Neuro-oncology advances最新文献

{"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":"https://doi.org/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}

{"title":"Early experience and perioperative risk of GammaTile for upfront brain metastases: Report from a prospective multicenter study.","authors":"Sabrina L Zeller, Sauson Soldozy, Shaye Busse, Clark C Chen, Andrew Venteicher, Clara Ferreira, Kathryn Dusenbery, Stuart Lee, Matthew Sean Peach, Vincent DiNapoli, Rupesh Kotecha, Manmeet S Ahluwalia, Kimberly Bojanowski-Hoang, Simon J Hanft","doi":"10.1093/noajnl/vdae156","DOIUrl":"10.1093/noajnl/vdae156","url":null,"abstract":"<p><strong>Background: </strong>GammaTile (GT), a form of brachytherapy utilizing cesium-131 seeds in a bioresorbable collagen tile, has gained popularity for the treatment of recurrent intracranial tumors and more recently for newly diagnosed metastases. This study reports early experience utilizing GT in upfront brain metastases with a focus on clinical applications and perioperative safety.</p><p><strong>Methods: </strong>The STaRT Registry (NCT04427384) was queried for all patients receiving GT for upfront metastases from August 2021 to August 2023. Data regarding patient demographics, procedure details, and adverse events (AEs) were extracted and analyzed.</p><p><strong>Results: </strong>Twenty-eight patients, median age 65 years (range 28-81), with 30 treated metastases were reported from 6 institutions. Patients had 2.8 metastases on average (range 1-15) at the time of surgery; however, most patients had a single metastasis (60.7%). The mean diameter of treated metastases was 3.4 cm (range 1.5-4.7). A median of 4.0 tiles (range 1-10) were used per tumor. The median follow-up was 3.0 months (range 1.0-11.2) with 6 attributed AEs (21.4%), including 1 grade ≥ 3 (infection). In the immediate postoperative period (<14 days), 2 patients reported pain or headache, and 1 reported facial edema. One patient developed seizures on postoperative day 8 requiring medication. At 1-month follow-up, there was 1 superficial wound infection, in a previously colonized patient, requiring surgical intervention without explantation of tiles. At 3-month follow-up, 1 patient reported facial pain not requiring treatment. There were no symptomatic hematomas.</p><p><strong>Conclusions: </strong>GT demonstrates a favorable safety profile in upfront brain metastases with a 3.6% rate of serious AEs (grade ≥ 3) within 90 days of the procedure.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae156"},"PeriodicalIF":3.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484590","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":"Spinal neuro-oncology-Not an appendix of neuro-oncology.","authors":"Suganth Suppiah, Ivo Tremont-Lukats, Manfred Westphal","doi":"10.1093/noajnl/vdae146","DOIUrl":"10.1093/noajnl/vdae146","url":null,"abstract":"","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 Suppl 3","pages":"iii1-iii2"},"PeriodicalIF":3.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484509","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":"Clinical, molecular, and genetic features of spinal meningiomas.","authors":"Dylan Deska-Gauthier, Laureen D Hachem, Justin Z Wang, Alex P Landry, Leeor Yefet, Chloe Gui, Yosef Ellengbogen, Jetan Badhiwala, Gelareh Zadeh, Farshad Nassiri","doi":"10.1093/noajnl/vdae123","DOIUrl":"10.1093/noajnl/vdae123","url":null,"abstract":"<p><p>Spinal meningiomas comprise 25%-46% of all primary spinal tumors. While the majority are benign and slow-growing, when left untreated, they can result in significant neurological decline. Emerging clinical, imaging, and molecular data have begun to reveal spinal meningiomas as distinct tumor subtypes compared to their intracranial counterparts. Moreover, recent studies indicate molecular and genetic subtype heterogeneity of spinal meningiomas both within and across the classically defined WHO grades. In the current review, we focus on recent advances highlighting the epidemiological, pathological, molecular/genetic, and clinical characteristics of spinal meningiomas. Furthermore, we explore patient and tumor-specific factors that predict prognosis and postoperative outcomes. We highlight areas that require further investigation, specifically efforts aimed at linking unique molecular, genetic, and imaging characteristics to distinct clinical presentations to better predict and manage patient outcomes.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 Suppl 3","pages":"iii73-iii82"},"PeriodicalIF":3.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484593","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":"Tumor volume features predict survival outcomes for patients diagnosed with diffuse intrinsic pontine glioma.","authors":"D'Andre Spencer, Erin R Bonner, Carlos Tor-Díez, Xinyang Liu, Kristen Bougher, Rachna Prasad, Heather Gordish-Dressman, Augustine Eze, Roger J Packer, Javad Nazarian, Marius George Linguraru, Miriam Bornhorst","doi":"10.1093/noajnl/vdae151","DOIUrl":"10.1093/noajnl/vdae151","url":null,"abstract":"<p><strong>Background: </strong>Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood central nervous system tumor. Diagnosis and monitoring of tumor response to therapy is based on magnetic resonance imaging (MRI). MRI-based analyses of tumor volume and appearance may aid in the prediction of patient overall survival (OS).</p><p><strong>Methods: </strong>Contrast-enhanced T1- and FLAIR/T2-weighted MR images were retrospectively collected from children with classical DIPG diagnosed by imaging (<i>n</i> = 43 patients). MRI features were evaluated at diagnosis (<i>n</i> = 43 patients) and post-radiation (<i>n</i> = 40 patients) to determine OS outcome predictors. Features included 3D tumor volume (T_wv), contrast-enhancing tumor core volume (T_c), T_c relative to T_wv (T_C/T_wv), and T_wv relative to whole brain volume. Support vector machine (SVM) learning was used to identify feature combinations that predicted OS outcome (defined as OS shorter or longer than 12 months from diagnosis).</p><p><strong>Results: </strong>Features associated with poor OS outcome included the presence of contrast-enhancing tumor at diagnosis, >15% T_c/T_wv post-radiation therapy (RT), and >20% ∆Tc/T_wv post-RT. Consistently, SVM learning identified T_c/T_wv at diagnosis (prediction accuracy of 74%) and ∆T_c/T_wv at <2 months post-RT (accuracy = 75%) as primary features of poor survival.</p><p><strong>Conclusions: </strong>This study demonstrates that tumor imaging features at diagnosis and within 4 months of RT can predict differential OS outcomes in DIPG. These findings provide a framework for incorporating tumor volume-based predictive analyses into the clinical setting, with the potential for treatment customization based on tumor risk characteristics and future applications of machine-learning-based analysis.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae151"},"PeriodicalIF":3.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484591","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}