tbuckley/cabot-search huggingface dataset:
Preliminary results of TATTON, a multi-arm phase Ib trial of AZD9291 combined with MEDI4736, AZD6094 or selumetinib in EGFR-mutant lung cancer.
Authors: Geoffrey R. Oxnard, Suresh S. Ramalingam, Myung-Ju Ahn, Sang-We Kim, Helena Alexandra Yu, Hideo Saka, Leora Horn, Koichi Goto, Yuichiro Ohe, Mireille Cantarini, Paul Frewer, Michael Lahn, James Chih-Hsin Yang
Journal: Journal of Clinical Oncology (2015)

2509 Background: AZD9291 is an irreversible, mutant-selective EGFR tyrosine kinase inhibitor (TKI) developed to have potency against EGFR mutations, including T790M, while sparing wildtype EGFR. In the previous phase I study of AZD9291, EGFR-mediated toxicity was reduced compared to available EGFR-TKIs. We hypothesized that the safety profile of AZD9291 would permit combinations with other targeted therapies in a tolerable fashion. Methods: TATTON (NCT02143466) is a multi-arm phase Ib trial studying AZD9291 in combination with MEDI4736 (anti-PD-L1 mAb), AZD6094 (MET inhibitor) or selumetinib (MEK1/2 inhibitor; AZD6244, ARRY-142886). Eligibility required advanced EGFR-mutant lung cancer, progression on any prior EGFR-TKI, measurable disease, adequate PS (0-1) and organ function, and tissue for correlatives. In each combination, AZD9291 was dosed at 80 mg daily and the 2nd agent was escalated from a dose below the phase II monotherapy dose. Using a rolling 6 design, patients (pts) were randomly allocated to a combination arm. Data included here are preliminary and will be updated for presentation. Results: As of 8 January 2015, 42 pts have been enrolled on combination therapy (MEDI4736 = 14 pts; AZD6094 = 7 pts, selumetinib = 21 pts). All 3 combination agents were escalated to their phase II monotherapy doses; an additional arm continues to explore intermittent dosing of selumetinib. Adverse event (AE) data is currently available for 20 pts from all arms and cycles and includes mild/moderate AEs in 16 pts (6 skin, 5 laboratory, 2 gastrointestinal, 3 other) and severe AEs in 4 pts (1 skin, 1 laboratory, 1 gastrointestinal and 1 metabolism); 2 DLTs were reported (fatigue – AZD6094 arm; transaminase elevation – selumetinib arm). To date, 3 partial responses (PR) have been seen with AZD9291/MEDI4736, 2 PR with AZD9291/AZD6094, and 2 PR with AZD9291/selumetinib. Combination dose finding is expected to complete by May 2015. Conclusions: The toxicity profile of AZD9291 makes rational combinations with potentially synergistic targeted therapies feasible at biologically active doses. Expansion cohorts are planned for pts with acquired resistance to third-generation EGFR-TKI. Clinical trial information: NCT02143466.
Abstract P133: Psychological Distress, Diabetes Self-Management, and Cardiovascular Disease Risk Factors Among a Primary Care Sample of Spanish Speaking Hispanic/Latinos With Type 2 Diabetes
Authors: Laura M Pompano, Linda C Gallo, Sheila F Castañeda, Melawhy Garcia, Fatima Muñoz, Paulina Mendoza, Gregory A Talavera
Journal: Circulation (2019)

Aims: The aim of this study was to examine the relationships between psychological distress (anxiety, depression, and diabetes-distress), diabetes self-management (DSM) behaviors, and cardiovascular disease (CVD) risk factors/diabetes control among adult primary care, non-insulin using Hispanic/Latino patients with type 2 diabetes. Methods: This abstract presents a cross-sectional analysis of the baseline data from an ongoing clinical trial of 456 Hispanic/Latino participants with type 2 diabetes (mean age 55.2 ± 9.8 years; 63.7% female) at a federally qualified health center in San Diego. General linear models were used to examine associations between anxiety, depression, and diabetes-distress (assessed using the Patient Health Questionnaire-8 [PHQ-8], the Generalized Anxiety Disorder 7-item scale [GAD-7], and the Diabetes Distress scale-2, respectively), DSM behaviors (assessed using the Summary of Diabetes Self-Care Activities Assessment [SDSCA]), and markers of CVD risk (glycated hemoglobin [HbA1c], body mass index, systolic and diastolic blood pressure, and HDL and LDL cholesterol), controlling for the demographics variables of age, sex, and education. Results: Moderate depression and anxiety symptoms (defined as a PHQ-8 and GAD-7 cutoff of 10) were present in the study sample at rates of 21.5% and 15.4%, respectively. Poorly controlled diabetes (HbA1c &gt; 8.0%) was present in 40.6% of the sample. After controlling for covariates, all three indicators of psychological distress showed significant, negative associations with SDSCA (DSM) scores (p &lt; 0.01). Depression and anxiety symptoms were positively associated with LDL cholesterol (p = 0.020 and p = 0.022, respectively). No other associations among psychological distress and CVD risk factors were significant. DSM behaviors were not associated with any CVD risk factors. Conclusions: Depression and anxiety affect a large percentage of the Hispanic/Latino population. As greater depression and anxiety symptoms were associated with worsened diabetes self-management behaviors, for example diet and glucose monitoring, there may be implications for DSM and other CVD risk factors. Psychosocial dimensions of health are important to consider when providing care and promoting self-management behaviors in this population, as promoted by frameworks such as the integrative care model.
Abstract P333: The Association of Sedentary Time in Obese Adolescents With Asthma
Authors: Jacob Hartz, Emily M Bucholz, Tiffany Powell-Wiley, Sarah de Ferranti
Journal: Circulation (2019)

Introduction: Over the past two decades, both asthma and obesity have increased in prevalence. Evidence suggests that the contemporaneous increase in asthma and obesity may not be coincidental, and that obesity may predispose a person to developing asthma. The mechanism for this relationship is unknown, but persistent, low-grade inflammation may be a key driver. As previous research suggests that increased amounts of sedentary time can lead to inflammation, we examined whether sedentary time was associated with asthma in adolescents with obesity. Methods: Using NHANES 2003-2006, we evaluated the average number of minutes of daily sedentary time and number of breaks in sedentary time in youth age 6-19 years old with obesity, defined as a body mass index (BMI) ≥95 th percentile, with and without asthma. We compared demographic variables, self-reported categories of sedentary time, and objectively measured sedentary time and breaks in sedentary time using an accelerometer. We used multivariate logistic regression analysis to determine associations between the risk of asthma in obese adolescents controlling for accelerometer wear time, gender, age, poverty-to-income ratio, C-reactive protein (CRP) as a marker of inflammation, and tobacco smoke exposure. Results: We found that among sample of adolescents with obesity, 13.2% had asthma. Objective measures of sedentary time did not differ between obese patients with and without asthma nor did CRP ( Table 1) . However, self-reported computer time was significantly higher in obese adolescents without asthma. Conclusions: As in our study, previous studies suggest that sedentary time classified as computer time may not increase the risk of cardiovascular disease as much as sedentary time spent watching television.
Inferior Outcome of Allogeneic Stem Cell Transplantation in First Complete Remission for Secondary AML As Compared to De Novo Disease: Results from a Retrospective, Registry-Based Analysis on Behalf of the Acute Leukemia Working Party of the EBMT
Authors: Christoph Schmid, Myriam Labopin, Gerard Socie, Maija Itälä-Remes, Didier Blaise, Ibrahim Yakoub-Agha, Noel Milpied, Jan J Cornelissen, Arnold Ganser, Dietrich W. Beelen, Hélène Labussière-Wallet, Jakob R. Passweg, Bipin N. Savani, Mohamad Mohty, Arnon Nagler
Journal: Blood (2018)
The OP-104 Anchor Study: A Phase 1/2 Study of Safety and Efficacy of Melflufen and Dexamethasone in Combination with Either Bortezomib or Daratumumab in Patients with Rrmm; First Report on Phase 1 Data
Authors: Ludek Pour, Miquel Granell, Roman Hajek, Albert Oriol, Yvonne Efebera, Jacques Delaunay, Katell Le Du, Jean-Richard Eveillard, Lionel Karlin, Vladimir Maisnar, Joaquin Martinez Lopez, Maria-Victoria Mateos, Jan Moreb, Vincent Ribrag, Paul Richardson, Jan Straub, Catriona Byrne, Christian Jacques, Hanan Zubair, Enrique Ocio
Journal: Blood (2018)
Phase 1 extension study of BBI503, a first-in-class cancer stemness kinase inhibitor, in patients with advanced colorectal cancer.
Authors: Derek J. Jonker, Scott Andrew Laurie, Gregory Michael Cote, Keith Flaherty, Charles S. Fuchs, Rashmi Chugh, David C. Smith, William Jeffery Edenfield, Paul R. Conkling, James Walter Mier, Rachel Anne Goodwin, Eunice Lee Kwak, Thomas Adam Abrams, Rakesh Goel, James M. Cleary, Wei Li, Youzhi Li, Jamileh Jemison, Matthew Hitron, Chiang Li
Journal: Journal of Clinical Oncology (2015)

3615 Background: Targeting cancer stem cells (CSC) has shown pre-clinical efficacy and holds therapeutic promise. BBI503 is a first-in-class cancer stemness kinase inhibitor with potent in vitro and in vivo activity against CSC. BBI503 works through inhibition of stemness pathways, including Nanog. High Nanog expression in patients with colorectal cancer (CRC) predicts poor prognosis. Patients with advanced CRC who had failed all standard treatments were enrolled in a phase I and disease-specific cohort expansion study. Methods: BBI503 was given orally and continuously in 28-day cycles until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Eligible patients with CRC received BBI503 monotherapy at 20 mg to 500 mg total daily. Archival tissue was evaluated by IHC for Nanog expression. Results: 47 patients with heavily pre-treated CRC were enrolled (median 4 prior lines standard therapy). Bevacizumab was used in 80%, anti-EGFR AB in 60%, and regorafenib in 23%. Most (N = 35, 75%) received BBI503 at RP2D, 300 mg once daily. Median treatment duration was 8 weeks (range < 1 to 46+). Common adverse events (AE) considered related to therapy were grade 1 to 2 diarrhea, abdominal pain, fatigue, and nausea/vomiting/anorexia. At RP2D, Grade 3 AE were diarrhea (N = 3), fatigue (N = 3), nausea (N = 2), and weight loss (N = 1). Archival tissue was available from 39 patients (83%). DCR (CR+PR+SD) in evaluated patients with high Nanog expression (biomarker positive) was 56%, while DCR in biomarker negative patients was 13% (p = 0.040). Median overall survival (mOS) in biomarker positive patients (ITT) was 38 weeks, while mOS in biomarker negative patients (ITT) was 16 weeks (p = 0.089 Log-Rank). Conclusions: BBI503, a first-in-class cancer stemness kinase inhibitor, demonstrated tolerability at the RP2D administered to patients with pre-treated mCRC. Disease control and prolonged overall survival were observed in CRC patients with positive Nanog expression in tumor tissues. Further clinical evaluation of BBI503 alone or in combination with standard chemotherapeutic agents in CRC is warranted. Clinical trial information: NCT01781455.
Abstract P265: History of Hypertensive Disorders of Pregnancy and Early Manifestation of Vasomotor Symptoms 8-10 Years Post Delivery
Authors: Vanessa Assibey-Mensah, Rebecca C Thurston, Janet M Catov
Journal: Circulation (2019)

Introduction: Women with hypertensive disorders of pregnancy (HDP) have excess cardiovascular disease (CVD) risk in the years following delivery compared with women with uncomplicated pregnancies, with black women having excess burden of both HDP and CVD. After pregnancy yet prior to the menopause transition, nearly 30% of women in their late reproductive years report having vasomotor symptoms (VMS) including night sweats and hot flashes. VMS, particularly, early-onset VMS, have also been associated with increases in blood pressure and subclinical CVD. However, it is unknown if underlying vascular dysfunction in women with a history of HDP may increase the risk of VMS and contribute to racial differences in symptom manifestation. Hypothesis: Women with a history of HDP will have an increased risk of VMS as compared with women without a history of HDP. Methods: Women with a singleton live birth at Magee-Womens Hospital (Pittsburgh, PA) during 2008-2009 were enrolled 8-10 years post-delivery (median age=37.5; interquartile range=8.0) in our ongoing prospective cohort study assessing maternal cardiometabolic and microvascular disease (n=312). Using log-binomial logistic regression, we estimated the risk of VMS associated with history of HDP, adjusting for race, body mass index, current smoking, age, and education. Additional adjustment was made for current hormonal contraceptive use. Women with single or double oophorectomy (n=7) were excluded in a sensitivity analysis. Given the excess burden of HDP and CVD, as well as early-onset VMS in black women, we also assessed effect measure modification by maternal race. Results: Thirty percent of women with a history of HDP reported having vasomotor symptoms compared with 18% of women without a history of HDP. This excess risk of VMS persisted after accounting for covariates (adjusted risk ratio (aRR) 1.61, 95% confidence interval (CI) 1.06, 2.47). Excess risk of VMS persisted in women with a history of HDP after excluding those with a single or double oophorectomy (aRR 1.60, 95% CI 1.03, 2.47). Additional adjustment for hormonal contraceptive use resulted in a non-statistically significant increased risk of VMS (aRR 1.59, 95% CI 0.98, 2.59). Race did not modify the association between history of HDP and VMS (P value for interaction = 0.79). Conclusions: History of HDP was associated with excess risk of VMS in young women prior to menopause transition. There may be common underlying vascular changes that contribute to HDP and VMS that may also place women at future risk for CVD. How these reproductive factors may converge and be related to excess cardiometabolic risk warrants additional study.
Oncologists' opinions about second opinions in cancer care.
Authors: Kenneth David Miller, Aman Opneja, Prashant Gyanendra Tripathi
Journal: Journal of Clinical Oncology (2015)

e17726 Background: There is a common sentiment that obtaining a second opinion is important for people with cancer. There is little data however on factors that lead to obtaining a second opinion, the process, or outcomes. Methods: A request to participate in a survey was emailed to 476 medical oncologists at U.S. academic cancer centers. Respondents were asked to provide demographic information and their opinions on second opinions. Results: 65 medical oncologists (14%) participated in this survey. 70% were men, median age was 63 years. Median duration in practice was 12 years, and 82% had seen over 100 patients for second opinions. 61% reported that second opinions were most common at the time of diagnosis and 66% that the patient/family requested the second opinion. 75% reported that > 10% of patients had not told their oncologist that they are seeking a second opinion and 17% asked them not to tell the first oncologist. Respondents perceived that > 25% of patients “did not seem to like or trust their primary oncologist” (28%), “communication with their first oncologist was not satisfactory” (44%), “were afraid that getting a second opinion would offend their oncologist” (31%), came for the second opinion without complete medical records (45%). 59%, 68%, and 83% of respondents reported that their opinion was clinically significant different, occasionally or more, in regards to diagnosis or staging, need for additional testing, or cancer treatment recommendations. 50% felt that second opinions would result in a better chance of remission or cure in > 10% of patients who were treated with curative intent and 69% reported that > 10% of patients would have prolonged survival when treated with palliative intent. Offering a second opinion was considered a good use of their time but third and fourth opinions were not likely to be helpful to patients. “Side effects” of second opinions were perceived to be delay in treatment and cost. Conclusions: Seeking a second opinion is commonly considered for patients with cancer. Medical Oncologists who provide second opinions report that communication and trust issues with the primary oncologist are not rare and that second opinions may improve the chance of cure or help prolong survival in some patients.
Abstract P117: Prediction of Undiagnosed Diabetes in Africans is Optimized by Using Fasting Plasma Glucose at a Threshold of 100 mg/dL: The Africans in America Study
Authors: Margrethe F Horlyck-Romanovsky, Regine Mugeni, Jessica Y Aduwo, Sara M Briker, Christopher DuBose, Lilian S Mabundo, Stephanie Chung, Joon Ha, Arthur Sherman, Anne E Sumner
Journal: Circulation (2019)

Introduction and Objectives: Detecting undiagnosed diabetes is the first step towards addressing the diabetes epidemic in Africa. Although there is little experience with diabetes prediction equations in Africans, the A1C-modified Atherosclerosis Risk in Communities (ARIC) diabetes prediction equation was optimized in African Americans. Therefore, we evaluated (a) the ability of the A1C-modified ARIC prediction equation to detect undiagnosed diabetes in African-born blacks living in the United States and (b) the contribution of each biochemical variable to the effectiveness of the equation. Methods: Participants were 400 self-identified healthy African-born blacks enrolled in the Africans in America study (age 38 ±10 (mean ±SD) years, BMI 27.5 ±4.5, range 18.2-42.4 kg/m 2 ). Glucose tolerance status was diagnosed by glucose criteria for the OGTT. The prediction equation had 9 variables; 5 clinical (age, parent history of diabetes, height, waist circumference, and systolic BP); and 4 biochemical (A1C, fasting plasma glucose (FPG), high density lipoprotein (HDL) and triglycerides (TG)). Area under the receiver operating characteristic curve (AUC-ROC) predicted discrimination and Youden Index identified optimal cut-points. Four models were tested. Model 1 determined the predictive value of the full equation. Model 2 included the clinical variables and 3 of the 4 biochemical variables at a time. Model 3 included the clinical variables and 1 biochemical variable at a time. Model 4 evaluated the independent prediction by each biochemical variable. Results: Diabetes, prediabetes and normal glucose tolerance were detected in 7% (26 of 400), 27% (108 of 400) and 66% (266 of 400), respectively. Model 1 had an AUC-ROC of 0.8. Model 2 with FPG excluded had an AUC-ROC of 0.7. When A1C, HDL or TG were the excluded AUC-ROC increased to &gt;0.8. Model 3 with clinical variables and FPG the AUC-ROC was 0.9. However, when A1C, HDL or TG were included AUC-ROC declined to ≤0.7. In Model 4, FPG as a single predictor had an AUC-ROC of 0.9. In contrast, A1C, HDL or TG as single predictors, all had AUC-ROC ≤0.7. For the prediction of diabetes, the optimal cut-point for FPG was 99 mg/dL (sensitivity 85%, specificity 87%). Conclusions: As the prediction of prevalent diabetes by the entire equation and FPG alone were similar, FPG ≥100 mg/dL in Africans may be a sufficient and cost-effective way forward.
A retrospective, single-institution experience of resected ampullary adenocarcincoma: predictors of clinical outcome.
Authors: Ronald Tang, Michael Sgroi, David Imagawa, Tara Elisabeth Seery
Journal: Journal of Clinical Oncology (2015)

e15229 Background: Ampullary adenocarcinoma (AA) is a rare gastrointestinal neoplasm and predictors of clinical outcomes are extrapolated from pancreatic adenocarcinoma. If detected early, the preferred treatment modality is pancreatoduodenectomy, however factors associated with improved survival are unknown. Methods: We retrospectively investigated factors associated with clinical outcomes among 50 patients who underwent pancreatoduodenectomy at UC-Irvine Medical Center from 1996 to 2013 for AA. Factors analyzed included: number of LN removed during surgery, LN involvement, diabetes, laboratory values at diagnosis: total bilirubin, alkaline phosphatase, WBC, and Ca 19-9. Univariate OS and PFS estimates were generated using Kaplan-Meier methods. Multivariate analysis of OS and PFS were performed using Cox proportional-hazard regression models, adjusting for age, gender, stage, and smoking. Results: R0 resection was achieved in 82% of patients with the remaining receiving ampullectomy. Median age, 67 years; 62% males; 54% Caucasian; 73% non-smokers, stages 0-3 represented. Mean lymph nodes removed during R0 resection was 19. Median OS was 30.5 months with 28% of patients alive at time of analysis. Thirty percent of patients received adjuvant chemotherapy with a median OS of 59.9 months compared to 26.9 months for patients without adjuvant chemotherapy (p-value = 0.001, HR = 0.449 (95% CI 0.201,1.00)). Adjuvant chemotherapy (p-value = 0.06) was associated with borderline significant increase in PFS. Patients received either 5-FU, combination 5-FU based treatment, or single agent gemcitabine. Normal WBC at time of diagnosis (p-value = 0.01) was associated with improved OS. Other factors (DM, race, age, alk phos, Ca 19-9 level, smoking, # of LN removed) were not statistically significant for OS or PFS. Conclusions: In this retrospective, single-institution study of ampullary adenocarcinoma, we found that patients who receive an R0 resection with adequate lymph node dissection benefit from adjuvant chemotherapy with a statistically significant OS. Normal WBC at diagnosis was associated with improved OS. We did not observe any other adjustment factors associated with OS or PFS.
Development and validation of a prognostic nomogram to predict overall survival (OS) in platinum-resistant ovarian cancer (PROC): An AURELIA substudy.
Authors: Chee Lee, Emma Gibbs, Felicia T Roncolato, Lucy Claire Davies, Christine Le Maignan, Werner Meier, Maria Angeles Arcusa Lanza, Per Rosenberg, Claudia Marchetti, Ignace Vergote, Petronella Witteveen, Aristotelis Bamias, Sebastian Serra, Jocelyne Provencal, Gaetan De Rauglaudre, Val Gebski, Michael Friedlander, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2015)

5547 Background: PROC describes a heterogeneous group of patients (pts) with a variable but generally poor prognosis and low response to chemotherapy. Predicting OS in PROC would help stratify pts in trials and guide treatment decisions. We developed a nomogram to predict OS in PROC. Methods: Data from two randomized phase III trials evaluating chemotherapy for PROC – CARTAXHY [Lortholary Ann Oncol 2012] and AURELIA [Pujade-Lauraine JCO 2014] (chemotherapy-alone arm) – were combined to form the training cohort (N = 331) for nomogram development. Baseline variables significantly associated with OS were identified using Cox regression analysis. Pts were assigned scores based on the weighted sum of the relative importance of each variable in the multivariate model. The nomogram was then validated in the chemotherapy plus bevacizumab arm of the AURELIA trial (N = 166). Nomogram performance was assessed by calculating the c statistic. A classification based on the nomogram’s score was generated to group pts according to prognosis. Results: Poor performance status, CA125 ≥ 100 U/mL, ascites, platinum-free interval < 3 months, primary platinum resistance, and largest tumor > 5cm were associated with shorter OS. The nomogram predicted OS with a c statistic of 0.69 (training) and 0.67 (validation). In the training cohort, the median OS in good (N = 93), intermediate (N = 162), and poor (N = 76) prognostic groups was 25.3, 15.6, and 6.9 months, respectively (P < 0.0001). In the validation cohort, median OS in good (N = 50), intermediate (N = 79), and poor (N = 37) prognostic groups was 26.7, 13.8, and 9.0 months, respectively (P < 0.0001). Conclusions: This nomogram combining six baseline factors accurately predicts OS in PROC pts treated with chemotherapy either alone or in combination with bevacizumab. It could help to select pts for treatment, counsel pts regarding prognosis, and stratify according to risk in trials. Clinical trial information: NCT00976911.