tbuckley/cabot-search huggingface dataset:
Docetaxel in advanced breast cancer (BC) in the community setting: Analysis of treatment and prognostic factors in 129 South African patients
Authors: P. Ruff, R. Pienaar, A. Gudgeon, F. Michaelis, H. Neethling
Journal: Journal of Clinical Oncology (2006)

10715 Background: Docetaxel has become a standard of care in BC, initially as salvage therapy, then as front line therapy for advanced disease and now in the adjuvant setting. Patients and Methods: A survey of the use of docetaxel in advanced BC in the community setting included 129 patients (128 females; 1 male) treated by 29 oncologists from 27 centers in South Africa from August 2002 until October 2003. Median age was 51 years (range 25–82 years). Median time between initial diagnosis and treatment was 27 months (range 6 days - 22 years). Although the survey was planned for advanced disease, 10 patients received adjuvant therapy; 59 received 1 st line docetaxel and the rest 2 nd line or more; major metastatic sites were bone (n = 57), liver (n = 45) and lung (n = 37); 47% patients were ER+, 30% ER- and 23% ER unknown; most had good PS (63 ECOG PS 0, 53 PS 1); 19 patients had no prior chemotherapy, 58 prior adjuvant therapy and 52 prior non-taxane chemotherapy for advanced disease. 62% patients received single agent docetaxel including 75–100mg/m 2 3–4 weekly (38%) and 20–50mg/m 2 weekly (19%) with 38% receiving docetaxel plus another drug. Results: At 1 year, 88 patients (68.8%) were alive. Log rank analysis showed age &gt;40 years (p = 0.025) and PS 0 (p = 0.0000) were prognostic factors for survival, while post docetaxel chemotherapy (p = 0.062), 1 st line vs more advanced disease (p = 0.3557), weekly vs 3–4 weekly docetaxel (p = 1.00), ER status (p = 0.1527) and menopausal status (p = 0.997) were not. Of 59 1 st line patients, 40 (67.8%) were alive at 1 year. Age &gt;40 years (p = 0.0015) and PS 0 (p = 0.031) as well as ER status (p = 0.011) and post docetaxel chemotherapy (p = 0.0436) were prognostic factors for survival, while menopausal status (p = 0.0609) and weekly vs 3–4 weekly docetaxel (p = 0.248) were not. 115 patients had 655 adverse events (AEs) including 111 serious AEs (SAEs) in 55 patients. 470 AEs were drug related with 54 SAEs including neutropenia (8), diarrhea (6) febrile neutropenia (5), emesis (5), cellulitis (3) and pneumonia (3). There were no treatment related deaths. Conclusions: Docetaxel alone or in combination is effective and well tolerated therapy in advanced BC especially in patients over 40 years of age with good PS (ECOG 0). Sponsored by Aventis Pharma (South Africa). No significant financial relationships to disclose.
STATINS ARE ASSOCIATED WITH LOWER RISK OF HEART FAILURE AFTER ANTHRACYCLINE AND TRASTUZUMAB CHEMOTHERAPY FOR EARLY STAGE BREAST CANCER
Authors: David Bobrowski, Limei Zhou, Peter Austin, Oscar Calvillo Arguelles, Eitan Amir, Douglas Lee, Paaladinesh Thavendiranathan, Husam Abdel-Qadir
Journal: Journal of the American College of Cardiology (2020)
Prospective assessment of hypercalcemia of malignancy and infectious complications.
Authors: Monique Celeste Tavares, Graziela Zibetti Dal Molin, Tiago Cordeiro Felismino, Marcello Ferretti Fanelli, Helano C. Freitas, Milton Jose Barros e Silva
Journal: Journal of Clinical Oncology (2013)

e20644 Background: The hypercalcemia of malignancy (HM) is the major metabolic disorder seen in oncologic patients. Is a poor prognostic factor, given the median survival of 60 to 90 days. One hypothesis for this high mortality is a predisposition to infections. In the immune system, the vitamin D receptor and the vitamin D are responsible for immunomodulatory activities and may lead to an inhibition of proinflammatory cytokines production. Consequently, it creates an immunosuppression environment favoring the presence of infections. Methods: Descriptive study with prospective data collection. Data of selected adult patients, with ionized calcium (ICA) levels greater than or equal to 1.4mmol/L, hospitalized on Hospital AC Camargo, São Paulo, Brazil, were prospectively colected. Main objective: correlate the HM with infection and mortality. Survival analysis was performed by Kapplan-Meier curve and group’s comparison by the log-rank test. Results: Between Jan/2012 to Jan/2013, 90 patients were assessed. Mean age: 61 years. Most male (54.4%), solid tumors (89.9%), adenocarcinoma (46%). Tumors with higher incidence were gastrointestinal, head and neck and gynecological. Immunosupressive therapy was used by 10% of patients and 5.6% were neutropenic. Infection was diagnosed by 74,4% overall. Pulmonary and urinary tract were the main infection sites. Infection was observed in 100% of patients with ICA above 2mmol/L and 71% with ICA above 1.7 mmol/L. Fever was present in 58.9% of patients. 71,6% of these developed infection. Among patients with infection, the agent was isolated in 33.8%. Related to these, 52.7% were Gram-negative (GN) and 34.7% Gram-positive (GP). The overall survival (OS) at 90 days was 63% for all. OS at 90 days was 82.1% in patients without fever versus 47% in febrile (p = 0.040) and 82.2% in patients without infection versus 42.1% with documented infection site (p = 0.002). When the agent has been isolated, OS at 90 days was 62.9% for GN versus 33.4% for GP (p = 0.027). Conclusions: This study suggests that the prognosis of HM may be associated with higher incidence of infection. In this study we observed that the association of HM, fever and GP infection contributed significantly to higher mortality.
Phase I dose-finding study of golvatinib (E7050), a c-Met and Eph receptor targeted multi-kinase inhibitor, administered orally QD to patients with advanced solid tumors.
Authors: Gennaro Daniele, Malcolm Ranson, Montserrat Blanco-Codesido, Emma Jane Dean, Krunal Jitendrakumar Shah, Matthew Krebs, Andre Brunetto, Alastair Greystoke, Claire Johnston, Galina Kuznetsov, Mark Matijevic, Bipin Mistry, Begona de las Heras, L Rhoda Molife
Journal: Journal of Clinical Oncology (2012)

3030 Background: Golvatinib is a highly potent, small molecule ATP-competitive inhibitor of the c-Met receptor tyrosine kinase and multiple members of the Eph receptor family as well as c-Kit and Ron, based on isolated kinase assays. Golvatinib showed preclinical evidence of anti-tumor activity. This phase 1 study was performed to determine the MTD, safety, PK, PD and preliminary activity of golvatinib. Methods: Patients (pts) with advanced solid tumors, ECOG PS 0-1, ≥ 18 years (yrs) and adequate organ function were eligible. Golvatinib was administered orally, once daily (QD), continuously. Blood samples for PK and PD analysis were collected at multiple time-points. Mandatory tumor biopsies for PD analysis were taken pre and post Cycle 1 in an expanded MTD cohort. Results: 34 pts (M/F: 21/13; median age 63.5yrs [range 32-78]) were treated at 6 dose levels: 100, 200, 270, 360, 450 and 400 mg. Tumor types were colorectal (n=15), lung (n=4), renal (n=4), esophageal (n=2), melanoma (n=2) and others (n=7). Three DLTs were observed: Gr3 GGT and alkaline phosphatase (n=1; 200mg) and repeated Gr2 (n=1) and Gr3 (n=1) fatigue, both at 450mg. The MTD was determined to be 400 mg QD. Frequently occurring adverse events ([AEs]; all grades) were fatigue: 68% (Gr3: 15%), diarrhea: 65%, nausea: 62%, vomiting: 53%, decreased appetite: 47% (Gr3: 9%), ALT increase: 38% and AST increase: 23%. No Gr4 AEs were observed. Best response was stable disease in 6 pts lasting &gt;84 days. PK showed high variability and plasma concentration increased with dose. The C max was reached within a median time of 4 hours. Plasma PD analysis showed an increase in soluble c-Met and Ang 2 levels after golvatinib treatment. Tumor PD analysis in 5 pts at 400 mg demonstrated a baseline elevated MET gene copy number, with c-Met overexpression and post treatment decline in phospho(p)-c-Met expression in 1 pt; post-treatment decline in p-c-Met in a 2 nd pt, and post-treatment decline in p-ERK in a 3 rd pt. Conclusions: Golvatinib at an MTD of 400 mg QD has manageable toxicity. Preliminary PD analysis demonstrated evidence of c-Met target modulation. Further evaluation will continue in phase 2 combination studies.
Multi-Omics Analysis of Primary Cell Culture Models Reveals Genetic and Epigenetic Basis of Intratumoral Phenotypic Diversity
Authors: Sixue Liu, Zuyu Yang, Guanghao Li, Chunyan Li, Yanting Luo, Qiang Gong, Xin Wu, Tao Li, Zhiqian Zhang, Baocai Xing, Xiaolan Xu, Xuemei Lu
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Uncovering the functionally essential variations related to tumorigenesis and tumor progression from cancer genomics data is still challenging due to the genetic diversity among patients, and extensive inter- and intra-tumoral heterogeneity at different levels of gene expression regulation, including but not limited to the genomic, epigenomic, and transcriptional levels. To minimize the impact of germline genetic heterogeneities, in this study, we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma (HCC). Multi-omics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient. Variations in the genome sequence, epigenetic modification, and gene expression are used to infer the phylogenetic relationships of these cell cultures. We find the discrepancy among the relationships revealed by single nucleotide variations (SNVs) and transcriptional/epigenomic profiles from the cell cultures. We fail to find overlap between sample-specific mutated genes and differentially expressed genes (DEGs), suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant. Moreover, copy number alterations (CNAs) and DNA methylation variation within gene bodies, rather than promoters, are significantly correlated with gene expression variability among these cell cultures. Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity, and such an observation is further confirmed by cellular experiments both in vitro and in vivo. Our systematic analysis reveals that CNAs and epigenomic changes, rather than SNVs, are more likely to contribute to the phenotypic diversity among subpopulations in the tumor. These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification should be considered in personalized cancer medicine. This culture model may be applied to the further identification of plausible determinants of cancer metastasis and relapse.
THE OBESITY PARADOX IN PATIENTS WITH MODERATE AND SEVERE TRICUSPID REGURGITATION: EFFECTS OF OBESITY ON RIGHT VENTRICULAR REMODELING AND LONG-TERM SURVIVAL
Authors: Marlieke Dietz, Edgard Prihadi, Pieter van der Bijl, Nina Ajmone Marsan, Jeroen Bax, Victoria Delgado
Journal: Journal of the American College of Cardiology (2020)
PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS HAVE A HIGH PREVALENCE OF CORONARY MICROVASCULAR DYSFUNCTION IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Brittany Weber, Emma Stevens, Corine Sinnette, Jenifer Brown, Sanjay Divakaran, Courtney Bibbo, Jon Hainer, Josh Klein, Viviany R. Taqueti, Sharmila Dorbala, Ron Blankstein, Elena Massarotti, Karen Costenbader, Marcelo Di Carli
Journal: Journal of the American College of Cardiology (2020)
Lung cancer in never-smokers: A single institutional experience
Authors: J. Subramanian, F. Gao, N. Sainani, A. K. Viswanathan, G. A. Pillot, M. Q. Baggstrom, S. Sorscher, R. Govindan
Journal: Journal of Clinical Oncology (2006)

17044 Background: Approximately 10% of patients (pts) with lung cancer do not have a history of tobacco smoking. The clinical presentation and outcomes of pts with LCINS have not been well characterized in the Western population. Methods: We reviewed our institutional tumor registry to identify patients with lung cancer from 1992 to 2002. Data regarding tobacco smoking, stage, histology and survival were collected. Results: Of the 5417 consecutive pts diagnosed with lung cancer, 254 were determined to be never-smokers with confirmed pathologic diagnosis of non-small cell lung cancer (NSCLC). The table below describes the patient demographics. The five-year survival for the entire population with LCINS was 22.56%, with 37 pts surviving beyond five years. The median overall survival for women was 21.08 months (95% CI 14.03–23.37) and for men 13.5 months (95% CI 8.5–32.492); p = 0.73. Among the different histologic subtypes, broncho-alveolar carcinoma was associated with better median overall survival of 61.67 months (p &lt; 0.0001). The median overall survival by TNM stage: I (71 months), II (32 months), III (15 months), and IV (6 months). Conclusions: 1. LCINS affects predominantly women. 2. Adenocarcinoma is the most common histological type. 3. Brain and bone are the most common sites of metastases. [Table: see text] No significant financial relationships to disclose.
Do patients with advanced-stage non-small cell lung cancer (AS NSCLC) live longer if managed within a clinical trial setting?
Authors: Taher Abu Hejleh, Elizabeth A. Chrischilles, Thorvardur Ragnar Halfdanarson, Jane F Pendergast, Dingfeng Jiang, Carmen J. Smith, Aaron T. Porter, Robert B Wallace
Journal: Journal of Clinical Oncology (2012)

6034 Background: Treatment outcomes of AS NSCLC (stages IIIB and IV) are poor. There is an argument that participation in a clinical trial (CT) may confer survival benefit, probably, through enhancing quality of care. In this study, we explore the survival outcomes and perceived care quality for AS NSCLC patients (pts) treated within vs outside a CT. Methods: Data were obtained from surveys of newly diagnosed AS NSCLC pts studied by the Cancer Care Outcomes Research and Surveillance Consortium (CanCORS), a large cohort of pts across the United States. Pts who did not complete the baseline survey were excluded as this was associated with worse performance status (PS). Baseline characteristics according to CT participation were determined. Association between CT enrollment and survival was explored utilizing univariate and multivariate survival analysis after adjusting for age, comorbidities and self-reported PS. Results: Of 815 AS NSCLC pts, 56 (7%) were enrolled on a CT. Chemotherapy trials comprised 67% of all trials. Of the 815 pts, 697 (86%) died. Median survival for pts within vs outside a CT was 62 vs 64 months. Neither age, comorbidities nor recalled PS differed significantly between pts within vs outside a CT (P=0.2085, 0.5818 and 0.1678 respectively). On the multivariate survival model, CT enrollment did not correlate with longer survival (P=0.8811) and only presence of comorbidities was associated with worse survival (P=0.0021). Comparing pts according to CT enrollment, there was no significant difference in symptom management, receiving hospice care (P=0.606), death location (P=0.2018), or following pts’ wishes (P=0.8321). However, perception of the overall cancer care quality was greater among CT enrollees (P=0.0171). Conclusions: Management of AS NSCLC pts within a CT setting conveyed a perception of superior care that did not translate into survival benefit after adjusting for differences in age, comorbidities, and self-reported PS. These findings suggest that providing cancer care within a CT should not imply a survival benefit when counseling AS NSCLC pts about entering CTs.
COVID-19 in a Long-Term Care Facility — King County, Washington, February 27–March 9, 2020
Authors: Temet M. McMichael, Shauna Clark, Sargis Pogosjans, Meagan Kay, James Lewis, Atar Baer, Vance Kawakami, Margaret D. Lukoff, Jessica Ferro, Claire Brostrom-Smith, Francis X. Riedo, Denny Russell, Brian Hiatt, Patricia Montgomery, Agam K. Rao, Dustin W. Currie, Eric J. Chow, Farrell Tobolowsky, Ana C. Bardossy, Lisa P. Oakley, Jesica R. Jacobs, Noah G. Schwartz, Nimalie Stone, Sujan C. Reddy, John A. Jernigan, Margaret A. Honein, Thomas A. Clark, Jeffrey S. Duchin, Meaghan S. Fagalde, Jennifer L. Lenahan, Emily B. Maier, Kaitlyn J. Sykes, Grace Hatt, Holly Whitney, Melinda Huntington-Frazier, Elysia Gonzales, Laura A. Mummert, Hal Garcia Smith, Steve Stearns, Eileen Benoliel, Shelly McKeirnan, Jennifer L. Morgan, Daniel Smith, Michaela Hope, Noel Hatley, Leslie M. Barnard, Leilani Schwarcz, Nicole Yarid, Eric Yim, Sandra Kreider, Dawn Barr, Nancy Wilde, Courtney Dorman, Airin Lam, Jeanette Harris, Hollianne Bruce, Christopher Spitters, Snohomish Health District, Rachael Zacks, Jonathan Dyal, Michael Hughes, Christina Carlson, Barbara Cooper, Michelle Banks, Heather McLaughlin, Arun Balajee, Christine Olson, Suzanne Zane, Hammad Ali, Jessica Healy, Kristine Schmit, Kevin Spicer, Zeshan Chisty, Sukarma Tanwar, Joanne Taylor, Leisha Nolen, Jeneita Bell, Kelly Hatfield, Melissa Arons, Anne Kimball, Allison James, Mark Methner, Joshua Harney
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

On February 28, 2020, a case of coronavirus disease (COVID-19) was identified in a woman resident of a long-term care skilled nursing facility (facility A) in King County, Washington.* Epidemiologic investigation of facility A identified 129 cases of COVID-19 associated with facility A, including 81 of the residents, 34 staff members, and 14 visitors; 23 persons died. Limitations in effective infection control and prevention and staff members working in multiple facilities contributed to intra- and interfacility spread. COVID-19 can spread rapidly in long-term residential care facilities, and persons with chronic underlying medical conditions are at greater risk for COVID-19-associated severe disease and death. Long-term care facilities should take proactive steps to protect the health of residents and preserve the health care workforce by identifying and excluding potentially infected staff members and visitors, ensuring early recognition of potentially infected patients, and implementing appropriate infection control measures.
Abstract 14643: Association of Urinary Sodium Excretion With Measures if Adiposity Among Adults in the United States
Authors: Lixia Zhao, Mary E Cogswel, Quanhe Yang, Zefeng Zhang, Stephen Onufrak, Sandra L Jackson, Te-Ching Chen, Catherine M Loria, Chia-Yih Wang, Jacqueline D Wright, Ana L Terry, Robert K Merritt, Cynthia L Ogden
Journal: Circulation (2017)

Introduction: Both excessive sodium intake and obesity are risk factors for hypertension and cardiovascular disease. The association between sodium intake and obesity is unclear, with few studies a...
IMMEDIATE POST-TAVR SIMULTANEOUS ECHOCARDIOGRAPHIC AND INVASIVE MEAN GRADIENTS IN BALLOON VS. SELF-EXPANDING VALVES: A MULTI-CENTER RETROSPECTIVE STUDY
Authors: Amr E. Abbas, Ramy Mando, George S. Hanzel, Francis Shannon, Michael Gallagher, Safwan Kassas, Karim Al-Azizi, Jared Christensen, Molly Szerlip, Srinivasa Potluri, Katherine Harrington, Michael Mack
Journal: Journal of the American College of Cardiology (2020)
Erlotinib (E) in non small cell lung cancer (NSCLC) patients (pts) ≥75 years old with comorbidities (cM): Experience at a tertiary referral center.
Authors: Konstantinos N. Syrigos, Evangelos Sarris, Alexios S Strimpakos
Journal: Journal of Clinical Oncology (2013)

e19111 Background: Besides chemotherapy, E is another option in NSCLC pts especially in those with EGFR mutations. Elderly pts enrolled in trials are fit without cM, but in clinical practice most suffer from cM. Methods: Medical records of 1221 pts diagnosed with NSCLC between 2008-2012 were screened. We examined pts ≥75 yrs for demographics, clinical data and Tx details. Results: 233/1221 NSCLC pts received E at any line. 53/233 (23%) were ≥75 yrs old. Male:female ratio was 34:19 and median age 79 yrs (range 75-88). NSCLC subtypes included 31 adenoca, 8 squamous cell, 9 NOS and 5 others. 50/53 pts had cM (≥2 in 46 pts, 1 in 4pt). Main cM were cardiovascular disease (n=41), COPD (n=14), other cancer (n=10) and diabetes (n=8). 8 pts were tested for EGFR mutations (5 -ve, 3 +ve). Performance Status was satisfactory (ECOG 0-1) in 8 pts and poor (2-3) in 45pts. 8pts were treated with E 100mg and 45 pts with E 150mg (12 pts needed dose reduction). Complete follow up data were found in 46pts. Mean duration of treatment was 79 days (range 9-662). 35/46 pts experienced side effects (s.e) [rash n=29, diarrhea n=17] which led to treatment discontinuation in 12pts. Pts with abnormal creatinine clearance (n=13) were more likely to stop treatment due to s.e (6/13 versus 6/33). 17/46 pts (37%) achieved disease control (5 PR, 12 SD) and a time to progression (TTP) of 157 days (range 106-662, 95% CI 132.79-270,74) while 22/46 pts had PD as best response (TTP 49d, range 19-88, CI 44,67-64,97). 7pts were not evaluable (stopped Tx due to s.e). All EGFR+ve pts had disease control (2PR, 1SD). Conclusions: E is a valuable option in elderly NSCLC patients with co-morbidities, especially if they harbor EGFR mutations. Impaired renal function might be associated with propensity to side effects and early Tx discontinuation.
MULTIVESSEL VS CULPRIT VESSEL ONLY PERCUTANEOUS CORONARY INTERVENTION IN ST-ELEVATION MYOCARDIAL INFARCTION AND MULTIVESSEL CORONARY ARTERY DISEASE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Varunsiri Atti, Mahesh Anantha Narayanan, Santiago Garcia, Yader Sandoval, Emmanouil Brilakis, Mir Basir, Mohit Turagam, Akshay Khandelwal, Carlos I. Mena-Hurtado, Mamas A. Mamas, Ajay Kirtane, J. Abbott, Deepak Bhatt, Poonam Velagapudi
Journal: Journal of the American College of Cardiology (2020)
LEFT ATRIAL APPENDAGE MORPHOLOGY AND CHALLENGES WITH PERCUTANEOUS LEFT ATRIAL APPENDAGE OCCLUSION
Authors: Arslan Naeem, Nachiket Apte, Sagar Ranka, Michael Pierpoline, Aman Patel, Lance Longmore, Amit Shrestha, Gregory Jackson, Jonathan Chandler, Daniel Jipescu, Matthew Earnest, Seth H. Sheldon, Arvindh Kanagasundram, Christopher R. Ellis, Senthil Thambidorai, Madhu Reddy
Journal: Journal of the American College of Cardiology (2020)
EFFECTS OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES ACROSS BODY MASS INDEX CATEGORIES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN THE DECLARE TIMI 58 TRIAL
Authors: Kazuma Oyama, Itamar Raz, Avivit Cahn, Julia Kuder, Sabina Murphy, Deepak Bhatt, Lawrence A. Leiter, Darren K. McGuire, John Wilding, Kyong-Soo Park, Assen Goudev, Rafael Diaz, Jindřich Špinar, Ingrid Gause-Nilsson, Ofri Mosenzon, Marc Sabatine, Stephen D. Wiviott
Journal: Journal of the American College of Cardiology (2020)
DETECTION OF AORTIC STENOSIS USING AN ARTIFICIAL INTELLIGENCE-ENABLED ELECTROCARDIOGRAM
Authors: Michal Shelly, Zachi Itzhak Attia, Wei-Yin Ko, Saki Ito, Benjamin Essayagh, Hector I. Michelena, Rickey Carter, Maurice Sarano, Paul Friedman, Jae K. Oh
Journal: Journal of the American College of Cardiology (2020)
MECHANISMS OF LEFT VENTRICULAR REMODELING AFTER CARDIAC RESYNCHRONIZATION THERAPY BASED ON POST DEVICE CARDIAC MAGNETIC RESONANCE IMAGING
Authors: Xu Gao, Mohammad Abdishektaei, Changyu Sun, Daniel Auger, Sula Mazimba, Michael Salerno, Frederick Epstein, Christopher Kramer, Kenneth C. Bilchick
Journal: Journal of the American College of Cardiology (2020)