tbuckley/cabot-search huggingface dataset:
Abstract 23086: Impact of Rivaroxaban Alone or in Combination With Aspirin versus Aspirin in Preventing Graft Occlusion in Patients With CABG Surgery COMPASS CABG
Authors: Andre Lamy, John Eikelboom, Stuart Connolly, Jackie Bosch, Keith A Fox, Salim Yusuf
Journal: Circulation (2017)

Background: Coronary artery bypass grafting (CABG) surgery reduces mortality in patients with severe ischemic heart disease. Patients with recent CABG surgery are at risk for early graft failure which is associated with an increased risk of myocardial infarction (MI) and death. Aspirin reduces the risk of graft failure and major adverse cardiovascular events (MACE) in patients with CABG, but is only modestly effective. We hypothesized that in patients with recent CABG surgery, rivaroxaban in combination with aspirin or rivaroxaban alone would be more effective than aspirin alone for the prevention of bypass graft failure. Methods: COMPASS CABG was designed to evaluate whether rivaroxaban 2.5mg twice-daily in combination with aspirin 100mg daily or rivaroxaban 5mg twice-daily is superior to aspirin 100mg daily for prevention of bypass graft failure and vascular events in patients with recent CABG surgery. The primary outcome was graft failure and the secondary outcome was a composite of MI, stroke, or CV death. Graft patency was assessed with a CT angiogram at 1 year after surgery. Results: Between March 2013 and May 2016, the COMPASS trial randomized 27,395 patients from 602 centers in 33 countries. Of these patients, 1,488 were randomized within 4-14 days after CABG surgery. Elective CABG was performed in 78.4% of these patients. Triple vessel disease was present in 77.8% of patients, double vessel disease in 17.1% and 24.1% of patients had a left main disease. The IMA was harvested as a pedicle in 70.9% of patients and with a skeletonized technique in 29.1%. Vein grafts were harvested in an open fashion in 87.8% of patients and with a minimally invasive approach in 12.2% of patients. Conclusion: The results of COMPASS CABG will be presented on the efficacy and safety of rivaroxaban, alone or in combination with aspirin on graft patency and MACE in the long-term management of patients with recent CABG surgery.
Final analysis of a randomized placebo-controlled double-blind phase II trial of perioperative cimetidine (CIM) in early colorectal cancer (CRC).
Authors: Michael B. Jameson, Michael Arendse, Avinesh Pillai, Judith Warren, Simione Lolohea, Ralph van Dalen, Frank Frizelle, John Keating, Claudia Romano, Ian Bissett, Michael P. N. Findlay
Journal: Journal of Clinical Oncology (2018)

e15678 Background: In a Cochrane meta-analysis of 5 randomised phase 2 trials CIM administered perioperatively with curative-intent surgery for CRC was associated with reduced mortality (HR 0.53, 95% CI 0.32-0.87). In one trial patients (pts) whose tumours expressed either sialyl Lewis antigen X (sLex Ag) or A (sLea = CA19-9) derived greater benefit from CIM. Preclinical studies show that CIM inhibits sLe Ag-mediated adhesion of circulating tumour cell to activated endothelium. Our trial evaluated this interaction in CRC pts having curative-intent surgery; interim analysis at median follow-up of 26 months reported a favourable disease-free survival (DFS) trend: HR 0.76, logrank p = 0.56 (J Clin Oncol 33, 2015 suppl; abstr e14598). The final intention-to-treat analysis is presented. Methods: Staged pts with stage 1-3 CRC were randomised to take cimetidine 800mg BD or placebo orally for 5 weeks, starting 2-7 days before curative-intent surgery. Tumours were immunostained for expression of both sLe Ag and scored independently by two pathologists. Results: Patient and tumour characteristics were reported earlier. In brief 65 pts were randomised to CIM and 63 to placebo and 29% had adjuvant chemotherapy. Postoperative TNM stage was 0-1, 2, 3 and 4 in 27%, 38%, 31%, and 2% respectively. At median follow-up of 65 (60-93) months 27 relapses and 37 deaths had occurred. 5-year DFS with CIM and placebo was 65.5% and 62.2% respectively (HR 1.04, logrank p = 0.92) and was not improved by CIM in pts with > 5% of tumour cells expressing either sLe Ag (seen in 97 of 103 tumours): 5-year DFS was 62.1% and 56.0% with CIM and placebo respectively (HR 1.13, p = 0.69). CIM did not improve 5-year overall survival compared to placebo in all pts (76.9% and 76.0% respectively, HR 0.84, p = 0.59) or in those with sLe Ag in > 5% of tumour cells (80.0% and 68.6% respectively, HR 0.63, p = 0.28). Multivariate Cox proportional hazards analysis revealed no impact of study treatment or sLe Ag expression but significantly worse survival with male sex (p = 0.044) and higher postoperative TNM stage (p = 0.019). Conclusions: Perioperative CIM for 5 weeks did not improve cancer outcomes in CRC regardless of sLe Ag expression. Clinical trial information: ACTRN12609000769280.
TCT-686 Mixed aortic valve disease: Impact on outcome after transcatheter aortic valve implantation
Authors: Konstantinos Stathogiannis, Konstantinos Toutouzas, Maria Drakopoulou, George Latsios, Andreas Synetos, Maria Xanthopoulou, Vasiliki Penesopoulou, George Trantalis, None George Oikonomou, None Maria Karmpalioti, Eleftherios Tsiamis, Dimitrios Tousoulis
Journal: Journal of the American College of Cardiology (2018)
Risk factors for hospitalizations (HOS) among older adults with gastrointestinal (GI) cancers receiving chemotherapy.
Authors: Daneng Li, Can-Lan Sun, Abrahm Levi, Heidi D. Klepin, Rawad Elias, Supriya Gupta Mohile, William P. Tew, Dean Lim, Vincent M. Chung, Joseph Chao, Cynthia Owusu, Hyman B. Muss, Stuart M. Lichtman, Cary Philip Gross, Andrew E. Chapman, Ajeet Gajra, Harvey Jay Cohen, Vani Katheria, Arti Hurria
Journal: Journal of Clinical Oncology (2017)

e21523 Background: Older adults undergoing chemotherapy for GI cancers are at increased risk of HOS due to treatment related toxicity; however, there are limited data regarding which individuals are at greatest risk. We therefore sought to identify risk factors for HOS among older adults with GI cancers receiving chemotherapy. Methods: We performed a secondary analysis of patients age ≥ 65 years with GI cancer who participated in either of 2 prospective studies used to develop (n = 500) and validate (n = 250) a geriatric assessment (GA) based chemotherapy toxicity score for older adults with cancer. The incidence of HOS within 30 days post treatment was determined. The following patient characteristics were captured pre-chemotherapy: demographics, cancer type, stage, laboratory values, chemotherapy type, and GA measures (functional status, comorbidity, psychological state, cognitive function, nutritional status, and social support). Univariate and multivariate logistic regressions were used to estimate the odds ratio (OR) to identify risk factors. Results: A total of 199 adults age 65+ (median 73; range 65-94) with GI cancers (colorectal 43%, gastric/esophageal 25%, pancreas/biliary 32%; Stage I-III 42%, stage IV 58%) receiving chemotherapy (67% poly-chemotherapy) were included. 5-FU chemotherapy was administered alone or in combination in 126 (63%) patients. Sixty five (33%) patients had ≥1 HOS (1 HOS: 55, 2 HOS: 9, 3 HOS: 1). In univariate analysis, hospitalized patients were more likely to be female (p = 0.02), have stage IV disease (p = 0.03), have a diagnosis of non-colorectal GI cancer (p = 0.04), have poly-pharmacy (≥ 5 medications, p &lt; 0.01), decreased hearing (p = 0.05), cardiac comorbidity (p &lt; 0.01), and low serum albumin (p = 0.05). On multivariate analyses, patients who were female (OR = 2.06, 95% CI: 1.05-4.06), with cardiac comorbidity (OR = 3.73, 95% CI: 1.78-7.83), or a diagnosis of stage IV non-colorectal GI cancer (OR = 3.75, 95% CI: 1.50-9.39) were more likely to be hospitalized. Conclusions: HOS during chemotherapy treatment are common among older adults with GI cancers. Female sex, cardiac comorbidity, and a diagnosis of stage IV non-colorectal GI cancer are risk factors for HOS.
Level of activated circulating endothelial cells to predict progression-free survival of Anlotinib treatment in patients with NSCLC: Analysis on ALTER-0303 study.
Authors: Kai LI, Jing Wang, Xinyue Wang, Zhujun Liu, Cuigui Zhang, Peng Chen, Zhaoting Meng, Jinliang Chen, Chun Huang, Xiangli Jiang, Yan Liang, Li Lin, Richeng Jiang, Liuchun Wang
Journal: Journal of Clinical Oncology (2017)

e20530 Background: Activated circulating endothelial cells (aCECs) have been indicated as a potential biomarker of angiogenesis in a variety of cancers. Several studies have revealed that aCECs may reflect the extent of tumor angiogenesis, and the level of aCECs counts may has correlation with progression-free survival (PFS) in anti-angiogenesis therapy on NSCLC patients. Therefore, we investigated the association between aCECs and PFS of Anlotinib treatment in ALTER-0303 study. Methods: NSCLC patients with aCECs counts in ALTER-0303 study were observed. Samples were prospectively collected at six time points: before treatment (baseline), on the 7 th , 15 th , 21 th , 42 th, 63 th day of Anlotinib treatment. aCECs was identified by Flow cytometry (FCM). The prognostic value of aCECs counts was analyzed and, the patients were stratified according to their ratio of the minimum aCECs counts in all time points and counts on baseline (aCECs min/baseline) as &lt;1 and ≥1. Results: Forty-nine patients were included of which 35 and 14 had an aCECs min/baseline&lt;1 and ≥1, respectively in Anlotinib arm. Median follow-up was 8.6 months. In univariate survival analysis, patients with min/baseline&lt;1 had longer PFS [HR=0.439, 95% CI (0.211-0.912), P = 0.023], the median PFS for the patients with aCECs min/baseline &lt;1 and ≥1 were 193 days and 124 days, respectively (shown in Table). However, there were no significant relation between PFS and such aCECs min/baseline ratio found in control arm of ALTER-0303 study. Conclusions: A decrease of aCECs counts from baseline during an initial period of Anlotinib therapy may predict longer PFS and good response in NSCLC patients. Information: NCT02029209, NCT02388919 Clinical trial information: NCT02029209. [Table: see text]
Current situation of re-biopsy in non small-cell lung cancer treated with EGFR-TKI.
Authors: Tomoyo Oguri, Fumiyoshi Ohyanagi, Natsuki Takano, Yosuke Kawashima, Satoru Kitazono, Yuichi Tambo, Noriko Yanagitani, Atsushi Horiike, Takeshi Horai, Makoto Nishio
Journal: Journal of Clinical Oncology (2016)

e20563 Background: Several EGFR-TKI are available in clinical practice and repeated biopsy become important to determine subsequence treatment after initial EGFR-TKI. We retrospectively analyzed the success rate of detect EGFR status of re-biopsy in NSCLC treated EGFR-TKI. Methods: We reviewed medical records of 303 patients treated with EGFR-TKI at our institution during January 2012 and December 2015 and obtained re-biopsy data. Results: 95 (31.4%) patients among 303 patients who had tumor progression with EGFR-TKI re-biopsied and analyzed the EGFR mutation status. Background of 95 patitents were median age :67 years (34-87), gender male/ female: 39 /56, PS0/1/2:65/25/5, stage IV/recurrence/other:48/34/13, smoking history never/ex/current: 48/34/13, histology : adeno/squamous/other 89/2/4, EGFR mutation type; 19del/L858R/Other = 41/49/5, prior EGFR-TKI; Gefitinib/Erlotinib/Afatinib:63/31/1.Tumor samples were obtained from 131 lesions. 26 samples (19.8%) were from primary lesion and 105 samples (80.2%) were from metastatic lesion. Cancer cells were cytologically positive in 113 samples (86.3%) but cancer cells were histologically positive in less half of samples (61 samples, 46.6%).The site of re-biopsies were intra-thoracic site(36 lung tissues, 6 mediastinal lymph node, 43 pleural effusion), 20 supraclavicular lymph nodes, 9 cerebrospinal fluid, 6 liver, 4 ascites and 7 others. Procedure for biopsy were 33 bronchoscopy, 43 thoracentesis, 24 US guided biopsy, 9 CT guided-needle, and 22 other.127 (96.9%) of 131 samples were able to analyzed EGFR mutation. Of them, 100 (76.9%) samples were analyzed EGFR mutation status from cytology samples. The same mutation as primary EGFR mutations were detected in 106 out of 127 (83.5 %). T790M mutations were detected in 46 samples and 5 samples were small cell transformation. Conclusions: About one third of patients treated with EGFR-TKI were re-biopsied and be able to examine EGFR status after failure of EGFR-TKI in clinical practice.
Efficacy and safety of entinostat (ENT) and pembrolizumab (PEMBRO) in patients with melanoma progressing on or after a PD-1/L1 blocking antibody.
Authors: Sanjiv S. Agarwala, Stergios J. Moschos, Melissa Lynne Johnson, Mateusz Opyrchal, Dmitry Gabrilovich, Patrick Danaher, Fang Wang, Susan Brouwer, Peter Ordentlich, Serap Sankoh, Emmett V. Schmidt, Michael L. Meyers, Ryan J. Sullivan
Journal: Journal of Clinical Oncology (2018)

9530 Background: Immune checkpoint inhibitors (ICIs) have improved prognosis for pts with advanced melanoma, but there is an unmet need for pts who progress after ICI. In this group, we reported that ENT, a class I selective histone deacetylase (HDAC) inhibitor, in combination with PEMBRO showed promising activity, through alteration of the immunosuppressive tumor microenvironment. Here we report the first 34 pts with further information on both prior therapies and pre/on treatment tumor samples. Methods: ENCORE-601 is a multicohort study evaluating ENT + PEMBRO. Pts enrolled in Cohort 3 had unresectable or metastatic melanoma, were previously treated with a PD-(L)1-blocking antibody, and experienced progression on or after therapy. The enrollment target was 34 pts and revised to 52 to increase statistical power and decrease Type I error. Pts were treated with ENT 5 mg PO weekly and PEMBRO 200 mg IV Q3W. Primary endpoint was ORR as assessed by irRECIST. Tumor biopsies and blood samples for immune correlates were obtained pre- and on-treatment. Results: Of the first 34 patients, 14 had refractory disease to prior PD-(L)1 therapy, and only 2 had a documented prior response. Median duration of prior PD-(L)1 therapy was < 6 months and the median time from last dose was 65 days. 22 pts had prior ipilimumab and 6 had progressed on a BRAF inhibitor. With ENT + PEMBRO, 6 of 34 pts achieved a confirmed PR (ORR = 18%, 95% CI: 6.8-34.5), and 10 pts continue on study (3 have been on treatment > 1 year). Frequent ( > 15%) related AEs include nausea, fatigue, diarrhea, and pruritus. Preliminary analysis of gene expression in pts with tumor samples pre- and on-treatment (n = 9) indicates increased inflammation in the tumor microenvironment after treatment; a decrease in MDSCs (–35.7%) and an increase in CD8+ T cells (47.4%) was also observed. Conclusions: ENT + PEMBRO continues to demonstrate promising anti-tumor activity and acceptable safety in patients with melanoma who have progressed on prior PD-(L)1 blockade. Preliminary biomarker analysis supports the hypothesis that the addition of ENT restores inflammation in the tumor microenvironment necessary for successful re-treatment with an anti–PD-(L)1. Clinical trial information: NCT02437136.
TCT-313 In-Vivo Acute Expansion of Bioresorbable Scaffolds and Metallic Stents in Normal Porcine Coronary Arteries: A Critical Appraisal of Compliance Chart Accuracy
Authors: Nicolas Isaza, Marco Ferrone, Gilberto Melnick, Yanping Cheng, Gerard Conditt, Juan Granada, Grzegorz Kaluza
Journal: Journal of the American College of Cardiology (2018)
Microbiota-gut-brain research: A critical analysis
Authors: Katarzyna B. Hooks, Jan Pieter Konsman, Maureen A. O'Malley
Journal: Behavioral and Brain Sciences (2018)

Abstract Microbiota-gut-brain (MGB) research is a fast-growing field of inquiry with important implications for how human brain function and behaviour are understood. Researchers manipulate gut microbes (“microbiota”) to reveal connections between intestinal microbiota and normal brain functions (e.g., cognition, emotion, and memory) or pathological states (e.g., anxiety, mood disorders, and neural developmental disorders such as autism). Many claims are made about causal relationships between gut microbiota and human behaviour. By uncovering these relationships, MGB research aims to offer new explanations of mental health and potential avenues of treatment. So far, limited evaluation has been made of MGB's methods and its core experimental findings, many of which are extensively reiterated in copious reviews of the field. These factors, plus the self-help potential of MGB, have combined to encourage uncritical public uptake of MGB discoveries. Both social and professional media focus on the potential for dietary intervention in mental health, and causal relationships are assumed to be established. Our target article has two main aims. One is to examine critically the core practices and findings of experimental MGB research and to raise questions about them for brain and behavioural scientists who may not be familiar with the field. The other is to challenge the way in which MGB findings are presented. Our positive goal is to suggest how current problems and weaknesses may be addressed, in order for both scientific and public audiences to gain a clearer picture of MGB research and its strengths and limitations.
First-in-human phase 1-2A study of CB-103, an oral Protein-Protein Interaction Inhibitor targeting pan-NOTCH signalling in advanced solid tumors and blood malignancies.
Authors: Jose Manuel Perez Garcia, Javier Cortés, Anastasios Stathis, Rogier Mous, Elena López-Miranda, Analía Azaro, Sofia Genta, Paolo Nuciforo, Ana Vivancos, Renata Ferrarotto, Francesco Bertoni, Davide Rossi, Nicole Spardy Burr, Oliver Schönborn-Kellenberger, Karin Jorga, Laura Beni, Rajwinder Lehal, Michael Bauer, Dirk Weber, Elena Garralda
Journal: Journal of Clinical Oncology (2018)

TPS2619 Background: NOTCH signalling is a key development pathway whose aberrant activation is recognised to play an oncogenic role in human cancers. When NOTCH signalling is inappropriately activated by genetic alterations, it becomes an oncogenic driver for NOTCH-dependent cancers, while upregulation of NOTCH receptors is linked to resistance to standard of care. CB-103 is a new small molecule protein-protein interaction (PPI) inhibitor able to target assembly of the NOTCH transcription complex in the cell nucleus leading to downregulation of NOTCH target genes (c-MYC, CCND1, HES1) and inhibition of NOTCH signalling independently of NOTCH mechanisms of activation. CB-103 has demonstrated efficacy and tolerability in different preclinical tumor models derived from various NOTCH-driven cancer indications and in blood from NOTCH-activated leukemia pts. Methods: This study is a multi-centre, open label, non-randomised, phase 1-2A dose escalation study in adult patients (pts), with expansion arms of oral CB-103. Aim of phase 1 is to find the MTD/RP2D. The starting dose is targeting a plasma exposure (daily AUC) that has reasonable safety margin and allows reliable determination of pharmacokinetics (PK). An adaptive Bayesian logistic regression model for dose escalation is implemented in phase 1 to guide determination of MTD/RP2D. Full PK sampling profiles will be taken on days 1 & 8 of cycle one (28 days) and day 1 of cycle two. NOTCH-related PD and Biomarker exploratory analyses are planned on tumour biopsies, hair follicles and blood samples (liquid biopsy). Administration schedule (once-daily) may be adapted depending on PK and safety. 3-6 eligible pts regardless of NOTCH pathway activation status are enrolled per dose group in phase 1, while pts in phase 2A will be selected for NOTCH pathway genetic alterations. Phase 2A will assess preliminary efficacy of CB-103 in expansion arms across different indications using Bayesian design. Enrolment into 1st dose group (15mg) started with first pt treated on 20Dec17: 7 pts registered with 2 screen failures, 1 discontinued due to early cancer progression and 4 in treatment in their first treatment cycle. Clinical trial information: NCT03422679.
Abstract 18468: Atrial Fibrillation Ablation in Patients With Complete Heart Block
Authors: Amr F. Barakat, Karim Abdur Rehman, Ayman A. Hussein, Oussama M. Wazni, Khaldoun Tarakji, Walid Saliba, Bruce Lindsay, Bryan Baranowski
Journal: Circulation (2016)

Introduction: Atrioventricular node (AVN) ablation with placement of a permanent pacemaker is typically reserved as the final therapeutic approach for patients with symptomatic atrial fibrillation ...
Implementation of strategies to increase genetic counseling referral rates for ovarian cancer patients.
Authors: Kara J. Milliron, Victoria Prince, Lauren Hipp, Shitanshu Uppal, Melissa Brackmann, R. Kevin Reynolds, Sofia Merajver, Karen McLean
Journal: Journal of Clinical Oncology (2018)

1590 Background: Genetic counseling is recommended for all women diagnosed with epithelial ovarian cancer, independent of family history. Despite the potential benefits to the patient and her family, referral rates remain low. We sought to assess referral rates at our institution and implement two strategies to improve both the rate of referral and the completion of counseling and testing – (1) discussion of referral for all patients reviewed at multidisciplinary treatment planning conference and (2) option of telephone counseling. Methods: Patients with a diagnosis of epithelial ovarian, fallopian tube or primary peritoneal cancer since 10/1/14 were identified through pathology reports and chart review was performed to obtain demographic data and cancer details including histology, grade and stage. Personal and family history of cancer, date of genetic counseling referral, method of genetic counseling (in-person vs. telephone), date of genetic testing and the result of genetic testing were also abstracted. Results: The rate of genetic counseling referral was 63.5% (214/337 patients). Of those referred, 61% (131/214) underwent counseling, with 77% (165/214) in person and the 23% (49/214) via telephone after initiation of the telephone counseling program in September 2017. Overall, 90% of patients who received genetic counseling underwent testing, including 92.7% of the in-person counseling cohort and 67.9% of the telephone counseling cohort to date. In total, 24.1% of patients harbored a pathogenic gene mutation, with BRCA1 mutations most common (16.5% of patients). Variants of undetermined significance were identified in 11.3% of patients. Conclusions: Telephone genetic counseling and mandatory discussion of referral at the time of treatment planning conference both appear to facilitate genetic counseling and ascertainment of actionable germline mutations. Overall, referral rates are high at our institution. The implementation of telephone-based genetic counseling programs has the potential to improve both counseling and testing rates, particularly when in-person counseling is not available or is delayed.