tbuckley/cabot-search huggingface dataset:
Topoisomerase expression in solid tumors: Analysis of 24,262 patient specimens.
Authors: Gregory M. Heestand, Maria Clemence Schwaederle, David Arguello, Sandeep K. Reddy, Zoran Gatalica, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2015)

e22077 Background: Topoisomerase I and IIα (TOPO1 and TOP2A) play key roles in DNA replication and increased expression has been associated with chemotherapy response incolorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential targets in other malignancies and, therefore, we analyzed TOPO1 protein expression and TOP2A amplification in patient specimens across cancer types. Methods: In total, 24,262 specimens were evaluated at a CLIA-certified laboratory. Tissue from 23,586 malignancies was assayed for TOPO1 protein by immunohistochemistry (1D6), with positivity defined as 2+ staining in ≥ 30% of cells. TOP2A, which encodes topo IIα protein, was assessed by fluorescence in-situ hybridization (Vysis TOP2/CEP17 probe) for amplification (5,171 tumors). Results: Overexpressed TOPO1 protein was present in 51% of all tumor types including: colon cancer (47%), small cell lung, gastroesophageal and esophageal, thymic, gastric, anal, breast, prostate, and poorly-differentiated neuroendocrine cancers, > 60%. Four percent of the tumors had TOP2A amplification including 5% of invasive breast cancers, 17% of gallbladder and 12% of gastroesophageal and esophageal cancers. Since HER2 and TOPO2A co-amplification have been investigated for predictive value for anthracycline benefit (albeit with inconsistent results), we analyzed specimens for HER2 amplification as well. Overall, 4903 specimens were assessed for both TOPO2A and HER2 amplification; 129 (2.6%) had co-amplification. Conclusions: Increased TOPO1 expression and TOP2A amplification are present in multiple malignancies, and TOPO2A may be co-amplified with HER2 in approximately 2.6% of cases. The correlation of these changes with sensitivity to chemotherapy not traditionally administered to these tumor types merits further investigation.
Abstract 12552: A Novel Predictor of Weight Change During Hospitalization in Patients With Acute Heart Failure Syndromes in the Emergency Department
Authors: Fumie Otomo, Mitsuaki Endo, Eiichi Akiyama, Yasushi Matsuzawa, Masaaki Konishi, Toru Suzuki, Shintaro Koga, Sae Saigo, Mitsuho Inoue, Kiyoshi Hibi, Hideo Himeno, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2015)

Introduction: Recent data showed acute heart failure syndromes (AHFS) could occur without weight gain, and often be triggered by rather a redistribution of fluids to the lungs without systemic congestion. In this subtype of AHFS, excessive diuretic and vasodilator therapy as first-line decongestion therapy in the emergency department (ED) may lead to dehydration and hypotension, subsequently resulting in serous organ hypoperfusion. Therefore, an accurate assessment of body fluid status is essential in AHFS. Methods: We studied 196 consecutive AHFS patients (77±12 years, 54% men, left ventricular ejection fraction 37±15%), who discharged after restoration of clinical stability (length of hospital stay 18±8 days). We collected clinical, laboratory, imaging and weight information. Measurements of total body water (TBW) and extracellular water (ECW) using bio-impedance analysis (BIA) were performed immediately at admission to the ED. Patients were divided into 2 groups according to the median % weight change (%WC) during hospitalization. Results: Weight and brain natriuretic peptide levels significantly decreased following decongestion therapy (from 59.0±14.3 to 52.9±12.9 kg, and from 779 [508-1289] to 285 [151-547] pg/ml, respectively, both p&lt;0.001). High-%WC group (≥9.4%) had lower systolic blood pressure (159±35 vs. 171±40 mmHg), and higher prevalence of day-time admission (79 vs. 54%), peripheral edema (82 vs. 43%) and pleural effusion on chest radiography (88 vs. 71%), and larger inferior vena cava diameter (20±5 vs. 17±5 mm) and lower tricuspid annular plane systolic excursion (14±4 vs. 16±4 mm) on echocardiography, and higher estimated glomerular filtration rate (eGFR) (58±29 vs. 46±21 ml/min/1.73m2), lower serum total protein level (6.5±0.6 vs. 6.8±0.7 g/dl), and higher ECW/TBW (0.423±0.015 vs. 0.405±0.013) compared with low-%WC group (p&lt;0.01 for all). Multiple linear regression analysis revealed that pleural effusion, eGFR, and ECW/TBW were significantly associated with %WC. ECW/TBW correlated most strongly with %WC (r=0.61, p&lt;0.0001). Conclusions: ECW/TBW helps enable emergency physicians to implement goal-directed treatment more rapidly and appropriately avoiding both dehydration and volume retention in AHFS.
Continued evaluation of a 31-gene expression profile test (GEP) for prediction of distant metastasis (DM) in cutaneous melanoma (CM).
Authors: David H. Lawson, Robert W. Cook, Clare Johnson, Maria C. Russell, Rodabe Navroze Amaria, Jeff Wilkinson, Pedram Gerami, Derek Maetzold, Laura Ferris, Kristen M. Oelschlager, Anthony Greisinger, Rene Gonzalez, T Christopher Windham, Brooke Middlebrook, Keith A. Delman, Stephen Lyle
Journal: Journal of Clinical Oncology (2015)

9066 Background: A GEP has been validated as an independent predictor of DM, distant metastasis free survival (DMFS) and overall survival (OS) (Gerami, CCR 2015; Gerami JAAD, 2015). This abstract combines the third validation cohort study with the two prior studies for analysis by T factor subgroups.Methods: 555 patients (pts) were enrolled in a multi-center IRB approved archival tissue study with a primary endpoint of DMFS. 492 CMs had T-factors available for analysis. Quantitative RT-PCR and Radial Basis Machine modeling classified CM tumors as low risk Class 1 vs. high risk Class 2. Results are reported for thin (T1), intermediate (T2/T3) and thick (T4) lesions. Most patients were node negative clinically or by sentinel node biopsy.Results: GEP Class 1 vs 2 was found to be a significant predictor of DMFS and OS (log-Rank p<0.0001), and GEP, Breslow’s thickness, and ulceration were independent predictors in Cox multivariate analysis (DMFS HR=2.7, p=0.0003; 2.2, p=0.03; 3.3, p<0.0001, respectively and OS HR=2.8, p=0.0002, 2.5, p=0.01, 1.7, p=0.01, respectively). In the T2/T3 N0 cohort (n=180) frequency of class 2 signature increases with depth [T2:35/78 (45%) Class 2; T3:75/102 (74%) Class 2] and ulceration [nonulcerated: 54/108 (50%) Class 2; ulcerated: 53/63 (84%) Class 2]. The table reflects survival analysis in this cohort. In the T1 group (median followup for non-DM group = 7.4 yrs) 14/173 (8%) reported DM. For T4 group: 42/80 (53%) developed DM. Data not considered adequate for further analysis of either group.Conclusions: GEP offers prognostic information that complements conventional staging at least in patients with T2/T3 CM. Ongoing studies will further define the role of GEP in evaluating these patients. T2/T3 N0 group (n=180) DM all cause deaths Total events 51/180 (28%) 47/180 (26%) Class 1 7/70 (10%) 7/70 (10%) Class 2 44/110 (40%) 40/110 (36%) Of ulcerated primaries Class 1 5/19 (26%) 5/19 (26%) Class 2 28/53 (53%) 21/53 (40%) K-M* analysis Class 1 5-yr rate 91% 90% Class 2 5-yr rate 58% 63% p-value <0.0001 <0.0001 Cox multivariate** HR (p-value) HR (p-value) GEP 3.9 (0.003) 5.3 (0.0007) ulceration 2.6 (0.002) 1.5 (0.203)
Assessing effectiveness in acne clinical trials: steps towards a core outcome measure set
Authors: D.M. Thiboutot, A.M. Layton, M.‐M. Chren, E.A. Eady, J. Tan
Journal: British Journal of Dermatology (2019)

Acne ranks second to dermatitis in terms of global burden of skin disease. As such, it is essential that data on treatment efficacy are generated in a way that maximizes the opportunity for comparison among treatments. Interest in developing core outcome sets for use in clinical trials to standardize data collection in skin disease is surging. The goal of this review is to provide an update on the efforts underway, challenges encountered and future directions in the development of an acne core outcome measure set for use in clinical trials. The activities of the Acne Core Outcomes Research Network (ACORN) are presented in the context of currently acceptable methodologies for core outcome set development. Emphasis is placed on following a rigorous methodology, involving patients and recognizing a role for emerging technologies.
THU-383-Dried blood spots: A useful tool for virologically caracterising the hepatitis C virus epidemic
Authors: Adrian Antuori Torres, Vincent Montoya, Verónica Saludes, Jeffrey Joy, Sara González-Gómez, Cinta Folch, Jordi Casabona, Núria Ibáñez, Joan Colom, Elisa Martró
Journal: Journal of Hepatology (2019)
PS-132-The acetyl-CoA carboxylase inhibitor PF-05221304 exerts direct effects on hepatic inflammation and fibrosis independent of benefits on steatosis
Authors: Trenton Ross, Kenneth Kelly, Anthony Rinaldi, Matthew Lech, Robert Martinez, Collin Crowley, Santos Carvajal Gonzalez, Magalie Boucher, Dinesh Hirenallur Shanthappa, Jeffrey Morin, Alan C. Opsahl, Sarah RVargas, Kendra Bence, Jeffrey A Pfefferkorn, William Esler
Journal: Journal of Hepatology (2019)
Abstract 12158: Population Thresholds for Systematically Applying Nurse-Led Chronic Heart Failure Management Programs to Reduce Recurrent Hospitalization and Prolong Survival
Authors: Simon Stewart, Tracey Gerber, Yih Kai Chan, Melinda Carrington
Journal: Circulation (2014)

Background: In many countries, a jurisdictional (regional or health fund membership) approach to applying nurse-led, multidisciplinary management programs for high risk individuals hospitalized with chronic heart failure (CHF) has led to their inconsistent application. A health service perspective was therefore used to determine the overall value of funding services for a whole population. Methods: Data from a contemporary study of the burden of CHF in Australia (population ~ 24 million of whom ~25% live in regional settings) to identify the number of de novo admissions for CHF per annum (n=19,397) were used. From these we estimated the proportion of cases readmitted (63% - all cause), days of related hospitalization (44,500 days from 5,300 admissions) and case-fatality (27%) within 12 months. Health economic data from a recent multicentre trial of CHF management were then applied to estimate the cost impact ($US) of applying gold-standard management to de novo CHF cases. Results: Total health care expenditure (excluding index admission and incremental CHF management) for managing de novo cases of CHF is estimated at ~$300 million/annum. Of this total, $240 million (68%) is attributable to hospital care plus device-based therapies. Applying nurse-led multidisciplinary CHF management to all cases (with up-titration of therapy and increased face-to-face and remote contacts as required) would cost ~ $35 million/annum. In order to achieve a cost-neutral state, this service would need to achieve a minimum reduction of 6,500 days (15% reduction) in recurrent hospital stay (all cause). At proven, evidence-based thresholds of impact, a 20% - 30% reduction in recurrent hospital stay would provide annual savings of $12 - 35 million/annum. A one third reduction in mortality at 12 months would also result in 2,100 lives saved at a minimum cost &gt;$17,000 per annum (neutral impact on recurrent hospital stay). Conclusions: These data provide a compelling case for adopting a whole population/health care system approach to systematically applying CHF management programs to reduce recurrent hospital stay and mortality in de novo cases of CHF.
Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis
Authors: Kiri A. Sandler, Ryan R. Cook, Jay P. Ciezki, Ashley E. Ross, Mark M. Pomerantz, Paul L. Nguyen, Talha Shaikh, Phuoc T. Tran, Richard G. Stock, Gregory S. Merrick, David Jeffrey Demanes, Daniel E. Spratt, Eyad I. Abu-Isa, Trude B. Wedde, Wolfgang Lilleby, Daniel J. Krauss, Grace K. Shaw, Ridwan Alam, Chandana A. Reddy, Daniel Y. Song, Eric A. Klein, Andrew J. Stephenson, Jeffrey J. Tosoian, John V. Hegde, Sun Mi Yoo, Ryan Fiano, Anthony V. D’Amico, Nicholas G. Nickols, William J. Aronson, Ahmad Sadeghi, Stephen C. Greco, Curtiland Deville, Todd McNutt, Theodore L. DeWeese, Robert E. Reiter, Jonathan W. Said, Michael L. Steinberg, Eric M. Horwitz, Patrick A. Kupelian, Christopher R. King, Amar U. Kishan
Journal: European Urology (2019)
Comment on Wright et al. Increased Reporting of Immune Checkpoint Inhibitor–Associated Diabetes. Diabetes Care 2018;41:e150–e151
Authors: Line Bisgaard Jørgensen, Knud Yderstræde
Journal: Diabetes Care (2019)

We find the article by Wright et al. (1) very interesting. They describe 283 cases of new-onset diabetes mellitus (DM) after treatment with checkpoint inhibitors (CPI) from the World Health Organization’s database. The aim of the study was to characterize this group of patients who developed DM after receiving treatment with CPI.

Recently, we performed a review including 25 cases with new-onset DM after treatment with CPI (2). In accordance with the findings of Wright et al. (1), we also found a wide range of time of DM onset, ranging from 7 to 365 days after receiving the first dose of CPI. In their article, Wright et al. …
SAT-341-MET409, an optimized sustained FXR agonist, was safe and well-tolerated in a 14-day phase 1 study in healthy subjects
Authors: Hubert Chen, Karl Cremer, Eric Bischoff, Kyoung-Jin Lee, Rozalyn Littler, Jeroen van de Wetering, Gerhard Arold, Minh-Nguyet Duong, Ken Song
Journal: Journal of Hepatology (2019)
FRI-021-Comparing the predictive performance of the Mayo risk score and the GLOBE score in a large cohort of patients with primary biliary cholangitis
Authors: Jorn Goet, Maren Harms, Annarosa Floreani, Tony Bruns, Florian Prechter, Harry Janssen, George Dalekos, Verhelst Xavier, Christophe Corpechot, Pietro Invernizzi, Marlyn J. Mayo, Pier Maria Battezzati, Frederik Nevens, Andrew L. Mason, Kris V. Kowdley, Cyriel Ponsioen, Douglas Thorburn, Anna Reig, Keith D. Lindor, Willem J Lammers, Nikolaos Gatselis, Gideon Hirschfield, Bettina Hansen, Adriaan Van der Meer, Albert Parés, Henk Van Buuren
Journal: Journal of Hepatology (2019)
PS-150-Evidence for the presence of infectious virus in the serum from chronic hepatitis B patients suppressed on nucleos (t)ide therapy with detectable but not quantifiable HBV DNA
Authors: Dara Burdette, Andrea Cathcart, Allyson Shauf, Rosanna Win, Shiva Zaboli, Charlotte Hedskog, Evguenia S Svarovskaia, Vivian Barry, David Inzunza, John F. Flaherty, Anuj Gaggar, Simon Fletcher, Henry Chan, Hongmei Mo, Scott Lazerwith, Becket Feierbach, Bill Delaney
Journal: Journal of Hepatology (2019)
Frailty and outcomes in older adults undergoing pancreaticoduodenectomy.
Authors: Tri Minh Le, Gradon Nielsen, Mark Smolkin, William Dale, Erika E. Ramsdale
Journal: Journal of Clinical Oncology (2015)

9530 Background: Pancreaticoduodenectomy (PD) is the only potentially curative treatment for pancreatic cancer. Studies show older adults are at higher risk for poor outcomes. The Balducci Frailty Criteria have been shown to risk-stratify older adults with cancer in non-surgical settings. The purpose of this retrospective, single-institution review is to examine the correlation between preop frailty criteria and postop outcomes in older cancer pts undergoing PD. Methods: Pts ≥ 65y who underwent PD for cancer of the pancreas, ampulla, duodenum, or bile ducts between January 2002 and October 2013 were eligible for the study. A pt was considered “frail” if at least 1 were true: 1. Age ≥ 85y; 2. ≥ 3 significant comorbidities; 3. Dependent for ≥ 1 ADL; 4. Geriatric syndrome present. Primary study endpoints were 30 and 90 day mortality, with secondary endpoints of postop surgical site infections, pneumonia, UTI, sepsis, ventilator dependence > 48 hours, unplanned re-intubation, 30-day readmission, discharge to home versus assisted living, and median hospital stay. P-values were calculated using a chi-square test. Length of hospital stay was analyzed using the Wilcoxon rank-sum test. Results: 201 consecutive pts were included, and 88 were considered
High expression of Bcl-2 to predict poor outcome in diffuse large B-cell lymphoma patients with low international prognostic index receiving CHOP-based chemotherapy.
Authors: Hyun Woo Lee, Mi Sun Ahn, Jae Ho Han, Seok Yun Kang, Seong Hyun Jeong, Jun Seong Park, Jang Hee Kim, Jin-Hyuk Choi
Journal: Journal of Clinical Oncology (2015)

e19511 Background: The prognostic significance of various drug resistance-related proteins was evaluated in diffuse large B cell lymphoma (DLBCL) patients (pts) treated with cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with or without rituximab (R). Methods: Pretreatment biopsy samples from 111 pts (stage I: 15, II: 29, III: 34, IV: 33 pts) with DLBCLwere analyzedforBcl-2, Bcl-6, p53, Bcl-6, Topoisomerase-II and β-tubulin expression by immunohistochemistry. Thirty-nine pts were treated with CHOP, while 72 pts with R-CHOP. Results: The median follow-up duration was 105 months in survivors and 8-year overall survival (OS) rate of all pts were 45.8%. In univariate analysis, 8-year OS rate of pts with high expression of Bcl-2 was significantly inferior compared to that of pts with low expression (29.4 % vs. 65.8 %, p = 0.001), while high expression of Bcl-6 (p = 0.469), p53 (p = 0.800), Topoisomerase-II (p = 0.783) and β-tubulin (p = 0.867) were not associated with outcome of pts. According to chemotherapy regimen, prognostic significance of high expression of Bcl-2 was observed in R-CHOP group (p = 0.001), but not in CHOP group (p = 0.264). In terms of international prognostic index (IPI), in pts with low IPI, high expression of Bcl-2 was associated with poor outcome not only in all pts (p = 0.003) but also in R-CHOP group (p = 0.004), without significant correlation with OS in pts with high IPI (p = 0.309), even in those of R-CHOP group (p = 0.205). In multivariate analysis, high expression of Bcl-2 was a significant independent prognostic factor of poor OS (p = 0.022), along with high IPI ( ≥ 3) (p < 0.0001) and CHOP chemotherapy (p = 0.014) in all pts. In R-CHOP group, both high expression of Bcl-2 (p = 0.007) and high IPI (p = 0.001) were independent prognostic factors of poor outcome. In pts with low IPI, high expression of Bcl-2 was independently associated with poor OS (p = 0.006). Conclusions: In DLBCL pts treated with R-CHOP, expression status of Bcl-2 may be a useful prognostic factor especially in pts with low IPI.
The effect of platinum and docetaxel based chemoradiotherapy on survival in locally advanced unresectable non-small cell lung cancer patients.
Authors: Cigdem Usul Afsar, Meral Gunaldi, Feryal Karaca, Ismail Oguz Kara, Berksoy Sahin, Berna Bozkurt Duman, Melek Erkisi, Semra Paydas
Journal: Journal of Clinical Oncology (2015)

e18538 Background: Lung cancer is the leading cause of cancer mortality worldwide. Chemotherapy (CT) is an integral part in the treatment of locally advanced NSCLC (LA-NSCLC) as it improves survival in all subgroups of patients, whether treated with surgery or radiotherapy, as shown in meta-analyses based on individual patient data. In this study, our aim was to overview our data retrospectively in LA-NSCLC patients and to explore which CT regimen is more effective. Methods: One hundred and thirty-two patients were included in this study. Seventy-six of the patients received 60 Gy radiotherapy (RT) and weekly 20 mg/m2 docetaxel and 20 mg/ m2 cisplatin (P) chemotherapy concomitantly. Five patients received P 50 mg/m2 intravenously (IV) on days 1, 8, 29, and 36 and etoposide (E) 50 mg/m2 IV on days 1-5 and 29-33 concurrently with chest RT to 60 Gy. Nine patients received weekly carboplatin AUC 2 and paclitaxel 50 mg/m2 and forty-two patients received only cisplatin 20 mg/m2 concurrently with 60 Gy chest RT. Results: Median age of the dead patients was 61,20±9,96 and 57,70±8,60 for living patients. One hundred and twenty patients were men and the remaining were women. Seventy five patients had adenocarcinoma, forty six patients had squamous cell carcinoma and eleven were nonsmall cell lung carcinoma. Following concomitant CRT, 26 patients (20%) showed complete and 66 patients (50%) showed partial response (total response rate was 70%). The median follow-up was 22 months (range: 8-36 months). The median overall survival was 40 months for stage II patients, 29 months for stage IIIA and 21 months for IIIB patients. Esophagitis in ten (13%) patients, neutropenia in fifteen (9%) patients and pneumonitis in eleven (12%) patients developed as grade III-IV toxicity due to concomitant CRT. Consolidation chemotherapy was given to patients with partial response. Conclusions: There are no clinical trials that have established the optimal regimen for concurrent chemoradiotherapy. In our study; patients were treated with different types of chemotherapy regimens during radiotherapy but the most effective one was cisplatin and docetaxel. This finding should be evaluated in larger clinical trials.
THU-145-High real-world effectiveness of elbasvir/grazoprevir in a HCV genotype 1 population with a migration background and predominant subtype 1b infection: Results from the German hepatitis C registry (DHC-R)
Authors: Dietrich Hüppe, Albrecht Stoehr, Markus Cornberg, Hartwig Klinker, Renate Heyne, Christine John, Karl-Georg Simon, Manfred Bilzer, Veronika Guenther, Vanessa Witte, Claus Niederau
Journal: Journal of Hepatology (2019)
A global genomic and small molecule inhibitor interrogation of KIT mutant melanoma to reveal underlying biology and novel molecular targets.
Authors: Junna Oba, Wei-Lien Wang, Agda Karina Eterovic, Clifford C. Stephan, Jason Roszik, Charuta Ravindra Kale, Cara L. Haymaker, Mark Routbort, Lauren Elaine Haydu, Chantale Bernatchez, Michael A. Davies, Alexander J. F. Lazar, Elizabeth A. Grimm, Scott Eric Woodman
Journal: Journal of Clinical Oncology (2015)

9039 Background: Activating mutations in KIT are present in 15-20% of acral lentiginous (AL), mucosal (MM) and chronic sun-damaged melanomas. Functional studies in KIT mutant melanoma have been hampered by a paucity of cell lines with recurrent mutations, and limited information about the molecular context in which they occur. This study analyzes the co-mutation status of a large set of cancer-related genes that could influence cell signaling programs in KIT mutant melanomas. Further, we perform first-to-date functional studies on a melanoma cell line with a common (10%) recurrent KIT mutation at amino acid position 822. Methods: Results of a CLIA-certified clinical next-generation sequencing (NGS) platform that interrogates regions of recurrent mutations in 46 cancer-related genes for 1430 melanoma patients were reviewed to identify tumors with mutations in KIT (n = 116). Those tumors were analyzed for associated clinical and molecular characteristics. A novel KIT mutant (N822Y) melanoma cell line was generated from an AL tumor, upon which global copy number, protein activation and high-throughput small molecule inhibitor testing were performed. Results: Among patients with clinical NGS results, 116 tumors with KIT mutations were identified (46 non-acral cutaneous [CM], 26 AL and 44 MM). Unlike KIT mutant CMs, AL and MM tumors harbored few non-redundant KIT missense mutations or mutations in known oncogenes (BRAF, N/H-RAS), and when present, mutations in tumor suppressor genes were more frequent in CM tumors by the technique employed. Low frequency hotspot mutations in CTNNB1 were present in all KIT mutant subtypes (2-12%). A bioactive 1,161 compound screen of an AL KIT N822Y cell line revealed a selective set of compound classes (KIT, RAF, PI3K-MTOR, CDK inhibitors) to meet threshold efficacy. Conclusions: AL and MM KIT mutant melanomas lack co-mutations frequently present in CMs. High-throughput compound screening test of KIT (N822Y) melanoma cell line suggests a small set of compound classes for combinatorial screening.