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Pediatric neuro-oncology

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https://www.readbyqxmd.com/read/28912153/comprehensive-genomic-profiling-of-282-pediatric-low-and-high-grade-gliomas-reveals-genomic-drivers-tumor-mutational-burden-and-hypermutation-signatures
#1
Adrienne Johnson, Eric Severson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Mandy Covert, Garrett M Frampton, Sigmund Hsu, Glenn J Lesser, Kimberly Stogner-Underwood, Ryan T Mott, Sarah Z Rush, Jennifer J Stanke, Sonika Dahiya, James Sun, Prasanth Reddy, Zachary R Chalmers, Rachel Erlich, Yakov Chudnovsky, David Fabrizio, Alexa B Schrock, Siraj Ali, Vincent Miller, Philip J Stephens, Jeffrey Ross, John R Crawford, Shakti H Ramkissoon
BACKGROUND: Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. MATERIALS AND METHODS: We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb])...
September 14, 2017: Oncologist
https://www.readbyqxmd.com/read/28887756/development-of-the-pediatric-neuro-oncology-rating-of-treatment-intensity-pnorti
#2
Matthew C Hocking, Wendy Hobbie, Michael J Fisher
Measures of treatment intensity for childhood cancer are needed in research in order to control for variability in treatments. Existing measures of treatment intensity for childhood cancers do not reflect the complexities of treatment protocols for central nervous system (CNS) tumors. This paper describes the development of the Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI). PNORTI development occurred in three phases. Phase 1: five experts in pediatric neuro-oncology created a 5-point scale of treatment intensity and 42 pediatric neuro-oncology providers completed a three-part online questionnaire to evaluate the classification system and apply the rating system to 16 sample patients...
September 8, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28871996/prognostic-relevance-of-treatment-failure-patterns-in-pediatric-high-grade-glioma-is-there-a-role-for-a-revised-failure-classification-system
#3
John T Lucas, David A Cooper, Scott Hwang, Christopher Tinkle, Xingyu Li, Yimei Li, Brent Orr, Thomas E Merchant, Alberto Broniscer
PURPOSE: We sought to investigate the pattern of treatment failure with respect to anatomic extent, radiation dose, and criteria for failure according to the Response Assessment in Neuro-Oncology (RANO). We evaluated the corresponding prognostic significance of these factors in patients with pediatric high-grade glioma (pHGG). METHODS AND MATERIALS: Fifty-six patients with pHGG were enrolled in an institutional phase 1 to 2 prospective trial that included maximal safe resection and radiation therapy with concurrent and adjuvant erlotinib...
October 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28860053/blood-brain-barrier-adapted-precision-medicine-therapy-for-pediatric-brain-tumors
#4
Bernard L Marini, Lydia L Benitez, Andrew H Zureick, Ralph Salloum, Angela C Gauthier, Julia Brown, Yi-Mi Wu, Dan R Robinson, Chandan Kumar, Robert Lonigro, Pankaj Vats, Xuhong Cao, Katayoon Kasaian, Bailey Anderson, Brendan Mullan, Benjamin Chandler, Joseph R Linzey, Sandra I Camelo-Piragua, Sriram Venneti, Paul E McKeever, Kathryn A McFadden, Andrew P Lieberman, Noah Brown, Lina Shao, Marcia A S Leonard, Larry Junck, Erin McKean, Cormac O Maher, Hugh J L Garton, Karin M Muraszko, Shawn Hervey-Jumper, Jean M Mulcahy-Levy, Adam Green, Lindsey M Hoffman, Katie Dorris, Nicholas A Vitanza, Joanne Wang, Jonathan Schwartz, Rishi Lulla, Natasha Pillay Smiley, Miriam Bornhorst, Daphne A Haas-Kogan, Patricia L Robertson, Arul M Chinnaiyan, Rajen Mody, Carl Koschmann
Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28853528/-neuro-oncology-a-new-field-in-davidoff-cancer-center-at-rabin-medical-center
#5
REVIEW
Shlomit Yust-Katz, Dror Limon, Ramez Abu-Shkara, Tali Siegal
Neuro-oncology is a subspecialty attracting physicians from medical disciplines such as neurology, neurosurgery, pediatrics, oncology, and radiotherapy. It deals with diagnosis and management of primary brain tumors, as well as metastatic and non-metastatic neurological manifestations that frequently affect cancer patients including brain metastases, paraneoplastic syndromes and neurological complications of cancer treatment. A neuro-oncology unit was established in Davidoff Cancer Center at Rabin Medical Center...
August 2017: Harefuah
https://www.readbyqxmd.com/read/28830841/molecular-pathogenesis-and-therapeutic-implications-in-pediatric-high-grade-gliomas
#6
REVIEW
Tareq A Juratli, Nan Qin, Daniel P Cahill, Mariella G Filbin
High-grade gliomas (HGG) are the most common malignant brain tumors in the pediatric population and account for a large subset of all pediatric central nervous system neoplasms. The management of pediatric HGG continues to be challenging, with poor outcome in many cases despite aggressive treatments. Consequently, parallel research efforts have been focused on identifying the underlying genetic and biological basis of pediatric HGG in order to more clearly define prognostic subgroups for treatment stratification as well as identify new treatment targets...
August 19, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28717752/challenges-of-treating-childhood-medulloblastoma-in-a-country-with-limited-resources-20-years-of-experience-at-a-single-tertiary-center-in-malaysia
#7
Revathi Rajagopal, Sayyidatul Abd-Ghafar, Dharmendra Ganesan, Anita Zarina Bustam Mainudin, Kum Thong Wong, Norlisah Ramli, Vida Jawin, Su Han Lum, Tsiao Yi Yap, Eric Bouffet, Ibrahim Qaddoumi, Shekhar Krishnan, Hany Ariffin, Wan Ariffin Abdullah
PURPOSE: Pediatric medulloblastoma (MB) treatment has evolved over the past few decades; however, treating children in countries with limited resources remains challenging. Until now, the literature regarding childhood MB in Malaysia has been nonexistent. Our objectives were to review the demographics and outcome of pediatric MB treated at the University Malaya Medical Center between January 1994 and December 2013 and describe the challenges encountered. METHODS: Fifty-one patients with childhood MB were seen at University Malaya Medical Center...
April 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28640708/medulloblastoma-from-myth-to-molecular
#8
REVIEW
Vijay Ramaswamy, Michael D Taylor
Current therapies for medulloblastoma were introduced primarily in the 1980s and consist of predominantly cytotoxic, nontargeted approaches. Mortality from medulloblastoma remains significant. In addition, many survivors suffer from severe treatment-related effects of radiation and cytotoxic chemotherapy. Further intensification of nonspecific therapy is unlikely to offer additional benefits, because survival rates have reached a plateau. Recent publications in medulloblastoma have revolved largely around the recognition that medulloblastoma per se does not exist, but rather, that there are a group of histologically similar but clinically and molecularly distinct entities that have been grouped under that rubric...
July 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640707/response-assessment-in-neuro-oncology-clinical-trials
#9
REVIEW
Patrick Y Wen, Susan M Chang, Martin J Van den Bent, Michael A Vogelbaum, David R Macdonald, Eudocia Q Lee
Development of novel therapies for CNS tumors requires reliable assessment of response and progression. This requirement has been particularly challenging in neuro-oncology for which contrast enhancement serves as an imperfect surrogate for tumor volume and is influenced by agents that affect vascular permeability, such as antiangiogenic therapies. In addition, most tumors have a nonenhancing component that can be difficult to accurately quantify. To improve the response assessment in neuro-oncology and to standardize the criteria that are used for different CNS tumors, the Response Assessment in Neuro-Oncology (RANO) working group was established...
July 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640705/genomic-analysis-of-childhood-brain-tumors-methods-for-genome-wide-discovery-and-precision-medicine-become-mainstream
#10
REVIEW
Stephen C Mack, Paul A Northcott
Recent breakthroughs in next-generation sequencing technology and complementary genomic platforms have transformed our capacity to interrogate the molecular landscapes of human cancers, including childhood brain tumors. Numerous high-throughput genomic studies have been reported for the major histologic brain tumor entities diagnosed in children, including interrogations at the level of the genome, epigenome, and transcriptome, many of which have yielded essential new insights into disease biology. The nature of these discoveries has been largely platform dependent, exemplifying the usefulness of applying different genomic and computational strategies, or integrative approaches, to address specific biologic and/or clinical questions...
July 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28603776/actionable-molecular-biomarkers-in-primary-brain-tumors
#11
Verena Staedtke, Omar Dildar A Dzaye, Matthias Holdhoff
Recent genome-wide studies of malignancies of the central nervous system (CNS) have revolutionized our understanding of the biology of these tumors. This newly gained knowledge provides a wealth of opportunity for biomarker driven clinical research. To date, however, only few of the available molecular markers truly influence clinical decision-making and treatment. The most widely validated markers in neuro-oncology presently are: 1) MGMT promoter methylation as a prognostic and predictive marker in glioblastoma, 2) co-deletion of 1p and 19q differentiating oligodendrogliomas from astrocytomas, 3) IDH1/2 mutations, and 4) select pathway-associated mutations...
July 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28561665/new-classification-for-central-nervous-system-tumors-implications-for-diagnosis-and-therapy
#12
Christine E Fuller, David T W Jones, Mark W Kieran
The 2016 World Health Organization Classification of Tumors of the Central Nervous System (WHO 2016) represents a noteworthy divergence from prior classification schemas. This new classification introduced the concept of "integrated diagnoses" based on a marriage of both phenotypic (microscopic) and genotypic parameters, with the intended goals of improving diagnostic accuracy and patient management. The result is a major restructuring in many of the brain tumor categories, with the codification of multiple new tumor entities and subgroups...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28453743/targeted-next-generation-sequencing-of-pediatric-neuro-oncology-patients-improves-diagnosis-identifies-pathogenic-germline-mutations-and-directs-targeted-therapy
#13
Cassie N Kline, Nancy M Joseph, James P Grenert, Jessica van Ziffle, Eric Talevich, Courtney Onodera, Mariam Aboian, Soonmee Cha, David R Raleigh, Steve Braunstein, Joseph Torkildson, David Samuel, Michelle Bloomer, Alejandra G de Alba Campomanes, Anuradha Banerjee, Nicholas Butowski, Corey Raffel, Tarik Tihan, Andrew W Bollen, Joanna J Phillips, W Michael Korn, Iwei Yeh, Boris C Bastian, Nalin Gupta, Sabine Mueller, Arie Perry, Theodore Nicolaides, David A Solomon
Background: Molecular profiling is revolutionizing cancer diagnostics and leading to personalized therapeutic approaches. Herein we describe our clinical experience performing targeted sequencing for 31 pediatric neuro-oncology patients. Methods: We sequenced 510 cancer-associated genes from tumor and peripheral blood to identify germline and somatic mutations, structural variants, and copy number changes. Results: Genomic profiling was performed on 31 patients with tumors including 11 high-grade gliomas, 8 medulloblastomas, 6 low-grade gliomas, 1 embryonal tumor with multilayered rosettes, 1 pineoblastoma, 1 uveal ganglioneuroma, 1 choroid plexus carcinoma, 1 chordoma, and 1 high-grade neuroepithelial tumor...
May 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28449033/response-assessment-in-medulloblastoma-and-leptomeningeal-seeding-tumors-recommendations-from-the-response-assessment-in-pediatric-neuro-oncology-committee
#14
Katherine E Warren, Gilbert Vezina, Tina Y Poussaint, Monika Warmuth-Metz, Marc C Chamberlain, Roger J Packer, Alba A Brandes, Moshe Reiss, Stewart Goldman, Michael J Fisher, Ian F Pollack, Michael D Prados, Patrick Y Wen, Susan M Chang, Christelle Dufour, David Zurakowski, Rolf D Kortmann, Mark W Kieran
Lack of standard response criteria in clinical trials for medulloblastoma and other seeding tumors complicates assessment of therapeutic efficacy and comparisons across studies. An international working group was established to develop consensus recommendations for response assessment. The aim is that these recommendations be prospectively evaluated in clinical trials, with the goal of achieving more reliable risk stratification and uniformity across clinical trials. Current practices and literature review were performed to identify major confounding issues and justify subsequently developed recommendations; in areas lacking scientific investigations, recommendations were based on experience of committee members and consensus was reached after discussion...
April 25, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28410300/applied-cancer-immunogenomics-leveraging-neoantigen-discovery-in-glioblastoma
#15
REVIEW
Tanner M Johanns, Gavin P Dunn
Glioblastoma (GBM) remains a significant cause of cancer-related mortality in pediatric and adult patients with limited treatment options. Immunotherapy represents a promising new therapeutic approach in many solid and hematologic malignancies, including GBM, although only a subset of patients responds clinically. Thus, current efforts are focused on identifying patients most likely to benefit from immune-based therapies. The cancer immunogenomics approach identifies candidate neoantigens from genomics information and represents a potentially exciting new space in precision neuro-oncology...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28290395/indian-society-of-neuro-oncology-consensus-guidelines-for-the-contemporary-management-of-medulloblastoma
#16
Tejpal Gupta, Chitra Sarkar, Vedantam Rajshekhar, Sandip Chatterjee, Neelam Shirsat, Dattatreya Muzumdar, Sona Pungavkar, Girish Chinnaswamy, Rakesh Jalali
INTRODUCTION: The high success rate in the management medulloblastoma achieved in the western world is not exactly mirrored in developing countries including India. Socio-demographic differences, health-care disparity, and lack in uniformity of care with resultant widespread variations in the clinical practice are some of the reasons that may partly explain this difference in outcomes. Patients with medulloblastoma require a multi-disciplinary team approach involving but not limited to neuro-radiology, neurosurgery; neuropathology, molecular biology, radiation oncology, pediatric medical oncology and rehabilitative services for optimizing outcomes...
March 2017: Neurology India
https://www.readbyqxmd.com/read/28257280/applying-the-international-classification-of-functioning-children-and-youth-version-to-pediatric-neuro-oncology
#17
Thomas Pletschko, Anna Felnhofer, Agathe Schwarzinger, Liesa Weiler, Irene Slavc, Ulrike Leiss
Given the increased survival rates in patients with pediatric central nervous system tumors, late effects such as treatment- and/or illness-related neurologic sequelae as well as neuropsychological deficits and social difficulties have moved into focus in follow-up care. In order to provide personalized treatment recommendations for pediatric brain tumor survivors, it is crucial not only to assess cognitive impairments but also to measure a patient's functional deficiencies, for example, restricted participation in everyday social activities...
January 2017: Journal of Child Neurology
https://www.readbyqxmd.com/read/28152843/building-a-new-process-nursing-verification-of-pediatric-oral-chemotherapy
#18
Erin Santacroce, Mary Ann Zimmerman, Melissa Freeman, Teresa Lau Greenberg, Phuong Nguyen, Susan N Chi, Pratiti Bandopadhayay, Sharon Lane, Audrea Szabatura, Kathleen Houlahan, Amy Billett
199 Background: While team-based safety checks ensure safe prescribing of parenteral chemotherapy, oral chemotherapy is usually prescribed by a single clinician. With the growing use of oral chemotherapy, processes are needed to protect these vulnerable patients from prescription errors. METHODS: A team of nurses, clinicians, pharmacists and administrators developed a new process and checklist for nursing verification of oral chemotherapy prescriptions at Dana-Farber's pediatric neuro-oncology program...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27978508/targeted-next-generation-sequencing-of-pediatric-neuro-oncology-patients-improves-diagnosis-identifies-pathogenic-germline-mutations-and-directs-targeted-therapy
#19
Cassie N Kline, Nancy M Joseph, James P Grenert, Jessica van Ziffle, Eric Talevich, Courtney Onodera, Mariam Aboian, Soonmee Cha, David R Raleigh, Steve Braunstein, Joseph Torkildson, David Samuel, Michelle Bloomer, Alejandra G de Alba Campomanes, Anuradha Banerjee, Nicholas Butowski, Corey Raffel, Tarik Tihan, Andrew W Bollen, Joanna J Phillips, W Michael Korn, Iwei Yeh, Boris C Bastian, Nalin Gupta, Sabine Mueller, Arie Perry, Theodore Nicolaides, David A Solomon
BACKGROUND: Molecular profiling is revolutionizing cancer diagnostics and leading to personalized therapeutic approaches. Herein we describe our clinical experience performing targeted sequencing for 31 pediatric neuro-oncology patients. METHODS: We sequenced 510 cancer-associated genes from tumor and peripheral blood to identify germline and somatic mutations, structural variants, and copy number changes. RESULTS: Genomic profiling was performed on 31 patients with tumors including 11 high-grade gliomas, 8 medulloblastomas, 6 low-grade gliomas, 1 embryonal tumor with multilayered rosettes, 1 pineoblastoma, 1 uveal ganglioneuroma, 1 choroid plexus carcinoma, 1 chordoma, and 1 high-grade neuroepithelial tumor...
November 14, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27889022/advanced-mr-imaging-in-pediatric-brain-tumors-clinical-applications
#20
REVIEW
Maarten Lequin, Jeroen Hendrikse
Advanced MR imaging techniques, such as spectroscopy, perfusion, diffusion, and functional imaging, have improved the diagnosis of brain tumors in children and also play an important role in defining surgical as well as therapeutic responses in these patients. In addition to the anatomic or structural information gained with conventional MR imaging sequences, advanced MR imaging techniques also provide physiologic information about tumor morphology, metabolism, and hemodynamics. This article reviews the physiology, techniques, and clinical applications of diffusion-weighted and diffusion tensor imaging, MR spectroscopy, perfusion MR imaging, susceptibility-weighted imaging, and functional MR imaging in the setting of neuro-oncology...
February 2017: Neuroimaging Clinics of North America
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