tbuckley/cabot-search huggingface dataset:
Abstract 18942: Is Bilirubin Protective Against Anthracycline-induced Cardiomyopathy?
Authors: Trinity Vera, Timothy M Morgan, Jennifer H Jordan, Matthew C Whitlock, Dalane Kitzman, W. G Hundley
Journal: Circulation (2014)

Introduction: Reductions in left ventricular ejection fraction (LVEF) may occur after the administration of anthracycline-based chemotherapeutic regimens. Oxidative stress at the myocellular level has been implicated in these reductions, and as a consequence, we hypothesized that bilirubin, an effective endogenous anti-oxidant, would ameliorate some of the reductions in LVEF associated with anthracyline administration. Methods: From 1/1/2002 to 12/31/2012, we identified 751 consecutive individuals who were treated with anthracyclines at Wake Forest Baptist Medical Center, received serial LVEF measures, and exhibited basal serum bilirubin levels &lt; 2mg/dl prior to their treatment for cancer. The correlation between pre-chemotherapy bilirubin levels and serial pre- to post-chemotherapy changes in LVEF was analyzed using linear regression models. For dose response analysis, the participants were divided into 3 groups based on their bilirubin levels. ANOVA was used to test for the difference in the mean LVEF change across groups. Tukey’s Studentized Range test was used in pairwise comparisons. Chi-square test was used for categorical variables. Results: There were 65 (35%), 86 (30%) and 68 (24%) participants whose LVEF decreased by more than 15% in Group 1 (bilirubin ≤0.5mg/dl), Group2 (bilirubin 0.6 - 0.8mg/dl) and Group 3 (bilirubin 0.9 - 1.9mg/dl) respectively (Table 1). On pairwise comparison, there was a significant decrease in LVEF between Group 1 and Group 3 (2.9, 95% CI: 0.15 - 5.7). After adjusting for age, BMI, race, CAD/MI, diabetes, hematocrit and medications; increased bilirubin and reduced BMI were associated with LVEF preservation (p = 0.028 and 0.033 respectively). Conclusions: In patients treated with anthracyclines, bilirubin level was negatively correlated with reduction in LVEF. These results have potential therapeutic implications for preserving left ventricular function in patients treated with anthracyclines.
Change in Measured GFR Versus eGFR and CKD Outcomes
Authors: Elaine Ku, Dawei Xie, Michael Shlipak, Amanda Hyre Anderson, Jing Chen, Alan S. Go, Jiang He, Edward J. Horwitz, Mahboob Rahman, Ana C. Ricardo, James H. Sondheimer, Raymond R. Townsend, Chi-yuan Hsu
Journal: Journal of the American Society of Nephrology (2015)

Measured GFR (mGFR) has long been considered the gold standard measure of kidney function, but recent studies have shown that mGFR is not consistently superior to eGFR in explaining CKD-related comorbidities. The associations between longitudinal changes in mGFR versus eGFR and adverse outcomes have not been examined. We analyzed a subset of 942 participants with CKD in the Chronic Renal Insufficiency Cohort Study who had at least two mGFRs and two eGFRs determined concurrently by iothalamate and creatinine (eGFR cr ) or cystatin C, respectively. We compared the associations between longitudinal changes in each measure of kidney function over 2 years and risks of ESRD, nonfatal cardiovascular events, and all-cause mortality using univariate Cox proportional hazards models. The associations for all outcomes except all-cause mortality associated most strongly with longitudinal decline in eGFR cr. Every 5-ml/min per 1.73 m 2 decline in eGFR cr over 2 years associated with 1.54 (95% confidence interval, 1.44 to 1.66; P &lt;0.001) times higher risk of ESRD and 1.23 (95% confidence interval, 1.12 to 1.34; P &lt;0.001) times higher risk for cardiovascular events. All-cause mortality did not associate with longitudinal decline in mGFR or eGFR. When analyzed by tertiles of renal function decline, mGFR did not outperform eGFR cr in the association with any outcome. In conclusion, compared with declines in eGFR, declines in mGFR over a 2-year period, analyzed either as a continuous variable or in tertiles, did not consistently show enhanced association with risk of ESRD, cardiovascular events, or death.
Therapeutic options in metastatic castration-resistant prostate cancer (mCRPC): A cost-effectiveness analysis.
Authors: Lixian Zhong, Sandy Srinivas, Vickie Pon, Nicole Nguyen, Meghan Frear, Sherry Kwan, Cynthia Gong, Robert Malmstrom, Aimee Loucks, Leslie Wilson
Journal: Journal of Clinical Oncology (2012)

e15154 Background: Initial therapy for metastatic prostate cancer is androgen deprivation therapy. Uniformly progression of disease occurs despite castration. Docetaxel is then the standard of care. Abiraterone (Abi) and cabazitaxel (Cab) are approved for mCRPC post docetaxel with improvements in survival We seek to evaluate the cost-effectiveness of Abi and Cab compared to mitoxantrone (Mit) and prednisone for mCRPC. Methods: A decision tree model was constructed comparing four treatments for mCRPC patients over an 18 month period: 1) Abi, 2) Cab, 3) Mit, and 4) prednisone only. Chance nodes included baseline pain as a severity indicator, grade III &amp; IV adverse events (AE) (neutropenia and cardiac ) and survival at 18mos. Survival rates and probabilities were from published data. Cost of drug regimens were based on 2010 US dollars and average wholesale price (AWP). Model cost inputs included drug-costs, administration costs, management of AE’s, radiation for pain, and costs associated with death. Health utilities for baseline pain, bone pain, neutropenia, cardiac events, and radiation were obtained from published data. Sensitivity analyses were conducted focused on baseline severity and costs of drug. Results: Base case estimates suggest that Cab and Abi are most effective. The incremental cost effectiveness ratio (ICER) for Mit vs. placebo is $110K/QALY, Abi vs. Mit is $76K/QALY and for Cab vs. Abi, the ICER is $925K/QALY. Model-sensitive parameters include Abi AWP and cost of Mit side effect management; Abi becomes less cost-effective as its AWP increases, or if the cost of Mit side effect management decreases. When baseline severity increases, Mit becomes cost-effective over placebo and Abi remains cost-effective over Mit. Cab remains not cost-effective at tolerable thresholds. Conclusions: Compared to Cab, Mit, and placebo, Abi is the most cost-effective option in docetaxel-refractory mCRPC patients due to its ability to prolong survival and maintain a willingness-to-pay threshold (WTP) of $100K. Despite higher survival with Cab, it is not cost-effective because of costs associated with treatment of neutropenia. In situations where illness is more severe, Abi remains the cost-effective choice.
A phase I/II study of induction oxaliplatin, 5FU chemoradiation in patients with locally advanced, unresectable pancreatic cancer
Authors: R. C. Leung, T. Ryan, H. Hochster, E. Newman, A. Chandra
Journal: Journal of Clinical Oncology (2007)

15027 Background: Newly diagnosed locally advanced and unresectable pancreatic cancer has a 5 yr survival rate of less than 5%. Aggressive local therapy may provide the best means of achieving local control and prolonging survival. We administered concomitant chemoRT with Oxaliplatin and continuous infusional (CIV) 5FU to determine the maximum tolerated dose (MTD) in the phase I portion. Methods: Pts with histologically proven locally advanced pancreatic cancer were enrolled in standard Phase I 3+3 fashion to determine MTD. ChemoRT included 5FU 200mg/m 2 CIV and Oxaliplatin wkly X5 wks. Radiation dose was 4500cGy in 25 fractions (180cGy/fx/d) over 5 wks followed by a conedown to the tumor and margin for an additional 540cGy x3 (total dose 5040 cGy in 28 fractions) Oxaliplatin was escalated from 30mg/m 2 in 10mg intervals up to 60mg/m 2 . Following chemoRT, unresectable pts were treated with mFOLFOX6 x 6. Results: 15 pts enrolled in the phase I portion, all completed neoadjuvant therapy. Most hematologic toxicities were gr 1 and 2. There was 1episode of gr 4 lymphopenia. The most common non-hematologic toxicities were gr1–2 fatigue, anorexia, nausea and vomiting. Gr 3 non-hematologic toxicities included 4 episodes hyperglycemia, 1 diarrhea, 1 anorexia, 3 nausea/vomiting and 2 hypokalemia. The highest planned dose level for weekly Oxaliplatin was tolerable and the RPTD is 60mg/m 2 /wk. Of the 15 pts: 2 progressed, 2 were explored but were unresectable, 2 await exploration and 9 were deemed still unresectable and proceeded to consolidation. 7/9 completed the planned 6 cycles. 1 pt was removed from protocol due to extended delay of treatment due to gr 3 neuropathy. 1 pt died due to progressive disease. 21% of planned cycles were delayed due to gr2 or 3 myelosuppression. 1 pt required dose reduction due to fever in setting of gr4 neutropenia but was able to complete treatment at the reduced dose. Conclusions: Combined modality treatment for locally advanced pancreatic cancer with Oxaliplatin, CIV 5FU and radiation is well tolerated at full doses of Oxaliplatin (60mg/m 2 /wk) and does not produce substantially more toxicity than standard chemoRT to the pancreatic bed. The phase II portion of the trial is ongoing. [Table: see text]
Late treatment effects, health behavior, and quality of life (QOL) in testicular cancer (TC) survivors
Authors: L. A. Jacobs, S. Palmer, G. Matthews, K. D. Robertson, A. T. Meadows, D. J. Vaughn
Journal: Journal of Clinical Oncology (2004)

8012 Background: TC is the most common solid tumor diagnosed among men aged 15 to 34 with almost 7000 new cases/year in the United States. Most of these patients will be cured and become long-term survivors. Although physiological late consequences of treatment are well articulated, the impact of late treatment effects and health behavior on QOL is not known. Methods: The Living Well After Cancer (LWAC) Survivorship Program at Penn monitors TC survivors ≥ 2 years since diagnosis and disease-free. To date, 55 subjects have been recruited from LWAC for this ongoing study. Treatment variables, subjective and objective measures of late effects, health behaviors, and the City of Hope QOL measure were examined. Results: Subjects were young (\(\underline{\mathrm{M}}\)=39 yrs) and 63% received cisplatin-based chemotherapy (CBCT). Physical (\(\underline{\mathrm{M}}\)=8.0) and Social well-being (\(\underline{\mathrm{M}}\)=7.0) were high; Psychological (\(\underline{\mathrm{M}}\)=4.6) and Spiritual well-being (\(\underline{\mathrm{M}}\)=5.0) moderate. Physical, Social, and Psychological well-being were positively related (all \(\underline{\mathrm{p}}\) < .03); Spiritual well-being was independent of other QOL indices. Time since diagnosis and receipt of CBCT were not related to QOL (\(\underline{\mathrm{p}}\) > .12). Total cholesterol was elevated in 43% and LDL in 32% of the survivors. Health behaviors were examined; 42% of subjects reported a smoking history. Smoking was a marker for decreased Social well-being; increased fatigue; anxiety; depression; uncertainty about the future; concern about second cancers, recurrences, or metastases; and interference from illness with home and financial responsibilities (all \(\underline{\mathrm{p}}\) < .05). Objective measures of late treatment effects including lipid levels were not related to cisplatin status, smoking history, or QOL (\(\underline{\mathrm{p}}\) > .23). Conclusions: These data suggest: 1) TC survivors report high physical and social well-being, but lower psychological and spiritual well-being; 2) Smoking may be a marker for overall social concerns and a number of specific QOL deficits in this group. Smoking cessation interventions may not only impact physiologic health, but psychosocial status. No significant financial relationships to disclose.
Abstract 16329: Small Aortic Root Dimension: A Contributor to Increased Arterial Stiffness in Hypertension (The Campania Salute Network Registry)
Authors: Mai Tone Lønnebakken, Raffaele Izzo, Marina De Marco, Giovanni Esposito, Eugenio Stabile, Nicola De Luca, Eva Gerdts, Bruno Trimarco, Giovanni de Simone
Journal: Circulation (2014)

Background: In preliminary analysis in a population-based study larger aortic root dimension (ARD) was associated with higher stroke volume, diastolic blood pressure (BP) and heart rate, but lower systolic BP. Thus we assessed whether ARD influences a 2-element windkessel model of arterial stiffness in the setting of arterial hypertension. Methods: Ultrasound carotid intima-media thickness (IMT), echocardiographic ARD and pulse pressure (brachial) / stroke index ratio (PP/SVi) were measured in 12392 hypertensive patients (age 53±12 years, 43% women) free of prevalent cardiovascular (CV) disease and with ejection fraction ≥ 50% from the Campania Salute Network Registry. ARD was compared with the value predicted by age, sex and height, using an equation previously generated in 1207 normal subjects, to predict ideal sex-specific ARD. A sex-specific Z-score was thereafter calculated (ARD-z). PP/SVi was categorized in normal (lowest and middle tertiles) and high (highest tertile). Results: High PP/SVi was slig...
Impact of chemotherapy (CT) on ex-vivo generation of dendritic cells (DCs) in advanced breast cancer (ABC) patients (pts)
Authors: S. Ferrari, B. Rovati, E. Collovà, D. Grasso, P. Sagrada, C. Porta, A. Riccardi, M. Danova
Journal: Journal of Clinical Oncology (2004)

2583 Background Among the several problems in planning and carrying out clinical trials with ex-vivo-generated, tumor antigen-loaded DCs for solid tumors, the pts selection, the optimal time to take blood for generating DCs and the impact on them of number and types of previous CT could also play a role. To date, high quantity of DCs can be generated after high-dose CT plus G-CSF in both BC and NHL pts. We investigated the DC yield obtainable from ABC pts in objective response after a SD, taxane-based CT program, considering these patients potentially candidate to DC-based vaccination programs. Patients and Methods Sixteen pts, aged 56 (range 43- 65), were studied 1 to 3 month after an objective response was obtained with a 1st-line CT (Epirubicin+Docetaxel combination at standard dosages, without the scheduled utilization of G-CSF) for their metastatic disease. DCs were generated from 25 ml of blood and following the standard procedure; the monocyte selection was performed with anti-CD14 microbeads (Miltenyi), followed by an immunomagnetic separation (MiniMacs, Miltenyi). DCs were analyzed for HLA-DR, CD14, and CD1a expression. Eight normal donors (NDs) were used as control and all the experiments were performed in duplicate. Results The % of DCs yielded from the same total number of monocytes was significant lower in pts compared with controls (34 vs 14, p=.00004). Irrespectively to the use of G-CSF rescue, in 3/16 pts, we were not able to generate DCs. In all pts, DCs showed very high expression of HLA-DR (> 90%) and CD1a (20–40%), demostrating a pure and immature phenotype. Conclusions Even though we were able to obtain DCs from the majority of the studied cases, a significantly lower % of DCs was generated from ABC pts with respect to the NDs. This indicate that besides clinical and biological characteristics, a potentially negative effect of the currently employed CT drugs on the phenomenon of ex vivo generation of DCs has to be taken into account when clinical trials are planned. No significant financial relationships to disclose.
Endogenous factors influencing the development of cancer in women with the syndrome of the operated breast.
Authors: A. F. Lazarev, T. V. Sinkina, I. A. Selezneva, V. D. Petrova
Journal: Journal of Clinical Oncology (2010)

e12064 Background: It is known that the presence of syndrome operated breast significantly increases risk of cancer in this organ. However, not all women, who had a history of breast surgery at the non-neoplastic diseases, develops breast cancer. The objectives of our study was to reliably identify significant factors influencing the development of breast cancer among women with the syndrome of the operated breast. Methods: The study is based on data on 505 women in history, who had a surgical trauma of breast over the non–neoplastic pathologies. In 73 of them (14.5%), subsequently, detected breast cancer. In both groups were analyzed more than 40 endo- and exogeneous factors. Processing of the results was performed using modern methods of biomedical statistics, the definition of relative risk (RR). Statistically significant differences taken at p < 0.05. Results: Among the endogenous endocrine factors, high relative risk (RR = 2.82 [1.59-4.98]) detected in women with the presence of the factor of obesity, with is 5.1 times higher than in patients with normal weight (RR = 0.55 [0.35-0.86]). In analyzing the factors of the reproductive late (after 35 years) increase in birth 6.0 times the risk of breast cancer - RR = 2.47 (1.03- 5.88); (RR at birth to 35 years = 0.41 [0.16-0.96]). At the beginning of menarche after 15 years of RR of 4.0 times higher (RR = 2.39 [1.27- 4.50]), than before 15 years. The presence of hyperplastic processes of internal female genital organs significantly increases the risk of breast cancer in 2.6 times. In the presence of this factor RR = 1.62 (1.02-2.56) in the absence - RR = 0.62 (0.38-0.97). In the analysis of other endogenous factors (mastitis, thyroid disease and others) significantly significant difference has been received. Conclusions: As endogenous factors as obesity, the reproductive late (after 35 years), the beginning of menarche after 15 years, the presence of hyperplastic processes of internal female genital organs significantly increase the risk of breast cancer. No significant financial relationships to disclose.
Molecular markers for epithelial-mesenchymal transition (EMT) and tumor aggressiveness in breast carcinoma.
Authors: S. Sethi, F. H. Sarkar, Q. Ahmed, S. Bandyopadhyay, Z. A. Nahleh, W. Sakr, A. Munkarah, R. Ali-Fehmi
Journal: Journal of Clinical Oncology (2010)

10604 Background: Epithelial-mesenchymal transition (EMT) is a transient process occurring during carcinogenesis that is characterized by phenotypic and molecular alterations resulting in increased invasive and metastatic capabilities of cancer cells and it has also been proposed to play a key role in drug resistance. Moreover, emerging evidence suggests that EMT is associated with increased enrichment of cancer stem cells (CSC) in neoplastic breast tissue. We interrogated the molecular alterations occurring in breast cancer using proposed EMT markers including E-cadherin, vimentin, EGFR, PDGF- D and NF-Kappa B to decipher their role in the EMT and breast cancer progression. Methods: Fifty-seven invasive ductal carcinomas of the breast were assessed for E-Cadherin, vimentin, EGFR, NF-kappa B and PDGF-D using immunohistochemical (IHC) analysis. Tumors were categorized into 3 groups A(ER+, and/or PR+, HER2/neu-); B (ER+, and/orPR+,HER2/neu+) and C (Triple negative; ER-, PR-,HER2/neu-). Immmunostained slides were microscopically evaluated and scored using intensity (0, +1, +2, +3) and percentage of positive cells. Data was statistically analyzed. Results: E-cadherin was positive in all 57 cases (100%). All group A cases were negative for vimentin and EGFR. There was statistically significant increased expression of vimentin (p < 0.0002), EGFR (p < 0.0001), and NF-Kappa B (p < 0.02) in triple-negative cases when compared to groups A and B. Conclusions: Vimentin, EGFR, and NF-kappa B were significantly increased in triple-negative tumors. These markers may be used as markers for EMT in breast cancers and in future serve as potential therapeutic targets to overcome drug resistance. Tumor class n Vimentin EGFR NF-kappa B PDGF-D Group A 19 0/19 (0%) 0/19 (0%) 6/19 (32%) 15/19 (79%) Group B 24 6/24 (25%) 2/24 (8%) 10/24 (42%) 18/24 (75%) Triple-negative 14 9/14 (64%) 14/14 (100%) 11/14 (79%) 9/14 (64%) p value p < 0.0002 p < 0.0001 p < 0.02 p < 0.62 No significant financial relationships to disclose.
Upregulation of monocyte chemotactic protein-1 and CD40 ligand in cancer patients and their modulation by subcutaneous enoxaparin-results from the ONCENOX study
Authors: O. Iqbal, M. Tobu, M. A. Demir, D. Hoppensteadt, J. Fareed, S. Cort, S. Deitcher
Journal: Journal of Clinical Oncology (2004)

6069 Background: Malignant cells constitutively produce monocyte chemotactic protein-1 (MCP-1). CD40 ligand (CD40L), a member of TNF superfamily is primarily expressed on CD40 positive T-cells and activated platelets. Methods: Blood samples were collected prior to and 3–7 days after the initiation of enoxaparin from cancer patients with acute symptomatic DVT and/or PE. These patients were enrolled in a randomized, open-label, multi-dose, active comparator, parallel design study and were allocated to an initial treatment with enoxaparin alone for 1 week (n=70–72).ELISA tecniques (R&D Systems, Minneapolis, MN, USA) were used. Results:The baseline levels of the CD40L in cancer patients with thrombosis were markedly elevated (1323.8± 29.0 pg/ml) in comparison to the normal plasma (n=47, 62.8± 18 pg/ml) and cancer-free patients with thrombosis (615± 236 pg/ml). The MCP-1 levels were also increased in cancer patients (564.3± 59 pg/ml) in comparison to the normal plasma (n= 47, 119.9± 23 pg/ml) and cancer-free patients with thrombosis (215± 75.5 pg/ml). Thirty-nine patients out of 70 (55%) exhibited >1000 pg/ml of CD40L. 39 patients out of 69 (58%) exhibited > 500 pg/ml of MCP-1. There was a good correlation (r2=0.83) between MCP-1 and CD40L expression. Plasma samples drawn 3–7 days after the initial treatment with 1 mg/kg SC enoxaparin, BID (n=32) exhibited marked reduction in the CD 40L (589.3± 125.6 pg/ml) and MCP-1 (342± 81.6 pg/ml) levels. The circulating anti-Xa levels ranged from 0.3–0.7 AXa U/ml (mean 0.56± 0.21U/ml). Conclusions: The circulating anti-Xa levels did not correlate with the decreased level of either MCP-1 or CD40L. The observed up-regulation of both of these markers of inflammation/immunoactivation in the baseline samples were consistent with a similar increase in von Willebrand Factor elevated in 97% of patients and CRP (elevated in 60% of patients). However, the relative decrease in these markers after enoxaparin treatment was not as dramatic as the one observed for the MCP-1 and CD 40L. Cancer-free patients with thrombosis did not exhibit similar increases in MCP-1 and CD40L. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Pfizer