tbuckley/cabot-search huggingface dataset:
Association between increasing body mass index (BMI) and breast cancer screening: Analysis of the 2016 behavioral risk factor surveillance system survey.
Authors: Randy C. Miles, Anand Narayan, Sarah Mercaldo, Rulla M. Tamimi, Constance Dobbins Lehman
Journal: Journal of Clinical Oncology (2018)

e18618 Background: Prior studies suggest that obese women demonstrate reduced breast cancer screening rates. These studies however were limited in their ability to adjust for potential confounding factors and obesity rates have increased considerably since these studies were performed. Our objective was to assess the current association between increasing BMI and mammography screening adherence. Methods: Self-reported breast cancer screening data was included for 116,343 women ages 50-74 years from the 2016 Behavioral Risk Factor Surveillance System, a nationally representative telephone survey. Proportions reporting mammography within the last two years were calculated by BMI categories (normal: 18.5-24.9 kg/m2, overweight: 25-29.9 kg/m2, obese Class I: 30-34.9 kg/m2, obese Class II: 35-39.9 kg/m2, and obese Class III: > 40 kg/m2) and by race (White, Black, Hispanic, and Asian), accounting for complex survey design elements. The effect of BMI on mammography adherence was examined using a multivariate logistic regression model, adjusting for age, income, insurance, marital status, and education, and stratified by race. Statistical significance was assessed using Wald tests. Results: Of survey respondents, 33.5% had a normal BMI, 32.6% were overweight, 19.3% were obese Class I, 8.4% were obese Class II, and 6.2% were obese Class III. After adjusting for age, income, insurance, marital status and education, BMI was positively associated with higher screening adherence among overweight (OR 1.15, p < 0.01) and obese Class II (OR 1.17, p = 0.02) White women, compared to White women with normal BMI. No statistically significant associations were found between screening adherence and BMI categories among Blacks (p = 0.22), Hispanics (p = 0.19) or Asians (p = 0.11). Using a Wald test, we found no evidence of effect modification of BMI category by race (p = 0.37). Conclusions: After controlling for potential confounding factors such as income and insurance status, we found no association between increased BMI and reduced screening adherence. Sociodemographic factors may represent primary drivers of mammography screening within this population.
Role of serum thymidine kinase-1 (TK1) activity in patients (pts) with hormone receptor positive (HR+) advanced breast cancer (ABC) treated with endocrine therapy (ET) in the EFECT trial.
Authors: Luca Malorni, Chiara Biagioni, Amelia McCartney, Gaia Schiavon, Mattias Bergqvist, Matteo Benelli, Ilenia Migliaccio, Laura Biganzoli, Martina Bonechi, Giulia Boccalini, Marta Pestrin, Francesca Galardi, Francesca De Luca, Martine J. Piccart-Gebhart, William John Gradishar, Stephen K. L. Chia, Angelo Di Leo
Journal: Journal of Clinical Oncology (2018)

12031 Background: TK1 plays a critical role in DNA synthesis and cell proliferation. The DiviTum assay measures serum TK1 activity (sTKa), reflecting cancer cell proliferation. Recent studies suggest this assay may provide real time prognostic information in ABC. However, its role in HR+ ABC needs further validation. Methods: EFECT (n = 693) was a double-blind, randomized trial of fulvestrant 250mg versus exemestane after progression on nonsteroidal aromatase inhibitor therapy for ABC. 58% of pts had received > 1 prior ET for ABC. sTKa was retrospectively assessed with DiviTum on serum samples from pts in the EFECT cohort. Samples were collected before start of ET (T0), after 3 (T3) and 6 (T6) months of ET, and at disease progression (PD). Pts were categorized as High/Low sTKa at T0 based on the median value. On-treatment sTKa changes were calculated from T0 to the next available time-point within 3 months from randomization (T3, or PD for those pts with early progression - ePD), accounting for a coefficient of variation of 10%, and defined as follows: Drop (T3 or ePD < T0); Increase (T3 or ePD > T0); No change (T3 or ePD = T0). Analyses were conducted regardless of study arms. Results: All available samples were successfully tested for sTKa (586 samples from 244 consenting pts). Median sTKa at T0 (n = 227), T3 (n = 135), T6 (n = 80) and PD (n = 137) was 97, 57, 57.5 and 132 Du/L, respectively. Median time to progression (mTTP) for pts with Low T0 sTKa (n = 111) was 5.03 months (m) (95% CI 3.91-5.89) vs 2.57 (95% CI 2.04-3.52) for pts with High T0 sTKa (n = 110) (p < 0.001). On-treatment sTKa changes from T0 were analysed in 159 pts (T3 = 116; ePD = 43). mTTP in pts with TK1 Drop (n = 53) was 5.4 m (95% CI 3.7-7.7) vs 3.4 (95% CI 2.1-4.1) in pts with Increase (n = 68) (p < 0.018). mTTP in pts with No change (n = 38) was similar to those with Drop. After adjustment for major prognostic factors, sTKa remained an independent marker. Conclusions: sTKa is a potential circulating prognostic marker in pts with ABC treated with ET, and may represent a tool for upfront identification of ET-resistant pts, and non-invasive monitoring of response to ET. Independent validation of these results is warranted.
Abstract 19167: Transcriptome Remodeling of Cardiac Autonomic Nervous System Following Myocardial Infarction In Porcine
Authors: Chen Gao, Kimberly Howard-Quijano, Tatsuo Takamiya, Wei Zhou, Christoph D Rau, Yang Song, Aman Mahajan, Yibin Wang
Journal: Circulation (2016)

Background: Cardiac autonomic nervous system (ANS), including spinal cord (SC), stellate ganglia (SG) and dorsal root ganglia (DRG), plays a critical role in cardiac regulation of contractile funct...
Abstract 16089: Activation of PPARα During the Progressive Phase of Heart Failure Improved Myocardial Energetics and Function in Pressure Overload Heart Failure
Authors: Satoshi Kaimoto, Atsushi Hoshino, Makoto Ariyoshi, Yoshifumi Okawa, Motoki Uchihashi, Kuniyoshi Fukai, Kazunori Ono, Shuhei Tateishi, Eri Iwai-Kanai, Satoaki Matoba
Journal: Circulation (2014)

Background:  Advanced failing heart loses its metabolic flexibility and relies more on glucose oxidation than fatty acid oxidation (FAO) as its preferential metabolism. Peroxisome proliferator-activated receptorα (PPARα) is known as a key regulator of this substrate shift. Recent studies have reported that neither cardiac specific PPARα transgenic mice nor PPARα deficient mice could protect against heart failure.   Method and Results:  To investigate the role of PPARα on cardiac metabolism , we used transverse aortic constriction (TAC)-induced heart failure model. After eight weeks of TAC, left ventricular (LV) function was decreased with the reduction of PPARα expression. Administration of WY14643 (specific PPARα agonist) for eight weeks after TAC operation could not decrease the development of heart failure. Next, we examined the effect of WY14643 for late four weeks (from the forth to the eighth week), which were the progressive phase of heart failure. TAC-operated mice were randomly allocated into two groups : a HF group of untreated mice with heart failure, and a WY-HF group of mice with heart failure receiving WY14643. Eight weeks after TAC operation, LV contraction was preserved significantly in the WY-HF group with remarkable reduction in fibrosis compared to HF-group. The levels of PPARα downstream genes involved in fatty acid metabolism were significantly increased in the WY-HF group in comparison with the HF group, and the level of BNP expression was significantly reduced in the WY-HF group. Myocardial high energy phosphates were significantly preserved in the WY-HF group.   Conclusions:  Present study suggested that activation of PPARα during the progressive phase of heart failure improved myocardial energetics and function in pressure-overloaded heart failure. Activation PPARα and upregulation of FAO will be a new therapeutic strategy for heart failure.
TCT-335 Predictors of Elevated Gradients After Transcatheter Aortic Valve Replacement for Failing Bioprosthetic Aortic Valve Replacement
Authors: Robert L. Richmond, Daniel P. O'Hair, Daniel R. Harland, Tanvir Bajwa, Suhail Q. Allaqaband, Amanda M. Kirby, Susan Olet, Bijoy K. Khandheria, Renuka Jain
Journal: Journal of the American College of Cardiology (2018)
Efficacy of chronic BACE1 inhibition in PS2APP mice depends on the regional Aβ deposition rate and plaque burden at treatment initiation
Authors: Matthias Brendel, Anna Jaworska, Felix Overhoff, Tanja Blume, Federico Probst, Franz-Josef Gildehaus, Peter Bartenstein, Christian Haass, Bernd Bohrmann, Jochen Herms, Michael Willem, Axel Rominger
Journal: Theranostics (2018)

Beta secretase (BACE) inhibitors are promising therapeutic compounds currently in clinical phase II/III trials.Preclinical [ 18 F]-florbetaben (FBB) amyloid PET imaging facilitates longitudinal monitoring of amyloidosis in Alzheimer's disease (AD) mouse models.Therefore, we applied this theranostic concept to investigate, by serial FBB PET, the efficacy of a novel BACE1 inhibitor in the PS2APP mouse, which is characterized by early and massive amyloid deposition.Methods: PS2APP and C57BL/6 (WT) mice were assigned to treatment (PS2APP: N=13; WT: N=11) and vehicle control (PS2APP: N=13; WT: N=11) groups at the age of 9.5 months.All animals had a baseline PET scan and follow-up scans at two months and after completion of the four-month treatment period.In addition to this longitudinal analysis of cerebral amyloidosis by PET, we undertook biochemical amyloid peptide quantification and histological amyloid plaque analyses after the final PET session.Results: BACE1 inhibitor-treated transgenic mice revealed a progression of the frontal cortical amyloid signal by 8.4 ± 2.2% during the whole treatment period, which was distinctly lower when compared to vehicle-treated mice (15.3 ± 4.4%, p<0.001).A full inhibition of progression was evident in regions with <3.7% of the increase in controls, whereas regions with >10% of the increase in controls showed only 40% attenuation with BACE1 inhibition.BACE1 inhibition in mice with lower amyloidosis at treatment initiation showed a higher efficacy in attenuating progression to PET.A predominant reduction of small plaques in treated mice indicated a main effect of BACE1 on inhibition of de novo amyloidogenesis.Conclusions: This theranostic study with BACE1 treatment in a transgenic AD model together with amyloid PET monitoring indicated that progression of amyloidosis is more effectively reduced in regions with low initial plaque development and revealed the need of an early treatment initiation during amyloidogenesis.
Analysis of overall survival in patients with multiple primary malignancies.
Authors: Long H. Dang, William Paul Skelton, Rohit Bishnoi, Azka Ali, Raphael Bosse, Cuc Nguyen, Roland-Austin Federico, Sarah Pang, Jacob Barish, Wissam Hanayneh, Nam H. Dang
Journal: Journal of Clinical Oncology (2018)

e14520 Background: Multiple primary malignancies (MPMs) are seen in ~5% of all tumors. The incidence of diagnosis of MPMs is increasing secondary to improved diagnostic techniques as well as novel treatment modalities leading to prolonged survival. The aim of this study was to determine quantitative impact on overall survival (OS) and treatment choices in patients with MPMs. Methods: A retrospective analysis to determine patients with MPMs was conducted over a 6 year period from 2011-2017 at the University of Florida (UF). Patients with two or more primary malignancies were included, while skin cancers and those not receiving treatment for their malignancies were excluded. Patients were defined as simultaneous MPMs if the second malignancy was discovered within 60 days of the first, and defined as sequential MPMs if discovered after 60 days of the first. This study was approved by the UF IRB. Results: 56 patients with MPMs as defined above were identified, 38 (68%) simultaneous and 18 (32%) sequential. Development of second malignancy did not affect treatment in 47 (84%) of patients. 48 patients (86%) were deceased at the end of the study. Median OS after diagnosis of first malignancy was 13.0 months (95% CI 10.3-15.8 months), compared to 10.6 months (95% CI 7.1-13.9 months) after the diagnosis of a second malignancy. Median OS for the simultaneous MPM group was 13.5 months (95% CI 7.1-19.9 months), compared to 3.2 months (95% CI 0.0-9.8 months) for the sequential MPM group. Conclusions: The development of a second malignancy impacts OS and treatment decisions. Patients who developed MPM later in the course of treatment (sequential) performed poorer than those who developed MPM earlier in treatment course (simultaneous). This was likely in part due to effects of existing treatment on performance status as well as patient treatment preferences when second MPM is diagnosed (as many patients opted for supportive care after second MPM). Further analysis with larger patient cohorts is necessary to ascertain the aforementioned effects of OS and treatment options with respect to tumor pathology, stage, and performance status.
Prognostic impact of tumour laterality in early-stage colon cancer: A population-based study.
Authors: Safiya Karim, Kelly Brennan, Sulaiman Nanji, Scott R. Berry, Christopher M. Booth
Journal: Journal of Clinical Oncology (2017)

e15148 Background: Recent data has suggested that disease biology and outcome of colon cancer may differ between right-sided and left-sided tumours. Here we explore differences in laterality based on disease characteristics and outcomes in a population-based cohort of early-stage colon cancer. Methods: Electronic records of treatment were linked to the Ontario Cancer Registry to identify all patients with colon cancer in 2002-2008. The study population included a 25% random sample of all patients with resected stage 0-III disease. Right-sided colon cancer was defined as any tumor arising in the cecum, ascending colon, hepatic flexure or transverse colon. Left-sided colon cancer was defined as any tumor arising from the splenic flexure, descending colon, sigmoid colon or rectosigmoid colon. Log binomial regression was used to identify factors associated with laterality. Cox models were used to explore the association between laterality and overall (OS) and cancer-specific (CSS) survival. Results: Among the study cohort (n = 6391) median age was 72 and 52% (3307/6391) had right-sided disease. Stage distribution was 2% (98/6391) stage 0, 17% (1091/6391) stage I, 38% (2446/6391) stage II, and 43% (2756/6391) stage III. Patients with right-sided colon cancer were more likely to be older (p &lt; 0.001), female (p &lt; 0.001) and have greater co-morbidity (p = 0.001). Right-sided cancer was more likely to be T4 (19% vs 16%, p = 0.001) and poorly differentiated (21% vs 10%, p &lt; 0.001) but less likely to be node positive (42% vs 45%, p = 0.029) compared to left-sided disease. In adjusted analyses there was no difference in long-term survival for right-sided compared to left-sided colon cancer: OS HR 1.00 (95%CI, 0.92-1.08); CSS HR 1.00 (0.91-1.10). These results were consistent when the survival analyses were restricted to stage III disease: OS HR 1.03 (95%CI 0.93-1.14); CSS HR 1.10 (0.97-1.24). Conclusions: In this population-based cohort of early-stage resected colon cancer disease laterality was not associated with long-term survival.
A single institutional experience of 261 patients with large granular lymphocytic leukemia (LGLL).
Authors: Magali Van den Bergh, Leidy Lismeri Isenalumhe, Emilie Wang, Braydon Schaible, Zhenjun Ma, Ling Zhang, Lubomir Sokol
Journal: Journal of Clinical Oncology (2017)

7555 Background: LGLL is a rare clonal lymphoproliferative disorder of post-thymic T-cell or natural killer (NK)-cell lineage associated with cytopenias, splenomegaly, autoimmune disorders, and recurrent mucocutaneous infections. Treatment is dictated by the presence of these manifestations and consists of immunosuppressive therapy. Methods: This is a retrospective analysis of clinical and laboratory features, treatment modalities, and outcomes of LGLL patients evaluated at Moffitt Cancer Center between 1995 and 2016. Continuous and categorical variables were tested via Kruskal-Wallis ANOVA and Fisher’s Exact Test. Kaplan-Meier curves were used for overall survival (OS). P-values were two-sided with significance set at &lt; 0.05. Results: We identified 261 patients with LGLL (91.6% T, 8.4% NK). Median age was 66 years [21-90] and M:F ratio 1.2:1. Median follow up was 3.07 years [0-21.88]. 42.9% presented with anemia, 37.1% neutropenia, 30.7% thrombocytopenia, 29.1% bicytopenia and 6.9% pancytopenia. Transfusion dependence was noted in 20.3%, splenomegaly in 27.2% and bone marrow (BM) involvement in 69.3%. 24.9% had autoimmune diseases and 9.2% autoimmune cytopenias. 45.6% were observed while the remainder required at least 1 line of therapy. 5-yr and 10-yr OS were 75.0% and 63.1% respectively. There was no statistically significant difference in OS, complete response or duration of response based on first line agent (methotrexate, cyclophosphamide, cyclosporine A). However, there was a statistically significant improved partial response with methotrexate versus other therapies (p=0.01). A marginally significant association between severe anemia/transfusion dependence and poor overall response rate (p=0.075) to any therapy was noted. There was no statistically significant difference in OS based on absolute LGL count. Mean number of therapies was 1.08 (range 0-6) and was higher in those with LGL count &lt;0.5 k/μL (p=0.0078), BM involvement (p&lt;0.0001), and splenomegaly (p&lt;0.0001). Conclusions: In this large retrospective study, we described the frequency of LGLL-associated manifestations and their impact on the course of LGLL. We confirmed that there is no difference in OS among first line therapies.
The emotional toll of caregiving for older patients with advanced cancer: Baseline data from a multicenter geriatric assessment (GA) intervention study in the University of Rochester NCI Community Oncology Research Program (UR NCORP).
Authors: Supriya Gupta Mohile, Huiwen Xu, Beverly E. Canin, Sandy Plumb, Megan Wells, Marie Anne Flannery, Michael Hoerger, Charles Stewart Kamen, Arti Hurria, William Dale, Charles E. Heckler, Eva Culakova, Javier Bautista, Judith O. Hopkins, Jijun Liu, Srihari Peri, Jodi Geer, Karen Michelle Mustian, Gary R. Morrow, Paul Duberstein
Journal: Journal of Clinical Oncology (2017)

10042 Background: Depression is common in caregivers (cgs) of patients (pts) with cancer. However, little is known about the association of health status of older pts with cancer with cg emotional health. Methods: Baseline data from a GA intervention study conducted at 68 oncology practices in the UR NCORP were analyzed. Pts aged ≥ 70 with an advanced solid tumor cancer or lymphoma with ≥ 1 GA impairment were enrolled; pts could enroll with 1 cg. Relationships between pt GA impairments (using 12 validated measures) and cg (spouses or live-in partners) emotional health including anxiety ( ≥ 5 on Generalized Anxiety Disorder-7 (GAD-7)), depression ( ≥ 2 on Patient Health Questionnaire-2), and distress ( ≥ 4 on distress thermometer) were evaluated in separate multivariate logistic models adjusted for pt (cancer type, treatment status) and cg (age, sex, race, education, income, comorbidity) characteristics. Results: Among 213 pts (mean age 76, 70-89), &gt;50% had ≥ 5 impaired GA measures. Of the 213 cg (mean age 73, 52-91), 23% screened positive for anxiety, 16% for depression, and 40% for distress. In bivariate analyses, number of GA impairments, ≥ 1 fall, pt anxiety ( ≥ 5 on GAD-7) and depression ( ≥ 5 on Geriatric Depression Scale (GDS)) were associated with all 3 cg outcomes; pt activities of daily living (ADL) deficits were associated with cg depression and distress. In multivariate analysis, number of GA impairments was associated with cg distress. In separate models, pt ADL deficit and depression were associated with cg distress, and pt ADL deficit was associated with cg depression. GA variables were not associated with cg anxiety in multivariate analysis. Conclusions: A high proportion of cg of older pts with cancer report distress. GA can help identify cg at risk for poor emotional health. Interventions for cgs should address the health status of older pts with cancer. [Table: see text]
Impact of perioperative blood transfusion on survival among women with breast cancer.
Authors: Rashid Nadeem, Mina Cha, Dinah Arafeh, Hiba Khan, Muhammad Yousaf, Banan Turkman, Raheel Memon, Amin Nadeem, Hassan Sajid, Shafaq Jawed
Journal: Journal of Clinical Oncology (2017)

e21591 Background: Blood transfusion has immune-modulating effect which may affect outcome in women with breast cancer including cancer recurrence and survival. Methods: PubMed, Embase and Cochrane libraries were searched by utilizing different combinations of keywords: blood transfusion, survival, mortality and breast cancer. Inclusion criteria were: (1) English articles and (2) studies with an adult population with the diagnosis of breast cancer undergoing resection which may or may not have received blood transfusion. Four hundred and seventy studies were reviewed, 13 studies meeting inclusion criteria were pooled for Meta-analysis. Results: Twenty five datasets from 13 studies with total N = 7384 subjects (transfused 2264, not transfused 5120) were pooled. Survival rates recorded at a specified time frame, this range from 4-12 years. Major confounding factors effecting survival in this population may include age, presence of other chronic illnesses, spread of breast cancer to lymph nodes, stage of cancer and extent of cancer treatment. Type, group and number of blood units transfused may also play a role. Survival rates among not transfused group range from 34% to 79% while in transfused group range from 41% to 78%. Significant heterogeneity was detected among studies; therefore random effect model was used. Comparing women without blood transfusion, women with transfusion have Odd ratio of overall survival 0.79 (0.72 to 0.86, I 2 = 47.3, P = 0.001). we also performed sensitivity and subgroup analysis. Conclusions: Perioperative blood transfusion appears to adversely impact survival among women with breast cancer