bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Effect of Financial Literacy Among Managers on the Performance of Small-Scale Enterprises
Authors: Tuffour Joseph Kwadwo , Amoako Awurabena Asantewa , Amartey Ernestina Otuko
Published: February 2020

The small-scale sub-sector continues to be a fundamental catalyst for job creation and economic growth in Ghana. About 35 per cent of labour is provided by the sub-sector and shows the importance of harnessing its potentials in developing the Ghanaian economy. It has been established that financial literacy has a significant influence on whether or not small-scale enterprises succeed. Yet, the exact effect of financial literacy on small-scale enterprise performance has not been fully identified in Ghana, hence the need for the present study. This study examines the effect of financial literacy (awareness, attitude and knowledge) of managers on the performance (financial and non-financial) of small-scale enterprises in the La Nkwantanang Madina Municipality of Ghana. Primary data were obtained from 200 small-scale managers through structured questionnaires. The data were analysed using structural equation model. The results revealed a significant effect of financial literacy on firm performance (both financial and non-financial performance). Also, all the three components of financial literacy (awareness, attitude and knowledge) have a significant positive effect on both financial and non-financial performance. However, individual characteristics (age of the individual, educational level and experience) have no significant effect on financial performance, whereas tax becomes useful when used as a regulatory tool of small enterprises. Capacity building programmes are therefore recommended to increase financial literacy among managers/owners of small-scale enterprises.
Emergency patient flow forecasting in the radiology department
Authors: Zhang Yumeng , Luo Li , Zhang Fengyi , Kong Ruixiao , Yang Jianchao , Feng Yabing , Guo Huili
Published: February 2020

The accurate forecast of radiology emergency patient flow is of great importance to optimize appointment scheduling decisions. This study used a multi-model approach to forecast daily radiology emergency patient flow with consideration of different patient sources. We constructed six linear and nonlinear models by considering the lag effects and corresponding time factors. The autoregressive integrated moving average and least absolute shrinkage and selection operator (Lasso) were selected from the category of linear models, whereas linear-and-radial support vector regression models, random forests and adaptive boosting were chosen from the category of nonlinear models. The models were applied to 4-year daily emergency visits data in the radiology department of West China Hospital in Chengdu, China. The mean absolute percentage error of six models ranged from 8.56 to 9.36 percent for emergency department patients, whereas it varied from 10.90 to 14.39 percent for ward patients. The best-performing model for total radiology visits was Lasso, which yielded a mean absolute percentage error of 7.06 percent. The arrival patterns of emergency department and total radiology emergency patient flows could be modeled by linear processes. By contrast, the nonlinear model performed best for ward patient flow. These findings will benefit hospital managers in managing efficient patient flow, thus improving service quality and increasing patient satisfaction.
Bayesian joint analysis using a semiparametric latent variable model with non-ignorable missing covariates for CHNS data
Authors: Ma Zhihua , Chen Guanghui
Published: February 2020

Motivated by the China Health and Nutrition Survey (CHNS) data, a semiparametric latent variable model with a Dirichlet process (DP) mixtures prior on the latent variable is proposed to jointly analyse mixed binary and continuous responses. Non-ignorable missing covariates are considered through a selection model framework where a missing covariate model and a missing data mechanism model are included. The logarithm of the pseudo-marginal likelihood (LPML) is applied for selecting the priors, and the deviance information criterion measure focusing on the missing data mechanism model only is used for selecting different missing data mechanisms. A Bayesian index of local sensitivity to non-ignorability (ISNI) is extended to explore the local sensitivity of the parameters in our model. A simulation study is carried out to examine the empirical performance of the proposed methodology. Finally, the proposed model and the ISNI index are applied to analyse the CHNS data in the motivating example.
Quantifying Energy Consumption in Household Surveys: An Alternative Device-based Accounting Approach
Authors: Wu Shimei , Zheng Xinye , Guo Jin , Li Chuan-Zhong , Wei Chu
Published: February 2020

The exercise of quantifying the energy consumption data assembled through household surveys, either by the recall-based approach or the meter-based approach, remains a challenging task, especially in rural areas of developing countries. In this article, we propose a device-based bottom-up accounting method for estimating household energy consumption. This method provides microlevel disaggregated estimates at the intensive margin and documents other difficult-to-measure energy consumption such as biomass at the extensive margin. Even though measurement errors of the household survey might still exist, the structured questionnaire of daily routine behavior questions should greatly alleviate the problem. The new method supplements the existing household energy statistical system, improves its flexibility, and is particularly applicable in developing countries and/or rural areas. We apply the method to a Chinese rural household survey and discuss its differences and similarities with the conventional methods.
A Game for All Seasons: Lessons and Learnings from the JRC’s Scenario Exploration System
Authors: Bontoux Laurent , Sweeney John A. , Rosa Aaron B. , Bauer Alice , Bengtsson Daniel , Bock Anne-Katrin , Caspar Ben , Charter Martin , Christophilopoulos Epaminondas , Kupper Frank , Macharis Cathy , Matti Cristian , Matrisciano Marco , Schuijer Jantien , Szczepanikova Alice , van Criekinge Tine , Watson Rosina
Published: February 2020

The European Commission Joint Research Centre’s (JRC) Scenario Exploration System (SES) is a foresight gaming system developed to facilitate the application of futures thinking to policy-making. It was originally geared at engaging EU policy-makers with scenarios in a facilitated process with a low learning curve. Specifically, the SES was designed to help participants, in less than three hours, to engage in systemic thinking with a long-term perspective and to explore alternative futures on specific issues and themes. When applied in various contexts, the SES proved to have a broader range of applications, which led to communities of practice emerging around the tool. Successful responses to various requests to apply the tool beyond its original focus demonstrated the versatility of the SES. Specifically, we discovered its ability to accommodate a large array of scenarios to discuss a very diverse range of issues. The experience accumulated through several adaptations of the SES allows the analysis of the various strengths and weaknesses of the tool as a platform for futures thinking and sharing more broadly the know-how for the creation and application of new versions. Ultimately, this article seeks to contribute a series of design suggestions for futures practitioners seeking to develop a playful mode of interaction with scenarios, or those seeking to repurpose the original SES system for use in their own project.
Moral Foundations Twitter Corpus: A Collection of 35k Tweets Annotated for Moral Sentiment
Authors: Hoover Joe , Portillo-Wightman Gwenyth , Yeh Leigh , Havaldar Shreya , Davani Aida Mostafazadeh , Lin Ying , Kennedy Brendan , Atari Mohammad , Kamel Zahra , Mendlen Madelyn , Moreno Gabriela , Park Christina , Chang Tingyee E. , Chin Jenna , Leong Christian , Leung Jun Yen , Mirinjian Arineh , Dehghani Morteza
Published: February 2020

Research has shown that accounting for moral sentiment in natural language can yield insight into a variety of on- and off-line phenomena such as message diffusion, protest dynamics, and social distancing. However, measuring moral sentiment in natural language is challenging, and the difficulty of this task is exacerbated by the limited availability of annotated data. To address this issue, we introduce the Moral Foundations Twitter Corpus, a collection of 35,108 tweets that have been curated from seven distinct domains of discourse and hand annotated by at least three trained annotators for 10 categories of moral sentiment. To facilitate investigations of annotator response dynamics, we also provide psychological and demographic metadata for each annotator. Finally, we report moral sentiment classification baselines for this corpus using a range of popular methodologies.
Inmates as Labour Pool: A Case of Inter-organizational Collaboration
Authors: Shree Sonal , Brahmankar Yogesh , Singh Ardhendu Shekhar
Published: February 2020

Businesses grapple with mounting costs of accessing labour pools for recruitment. At the same time, the jail administrations struggle to find recruiters for a skilled group of convicts. Can collaboration help? It is in this light that the case focusses on the prison system in India and the provision of training and employment within the jail premises. The jail industries serve the dual role of production and training units for convicts and equip them with the necessary skills to help them earn wages as their source of livelihood for the present as well as to secure their future.

Inter-organizational collaboration in this case has the potential to provide the much-needed impetus by offering a much larger number of tasks required to engage all convicts.

The case highlights the challenges faced by jail authorities in the absence of sufficient tasks versus the increasing number of convicts, and the dilemma and scepticism of businesses in recruiting from prisons. It also leads to the innovative and socially responsible aspect of training and recruitment in organizations through initiatives at the Yerwada and Kolhapur Central jails in Maharashtra, India.

Dilemma

Purposive engagement of prisoners outside the prison without any breach of security was a prime concern. An opportunity or risk, what could it turn out to be? Theory: Inter-organizational collaboration Type of the Case: Problem solving, Primary data Protagonist: DIG Sathe

Options

The jobs were selected based on the security needs, matching competency, low set-up and training cost and future expansions. Initially jail authorities leased out portions of premises to firms. Inventory were brought in the jail and finished items were transported back to the user.

Discussions and Case Questions

How to change the stereotypical portrayal of jail environment as a place to torture inmates in an effort to transform? How can firms be attracted to recruit prison inmates? Which processes will lead to reformation and rehabilitation of inmates? How can the operation be scaled up without posing a threat to security? Which measures will help in diffusing tension within a jail? Whether any inter-organizational collaboration leading to recruitment from prisons would mean an opportunity for corporate or corrective reform for inmates or a morsel of both?
Phthalate Exposures and MicroRNA Expression in Uterine Fibroids: The FORGE Study
Authors: Zota Ami R , Geller Ruth J , VanNoy Brianna N , Marfori Cherie Q , Tabbara Sana , Hu Lisa Y , Baccarelli Andrea A , Moawad Gaby N
Published: February 2020

Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (β = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (β = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (qinteraction < 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids.
The secondary KIT mutation p.Ala510Val in a cutaneous mast cell tumour carrying the activating mutation p.Asn508Ile confers resistance to masitinib in dogs
Authors: Gentilini Fabio , Turba Maria Elena , Dally Claire , Takanosu Masamine , Kurita Sena , Bonkobara Makoto
Published: February 2020

Background

Gain-of-function mutations in KIT are driver events of oncogenesis in mast cell tumours (MCTs) affecting companion animals. Somatic mutations of KIT determine the constitutive activation of the tyrosine kinase receptor leading to a worse prognosis and a shorter survival time than MCTs harbouring wild-type KIT. However, canine MCTs carrying KIT somatic mutations generally respond well to tyrosine kinase inhibitors; hence their presence represents a predictor of treatment effectiveness, and its detection allows implementing a stratified medical approach. Despite this, veterinary oncologists experience treatment failures, even with targeted therapies whose cause cannot be elucidated. The first case of an MCT-affected dog caused by a secondary mutation in the tyrosine kinase domain responsible for resistance has recently been reported. The knowledge of this and all the other mutations responsible for resistance would allow the effective bedside implementation of a deeply stratified and more effective medical approach.

Case presentation

The second case of a canine MCT carrying a different resistance mutation is herein described. The case was characterised by aggressive behaviour and early metastasis unresponsive to both vinblastine- and masitinib-based treatments. Molecular profiling of the tumoural masses revealed two different mutations; other than the already known activating mutation p.Asn508Ile in KIT exon 9, which is tyrosine kinase inhibitor-sensitive, a nearly adjacent secondary missense mutation, p.Ala510Val, which had never before been described, was detected. In vitro transfection experiments showed that the secondary mutation did not cause the constitutive activation by itself but played a role in conferring resistance to masitinib.

Conclusions

This study highlighted the importance of the accurate molecular profiling of an MCT in order to improve understanding of the molecular mechanism underlying tumourigenesis and reveal chemoresistance in MCTs for more effective therapies. The detection of the somatic mutations responsible for resistance should be included in the molecular screening of MCTs, and a systematic analysis of all the cases characterised by unexpected refractoriness to therapies should be investigated in depth at both the genetic and the phenotypic level.
Allergic reactions to genus Morus plants: a review
Authors: Papia F. , Incorvaia C. , Genovese L. , Gangemi S. , Minciullo P. L.
Published: February 2020

Mulberry is a plant belonging to the family Moraceae, and genus Morus. Allergic sensitization to mulberries has been reported as both food allergy or respiratory allergy, and cross-reactivity between mulberries and other pollens or fruits was described. Clinically, in the articles reporting mulberry allergy, the reactions included respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria. As far as cross-reactivity is concerned, the allergens identified thus far in mulberries include pathogenesis-related (PR)10 proteins, with sequence identity to Bet v 1 from birch, lipid transfer (LTP)1 proteins with identity with LTPs from Rosaceae family plants, panallergens groups, and also ubiquitin-like protein and cystatin-like protein. The two latter proteins account for cross-reactions with Parietaria judaica and Olea europaea. Such large cross-reactivity warrants to pay particular attention to the risk of systemic reactions to foods, particularly in subjects sensitized to birch, parietaria or olive pollens. In fact, the increasing use of mulberry as a food product, which is encouraged by its remarkable antioxidant power, expose sensitized patients to possible reactions after ingesting foods, dietary supplements or nutraceuticals containing mulberry. Mulberry allergenicity can vary according to the processing methods used since some allergens are thermostable and other loss their reactivity during heating.
Initiating renal replacement therapy through incremental haemodialysis: Protocol for a randomized multicentre clinical trial
Authors: Fernández Lucas M. , Ruíz-Roso G. , Merino J. L. , Sánchez R. , Bouarich H. , Herrero J. A. , Muriel A. , Zamora J. , Collado A.
Published: February 2020

Background

Thrice-weekly haemodialysis is the usual dose when starting renal replacement therapy; however, this schedule is no longer appropriate since it does not consider residual renal function. Several reports have suggested the potential benefit of beginning haemodialysis less frequently and incrementally increasing the dose as the residual renal function decreases. However, all the data published so far are from observational studies. Thus, this clinical trial avoids any potential selection bias and will assess the possible benefits that have been observed in observational studies.

Methods/design

This report describes the study protocol of a randomized prospective multi-centre open-label clinical trial to evaluate whether starting renal replacement therapy with twice-weekly haemodialysis sessions preserves residual renal function better than the standard thrice-weekly regimen. We also explore other clinical parameters, such as concentrations of uremic toxins, dialysis doses, control of anaemia, removal of medium-weight uremic toxins, nutritional status, quality of life, hospital admissions and mortality. Only incident haemodialysis patients who can maintain a urea clearance rate KrU ≥ 2.5 mL/min/1.73 m2 are eligible. Patient recruitment began on 1 January 2017 and will last for 2 years or until the required sample size has been recruited to ensure the established statistical power has been reached. The minimum follow-up period will be 1 year. Anuric patients with acute renal failure and patients who return to haemodialysis after a kidney transplant failure are excluded. It has been calculated that 44 patients should be recruited into each group to achieve a power of 80% in a two-sided comparison of means with a usual significance level of 0.05. A time-to-event analysis will estimate the probability of kidney function survival in both groups using the Kaplan–Meier method. Survival curves will be compared with log-rank tests. This survival analysis will be complemented with a proportional hazard model to estimate the hazard ratio of kidney function survival adjusted for any confounding factors. Analyses will be carried out in accordance with the intention-to-treat principle.

Discussion

The incremental initiation of dialysis may preserve residual renal function better than the conventional treatment, with similar or higher survival rates, as reported by observational studies. To our knowledge, this is the first clinical trial to evaluate whether initiating renal replacement therapy with twice-weekly haemodialysis sessions preserves residual renal function better than beginning with the standard thrice-weekly regimen.

Trial registration

ClinicalTrials.gov, NCT03302546. Registered on 5 October 2017.
A potential global surveillance tool for effective, low-cost sampling of invasive Aedes mosquito eggs from tyres using adhesive tape
Authors: Dallimore Thom , Goodson David , Batke Sven , Strode Clare
Published: February 2020

Background

The international movement of used tyres is a major factor responsible for global introductions ofAedesinvasive mosquitoes (AIMs) (Diptera: Culicidae) that are major disease vectors (e.g. dengue, Zika, chikungunya and yellow fever). Surveillance methods are restricted by expense, availability and efficiency to detect all life stages. Currently, no tested method exists to screen imported used tyres for eggs in diapause, the life stage most at risk from accidental introduction. Here we test the efficiency of adhesive tape as an affordable and readily available material to screen tyres for eggs, testing its effect on hatch rate, larval development, DNA amplification and structural damage on the egg surface.

Results

We demonstrated that the properties of adhesive tape can influence pick up of dormant eggs attached to dry surfaces. Tapes with high levels of adhesion, such as duct tape, removed eggs with high levels of efficiency (97% ± 3.14). Egg numbers collected from cleaned used tyres were found to explain larval hatch rate success well, particularly in subsequent larval to adult emergence experiments. The strength of this relationship decreased when we tested dirty tyres. Damage to the exochorion was observed following scanning electron microscopy (SEM), possibly resulting in the high variance in the observed model. We found that five days was the optimal time for eggs to remain on all tested tapes for maximum return on hatch rate success. Tape type did not inhibit amplification of DNA of eggs from three, five or ten days of exposure. Using this DNA, genotyping of AIMs was possible using species-specific markers.

Conclusions

We demonstrated for the first time that adhesive tapes are effective at removing AIM eggs from tyres. We propose that this method could be a standardised tool for surveillance to provide public health authorities and researchers with an additional method to screen tyre cargo. We provide a screening protocol for this purpose. This method has a global applicability and in turn can lead to increased predictability of introductions and improve screening methods at high risk entry points.
A high capacity reversible data hiding through multi-directional gradient prediction, non-linear regression analysis and embedding selection
Authors: Hung Kuo-Ming , Yih Chi-Hsiao , Yeh Cheng-Hsiang , Chen Li-Ming
Published: February 2020

The technique of reversible data hiding enables an original image to be restored from a stego-image with no loss of host information, and it is known as a reversible data hiding algorithm (RDH). Our goal is to design a method to predict pixels effectively, because the more accurate the prediction is, the more concentrated the histogram is, and it minimizes shifting to avoid distortion. In this paper, we propose a new multi-directional gradient prediction method to generate more accurate prediction results. In embedding stage, according to the embedding capacity of information, we generate the best decision based on non-linear regression analysis, which can differentiate between embedding region and non-embedding region to reduce needless shifting. Finally, we utilize the automatic embedding range decision. With sorting by the amount of regional variance, the easier predicted region is prior for embedding, and the quality of the image is improved after embedding. To evaluate the proposed reversible hiding scheme, we compared other methods on different pictures. Results show that the proposed scheme can embed much more data with less distortion.
Update on KEYNOTE-199, cohorts 1-3: Pembrolizumab (pembro) for docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC).
Authors: Antonarakis Emmanuel S. , Piulats Josep M. , Gross-Goupil Marine , Goh Jeffrey C. , Vaishampayan Ulka N. , De Wit Ronald , Alanko Tuomo , Fukasawa Satoshi , Tabata Kenichi , Feyerabend Susan , Berger Raanan , Wu Helen , Kim Jeri , Schloss Charles , De Bono Johann S.
Published: February 2020

104

Background: The KEYNOTE-199 multicohort phase 2 study (NCT02787005) showed that pembro monotherapy has antitumor activity and acceptable safety in patients (pts) with mCRPC previously treated with a next-generation hormonal agent (NHA) and docetaxel in cohort 1 (C1) (RECIST-measurable, PD-L1+ disease), C2 (RECIST-measurable, PD-L1− disease), and C3 (bone-predominant disease, irrespective of PD-L1). Updated results with additional follow-up for C1-3 are presented. Methods: Pts previously received ≥1 NHAs and 1 or 2 chemotherapies, including docetaxel. Pts received pembro 200 mg Q3W for 35 cycles or until progression or intolerable toxicity. Primary end point was ORR. Key secondary end points were DCR, DOR, PSA (≥50%) response rate, rPFS, OS, and safety. Results: Of 258 pts enrolled (C1=133; C2=67; C3=58), 6 completed (C1=4; C3=2) and 252 discontinued (C1=129; C2=67; C3=56) therapy, primarily due to progression (C1=106; C2=61; C3=45). Median follow-up was 9.6 mo (C1, 9.5; C2, 7.9; C3, 14.2). ORR (95% CI) for pts with measurable disease was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2 (Table; includes other efficacy results). Treatment-related AEs of any grade/grade 3-5 occurred in 57%/16% in C1, 60%/15% in C2, and 71%/17% in C3. 1 pt in each cohort died of a treatment-related AE (C1, sepsis; C2, unknown; C3, immune-related pneumonitis). Conclusions: With additional follow-up, pembro monotherapy continued to show antitumor activity and disease control in pts with RECIST-measurable and bone-predominant mCRPC previously treated with both NHA and docetaxel. Pts experienced durable responses. Safety was consistent with the known safety profile of pembro. Clinical trial information: NCT02787005. [Table: see text]
KEYNOTE-046 (Part B): Effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel.
Authors: Stein Mark N. , Fong Lawrence , Mega Anthony E. , Lam Elaine Tat , Heyburn John W. , GUTIERREZ ANDRES A. , Parsi Megan , Vangala Surya , Haas Naomi B.
Published: February 2020

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Background: ADXS-PSA, an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), is currently being evaluated in combination with pembrolizumab as a treatment for progressive metastatic castration-resistant prostate cancer (mCRPC) in the phase 1/2 KEYNOTE-046 trial (Part B). Methods: A total of 37 patients received 1x109 CFU + 200 mg pembro IV every 3 wks, for up to 2 yrs or until progression/toxicity. Results: At entry, patients were ~70 yrs with median a Gleason score of 9, and bone predominant disease (70%). MSI-High was negative in 36 pts who were able to be tested. Eighteen (48.6%) patients had received prior docetaxel, 15 pts of whom (83.3%) had also received 1-2 next generation hormonal agents (NGHAs). Nineteen (51.3%) had not received prior docetaxel and 16 of these pts (84.2%) had received 1-2 NGHAs. Overall, 16 out of 37 pts (43%) had a decreased PSA post-BL with 6/37 (16%) pts achieving a confirmed PSA reduction ≥50% from baseline. The median OS (months) for the whole group (37 pts) was 33.6 m (95% CI, range 15.4-33.6 months). The mOS for pts with and without prior exposure to docetaxel was 16 m (5.9 -33.6) and NR at 30 months of follow-up (15.4-NR), respectively. Prolonged survival was observed in pts regardless of prior therapies, microsatellite stable (MSS) status or PSA delta <50% or ≥50%. Conclusions: Results with ADXS-PSA in combination with pembrolizumab in mCRPC, with or without prior docetaxel, show promising clinical activity to be further assessed in randomized studies. Clinical trial information: NCT02325557.
Relationship between Geriatric 8 screening score and treatment selection in patients with prostate cancer.
Authors: Hatakeyama Shingo , Momota Masaki , Hamano Itsuto , Okamoto Teppei , Yamamoto Hayato , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara
Published: February 2020

206

Background: This study aimed to evaluate the geriatric 8 (G8) screening tool for detecting frailty in patients with prostate cancer. Methods: Between January 2017 and June 2019, we prospectively evaluated the G8 in 540 prostate cancer patients, 444 with localized stage M0 and 96 with metastatic stage M1 disease. The primary endpoint was the comparison of G8 scores in patients treated with robot-assisted radical prostatectomy (RARP), radiotherapy, androgen deprivation therapy alone (ADT-alone) for localized disease, and standard care for the M1 disease. Secondary endpoint included the cutoff estimation of G8 score and the influence of G8 on prognosis. Results: The median age was 75 years. G8 scores ≤14 indicating frailty were seen in 36% of RARP (n = 214), 57% of RT (n = 209), 91% of ADT-alone (n = 21), and 70% of M1 disease (n=96). The median G8 score in M0 patients was significantly higher than that in M1 patients (14.5 vs 12.8, respectively). The median G8 score in patients treated with RARP, RT and ADT-alone was 15, 14, and 12, respectively. The patients with RARP had significantly higher G8 score than that of RT or ADT-alone. The optimal G8 cutoff score for patients with M0 and M1 disease was 13.0 (AUC: 0.681). The overall survival was significantly shorter in patients with G8 <13 than that of ≥13. Conclusions: The G8 score of patients with localized and metastatic PC was significantly different. Frailty was significantly associated with treatment selection and prognosis in patients with PC.
The role of 68Ga-DOTATATE for evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Bilen Mehmet Asim , Akintayo Akinyemi A , Abiodun-Ojo Olayinka A. , Kucuk Omer , Carthon Bradley Curtis , Schuster David M. , Parent Ephraim E
Published: February 2020

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Background: Neuroendocrine transformation (NE) of prostate cancer is difficult to diagnose and treat. 68Ga-DOTATATE PET is useful to detect well-differentiated neuroendocrine tumors, but its application in prostate cancer is not well understood. We evaluated DOTATATE PET in patients with mCRPC and suspected or known NE. Methods: DOTATATE PET/CT were performed in 17 patients with mCRPC. Summed SUVmax of up to 5 bone and 5 soft tissue lesions in each patient were correlated with histologic presence of NE and response to standard of care treatment and clinical outcome (NCT03448458). Results: Mean age was 62.3±9.2 years. Median PSA was 39.0 ng/ml. 2/17 patients had biopsy proven NE. 1/17 was found to have squamous cell cancer and therefore excluded from analysis. 2 patients with NE had platinum-based chemotherapy. Of the 14 patients without NE, 7/14 received enzalutamide or abiraterone, and 7/14 received taxane based chemotherapy after DOTATATE PET. On PET, all patients had at least one lesion (median 7 [interquartile range 6-9]) with uptake. 11/16 patients had bone and visceral/nodal lesions, 4/16 had only bone lesions, and 1 had only nodal disease. Summed SUVmax was significantly higher in 2/16 patients with proven NE compared to the 14/16 non-NE patients (99.1± 16.5 ng/ml vs 48.4± 40.6 ng/ml; p=0.04). There was no correlation between summed SUVmax and PSA. Follow-up was available in 15/16 patients. SUVmax was higher in patients who did not respond to treatment, however, the trend was non-significant (69.5 ± 46.6 vs 39.3 ± 29.6; p=0.20). There was no significant association between survival and DOTATATE uptake. 6/16 patients had next generation sequencing. Of these, 1 patient without NE had BRCA2 mutation, and also had the highest summed uptake in this study. Conclusions: DOTATATE uptake is higher in mCRPC patients with NE or with BRCA mutation. Uptake was higher in patients who did not respond to standard of care treatment, though this was a nonsignificant trend, possibly due to small sample size. Larger studies are therefore recommended. Clinical trial information: NCT03448458.
Radium-223 in the treatment of metastatic castrate-resistant prostate cancer: A real-world Irish experience.
Authors: Peters Niamh , Gaffney John , Connolly Emma , Bambury Richard , Power Derek Gerard , Kelly Paul J. , Jamaluddin Muhammad faisal
Published: February 2020

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Background: Radium 223 (Ra-223) has been successfully utilised in the trial setting for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods: From September 2016 to March 2019, data from men referred for Ra-223 treatment at our institution was retrospectively collected. We recorded patient characteristics, treatments received and outcomes. Overall Survival (OS) was analysed using the Kaplan-Meier method. Results: 81 men were referred for Ra 223. Complete data was available for 56 men. Median age was 75. 79%(45/56) had over 6 bone metastases and 21%(12/56) had lymph node involvement. The median number of prior systemic treatments for mCRPC was 2. 84%(47/56) of patients were previously treated with Androgen deprivation therapy (ADT); 48%(27/56) Abiraterone, 36%(20/56) Docetaxel, 45%(25/56) Enzalutamide and 9%(5/56) Cabazitaxel. All patients were receiving bone protection agents; 57%(32/56) Zolendronic acid and 43%(24/56) Denosumab. Median ECOG was 1 at the start of treatment and 2 at completion. The median number of treatments received was 4 with 36%(20/56) completing all 6 treatments. The most common toxicity seen was grade1 fatigue occurring in10% (6/56). 17% (10/56) required a blood transfusion during their treatment course. 53%(30/56) required opioid analgesia prior to Ra 223 treatment. 76% of these men (22/30) described improved pain following Rad-223. At a median follow up of 13 months,41%(23/56) were alive. The median OS for the entire group was 7 months. Factors associated with improved OS included ECOG 0-1,fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and no prior chemotherapy use. Median OS for those who had not received prior chemotherapy was significantly better than those who had (9 vs 5 months p=0.04). Conclusions: This real world study demonstrates Ra 223 is a well tolerated palliative treatment amongst Irish men with mCRPC. Good performance status, lower alkaline phosphatase, chemotherapy naivety and a low burden of metastatic disease are factors associated with an improved overall survival.
Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer.
Authors: Hamano Itsuto , Hatakeyama Shingo , Narita Shintaro , Takahashi Masahiro , Sakurai Toshihiko , Kawamura Sadafumi , Hoshi Senji , Kawaguchi Toshiaki , Ishidoya Shigeto , Shimoda Jiro , Sato Hiromi , Mitsuzuka Koji , Tochigi Tatsuo , Tsuchiya Norihiko , Arai Yoichi , Habuchi Tomonori , Ohyama Chikara
Published: February 2020

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Background: It is unknown whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration resistant prostate cancer (mCRPC) patients. Methods: We reviewed the Michinoku Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW) adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis. Results: Median age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir >0.64 ng/mL and TTN <7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC and CRPC-free survival. The Cox proportional and IPTW-adjusted multivariate analyses revealed that the unfavorable group had a negative impact on OS in mCRPC patients (hazards ratio [HR] 2.98, P < 0.001). Conclusions: Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.[Table: see text]
Prostate cancer survivorship care plans: What we are failing to tell men after treatment?
Authors: Choi Youngjee , Smith Katherine C. , Shukla Aishwarya , Blackford Amanda L. , Tran Phuoc T. , Peairs Kimberly S. , DeMarco Thomas M. , Choflet Amanda , Farling Kristen , Kelso Madeline , Carducci Michael Anthony , Mayonado Nancy , Tolbert Elliott , Snyder Claire Frances
Published: February 2020

311

Background: Survivorship care plans (SCPs) present essential information about cancer treatment and follow-up recommendations for cancer survivors. We describe the completeness of prostate cancer SCPs and evaluate guideline concordance of follow-up recommendations. Methods: We analyzed 125 prostate cancer SCPs from an academic and community cancer center, abstracting demographics, cancer/treatment details and follow-up recommendations. Follow-up recommendations were compared to national guidelines. Results: Content provided in >90% of SCPs included cancer TNM stage; PSA at diagnosis; radiation treatment details (98% of men received radiation); and PSA monitoring recommendations. Potential treatment-specific side effects were listed for 69% of men who had surgery, 78% for androgen deprivation therapy (ADT) and 97% for radiation. The presence of post-treatment symptoms were noted in 67% of plans – several ADT-related side effects (e.g., bone thinning, cognitive changes, muscle atrophy) were noted for 0/21 men who completed all ADT. Guidelines recommend an annual digital rectal exam (DRE) with no physical exam otherwise specified. No SCPs specified DRE, but all 68 SCPs at the community site recommended at least annual follow-up visits with urology, radiation oncology, and primary care. Only 5/57 SCPs at the academic site specified follow-up visits (radiation oncology every 6 months). Guidelines recommend PSA testing every 6-12 months (optional 3 months if high risk) for 5 years, then annually; while duration was not specified in any SCPs, if applied to the first 5 years, 91% of SCP recommendations were guideline concordant, 7% suggested oversurveillance, and 2% were incomplete. In men who received ADT, guidelines recommend assessing bone density (by imaging or FRAX score), and goal testosterone level. Of 80 men who completed or had ongoing ADT, 2% were recommended for bone density imaging (0 had FRAX scores) and 19% for testosterone levels. Conclusions: SCP content is more complete for demographic and treatment summary information with gaps in addressing treatment effects and follow-up recommendations beyond PSA testing. These findings highlight the need to improve the quality of information in SCPs. Clinical trial information: NCT03035773.
The intraprostatic immune balance after prostate SBRT in patients.
Authors: Nickols Nicholas George , Ganapathy Ekambaram , Nguyen Christine , Kane Nathanael , Lin Lin , Diaz-Perez Silvia , Nazarian Ramin , Kishan Amar Upadhyaya , King Christopher R. , Kupelian Patrick , Rettig Matthew , Steinberg Michael L. , Cao Minsong , Knudsen Beatrice , Chu Fang-I , Elashoff David , Reiter Robert Evan , Schaue Dörthe
Published: February 2020

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Background: Stereotactic Body Radiotherapy (SBRT) delivers high dose per fraction radiotherapy to targets with high precision. Such hypofractionated RT appears to act as an immune adjuvant, altering the tumor infiltrating immune landscape and enriching it for lymphocytes as numerous preclinical investigations would suggest. Based on this hypothesis, hundreds of ongoing trials listed in clinicaltrials.gov currently test the combination of RT (largely SBRT) with various immunotherapies. However, studies directly measuring the representation of infiltrating immune cells after SBRT in patients are few and far between and none exist in the context of prostate cancer. We therefore sought to interrogate the tumor-immune interface after prostate SBRT using fresh tissue in patients. Methods: Fresh prostate tissue from patients (N=10) enrolled in a clinical trial of prostate SBRT (three fractions of 8 Gy directed to the prostate and seminal vesicles) in the neoadjuvant setting two weeks prior to radical prostatectomy was subjected to multicolor flow cytometry and compared to that of Gleason Grade and T stage matched controls who did not undergo neoadjuvant therapy. Results: With a threshold of significance level of 0.05 for unadjusted p-values, using two-sided two-sample t-test, myeloid cells and particularly CD14+/hiCD16+DR+ intermediate monocytes/macrophages were enriched, while lymphocytes, including T cells and CD56+16− NK cells were decreased in SBRT-treated prostates as compared to unirradiated controls. Conclusions: The immune infiltrates in prostates two weeks after SBRT demonstrates a significant lymphoid to myeloid shift consistent with a tumor microenvironment after SBRT that is likely immunosuppressive beyond what can be targeted through the PD-1/L1 or CTLA-4 axis alone. This may have implications for the design of immunotherapy trials, especially in prostate cancer, that test SBRT in combination with immunotherapies.
Lower odds of cardiac events for gonadotropic releasing hormone antagonists versus agonists.
Authors: Cone Eugene Blanchard , Marchese Maya , Reese Stephen , Nabi Junaid , Kilbridge Kerry L. , Trinh Quoc-Dien
Published: February 2020

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Background: Gonadotropic releasing hormone (GnRH) agonists and antagonists are first-line for advanced prostate cancer, but may be associated with cardiac toxicity. Observational studies show a relatively lower risk for GnRH antagonists, but a randomized trial found no difference. We compared the reporting of cardiac events for GnRH agonists and antagonists. Methods: We used VigiBase, the World Health Organization global database of case safety reports, which collects data from more than 130 countries to extract drug-adverse event (AE) pairs. Using Medical Dictionary for Regulatory Activities terminology, we identified AEs related to GnRH antagonist (degarelix) or agonist (leuprolide, goserelin, triptorelin, histrelin) therapy for prostate cancer, including myocardial infarction, heart failure, cardiomyopathies, new-onset valvular dysfunction, and other major cardiac events. To explore a possible relationship we used the reporting odds ratio (ROR), a surrogate measure of association using all other reactions as non-cases. A lower bound of a 95% confidence interval of ROR > 1 reflects a disproportionality signal that more AEs are observed than expected. Results: We found 10,504 AEs for GnRH agonists, and 1,606 for GnRH antagonists; 805 (7.7%) were cardiac for agonists, and 102 for antagonists (6.4%). We found no signal for overall cardiac events or any subgrouping for GnRH antagonists, but identified a signal both for overall cardiac events (ROR 1.20, 95% CI 1.12-1.29) and myocardial infarction (1.76, 1.57-1.97) for GnRH agonists. Conclusions: Using validated pharmacovigilance methodology, we found a signal for myocardial infarction for GnRH agonists, but did not detect one for GnRH antagonists. As cardiovascular disease is the most common cause of non-cancer death in prostate cancer patients, this finding is of specific relevance in the current era of novel second-line anti-androgen therapies which may compound toxicity when added to first-line therapy. The relative cardiac toxicity of GnRH agonist therapy compared to GnRH antagonists merits renewed attention.
Rucaparib for recurrent, locally advanced, or metastatic urothelial carcinoma (mUC): Results from ATLAS, a phase II open-label trial.
Authors: Grivas Petros , Loriot Yohann , Feyerabend Susan , Morales-Barrera Rafael , Teo Min Yuen , Vogelzang Nicholas J. , Grande Enrique , Zakharia Yousef , Adra Nabil , Alva Ajjai Shivaram , Necchi Andrea , Gupta Sumati , Josephs Debra Hannah , Rodriguez-Vida Alejo , Srinivas Sandy , Wride Kenton , Thomas Daleen , Dusek Rachel , Nepert Dale L. , Chowdhury Simon
Published: February 2020

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Background: ATLAS (NCT03397394) evaluated the efficacy/safety of the PARP inhibitor (PARPi) rucaparib in patients (pts) with previously treated locally advanced/unresectable UC or mUC. Methods: Pts with measurable disease who had progressed after 1–2 prior regimens (ie, platinum-based chemotherapy [PBC] and/or immune checkpoint inhibitors [ICI]) were enrolled regardless of tumor homologous recombination deficiency (HRD) status. Prior PARPi was not allowed. Pts received rucaparib 600 mg PO BID. Baseline tumor tissue or archival tissue ≤6 mo without intervening therapy was required; serial circulating tumor DNA samples were collected. Primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (defined as genomic loss of heterozygosity ≥10%) populations. Key secondary endpoints: progression-free survival (PFS) and safety. Clinical benefit rate (CBR) was defined as complete or partial response or stable disease (SD) lasting ≥16 weeks. Results: As of Oct 7, 2019, 97 pts were enrolled (median age 66 y [range, 39–87]); most were men (n=76, 78.4%) and had ECOG PS 1 (n=65, 67.0%). Sixty-six pts (68.0%) had both prior PBC and ICI. Twenty pts (20.6%) were HRD-positive, 30 (30.9%) were HRD-negative and 47 (48.5%) had unknown HRD status; 4 pts had a deleterious BRCA1/2 alteration. Median time on treatment was 54 d (range, 2–224). There were no confirmed responses. Of 96 evaluable pts, 27 (28.1%) had a best response of SD; CBR was 12.5% and median PFS was 1.8 mo. No relationship was observed between HRD status and clinical activity. Treatment was discontinued by 93 pts (95.9%), mainly due to radiologic or clinical progression (73.1%). Most frequent any grade treatment-emergent (any cause) adverse events were asthenia/fatigue (n=56, 57.7%), nausea (n=40, 41.2%), and anemia (n=34, 35.1%). Conclusions: Single agent rucaparib did not show activity in pts with previously treated advanced UC and enrollment was suspended at the first interim analysis. The safety profile was consistent with that observed in pts with ovarian cancer. Next generation sequencing–based characterization of the genomic landscape of mUC will be presented. Clinical trial information: NCT03397394.