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https://www.readbyqxmd.com/read/29315108/review-of-molecular-classification-and-treatment-implications-of-pediatric-brain-tumors
#1
Ana S Guerreiro Stucklin, Vijay Ramaswamy, Craig Daniels, Michael D Taylor
PURPOSE OF REVIEW: Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors...
February 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29285383/effect-of-o6-methylguanine-dna-methyltransferase-methylation-in-medulloblastoma
#2
Tomoko Kurimoto, Akihide Kondo, Ikuko Ogino, Junya Fujimura, Atsushi Arakawa, Hajime Arai, Toshiaki Shimizu
Medulloblastoma is a highly malignant brain tumor that predominately affects children and requires multimodal treatment, including chemotherapy with alkylating agents. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that plays an important role in tumor resistance to alkylating agents. Recent studies demonstrated that MGMT promoter methylation suppresses the expression of MGMT and is associated with favorable outcomes of malignant glioma patients. However, the MGMT methylation status and its prognostic impact on medulloblastoma have not been fully elucidated to date...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29248974/management-and-outcome-of-children-and-adolescents-with-non-medulloblastoma-cns-embryonal-tumors-in-spain-room-for-improvement-in-standards-of-care
#3
Teresa de Rojas, Francisco Bautista, Miguel Flores, Lucía Igual, Raquel Rubio, Eduardo Bardón, Lucía Navarro, Laura Murillo, Raquel Hladun, Adela Cañete, Miguel Garcia-Ariza, Carmen Garrido, Ana Fernández-Teijeiro, Eduardo Quiroga, Carlota Calvo, Anna Llort, Inmaculada de Prada, Luis Madero, Ofelia Cruz, Lucas Moreno
Non-medulloblastoma CNS embryonal tumors (former PNET/Pineoblastomas) are aggressive malignancies with poor outcome that have been historically treated with medulloblastoma protocols. The purpose of this study is to present a tumor-specific, real-world data cohort of patients with CNS-PNET/PB to analyze quality indicators that can be implemented to improve the outcome of these patients. Patients 0-21 years with CNS-PNET treated in eight large institutions were included. Baseline characteristics, treatment and outcome [progression-free and overall survival (PFS and OS respectively)] were analyzed...
December 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29237970/a-dosimetric-comparison-between-three-dimensional-conformal-radiation-therapy-and-intensity-modulated-radiation-therapy-in-the-treatment-of-posterior-fossa-boost-in-medulloblastoma
#4
Meenu Gupta, Ravi Kant, Vipul Nautiyal, Jyoti Bisht, Shalindra Raghuvanshi, Manju Saini, B P Kalra, Mushtaq Ahmad
AIMS: To compare three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) in posterior fossa (PF) boost in children with medulloblastoma (MB); dosimetrically evaluating and comparing both techniques with regard to target coverage and doses to organs at risk. SETTINGS AND DESIGN: Structured. SUBJECTS AND METHODS: Seven previously irradiated patients of MB were retrieved and re-planned with both 3DCRT and IMRT techniques...
October 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29236237/outcome-of-children-and-adolescents-with-central-nervous-system-tumors-in-phase-i-trials
#5
Fernando Carceller, Francisco Bautista, Irene Jiménez, Raquel Hladun-Álvaro, Cécile Giraud, Luca Bergamaschi, Madhumita Dandapani, Isabelle Aerts, François Doz, Didier Frappaz, Michela Casanova, Bruce Morland, Darren R Hargrave, Gilles Vassal, Andrew D J Pearson, Birgit Geoerger, Lucas Moreno, Lynley V Marshall
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses...
December 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29219788/differential-patterns-of-metastatic-dissemination-across-medulloblastoma-subgroups
#6
Michal Zapotocky, Daddy Mata-Mbemba, David Sumerauer, Petr Liby, Alvaro Lassaletta, Josef Zamecnik, Lenka Krskova, Martin Kyncl, Jan Stary, Suzanne Laughlin, Anthony Arnoldo, Cynthia Hawkins, Uri Tabori, Michael D Taylor, Eric Bouffet, Charles Raybaud, Vijay Ramaswamy
OBJECTIVE Metastatic dissemination is a major treatment challenge and cause of death in patients with medulloblastoma. However, the influence of molecular biology on the pattern of metastatic dissemination at diagnosis is not known. In this study, the authors sought to define the location, pattern, and imaging characteristics of medulloblastoma metastases across subgroups at diagnosis. METHODS A consecutive cohort of patients with metastatic medulloblastoma at The Hospital for Sick Children and the University Hospital Motol, who underwent up-front MRI of the craniospinal axis, was assembled and allocated to subgroups using NanoString limited gene-expression profiling...
December 8, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/29204199/clinicopathological-study-of-pediatric-posterior-fossa-tumors
#7
Kadali Satya Vara Prasad, D Ravi, Vijay Pallikonda, Bhavana Venkata Satya Raman
Context: Brain tumor is one of the most devastating forms of human illness, especially when occurring in the posterior fossa and involving the brainstem. Tumors in the posterior fossa are considered some of the most critical brain lesions. This is primarily due to the limited space within the posterior fossa, as well as the potential involvement of the vital brainstem nuclei. Aims: The aim of this study is to analyze the incidence, clinical features, surgical outcome, complications, and prognosis in a series of 37 pediatric patients with posterior fossa tumors who underwent surgery between September 2012 and January 2015 from the Department of Neurosurgery, King George Hospital, Visakhapatnam (both prospective and retrospective study)...
July 2017: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/29204198/profile-and-outcome-of-pediatric-brain-tumors-experience-from-a-tertiary-care-pediatric-oncology-unit-in-south-india
#8
Supriya Gujjar Suresh, Arathi Srinivasan, Julius Xavier Scott, Santosh Mohan Rao, Balasubramaniam Chidambaram, Sanjay Chandrasekar
Context: Tumors of the central nervous system (CNS) constitute the second most common pediatric cancers. Unlike leukemia, management of CNS tumors requires a good multidisciplinary team. Higher rates of treatment abandonment are documented in view of complexity of the treatment with long duration, involving neurosurgery, radiation, chemotherapy, and high cost of treatment. Morbidity associated with CNS tumors may be significant in terms of physical deficits as well as neuropsychological and neuroendocrine sequelae...
July 2017: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/29189165/childhood-medulloblastoma-current-therapies-emerging-molecular-landscape-and-newer-therapeutic-insights
#9
Soumen Khatua, Anne Song, Divyaswathi Citla Sridhar, Stephen C Mack
Medulloblastoma is the most common malignant brain tumor in children, currently treated uniformly based on histopathology and clinico-radiological risk stratification. This approach has been undermined by unpredictable relapses and therapeutic failures. Research endeavors over the last decade have clearly identified four molecular variants (WNT, SHH, Group 3, and Group 4) and their demographic, genomic, and epigenetic profile. Improved understanding of the signaling pathways and key oncogenic drivers in these subgroups, has shed light on the reasons for suboptimal clinical outcome and mechanisms of therapeutic resistance...
November 28, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/29180935/atypical-bilateral-cerebellopontine-angle-medulloblastoma-differential-diagnosis-immunohistochemical-features-and-radiological-presentation
#10
Kelvin M Piña Batista, Sayoa Alvarez de Eulate-Beramendi, María Rico, Victor Rodrigo, Yordy E Batista Batista, Kenia Y Alvarez Reyes
Medulloblastoma (MB) is a highly aggressive soft tissue neoplasm, classified as a primitive neuroectodermal tumor. It is the most common posterior fossa tumor in children, but occurs rarely in adults. MB accounts for approximately 20% of all primary central nervous system (CNS) tumors of childhood, while its incidence is around 1% of adult brain tumors. Most often it occurs in the cerebellum. We report a case of multicentric MB involving the bilateral cerebellopontine angle (CPA) and right cerebellar hemisphere...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29178021/epigenetic-drivers-in-pediatric-medulloblastoma
#11
REVIEW
Martine F Roussel, Jennifer L Stripay
Epigenetics is the process by which gene expression is regulated by events other than alterations of the genome. This includes DNA methylation, histone modifications, chromatin remodeling, microRNAs, and long non-coding RNAs. Methylation of DNA, chromatin remodeling, and histone modifications regulate the chromatin and access of transcription factors to DNA and in turn gene transcription. Alteration of chromatin is now recognized to be deregulated in many cancers. Medulloblastoma is an embryonal tumor of the cerebellum and the most common malignant brain tumor in children, that occurs only rarely in adults...
November 25, 2017: Cerebellum
https://www.readbyqxmd.com/read/29168692/jak2-mediated-phosphorylation-of-atoh1-is-critical-for-medulloblastoma-growth
#12
Tiemo J Klisch, Anna Vainshtein, Akash J Patel, Huda Y Zoghbi
Treatment for medulloblastoma, the most common malignant brain tumor in children, remains limited to surgical resection, radiation, and traditional chemotherapy; with long-term survival as low as 50-60% for Sonic Hedgehog (Shh)-type medulloblastoma. We have shown that the transcription factor Atonal homologue 1 (Atoh1) is required for Shh-type medulloblastoma development in mice. To determine whether reducing either Atoh1 levels or activity in the tumor after its development, we studied Atoh1 dosage and modifications in Shh-type medulloblastoma...
November 23, 2017: ELife
https://www.readbyqxmd.com/read/29156007/desmoplastic-nodular-medulloblastoma-in-young-children-a-management-dilemma
#13
Mohamed S AbdelBaki, Daniel R Boué, Jonathan L Finlay, Mark W Kieran
Background: Children with desmoplastic nodular medulloblastoma (DNMB) have excellent survival, leading multiple groups globally to attempt reduction of treatment-related morbidity. In 2013, the Children's Oncology Group began a clinical trial (ACNS1221) eliminating both radiation therapy (RT) and intraventricular methotrexate for children under 3 years of age with localized DNMB, aiming to build upon the excellent outcomes of the German (HIT) trials. ACNS1221 has recently closed due to increased incidence of recurrences noted at the 2-year interim analysis, raising important questions regarding optimal therapy for DNMB...
November 15, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29143922/pre-treatment-lymphopenia-and-indication-of-tumor-induced-systemic-immunosuppression-in-medulloblastoma
#14
Seema Patel, Shiyang Wang, Matija Snuderl, Matthias A Karajannis
The presence of tumor-induced systemic immune suppression, including lymphopenia, has been recognized in adult patients with glioblastoma for several decades, and pre-treatment neutrophil-to-lymphocyte count ratio (NLCR) is associated with inferior clinical outcome in patients with glioblastoma. Whether tumor-induced systemic immune suppression is also present in children with malignant brain tumors is not known. We performed a retrospective analysis of pretreatment neutrophil and lymphocyte counts in pediatric patients with medulloblastoma (MB) compared to a control group of children with posterior fossa pilocytic astrocytoma (PA)...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29070607/contribution-of-de-novo-and-mosaic-tp53-mutations-to-li-fraumeni-syndrome
#15
Mariette Renaux-Petel, Françoise Charbonnier, Jean-Christophe Théry, Pierre Fermey, Gwendoline Lienard, Jacqueline Bou, Sophie Coutant, Myriam Vezain, Edwige Kasper, Steeve Fourneaux, Sandrine Manase, Maud Blanluet, Bruno Leheup, Ludovic Mansuy, Jacqueline Champigneulle, Céline Chappé, Michel Longy, Nicolas Sévenet, Brigitte Bressac-de Paillerets, Léa Guerrini-Rousseau, Laurence Brugières, Olivier Caron, Jean-Christophe Sabourin, Isabelle Tournier, Stéphanie Baert-Desurmont, Thierry Frébourg, Gaëlle Bougeard
BACKGROUND: Development of tumours such as adrenocortical carcinomas (ACC), choroid plexus tumours (CPT) or female breast cancers before age 31 or multiple primary cancers belonging to the Li-Fraumeni (LFS) spectrum is, independently of the familial history, highly suggestive of a germline TP53 mutation. The aim of this study was to determine the contribution of de novo and mosaic mutations to LFS. METHODS AND RESULTS: Among 328 unrelated patients harbouring a germline TP53 mutation identified by Sanger sequencing and/or QMPSF, we could show that the mutations had occurred de novo in 40 cases, without detectable parental age effect...
October 25, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29050204/irreversible-growth-plate-fusions-in-children-with-medulloblastoma-treated-with-a-targeted-hedgehog-pathway-inhibitor
#16
Giles W Robinson, Sue C Kaste, Wassim Chemaitilly, Daniel C Bowers, Stephen Laughton, Amy Smith, Nicholas G Gottardo, Sonia Partap, Anne Bendel, Karen D Wright, Brent A Orr, William C Warner, Arzu Onar-Thomas, Amar Gajjar
The permanent defects in bone growth observed in preclinical studies of hedgehog (Hh) pathway inhibitors were not substantiated in early phase clinical studies of vismodegib in children. Consequently, vismodegib advanced into pediatric trials for malignancies suspected of being driven by aberrant activation of the Hh pathway. In one multicenter phase II trial, vismodegib was added to the therapy regimen for newly diagnosed Hh pathway activated medulloblastoma. Herein, we report on 3 children (2 on trial and one off trial) treated with vismodegib who developed widespread growth plate fusions that persist long after cessation of therapy...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045264/patterns-of-failure-in-patients-with-adult-medulloblastoma-presenting-without-extraneural-metastasis
#17
Meriem Mokhtech, Christopher G Morris, Daniel J Indelicato, Michael S Rutenberg, Robert J Amdur
OBJECTIVES: The objective of this study is to evaluate long-term outcomes, specifically patterns of tumor recurrence, in patients with adult medulloblastoma treated with radiotherapy. METHODS: We recorded outcomes of 28 (median age, 25 y) patients 18 years old or above with M0 to M3 medulloblastoma treated between 1971 and 2012. Among them, 61% had standard-risk disease. All received craniospinal irradiation with a posterior fossa boost. Median dose to the craniospinal axis was 36 Gy...
October 17, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29028423/2016-updates-to-the-who-brain-tumor-classification-system-what-the-radiologist-needs-to-know
#18
Derek R Johnson, Julie B Guerin, Caterina Giannini, Jonathan M Morris, Lawrence J Eckel, Timothy J Kaufmann
Radiologists play a key role in brain tumor diagnosis and management and must stay abreast of developments in the field to advance patient care and communicate with other health care providers. In 2016, the World Health Organization (WHO) released an update to its brain tumor classification system that included numerous significant changes. Several previously recognized brain tumor diagnoses, such as oligoastrocytoma, primitive neuroectodermal tumor, and gliomatosis cerebri, were redefined or eliminated altogether...
November 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29016818/posterior-fossa-syndrome-and-long-term-neuropsychological-outcomes-among-children-treated-for-medulloblastoma-on-a-multi-institutional-prospective-study
#19
Jane E Schreiber, Shawna L Palmer, Heather M Conklin, Donald J Mabbott, Michelle A Swain, Melanie J Bonner, Mary L Chapieski, Lu Huang, Hui Zhang, Amar Gajjar
Background: Patients treated for medulloblastoma who experience posterior fossa syndrome (PFS) demonstrate increased risk for neurocognitive impairment at one year post diagnosis. The aim of the study was to examine longitudinal trajectories of neuropsychological outcomes in patients who experienced PFS compared with patients who did not. Methods: Participants were 36 patients (22 males) who experienced PFS and 36 comparison patients (21 males) who were matched on age at diagnosis and treatment exposure but did not experience PFS...
July 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28980418/medulloblastoma-in-children-and-adolescents-a-systematic-review-of-contemporary-phase-i-and-ii-clinical-trials-and-biology-update
#20
REVIEW
Francisco Bautista, Victoria Fioravantti, Teresa de Rojas, Fernando Carceller, Luis Madero, Alvaro Lassaletta, Lucas Moreno
Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early-phase trials evaluating new agents in patients with relapsed medulloblastoma...
November 2017: Cancer Medicine
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