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https://www.readbyqxmd.com/read/28640707/response-assessment-in-neuro-oncology-clinical-trials
#1
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
#2
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/28640695/gadolinium-brain-deposition-after-macrocyclic-gadolinium-administration-a-pediatric-case-control-study
#3
Daniel Tibussek, Christin Rademacher, Julian Caspers, Bernd Turowski, Jörg Schaper, Gerald Antoch, Dirk Klee
Purpose To determine whether signal intensity (SI) in T1 sequences as a potential indicator of gadolinium deposition increases after repeated administration of the macrocyclic gadolinium-based contrast agents (GBCAs) gadoteridol and gadoterate meglumine in a pediatric cohort. Materials and Methods This retrospective case-control study of children with brain tumors who underwent nine or more contrast material-enhanced brain magnetic resonance (MR) imaging studies from 2008 to 2015 was approved by the local ethics board...
June 21, 2017: Radiology
https://www.readbyqxmd.com/read/28626255/underlying-cause-of-death-recorded-during-2013-to-2015-at-a-tertiary-general-hospital-in-vientiane-capital-lao-pdr
#4
Bounfeng Phoummalaysith, Viengsakhone Louangpradith, Tavanh Manivon, Bounxou Keohavong, Eiko Yamamoto, Nobuyuki Hamajima
In Lao People's Democratic Republic (Lao PDR), the cause of death is not registered in death reports. As a result, the government cannot produce official reports that show mortality according to cause of death. This study aimed to report the underlying cause of death in a tertiary general hospital (Mittaphab Hospital) in Vientiane capital. Mittaphab hospital is a governmental teaching hospital with 300 beds for inpatient services specialized in orthopedics, neurology, and hemodialysis. Since a children hospital exists beside Mittaphab Hospital, severe pediatric cases are referred to the child hospital...
February 2017: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/28625338/acute-diplopia-in-the-pediatric-emergency-department-a-cohort-multicenter-italian-study
#5
Umberto Raucci, Pasquale Parisi, Nicola Vanacore, Francesco La Penna, Valentina Ferro, Lucia Calistri, Claudia Bondone, Fabio Midulla, Agnese Suppiej, Raffaele Falsaperla, Duccio Maria Cordelli, Antonella Palmieri, Alberto Verrotti, Sabrina Becciani, Sonia Aguzzi, Mario Mastrangelo, Federica Pelizza, Filippo Greco, Giulia Carbonari, Ramona Tallone, Gabriella Bottone, Italo Trenta, Stefano Masi, Maria Pia Villa, Antonino Reale
BACKGROUND: Acute diplopia (AD) is an uncommon and distressing symptom of numerous ocular and neurological conditions, with potentially serious sequelaes. No data are present in pediatrics on the presentation and management of AD. AIM: This study investigated characteristics, etiology and health care utilization of the pediatric population with AD accessed to pediatric Emergency Departments (ED), trying to identify "red flags" associated with potentially life-threatening (LT) conditions...
June 3, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28621573/update-on-the-diagnostic-value-and-safety-of-stereotactic-biopsy-for-pediatric-brainstem-tumors-a-systematic-review-and-meta-analysis-of-735-cases
#6
Christina Hamisch, Philipp Kickingereder, Matthias Fischer, Thorsten Simon, Maximilian I Ruge
OBJECTIVE Recent studies have shed light on the molecular makeup of diffuse intrinsic pontine gliomas and led to the identification of potential treatment targets for these lesions, which account for the majority of pediatric brainstem tumors (pedBSTs). Therefore, stereotactic biopsy-driven molecular characterization of pedBSTs may become an important prerequisite for the management of these fatal brain tumors. The authors conducted a systemic review and meta-analysis to precisely determine the safety and diagnostic success of stereotactic biopsy of pedBSTs...
June 16, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28620009/recommendations-for-cancer-surveillance-in-individuals-with-rasopathies-and-other-rare-genetic-conditions-with-increased-cancer-risk
#7
REVIEW
Anita Villani, Mary-Louise C Greer, Jennifer M Kalish, Akira Nakagawara, Katherine L Nathanson, Kristian W Pajtler, Stefan M Pfister, Michael F Walsh, Jonathan D Wasserman, Kristin Zelley, Christian P Kratz
In October 2016, the American Association for Cancer Research held a meeting of international childhood cancer predisposition syndrome experts to evaluate the current knowledge of these syndromes and to propose consensus surveillance recommendations. Herein, we summarize clinical and genetic aspects of RASopathies and Sotos, Weaver, Rubinstein-Taybi, Schinzel-Giedion, and NKX2-1 syndromes as well as specific metabolic disorders known to be associated with increased childhood cancer risk. In addition, the expert panel reviewed whether sufficient data exist to make a recommendation that all patients with these disorders be offered cancer surveillance...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28620008/pten-dicer1-fh-and-their-associated-tumor-susceptibility-syndromes-clinical-features-genetics-and-surveillance-recommendations-in-childhood
#8
REVIEW
Kris Ann P Schultz, Surya P Rednam, Junne Kamihara, Leslie Doros, Maria Isabel Achatz, Jonathan D Wasserman, Lisa R Diller, Laurence Brugières, Harriet Druker, Katherine A Schneider, Rose B McGee, William D Foulkes
PTEN hamartoma tumor syndrome (PHTS), DICER1 syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome are pleiotropic tumor predisposition syndromes that include benign and malignant neoplasms affecting adults and children. PHTS includes several disorders with shared and distinct clinical features. These are associated with elevated lifetime risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as melanoma. Thyroid cancer represents the predominant cancer risk under age 20 years...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28620006/cancer-surveillance-in-gorlin-syndrome-and-rhabdoid-tumor-predisposition-syndrome
#9
REVIEW
William D Foulkes, Junne Kamihara, D Gareth R Evans, Laurence Brugières, Franck Bourdeaut, Jan J Molenaar, Michael F Walsh, Garrett M Brodeur, Lisa Diller
Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (PTCH1) and Suppressor of fused (SUFU)SUFU mutation carriers appear to have an especially high risk of early-onset medulloblastoma...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28620005/cancer-and-central-nervous-system-tumor-surveillance-in-pediatric-neurofibromatosis-2-and-related-disorders
#10
REVIEW
D Gareth R Evans, Hector Salvador, Vivian Y Chang, Ayelet Erez, Stephan D Voss, Harriet Druker, Hamish S Scott, Uri Tabori
The neurofibromatoses consist of at least three autosomal-dominant inherited disorders: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis. For over 80 years, these conditions were inextricably tied together under generalized neurofibromatosis. In 1987, the localization of NF1 to chromosome 17q and NF2 (bilateral vestibular schwannoma) to 22q led to a consensus conference at Bethesda, Maryland. The two main neurofibromatoses, NF1 and NF2, were formally separated. More recently, the SMARCB1 and LZTR1 genes on 22q have been confirmed as causing a subset of schwannomatosis...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28616573/yap-and-the-hippo-pathway-in-pediatric-cancer
#11
REVIEW
Atif A Ahmed, Abdalla D Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada
The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28606795/endothelium-independent-primitive-myxoid-vascularization-creates-invertebrate-like-channels-to-maintain-blood-supply-in-optic-gliomas
#12
Matija Snuderl, Guoan Zhang, Pamela Wu, Tara S Jennings, Seema Shroff, Valerio Ortenzi, Rajan Jain, Benjamin Cohen, Jason J Reidy, Mitchell S Dushay, Jeffrey H Wisoff, David H Harter, Matthias A Karajannis, David Fenyo, Thomas A Neubert, David Zagzag
Optic gliomas are brain tumors characterized by slow growth, progressive loss of vision, and limited therapeutic options. Optic gliomas contain various amounts of myxoid matrix, which can represent most of the tumor mass. We sought to investigate biological function and protein structure of the myxoid matrix in optic gliomas to identify novel therapeutic targets. We reviewed histological features and clinical imaging properties, analyzed vasculature by immunohistochemistry and electron microscopy, and performed liquid chromatography-mass spectrometry on optic gliomas, which varied in the amount of myxoid matrix...
June 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28605510/phase-i-study-of-oral-sonidegib-lde225-in-pediatric-brain-and-solid-tumors-and-a-phase-ii-study-in-children-and-adults-with-relapsed-medulloblastoma
#13
Mark W Kieran, Julia Chisholm, Michela Casanova, Alba A Brandes, Isabelle Aerts, Eric Bouffet, Simon Bailey, Sarah Leary, Tobey J MacDonald, Francoise Mechinaud, Kenneth J Cohen, Riccardo Riccardi, Warren Mason, Darren Hargrave, Stacey Kalambakas, Priya Deshpande, Feng Tai, Eunju Hurh, Birgit Geoerger
Background.: Sonidegib (LDE225) is a potent, selective Hedgehog (Hh) inhibitor of SMOOTHENED. This study explored the safety and pharmacokinetics (PK) of sonidegib in children with relapsed/recurrent tumors followed by a phase II trial in pediatric and adult patients with relapsed medulloblastoma (MB) to assess tumor response. Methods.: Pediatric patients aged ≥1-<18 years were included according to a Bayesian design starting at 372mg/m2 of continuous once daily oral sonidegib...
June 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28603776/actionable-molecular-biomarkers-in-primary-brain-tumors
#14
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/28600472/precision-medicine-in-pediatric-oncology-translating-genomic-discoveries-into-optimized-therapies
#15
Thai Hoa Tran, Avanthi Tayi Shah, Mignon L Loh
Survival of children with cancers has dramatically improved over the past several decades.  This success has been achieved through improvement of combined modalities in treatment approaches, intensification of cytotoxic chemotherapy for those with high-risk disease and refinement of risk stratification incorporating novel biologic markers in addition to traditional clinical and histologic features. Advances in cancer genomics have shed important mechanistic insights on disease biology and have identified "driver" genomic alterations, aberrant activation of signaling pathways, and epigenetic modifiers that can be targeted by novel agents...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28598565/atypical-teratoid-rhabdoid-tumors-in-children-treated-with-multimodal-therapies-the-necessity-of-upfront-radiotherapy-after-surgery
#16
Jeongshim Lee, Dong-Seok Kim, Jung Woo Han, Chang-Ok Suh
BACKGROUND: Atypical teratoid/rhabdoid tumor (ATRT) is a rare malignant pediatric brain tumor with a dismal prognosis. We evaluated the efficacy of multimodal therapy in children with ATRT. PROCEDURE: Nine children diagnosed with cranial ATRT, who received multimodal therapy between 2005 and 2014, including surgical resection followed by radiotherapy (RT), systemic chemotherapy (CT), and high-dose chemotherapy/stem cell transplantation (HDCT/SCT), were analyzed retrospectively...
June 9, 2017: Pediatric Blood & Cancer
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
#17
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/28591729/bmi-1-is-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#18
Shiva Senthil Kumar, Satarupa Sengupta, Kyungwoo Lee, Nanki Hura, Christine Fuller, Mariko DeWire, Charles B Stevenson, Maryam Fouladi, Rachid Drissi
Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28582547/the-torc1-2-inhibitor-tak228-sensitizes-atypical-teratoid-rhabdoid-tumors-to-cisplatin-induced-cytotoxicity
#19
Jeffrey A Rubens, Sabrina Z Wang, Antoinette Price, Melanie F Weingart, Sariah J Allen, Brent A Orr, Charles G Eberhart, Eric H Raabe
Background: Atypical teratoid/rhabdoid tumors (AT/RTs) are deadly pediatric brain tumors driven by LIN28. Mammalian target of rapamycin (mTOR) is activated in many deadly, drug-resistant cancers and governs important cellular functions such as metabolism and survival. LIN28 regulates mTOR in normal cells. We therefore hypothesized that mTOR is activated downstream of LIN28 in AT/RT, and the brain-penetrating mTOR complex 1 and 2 (mTORC1/2) kinase inhibitor TAK228 would reduce AT/RT tumorigenicity...
June 3, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28574315/the-effect-of-nachri-children-s-hospital-designation-on-outcome-in-pediatric-malignant-brain-tumors
#20
Daniel A Donoho, Timothy Wen, Jonathan Liu, Hosniya Zarabi, Eisha Christian, Steven Cen, Gabriel Zada, J Gordon McComb, Mark D Krieger, William J Mack, Frank J Attenello
OBJECTIVE Although current pediatric neurosurgery guidelines encourage the treatment of pediatric malignant brain tumors at specialized centers such as pediatric hospitals, there are limited data in support of this recommendation. Previous studies suggest that children treated by higher-volume surgeons and higher-volume hospitals may have better outcomes, but the effect of treatment at dedicated children's hospitals has not been investigated. METHODS The authors analyzed the Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) from 2000-2009 and included all patients undergoing a craniotomy for malignant pediatric brain tumors based on ICD-9-CM codes...
June 2, 2017: Journal of Neurosurgery. Pediatrics
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