bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medications for urologic malignancies in the open payments data: Financial relationships between industry and urologists.
Authors: Maruf Mahir , Sidana Abhinav , Purnell Stephanie , Fleischman William , Brancato Sam Joseph , Agrawal Shantanu , Agarwal Piyush K. 
Published: March 2017

74 Background: The Open Payments program was enacted to increase transparency of the financial relationships between physicians and the pharmaceutical industry. We examined the non-research related financial relationships between urologists and industry in the US using the 2014 Open Payments data as it pertains to payments associated with drugs used in the treatment of urologic cancers. Methods: A descriptive analysis of the Open Payments data released by the Centers for Medicare & Medicaid Services for 2014 was performed. The total payment amount associated with medications prescribed by urologists to treat urologic malignancies was calculated. Results: For drugs associated with all urologic cancers, 44,200 payments, totaling $4,693,561, were made to 5666 urologists. Approximately 82% of payments (76% of the financial value) associated with urologic cancers were for prostate cancer. Of these, payments were primarily associated with anti-androgen therapy ($2,803,435, 79%), followed by hormonal therapy ($672,342, 19%) and chemotherapy ($63,693, 2%). Payments were most commonly in the form of food and beverage (90%), but were only 18% (0.8M) of the total payment amount. Janssen Scientific Affairs reported the largest proportional value of financial ties (24% or 1.1M) but this only accounted for 3% of the number of payments. Conclusions: Nearly 66% of urologists have received a non-research related payment associated with a urologic cancer drug from industry in 2014. Payments associated with prostate cancer drugs were largest in sum and frequency, and consisted largely of payments associated with anti-androgen therapy. This likely coincides with the fact that urologists predominantly prescribe anti-androgens and the recent FDA approval of newer anti-androgens within the last decade.
Can focal therapy impact perioperative, oncological, and functional outcomes in men who underwent focal therapy salvage robotic-assisted radical prostatectomy? A retrospective matched-pair comparative study.
Authors: Nunes-Silva Igor , Barret Eric , Srougi Victor , Baghdadi Mohammed , Barreras Silvia Garcia , Capogrosso Paolo , Rembeyo Gregory , Carneiro Arie , Sanchez-Salas Rafael , Rozet François , Galiano Marc , Cathelineau Xavier 
Published: March 2017

76 Background: Salvage surgery is an option for recurrent prostate cancer(PCa) after focal therapy(FT). This is the first study to assess the impact of FT on surgical outcomes comparing salvage robotic-assisted radical prostatectomy(S-RARP) versus primary-RARP(P-RARP). We aimed to compare the impact of FT on perioperative, oncological and functional outcomes in men underwent S-RARP versus P-RARP. Methods: Prospective data of 2775 men underwent RARP for localized PCa from 2000 to 2016 were reviewed. Twenty-five men underwent S-RARP after FT failure(S-RARP group). Total 2750 underwent RARP as primary treatment. Matched-pair 1:2 selection of 44 out of 2750 patients by age, IPSS and IIEF5 defined P-RARP group. Primary endpoint was between-groups differences on functional outcomes. Secondary endpoint was oncological data. p < 0.05 was significant. Results: Surgical time, transfusion and complication rates were comparable(p > 0.05). Rates of continence probability[49.5%(SE 0.13) versus 62.4%(SE 0.08), p = 0.8 and 73%(SE 0.14) versus 76.5%(SE 0.07), p = 0.8, at 1 and 2 years, respectively] and the chance for achieving continence[HR 1.062, 95%CI 0.54-2.08, p = 0.861] were comparable between-groups. Potency recovery was significant lower on S-RARP[3±2 versus 9.22±6.55, p = 0.008]. S-RARP showed significant lower rates of cumulative BCR-free survival probability[67.6%(SE 0.12) versus 95.1%(SE 0.03), p = 0.001 and 56.3%(SE 0.15) versus 92.4%(SE 0.04), p = 0.001, at 1 and 2 years, respectively]. S-RARP presented significant increased risk of BCR[HR 4.8, 95%CI 1.67-13.76, p = 0.004]. Upstaging was an independent predictor factor for BCR on S-RARP[HR 14.65, 95%CI 1.46-146.37, p = 0.022] (Table 1). Conclusions: Salvage-RARP following FT failure is feasible and safe with acceptable complications rates. Patients assigned to FT should be previously advised about lower erectile recovery rates in case of a salvage surgery. Urologists may be warned about the risk of undertreatment in patients presenting failure along FT follow-up.
The IMPACT of 68GA-PSMA-PET in definitive radiotherapy planning for prostate cancer patients.
Authors: Onal Cem , Torun Nese , Akkus Yildrim Berna 
Published: March 2017

79 Background: The implementation of 68Ga-PSMA-PET-imaging for staging and the impact on stage adaption during treatment radiotherapy (RT) planning is not well studied yet. The present work is to evaluate the integration of 68Ga-PSMA-PET into standard RT planning and to determine the influence on staging and on changes in the initially planned treatment concept for definitive RT in prostate cancer patients. Methods: A total of 66 prostate cancer patients with PSMA-PET delivered before treatment were retrospectively analyzed. All patients had bone scintigraphy and magnetic resonance imaging (MRI) of abdomen (52 patients; 79%) or thoraco-abdominal computed tomography (CT) (14 patients; 21%). After PSMA-imaging, all information was reviewed and re-classification was performed with the additional information taken into account. Thereafter, patients were evaluated with the information obtained by PSMA-PET imaging led to a change in staging and subsequently resulted in a change of the RT concept and treatment fields. Results: Median age of patients was 66 years (range 46 – 84 years). Median pretreatment PSA level was 25.2 ng/mL (range 4.4 – 130.8 ng/mL). The initial stage was changed in 27 patients (41%); 8 patients (12%) under-staged, 11 patients (17%) over-staged and 8 patents (12%) had distant metastasis. RT fields changed in 9 patients (14%) and RT cancelled because of distant metastasis detected with PSMA-PET in 6 patients (9%). The mean pretreatment PSA values were significantly higher in over-staged patients or patient with distant metastasis compared to under-staged patients (55.0±38.8 ng/mL vs. 28.1±19.1 ng/mL; p = 0.02). Also upstaging was observed more frequently in patients with ≥ T3a disease compared to patients with < T3 disease (15 patients [56%] vs. 4 patients [15%]; p = 0.04). However, Gleason score and primary tumor SUV had no significant impact on stage change and particularly on RT decision and treatment plan changes. Conclusions: The performance of a PSMA-PET frequently leads to changes in the stage, altering the RT treatment regimen especially in patients with extensive stage disease and higher pretreatment PSA values.
EZH2 expression and clinical outcome in African-American men with prostate cancer.
Authors: Narayan Vivek , Lal Priti , Zeigler-Johnson Charnita , Malkowicz S. Bruce , Rebbeck Timothy 
Published: March 2017

81 Background: Despite increasing recognition of molecular differences in prostate cancers from African-American men (AAM) and European-American men (EAM), the prognostic utility of novel tissue biomarkers in AAM remains poorly defined. Overexpression of the oncogenic transcriptional regulator EZH2 has been associated with clinical outcome in localized prostate cancer, but it has not been adequately evaluated in AAM. We sought to define the prognostic significance of EZH2 overexpression in a racially-balanced cohort of men with localized prostate cancer and to explore potential race-specific differences. Methods: This was a retrospective analysis of men who underwent radical prostatectomy at the University of Pennsylvania between 1991 and 2010. Subjects with formalin fixed paraffin embedded tissue available for EZH2 immunohistochemistry were included. Slides were graded in a semi-quantitative manner for both the volume and the intensity of EZH2 staining. Multivariate Cox regression models were used to evaluate the independent association of clinicopathologic parameters, including EZH2 staining index, and biochemical recurrence (BCR)-free survival. Results: 121 patients (62 AAM, 59 EAM) were eligible for analysis. 56 patients (46.3%) demonstrated EZH2 overexpression, which was balanced between AAM and EAM subgroups (43.6% vs 49.2%, respectively). Extracapsular extension, positive surgical margins, and EZH2 overexpression were independently associated with BCR-free survival (HR of 2.02 for EZH2 overexpression, 95% CI 1.05 – 3.86, p = 0.035). Potential effect modification by race was identified (p for interaction = 0.056). While EZH2 overexpression was independently associated with BCR-free survival in AAM (HR 2.78, 95% CI 1.06 – 7.32, p = 0.038), no significant association was identified in the EAM subset (HR 0.89, 95% CI 0.35 – 2.29, p = 0.812). Conclusions: EZH2 overexpression is a valid prognostic marker in AAM treated with prostatectomy. The potential for enhanced prognostic significance of EZH2 overexpression in AAM may lend insight into observed racial disparities. These results highlight the need for adequate representation of AAM in clinical trials evaluating novel EZH2-directed therapies.
Risk prediction-modeling approach to identify best predictive parameters for urethral strictures after prostate brachytherapy.
Authors: Singhal Sandeep , Parliament Matthew , Jamaluddin Muhammad Faisal , Lee Emma , Sloboda Ron , Usmani Nawaid 
Published: March 2017

87 Background: Urethral strictures (US) are a rare complication of prostate brachytherapy (BXT), with prior studies showing radiation dose to the bulbomembranous urethra is associated with stricture formation. This retrospective case-control study explored clinical and dosimetric parameters associated with the development of BXT-related urethral strictures. Methods: A cohort of 34 patients developed urethral strictures after BXT at our institution for the period of 2008-2014. Each case was matched with two controls (68 controls) that had not developed a US according to similar baseline International Prostate Symptom Score (IPSS), planned prostate volume, post-implant prostate V150, and post-implant prostate D90 dosimetry parameters. US development was compared with clinical (i.e. age, IPSS, etc) and dosimetric (i.e. prostate, urethra, urethra segments) variables. Statistical modeling for risk prediction was applied, which included adjusted R2, Mallows’ C Selection (Cp), Schwartz’s information criterion (BIC), forward selection (FS), and backward selection (BS) to identify the parameters with prediction ability of toxicity. CV analysis was performed to select the best subset selection on the full data set in order to obtain the most predictive parameter selection. Results: The results show that the R2statistic increases from 6% (only one) to 33 %, (all of the parameters included). The table demonstrates minimum best-fit parameters in the different models. (See table.) CV with minimum standard error (MSE) identified a model with 5 parameters that included age, baseline IPSS, UD30, UD5, and U5mm V200Apex shows best prediction ability for US. Conclusions: This modeling approach, which is novel in BXT, helped to identify a combination of parameters with some predictive ability of radiation toxicity. Further evaluation is required to validation. [Table: see text]
Genome-wide alterations in gene expression of prostate cancer (PC) cells surviving neoadjuvant androgen deprivation therapy (ADT).
Authors: Ferrari Anna C. , Chen Ying , Sabaawy Hatem E. , Stein Mark N. , Foran David , Yegnasubramanian Srinivasan T. 
Published: March 2017

88 Background: Although androgen deprivation therapy initially decreases PC tumor burden, resistance to further androgen receptor (AR)-directed treatments or chemotherapy is inevitable once CRPC is established. We postulated that the stress of ADT triggers widespread alterations in expression that renders a metastable physiologic state conditioned by epigenetic changes that might be initially reversible by targeting non-androgen pathways. We conducted a pilot study to explore genome-wide expression alterations in PC foci surviving 3 months ADT (eADT). Methods: mRNA from 7 frozen microdissected PC foci and normal counterparts (NC) were processed for RNA-seq. RNA-seq changes in eADT specimens were compared first with NC and the untreated PC in the TCGA PRAD (TCGA) database to castrate resistant (mCRPC) specimens in the dbGAP study phs000915.v1.p1database. The raw data (fastq files) was quantified using kallisto, normalized by TMM using R package edgeR, batch effects corrected using R package SVA. Analysis of differential gene expression by R package sleuth. Pathway and gene set by GSEA, GAGE/pathview packages for Gene Ontology (GO) and KEGG. Results: TMPRSS2-ERG+, 5/7. Highest DEG in eADT vs. TCGA vs mCRPC were non-coding RNA’s. Among 17431 differentially regulated paths; GSEA of eADT vs TCGA or mCRPC: 341 (1.95%) and 1366 (7.84%) up- vs 46 (0.26%) and 59 (0.34%) down-regulated. KEGG paths, eADT vs. TCGA or mCRPC, 11 and 53 up vs. 2 and 3 down- respectively. Highly down- path in eADT vs TCGA (log q < 10-17) was ribosomal vs. cell cycle and DNA replication in mCRPC. Six paths significantly up- in eADT vs TCGA or mCRPC: Wnt, adherence junction, steroid biosynthesis, unsaturated fatty acids, citrate cycle, ErbB. Calcium, MAPK, insulin, GnRH and Hedgehog were also up- in eADT vs mCRPC. AR full-length was marginally higher in eADT than TCGA and lower than mCRPC, no differences in gene targets. Conclusions: This pilot data shows that ADT triggers a wide range of gene expression alterations that support PC cell survival and may be vulnerable to therapeutic targeting in addition to the androgen pathway. Validation of these findings is planned in a larger set of samples from the same bank.
Prostate cancer specific mortality and overall survival outcomes for salvage radiation therapy after radical prostatectomy.
Authors: Agrawal Shree , Efstathiou Jason A. , Michalski Jeff M. , Pisansky Thomas Michael , Koontz Bridget F. , Liauw Stanley L. , Abramowitz Matthew , Pollack Alan , Anscher Mitchell Steven , Moghanaki Drew , Den Robert B. , Zietman Anthony L. , Lee W. Robert , Stephans Kevin L. , Hearn Jason W.D. , Spratt Daniel Eidelberg , Gao Tianming , Kattan Michael W. , Stephenson Andrew J. , Tendulkar Rahul D. 
Published: March 2017

9 Background: Early salvage radiation therapy (SRT) following radical prostatectomy (RP) has been shown to reduce biochemical recurrence and distant metastases. We aim to identify factors predictive of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) from a consortium database from 10 academic institutions. Methods: 2,454 node-negative patients (pts) with detectable post-prostatectomy PSA ( ≥ 0.01 ng/mL) treated with SRT ± neoadjuvant/concurrent androgen deprivation therapy (N/C ADT) were included. Cumulative incidence and Kaplan-Meier methods were used to estimate rates of PCSM and ACM, respectively. Univariate and multivariable analyses (MVA) were performed by competing risks regression and Cox proportional hazards methods for PCSM and ACM. Results: Median follow-up was 5 years from SRT completion and 8 years from date of RP; 24% had pathologic Gleason score (GS) of ≤ 6, 56% GS 7, and 19% GS ≥ 8; 56% extraprostatic extension (EPE), 18% seminal vesicle invasion (SVI), 58% positive surgical margins, and 16% received N/C ADT. Median age at RP and SRT were 62 years (IQR 56-66) and 64 years (59-69), respectively. Median SRT dose was 66 Gy (IQR 65-68) and median pre-SRT PSA was 0.5 ng/mL (IQR 0.3-1.1). MVA performed from SRT completion date demonstrated higher pre-SRT PSA (HR = 2.1), higher GS (GS 7 vs. ≤ 6: HR 2.0; GS ≥ 8 vs. 6: HR 3.3) , SVI (HR 2.5), year of SRT (2000-2004, 1995-1999, 1985-1994 vs. 2005-2012; HR 2.9, HR 2.5, HR 3.6, respectively) were significantly associated with higher PCSM. These same variables were all significantly associated with higher PCSM and ACM rates calculated from both SRT completion date and date of RP. Conclusions: Initiation of early SRT at lower post-operative PSA levels following RP is associated with reduced risk of PCSM and ACM, even when calculated from RP date to account for lead time bias. Other factors significantly associated with PCSM include higher GS, SVI, and earlier year of SRT. [Table: see text]
Prospective comparative analysis of oncologic and functional outcomes between focal therapy and robotic radical prostatectomy.
Authors: Barreras Silvia Garcia , Sanchez-Salas Rafael , Sivaraman Arjun , Barret Eric , Secin Fernando P. , Redondo Cristina , Velilla Guillermo , Nunes-Silva Igor , Srougi Victor , Rembeyo Gregory , Baghdadi Mohammed , Rozet François , Galiano Marc , Cathala Nathalie , Mombet Annick , Prapotnich Dominic , Cathelineau Xavier 
Published: March 2017

90 Background: Focal therapy (FT) is an emerging treatment alternative for organ-confined Prostate cancer (PCa). The aim is to perform a non-randomized prospective analysis to compare oncological, functional and morbidity outcomes after FT and robotic radical prostatectomy (RARP). Methods: From July 2009 to September 2015, 1883 patients underwent RARP and 373 FT. Of those, we selected 1410 men (1222 RARP and 236 FT) according to the NCCN PCa risk classification: 402(27.5%),388(26.6%) and 668(45.8%) patients were very low risk, low risk and intermediate risk, respectively. Within FT, 188 men underwent focal high-intensity focused ultrasound (HIFU) and 48 cryotherapy. Oncologic outcomes were analyzed in terms of biochemical recurrence (BCR) free survival (Phoenix definition for FT, and PSA >0.2 ng/dl in RARP), and the need for further treatment. FT failure was defined as any positive control biopsy after treatment. Overall suvival and metastasis free survival were estimated using Cox regression and Kaplan-Meier methods. Complications were graded as Clavien-Dindo classification. Functional outcomes were assessed with validated questionnaries for genitourinary symptoms and sexual function. Results: Median follow-up was 45.4 mo (IQR: 25.3-65.5). BCR-free survival was comparable among RARP and FT ( 10.6% RARP vs 9% FT, p 0.69). Patients with intermediate risk PCa were significantly associated with BCR in both groups (HR 8.47;95% CI 4.57-15.71; p< 0.001). In FT group positive biopsy in the treated lobe was seen in 42(17.7%) men. No differences were found in overall survival, neither mestastases free survival between treatments; (p 0.85 and p 0.142 respectively). FT was associated with higher risk of further treatments (HR 5.21; 95% CI 3.7-7.35; p <0.001). FT had higher rates of complications (15.3% vs 9% for RARP, p 0.004). RARP was associated with less continence recovery vs FT at 3, 6 and 12 mo (p <0.001). Potency is higher between FT men at 3,6 and 12 mo (<p 0.001). Conclusions: For selected patients with organ confined PCa, RARP and FT offered comparable oncological control with FT requiring higher additional treatments. Potency and continency appears to be better preserved in FT patients.
Influence of common comorbid conditions on a 17-gene assay for prediction of adverse pathology in clinically low-risk prostate cancer.
Authors: Cullen Jennifer , Sesterhenn Isabell , Lawrence H. Jeffrey , Kuo Huai-Ching , Srivastava Shiv , Rosner Inger L. , Zhang Nan , Brand Timothy C. , Shindel Alan W 
Published: March 2017

91 Background: Well-validated molecular biomarkers can improve risk stratification in newly diagnosed PCa. It is important to demonstrate that biomarkers are not influenced by common clinical conditions. A 17-gene biopsy-based RT-PCR assay (Oncotype Genomic Prostate Score, GPS) has been validated as an independent predictor of adverse pathology and biochemical recurrence after surgery. We sought to explore the association between comorbid conditions and GPS. Methods: We examined the association between GPS and obesity (OB), diabetes mellitus (DM), hypertension (HTN), hypercholesterolemia (HC), coronary artery disease (CAD) and Low Testosterone (Low T) in a cohort of surgically treated men with clinically low-risk PCa. All men were seen and treated at Madigan Army Medical Center or Walter Reed National Military Medical Center. Diagnoses were abstracted from the electronic medical record. OB was defined as body mass index (BMI) > 30 kg/m2. Low T was defined as total T < 300 ng/mL. Student’s T test and ANOVA were used to assess differences in GPS between the groups of men with or without relevant diagnoses. Results: GPS results were available in 402 patients; 389 (97%) had BMI data. Pre-treatment serum testosterone (T) levels were available for 120 patients. There were no significant differences in mean GPS between men with or without OB, HTN, HCL, DM, and low T (p > 0.05). This relationship persisted when men with no vascular risk factors were compared to men with any vascular risk factor (DM/HTN/HCL) and/or with diagnosed coronary artery disease. There was a modest but statistically significant inverse correlation between GPS and continuous serum T (r = -0.18; p = 0.049). Conclusions: Comorbidities that are common in older men with prostate cancer do not appear to influence GPS results. Although Low T was not associated with GPS, there was a weakly negative association between GPS and continuous T. This may reflect the more aggressive PCa phenotype that has been reported in patients with progressively lower serum T.
OncotypeDx genomic scores independent of disease volume in men with favorable-risk prostate cancer.
Authors: Grimberg Dominic C. , Nyame Yaw A. , Greene Daniel J. , Gupta Karishma , Berglund Ryan Kent , Gong Michael C. , Stephenson Andrew J. , Klein Eric A. 
Published: March 2017

93 Background: To determine if disease volume at biopsy correlates with GPS among men with favorable risk prostate cancer. Methods: All men with NCCN very low (VLR) and low risk (LR) and GPS from 2013-2016 were identified. Disease volume was characterized by percent of positive cores, number of cores with >50% involvement, and largest involvement of any single core. Nonparametric equality of medians was performed to compare the median likelihood of favorable pathology between quartiles. Results: 112 (37.8%) with VLR and 184 (62.2%) with LR disease were identified. The likelihood of favorably pathology by quartile are listed in Table 1. 7/105 (6.3%) with VLR were reclassified as LR, and 13/181 (7.2%) with LR were reclassified as intermediate risk (IR). Patients reclassified to IR by GPS had a median likelihood favorable pathology of 63.0% (IQR 62.0-63.0), 20.0% positive cores (IQR 13.0-29.0), 0 cores with > 50% involved (IQR 0-1), largest core involvement of 20.0% (IQR 10.0-20.0), and PSA density of 0.12 ng/ml/cc (IQR 0.10-0.14). Conclusions: Differences in the likelihood of favorable pathology by disease volume were not clinically significant in men with favorable risk disease. [Table: see text]