tbuckley/cabot-search huggingface dataset:
RARE-36. DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS: A REVIEW OF CLINICAL AND MOLECULAR CHARACTERISTICS, AND OUTCOME IN A PEDIATRIC POPULATION AT A SINGLE CENTER
Authors: Valerie Cruz Flores, Thomas Geller, Ignacio Gonzalez Gomez, Luis Rodriguez, Javier Quintana, Stacie Stapleton
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Neuronal and mixed neuro-glial tumors of the central nervous system (CNS) are relatively rare. Dysembryoplastic neuroepithelial tumor (DNET) is a benign, rare, slow-growing tumor, but in many cases is associated with intractable epilepsy. OBJECTIVE To report the experience with DNET at a single free-standing children’s institution. METHODS A retrospective chart review of 24 patients with confirmed DNET between 2001 and 2019 was performed. Data was collected on clinical characteristics, tumor location, surgical management, histopathological and molecular findings, and outcomes. RESULTS Mean age at diagnosis was 10 years (range 2 to 19 years), with female predominance (54.2%). Most common presenting symptoms were seizures (79.2%) and headaches (12.5%). Location of the tumor was temporal (29.2%), frontal (25.0%), parietal (16.7%), cerebellar (12.5%) and occipital (4.2%). A gross total resection was achieved in half the cases. Recurrence occurred in 4 patients (16.7%), all of whom had subtotal resections. The average follow up since diagnosis was 4.6 years (range 0.3 to 14 years). Nineteen patients presented with seizures, of which 63.2% were seizure free after surgery. The samples with molecular genetic testing (microarrays or FISH), were all normal except one patient positive for BRAF V600E mutation. CONCLUSIONS This is the first and largest review of pediatric DNETs in the last 10 years. Despite majority of patients having a favorable outcome after surgery, a subset of patients remains symptomatic. As molecular mechanisms in DNET remain unknown, future aim is to describe the molecular characteristics of our DNET population, and correlate with outcomes.
QOL-37. USE OF COMPUTERIZED NEUROPSYCHOLOGICAL MEASURES TO ASSESS COGNITIVE MORBIDITY IN CHILDREN UNDERGOING ACTIVE RADIATION THERAPY
Authors: Lorri Kais, Kellie Roesser, Michelle Kleman, Greta Wilkening, Arthur Liu, Todd Hankinson, Nicholas Foreman, Christa Hutaff-Lee
Journal: Neuro-Oncology (2020)

Abstract Cognitive late effects of brain tumors and related treatments are well-established; however, limited information regarding changes in cognition during radiation therapy (RT) is available. Recent advances in computerized neuropsychological assessments for monitoring of acute and late treatment effects have been developed, though the feasibility of using these tools in a population undergoing active RT has limited empirical evidence. This study investigated performance of pediatric patients with brain tumors actively undergoing RT on the NIH Toolbox (N = 10; M age = 11.29 ± 3.35 years; 86% Caucasian; 86% female). Given significant individual variability, one-sample proportion tests were calculated to assess whether the proportion of patients with performances &amp;gt;1 standard deviation below the mean significantly differed from normative expectations. Of the 12 participants that were enrolled in the study, 10 completed the NIH Toolbox during active RT. Compared to normative expectations, a greater proportion of participants undergoing active RT exhibited deficits on measures of processing speed, working memory, and response inhibition (p=&amp;lt;.01). Differences between participants and normative expectations were not seen on measures of visual memory and vocabulary (p=&amp;gt;.05). Seventy-seven percent of recruited participants completed computerized assessment during active RT, suggesting reasonable feasibility within the small cohort recruited. Consistent with the literature regarding late effects of RT, performance on computerized measures of cognitive functioning mediated by processing speed and aspects of executive functioning were lower for patients undergoing active RT. Further investigation will focus on clarifying the trajectory of deficits across treatment course and comparing computerized measures to traditional neuropsychological measures.
EPEN-37. TREATMENT OUTCOME OF RECURRENT EPENDYMOMA IN CHILDREN IN NORTHERN EGYPT
Authors: Shady Fadel, Zeyad Abdelaziz, Amr Abdel Kerim, Mahmoud Abbassy, Samer Samy, Basma Elsaba
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION 1/3 of Ependymoma patients will develop recurrence with only 25% are long term survivors. Treatment is usually between surgery, radiotherapy or combinations. PATIENTS AND METHODS Retrospective review of children with recurrent Ependymoma in northwest of Egypt between 2005 and 2019 in Alexandria School of medicine records. RESULTS 27 patients were identified 19 of them after 2010. The median age is 9.7 years (1.5–19), with 16 males and 11 females. Pathology were 11 grade II Ependymoma and 16 anaplastic Ependymoma. 16 had gross residual disease after 1st surgery and 22 received radiotherapy initially at median dose of 53.5 Gy, 4 patients received suboptimal radiotherapy. The initial site was14 supratentorial tumors and 13 infratentorial. Median time to recurrence is 27.6 months(3–84), and recurrences were 17 local and 9 CSF disseminated, and one patient had recurrence at the scar with lung metastasis. At a median follow up of 56.6 months 14(51.8%) are still alive. Treatment was surgery only in 6(4 alive) radiotherapy alone in 2(1alive), combined in 15(9 alive) and 4 patients received neither. The best outcome were in patients with late local relapse treated with complete resection and CSI after 2010. Radiotherapy dose was between 54 to 57.3 Gy and one patient developed reirradiation injury at brain stem. 5 of the 14 living patients is having toxicity in form of hearing aids (4) and low TSH(1). CONCLUSION Aggressive treatment of recurrent Ependymoma with surgery and radiotherapy is feasible and about half of the patients are salvageable.
RONC-06. VOLUMETRIC-MODULATED ARC WHOLE-BRAIN RADIOTHERAPY FOR THE PREVENTION OF PERMANENT ALOPECIA IN PEDIATRIC PATIENTS
Authors: Megumi Uto, Katsutsugu Umeda, Yoshiki Arakawa, Keiichi Takehana, Tatsuya Kamitori, Atsushi Iwai, Itaru Kato, Satoshi Saida, Hidefumi Hiramatsu, Yohei Mineharu, Masahiro Tanji, Junko Takita, Takashi Mizowaki
Journal: Neuro-Oncology (2020)

Abstract Permanent alopecia is a grave late complication of multi-drug chemotherapy (CTx) plus cranial irradiation, reducing both patient self-esteem and quality of life in pediatric patients. We started to use craniospinal irradiation (CSI) using the volumetric-modulated arc whole-brain radiotherapy (VMAT-WBRT) in order to prevent permanent alopecia. We treated 5 pediatric patients with CSI using VMAT-WBRT, and report the initial clinical outcome. Five consecutive patients (4–11 years old) who received CSI using VMAT-WBRT from June 2015 to November 2018 were included into this study. One patient with embryonic carcinoma received radiotherapy (RT) with concurrent CTx; four patients with medulloblastoma (two patients with standard risk, and two patients with high risk) received RT followed by CTx. The prescribed doses of CSI were 23.4–35.2 Gy in 13–22 fractions, respectively. Optimization for VMAT-WBRT was performed to reduce doses to the hair follicles with keeping the dose coverage to the planning target volume. Although all patients experienced temporary alopecia, their hair fully recovered over the whole scalp within 8 months after finishing RT. One patient had disease progression after 6 months after completing CTx; this patient who was diagnosed as Group 3 subtype had diffuse meningeal dissemination confirmed with contrast enhanced spinal MRI before RT. The other four patients had no evidence of recurrence. Although CSI with VMAT-WBRT might be one of considerable options, more cases are needed to verify the efficacy to prevent permanent alopecia for pediatric patients who receive multi-drug CTx and cranial irradiation.
A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemic Pathogenesis
Authors: Andrew Volk, Kaiwei Liang, Jianyun Zhao, Xinyu Li, Marinka Bulic, Stacy Marshall, Jeffrey W. Taub, Yubin Ge, Sebastien Malinge, Elizabeth Bartom, Ali Shilatifard, John D. Crispino
Journal: Blood (2017)
LGG-26. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) IN CHILDREN: DIFFERENT CLINICAL PRESENTATIONS AND OUTCOMES
Authors: Andge Valiakhmetova, Ludmila Papusha, Ludmila Yasko, Alexander Druy, Alexander Karachunsky, Galina Novichkova, Eugene I Hwang, Roger J Packer
Journal: Neuro-Oncology (2020)

Abstract Diffuse leptomeningeal glioneuronal tumor (DLGNT) is an extremely rare disease, newly recognized in the 2016 WHO classification of tumors of the CNS. Most DLGNTs are low-grade neuroepithelial tumors with variable elements of neuronal/neurocytic and glial differentiation, have diffuse leptomeningeal enhancement on MRI, and typically harbor KIAA1549-BRAF fusions. Other alterations, such as the BRAF V600E substitution, are less common. Here, we present three cases of DLGNT with different presentations and outcomes. The first patient is a 2yr-old male with KIAA1549-BRAF fusion, and was treated with Carbo/VCR chemotherapy after a biopsy, with resultant ongoing stable disease for 3.5 years. The second patient, an 8yr-old male had the BRAF V600E point mutation and was treated with conventional chemotherapy (VCR/carboplatin). On progression, he received the BRAF inhibitor vemurafenib, achieving a complete response which last 14 month. The third patient, a 27 month old male, harbored a KIAA1549-BRAF fusion and was treated at diagnosis with the MEK inhibitor trametinib. The tumor has been radiographically stable in the context of clinical improvement for 21 months since the treatment initiation, ongoing 24 month. In summary, we present further evidence of MAPK pathway alterations in children with DLGNT. We describe a range of molecular presentations and clinical outcomes, including one patient treated with conventional chemotherapy with further stabilization of disease during 3.5 years and two patients who were successfully treated with targeted therapy.
Apolipoprotein A-I and high-density lipoprotein: Is this the beginning of the era of noninvasive angioplasty?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Christie M. Ballantyne, Vijay Nambi
Journal: Journal of the American College of Cardiology (2004)
TBIO-03. THE GIFT FROM A CHILD PROGRAM IS EMPOWERING POST-MORTEM TISSUE DONATION ACROSS THE UNITED STATES
Authors: Angela Waanders, Melissa Williams, Nitin Wadwhani, Xiao-Nan Li, Stewart Goldman, Kella Tran-Du, Jane Minturn, Jennifer Mason, Mariarita Santi, Angela Viaene, Mateusz Koptyra, Michelle Monje-Deisseroth, Javad Nazarian, Madhuri Kambhampati, Augustine Eze, Mark Souweidane, Nicole Lyons, Ginny McLean, Patti Gustafson, Allen Gustafson
Journal: Neuro-Oncology (2020)

Abstract The Gift from a Child (GFAC) program was inspired by the dream of one child to donate his brain for research, recognizing the need to study tumor tissue collected at diagnosis, recurrence, and at the time of death. Founded by the Swifty Foundation in 2016, GFAC currently is comprised of five “Centers of Excellence” at institutions with expertise in pediatric neuro-oncology. Partnering with the Children’s Brain Tumor Network, the program’s mandate is twofold: make it possible for families to donate no matter where they live in the United States and make tissue available to scientists globally to empower discovery. In order to overcome barriers that have stifled postmortem collection in the past, GFAC has invested in Tissue Navigators - individuals at each center who coordinate all aspects of donation and communicate with families, medical providers, and laboratory scientists. In 2019 alone, GFAC coordinated 55 autopsy collections from multiple diagnosis. A key metric of the program is also capturing the global sharing and usage of each tissue sample, ensuring that tissue isn’t simply “banked” but is actively being actively used to help unravel tumor biology. To date, tissue has been used for genomic and molecular data generation, preclinical model development including cell lines and PDX models, and for novel drug screening. Together with Children’s Brain Tumor Network, the Gift from a Child program is helping to ensure the most precious gift that a family can make is used to accelerate the path to cures.
Hepatitis C reference viruses highlight potent antibody responses and diverse viral functional interactions with neutralising antibodies
Authors: Dorothea Bankwitz, Akash Bahai, Maurice Labuhn, Mandy Doepke, Corinne Ginkel, Tanvi Khera, Daniel Todt, Luisa J Ströh, Leona Dold, Florian Klein, Frank Klawonn, Thomas Krey, Patrick Behrendt, Markus Cornberg, Alice C McHardy, Thomas Pietschmann
Journal: Gut (2020)

Objective Neutralising antibodies are key effectors of infection-induced and vaccine-induced immunity. Quantification of antibodies’ breadth and potency is critical for understanding the mechanisms of protection and for prioritisation of vaccines. Here, we used a unique collection of human specimens and HCV strains to develop HCV reference viruses for quantification of neutralising antibodies, and to investigate viral functional diversity. Design We profiled neutralisation potency of polyclonal immunoglobulins from 104 patients infected with HCV genotype (GT) 1–6 across 13 HCV strains representing five viral GTs. Using metric multidimensional scaling, we plotted HCV neutralisation onto neutralisation maps. We employed K-means clustering to guide virus clustering and selecting representative strains. Results Viruses differed greatly in neutralisation sensitivity, with J6 (GT2a) being most resistant and SA13 (GT5a) being most sensitive. They mapped to six distinct neutralisation clusters, in part composed of viruses from different GTs. There was no correlation between viral neutralisation and genetic distance, indicating functional neutralisation clustering differs from sequence-based clustering. Calibrating reference viruses representing these clusters against purified antibodies from 496 patients infected by GT1 to GT6 viruses readily identified individuals with extraordinary potent and broadly neutralising antibodies. It revealed comparable antibody cross-neutralisation and diversity between specimens from diverse viral GTs, confirming well-balanced reporting of HCV cross-neutralisation across highly diverse human samples. Conclusion Representative isolates from six neutralisation clusters broadly reconstruct the functional HCV neutralisation space. They enable high resolution profiling of HCV neutralisation and they may reflect viral functional and antigenic properties important to consider in HCV vaccine design.
RONC-03. NEUROCOGNITIVE CHANGES AFTER RADIATION FOR PEDIATRIC BRAIN TUMOURS: WHICH BRAIN SUBSTRUCTURES ARE MOST IMPORTANT?
Authors: Derek S Tsang, Laurence Kim, Donald Mabbott, Mohammad Khandwala, Zhihui Amy Liu, Normand Laperriere, Lauran Janzen, Hitesh Dama, Vijay Ramaswamy, Dana Keilty, Eric Bouffet, David C Hodgson
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The contribution of different intracranial structures on neurocognitive decline after radiation therapy (RT) in children is unclear. METHODS This was a retrospective study of children with brain tumours treated from 2005 to 2017. Patients with longitudinal neurocognitive assessments and photon dosimetric data (if RT given) were included. Full scale intelligence quotient (FSIQ) was the primary endpoint; sub-indices of neurocognition were modelled separately (perceptual reasoning [PRI], processing speed [PSI], verbal comprehension [VCI] and working memory [WMI]). Multivariable linear mixed effects models were used to model endpoints, with age at diagnosis &amp; dose to different brain regions as fixed effects and patient-specific random intercepts. RESULTS Sixty-nine patients were included; ten patients did not receive any RT (i.e. low-grade glioma). Median neurocognitive follow-up was 3.2 years. Right hippocampus mean dose was a strong predictor of declines in FSIQ (p &amp;lt; .001), VCI (p = 0.002) and PRI (p = 0.049). Dose to 50% of the supratentorial brain (D50) was the strongest predictor for WMI (p &amp;lt; .001) and PSI (p &amp;lt; .001). Each gray increase in mean right hippocampus dose resulted in a decrease of 0.038 FSIQ points/year. After adjusting for dose to brain substructures, younger age &amp; presence of a ventriculoperitoneal shunt were also associated with decreased FSIQ. CONCLUSIONS Mean dose to the right hippocampus was associated with declines in FSIQ, VCI and PRI, while supratentorial brain D50 was associated with WMI and PSI. Efforts should be made to reduce unnecessary dose to these brain structures.
Clinical pathways for patients with giant cell arteritis during the COVID-19 pandemic: an international perspective
Authors: Sarah L Mackie, Elisabeth Brouwer, Richard Conway, Kornelis S M van der Geest, Puja Mehta, Susan P Mollan, Lorna Neill, Michael Putman, Philip C Robinson, Sebastian E Sattui
Journal: The Lancet Rheumatology (2020)

Giant cell arteritis, a common primary systemic vasculitis affecting older people, presents acutely as a medical emergency and requires rapid specialist assessment and treatment to prevent irreversible vision loss. Disruption of the health-care system caused by the COVID-19 pandemic exposed weak points in clinical pathways for diagnosis and treatment of giant cell arteritis, but has also permitted innovative solutions. The essential roles played by all professionals, including general practitioners and surgeons, in treating these patients have become evident. Patients must also be involved in the reshaping of clinical services. As an international group of authors involved in the care of patients with giant cell arteritis, we reflect in this Viewpoint on rapid service adaptations during the first peak of COVID-19, evaluate challenges, and consider implications for the future.
EXTH-48. BMP4 BINDING PEPTIDE AMPHIPHILE NANOFIBERS FOR THE TREATMENT OF PEDIATRIC HIGH-GRADE GLIOMAS
Authors: Cara Smith, Sonali Nayak, Ashorne Mahenthiran, Yufen Wang, Timmy Fyrner, Mark McClendon, Barbara Mania-Farnell, John Kessler, Tadanori Tomita, Charles James, Samuel Stupp, Guifa XI
Journal: Neuro-Oncology (2020)

Abstract Pediatric high-grade glioma (pHGG) is among the most formidable cancers occurring in childhood. Bone morphogenetic protein 4 (BMP4) reduces the number of glioma stem-like cells and induces apoptosis. Treating tumors with exogenous BMP4 could prove effective in treating gliomas. However, a short half-life limits its clinical application. Glycosylated peptide amphiphile (GlycoPA), with a design inspired by heparin’s natural ability to bind growth factors including BMP4 through non-covalent interactions, was previously characterized and found to form high-aspect ratio supramolecular nanofibers that present growth-factor binding sulfated monosaccharides on their surface. These supramolecular nanofibers could carry excessive amounts of growth factor and markedly enhance their biological function. In this study, we verified that GlycoPA is able to bind BMP4 and dramatically increase its half-life with an ELISA assay. We also show that GlycoPA-BMP4, in comparison to free BMP4, significantly decreases pHGG cells’ proliferation in vitro. Initial in vivo intracranial distribution experimental results showed that GlycoPA has a superior normal brain distribution in comparison to a control PA (E2 PA) that has the same base structure as GlycoPA except with no glycosylated group. Preliminary results show that GlycoPA-BMP4 markedly decreases pediatric glioma tumor growth in comparison to free BMP4. Our combined in vitro and in vivo results demonstrate PA supramolecular nanofibers as an innovative and promising BMP4 delivery platform for clinical application in the treatment of brain tumors. Our future directions will investigate the therapeutic efficacy of GlycoPA-BMP4 in pediatric HGG through testing large numbers of animals and introducing first-line clinical chemotherapy drugs in combination and in various consequence.
PATH-01. MOLECULAR PROFILING OF PAEDIATRIC CENTRAL NERVOUS SYSTEM TUMOURS IN AUSTRALASIA – AN UPDATE ON THE AIM BRAIN AND MNP2.0 PROJECTS
Authors: Elizabeth Algar, White Christine, Kathryn Kinross, Molly Buntine, David Jones, Stefan Pfister, Robyn Strong, Nicholas Gottardo, Jordan Hansford
Journal: Neuro-Oncology (2020)

Abstract The Access to Innovative Molecular Profiling for Paediatric Brain Cancers (AIM BRAIN) project is a trial testing the feasibility of clinical implementation of diagnostic methylation and molecular profiling for central nervous system (CNS) tumours in Australia and New Zealand. AIM BRAIN builds on an existing study, MNP2.0, and allows cross-validation of results derived from identical samples in separate laboratories in Melbourne, Australia, and DKFZ, Heidelberg, Germany. Parallel methylation profiling (Illumina 850K EPIC array) from co-enrolled cases has revealed excellent concordance between laboratories with 50/51 cases (98%) yielding identical classification using the DKFZ Molecular Neuropathology 2.0 Classifier v11b4. 77/91 (85%) of AIM BRAIN cases classified concordantly by methylation array when compared to their diagnostic histopathology. Of these 77 cases, 16 had classifications below a threshold of 0.90, however still classified correctly. In 14 discordant cases either the histopathology was not well defined, not represented on the classifier, or a very low classification score was obtained. Molecular profiling through MNP2.0 identified 49/167 (29.3%) tumours with gene fusions including BRAF-KIAA1549 (n=29), RELA-C1lorf95 (n=5) and 15 rare or novel fusions. BRAF-KIAA1549 was almost exclusively associated with pilocytic astrocytoma (28/29) and RELA-C1lorf95 with ependymoma. Six pathogenic germline mutations were identified in TP53 (n=2), BRCA1, NF1, LZTR1 and ATM. The incidence of germline predisposition was low (4%) and sex biased towards females (5F:1M), (p&amp;lt;0.08). Our findings confirm methylation profiling as a robust platform for classifying CNS tumours with potential to reveal new CNS tumour entities when combined with molecular profiling.