tbuckley/cabot-search huggingface dataset:
Cancer risk assessment using an automated electronic patient-facing tool for the collection and evaluation of family history.
Authors: Leigh A Baumgart, Kristen J Vogel Postula, Shaun A Walters, Jonathan C Silverstein, William A Knaus
Journal: Journal of Clinical Oncology (2016)

e13055 Background: Family history serves as a foundation for identifying patients with elevated cancer risk who may benefit from genetic evaluation or early and more intensive cancer surveillance. Many guidelines and other evidence-based literature are available to aid in the identification and management of at-risk patients. However, they are complex and ever-changing, hindering optimal use, especially in primary care settings. To address this need, we developed Health Heritage, a patient-facing web-based tool that combines clinical data automatically extracted from electronic medical records (EMR) with information entered by patients and shared between family members. Its evidence-based risk engine stratifies risk for seven common cancers and provides personalized recommendations directly to the patient. One key recommendation provided to patients identified to be at risk for a hereditary cancer syndrome is referral for further genetic evaluation, and details on how to schedule an appointment are provided. Patients may elect to share their Health Heritage assessment with their providers by requesting Health Heritage to automatically send its results to the EMR. Methods: Health Heritage has been available to patients at NorthShore University HealthSystem (NorthShore) since May 2014 via a link in their patient portal. We characterized the outcomes of its risk assessment and recommendations to date. Results: Approximately 3000 patients have registered and actively used Health Heritage. Of those patients, 27% were identified to have elevated risk for at least one cancer, and 12% were identified to have high or potentially high risk (pending genetic evaluation). Fifteen percent of all patients were referred for further genetic evaluation and counseling at NorthShore, and 12% of patients received counseling. Only 7% of total patients and 17% of patients with elevated risk elected to share their results with their providers directly through Health Heritage. Conclusions: Health Heritage is actively identifying patients with elevated cancer risk and providing actionable recommendations that appear to directly empower patients to independently seek appropriate genetic evaluation.
CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children’s Oncology Group Trial AAML0531
Authors: Jatinder K. Lamba, Lata Chauhan, Miyoung Shin, Michael R. Loken, Jessica A. Pollard, Yi-Cheng Wang, Rhonda E. Ries, Richard Aplenc, Betsy A. Hirsch, Susana C. Raimondi, Roland B. Walter, Irwin D. Bernstein, Alan S. Gamis, Todd A. Alonzo, Soheil Meshinchi
Journal: Journal of Clinical Oncology (2017)

Purpose Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C>T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy. Patients and Methods CD33 splicing single nucleotide polymorphism was evaluated in newly diagnosed patients with AML randomly assigned to receive standard five-course chemotherapy alone (No-GO arm, n = 408) or chemotherapy with the addition of two doses of GO once during induction and once during intensification (GO arm, n = 408) as per the Children's Oncology Group AAML0531 trial. Results The rs12459419 genotype was CC in 415 patients (51%), CT in 316 patients (39%), and TT in 85 patients (10%), with a minor allele frequency of 30%. The T allele was significantly associated with higher levels of D2-CD33 transcript ( P < 1.0E-6) and with lower diagnostic leukemic cell surface CD33 intensity ( P < 1.0E-6). Patients with the CC genotype had significantly lower relapse risk in the GO arm than in the No-GO arm (26% v 49%; P < .001). However, in patients with the CT or TT genotype, exposure to GO did not influence relapse risk (39% v 40%; P = .85). Disease-free survival was higher in patients with the CC genotype in the GO arm than in the No-GO arm (65% v 46%, respectively; P = .004), but this benefit of GO addition was not seen in patients with the CT or TT genotype. Conclusion Our results suggest that patients with the CC genotype for rs12459419 have a substantial response to GO, making this a potential biomarker for the selection of patients with a likelihood of significant response to GO.
Use of oseltamivir in 12 European countries between 2002 and 2007 – lack of association with the appearance of oseltamivir-resistant influenza A(H1N1) viruses
Authors: P Kramarz, D Monnet, A Nicoll, C Yilmaz, B Ciancio
Journal: Eurosurveillance (2009)

Variable levels of oseltamivir resistance among seasonal influenza A(H1N1) isolates have been reported in Europe during the 2007-8 northern Hemisphere influenza season. It has been questioned whether oseltamivir use could have driven the emergence and predominance of resistant viruses. This study aimed at describing the levels of use of oseltamivir in 12 European Union (EU) Member States and European Economic Area (EEA)/European Free Trade Area (EFTA) countries. The data were converted into prescription rates and compared with the national proportions of resistant influenza A(H1N1) viruses through regression analysis. Overall use of oseltamivir in European countries between 2002 and 2007 was low compared to e.g. the use in Japan. High variability between the countries and over time was observed. In eight of the 12 countries, there was a peak of prescriptions in 2005, coinciding with concerns about a perceived threat from an influenza pandemic which might have lead to personal stockpiling. Ecological comparison between national levels of use of oseltamivir in 2007 and the proportions of A(H1N1) viruses that were resistant to oseltamivir showed no statistical association. In conclusion, our results do not support the hypothesis that the emergence and persistence of these viruses in 2007-8 was related to the levels of use of oseltamivir in Europe. Further investigation is needed to elucidate the reasons for different level of use between the countries.
High-Dose Chemotherapy and Autologous Blood Stem Cell Transplantation in Refractory/Metastatic Non-Seminomatous Germ Cell Tumors: Gata Single Center Results
Authors: N. Karadurmus, A.S. Ataergin, G. Erdem, M. Cakar, I. Barista, T. Turker, S. Ozaydin, M. Ozturk, F. Arpaci
Journal: Annals of Oncology (2012)
11 Year Expereince with a Web-based Reporting Tool in a Community Outpatient Oncology Practice.
Authors: J. Russell Hoverman, Tae W Jang, Jim R. Schwartz
Journal: Journal of Clinical Oncology (2015)

e17646 11 Year Experience with a Web-based Medication Reporting Tool in a Community Outpatient Oncology Practice Hoverman J, Jang T, Riegel G and Schwartz J Background: At ASCO 2007 we presented 2 year experience with a web-based medication occurrence (MO) reporting tool. We now present the 11 year experience in a single outpatient oncology practice. Methods: Since December, 2003 Texas Oncology sites have been entering information on medication-related occurrence reports in the electronic Variance reporting tool supported by US Oncology. On a monthly basis the pharmacy management team is able to print out all reports for an analysis to be presented to the Texas Oncology Quality Oversight Committee. The results (as well as a summary of each individual occurrence) are made available to the committee for analysis and follow-up action. The data gathering is analyzed according to a pre-set group of parameters (retail vs. clinic, near miss vs. actual occurrence, severity level 1-8, category of occurrence (e.g. omitted/extra dose, wrong drug, adverse drug reaction, etc.) and those related to use of the EHR). Recently these electronically-saved data were analyzed for the years 2004-2014 to analyze trends in MOs. Results: Over 11 years there were 2163249 transactions for a chemotherapy infusion or injection. There were 10845 MOs of which 5143 were adverse drug reactions (ADRs). Near misses accounted for 16.7 of unadjusted MO rate and 31.8% when ADRs were excluded. MO rate with ADR was 0.46%, without ADR 0.24%. Retail MO rate was 0.02% on 1771148 transactions. Rituximab was 20.9% and paclitaxel 16.4% of ADRs. Tying reporting to clinic performance increased reporting by site and number of sites. EHR related MOs and Near Misses were each reported as MOs and artificially inflate numbers due to double counting. There were 10 deaths over 11 years. Physician numbers ranged from 164 in 2004 to 363 in 2014. Conclusions: Web-based reporting in the outpatient community setting is feasible and identified many topics for quality improvement initiatives. The importance of double-checking and a culture of safety is reinforced by the number of avoided MOs indicated by the near miss percentage. The full data set will be presented at the meeting.
MCP-1 and CCR2 gene polymorphisms in Czech patients with allergic disorders
Authors: František Mrázek, Lydie Izakovičová Hollá, Michal Jurajda, Martin Petřek
Journal: European Respiratory Journal (2007)

Summary Several lines of evidence suggest that chemokines play an important role in asthma and allergy. We analysed polymorphisms at ‐2518A/G and ‐2076A/T of MCP-1 and V64I of CCR2 gene in healthy subjects ( n = 306) and allergic patients ( n = 332). Allele and genotype frequencies did not differ significantly between groups. Nevertheless, MCP-1 variants were associated with allergen sensitization. The results suggest that MCP-1, but not CCR2 gene variants, may participate in the pathogenesis of allergic phenotypes at least in the Caucasian population.
Human interleukin 10 receptor 1 (IL-10R1)-Ig G1 fusion protein: A decoy for IL-10
Authors: Mizue Terai, Yutaka Tamura, Eiko Otsuka, David Berd, Michael J. Mastrangelo, Takami Sato
Journal: Cancer Research (2004)

655  IL-10 plays an important physiological role in negative regulation of cell-mediated immune responses. We previously reported that IL-10 is produced by more than 85 % of single cell suspensions from metastatic melanomas. We also reported that circulating IL-10 protein is detectable in melanoma patients with bulky metastases. Furthermore, IL-10 production in melanoma tissues is negatively correlated to the survival of patients who received autologous melanoma vaccine. Therefore, modulation of IL-10 would be a reasonable approach to enhance an anti-tumor immune response. We have developed IL10R1-IgG1 plasmid vectors that contains the extra-cellular domain of human IL-10R1 and Fc portion of human immunoglobulin G1 (hinge+CH2+CH3) as a molecular trap for IL-10. The following plasmid vectors were developed and tested for their ability to trap the human IL-10 protein; V0: pVAX1 (no gene insertion), V12: pVAX1-IL10R1(EC*), V15: pVAX1-IL10R1(EC)/IgG1-Fc (mut-hinge**), V51: pVAX1-IL10R1(EC)/IgG1-Fc (no-hinge), V54: pVAX1-IL10R1(EC)/IgG1-Fc (wt-hinge***) *Extracellular domain, ** three cysteines of a wild type were mutagenized to serine preventing self dimerization, ***wild type hinge The plasmid vectors were transfected into an IL-10 producing melanoma cell line (producer) and a non-IL-10 producing melanoma cell line (non-producer). After transfection, supernatants from these cell lines were collected and they were tested with a trapping assay using an ELISA kit for human IL-10. Unbound IL-10 protein in supernatants from the IL-10 producer significantly decreased after transfection with V15 (mut-hinge) or V51(no-hinge) (81.9 % and 96.1% reduction, respectively). In contrast, the V54 vector (dimeric IL10-R1) had less effect (51.3% reduction). The vector V0 (no gene insertion) and V12 (IL10R1 extracellular domain alone) had no trapping effects. In separate experiments, supernatants from the IL-10 non-producer were collected after transfection with plasmid vectors. The supernatants were then mixed with exogenous human IL-10 and the trapping effect of supernatants was checked with the human IL-10 ELISA kit. The supernatants from the non-IL-10 producer transfected with V15 or V51 efficiently blocked the binding of exogenous IL-10 to the ELISA plate (79.8% and 73.5% blocking at 500 pg/ml). These results show that IL10R1-IgG1 fusion protein binds IL-10 and may thereby reduce immunomodulatory effects of IL-10.
A multi-institutional study of racial differences in androgen receptor status among triple-negative breast cancers.
Authors: Shristi Bhattarai, Jun Xia, Ceyda Sonmez Wetherilt, Sonal Pattni, Sergey Klimov, Ansa Riaz, Mohammad Aleskandarany, Andrew R. Green, Emad Rakha, Ian O. Ellis, Guilherme Henrique Cantuaria, Xiaoxian Li, Uma Krishnamurti, Remus Osan, Padmashree C.G. Rida, Ritu Aneja
Journal: Journal of Clinical Oncology (2016)

1089 Background: Triple Negative Breast Cancer (TNBC) is a highly heterogeneous and aggressive breast carcinoma subtype typified by high recurrence and mortality rates. To date, no targeted therapies are available for TNBC. Recently, androgen receptor (AR), a nuclear steroid hormone receptor expressed in 10-43% of TNBCs, has emerged as a promising new biomarker with potential predictive value for certain TNBC subtypes. Compared to European-American (EA) women, African Americans (AAs) are twice as likely to develop TNBC and have poorer outcomes, than EA TNBC patients, after adjusting for treatment and healthcare access. This study aimed to determine the prognostic value of AR in a large TNBC cohort and evaluate racewise trends in AR expression status among TNBCs. Methods: AR expression was evaluated immunohistochemically in formalin-fixed paraffin-embedded samples from 822 TNBC patients (142, 95 and 264 patients from Emory, Northside and Grady Memorial Hospitals, respectively, in Atlanta, and 321 from Nottingham Hospital, UK) for whom complete clinicopathologic and overall survival (OS) data were available. Ethnicity data were available for 138 AA and 675 EA TNBC cases. Samples with < 1% nuclear-stained cells were considered quadruple-negative (QN). Associations between nuclear AR status, race, other clinicopathologic variables and OS were evaluated through survival analyses and multivariate Cox regression. Results: In this study, 45.6% of the TNBC cases were QN. QN receptor status was significantly associated with older age (age > 25) at diagnosis, AA ethnicity and lower (KI < 14%) proliferative index (p < 0.001 for all) in univariate analyses. In multivariate analyses, loss of AR expression was associated with poorer OS (p < 0.05, HR = 2.8) after adjusting for grade, stage and adjuvant therapy. Interestingly, AAs had a much higher proportion (80.8%) of QN cases than EAs (40.1%, p < 0.0001). Conclusions: These data strongly support a prognostic role of AR in TNBC and suggest that a higher prevalence of QN breast cancer among AAs may be a plausible reason for the ethnic disparity in outcomes among TNBC patients.
Routine clinical use of nab-paclitaxel for advanced / metastatic breast cancer in Germany: Final results of the prospective observational study NABUCCO.
Authors: Jan Schroeder, Karin Potthoff, Christoph Salat, Ulrike Soeling, Richard Hansen, Sina Grebhardt, Johanna Harde, Arnd Nusch, Norbert Marschner
Journal: Journal of Clinical Oncology (2017)

e12555 Background: nab-Paclitaxel ( nab-P) is approved for treatment of metastatic breast cancer (MBC) on a 3-week schedule based on results from the pivotal trial in which nab-P 260 mg/m 2 showed a significant increase of progression-free survival compared with solvent-based paclitaxel. However, numerous studies suggest a weekly schedule might be a more effective and less toxic option (Gradishar 2011). Data beyond clinical trials is limited. Here we report on prospective non-interventional real-world effectiveness and safety data. Methods: The NABUCCO study was designed to collect data on routine treatment of 700 patients (pts) with MBC in Germany. Primary objective was time to progression (TTP), secondary objectives were overall response rate (ORR), overall survival (OS), dosage scheme of nab-P and safety parameters. Descriptive statistics were used to analyze the data. TTP and OS were calculated using the Kaplan-Meier method. Results: Between 4/2012 and 4/2015 697 evaluable pts at 128 sites had been enrolled. Baseline characteristics: Median age 62.3 years (range 29.2-89.3), age ≥ 70 years n = 200 (28.7%), ECOG PS ≥ 2 n = 49 (7.0%), visceral metastases n = 511 (73.3%). The majority of pts received nab-P as 1 st -line (n = 280, 40.2%) or 2 nd -line (n = 169, 24.2%) chemotherapy. 194 pts (27.8%) received a 3-week schedule, 491 pts (70.4%) a weekly schedule, 12 pts (1.7%) other. In the overall population, median TTP was 5.9 months (95% CI 5.6-6.4), median OS 15.5 months (95 % CI 14.2-17.3). For pts ≥ 70 years median TTP was 6.9 months (95 % CI 5.7-8.5), median OS 14.8 months (95 % CI 12.6-18.8). In the 3-week group median TTP was 5.7 months (95 % CI 5.2-6.9), median OS 15.1 months (95 % CI 12.3-17.5). In the weekly group median TTP was 6.0 months (95 % CI 5.6-6.5), median OS 16.3 months (95 % CI 14.4-18.5). 34.3% of pts developed adverse events grade 3/4 including leukopenia (7.9%), peripheral sensory neuropathy (4.3%) and infections (4.2%). Further subgroup analyses will be presented. Conclusions: nab-P is an effective and safe therapy for pts with MBC in a real world setting. It is as effective in older women as it is in their younger counterparts. A weekly schedule could be a reasonable option.
Role of information handout in counselling patients undergoing gastroscopy
Authors: AZS Janjua, R Goubran, RB Salih, O Clinton
Journal: Endoscopy (2005)

Aims: Present day best practice entails that patients fully comprehend their condition, risks and benefits associated with treatment options and procedures. Effective counselling is augmented by using information handout. This study surveys patient satisfaction and evaluates the role of 'Information handout' as an adjunct to effective communication in patients undergoing gastroscopy.
Randomized trial of medroxyprogesterone acetate for prevention of endometrial pathology from adjuvant tamoxifen for breast cancer: SWOG S9630.
Authors: Kathy S. Albain, Joseph M. Unger, Robert B. Livingston, Katherine D. Crew, Sharon P. Wilczynski, Caryl G. Salomon, Barbara L. Smith, Lucas Wong, David Campbell, David E. Einspahr, Garnet L Anderson, Dawn L. Hershman, Gary E. Goodman, Powel Brown, Frank L. Meyskens, Ronald Potkul
Journal: Journal of Clinical Oncology (2016)

547 Background: Tamoxifen provides significant survival benefit in the adjuvant treatment of estrogen receptor-positive (ER+) breast cancer. However, its proliferative effect on the endometrium potentially can result in endometrial abnormalities including cancer. This trial assessed whether adding a cyclical progestin, medroxyprogesterone acetate (MPA), to tamoxifen could prevent endometrial pathology. Methods: We conducted a randomized controlled trial to compare rates of an endometrial pathologic diagnosis in postmenopausal women with early stage ER+ breast cancer assigned to tamoxifen alone versus tamoxifen + MPA (10 mg for 14 days every 3 months) for 5 years. Endovaginal sonograms (EVS) +/- endometrial biopsies (EMB) were required at baseline, 2 and 5 years, with no endometrial pathology allowed on the baseline studies. The accrual goal was 176 (88 per arm) evaluable patients (defined as completing the year 2 EVS and undergoing EMB if stripe width was ≥ 5 mm). Based on the literature, an endometrial abnormality rate of 30% was projected for the tamoxifen control arm. Results: Of 313 patients registered, 296 were eligible and 169 (57%) were evaluable at year 2 (89, tamoxifen; 80, tamoxifen+MPA). Of these, 60 (67%) in the tamoxifen arm had an endometrial stripe width ≥ 5 mm (and underwent subsequent EMB) compared to 48 (60%) in the tamoxifen+MPA arm (p = 0.40). There were 4 cases of proliferative endometrium and one simple hyperplasia on the tamoxifen arm (rate of 6% [95% CI: 2%-13%] among evaluable patients) and one case of proliferative endometrium on the tamoxifen+MPA arm (p = 0.11). The overall fraction with benign endometrial abnormalities at year 2 was 3.6% (6/169; 95% CI: 1.3-7.6%), with only 1 (of 102) new benign proliferative event at year 5. Conclusions: The event rate in both arms was much lower than projected, making treatment arm comparisons less informative. A normal endometrium prior to tamoxifen may provide reassurance regarding future endometrial events. However, validation in a larger trial is needed before changing practice in asymptomatic postmenopausal women. Support: NIH/NCI grants CA180888, CA180819 and CA189974 Clinical trial information: ClinicalTrials.gov NCT00002920.
Abstract P294: Cardiomyocyte-Specific RBPJ Regulates Angiogenesis and Stress Response in the Adult Heart
Authors: Ramon Diaz Trelles, Maria Cecilia Scimia, Pilar Ruiz Lozano, Mark Mercola
Journal: Circulation Research (2011)

Regulation of adult myocardial angiogenesis is critical for an appropriate cardiac function. We found that lack of RBPJ on isolated mouse adult cardiomyocytes increases angiogenic factors gene expresión and promoter hyperacetylation and hypermethylation of Notch target gene promoters (HEY2) and angiogenic factors. Accordingly, cardiomyocyte specific RBPJ KO adult mice show a denser microvasculature. RBPJ KO mice suggest an angiogenesis repressive role of RBPJ during homeostasis. Stress induced by myocardial infarction (MI) or cardiac overload (TAC) activate an angiogenic response to compensate the increased oxygen demand. We have found that Notch pathway is activated and RBPJ accumulated in the nucleus after MI and TAC. On isolated mouse adult cardiomyocytes, RBPJ is also able to control angiogenesis by mediating a hypoxia-induced response independent of Notch receptor activation. Mice lacking RBPJ in cardiomyocytes present a blunted angiogenic response. Suprisingly RBPJ KO mice had a better cardiac performance alter MI. We propose that RBPJ is a critical effector of the hypoxic response in the heart and the mechanisms by which RBPJ KO could protect from injury will be discussed on the presentation.