bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective evaluation of prescribing preferences (PPref) by U.S.-based oncologists in the postdocetaxel mCRPC patient.
Authors: Ryan Charles J. , Green Mark R. , Britton Susan L. , Buettner Arden , Lankford Maria , Neely Douglas 
Published: February 2017

258 Background: In May 2013 we studied the PPref of 90 U.S.-based medical oncologists (MOs) in the setting of various progression patterns during/after docetaxel-prednisone (DP) therapy for mCRPC using a validated, proprietary, live, case-based market research tool. A core case scenario with 4 DP therapy outcomes was constructed. Data were acquired using blinded audience response technology. Research support sources were double blinded. Methods: Core case - 59 y.o. with radical prostatectomy followed by PSA failure at 15 months (MOS) followed by salvage RT. 16 MOS post RT followed by rise in PSA and 3.5 cm pelvic node followed by over 42 MOS he responds to multiple systemic therapies (ST) including CAB, anti-androgen withdrawal, sipuleucel-T (Provenge) therapy, abiraterone-prednisone (AP). Now again has PSA progression, increasing bone disease and bone related symptoms followed by initiation of DPCT. PPref for 4 outcomes of DP were probed: (1.) 6 cycles (cy) of DP 75 mg/m2 Q 3 wk followed by pain elimination and PSA response followed by stop of DP due to cumulative myelosuppression and progressive fatigue. The pt. is more active off CT and he is PS1. 3 MOS later followed by asymptomatic 30% rise in PSA. (2.) 4 cy of DP followed by decrease in PSA, bone pain, and node size. Prior to cy 6, he has asymptomatic PSA progression. (3.) 4 cy of DP → decrease in PSA, node size, and bone pain. Prior to cy 6, he has PSA and pain progression. (4.) 2nd cy of DP followed by progression as best response, with increased bone pain, PSA, and pelvic nodal disease. Results: See Table. Conclusions: Second-line PPrefs following DPCT were scenario dependent. ENZ-based therapy is most common, even in this AP refractory patient population. Chemotherapy selection is more likely in the presence of more rapid and symptomatic disease progression. Despite the availability of active therapies, surveillance is still chosen by many in asymptomatic patients. [Table: see text]
Using NBN to predict biochemical relapse following image-guided radiotherapy (IGRT) for intermediate-risk prostate cancer (IR-PCa).
Authors: Berlin Alejandro , Lalonde Emilie , Zafarana Gaetano , Sykes Jenna , Ramnarine Varune Rohan , Lam Wan , Meng Alice , Milosevic Michael , van der Kwast Theodorus , Boutros Paul C , Bristow Robert Glen 
Published: February 2017

26 Background: Despite the use of clinical prognostic factors, 20 to 40% of patients with intermediate-risk prostate cancer (IR-PCa) fail local treatment for unexplained reasons. Given that an accurate DNA damage response (DDR) may be associated with genetic instability and radioresponse, we investigated whether copy number alterations (CNAs) in DDR genes are predictive or prognostic following local treatment. Methods: Using array comparative genomic hybridization (aCGH), we characterized CNAs in biopsies derived from 126 IR-PCa pts. who underwent image-guided radiotherapy (IGRT). We studied the DDR-sensing genes: MRE11A, RAD50, NBN, ATM, and ATR. The IGRT cohort (median dose: 76.4Gy; median follow-up: 7.8yrs) was compared to a radical prostatectomy (RP) cohort (154 pts. from Memorial Sloan-Kettering Cancer Center database; median follow-up: 4.8yrs). CNAs were then tested for their independent prognostic capability using Kaplan-Meir method and Cox proportional hazard models. Results: In our IGRT cohort, m,ost frequent DDR gene CNAs were: NBN 20 of 126 (15.9%), ATR 11of 126 (8.7%), and ATM 7 of 126 (5.5%). NBN CNAs were mainly gains (19/20) and strongly correlated with increased NBN-mRNA abundance compared to NBN-neutral cases (p=0.016). CNAs in DDR genes were not associated with GS, prostate-specific antigen, or T-stage. Importantly, NBN gain ranked among the top 3.3% of all genes in terms of its strength of association with the percent of the genome altered (PGA). After adjusting for clinical factors in a multivariate model, NBN gain was a significant independent predictor of 5 years-biochemical relapse-free rate (bRFR) following IGRT (48.6% versus 78.8%; HR = 3.14, 95% CI: 1.42-6.94, p=0.004). No DDR CNA was prognostic in the RP cohort. Increased NBN mRNA expression correlated to radioresistance in vitro (i.e. clonogenic surviving fraction after 3Gy) in five prostate cancer cell lines (R2= 0.665). This relationship was not observed for any of the other DDR genes. Conclusions: NBN copy number gain or increased expression correlates with tumor genomic instability, decreased bRFR (IGRT- but not surgery-treated pts.) and intrinsic prostate cancer cell radioresistance. If validated in independent IGRT cohorts, NBN gain could be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches.
Exosomal microRNA as prognostic biomarkers in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Kohli Manish , Huang Xiaoyi , Yuan Tiezheng , Sun Zhifu , Costello Brian Addis , Quevedo Fernando , Tan Winston , Nandy Debashis , Longenbach Sherri , Wang Liang 
Published: February 2017

260 Background: The purpose of this study was to evaluate cell free nucleic acid based biomarkers for prognosis in mCRPC stage. Methods: Uniformly collected blood from mCRPC patients was processed for plasma which was used for exosomal RNA extraction. RNA sequencing was applied to examine microRNA (miRNA) profiles initially in a discovery cohort of 23 mCRPC patients. The sequences from fastq files were mapped to human miRBase (release 19) for known miRNA read counts. A software package (miRDeep2) was used for novel miRNA prediction. Cox regression was used for association of candidate miRNAs with overall survival (OS), defined as time from development of mCRPC to death or last follow up after adjusting for Gleason Score (GS) and time on androgen deprivation (AD) for hormone sensitive disease. miRNAs significantly associated with OS (FDR<0.05) were then validated in an independent cohort of 100 mCRPC subjects using univariate Cox regression. Results: RNA sequencing generated >10 million mappable reads per specimen in the discovery cohort. Among these reads ~50% were known miRNAs which included 1237 unique RNA sequences. Due to low abundance of most RNA transcripts, only miRNAs (n=250) with >/= 32 reads (on average) were analyzed. Four mRNAs (miR-1290, -1246, -375 and a predicted miRNA on chr. 12) were associated with OS(FDR<0.05). These were evaluated as prognotic markers in the independent cohort (N=100) using real time RT-PCR. Median time on AD for this cohort prior to progression to mCRPC was 35.7 (range: 3.5-136) months; median GS was 7; median follow up after mCRPC development was 12.5 (1-41) months at which time 28 patients had died. Elevated expression for miR-1290 and -375 were associated with shorter OS after adjusting for GS and AD time with a Hazard Ratio (HR) for miR-375 of 1.19 (CI: 1.006-1.18); (p=0.04) and a HR for miR1290 of 1.58 (CI:1.01-2.4); (p=0.04). A stronger association with shorter OS was observed for elevated expression of both miRs-HR of 2.02 (CI: 1.1-3.6) (p=0.01). Conclusions: Blood-based nucleic acid assays are easily accessible for biomarker development in mCRPC. Results from this study suggest specific exosomal miRs are of prognostic value in mCRPC and should be validated in larger cohorts.
Presence of intraductal carcinoma of the prostate on needle biopsy as a prognostic factor for prostate cancer in radical prostatectomy patients.
Authors: Kato Masashi 
Published: February 2017

268 Background: Intraductal carcinoma of the prostate (IDCP) is seen with widely invasive, biologically aggressive prostate cancer. A recent study has shown this morphologic pattern is useful for prognostication of biochemical recurrence after radical prostatectomy, whereas there is no paper to report biopsy finding of IDCP to be a positive predictor of progression-free survival (PFS) and cancer-specific survival (CSS). Methods: This retrospective study included men with high-risk prostate cancer treated with radical prostatectomy between 1991 and 2005, and we reviewed slides of biopsy samples. Presence of IDCP was defined using previously published diagnostic criteria by a single genitourinary pathologist. Analyzed factors included age, prostate-specific antigen (PSA), clinical T stage, higher biopsy Gleason score (bGS), presence of Gleason pattern five, and IDCP on biopsy samples. Finally, a total of 205 patients with high-risk prostate cancer were entered in our retrospective clinicopathological analysis. Results: Patient mean age was 68. Baseline characteristics included a PSA greater than 20 ng/ml at diagnosis in 122 cases (60%), clinical stage greater than T2 (cT) in 86 (42%), and bGS ³a8 in 150 (73%) in all patients. Follow-up period was 86 months on average. The presence of IDCP on needle biopsy was in 75 (37%). Forty-four patients showed clinical failure, and 20 patients died of the disease. Patients with IDCP showed a higher increased PSA level, higher increased bGS, and more advanced cT than those without IDCP (p < 0.0001). In univariate analysis, IDCP (p < 0.0001), cT (p < 0.0001), bGS (p = 0.0002), and presence of Gleason pattern five (p=0.004) were significantly associated with PFS; IDCP (p < 0.001) and cT (p = 0.02) were significantly associated with CSS. In multivariate analysis, IDCP (p< 0.0001; hazard ratio (HR), 3.574) and cT (p= 0.004; HR, 3.087) were significantly associated with PFS; IDCP (p = 0.001; HR, 8.405) and PSA level (p = 0.0044; HR, 2.920) were significantly associated with CSS. Conclusions: Presence of IDCP on needle biopsy can be a significant predictor of PFS and CSS when analyzing factors of biopsy samples in high risk prostate cancer.
Cytoreductive radical prostatectomy (CRP) in patients with prostate cancer (PCA) and low-volume osseous metastases.
Authors: Heidenreich Axel , Thissen Andrea K. , Piper Charlotte , Pfister David J. K. P. , Porres Daniel 
Published: February 2017

272 Background: Androgen deprivation (ADT) represents the standard treatment in men with prostate cancer (PCA) and osseous metastases. Unlike therapeutic approaches in other solid tumors, RP is usually ignored due to the common view that the biology of the disease is attributed to preexisting metastases. Recently, it has been shown that potentially lethal cancers persist even after neoadjuvant ADT and chemotherapy. We explored the outcome of patients with PCA and low volume skeletal metastases who were subjected to ADT and cytoreductive radical prostatectomy (CRP). Methods: Eighteen patients with biopsy proven, completely resectable PCA, minimal osseous metastases (equal to or less than three hot spots on bone scan), absence of visceral or extensive lymph node metastases were included in the pilot study. All patients (pts) underwent neoadjuvant ADT with luteinizing hormone-releasing hormone (LHRH) analogues for 6 months. If the PSA serum level decreased to less than 0.4 ng/ml and osseous lesions disappeared on control scan, pts were considered suitable for extended RP followed by 2 years adjuvant ADT. Results: Mean age was 61 (42 to 69), the mean PSA was 96.3 (72 to 139) ng/ml and 0.29 (0 to 0.39) ng/ml at recruitment and at 6 months, respectively. Mean number of bone lesions was 1.9 (1 to 3) and all lesions disappeared after 6 months of ADT. Pathohistology revealed pT2c in 4 (22.2%), pT3a and pT3b in 3 (16.7%) and 11 (61.11%) pts, respectively. Seven (38.9%) pts and three (16.7%) pts had lymph node metastases or positive surgical margins (PSM). PSM were treated with adjuvant radiation therapy ad 66.6Gy. No Clavien grade 3 to 5 complications occurred. The mean follow-up is 29 (3 to 52) months, three (16.7%) pts relapsed. The remainder is without evidence of disease. Conclusions: CRP is feasible in well selected men with low volume osseous metastases who respond well to neoadjuvant ADT. These men have a life expectancy of around 7 years and CRP reduces the risk of locally recurrent PCA and local complications. CRP might be a new treatment option in the multimodality management of PCA and minimal metastatic disease.
Meta-analysis of randomized trials to study the impact of prednisone on toxicities and survival in metastatic castration-resistant prostate cancer.
Authors: Naik Gurudatta , Morgan Charity , Galsky Matt D. , Oh William K. , Sonpavde Guru 
Published: February 2017

28 Background: The impact of daily oral prednisone (P) on toxicities and outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) is unclear. We conducted a meta-analysis of randomized trials comparing regimens that included P in only one arm. Methods: PubMed, conferences and clinicaltrials.gov databases were searched for articles reported from January 1966 to June 2013. Eligible studies were selected in an unbiased manner and limited to randomized trials enrolling patients with mCRPC and comparing regimens administering P in only one arm. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Arms containing P were compared with arms without P for severe toxicities grade 3 or higher and overall survival (OS). Results: Five randomized trials were published or presented with P in only one arm: by Scher and colleagues comparing docetaxel (D) plus P versus D plus DN101 (n=953), by Higano and colleagues comparing DP versus GVAX (n=621), by Small and colleagues comparing DP versus GVAX plus D (n=394), by Fossa and colleagues comparing P versus flutamide (n=201) and by Petrylak and colleagues comparing mitoxantrone plus P versus D plus estramustine phosphate (n=770). The total number of patients was 2,939, of whom 1,471 received therapy not containing P and 1,468 received therapy containing P. All five trials were eligible for analysis of toxicities, but the Fossa trial was excluded for the OS analysis due to lack of required parameters. There was no difference between the non-P and P groups for severe toxicities (incidence rate ratio [IRR] = 0.82, p = 0.712, I2 = 97.9%). When examining toxicities as a reason for discontinuing therapy, the non-P groups were not different from the P groups (relative risk [RR] = 1.24, p = 0.413, I2 = 86.8%). The non-P groups demonstrated no difference in OS compared to the P groups (HR = 1.09, p = 0.531, I2= 79.7%). The meta-analysis is limited by the trial level design and small number of patients and does not exclude a favorable palliative impact of P. Conclusions: This meta-analysis of randomized trials in mCRPC suggests no significant impact on severe toxicities and OS with the use of daily oral prednisone.
In vitro efficacy of MAGMAS inhibition in prostate cancer.
Authors: Powers Benjamin C. , Das Bhaskar , Bouzahzah Boumediene , Van Veldhuizen Peter J. , Borrego-Diaz Reyes Emma 
Published: February 2017

281 Background: Prostate cancer is the second most common cancer worldwide in males. The initial treatment in advanced cases is medical or surgical castration. The outlook declines when prostate cancer advances independently, despite the aforementioned castration. Within the last ten years, a handful of new agents have proven effective in this castration-resistant phase, but finding more effective, novel ways of treating advanced prostate cancer is warranted. MAGMAS (mitochondria-associated, granulocyte-macrophage colony stimulating factor (GM-CSF) signaling molecule) is a protein ubiquitously expressed in eukaryotic cells that plays a key role in embryonal development in a variety of species. Overexpression of MAGMAS has anti-apoptotic effects, as GM-CSF is a growth factor essential for survival, proliferation and differentiation of cells. MAGMAS and GM-CSF receptor levels have been shown to be overexpressed in prostate cancer, but do not correlate with pathological grade or clinical stage. The purpose of our study was to evaluate the efficacy of a MAGMAS inhibitor, synthesized by Dr Bhaskar Das, in androgen-dependent and androgen-independent prostate cancer cell lines, as well as in a normal prostate cell line as another control. Methods: The different cell lines were treated with MAGMAS inhibitor at various concentrations in vitro. For analysis, we used MTT Cell Proliferation assay at 24 and 48 hours, per manufacturer’s protocol. We tested MAGMAS inhibitor effect on apoptosis/necrosis, cell migration and microtubule destabilization as well. Results: After prostate cancer cell lines were treated with MAGMAS inhibitor in vitro, cell proliferation and migration decreased, apoptosis and necrosis were induced, and microtubules were destabilized, all showing more impressive results in the androgen-independent cells. MAGMAS inhibition did not affect cell proliferation in the normal prostate cells. Conclusions: In vitro studies show MAGMAS inhibition proves efficacious in both androgen-dependent and androgen-independent prostate cancer cell lines. This will be evaluated further in a xenograft mouse model.
Prevalence and adverse impact of extended antibiotic prophylaxis in urologic oncology surgery.
Authors: Mossanen Matthew , Calvert Josh , Holt Sarah , James Andrew Callaway , Wright Jonathan L. , Porter Michael P. , Gore John L. 
Published: February 2017

294 Background: Providers exhibit variation in the selection of the class, dose, and duration of prescribed antibiotic prophylaxis (ABP) to prevent postsurgical infections. We sought to evaluate ABP practice patterns for common inpatient urologic oncology surgeries and ascertain the association between extended ABP and hospital-acquired Clostridium difficile (C. diff) infections. Methods: From the PREMIER database for 2007–2012, we identified patients who underwent radical prostatectomy (RP), radical or partial nephrectomy (Nephx), or radical cystectomy (RC). We defined extended ABP from charges for antibiotics ≥ 2 days after surgery; exclusive of patients with a switch in antibiotic class within 2 postoperative days for presumption of infection. We identified postoperative C. diff infections using ICD-9 diagnosis codes. Hierarchical linear regression models were constructed by procedure to identify patient and provider factors associated with extended ABP. Logistic regression models evaluated the association between extended ABP and postoperative C. diff infection, adjusting for patient and provider characteristics. Results: We identified 59,184 RP patients, 27,921 Nephx patients, and 5,425 RC patients. RC patients were more likely to receive extended ABP (56%) than RP (18%) or Nephx (29%) patients (p<0.001). Other factors associated with extended ABP included prolonged postoperative length of stay (OR ≥ 1.69, p<0.001 for all procedures), and surgical volume (p<0.001 for highest vs. lowest volume quartiles). Hospital identity explained 35% of the variability in ABP after RP, 23% after Nephx, and 20% after RC. Among Nephx and RC patients, extended ABP was associated with significantly higher odds of postoperative C. diff infection (OR 3.79, 95% CI 2.46–5.84, and OR 1.64, 95% CI 1.12–2.39, respectively). Conclusions: We identified marked hospital-level variability in extended ABP following RP, Nephx, and RC, which was associated with significantly increased odds of hospital-acquired C. diff infections. Efforts to increase provider compliance with national ABP guidelines may decrease preventable hospital-acquired infections after urologic cancer surgery.
NeuACT, a phase II, randomized, open-label trial of DN24-02: Updated analysis of HER2 expression, immune responses, product parameters, and safety in patients with surgically resected HER2+ urothelial cancer.
Authors: Bajorin Dean F. , Sharma Padmanee , Gomella Leonard G. , Plimack Elizabeth R. , O'Donnell Peter H. , Hoffman-Censits Jean H. , Flaig Thomas W. , Quinn David I. , Sims Robert Brownell , Locker Michael , Sheikh Nadeem A. , DeVries Todd , Lerner Seth P. 
Published: February 2017

296^ Background: DN24-02 is an investigational autologous cellular immunotherapy (ACI) consisting of antigen presenting cells (APCs) cultured with BA7072, a recombinant HER2-derived antigen (HER500) linked to granulocyte-macrophage colony-stimulating factor. In the ongoing NeuACT (N10-1; NCT01353222) trial, patients (pts) with high-risk, HER2+ urothelial cancer (UC) are randomized 1:1 to either adjuvant DN24-02 or surveillance. Updated analyses are presented. Methods: Eligibility criteria include radical surgical resection of primary ≥pT2 or pN+ UC (bladder or upper tract) with HER2 expression ≥1+ by immunohistochemistry. Pts randomized to DN24-02 undergo 3 cycles of leukapheresis and infusion at 2-week intervals. Product potency is assessed at each infusion. Immune responses and adverse events (AEs) are measured at multiple time points. Results: By July 2013, tumor specimens from 226 pts had been screened. Of these, 75% (95% CI 69–81%) had HER2 expression of ≥1+ in the primary tumor, 32% had ≥2+ and 8% had 3+. In pts with available lymph node samples (n=83), 84% (95% CI 75–91%) had a HER2 score of ≥1+ in the lymph nodes; 49% and 14% had ≥2+ and 3+, respectively. Pts with 1+ HER2 expression had similar immune responses to BA7072 as those with higher HER2 levels. APC activation (CD54 upregulation) was observed at each infusion in the first 30 pts who had completed the 3 infusions, but was typically greater at infusions 2 (median 15.56; range: 6.42–23.97) and 3 (14.69; 8.24–30.86) than infusion 1 (7.35; 4.04–14.34). In the 5 pts with available data, BA7072 and HER500 specific antibody responses increased from baseline for at least 12 months. Most (92.3%) AEs were grade 1–2 in severity, including all AEs that occurred ≤1 day after infusion. Conclusions: The high frequencies (≥75%) of ≥1+ HER2 scores in primary tumor and lymph node samples confirm that HER2 expression is common in muscle-invasive and node+ UC. DN24-02 product potency data suggest an immunologic prime-boost effect. The observed humoral responses are the first data suggesting prolonged immune responses with an ACI in UC. Most AEs were grade 1–2 in severity. Clinical trial information: NCT01353222.
Geographic and racial disparities in the utilization of low-volume cystectomy hospitals for bladder cancer.
Authors: Casey Martin Francis , Gross Tal , Stensland Kristian D. , Oh William K. , Galsky Matt D. 
Published: February 2017

302 Background: Extensive research has demonstrated volume-outcome benefits for select cancer surgeries, such as cystectomy. However, barriers to the use of high volume cystectomy hospitals have not been comprehensively explored. Methods: The New York Statewide Planning and Research Cooperative System was utilized to obtain data on all inpatients who underwent cystectomy for bladder cancer from 1997-2011. Volume status was defined by dividing patients into quintiles based on the number of cystectomies performed by each hospital in 1997-2001. Multiple logistic regression was used to assess the impact of distance and race on use of low volume hospitals. Driving distances were calculated using a geographic information system. Race was stratified by the racial profile of a subject’s community to explore the underlying causes of racial disparities. Results: A cohort of 8,712 cystectomy patients was identified. The number of available high volume hospitals increased over time, consistent with regionalization of surgeries. Minimum travel distance to high volume hospitals decreased over time for the general population, but living >21 miles still increased risk for low volume hospital utilization (see Table). Racial disparities were most prominent among blacks living in black communities, despite generally living closer to high volume hospitals (median travel distance of 5.3 miles versus 16.6 miles for whites living in white communities). Conclusions: Regionalization of cystectomies has occurred in New York State, as has been observed in multiple other regions of the United States. However, geographic and racial disparities exist in the use of high volume cystectomy hospitals. [Table: see text]