bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation-guided stratification of patients with high-risk prostate cancer for the prediction of clinical failure.
Authors: Litovkin Kirill , Joniau Steven , Lerut Evelyne , Laenen Annouschka , Gevaert Olivier , Spahn Martin , Kneitz Burkhard , Isebaert Sofie , Haustermans Karin , Beullens Monique , Van Eynde Aleyde , Bollen Mathieu 
Published: February 2017

155 Background: To explore differential DNA methylation of APC, CCDN2, GSTP1, PTGS2, and RARBas a tool to predict clinical failure (CF) in surgically treated patients with high-risk prostate cancer (PCa), as defined by a clinical stage T3a or higher, a biopsy Gleason score of 8 to 10 and/or pre-operative prostatic serum antigen levels more than 20 ng/ml. Methods: A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the marker genes. Formalin-fixed, paraffin-embedded radical prostatectomy samples from 218 patients with high-risk PCa, classified in a training and validation cohort, were analyzed. Kaplan-Meier analysis and Cox multivariate models were used. Results: First, high-risk PCa patients were ranked according to their GSTP1 methylation level, which varied from 0 to 80% in both cohorts. Next, we categorizedthe tumors into three groups based upon the GSTP1 methylation level: low methylation (LM, methylation less than 15%), moderate methylation ([MM], methylation 15 to 50%) and high methylation (HM, methylation more than 50%). When all five marker genes were combined, the median methylation values in the LM groups did not exceed 6% in both cohorts. In contrast, the median methylation values for the marker genes in the HM groups reached 45% in the training cohort and 50% in the validation cohort. Finally, the median methylation values in the MM groups amounted to 18% and 28% for the training and validation cohorts, respectively. Remarkably, patients belonging to the LM, HM, and the combined LM+HM groups had a 2- to 11-fold higher risk of CF as compared to those of the MM group, when correcting for established clinico-pathologic prognostic factors. In addition, the combined LM+HM group showed a significant association with cancer-related death in a multivariate analysis (Hazard ratio, 3.59) compared to the MM group, when both cohorts were combined for analysis. Conclusions: We found that differential methylation of GSTP1 allows the stratification of high-risk PCa patients into three molecular episubtypes, i.e. low, moderate and high DNA methylation level groups. Surprisingly, our data revealed that both low and high methylation levels of GSTP1 are independent predictors of CF.
Modeling acute urinary toxicity after radiotherapy for prostate cancer.
Authors: Carillo Viviana , Rancati Tiziana , Cozzarini Cesare , Villa Sergio , Botti Andrea , Casanova Borca Valeria , Cattari Gabriella , Civardi Francesco , Degli Esposti Claudio , Franco Pierfrancesco , Girelli Giuseppe , Maggio Angelo , Muraglia Alessandro , Palombarini Marcella , Pierelli Alessio , Pignoli Emanuele , Vavassori Vittorio , Zeverino Michele , Valdagni Riccardo , Fiorino Claudio 
Published: February 2017

156 Background: DUE-01 is a multi-centric observational study aimed at developing predictive models of genito-urinary toxicity and erectile dysfunction for prostate cancer patients treated with conventional (1.8-2Gy/fr, CONV) or moderate hypofractionation (2.5-2.7Gy/fr, HYPO). Current analysis focused on modelling the relationship between the risk of IPSS≥15 (IPSS15end) at the end of radiotherapy and clinincal/dosimetric risk factors. Methods: Planning data and relevant clinical factors were prospectively collected, including DVH/DSH referred to the whole treatment and to the weekly delivered dose (DVHw/DSHw). Best discriminating DVH/DSH parameters were selected by the differences between patients with/without IPSS15end=1 (t-test). Bootstrap variable selection techniques (300 resamples) in the framework of logistic backward feature selection was used to improve model building (El Naqa, IJROBP 2006). Graphical and quantitative analyses of the variable selection process applied to bootstrap data replicates was used to avoid underfitting/overfitting and to assess the final multivariable model. Results: 247 patients were available (CONV:116, HYPO:131). Seventy one out of 247 (28.7%) reported IPSS15end=1. The most predictive dosimetric tools were the absolute weekly delivered dose (DSHw and DVHw). DSHw and DVHw were alternatively inserted in the bootstrap variable selection flow, together with clinical risk factors. Due to the number of events, a logistic model containing six variables was accepted On the basis of observed frequency of variables in the top six positions, a model including basal IPSS (median OR=1.22, p=0.00001), use of anti-hypertensives (median OR=2.7, p=0.01), absolute bladder surface receiving more than 10.5 Gy/week (s10.5w, median OR=1.16, p=0.0001), and s12.5w (median OR=1.07, p=0.005), was choosen. AUC of this model was 0.80. Silmilar results were obtained when using DVHw. Conclusions: Basal IPSS, use of anti-hypertensive drugs, s10.5w/v10.5w and s12.5w/v12.5w are the main predictors of IPSS>=15 at the end of radiotherapy Bootstrap variable selection technique gives the modeler more insight into the importance and stability of the different variables selected and allows development of more robust models
Using a combination of urine and plasma biomarkers for the development of a scoring sytem that can diagnose and predict prognosis of prostate cancer.
Authors: Albitar Maher , Ma Wanlong , Diep Kevin , Albitar Ferras S. , Fritsche Herbert A. , Shore Neal D. 
Published: February 2017

163 Background: Relying solely on serum prostate-specific antigen (sPSA) to screen for prostate cancer (PCa) can lead to unnecessary biopsies. Biomarkers from urine and plasma were isolated to develop a detection scoring system for the presence of prostate cancer as well as to better predict aggressiveness. Methods: Urine and plasma specimens were analyzed from 141 patients (61 newly diagnosed PCa patients, 60 benign prostate hyperplasia (BPH) patients, and 20 post-prostatectomy patients) using polymerase chain reaction (PCR) for the levels of UAP1, PDLIM5, IMPDH2, HSPD1, PCA3, PSA, TMPRSS2, ERG, GAPDH, and B2M genes. Patient age, sPSA level, and PCR data were entered through multiple algorithms to determine models most useful for detection of cancer and predicting aggressiveness. Results: We developed an algorithm for distinguishing PCa from BPH (area under the receiver operating characteristic curve [AUROC] of 0.78). Another algorithm distinguishes patients with Gleason Score (GS) ≥ 7 from GS < 7 cancer or BPH (AUROC of 0.88). By incorporating the two algorithms into a scoring system, 75% of the analyzed samples showed concordance between the two models (99% specificity and 68% sensitivity for predicting GS ≥ 7), and 25% showed discordance. Conclusions: A scoring system incorporating two algorithms using urine and plasma biomarkers highly predicts the presence of GS ≥ 7 PCa in 75% of patients. In 25% of patients, the system can be used only to distinguish between the presence of cancer and benign pathology. Our algorithms may assist with both biopsy indication as well as patient prognosis. [Table: see text]
Prognostic utility of the cell cycle progression (CCP) score generated from needle biopsy in men treated with prostatectomy.
Authors: Bishoff Jay T. , Freedland Stephen J. , Gerber Leah , Tennstedt Pierre , Welbourn William , Reid Julia E. , Graefen Markus , Sangale Zaina , Tikishvili Eliso , Park Jimmy , Younus Adib , Gutin Alexander , Lanchbury Jerry S. , Sauter Guido , Brawer Michael K. , Stone Steven , Schlomm Thorsten 
Published: February 2017

17 Background: We developed a prognostic RNA signature that is strongly associated with prostate cancer outcomes. The cell cycle progression (CCP) score has proven to have prognostic utility in predicting disease progression in various clinical settings utilizing biopsy, transurethral resection of the prostate (TURP) and post-prostatectomy specimens. Previous studies evaluating post-surgical outcomes were conducted using CCP gene expression measured in the prostatectomy specimen. Here, we demonstrate the ability of the CCP score to predict cancer progression, as measured by both biochemical recurrence (BCR) and metastatic disease after radical prostatectomy, using needle biopsy tissue. Methods: We evaluated the CCP score in three patient cohorts. These included men from the Martini Clinic (MC, N=283), the Durham VA Medical Center (DVA, N=176), and Intermountain Healthcare (IHC, N=123). The CCP score was derived from a simulated biopsy (MC) or diagnostic biopsy (DVA and IHC), and evaluated for association with BCR and metastatic disease in univariable analysis and after adjusting for other clinical information. Results: In all three cohorts, the CCP score was associated with BCR and metastatic disease. The association with BCR remained significant after adjusting for other prognostic clinical variables. In a combined analysis of all three cohorts (N=582), the CCP score was a strong predictor of BCR in both univariable (HR per Interquartile Range [IQR] = 1.68 [95% CI: 1.41, 1.99), p value<10−6]) and multivariable analyses (HR per IQR = 1.53 [95%CI: 1.28, 1.84], p value < 10−4). CCP score was the strongest predictor of metastatic disease in both univariable analysis (HR per IQR = 6.32 [95% CI: 3.41, 11.71, p value<10−7]), and after adjusting for clinical variables (HR per IQR = 4.83 [95% CI: 2.40, 9.74, p value<10−5]). Conclusions: The CCP score derived from a needle biopsy sample was strongly associated with adverse outcome after surgery. It was the strongest predictor of eventual metastatic disease of the tested variables including Gleason and PSA. These results indicate that the CCP score can be used at disease diagnosis to better define patient prognosis and appropriate clinical care.
Patterns and trends in management of locoregional prostatic adenocarcinoma with PSA ≥20 ngm/ML.
Authors: Trulson Jerry J , Huynh Danny , Islam Majdee , Rao Abishek , Pokala Naveen 
Published: February 2017

172 Background: Extremely high prostate specific antigen (PSA) at diagnosis has traditionally precluded a surgical approach for prostate cancer. This database study evaluates the national trends in management of patients with high PSA at prostate cancer diagnosis. Methods: Men age 75 or less with a diagnosis of prostatic adenocarcinoma and a PSA of 20ngm/ml and over were identified from the SEER 18 Database (2004 to 2009). Exclusion criteria included patients with metastatic disease at diagnosis, more than one primary cancer, unknown stage, unknown Gleason score, unknown treatment, or diagnosis at autopsy. Patients were analyzed for demographics, stage at presentation, treatment patterns, and survival using appropriate statistics. Results: A total of 15,485 patients with PSA between 20 and 98.8ngm/ml were identified. Mean age at diagnosis was 64±7.3 years. A total of 4,510 (29.1%) patients did not receive any definitive treatment (NDT group), 6,503 (52%) received Radiation, and 4,472 (28.9%) underwent surgery. A total of 531 patients underwent adjuvant radiation after surgery. The mean PSA of patients who underwent surgery (47.3ngm.ml) or RT (44.3 ngm/ml) was lower than the patients who did not have any definitive treatment (50.9 ngm/ml). Increasing age and increasing T and N stage were associated with a trend towards a surgical approach while Gleason score and PSA levels were not associated a trend towards surgery. Increasing age and Gleason score were associated with an increasing trend towards radiation while increasing PSA, T stage, and N stage were associated with a decreasing trend towards radiation. Increasing age and PSA was associated with an increasing trend towards NDT, while an increasing stage was associated with a reduced trend towards NDT. The N stage and Gleason score did not predict a trend for the NDT. Conclusions: The PSA level, even when very high, is not the sole factor that determines whether or not patients with prostate cancer receive surgery. Nationwide trends suggest that while radiation is the most common treatment modality undertaken by patients with PSA over 20 ngm/ml, patients younger than age 50 are more likely to undergo surgery irrespective of the PSA level.
Real-world utilization of the novel AR-targeted therapies in mCRPC management: An electronic medical records retrospective study.
Authors: Sartor A. Oliver , Mehta Jyotsna , Fonseca Eileen , McGuiness Catherine Balderston , Petrilla Allison , Su Zhen 
Published: February 2017

176 Background: New androgen receptor (AR) targeted therapies, including abiraterone (AA) and enzalutamide (EZ), have recently been approved for mCRPC management. This study examined use of AA in community oncology practices to understand real world practice patterns. Methods: Deidentified EMRs were retrospectively analyzed for cancer staging, tumor histology, metastatic coding, lab results and drug orders from 78 practices (300+ locations; 37 states; >500,000 cancer patients) to identify mCRPC patients initiating AA between May 2011-Jan 2013, provided there was one year of baseline data prior to starting AA and 3 mos of data after initiating AA. Patients were excluded if participating in clinical trials, diagnosed with other primary neoplasms, or from practices inconsistently reporting data. Key outcomes were changes in systemic anti-cancer therapy, discontinuation of AA, and death during the first 3 mos after AA initiation. Results: Of 3,930 mCRPC patients observed with an oncology visit during study period, 356 met criteria for analysis (mean age at AA initiation 73.3 yrs); 37% of patients (n=131) received prior docetaxel (D) and 16% of patients (n=56) received prior cabazitaxel (C) before starting AA. Of these 356 patients, 153 (43%) experienced a change of therapy or death in the 3 mos post-starting AA. Of the total patients, 19% (n=66) discontinued AA, while 17% (n=62) changed systemic therapy. Of those changing therapy, 5 patients started EZ, 20 CBZ, 24 D. A total of 11% of the total patients (n=39) died within 3 mos of starting AA. Conclusions: Real-world treatment data suggests more than 57% of patients were alive and continuing AA while 43% discontinued AA/changed treatments, or died within 3 mos of starting AA. EMR data provide important insights into real world practice; limitations include inconsistency in data entry and difficulty in aligning prescription start dates with actual dispensed medication. [Table: see text]
Evidence for circulating tumor cell (CTC) alkaline phosphatase (AP) expression in men with bone-metastatic castration-resistant prostate cancer (CRPC) during abiraterone acetate treatment.
Authors: Armstrong Andrew J. , Bitting Rhonda Lynn , Kemeny Gabor , George Daniel J. 
Published: February 2017

178 Background: Serum alkaline phosphatase (AP) changes in men with metastatic prostate cancer have been described since the Nobel Prize winning discovery of the hormonal dependence of PC. High serum AP is independently associated with mortality in men with castration-resistant prostate cancer (CRPC) and reductions in AP with treatment are favorably prognostic. Transient rises in AP may occur during treatment initiation and reflect bone remodeling/healing. The source of serum AP in men with metastatic prostate cancer, however, remains unclear. We hypothesize that cancer cell osteomimicry and epithelial plasticity may contribute to serum AP elevations in these men. Methods: We examined the expression of AP in the circulating tumor cells (CTCs) of men with metastice CRPC on abiraterone acetate who had elevated serum AP to determine if one possible source of serum AP may be tumor-derived rather than host/bone derived. CTCs were isolated using the CellSearch method and EpCAM ferromagnetic capture, and only CD45 negative cells were considered CTCs. AP was evaluated using immunofluorescence and real time positive and negative controls. Liver function was evaluated to ensure lack of confounding with liver-derived AP. Results: We identified AP to be commonly expressed in the CTCs of men with CRPC who had high serum AP, with no expression in patient leukocytes. One patient had a transient rise in serum AP with no change in other liver enzymes during a dramatic response to abiraterone acetate while his prostate-specific antigen and CTC declined. AP expression was evident and common in his CTCs during this serum AP flare. A second patient was found to have common CTC AP expression in both CK+ and CK- CTCs. This patient had evidence of AR amplification, PTEN loss, and TMPRSS2-ERG fusion in his CK- and CK+ CTCs, accompanied by a high number of OB-cadherin + CTCs, indicating likely osteomimicry and plasticity of these clonal epithelial tumor cells. Conclusions: We provide clinical evidence that PC CTCs express AP, supporting the hypothesis that AP expression is associated with osteomimicry as part of the biology of epithelial plasticity in prostate cancer. These findings support the existence of multiple CTC phenotypes, the clinical significance of which is unknown.
Predicting positive bone marrow biopsies (BMBs) in patients (PTS) with advanced prostate cancer (APC).
Authors: Lorente David , Omlin Aurelius Gabriel , Pezaro Carmel Jo , Tunariu Nina , Ferraldeschi Roberta , Riisnaes Ruth , Mateo Joaquin , Sheridan Elizabeth , Perez Lopez Raquel , Nava Rodrigues Daniel , Crespo Mateus , Figueiredo Ines , Zafeirou Zafeiris , Altavilla Amelia , Attard Gerhardt , De Bono Johann Sebastian 
Published: February 2017

180 Background: Advanced prostate cancer (APC) is a molecularly heterogeneous disease, with evidence of clonal evolution that could be responsible for resistance to treatment. About 90% of patients (pts) with APC have bone metastases. The acquisition of a bone marrow biopsies (BMBs) is a safe and feasible technique for obtaining tissue, with a low rate of complications. We hypothesized that pre-biopsy clinical variables may increase the success rate of BMBs in APC. Methods: Standard BMBs of the iliac crest were performed in APC pts between October 2011 and June 2013. All pts signed ethics approved consent. In the control cohort (n=10) BMBs were collected in pts with normal CT and bone scan appearance. Minimum, maximum, and mean Hounsfield Units (HU) of the iliac crest on pre-biopsy CTs were determined. Clinical and laboratory variables were collected from the electronic record system. Biopsies were defined as containing 50 or more or 1 to 50 malignant cells or none (negative). Univariate analysis was performed to determine variables associated with biopsy positivity with 50 or more cells. For variables with p value<0.1, the optimal cut-off point was determined by ROC curve analysis. A multivariate analysis with optimal cut-off points was then performed. Results: A total of 71 BMBs were performed in 57 pts. None of the control biopsies in pts with normal CT and bone scan (10 of 10) contained tumor. A total of 46 of 61 BMBs (75.4%) were positive. 38 of 61 (62.3%) contained 50 or more cells. Prior treatments were docetaxel in 57 (79.2%) and abiraterone in 42 (58%) pts. Bisphosphonates had been used in 21 (28.8%) pts. The significant variables on univariate analysis were ALP more than or equal to 200 IU/L (p=0.059), prostate-specific antigen (PSA) more than or equal to 225 ng/mL (p=0.008), lactate dehydrogenase (LDH) more than or equal to 200 IU/L (p=0.09), mean HU more than or equal to 125 (p=0.000) and maximum HU more than or equal to 550 (p=0.001). These factors were tested in multivariate analysis. Only PSA and mean HU were significant in multivariate analysis. The combined PSA and mean HU score had an ROC AUC of 0.79. Conclusions: A combination of PSA and mean HU on CT could assist physicians in selecting APC patients/ iliac crest site more likely to have a positive BMB. Prospective evaluation is ongoing in a validation set.
Comprehensive geriatric assessment (CGA) in men age 70 or over with localized prostate cancer.
Authors: Osborne Georgina E.C. , Gilbert Duncan Charles , Robinson Angus , Nikapota Ashok , McKinna Fiona , Villanueva Michelle , Ring Alistair E. 
Published: February 2017

184 Background: There has been a four-fold increase in incidence of prostate cancer (PC) in men age 70 or older in England in the last 30 years. Which treatment (surgery, radiotherapy, or surveillance) is right for which patient depends on a number of factors including the risk of death from competing causes and fitness for the proposed treatment. Objective assessments such as those included in a Comprehensive Geriatric Assessment (CGA) might be helpful in this regard. The primary objective of this study is to describe CGA scores of a cohort of older men with PC. The secondary objectives are to examine if a single score (the Vulnerable Elders Survey [VES-13]), is a suitable screening test for a full CGA and to assess whether scores predict radiotherapy toxicity. Methods: Patients age 70 and older with localised PC completed a CGA prior to commencement of radical radiotherapy. The CGA assessed WHO performance status (PS), activities of daily living (ADL), instrumental activities of daily living (IADL), Charlson co-morbidity index, number of medications, mini-nutritional assessment (MNA), social network index (SNI), G8 score, and VES-13. Participants had acute radiotherapy toxicity assessed 12 weeks post-treatment completion. Results: As of September 2013, 100 patients had been recruited. Median age was 74.5 (range 70 to 82). Ninety five percent of patients had a PS less than two. Using the VES-13 tool, 5.2% scored greater than two. 22.6% scored less than 14 on G8 scoring. Additionally, 13.5% were not fully independent on ADLs, 4.2% were not fully independent on IADLs, 32.3% scored greater than one on the Charlson Index, 12.3% had a history of depression or dementia, and 52.9% were on more than three prescription medications. Fourteen percent were at risk of malnutrition and 2.3% were malnourished according to MNA scores, 25.0% had SNI scores less than three and 9.3% of patients had fallen at least once in the preceding three months. Twelve week follow-up data regarding acute radiotherapy toxicity is currently being collected; these will be correlated with the CGA components and presented at the 2014 ASCO Genitourinary Cancers Symposium. Conclusions: These data demonstrate that many older men with localised prostate cancer are vulnerable according to a CGA. Correlations observed between radiotherapy toxicity and CGA scores would have important implications for therapeutic decisions.