Neuro-oncology advancesPub Date : 2025-08-09eCollection Date: 2025-01-01DOI: 10.1093/noajnl/vdaf167
{"title":"Correction to: Consortium for Intracranial Metastasis Academic Research (CIMARa): Global interdisciplinary collaborations to improve outcomes of patients with brain metastases.","authors":"","doi":"10.1093/noajnl/vdaf167","DOIUrl":"https://doi.org/10.1093/noajnl/vdaf167","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/noajnl/vdaf049.].</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf167"},"PeriodicalIF":4.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839539","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}
Neuro-oncology advancesPub Date : 2025-08-09eCollection Date: 2025-01-01DOI: 10.1093/noajnl/vdaf175
Joo Whan Kim, Seung Ah Choi, Sungyoung Lee, Hongseok Yun, Ji Hoon Phi, Sung-Hye Park, Seung-Ki Kim
{"title":"Revisiting pediatric HGGs and PNETs according to the WHO CNS5 criteria: A clinical and genomic retrospective analysis.","authors":"Joo Whan Kim, Seung Ah Choi, Sungyoung Lee, Hongseok Yun, Ji Hoon Phi, Sung-Hye Park, Seung-Ki Kim","doi":"10.1093/noajnl/vdaf175","DOIUrl":"10.1093/noajnl/vdaf175","url":null,"abstract":"<p><strong>Background: </strong>The 2021 WHO Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5), introduced revised diagnostic criteria for pediatric brain tumors (BTs), redefining pediatric-type diffuse high-grade gliomas (pHGGs) into 4 subtypes: diffuse midline glioma, H3 K27-altered (DMG-H3K27), diffuse hemispheric glioma, H3 G34-mutant (DHG-H3G34), diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (DpHGG-H3wt/IDHwt), and infant-type hemispheric glioma (IHG). This study revisits prior diagnoses of HGGs and primitive neuroectodermal tumors (PNETs) in children and incorporates next-generation sequencing (NGS) to classify tumors according to the revised criteria and analyze their clinicogenomic characteristics and outcomes.</p><p><strong>Methods: </strong>A retrospective review of pediatric patients diagnosed with glioblastoma (GBM), anaplastic astrocytoma, anaplastic oligoastrocytoma (AOA), gliomatosis cerebri, or PNET between 1997 and 2023 was conducted. Cases underwent pathology review, immunohistochemistry (IHC), and BT-targeted NGS for reclassification per WHO CNS5. An additional 20 patients diagnosed with pHGG via genetics-integrated diagnosis since 2020 were included. Clinical characteristics, genomic alterations, and outcomes were analyzed.</p><p><strong>Results: </strong>Among the 78 reviewed cases, 41 were reclassified as pHGGs. <i>TP53</i> mutations were the most prevalent, particularly in DpHGG-H3wt/IDHwt, which showed associations with cancer predisposition syndrome (CPS). Two patients with Li-Fraumeni syndrome (LFS) developed DpHGG-H3wt/IDHwt adjacent to prior radiation fields. The 2-year overall survival (OS) rates were lowest in DpHGG-H3wt/IDHwt (23.2%) and highest in IHG (92.3%). Long-term survival was observed in IHG patients, with a 5-year OS rate of 73.8%, indicating the need for different adjuvant treatment strategies compared to other pHGGs.</p><p><strong>Conclusions: </strong>BT-targeted NGS facilitates the reclassification of pHGGs, revealing associations with CPS. Routine germline sequencing is warranted, and accurate molecular diagnosis enables a shift in treatment strategies tailored to specific pHGG subtypes.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf175"},"PeriodicalIF":4.1,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115770","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":"Prognostic implication of <i>CDKN2A/B</i> homozygous deletion on histological grades in isocitrate dehydrogenase-mutant astrocytomas: A systematic review and meta-analysis.","authors":"Satoshi Nakasu, Shoichi Deguchi, Koichi Mitsuya, Akifumi Notsu, Yoko Nakasu","doi":"10.1093/noajnl/vdaf171","DOIUrl":"10.1093/noajnl/vdaf171","url":null,"abstract":"<p><strong>Background: </strong>Isocitrate dehydrogenase-mutant astrocytomas (A-IDHm) with the homozygous deletion of <i>cyclin-dependent kinase 2A/B</i> (<i>CDKN2A/B</i>-HD) have been classified as grade 4 in the WHO 2021 classification (WHO2021). This study aimed to find survival differences in subgroups stratified by <i>CDKN2A/B</i> status and traditional histological grades (hGs).</p><p><strong>Methods: </strong>The frequency and prognostication of <i>CDKN2A/B</i>-HD in primary A-IDHm were analyzed based on hGs. A systematic review and meta-analysis were performed following the PRISMA guidelines using three databases (registration CRD42024570409). Effect sizes were evaluated using the hazard ratio (HR) and restricted mean survival time (RMST) for overall survival (OS).</p><p><strong>Results: </strong>Thirty-three articles with 3739 A-IDHm patients were included. The pooled frequencies of <i>CDKN2A/B</i>-HD were 3.3% [95% confidence interval (CI): 1.9-5.8], 11.0% [CI: 8.6-14.0], and 39.1% [CI: 34.0-44.5] in hG-II, hG-III, and hG-IV, respectively, after excluding the outliers. <i>CDKN2A/B</i>-HD significantly impaired OS in patients with hG-III (pooled HR (pHR), 3.61; CI, 2.72-4.78) and hG-IV (pHR, 1.93; CI, 1.43-2.61), and it was not evident in hG-II due to the paucity of the data. pHR showed better survival in patients with grade-2 tumors over grade-3 (WHO2021) (pHR 1.44, CI 1.09-1.90, <i>P</i> = .01, 1184 patients), although the RMST difference was only 7.1 months at 100 months (<i>N</i> = 1162). Among the grade-4 tumors, <i>CDKN2A/B</i>-HD hG-IV had the worst survival (RMST at 60 months, 32 months).</p><p><strong>Conclusion: </strong>The prognosis of A-IDHm can be stratified by hG and <i>CDKN2A/B</i>-HD. However, evidence is insufficient for the classification of hG-II with <i>CDKN2A/B</i>-HD.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf171"},"PeriodicalIF":4.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115747","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}
Neuro-oncology advancesPub Date : 2025-08-06eCollection Date: 2025-01-01DOI: 10.1093/noajnl/vdaf174
Montse Alemany, Jordi Bruna, Victor J Yuste
{"title":"Reaching the point-of-no-return: The cornerstone of glioblastoma treatment?","authors":"Montse Alemany, Jordi Bruna, Victor J Yuste","doi":"10.1093/noajnl/vdaf174","DOIUrl":"10.1093/noajnl/vdaf174","url":null,"abstract":"<p><p>The activation of cellular death programs does not necessarily predetermine an inevitable outcome. Identifying the precise moment when a cell irreversibly transitions from life to death presents a significant challenge in its assessment and measurement. In this review, we explore the critical alterations in cellular structures that have been proposed as the <i>point-of-no-return</i>. Using glioblastoma as a model-one of the most aggressive and lethal tumor types with a remarkable ability to evade cell death-we highlight the challenge of reaching the <i>point-of-no-return</i>. Glioblastoma cells often exhibit impaired function of the apoptotic endonuclease, DFF40/CAD/CPAN, leading to incomplete apoptosis and genomic instability. The sublethal activation of DFF40/CAD/CPAN not only allows tumor cells to survive but can also drive more aggressive phenotypes and enhance therapeutic resistance. We underscore the need to reassess glioblastoma treatment strategies from broad cytotoxic approaches to more targeted therapies that exploit specific vulnerabilities within regulated cell death (RCD) pathways.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf174"},"PeriodicalIF":4.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115737","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}
Neuro-oncology advancesPub Date : 2025-08-05eCollection Date: 2025-01-01DOI: 10.1093/noajnl/vdaf162
Amirah Alsaedi, Walaa Alsharif, Awadia Gareeballah, Sultan Alshoabi, Fahad Alhazmi, Khalid Alshamrani, Lama Alofy, Rahaf Samman, Raneem Al-Bakri, Yara Shukr
{"title":"Assessment of the emerging role of AI in diagnosing gliomas using MRI: Systematic review and meta-analysis.","authors":"Amirah Alsaedi, Walaa Alsharif, Awadia Gareeballah, Sultan Alshoabi, Fahad Alhazmi, Khalid Alshamrani, Lama Alofy, Rahaf Samman, Raneem Al-Bakri, Yara Shukr","doi":"10.1093/noajnl/vdaf162","DOIUrl":"10.1093/noajnl/vdaf162","url":null,"abstract":"<p><p>Despite the emerging role of artificial intelligence (AI) in glioma grading, its clinical adoption remains in its early stages. This meta-analysis aims to assess the role of AI in differentiating glioma grades using magnetic resonance imaging (MRI). Twenty-five studies matched the inclusion criteria and were included after systematic searches through \"PubMed\" electronic database. The quality of the included studies was assessed utilizing Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A bivariate random-effects model was employed to estimate the pooled effect of the sensitivity and specificity, followed by an estimation of the summary receiver operating characteristic (SROC) curve. The overall results suggest relatively high sensitivity and specificity among the assessed AI methods for discriminating glioma grades. Convolutional Neural Networks (CNN) demonstrated the highest diagnostic accuracy, with a sensitivity of 93% (95% CI: 88%-97%) and specificity of 92% (95% CI: 90%-94%). This meta-analysis highlights the potential role of AI models based on MRI in supporting clinicians in glioma grading.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf162"},"PeriodicalIF":4.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115769","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}
Neuro-oncology advancesPub Date : 2025-08-04eCollection Date: 2025-01-01DOI: 10.1093/noajnl/vdaf169
Vincent Rock, Manmeet S Ahluwalia, Matt Anthony, David Arons, Jean Arzbaecher, Erin Dunbar, Catherine Fraher, Mindy Freund, Vinai Gondi, Shanu Khanuja, Danielle Leach, Ashlee R Loughan, Al Musella, Kathy Oliver, Kendra Paabo, Vinay K Puduvalli, Geri-Dee Shaffer, Alissa A Thomas, Kimberly Wallgren, Jeffrey S Wefel, Jennifer S Yu, Gabriel Zada, Nicole Willmarth, Ralph DeVitto
{"title":"Guiding principles for adult CNS tumor treatment programs.","authors":"Vincent Rock, Manmeet S Ahluwalia, Matt Anthony, David Arons, Jean Arzbaecher, Erin Dunbar, Catherine Fraher, Mindy Freund, Vinai Gondi, Shanu Khanuja, Danielle Leach, Ashlee R Loughan, Al Musella, Kathy Oliver, Kendra Paabo, Vinay K Puduvalli, Geri-Dee Shaffer, Alissa A Thomas, Kimberly Wallgren, Jeffrey S Wefel, Jennifer S Yu, Gabriel Zada, Nicole Willmarth, Ralph DeVitto","doi":"10.1093/noajnl/vdaf169","DOIUrl":"10.1093/noajnl/vdaf169","url":null,"abstract":"<p><p>Central nervous system (CNS) tumors require specialized care to promote better patient survival outcomes and life quality. Before this paper, there were no published guidelines identifying what constitutes specialized, comprehensive CNS tumor treatment and care in the United States. Consequently, members of several CNS tumor patient advocacy and not-for-profit organizations established a set of Guiding Principles by which adult CNS tumor treatment programs could be evaluated for the availability of specialized services offered. These Guiding Principles for CNS tumor treatment programs are the first tool of its kind in the United States. Patient advocacy and not-for-profit organizations that support the CNS tumor population can use these guiding principles to help patients and their loved ones make more informed decisions about where to seek treatment and care.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf169"},"PeriodicalIF":4.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115734","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}
Neuro-oncology advancesPub Date : 2025-08-04eCollection Date: 2025-01-01DOI: 10.1093/noajnl/vdaf176
Philipp Lohmann, Laura Schäfer, Sandra Krause, Betül Altunay, Antje Willuweit, Jan-Michael Werner, Norbert Galldiks, Karl-Josef Langen, Felix M Mottaghy, Susanne Lütje
{"title":"Advancements in noninvasive visualization of the immune environment in glioblastoma: A systematic review.","authors":"Philipp Lohmann, Laura Schäfer, Sandra Krause, Betül Altunay, Antje Willuweit, Jan-Michael Werner, Norbert Galldiks, Karl-Josef Langen, Felix M Mottaghy, Susanne Lütje","doi":"10.1093/noajnl/vdaf176","DOIUrl":"10.1093/noajnl/vdaf176","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is known for its highly immunosuppressive microenvironment, hindering the efficacy of immunotherapies. Noninvasive imaging like immuno-positron emission tomography (PET) offers the potential for visualizing immune dynamics within glioblastoma, potentially aiding in patient selection and treatment monitoring. This systematic review evaluates immuno-PET tracers currently under investigation for the noninvasive visualization of the immune environment in glioblastoma.</p><p><strong>Methods: </strong>A literature search was conducted in PubMed and Web of Science up to March 2025, using keywords related to glioblastoma, immuno-PET, immune compartments, and specific tracers. Studies were screened based on predefined inclusion and exclusion criteria, focusing on the development, characterization, or application of immuno-PET tracers targeting immune cells or immune checkpoint molecules in glioblastoma.</p><p><strong>Results: </strong>Nineteen studies met the inclusion criteria, exploring tracers targeting immune checkpoints and immune cell populations. Full-length antibodies demonstrated higher tumor specificity and retention compared to smaller fragments but showed longer circulation times. Peptide-based tracers and affibodies offered improved pharmacokinetics with rapid clearance and lower nonspecific uptake but encountered hurdles in ensuring adequate tumor targeting and retention. Advancements included dual-modal tracers combining PET and near-infrared fluorescence imaging for enhanced diagnostic and intraoperative applications.</p><p><strong>Conclusions: </strong>Significant progress has been made in developing immuno-PET tracers for noninvasive visualization of immune reactions in glioblastoma. Challenges persist in clinical translation due to issues like blood-brain barrier permeability and safety profiles. Continued research and clinical evaluations are essential to harness the potential of immuno-PET in improving glioblastoma diagnosis, assessment of treatment response, and guiding personalized immunotherapy strategies, ultimately aiming to enhance patient outcomes.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf176"},"PeriodicalIF":4.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188178","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}
Neuro-oncology advancesPub Date : 2025-08-03eCollection Date: 2025-01-01DOI: 10.1093/noajnl/vdaf154
Alexandros Ferles, Paulina Majewska, Ragnhild Holden Helland, Ivar Kommers, André Pedersen, Mario Tranfa, Hilko Ardon, Lorenzo Bello, Mitchel S Berger, Tora Dunås, Marco Conti Nibali, Julia Furtner, Shawn L Hervey-Jumper, Albert J S Idema, Barbara Kiesel, Rishi Nandoe Tewarie, Emmanuel Mandonnet, Pierre A Robe, Marco Rossi, Tommaso Sciortino, Tom Aalders, Michiel Wagemakers, Georg Widhalm, Aeilko H Zwinderman, Lisa Millgård Sagberg, Asgeir Store Jakola, Erik Thurin, Ingerid Reinertsen, David Bouget, Ole Solheim, Roelant S Eijgelaar, Philip C de Witt Hamer, Frederik Barkhof
{"title":"Estimating overall survival of glioblastoma patients using clinical variables, tumor size, and location.","authors":"Alexandros Ferles, Paulina Majewska, Ragnhild Holden Helland, Ivar Kommers, André Pedersen, Mario Tranfa, Hilko Ardon, Lorenzo Bello, Mitchel S Berger, Tora Dunås, Marco Conti Nibali, Julia Furtner, Shawn L Hervey-Jumper, Albert J S Idema, Barbara Kiesel, Rishi Nandoe Tewarie, Emmanuel Mandonnet, Pierre A Robe, Marco Rossi, Tommaso Sciortino, Tom Aalders, Michiel Wagemakers, Georg Widhalm, Aeilko H Zwinderman, Lisa Millgård Sagberg, Asgeir Store Jakola, Erik Thurin, Ingerid Reinertsen, David Bouget, Ole Solheim, Roelant S Eijgelaar, Philip C de Witt Hamer, Frederik Barkhof","doi":"10.1093/noajnl/vdaf154","DOIUrl":"10.1093/noajnl/vdaf154","url":null,"abstract":"<p><strong>Background: </strong>Accurate prognosis of glioblastoma is crucial for better-informed treatment decisions, potentially leading to improved disease management. We investigated whether clinical variables, tumor size, and location, can serve as prognostic factors.</p><p><strong>Methods: </strong>A retrospective, multicenter study enrolled 1318 adult patients with histopathologically confirmed glioblastoma undergoing first-time surgery, with survival censored for 188 patients. Pre-operative brain MRIs were used to compute tumor size and derive advanced radiological features describing tumor location, later refined by expert-based opinion. Post-operative MRIs were used to measure the enhancing residual tumor volume. The prognostic quality of all variables, measurements, and features was assessed as inputs of three survival regression models (CoxPH, Random Survival Forests, DeepSurv) to predict overall survival, under five timepoints of patient treatment: onset presentation, assessment by multidisciplinary board, intervention planning, post-intervention evaluation, and chemoradiotherapy planning. Model evaluation was performed with the C-index, Brier Score over Time, and Integrated Brier Score.</p><p><strong>Results: </strong>Multivariable Cox analysis identified most clinical variables and tumor size as strong predictors of patient survival, with varying hazard ratios across timepoints. DeepSurv was consistently the top performing model under all possible inputs and at all timepoints, yielding mean test C-index scores ranging from 61.71% to 70.29%, and mean Integrated Brier Scores ranging from 8.57% to 7.63%.</p><p><strong>Conclusion: </strong>Clinical variables, tumor size, and location carry prognostic value for the overall survival of patients with glioblastoma. The best predictive performance was observed under a Deep Survival model using all variables at the stage of chemoradiotherapy planning.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf154"},"PeriodicalIF":4.1,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984231","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}