bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PROFILE feasibility study: Genetic prostate cancer risk stratification for targeted screening.
Authors: Mikropoulos Christos , Castro Elena , Bancroft Elizabeth , Page Elizabeth , Taylor Natalie , Dadaev Tokhir , Kote-Jarai Zsofia , Antoniou Antonis C. , DeSouza Nandita , Keating Diana , Saunders Edward , Easton Doug , Borley Nigel , Ahmed Mahbubl , Lee Andrew , Eeles Ros A. 
Published: February 2017

22 Background: Prostate cancer (PC) screening is controversial and a better assessment of individualized PC risk is needed. Several single nucleotide polymorphisms (SNPs) conferring a cumulative risk of PC have been identified. We have explored the potential role of genetic markers for targeted screening in a population with increased risk of PC due to family history (FH). Methods: PROFILE was developed as a pilot study to determine the feasibility of targeted PC screening using prostatic biopsy (PB) and its association with specific genetic profiles in men with FH. We also evaluated the role of PSA and Diffusion Weighted MRI (DW-MRI) as screening tools. One hundred sixteen men age 40 to 69 with FH of PC were enrolled between October 2009 and December 2012. Cumulative SNP risk scores were calculated by summing 59 risk alleles for each locus using the weighted effect (log-additive model). DW-MRI was performed in 50 patients. Participants were asked to undergo a 10 core PB regardless of baseline PSA. Results: Median age 53 (40 to 69) and median PSA was 1.15. One hundred and two men accepted to undergo a PB as primary PC screening. Twenty-three tumours were found (22.5% of biopsies) as well as seven men diagnosed with atypical small acinar proliferation (ASAP) (6.8%) and eight men with high-grade prostatic intraepithelial neoplasia (HG-PIN) (7.8%). In total 37.1% received an abnormal result. Out of the diagnosed PC 41% were intermediate or high risk and requiring treatment, which compares with 24% in general population screening. The predictive performance of DW-MRI, PSA, genetic model and genetic model plus PSA measured by AUC were: 0.85, 0.73, 0.57 and 0.74, respectively. The genetic model performed best in men with a normal PSA of <3(AUC 0.63). Analyses of a 78 SNP profile from the recent COGS results are underway. Conclusions: Ourresults indicate that PB is acceptable for PC screening in men with FH of PC. The significant AUC for DW-MRI would warrant a larger study. The incidence of ASAP is higher in this group than the general population.The SNP risk score was more predictive in men with PSA less than three where PB would not normally be undertaken, therefore an expanded study to investigate the role of genetic profiling in directing PB in PC screening is indicated.
Exploration of alternative digit ratios as a predictor of prostate cancer aggressiveness.
Authors: Stolten Michael , Ledet Elisa , Dotiwala Aryeneesh , Luk Eric , Sartor A. Oliver , Wood Byron 
Published: February 2017

231 Background: During gestation, development of the prostate is dependent on a functional androgen receptor and the presence of dihydrotestosterone. Prenatal androgen exposure has been correlated with a range of diseases including prostate cancer (PCa). Historically, the ratio of the second to the fourth digit (2D:4D) has been linked to prenatal androgen levels; however, the use of alternate finger ratios have been shown to be a greater indicator of prenatal androgen exposure compared to the traditional 2D:4D ratio. Studies have shown that the distal fingertip extent of the second digit (2T:2D) was also associated with prenatal androgens. This study aims to use alternative digit ratio measurements to determine aggressiveness of PCa. Our hypothesis is that alternative digit ratios are more sensitive to prenatal androgen levels, and a better predictor of disease than the traditional 2D:4D ratio. Methods: Digital measurements were made from hand scans of PCa patients. All fingers on the right hand were measured from the basal crease to the fingertip as well as the distal fingertip extent of the second digit. Race, family history (FH) (first degree relatives with PCa), and age at diagnosis were recorded. These clinical covariates were then compared to the finger length ratios which were dichotomized based on the median values and analyzed for possible correlations. Results: Hand measurements were taken on 350 Caucasian (CA) and 100 African American (AA) PCa patients. AA men were more likely to have a smaller 2D:3D (P < 0.0001) and 2D:4D digit ratio (P < 0.0001), and larger 3D:5D (P = 0.0002) and 4D:5D (P = 0.0125) when compared to CA men. AA men with a smaller 2T:2D ratio were younger at the time of diagnosis (P = 0.0446). Additionally, AA men with a larger 2D:5D ratio were more likely to have a FH of PCa (P= 0.0238). Conclusions: Alternative finger length ratios show strong differences between AA and CA men. In AA men, alternative digit ratios are associated with age of PCa diagnosis and FH of PCa. These hypothesis generating results require validation in a larger cohort, but may provide insight to the underlying racial disparity observed in PCa. Finger length may represent a unique, non-invasive predictor of PCa, specifically age of onset and FH in AA men.
Compliance of subjects using electronic patient-reported outcomes (ePRO) in multinational prostate trials.
Authors: Dallabrida Susan M. 
Published: February 2017

232 Background: Patient Reported Outcomes (PRO) and electronic PRO (ePRO) are increasingly becoming an important aspect of cancer clinical trials and patient care, especially with regard to measuring drug efficacy, patient quality of life and drug safety. Subject compliance with completion of PRO/ePRO assessments is an important component for obtaining accurate and high-quality data when conducting clinical trials. It has been hypothesized that patient health status, length of time in a trial and country of origin, may affect compliance. Methods: To address this hypothesis, an operational analysis was conducted to assess oncology subject completion compliance of PRO reports using an electronic tablet to determine its suitability and performance in use. Toward this objective, the compliance of prostate cancer patients in completing three electronic questionnaires that were administered at clinic visits was evaluated. Subjects were asked to complete the Brief Pain Inventory – Short Form (BPI-SF) at every clinic visit. At some clinic visits, subjects were asked to additionally complete the Functional Assessment of Cancer Therapy – Prostate (FACT-P) and the Euro Quality of Life 5 Dimensions (EQ-5D). Questionnaires were completed electronically on the tablet. Percent completion was calculated as the number of questionnaires completed divided by the number of questionnaires expected, based on attended clinic visits compiled for this review and the administration schedule for the questionnaires. Results: This review draws on the experience of over 1,000 subjects from 21 countries, and describes the individual and overall compliance with the expected questionnaire completion, the variance between subsequent visits, and compliance by country. Conclusions: The collection of ePRO using a clinic-based tablet yielded a highly complete data set in prostate cancer subjects demonstrating that this is an effective and feasible approach for recording symptoms and quality of life assessments.
Meaningful survival after cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): The Spanish experience.
Authors: Gonzalez Maeso Iria , Castellano Daniel E. , Campos Balea Begona , Esteban Emilio , Pérez Arnillas Quionia , Villalobos Leon M. Laura , Munarriz Javier , Rubio Gustavo , Cumplido Buron Jose David , Garcia Sanchez Jose , Martin Almudena , Garcia-Bueno Jose Maria , Reyes Garcia Ana , Perez-Valderrama Begoña , Anido Herranz Urbano , Bellmunt Joaquim 
Published: February 2017

235 Background: New emerging therapies for metastatic castration resistant prostate cancer (mCRPC), such as cabazitaxel (CBZ), have prompted the need to identify appropriate patients (pts) for each specific treatment. We describe preliminary data on the experience with CBZ in patients (pts) with mCRPC in Spain. Methods: Medical records from docetaxel-resistant mCRPC pts receiving CBZ at 15 centers in Spain were reviewed retrospectively. Baseline characteristics, PSA response, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Results: Data from 79 consecutive pts (median age 70) were reviewed: Eastern Cooperative Oncology Group (ECOG) zero to one (87.3%), Gleason score of 7 to 10 (87.1%), visceral involvement (24.1%), pain (74.7%), and radiological progression (68.4%) at CBZ initiation. Median duration of response to first-line androgen deprivation therapy was 20.8 months (mo). Most pts received less than or equal to two hormonal lines (72.2%) and only one docetaxel line (74.7%) before CBZ. Thirty-five (44.3%) pts had progressed on docetaxel. Progression less than six mo or greater than six mo after last docetaxel treatment was observed in 23 (29.1%) and 21 (26.6%) pts, respectively. New hormonal agents (abiraterone or enzalutamide) were given before CBZ in 2.5% of pts and after CBZ in 17.7%. Pts received a median of seven cycles (range 2 to 22) of CBZ. CBZ dose-reductions or -delays for any cause occurred in eight (10.1%) and 20 (25.3%) pts, respectively. Prophylactic G-CSF was given in 32 (40.5%) pts. A PSA decrease of greater than or equal to 50% and greater than or equal to 30% was reached in 41.2% and 48.6% of pts treated with CBZ. Median OS from first CBZ cycle was 16.2 [CI: 10.4;-] mo and median clinical and/or radiographic progression-free survival (rPFS) was 9.9 mo [CI: 7.4; 13.1]. Fourteen (17.7%) pts experienced at least one grade greater than or equal to 3 treatment-related AE, the most common being neutropenia (n=4), febrile neutropenia (n=2), asthenia (n=4), and diarrhoea (n=2). No grade greater than or equal to 3 peripheral neuropathy was reported. An analysis of factors predicting outcome will be presented. Conclusions: CBZ administered in real-life practice and in the adequate treatment setting in Spain is associated with meaningful PFS and OS and an acceptable safety profile. Dose delays and reductions were low. Prophylactic G-CSF use in 4 out of 10 pts may have contributed to these good results.
Experience with artificial urinary sphincter implantation in men who underwent prior pelvic radiation therapy for prostate cancer.
Authors: Jhavar Sameer G. , Bird Erin , Swanson Gregory P. 
Published: February 2017

236 Background: To assess outcomes after artificial urinary sphincter implantation in men who received prior pelvic radiation therapy. Methods: Between 1997 and 2012, 107 patients were identified from the Scott and White Hospital database who underwent artificial urinary sphincter implantation for urinary incontinence after prostate cancer treatment. Of these 17 were excluded for lack of follow-up data. Of the remaining 90 patients, 59 patients underwent prior surgery alone (group 1), 25 underwent prior surgery followed by pelvic radiation therapy (group 2); and 6 patients underwent prior radiation therapy alone. Results: Average ages at sphincter implantation were 69 yrs. (range 54 - 82), 73 yrs. (range 63 - 81), and 70 yrs. (range 60 - 80) respectively for groups 1, 2 and 3. Social continence rates were 80% (47/59) for group 1, 72% (18/25) for Group 2 and 50% (3/6) for group 3 at an average follow-up of 6 yrs. (range 0 - 17), 4 yrs. (range 1 - 12) and 3 yrs. (range 0 - 6) respectively. Average time between surgery and sphincter implantation was 5 yrs. (range 1-27) in group 1. Average time between radiation and sphincter implantation was 7 yrs. (range 1 - 18) and 6 yrs. (range 1 - 17) in Groups 2 and 3. Re-operation rates were 42% (25/59); 48% (12/25); and 50% (3/6) in groups 1, 2, and 3, respectively. In men who were incontinent at last follow-up, the average time between pelvic radiation and sphincter placement was relatively shorter as compared to those who were continent [5 yrs. (range 1 -11) vs. 7 yrs. (range 1 - 18) in Group 2; and 4 yrs. (range 1 -5) vs.10 yrs. (range 4 - 17) in group 3]. The rates of erosions were 10/59 (17%); 4/25 (16%); and 0/6 (0%) in groups 1, 2, and 3, respectively. The rates of infection were 5/59 (8%), 0/25 (0%), and 2/6 (33%) in groups 1, 2, and 3, respectively. Conclusions: Our experience with artificial urinary sphincter in men who underwent prior pelvic radiation therapy is comparable to that reported in the literature. Our results identify factors associated with worse continence after artificial urinary sphincter in men who underwent prior pelvic radiation therapy.
Isoflavones in Japanese and Caucasian men with prostate cancer in Hawaii.
Authors: Fukagai Takashi , Akaza Hideyuki , Ogawa Yoshio , Carlile Robert , Namiki Thomas , Lederer John Leslie , Maskarinec Gertraud , Tsuji Hirokazu , Moriyama Kaoru , Fujimoto Kiyohide , Hirao Yoshihiko , Namiki Mikio 
Published: February 2017

241 Background: Recently, several studies have reported that soy isoflavones and the ability to produce Equol, an active derivative of soy isoflavone, may play a role in the suppression of prostate cancer. An Equol-producing bacterium, Slackia sp. strain NATTS has been identified in stool cultures. To further investigate this relationship, we evaluated Japanese-Americans (JA) and whites (W) in Hawaii, with and without prostate cancer, with regards to dietary soy intake, serum isoflavone levels, and the presence of stool NATTS. Methods: The serum levels of Daidzein, Genistein, Glysitein, Dihydrodaidzein (DHD), Equol, o-desmethylangolensin (o-DMA) and total isoflavone was determined in 65 JA (34 patients with prostate cancer , 31 controls) and 68 W (34 patients with prostate cancer , 34 controls) subjects. The control group consisted of age matched cancer-free male subjects. To evaluate Equol producing ability, we assessed the presence of NATTS in stool samples. All subjects completed a lifetime dietary soy consumption survey. Results: The serum level of Genistein and o-DMA were significantly higher in JA (Genistein: W 21.5±54.0, JA 61.8±150.9, p=0.04; o-DMA: W 0, JA 2.0±7.9, p=0.04). Daizein level trended higher in JA (W 13.9±34.7, JA 33.3±84.0, p=0.09). Glysitein level was significantly higher in W (W 35.7±10.4, JA 30.7±15.5, p=0.03). No differences were noted in DHD and Equol levels between W and JA. Total isoflavone level trended higher in JA (W 76.3±104.9, JA 135.1±245.6, p=0.07). There were no differences in serum isoflavone level between prostate cancer patients and controls for both JA and W. Only 10 of 120 stool samples were positive for NATTS (8.6%), a rate much lower than seen in Japan. JA showed higher intake of soy than W. Conclusions: The high soy consumption and isoflavone levels in JA may be related to the observed lower incidence of prostate cancer relative to W in Hawaii. The near absence of equal producers in Hawaii JA may contribute to their higher incidence of prostate cancer compared to Japan based Japanese. These results suggest that both soy isoflavone levels and Equol production may be inversely associated with prostate cancer incidence.
Consideration of height-based rather than weight-based dosing as a more appropriate method of treating with radium-223.
Authors: Longo Thomas Andrew , McDonald Matthew , Mehr Samuel H. , Nordquist Luke T. 
Published: February 2017

249 Background: Radium 223 is approved for use in patients with symptomatic bone metastasis from castrate resistant prostate cancer, and no known visceral metastatic disease. It is currently dosed in a weight based fashion, however it is only active in the skeleton, and it is distributed primarily to the bone. A more rational dosing regimen may be based off a patient’s height, and the highest safe dose has yet to be determined. Our study looks at the safety profile of radium 223 in the context of a height based dosing regimen. Methods: This is a retrospective, observational study of all patients receiving radium 223 at the Urology Cancer Center. The patients were dosed at 50 kilobecquerels per kilogram as prescribed in the product insert. The dose each patient received was then recalculated based upon the patient’s height. The medical record was then examined for side effects. Results: As of September 2013 total of 30 discreet patients have received a total of 58 doses at our site since radium 223 was approved. The lowest dose received based on height was 17.39 kBq/cm and the highest dose was 40.7 kBq/cm with an average dose of 27.4 kBq/cm. There were eight grade 1 toxicities. The side effect profile did not show any trends across the different levels of dosing regarding the number or grade of toxicity with a greater number occurring below the median dose. Six of the eight men with significant GI distress have had prior radiation. Conclusions: A height based dosing regimen may be more appropriate for a drug designed to treat only the skeleton. In our population, we administered a wide variety of doses when administered by height. Higher doses appear to be well tolerated, and the optimal dose has yet to be determined. We propose future studies with height-based dosing escalation to look at the safety and efficacy.
Tumor-directed PET imaging of bone metastases in metastatic castration-resistant prostate cancer (mCRPC) using Zr-89 labeled anti-prostate specific membrane antigen (PSMA) antibody J591.
Authors: Morris Michael J. , Pandit-Taskar Neeta , Tagawa Scott T. , Nanus David M. , Solomon Stephen Barnett , Carrasquillo Jorge A. , Reuter Victor E. , Lewis Jason Stuart , Beylergil Volkan , O' Donoghue Joseph A. , Lyashchenko Serge K. , Martinez Danny F. , Curtis Kristen Rebecca , Durack Jeremy C. , Cheal Sarah M. , Bander Neil Harrison , Scher Howard I. , Larson Steven M. 
Published: February 2017

25 Background: There is no standard imaging modality that specifically and accurately images prostate cancer metastases, hampering assessments of tumor distribution, prognostication, and response. J591 is a humanized antibody that targets the external domain of PSMA, which is copiously expressed in metastatic disease and upregulated in mCRPC. We have previously reported on the feasibility, and PK and biodistribution properties of Zr-89-J591 in 10 patients (Morris et al, GU ASCO 2013). We now report on the targeting/accuracy in 49 patients with mCRPC. Methods: Following standard CT/MRI, bone scintigraphy, and FDG PET imaging, 5 mCi of Zr-89-J591 was administered intravenously. Zr-89-J591 was imaged 6-8 days after injection. Positive scan findings were confirmed, where possible, with biopsies in the following preference: Zr-89-J591 and FDG positivity, then Zr-89-J591 and FDG mismatch, and lastly standard imaging and any PET mismatch. Results: A total of 535 unique bone lesions in 49 patients were identified using all imaging modalities. 339 (63%) of these were evident on bone scans, 302 (56%) on CT, 202 (38%) on FDG PET, and 490 (92%) on Zr-89-J591 PET. The concordance between bone scans and Zr-89-J591 was 303/490 (62%). 102 sites were seen only on Zr-89-J591 and not on any other imaging modality. 44 biopsies were performed from 33 patients; 21 of those biopsies were bone. The histopathologic correlation for bone is provided in the table below. All positive biopsies were J591 positive (16/16); sensitivity of J591 was =100%, and positive predictive value (16/18) was 89%. Conclusions: Imaging using J591 PET/CT detects bone disease at greater rates than any other imaging modality tested. Biopsy data of J591 positive lesions suggest that most J591 positive lesions represent biopsy confirmed prostate metastasis. We are now testing minibodies based on J591 that may target faster, offering a more favorable imaging schedule. Clinical trial information: NCT01543659. [Table: see text]
Interstitial fibrosis in radical prostatectomy specimen treated with neoadjuvant therapy and its relationship to biochemical outcome and castration-resistant status in high-risk prostate cancer.
Authors: Hashimoto Yasuhiro , Okamoto Akiko , Yamamoto Hayato , Imai Atsushi , Hatakeyama Shingo , Yoneyama Takahiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

251 Background: Interstitial fibrosis (IF) have been known to occur in radical prostatectomy specimens treated with hormonal therapy. We previously reported that neoadjuvant therapy for high-risk prostate cancer (Pca) with luteinizing hormone-releasing hormone (LHRH) agonist and low-dose estramustine phosphate (EMP) (LHRH + EMP) significantly improved biochemical recurrence (BCR) free survival. In this study, we quantified IF in radical prostatectomy specimens treated with neoadjuvant LHRH + EMP, and we examined whether degree of IF has impact on BCR free survival or subsequent castration-resistant status. Methods: High-risk Pca was defined by the D’Amico stratification system. A total of 103 patients with high-risk Pca were enrolled in this study from July 2005 to August 2010. The LHRH + EMP therapy included the administration of the LHRH agonist and 280 mg/day of EMP for six months before the radical prostatectomy. BCR was defined as the prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after the prostatectomy. Castration-resistant prostate cancer (CRPC) is defined by PSA or radiographic progression in the castrate levels of testosterone (< 50 ng/dL). A quantitative analysis of IF was performed using computer-assisted imaging. Results: The average patient age was 67.2 (49 to 78), and the median initial PSA level was 18.8 ng/mL (4.2–95.6). All patients completed six months of LHRH + EMP neoadjuvant therapy with no delays in the radical prostatectomy. At a median follow-up period of 64.0 months, BCR occurred in 41 patients (39.8%) and CRPC occurred in nine patients (8.7%). The average IF rate was 0.43 (0.33–0.55). The five year BCR-free survival rates for the groups with IF rates less than 0.42 and greater than 0.42 were 74.7% and 50.0%, respectively. The log-rank test was significantly different between the two groups (p = 0.010). We could not identify CRPC in the patients with IF rates less than 0.42. Conclusions: Although the present study was small and preliminary, the IF rate may have a predictive potential for biochemical outcome and the occurrence of CRPC after neoadjuvant therapy for high-risk Pca. Further study is warranted to elucidate its clinical significance.