bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Gleason upgrading rates in transrectal ultrasound systematic random biopsies versus US-MRI fusion biopsies for prostate cancer.
Authors: Carneiro Arie , Kayano Paulo Priante , Castilho Tiago MendonÃÂ§a Lopez , Sivaraman Arjun , Claros Oliver Rojas , Serpa Neto Ary , Filippi Renee Zon , Baroni Ronaldo Hueb , Lemos Gustavo Caserta 
Published: March 2017

57 Background: US-MRI fusion biopsy (FB) showed that it improves the detection of clinically significant prostate cancer (PCa). A more accurate diagnostic method is desirable to avoid misclassification, which in turn is particularly important in appropriate decision making on treatment for PCa (active surveillance or focal therapy or radical treatment). We aimed to compare the Gleason upgrading (GU) rates and the concordance of the Gleason scores in the biopsy versus final pathology after the surgery in patients who underwent only TRUS systematic random biopsies versus US-MRI FB for PCa. Methods: A retrospective analysis of patients’ prospective collected data that underwent prostate biopsy and subsequent radical prostatectomy were included from January 2011 to June 2016 at our institution. The study cohort was divided into: US-MRI FB (Group A) and only TRUS systematic random biopsy (Group B). US-MRI FB was performed in patients who had a previous MRI with a focal lesion classified by Likert score ≥ 3, otherwise a TRUS systematic random biopsy was performed. All biopsies and surgical specimens were analyzed by the same uropathologist and MRIs were analyzed by two expert urological radiologists. Results: 73 men underwent US-MRI FB and 89 TRUS systematic random biopsy. The GU rate was higher in group B (31.5% vs 16.4%; p = 0.027). GU according to Gleason grade pattern was higher in Group B against Group A (40.4% vs 23.3%; p = 0.02). Analyses from separate Gleason grade pattern showed that Gleason score 3+4 presented less GU in group A (24.1% vs 52.6%; p = 0.043). The Bland-Altman plot analysis showed a higher bias in Group B compared to group A (-0.27 [-1.40 to 0.86] vs -0.01 [-1.42 to 1.39]). In the multivariable logistic regression the only independent predictor of GU was the use of TRUS systematic random biopsy (2.64 [1.11 – 6.28]; p = 0.024). Conclusions: The US-MRI FB appears to be related to a decrease in GU rate and an increase in the concordance between biopsy and final pathology in comparison to TRUS random biopsy, that leads to greater accuracy on diagnosis and better treatment decision.
Validation of GEMCaP as a DNA based biomarker to predict disease recurrence in patients undergoing prostatectomy for prostate cancer.
Authors: Nguyen Hao Gia , Welty Christopher , Lindquist Karla , Ngo Vy , Gilbert Elizabeth , Bengtsson Henrik , Magi-Galluzzi Cristina , Jean-Gilles Jerome , Yao Jorge , Cooperberg Matthew R. , Messing Edward M. , Klein Eric A. , Carroll Peter , Paris Pamela 
Published: March 2017

58 Background: There are currently no validated DNA based biomarkers available for routine clinical use to predict prostate cancer recurrence after prostatectomy. The Genomic Evaluators of Metastatic Cancer of the Prostate (GEMCaP) assay is a tumor genotype using copy number for a set of genomic loci. We aim to validate the GEMCaP assay using an external cohort of intermediate and high risk patients. Methods: We randomly identified 203 patients who had undergone radical prostatectomy at the Cleveland Clinic (CC) and University of Rochester (UR) from 2000-2005. DNA from macrodissected cancer tissues were subjected to high resolution array comparative genomic hybridization (aCGH) using Agilent’s oligonucleotide microarray platform. A high GEMCaP score was defined as > 20% of the genomic loci exhibiting copy number gain or loss in a given tumor. Cox regression was used to evaluate associations between the GEMCaP score and risk of biochemical recurrence in univariate and multivariate analyses adjusted for the CAPRA-S score. The outcome was biochemical failure defined as PSA > 0.2. Results: We report the results from 140 patients, with sufficient DNA and acceptable aCGH, 54 from the CC cohort and 86 from the UR cohort. Median time to recurrence was 45.3 months and median follow-up among those who did not recur was 120.2 months. Based on the CAPRA-S score, 39.3% were low-risk, 42.2% were intermediate-risk and 18.5% were high-risk. 30.7% of the cohort had a high GEMCAP score ( ≥ 20%). A high GEMCaP score was associated with higher risk of biochemical recurrence (HR 2.69, 95%CI 1.51-4.77) and remained associated with biochemical recurrence after adjusting for the CAPRA-S score (HR 1.91, 95% CI 1.05-3.48). The C-index for GEMCaP alone was 0.64, and improved when combined with CAPRA-S (C-index = 0.76). Conclusions: In this validation study, a high GEMCaP score was associated with biochemical recurrence in two external cohorts. This remained true after adjusting for clinical and pathologic factors as accounted for by the CAPRA-S score. The GEMCaP biomarker could be an efficient and effective clinical risk assessment tool to identify prostate cancer patients for early adjuvant therapy.
Incidence of periprostatic white adipose tissue inflammation in men with prostate cancer.
Authors: Gucalp Ayca , Iyengar Neil M. , Zhou Xi K. , Giri Dilip D. , Falcone Domenick J. , Wang Hanhan , Williams Samantha , Krasne Margaret D. , Yaghnam Ibrahim , Kunzel Brian , Morris Patrick G. , Jones Lee , Pollak Michael N. , Laudone Vincent Paul , Scher Howard I. , Hudis Clifford A. , Scardino Peter T. , Eastham James Andrew , Dannenberg Andrew J. 
Published: March 2017

63 Background: Obesity, a common cause of chronic inflammation, is associated with an increased risk of high grade, lethal prostate cancer (PC) and poor outcomes. The existence or clinical importance of periprostatic white adipose tissue inflammation (WATi) in patients (pts) with PC has not been previously described. We examined the relationships among periprostatic WATi and 1) tumor clinicopathologic features, and 2) host factors including age, body mass index (BMI), and circulating metabolic factors. Methods: Periprostatic WAT was collected prospectively from men with PC undergoing radical prostatectomy. WATi was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS). Tumor characteristics and host factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher’s exact tests were used to examine the relationship between WATi and tumor and host characteristics. Results: From 11/2011-8/2015, periprostatic WAT was obtained from 169 pts (median age 62 years, range: 39 -77). Fasting blood samples were collected from 154 pts. CLS were present in 84 (49.7%) of pts. Presence of CLS was associated with higher median BMI (P = 0.02); 40/65 (61.5%) obese pts, 36/83 (43.4 %) overweight pts, and 8/21 (38.1 %) normal weight pts had CLS. Pts with CLS were more likely to have high grade prostate cancer (Gleason grade group IV/V, P = 0.02), larger adipocytes (P = 0.004), and positive surgical margins at the time of surgery (P = 0.04). WATi correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to pts without WATi (P’s < 0.05). Conclusions: Periprostatic WATi is common in men with PC. It is associated with high grade PC and alterations in systemic factors that contribute to PC development and progression. Periprostatic WATi may represent a therapeutic target for improving PC risk and outcomes.
A systematic review and meta-analysis to evaluate the influence of surgical method on specimen margins and biochemical recurrence after radical prostatectomy for high-risk prostate cancer.
Authors: Srougi Victor , Bessa Jose , Baghdadi Mohammed , Nunes-Silva Igor , Barreras Silvia Garcia , Barret Eric , Rozet Francois , Galiano Marc , Sanchez-Salas Rafael , Cathelineau Xavier 
Published: March 2017

65 Background: To date there is no robust evidence comparing the outcomes of robotic and open radical prostatectomies in patients with high-risk prostate cancer. The purpose of this study is to perform a meta-analysis comparing the rates of positive surgical margins (PSM) and biochemical recurrence (BCR) between open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP) in patients with high-risk prostate cancer. Methods: A systematic review was performed on Pubmed, Embase and Scopus databases in August 2016, according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. References retrieved were evaluated using the Newcastle-Ottawa scale and the Black and Down’s tool for quality assessment. Nine retrospective cohorts comparing ORP and RARP were selected and included in the meta-analysis. Results: Nine studies reported the PSMs. Patients treated with RARP presented less risk of PSMs (risk difference -0.04, p 0.02) than those treated with ORP. Five articles reported hazard ratios for BCR-free survival. Patients treated with RARP had less risk of BCR (HR 0.72, 95% CI 0.58-0.89) than those treated with ORP. Reports for PSM assessment were considered of adequate quality, while the studies retrieved for BCR assessment were considered limited because of the heterogeneity of their results. Conclusions: Patients with high-risk prostate cancer treated with RARP have less risk of having PSM and BCR when compared to those treated with ORP. A strong conclusion is precluded due to the observational nature of the studies retrieved for our analysis.
Radiotherapy versus radical prostatectomy for Gleason score 9-10 prostate adenocarcinoma: A multi-institutional comparative analysis of 1001 patients treated in the modern era.
Authors: Kishan Amar Upadhyaya , Ciezki Jay P. , Shaikh Talha , Stock Richard , Merrick Gregory Stephen , Jeffrey Demanes D. , Wang Jason , Said Jonathan W. , Fiano Ryan , Raghavan Govind , Sandler Kiri Ann , Reddy Chandana A. , Nickols Nicholas George , Aronson William J. , Sadeghi Ahmad , Kamrava Mitchell , Steinberg Michael L. , Horwitz Eric M. , Kupelian Patrick , King Christopher R. 
Published: March 2017

7 Background: To compare the outcomes of a modern cohort of patients with Gleason Score (GS) 9-10 prostate adenocarcinoma (CaP) following treatment with external beam radiotherapy (EBRT), extremely dose-escalated radiotherapy (as exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP). Methods: One-thousand-and-one patients with biopsy GS 9-10 CaP who received definitive treatment between 2000 and 2013 were included (347 treated with EBRT, 330 with EBRT+BT, and 324 with RP). Kaplan-Meier analysis and multivariate Cox regression compared 5- and 10-year rates of distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Prostate cancer-mortality (PCSM) rates were compared with a competing risk analysis. Results: The median followup periods were 4.8, 6.4, and 5.1 years among patients receiving EBRT, EBRT + BT, and RP. The median doses among EBRT and EBRT+BT patients were equivalent to 78 Gy and 90 Gy in 2 Gy fractions. Over 90% of patients treated with EBRT or EBRT+BT received ADT (median durations of 18 months and 12 months, respectively). Nearly 40% of RP patients received postoperative RT, primarily in the salvage setting. Five- and 10-year DMFS rates were significantly higher with EBRT+BT (91.6% and 81.3%) than with EBRT (79.6% and 65.8%; p < 0.0001) or RP (77.9% and 60.1%; p < 0.0001). Five- and 10-year PCSM rates were significantly lower with EBRT+BT (3.8% and 14.1%) than with EBRT (10.3% and 25.2%; 5- and 10-year hazard ratios of 0.38 and 0.47; p = 0.003) or RP (8.9% and 20.3%; 5- and 10-year hazard ratios of 0.39 and 0.55; p = 0.02). Overall 5- and 10-year OS rates were 85.7% and 64.7% and were similar between cohorts (p > 0.1). Conclusions: Extremely dose-escalated radiotherapy offered improved systemic control and reduced PCSM when compared with either EBRT or RP. Notably, this was achieved despite a significantly shorter median duration of ADT than in the EBRT arm. This is hypothesis generating as it suggests that improved local control via dose-escalation may have systemic control and survival implications even for patients with very high risk disease.
Effect of dose to penile bulb (PB) on patient and clinician-reported erectile function (EF) in standard (SF) and hypofractionated (HF) prostate IGRT.
Authors: Murray Julia , Dean Jamie , Mossop Helen , Griffin Clare , Hall Emma , Dearnaley David P. , Gulliford Sarah 
Published: March 2017

71 Background: PB dose has been hypothesised as predictor of EF post RT, however, PB dose volume effects are not well established. We determined PB dose response characteristics & dose volume constraints using data from randomised trial of prostate IGRT with patient (PRO) & clinician reported (CRO) outcomes. Methods: 293 men were treated within CHHiP IGRT substudy (CRUK/06/16) & randomised to receive 2Gy (SF) or 3Gy (HF) per fraction, without or with daily online IGRT with standard (SM) or reduced (RM) CTV-PTV margins. EF was assessed with RMH CRO & at one time-point (>3 years after RT) with IIEF-5. Men were excluded if impotent at baseline. Planning CT & dose distributions were imported into analysis software (VODCA) & PB contoured. All dose distributions were converted into EQD2 (α/β ratio 3Gy), a separate analysis was done using physical dose (PD) for HF cohort. PB dose volume parameters were analysed & atlases of complication incidence (ACI) evaluated using PRO & CRO. Dose volume constraints using PD & EQD2 were derived using ROC analysis (Youden index) & assessed against the no information rate. Results: Complete dosimetric with CRO & PRO data were available for 175 & 100 men respectively. Of these, men treated with SM vs RM had a higher rate of impotence at 2 & 4 years (49% vs 40% & 47% vs 39%). This was also seen in men recording severe ED (46% vs 37%). ACI indicated a dose volume response. Statistically significant PB dose constraints were derived using EQD2 (SF & HF) & PD for HF cohort (Table). Results using PRO were more pronounced than with CRO. Conclusions: There is a dose volume effect between PB & EF characterised using PRO & CRO. Results suggest that reduction of mean PB dose to <20Gy may lead to an increase of potency preservation rates after prostate RT for both 2Gy & 3Gy schedules. Clinical trial information: ISRCTN97182923. [Table: see text]
The diverse genomic landscape of low-risk prostate cancer.
Authors: Cooperberg Matthew R. , Erho Nicholas , Chan June M. , Feng Felix Yi-Chung , Cowan Janet E. , Ong Kaye , Alshalalfa Mohammed , Kolisnik Tyler , Margrave Jennifer , Aranes Maria , du Plessis Marguerite , Buerki Christine , Zhao Shuang , Tenggara Imelda , Davicioni Elai , Carroll Peter 
Published: March 2017

72 Background: Active surveillance (AS) is becoming standard of care for men with low-risk prostate cancer; however a need exists for better tools to assess which men are optimal candidates for AS. In this study we compare genomic expression profiles of AS candidates against higher-risk radical prostatectomy (RP) patients to characterize the genomics of clinically low-risk prostate cancer. Methods: Biopsies from 473 UCSF patients potentially suitable for AS (stage ≤ cT2N0M0, PSA ≤ 10 ng/ml, Gleason 3+3 or low-volume 3+4 ) were profiled using the Affymetrix HuEx microarray to generate RNA expression data. These cases were compared to 2043 RP cases previously profiled on the same microarray platform. Scores for 21 published prognostic signatures were calculated and pathway associated genes were summarized to provide levels of patient risk and pathway activity. Results: Of the 473 AS biopsies profiled, 408 (86%) passed quality control and were used for analysis. Based on the quartiles of average scores for 21 prognostic signature risk models, 49%, 36%, 11%, and 4%, respectively, were classified into the 1st, 2nd, 3rd, or 4th score quartiles. Considering only the clinically low-risk patients at diagnosis, 356 (87%) were low, 45 (11%) were intermediate and 7 (2%) were high risk. Genomic risk was positively associated with cell cycle related pathways (p < 0.001) and negatively associated with apical junction (p < 0.001), epithelial−mesenchymal transition (p < 0.001), and androgen receptor (p < 0.05) pathways. Clustering of patients based on the expression of 36 pathways revealed two biologic groups corresponding to putative basal and luminal subtypes. Compared to higher risk RP patients, the low risk prostate cancer tumors at diagnosis were enriched for basal-like tumors (20% vs 33%, p < 0.001). Conclusions: Although only 2% of low risk AS candidates have high risk genomic characteristics, very substantial genomic heterogeneity exists in this population, and pathway activation overlaps significantly with higher-risk RP patients. These results suggest that even in potential AS candidates, genomic profiling could eventually be used to better guide management.
A clinical trial for the safety and immunogenicity of a DNA-based immunotherapy in men with biochemically (PSA) relapsed prostate cancer.
Authors: Shore Neal D. , Heath Elisabeth I. , Nordquist Luke T. , Cheng Heather H. , Bhatt Kamalnayan , Carroll Nicholas , Kraynyak Kimberly , Lee Jessica , Van Tornout Jan , Sacchetta Brian , Tagawa Scott T. , Parikh Rahul Atul , Tutrone Ronald F. , Garcia Jorge A. , Whang Young E. , Lin Jianqing , Kelly William Kevin , Csiki Ildiko , Bagarazzi Mark L. 
Published: March 2017

80 Background: Introducing amino acid sequence changes in highly expressed self-antigens for androgen sensitive prostate cancer pts might be sufficient to break tolerance, thus a DNA vaccine was developed using SynCon PSA and PSMA (INO-5150) that share 96.8 and 91.6% sequence identities to these native antigens, respectively. Administration of these antigens to prostate cancer pts along with plasmid encoded adjuvant IL-12 (INO-9012) via electroporation (EP) using the CELLECTRA5P device is postulated to break tolerance, resulting in an antigen-specific immune response which could lead to stabilization of disease progression. Methods: This Phase I, open-label, multicenter study included prostate cancer pts post-definitive therapy with a rising PSA ≥ 1.0 ng/ml after surgery, or ≥ 2.0 ng/ml above nadir after RT and PSA doubling time > 3 months, testosterone > 150 ng/dL and no evidence of metastasis within 12 months. INO-5150 with or without INO-9012 was administered IM followed by EP in 4 arms: low (2 mg) or high dose (8.5 mg) INO-5150 alone or with 1 mg INO-9012 on Day 0 and at week 3, 12, and 24 in 60 planned pts (15 pts/arm). DLT assessments were performed after dosing of the first 3 pts of each arm at Week 4. Results: Enrollment is complete in all 4 arms and at data cut-off (10Oct16), 62 enrolled pts received at least one, 60 pts received 3 and about half, 28 pts (10 in arm A, 8 in B, 7 in C, and 3 in D) received all 4 vaccinations. Safety: there were no DLTs noted. Four pts had five Grade 3 SAEs noted as pre-syncope, cardiac disorder, hospitalization for fall, ALT and AST elevation. No Grade 4-5 AEs were noted. Grade 1-3 treatment-emergent AEs occurred in 50 (81%) pts: 12 (75%) in arm A, 13 (87%) B, 13 (87%) C, and 12 (75%) in D. The most common AEs were injection site pain (24/39%), erythema (13/21%), swelling (12/19%), bruising (10/16%), hyperglycemia (8/13%) and fatigue (6/10%), all Grade 1-2. Assessments of immunological response, PSA kinetics and correlation with clinical outcome are ongoing and will be presented. Conclusions: INO-5150 (+) or (-) INO-9012 is generally safe and well-tolerable at all 4 dose levels in a biochemically relapsed prostate cancer patient population. Clinical trial information: NCT02514213.
Gender disparity: Overlooking hereditary prostate cancer.
Authors: Bowling Lauren , Espenschied Carin , Jackson Michelle , Mak Bryan , LaDuca Holly 
Published: March 2017

85 Background: Prostate cancer (PC) has been associated with germline mutations in several genes, most often BRCA2. Recently, 11.8% of men with metastatic PC were found to have germline mutations in BRCA and other DNA-repair genes. These mutations are equally inherited by men and women, both have elevated cancer risks, and National Comprehensive Cancer Network (NCCN) testing and management guidelines exist for male and female carriers. Despite this, over 95% of patients who have hereditary cancer multi-gene panel testing (MGPT) are women. We sought to describe detection rate and mutation spectrum of MGPT in men with PC compared to women with breast cancer (BC). Methods: Test results were reviewed for PC patients and female BC patients who had MGPT (Jun 2013 – May 2016) for up to 49 genes. Clinical history was obtained from test request forms. Results: Of 654 PC probands, 100 germline mutations were identified in 93 men (14.2%), significantly more than women with BC (8.6%; 6,215/71,728; p = 2.5e-5). Most mutations in PC patients were in BRCA (40.9%), followed by ATM (20.4%), CHEK2 (15.0%) and Lynch syndrome-associated genes (9.7%). Of the 100 total mutations, 94% were in genes that would impact management recommendations for them and/or their relatives. The median time from PC diagnosis to MGPT was 6 years, compared to 1 year for female BC. Nearly 57% (53/93) of mutation-positive men had multiple primary cancers, 79.2% of which had PC first. Of BRCA positives with multiple primaries (n = 21), over 90% developed PC followed by subsequent cancers, yet testing was not initiated until another cancer developed. Conclusions: In this cohort of men with PC, MGPT identified germline mutations at significantly higher rates than females with BC. Furthermore, 59.1% (55/93) of mutation positive PC probands had BRCA and/or ATM, making them possibly eligible for a PARP-inhibitor clinical trial. Unfortunately, time from PC diagnosis to MGPT was several years longer than women, allowing many to develop subsequent cancers that may have been prevented or detected earlier with knowledge of the germline mutation. Increased awareness among clinicians is needed to identify more male mutation carriers to enable appropriate cancer risk management for themselves and their relatives.