Citations

389 Background: Venous thromboembolism (VTE) has been reported in approximately 5-7% of patients undergoing radical cystectomy (RC). While extended-duration pharmacologic prophylaxis (EDPP) has been investigated following surgery for a variety of malignancies, limited data exist in bladder cancer. Herein, we evaluated the efficacy and safety of EDPP after RC. Methods: We instituted a change in our clinical practice beginning in May 2014 such that patients undergoing RC were prescribed 30 days of enoxaparin at discharge. We recorded symptomatic VTE and lymphocele rates within 30 days of RC among patients treated from 5/14-6/15, and compared these outcomes to the cohort of all patients who underwent RC at our institution in the year prior to EDPP implementation. Patients in both groups received subcutaneous unfractionated heparin and mechanical prophylaxis during hospitalization. Patients with a history of VTE prior to surgery (n = 24) were excluded from study. Unadjusted descriptive statistics and univariate analyses were performed using the Pearson or Fisher chi-square test for categorical variables and Wilcoxon rank-sum test for continuous variables. Results: In total, 58 patients who received EDPP and 82 patients who had not received EDPP after RC were included for analysis. Baseline clinicopathologic demographics were similar between the cohorts. We found that only 1 patient (1.9%) discharged with EDPP was diagnosed with a VTE within 30 days of RC, compared to 5 (6.1%) who had not received EDPP. Mean time to VTE was 18.0 days after RC (range 9-28 days). Events consisted of DVT alone (n = 2), DVT and PE (n = 2), and PE alone (n = 2). The odds ratio for VTE in the absence of EDPP was 3.31 (95% CI 0.38, 29.2). Overall, 3 patients developed a symptomatic lymphocele within 30 days of RC: 1 (1.9%) who received EDPP and 2 (2.4%) who had not (p = 0.84). No patient in either cohort was rehospitalized for bleeding complications. Conclusions: Our initial experience suggests that EDPP was associated with a lower rate of VTE following RC, and does not increase the risks of bleeding or symptomatic lymphocele. Future evaluation in a larger-scale prospective clinical trial setting is needed to confirm the benefit of EDPP in RC patients.

353 Background: One mechanism leading to castrate-resistant prostate cancer (CRPC) is upregulation of CYP17. Abiraterone acetate (AA) inhibits CYP17 and continuous AA administration (CAAA) is one the most common and effective CRPC treatments. Mathematical models can be potentially powerful clinical tools for optimizing treatment strategies and eliminating guess work. Here, we introduce a new model which builds on our previous work (Morken JD, Packer A, Everett RA, Nagy JD, Kuang Y. Mechanisms of resistance to intermittent androgen deprivation therapy identified in prostate cancer patients by novel computational method. Cancer Res 2014;74:2673-83.) and may be capable of predicting how patients will respond to CAAA and intermittent AA administration (IAAA). We are currently proposing a personalized IAAA protocol on the basis of these results. Methods: In this ongoing retrospective study, we use PSA data from patients whom underwent CAAA to validate the accuracy of our model of tumor growth and evolution. The PSA output is driven by dynamics of three cell populations—castration-sensitive (CS), castration-resistant abiraterone-sensitive (CSAS), and castration-sensitive abiraterone-resistant (CSAR) cells. We fit the model output to PSA data to find parameter values which minimize normalized mean squared error (NMSE). Once parameters are obtained, we ran simulations employing various IAAA protocols. Results: The model’s PSA dynamics are highly accurate. NMSE is very low across patients ranging from 0.0001-0.0085. Conclusions: Our results suggest that there exists an IAAA protocol for each patient that, at worst, yields the same time to tumor progression as CAAA, yet improves quality of life and reduces cost. In nearly 20% of patients, IAAA appears to delay tumor progression over CAAA. The model is accurate at predicting how patients will respond to CAAA and IAAA for patients whose PSA is regularly monitored. Near-future work aims to personalize IAAA protocol based on patient pre CRPC PSA dynamics and to identify a protocol which delays progression for most patients.

54 Background: After diagnosis and treatment, lung cancer survivors do not return to a health-related quality of life (QOL) and function comparable to pre-diagnosis levels as observed in other adult cancer survivors. We hypothesize that inadequate attention has been paid to addressing and improving QOL and function among lung cancer survivors. Our primary goal is to evaluate existing symptoms and QOL deficits among lung cancer survivors. Methods: We are evaluating patterns of QOL deficits (scored 5 or less on the scale from 0 [worst] to 10 [best]) in relation to time of lung cancer diagnosis, treatments, progression and/or recurrence, and health-related conditions. We are collecting and analyzing relevant health care utilization for selected QOL deficits, and identifying availability, accessibility, and effectiveness of evidence-based interventions. The expected outcomes will be new knowledge on patterns of QOL deficits, quality-adjusted life years in relation to the availability, accessibility, and adequacy of needed care and the effectiveness of interventions targeting improvement in QOL and symptoms. Results: In our initial analysis, among 3,707 lung cancer survivors who were diagnosed in 1999 to 2010, post-cancer treatment, and followed through 2011, 39% (1,442) reported deficits in overall QOL, 71% fatigue, 60% dyspnea, 41% being sedentary, 17% low spiritual well-being (SWB), and 10% currently smoking cigarettes. Among the 1,442 lung cancer survivors with a deficit in overall QOL, 97.5% reported severe fatigue or dyspnea, being sedentary or smoking, or having low SWB. In the remaining 36 of the 1,442, 24 had pain, cough, poor appetite, or other symptoms; only 12 (<1%) did not report deficit in any of the measured QOL domains. Analyses are ongoing. Conclusions: Based on evidence gained to date, we are developing and testing interventions targeting symptoms and QOL deficits. We expect to gain strong evidence for recommendations in redefining and delivering care and support that are necessary for improving the health and QOL of lung cancer survivors.

Lung cancer is the deadliest cancer in the United States, killing roughly one of four cancer patients in 2016. While it is well-established that lung cancer is caused primarily by environmental effects (particularly tobacco smoking), there is evidence for genetic susceptibility. Lung cancer has been shown to aggregate in families, and segregation analyses have hypothesized a major susceptibility locus for the disease. Genetic association studies have provided strong evidence for common risk variants of small-to-moderate effect. Rare and highly penetrant alleles have been identified by linkage studies, including on 6q23–25. Though not common, some germline mutations have also been identified via sequencing studies. Ongoing genomics studies aim to identify additional high penetrance germline susceptibility alleles for this deadly disease.

Abstract Renal fibrosis is the common pathological hallmark of progressive chronic kidney disease ( CKD ) with diverse aetiologies. Recent researches have highlighted the critical role of hypoxia during the development of renal fibrosis as a final common pathway in end‐stage kidney disease ( ESKD ), which joints the scientist's attention recently to exploit the molecular mechanism underlying hypoxia‐induced renal fibrogenesis. The scaring formation is a multilayered cellular response and involves the regulation of multiple hypoxia‐inducible signalling pathways and complex interactive networks. Therefore, this review will focus on the signalling pathways involved in hypoxia‐induced pathogenesis of interstitial fibrosis, including pathways mediated by HIF , TGF ‐β, Notch, PKC / ERK , PI 3K/Akt, NF ‐κB, Ang II / ROS and micro RNA s. Roles of molecules such as IL ‐6, IL ‐18, KIM ‐1 and ADO are also reviewed. A comprehensive understanding of the roles that these hypoxia‐responsive signalling pathways and molecules play in the context of renal fibrosis will provide a foundation towards revealing the underlying mechanisms of progression of CKD and identifying novel therapeutic targets. In the future, promising new effective therapy against hypoxic effects may be successfully translated into the clinic to alleviate renal fibrosis and inhibit the progression of CKD .