tbuckley/cabot-search huggingface dataset:
DIPG-67. HYPOXIA-INDUCIBLE FACTORS REGULATE DIFFUSE INTRINSIC PONTINE GLIOMA GROWTH IN NORMOXIC CULTURE
Authors: Christopher Waker, Chanel Keoni, Brianna Schurko, Thomas Brown, Robert Lober
Journal: Neuro-Oncology (2018)

Diffuse intrinsic pontine glioma (DIPG) are incurable tumors and the leading cause of pediatric brain tumor deaths. They exhibit low blood perfusion and regions of necrosis, indicative of a low-oxygen environment that supports activation of hypoxia-inducible factors (HIF) that are associated with increased proliferation, invasion, and therapy resistance. However, previous reports suggest that HIF2-alpha slows growth in some glioma models. We therefore sought to test the hypothesis that HIFs regulate DIPG growth. We cultured the human DIPG tumors SU-DIPG-IV, VUMC-DIPG-X, and SU-DIPG-XIII at ambient oxygen tension and 5% carbon dioxide. We measured protein expression by Western blot and growth by trypan blue exclusion or tetrazolium reduction following exposure to the hypoxia-mimetic (HM) compounds, cobalt (II) chloride or deferoxamine, or selective HIF inhibitors. All three DIPG cultures retained stable expression of HIF1-alpha and HIF2-alpha protein at ambient oxygen tension, unchanged by HM treatment. Selective inhibition of HIF2-alpha by TC-S 7009 increased apparent growth, whereas selective inhibition of HIF1-alpha by CAY10585 did not. We conclude that hypoxia-independent HIF expression unchanged by either HM treatment or HIF inhibition suggests impaired HIF degradation, in which hypoxia-induced activation of HIF target genes more likely depends on transcriptional co-activators rather than blocked proteasomal degradation. In both ambient and hypoxic conditions, HIF2-alpha activity may oppose DIPG growth. Future experiments will investigate whether the effects of HIF2-alpha inhibition on tumor growth can be explained by enhanced HIF1-alpha activity through desequestration of common binding partners, or through direct action of HIF2-alpha on previously reported apoptotic pathways.
Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch &amp; Wait Database (IWWD): an international multicentre registry study
Authors: Maxime J M van der Valk, Denise E Hilling, Esther Bastiaannet, Elma Meershoek-Klein Kranenbarg, Geerard L Beets, Nuno L Figueiredo, Angelita Habr-Gama, Rodrigo O Perez, Andrew G Renehan, Cornelis J H van de Velde, Madeleine Ahlberg, Ane Appelt, Oktar Asoglu, Maria-Theresa Bär, Rita Barroca, Regina G H Beets-Tan, Eric H J Belgers, Robbert J I Bosker, Stéphanie O Breukink, Krysztof Bujko, Carlos Carvalho, Christopher Cunningham, Ben Creavin, André D'Hoore, Jean-Pierre Gérard, Simon Gollins, Christiaan Hoff, Fabian A Holman, Britt J P Hupkens, Soledad Iseas, Anders Jakobsen, Amir Keshvari, Sietze A Koopal, Miranda Kusters, Melanie Langheinrich, Jeroen W A Leijtens, Monique Maas, Lee Malcomson, Zamam Z Mamedli, Anna Martling, Klaus E Matzel, Jarno Melenhorst, María L Morici, Sthela M Murad-Regadas, Sarah T O'Dwyer, Koen C M J Peeters, Isadora Rosa, Gustavo Rossi, Harm J T Rutten, Fernando Sanchez Loria, Marit E van der Sande, Guilherme P São Julião, Mark Saunders, Arthur Sun Myint, Hedwig van der Sluis, Renaud Schiappa, Nigel Scott, Jan H M B Stoot, A Koen Talsma, Isabelle Terrasson, Handan Tokmak, Carlos A Vaccaro, Alexander L Vahrmeijer, Daria K Wasowicz, Henderik L Westreenen, Des C Winter, Albert M Wolthuis, David D E Zimmerman
Journal: The Lancet (2018)
Abstract 13384: Prognosis of Patients With Myocardial Infarction With Non-Obstructive Coronary Arteries as Compared With Obstructive Coronary Disease
Authors: Rachel P Dreyer, Rosanna Tavella, Jeptha P Curtis, Yongfei Wang, Sivabaskari Pauspathy, John Messenger, John S Rumsfeld, Thomas M Maddox, Harlan M Krumholz, John A Spertus, John F Beltrame
Journal: Circulation (2016)

Introduction: The prognosis of patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is poorly understood. We examined the prevalence of adverse events (mortality, re-infarction and readmission) in patients with MINOCA over 1 year versus patients with acute myocardial infarction (AMI) and obstructive coronary artery disease (MICAD). Methods: Between July 2009 and December 2010, both patients with STEMI and NSTEMI, aged &gt;65 years, from the National Cardiovascular Data Registry (NCDR ® ) CathPCI Registry were classified as having either obstructive or non-obstructive CAD (n=570,219) on the basis of their angiographic reports revealing no epicardial vessel with stenosis ≥50% (MINOCA) or at least one stenosis ≥50% (MICAD). Re-hospitalizations, repeat AMI, and mortality were assessed via linkage to Medicare data. We had the following exclusion criteria: (a) patients presenting with cardiac arrest within 24 hours (n=3,510), (b) patients with AMI as a complication during hospitalization (n=1,751), and (c) patients not in the Medicare data, or that could not be matched with Medicare through the patient beneficiary ID and discharge date (n=469,722). Analyses comparing MINOCA and MICAD were performed using the chi-squared test for categorical variables and the T-test for continuous variables. Results: Among 95,236 AMI patients, 4,831 patients (5.1%) had MINOCA. Compared to those with MICAD, patients with MINOCA were younger (75±7 vs 76±7, P&lt;0.001), more likely to be female (78% vs 42%, P&lt;0.001), and were predominately white (89% vs 91%, P&lt;0.001). Outcomes over 1 year are described in the Table. Conclusion: In an elderly AMI population, the occurrence of MINOCA accounts for 5% of AMI presentations. Although MINOCA patients had fewer adverse events over 1 year compared with MICAD patients, they remain at modest to high risk for readmission and mortality. Further studies are needed to define whether or not these events are preventable.
NURS-15. DEVELOPMENT OF A CARE PATHWAY FOR THE CHILD WITH A BRAIN TUMOR: FROM MULTIDISCIPLINARY TO INTERDISCIPLINARY COLLABORATION
Authors: Elsie Willems, Annelies Mannaerts, Geneviève Laureys, Leen Willems
Journal: Neuro-Oncology (2018)

The care for children suffering from a brain tumor is complex and involves a lot of different (para-) medical disciplines. All health care professionals have their own expertise in taking care of a child with a brain tumor. In 2013, a nurse-led clinic for children with brain tumors was introduced in our ward. The goal of this clinic was to improve patient care by introducing a nurse consultant as case manager during the pathway of their diagnosis and treatment. Working in this structure made us clear that we needed to align all the concerned disciplines and to insert transparency in the various functions of the team. Moreover, the role of the nurse consultant had to be anchored in this pathway. As first action in the development of our care pathway, we enumerated and analyzed the bottlenecks in the care. We listened and talked to every single partaker of other disciplines and critically observed the current workflow. We decided that a monthly multidisciplinary meeting could improve the communication and co-operation between the health care professionals. Our final care pathway is a detailed description of all steps: registration, diagnosis, treatment and follow up. It is available throughout the entire hospital, via an easily accessible document managing system in which it is possible to have a quick overview of all tasks for each care professional, in each care-episode. Our future plans are to organize a transition of our adolescent patients to a clinic specialized in late effects after brain tumor treatment.
Unexpected discordance in 5-year OS rates between Nx colon cancer patients and those in stages II plus III
Authors: I. Tonev, N. Conev, A. Petrov, I. Donev
Journal: Annals of Oncology (2018)

Introduction: One of the most commonly diagnosed types of cancer among men and women is colon cancer. Pathological stage at surgery is one of the most important prognostic features in that type of cancer. The number of lymph nodes found during surgery and the presence of nodal metastases is determining for prognosis and further adjuvant treatment decisions. Unknown nodal status is defined as Nx and the results from an analysis performed by Surveillance, Epidemiology, and End Results Program show that 14% of colon cancer patients are defined as Nx. The prognosis in the Nx group of patients is not known. Theoretically, the overall survival (OS) in Nx subgroup should be equal to OS in N0+N1+N2 patients. The potential benefit of chemotherapy in Nx patients is not known. Methods: A total of 1187 patients with colon cancer that underwent surgery at the Complex Cancer Center Plovdiv from 01.2004 to 12.2011 (734 stage II, 329 stage III and 124 Nx patients) were analyzed retrospectively. Studied data included date of surgery, age, gender, tumor location, lymph node status and tumor differentiation. All stage III patients, Nx patients and 21.9% of stage II patients underwent adjuvant chemotherapy. Survival analysis was performed using Kaplan-Meier method and Cox regression model. Results: For stage II, III and Nx cancer patients, overall survival rates at five years after surgery were 92.4%, 88.3% and 33.9%, respectively. Moreover, the patients with Nx lymph node status were associated with higher risk of death HR- 1.44 (95% CI, 1.028-2.022; p = 0.03). Conclusion: This study shows an unexpected discordance in 5-year overall survival rates between Nx colon cancer patients and patients in stages II plus III. Further investigations are needed to confirm that Nx lymph node status is an independent negative prognostic marker for colon cancer patients.
Impaired quality of life of caregivers of patients with gastrointestinal cancer undergoing palliative chemotherapy
Authors: N. Takeuchi, K. Koike, S. Yoshida, N. Sekiguchi, T. Noguchi
Journal: Annals of Oncology (2018)

Introduction: Support of caregivers to patients with gastrointestinal (GI) cancer undergoing palliative chemotherapy is an essential factor in maintaining the safety and continuity of the treatment. Given the insufficient knowledge regarding the quality of life (QOL) of caregivers, no durable strategy exists for their support through the treatment. We aimed to assess the QOL of caregivers of patients with GI cancer undergoing palliative chemotherapy. Methods: This single institutional prospective observational study was approved by the institutional review board of Ina Central Hospital held on 20 July 2016. Fifty-nine patients with GI cancer and their caregivers have been included in this study. EORTC QL-C-30 was used for measuring QOL. This study included 36 male and 23 female patients aged 68.7 years in average, and 18 male and 41 female caregivers aged 64.4 years in average. The locations of the primary lesions were identified as follows: pancreas (19), colorectal (13), stomach, (13), biliary tract (7) and oesophagus (7). QOL measurement was conducted at the commencement of the first-line chemotherapy in 45 patients and on the second-line chemotherapy after the failure of the first line in 14 patients. Of the 59 patients, 15 were evaluated both at the commencement of the first- and second-line chemotherapies. The average period between the two assessments was 5.5 months. The change in their QOL scores and scales along the treatment has been included in the discussion. Statistical analysis was performed using JMP® 13 software (SAS Institute Inc., Cary, NC, USA). Results: Global health score (GHS) and Summary Score (SS) of caregivers were 62.8 and 85.0, respectively. Both scores are significantly higher than those of the patients (46.2 and 73.5, respectively). Among each score and scale of QOL identified from QL-C-30, "emotional function" (73.1 for caregivers, 70.3 for patients), "cognitive function" (77.2 for patients, 79.7 for caregivers) and "insomnia scales" (24.3 for patients, 19.8 for caregivers) did not show a significant difference between patients and their caregivers. All scores and scales other than the three were significantly higher in caregivers. In the comparison of the QOL of patients during first-line and second-line chemotherapies, no significant concordance of improvement or worsening of GHS and SS during treatment (χ2 = 0.00, P = 1.00 in both scores) was found between patients and caregivers. Conclusion: Even at the commencement of the treatment, caregivers of patients with GI cancer suffered from the impairment of their daily QOL, especially in emotional and cognitive functions comparable with those of the patients. This impairment did not seem to improve with the improvement of the QOL of the patients; therefore, this necessitates the continuous and independent support from the commencement of the treatment for caregivers of patients with cancer.
Sixty seconds on . . . parkrun
Authors: Gareth Iacobucci
Journal: BMJ (2018)

No, you’re thinking of Parklife , the 90s Britpop anthem by Blur. Parkrun, on the other hand, is the free 5 km running events that take place every Saturday morning across the globe and in the UK, where the scheme first originated in the 2000s.

Not at all. The events are coordinated by local volunteers, and are designed to widen participation in outdoor physical activity …
TBIO-20. CLINICAL TUMOR WHOLE EXOME SEQUENCING FOR PEDIATRIC NEURO-ONCOLOGY PATIENTS – RESULTS FROM THE BAYLOR ADVANCING SEQUENCING IN CHILDHOOD CANCER CARE (BASIC3) CLINICAL SEQUENCING STUDY
Authors: Frank Lin, Samara Potter, Michelle Ting, Raghu Chandramohan, Nipun Kakkar, Tao Wang, Robin Raesz-Martinez, Sarah Scollon, Katie Bergstrom, Dolores Lopez-Terrada, Adekunle Adesina, Carrie Mohila, William Whitehead, Uma Ramamurthy, Susan Hilsenbeck, David Wheeler, Stacey Berg, Murali Chintagumpala, Christine Eng, Richard Gibbs, Angshumoy Roy, Sharon Plon, D Williams Parsons
Journal: Neuro-Oncology (2018)

Tumor mutations detected by genomic tests such as whole-exome sequencing (WES) have the potential to affect clinical management; however, data regarding clinical utility in pediatric neuro-oncology are limited. In order to investigate this topic, enrollment onto the BASIC3 clinical exome sequencing study was offered to children with newly-diagnosed CNS and non-CNS solid tumors. WES was performed on tumor (when available) and blood specimens in a certified clinical laboratory, with resulting genetic variants categorized by perceived clinical relevance and reported to the electronic health record. Mutations were also annotated following recent consensus guidelines (Li et al. J Mol Diagn 2017). WES was performed on 71 tumors obtained from 70 of 98 patients with CNS tumors on the BASIC3 study (71%), including embryonal tumors (medulloblastoma, n=18; PNET or pineoblastoma, n=5), LGG (n=9), HGG (n=7), and ependymal tumors (n=9). Analysis per the new guidelines revealed 21% (15/71) of tumors harbored a variant of “Strong Clinical Significance” (Tier 1) and 27% (19/71) a variant of “Potential Clinical Significance” (Tier 2). Targetable mutations involved the MAPK pathway (BRAF x 6, KRAS, FGFR1), PI3K/MTOR pathway (TSC1, PIK3CA), SWI/SNF family (SMARCB1, SMARCA4), and other protein kinases (PDGFRA x 2). The rate of clinically relevant mutations differed by histology, with frequent variants in LGG (4/9, 44%), HGG (6/7, 86%), and medulloblastoma (7/18, 39%), but not ependymal tumors (0/9, 0%). These data highlight the promise of clinical genomic testing for pediatric brain tumor patients as well as the need for integrated (DNA/RNA) genomic tumor testing to maximize diagnostic yield.
NURS-08. METRONOMIC CHEMOTHERAPY AND THE USE OF A NOVEL APP (CAREZONE) FOR FACILITATION OF MEDICATION ADMINISTRATION AND COMPLIANCE
Authors: Eileen Gillan, Jeanne Walczak, Heather Rea
Journal: Neuro-Oncology (2018)

Metronomic chemotherapy can be an alternative approach to conventional chemotherapy by inhibition of endothelial cell function and resultant neovascularization. During the last 3 years our center has successfully treated 5 patients with either high grade glioma or recurrent ependymomal brain tumors. The antiangiogenic multidrug combination regimen consists of IV bevacizumab, 5 oral drugs; thalidomide, celecoxib, fenofibrate, etoposide, and cyclophophamide plus intraventricular therapy (etoposide and liposomal cytarabine). This drug regimen has a complicated schedule with the administration of 5 oral drugs on varying schedules with modifications based on blood counts plus IV and IT medications. In an effort to improve patient/parent understanding of regimen and subsequent compliance we chose a mobile app for iOS and Android. named CareZone. Based upon patient and staff comments the CareZone app was the most comprehensive in simplifying this regimen with improved patient satification and adherence to drug administration. This app has the following features that are desirable in our pediatric oncology population: 1) the bottle barcode can be photographed and converted directly into text 2) roadmaps and other documents can be photographed into app 3) reminders for med administration with administration documentation is available to share with other caregivers and providers, 4) reminders for drug refill dates and speciality pharmacy contact information 5) lab flowsheets are to be added by developer for oncology population. Mobile apps are familiar with patient and care providers and simplify complicated metronomic drug administration and compliance data for physicians.
TMOD-17. DEVELOPMENT AND CHARACTERIZATION OF DIFFUSE INTRINSIC PONTINE GLIOMA MOUSE MODELS GENERATED BY BRAINSTEM IN UTERO ELECTROPORATION
Authors: Smruti Patel, Rachel Hartley, Heather Bear, Christine Fuller, Timothy Phoenix
Journal: Neuro-Oncology (2019)

Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric cancer arising in the brainstem of children. Their unique brainstem location and pathology, including limited disruption of the blood-brain barrier (BBB), present a significant challenge to treatment. Developing mouse models that accurately reflect the genetic landscape and brainstem location of DIPG will be critical to delineate the role of newly identified mutations in DIPG pathogenesis. Here we describe the efficient generation of DIPG mouse models by targeted transfection of the developing brainstem using in utero electroporation, and characterize the pathological and molecular features associated with PDGFB, Pdgfra, and H3.3 K27M genetic variants. Both PDGFB and PdgfraD842V expression, in combination dominant negative Trp53 (DNp53), develop fully penetrate high-grade gliomas that display distinct differences in latency, histology, and molecular profiles. Addition of the H3.3 K27M mutation alters gene expression in both PDGFB and PdgfraD842V tumors, but only significantly accelerated PdgfraD842V tumors in this system, likely due to the already aggressive nature of PDGFB tumors. Compared to PDGFB tumors, PdgfraD842V brainstem tumors maintain BBB function. Paracrine effects of PDGFB expression in the tumor microenvironment are associated with disruption of pericyte-endothelial interactions, extracellular matrix remodeling, and increased angiogenesis and BBB disruption. This DIPG mouse modeling system provides a rapid and flexible in vivo platform to perform functional genomic studies to fundamentally advance our understanding of the cellular and molecular basis underlying DIPG, and conduct preclinical studies of molecularly targeted therapies that aim to improve survival rates and outlook for DIPG patients and their families.
ATRT-28. RETROSPECTIVE ANALYSIS OF ATYPICAL TERATOID RHABDOID TUMOR IN THE ERA OF MULTIMODAL TREATMENT IN JAPAN
Authors: Kai Yamasaki, Yuko Watanabe, Kiyotaka Isobe, Yuhki Koga, Chikako Kiyotani, Keita Terashima, Yoshiki Arakawa, Daiichiro Hasegawa, Yoshiyuki Kosaka, Hiroaki Goto, Katsuyoshi Koh, Junichi Hara
Journal: Neuro-Oncology (2018)

Recent progress of multimodal therapy including intrathecal and/or intraventricular chemotherapy improved the prognosis of atypical teratoid rhabdoid tumor (ATRT). To know historical control data for a new trial, we retrospectively collected clinical information of locally diagnosed ATRT in eight major pediatric cancer centers in Japan. From 2005 to 2016, 38 ATRT cases with INI-1 immunostaining negative were enrolled in this analysis. Median age was 1.3 years (2m to 11.8yr) and male to female ratio was 2:1. More than half of patients were positive for metastases (M1: 6, M2: 7, M3: 7, M4: 2). Four patients died of cerebral herniation or intratumoral hemorrhage before the initiation of chemotherapy. Postoperative chemotherapy was performed in all remaining patients. Intrathecal methotrexate was added in 30/34 (88.2%) cases. Most patients received high-dose chemotherapy (n=8), radiotherapy (n=9) or both (n=13). By a median follow up of 40.9 month, the 3-year progression free survival (PFS) and overall survival (OS) in treated patients were 39.1 ± 8.7% and 58.5 ± 9.1%, respectively. 3yr-PFS was 56.0 ± 11.8% for M0-1 and 21.4 ± 11.0% for M2-3 cases (p=0.0427) and 76.2 ± 14.8% for GTR and 25.8 ± 9.2% for non GTR (p=0.0361). Neither HDC nor radiotherapy was prognostic, however, all three patients treated with chemotherapy alone relapsed (n=3). Notably, three patients with late relapse survived long periods after relapse (40m, 46m, 80m). A comparable result as previous reports was shown in Japan. We are currently planning a new clinical trial for ATRT.
RADI-03. ASL PERFUSION IMAGING OF THE FRONTAL LOBES PREDICTS THE OCCURRENCE AND RESOLUTION OF POSTERIOR FOSSA SYNDROME
Authors: Derek Yecies, Katie Shpanskaya, Gerald Grant, Samuel Cheshier, David Hong, Michael Edwards, Kristen Yeom
Journal: Neuro-Oncology (2018)

Posterior fossa syndrome (PFS) is a common complication following the resection of posterior fossa tumors in children. The pathophysiology of PFS remains incompletely elucidated, however the wide-ranging symptoms of PFS suggest the possibility of wide-spread cortical dysfunction. In this study, we utilize arterial spin labeling (ASL), an MR perfusion modality that provides quantitative measurements of cerebral blood flow without the use of intravenous contrast, to assess cortical blood flow in patients with PFS. A database of pediatric brain tumor patients treated at Stanford from 2004-2016 was retrospectively reviewed and 15 patients with PFS were identified. Immediate postoperative ASL for patients with PFS and age-matched medulloblastoma patients who did not develop PFS were compared. Additionally, in patients with PFS, ASL following the return of speech was compared with immediate postoperative ASL. On immediate postoperative ASL, patients who subsequently developed PFS had statistically significant decreases in right frontal lobe perfusion and a trend towards decreased perfusion in the left frontal lobe compared to controls. Patients with PFS had statistically significant increases in bilateral frontal lobe perfusion after the resolution of symptoms compared to their immediate postoperative imaging. ASL perfusion imaging identifies decreased frontal lobe blood flow as a strong physiologic correlate of PFS that is consistent with the symptomatology of PFS. This is the first study to demonstrate that decreases in frontal lobe perfusion are present in the immediate postoperative period and resolve with the resolution of symptoms, suggesting a physiologic explanation for the transient symptoms of PFS.