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Pediatric neuro-oncology

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https://www.readbyqxmd.com/read/28640708/medulloblastoma-from-myth-to-molecular
#1
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...
June 22, 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
#2
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...
June 22, 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
#3
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...
June 22, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27864705/the-clinical-and-financial-impact-of-a-pediatric-surgical-neuro-oncology-clinical-trial
#14
Eric M Thompson, Sridharan Gururangan, Gerald Grant, Duane Mitchell, John H Sampson
Pediatric surgical trials are rare and the impact of such trials on the institutions in which they are conducted is unknown. The purpose of this study was to analyze the clinical and financial impact of The Re-MATCH trial, a Phase I clinical trial requiring the biopsy or resection of recurrent medulloblastoma or PNET for enrollment. Inpatient financial and clinical volume information was collected during the 3 years of trial enrollment and the years preceding and following it. The primary endpoints were the difference in direct contribution margin (DCM), or net gain, of study and non-study patients and the difference in surgical volume during the study and non-study periods...
March 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27817916/orbital-periorbital-plexiform-neurofibromas-in-children-with-neurofibromatosis-type-1-multidisciplinary-recommendations-for-care
#15
Robert A Avery, James A Katowitz, Michael J Fisher, Gena Heidary, Eva Dombi, Roger J Packer, Brigitte C Widemann
TOPIC: Children and adults with neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas (PNs) involving the eyelid, orbit, periorbital, and facial structures (orbital-periorbital plexiform neurofibroma [OPPN]) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem...
January 2017: Ophthalmology
https://www.readbyqxmd.com/read/27742111/response-assessment-in-neuro-oncology-criteria-and-clinical-endpoints
#16
REVIEW
Raymond Y Huang, Patrick Y Wen
The Response Assessment in Neuro-Oncology (RANO) Working Group is an international multidisciplinary group whose goal is to improve response criteria and define endpoints for neuro-oncology trials. The RANO criteria for high-grade gliomas attempt to address the issues of pseudoprogression, pseudoresponse, and nonenhancing tumor progression. Incorporation of advanced MR imaging may eventually help improve the ability of these criteria to define enhancing and nonenhancing disease better. The RANO group has also developed criteria for neurologic response and evaluation of patients receiving immunologic therapies...
November 2016: Magnetic Resonance Imaging Clinics of North America
https://www.readbyqxmd.com/read/27659837/mri-guided-laser-interstitial-thermal-therapy-for-the-treatment-of-low-grade-gliomas-in-children-a-case-series-review-description-of-the-current-technologies-and-perspectives
#17
Zulma Tovar-Spinoza, Hoon Choi
BACKGROUND: Pediatric low-grade gliomas (LGGs) account for approximately half of all pediatric central nervous system tumors. The low-grade gliomas' first line of treatment is gross total resection. However, when gross total resection is not possible, options for adjuvant therapy are limited. MRI-guided laser ablation (magnetic resonance-guided laser interstitial thermal therapy (MRgLITT)) offers a new option for treatment in selected cases. We present a description of the current MRgLITT technology and an exemplary case-series review of our experience in its use in LGGs...
October 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/27616346/clinical-trials-in-pediatric-neuro-oncology-what-is-missing-and-how-we-can-improve
#18
REVIEW
Lennox Byer, Cassie Kline, Sabine Mueller
Brain tumors are the most common solid tumor in childhood, yet outcomes vary dramatically. High-grade gliomas have dismal outcomes with poor survival. By contrast, low-grade gliomas, have high survival rates, but children suffer from morbidity of tumor burden and therapy-associated side effects. In this article, we discuss how current trial designs often miss the opportunity to include end points beyond tumor response and thus fail to offer complete assessments of therapeutic approaches. Quality of life, neurocognitive function and neurofunctional deficits need to be considered when assessing overall success of a therapy...
October 2016: CNS Oncology
https://www.readbyqxmd.com/read/27593248/clinical-pet-mr-imaging-in-dementia-and-neuro-oncology
#19
REVIEW
Otto M Henriksen, Lisbeth Marner, Ian Law
The introduction of hybrid PET/MRI systems allows simultaneous multimodality image acquisition of high technical quality. This technique is well suited for the brain, and particularly in dementia and neuro-oncology. In routine use combinations of well-established MRI sequences and PET tracers provide the most optimal and clinically valuable protocols. For dementia the [18F]-fluorodeoxyglucose (FDG) has merit with a simultaneous four sequence MRI protocol of 20 min supported by supplementary statistical reading tools and quantitative measurements of the hippocampal volume...
October 2016: PET Clinics
https://www.readbyqxmd.com/read/27554756/pediatric-malignant-germ-cell-tumors-a-comparison-of-the-neuro-oncology-and-solid-tumor-experience
#20
REVIEW
Ashley S Plant, Susan N Chi, Lindsay Frazier
Malignant germ cell tumors (GCT) arise from abnormal migration of primordial germ cells and are histologically identical whether they occur inside or outside the central nervous system (CNS). However, the treatment strategy for GCTs varies greatly depending on the location of the tumor. These differences are in part due to the increased morbidity of surgery in the CNS but may also reflect differential sensitivity of the tumors to chemotherapy and radiation therapy (RT) or not-yet-understood biologic differences between these tumors...
December 2016: Pediatric Blood & Cancer
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