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Christian Grommes, Lakshmi Nayak, Han W Tun, Tracy T Batchelor
Novel insights into the pathophysiology of Primary Central Nervous System Lymphoma (PCNSL) have identified the B-cell receptor and Toll-like receptor pathway as well as immune evasion and suppressed tumor immune microenvironment as a key mechanism in the pathogenesis of PCNSL. Small molecules and novel agents targeting these aberrant pathways have been introduced into clinical trials targeting the recurrent or refractory PCNSL patient population. Agents like the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib or immunomodulatory drugs (IMiDs) like pomalidomide and lenalidomide have shown promising high response rates in the salvage setting...
November 13, 2018: Neuro-oncology
Christian Grommes, James L Rubenstein, Lisa M DeAngelis, Andres J M Ferreri, Tracy T Batchelor
Primary central nervous system (CNS) lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that affects the brain parenchyma, spinal cord, eyes, and cerebrospinal fluid without evidence of systemic, non-CNS involvement. PCNSL is uncommon and only a few randomized trials have been completed in the first-line setting. Over the past decades, the prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate, which is now the backbone of all first-line treatment polychemotherapy regimens...
November 12, 2018: Neuro-oncology
Tanja Eisemann, Barbara Costa, Patrick N Harter, Wolfgang Wick, Michel Mittelbronn, Peter Angel, Heike Peterziel
Background: Treatment options of glioblastoma, the most aggressive primary brain tumor with frequent relapses and high mortality, are still very limited urgently calling for novel therapeutic targets. Expression of the glycoprotein podoplanin correlates with poor prognosis in various cancer entities including glioblastoma. Furthermore, podoplanin has been associated with tumor cell migration and proliferation in vitro; however, experimental data on its function in gliomagenesis in vivo is still missing...
November 10, 2018: Neuro-oncology
Lindsay Angus, John W M Martens, Martin J van den Bent, Peter A E Sillevis Smitt, Stefan Sleijfer, Agnes Jager
Leptomeningeal metastases (LM) in breast cancer patients are rare but often accompanied by devastating neurological symptoms and carries a very poor prognosis, even if treated. To date, two diagnostic methods are clinically used to diagnose LM: gadolinium MRI of the brain and/or spinal cord and cytological examination of cerebrospinal fluid (CSF). Both techniques are however hampered by limited sensitivities, often leading to a long diagnostic process requiring repeated lumbar punctures and MRI examinations...
November 10, 2018: Neuro-oncology
Daniel Lewis, Federico Roncaroli, Erjon Agushi, Dominic Mosses, Ricky Williams, Ka-Loh Li, Xiaoping Zhu, Rainer Hinz, Ross Atkinson, Andrea Wadeson, Sharon Hulme, Helen Mayers, Emma Stapleton, Simon K L Lloyd, Simon R Freeman, Scott A Rutherford, Charlotte Hammerbeck-Ward, D Gareth Evans, Omar Pathmanaban, Alan Jackson, Andrew T King, David Coope
Background: Inflammation is hypothesized to be a key event in the growth of sporadic vestibular schwannoma (VS). In this study we sought to investigate the relationship between inflammation and tumor growth in vivo using the PET tracer 11C-(R)-PK11195 and dynamic contrast enhanced (DCE) MRI derived vascular biomarkers. Methods: Nineteen patients with sporadic VS (8 static, 7 growing and 4 shrinking tumors), underwent prospective imaging with dynamic 11C-(R)-PK11195 PET and a comprehensive MR protocol; including high temporal resolution DCE-MRI in fifteen patients...
November 2, 2018: Neuro-oncology
Bill H Diplas, Heng Liu, Rui Yang, Landon J Hansen, Alexis L Zachem, Fangping Zhao, Darell D Bigner, Roger E McLendon, Yuchen Jiao, Yiping He, Matthew S Waitkus, Hai Yan
Background: Mutations in the promoter of telomerase reverse transcriptase (TERTp) and isocitrate dehydrogenase 1 (IDH1) offer objective markers to assist in classifying diffuse gliomas into genetic subgroups. However, traditional mutation detection techniques lack sensitivity, or have long turnaround times, or high costs. We developed GliomaDx, an allele-specific, locked nucleic acid (LNA)-based qPCR assay to overcome these limitations and sensitively detect TERTp and IDH mutations. Methods: We evaluated the performance of GliomaDx on cell line DNA and frozen tissue diffuse glioma samples with variable tumor percentage to mimic use in clinical settings and validated low percentage variants using sensitive techniques including droplet digital PCR (ddPCR) and next generation sequencing...
October 22, 2018: Neuro-oncology
Flóra John, Edit Bosnyák, Natasha L Robinette, Alit J Amit-Yousif, Geoffrey R Barger, Keval D Shah, Sharon K Michelhaugh, Neil V Klinger, Sandeep Mittal, Csaba Juhász
BACKGROUND: Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value. METHODS: Contrast-enhanced T1, T2/FLAIR MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[ 11C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly-diagnosed glioblastoma...
October 22, 2018: Neuro-oncology
E Antonio Chiocca, Farshad Nassiri, Justin Wang, Pierpaolo Peruzzi, Gelareh Zadeh
A phase 1 trial of an engineered poliovirus for the treatment of rGBM (GBM) has attracted attention due to 8 survivors reaching the 24-month and 5 reaching the 36-month survival landmarks1. Genetically engineered viruses (oncolytic viruses) have been in trials for GBM for almost two decades2. These replication-competent (tumor-selective, oncolytic, replication-conditional) viruses or replication-defective viral vectors (gene therapy) deliver cytotoxic payloads to tumors, leading to immunogenic death and intratumoral inflammatory responses...
October 22, 2018: Neuro-oncology
Charles N de Leeuw, Michael A Vogelbaum
Background: Emerging evidence suggests survival benefit from resection beyond all MRI abnormalities present on T1-enhanced and T2-FLAIR modalities in glioma (supratotal resection); however, the quality of evidence is unclear. We addressed this question via systematic review of the literature. Methods: EMBASE, MEDLINE, Scopus, and Web of Science databases were queried. Case studies, reviews or editorials, non-English, abstract-only, brain metastases, and descriptive works were excluded...
October 15, 2018: Neuro-oncology
Miikka Korja, Rahul Raj, Karri Seppä, Tapio Luostarinen, Nea Malila, Matti Seppälä, Hanna Mäenpää, Janne Pitkäniemi
Background: We assessed population-level changes in glioblastoma survival between 2000 and 2013 in Finland, with focus on elderly patients (>70 years) in order to assess if changes in treatment of glioblastoma are reflected also in population-based survival rates. Methods: We identified all patients (age ≥18 years) from the Finnish Cancer Registry (FCR) with a histopathological diagnosis of primary glioblastoma in 2000-2013. Patients were followed up until December 2015...
October 12, 2018: Neuro-oncology
Rebecca L Achey, Haley Gittleman, Julia Schroer, Vishesh Khanna, Carol Kruchko, Jill S Barnholtz-Sloan
Background: Meningioma incidence increases significantly with age. In the expanding elderly population, we lack complete understanding of population-based trends in meningioma incidence/survival. We provide an updated, comprehensive analysis of meningioma incidence and survival for individuals aged over 65. Methods: Data were obtained from the Central Brain Tumor Registry of the United States (CBTRUS) from 2005-2015 for non-malignant and malignant meningioma. Age-adjusted incidence rates per 100,000 person-years were analyzed by age, sex, race, ethnicity, location, and treatment modalities...
October 6, 2018: Neuro-oncology
Mattias Belting, Anna Bång-Rudenstam, Elisabet Englund, Torsten Pietsch
No abstract text is available yet for this article.
October 5, 2018: Neuro-oncology
Wolfgang Wick, Susan Dettmer, Anne Berberich, Tobias Kessler, Irini Karapanagiotou-Schenkel, Antje Wick, Frank Winkler, Elke Pfaff, Benedikt Brors, Jürgen Debus, Andreas Unterberg, Martin Bendszus, Christel Herold-Mende, Andreas Eisenmenger, Andreas von Deimling, David T W Jones, Stefan M Pfister, Felix Sahm, Michael Platten
Background: Patients with glioblastoma without O6-methyl guanine O6-methylatransferase (MGMT) promoter hypermethylation are unlikely to benefit from alkylating chemotherapy with temozolomide (TMZ). Trials aiming at replacing TMZ with targeted agents in unselected patient populations have failed to demonstrate any improvement of survival. Advances in molecular understanding and diagnostic precision enable identification of key genetic alterations in a timely manner and in principle allow treatments with targeted compounds based on molecular markers...
October 1, 2018: Neuro-oncology
Ramon F Barajas, Bronwyn E Hamilton, Daniel Schwartz, Heather L McConnell, David R Pettersson, Andrea Horvath, Laszlo Szidonya, Csanad G Varallyay, Jenny Firkins, Jerry J Jaboin, Charlotte D Kubicky, Ahmed M Raslan, Aclan Dogan, Justin S Cetas, Jeremy Ciporen, Seunggu J Han, Prakash Ambady, Leslie L Muldoon, Randy Woltjer, William D Rooney, Edward A Neuwelt
Background: Noninvasively differentiating therapy-induced pseudo-progression from recurrent disease in patients with glioblastoma is prospectively difficult due to the current lack of a biologically specific imaging metric. Ferumoxytol iron oxide nanoparticle MRI contrast characterizes innate immunity mediated neuroinflammation; therefore, we hypothesized that combined ferumoxytol and gadolinium enhanced MRI could serve as a biomarker of glioblastoma pseudo-progression. Methods: In this institutional review board approved, retrospective study, we analyzed ferumoxytol and gadolinium contrast enhanced T1-weighted 3T MRI in 45 patients with glioblastoma over multiple clinical time points...
October 1, 2018: Neuro-oncology
Fabio Y Moraes, Jeff Winter, Eshetu G Atenafu, Archya Dasgputa, Hamid Raziee, Catherine Coolens, Barbara-Ann Millar, Normand Laperriere, Maitry Patel, Mark Bernstein, Paul Kongkham, Gelareh Zadeh, Tatiana Conrad, Caroline Chung, Alejandro Berlin, David B Shultz
Background: At our institution, we have historically treated brain metastasis (BM) ≤2cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes. Methods: We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariable analyses (MVA)...
September 28, 2018: Neuro-oncology
Hongyi Zhang, Jianlong Liao, Xinxin Zhang, Erjie Zhao, Xin Liang, Shangyi Luo, Jian Shi, Fulong Yu, Jinyuan Xu, Weitao Shen, Yixue Li, Yun Xiao, Xia Li
Background: x differences in glioma incidence and outcome have been previously reported but remain poorly understood. Many sex differencesthat affect the cancer risk were thought to be associated with cancer evolution. Material/Methods: In this study, we used an integrated framework to infer the timing and clonal status of mutations in ~600 diffuse gliomas from The Cancer Genome Atlas including glioblastomas (GBM) and low grade gliomas (LGG), and investigated the sex difference of mutation clonality...
September 25, 2018: Neuro-oncology
Andrey Korshunov, Felix Sahm, Olga Zheludkova, Andrey Golanov, Damian Stichel, Daniel Schrimpf, Marina Ryzhova, Alexander Potapov, Antje Habel, Jochen Meyer, Peter Lichter, David T W Jones, Andreas von Deimling, Stefan M Pfister, Marcel Kool
Background: WNT activated medulloblastoma (WNT MB) represent a well-characterized molecular variant accounting for 10-15% of all MB and is associated with a favorable clinical outcome. Patients with localized WNT MBs could benefit from de-intensification of combined treatment, which would require an accurate diagnosis of these tumors. However, despite the presence of molecular features related with a WNT MB signature (nuclear ß-catenin immunoexpression, CTNNB1 mutation and monosomy 6), a prompt and reliable diagnostic verification of these tumors is not yet feasible...
September 25, 2018: Neuro-oncology
Thankamma Ajithkumar, Naduni Imbulgoda, Elliott Rees, Fiona Harris, Gail Horan, Amos Burke, Sarah Jefferies, Stephen Price, Justin Cross, Kieren Allinson
An initial search of PubMed used broad search terms 'brain tumors', 'low-grade', 'radiotherapy, 'chemotherapy', 'surgery' and 'treatment' from January 1990 to March 2018. A subsequent focused search was undertaken using the names of individual histological subtypes of low-grade brain tumors as in the 2016 WHO classification. Only papers published in English were reviewed. The final reference list was generated on the basis of originality and relevance to the broad scope of this review.
September 20, 2018: Neuro-oncology
Brad Poore, Ming Yuan, Antje Arnold, Antoinette Price, Jesse Alt, Jeffrey A Rubens, Barbara S Slusher, Charles G Eberhart, Eric H Raabe
Background: Pediatric low-grade glioma (pLGG) often initially respond to front-line therapies such as carboplatin, but more than 50% of treated tumors eventually progress and require additional therapy. The discovery that pLGG often contain mammalian Target of Rapamycin (mTOR) activation, new treatment modalities and combinations are now possible for patients. The purpose of this study was to determine if carboplatin is synergistic with the mTORC1 inhibitor everolimus in pLGG. Methods: We treated four pLGG cell lines and one patient-derived xenograft line representing various pLGG genotypes, including NF1 loss, BRAF-KIAA1549 fusion, and BRAF V600E mutation, with carboplatin and/or everolimus and performed assays for growth, cell proliferation, and cell death...
September 18, 2018: Neuro-oncology
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
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