Neuro-oncology advances最新文献

{"title":"Lack of ST2 aggravates glioma invasiveness, vascular abnormality, and immune suppression.","authors":"Grzegorz Wicher, Ananya Roy, Alessandra Vaccaro, Kalyani Vemuri, Mohanraj Ramachandran, Tommie Olofsson, Rebeca-Noemi Imbria, Mattias Belting, Gunnar Nilsson, Anna Dimberg, Karin Forsberg-Nilsson","doi":"10.1093/noajnl/vdaf010","DOIUrl":"10.1093/noajnl/vdaf010","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, characterized by aggressive growth and a dismal prognosis. Interleukin-33 (IL-33) and its receptor ST2 have emerged as regulators of glioma growth, but their exact function in tumorigenesis has not been deciphered. Indeed, previous studies on IL-33 in cancer have yielded somewhat opposing results as to whether it is pro- or anti-tumorigenic.</p><p><strong>Methods: </strong>IL-33 expression was assessed in a GBM tissue microarray and public databases. As in vivo models we used orthotopic xenografts of patient-derived GBM cells, and syngenic models with grafted mouse glioma cells.</p><p><strong>Results: </strong>We analyzed the role of IL-33 and its receptor ST2 in nonmalignant cells of the glioma microenvironment and found that IL-33 levels are increased in cells surrounding the tumor. Protein complexes of IL-33 and ST2 are mainly found outside of the tumor core. The IL-33-producing cells consist primarily of oligodendrocytes. To determine the function of IL-33 in the tumor microenvironment, we used mice lacking the ST2 receptor. When glioma cells were grafted to ST2-deficient mouse brains, the resulting tumors exhibited a more invasive growth pattern, and are associated with poorer survival, compared to <i>wild-type</i> mice. Tumors in ST2-deficient hosts are more invasive, with increased expression of extracellular matrix remodeling enzymes and enhanced tumor angiogenesis. Furthermore, the absence of ST2 leads to a more immunosuppressive environment.</p><p><strong>Conclusions: </strong>Our findings reveal that glia-derived IL-33 and its receptor ST2 participate in modulating tumor invasiveness, tumor vasculature, and immunosuppression in glioma.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf010"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392464","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":"Rise in post-resection neutrophil-to-lymphocyte ratio correlates with decreased survival in glioblastoma patients.","authors":"Amro H Mohammad, Rawan Sakalla, William Davalan, Miguel Angel Ruiz-Barerra, Sukhdeep Jatana, Roy Khalaf, Hongda Li, Rebecca Aberra, Tariq Al-Saadi, Roberto J Diaz","doi":"10.1093/noajnl/vdaf014","DOIUrl":"10.1093/noajnl/vdaf014","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil-to-lymphocyte ratio (NLR) is used in the prognostication of multiple malignancies. However, the NLR value in glioblastoma (GBM) is controversial. This controversy may be due to the unaccounted effect of dexamethasone on NLR. Using retrospective data from 230 isocitrate dehydrogenase-1 (<i>IDH</i>) wild-type GBM patients, we studied the prognostic value of NLR in relation to dexamethasone treatment in GBM.</p><p><strong>Methods: </strong>We retrospectively analyzed 230 patients with GBM. NLR and dexamethasone use were used as dichotomous variables with cutoff values of 9.5 and 8 mg, respectively. Correlations between high NLR, as well as NLR change after surgery, and patient outcome measures, including post-surgical complications and survival, were assessed using Kaplan-Meier curves, logistic, and Cox regression analyses.</p><p><strong>Results: </strong>We demonstrate in this study that high perioperative NLR (≥9.5 NLR) does not associate with survival of GBM patients (274 days, 95% confidence interval [CI] 211-337, vs. 229 days, 95% CI 52-406, <i>P</i> = .9). However, high positive change in NLR (≥6 units) (higher postoperative NLR relative to preoperative NLR) has a significant association with decreased survival in GBM patients (196 days, 95% CI 121-270, vs. 304 days, 95% CI 223-384, <i>P</i> = .01). High preoperative and perioperative average dexamethasone (≥8 mg) treatment did not change the perioperative NLR trend and were not associated with decreased survival.</p><p><strong>Conclusions: </strong>We demonstrate that an increase in NLR after surgery associates with decreased GBM patient survival.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf014"},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573790","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":"The Slovenian translational platform GlioBank for brain tumor research: Identification of molecular signatures of glioblastoma progression.","authors":"Metka Novak, Bernarda Majc, Marta Malavolta, Andrej Porčnik, Jernej Mlakar, Matjaž Hren, Anamarija Habič, Mateja Mlinar, Ivana Jovčevska, Neja Šamec, Alja Zottel, Marija Skoblar Vidmar, Tina Vipotnik Vesnaver, Andrej Zupan, Alenka Matjašič, Saša Trkov Bobnar, Dejan Georgiev, Aleksander Sadikov, Roman Bošnjak, Borut Prestor, Radovan Komel, Tamara Lah Turnšek, Barbara Breznik","doi":"10.1093/noajnl/vdaf015","DOIUrl":"10.1093/noajnl/vdaf015","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Glioblastoma (GB) is one of the most lethal solid tumors in humans, with an average patient life expectancy of 15 months and a 5-year survival rate of 5%-10%. GB is still uncurable due to tumor heterogeneity and invasive nature as well as therapy-resistant cancer cells. Centralized biobanks with clinical data and corresponding biological material of GB patients facilitate the development of new treatment approaches and the search for clinically relevant biomarkers, with the goal of improving outcomes for GB patients. The aim of this study was firstly to establish a Slovenian translation platform, GlioBank, and secondly to demonstrate its utility through the identification of molecular signatures associated with GB progression and patient survival.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;GlioBank contains tissue samples and corresponding tumor models as well as clinical data from patients diagnosed with glioma, with a focus on GB. Primary GB cells, glioblastoma stem cells (GSCs), and organoids have been established from fresh tumor biopsies. We performed expression analyses of genes associated with GB progression and bioinformatics analyses of available clinical and research data obtained from a subset of 91 GB patients. qPCR was performed to determine the expression of genes associated with therapy resistance and cancer cell invasion, including markers of different GB subtypes, GSCs, epithelial-to-mesenchymal transition, and immunomodulation/chemokine signaling in tumor tissues and corresponding cellular models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;GlioBank contains biological material and research, and clinical data collected in the SciNote electronic laboratory notebook. To date, more than 240 glioma tissue samples have been collected and stored in GlioBank, most of which are GB tissues (205) and were further processed to establish primary GB cells (&lt;i&gt;n&lt;/i&gt; = 64), GSCs (&lt;i&gt;n&lt;/i&gt; = 14), and GB organoids (&lt;i&gt;n&lt;/i&gt; = 17). Corresponding blood plasma (&lt;i&gt;n&lt;/i&gt; = 103) and peripheral blood mononuclear cells (&lt;i&gt;n&lt;/i&gt; = 101) are also stored. GB tumors were classified into 4 different subtypes that differed regarding patient survival; the mixed subtype exhibited the longest patient survival. High &lt;i&gt;DAB2, S100A4&lt;/i&gt;, and &lt;i&gt;STAT3&lt;/i&gt; expression were associated with poor overall patient survival, and &lt;i&gt;DAB2&lt;/i&gt; was found to be an independent prognostic marker for GB survival. We analyzed the molecular signatures between different tumor regions (core vs. rim). &lt;i&gt;STMN4, ERBB3&lt;/i&gt;, and &lt;i&gt;ACSBG1&lt;/i&gt; were upregulated in the tumor rim, suggesting that these genes are associated with the invasive nature of GB.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;GlioBank is a centralized biobank that has been built by a multidisciplinary network with the aim of facilitating disease-oriented basic and clinical research. The advantages of GlioBank include the molecular characterization of GB based on targeted gene expression, the availability of diverse cel","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf015"},"PeriodicalIF":3.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443135","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 reirradiation of recurrent high-grade gliomas: Safety with higher reirradiation dose and larger targets.","authors":"Michael C LeCompte, Neil Vuppala, Juan M Reyes, Brandi Page, Victoria Croog, Ellen Huang, Kristin J Redmond, Lawrence R Kleinberg","doi":"10.1093/noajnl/vdaf004","DOIUrl":"10.1093/noajnl/vdaf004","url":null,"abstract":"<p><strong>Background: </strong>The optimal regimen, normal tissue tolerances, and appropriate indications for reirradiation for recurrent high-grade glioma (HGG) are uncertain. The aim of this study was to determine whether higher reirradiation dose was associated with toxicity or survival.</p><p><strong>Methods: </strong>Patients with HGG treated with fractionated reirradiation at a single institution from 2007 to 2022 were retrospectively reviewed. Metrics evaluated included overall survival (OS), prognostic factors for survival, and treatment-related toxicity.</p><p><strong>Results: </strong>Two hundred and thirty patients with recurrent HGG were reviewed. Median follow-up was 8.8 months. Median reirradiation dose was 41.4 Gy with 80.4% receiving concurrent systemic therapy. Median cumulative maximum doses to brainstem and optic structures were 77.9 Gy (range: 4.6-146.0 Gy) and 55.1 Gy (3.3-106.3 Gy), respectively. No injuries to these structures were identified. Radiation necrosis (RN) was identified in 9.4%. There were no significant associations between RN and target size, systemic therapy use, or reirradiation dose. Median OS was 10.2 months from reirradiation start. On multivariate analysis, improved OS was associated with better KPS, longer interval between radiotherapy sessions, reirradiation at first recurrence, and reirradiation dose ≥ 41.4 Gy. Median OS for those with IDH wildtype glioblastoma was 8.7 months. On multivariate analysis of an IDH wildtype disease subanalysis, improved OS was associated with longer interval between radiotherapy sessions and higher reirradiation dose.</p><p><strong>Conclusions: </strong>These data support the safety and efficacy of fractionated reirradiation for recurrent HGG. They suggest higher reirradiation dose may be feasible, including for large treatment volumes and for tumors near the brainstem or optic structures.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf004"},"PeriodicalIF":3.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484891","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":"A multi-institutional retrospective cohort of adult-onset medulloblastoma in the modern era.","authors":"Alipi V Bonm, Michael S Rutenberg, Kate E Therkelsen, John Herbst, Anurag Sanaf, Marissa A Sherwood, John Y Rhee, Tresa M McGranahan, Patrick J Cimino, L Nicolas Gonzalez Castro, Derek S Tsang, Matthias A Karajannis, Seema Nagpal, Robert J Amdur, Helen Shih, Jason Barber, Lynne P Taylor","doi":"10.1093/noajnl/vdae231","DOIUrl":"10.1093/noajnl/vdae231","url":null,"abstract":"<p><strong>Background: </strong>Adult onset medulloblastoma (aMB) is a rare tumor with limited available evidence. We present a large multi-institutional retrospective cohort of aMB patients treated in the modern era, with an emphasis on understanding the role of chemotherapy at initial diagnosis.</p><p><strong>Methods: </strong>We included 267 consecutive patients with aMB treated at 7 different institutions from 2000-present, controlling for chemotherapy regimen and cycles received.</p><p><strong>Results: </strong>Treatment factors were highly intercorrelated with one another and with treating institution. Concurrent chemotherapy was not associated with overall survival (OS). Adjuvant chemotherapy was associated with OS on univariable analyses (HR = 0.55, <i>P</i> = .029) and on multivariable analysis when adjusting for risk status (HR 0.55, <i>P</i> = .026) but not when also adjusting for treating institution. Proton craniospinal irradiation was associated with improved survival on univariable (HR = 0.50, <i>P</i> = .019) and multivariable analysis adjusting for risk status (HR = 0.51, <i>P</i> = .024) but not when treating institution was also considered. On subgroup analysis, adjuvant chemotherapy was associated with improved survival in M0 (HR = 0.55, <i>P</i> = .043) but not M1 disease, in patients with subtotal resection (HR = 0.43, <i>P</i> = .048) but not those with GTR. Similarly, progression-free survival was improved with chemotherapy in patients with M0 (HR = 0.57, <i>P</i> = .032) but not M1 disease, and in patients with subtotal (HR = 0.50, <i>P</i> = .054) but not gross total resection.</p><p><strong>Conclusions: </strong>There was no benefit of concurrent chemotherapy. Adjuvant chemotherapy was associated with improved overall survival and this effect was driven by select subgroups, specifically those with M0 disease and those with residual tumor. We could not confirm that these associations are independent of the treating institution.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdae231"},"PeriodicalIF":3.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484650","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":"AI-guided virtual biopsy: Automated differentiation of cerebral gliomas from other benign and malignant MRI findings using deep learning.","authors":"Mathias Holtkamp, Vicky Parmar, René Hosch, Luca Salhöfer, Hanna Styczen, Yan Li, Marcel Opitz, Martin Glas, Nika Guberina, Karsten Wrede, Cornelius Deuschl, Michael Forsting, Felix Nensa, Lale Umutlu, Johannes Haubold","doi":"10.1093/noajnl/vdae225","DOIUrl":"10.1093/noajnl/vdae225","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop an automated algorithm to noninvasively distinguish gliomas from other intracranial pathologies, preventing misdiagnosis and ensuring accurate analysis before further glioma assessment.</p><p><strong>Methods: </strong>A cohort of 1280 patients with a variety of intracranial pathologies was included. It comprised 218 gliomas (mean age 54.76 ± 13.74 years; 136 males, 82 females), 514 patients with brain metastases (mean age 59.28 ± 12.36 years; 228 males, 286 females), 366 patients with inflammatory lesions (mean age 41.94 ± 14.57 years; 142 males, 224 females), 99 intracerebral hemorrhages (mean age 62.68 ± 16.64 years; 56 males, 43 females), and 83 meningiomas (mean age 63.99 ± 13.31 years; 25 males, 58 females). Radiomic features were extracted from fluid-attenuated inversion recovery (FLAIR), contrast-enhanced, and noncontrast T1-weighted MR sequences. Subcohorts, with 80% for training and 20% for testing, were established for model validation. Machine learning models, primarily XGBoost, were trained to distinguish gliomas from other pathologies.</p><p><strong>Results: </strong>The study demonstrated promising results in distinguishing gliomas from various intracranial pathologies. The best-performing model consistently achieved high area-under-the-curve (AUC) values, indicating strong discriminatory power across multiple distinctions, including gliomas versus metastases (AUC = 0.96), gliomas versus inflammatory lesions (AUC = 1.0), gliomas versus intracerebral hemorrhages (AUC = 0.99), gliomas versus meningiomas (AUC = 0.98). Additionally, across all these entities, gliomas had an AUC of 0.94.</p><p><strong>Conclusions: </strong>The study presents an automated approach that effectively distinguishes gliomas from common intracranial pathologies. This can serve as a quality control upstream to further artificial-intelligence-based genetic analysis of cerebral gliomas.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdae225"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061842","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":"Radiotherapy and radiosurgery for intracranial lesions in Africa: Insights from 3 country case studies: A systematic review.","authors":"Ishav Shukla, Jason Wang, Mina Guirguis, Kwadwo Darko, Salah G Aoun, Umaru Barrie, Mabel Banson, Teddy Totimeh","doi":"10.1093/noajnl/vdaf013","DOIUrl":"10.1093/noajnl/vdaf013","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy (RT) and stereotactic radiosurgery (SRS) are important treatment options for central nervous system (CNS) lesions. This review explores the current evidence on the use of radiotherapy and SRS for CNS lesions across Africa.</p><p><strong>Methods: </strong>A systematic review of the literature was completed according to the PRISMA guidelines. The results were synthesized to provide an overview of the current landscape of RT and SRS, highlighting treatment gaps and areas for further research and collaboration.</p><p><strong>Results: </strong>Nine studies, involving a total of 397 patients, were included. South Africa contributed the most studies with 4 (44.4%), followed by Nigeria with 3 studies (33.3%). Brain tumors were the most common lesion type, found in 88.8% of cases (95% CI: 66.9-100.0) with metastatic tumors being prevalent in 37.5% of cases (95% CI: 1.6-73.4). The breast was the most frequent origin of metastases seen in 93.67% (95% CI: 80-100). Whole brain radiation therapy was used in 33.3% of patients (95% CI: 0.7-66.0), stereotactic proton beam therapy in 33.3% (95% CI: 0.7-66.1), and gamma knife radiosurgery in 22.3% (95% CI: 0-51.1).</p><p><strong>Conclusion: </strong>RT and SRS are being implemented for CNS lesions in settings across Africa. Improving access and efficiency of these treatments will require both local and international collaboration to address challenges related to resource management and distribution.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf013"},"PeriodicalIF":3.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412190","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":"Real-world analysis of treatment patterns and survival outcome of glioblastoma patients in a German single-center study: Can survival rates of randomized controlled trials be achieved?","authors":"Samuel Paus, Johannes Hoffmann, Julia Roeper, Frank Griesinger","doi":"10.1093/noajnl/vdaf009","DOIUrl":"10.1093/noajnl/vdaf009","url":null,"abstract":"<p><strong>Background: </strong>The reported survival data for glioblastoma patients vary strongly between different studies. In our study, we therefore examined which data are applicable in a real-world population in a German center and how these real-world data perform in comparison to survival data presented in randomized controlled trials (RCTs).</p><p><strong>Methods: </strong>Data of all patients treated with newly diagnosed glioblastoma in a single German center between 2010 and 2019 were analyzed and treatment patterns plus survival rates were matched to existing real-world data and results of RCTs.</p><p><strong>Results: </strong>Two hundred thirty-three patients were analyzed. Median age was 63 years, f/m ratio was 1:162, and 73% of patients underwent surgery, while 27% had biopsy only. The extent of resection had a significant impact on overall survival (OS; <i>P</i> <.001), as well as age (<i>P</i> <.001), methylguanine methyltransferase methylation status (<i>P</i> <.001), and eastern cooperative oncology group performance status (<i>P</i> <.001). The median OS of our whole study population was 10.55 months. While a fictitious Stupp study cohort (built by using eligibility criteria of the EORTC-22981-26981 trial) with an OS of 14.3 months nearly achieved the survival results of the presented data from the EORTC-22981-26981 trial, the OS of the patients who did not fulfill the eligibility criteria was only 6.9 months.</p><p><strong>Conclusion: </strong>Survival of patients with unfavorable prognostic factors is still poor and these patients are not represented in recent RCTs. Outcome data of RCTs can be transferred to real world cohorts, if in- and exclusion criteria are fulfilled, while outcome is significantly inferior in cohorts that do not fulfill these criteria.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf009"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416032","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":"A single-arm phase 2 study of abemaciclib in adult patients with recurrent grade 3 oligodendroglioma.","authors":"Carson A Wills, Suyash Mohan, Ali Nabavizadeh, Thara Patel, Timothy Prior, Maikel Mansour, Emily McCoy, Shivani Shah, Natalie Angeloni, Meghan O'Neill, Suzanne Frangos, Caroline Blessing, Leah Coghlan, Eileen Maloney, E Paul Wileyto, Arati S Desai, Stephen J Bagley","doi":"10.1093/noajnl/vdaf011","DOIUrl":"10.1093/noajnl/vdaf011","url":null,"abstract":"<p><strong>Background: </strong>Novel treatments are needed for oligodendroglioma that has recurred following radiotherapy (RT) and chemotherapy. The cyclin D1-CDK4 axis is frequently dysregulated in oligodendroglioma. Abemaciclib is a selective CDK4/6 inhibitor that achieves pharmacologically relevant concentrations in brain tumor tissue.</p><p><strong>Methods: </strong>We conducted a single-arm, phase 2 trial evaluating the efficacy of abemaciclib in patients with recurrent oligodendroglioma, isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted, WHO grade 3, following prior RT and ≥1 line of alkylating chemotherapy. Patients received abemaciclib 200 mg twice daily. The primary endpoint was progression-free survival at 6 months (PFS-6).</p><p><strong>Results: </strong>Ten patients were enrolled. The most common treatment-related adverse event was grade 1-2 diarrhea, occurring in all patients. Five patients (50%) were alive and progression-free at 6 months, below the minimum required (80%) to meet the primary endpoint. In patients with enhancing tumor (<i>n</i> = 9), best response was partial response in 2 patients (objective radiographic response = 22.2%; duration of response [DOR] 13.1 and 7.7 months), stable disease (SD) in 3 patients (33.3%; duration of SD 17.0, 6.7, and 2.5 months), progressive disease in 3 patients (33.3%), and nonevaluable in 1 patient (11.1%). The patient with nonenhancing tumor showed SD lasting 10.2 months. Median PFS was 7.7 months (95% CI, 1.7-13.1 months); median overall survival was not reached (median follow-up 17 months).</p><p><strong>Conclusions: </strong>The efficacy of abemaciclib in recurrent grade 3 oligodendroglioma was inadequate to warrant further evaluation as monotherapy in unselected patients. However, given the objective responses and durable disease control observed in a subset of patients, further studies are warranted to identify subgroups that may benefit.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf011"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412187","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":"ICAM-1 and IL-10 are associated with cognitive dysfunction using the MoCA test in glioma: Findings from the NCI Neuro-Oncology Branch Natural History Study.","authors":"Kaitlynn Slattery, McKenzie C Kauss, Dhaivat Raval, Emory Hsieh, Ann Choi, Tara S Davis, Kimberly R Robins, Hope Miller, Elizabeth Vera, Michelle L Wright, Marta Penas-Prado, Mark R Gilbert, Tito Mendoza, Terri S Armstrong, Vivian A Guedes","doi":"10.1093/noajnl/vdaf002","DOIUrl":"10.1093/noajnl/vdaf002","url":null,"abstract":"<p><strong>Background: </strong>Cognitive dysfunction is common among patients with malignant glioma, yet the underlying mechanisms of this dysfunction remain unclear. Protein markers of neurodegeneration, inflammation, and vascular damage have been associated with central nervous system pathology and with cognitive changes in neurological diseases, but their clinical utility in gliomas is unknown. This study examined the relationships between cognitive dysfunction, tumor isocitrate dehydrogenase (IDH) mutation status in gliomas, and a panel of blood-based protein biomarkers.</p><p><strong>Methods: </strong>This retrospective cohort study included 73 glioma patients with either IDH-mutant (<i>n</i> = 45) or IDH-wildtype tumors (<i>n</i> = 28) enrolled in a natural history study. Cognitive function was assessed using the Montreal Cognitive Assessment (scores <26 indicated cognitive dysfunction). Serum levels of 17 proteins were measured using ultrasensitive assays.</p><p><strong>Results: </strong>Cognitive dysfunction was present in 53% of participants (<i>n</i> = 39), and more frequently in the IDH-wildtype group (75%) than in the IDH-mutant group (40%). Patients with wildtype tumors had higher levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin-6 (IL-6), and tumor necrosis factor-α than patients with IDH-mutant tumors, which remained in multivariate analysis. ICAM-1 and IL-10 were higher in patients with cognitive dysfunction compared to those with normal cognition, even after adjusting for tumor IDH-mutation status, age, tumor grade, and surgery history.</p><p><strong>Conclusions: </strong>Cognitive dysfunction was associated with protein markers linked to vascular damage and inflammation regardless of tumor IDH status. Our findings suggest an association of cognitive dysfunction with heightened systemic inflammatory status that requires further interrogation for its role in pathophysiologic mechanisms.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf002"},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560433","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}