Neuro-oncology advances最新文献

{"title":"A human embryonic stem cell-based model reveals the cell of origin of FOXR2-activated CNS neuroblastoma.","authors":"Hitomi N Royston, Autumn B Hampton, Dhruv Bhagat, Evonne F Pinto, Miriam D Emerson, Kosuke Funato","doi":"10.1093/noajnl/vdae144","DOIUrl":"10.1093/noajnl/vdae144","url":null,"abstract":"<p><strong>Background: </strong>FOXR2-activated central nervous system (CNS) neuroblastoma (CNS NB-FOXR2) is a recently identified subtype of brain tumor characterized by the elevated expression of the transcription factor FOXR2 mainly due to genomic rearrangements. However, the precise pathogenic mechanisms, including the cell type of origin, remain elusive.</p><p><strong>Methods: </strong>A gene expression analysis of patient tumors was performed to identify putative cell types of origin. Based on this prediction, a new human embryonic stem cell-based model was developed to validate the origin and to examine the molecular and cellular mechanisms underlying the formation of CNS NB-FOXR2.</p><p><strong>Results: </strong>Our data showed that CNS NB-FOXR2 tumors express a high level of lineage marker genes associated with the medial ganglionic eminence (MGE), a transient structure located in the developing ventral forebrain. Our model confirmed the cell-type-specific effect of FOXR2 on the proliferation and in vivo tumorigenicity. Additionally, we found that FOXR2 overexpression activated the MEK/ERK signaling pathway through a suppression of the endogenous RAS inhibitor DIRAS3. The MEK inhibitor trametinib suppressed the proliferation of FOXR2-expressing MGE progenitors more than nonexpressing cells.</p><p><strong>Conclusions: </strong>Our study collectively demonstrates that MGE progenitors are the cell of origin of CNS NB-FOXR2 and that FOXR2 activates the MEK/ERK signaling pathway, providing a potential therapeutic target.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae144"},"PeriodicalIF":3.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116541","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":"Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review.","authors":"Jakub Jarmula, Juyeun Lee, Adam Lauko, Prajwal Rajappa, Matthew M Grabowski, Andrew Dhawan, Peiwen Chen, Richard Bucala, Michael A Vogelbaum, Justin D Lathia","doi":"10.1093/noajnl/vdae142","DOIUrl":"10.1093/noajnl/vdae142","url":null,"abstract":"<p><p>Primary central nervous system (CNS) tumors affect tens of thousands of patients each year, and there is a significant need for new treatments. Macrophage migration inhibitory factor (MIF) is a cytokine implicated in multiple tumorigenic processes such as cell proliferation, vascularization, and immune evasion and is therefore a promising therapeutic target in primary CNS tumors. There are several MIF-directed treatments available, including small-molecule inhibitors, peptide drugs, and monoclonal antibodies. However, only a small number of these drugs have been tested in preclinical models of primary CNS tumors, and even fewer have been studied in patients. Moreover, the brain has unique therapeutic requirements that further make effective targeting challenging. In this review, we summarize the latest functions of MIF in primary CNS tumor initiation and progression. We also discuss advances in MIF therapeutic development and ongoing preclinical studies and clinical trials. Finally, we discuss potential future MIF therapies and the strategies required for successful clinical translation.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae142"},"PeriodicalIF":3.7,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134964","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":"Mitigating radiation-induced cognitive toxicity in brain metastases: More questions than answers.","authors":"Marta Simó, Antoni Rodríguez-Fornells, Valentín Navarro, Arturo Navarro-Martín, Ernest Nadal, Jordi Bruna","doi":"10.1093/noajnl/vdae137","DOIUrl":"10.1093/noajnl/vdae137","url":null,"abstract":"<p><p>The emergence of advanced systemic therapies added to the use of cranial radiation techniques has significantly improved outcomes for cancer patients with multiple brain metastases (BM), leading to a considerable increase in long-term survivors. In this context, the rise of radiation-induced cognitive toxicity (RICT) has become increasingly relevant. In this critical narrative review, we address the controversies arising from clinical trials aimed at mitigating RICT. We thoroughly examine interventions such as memantine, hippocampal avoidance irradiation during BM treatment or in a prophylactic setting, and the assessment of cognitive safety in stereotactic radiosurgery (SRS). Our focus extends to recent neuroscience research findings, emphasizing the importance of preserving not only the hippocampal cortex but also other cortical regions involved in neural dynamic networks and their intricate role in encoding new memories. Despite treatment advancements, effectively managing patients with multiple BM and determining the optimal timing and integration of radiation and systemic treatments remain areas requiring further elucidation. Future trials are required to delineate optimal indications and ensure SRS safety. Additionally, the impact of new systemic therapies and the potential effects of delaying irradiation on cognitive functioning also need to be addressed. Inclusive trial designs, encompassing patients with multiple BM and accounting for diverse treatment scenarios, are essential for advancing effective strategies in managing RICT and the treatment of BM patients.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae137"},"PeriodicalIF":3.7,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157072","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":"Dosimetric comparison of hippocampal-sparing technologies in patients with low-grade glioma.","authors":"Aoife Williamson, Peter Houston, Jennifer Paterson, Anthony J Chalmers, Philip McLoone, Natasha Fullerton, Sin Yee Foo, Allan James, Stefan Nowicki","doi":"10.1093/noajnl/vdae131","DOIUrl":"10.1093/noajnl/vdae131","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy (RT) plays an integral role in the management of low-grade gliomas (LGG). Late toxicity from RT can cause progressive neurocognitive dysfunction. Radiation-induced damage to the hippocampus (HCP) plays a considerable role in memory decline. Advancements in photon planning software have resulted in the development of multi-criteria optimization (MCO) and HyperArc technologies which may improve HCP sparing while maintaining planning target volume (PTV) target coverage.</p><p><strong>Methods: </strong>Three planning methods for hippocampal sparing (HS) were compared, volumetric modulated arc therapy (VMAT) without HS (VMAT_noHS), VMAT with HS (VMAT_HS), MCO with HS (MCO_HS), and HyperArc with HS (HyperArc_HS).</p><p><strong>Results: </strong>Twenty-five patients were identified. The contralateral HCP was spared in 16 patients and bilateral HCP in 9 patients with superiorly located tumors. All 3 HS planning techniques showed significant reductions in dose to the spared HCP in contralateral cases but only VMAT_HS and MCO_HS achieved this in bilateral cases (<i>P</i> < .008). Only MCO_HS was superior to VMAT_HS in lowering the dose to both contralateral HCP and bilateral HCP in all measured metrics (<i>P</i> < .008). PTV and OAR (organ at risk) dose constraints were achieved for all plans.</p><p><strong>Conclusions: </strong>This retrospective dosimetric study demonstrated the feasibility of HS for low-grade glioma. All 3 HS planning techniques achieved significant dose reductions to the spared contralateral hippocampus, but only MCO_HS and VMAT_HS achieved this in bilateral cases. MCO was superior to other planning techniques for sparing both bilateral and contralateral hippocampi.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae131"},"PeriodicalIF":3.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116554","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":"Durable benefit and slowdown in tumor growth dynamics with erdafitinib in a FGFR3-TACC3 fusion-positive IDH-wild type glioblastoma.","authors":"Santiago Cabezas-Camarero, Rebeca Pérez-Alfayate, Carmen Polidura, María Natividad Gómez-Ruiz, Lidia Gil-Martínez, Isabel Casado-Fariñas, Jorge Bartolomé, Pedro Pérez-Segura","doi":"10.1093/noajnl/vdae139","DOIUrl":"https://doi.org/10.1093/noajnl/vdae139","url":null,"abstract":"<p><p>FGFR3-TACC3 fusion-positive IDH-wild-type (IDH-WT) glioblastoma (GB) is a rare GB subtype occurring in approximately 3% of cases. It is clinical behavior and molecular profile is different from those of fusion-negative IDH-WT GBs. Evidence on the role of FGFR inhibitors in FGFR-altered gliomas is limited. We present the case of a patient with a FGFR3-TACC3 fusion-positive IDH-WT GB that at its second recurrence was treated with the FGFR inhibitor erdafitinib through a compassionate use program. Although no objective response was achieved, an overt deceleration in tumor growth was evidenced and the patient remained on treatment for 5.5 months.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae139"},"PeriodicalIF":3.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116555","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":"Survival probability of epigenetically defined IDH-wild-type glioblastoma without necrosis or vascular proliferation.","authors":"Patrick N Harter, Katharina J Weber, Franz L Ricklefs, Richard Drexler, Ulrich Schüller, Marcel Hack, Tim Hanke, Hildegard Dohmen, Till Acker, Andreas von Deimling, Martin Hasselblatt, Iris Divé, Kristian Unger, Joachim P Steinbach, David Capper, Michael W Ronellenfitsch","doi":"10.1093/noajnl/vdae138","DOIUrl":"10.1093/noajnl/vdae138","url":null,"abstract":"","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae138"},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057646","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":"Racial distribution of molecularly classified brain tumors.","authors":"Camila S Fang, Wanyi Wang, Chanel Schroff, Misha Movahed-Ezazi, Varshini Vasudevaraja, Jonathan Serrano, Erik P Sulman, John G Golfinos, Daniel Orringer, Kristyn Galbraith, Yang Feng, Matija Snuderl","doi":"10.1093/noajnl/vdae135","DOIUrl":"10.1093/noajnl/vdae135","url":null,"abstract":"<p><strong>Background: </strong>In many cancers, specific subtypes are more prevalent in specific racial backgrounds. However, little is known about the racial distribution of specific molecular types of brain tumors. Public data repositories lack data on many brain tumor subtypes as well as diagnostic annotation using the current World Health Organization classification. A better understanding of the prevalence of brain tumors in different racial backgrounds may provide insight into tumor predisposition and development, and improve prevention.</p><p><strong>Methods: </strong>We retrospectively analyzed the racial distribution of 1709 primary brain tumors classified by their methylation profiles using clinically validated whole genome DNA methylation. Self-reported race was obtained from medical records. Our cohort included 82% White, 10% Black, and 8% Asian patients with 74% of patients reporting their race.</p><p><strong>Results: </strong>There was a significant difference in the racial distribution of specific types of brain tumors. Blacks were overrepresented in pituitary adenomas (35%, <i>P</i> < .001), with the largest proportion of FSH/LH subtype. Whites were underrepresented at 47% of all pituitary adenoma patients (<i>P</i> < .001). Glioblastoma (GBM) IDH wild-type showed an enrichment of Whites, at 90% (<i>P</i> < .001), and a significantly smaller percentage of Blacks, at 3% (<i>P</i> < .001).</p><p><strong>Conclusions: </strong>Molecularly classified brain tumor groups and subgroups show different distributions among the three main racial backgrounds suggesting the contribution of race to brain tumor development.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae135"},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116558","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 the discontinuation and nonpublication of neurooncological randomized clinical trials.","authors":"Molly Butler, Mehul Mehra, Abdullah Chandasir, Lydia Kaoutzani, Fernando L Vale","doi":"10.1093/noajnl/vdae136","DOIUrl":"https://doi.org/10.1093/noajnl/vdae136","url":null,"abstract":"<p><strong>Background: </strong>Premature discontinuation and nonpublication of clinical trials contribute to research waste and compromise our ability to improve patient outcomes. However, the extent to which these problems exist in neurooncological randomized clinical trials (RCTs) is not known. This study aimed to evaluate the prevalence of discontinuation and nonpublication of neurooncological RCTs, identify contributing factors, and assess trial characteristics associated with each.</p><p><strong>Methods: </strong>We performed a retrospective, cross-sectional study of neurooncological RCTs registered in Clinicaltrials.gov before March 7, 2023. Data were collected from Clinicaltrials.gov and associated publications were located. We attempted to contact authors for all trials without associated publications or an identified reason for discontinuation.</p><p><strong>Results: </strong>Of 139 included RCTs, 57 (41%) were discontinued. The most common reason for discontinuation identified was slow enrollment or accrual (23%), though 30 trials (53%) were discontinued for unknown reasons. Trials funded by sources other than industry or the National Institutes of Health were more likely to be discontinued (odds ratio 4.2, 95% confidence interval 1.3-13.8). In total, 67 of the 139 (48%) RCTs were unpublished, including 50 of the 57 (88%) discontinued studies and 17 of the 82 (21%) completed studies.</p><p><strong>Conclusions: </strong>In our study, discontinuation of neurooncological clinical trials was common and often occurred for unknown reasons. Trials were also frequently unpublished, particularly those that were discontinued. Addressing these findings may provide an opportunity to reduce research waste and improve outcomes for patients with neurological cancers.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae136"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116553","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":"When genetics and pediatric cancer collide: Understanding and optimizing families' experiences.","authors":"Kate Hetherington, Claire E Wakefield, Brittany C McGill, Katherine M Tucker, Mark W Donoghoe, Rebecca Daly, Jacqueline D Hunter, Mandy Ballinger, Noemi A Fuentes-Bolanos, David S Ziegler","doi":"10.1093/noajnl/vdae133","DOIUrl":"10.1093/noajnl/vdae133","url":null,"abstract":"<p><strong>Background: </strong>Advances in our understanding of the genetic basis of childhood cancer, including primary central nervous system cancers, are improving the diagnosis, treatment, and clinical management of pediatric patients. To effectively translate scientific breakthroughs into enhanced clinical care, it is essential we understand and learn from the experiences of patients, families, and health professionals.</p><p><strong>Methods: </strong>This report summarizes findings from 4 Australian psychosocial substudies exploring the perspectives of patients, parents, clinicians, and scientists participating in research related to childhood cancer genetics. Specifically, these studies focus on the psychosocial impact of germline testing in children, surveillance for children with a cancer predisposition syndrome and the perspectives of healthcare professionals who deliver this testing and surveillance.</p><p><strong>Results: </strong>Data presented highlight some of the opportunities and challenges associated with the changing context of genetic predisposition testing for children, adolescents and yound adults with cancer and illustrate how embedding psychosocial data collection in clinical research can answer important questions in the field and inform the design of patient-centric models of care, resources, and workforce training.</p><p><strong>Conclusions: </strong>By embracing these perspectives, we can ensure that advances in genetic research translate into enhanced family experiences, and, ultimately, improved outcomes for children and young people with cancer, and their families.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae133"},"PeriodicalIF":3.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116629","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":"Is pulsed saturation transfer sufficient for differentiating radiation necrosis from tumor progression in brain metastases?","authors":"Rachel W Chan, Wilfred W Lam, Hanbo Chen, Leedan Murray, Beibei Zhang, Aimee Theriault, Ruby Endre, Sangkyu Moon, Patrick Liebig, Pejman J Maralani, Chia-Lin Tseng, Sten Myrehaug, Jay Detsky, Mary Jane Lim-Fat, Katrina Roberto, Daniel Djayakarsana, Bharathy Lingamoorthy, Hatef Mehrabian, Benazir Mir Khan, Arjun Sahgal, Hany Soliman, Greg J Stanisz","doi":"10.1093/noajnl/vdae132","DOIUrl":"10.1093/noajnl/vdae132","url":null,"abstract":"<p><strong>Background: </strong>Stereotactic radiosurgery (SRS) for the treatment of brain metastases delivers a high dose of radiation with excellent local control but comes with the risk of radiation necrosis (RN), which can be difficult to distinguish from tumor progression (TP). Magnetization transfer (MT) and chemical exchange saturation transfer (CEST) are promising techniques for distinguishing RN from TP in brain metastases. Previous studies used a 2D continuous-wave (ie, block radiofrequency [RF] saturation) MT/CEST approach. The purpose of this study is to investigate a 3D pulsed saturation MT/CEST approach with perfusion MRI for distinguishing RN from TP in brain metastases.</p><p><strong>Methods: </strong>The study included 73 patients scanned with MT/CEST MRI previously treated with SRS or fractionated SRS who developed enhancing lesions with uncertain diagnoses of RN or TP. Perfusion MRI was acquired in 49 of 73 patients. Clinical outcomes were determined by at least 6 months of follow-up or via pathologic confirmation (in 20% of the lesions).</p><p><strong>Results: </strong>Univariable logistic regression resulted in significant variables of the quantitative MT parameter 1/(R_A·T_2A), with 5.9 ± 2.7 for RN and 6.5 ± 2.9 for TP. The highest AUC of 75% was obtained using a multivariable logistic regression model for MT/CEST parameters, which included the CEST parameters of AREX_{Amide,0.625µT} (<i>P</i> = .013), AREX_NOE,0.625µT (<i>P</i> = .008), 1/(R_A·T_2A) (<i>P</i> = .004), and T₁ (<i>P</i> = .004). The perfusion rCBV parameter did not reach significance.</p><p><strong>Conclusions: </strong>Pulsed saturation transfer was sufficient for achieving a multivariable AUC of 75% for differentiating between RN and TP in brain metastases, but had lower AUCs compared to previous studies that used a block RF approach.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"6 1","pages":"vdae132"},"PeriodicalIF":3.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116557","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}