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NF1 mutation-driven neuronal hyperexcitability sets a threshold for tumorigenesis and therapeutic targeting of murine optic glioma Neuro Oncol. (IF 15.9) Pub Date : 2024-04-12 Corina Anastasaki, Jit Chatterjee, Joshua P Koleske, Yunqing Gao, Stephanie L Bozeman, Chloe M Kernan, Lara I Marco Y Marquez, Ji-Kang Chen, Caitlin E Kelly, Connor J Blair, Dennis J Dietzen, Robert A Kesterson, David H Gutmann
Background With the recognition that noncancerous cells function as critical regulators of brain tumor growth, we recently demonstrated that neurons drive low-grade glioma initiation and progression. Using mouse models of neurofibromatosis type 1 (NF1)-associated optic pathway glioma (OPG), we showed that Nf1 mutation induces neuronal hyperexcitability and midkine expression, which activates an immune
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Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: a RANO review Neuro Oncol. (IF 15.9) Pub Date : 2024-04-10 Lakshmi Nayak, Chetan Bettegowda, Florian Scherer, Norbert Galldiks, Manmeet Ahluwalia, Alexander Baraniskin, Louisa von Baumgarten, Jacoline E C Bromberg, Andrés J M Ferreri, Christian Grommes, Khê Hoang-Xuan, Julia Kühn, James L Rubenstein, Roberta Rudà, Michael Weller, Susan M Chang, Martin J van den Bent, Patrick Y Wen, Riccardo Soffietti
Background The utility of liquid biopsies is well documented in several extracranial and intracranial (brain/leptomeningeal metastases, gliomas) tumors. Methods The RANO (Response Assessment in Neuro-Oncology) group has set up a multidisciplinary Task Force to critically review the role of blood and CSF-liquid biopsy in central nervous system lymphomas, with a main focus on primary central nervous
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Secondary cerebro-cerebellar and intracerebellar dysfunction in cerebellar mutism syndrome Neuro Oncol. (IF 15.9) Pub Date : 2024-04-06 Samuel S McAfee, Giles Robinson, Amar Gajjar, Nicholas S Phillips, Silu Zhang, Ping Zou Stinnett, Ranganatha Sitaram, Darcy Raches, Heather M Conklin, Raja B Khan, Matthew A Scoggins
Background Cerebellar mutism syndrome (CMS) is characterized by deficits of speech, movement, and affect that can occur following tumor removal from the posterior fossa. The role of cerebrocerebellar tract injuries in the etiology of CMS remains unclear, with recent studies suggesting that cerebrocerebellar dysfunction may be related to chronic, rather than transient, symptomatology. Methods We measured
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Radical surgical resection with molecular margins is associated with improved survival in IDH wildtype GBM Neuro Oncol. (IF 15.9) Pub Date : 2024-04-05 Elie Massaad, William J Smith, Joseph Bradley, Eric Esposito, Mihir Gupta, Evan Burns, Ryan Burns, José K Velarde, Inka K Berglar, Rajiv Gupta, Maria Martinez-Lage, Jorg Dietrich, Jochen K Lennerz, Gavin P Dunn, Pamela S Jones, Bryan D Choi, Albert E Kim, Matthew Frosch, Fred G Barker, William T Curry, Bob S Carter, Brian V Nahed, Daniel P Cahill, Ganesh M Shankar
Background Survival is variable in patients with glioblastoma IDH wild-type (GBM), even after comparable surgical resection of radiographically-detectable disease, highlighting the limitations of radiographic assessment of infiltrative tumor anatomy. The majority of post-surgical progressive events are failures within 2cm of the resection margin, motivating supramaximal resection strategies to improve
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Treatment response as surrogate to predict risk for disease progression in pediatric medulloblastoma with persistent MRI lesions after first-line treatment Neuro Oncol. (IF 15.9) Pub Date : 2024-04-04 Denise Obrecht-Sturm, Lena Schömig, Martin Mynarek, Brigitte Bison, Rudolf Schwarz, Torsten Pietsch, Stefan M Pfister, Martin Sill, Dominik Sturm, Felix Sahm, Rolf-Dieter Kortmann, Nicolas U Gerber, André O von Bueren, Gudrun Fleischhack, Ulrich Schüller, Gunther Nussbaumer, Martin Benesch, Stefan Rutkowski
Background This study aims at clarifying the impact of persistent residual lesions following first-line treatment for pediatric medulloblastoma. Methods Data on 84 pediatric patients with medulloblastoma and persistent residual lesions on centrally reviewed MRI at the end of first-line therapy were analyzed. Results Twenty patients (23.8%) had residual lesions in the tumor bed (R+/M0), 51 (60.7%) had
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Circulating extracellular vesicles as biomarker for diagnosis, prognosis and monitoring in glioblastoma patients Neuro Oncol. (IF 15.9) Pub Date : 2024-04-02 Franz L Ricklefs, Kathrin Wollmann, Amanda Salviano-Silva, Richard Drexler, Cecile L Maire, Michael G Kaul, Rudolph Reimer, Ulrich Schüller, Sarina Heinemann, Katharina Kolbe, Tobias Mummert, Markus Glatzel, Sven Peine, Jens Gempt, Manfred Westphal, Lasse Dührsen, Katrin Lamszus
Background Extracellular vesicles (EVs) obtained by noninvasive liquid biopsy from patient blood can serve as biomarkers. Here, we investigated the potential of circulating plasma EVs to serve as an indicator in the diagnosis, prognosis and treatment response of glioblastoma patients. Methods Plasma samples were collected from glioblastoma patients at multiple timepoints before and after surgery. EV
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Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia Neuro Oncol. (IF 15.9) Pub Date : 2024-03-29 Han Xie, Yanyi Jiang, Yufei Xiang, Baoming Wu, Jiajia Zhao, Ruixiang Huang, Mengting Wang, Yunlong Wang, Jun Liu, Dejun Wu, Dasheng Tian, Erbao Bian
Background The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored. Methods Identification of microglial heterogeneity by bioinformatics analysis. Transwell migration, invasion assays, and tumor models were used to determine gene function and the role
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The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models Neuro Oncol. (IF 15.9) Pub Date : 2024-03-29 Daniel de la Nava, Iker Ausejo-Mauleon, Virginia Laspidea, Marisol Gonzalez-Huarriz, Andrea Lacalle, Noelia Casares, Marta Zalacain, Lucía Marrodan, Marc García-Moure, Maria C Ochoa, Antonio Carlos Tallon-Cobos, Reyes Hernandez-Osuna, Javier Marco-Sanz, Laasya Dhandapani, Irati Hervás-Corpión, Oren J Becher, Javad Nazarian, Sabine Mueller, Timothy N Phoenix, Jasper van der Lugt, Mikel Hernaez, Elizabeth
Background Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated. Methods The production of functional viruses was assessed by immunoblotting and replication
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[Ga68] DOTATATE PET/MRI-Guided Radiosurgical Treatment Planning and Response Assessment in Meningiomas Neuro Oncol. (IF 15.9) Pub Date : 2024-03-29 Jana Ivanidze, Se Jung Chang, Arsalan Haghdel, Joon Tae Kim, Arindam RoyChoudhury, Alan Wu, Rohan Ramakrishna, Theodore H Schwartz, Babacar Cisse, Philip Stieg, Leland Muller, Joseph R Osborne, Rajiv S Magge, Nicolas A Karakatsanis, Michelle Roytman, Eaton Lin, Susan C Pannullo, Joshua D Palmer, Jonathan P S Knisely
Background Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. Methods Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post radiosurgery. Maximum
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EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models Neuro Oncol. (IF 15.9) Pub Date : 2024-03-20 Andrea Álvarez-Vázquez, Laura San-Segundo, Pilar Cerveró-García, Raquel Flores-Hernández, Claudia Ollauri-Ibáñez, Berta Segura-Collar, C G Hubert, Gillian Morrison, Steven M Pollard, Justin D Lathia, Pilar Sánchez-Gómez, Arantxa Tabernero
Background Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266-283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266-283. Methods The effect of TAT-Cx43266-283
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ARF4-mediated retrograde trafficking as a driver of chemoresistance in GBM Neuro Oncol. (IF 15.9) Pub Date : 2024-03-20 Shreya Budhiraja, Graysen McManus, Shivani Baisiwala, Ella N Perrault, Sia Cho, Miranda Saathoff, Li Chen, Cheol H Park, Hasaan A Kazi, Crismita Dmello, Peiyu Lin, C David James, Adam M Sonabend, Dieter H Heiland, Atique U Ahmed
Background Cellular functions hinge on the meticulous orchestration of protein transport, both spatially and temporally. Central to this process is retrograde trafficking, responsible for targeting proteins to the nucleus. Despite its link to many diseases, the implications of retrograde trafficking in glioblastoma (GBM) are still unclear. Methods To identify genetic drivers of TMZ resistance, we conducted
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Insights from a Multicenter Study on Adult H3 K27M-Mutated Glioma: Surgical Resection's Limited Influence on Overall Survival, ATRX as Molecular Prognosticator Neuro Oncol. (IF 15.9) Pub Date : 2024-03-19 A Ryba, Z Özdemir, N Nissimov, L Hönikl, N Neidert, M Jakobs, D Kalasauskas, A Krigers, C Thomé, C F Freyschlag, F Ringel, A Unterberg, P Dao Trong, J Beck, D H Heiland, B Meyer, P Vajkoczy, J Onken, W Stummer, E Suero Molina, J Gempt, M Westphal, U Schüller, M Mohme
Background H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 WHO classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults. Methods We included molecularly confirmed H3
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Challenges, Limitations and Pitfalls of PET and Advanced MRI in Patients with Brain Tumors - A Report of the PET/RANO Group Neuro Oncol. (IF 15.9) Pub Date : 2024-03-11 Norbert Galldiks, Timothy J Kaufmann, Philipp Vollmuth, Philipp Lohmann, Marion Smits, Michael C Veronesi, Karl-Josef Langen, Roberta Rudá, Nathalie L Albert, Elke Hattingen, Ian Law, Markus Hutterer, Riccardo Soffietti, Michael A Vogelbaum, Patrick Y Wen, Michael Weller, Joerg-Christian Tonn
Brain tumor diagnostics have significantly evolved with the use of PET and advanced MRI techniques. In addition to anatomical MRI, these modalities may provide valuable information for several clinical applications such as differential diagnosis, delineation of tumor extent, prognostication, differentiation between tumor relapse and treatment-related changes, and the evaluation of response to anticancer
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Comprehensive analysis of MYB/MYBL1-altered pediatric-type diffuse low-grade glioma Neuro Oncol. (IF 15.9) Pub Date : 2024-03-11 Daniel C Moreira, Ibrahim Qaddoumi, Susan Spiller, Thomas W Bouldin, Alan Davidson, Nasjla Saba-Silva, Daniel V Sullivan, Ryuma Tanaka, Aaron S Wagner, Matthew Wood, Paul Klimo, Godwin Job, Meenakshi Devidas, Xiaoyu Li, Amar Gajjar, Giles W Robinson, Jason Chiang
Background Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies. Methods We retrospectively reviewed details of pLGG with MYB or
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Executive Summary of the American Radium Society Appropriate Use Criteria for Brain Metastases in EGFR-mutated and ALK-fusion Non-Small Cell Lung Cancer Neuro Oncol. (IF 15.9) Pub Date : 2024-03-08 Seema Nagpal, Michael T Milano, Veronica L Chiang, Scott G Soltys, Alexandria Brackett, Lia M Halasz, Amit K Garg, Arjun Sahgal, Manmeet S Ahluwalia, Martin C Tom, Joshua D Palmer, Jonathan P S Knisley, Samuel T Chao, Melanie Hayden Gephart, Tony J C Wang, Simon S Lo, Eric L Chang
Background The American Radium Society (ARS) Central Nervous System (CNS) committee reviewed literature on epidermal growth factor receptor mutated (EGFRm) and ALK-fusion (ALK+) tyrosine kinase inhibitors (TKIs) for the treatment of brain metastases (BrMs) from non-small cell lung cancers (NSCLC) to generate appropriate use guidelines addressing use of TKIs in conjunction with or in lieu of radiotherapy
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Very long-term outcomes of pediatric patients treated for optic pathway gliomas: A longitudinal cohort study Neuro Oncol. (IF 15.9) Pub Date : 2024-03-07 Alice Morin, Rodrigue Allodji, Dulanjalee Kariyawasam, Philippe Touraine, Stéphanie Puget, Kevin Beccaria, Emilie De Carli, Virginie Kieffer, Sophie Rivollet, Samuel Abbou, Chiraz Fayech, Vincent Souchard, Christelle Dufour, Florent De Vathaire, Stéphanie Bolle, Jacques Grill, Brice Fresneau
Background Optic pathway gliomas (OPG) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications. Methods We included patients treated at Gustave Roussy (GR) between 01.1980 and 12.2015 for OPG, before 18 years-old and alive at 5 years from diagnosis. Mortality and physical health conditions data were extracted from medical data files and
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3D volume growth rate evaluation in the EORTC-BTG-1320 clinical trial for recurrent WHO grade 2 and 3 meningiomas Neuro Oncol. (IF 15.9) Pub Date : 2024-03-06 E Tabouret, J Furtner, T Graillon, A Silvani, E Le Rhun, R Soffietti, G Lombardi, J M Sepúlveda-Sánchez, P Brandal, M Bendszus, V Golfinopoulos, T Gorlia, M Weller, F Sahm, W Wick, M Preusser
Background We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using three main classes and a total of five subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the efficacy of trabectedin for
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ACTION: A randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma Neuro Oncol. (IF 15.9) Pub Date : 2024-03-05 Isabel Arrillaga-Romany, Andrew Lassman, Susan L McGovern, Sabine Mueller, Burt Nabors, Martin van den Bent, Michael Vogelbaum, Joshua E Allen, Allen S Melemed, Rohinton S Tarapore, Patrick Y Wen, Timothy Cloughesy
Background H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma. Methods ACTION (NCT05580562) is a
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The role of radiotherapy in immunotherapy strategies in the central nervous system Neuro Oncol. (IF 15.9) Pub Date : 2024-03-04 Matthew Gallitto, Peter C Pan, Michael D Chan, Michael T Milano, Tony J C Wang
The clinical efficacy and relative tolerability of adverse effects of immune checkpoint immunotherapy have led to its increasingly routine use in the management of multiple advanced solid malignancies. Radiation therapy (RT) is well-known to have both local and distant immunomodulatory effects, which has led to extensive investigation into the synergism of these 2 therapies. While the central nervous
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The dilemma of radiation necrosis from diagnosis to treatment in the management of brain metastases Neuro Oncol. (IF 15.9) Pub Date : 2024-03-04 Zachary S Mayo, Cole Billena, John H Suh, Simon S Lo, Samuel T Chao
Radiation therapy with stereotactic radiosurgery (SRS) or whole brain radiation therapy is a mainstay of treatment for patients with brain metastases. The use of SRS in the management of brain metastases is becoming increasingly common and provides excellent local control. Cerebral radiation necrosis (RN) is a late complication of radiation treatment that can be seen months to years following treatment
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Integrating multi-modal imaging in radiation treatments for glioblastoma Neuro Oncol. (IF 15.9) Pub Date : 2024-03-04 William G Breen, Madhava P Aryal, Yue Cao, Michelle M Kim
Advances in diagnostic and treatment technology along with rapid developments in translational research may now allow the realization of precision radiotherapy. Integration of biologically informed multimodality imaging to address the spatial and temporal heterogeneity underlying treatment resistance in glioblastoma is now possible for patient care, with evidence of safety and potential benefit. Beyond
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How proton therapy fits into the management of adult intracranial tumors Neuro Oncol. (IF 15.9) Pub Date : 2024-03-04 Rupesh Kotecha, Alonso La Rosa, Minesh P Mehta
Intracranial tumors include a challenging array of primary and secondary parenchymal and extra-axial tumors which cause neurologic morbidity consequential to location, disease extent, and proximity to critical neurologic structures. Radiotherapy can be used in the definitive, adjuvant, or salvage setting either with curative or palliative intent. Proton therapy (PT) is a promising advance due to dosimetric
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Evolving concepts in margin strategies and adaptive radiotherapy for glioblastoma: A new future is on the horizon Neuro Oncol. (IF 15.9) Pub Date : 2024-03-04 Chia-Lin Tseng, K Liang Zeng, Eric A Mellon, Scott G Soltys, Mark Ruschin, Angus Z Lau, Natalia S Lutsik, Rachel W Chan, Jay Detsky, James Stewart, Pejman J Maralani, Arjun Sahgal
Chemoradiotherapy is the standard treatment after maximal safe resection for glioblastoma (GBM). Despite advances in molecular profiling, surgical techniques, and neuro-imaging, there have been no major breakthroughs in radiotherapy (RT) volumes in decades. Although the majority of recurrences occur within the original gross tumor volume (GTV), treatment of a clinical target volume (CTV) ranging from
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Novel radiotherapeutic strategies in the management of brain metastases: Challenging the dogma Neuro Oncol. (IF 15.9) Pub Date : 2024-03-04 Joshua D Palmer, Haley K Perlow, Eric J Lehrer, Zabi Wardak, Hany Soliman
The role of radiation therapy in the management of brain metastasis is evolving. Advancements in machine learning techniques have improved our ability to both detect brain metastasis and our ability to contour substructures of the brain as critical organs at risk. Advanced imaging with PET tracers and magnetic resonance imaging-based artificial intelligence models can now predict tumor control and
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Stereotactic body radiation therapy for spinal metastases: A new standard of care Neuro Oncol. (IF 15.9) Pub Date : 2024-03-04 Amanda N Sacino, Hanbo Chen, Arjun Sahgal, Chetan Bettegowda, Laurence D Rhines, Pejman Maralani, Kristin J Redmond
Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed
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HIF1α/ATF3 partake PGK1 K191/K192 succinylation by modulating P4HA1/succinate signaling in glioblastoma Neuro Oncol. (IF 15.9) Pub Date : 2024-03-02 Yang Shixue, Zhan Qi, Su Dongyuan, Cui Xiaoteng, Zhao Jixing, Wang Qixue, Hong Biao, Ju Jiasheng, Cheng Chunchao, Yang Eryan, Chunsheng Kang
Background Hypoxia is a pathological hallmark in most cancers, including glioblastoma (GBM). Hypoxic signaling activation and posttranslational modification (PTM) of oncogenic proteins are well-studied in cancers. Accumulating studies indicate glycolytic enzyme PGK1 plays a crucial role in tumorigenesis, yet the underlying mechanisms remain unknown. Methods We first used ChIP assays to uncover the
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Novel molecular subtypes of intracranial germ cell tumours expand therapeutic opportunities Neuro Oncol. (IF 15.9) Pub Date : 2024-03-02 Bo Li, Shuang Zhao, Shouwei Li, Chunde Li, Wei Liu, Lin Li, Bowen Cui, Xing Liu, Huiyuan Chen, Jing Zhang, Yin Ren, Fei Liu, Ming Yang, Tao Jiang, Yu Liu, Xiaoguang Qiu
Background Intracranial germ cell tumours (IGCTs) are a rare group of malignancies that are clinically classified as germinomas and nongerminomatous germ cell tumours (NGGCTs). Previous studies have found that somatic mutations involving the MAPK/mTOR signalling pathway are common early events. However, a comprehensive genomic understanding of IGCTs is still lacking. Methods We established a cohort
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Secreted Clusterin Inhibits Tumorigenesis by Modulating Tumor Cell and Macrophage in Human Meningioma Neuro Oncol. (IF 15.9) Pub Date : 2024-02-27 Chao Ke, Boya Huang, Jian Xiang, Jinlian Liang, Guangjie Wu, Minghui Qiu, Kai Cheng, Lipeng Mao, Wen Lei, Yang Hu, Xiaogen Tang, Yizhen Tian, Guobing Chen, Oscar Junhong Luo, Hongyi Zhang
Background Meningioma is the most common primary intracranial tumor with high frequency of postoperative recurrence, yet the biology of meningioma malignancy process is still obscure. Methods To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high
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Sexual-biased necroinflammation is revealed as a predictor of bevacizumab benefit in Glioblastoma Neuro Oncol. (IF 15.9) Pub Date : 2024-02-27 Sara Hiller-Vallina, Lucia Mondejar-Ruescas, Marta Caamaño-Moreno, Blanca Cómitre-Mariano, Denisse Alcivar-López, Juan M Sepulveda, Aurelio Hernández-Laín, Ángel Pérez-Núñez, Berta Segura-Collar, Ricardo Gargini
Background Glioblastoma (GBM) is a highly malignant brain tumor that affects men more often than women. In addition, the former shows a poorer survival prognosis. To date the reason for this sex-specific aggressiveness remains unclear. Therefore, the aim of this study is to investigate tumor processes that explain these sex differences. Methods This was a retrospective study of GBM patients which was
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Safety and pharmacokinetics of ONC201 (dordaviprone) administered two consecutive days per week in pediatric patients with H3K27M-mutant glioma Neuro Oncol. (IF 15.9) Pub Date : 2024-02-24 Yazmin Odia, Carl Koschmann, Nicholas A Vitanza, Peter de Blank, Dolly Aguilera, Jeffrey Allen, Doured Daghistani, Matthew Hall, Ziad Khatib, Cassie Kline, Tobey MacDonald, Sabine Mueller, Shamia L Faison, Joshua E Allen, Odin J Naderer, Samuel C Ramage, Rohinton S Tarapore, Susan Lynne McGovern, Soumen Khatua, Wafik Zaky, Sharon L Gardner
Background This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma. Methods This phase 1 dose-escalation and expansion study included pediatric patients with H3 K27M-mutant glioma and/or DIPG following ≥1 line of therapy (NCT03416530). ONC201
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Selective DRD2 Antagonist and ClpP Agonist ONC201 in a Recurrent Non-midline H3 K27M-mutant Glioma Cohort Neuro Oncol. (IF 15.9) Pub Date : 2024-02-22 Yazmin Odia, Matthew D Hall, Timothy Francis Cloughesy, Patrick Y Wen, Isabel Arrillaga-Romany, Doured Daghistani, Minesh P Mehta, Rohinton S Tarapore, Samuel C Ramage, Joshua E Allen
Background Diffuse midline glioma, H3 K27-altered (H3 K27M-altered DMG) are invariably lethal, disproportionately affecting the young and without effective treatment besides radiotherapy. The 2016 WHO CNS Tumors Classification defined H3K27M mutations as pathognomonic but restricted diagnosis to diffuse gliomas involving midline structures by 2018. Dordaviprone (ONC201) is an oral investigational small
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Dual p38MAPK and MEK inhibition disrupts adaptive chemoresistance in mesenchymal glioblastoma to temozolomide Neuro Oncol. (IF 15.9) Pub Date : 2024-02-17 Hong Sheng Cheng, Yuk Kien Chong, Eldeen Kai Yi Lim, Xin Yi Lee, Qing You Pang, Wisna Novera, Charlie Marvalim, Jeannie Xue Ting Lee, Beng Ti Ang, Carol Tang, Nguan Soon Tan
Background Precision treatment of glioblastoma is increasingly focused on molecular subtyping, with the mesenchymal subtype particularly resistant to temozolomide. Here, we aim to develop a targeted therapy for temozolomide resensitization in the mesenchymal subtype. Methods We integrated kinomic profiles and kinase inhibitor screens from patient-derived proneural and mesenchymal glioma-propagating
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Distinct uptake and elimination profiles for trastuzumab, human IgG and biocytin-TMR in experimental HER2+ brain metastases of breast cancer Neuro Oncol. (IF 15.9) Pub Date : 2024-02-16 Vanesa L Silvestri, Andy D Tran, Monika Chung, Natalie Chung, Brunilde Gril, Christina Robinson, Simone Difilippantonio, Debbie Wei, Michael J Kruhlak, Cody J Peer, W Douglas Figg, Imran Khan, Patricia S Steeg
Background The aim of this study is an improved understanding of drug distribution in brain metastases. Rather than single point snapshots, we analyzed the time course and route of drug/probe elimination (clearance), focusing on the Intramural Periarterial Drainage (IPAD) pathway. Methods Mice with JIMT1-BR HER2+ experimental brain metastases were injected with biocytin-TMR and either trastuzumab or
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Interim FDG-PET improves treatment failure prediction in primary central nervous system Lymphoma: a LOC network prospective multicentric study Neuro Oncol. (IF 15.9) Pub Date : 2024-02-15 Laura Rozenblum, Caroline Houillier, Amandine Baptiste, Carole Soussain, Véronique Edeline, Philippe Naggara, Marine Soret, Valérie Causse-Lemercier, Lise Willems, Sylvain Choquet, Renata Ursu, Damien Galanaud, Lisa Belin, Khê Hoang-Xuan, Aurélie Kas
Purpose The purpose of our study was to assess the predictive and prognostic role of 2-18F-fluoro-2-deoxy-D-glucose (FDG) PET/MRI during high-dose methotrexate-based chemotherapy (HD-MBC) in de novo primary central nervous system lymphoma (PCNSL) patients aged 60 and above. Methods This prospective multicentric ancillary study included 65 immunocompetents patients who received induction HD-MBC as part
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Unraveling the Complexity of the Senescence-Associated Secretory Phenotype in Adamantinomatous Craniopharyngioma Using Multi-Modal Machine Learning Analysis Neuro Oncol. (IF 15.9) Pub Date : 2024-02-09 Eric W Prince, John R Apps, John Jeang, Keanu Chee, Stephen Medlin, Eric M Jackson, Roy Dudley, David Limbrick, Robert Naftel, James Johnston, Neil Feldstein, Laura M Prolo, Kevin Ginn, Toba Niazi, Amy Smith, Lindsay Kilburn, Joshua Chern, Jeffrey Leonard, Sandi Lam, David S Hersh, Jose Mario Gonzalez-Meljem, Vladimir Amani, Andrew M Donson, Siddhartha S Mitra, Pratiti Bandohpadhayay, Juan Pedro Martinez-Barbera
Background Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous Craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing
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Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas Neuro Oncol. (IF 15.9) Pub Date : 2024-01-29 Matthew S Waitkus, Elise N Erman, Zachary J Reitman, David M Ashley
A majority of cancers (~85%) activate the enzyme telomerase to maintain telomere length over multiple rounds of cellular division. Telomerase-negative cancers activate a distinct, telomerase-independent mechanism of telomere maintenance termed Alternative lengthening of telomeres (ALT). ALT uses homologous recombination to maintain telomere length and exhibits features of break-induced DNA replication
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Glioblastoma and Radiotherapy: a multi-center AI study for Survival Predictions from MRI (GRASP study) Neuro Oncol. (IF 15.9) Pub Date : 2024-01-29 Alysha Chelliah, David A Wood, Liane S Canas, Haris Shuaib, Stuart Currie, Kavi Fatania, Russell Frood, Chris Rowland-Hill, Stefanie Thust, Stephen J Wastling, Sean Tenant, Karen Foweraker, Matthew Williams, Qiquan Wang, Andrei Roman, Carmen Dragos, Mark MacDonald, Yue Hui Lau, Christian A Linares, Ahmed Bassiouny, Aysha Luis, Thomas Young, Juliet Brock, Edward Chandy, Erica Beaumont, Tai-Chung Lam
Background The aim was to predict survival of glioblastoma at eight months after radiotherapy (a period allowing for completing a typical course of adjuvant temozolomide), by applying deep learning to the first brain MRI after radiotherapy completion. Methods Retrospective and prospective data were collected from 206 consecutive glioblastoma, IDH-wildtype patients diagnosed between March 2014-February
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Copy number gain of FAM131B-AS2 promotes the progression of glioblastoma by mitigating replication stress Neuro Oncol. (IF 15.9) Pub Date : 2024-01-29 Shaobo Wang, Yanhua Qi, Rongrong Zhao, Ziwen Pan, Boyan Li, Wei Qiu, Shulin Zhao, Xiaofan Guo, Shilei Ni, Gang Li, Hao Xue
Background Glioblastoma (GBM) is characterized by chromosome 7 copy number gains, notably 7q34, potentially contributing to therapeutic resistance, yet the underlying oncogenes have not been fully characterized. Pertinently, the significance of long noncoding RNAs (lncRNAs) in this context has gained attention, necessitating further exploration. Methods FAM131B-AS2 was quantified in GBM samples and
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Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes Neuro Oncol. (IF 15.9) Pub Date : 2024-01-25 Matthew Dankner, Sarah M Maritan, Neibla Priego, Georgia Kruck, Andriniaina Nkili-Meyong, Javad Nadaf, Rebecca Zhuang, Matthew G Annis, Dongmei Zuo, Alexander Nowakowski, Marco Biondini, Alexander Kiepas, Caitlyn Mourcos, Phuong Le, Francois Charron, Yanis Inglebert, Paul Savage, Louis Théret, Marie-Christine Guiot, R Anne McKinney, William J Muller, Morag Park, Manuel Valiente, Kevin Petrecca, Peter
Background Compared to minimally invasive brain metastases (MI BrM), highly invasive (HI) lesions form abundant contacts with cells in the peritumoral brain parenchyma and are associated with poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether BrM invasion pattern is influenced by
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Prognostic value of DNA methylation subclassification, aneuploidy, and CDKN2A/B homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas Neuro Oncol. (IF 15.9) Pub Date : 2024-01-20 Kristyn Galbraith, Mekka Garcia, Siyu Wei, Anna Chen, Chanel Schroff, Jonathan Serrano, Donato Pacione, Dimitris G Placantonakis, Christopher M William, Arline Faustin, David Zagzag, Marissa Barbaro, Maria Del Pilar Guillermo Prieto Eibl, Mitsuaki Shirahata, David Reuss, Quynh T Tran, Zahangir Alom, Andreas von Deimling, Brent A Orr, Erik P Sulman, John G Golfinos, Daniel A Orringer, Rajan Jain, Evan
Introduction IDH mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System WHO introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma. Methods We analyzed 98 IDH mutant astrocytomas diagnosed at NYU
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Generative AI in glioma: ensuring diversity in training image phenotypes to improve diagnostic performance for IDH mutation prediction Neuro Oncol. (IF 15.9) Pub Date : 2024-01-19 Hye Hyeon Moon, Jiheon Jeong, Ji Eun Park, Namkug Kim, Changyong Choi, Young-Hoon Kim, Sang Woo Song, Chang-Ki Hong, Jeong Hoon Kim, Ho Sung Kim
Background This study evaluated whether generative artificial intelligence-based augmentation (GAA) can provide diverse and realistic imaging phenotypes and improve deep learning-based classification of isocitrate dehydrogenase (IDH) type in glioma compared with neuroradiologists. Methods For model development, 565 patients (346 IDH-wildtype, 219 IDH-mutant) with paired contrast-enhanced T1 and FLAIR
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Leveraging External Control Data in the Design and Analysis of Neuro-Oncology Trials: Pearls and Perils Neuro Oncol. (IF 15.9) Pub Date : 2024-01-19 Mei-Yin C Polley, Daniel Schwartz, Theodore Karrison, James J Dignam
Randomized controlled trials (RCT) have been the gold standard for evaluating medical treatments for many decades but they are often criticized for requiring large sample sizes. For newly-diagnosed glioblastoma (GBM), the clinical trial landscape has seen little progress since the establishment of the standard of care (known as the “Stupp” regimen). Given the urgent need for better therapies, it has
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Triggering receptor expressed on myeloid cells 2 (TREM2) regulates phagocytosis in glioblastoma Neuro Oncol. (IF 15.9) Pub Date : 2024-01-18 Mekenzie M Peshoff, Pravesh Gupta, Shivangi Oberai, Rakesh Trivedi, Hiroshi Katayama, Prashanth Chakrapani, Minghao Dang, Simona Migliozzi, Joy Gumin, Divya B Kadri, Jessica K Lin, Nancy K Milam, Mark E Maynard, Brian D Vaillant, Brittany Parker-Kerrigan, Frederick F Lang, Jason T Huse, Antonio Iavarone, Linghua Wang, Karen Clise-Dwyer, Krishna P Bhat
Background Glioblastomas (GBMs) are central nervous system tumors that resist standard of care interventions and even immune checkpoint blockade. Myeloid cells in the tumor microenvironment can contribute to GBM progression; therefore, emerging immunotherapeutic approaches include reprogramming these cells to achieve desirable anti-tumor activity. Triggering receptor expressed on myeloid cells 2 (TREM2)
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Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors Neuro Oncol. (IF 15.9) Pub Date : 2024-01-17 Arthur Wagner, Maria Charlotte Brielmaier, Charlotte Kampf, Lea Baumgart, Amir Kaywan Aftahy, Hanno-Sebastian Meyer, Victoria Kehl, Julius Höhne, Karl-Michael Schebesch, Nils O Schmidt, Saida Zoubaa, Markus J Riemenschneider, Miriam Ratliff, Frederik Enders, Andreas von Deimling, Friederike Liesche-Starnecker, Claire Delbridge, Jürgen Schlegel, Bernhard Meyer, Jens Gempt
Background The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by Neuropathology. Methods In this phase II non-inferiority, prospective, multicenter, non-randomized, off-label clinical trial (Eudra-CT: 2019-004512-58)
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Treatment-associated imaging changes in newly diagnosed MGMT promoter-methylated glioblastoma undergoing chemoradiation with or without cilengitide Neuro Oncol. (IF 15.9) Pub Date : 2024-01-10 Christina Maria Flies, Michel Friedrich, Philipp Lohmann, Karin Alida van Garderen, Marion Smits, Joerg-Christian Tonn, Michael Weller, Norbert Galldiks, Tom Jan Snijders
Background Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in MGMT promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified RANO criteria of 2017. Methods Patients with ≥3 follow-up MRIs were
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Automated Segmentation of Ablated Lesions Using Deep Convolutional Neural Networks: A Basis for Response Assessment Following Laser Interstitial Thermal Therapy Neuro Oncol. (IF 15.9) Pub Date : 2024-01-03 Aden P Haskell-Mendoza, Ellery Hepburn Reason, Ariel T Gonzalez, Joshua D Jackson, Eric W Sankey, Ethan S Srinivasan, James E Herndon, Peter E Fecci, Evan Calabrese
Background Laser interstitial thermal therapy (LITT) of intracranial tumors or radiation necrosis enables tissue diagnosis, cytoreduction, and rapid return to systemic therapies. Ablated tissue remains in situ, resulting in characteristic post-LITT edema associated with transient clinical worsening and complicating post-LITT response assessment. Methods All patients receiving LITT at a single center
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Hypoxia induced Galectin-8 maintains stemness in glioma stem cells via autophagy regulation Neuro Oncol. (IF 15.9) Pub Date : 2023-12-29 Dan Liu, Hongtao Zhu, Lidong Cheng, Ran Li, Xiaoyu Ma, Jing Wang, Junwen Wang, Suojun Zhang, Yingjie Li, Kai Shu, Xingjiang Yu, Chuanzhou Li
Background Glioma stem cells (GSCs) are the root cause of relapse and treatment resistance in glioblastoma (GBM). In GSCs, hypoxia in the microenvironment is known to facilitate the maintenance of stem cells, and evolutionally conserved autophagy regulates cell homeostasis to control cell population. The precise involvement of autophagy regulation in hypoxic conditions in maintaining the stemness of
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Integrated proteomics spotlight the proteasome as a therapeutic vulnerability in Embryonal Tumors with Multilayered Rosettes Neuro Oncol. (IF 15.9) Pub Date : 2023-12-29 Matthias Dottermusch, Ali Biabani, Tasja Lempertz, Yannis Schumann, Jelena Navolic, Shweta Godbole, Denise Obrecht, Stephan Frank, Mario M Dorostkar, Hannah Voß, Hartmut Schlüter, Stefan Rutkowski, Ulrich Schüller, Julia E Neumann
Background Embryonal tumors with multilayered rosettes (ETMR) are rare malignant embryonal brain tumors. The prognosis of ETMR is poor and novel therapeutic approaches are desperately needed. Comprehension of ETMR tumor biology is currently based on only few previous molecular studies, which mainly focused on the analyses of nucleic acids. In this study, we explored integrated ETMR proteomics. Methods
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Cluster-based prognostication in glioblastoma: Unveiling heterogeneity based on diffusion and perfusion similarities Neuro Oncol. (IF 15.9) Pub Date : 2023-12-28 Martha Foltyn-Dumitru, Tobias Kessler, Felix Sahm, Wolfgang Wick, Sabine Heiland, Martin Bendszus, Philipp Vollmuth, Marianne Schell
Background While the association between diffusion and perfusion MRI and survival in glioblastoma is established, prognostic models for patients are lacking. This study employed clustering of functional imaging to identify distinct functional phenotypes in untreated glioblastomas, assessing their prognostic significance for overall survival. Methods A total of 289 patients with glioblastoma who underwent
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IRE1 endoribonuclease signaling promotes myeloid cell infiltration in glioblastoma Neuro Oncol. (IF 15.9) Pub Date : 2023-12-28 Joanna Obacz, Jérôme Archambeau, Elodie Lafont, Manon Nivet, Sophie Martin, Marc Aubry, Konstantinos Voutetakis, Raphael Pineau, Rachel Boniface, Daria Sicari, Diana Pelizzari-Raymundo, Gevorg Ghukasyan, Eoghan McGrath, Efstathios-Iason Vlachavas, Matthieu Le Gallo, Pierre Jean Le Reste, Kim Barroso, Tanya Fainsod-Levi, Akram Obiedat, Zvi Granot, Boaz Tirosh, Juhi Samal, Abhay Pandit, Luc Négroni,
Background Intrinsic or environmental stresses trigger the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), leading to ER stress. To cope with this, cells have evolved an adaptive mechanism named the unfolded protein response (UPR) which is hijacked by tumor cells to develop malignant features. Glioblastoma (GB), the most aggressive and lethal primary brain tumor, relies
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Consensus framework for conducting phase I/II clinical trials for children, adolescents, and young adults with pediatric low-grade glioma: Guidelines established by the International Pediatric Low-Grade Glioma Coalition Clinical Trial Working Group Neuro Oncol. (IF 15.9) Pub Date : 2023-12-26 Sabine Mueller, Jason Fangusaro, Arzu Onar Thomas, Thomas S Jacques, Pratiti Bandopadhayay, Peter de Blank, Roger J Packer, Maryam Fouladi, Antoinette Schouten van Meeteren, David Jones, Arie Perry, Yoshiko Nakano, Darren Hargrave, David Riedl, Nathan J Robinson, Marita Partanen, Michael J Fisher, Olaf Witt
Within the last few decades, we have witnessed tremendous advancements in the study of pediatric low-grade gliomas (pLGG), leading to a much-improved understanding of their molecular underpinnings. Consequently, we have achieved successful milestones in developing and implementing targeted therapeutic agents for treating these tumors. However, the community continues to face many unknowns when it comes
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Management of sporadic intracanalicular vestibular schwannomas: A Critical Review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines Neuro Oncol. (IF 15.9) Pub Date : 2023-12-23 Anne Balossier, Arjun Sahgal, Rupesh Kotecha, Laura Fariselli, Alessandra Gorgulho, Marc Levivier, Lijun Ma, Ian Paddick, Bruce E Pollock, Jason P Sheehan, John H Suh, Shoji Yomo, Zhenwei Zhang, Jean Regis
Background The choice of an appropriate strategy for intracanalicular vestibular schwannoma (ICVS) is still debated. We conducted a systematic review and meta-analysis with the aim to compare treatment outcomes amongst management strategies (conservative surveillance (CS), microsurgical resection (MR), or stereotactic radiosurgery (SRS)) aiming to inform guideline recommendations on behalf of the International
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The ERK inhibitor LY3214996 augments anti-PD-1 immunotherapy in preclinical mouse models of BRAFV600E melanoma brain metastasis Neuro Oncol. (IF 15.9) Pub Date : 2023-12-23 Magali A de Sauvage, Consuelo Torrini, Edwin Nieblas-Bedolla, Elizabeth Summers, Emily Sullivan, Britney S Zhang, Emily Batchelor, Braxton Marion, Erika Yamazawa, Samuel C Markson, Hiroaki Wakimoto, Naema Nayyar, Priscilla Brastianos
Background Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment; however, only a subset of patients with brain metastasis (BM) respond to ICI. Activating mutations in the mitogen-activated protein kinase (MAPK) signaling pathway are frequent in BM. The objective of this study was to evaluate whether therapeutic ERK inhibition can improve the efficacy of ICI for BM. Methods We used
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Developing a computable phenotype for glioblastoma Neuro Oncol. (IF 15.9) Pub Date : 2023-12-23 Sandra Yan, Kaitlyn Melnick, Xing He, Tianchen Lyu, Rachel S F Moor, Megan E H Still, Duane A Mitchell, Elizabeth A Shenkman, Han Wang, Yi Guo, Jiang Bian, Ashley P Ghiaseddin
Background Glioblastoma (GBM) is the most common malignant brain tumor, and thus it is important to be able to identify patients with this diagnosis for population studies. However, this can be challenging as diagnostic codes are non-specific. The aim of this study was to create a computable phenotype (CP) for GBM from structured and unstructured data to identify patients with this condition in a large
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Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression Neuro Oncol. (IF 15.9) Pub Date : 2023-12-23 Christina L Appin, Chibo Hong, Abigail K Suwala, Stephanie Hilz, Radhika Mathur, David A Solomon, Ivan V Smirnov, Nicholas O Stevers, Anny Shai, Albert Wang, Mitchel S Berger, Susan M Chang, Joanna J Phillips, Joseph F Costello
Background The TERT promoter mutation (TPM) is acquired in most IDH-wildtype glioblastomas (GBM) and IDH-mutant oligodendrogliomas (OD) enabling tumor cell immortality. Previous studies on TPM clonality show conflicting results. This study was performed to determine whether TPM is clonal on a tumor-wide scale. Methods We investigated TPM clonality in relation to presumed early events in 19 IDH-wildtype
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Abrogation of the G2/M checkpoint as a chemo sensitization approach for alkylating agents Neuro Oncol. (IF 15.9) Pub Date : 2023-12-22 Fengchao Lang, James A Cornwell, Karambir Kaur, Omar Elmogazy, Wei Zhang, Meili Zhang, Hua Song, Zhonghe Sun, Xiaolin Wu, Mirit I Aladjem, Michael Aregger, Steven D Cappell, Chunzhang Yang
BACKGROUND The cell cycle is tightly regulated by checkpoints, playing a vital role in controlling its progression and timing. Cancer cells exploit the G2/M checkpoint, which serves as a resistance mechanism against genotoxic anti-cancer treatments, allowing for DNA repair prior to cell division. Manipulating cell cycle timing has emerged as a potential strategy to augment the effectiveness of DNA
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Visualizing Cancer-Originating Acetate Uptake Through MCT1 in Reactive Astrocytes in the Glioblastoma Tumor Microenvironment Neuro Oncol. (IF 15.9) Pub Date : 2023-12-12 Dongwoo Kim, Hae Young Ko, Jee-In Chung, Yongmin Mason Park, Sangwon Lee, Seon Yoo Kim, Jisu Kim, Joong-Hyun Chun, Kyung-Seok Han, Misu Lee, Yeon Ha Ju, Sun Jun Park, Ki Duk Park, Min-Ho Nam, Se Hoon Kim, Jin-Kyoung Shim, Youngjoo Park, Hyunkeong Lim, Jaekyung Park, Hyunjin Kim, Suhyun Kim, Uiyeol Park, Hoon Ryu, So Yun Lee, Sunghyouk Park, Seok-Gu Kang, Jong Hee Chang, C Justin Lee, Mijin Yun
Background Reactive astrogliosis is a hallmark of various brain pathologies, including neurodegenerative diseases and glioblastomas. However, the specific intermediate metabolites contributing to reactive astrogliosis remain unknown. This study investigated how glioblastomas induce reactive astrogliosis in the neighboring microenvironment and explores 11C-acetate PET as an imaging technique for detecting
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Efficacy and toxicity of bimodal radiotherapy in WHO grade 2 meningiomas following subtotal resection with carbon ion boost: prospective phase 2 MARCIE trial Neuro Oncol. (IF 15.9) Pub Date : 2023-12-12 Maximilian Y Deng, Sybren L N Maas, Felix Hinz, Christian P Karger, Philipp Sievers, Tanja Eichkorn, Eva Meixner, Philipp Hoegen-Sassmannshausen, Juliane Hörner-Rieber, Jonathan W Lischalk, Katharina Seidensaal, Denise Bernhardt, Christine Jungk, Andreas Unterberg, Antje Wick, Wolfgang Wick, Andreas von Deimling, Felix Sahm, Stephanie Combs, Klaus Herfarth, Jürgen Debus, Laila König
Background Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing the radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal
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Defining interventions and metrics to improve diversity in CNS clinical trial participation: a SNO and RANO effort Neuro Oncol. (IF 15.9) Pub Date : 2023-12-10 Joshua A Budhu, Ugonma N Chukwueke, Sadhana Jackson, Eudocia Q Lee, J Ricardo McFaline-Figueroa, Nicole Willmarth, Mahalia Dalmage, Ichiro Kawachi, David Arons, Susan M Chang, Evanthia Galanis, Shawn L Hervey-Jumper, Patrick Y Wen, Alyx B Porter
Despite major strides in cancer research and therapy, these advances have not been equitable across race and ethnicity. Historically marginalized groups (HMG) are more likely to have inadequate preventive screening, increased delays in diagnosis, and poor representation in clinical trials. Notably, Black, Hispanic, and Indigenous people represent 30% of the population but only 9% of oncology clinical
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Abnormal vascular structure and function within brain metastases is linked to pembrolizumab resistance Neuro Oncol. (IF 15.9) Pub Date : 2023-12-09 Albert E Kim, Kevin W Lou, Anita Giobbie-Hurder, Ken Chang, Mishka Gidwani, Katharina Hoebel, Jay B Patel, Mason C Cleveland, Praveer Singh, Christopher P Bridge, Syed Rakin Ahmed, Benjamin A Bearce, William Liu, Elies Fuster-Garcia, Eudocia Q Lee, Nancy U Lin, Beth Overmoyer, Patrick Y Wen, Lakshmi Nayak, Justine V Cohen, Jorg Dietrich, April Eichler, Rebecca Heist, Ian Krop, Donald Lawrence, Jennifer
Background We recently conducted a phase 2 trial (NCT028865685) evaluating intracranial efficacy of pembrolizumab for brain metastases (BM) of diverse histologies. Our study met its primary efficacy endpoint and illustrates that pembrolizumab exerts promising activity in a select group of patients with BM. Given the importance of aberrant vasculature in mediating immunosuppression, we explored the