanisms that lead to cognitive dysfunction.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141348480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility of DNA Methylation Profiling for Choroid Plexus Tumors","authors":"K. Yeo, Cassie B Macrae, Bradley Gampel, Jared T Ahrendsen, H. Lidov, Karen D Wright, Susan Chi, Katie Fehnel, Lissa Baird, Jessica Clymer, Kenneth J Aldape, S. Alexandrescu","doi":"10.1093/noajnl/vdae097","DOIUrl":"https://doi.org/10.1093/noajnl/vdae097","url":null,"abstract":"\u0000 \u0000 \u0000 Choroid plexus tumors (CPTs) are rare, potentially aggressive CNS tumors with defined histologic criteria for grading. In recent years, several patients within our practice have demonstrated discordance between the histologic diagnosis and clinical behavior. DNA methylation profiling has emerged as a potential diagnostic adjunct for aiding the clinical approach.\u0000 \u0000 \u0000 \u0000 We reviewed the clinical and pathologic data of all CPTs diagnosed at Boston Children’s Hospital from 1995-2023. All cases with available material (38/48) underwent DNA methylation profiling at NIH/NCI, and the classifier results were correlated with the WHO histologic grade and patient outcomes. Survival information was analyzed using Kaplan Meier curves.\u0000 \u0000 \u0000 \u0000 There was good correlation (11/12, 92%) between methylation class and WHO histologic grade for choroid plexus carcinomas (CPC); one histologic CPC grouped with choroid plexus papilloma (CPP) group pediatric (P). Five CPPs grouped with methylation class CPC (5/17, 29%). In the group of atypical CPPs (n=9), there were two that grouped with methylation class CPC. Survival analysis showed utility of methylation classes in the prediction of biologic behavior.\u0000 \u0000 \u0000 \u0000 Results indicated that methylation profiling may serve as a valuable tool in the clinical decision-making process for patients with CPTs, providing additional prognostic information compared to WHO histologic grade alone. The value of methylation array analysis is particularly important given the lack of consensus on treatment regimens for CPTs.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141354422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEO212, temozolomide conjugated to NEO100, exerts superior therapeutic activity over temozolomide in preclinical chemoradiation models of glioblastoma.","authors":"Radu O Minea, Thu Zan Thein, Zhuoyue Yang, Mihaela Campan, Pamela M Ward, Axel H Schönthal, Thomas C Chen","doi":"10.1093/noajnl/vdae095","DOIUrl":"10.1093/noajnl/vdae095","url":null,"abstract":"<p><strong>Background: </strong>The chemotherapeutic standard of care for patients with glioblastoma (GB) is radiation therapy (RT) combined with temozolomide (TMZ). However, during the twenty years since its introduction, this so-called Stupp protocol has revealed major drawbacks, because nearly half of all GBs harbor intrinsic treatment resistance mechanisms. Prime among these are the increased expression of the DNA repair protein O6-guanine-DNA methyltransferase (MGMT) and cellular deficiency in DNA mismatch repair (MMR). Patients with such tumors receive very little, if any, benefit from TMZ. We are developing a novel molecule, NEO212 (TMZ conjugated to NEO100), that harbors the potential to overcome these limitations.</p><p><strong>Methods: </strong>We used mouse models that were orthotopically implanted with GB cell lines or primary, radioresistant human GB stem cells, representing different treatment resistance mechanisms. Animals received NEO212 (or TMZ for comparison) without or with RT. Overall survival was recorded, and histology studies quantified DNA damage, apoptosis, microvessel density, and impact on bone marrow.</p><p><strong>Results: </strong>In all tumor models, replacing TMZ with NEO212 in a schedule designed to mimic the Stupp protocol achieved a strikingly superior extension of survival, especially in TMZ-resistant and RT-resistant models. While NEO212 displayed pronounced radiation-sensitizing, DNA-damaging, pro-apoptotic, and anti-angiogenic effects in tumor tissue, it did not cause bone marrow toxicity.</p><p><strong>Conclusions: </strong>NEO212 is a candidate drug to potentially replace TMZ within the standard Stupp protocol. It has the potential to become the first chemotherapeutic agent to significantly extend overall survival in TMZ-resistant patients when combined with radiation.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636358","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":"Advancing Precision Prognostication in Neuro-Oncology: Machine Learning Models for Data-Driven Personalized Survival Predictions in IDH-Wildtype Glioblastoma","authors":"Mert Karabacak, Pemla Jagtiani, L. Di, Ashish H Shah, Ricardo J Komotar, Konstantinos Margetis","doi":"10.1093/noajnl/vdae096","DOIUrl":"https://doi.org/10.1093/noajnl/vdae096","url":null,"abstract":"\u0000 \u0000 \u0000 Glioblastoma (GBM) remains associated with a dismal prognosis despite standard therapies. While population-level survival statistics are established, generating individualized prognosis remains challenging. We aim to develop machine learning (ML) models that generate personalized survival predictions for GBM patients to enhance prognostication.\u0000 \u0000 \u0000 \u0000 Adult patients with histologically confirmed IDH-wildtype GBM from the National Cancer Database (NCDB) were analyzed. ML models were developed with TabPFN, TabNet, XGBoost, LightGBM, and Random Forest algorithms to predict mortality at 6, 12, 18, and 24 months post-diagnosis. SHapley Additive exPlanations (SHAP) were employed to enhance the interpretability of the models. Models were primarily evaluated using the area under the receiver operating characteristic (AUROC) values, and the top-performing models indicated by the highest AUROCs for each outcome were deployed in a web application that was created for individualized predictions.\u0000 \u0000 \u0000 \u0000 A total of 7,537 patients were retrieved from the NCDB. Performance evaluation revealed the top-performing models for each outcome were built using the TabPFN algorithm. The TabPFN models yielded mean AUROCs of 0.836, 0.78, 0.732, and 0.724 in predicting 6-, 12-, 18-, and 24-month mortality, respectively.\u0000 \u0000 \u0000 \u0000 This study establishes ML models tailored to individual patients to enhance GBM prognostication. Future work should focus on external validation and dynamic updating as new data emerge.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141360010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced diffusion imaging reveals microstructural characteristics of primary CNS lymphoma, allowing differentiation from glioblastoma","authors":"U. Würtemberger, M. Diebold, A. Rau, Veysel Akgün, L. Becker, J. Beck, P. Reinacher, Christian A Taschner, Marco Reisert, Luca Fehrenbacher, D. Erny, Florian Scherer, M. Hohenhaus, H. Urbach, T. Demerath","doi":"10.1093/noajnl/vdae093","DOIUrl":"https://doi.org/10.1093/noajnl/vdae093","url":null,"abstract":"\u0000 \u0000 \u0000 Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL from GBM with conventional MRI can be challenging when atypical imaging features are present. We employed advanced dMRI for non-invasive characterization of the microstructure of PCNSL and differentiation from GBM as the most frequent primary brain malignancy.\u0000 \u0000 \u0000 \u0000 Multiple dMRI metrics including DTI, NODDI and DMI were extracted from the contrast-enhancing tumor component in 10 PCNSL and 10 age-matched GBM on 3T MRI. Imaging findings were correlated with cell density and axonal markers obtained from histopathology.\u0000 \u0000 \u0000 \u0000 We found significantly increased intraaxonal volume fractions (V-intra, ICVF) and microFA in PCNSL compared to GBM (all p<0.001). In contrast, mean (MD) and axial diffusivity (aD), and microADC (all p<0.001), and also free water fractions (V-CSF, V-ISO) were significantly lower in PCNSL (all p<0.01). ROC analysis revealed high predictive values regarding the presence of a PCNSL for MD, aD, microADC, V-intra, ICVF, microFA, V-CSF and V-ISO (AUC in all >0.840, highest for MD and ICVF with an AUC of 0.960). Comparative histopathology between PCNSL and GBM revealed a significantly increased cell density in PCNSL and the presence of axonal remnants in a higher proportion of samples.\u0000 \u0000 \u0000 \u0000 Advanced diffusion imaging enables the characterization of the microstructure of PCNSL and reliably distinguishes PCNSL from GBM. Both imaging and histopathology revealed a relatively increased cell density and a preserved axonal microstructure in PCNSL.\u0000","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141370673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}