bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain metastasis in metastatic renal cell carcinoma: Predictive factors of occurrence and survival with or without antiangiogenic therapy.
Authors: Vanhuyse M. , Penel N. , Caty A. , Fumagalli I. , Alt M. , Zini L. , Adenis A. 
Published: February 2017

394 Background: We analyzed renal cell carcinoma (RCC) brain metastasis (BM) risk factors and compared BM occurrence in advanced RCC treated with or without antiangiogenic agents (AAA). Methods: Data from all consecutive metastatic RCC patients (pts) treated in the Northern France Cancer Center (Centre Oscar Lambret, Lille) between 1995 and 2008 were reviewed. Eligible pts had histologically confirmed advanced RCC without synchronous BM at the time of metastasis diagnosis. Bellini duct and neuroendocrine carcinoma and sarcoma were excluded. AAA were sorafenib, sunitinib, bevacizumab, temsirolimus, and everolimus. Characteristics of the two groups, treated with or without AAA, were compared with a Fisher exact test. Impact of AAA on overall survival (OS) and BM-free survival (BMFS) was explored by Kaplan-Meier method and adjusted to confounders parameters in a Cox model. Results: A total of 199 pts with advanced RCC were identified, 51 treated with AAA and 148 treated without AAA. The median follow-up duration was 40 months. BM occurred in 35 pts. As expected in this retrospective analysis, characteristics between AAA treated and non AAA treated groups were unbalanced for 11 parameters including age, Motzer prognostic factors, performance status and favoring better prognostic factors in the AAA treated group. The median overall survival was 24 months. Overall survival was higher in patients with AAA versus patients without AAA (31 versus 18 months, hazard ratio (HR) 0.67 [0.45–0.97], p=0.038). The AAA were not associated with better BMFS (HR=0.58 [0.26–1.30], p=0.187). The alkaline phosphatase was an independent prognostic factor for BM (p=0.05). In multivariate cox model, AAA treatment improved the OS (adjusted HR 0.60 [0.38–0.94] but not the BMFS (adjusted HR 0.53 [0.22–1.32]. Conclusions: In this retrospective single center study, elevated alkaline phosphatase is a predictive factor for brain metastasis in metastatic RCC. AAA significantly improved overall survival in advanced RCC without any significant impact on brain-metastasis-free survival. No significant financial relationships to disclose.
Cost comparison of laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy.
Authors: O'Malley R. L. , Kowalik T. , Hayn M. H. , Collins T. B. , Kim H. L. , Schwaab T. 
Published: February 2017

402 Background: Although nephron-sparing surgery is the standard of care for the treatment of small renal masses, partial nephrectomy (PN) remains under-utilized. A potential reason for the discrepancy is the desire for minimally invasive surgical approaches but limitation of the advanced laparoscopic techniques needed to perform PN. Robot-assisted surgery has eased the transition to minimally invasive prostate surgery and may also do so for PN, although some believe costs may be prohibitive. The purpose of this investigation was to quantify the cost of robot-assisted PN (RAPN) compared to laparoscopic PN (LPN). Methods: An institutional renal tumor database was used to identify consecutive patients with normal renal function who underwent RAPN for a localized renal mass by a single surgeon who had performed < 25 previously. The 35 RAPN patients were compared to the last 35 similar patients who underwent LPN by a surgeon who had performed > 150 previous LPNs. Surgical outcomes were compared. Because room time, length of stay and Cxs were similar, cost was compared based only on the total operating room charges (ORC). Total ORC included surgeon and anesthesia fees, as well as labor and supply costs. The depreciation of the robot was included in the ORC as a higher per unit time charge than for LPN. Data on charges were available for the first 29 RAPN patients which were then compared to the last 29 LPN patients. Results: Dates of operation ranged from October 2008 to July 2009 for LPN and January 2010 to August 2010 for RAPN. Patient and tumor characteristics were similar between groups, except tumor size, which was larger in the RAPN group (3.6 ± 1.8 cm vs. 2.7 ± 0.9 cm, p = 0.007). Cxs, surgical and oncologic outcomes were similar. Mean ORC (IQR) for the LPN group was $28,606 (4,796) and for the RAPN group was $30,874 (20,389) representing a difference of $2,269. If you subtract an additional $858 for the average yearly inflation rate (3%), the difference is $1,411. Conclusions: RAPN is a safe option with perioperative outcomes similar to those of LPN performed by an experienced surgeon. A cost difference of $2,269 per procedure as estimated using ORC may decrease as the experience of the operating room staff and surgeon increase. No significant financial relationships to disclose.
Use of genetic instability to predict biochemical recurrence in intermediate-risk prostate cancer.
Authors: Bristow R. G. , Ishkanian A. S. , Malloff C. , Milosevic M. , Pintilie M. , van der Kwast T. , Lam W. 
Published: February 2017

42 Background: Biomarkers of local and systemic recurrence are needed to individualize patient risk categories and better define treatment. We hypothesized that genomic instability, as measured by percent genome alteration (PGA), can predict for biochemical failure in intermediate- risk prostate cancer. Methods: High-resolution array comparative genomic hybridization (arrayCGH) was used to identify PGA in frozen biopsies from 120 intermediate-risk prostate cancer patients. Our cohort included 39 T1c tumors, 78 T2 tumors and 2 T3 tumors. The Gleason score was 6 in 32 tumors, 7 in 82 tumors and 8–9 in 6 tumors. PSA ranged from 2.1–33 (median 8.0). Patients were treated with intensity-modulated radiotherapy (IMRT) with doses of 75.6–79.8 Gy in 1.8–2Gy fractions, or 60–66 Gy in 3 Gy fractions.. Twenty-five percent of patients also received neoadjuvant-concurrent bicalutamide (150mg po od). Biochemical failure, defined by Phoenix criteria or the initiation of salvage therapy, was observed in 35 patients after median follow-up of 5.4 years (range 0.9–8.8). Results: Array CGH showed variable PGA ranging from <1% to 35% (median 6.7%). PSA and the use of hormonal therapy independently influenced biochemical relapse, and formed a baseline clinical model to which PGA was added. PGA was found to be a strong predictor of biochemical relapse (p<0.0001) independent of the clinical prognostic factors (pre-treatment PSA, Gleason score and T-category). PGA was also found to be associated with unique tumour suppressor and oncogene gene loci clusters involved in genetic stability (e.g. loss of PTEN, p53, RB, NKX3.1, ATM, PARP-1 and gain of c-MYC; validated by in situ FISH). Conclusions: This is the first report to show genetic instability can independently predict for biochemical recurrence in intermediate-risk prostate cancer. Current studies are associating specific gene loci regions with clinical outcome. Our results could provide a way forward for individualized medicine for non-indolent prostate cancer based on initial daignostic biopsy material. Supported by Prostate Cancer Canada, The Terry Fox Foundation and the Canadian Cancer Society. No significant financial relationships to disclose.
Association of PTEN loss with outcome of patients (pts) with early high-risk prostate cancer (CaP) treated with adjuvant docetaxel following radical prostatectomy (RP).
Authors: Keizman D. , Zhang Z. , DeMarzo A. , Gurel B. , Lotan T. , Hicks J. , Rosenbaum E. , Antonarakis E. S. , Carducci M. A. , Eisenberger M. A. 
Published: February 2017

43 Background: Loss of the PTEN tumor suppressor and subsequent activation of the PI3K pathway is common and has potential clinical and therapeutic value in CaP. We examined the PTEN status of primary tumors in pts who underwent adjuvant docetaxel tx in a prospective clinical trial. Methods: Of the 77 pts enrolled in a prospective multi-institutional adjuvant docetaxel trial (TAX 2501, J Urol 2007), we prospectively collected 56 primary tumor pathology specimens suitable for analysis of PTEN status by immunoreactivity (IHC) and/or fluorescence in situ hybridisation (FISH) assay. Protocol defined progression included a PSA of ≥ 0.4 ng/mL, radiological/pathological evidence of recurrent disease or death from any cause. Univariate and multivariable analyses based on the Cox proportional hazards regression model were used to analyze the independent association of PTEN and other known prognostic factors with progression free survival (PFS). Results: PTEN loss was observed in 37/56 pts (66%). Pts with PTEN loss vs detectable PTEN were balanced regarding clinical stage, combined Gleason score, seminal vesicles and surgical margins involvement, and lymph nodes status. Pts with a detectable PTEN had a significantly higher pre-RP PSA (median 14 vs 8.6 ng/mL, p=0.015). 41/56 (73.2%, median followup of 37.5 months, range 10.4 to 44.5) progressed with an overall median PFS of 13 months (mos) (95% CI 9.8–15.8). Independent prognostic factors of progression by multivariate analysis were: seminal vesicles involvement (HR 2.19, p=0.024), combined Gleason score 9–10 (HR 2.46, p=0.027) and PTEN loss (HR 2.36, p=0.037). PFS on pts without PTEN loss (median not reached at a followup time of 37.5 mos, range 10.4–44.5 mos) was significantly longer (log rank test, p = 0.026) compared to those with undetectable PTEN (median PFS 12.9 mos, 95% CI 9.7–15.3). Conclusions: PTEN loss may be an independent prognostic factor associated with poorer outcome of pts with early high-risk CaP treated with adjuvant docetaxel following RP. These findings may have important prognostic and therapeutic implications in CaP. No significant financial relationships to disclose.
Variation in UDP glucouronyltransferase (UGT) genes associated with prostate cancer mortality.
Authors: Kohli M. , Mahoney D. W. , Chai H. S. , Hillman D. W. , Rider D. R. , Costello B. A. , Cerhan J. R. 
Published: February 2017

44 Background: We investigated the association of germline genetic variation in hormone biosynthesis and metabolism genes with prostate cancer specific mortality in a cohort of advanced prostate cancer patients. Methods: We successfully genotyped 852 single nucleotide polymorphisms (SNPs) from 97 genes in a cohort of 267 advanced prostate cancer patients at the time of progression to castration recurrence (CRPC) during on-going androgen ablation. Tagging SNPs with minor allele frequency (MAF) of >5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. Medical records were queried for cause of death. The primary endpoint of time to prostate cancer specific mortality (PCSM), was pre-defined as time from development of CRPC to death from prostate cancer progression. Principle components analysis was used for gene-levels tests, and to account for multiple testing, we calculated the false discovery rate (FDR). For SNP level results, hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox regression. Results: The median age of the cohort was 72 years at CRPC. 43% had a Gleason score (GS)=8-10, 33% a GS=7, and 24% a GS<7. After a median follow-up of 1.8 years (IQ range: 0.8–3.3 years), 139 patients died, of which 107 were due to prostate cancer progression. In unadjusted gene level analyses, UGT1A7 (p=0.0059; FDR=0.19), UGT1A10 (p=0.0017; FDR=0.17) and UGT1A3 (p=0.0037; FDR=0.18) were associated with PCSM. After adjusting for age and GS, SNPs strongly associated with PCSM are listed in the Table . Conclusions: Variation in UGT genes involved in hormone metabolism yield prognostic information in CRPC. Further validation is needed to develop these as prognostic biomarkers. [Table: see text] No significant financial relationships to disclose.
Caveolin-1 as a biomarker of Src family kinase/Abl inhibition in castrate-resistant prostate cancer.
Authors: Carthon B. C. , Tahir S. , Araujo J. C. , Wen S. , Gallick G. E. , Logothetis C. , Thompson T. C. 
Published: February 2017

45 Background: Bone metastases cause significant morbidity in men with castrate-resistant prostate cancer (CRPC). Caveolin-1 (Cav-1), a Src kinase substrate, is overexpressed in primary prostate cancer (PCa) and in PCa bone metastases. In addition, PCa-derived and secreted Cav-1 contributes to malignant progression. We reasoned that Cav-1 may serve as a biomarker of dasatinib (a Src family kinase [SFK]/Abl inhibitor) activity in CRPC patients enrolled in a phase II clinical trial of docetaxel plus dasatinib. Methods: Levels of prostate-specific antigen (PSA), Cav-1, and markers of bone turnover were measured from baseline and cycle-2, day-1 samples from patients (n = 32) enrolled in this trial. Changes in these markers were stratified by response (responders [R] vs. nonresponders [NR]) and by predominant disease site (lymph node vs. bone). We evaluated Cav-1 expression in human PCa bone metastases samples from trial patients by immunohistochemistry. In parallel, Cav-1 secretion in response to dasatinib treatment was analyzed in PCa cells and osteoblasts. Results: Serum Cav-1 levels correlated directly with PSA levels in responding patients with node-positive disease (R vs. NR, p = 0.08) but correlated inversely in responding patients with bone-predominant disease (R vs. NR, p = 0.001). Serum from a separate cohort of patients treated with docetaxel only showed no effect on serum Cav-1 levels (R vs. NR, p = 0.85). Levels of Cav-1 were high in the active OBLs in bone specimens with PCa metastases, but not in bone specimens without metastases. Dasatinib treatment led to reduced secretion of Cav-1 in PC-3 and DU145 PCa cells but to increased secretion of Cav-1 in primary mouse osteoblasts or pre-osteoblast MC3T3-E1 cells. Conclusions: Our results suggest that serum Cav-1 serves as a novel discriminating biomarker for SFK/Abl inhibition in both node-positive and bone-metastatic CRPC. The expression of Cav-1 in OBLs of patients with PCa bone metastases suggests that tumor-associated OBLs are an important source of Cav-1 production in bone marrow. Our data provide evidence that the increase in serum Cav-1 in these patients with bone disease likely occurs through a direct effect of dasatinib on osteoblasts. No significant financial relationships to disclose.
Use of protein-network modeling of prostate cancer gene signatures to investigate essential pathways in disease recurrence.
Authors: Chen J. L. , Li J. , Stadler W. M. , Lussier Y. A. 
Published: February 2017

46 Background: Numerous molecular pathways have been implicated in aggressive prostate cancer. However, it has been difficult to gain an overview of the dominant pathways involved. By analyzing multiple prostate cancer gene signatures of poor prognosis through a protein interaction network, we are able to in an unbiased manner prioritize shared key biological mechanisms. Methods: We evaluate prostate gene signatures through a previously published Single Protein Analysis of Network (SPAN) methodology to develop a prostate cancer network signature. We assess this signature using a Gene Ontology based information-theoretic metric as well as assess its prognostic ability in an independent clinical dataset. We then examine the interconnectivity of the network signature to develop a phenotype-pathway map that provides an executive summary of critical mechanisms involved in advanced prostate cancer. Results: Of the 13 prostate cancer signatures that were evaluated, nine gene signatures plus a previously unpublished gene signature met criteria for evaluation. SPAN analysis of these protein interactions resulted in a 42-gene network signature. This network signature had the highest information-theoretic score based on Gene Ontology annotation similarity. Further, the signature identified a statistically significant survival difference (p=0.009) in a cohort of men with prostate cancer in an independent dataset. Additional analysis of the signature generated a phenotype-pathway map that not only recapitulated the centrality of PIK3/NF-κB signaling, but also highlighted less well-established pathways such as the JAK2 kinase activation cascade. Conclusions: SPAN analysis provides a robust means of abstracting disparate prostate cancer gene expression signatures into clinically useful, prioritized pathways that may ultimately serve as attractive, therapeutic targets. No significant financial relationships to disclose.
Utility of PCA3 urine assay in Japanese men undergoing prostate biopsy.
Authors: Okihara K. , Ochiai A. , Kamoi K. , Miki T. 
Published: February 2017

50 Background: Studies have shown the high specificity of PCA3 urine assay for biopsy detection of prostate cancer in European and American. We determined the diagnostic performance of PCA3 urine test in predicting prostate cancer in Japanese men. Methods: The study group included 261 men who underwent extended prostate biopsy at our institutions. 79 men of them had repeated biopsy. In all cases, race was Asian. Urine specimens were collected after digital rectal examination. On PROGENSA PCA3 assay, PCA3 score was calculated using PCA3 mRNA copy divided by PSA mRNA copy. PCA3 score was correlated with biopsy outcome and compared with serum PSA and free-total PSA. Results: 257 urine samples collected were successfully analyzed (i.e., the informative specimen rate was 98%). Biopsy revealed prostate cancer in 104 men (40%). There was no significant relationship between serum PSA and PCA3 score. PCA3 score in prostate cancer was significantly higher than that in negative (median 54.5 vs 17.0, p<0.001). The probability of positive biopsy increased as PCA3 score increased. Using a PCA3 cutoff value of 35.0, sensitivity, specificity and diagnostic accuracy were 65%, 75% and 71%, respectively (p<0.01). Area under the curve (AUC) for PCA3 score was 0.757 and AUC for serum PSA was 0.599 in all men. There was a significant difference in AUC between PCA3 score and serum PSA (p<0.001). In men with serum PSA 4 to 10ng/ml, AUCs of PCA3 score, free-total PSA, and serum PSA were 0.759, 0.681, and 0.542, respectively. Conclusions: The specificity of PCA3 urine assay was high for detection of prostate cancer in Japanese men. PCA3 urine assay could improve the prediction for prostate cancer and help better decision making for prostate biopsy. No significant financial relationships to disclose.
Germ-line single nucleotide polymorphism (SNP) predictors of progression-free survival and overall survival in patients with advanced prostate cancer treated with androgen-deprivation therapy (ADT).
Authors: Campbell M. T. , Jung J. , Philips S. , Mohammadi Y. , Carr K. A. , Davis T. L. , Li L. , Sweeney C. , Skaar T. C. , Hahn N. M. 
Published: February 2017

51 Background: Significant variation in response duration and overall survival exists among prostate cancer (PCa) patients treated with ADT. Germ-line SNPs affecting function of genes critical to hormone synthesis, transport, metabolism, binding sites, and degradation may contribute to variability in clinical outcomes observed in PCa patients treated with ADT. Methods: Between 1/07 and 10/08, all PCa patients seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a peripheral blood sample. Only patients with confirmed ADT initiation dates were included in this analysis. Germ-line DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit (Applied Biosystems). The chip included genes critical to hormone signaling, transport, and elimination pathways with minor allele frequencies > 5%. Patients were followed for progression-free survival (PFS) and overall survival (OS) endpoints. Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: 107 patients with PCa initiated on ADT enrolled. Demographics included: age (median)–69 yrs, prostate specific antigen (PSA) (median)–28.0 ng/ml, PSA doubling time (median)–4.9 months, biochemical/metastatic–25%/75%, concurrent anti-androgen therapy–44%. No clinical parameters were associated with PFS and OS. Significant SNP associations with PFS and OS are summarized in the Table. Conclusions: Interpatient differences in hormone pathway germ-line SNPs may contribute to variability in clinical outcomes in patients treated with ADT. [Table: see text] [Table: see text]
Use of germ-line single nucleotide polymorphisms (SNPs) in drug transporters (ABCG2/ABCB1) and tubulin (TUBB4) to predict survival in patients with metastatic castrate-resistant prostate cancer (CRPC) receiving docetaxel.
Authors: Hahn N. M. , Jung J. , Philips S. , Patel Y. R. , Carr K. A. , Mohammadi Y. , Magjuka D. , Li L. , Sweeney C. , Skaar T. C. 
Published: February 2017

58 Background: Multiple treatment options now exist for metastatic CRPC patients (pts). Germ-line SNPs in docetaxel (D) transport, metabolism, binding site, and degradation genes may contribute to variability in outcomes observed in D treated CRPC pts. Methods: Between 1/07 and 10/08, all PCa pts seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a blood sample. Only CRPC pts treated with D were included in this analysis. Germ-line DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit (Applied Biosystems). The chip included genes critical to D signaling, transport, and elimination with minor allele frequencies > 5%. Pts were followed for progression-free (PFS) and overall survival (OS). Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: 60 pts with metastatic CRPC initiated on D enrolled. Demographics included: age (median) – 69 yrs, ECOG PS 0– 40%, prostate specific antigen (PSA) (median) – 129.9 ng/ml, PSA doubling time (median) – 1.8 months, visceral mets –25%. No clinical parameters were associated with PFS and OS. Significant SNP associations are summarized below. Conclusions: Differences in germ-line ABCG2, ABCB1, and TUBB4 SNPs may contribute to variation in clinical outcomes in CRPC pts treated with D. [Table: see text] [Table: see text]