bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of decipher test on adjuvant treatment decision-making among men with high-risk pathology at radical prostatectomy: Results from a multicenter prospective PRO-IMPACT study.
Authors: Gore John L. , du Plessis Marguerite , Santiago-Jimenez Maria , Yousefi Kasra , Thompson Darby , Chen David , Clark William , Franks Michael , Karsh Lawrence Ivan , Kibel Adam S. , Kim Hyung Lae , Lane Brian R. , Lotan Yair , Lowrance William Thomas , Maroni Paul , Perrapato Scott David , Trabulsi Edouard John , Waterhouse Robert J. , Davicioni Elai , Lin Daniel W. 
Published: March 2017

24 Background: The decision to provide adjuvant therapy to men with high risk pathology after radical prostatectomy (RP) is confounded by tremendous uncertainty. We prospectively evaluated the impact of the Decipher test, which predicts metastases after RP, on men and providers decision quality. Methods: 150 adjuvant pts were enrolled by 43 urologists from 19 practices. Pts with pathologic T3 stage or positive surgical margins (SM+) after RP were included. Participating physicians provided a treatment (Tx) recommendation before and after exposure to Decipher test results. Pts completed validated surveys on health-related quality of life, decisional conflict, and PCa-related anxiety. Results: Median patient age at RP was 64 years; 67% and 50% had pT3 and SM+ pathology, respectively. Decipher classified 46%, 22% and 32% of men as low-, intermediate- and high-risk, respectively. Pre-Decipher, observation was recommended for 89%. Post-Decipher, 18% (95% CI 12-25%) of Tx recommendations changed. Men’s Decisional Conflict Scale (DCS) scores decreased (indicating higher decision quality) after exposure to Decipher results (median DCS pre-Decipher 25 [IQR 8-44], median DCS post-Decipher 19 [IQR 2-30], p<0.001), with greatest decreases in the subdomains of decision uncertainty and decision support. Low-risk Decipher results experienced a trend toward decreased PCa-specific anxiety (p=0.13) and a significant reduction in fear of PCa recurrence (p=0.02). Physicians’ median DCS scores decreased from 32 [IQR 28-36] to 28 [IQR 12-42] (p<0.001). Decipher results were associated with the decision to pursue ART in an MVA analysis (OR 1.48; 95% CI 1.19-1.85, p<0.001). Conclusions: Observation is the predominantly prescribed management strategy for men with high risk features at RP. Knowledge of Decipher results was associated with Tx decision-making: men at low risk for metastasis had higher rates of observation recommendations and men at high risk had higher rates of ART recommendations. Decision quality was improved and PCa-specific anxiety was decreased for men exposed to Decipher results. Clinical trial information: NCT02080689.
Charlson Score as prognostic factor in patients with castration-resistant prostate cancer.
Authors: Jankilevich Gustavo , Gennari Luciana , Salazar Matias , Graziano Claudio , Saravia Eduardo , Belinky Javier , Rey Horacio , Chirino Daniel 
Published: March 2017

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI < 7.6 was 75 months versus 62 months for those with CCI > 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]
Impact of income in stage IV prostate cancer.
Authors: Ahmed Aabra , Malouff Timothy Dean , Walters Ryan W , Marsh Sydney , Silberstein Peter T. 
Published: March 2017

244 Background: There is growing evidence of the impact of socioeconomic status on survival in cancer patients. To our knowledge, this is the largest study to examine demographics and the association between income and survival in patients with stage IV prostate cancer. Methods: Using the National Cancer Database, 50,639 patients diagnosed with stage IV prostate cancer between 2004-2011 were identified. Income was evaluated using the median income of the patient’s zip code. Between-income survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p < .05 indicated statistical significance. Results: Survival differences were indicated between all income quartiles. Median survival was highest for patients in zip codes with a median income ≥ $63,000 and lowest for patients in zip codes with an income < $38,000 (46.1 months vs. 31.6 months, respectively; p < .001). As such, 41% of patients in zip codes with a median income ≥ $63,000 were alive five years following diagnosis, compared to 31% of patients in zip codes with median income < $38,000. Additionally, compared to patients in zip codes in which the median income was < $38,000, patients in zip codes with a median income ≥ $63,000 had a higher rate of zero comorbidities (81% vs. 76%), a greater percentage of patients living in an area where >93% people have a high school degree (58% vs 1%), and a lower proportion of African Americans (8% vs 41%). Conclusions: Compared to patients with a median income < $38,000, patients in zip codes with a median income > $63,000 had a median survival nearly 15 months longer, had 10% more patients alive after 5 years, and had fewer comorbidities. [Table: see text]
Eligibility criteria requirements and adherence in advanced prostate cancer trials.
Authors: Wong Sarah , Sweeney Christopher , Sridhar Srikala S. 
Published: March 2017

245 Background: Eligibility criteria for advanced (metastatic and locally advanced) prostate cancer trials vary between trials and are specific to the therapy evaluated, and may not represent the general population. This reduces comparability between studies, generalizability of results, and may contribute to high screen failure rates (~25%). In this study, we aimed to better understand the eligibility criteria across trials and adherence to eligibility criteria. Methods: We compared eligibility criteria between trials and collected baseline demographics to assess for adherence to criteria for 13 phase III advanced prostate cancer trials published from 1999-2016. Results: Disease characteristics, age, performance status, tumor markers, and most hepatic, renal, and hematological criteria were consistent across trials. However, discrepancies in hemoglobin, absolute neutrophil count, glomerular filtration rate (GFR) and bilirubin criteria were observed (Table). Overall, 8/13 trials included patients that did not meet criteria but were analyzed by intent-to-treat. Criteria that were not followed included: hemoglobin and albumin (lower than permitted); while testosterone, serum creatinine, pain scores, and ECOG performance status were higher (more unwell) than permitted. Conclusions: Specific eligibility criteria vary across the trials, and a number of trials accrued ineligible patients. After accounting for drug-specific criteria, greater standardization of and consideration of general population for eligibility criteria is needed to improve homogeneity of trial populations across studies, generalizability of results, and possibly reduce screen failure rates in prostate cancer trials. [Table: see text]
ODM-204 a novel dual inhibitor of CYP17A1 and androgen receptor: Early results from phase I dose escalation in men with castration-resistant prostate cancer.
Authors: Fizazi Karim , Jones Robert Hugh , Massard Christophe , Vjaters Egils , Peltola Katriina Johanna , Nykänen Pirjo , Vuorela Annamari , Oksala Riikka , Pohjanjousi Pasi , Mustonen Mika VJ , Bono Petri 
Published: March 2017

246 Background: Castration-resistant prostate cancer (CRPC) is characterized by high androgen receptor (AR) expression, various AR mutations and persistent activation of AR signaling axis by residual tissue androgens and other steroids. Inhibiting both the AR and androgen biosynthesis may be more effective than inhibiting either alone to treat CRPC. ODM-204 is a potent, orally administered investigational non-steroidal dual inhibitor of CYP17A1 and the AR that has shown activity in nonclinical tumor models. Methods: We report early data of the DUALIDES phase I dose escalation part (NCT02344017), in which patients with metastatic CRPC (mCRPC) were enrolled into ODM-204 dose levels of 50, 100, 200, 300, 500 mg twice daily. Data cut-off was Oct 14th2016. Results: In the trial 23 patients with progressive mCRPC received increasing doses of ODM-204. At baseline, the median age of patients was 70 yrs (57-84 yrs), and median PSA was 46.5 ng/mL (0.7-249.6 ng/mL). Median time on treatment was 11.6 weeks (0.3-60.4 wks). Nine (39%) patients continued treatment for more than 12 weeks, and 4 (17.4%) patients were still receiving treatment at the time of data cutoff. ODM-204 was generally well tolerated, and the most commonly reported adverse events (AEs) were fatigue (n = 6, 26%), nausea (n = 6, 26%), decreased appetite (n = 5, 22%,) diarrhea (n = 5, 22%), and vomiting (n = 5, 22%). Two patients discontinued treatment due to an AE. The AUCt and Cmax values of ODM-204 in plasma increased with dose up to 300 mg after a single dose. Steady state values on day 8 were unexpectedly decreased in most patients, especially at higher doses, contrary to what was observed in the nonclinical monkey studies. Further, decreased predose concentrations were observed on day 29. PSA decreases were seen in 7 (30%) patients, and the median decrease was 47% (2-99%). At 12 weeks, 3 (13%) patients had a PSA response ( ≥ 50% reduction from baseline). Conclusions: Although evidence of anticancer activity was provided with ODM-204 in mCRPC, decreasing steady state concentration was observed. Clinical trial information: NCT02344017.
Novel biomarker of specific castration-resistant prostate cancer (CRPC) by exploring the proteome analysis.
Authors: Uemura Hiroji , Arakawa Noriaki , Itoh Yusuke , Kawahara Takashi , Miyoshi Yasuhide , Akiba Shouhei , Ohtake Norihisa 
Published: March 2017

247 Background: It is well known that prostate specific antigen (PSA) level has no reliable correlation with pathological malignancy of prostate cancer and is not a predictor for the development of castration resistant prostate cancer (CRPC). The aim of this study is to explore novel biomarkers to predict the development of CRPC by using proteomics from secreted proteins from human prostate cancer cells. Methods: The proteins secreted from 6 prostate cancers in culture medium were analyzed and compared with 8 other cancer cells including renal and urothelial cancers using LTQ Orbitrap mass spectrometer. With the focus on high tissue specificity, the candidate biomarker proteins were then identified through analysis of gene expressions in proteins common to human prostate cancers by real time qPCR. Next, a system to measure the identified mouse monoclonal antibodies against the focused proteins was established. Finally, serum levels of these proteins from 33 patients with benign prostate hyperplasia (BPH), 31 with untreated prostate cancer (PCa) and 35 with CRPC, were measured. Results: The proteome analysis identified 12 candidates of secreted cell membrane proteins as new biomarkers. The proteome analysis indicated that not only matured GDF15, but pro-peptide as well as fragments (GDDP) are released from prostate cancer cells. Patients’ serum was analyzed for matured and pro-peptide GDF15 using ELISA and immunoprecipitation-MRM mass spectrometry. The results showed that the serum level of GDDP-1, one of the processing forms of GDDP, was significantly higher in CRPC than those in BPH and untreated PCa (P < 0.01). ROC analysis also showed that the AUC of GDDP-1(0.86) was higher than that of matured GDF15 (0.76). When the cutoff value of GDDP-1 was set at 4.0 ng/mL, there was a significant difference of overall survival (OS) in CRPC patients between those with more than 4.0 ng/mL compared to less than 4.0 ng/mL of GDDP-1, whereas there was no significant difference of OS measurable by PSA in CRPC patients. These data suggest that GDDP-1 may be a novel biomarker for CRPC. Conclusions: GDDP-1 shows potential as a novel biomarker for CRPC.
Impact of circulating tumor cell (CTC) nucleus size on outcomes with abiraterone acetate (AA) therapy in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gill David Michael , Agarwal Neeraj , Hahn Andrew W. , Johnson Eric , Poole Austin , Carroll Emma , Boucher Kenneth M. , Salama Mohamed E. , Agarwal Archana M. 
Published: March 2017

253 Background: CTC enumeration but not CTC morphology has been reported to predict outcomes to treatment in men with mCRPC. Recently Chen JF et. al (Cancer, 2015) showed an association with nuclear size and incidence of visceral disease in metastatic prostate cancer. In this study, we investigate the impact of CTC nucleus size on outcomes in men treated with AA for mCRPC. Methods: In a cohort of men with mCRPC treated with first-line AA, who had CTCs identified by CellSearch (CS) analysis prior to initiating treatment, we retrospectively quantified the nuclear size of CTCs by ImageJ/Fiji 1.46 software and correlated with progression free survival (PFS) on AA. We analyzed with univariate in addition to pre-specified multivariable analysis adjusted for Gleason score and baseline log PSA to assess independent predictive value of CTC nuclear size on PFS. Median PFS was calculated by Kaplan-Meier analysis and p-values were determined from Cox proportional hazards model. Results: 22 men treated with AA for mCRPC were included. Median nucleus size was 23.8 µm. Patients were divided in to 2 cohorts: small nuclear cohort (CTC nucleus size < 23.8 µm) vs large nuclear cohort (CTC nucleus size ≥23.8 µm). There was a non-significant trend towards worsened PFS (5.8 versus 6.8 months) in the larger nuclear size arm (Table). Conclusions: In this cohort of men with CRPC treated with AA, there is a non-significant trend towards decreased PFS associated with larger CTC nucleus size. Data are hypothesis generating and require further interrogation in a larger cohort. [Table: see text]
Patients with metastatic castration-resistant prostate cancer (mCRPC) who are long-term responders (LTR) to the new agent (NA)-based second line: Clinical outcomes and prognostic factors of subsequent treatment with another NA.
Authors: Caffo Orazio , Bria Emilio , De Giorgi Ugo , Tucci Marcello , Biasco Elisa , Fratino Lucia , Rossetti Sabrina , Iacovelli Roberto , Mucciarini Claudia , Zucali Paolo Andrea , Vicario Giovanni , Carrozza Francesco , Sirotova Zuzana , Messina Caterina , Amadio Placido , Maestri Antonio , Sacco Cosimo , Veccia Antonello , Sperduti Isabella , Zagonel Vittorina 
Published: March 2017

254 Background: Three NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] are able to significantly prolong their overall survival (OS) after docetaxel failure. A quote of pts can obtain a prolonged disease control over 12 months with a second line NA and it is unclear if a clinical benefit may result from a subsequent treatment with another NA. The present study is aimed to assess the clinical outcomes and prognostic factors of subsequent NA treatment in those pts LTR to a second line NA. Methods: We collected data of pts who received sequentially two NAs after DOC. For each pt we recorded the clinical outcome of treatments received after DOC. We consider as LTR pts without progression over 12 months from the start of the NA second line. We assessed the independent prognostic value of a series of third-line baseline covariates, in terms of progression free survival (PFS) and OS by Cox regression analysis. Results: A consecutive series of 476 mCRPC pts received a NA-based second line: AA (261 pts), CABA (151), and ENZ (64): we identified 116 LTR pts (AA 71 – CABA 28 – ENZ 17). All pts received a subsequent NA-based third line: 27 received AA, 59 CABA, and 30 ENZ. Comparing the third-line outcomes of LTR and no-LTR pts , no statistically significant differences were observed in terms of both biochemical and objective response rate, and PFS, while LTR showed a statistically significant longer OS (median 18 vs 11.4 mos; p< 0.0001). The third line OS was statistically significant different (p = 0.01) according to the sequence adopted (Table). At the multivariate analysis , performance status (PS) and the presence of visceral metastases were independent prognostic factors for PFS in third line, while PSA, PS and lactate dehydrogenase were independent prognostic factors for OS. Conclusions: In our experience, NA-based third line is active also in mCRPC LTR population with highest benefit in sequences with CABA and some factors may help in selecting patients with higher probability of achieving a disease control. [Table: see text]
Short- and long-term outcomes of salvage lymph node dissection in patients with clinically recurrent prostate cancer.
Authors: Gandaglia Giorgio , Fossati Nicola , Stabile Armando , Bandini Marco , Zaffuto Emanuele , Dell'oglio Paolo , Suardi Nazareno , Montorsi Francesco , Briganti Alberto 
Published: March 2017

255 Background: Salvage lymph node dissection (sLND) has been proposed to improve oncologic outcomes in nodal recurrence after radical prostatectomy (RP). We aimed at reporting the results of sLND in patients with recurrent PCa limited to the nodes. Methods: 140 patients treated with sLND for nodal recurrence after RP documented by PET/CT scan between 2002 and 2016 were identified. Transfusions, length of stay (LoS), and 30-day complications were analyzed. Biochemical response (BR) was defined as PSA < 0.2ng/ml at 40-day. Clinical recurrence (CR) was defined as positive findings at postoperative imaging. Kaplan-Meier and Cox regression analyses were used. Results: Median age sLND was 66 years. Median PSA at sLND was 2.0ng/ml. Overall, 58.6, 14.4, and 15.0% patients had positive spots in the pelvic, retroperitoneal, and pelvic + retroperitoneal regions. Overall, 19.3, 2.9, and 77.8% patients received a LND in the pelvic, retroperitoneal, and pelvic + retroperitoneal regions. The median number of nodes removed was 27. Overall, 107 (76.4%) patients had positive nodes at sLND. Overall, 10 (7.1%) experienced grade 3-5 complications according to Clavien-Dindo and 12 (11.8%) patients received blood transfusions. Median LoS was 7 days. Median follow-up was 71 months. Overall, 54 (38.6%) patients achieved BR. The 8-year BCR free-survival rate in patients with BR was 44.7%. CR and CMS was observed in 50 and 25 patients. The 8-year CR and CSM-free-survival rates were 43.2 and 66.4%. In the preoperative model, retroperitoneal spots (Hazard ratio [HR]: 1.89; 95% confidence interval [CI]: 1.02-3.69) and the number of positive spots (HR: 1.26; 95%CI: 1.04-1.57) were predictors of CR. In the postoperative model, BR (HR: 0.33; 95%CI: 0.17-0.72), retroperitoneal involvement (HR: 3.48; 95%CI: 1.22-8.19), and the number of positive nodes (HR: 1.03; 95%CI: 1.01-1-06) were predictors of CR. Conclusions: sLND was associated with a low rate of high-grade complications. At 8-year, more than 40% of patients were free from CR. Retroperitoneal involvement and nodal burden were predictors of response. sLND might represent a therapeutic option for selected patients with nodal recurrence after RP.
Genomic architecture of radioresistant prostate cancer.
Authors: Chua Melvin , Holgersen Erle , Sabelnykova Veronica , Salcedo Adriana , Meng Alice , Fraser Michael , Van Der Kwast Theodorus , Boutros Paul Christopher , Bristow Robert G. 
Published: March 2017

26 Background: Spatial intra-tumoral heterogeneity of prostate cancer is secondary to genomic diversity and multi-clonality. These unique features potentially promote resistance to treatment. Here, we investigated if clonal selection or adaptation of new clones dominates in prostate cancer at the time of recurrence following radiotherapy. Methods: We identified 11 patients with biopsy-proven multifocal recurrent prostate cancer following radiotherapy. Copy number aberration (CNA) profiling was performed on 33 anatomically distinct tumor foci with 11 matched-normals. 4 cases had matched pre-radiotherapy tumors for CNA profiling to assess for clonality. We evaluated for recurrent gene amplifications and deletions, and determined genomic instability by percent genome aberration (PGA). We also compared these genomic indices against 373 sporadic prostate cancers from the Canadian Prostate Cancer Gene Network. Results: We observed large intra- and inter-patient variation (p <0.001, one-way ANOVA) in PGA scores among the radioresistant tumors. Interestingly, although total CNA counts did not differ between the radioresistant and sporadic cohorts (median = 40, radioresistant vs 33, sporadic, p = 0.20], there was a trend for increased genomic instability in the radioresistant cohort (median PGA = 8.8 vs 4.9, p = 0.059). Spatial resolution of gene-level CNAs revealed the acquisition of CNAs that were both common and non-recurrent in the multi-focal radioresistant tumors, thus suggesting a common clonal origin, with subsequent divergent evolution. Importantly, we observed a mixture of CNAs, including known prognostic genes in prostate cancer, namely NKX3-1, PTEN, TP53, CDKN1B, and CDH1,that was shared between pre-treatment and radioresistant tumors, favoring clonal selection. We also discovered a novel deleted region on Chr3p, consisting of RAD18 and FANCD2, which was uniquely present in the radioresistant tumors. Conclusions: Our novel observations in a small cohort of radioresistant prostate cancers favor the model of clonal selection, as opposed to new-onset tumors. These results support the discovery of biomarkers a priori, and targeted treatment of these radioresistant clones to improve the therapeutic ratio of precision radiotherapy.