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Alireza Mansouri, Laureen D Hachem, Sheila Mansouri, Farshad Nassiri, Normand J Laperriere, Daniel Xia, Neal I Lindeman, Patrick Y Wen, Arnab Chakravarti, Minesh P Mehta, Monika E Hegi, Roger Stupp, Kenneth D Aldape, Gelareh Zadeh
Glioblastoma (GBM) is the most common primary malignant brain tumor, with a universally poor prognosis. The emergence of molecular biomarkers has had a significant impact on histological typing and diagnosis, as well as predicting patient survival and response to treatment. The methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter is one such molecular biomarker. Despite the strong evidence supporting the role of MGMT methylation status in prognostication, its routine implementation in clinical practice has been challenging...
September 5, 2018: Neuro-oncology
Alex Shimura Yamashita, Marina da Costa Rosa, Alexandra Borodovsky, William T Festuccia, Timothy Chan, Gregory J Riggins
Background: Isocitrate Deyhydrogenase (IDH) mutant gliomas are comprised of the majority of grade II-III gliomas and nearly all secondary glioblastomas. These progressive gliomas arise from mutations in IDH1 or IDH2 that pathologically produces D-2-hydroxyglutarate (2HG). 2-HG interferes with cell reactions using alpha ketoglutarate leading to a hypermethylated genome and epigenetic dysregulation of gene expression initiating tumorigenesis. Methods: Human IDH1 WT and IDH1R132H cell lines and patient derived xenografts (PDX) were used to evaluate the FDA-approved DNA demethylating agent 5-Azacytidine (5-Aza)...
September 3, 2018: Neuro-oncology
Jürgen Hench, Michel Bihl, Ivana Bratic Hench, Per Hoffmann, Markus Tolnay, Nemya Bösch Al Jadooa, Luigi Mariani, David Capper, Stephan Frank
No abstract text is available yet for this article.
August 30, 2018: Neuro-oncology
Nicole A P Lieberman, Kole DeGolier, Heather M Kovar, Amira Davis, Virginia Hoglund, Jeffrey Stevens, Conrad Winter, Gail Deutsch, Scott N Furlan, Nicholas A Vitanza, Sarah E S Leary, Courtney A Crane
Background: Diffuse Intrinsic Pontine Glioma (DIPG) is a uniformly fatal CNS tumor diagnosed in 300 American children per year. Radiation is the only effective treatment and extends overall survival to a median of 11 months. Due to its location in the brainstem, DIPG tumors cannot be surgically resected. Immunotherapy has the ability to target tumor cells specifically, however, little is known about the tumor microenvironment in DIPGs. We sought to characterize infiltrating immune cells and immunosuppressive factor expression in pediatric low- and high-grade gliomas and DIPG...
August 28, 2018: Neuro-oncology
Daniel I Jacobs, Kazutaka Fukumura, Matthew N Bainbridge, Georgina N Armstrong, Spiridon Tsavachidis, Xiangjun Gu, Harsha V Doddapaneni, Jianhong Hu, Joy C Jayaseelan, Donna M Muzny, Jason T Huse, Melissa L Bondy
Background: The genomic characterization of sporadically arising gliomas has delineated molecularly and clinically distinct subclasses of disease. However, less is known about the molecular nature of gliomas that are familial in origin. We performed molecular subtyping of 163 tumor specimens from individuals with a family history of glioma and integrated germline and somatic genomic data to characterize the pathogenesis of 20 tumors in additional detail. Methods: Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tumor sections to determine molecular subtypes of glioma...
August 24, 2018: Neuro-oncology
Simone P Niclou
No abstract text is available yet for this article.
August 21, 2018: Neuro-oncology
Fredrik Svensson, Bart Westerman, Thomas Würdinger, David Bailey
No abstract text is available yet for this article.
August 20, 2018: Neuro-oncology
Raymond Y Huang, Wenya Linda Bi, Michael Weller, Thomas Kaley, Jaishri Blakeley, Ian Dunn, Evanthia Galanis, Matthias Preusser, Michael McDermott, Leland Rogers, Jeffrey Raizer, David Schiff, Riccardo Soffietti, Jörg-Christian Tonn, Michael Vogelbaum, Damien Weber, David A Reardon, Patrick Y Wen
No standard criteria exist for assessing response and progression in clinical trials involving patients with meningioma and there is no consensus on the optimal endpoints for trials currently underway. As a result, there is substantial variation in the design and response criteria of meningioma trials, making comparison between trials difficult. In addition, future trials should be designed with accepted standardized endpoints. The Response Assessment in Neuro-Oncology Meningioma Working Group is an international effort to develop standardized radiologic criteria for treatment response for meningioma clinical trials...
August 18, 2018: Neuro-oncology
Quinn T Ostrom, Warren Coleman, William Huang, Joshua B Rubin, Justin D Lathia, Michael E Berens, Gil Speyer, Peter Liao, Margaret R Wrensch, Jeanette E Eckel-Passow, Georgina Armstrong, Terri Rice, John K Wiencke, Lucie S McCoy, Helen M Hansen, Christopher I Amos, Jonine L Bernstein, Elizabeth B Claus, Richard S Houlston, Dora Il'yasova, Robert B Jenkins, Christoffer Johansen, Daniel H Lachance, Rose K Lai, Ryan T Merrell, Sara H Olson, Siegal Sadetzki, Joellen M Schildkraut, Sanjay Shete, Ulrika Andersson, Preetha Rajaraman, Stephen J Chanock, Martha S Linet, Zhaoming Wang, Meredith Yeager, Beatrice Melin, Melissa L Bondy, Jill S Barnholtz-Sloan
Background: To date, genome-wide association studies (GWAS) have identified 25 risk variants for glioma, explaining 30% of heritable risk. Most histologies occur with significantly higher incidence in males, and this difference is not explained by currently-known risk factors. A previous GWAS identified sex-specific glioma risk variants, and this analysis aims to further elucidate risk variation by sex using gene- and pathway-based approaches. Methods: Results from the Glioma International Case-Control Study were used as a testing set, and results from three GWAS were combined via meta-analysis and used as a validation set...
August 14, 2018: Neuro-oncology
Jung Youn Kim, Ji Eun Park, Youngheun Jo, Woo Hyun Shim, Soo Jung Nam, Jeong Hoon Kim, Roh-Eul Yoo, Seung Hong Choi, Ho Sung Kim
Background: Pseudoprogression is a diagnostic challenge in early post-treatment glioblastoma. We therefore developed and validated a radiomics model using multiparametric MRI to differentiate pseudoprogression from early tumor progression in patients with glioblastoma. Methods: The model was developed from the enlarging contrast-enhancing portions of 61 glioblastomas within 3 months after standard treatment with 6472 radiomic features being obtained from contrast-enhanced T1-weighted imaging, fluid-attenuated inversion recovery imaging, and apparent diffusion coefficient (ADC), and cerebral blood volume (CBV) maps...
August 11, 2018: Neuro-oncology
Miguel Angel Tejada Neyra, Ulf Neuberger, Annekathrin Reinhardt, Gianluca Brugnara, David Bonekamp, Martin Sill, Antje Wick, David T W Jones, Alexander Radbruch, Andreas Unterberg, Jürgen Debus, Sabine Heiland, Heinz-Peter Schlemmer, Christel Herold-Mende, Stefan Pfister, Andreas von Deimling, Wolfgang Wick, David Capper, Martin Bendszus, Philipp Kickingereder
Background: This study aims to evaluate the impact of tumor location on key molecular alterations on a single voxel level in patients with newly-diagnosed glioma. Methods: A consecutive series of n=237 patients with newly diagnosed glioblastoma and n=131 patients with lower-grade glioma was analyzed. Volumetric tumor segmentation was performed on preoperative MRI with a semi-automated approach and images were registered to the standard Montreal Neurological Institute-152 space...
August 9, 2018: Neuro-oncology
Judith L Kok, Jop C Teepen, Flora E van Leeuwen, Wim J E Tissing, Sebastian J C M M Neggers, Helena J van der Pal, Jacqueline J Loonen, Dorine Bresters, Birgitta Versluys, Marry M van den Heuvel-Eibrink, Eline van Dulmen-den Broeder, Margriet van der Heiden-van der Loo, Berthe M P Aleman, Laurien A Daniels, Cornelis J A Haasbeek, Bianca Hoeben, Geert O Janssens, John H Maduro, Foppe Oldenburger, Caroline van Rij, Robbert J H A Tersteeg, Michael Hauptmann, Leontien C M Kremer, Cécile M Ronckers
Background: Pediatric cranial radiotherapy (CrRT) markedly increases risk of meningiomas. We studied meningioma risk factors with emphasis on independent and joint effects of CrRT dose, exposed cranial volume, exposure age, and chemotherapy. Methods: The DCOG-LATER cohort includes five-year childhood cancer survivors (CCSs) diagnosed 1963-2001. Histologically confirmed benign meningiomas were identified from the population-based Dutch Pathology Registry (PALGA; 1990-2015)...
August 7, 2018: Neuro-oncology
Yolanda D Tseng, William Hartsell, Henry Tsai, Shahed Badiyan, Chiachien J Wang, Carl Rossi, Rupesh Kotecha, Sujay Vora, Carlos Vargas, Gary Larson, Lia M Halasz
No abstract text is available yet for this article.
August 4, 2018: Neuro-oncology
Raymond Y Huang, Prashin Unadkat, Wenya Linda Bi, Elizabeth George, Matthias Preusser, D Jay McCracken, Joseph R Keen, William L Read, Jeffrey J Olson, Katharina Seystahl, Emilie Le Rhun, Ulrich Roelcke, Susanne Koeppen, Julia Furtner, Michael Weller, Jeffrey J Raizer, David Schiff, Patrick Y Wen
Background: Meningiomas are the most common primary brain tumors in adults. Due to their variable growth rates and irregular tumor shapes, response assessment in clinical trials remains challenging and no standard criteria has been defined. We evaluated 1D, 2D, and volume imaging criteria to assess whether a volumetric approach might be a superior surrogate for overall survival (OS). Methods: In this retrospective multicenter study, we evaluated the clinical and imaging data of 93 patients with recurrent meningiomas treated with pharmacotherapy...
August 2, 2018: Neuro-oncology
Hee Jin Cho, Junfei Zhao, Sang Won Jung, Erik Ladewig, Doo-Sik Kong, Yeon-Lim Suh, Yeri Lee, Donggeon Kim, Sun Hee Ahn, Mykola Bordyuh, Hyun Ju Kang, Jason K Sa, Yun Jee Seo, Sung Tae Kim, Do Hoon Lim, Yun-Sik Dho, Jung-Il Lee, Ho Jun Seol, Jung Won Choi, Woong-Yang Park, Chul-Kee Park, Raul Rabadan, Do-Hyun Nam
Background: Despite extensive efforts on the genomic characterization of gliomas, very few studies have reported the genetic alterations of cerebellar glioblastomas (C-GBM), a rare and lethal disease. Here, we provide a systematic study of C-GBM to better understand the specific genomic features of C-GBM. Methods: We collected a cohort of C-GBM patients and compared patient demographics and tumor pathologies to supratentorial glioblastoma (S-GBM). To uncover the molecular characteristics, we performed DNA- and mRNA-sequencing, and DNA methylation arrays on 19, 6, and 4 C-GBM cases, respectively...
July 31, 2018: Neuro-oncology
Ae Kyung Park, Pora Kim, Leomar Y Ballester, Yoshua Esquenazi, Zhongming Zhao
Background: A high heterogeneity and activation of multiple oncogenic pathways have been implicated in failure of targeted therapies in glioblastoma. Methods: Using TCGA data, we identified subtype-specific prognostic core genes by a combined approach of genome-wide Cox regression and Gene Set Enrichment Analysis. The results were validated with combined eight public datasets containing 608 glioblastomas. We further examined prognostic chromosome aberrations and mutations...
July 25, 2018: Neuro-oncology
Hendrik Witt, Dorothee Gramatzki, Bettina Hentschel, Kristian W Pajtler, Jörg Felsberg, Gabriele Schackert, Markus Löffler, David Capper, Felix Sahm, Martin Sill, Andreas von Deimling, Marcel Kool, Ulrich Herrlinger, Manfred Westphal, Torsten Pietsch, Guido Reifenberger, Stefan M Pfister, Jörg C Tonn, Michael Weller
Background: Ependymal tumors are glial tumors that commonly manifest in children and young adults. Their classification has remained entirely morphological until recently, and surgery and radiotherapy are the main treatment options, especially in adults. Here we sought to correlate DNA methylation profiles with clinical and pathological characteristics in the prospective cohort of the German Glioma Network. Methods: Tumors from 122 adult patients with myxopapillary ependymoma, ependymoma, anaplastic ependymoma, subependymoma or RELA fusion-positive ependymoma classified according to the World Heath Organization classification (WHO) 2016 were subjected to DNA methylation profiling using the Illumina HumanMethylation450 BeadChip platform...
July 24, 2018: Neuro-oncology
Annegret Kathagen-Buhmann, Cecile L Maire, Jonathan Weller, Alexander Schulte, Jakob Matschke, Mareike Holz, Keith L Ligon, Markus Glatzel, Manfred Westphal, Katrin Lamszus
Background: Aerobic glycolysis confers several advantages to tumor cells, including shunting of metabolites into anabolic pathways. In glioblastoma cells, hypoxia induces a flux shift from the pentose phosphate pathway towards glycolysis and a switch from proliferation to migration. The mechanistic link between glycolysis and migration is poorly understood. Since glucose-6-phosphate isomerase (GPI) is identical to the secreted autocrine motility factor (AMF), we investigated whether GPI/AMF regulates glioblastoma cell invasion...
July 24, 2018: Neuro-oncology
Chong Hyun Suh, Ho Sung Kim, Seung Chai Jung, Choong Gon Choi, Sang Joon Kim
Background: Noninvasive and accurate modality to predict Isocitrate dehydrogenase (IDH) mutant glioma may have great potential in routine clinical practice. We aimed to investigate the diagnostic performance of 2-hydroxyglutarate (2HG) magnetic resonance spectroscopy (MRS) for prediction of IDH mutant glioma and provide an optimal cut-off value for 2HG. Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed to identify original articles investigating the diagnostic performance of 2HG MRS up to March 20, 2018...
July 18, 2018: Neuro-oncology
Johannes Nowak, Karolina Nemes, Annika Hohm, Lindsey A Vandergrift, Martin Hasselblatt, Pascal D Johann, Marcel Kool, Michael C Frühwald, Monika Warmuth-Metz
Background: Recently, three molecular subgroups of atypical teratoid/rhabdoid tumor (ATRT) were identified, but little is known on their clinical and magnetic resonance imaging (MRI) characteristics. Methods: A total of 43 patients with known molecular subgroup status (ATRT-SHH n=17, ATRT-TYR n=16, ATRT-MYC n=10) were retrieved from the EU-RHAB registry and analyzed for clinical and MRI features. Results: On MRI review, differences in preferential tumor location were confirmed, with ATRT-TYR being predominantly located infratentorially (p<...
July 13, 2018: Neuro-oncology
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