bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the long noncoding RNA SChLAP1 as a prognostic tissue and urine biomarker in prostate cancer.
Authors: Feng Felix Yi-Chung , Zhao Shuang , Prensner John , Erho Nicholas , Schipper Matthew J , Shi Yang , Magi-Galluzzi Cristina , Siddiqui Javed , Davicioni Elai , Den Robert Benjamin , Dicker Adam , Karnes R. Jeffrey , Wei John Thomas , Klein Eric A. , Jenkins Robert B. , Chinnaiyan Arul M. , Mehra Rohit 
Published: February 2017

7 Background: Improved prognostic biomarkers are needed for localized prostate cancer. We undertook an unbiased large-scale analysis of genes associated with metastatic progression and validated the prognostic ability of the top candidate gene. Methods: Prostate cancer samples from prostatectomy patients were analyzed for gene expression using a clinical-grade, high-density Affymetrix GeneChip platform, encompassing >1 million genomic loci and assessed in a CLIA-certified laboratory. Nomination of prognostic candidate genes was performed on a discovery cohort (n=545) and validated on 3 independent cohorts (n=463). Multivariate analyses were performed for the primary endpoint of metastasis. The top prostate-specific gene was further evaluated in 208 additional tumor samples with a novel RNA in-situ hybridization (ISH) assay and in urine samples from 230 patients using PCR. Results: Of all known genes, the long noncoding RNA SChLAP1 ranked first for elevated expression in patients with metastatic progression by receiver-operator-curve analyses. Validation in three independent cohorts confirmed the prognostic value of SChLAP1. On multivariate modeling, SChLAP1 expression independently predicted metastasis within 10 years (odds ratio (OR) = 2.45, 95% confidence interval (CI) 1.70 – 3.53), death within 10 years (OR = 1.93, 95% CI 1.31 – 2.85), and biochemical recurrence within 5 years (OR = 1.76, 95% CI 1.28 – 2.41) with ORs comparable to Gleason score. Evaluation of SChLAP1 expression by RNA ISH confirmed a significant association with disease recurrence (OR = 1.99, 95% CI 1.06 – 3.73). Evaluation of urine SChLAP1 levels demonstrated increased expression in patients at higher risk for disease progression. Conclusions: We perform the largest high-throughput, unbiased study of prostate cancer prognostic biomarkers to date and discover SChLAP1 as a top gene predictive of metastatic progression. We validate SChLAP1 extensively with a clinical-grade assay. We show feasibility of a RNA ISH assay and a non-invasive urine test for SChLAP1. Our results, spanning 1,446 patients from 6 independent patient cohorts, suggest that SChLAP1 represents a very promising biomarker for aggressive clinical course.
Fluorescence-targeted laparoscopic lymph node dissection in prostate cancer.
Authors: Hruby Stephan , Englberger Christine , Lusuardi Lukas , Schaetz Tobias , Kunit Thomas , Magdy Ahmed , Hager Martina , Janetschek Guenter 
Published: February 2017

70 Background: Recently we have introduced fluorescence by means of Indocyanin Green(ICG) in addition to radio-guided dissection using Technetium 99(Tc99) for laparoscopic pelvic sentinel node dissection (Urology 2012). Hence we could show that ICG alone gave equal results compared to TC99. Since ICG visualizes the complete drainage system we have as an evolution now left the sentinel concept to completely remove this template. Methods: 38 consecutive men with intermediate and high risk prostate cancer have undergone targeted Lymphnode dissection during laparoscopic radical prostatectomy. 2ml ICG were injected transpeineally into each lobe under TRUS guidance. After removal of the complete ICG visualized Lymphnode template of each side, a standard ePLND was added as control. All Lymphnodes were evaluated by 250 ym sections and imunohistochemistry. Results: Transperineal Injection allowed for precise deposit without any periprostatic extravasation. Fluorescence stained (F+) nodes were found on both sides in all patients except one. In total 596 nodes (17,9 +-8,4/patient) were removed, of which 473 nodes (14,3 +- 8,51/pat.) were F+. LN Metastases were found in 15 pat.(39,5%), of which 2 pat. (5,3 %) had solitary micrometastases. In addition 3 patients (7,9 %) the LN contained Tumor Cell Cluster. No non-stained metastases were found in addition to F+ Metastases. Met outsi de the template of extended PLND occurred in 5 patients(27,8% of N+). Conclusions: Fluorescence-targeted lymphnode dissection allows to identify the lymphatic drainage of the prostate with great reliability. It proved to be more precise than extended lymphnode dissection in patients with intermediate and high grade prostate cancer
Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the SEARCH database.
Authors: McGinley Kathleen F. , Sun Xizi , Howard Lauren E. , Aronson William J. , Terris Martha K. , Kane Christopher J. , Amling Christopher L. , Cooperberg Matthew R. , Freedland Stephen J. 
Published: February 2017

73 Background: Performance of a pelvic lymph node dissection (PLND) with radical prostatectomy (RP) is critical for staging and treatment of high-risk prostate cancer (PC). Conversely, performance of a PLND in low-risk PC contributes to morbidity with minimal benefit. Robot-assisted laparoscopic RP (RARP) is associated with decreased PLND use. We evaluated PLND use over time, stratified by PC risk group and surgical technique. Methods: We used SEARCH to identify men who had open RP (ORP) or RARP from 2006-2013 with complete data. Univariable logistic regression was used to test the association between age, race, BMI, number of positive cores, AUA risk group, year, center, and surgical technique on PLND use. Multivariable logistic analysis was used to examine surgical technique and PLND performance stratified by AUA risk-group. Spearman correlation was used to examine temporal changes in PLND utilization stratified by risk-group and surgical technique. Results: 1,439 men met inclusion criteria. Of these, 66% had a PLND. On univariable analysis, age, year, number of positive cores, AUA risk group, center, and surgical technique were significantly associated with PLND performance (all p<0.02). On multivariable analysis, when adjusted for age, race, BMI, number of positive cores, year, and center, RARP was associated with a 89% decreased use of PLND in the low-risk group, 85% decreased in intermediate risk, and 86% decreased in high risk men (all p≤0.002). Over time, PLND was increasingly used with RARP in low-risk patients (p=0.022); a trend of increased PLND performance with RARP in high risk men was noted (p=0.077) reaching ~85% in 2012-2013 vs. ~95% in ORP. For ORP, PLND use did not significantly change over time except a trend of fewer PLND in low-risk men which decreased to ~35% (p=0.064) in 2012-2013. Conclusions: Regardless of risk group, PLND is markedly less likely to be performed when a RARP is done. While improved over time, PLND remains over-utilized in low-risk men and under-utilized in high risk men regardless of surgical technique.
Association of magnitude of cancer of the prostate risk assessment score change following biopsy gleason upgrade during prostate cancer active surveillance with adverse pathology at prostatectomy.
Authors: Leapman Michael S. , Ameli Niloufar , Chu Carissa , Welty Christopher J. , Hussein Ahmed , Cooperberg Matthew R. , Carroll Peter 
Published: February 2017

76 Background: The occurrence of pathologic upgrading in men with prostate cancer (PCa) managed with active surveillance (AS) is a cause for concern and may prompt treatment; however the degree to which upgrading impacts further risk status is unclear. We evaluated the association between the Cancer of the Prostate Risk Assessment (CAPRA) score and adverse pathological outcomes following biopsy Gleason upgrading in men with PCa on AS. Methods: We retrospectively evaluated men with low and intermediate risk PCa managed with AS at our institution between 1993 and 2013 who received a minimum of two biopsies. We assessed change in CAPRA score between initial diagnosis and Gleason upgrade at repeat biopsy. Among patients proceeding to radical prostatectomy, multivariate models incorporating CAPRA change and reclassified CAPRA score were constructed to evaluate factors associated with adverse pathology and time to treatment. Results: We identified 312 men with PCa on AS who experienced pathologic upgrade on surveillance biopsy at a median of 24 months (IQR 12-47) and at a median age of 65.7 years (IQR 61-71). The median CAPRA score at diagnosis was 1 (IQR 1-2), and median change at upgrade was +2 (IQR 1-3). 196 patients (63.0%) were reclassified to higher CAPRA scores at upgrade, while 108 (34.7%) had CAPRA classification that remained unchanged. Seven (2.3%) patients had a decrease in CAPRA risk category after biopsy upgrade. In a multivariate logistic regression model, reclassification to high CAPRA risk category at upgrade was significantly associated with adverse pathology at RP (OR=21.34, 95% CI 2.58-176.57, p=0.0097). Conclusions: Recalculated CAPRA score following biopsy Gleason upgrade during AS is a strongly associated with adverse surgical pathology among treated patients. This finding supports the role of refined risk reassessment in men with PCa on AS, particularly in those experiencing upgrading on subsequent biopsy.
Cost-effectiveness of a biopsy-based 8-protein prognostic assay to optimize treatment decisions in intermediate-risk early-stage prostate cancer.
Authors: Roth Joshua A. , Ramsey Scott David , Carlson Josh John 
Published: February 2017

77 Background: Clinico-pathologic factors alone are insufficient to predict the likelihood of progression of Gleason 3+3 and 3+4 prostate cancer at the time of biopsy. As a result, many patients receive treatment, despite having unaggressive tumors. There is a need for tests that provide a clearer picture of risk to enable more individualized treatment decisions. A novel prognostic assay (ProMark) that uses quantitative measurements of protein biomarkers has been validated to predict prostate cancer aggressiveness at the time of biopsy. Our objective was to evaluate the potential cost-effectiveness of using the 8-protein assay to inform treatment decisions. Methods: We developed a simulation model to estimate quality-adjusted life-year (QALY) and cost outcomes for assay and usual care (NCCN guidelines) strategies. The proportion of patients classified as low, intermediate, and high-risk by the assay and guidelines was derived from the assay’s validation study. Treatment distributions, costs, health state utilities, and mortality rates were derived from peer-reviewed literature. The health outcome impacts of the assay strategy come from increased use of active surveillance (AS) vs treatment, and we evaluated a base case increase in AS of 14.5% (vs usual care), and small and large shift scenarios with 7.8% and 20.2% increases, respectively. We calculated the incremental QALYs, costs, and cost-effectiveness ratio in each scenario. Results: The assay strategy was dominant in all scenarios evaluated. In the base case, the assay strategy resulted in 0.04 more QALYs and $700 less in costs. The small and large shift scenarios resulted 0.02 and 0.05 more QALYs, and $5 and $1,300 less in costs, respectively. Cost-effectiveness outcomes were most sensitive to the assay cost, the AS health state utility, and the proportion of low-risk patients receiving AS in usual care. Conclusions: Our results suggest that the 8-protein prognostic assay has the potential to be a cost-effective alternative to usual care in patients with Gleason 3+3 and 3+4 prostate cancer. Future studies will evaluate the impact of the assay on patient and physician treatment choices in real-world settings.
An impact of pelvic MRI (PMRI) to radiotherapy (RT) target volumes definition in prostate cancer patients (pts).
Authors: Rouvinov Keren , Mermershtain Wilmosh , Beloshicki Olga , Ariad Shmuel , Lavrenkov Konstantin 
Published: February 2017

78 Background: PMRI is a standard pre-RT evaluation procedure in pts with intermediate and high-risk prostate cancer. We conducted a retrospective study to evaluate an influence of PMRI to delineation of RT clinical target volume (CTV). Methods: Medical records of prostate cancer pts treated with intensity-modulated RT (IMRT) in single institution retrieved and examined retrospectively. Initial risk group affiliation was defined using D'Amico method. PMRI reports of pts with intermediate and high-risk prostate cancer were reviewed and risk group affiliation was re-defined in regards of T- and N-stage. IMRT treatment plans were re-assessed. In regards to PMRI T-stage, extra-capsular extension (ECE) and seminal vesicles invasion (SVI) were included to high-dose CTV. Pelvic lymph nodes (PLN) were planned to treat in all high-risk pts. PLN considered pathological by PMRI were included to separate CTV to receive RT dose higher than unaffected PLN stations. Results: Between 2008 and 2014, 169 pts with intermediate and high-risk prostate cancer underwent PMRI at around 1 month before commencing IMRT. Initially, 89 pts were affiliated to intermediate-risk and 80 to high-risk group. In general, PTV-changes based on PMRI data required in 77 pts (45.5%). Thirty seven of 89 intermediate-risk pts (41.6%) have been switched to high-risk group, necessitating irradiation of PLN. ECE and SVI were included to high-dose CTV in 64 (37.8%) and 29 pts (17.2%) respectively. PLN were thought pathological in 10 pts (5.9%), which demanded contouring of a separate CTV. Conclusions: In our series PMRI-scans had a significant impact on RT target coverage decision in pts with intermediate and high-risk prostate cancer.
A biomarker panel associated with distant metastasis in prostate cancer patients treated with radiotherapy as prognostic for DM in a large cohort of prostatectomy patients.
Authors: Pollack Alan , Erho Nicholas , Noronha Roshan , Lam Lucia L.C. , Buerki Christine , Abraham Sakhi , Klein Eric A. , Karnes R. Jeffrey , Den Robert Benjamin , Dicker Adam , Ishkanian Adrian , Davicioni Elai , Feng Felix Yi-Chung , Stoyanova Radka 
Published: February 2017

8 Background: A number of biomarkers related to cell cycle, angiogenesis or apoptosis have been found to be associated with patient outcome in tissue samples from men treated with first line radiation therapy in RTOG clinical trials using immunohistochemical staining and analysis. In a prior study, four biomarkers (Ki-67, MDM2, p16 and Cox-2) and clinical covariates were included in a model of distant metastasis (DM; Pollack et al, Clin Cancer Res, 2014 [epub ahead of print]) risk. The current study tested the hypothesis that these genes are prognostic for DM in men treated primarily with total prostatectomy using RNA expression profiling. Methods: RNA fromprostatectomy samples from Cleveland Clinic (CC, n=182); Mayo Clinic (MC)-I (n = 545) and II (n=235); Memorial Sloan Kettering Cancer Center (MSKCC, n=131); Erasmus Medical Center (EMC, n=48) and Thomas Jefferson University (TJU, n=130) were profiled using 1.4 million RNA features. A Cox proportional hazards model was built on the MC-I training set to combine the 4 biomarkers into a prognostic risk score (4BMSig). 4BMSig was subsequently evaluated for its prognostic significance separately and in combination with clinical risk factors (biopsy Gleason Score, cT-category and Preop-PSA) for DM. Results: 4BMSig was found to discriminate DM patients significantly for the MC-II (AUC = 0.66, p < 0.001), CCF (AUC = 0.68, p < 0.001), and MSKCC (AUC = 0.71, p = 0.04) datasets, and achieved borderline significance for EMC (AUC = 0.70, p = 0.06). 4BMSig did not discriminate DM in the TJU dataset (only 10 DM events). Pooled multivariable analysis (n = 726) with clinical covariates revealed that 4BMSig is a strong independent prognostic covariate for DM (p < 0.001) and prostate cancer specific mortality (p = 0.005). Conclusions: The four genes identified previously as being associated with DM in radiotherapy patients were incorporated herein into 4BMSig, which was found to have potential as a pretreatment prognostic DM risk assessment tool for men treated with prostatectomy. Further validation would consist of testing 4BMSig from RNA in diagnostic tissue from prostate cancer patients prior to prostatectomy.
Expression of the leukocyte chemoattractant chemerin in human prostate tumors.
Authors: Pachynski Russell Kent , Zabel Brian , Leong Weng-In , Crowder Robert , Peehl Donna , Butcher Eugene 
Published: February 2017

81 Background: The infiltration of immune cells into the tumor microenvironment can regulate growth and survival of neoplastic cells. Several studies have shown a correlation between increases in the number of effector immune cells present in a tumor and clinical outcomes in many human tumors, including prostate. The field of prostate cancer immunotherapy continues to grow, with sipuleucel-T already approved and a recombinant vaccinia-PSA (Prostvac) currently in a Phase III clinical trial. Recent studies have shown immune cell infiltration into prostate tumors after systemic administration of sipuleucel-T, suggesting infiltration of these cells may be a key step in the mechanism of action. Methods: Here, in a survey of public whole genome expression datasets we found that the gene for chemerin (RARRES2), a widely expressed endogenous chemoattractant protein for immune cells, is downregulated in prostate cancer. In mouse models, we have previously shown that forced re-expression of chemerin at sites of tumor results in an increase in immune cell infiltration (e.g. NK and T cells), as well as significantly reduced tumor growth (Pachynski JEM 2012). Results: In addition to this published analysis, using RT-qPCR we have gone on to confirm that human prostate tumors have significantly less chemerin (RARRES2) compared to normal prostate tissue. Preliminary immunohistochemistry results in human tumors using an anti-human chemerin antibody, are consistent with our qPCR results, suggesting human prostate tumors downregulate chemerin during their malignant transformation. Conclusions: We have shown, for the first time, that human prostate tumors downregulate chemerin compared to normal prostate tissue. We hypothesize that this is one mechanism of “immune escape.” Therapeutic forced re-expression of chemerin in human tumors may restore anti-tumor immunity within the tumor microenvironment resulting in slowed growth and regression of established tumors. Additionally, chemerin’s ability to recruit NK and T cells into the tumor microenvironment may make it an ideal therapy to combine with other treatments aimed at boosting the immune response, such as sipuleucel-T or checkpoint inhibition (e.g. anti-CTLA4, anti-PD1/PDL1).
Charlson score to predict overall survival and cancer-related death in elderly patients featuring high-risk prostate cancer.
Authors: Ordaz Guzman , Sanchez-Salas Rafael , Sivaraman Arjun , Joniau Steven , Bianchi Marco Giorgio , Briganti Alberto , Spahn Martin , Bastian Patrick , Chun Jongi , Chlosta Piotr , Gontero Paolo , Graefen Marcus , Karnes R. Jeffrey , Marchioro Giansilvio , Tombal Bertrand F. , Tosco Lorenzo , Van Der Poel Henk , Cathelineau Xavier ,   European Multicenter Prostate Cancer Clinical and Translational research group (EMPaCT), Lier, Belgium
Published: February 2017

84 Background: In elderly patients, Charlson score among other features, might allow clinicians to limit the use of aggressive adjuvant treatment strategies or even primary surgical treatment to those who might not achieve benefit during their lifetime. Methods: Retrospective analysis, 7,650 case multicenter high-risk prostate cancer (Pca) radical prostatectomy database selecting >= 70 years old cases. We predicted death from all causes (DAC) and cancer related death (CRD) including all clinical and pathological data. Multivariable analysis were performed to identify independent predictors of DAC and CRD with binary logistic regression, using STATA® software, version 13.1. Results: 2,106 patients from 14 high-volume centers were included. Mean age was 72.8 years (SD 2.46). 206 (9.78%) patients were classified as ASA 3-4 and 497 (23.6%) as CS >=1. Mean PSA was 21.7 ng/ml (SD 50.5). At final histopathology, 800 (38%) had pT3b-T4 disease, GS was 8-10 in 589 (28%), LNI was found in 518 (24.6%) and 822 (39%) PSM. Adjuvant RT, ADT and RT+ADT were administered in 359 (17%), 391 (18.6%) and 437 (20.7%), respectively. Mean follow up was 5.18 years (DS 4.47). BCR occur in 649 (30.8%) and CF in 150 (7.1%) of which distant in 59 (2.8%). Total deaths accounted 341 (16.2%) and CRD for 100 (4.7%) cases. Conclusions: Multicenter data confirms that elderly patients survival harboring high risk prostate cancer will benefit from radical treatment if they are Charlson score 1 or less. [Table: see text] [Table: see text]
Accuracy of manual and automated rectal contours using helical tomotherapy image guidance scans during prostate radiotherapy.
Authors: Scaife Jessica Elizabeth , Harrison Karl , Drew Amelia , Cai Xiaohao , Lee Juheon , Schonlieb Carola-Bibiane , Sutcliffe Michael , Parker M Andy , Freeman Sue , Romanchikova Marina , Thomas Simon , Jena Raj , Bates Amy , Burnet Neil 
Published: February 2017

94 Background: Prostate radiotherapy can be delivered using daily image-guided helical tomotherapy. Previous work has shown that contouring the rectum on the kV planning CT scan has a Jaccard conformity index (JCI) of 0.78 for different oncologists (inter-observer variability) and 0.82 for a single oncologist (intra-observer variability) (Lutgendorf-Caucig C et al. Feasibility of CBCT-based target and normal structure delineation in prostate cancer radiotherapy: multi-observer and image multi-modality study. Radiother Oncol. 2011;98(2):154-61.). Using the daily image guidance MV CT scan we have developed automated methods to contour the rectum in order to investigate the dose delivered over a course of treatment. We sought to quantify the accuracy of MV manual and automated contours. Methods: A single oncologist (JES) contoured the rectum on 370 MV scans for 10 participants treated with helical tomotherapy to prostate and pelvic lymph nodes. Accuracy of MV manual contours was tested using a scalar algorithm to enlarge and reduce the contours and intra-observer re-contouring at a 3-month interval. Automated contouring, incorporating the Chan-Vese algorithm, was developed and outputs were compared with manual contours. Results: JES could identify differences in MV manual contour size at the level of ±2.2 mm, equivalent to 1.7 pixels. The median JCI for MV re-contouring was 0.87 with inter-quartile range (IQR) 0.78 to 0.90. When compared with manual contours, automated outputs had a median JCI of 0.79 (IQR 0.74 to 0.79). These results were obtained after 3 iterations, each taking less than 10 seconds. Conclusions: Manual contouring using MV scans was accurate, at a level of approximately 2 mm, and reproducible, with JCI of 0.87. The time taken to contour was approximately 20 minutes per scan. Automated contouring was also reproducible with JCI of 0.79 and, in contrast, took less than a minute per scan. Both manual and automated methods produced results comparable to those for contouring using kV scans. We plan to use auto-contouring to calculate accumulated dose to the rectum in an initial cohort of 100 participants. These doses will be correlated with toxicity as part of the VoxTox Study.