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Low grade glioma children

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https://www.readbyqxmd.com/read/28525381/the-cell-of-origin-dictates-the-temporal-course-of-neurofibromatosis-1-nf1-low-grade-glioma-formation
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
March 22, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28293736/5ala-in-pediatric-brain-tumors-is-not-routinely-beneficial
#11
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
#12
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
https://www.readbyqxmd.com/read/28213194/subcortical-mapping-using-an-electrified-cavitron-ultrasonic-aspirator-in-pediatric-supratentorial-surgery
#13
Jonathan Roth, Akiva Korn, Yifat Bitan-Talmor, Rivka Kaufman, Margaret Ekstein, Shlomi Constantini
BACKGROUND: Intraoperative electrophysiology is increasingly used for various lesion resections, both in adult and pediatric brain surgery. Subcortical mapping is often used in adult surgery when lesions lie in proximity to the corticospinal tract (CST). We describe a novel technique of continuous subcortical mapping using an electrified Cavitron UltraSonic Aspirator (CUSA) in children with supratentorial lesions. METHODS: We evaluated the method of subcortical mapping using a CUSA as a stimulation probe...
May 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28062673/dabrafenib-effective-in-pediatric-glioma
#14
(no author information available yet)
A phase I/II clinical trial suggests that dabrafenib shrinks or stabilizes low-grade gliomas in children with the BRAF V600E mutation. Objective, durable responses occurred in 38% of patients, and the side effects were less severe than with chemotherapy. The researchers have started a second trial for patients with glioma and other BRAF-mutant tumor types, this time evaluating dabrafenib combined with trametinib.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28009226/report-of-effective-trametinib-therapy-in-2-children-with-progressive-hypothalamic-optic-pathway-pilocytic-astrocytoma-documentation-of-volumetric-response
#15
Catherine Miller, Daniel Guillaume, Kathryn Dusenbery, H Brent Clark, Christopher Moertel
Brain tumors are the most common solid tumor in childhood, and astrocytomas account for the largest proportion of these tumors. Increasing sophistication in genetic testing has allowed for the detection of specific mutations within tumor subtypes that may represent targets for individualized tumor treatment. The mitogen-activating protein kinase (MAPK) pathway and, more specifically, BRAF mutations have been shown to be prevalent in pediatric pilocytic astrocytomas and may represent one such area to target...
March 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/27997032/k27m-midline-gliomas-display-malignant-progression-by-imaging-and-histology
#16
Franziska J Vettermann, Julia E Neumann, Bogdana Suchorska, Peter Bartenstein, Armin Giese, Mario M Dorostkar, Nathalie L Albert, Ulrich Schüller
K27M midline gliomas are diffuse gliomas that usually occur in children and young adults and arise in midline structures of the brain, the brain stem and the spinal cord. They are defined by point mutations within the chromatin modifiers H3 and are usually associated with a bad clinical outcome [1,2,3]. As such, they are represented as a new separate entity in the new version of the WHO classification for tumors of the central nervous system. Interestingly, these tumors display a huge histological variability [4] and diagnoses currently range from low grade astrocytoma (WHO-grade II) to glioblastoma (WHO-grade IV)...
December 20, 2016: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/27923908/estrogen-activation-of-microglia-underlies-the-sexually-dimorphic-differences-in-nf1-optic-glioma-induced-retinal-pathology
#17
Joseph A Toonen, Anne C Solga, Yu Ma, David H Gutmann
Children with neurofibromatosis type 1 (NF1) develop low-grade brain tumors throughout the optic pathway. Nearly 50% of children with optic pathway gliomas (OPGs) experience visual impairment, and few regain their vision after chemotherapy. Recent studies have revealed that girls with optic nerve gliomas are five times more likely to lose vision and require treatment than boys. To determine the mechanism underlying this sexually dimorphic difference in clinical outcome, we leveraged Nf1 optic glioma (Nf1-OPG) mice...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27859985/leptomeningeal-dissemination-and-vertebral-bone-involvement-in-a-child-with-pilocytic-astrocytoma
#18
Metin Demirkaya, Betül Sevinir, Salih Güler, Candan Demiröz, Özgür Taskapilioglu, Selcuk Yilmazlar, Figen Palabiyik, Sahsine Tolunay
In low-grade glioma, metastasis is rarely seen. Few cases of leptomeningeal dissemination have been reported in children. Vertebral bone metastasis has not been reported so far. Herein is described the case of a pediatric patient with the diagnosis of pilocytic astrocytoma, and leptomeningeal dissemination detected at the time of diagnosis, who then received radiotherapy and chemotherapy upon development of vertebral bone metastasis during treatment.
December 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27810966/brainstem-low-grade-gliomas-in-children-excellent-outcomes-with-multimodality-therapy
#19
Santhosh A Upadhyaya, Carl Koschmann, Karin Muraszko, Sriram Venneti, Hugh J Garton, Daniel A Hamstra, Cormac O Maher, Bryan L Betz, Noah A Brown, Daniel Wahl, Helmut C Weigelin, Kathleen E DuRoss, Annette S Leonard, Patricia L Robertson
Safe maximal surgical resection is the initial treatment of choice for pediatric brainstem low-grade gliomas. Optimal therapy for incompletely resected tumors or that progress after surgery is uncertain. We reviewed the clinical characteristics, therapy, and outcomes of all children with nontectal brainstem low-grade gliomas treated at the University of Michigan between 1993 and 2013. Median age at diagnosis was 6 years; histology was confirmed in 23 of 25 tumors, 64% were pilocytic astrocytoma. Nineteen patients underwent initial tumor resection; 14/19 received no upfront adjuvant therapy...
November 3, 2016: Journal of Child Neurology
https://www.readbyqxmd.com/read/27799506/personalized-treatment-for-a-patient-with-a-braf-v600e-mutation-using-dabrafenib-and-a-tumor-treatment-fields-device-in-a-high-grade-glioma-arising-from-ganglioglioma
#20
Silviya K Meletath, Dean Pavlick, Tim Brennan, Roy Hamilton, Juliann Chmielecki, Julia A Elvin, Norma Palma, Jeffrey S Ross, Vincent A Miller, Philip J Stephens, George Snipes, Veena Rajaram, Siraj M Ali, Isaac Melguizo-Gavilanes
BACKGROUND: Gangliogliomas are slow-growing, low-grade central nervous system tumors affecting children and young adults. However, some patients will experience tumor recurrence and/or malignant progression. This article reports on the clinical history, molecular findings, and treatment response in a patient with BRAF V600-mutated high-grade glioma arising from ganglioglioma. METHODS: Hematoxylin-eosin staining and comprehensive genomic profiling via Foundation One were performed on the tumor sample from a male patient undergoing treatment at the Department of Neuro-Oncology at Baylor University Medical Center...
November 2016: Journal of the National Comprehensive Cancer Network: JNCCN
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