Neuro-oncology advances最新文献

{"title":"Enhancing clinical decision-making: An externally validated machine learning model for predicting isocitrate dehydrogenase mutation in gliomas using radiomics from presurgical magnetic resonance imaging.","authors":"Jan Lost, Nader Ashraf, Leon Jekel, Marc von Reppert, Niklas Tillmanns, Klara Willms, Sara Merkaj, Gabriel Cassinelli Petersen, Arman Avesta, Divya Ramakrishnan, Antonio Omuro, Ali Nabavizadeh, Spyridon Bakas, Khaled Bousabarah, MingDe Lin, Sanjay Aneja, Michael Sabel, Mariam Aboian","doi":"10.1093/noajnl/vdae157","DOIUrl":"10.1093/noajnl/vdae157","url":null,"abstract":"<p><strong>Background: </strong>Glioma, the most prevalent primary brain tumor, poses challenges in prognosis, particularly in the high-grade subclass, despite advanced treatments. The recent shift in tumor classification underscores the crucial role of isocitrate dehydrogenase (IDH) mutation status in the clinical care of glioma patients. However, conventional methods for determining IDH status, including biopsy, have limitations. Exploring the use of machine learning (ML) on magnetic resonance imaging to predict IDH mutation status shows promise but encounters challenges in generalizability and translation into clinical practice because most studies either use single institution or homogeneous datasets for model training and validation. Our study aims to bridge this gap by using multi-institution data for model validation.</p><p><strong>Methods: </strong>This retrospective study utilizes data from large, annotated datasets for internal (377 cases from Yale New Haven Hospitals) and external validation (207 cases from facilities outside Yale New Haven Health). The 6-step research process includes image acquisition, semi-automated tumor segmentation, feature extraction, model building with feature selection, internal validation, and external validation. An extreme gradient boosting ML model predicted the IDH mutation status, confirmed by immunohistochemistry.</p><p><strong>Results: </strong>The ML model demonstrated high performance, with an Area under the Curve (AUC), Accuracy, Sensitivity, and Specificity in internal validation of 0.862, 0.865, 0.885, and 0.713, and external validation of 0.835, 0.851, 0.850, and 0.847.</p><p><strong>Conclusions: </strong>The ML model, built on a heterogeneous dataset, provided robust results in external validation for the prediction task, emphasizing its potential clinical utility. Future research should explore expanding its applicability and validation in diverse global healthcare settings.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae157"},"PeriodicalIF":3.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808950","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":"Empowering the next generation in neuro-oncology: Introduction of the EANO Career Boost Initiative.","authors":"Philipp Lohmann, Johnny Duerinck, Matthijs van der Meulen, Dan Mitrea, Susan Short, Marjolein Geurts","doi":"10.1093/noajnl/vdae167","DOIUrl":"https://doi.org/10.1093/noajnl/vdae167","url":null,"abstract":"","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae167"},"PeriodicalIF":3.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515558","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":"Distinction of pseudoprogression from true progression in glioblastomas using machine learning based on multiparametric magnetic resonance imaging and O⁶-methylguanine-methyltransferase promoter methylation status.","authors":"Virendra Kumar Yadav, Suyash Mohan, Sumeet Agarwal, Laiz Laura de Godoy, Archith Rajan, MacLean P Nasrallah, Stephen J Bagley, Steven Brem, Laurie A Loevner, Harish Poptani, Anup Singh, Sanjeev Chawla","doi":"10.1093/noajnl/vdae159","DOIUrl":"10.1093/noajnl/vdae159","url":null,"abstract":"<p><strong>Background: </strong>It is imperative to differentiate true progression (TP) from pseudoprogression (PsP) in glioblastomas (GBMs). We sought to investigate the potential of physiologically sensitive quantitative parameters derived from diffusion and perfusion magnetic resonance imaging (MRI), and molecular signature combined with machine learning in distinguishing TP from PsP in GBMs in the present study.</p><p><strong>Methods: </strong>GBM patients (<i>n</i> = 93) exhibiting contrast-enhancing lesions within 6 months after completion of standard treatment underwent 3T MRI. Final data analyses were performed on 75 patients as O⁶-methylguanine-DNA-methyltransferase (MGMT) status was available only from these patients. Subsequently, patients were classified as TP (<i>n</i> = 55) or PsP (<i>n</i> = 20) based on histological features or mRANO criteria. Quantitative parameters were computed from contrast-enhancing regions of neoplasms. PsP datasets were artificially augmented to achieve balanced class distribution in 2 groups (TP and PsP). A random forest algorithm was applied to select the optimized features. The data were randomly split into training and testing subsets in an 8:2 ratio. To develop a robust prediction model in distinguishing TP from PsP, several machine-learning classifiers were employed. The cross-validation and receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic performance.</p><p><strong>Results: </strong>The quadratic support vector machine was found to be the best classifier in distinguishing TP from PsP with a training accuracy of 91%, cross-validation accuracy of 86%, and testing accuracy of 85%. Additionally, ROC analysis revealed an accuracy of 85%, sensitivity of 70%, and specificity of 100%.</p><p><strong>Conclusions: </strong>Machine learning using quantitative multiparametric MRI may be a promising approach to distinguishing TP from PsP in GBMs.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae159"},"PeriodicalIF":3.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584923","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 phase 1 dose escalation of pritumumab in patients with refractory or recurrent gliomas or brain metastases.","authors":"Jose Carrillo, Jaya Mini Gill, Charles Redfern, Ivan Babic, Natsuko Nomura, Dhaval K Shah, Sean Carrick, Santosh Kesari","doi":"10.1093/noajnl/vdae166","DOIUrl":"10.1093/noajnl/vdae166","url":null,"abstract":"<p><strong>Background: </strong>This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.</p><p><strong>Methods: </strong>Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.</p><p><strong>Results: </strong>Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).</p><p><strong>Conclusions: </strong>Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae166"},"PeriodicalIF":3.7,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515555","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":"Development of an intraventricular adeno-associated virus-based labeling strategy for glioblastoma cells nested in the subventricular zone.","authors":"Arnaud Lombard, Damla Isci, Gilles Reuter, Emmanuel Di Valentin, Alexandre Hego, Didier Martin, Bernard Rogister, Virginie Neirinckx","doi":"10.1093/noajnl/vdae161","DOIUrl":"https://doi.org/10.1093/noajnl/vdae161","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a dreadful brain tumor, with a particular relationship to the adult subventricular zone (SVZ) that has been described as relevant to disease initiation, progression, and recurrence.</p><p><strong>Methods: </strong>We propose a novel strategy for the detection and tracking of xenografted GBM cells that are located in the SVZ, based on an intracerebroventricular (icv) recombinant adeno-associated virus (AAV)-mediated color conversion method. We used different patient-derived GBM stem-like cells (GSCs), which we transduced first with a retroviral vector (LRLG) that included a lox-dsRed-STOP-lox cassette, upstream of the eGFP gene, then with rAAVs expressing the Cre-recombinase. Red and green fluorescence is analyzed in vitro and in vivo using flow cytometry and fluorescence microscopy.</p><p><strong>Results: </strong>After comparing the efficiency of diverse rAAV serotypes, we confirmed that the in vitro transduction of GSC-LRLG with rAAV-Cre induced a switch from red to green fluorescence. In parallel, we verified that rAAV transduction was confined to the walls of the lateral ventricles. We, therefore, applied this conversion approach in 2 patient-derived orthotopic GSC xenograft models and showed that the icv injection of an rAAV-DJ-Cre after GSC-LRLG tumor implantation triggered the conversion of red GSCs to green, in the periventricular region. Green GSCs were also found at distant places, including the migratory tract and the tumor core.</p><p><strong>Conclusions: </strong>This study not only sheds light on the putative outcome of SVZ-nested GBM cells but also shows that icv injection of rAAV vectors allows to transduce and potentially modulate gene expression in hard-to-reach GBM cells of the periventricular area.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae161"},"PeriodicalIF":3.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515557","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":"Evolutionary evidence precludes <i>ELP1</i> as a high-penetrance pediatric cancer predisposition syndrome gene.","authors":"Kasper Amund Henriksen, Thomas Van Overeem Hansen, Karin Wadt, Kjeld Schmiegelow, Jon Foss-Skiftesvik, Ulrik Kristoffer Stoltze","doi":"10.1093/noajnl/vdae165","DOIUrl":"10.1093/noajnl/vdae165","url":null,"abstract":"","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae165"},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515559","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":"Development and epigenetic regulation of Atypical teratoid/rhabdoid tumors in the context of cell-of-origin and halted cell differentiation.","authors":"Laura Huhtala, Goktug Karabiyik, Kirsi J Rautajoki","doi":"10.1093/noajnl/vdae162","DOIUrl":"10.1093/noajnl/vdae162","url":null,"abstract":"<p><p>Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors primarily observed in infants. The only characteristic, recurrent genetic aberration of AT/RTs is biallelic inactivation of SMARCB1 (or SMARCA4). These genes are members of the mSWI/SNF chromatin-remodeling complex, which regulates various developmental processes, including neural differentiation. This review explores AT/RT subgroups regarding their distinct SMARCB1 loss-of-function mechanisms, molecular features, and patient characteristics. Additionally, it addresses the ongoing debate about the oncogenic relevance of cell-of-origin, examining the influence of developmental stage and lineage commitment of the seeding cell on tumor malignancy and other characteristics. Epigenetic dysregulation, particularly through the regulation of histone modifications and DNA hypermethylation, has been shown to play an integral role in AT/RTs' malignancy and differentiation blockage, maintaining cells in a poorly differentiated state via the insufficient activation of differentiation-related genes. Here, the differentiation blockage and its contribution to malignancy are also explored in a cellular context. Understanding these mechanisms and AT/RT heterogeneity is crucial for therapeutic improvements against AT/RTs.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae162"},"PeriodicalIF":3.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515556","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":"Analysis of safety and efficacy of proton radiotherapy for optic nerve sheath meningioma.","authors":"Maximilian Y Deng, Sophie Rauh, Günes Anil, Jonathan W Lischalk, Laura Hahnemann, Tanja Eichkorn, Juliane Hörner-Rieber, Angela Paul, Elisabetta Sandrini, Philipp Hoegen-Sassmannshausen, Thomas Held, Sebastian Regnery, Lukas Bauer, Felix Sahm, Andreas von Deimling, Antje Wick, Wolfgang Wick, Christine Jungk, Sandro M Krieg, Klaus Herfarth, Jürgen Debus, Laila König","doi":"10.1093/noajnl/vdae160","DOIUrl":"10.1093/noajnl/vdae160","url":null,"abstract":"<p><strong>Background: </strong>Primary optic nerve sheath meningiomas (ONSMs) represent a group of benign tumors originating from the optic nerve sheath, typically causing painless, gradual onset monocular visual loss, which can result in blindness if left untreated. Radiation therapy represents an important treatment option for patients with ONSM, allowing for preservation and potential improvement in visual function. In particular, proton radiotherapy may enable a reduction of the side effects due to its physical advantage of an inverted dose profile with a steep dose gradient. The study investigates the visual acuity, local tumor control, and treatment-related toxicities following proton beam radiotherapy with a single institutional cohort comprising 32 patients treated for ONSM.</p><p><strong>Methods: </strong>Patients with primary ONSM, either histologically (16/32) or radiologically confirmed (16/32), which were treated at the Department of Radiation Oncology at the University Hospital Heidelberg (Germany) were assessed in regard to their visual outcomes, treatment toxicity, and local tumor control following radiotherapy according to response assessment in neuro-oncology criteria.</p><p><strong>Results: </strong>After a median follow-up time of 39.5 months, the 5-year local progression-free survival was estimated at 100%, with 84.4% of patients reporting improvement or stability in visual acuity during their last follow-up. Radiation-induced optic neuropathy (RION) was encountered in 9.4%.</p><p><strong>Conclusions: </strong>Our study demonstrates proton beam therapy as a safe and effective treatment alternative in the therapeutic management of ONSMs. RION represents a rare but dreaded complication after treatment. Future head-to-head comparisons with photon radiotherapy in a prospective setting are required to demonstrate a potential, additional clinical benefit.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae160"},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484588","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 phase II, open-label, single-arm trial of pembrolizumab for recurrent meningioma and solitary fibrous tumor.","authors":"Dror Limon, Alexandra Amiel, Shaked Even Haim, Noa Gordon, Roi Tschernichovsky, Salomon Stemmer, Omer Gal, Yosef Laviv, Andrew Kanner, Tali Siegal, Shlomit Yust-Katz","doi":"10.1093/noajnl/vdae154","DOIUrl":"10.1093/noajnl/vdae154","url":null,"abstract":"<p><strong>Background: </strong>Atypical and anaplastic meningiomas account for 20% of all meningioma cases. Solitary fibrous tumor (SFT) is a type of soft tissue sarcoma with similar attributes to meningioma. For patients with refractory or recurrent disease after previous surgery or radiotherapy, there is no effective treatment. Pembrolizumab, an anti-programmed cell death 1 (PD-1) antibody, is an effective treatment for various solid tumors. PD-1 ligand is highly expressed in aggressive meningiomas. We aimed to assess the effectiveness of pembrolizumab in treating meningioma and SFT recurrence after surgery and radiation therapy.</p><p><strong>Methods: </strong>This prospective single-arm phase II trial comprised 15 patients with recurrent meningioma and 3 with anaplastic SFT, treated at a single institution during 2018 to 2022. The study was terminated due to a lack of efficacy and slow accrual. The primary endpoint was 6-month progression-free survival (PFS-6).</p><p><strong>Results: </strong>Median progression-free survival (PFS) was 2.6 months, and median overall survival (OS) was 40 months. The 6- and 12-month PFS were both 11.1%. The 6- and 12-month OS were 94.4% and 61.1%, respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the overall response rate was 11%, with 2 patients achieving stable disease and 2 with partial response. Three patients (16.7%) developed grade 3 toxicity.</p><p><strong>Conclusions: </strong>Our results showed that pembrolizumab failed to improve PFS-6 in patients with aggressive meningioma or anaplastic SFT. However, two patients, one with atypical meningioma and one with anaplastic SFT, achieved a partial response. More clinical studies are needed to identify which subset of patients may benefit from this treatment.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae154"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484587","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":"Approaches for prevention of tumors in patients with rhabdoid tumor predisposition syndrome.","authors":"Anupa Geethadevi, Eric H Raabe","doi":"10.1093/noajnl/vdae158","DOIUrl":"10.1093/noajnl/vdae158","url":null,"abstract":"<p><p>Patients with rhabdoid tumor predisposition syndrome (RTPS) harbor germline alterations in the epigenetic regulator genes <i>SMARCB1</i> or <i>SMARCA4</i>. Patients usually present with atypical teratoid/rhabdoid tumor (AT/RT) of the brain or malignant rhabdoid tumor (MRT) arising outside the central nervous system. Intensive treatment can lead to remissions, however tumors frequently recur or synchronous or metachronous tumors appear. A maintenance or secondary prevention regimen may prevent these aggressive tumors. Potential maintenance regimens may include low-dose traditional chemotherapy or different epigenetic therapies designed to target the epigenetic imbalance that drives RTs. We here review several potential maintenance regimens that may be useful in RTPS.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae158"},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484589","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}