tbuckley/cabot-search huggingface dataset:
Variations at HER2 and hormone receptor status in primary and metastatic sites of breast cancer patients.
Authors: Nurcan Alhan, Samed Rahatli, Nadire Kucukoztas, Selim Yalcin, Mahmut Can Yagmurdur, Omer Dizdar, Alev Atilgan, Handan Ozdemir, Ozden Altundag, Ozgur Ozyilkan
Journal: Journal of Clinical Oncology (2012)

e11023 Background: Evaluation of hormone receptors (ER/PR) and Her2-Neu is important for hormonal and anti-Her2 treatments. The parameters are generally estimated in primary tumors and it is unclear whether re-evaluation of metastatic lesions will be effective during follow-up. Methods: The primary aim of this study was the compare Her2 and HR (ER/PR) status in primary and metastatic tissues of breast cancer patients. HR and Her2 expression in biopsy specimens obtained from primary tumor and their metastatic lesions of 44 breast cancer patients, followed-up during 1995-2010 at Baskent University Hospital were analyzed. Results: Of 44 patients 29.5% were found Her2 (+), 54,5 % ER (+) and 45.4% PR (+) in primary site. Metastatic regions excised or biopsied as following: Bone 31.8% (14/44), liver 27.3% (12/44), skin 25% (11/44), lung 9.1% (4/44), brain 4.5% (2%44), bone marrow 4.5 (2/44), ovaries 4.5% (2/44), stomach, abdominal LAP and pelvic mass 2.3% (3/44). Positification rate of ER status in metastatic sites was detected as 4.5% (2/44), when positive in primary tumors, negatification rate was detected as 20.5%. The positification rate of PR status in metastatic sites, while being negative in primary tissue was 13.6% (6/44); and negativication rate in metastatic lesions, being positive in primary tumor was 27.3% (12/44). The positivication rate of Her2 expression in metastatic lesions while being negative in primary tissue was 4.5% (2/44); and negativication rate while being positive in primary tumor was detected as 13.6% (6/44). When the hormone receptor status and Her2 expression of the patients followed-up are evaluated, receptor variation was detected in 23 of 44 patients. Conclusions: Our study confirms that biological properties of breast cancer may vary among primary tumors and asynchronised metastatic lesions. Further prospective studies are needed to better define the discordance of Her2 or HR status at primary tissue and metastatic sites.
IMMU-11. AN ANALYSIS OF IMMUNOPHENOTYPE, INCLUDING PD-L1 AND PD1 EXPRESSION, IN PEDIATRIC CNS MALIGNANCIES: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY
Authors: Eugene Hwang, Changling Yang, Arzu Onar-Thomas, Jason Fangusaro, Sridharan Gururangan, Jennifer Yearley, Wendy Blumenschein, Terri McClanahan, Lakshman Annamalai, Mehmet Kocak, Sonia Partap, Trent Hummel, Ira Dunkel, Maryam Fouladi, Duane Mitchell
Journal: Neuro-Oncology (2017)

BACKGROUND: Primary pediatric central nervous system (CNS) malignancies often have poor outcomes despite intensive treatment. Clinical immunotherapeutic trials targeting the programmed cell death receptor (PD-1) and its ligand (PD-L1) have been successful in some cancers. One of the most promising biomarkers for response has been the expression of PD-L1, although this has been not universally predictive and its presence in pediatric CNS tumors remains unknown. METHODS: One hundred formalin-fixed, paraffin embedded samples from children with various pediatric CNS malignancies were collected, including twenty-five of each of the following: ependymoma, high-grade glioma (HGG), supratentorial primitive neuroectodermal tumor (sPNET), and medulloblastoma. Patient characteristics and disease outcomes were also obtained. Chromogenic immunohistochemical staining of PD-L1 and PD1 was completed with prevalence of stained cells scored on a 0–5 scale. ‘Positive’ expression was assigned to scores of three or greater. Gene expression was analyzed using an nCounter Nanostring immunologic gene expression codeset. RESULTS: IHC was successful except in one patient with sPNET and two with HGG. PDL1 expression was robust in a subset of tumors, with ‘positive’ staining in 8 (33%) ependymomas, 4 (17%) high-grade gliomas, 2 (8%) sPNETs, and 0 medulloblastomas; PD1 staining was similarly heterogeneous. RNA extraction and expression analysis was successful in all but one sPNET and one HGG. Hierarchical clustering with respect to genes involved in inflammatory pathways identified distinct subgroups within each tumor type; in particular, medulloblastoma was noted to demonstrate activation of inflammatory genes. PD1/PD-L1 expression data did not correlate with histologic staining. Further analysis of the relationship between clinical information and gene expression is ongoing. CONCLUSIONS: This study demonstrates the tumor-specific PDL1/PD1 expression across tumor types and also provides immunologic phenotypic information that may be useful for future rational immunotherapy development in children with CNS malignancy.
Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta‐analysis
Authors: Agustín Albillos, Javier Zamora, Javier Martínez, David Arroyo, Irfan Ahmad, Joaquin De‐la‐Peña, Juan‐Carlos Garcia‐Pagán, Gin‐Ho Lo, Shiv Sarin, Barjesh Sharma, Juan G. Abraldes, Jaime Bosch, Guadalupe Garcia‐Tsao
Journal: Hepatology (2017)

Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013).Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231).
Abstract MP88: Sodium, Sugar and Fat Content in Commercial Infant and Toddler Foods, 2015
Authors: Joyce Maalouf, Mary E Cogswell, Marlana Bates, Kelley Scanlon, Janelle P Gunn, Keming Yuan, Robert Merritt
Journal: Circulation (2016)

Introduction: Early intake of foods with excess sodium, sugar, and saturated fat can influence later dietary habits and health, potentially increasing the risk of cardiovascular disease. A 2012 analysis indicated that 72% of commercial toddler meals were high in sodium (average: 361 mg per serving) and 32% of toddler meals and &gt;70% of infant and toddler snacks, desserts, and juice drinks contained one or more added sugars. Given manufacturer reported changes in commercial infant and toddler foods the study objective is to determine the sodium, sugar and fat content of commercial infant and toddler foods sold in the U.S. in 2015. Methods: Major brands of infant and toddler food products were identified. Nutrition information was collected from manufacturer websites and grocery stores (e.g. private label products) from May to July, 2015. A total of 1,045 food products were categorized according to main ingredients, target eater and serving sizes. Serving sizes were standardized to the FDA Reference Amount Customarily Consumed (RACC) per eating occasion for the specific category. Mean sodium, sugar and saturated fat content was computed per serving, per 100g, and in relation to calories (mg/1000 Kcal for sodium and as a percent of calories for sodium and fat). High sodium content was defined as &gt;210 mg/serving or &gt;200 mg/100g, the CODEX standard used by manufacturers. Presence of added sugar and industrially produced trans fat was determined from the ingredients list. Results: Mean sodium content ranged from 4 mg/serving (mixed grains and fruits) to 290 (toddler meals) and 73 mg/1000 Kcal (cereals, dry/instant) to 997 mg/1000 Kcal (savory snacks).Mean percent of calories from sugar ranged from 7% (savory snacks) to 82% (juices/drinks), and percent of calories from saturated fat from 0% (infant vegetables, dinners, fruits, dry cereals) to 7.5% (toddler meals). Almost all infant foods were low in sodium. Few infant foods contained added sugars except 44% of infant pureed fruits and 27% of mixed grains with fruits. Eighty-one percent of toddler meals exceeded 210 mg/serving, while 5% were &gt;200 mg/100 g with an average of 170 mg/100g. More than 70% of toddler’s meals, cereal bars/breakfast pastries, and infant/toddler desserts and dairy products contained added sugar. None of the products contained industrially produced trans fat. Conclusions: In 2015 average sodium content of commercial toddler meals was about 20% lower than in 2012, with the majority meeting the CODEX standard, but still above 210 mg per serving. Commercial toddler meals, infant mixed grain with fruits and infant or toddler cereal bars/breakfast pastries and desserts remain of concern due to added sugars. Commercial infant and toddler foods are generally low in their saturated fat content with no industrially produced trans fat.
Cerebral vasculitis mimicking intracranial metastatic progression of lung cancer during PD-1 blockade
Authors: Heinz Läubli, Jürgen Hench, Michal Stanczak, Ingmar Heijnen, Alexandros Papachristofilou, Stephan Frank, Alfred Zippelius, Frank Stenner-Liewen
Journal: Journal for ImmunoTherapy of Cancer (2017)

Stimulation of the immune system by targeting the PD-1/PD-L1 pathway can result in activation of anti-tumor immunity. Besides its clinical benefit immune checkpoint therapy leads to significant immune-related adverse events (irAEs). Some rare irAEs are not well described yet but are critical in patient management.Here, we describe a case of autoimmune cerebral vasculitis/encephalitis after PD-1 inhibitor treatment for metastatic adenocarcinoma of the lung. Upon PD-1 blockade, the patient developed cerebral lesions, while having disease stabilization of extracranial metastases. Imaging suggested that the patient had new progressing brain metastases. Despite stereotactic irradiation the lesions progressed further. The largest lesion became symptomatic and had to be surgically resected. On examination, cerebral vasculitis was detected but not evidence of metastatic lung cancer. Analysis of the patient's serum revealed the presence of antinuclear antibodies that were already present before starting PD-1 blockade. In addition, we also found anti-vascular endothelial antibodies in the serum.This finding suggests that the patient had preformed autoantibodies and the checkpoint inhibitor induced a clinically relevant autoimmune disease. Taken together, encephalitic lesions in patients under PD-1/PD-L1 blockade can mimic metastatic brain lesions and this rare irAE has to be considered as a differential diagnosis in patients treated with immunotherapy.
Association of Long-term Opioid Therapy With Functional Status, Adverse Outcomes, and Mortality Among Patients With Polyneuropathy
Authors: E. Matthew Hoffman, James C. Watson, Jennifer St Sauver, Nathan P. Staff, Christopher J. Klein
Journal: JAMA Neurology (2017)

Polyneuropathy is one of the most common painful conditions managed within general and specialty clinics. Neuropathic pain frequently leads to decisions about using long-term opioid therapy. Understanding the association of long-term opioid use with functional status, adverse outcomes, and mortality among patients with polyneuropathy could influence disease-specific decisions about opioid treatment.
Using neurophysiological measures to assess concussion. a case control study in one player
Authors: Adrian Cohen, King Doug, Pearce J Alan
Journal: British Journal of Sports Medicine (2017)

Objective case study presents data using multimodal assessment using impact sensors, oculomotor function and transcranial magnetic stimulation (TMS) to quantify neurophysiological changes in the acute period following concussion. Design Case control study. Participants Over one season, we evaluated a male rugby union player (age: 29 years; prior concussions: 1; last concussed &gt;120 months) for head impacts using impact sensors (X2 Biosystems, USA) and oculomotor function (King-Devick test). 1 TMS (MagVenture, Denmark) protocols utilised previously published methods for concussion studies 2,3 with data compared to our normative database of age-group controls (33 males; mean age: 28.6±3.9 years). Intervention Any impact that resulted in a concussion, confirmed by the team doctor, required post-match testing utilising the King-Devick test and follow up testing for TMS at 5 d and 12 d. Outcome measures Time and errors completing the King-Devick test. TMS measures included latency (TMS stimulus to evoked potential onset ), evoked potential amplitude, and intracortical inhibition (TMS onset to return of uninterrupted electromyography activity). Main results An impact of 60.7 g/17, 114.1 rads/s 2 revelead a decreased King-Devick performance of 3.8 s. At 30 d King Devick remained below pre concussion baseline. Compared to controls, TMS revealed increased intracortical inhibition duration of 20.6 ms at 5 d post concussion, and returning to baseline/control levels by 12 d. Conclusions This novel case study demonstrates the value of using multimodal measurements in the assessment of concussion and return to play decisions. Competing interests None. AJP is supported, in part, by a research grant by the Australian Football League.
MEDU-10. THE PROTEO(EPI)GENOMICS OF MEDULLOBLASTOMA
Authors: Ling San Lau, Mojca Stampar, Samuel Rivero-Hinojosa, Jerome Staal, Huizhen Zhang, Heather Gordish-Dressman, Javad Nazarian, Yetrib Hathout, Kristy Brown, Brian Rood
Journal: Neuro-Oncology (2017)

The genomic characterization of medulloblastoma at the level of the chromosome, epigenome and transcriptome has radically redefined diagnostic classifications and reoriented disease definitions toward a biological underpinning. However, it still remains a challenge to leverage this wealth of data toward a true understanding of disease biology and subsequently to capitalize on the promise of biologically based therapies. One reason for this difficulty is the loose correlation between the genetic and the functional aspects of the cancer cell resulting from multilayered regulatory mechanisms governing protein production, the predominant functional moiety of the cell. To better actualize the promise of genomics, it is necessary to add an understanding of the proteomic dimension to cancer cell biology. We have undertaken a super-SILAC based quantitative proteomics survey of 42 tissue samples spanning the 4 genomic subgroups of medulloblastoma and control cerebellum. We have identified and quantitated thousands of proteins across these groups and find that we are able to recapitulate the genomic subgroups based upon subgroup restricted and differentially abundant proteins while also identifying one additional subgroup. Adding array gene expression data to this analysis, we calculate a relatively poor correlation between mRNA and protein abundance with the best concordance found among stable proteins. EPIC 850k methylation array data performed on the same samples extend this analysis to the epigenome yielding chromosomal copy number variations and correlations to gene promoter methylation. From the quantitative proteomic data, we are able to discern networks of functional pathways with differential activation between the medulloblastoma subgroups and normal control cerebellum yielding potential avenues for clinical intervention. This work demonstrates that quantitative proteomics can further elucidate the biology inherent in a genomically based classification regime.
Assesment of distress among breast cancer survivors.
Authors: Anu Radha Neerukonda, Michelle M. Stevens, Lisa Reagan, Jules Cohen, Lea N. Baer, Catherine Messina, Barbara Nemesure
Journal: Journal of Clinical Oncology (2015)

e12610 Background: Several studies have documented distress in breast cancer patients during the diagnosis and treatment phases of cancer care, however, data are more scarce regarding the prevalence of distress experienced during survivorship. The purpose of this investigation was to assess level of distress among breast cancer survivors and to identify demographic, psychosocial, and other related variables that may be associated with distress in this population. Methods: A retrospective chart review was conducted to identify female breast cancer survivors attending the Stony Brook Cancer Center Survivorship Clinic between 2012 and 2014. Eligible patients were > = 21 years of age and completed primary treatment for breast cancer and the National Comprehensive Cancer Network Distress Thermometer (DT) at their first survivorship care visit. Descriptive statistics were used to describe the demographic, psychosocial, tumor-related and treatment characteristics for the study sample, as well as those factors included in the DT. A value of 4 or higher reported on the DT was used to define “clinically significant distress”. Logistic regression models were used to evaluate the relationship between elevated distress and the factors outlined above. Results: This investigation included 81 women with mean (SD) age of 53 (8) years. The study sample was predominantly Caucasian (85%) and more than three-quarters of the subjects were married. Most patients had stage 1 (43%) or stage 2 (41%) breast cancer and the mean (SD) distress score in the overall sample was 3.78 (3.02). Approximately one-half of patients reported a clinically significant distress level (4 or higher). Breast cancer survivors who were on an anxiolytic or anti-depressant medications tended to have higher levels of distress (OR: 3.10; 95% CI: 0.90-10.74; P value = 0.07) and age greater than 60 years at the time of diagnosis was negatively correlated with distress (OR: 0.24; 95% CI: 0.07-0.84; P = 0.025). Conclusions: Significant distress was reported by 50% of breast cancer survivors in this investigation. These data suggest the need to screen women at the early stage of survivorship to assess the presence of distress so that strategies can be implemented to improve quality of life among breast cancer survivors.
Clinicopathological Features and Outcomes of Progression for Chronic Lymphocytic Leukaemia (CLL) Treated with the BCL2 Inhibitor Venetoclax
Authors: Thomas E Lew, Mary Ann Anderson, Constantine S. Tam, David C.S. Huang, Surender Juneja, David A Westerman, John F Seymour, Andrew W. Roberts
Journal: Blood (2016)
TRTH-15. RESISTANCE MECHANISMS TO BET-BROMODOMAIN INHIBITION IN MYC-AMPLIFIED MEDULLOBLASTOMA
Authors: Pratiti Bandopadhayay, Brenton Paolella, Ryan O’Rourke, Patricia Ho, Noah Greenwald, Ofer Sharpira, Sasha Pantel, Mukta Bagul, Adam Tracy, Giovanni Roti, Amanda Balboni, Francisca Vazquez, Keith Ligon, Federica Piccioni, Kimberly Stegmaier, Cory Johannessen, Rameen Beroukhim
Journal: Neuro-Oncology (2017)

INTRODUCTION: Children with MYC-amplified medulloblastoma face a dismal prognosis. We have previously found BET-bromodomain inhibition to have preclinical promise as a therapeutic strategy for MYC-amplified medulloblastoma. However, the mechanisms of action of these inhibitors have not been fully elucidated. In addition, the development of resistance is likely to impact their clinical efficacy. To address this, we characterized cancer cell evolution in response to BET-bromodomain inhibition in MYC-amplified medulloblastoma models. METHODS: We applied genome wide over-expression (ORF) and CRISPR-cas9 screens to identify pathways which, when altered, rescue cells from the phenotypic effects of BET-bromodomain inhibition in MYC-amplified medulloblastoma cell lines. Candidate genes were validated as resistance drivers in medulloblastoma cell lines chronically passaged with BET-bromodomain inhibitors until the acquisition of resistance. These lines were also subjected to whole-exome sequencing to uncover genomic alterations that confer resistance. RESULTS: Altered expression of the anti-apoptosis pathway, cell cycle activation and PI3-kinase signaling, in addition to several lineage-specific transcription factors, rescued MYC-amplified cells from BET-bromodomain inhibition. Cell-lines that had acquired resistance to BET-bromodomain inhibitors exhibited altered cell-state and increased expression of candidate resistance proteins. These lines were resistant to structurally distinct BET-bromodomain inhibitors, and whole-exome sequencing did not reveal mutations in BRD2, BRD3 or BRD4. Resistant cell-lines were sensitive to inhibitors targeting candidate resistance drivers. CONCLUSIONS: MYC-amplified medulloblastoma cell-lines evolve to increase expression of candidate resistant pathways to acquire resistance to BET-bromodomain inhibition. These represent potential therapeutic targets for combination therapies to increase the clinical efficacy of BET-bromodomain inhibitors for children with MYC-amplified medulloblastoma.
EPND-10. PRE- AND PERINATAL FACTORS ASSOCIATED WITH DEVELOPMENT OF PEDIATRIC EPENDYMOMA: RESULTS OF CASE-CONTROL ANALYSIS
Authors: Cassie Kline, Libby Morimoto, Joseph Wiemels, Catherine Metayer, Kyle Walsh
Journal: Neuro-Oncology (2017)

BACKGROUND: Ependymoma is the 3rd most common brain tumor in children. Few studies have investigated factors contributing to development of pediatric ependymoma. We investigate pre- and perinatal factors associated with ependymoma diagnosis in the largest, multi-ethnic cohort assembled to date. METHODS: A population-based, case-control analysis was nested within the California Cancer Registry. Cases and controls were born in California between 1978 and 2009 and linked to birth data from the California Department of Public Health vital statistics unit. Cases were diagnosed between 0–19 years of age and matched to four controls based on sex, birth year, and race/ethnicity. A total of 475 cases were included, matched to 1900 controls. RESULTS: Ependymoma cases included 273 (57%) males. Most frequent age at diagnosis was 0–5 years (42%). The most common tumor histology based on ICD-O-3 code was ependymoma, NOS (50%). When grade was reported, grade 4 was most common (24%). Birth weight and gestational age were not different between cases and controls. Mean maternal age for cases was 28.7 years versus 27.5 years for controls (p=0.0003). Each five-year increase in maternal age was associated with a 1.18-fold increased risk of ependymoma (p<0.001). Mean paternal age for cases was 31.3 years versus 30.3 years in controls (p=0.01). Older paternal age was associated with increased incidence of grade 4 lesions (p=0.01). Patient age at diagnosis differed by tumor histology and grade, with younger age associated with higher tumor grade (p=0.0001). Notable gender differences occurred across histology, grade, and anatomic site. Incidence of pregnancy, labor, or congenital abnormalities was similar between cases and controls. CONCLUSIONS: Older parental age at birth is associated with the development of ependymoma in case-control analyses, with the strongest effect observed for maternal age. Differences in patient gender and age are seen across groupings of histology, grade, and anatomic site.