bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of bladder cancer stage on work impairment and financial toxicity.
Authors: Filippou Pauline , McCabe Sean , McCloskey Hannah , Gessner Kathryn , Hamad Judy , Deal Allison Mary , Smith Angela , Gore John L.
Published: February 2020

460

Background: Bladder cancer has been linked to financial toxicity with conflicting results regarding the impact of stage. Our objective was to evaluate financial toxicity and work impairment among bladder cancer patients in a large cross-sectional bladder cancer cohort. Methods: We surveyed bladder cancer patients in the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine financial toxicity and work impairment. We measured financial toxicity with the COST measure and Work Productivity and Activity Impairment General Health questionnaires. Patients were also queried regarding demographic, socioeconomic and clinical characteristics with specific attention to insurance status, income, and education. Results: 972 respondents self-identified as patients with bladder cancer. Among respondents, 41% were female and 97% were white. The mean age was 67.6 years, ranging from 29 to 93 years. Respondents were highly educated (67% completed college). Most patients identified as having non-invasive bladder cancer (NMIBC, n=578 [63%]); 30% (n=270) had MIBC, 7% (n=63) had metastatic cancer. Although patients with metastatic cancer had higher average COST scores (worse financial toxicity, Table below), stage was not significantly associated with COST on bivariable (p=0.07) or multivariable analysis (p=0.14). Patients with metastatic disease were more likely to report more work time missed and activity impairment due to health on bivariable analysis; only activity impairment was statistically associated with stage on multivariable analysis (p<0.001) when controlling for age, gender, race, comorbidity, insurance, and education. Conclusions: Bladder cancer stage significantly impacts activity impairment but not percentage work time missed due to health nor financial toxicity. [Table: see text]
Recombinant humanized anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma: Preliminary results of an open-label phase II clinical study (POLARIS-03).
Authors: Sheng Xinan , Chen Haige , Hu Bin , Yao Xudong , Liu Ziling , Yao Xin , Guo Hongqian , Hu Yi , Ji Zhigang , Luo Hong , Shi Benkang , Liu Jiyan , WU Jin , Zhou Fang-Jian , He Zhisong , Huang Yiran , Guo Jun
Published: February 2020

504

Background: Patients with advanced metastatic urothelial carcinoma (UC) who experience disease progression after standard therapy have limited treatment options. Phase I studies of toripalimab in subjects with heavily pretreated metastatic UC have demonstrated an acceptable safety profile and promising clinical activity. Here we report the preliminary safety and efficacy result of toripalimab in a Phase II clinical study in Chinese patients with refractory/metastatic UC (Clinical trial ID: NCT03113266). Methods: Metastatic UC patients received toripalimab, also known as JS001, 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease were assessed for clinical response every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression and tumor mutational burden was measured for correlation with clinical response. Results: From May 2017 to Sep 2019, 151 patients were enrolled from 15 participating centers. Patient enrollment was completed for this study. The median age was 62.0 years with 66.9% of the population being male. By the cut-off date of 21 Oct 2019, common treatment related AEs were mostly Grade 1 or 2, including anemia, blood triglycerides increased, fever, protein urine present and blood glucose increased. Among 128 efficacy evaluable patients, 4 complete responses, 25 partial responses, and 35 stable diseases were observed, for an objective response rate (ORR) of 22.7% and a disease control rate of 50.0%. 62.1% (18/29) of responses were ongoing at the cut-off date. PD-L1 expression results were obtained from 121 efficacy evaluable subjects. PD-L1+ patients (n = 39, 32.2%) had significant better ORR than PD-L1- patients (n = 82), 38.5% versus 13.4%. Conclusions: Toripalimab has demonstrated encouraging clinical activity in chemo-refractory UC patients and a manageable safety profile. Toripalimab elicited a favorable 38.5% ORR in PD-L1+ patients. Nevertheless PD-L1- patients also achieved a 13.4% ORR, including one complete response. Patients will be continuously monitored for additional safety and efficacy readouts (DOR, PFS and OS). Clinical trial information: NCT03113266.
Safety, dose tolerance, pharmacokinetics, and pharmacodynamics of fosciclopirox (CPX-POM) in patients with advanced solid tumors.
Authors: Patel Manish R. , Ulahannan Susanna Varkey , Weir Scott James , Wood Robyn , Ham Tammy , Casey Crista , Reed Greg , Dandawate Prasad , Ramamoorthy Prabhu , Baltezor Michael Jay , Jensen Roy A. , Woolbright Benjamin L. , Taylor John Arthur , Anant Shrikant , Dalton Michael , Zhukova-Harrill Valentina , McCulloch William , Jones Suzanne Fields , Burris Howard A. , Falchook Gerald Steven
Published: February 2020

518

Background: Fosciclopirox (CPX-POM) is being developed for the treatment of non-muscle invasive and muscle invasive bladder cancer. CPX-POM selectively delivers its active metabolite, ciclopirox (CPX), to the entire urinary tract following systemic administration. In a chemical carcinogen mouse model of bladder cancer, CPX-POM treatment resulted in significant decreases in bladder weight, migration to lower stage tumors, inhibition of cell proliferation as well as Notch 1 and Wnt signaling pathways. Methods: Study CPX-POM-001 (NCT03348514) is US multi-site, Phase I, open-label, dose escalation study characterizing the safety, dose tolerance, pharmacokinetics (PK) and pharmacodynamics of IV CPX-POM in advanced solid tumor patients. The PK of CPX-POM, CPX and ciclopirox glucuronide (CPX-G), were characterized in plasma and urine. Circulating biomarkers of Wnt and Notch, IL-6, IL-8 and VEGF were determined. Results: Nineteen patients were enrolled in the study. The starting dose of 30 mg/m2 was administered once daily on Days 1-5 of each 21-day treatment cycle. Doses were escalated to 1200 mg/m2. The MTD was determined to be 900 mg/m2. Overall, the number of treatment-related AE's tended to increase in frequency with dose, nausea and vomiting being the most common. Grade 3 confusion was observed in the 1200 mg/m2 cohort. Four AE's of Grade 1 confusion at 600 and 900 mg/m2. There was no evidence of QTc prolongation or other ECG abnormality. One patient in the 240 mg/m2 dose cohort, with a diagnosis of indolent primary fallopian tube tumor, achieved a partial response per RECIST 1.1. Metabolism of CPX-POM was rapid and complete. The clearance of CPX was dose proportional and time-independent. At MTD, steady-state 24-hour urine CPX concentrations of 215 µM were achieved. Evidence of Notch and Wnt inhibition was observed. Conclusions: IV CPX-POM was well tolerated with treatment-related AEs primarily CNS-related. At MTD, systemic and urinary CPX exposures exceeding in vitro IC50 values by several-fold. The 900 mg/m2 dose is currently being evaluated in an expansion cohort study in cisplatin-ineligible muscle invasive bladder cancer patients scheduled for cystectomy. Clinical trial information: NCT03348514.
Sequencing chemotherapy and surgery in upper tract urothelial cancers.
Authors: Parasramka Saurabh , Cook Alex , Myint Zin , Xue Ding , Wu Jianrong , Wang Peng
Published: February 2020

521

Background: Prognosis for high grade, non-metastatic upper tract urothelial carcinoma (UTUC) (renal pelvis or ureter) has not improved in past two decades. Given improvements in disease-free survival in phase III POUT study, adjuvant chemotherapy (AC) has been the preferred approach. Neoadjuvant chemotherapy (NAC) is favored based on median survival (OS) benefit seen in urothelial bladder cancer. We studied National Cancer Database (NCDB) to answer this question. Methods: We identified adults > 18 years with non-metastatic, high grade, UTUC. All patients received surgery of the primary site and chemotherapy in the neoadjuvant or adjuvant setting. Patient’s receiving radiation therapy or who died within 90 days of surgery were not included. Descriptive statistics, log-rank tests and cox-regression tests were performed. Patients achieving complete pathological response (pCR) defined as (pTis, pT0, pTa and N0) were assessed for OS. Results: 1191 patients with complete data were identified; 225 (19%) received NAC and 966 (81%) received AC. 60% were males, median age was 68 and 73% had Charlson score (CS) of ‘0’. Median follow-up time for alive patients was 30.4 and 36.7 months in the NAC and AC groups respectively. Renal pelvis was the primary in 760 cases (63%) and ureter in 441 (37%). On univariate analysis receiving NAC, age < 75 years and CS score ‘0’ was associated with significant survival benefit (p < 0.05). Similarly on multivariate analysis receiving NAC and having CS of ‘0’ had significantly better survival with HR 0.75 (CI 0.58-0.96) and 0.8 (CI 0.65-0.96) respectively. Age > 75 years had worse survival HR 1.34 (CI 1.08-1.66). Thirty-seven patients (17%) in the NAC group achieved pCR with OS > 71.6 months which was significantly better than AC group and non-responders in the NAC group (p < 0.05). There was a trend towards more benefit with NAC compared to AC in Stage 1 and 2 UTUC than in Stage 3 and 4. Conclusions: Our study indicates that subset of early stage UTUC benefit more from NAC comparing to AC. However, randomized prospective study is warranted to further explore the role of NAC in UTUC.
Racial and sex differences in somatic mutations in bladder cancer patients: An analysis of the cBioPortal for Cancer Genomics.
Authors: Nyame Yaw A. , Baker Kelsey K. , Montgomery Robert B. , Grivas Petros , Redman Mary Weber , Wright Jonathan L.
Published: February 2020

556

Background: Disparities in bladder cancer outcomes exist by race/ethnicity and sex. However, limited data exists on differences in tumor biology by race/ethnicity and sex. Methods: This is a retrospective analysis of non-synonymous mutational data from the cBioPortal open access platform. A total of eight unique cohorts were identified. The cohort was divided into groups by sex and race. Somatic mutations were selected from those with frequency > 7% from TCGA and DNA damage repair (DDR) genes. Univariable analysis was performed using Student’s t-test and Fischer’s exact test. For those genes with significant differences, multivariate Cox regression analysis was performed, including a test for interaction for genes significantly associated with race or gender. Results: A total of 917 unique patients were identified from cBioPortal for this analysis. Median age for the cohort was 68 years (range: 25-98) and 227 (25%) were identified as female. The cohort was majority white (85%). TP53 (54% vs. 31%, p < 0.001), ARID1A (29% vs. 7%, p < 0.001), ERBB3 (12% vs. 3%, p = 0.01) and CDKN1A (8% vs 18%, p = 0.02) were differentially mutated in white tumors compared to non-white tumors. ERBB2 was more common among male (13%) compared to female (6%) patients in the cohort (p < 0.01). There were no differences in DDR genes by race/ethnicity and sex. The median age for those with ERCC2 (70.4 vs. 66.8 years) and RAD51 (76.3 vs. 67.0 years) mutations was higher compared to those without the mutations, respectively. On multivariable analysis, ERCC2 (HR 0.45, 95% CI 0.25, 080), SPTAN1 (HR 0.50, 95% CI 0.29, 0.84), and EP300 (HR 0.60, 95% CI 0.39, 0.92) were associated with survival. There was a significant interaction between white race and CDKN1A in the survival analysis, with non-white patients with CKDN1A mutations having increased hazard for mortality (HR 3.1, 95% CI 1.14, 8.42). Conclusions: Somatic mutational differences existed by both race and gender in a large cohort of patients with bladder cancer. These findings are limited by poor representation of non-white patients and retrospective design; advocating for representative patient cohorts to assess tumor biology in bladder cancer disparities research.
NIVOREN GETUG-AFU 26 translational study: Association of PD-1, AXL, and PBRM-1 with outcomes in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) treated with nivolumab (N).
Authors: Vano Yann-Alexandre , Rioux-Leclercq Nathalie , Dalban Cécile , Sautes-Fridman Catherine , Bougoüin Antoine , Chaput Nathalie , Chouaib Salem , Beuselinck Benoit , Chevreau Christine , Gross-Goupil Marine , Negrier Sylvie , Laguerre Brigitte , Borchiellini Delphine , Colina-Moreno Irelka , Fridman Wolf-Herman , Chabaud Sylvie , Tantot Florence , Barros Monteiro Janice , Escudier Bernard , Albiges Laurence
Published: February 2020

618

Background: The NIVOREN GETUG-AFU 26 study reported safety and efficacy of N in mccRCC pts in a “real world setting”. A translationnal research program was launched to characterize immune cell populations in the tumor by immunohistochemistry (IHC) and correlate them with outcome on N. Methods: All pts treated with N in the GETUG AFU 26 NIVOREN trial who consented for translational program and with available archived paraffin- embedded (FFPE) tumor tissue samples were eligible. Tumor were centrally reviewed. Using IHC we quantified main immune populations (B-cells, CD8 T-cells, macrophages), and immune checkpoints receptors (TIM-3, LAG-3, PD-1) at the invasive margin (IM) and at the core of the tumor (CT). We also identified AXL and PBRM1/BAP1 expression. Results: Overall 324 pts were included. Pts had similar baseline characteristics (IMDC Good, Intermediate, Poor in 18%, 60% and 22%, respectively) and comparable outcomes than overall trial population (PFS/OS = 4.5 / 25.4 months). PD-1 (IM) expression was associated with better PFS whereas AXL expression by tumor cells (TC) was associated with worse PFS (table). LAG-3 expression tend to be associated with worse OS. PBRM-1 loss (15%) was associated with better OS and PFS and with a higher density of CD8 T-cells (p = 0.001) and CD163-macrophages (p = 0.01) (CT) and a higher expression of LAG-3 (CT) (p = 0.01) and PD-1 (CT) (p = 0.02). BAP-1 loss was not associated with PFS (p = 0.6) nor OS (p = 0.9) in this cohort. Conclusions: We report the largest translational analysis supporting that PD-1 and AXL expression are associated with PFS in pts with mccRCC receiving N. We further confirm that PBRM-1 loss is a strong prognostic factor in this setting.[Table: see text]
Factors associated with clinical trial participation for patients with renal cell carcinoma.
Authors: Shinder Brian , Kim Sinae , Srivastava Arnav , Patel Hiren V. , Mayer Tina M. , Saraiya Biren , Singer Eric A.
Published: February 2020

670

Background: Clinical trials are critical for the development of new treatment paradigms for renal cell carcinoma (RCC). The primary objective of this study was to characterize the factors associated with clinical trial participation for patients with RCC. The secondary objective was to examine survival outcomes in the clinical trial and control cohorts. Methods: The National Cancer Database (NCDB) was queried for patients with RCC who were coded as having enrolled in a clinical trial. Trial patients were matched in a 1:5 ratio to controls from the same institution based on clinical stage. Sociodemographic variables were compared between the two groups and univariate and multivariate logistic regression models evaluated factors associated with clinical trial participation. Kaplan-Meier product limit estimate was used to compare overall survival (OS) between the groups. Results: From 2004-2015, 681 patients enrolled in clinical trials were included for analysis. The mean age of trial patients was 56.4 compared to 62 in the matched cohort (p<0.0001). More patients in the trial group had a Charlson-Deyo comorbidity score of 0 (81.6% vs. 73.9%, p<0.0001). On multivariate analysis, male patients (OR 1.27; 95%CI 1.06-1.54, p=0.012) and white patients (OR 1.88, 95%CI 1.23-2.87; p=0.003) were more likely to participate in a trial. Having Medicaid (OR 0.42; 95%CI 0.27-0.64; p<0.0001) or Medicare (OR 0.6; 95%CI 0.46-0.77; p<0.0001) was negatively associated with clinical trial participation. Median OS was greater among clinical trial participants than that the control cohort (106.61 vs 87.62 months, p<0.0001). Conclusions: In this contemporary analysis of RCC patients from a national hospital registry database, we found that patient sociodemographic factors remain associated with clinical trial participation and that clinical trial participants experienced superior OS. Further work, both qualitative and quantitative, is necessary to identify clinical and non-clinical barriers to research participation in order to improve the validity of RCC trials.
A phase II study of lenvatinib plus everolimus in patients with advanced non-clear cell renal cell carcinoma (nccRCC).
Authors: Hutson Thomas E. , Michaelson M Dror , Kuzel Timothy M. , Agarwal Neeraj , Molina Ana M. , Hsieh James J , Vaishampayan Ulka N. , Xie Sharon , Bapat Urmi , Jain Rohit K. , Fishman Mayer N.
Published: February 2020

685

Background: Non-clear cell renal cell carcinoma (nccRCC) is an umbrella term that encompasses multiple RCC histological subtypes, including papillary, chromophobe, and undetermined RCC. Both increased expression of the vascular endothelial growth factor (VEGF) and dysregulation of the mammalian target of rapamycin (mTOR) pathway occur in nccRCC. Lenvatinib (LEN) is a multitarget tyrosine kinase inhibitor that inhibits the VEGF receptor and other targets; everolimus (EVE) is a mTOR inhibitor. LEN + EVE is approved for the treatment of patients with advanced RCC following 1 prior antiangiogenic therapy. This phase 2 study examined the efficacy and tolerability of LEN + EVE in patients with nccRCC. Methods: This single-arm, multicenter, phase 2 trial assessed the safety and efficacy of LEN (18 mg once daily) + EVE (5 mg once daily) in patients with unresectable advanced or metastatic nccRCC who had not received any chemotherapy for advanced disease. The primary objective was objective response rate (ORR) as assessed by investigators using RECIST v1.1. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety assessments. Results: At the time of data cutoff (July 17, 2019), 31 patients with nccRCC (papillary, n = 20; chromophobe, n = 9; unclassified, n = 2) were enrolled and treated. The ORR was 25.8% (95% confidence interval [CI]: 11.9–44.6%); 8 patients achieved a partial response (PR; papillary, n = 3; chromophobe, n = 4; unclassified, n = 1) and no patients had a complete response (CR). The median duration of response was not reached. Additionally, 18 patients (58.1%) had stable disease (SD) and the clinical benefit rate (CR + PR + durable SD [duration ≥ 23 weeks]) was 61.3% (95% CI: 42.2–78.2%). The median PFS was 9.23 months (95% CI: 5.49- not estimable [NE]) and median OS was 15.64 months (95% CI: 9.23–NE). The safety profile observed in this study was similar to the established profile of the study drug combination (LEN + EVE). Conclusions: The combination of LEN + EVE showed promising antitumor activity as first-line therapy in patients with advanced nccRCC. The ORR was 25.8%, which compares favorably to historical reports with EVE monotherapy. Clinical trial information: NCT02915783.
Clinical correlation of circulating tumor cell (CTC) PD-L1 and HLA I expression in metastatic renal cell carcinoma (mRCC) using exclusion-based sample preparation technology.
Authors: Emamekhoo Hamid , Schehr Jennifer L. , Bade Rory M. , Wei Xiao X. , McKay Rana R. , Choueiri Toni K. , Lang Joshua Michael
Published: February 2020

721

Background: Despite therapeutic advancement in Vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) for mRCC treatment, there is currently no reliable predictive biomarkers of response or resistance. Single site biopsies provide limited information given the heterogenous nature of mRCC. Liquid biopsies may overcome these limitations; however, prior CTC capture platforms lacked sufficient sensitivity and specificity to achieve clinically useful detection rates. Methods: Given the prevalence of VEGF dependency, and its reliance on hypoxia, we aimed to increase sensitivity and specificity of capturing and identifying mRCC CTCs using carbonic anhydrase IX (CA IX) and CA XII. In addition, traditional markers for cell capture and identification with epithelial cellular adhesion molecule (EpCAM) and cytokeratin (CK) were included. Exclusion-based Sample Preparation technology was used to maximize cell yield. CD45/34/66b positive blood cells were excluded to ensure high specificity in evaluation of PD-L1 and HLA I expression on CTCs. Results: In a preliminary cohort of 21 mRCC pts (treatment: TKI=12, ICI=5, TKI+ICI=2, baseline=2), we identified heterogeneous populations of CTCs with differential expression of CA XII and CK. We detected CK+ CTCs in 20/21 pts (mean= 5/mL; range 0-53), CAXII+ CTCs in 21/21 pts (mean= 1/mL; range 1-9), and CK+/CAXII+ CTCs in 19/21 pts (mean=7/mL; range 0-102). In pts with multiple CTC samples on treatment, there was a high correlation between the number of CK+ CTCs and treatment response (ROC AUC 0.88). PD-L1 expression in CAXII+ CTCs correlated with response to ICI (ROC AUC 0.77) and TKI (ROC AUC 0.73). HLA I expression in CAXII+ CTCs correlated with response to TKI (ROC AUC 0.73) better than ICI (ROC AUC 0.59). Conclusions: Assessment of CTC heterogeneity may provide valuable molecular insights and diversify tools for early detection of therapeutic response and resistance that may guide treatment decision making. This assay is being tested in ongoing Phase II clinical trials.
The effect of docetaxel, enzalutamide, abiraterone, and radium-223 on cognitive function in older men with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Alibhai Shabbir M.H. , Breunis Henriette , Timilshina Narhari , Hansen Aaron Richard , Joshua Anthony M. , Warde Padraig Richard , Gregg Richard William , Fleshner Neil Eric , Tomlinson George , Hotte Sebastien J. , Emmenegger Urban
Published: February 2020

73

Background: Older adults are at greater risk of cognitive decline with various oncologic therapies. Emerging data suggest cognitive effects of various therapies for mCRPC but study populations are highly selected and published data are limited and focus mostly on self-reported cognitive function. We evaluated the effects of treatment with docetaxel chemotherapy (CHEMO), abiraterone (ABI), enzalutamide (ENZA), and radium 223 (Ra223) on cognitive function in older men with mCRPC. Methods: Men age 65+ with mCRPC starting any of the 4 treatments for mCRPC were enrolled in this multicenter prospective cohort study. Three short yet reliable and sensitive measures in older adults were administered at baseline and final visit (6 months with CHEMO and Ra223, mean 14-16 months with ENZA and ABI) using the Montreal Cognitive Assessment (MoCA), Trails A, and Trails B to assess global cognition, attention, and executive function, respectively. Absolute changes in cognitive scores over time were analyzed using multivariable linear regression, and the percentage of individuals with a decline of 1.5 SD in each domain were calculated. Higher scores on MoCA are better but worse for Trails A/B. Results: A total of 51, 26, 49, and 21 men starting CHEMO, ABI, ENZA, and Ra223 with complete data were included. Mean age, education, and baseline cognition were similar between groups (Table). Most patients demonstrated stable cognition or slight reductions. Executive function was the most sensitive of the 3 cognitive domains, and declined by at least 1.5 SD in about one-fifth of each cohort. Although ABI had numerically smaller declines than ENZA, differences were generally small and clinically unimportant. Conclusions: Most older men do not experience significant cognitive decline while on treatment for mCRPC regardless of treatment used.[Table: see text]
The use of intermittent enzalutamide dosing in the treatment of metastatic castrate-resistant prostate cancer.
Authors: Rowe Michael , Hidayat Ayesha , Walter Stuart , Pollard Adam , Norris Timothy , Victor Deborah , McGrane John , Thomson Alastair
Published: February 2020

81

Background: Intermittent hormone manipulation in castrate-sensitive prostate cancer can improve quality of life whilst maintaining comparable disease outcomes with continuous scheduling. Enzalutamide is effective in metastatic castrate-resistant prostate cancer (mCRPC) treatment but can have significant side-effects. We conducted a retrospective analysis of patients treated with intermittent enzalutamide compared with continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC at Royal Cornwall Hospital from September 2011 to February 2018 were included. Data was collected from electronic medical records, selecting patients with at least a 1 month treatment break. Kaplan-Meier analysis of overall survival from enzalutamide start (OS), time to PSA failure (TTF) and total enzalutamide treatment time (TTT) was calculated for intermittent and continuous responders (>50% PSA drop), assigned significance level of 0.05. Results: 243 patients received enzalutamide, 110 (45%) were continuous responders and 29 (12%) had intermittent dosing. All patients treated intermittently had a PSA response prior to first treatment break, which was most commonly for fatigue (60%). 25% were still receiving enzalutamide. Median number of breaks was 1 (range 1-7), time on treatment was 70% and time to first break was 5 months. The intermittent group had significantly improved OS with median not reached, median OS for continuous responders was 19 months (HR 2.39, 95% CI 1.53-3.76, p=0.002). The intermittent group had prolonged TTF (median 13 vs 6 months, p=0.001) and TTT (median 30 vs 10 months, p=0.0003). Conclusions: Intermittent dosing of enzalutamide in these mCRPC patients does not adversely impact OS, increasing time patients remain on treatment. However, this was a small, retrospective, single-centre study; prospective trials are necessary to clarify the role of intermittent enzalutamide.[Table: see text]
Single-arm, phase II study to evaluate the safety and efficacy of sacituzumab govitecan in patients with metastatic castration-resistant prostate cancer who have progressed on second generation AR-directed therapy.
Authors: Lang Joshua Michael , Kyriakopoulos Christos , Slovin Susan F. , Eickhoff Jens C. , Dehm Scott , Tagawa Scott T.
Published: February 2020

TPS251

Background: In patients with mCRPC, androgen receptor (AR) pathway inhibitors such as enzalutamide or abiraterone acetate are often used as first-line systemic therapy. After progression on either of these inhibitors, the likelihood of response to the other is significantly lower than in the first-line setting. Multiple resistance mechanisms have been identified, including the emergence of AR splice variants. Trop2 is a cell-surface antigen that is expressed in > 70% of prostate cancers and is enriched in mCRPC expressing AR splice variants. Sacituzumab govitecan (SG; IMMU-132) is a novel antibody drug conjugate composed of humanized anti-Trop2 antibody conjugated to SN-38 payload by hydrolyzable linker. SG has potential to be an effective therapy after progression on initial AR pathway inhibitors to meet this significant unmet clinical need. Methods: This is a single-arm, open-label, multicenter phase 2 trial (NCT03725761) to determine the efficacy and safety of SG. The primary endpoint is PSA response rate (≥50% PSA decline at or within 9 weeks of starting treatment); secondary endpoints include rPFS and overall survival. 55 subjects with mCRPC who have progressed on second-generation AR-directed therapy in either the hormone sensitive or CRPC setting will be included. Fresh or archived metastatic site biopsy is required. Subjects will be treated with SG IV at 10 mg/kg on Day 1 and Day 8 of 21-day cycles until disease progression. Subjects who receive ≥1 SG dose and have ≥1 PSA post-dose assessment will be included in final efficacy analysis. Circulating tumor cell biomarker studies will be performed throughout treatment and at progression to investigate potential mechanisms of response/resistance to SG. Tumor biopsies at baseline and after 3 therapy cycles will evaluate genomic alterations that predict treatment response. Subjects who remain progression free will undergo repeated evaluations of extent of disease every 9 weeks. The trial is actively accruing. Managed by: Prostate Cancer Clinical Trials Consortium; Funding: Immunomedics; Support: Prostate Cancer Foundation. Clinical trial information: NCT03725761.
Equivalent Local Potentials for the coupled channel system and the optical potential
Authors: Daskaloyannis C.
Published: February 2020

The explicit formulae of the equivalent local potentials for a coupled channel problem are calculated. We prove that the equivalent local potential of the coupled channel system coincides with the equivalent local potential of the Feshbach optical potential.
Anècdotes de la meva facultat.
Authors: IGLESIAS i GUIU Xavier
Published: February 2020

ANECDOTES RECORD OF MY FACULTY OF MEDICINE: The history of academic institutions and the biography on many individual characters have left many anecdotes aside that surround them and that complement the vision we have of them. The present article is a brief anthology of the anecdotes the author have collected or lived himself during his academic career in the Faculty of Medicine and Hospital Clinico of Barcelona.
European cinema: Between Mit-sein, Da-sein and Nah-sein
Authors: Elsaesser Thomas
Published: February 2020

This article expands on some of the polemical theses the author proposes in his book European Cinema and Continental Philosophy (2018), focusing on the idea of European cinema as 'thought experiment', the notion of 'double occupancy', which the author now articulates in terms of a 'cinema of abjection' and the idea of 'mutual interference', which is now re-examined as part of a broader re-assessment of the core Enlightenment values of 'liberty-equality-fraternity' viewed under present-day conditions of asymmetry, but also in light of their 'antagonistic mutuality'. These concepts, taken together, are an attempt to put forward a change of both model and method when studying European cinema, one based neither on the 'Europe-Hollywood' binaries, nor on an ever-elusive identity, but rather on Europe's self-understanding as a 'work-in-progress', as well as on its position in a globalized world, in which it is no longer the central player. Elsaesser proposes to 'enlarge the context' – a phrase coined by the European politician, diplomat and thinker Jean Monnet: if you cannot solve a problem, enlarge the context. Enlarging the context means taking a step back and focusing not on cinema, but on what in this period of intense internal and external crises we mean by 'Europe', before evaluating some of the ways in which certain films and filmmakers have positioned themselves in light of the challenges that are in play today.
Use of Computer Experiments to Study the Current Collected by Cylindrical Langmuir Probes
Authors: Tejero-del-Caz A. , Díaz-Cabrera J. M. , Fernández Palop J. I. , Ballesteros J.
Published: February 2020

A particle-in-cell simulation has been developed to study the behaviour of ions in the surroundings of a negatively biased cylindrical Langmuir probe. Here, we report our findings on the transition between radial and orbital behaviour observed by means of the aforementioned code. The influence of the ion to electron temperature ratio on the transition for different dimensionless probe radius is discussed. Two different behaviours have been found for small and large probe radii.
Investigation of Microwave Energy Distribution Character in a Resonator Type Plasmatron
Authors: Bordusau S. , Madveika S. , Dostanko A.
Published: February 2020

An investigation of microwave energy distribution character in a plasma of microwave discharge inside a plasmatron based on a rectangular resonator has been carried out. The experiments were done applying the "active probe" method. Microwave discharge was excited in the air and oxygen. It has been found out that the readings of the "active probe" along the discharge chamber are of periodic character. The readings of the "active probe" and data on the local electric conductivity of plasma obtained using electrical probes have been compared.
Study of the Effect of Low-Temperature Plasma Exposure on Mould Fungi Colonizing Paper
Authors: Gontcharova I. , Arashkova A. , Bordusau S. , Madveika S. , Filatova I. , Lyushkevich V. , Brablec A.
Published: February 2020

The influence of radiofrequency cold plasma in ambient air at 200 Pa pressure on mould fungi of the genus Aspergillus was studied. It was shown that 20 min plasma treatment of paper with mould and contamination reduced the number of colony forming units but didn't lead to complete suppression of fungal viability. Strains of A. versicolor after plasma treatment lost the ability to excrete pink pigment to the environment. A. niger strains were more resistant and kept acidification ability. One of the possible plasma inactivation factors was formation of reactive hydroxyl (OH) radical.
Amber
Authors: Kumar Avinash , Wang Zuozhi , Ni Shengquan , Li Chen
Published: February 2020

A long-running analytic task on big data often leaves a developer in the dark without providing valuable feedback about the status of the execution. In addition, a failed job that needs to restart from scratch can waste earlier computing resources. An effective method to address these issues is to allow the developer to debug the task
during
its execution, which is unfortunately not supported by existing big data solutions. In this paper we develop a system called Amber that supports responsive debugging during the execution of a workflow task. After starting the execution, the developer can pause the job at will, investigate the states of the cluster, modify the job, and resume the computation. She can also set conditional breakpoints to pause the execution when certain conditions are satisfied. In this way, the developer can gain a much better understanding of the run-time behavior of the execution and more easily identify issues in the job or data. Amber is based on the actor model, a distributed computing paradigm that provides concurrent units of computation using actors. We give a full specification of Amber, and implement it on top of the Orleans system. Our experiments show its high performance and usability of debugging on computing clusters.
Credibility, Reputation and De-Risking in Global Banking: Evidence from a Theoretical Model
Authors: Brei Michael , Cato Lauren , Worrell R. DeLisle
Published: February 2020

This paper investigates the de-risking phenomenon from the perspective of an international bank’s decision to de-risk in a foreign market, where there is asymmetric information and costly monitoring. We consider three adverse shocks to a foreign affiliate’s (i) perceived credibility, (ii) costs of monitoring, and (iii) reputation, as reflected in a loss of franchise value. We show that the headquarters’ incentives to reduce international exposures are prompted by increasing funding and monitoring costs and by falling franchise values. Distortions arise because adverse credibility shocks make funding rates less responsive to actual risk choices, and impairments in the bank’s reputation negatively affect franchise values. All else equal, this reduces the bank’s incentives to retain and monitor the foreign affiliate, and risks increase. The risk effects are most pronounced in the case of credibility shocks, and incentives to reduce international exposures are strongest when reputational risks affect headquarters.
Rural Folks Perception of Suicide Drivers in rural communities of Delta State, Nigeria: Implications for Societal and Agricultural Security
Authors: Ebewore Solomon Okeoghene
Published: February 2020

The study examined rural folks’ perception of suicide drivers in rural communities of Delta state, Nigeria and the resultant implications for societal and agricultural security. The objectives of the study are to: describe the socio-economic characteristics of the respondents, ascertain the perceived suicide rates in rural households; identify the main causes (or drivers) of suicide in rural communities, ascertain the means of committing suicide, and determine respondents’ perception of the effect of suicide on agricultural production and their families. A multi-stage sampling procedure was used in composing 351 respondents who furnished information on suicide situation in the study area. Results indicated some cases of suicide in the area; several perceived suicide drivers were identified by the respondents, and the respondents identified some perceived deleterious effects of suicide as illness among family members, depression of surviving members, loss of income and output of agricultural production and scattering of family of suicide victim. Logistic regression of relationship between perceived social economic characteristics and suicidal death indicated that marital status, education, family size, family income, membership of association and extension contact were significant in preventing suicide. From the findings, it was recommended that all stakeholders including the government, private sector, religion organizations, health and welfare institutions, rural communities, and individuals have crucial role to play in curbing suicidal deaths in rural communities.
Characteristic Graph vs Benzenoid Graph
Authors: Sufia Aziz
Published: February 2020

A characteristic graph is a tree representative of its corresponding benzenoid (cyclic) graph. It may contain necessary information of several properties of benzenoids. The PI-index of benzenoids and their characteristic graphs are compared by correlating it to a structural property (π-electron energy) of the benzenoids using MLR analysis. PI index being applicable to both trees and cyclic graphs, yielded required results for benzenoid and their characteristic graph.
testfileInProgress
Authors: Natarajan Sriraam
Published: February 2020

testing in porgress_do not touch
Análisis de las dificultades que presentan los estudiantes universitarios en matemática básica
Authors: Soto Quiroz Roger Iván , Yogui Takaesu Daniel Noboru
Published: February 2020

El presente estudio pretende analizar las diferentes dificultades—tanto académicas como actitudinales—que se les presenta a los estudiantes universitarios que llevan por segunda vez el curso de Matemática Básica. Esta es una investigación cualitativa, con diseño fenomenológico, con aplicación de la técnica de la entrevista no estructurada. El sustento teórico se basa en la comprensión lectora, competencias escolares, aprendizaje significativo, razonamiento cuantitativo y las actitudes hacia la matemática. La muestra la conformaron 10 estudiantes que llevan por segunda vez el curso de Matemática Básica: 03 son de la carrera de Diseño Profesional Gráfico, 03 de Diseño de interiores y 04 de Diseño y Gestión de Modas; 03 docentes que enseñan el curso y 05 tutores académicos que realizan actividades de tutoría académica y talleres de reforzamiento del curso. Los resultados permitieron afirmar que se descubrieron seis dificultades: 1) Dificultad en la comprensión lectora de los problemas matemáticos, 2) dificultad en comprender contenidos matemáticos básicos, 3) dificultad con la asistencia a clases, 4) dificultad en el interés y motivación por el curso, 5) dificultad en repasar los temas matemáticos, 6) dificultad en la asistencia a tutoría y talleres de reforzamiento.
Formation of Leading Universities: World Practice and Russian Perspective
Authors: Efimov Valerii S. , Lapteva Alla V.
Published: February 2020

The subject of the research presented is the phenomenon of university leadership and its conditions and factors. The study is based on “success stories” of leading universities in various countries: Harvard and Stanford Universities (USA), Massachusetts Institute of Technology (USA), Shanghai Jiao Tong University (China), Indian Institute of Technology Bombay (India), Pohang University of Science and Technology (Korea), National Research University Higher School of Economics (Russia). We can conclude that universities become leaders if they manage to “ride the wave” of important changes for society and support the deployment of these processes, as well as use their energy and the emerging opportunities. An important factor is the activity of key partners that support the development of a leading university: professional communities, authorities, governmental institutions and large companies. The impact of leading universities on the development of the regions and countries where they are located is formulated as follows: they form elites; create an educated society, bring up professionals; produce and distribute new knowledge, technological, organizational and institutional solutions; directly develop the economy through the creation of new enterprises and jobs. Leading universities initiate cooperation on a regional and global scale; solving the problems faced by the humanity; they set new future-oriented objectives and goals. In the history of universities, we can observe various relations with the state: partnership of universities and authorities or state domination over universities. The implementation of the strategic interests of the state can be combined with the freedom and activeness of universities, modelling the promising practices of the future “on themselves”. At the same time, the situation in Russia is characterized by the actual absence of “universities as communities” demonstrating a high level of academic autonomy, their own vision of the prospects for the economy, technology, science, education and formulating their own independent strategies
Análise emergética uma proposta para o setor sucroalcooleiro do Estado de Alagoas – Brasil
Authors: Timóteo Ivanildo Cavalcanti , Silva Júnior Pavão Jessé Marques da , Sant'Anna Selenobaldo Alexinaldo Cabral
Published: February 2020

RESUMO: A cana-de-açúcar destaca-se como um dos principais produtos agrícolas no Brasil e de grande importância sócio, econômico e ambiental. No Estado de Alagoas ela tem um papel marcante no desenvolvimento social e econômico do Estado e que é marcado por um processo histórico de utilização da terra, dos recursos hídricos, de insumos agrícolas e mecanização. Uma análise da produção de cana-de-açúcar e seus produtos no Estado de Alagoas, que leve em consideração os serviços ecossistêmicos dos solos dos tabuleiros costeiros deve considerar a metodologia emergética. Assim, o presente trabalho tem como objetivo realizar um estudo de caso dos serviços ecossistêmicos dos solos nos tabuleiros costeiros no Estado de Alagoas, através da análise emergética de uma agroindústria do setor sucroalcooleiro. O estudo será realizado junto a unidade sucroalcooleira energética no Município de Rio Largo-AL, localizado na região dos Tabuleiros Costeiros, o levantamento dos dados agrícolas e industriais serão obtidos junto a unidade sucroalcooleira energética. Os fluxos de entrada e saída de energia, materiais e capital da unidade sucroalcooleira energética serão identificados e quantificados. Em seguida serão utilizadas tabelas de transformidades para os cálculos emergéticos, construídos os respectivos diagramas e avaliada a capacidade de suporte de cada etapa dos processos da usina e por fim, os dados serão interpretados sobre a ótica da sustentabilidade. No município de Rio Largo-AL foi selecionado uma sucroalcooleira energética pertencente ao grupo Santa Clotilde, fundada em 1967, e que se encontra em atividade e com produção de açúcar, álcool e energia e que são expressivos para a região dos Tabuleiros Costeiros. As atividades do projeto encontram-se na fase de levantamento de dados das atividades agrícolas e industrial da unidade. O presente trabalho contribui com um melhor entendimento dos processos ecológico e econômico do setor sucroalcooleiro energético no Nordeste do Brasil. Dessa forma, o estudo possibilitará agregar informações que possam ser utilizadas na comparação entre outras unidades sucroalcooleiro energético da região.

PALAVRAS-CHAVES: Cana-de-açúcar, Transformidade, Sustentabilidade
Suscetibilidade induzida a escorregamentos, via aplicação do método AHP
Authors: Bispo Carlos de Oliveira , Listo Fabrizio  de Luiz Rosito , Listo Danielle Gomes da Silva , Falcão Nivaneide Alves de Melo
Published: February 2020

RESUMO: Os escorregamentos são processos da dinâmica natural da terra, amplificados diante da ocupação inadequada de áreas suscetíveis a movimentos de massa, podendo acarretar em desastres com prejuízos materiais e humanos. Em consonância com esta realidade o presente artigo tem como objetivo, avaliar a suscetibilidade induzida a escorregamentos no litoral norte de Maceió – AL, por meio da aplicação do método Analytic Hierarchy Process – AHP, em ambiente SIG. Foram utilizados fatores relativos à geologia, geomorfologia, solos, declividade e forma do terreno e uso da terra. A análise espacial foi realizada por meio de métodos multicritérios e álgebra de mapas com a ponderação das variáveis via AHP. Para validar os resultados, utilizou-se um mapa inventário contendo 29 cicatrizes de escorregamentos, identificadas em 2017. Os resultados apontam que a área estudada possui médio potencial para ocorrência de processos de escorregamentos, em que as classes de suscetibilidade baixa, média, alta, apresentaram respectivamente uma frequência de 10%, 75% e 15%. Na validação nota-se que 74% dos escorregamentos estão concentrados na classe de suscetibilidade alta, 25% na classe de suscetibilidade média e apenas 1% na classe de suscetibilidade baixa. Destarte, o mapa obtido pode ser considerado útil para monitorar as áreas suscetíveis a escorregamentos.

PALAVRAS-CHAVE: Geomorfologia. Escorregamentos. Geoprocessamento.
Nostalgia as the cultural phenomenon
Authors:   Kiev National University of Trade and Economics, Morozov A. Y.
Published: February 2020

The article is devoted to the observation of the cultural phenomenon of nostalgia, its social, psychological, ethical and general philosophical aspects. It is shown that nostalgia is based on value-laden memory that helps us differ pleasant and unpleasant, useful and useless, meaningful and meaningless. This value-laden memory has its ethical dimension that deals with moral tradition, our concepts of good and evil, justice and injustice, sense of life and sense of death. We may say that ethical memory is a part of a larger “cultural memory” that enables every kind of social and individual identity. Due to nostalgia the generation`s continuity is established. In the act of nostalgia a person recalls the past but also rebels against actual state of presence. It is affirmed that our time-arrangement of “bad presence” and “good past” is possible because of ontological time regress. Nostalgizing for the past, a man is trying not only to mythologize the latter, but to resurrect it symbolically. Nostalgia’s faith in revival contains a hope for annihilation of time and triumph of eternity. We may call it an archetypical need, a manifestation of ancient mythological and religious motive of death and resurrection. Longing for past accompanies mankind during all its history and especially rises in the postmodern culture – in forms of metaphysical, political and aesthetical nostalgias. Metaphysical nostalgia is the lust for Logos, (God, meaning, truth, the good and the beauty) in the post-nihilistic absurd world, where god is claimed to be dead, and all supreme values are seemed to be devalued. It is also longing for the sacred reality, the being, that postmodern culture is lacked. Political nostalgia is the lust for the real power, subconscious desire for its increasing, expanding, absolutization. Aesthetical nostalgia is the sadness for the art as symbolic hierarchical structure with definite cultural and historical code as today we observe fakes and simulations, chaos and “metastases of cultural codes” (J. Baudrillard).