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https://www.readbyqxmd.com/read/28640700/cns-tumors-in-neurofibromatosis
#1
Jian Campian, David H Gutmann
Neurofibromatosis (NF) encompasses a group of distinct genetic disorders in which affected children and adults are prone to the development of benign and malignant tumors of the nervous system. The purpose of this review is to discuss the spectrum of CNS tumors arising in individuals with NF type 1 (NF1) and NF type 2 (NF2), their pathogenic etiologies, and the rational treatment options for people with these neoplasms. This article is a review of preclinical and clinical data focused on the treatment of the most common CNS tumors encountered in children and adults with NF1 and NF2...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640698/pediatric-gliomas-current-concepts-on-diagnosis-biology-and-clinical-management
#2
Dominik Sturm, Stefan M Pfister, David T W Jones
Gliomas are the most common CNS tumors in children and adolescents, and they show an extremely broad range of clinical behavior. The majority of pediatric gliomas present as benign, slow-growing lesions classified as grade I or II by the WHO classification of CNS tumors. These pediatric low-grade gliomas (LGGs) are fundamentally different from IDH-mutant LGGs occurring in adults, because they rarely undergo malignant transformation and show excellent overall survival under current treatment strategies. However, a significant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classified as WHO grade III or IV high-grade gliomas (HGGs)...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28636543/high-grade-glioma-in-very-young-children-a-rare-and-particular-patient-population
#3
REVIEW
Moatasem El-Ayadi, Marc Ansari, Dominik Sturm, Gerrit H Gielen, Monika Warmuth-Metz, Christof M Kramm, Andre O von Bueren
In the past years, pediatric high-grade gliomas (HGG) have been the focus of several research articles and reviews, given the recent discoveries on the genetic and molecular levels pointing out a clinico-biological uniqueness of the pediatric population compared to their adult counterparts with HGG. On the other hand, there are only scarce data about HGG in very young children (below 3 years of age at diagnosis) due to their relatively low incidence. However, the few available data suggest further distinction of this very rare subgroup from older children and adults at several levels including their molecular and biological characteristics, their treatment management, as well as their outcome...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623604/craniospinal-irradiation-for-treatment-of-metastatic-pediatric-low-grade-glioma
#4
Derek S Tsang, Erin S Murphy, Sharon E Ezell, John T Lucas, Christopher Tinkle, Thomas E Merchant
Patients with disseminated pediatric low-grade glioma (LGG) initially treated with chemotherapy frequently experience disease progression, with 5-year event-free survival (EFS) of <20% and 10-year overall survival (OS) of approximately 70%. This study aimed to describe outcomes of metastatic pediatric LGG treated with craniospinal irradiation (CSI). A retrospective study was performed of all patients with metastatic pediatric LGG treated with CSI at a single institution. EFS was defined as survival without disease progression or secondary high-grade glioma...
June 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#5
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
June 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28561225/feasibility-risk-profile-and-diagnostic-yield-of-stereotactic-biopsy-in-children-and-young-adults-with-brain-lesions
#6
Christina Hamisch, Tobias Blau, Katharina Klinger, Philipp Kickingereder, Daniel Ruess, Norbert Galldiks, Frank Berthold, Thorsten Simon, Stefan Grau, Maximilian I Ruge
Objective To evaluate the feasibility, safety, and diagnostic yield of stereotactic biopsy (SB) in children and adolescents with cerebral lesions. Methods We performed a systematic review of the literature and a retrospective analysis of all pediatric and adolescent patients who underwent SB for unclear brain lesions at our center. We collected patient and lesion-associated parameters, analysed the rate of procedural complications and diagnostic yield. Results Our institutional series consisted of 285 SBs in 269 children and young adults between 1989 and 2016 (median age, 9 (range 1-18) years)...
May 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28544746/clinical-outcomes-following-proton-therapy-for-children-with-central-nervous-system-tumors-referred-overseas
#7
Daniel J Indelicato, Julie A Bradley, Eric S Sandler, Philipp R Aldana, Amy Sapp, Jennifer E Gains, Adrian Crellin, Ronny L Rotondo
BACKGROUND: International, multidisciplinary care of children with central nervous system (CNS) tumors presents unique challenges. The aim of this study is to report patient outcomes of U.K. children referred for proton therapy to a North American facility. METHODS: From 2008 to 2016, 166 U.K. children with approved CNS tumors were treated with proton therapy at a single academic medical center in the United States. Median age was 7 years (range, 1-19). Median follow-up was 2...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28535583/molecular-testing-of-brain-tumor
#8
REVIEW
Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi
The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53 , and ATRX , oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC , FUBP1 , and the promoter region of telomerase reverse transcriptase ( TERTp )...
May 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28525381/the-cell-of-origin-dictates-the-temporal-course-of-neurofibromatosis-1-nf1-low-grade-glioma-formation
#9
Anne C Solga, Joseph A Toonen, Yuan Pan, Patrick J Cimino, Yu Ma, Guillaume A Castillon, Scott M Gianino, Mark H Ellisman, Da Yong Lee, David H Gutmann
Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2+ cells and that Olig2+ oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2+ OPCs could be tumor-initiating cells for Nf1 optic glioma...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522280/primary-spinal-glioma-in-children-results-from-a-referral-pediatric-institution-in-shanghai
#10
J Khalil, Z Chuanying, Z Qing, Y Belkacémi, J Mawei
PURPOSE: Primary spinal cord glioma is a rare entity especially in children; accounting for less than 10% of all central nervous system tumors. Low grade is the most reported subtype. Treatment modalities have largely evolved; large improvements have been made in the surgical field but also in both of radiotherapy and chemotherapy. Nevertheless, the optimal treatment is yet to be defined. MATERIAL AND METHODS: A chart review of 11 pediatric patients with a diagnosis of low grade spinal cord glioma at Xhinhua hospital in Shanghai was conducted...
May 15, 2017: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/28460484/the-%C3%AE-catenin-cbp-antagonist-icg-001-inhibits-pediatric-glioma-tumorigenicity-in-a-wnt-independent-manner
#11
Maria Wiese, Neele Walther, Christopher Diederichs, Fabian Schill, Sebastian Monecke, Gabriela Salinas, Dominik Sturm, Stefan M Pfister, Ralf Dressel, Steven A Johnsen, Christof M Kramm
Pediatric high-grade gliomas (pedHGG) belong to the most aggressive cancers in children with a poor prognosis due to a lack of efficient therapeutic strategies. The β-catenin/Wnt-signaling pathway was shown to hold promising potential as a treatment target in adult high-grade gliomas by abrogating tumor cell invasion and the acquisition of stem cell-like characteristics. Since pedHGG differ from their adult counterparts in genetically and biologically we aimed to investigate the effects of β-catenin/Wnt-signaling pathway-inhibition by the β-catenin/CBP antagonist ICG-001 in pedHGG cell lines...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445745/increased-tissue-stiffness-in-tumors-from-mice-with-neurofibromatosis-1-optic-glioma
#12
Christopher Walter, Lindsey Crawford, Melinda Lai, Joseph A Toonen, Yuan Pan, Shelly Sakiyama-Elbert, David H Gutmann, Amit Pathak
Children with neurofibromatosis type 1 (NF1) cancer predisposition syndrome are prone to the development of low-grade brain tumors (gliomas) within the optic pathway (optic gliomas). One of the key obstacles to developing successful therapeutic strategies for these tumors is the striking lack of information about the mechanical properties that characterize these tumors relative to non-neoplastic optic nerve tissue. To study the physical changes that may occur when an optic nerve glioma is present, we employed atomic force microscopy to measure the stiffness of healthy versus tumor-bearing optic nerve tissue...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28439238/rechallenge-to-carboplatin-in-children-with-low-grade-glioma-and-carboplatin-hypersensitivity-reactions
#13
Antonio Ruggiero, Daniela Rizzo, Martina Catalano, Palma Maurizi, Stefano Mastrangelo, Giorgio Attinà, Riccardo Riccardi
Background: Carboplatin based regimens have demonstrated activity in pediatric patients with low grade gliomas (LGG). However, carboplatin hypersensitivity reactions (CHRs) may be a major problem leading to premature cessation of an effective therapy. The objectives of this study were to describe the prevalence, characteristics and management of CHR. Methods: We performed a retrospective review of children with LGG treated between January 1994 and July 2015 with carboplatin and vincristine who had a documented CHR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28365895/does-proton-therapy-have-a-future-in-cns-tumors
#14
REVIEW
Stephanie E Combs
Proton therapy is characterized by certain physical properties leading to a reduction in integral dose. As proton therapy becomes more widely available, the ongoing discussion on the real indications for proton therapy becomes more important. In the present article, data on proton therapy for tumors of the central nervous system (CNS) is summarized and discussed in view of modern photon treatments. Still today, no randomized controlled trials are available confirming any clinical benefit of protons in CNS tumors...
March 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28357536/pediatric-high-grade-glioma-current-molecular-landscape-and-therapeutic-approaches
#15
REVIEW
Steve Braunstein, David Raleigh, Ranjit Bindra, Sabine Mueller, Daphne Haas-Kogan
High-grade pediatric central nervous system glial tumors are comprised primarily of anaplastic astrocytomas (AA, WHO grade III) and glioblastomas (GBM, WHO grade IV). High-grade gliomas are most commonly diagnosed in the primary setting in children, but as in adults, they can also arise as a result of transformation of a low-grade malignancy, though with limited frequency in the pediatric population. The molecular genetics of high-grade gliomas in the pediatric population are distinct from their adult counterparts...
March 29, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28342104/a-comprehensive-review-of-paediatric-low-grade-diffuse-glioma-pathology-molecular-genetics-and-treatment
#16
Scott Ryall, Uri Tabori, Cynthia Hawkins
Gliomas are the most common central nervous system neoplasms affecting children and can be both high- and low-grade. Paediatric low-grade glioma may be either World Health Organization grade I or grade II. Despite being classified as grade II diffuse astrocytoma, these neoplasms arising in children are distinct clinically and molecularly from their adult counterparts. They do not tend to progress to higher grade lesions and only rarely harbour an IDH mutation. Here, we review the clinical, histologic and molecular features of paediatric grade II diffuse glioma, highlighting their diagnostic criteria, prevalence across brain locations, their most common molecular features and how to test for them, and lastly the current status of therapeutic options available for their treatment...
April 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28339824/a-phase-i-trial-of-the-mek-inhibitor-selumetinib-azd6244-in-pediatric-patients-with-recurrent-or-refractory-low-grade-glioma-a-pediatric-brain-tumor-consortium-pbtc-study
#17
Anuradha Banerjee, Regina I Jakacki, Arzu Onar-Thomas, Shengjie Wu, Theodore Nicolaides, Tina Young Poussaint, Jason Fangusaro, Joanna Phillips, Arie Perry, David Turner, Michael Prados, Roger J Packer, Ibrahim Qaddoumi, Sridharan Gururangan, Ian F Pollack, Stewart Goldman, Lawrence A Doyle, Clinton F Stewart, James M Boyett, Larry E Kun, Maryam Fouladi
Background.: Activation of the mitogen-activated protein kinase pathway is important for growth of pediatric low-grade gliomas (LGGs). The aim of this study was to determine the recommended phase II dose (RP2D) and the dose-limiting toxicities (DLTs) of the MEK inhibitor selumetinib in children with progressive LGG. Methods.: Selumetinib was administered orally starting at 33 mg/m2/dose b.i.d., using the modified continual reassessment method. Pharmacokinetic analysis was performed during the first course...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28326681/population-pharmacokinetics-of-selumetinib-and-its-metabolite-n-desmethyl-selumetinib-in-adult-patients-with-advanced-solid-tumors-and-children-with-low-grade-gliomas
#18
Y T Patel, V M Daryani, P Patel, D Zhou, J Fangusaro, D J Carlile, P D Martin, L Aarons, C F Stewart
Selumetinib (AZD6244, ARRY-142886), a mitogen activated protein kinases (MEK1 and 2) inhibitor, has been granted orphan drug designation for differentiated thyroid cancer. The primary aim of this analysis was to characterize the population pharmacokinetics of selumetinib and its active metabolite N-desmethyl-selumetinib in patients with cancer. Concentration-time data from adult and pediatric clinical trials were pooled to develop a population pharmacokinetic model using a sequential approach where selumetinib and N-desmethyl-selumetinib data were modeled separately...
May 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28293736/5ala-in-pediatric-brain-tumors-is-not-routinely-beneficial
#19
Jonathan Roth, Shlomi Constantini
PURPOSE: Over recent years, 5-aminoluvolinic acid (5ALA) has been increasingly used for resection guidance in adult high-grade gliomas. However, amongst pediatric patients, publication of intraoperative fluorescence has been limited, with inconsistent outcomes. We describe our experience and intraoperative finding amongst children with various brain tumors that were given 5ALA prior to tumor resection. METHODS: Since October 2014, data regarding intraoperative findings amongst children that received 5ALA prior to tumor resection were prospectively collected...
March 14, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28271343/new-molecular-considerations-for-glioma-idh-atrx-braf-tert-h3-k27m
#20
REVIEW
Michael Karsy, Jian Guan, Adam L Cohen, Randy L Jensen, Howard Colman
PURPOSE OF REVIEW: This review will discuss the role of several key players in glioma classification and biology, namely isocitrate dehydrogenase 1 and 2 (IDH1/2), alpha thalassemia/mental retardation syndrome X-linked (ATRX), B-Raf (BRAF), telomerase reverse transcriptase (TERT), and H3K27M. RECENT FINDINGS: IDH1/2 mutation delineates oligoden-droglioma, astrocytoma, and secondary glioblastoma (GBM) from primary GBM and lower-grade gliomas with biology similar to GBM...
February 2017: Current Neurology and Neuroscience Reports
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