tbuckley/cabot-search huggingface dataset:
Abstract P5-08-30: Utilization of oncotype DX for breast cancer in different facility types in Louisiana
Authors: M Loch, X Li, B Mumphrey, A Garcia, X-C Wu
Journal: Cancer Research (2017)

Abstract Background: Oncotype DX, a 21-gene recurrence score, is the most validated prognostic assay that may identify both women most and least likely to benefit from adjuvant chemotherapy. It was added to the ASCO guidelines in 2007 and the NCCN guidelines in 2008 for use in node negative, hormone receptor (HR)+, HER2- breast cancer patients who will undergo 5 years of endocrine therapy. We explored its utilization in different cancer care settings to assess differences in the tool's utilization. Methods: We analyzed data from the Louisiana Tumor Registry, one of the NCI funded SEER registries for cases of HR+ HER2- localized breast cancer from 2010-2012 and explored differences in utilization of the Oncotype DX by facility type – teaching hospital cancer program (THCP), community hospital comprehensive cancer program (COMP), community hospital cancer program (CHCP), commission on cancer program (COC) and public hospital program. Chemotherapy administration data was collected on the 2011 cases with chemotherapy data collected from a CDC funded special project Enhancing Cancer Registry Data for Comparative Effectiveness Research (CER). Hospital sites were identified by the location where patients underwent surgery. Demographic and clinical factors were adjusted for using multivariate logistic regression. Results: Of the patients who did have the Oncotype DX, 39.2% were white, 32.3% black. Women over 70 were much less likely (29.3% vs. &amp;gt;45% in women &amp;lt;70) to have the test. Patients who received surgery at public hospitals had the lowest chance (16.7%), whereas those who received surgery at COMP were most likely to have the test (43.1%) and at teaching hospitals, 31.8% had the test. The odds of not using Oncotype DX were significantly higher in public hospitals than THCP even after adjusting for demographic and clinical factors (OR=2.44; 95% CI: 1.39-4.27). Odds Ratios and 95% CIs for Oncotype DX (No/Yes) in HR+/HER2- localized breast cancer in 2010-2012, LouisianaHospital type#Crude Odds Ratio and 95% CIAdjusted Odds Ratio and 95% CITHCP422referencereferenceCOMP4891.63 (1.24-2.14)0.56 (0.41-0.76)CHCP8101.35 (1.06-1.74)0.74 (0.56-0.98)Public1140.43 (0.25-0.73)2.44 (1.39-4.27)NonCOC/Non Public10321.37 (1.07-1.74)0.70 (0.53-0.92) Conclusions: Patients who had the Oncotype DX performed in our Louisiana database were most likely white, &amp;lt;70 and had their surgeries at COMP. The odds of not having the Oncotype DX performed were significantly higher in public hospitals as compared with teaching hospitals when adjusting for demographic and clinical factors. Citation Format: Loch M, Li X, Mumphrey B, Garcia A, Wu X-C. Utilization of oncotype DX for breast cancer in different facility types in Louisiana [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-30.
Tumor Sequencing and Patient-Derived Xenografts in the Neoadjuvant Treatment of Breast Cancer
Authors: Matthew P. Goetz, Krishna R. Kalari, Vera J. Suman, Ann M. Moyer, Jia Yu, Daniel W. Visscher, Travis J. Dockter, Peter T. Vedell, Jason P. Sinnwell, Xiaojia Tang, Kevin J. Thompson, Poulami Barman, Douglas W. Mahoney, Erin Carlson, Steven N. Hart, Ping Yin, Bo Qin, Sara J. Felten, Sarah A. McLaughlin, Alvaro Moreno-Aspitia, John A. Copland, Donald W. Northfelt, Richard J. Gray, Katie Hunt, Amy Conners, Hugues Sicotte, Jeanette E. Eckel-Passow, Jean-Pierre Kocher, James N. Ingle, Marissa S. Ellingson, Michelle McDonough, Eric D. Wieben, Richard Weinshilboum, Liewei Wang, Judy C. Boughey
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Breast cancer patients with residual disease after neoadjuvant chemotherapy (NAC) have increased recurrence risk. Molecular characterization, knowledge of NAC response, and simultaneous generation of patient-derived xenografts (PDXs) may accelerate drug development. However, the feasibility of this approach is unknown. Methods: We conducted a prospective study of 140 breast cancer patients treated with NAC and performed tumor and germline sequencing and generated patient-derived xenografts (PDXs) using core needle biopsies. Chemotherapy response was assessed at surgery. Results: Recurrent "targetable" alterations were not enriched in patients without pathologic complete response (pCR); however, upregulation of steroid receptor signaling and lower pCR rates (16.7%, 1/6) were observed in triple-negative breast cancer (TNBC) patients with luminal androgen receptor (LAR) vs basal subtypes (60.0%, 21/35). Within TNBC, TP53 mutation frequency (75.6%, 31/41) did not differ comparing basal (74.3%, 26/35) and LAR (83.3%, 5/6); however, TP53 stop-gain mutations were more common in basal (22.9%, 8/35) vs LAR (0.0%, 0/6), which was confirmed in The Cancer Genome Atlas and British Columbia data sets. In luminal B tumors, Ki-67 responses were observed in tumors that harbored mutations conferring endocrine resistance (p53, AKT, and IKBKE). PDX take rate (27.4%, 31/113) varied according to tumor subtype, and in a patient with progression on NAC, sequencing data informed drug selection (olaparib) with in vivo antitumor activity observed in the primary and resistant (postchemotherapy) PDXs. Conclusions: In this study, we demonstrate the feasibility of tumor sequencing and PDX generation in the NAC setting. "Targetable" alterations were not enriched in chemotherapy-resistant tumors; however, prioritization of drug testing based on sequence data may accelerate drug development.
Shc test as a strong prognostic indicator of disease outcome in early stage gastric cancer
Authors: H. J. Wanebo, A. R. Frackelton, L. J. Hafer, R. Bagdasaryan, R. Lis, E. Sabo, M. B. Resnick
Journal: Journal of Clinical Oncology (2006)

10090 Background: Treatment planning for gastric cancer is primarily based on clinical staging of disease. Markers predicting likelihood of disease outcome would help guide treatment decisions, especially for early stage disease. The Shc proteins, implicated in many aggressive cancers, and measured in tumor specimens by the immunohistochemical (IHC) Shc Test, have shown strong ability to predict disease outcome in breast cancer. We report here that the Shc Test is a strong prognostic indicator of disease outcome in early stage gastric cancer. Methods: Histopathology was examined in one hundred and seventeen (117) primary gastric cancer patient samples from Rhode Island Hospital in tissue microarray format (21 disease recurrences; 63 disease-specific deaths; average follow-up of 2.7 yrs). IHC staining of the Shc proteins was independently scored on a 0–5 scale by two pathologists, blinded to patient information. Results: Stage I or II gastric cancers (n=62) could be clearly separated at a cutpoint of 1.1 on a 0–5 scale, into good prognosis (16% 4yr relapse risk; demonstrating high PY-Shc) and poor prognosis (46% 4yr relapse risk; showing low PY-Shc) (log-rank, P=0.003). p66 Shc showed similar prognostic abilities. High PY-Shc in patients with early stage disease showed a significant protective effect on overall survival (P=0.003) by univariate log rank analysis. As a continuous variable, PY-Shc had a strong predictive ability (HR = 0.09, P=0.055) that approached significance. By univariate Cox proportional hazards, patients with high PY-Shc had a 5-fold reduction in disease specific death (DSD) compared to patients with low PY-Shc (P=0.002). By multivariate Cox proportional hazards, adjusted for grade, stage, chemotherapy and radiation therapy, only PY-Shc (HR = 0.22, P=0.015) and Intestinal tumor type (HR = 0.38, P=0.046) remained as significant predictors of survival. Conclusions: The Shc Test shows a strong prognostic ability to stratify early stage gastric cancer patients by risk, making it a valuable tool in selecting therapy for these patients. [Table: see text]
PP61. THE ROLE OF NICOTINAMIDE METABOLISM IN CHEMOSENSITIVITY IN GLIOBLASTOMA MULTIFORME
Authors: Mr Richard Perryman, Mr Kevin O’Neill, Dr Hector Keun, Dr Nelofer Syed
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) is a highly aggressive grade IV glial cancer that shows a high degree of intra tumour heterogeneity, with a median survival time of only 18 months. The standard of care is surgical resection followed by combined radiation and chemotherapy in the form of the alkylating agent temozolomide (TMZ). However, tumour recurrence is common with acquired resistance to both TMZ and radiation. Novel drug combinations are desperately required to improve outcomes for patients with this devastating form of cancer. Targeting tumour metabolism is a promising strategy. Ecto-5’-nucleotidase (NT5E) is a metabolic enzyme bound to the extracellular membrane. Although its primary role is involved in nucleotide metabolism, where it catalyses the removal of phosphate groups from nucleoside monophosphates, it has been implicated as playing a significant role in the development and progression of cancer. Recent studies have highlighted its role in the salvage of extracellular nicotinamide metabolites, enabling cells to fuel NAD dependent reactions. In addition, data from the TCGA database shows that the expression of enzymes involved in nicotinamide metabolism, including NT5E, NAMPT and NNMT, are predictive of survival in patients with GBM. Results from our in vitro studies indicate that pharmacological inhibition (using APCP) or knockdown of NT5E sensitises GBM cells to the NAD depleting agent FK866 and to TMZ as assessed by a reduction in proliferation. Moreover, NT5E null cells exhibit increased activation of apoptosis and a greater degree of cell death in the presence of TMZ and FK866, and the drugs in combination show enhanced effects. Furthermore, treatment of GBM cells with FK866 significantly reduces intracellular NAD and NADH levels. This depletion of NAD could result in a reduced glycolytic capacity, loss of efficient DNA repair mechanisms mediated via the PARP family, and disruption to the cell cycle through loss of normal sirtuin activity. FK866 has already been shown to have a clear, safe toxicity profile in clinical trials of other cancers and importantly it is predicted to cross the blood brain barrier. The combined use of FK866 and TMZ is a strategy that could be explored to combat GBM recurrence and improve patient survival, stratified on NT5E status.
Epidemiology of Transfusion Related Acute Lung Injury in e-FIT, the French Hemovigilance Database: 1994 to 2006. A Study of the French Hemovigilance Network.
Authors: Philippe Renaudier, Mai Phuong Vo Mai, Nadra Ounnoughene, Beatrice Willaert, Cyril Caldani
Journal: Blood (2006)
Gene Therapy in a Patient with Sickle Cell Disease
Authors: Jean-Antoine Ribeil, Salima Hacein-Bey-Abina, Emmanuel Payen, Alessandra Magnani, Michaela Semeraro, Elisa Magrin, Laure Caccavelli, Benedicte Neven, Philippe Bourget, Wassim El Nemer, Pablo Bartolucci, Leslie Weber, Hervé Puy, Jean-François Meritet, David Grevent, Yves Beuzard, Stany Chrétien, Thibaud Lefebvre, Robert W. Ross, Olivier Negre, Gabor Veres, Laura Sandler, Sandeep Soni, Mariane de Montalembert, Stéphane Blanche, Philippe Leboulch, Marina Cavazzana
Journal: New England Journal of Medicine (2017)

Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling β-globin remained high (approximately 50% of β-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB-205 ClinicalTrials.gov number, NCT02151526 .).
Comprehensive genomic analysis of small cell lung cancer in Asian patients.
Authors: Shigeki Umemura, Koichi Goto, Sachiyo Mimaki, Genichiro Ishii, Hironobu Ohmatsu, Seiji Niho, Kiyotaka Yoh, Shingo Matsumoto, Akiko Takahashi, Kanji Nagai, Yuichiro Ohe, Hiroyasu Esumi, Katsuya Tsuchihara
Journal: Journal of Clinical Oncology (2013)

7512 Background: Small cell lung cancer (SCLC) is an aggressive disease with poor prognosis. There is an urgent need for detecting well-defined therapeutic targets, however, little is known about the molecular events causing SCLC. This report describes findings from the integrated genomic analyses of 47 human SCLC samples in Asian population. Methods: We performed whole exome sequencing and copy number analysis on surgically resected tumor and matched normal samples from previously untreated Japanese patients with SCLC. Frequency of driver gene alterations were compared with previous two reports intended for non-Asian population (Peifer et al. Nature Gen 2012 and Rudin et al. Nature Gen 2012). Results: The demographics of 47 patients were as follows: median age 67 years (range: 42-86); female 8 (17%); history of smoking 47 (100%) and pathological stage I/II/III/IV=26/12/8/1. The average of protein-altering mutations was 193 (range: 51-633, standard deviation: 129). Genomic alterations including copy number amplifications and deletions in at least one of three frequently occurred driver genes, TP53, RB1, and MYC family, were detected in 93.6% of tumors. Mutation frequencies were 76.6%, 42.6%, and 12.8% for TP53, RB1, and MYC family respectively, which were equivalent to the previous reports. Recently reported candidate new driver genes were also recurrently confirmed in the present study: PTEN 4.3%, CREBBP 4.3%, EP300 4.3%, SLIT2 4.3%, MLL 4.3%, CCNE1 8.5% and SOX2 2.1%. Many of them were potentially targetable with currently available drugs. Conclusions: The genomic landscape of SCLC was not significantly different between Asian and non-Asian population. We perform additional targeted re-sequencing on biopsy samples obtained from metastatic SCLC to further assess the relevance of our results.
Valproic Acid (VPA) Achieves High Response Rates in Patients with Low-Risk Myelodysplastic Syndromes.
Authors: Andrea Kuendgen, Mathias Schmid, Sabine Knipp, Akos Czibere, Barbara Hildebrandt, Christian Steidl, Rainer Haas, Ulrich Germing, Hartmut Doehner, Norbert Gattermann
Journal: Blood (2005)
Level of γ-glutamyltransferase in 2-Year-old Children With Biliary Atresia Associates With Progression of Portal Hypertension
Authors: A. Jay Freeman, Vicky Lee Ng, Sanjiv Harpavat, Alexander Hrycko, Zoe Apted, Pinar Bulut, Traci Leong, Saul J. Karpen
Journal: Clinical Gastroenterology and Hepatology (2017)
Prevention of psychosocial morbidity and improvement of coping strategies: Effects of a cancer patient and caregiver centred information series.
Authors: Andrea Thekla Petermann-Meyer, Jana Kaiser, Irene Savakis, Stefan Wilop, Tim H. Brümmendorf, Jens Peter Panse
Journal: Journal of Clinical Oncology (2014)

e20566 Background: As cancer generates physical, psycho-social and emotional concerns in patients and caregivers, timely information, support and advice regarding these issues may be helpful. We established a string of lectures in analogy to dialysis or diabetes information series as a new type of support at our cancer centre. Each string consists of 6 or 7 weekly symposia (120 minutes) targeting psycho-social issues, nutrition, sexuality, sports, coping strategies and communication. Aim of this study was to evaluate if this strategy allows improvement of attendees’ coping strategies and prevents psycho-social distress. Methods: Attendees filled out the NCCN distress thermometer (DT) including a problem list (PL) covering physical, practical, emotional, interpersonal, and spiritual problems and a 24 item questionnaire evaluating attitudes towards disease burden and subjective coping abilities. Using an encoding strategy, we could identify attendees in each session to evaluate participation patterns of various lecture themes. Results: After five lecture series, 1,501 attendees were evaluated. 71% were female (N=1,035), 29% male (N= 421). 764 (51.6%) were patients, 422 (28.5%) relatives, and 294 (19.9%) attended due to general or professional interest. Lectures covering caregivers’ situation, and possibilities of support for children of cancer parents attracted more relatives (42.3%) than patients (35.2%, others 22.5%). Patients average distress-level was 4.8, caregivers 4.8, and others 3.1 (p<0.0001). 65.9% of the patients and relatives indicated need for more support, 9.2% had no one at all to talk about their problems. 91.6% received useful information, while 90.8% felt that the information given was helpful in improving their coping strategies. Conclusions: Cancer patients and relatives participating in this lecture series show a high degree of emotional distress as well as intra- and interpersonal problems. Our newly established support and education program was frequently used, improved coping strategies, successfully supplied useful information and practical tips for patients and caregivers and has already been adopted by other cancer centres.
Prognostic significance of Focal Adhesion Kinase (FAK) in node-negative breast cancer.
Authors: Marcus Schmidt, Leonie van de Sandt, Katrin Almstedt, Marco Johannes Battista, Anne-Sophie Heimes, Antje Lebrecht, Gerald Hoffmann, Joerg Rahnenfuehrer, Jan G Hengstler
Journal: Journal of Clinical Oncology (2015)

552 Background: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase playing an important role as a key mediator for signal transduction. We examined the subtype specific prognostic significance of FAK in node-negative breast cancer. Methods: Using microarray based gene-expression data, we analysed the prognostic significance of FAK (208820_at). The subtype specific prognostic role of FAK was analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of FAK for metastasis-free survival (MFS) was examined in the whole cohort of patients as well as in different molecular subtypes: luminal A (ER+/HER2-/aurora kinase A [AURKA]low, luminal B (ER+/HER2-/AURKAhigh), basal-like (ER-/HER2-), and HER2+. Results: Prognostic significance of FAK was seen in the whole cohort of patients (HR 1.48, 95% CI 1.16-1.87, P = 0.001). Considering the different molecular subtypes, the prognostic effect was most pronounced in luminal B carcinomas (HR 1.67, 95% CI 1.07-2.62, P = 0.0233). FAK expression was neither significantly associated with MFS in luminal A (HR 1.69, 95% CI 0.96-2.98, P = 0.0692), basal-like (HR 0.98, 95% CI 0.64-1.50, P = 0.9400) nor HER2+ (HR 1.63, 95% CI 0.49-5.46, P = 0.8512) carcinomas of the breast. Conclusions: A higher expression of FAK was associated with worse MFS in node-negative breast cancer. The prognostic significance was confined to luminal B carcinomas.
Front-Line High Dose Therapy with Following Autologous Stem Cell Transplantation (ASCT) for Follicular Lymphoma Patients
Authors: Ekaterina S. Nesterova, Sergey K. Kravchenko, Alla M. Kovrigina, Eduard G. Gemdzhian, Aminat U. Magomedova, Elena A. Bariakh, Vladimir I. Vorobyev, Ekaterina A. Iliushkina, Dmitry S. Mariin, Natalia G. Chernova, Olga A. Gavrilina, Anna E. Lukina, Valeri G. Savchenko
Journal: Blood (2014)
Retrospective Analysis of Treatment Outcomes for Patients with Follicular Lymphoma and Comorbidities
Authors: Aya Watanabe, Yoichi Imai, Kenjiro Mitsuhashi, Akihito Shinohara, Norina Tanaka, Kentaro Yoshinaga, Masayuki Shiseki, Naoki Mori, Junji Tanaka
Journal: Blood (2015)
Apoptotic Lymphoma Cells Evoke a Pro-Senescent Stromal Signal That Limits Lymphoma Development.
Authors: Maurice Reimann, Soyoung Lee, Christoph Loddenkemper, Jan Dörr, Vedrana Tabor, Harald Stein, Bernd Dörken, Thomas Jenuwein, Clemens Schmitt
Journal: Blood (2009)
Serum Uromodulin and Mortality Risk in Patients Undergoing Coronary Angiography
Authors: Graciela E. Delgado, Marcus E. Kleber, Hubert Scharnagl, Bernhard K. Krämer, Winfried März, Jürgen E. Scherberich
Journal: Journal of the American Society of Nephrology (2017)

The mucoprotein uromodulin is the most abundant protein in mammalian urine and has important roles in ion transport, maintenance of water and electrolyte balance, and clearance of bacteria from the urinary tract. Low urinary uromodulin concentrations have been associated with increased mortality risk. However, measuring uromodulin in urine has several preanalytic drawbacks, and sensitive assays for the detection of uromodulin in blood have become available. In this study, we investigated the association of serum uromodulin concentration with cardiovascular biomarkers and mortality risk in a large cohort of patients referred for coronary angiography. Uromodulin concentrations were available in 3057 of 3316 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Higher serum uromodulin concentration associated with a favorable metabolic profile, lower prevalence rates of comorbidities (arterial hypertension, diabetes mellitus, and heart failure), and a lower risk for 10-year mortality, with hazard ratios (95% confidence intervals) of 0.65 (0.54 to 0.78), 0.71 (0.58 to 0.88), and 0.57 (0.45 to 0.73) in the second, third, and fourth quartiles, respectively, compared with the first quartile. The association with reduced mortality was independent of other cardiovascular risk factors, including eGFR, and stronger after adjustment for the genotype of the rs12917707 polymorphism at the UMOD locus. Adding serum uromodulin concentration to established cardiovascular risk prediction scores improved risk prediction. Uromodulin may, therefore, be a useful marker for cardiovascular and renal health.
Interleukin 13-mediated colitis in the absence of IL-4Rα signalling
Authors: Jennifer C Hoving, Antony J Cutler, Mosiuoa Leeto, William G C Horsnell, Benjamin G Dewals, Natalie E Nieuwenhuizen, Frank Brombacher
Journal: Gut (2017)

Sufficient evidence points to interleukin 13 (IL-13) as an important pathological factor in UC and raises hopes to a promising new treatment strategy.1–3 However, the outcomes of two recent clinical trials, both published in Gut 2015, suggest otherwise.4 ,5 A commentary published in the same issue described these results as crushing the enthusiasm for anti-IL-13 treatment in UC.6 In this letter, we show evidence that the disease outcome is determined by the type of signalling pathway used by IL-13 in mice. Therefore, we suggest that directly blocking IL-13 remains a potential treatment strategy for a subset of patients with UC that have elevated tissue IL-13 production.

In the first clinical study using anrukinzumab treatment, which targets the IL-4 receptor-alpha (IL-4Rα) and not IL-13 directly, had no effect on improving the clinical response or remission rates of patients with UC.4 In contrast, although patients treated with tralokinumab, which blocks IL-13 directly, showed no improved clinical response rate, there was …
Nivolumab (Anti-PD1) Therapy for Relapsed/ Refractory Primary Central Nervous System Lymphoma and Primary Testicular Lymphoma
Authors: Lakshmi Nayak, Fabio Iwamoto, Ann S. LaCasce, Srinivasan Mukundan, Margaretha G M Roemer, Bjoern Chapuy, Philippe Armand, Scott J. Rodig, Margaret A. Shipp
Journal: Blood (2016)