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Denis Migliorini, Valérie Dutoit, Mathilde Allard, Nicole Grandjean Hallez, Eliana Marinari, Valérie Widmer, Géraldine Philippin, Francesca Corlazzoli, Robin Gustave, Mario Kreutzfeldt, Nathalie Blazek, Joëlle Wasem, Andreas Hottinger, Avinash Koka, Shahan Momjian, Alexander Lobrinus, Doron Merkler, Maria-Isabel Vargas, Paul R Walker, Anna Patrikidou, Pierre-Yves Dietrich
Background: Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC in HLA-A2 + glioma patients. Methods: Adult patients with newly diagnosed glioblastoma (n=16) and grade III astrocytoma (n=3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination...
February 12, 2019: Neuro-oncology
Lin Yu, Jinling Xu, Jing Liu, Huibian Zhang, Cuiyun Sun, Qian Wang, Cuijuan Shi, Xuexia Zhou, Dan Hua, Wenjun Luo, Xiuwu Bian, Shizhu Yu
Background: SND1 upregulation is a common phenomenon in different human malignant tissues. However, little information is available on the underlying mechanisms through which SND1 affects glioma cell proliferation and invasion. Methods: SND1, RHOA and MKI67 were analysed in 187 gliomas by immunostaining. The correlation between those markers and patients' prognoses was assessed using the Kaplan-Meier estimator. Gene Ontology, ChIP, EMSA and 3C were applied to identify SND1-activated target genes...
February 12, 2019: Neuro-oncology
David Schiff, Martin van den Bent, Michael A Vogelbaum, Wolfgang Wick, C Ryan Miller, Martin Taphoorn, Whitney Pope, Paul D Brown, Michael Platten, Rakesh Jalali, Terri Armstrong, Patrick Y Wen
The finding that most grade II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and CDKN2A/B deletional analysis...
February 8, 2019: Neuro-oncology
Ethan B Ludmir, Anita Mahajan, Arnold C Paulino, Jeremy Y Jones, Leena M Ketonen, Jack M Su, David R Grosshans, Mary Frances McAleer, Susan L McGovern, Yasmin A Lassen-Ramshad, Adekunle M Adesina, Robert C Dauser, Jeffrey S Weinberg, Murali M Chintagumpala
Background: Pseudoprogression (PsP) is a recognized phenomenon after radiotherapy (RT) for high-grade glioma, but is poorly characterized for low-grade glioma (LGG). We sought to characterize PsP for pediatric LGG patients treated with RT, with particular focus on the role of RT modality using photon-based intensity-modulated RT (IMRT) or proton beam therapy (PBT). Methods: Serial MRI scans from 83 pediatric LGG patients managed at two institutions between 1998 and 2017 were evaluated...
February 7, 2019: Neuro-oncology
Sophie J M Rijnen, Ikram Meskal, Marjan Bakker, Wouter De Baene, Geert-Jan M Rutten, Karin Gehring, Margriet M Sitskoorn
Background: Meningioma patients are known to face cognitive deficits before and after surgery. We examined individual changes in cognitive performance over time and identified preoperative predictors of cognitive functioning 12 months after surgery in a large sample of meningioma patients. Methods: Patients underwent neuropsychological assessment (NPA) using CNS Vital Signs 1 day before (T0), and 3 (T3) and 12 (T12) months after surgery. Patients' sociodemographically-corrected scores on 7 cognitive domains were compared to performance of a normative sample using one-sample z tests and Chi-square tests of independence...
February 7, 2019: Neuro-oncology
Lisa S Kahalley, M Douglas Ris, Anita Mahajan, M Fatih Okcu, Murali Chintagumpala, Arnold C Paulino, William E Whitehead, Charles G Minard, Heather H Stancel, Jessica Orobio, Judy J Xue, Emily A Warren, David R Grosshans
Background: Proton radiotherapy (PRT) reduces the volume of normal tissue receiving radiation dose, which may lead to better neurocognitive outcomes. We examined change in neurocognitive scores over time in pediatric brain tumor patients treated with proton craniospinal irradiation (CSI), proton focal RT, or surgery only. Methods: Patients received annual neurocognitive evaluations for up to 6 years. We examined Full Scale IQ (FSIQ), Verbal Comprehension (VCI), Perceptual Reasoning (PRI), Working Memory (WMI), and Processing Speed Index (PSI) scores...
February 7, 2019: Neuro-oncology
Jason C H Chiang, Julie H Harreld, Ryuma Tanaka, Xiaoyu Li, Ji Wen, Chenran Zhang, Daniel R Boué, Tracy M Rauch, J Todd Boyd, Jie Chen, Joseph C Corbo, Thomas W Bouldin, Scott W Elton, Le-Wen L Liu, Deborah Schofield, Sunhee C Lee, John-Paul Bouffard, Maria-Magdalena Georgescu, Rimal H Dossani, Maria A Aguiar, Richard A Sances, Ali G Saad, Frederick A Boop, Ibrahim Qaddoumi, David W Ellison
Background: Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults and associated with intractable seizures. Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed 'DNET-like neoplasms of the septum pellucidum'. Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series...
February 6, 2019: Neuro-oncology
Joseph M Kim, Jacob A Miller, Rupesh Kotecha, Samuel T Chao, Manmeet S Ahluwalia, David M Peereboom, Alireza M Mohammadi, Gene H Barnett, Erin S Murphy, Michael A Vogelbaum, Lilyana Angelov, Jame Abraham, Halle Moore, G Thomas Budd, John H Suh
Background: Patients with breast cancer positive for human epidermal growth factor receptor 2 (HER2) remain at high risk of intracranial relapse following treatment and experience increased rates of intracranial failure after stereotactic radiosurgery (SRS). We hypothesized that the addition of concurrent lapatinib to SRS would improve intracranial complete response rates. Methods: Patients with newly diagnosed HER2-amplified breast cancer brain metastases from 2005-2014 who underwent SRS were included and divided into 2 cohorts based on timing of treatment with lapatinib...
February 6, 2019: Neuro-oncology
Francesca Branzoli, Clément Pontoizeau, Lucien Tchara, Anna Luisa Di Stefano, Aurélie Kamoun, Dinesh K Deelchand, Romain Valabrègue, Stéphane Lehéricy, Marc Sanson, Chris Ottolenghi, Malgorzata Marjanska
Background: Codeletion of chromosome arms 1p and 19q (1p/19q codeletion) highly benefit diagnosis and prognosis in gliomas. In this study, we investigated the effect of 1p/19q codeletion on cancer-cell metabolism and evaluated possible metabolic targets for tailored therapies. Methods: We combined in vivo 1H magnetic resonance spectroscopy (MRS) measurements in human gliomas with the analysis of a series of standard amino acids by liquid chromatography-mass spectroscopy (LC-MS) in human glioma biopsies...
February 6, 2019: Neuro-oncology
Alexander Pemov, Nancy F Hansen, Sivasish Sindiri, Rajesh Patidar, Christine S Higham, Eva Dombi, Markku M Miettinen, Patricia Fetsch, Hilde Brems, Settara Chandrasekharappa, Kristine Jones, Bin Zhu, Jun S Wei, James C Mullikin, Margaret R Wallace, Javed Khan, Eric Legius, Brigitte C Widemann, Douglas R Stewart
Background: Neurofibromatosis type 1 (NF1) is a tumor-predisposition disorder caused by germline mutations in NF1. NF1 patients have an 8-16% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST), a highly-aggressive soft-tissue sarcoma, often arising from pre-existing benign plexiform neurofibromas (PN) and atypical neurofibromas (ANF). ANF are distinct from both PN and MPNST, representing an intermediate step in malignant transformation. Methods: In the first comprehensive genomic analysis of ANF originating from multiple patients, we performed tumor/normal whole-exome sequencing (WES) of 16 ANFs...
February 5, 2019: Neuro-oncology
Hayet Pigeon, Elodie A Pérès, Charles Truillet, Benoit Jego, Fawzi Boumezbeur, Fabien Caillé, Bastian Zinnhardt, Andreas H Jacobs, Denis Le Bihan, Alexandra Winkeler
Background: Glioblastoma is the most devastating brain tumor. Despite the use of multimodal treatments, most patients relapse, often due to the highly invasive nature of gliomas. However, the detection of glioma infiltration remains challenging. The aim of this study was to assess advanced positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques for visualizing biological activity and infiltration of the tumor. Methods: Using multi-modality imaging, we investigated [18F]DPA-714, a radiotracer targeting the 18kDa translocator protein (TSPO), [18F]FET PET, non-Gaussian diffusion MRI (ADC0, Kurtosis), and the S-index, a composite diffusion metric, to detect tumor infiltration in a human invasive glioma model...
February 5, 2019: Neuro-oncology
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January 28, 2019: Neuro-oncology
Ted K Yanagihara, J Ricardo McFaline-Figueroa, Nicholas J Giacalone, Albert W Lee, Vikram Soni, Mark E Hwang, Kristin T Hsieh, Anurag Saraf, Cheng-Chia Wu, Daniel Yang, Patrick Y Wen, Hani Ashamalla, Ayal A Aizer, Tony J C Wang, Raymond Y Huang
Background: Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized BMs are not evenly distributed across the brain and that several additional areas may be avoided in WBRT based on a low risk of developing a BM. Methods: We contoured 2,757 lesions in a large, single-institution database of patients with newly diagnosed BMs...
January 23, 2019: Neuro-oncology
Emilie Le Rhun, Patrick Devos, Thomas Boulanger, Marion Smits, Dieta Brandsma, Roberta Rudà, Julia Furtner, Johann-Martin Hempel, Tjeerd J Postma, Patrick Roth, Tom J Snijders, Frank Winkler, Sebastian Winklerhofer, Antonella Castellano, Elke Hattingen, Jaume Capellades, Thierry Gorlia, Martin van den Bent, Patrick Y Wen, Martin Bendzus, Michael Weller
Background: A scorecard to evaluate magnetic resonance imaging (MRI) findings during the course of leptomeningeal metastases (LM) has been proposed by the Response Assessment in Neuro-Oncology (RANO) group. Methods: To explore the feasibility of the LANO scorecard, cerebrospinal MRI of 22 patients with LM from solid tumors were scored by 10 neuro-oncologists and 9 neuroradiologists at baseline and at follow-up after treatment. Raters were blinded for clinical data including treatment...
January 23, 2019: Neuro-oncology
Johannes Berlandi, Amel Chaouch, Nicolas De Jay, Isabel Tegeder, Katharina Thiel, Margret Shirinian, Claudia L Kleinman, Astrid Jeibmann, Paul Lasko, Nada Jabado, Martin Hasselblatt
Background: Recurrent specific mutations in evolutionarily conserved Histone 3 (H3) variants drive pediatric high-grade gliomas (HGG), but little is known about their downstream effects. The aim of this study was to identify genes involved in the detrimental effects of mutant H3.3-K27M, the main genetic driver in lethal midline HGG, in a transgenic Drosophila model. Methods: Mutant and wild-type histone H3.3 expressing flies were generated using a φC31-based integration system...
January 23, 2019: Neuro-oncology
Ai Seon Kuan, Jane Green, Cari M Kitahara, Amy Berrington de González, Tim Key, Gillian Reeves, Sarah Floud, Angela Balkwill, Kathryn Bradbury, Linda M Liao, Neal D Freedman, Valerie Beral, Siân Sweetland
Background: Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, we present findings from three large prospective studies. Methods: Participants included 692,176 from (UK) Million Women Study, 470,780 from (US) NIH-AARP Study, and 99,148 from (US) PLCO Study. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse-variances of the relative risks...
January 23, 2019: Neuro-oncology
Julie J Miller, Franziska Loebel, Tareq A Juratli, Shilpa S Tummala, Erik A Williams, Tracy T Batchelor, Isabel Arrillaga-Romany, Daniel P Cahill
Background: Isocitrate dehydrogenase (IDH) mutant gliomas are a distinct subtype, reflected in WHO 2016 revised diagnostic criteria. To inform IDH-targeting trial design, we sought to characterize outcomes exclusively within IDH mutant gliomas. Methods: We retrospectively analyzed 275 IDH mutant glioma patients treated at our institution. Progression was determined using low-grade glioma RANO criteria. We calculated survival statistics with the Kaplan-Meier method and survival proportions were correlated with molecular, histologic and clinical factors...
January 22, 2019: Neuro-oncology
Anna Wenger, Sandra Ferreyra Vega, Teresia Kling, Thomas Olsson Bontell, Asgeir Store Jakola, Helena Carén
Background: A feature of glioblastoma (GBM) is cellular and molecular heterogeneity, both within and between tumors. This variability causes a risk for sampling bias and potential tumor escape from future targeted therapy. Heterogeneous intra-tumor gene expression in GBM is well documented, but little is known regarding the epigenetic heterogeneity. Variability in DNA methylation within tumors would have implications for diagnostics, as methylation can be used for tumor classification, subtyping and determination of the clinically used biomarker MGMT promoter methylation...
January 22, 2019: Neuro-oncology
Adrienne Boire, Dieta Brandsma, Priscilla K Brastianos, Emilie Le Rhun, Manmeet Ahluwalia, Larry Junk, Michael Glantz, Morris D Groves, Eudocia Q Lee, Nancy Lin, Jeffrey Raizer, Roberta Rudà, Michael Weller, Martin J van den Bent, Michael A Vogelbaum, Susan Chang, Patrick Y Wen, Riccardo Soffietti
Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a surrogate for tumor tissue in the management of both primary and secondary brain tumors. Herein we critically review available literature on spinal fluid and plasma circulating tumor cells (CTCs) and cell-free tumor (ctDNA) for diagnosis and monitoring of leptomeningeal and parenchymal brain metastases. We discuss technical issues and propose several potential applications of liquid biopsies in different clinical settings, i...
January 22, 2019: Neuro-oncology
Aida Karachi, Changlin Yang, Farhad Dastmalchi, Elias Sayour, Jianping Huang, Hassan Azari, Yu Long, Catherine Flores, Duane A Mitchell, Maryam Rahman
Background: The changes induced in host immunity and the tumor microenvironment by chemotherapy have been shown to impact immunotherapy response in both a positive and negative fashion. Temozolomide is the most common chemotherapy used to treat glioblastoma (GBM) and has been shown to have variable effects on immune response to immunotherapy. Therefore, we aimed to determine the immune modulatory effects of temozolomide that would impact response to immune checkpoint inhibition in the treatment of experimental GBM...
January 22, 2019: Neuro-oncology
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