bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigen-specific immunity and tumor inflammation after vaccination with BPX-101, a drug-activated dendritic cell vaccine for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Wheeler T. M. , Zhao B. , Sonpavde G. , McMannis J. D. , Bai Y. , Lapteva N. , Seethammagari M. , Levitt J. M. , Spencer D. M. , Slawin K. M. 
Published: February 2017

176 Background: We report evidence of antigen-specific immunity and severe prostate cancer inflammation and necrosis after vaccination in patients enrolled in a phase I-IIa clinical trial of BPX-101, a drug-activated DC vaccine for mCRPC. Methods: Twelve men with progressive, mCRPC were enrolled in a 3+3 dose escalation trial evaluating BPX-101 and activating agent AP1903. BPX-101, which targets prostate-specific membrane antigen (PSMA), was administered intradermally every 2 weeks for 6 doses, followed 24 hours after each dose by infusion of AP1903 (0.4 mg/kg). Injection site skin biopsies were performed after the fourth vaccination. T cells cultured from the skin biopsy ex vivo were stimulated with PSMA protein or control antigens, and were analyzed using Luminex microspheres for 30 inflammatory cytokines/chemokines. One patient (#1007) with an intact prostate developed lower urinary tract bleeding after the fifth vaccination and underwent a transurethral resection of bleeding prostate cancer tissue. Paraffin-embedded blocks were stained for hematoxylin and eosin (H&E). Immunohistochemical stains for CD3, CD4, CD8 and CD34 were also performed. Results: Of 5 subjects with evaluable injection site biopsy results, all exhibited PSMA-specific immunity (3 TH1-biased and 2 TH2- biased). Subject 1007's injection site biopsy demonstrated a significant >10-fold increase in IFN-gamma and IL-2 after stimulation by PSMA, compared to stimulation by ovalbumin, consistent with induction of a strong PSMA-specific CTL or TH1-biased immune response. H&E stained resected prostate tissue demonstrated Gleason 8 (4+4) prostate adenocarcinoma exhibiting a severe inflammatory response, consisting of infiltrating plasma cells and CD4+ and CD8+ T cells. Large areas of necrosis were seen adjacent to inflamed prostate cancer tissue. Conclusions: Vaccination with BPX-101 followed by AP1903 can induce a strong, PSMA-specific immune response. Furthermore, evidence of severe prostate cancer-specific inflammation and necrosis, associated with a strong PSMA-specific immune response has been observed after multiple doses of BPX-101. [Table: see text]
A phase II, open-label, single-arm, efficacy, and safety study of MDV3100 in patients with hormone-naïve prostate cancer.
Authors: Baskin-Bey E. S. , Holtkamp G. M. , Smith M. R. , Ouatas T. , Phung D. , Tombal B. 
Published: February 2017

177 Background: MDV3100 is a novel androgen receptor (AR) antagonist in clinical development for the treatment of prostate cancer (PCa). Compared to bicalutamide, MDV3100 has higher in vitro AR binding affinity and no evidence of partial agonism. Preliminary phase I-II data show antitumor activity with MDV3100 in men with advanced PCa who were concurrently using androgen deprivation therapy (ADT; Scher HI, et al. Lancet. 2010;375:1437-46). Phase II and III studies in men with progressive and earlier-stage PCa are ongoing. This abstract describes the design of a phase II study of MDV3100 in men with hormone-naïve PCa (HNPCa) who are candidates for ADT. Methods: This 25-week, open-label, single-arm, efficacy and safety study of MDV3100 (160 mg/d orally) will be initiated at ∼20 investigational sites in late 2010 (planned countries: Austria, Belgium, Czech Republic, Denmark, Germany). Inclusion criteria include histologically confirmed, locally advanced PCa (all stages), noncastrate testosterone (T; ≥230 ng/dL), prostate-specific antigen (PSA) ≥2 ng/mL (screening), Eastern Cooperative Oncology Group score of 0, and life expectancy ≥1 year. Exclusion criteria include, among others, previous/current hormonal therapy or chemotherapy for PCa. The primary endpoint is PSA response, defined as an ≥80% decrease from baseline to wk 25. A binary PSA response per patient (wk 25) will be determined, allowing for generation of a PSA response rate (95% CI) from all patients for the study. Secondary endpoints include: PSA dynamics; pharmacokinetics; change in gonadotropin, T, dihydrotestosterone, estradiol, sex-hormone binding globulin, and prolactin levels; and safety/tolerability. Exploratory endpoints include changes in bone mineral density, bone turnover markers, metabolic parameters, and quality of life. Results: The planned enrollment is 60 patients. With a 20% dropout rate, the study will have 80% power to reject the unwanted PSA response rate of ≤50% (5% significance). Efficacy and safety data will be published later. Conclusions: Previous data were in men with castrate levels of T (≤50 ng/dL). This trial will be the first to investigate the use of MDV3100 monotherapy in HNPCa. [Table: see text]
Cost of care for prostate cancer patients: An observational cohort study comparing clinical trials to standard care.
Authors: Jones B. , Syme R. , Eliasziw M. , Eigl B. J. 
Published: February 2017

184 Background: Monetary support of clinical trials is a fundamental necessity for improving treatment and prevention methods; however, current economic data pertaining to the per-patient costs of treating prostate cancer are limited. A concurrent lack of certainty regarding the cost requirements of standard care patients makes it difficult for healthcare professionals and policy makers to generate informed decisions regarding budgets and funding needs. Prostate cancer clinical trials are facing a national funding crisis due to the perception that patients enrolled in clinical trials consume more resources than patients receiving standard care. Methods: A retrospective observational cohort study was conducted to examine the costs incurred by prostate cancer patients at the Tom Baker Cancer Center over one year. Costs for 36 patients enrolled in one of nine cancer trials were compared with costs for 36 matched control subjects who received standard care. Resource utilization was tracked using medical charts and quantified by prices listed in the TBCC's 2009 Clinical Trials Budget template. Results: No evidence was found to support a difference in overall resource utilization between clinical trial patients and standard of care patients (Paired two-tailed t- test, N= 36, p =0.90). There was, however, variability in the types of resources used by each patient population, indicating that, while trial patients may take up significantly more clinic time (p =0.04), undergo more tests and procedures (p < 0.001) and require more diagnostic imaging (p = 0.01), standard care patients are more likely to receive costly interventions such as radiation therapy (p =0.06). Pharmaceutical costs have not yet been included in the analysis and could drastically alter the final results. Conclusions: This study revealed differences in the cost distribution of clinical trials patients versus standard of care patients, which could be used by administrators to improve budgeting and time allocation. The lack of difference in overall cost may be helpful to research advocates attempting to encourage centers to take on more trials. Further analysis is required before definitive conclusions can be drawn. No significant financial relationships to disclose.
Patient preference for prostate-specific antigen testing: A population-based analysis.
Authors: Chang S. L. , Presti J. C. , Richie J. P. 
Published: February 2017

188 Background: The AUA and American Cancer Society both recommend a shared decision-making process between clinicians and patients for prostate cancer screening with PSA testing. Data are limited data regarding patient preferences for PSA evaluation in the United States. We assessed the sociodemographic and clinical characteristics of men who proceeded with or opted out of PSA testing in a nationally representative population-based cohort. Methods: We analyzed male participants from the 2001 to 2008 cycles of the National Health and Nutrition Examination Survey (NHANES) who were 40 years old or older without a history of prostate cancer, recent prostate manipulation, or hormone therapy use (n = 6,032). All men underwent or refused PSA testing after a standardized explanation about prostate cancer screening by a physician. A multivariate logistic regression was conducted after adjusting for survey weights to identify independent sociodemographic and clinical predictors for opting out of PSA testing. Results: Overall, 5% of the study cohort refused PSA testing. The analysis revealed predictors for refusing PSA testing (Table). PSA testing preference was not influenced by a family history of prostate cancer, previous prostate cancer screening, education level, socioeconomic status, insurance status, or tobacco history. There were no significant time trends for PSA testing. Conclusions: Despite equal access to PSA testing in our study, there was unequal utilization. We found that Black men were more likely to refuse PSA testing. Our analysis also suggests that a perception of suboptimal health or uncertain future outlook may discourage men from undergoing PSA evaluation. These patient preferences for PSA evaluation should be factored into the shared decision-making process for prostate cancer screening. [Table: see text] No significant financial relationships to disclose.
The impact of screening for prostate cancer on the development of metastatic disease.
Authors: Ciezki J. P. , Reddy C. A. , Kupelian P. , Klein E. A. 
Published: February 2017

192 Background: Routine screening for prostate cancer (CaP) was first advocated in 1993 in the US. Opponents of screening argue that the implementation of routine screening has not resulted in a meaningful improvement in survival. Since we are essentially unable to cure metastatic disease, the best measure of the efficacy of screening may not be overall survival but instead its ability to lessen the metastatic disease burden of the screened population. We assess the effect of screening on this endpoint. Methods: From 1986-1996, 1,721 patients with CaP were definitively treated with radical prostatectomy (RP) or radiotherapy (RT) at our institution. The cohort was divided into a pre screening era group (1986-1992; PRE, n=575) and a post screening era group (1993-1996; POST, n=1,146). Due to the potential for an imbalance in follow up time between the two groups, all patients were censored at ten years. Kaplan- Meier analysis was used to calculate the ten year metastases free survival rates (MFSR). Cox proportional hazards regression was used to examine if screening era along with disease, treatment, and follow-up characteristics was associated with an increased risk of developing metastatic disease. Results: The median follow up for all patients was 10 yrs (range: 0.1-10), 9.6 yrs (range: 0.1-10) for PRE patients, and 10 yrs (range: 0.1-10) for POST patients. The distribution by NCCN risk classification for the PRE patients was 44% high risk (H), 21% intermediate risk (I) and 28% low risk (L) vs. 36% H, 27% I, and 37% L for the POST patients (p < 0.0001). Within 10 years of treatment, 13% of all patients had developed metastatic disease. The 10 year MFSR for high risk PRE vs POST patients was 58% vs. 82% (p < 0.0001), 79% vs. 93% for I (p < 0.0001), and 90% vs. 98% (p = 0.0001) for L patients. On multivariable analysis, screening era (p < 0.0001, HR = 4.6, 95% CI = 3.4-6.1), T-stage, biopsy Gleason score, and post-treatment PSA testing frequency were significant. Conclusions: Screening for CaP results in a significant decrease in the risk of a patient developing metastatic disease within 10 years of treatment even after controlling for severity of disease. This risk reduction may yield improved quality of life and a cost savings to the medical care system. No significant financial relationships to disclose.
Got central prostate pathology review? A cross-sectional audit of 2009 versus 2003 outcomes.
Authors: D'Souza N. , Loblaw D. A. , Mamedov A. , Klotz E. , Sugar L. , Nam R. 
Published: February 2017

196 Background: Prostate cancer is the most common non-cutaneous cancer in Canadian men; over 24,000 will be newly diagnosed and 4,300 will die from it in 2010. Estimating an individual's risk of disease spreading across the capsule and probability of recurrence with different treatment modalities is common practice in prostate cancer management and often drive the choice or extent of treatment options. A strong predictor of recurrence and organ confined disease is tumor grade. The literature recognizes differences in grading prostate cancer between genitourinary and non-specialized pathologists; we previously reported a 30% change in risk category (Low, GS 2-6; Int., GS 7; High, GS 8-10). However, this report was based on data from 2003/2004. A repeat audit was necessary given Gleason grading practice changes following the 2005 ISUP Consensus Conference. Methods: Log books from 2009/10 where our Genitourinary Pathologists (GUP) reviewed prostate needle core biopsies were used to identify cases; a retrospective chart review was completed. The following variables were extracted: 1° Gleason score; 2° Gleason score; number of sites; % Gleason 4/5 pattern (overall); perineural invasion (present/absent); extracapsular extension (present/absent). Descriptive statistics were used to summarize the results. Results: The charts of 132 patients having a GUP biopsy review were extracted. Seventeen percent (22/132) of cases changed risk category. Of the 47 low risk cases, 23% (11/47) were up-graded in risk category (21% by 1 category; 2% by 2 categories). Of the 46 intermediate risk cases, 15% (7/46) were up-graded and 2% (1/46) were down-graded. Of the 39 high risk cases, only 8% (3/39) were down-graded by 1 risk category. Comparatively, there was a 43% reduction in risk category change between 2003/04 (30%) and 2009/10 (17%). Conclusions: Despite this reduction, a clinically significant proportion of patients changed pathologic risk category upon GUP review. Thus, it is recommended that prostate cancer pathology be routinely reviewed by a GUP as a best practice to optimize management and quality of care. Strategies are still needed to address disparities in pathologic grading and represent a potential area for further investigation. No significant financial relationships to disclose.
Risk of death from prostate cancer after radical prostatectomy or brachytherapy in men with low- or intermediate-risk disease.
Authors: Arvold N. D. , Chen M. , Moul J. W. , Moran B. J. , Dosoretz D. E. , Banez L. L. , Katin M. J. , Braccioforte M. H. , D'Amico A. V. 
Published: February 2017

198 Background: Radical prostatectomy (RP) and brachytherapy (BT) are widely utilized treatments for favorable-risk prostate cancer (PC). We estimated the risk of PC-specific mortality (PCSM) following RP or BT in men with low- or intermediate-risk PC using prospectively collected data. Methods: The study cohort comprised 5,760 men with low-risk PC (prostate-specific antigen [PSA] level ≤ 10 ng/mL, clinical category T1c or 2a, and Gleason score ≤ 6), and 3,079 men with intermediate-risk PC (PSA level 10-20 ng/mL, clinical T2b or T2c, or Gleason score 7). Competing risks multivariable regression was performed to assess risk of PCSM after RP or BT, adjusting for age, treatment year, cardiovascular comorbidity, and known PC prognostic factors. Results: There was no significant difference in the risk of PCSM among men with low-risk PC (11 vs. 6 deaths: adjusted hazard ratio [AHR], 1.62; 95% CI, 0.59–4.45; P = 0.35) who received BT compared to RP. However among men with intermediate-risk PC, despite significantly shorter median follow-up for men undergoing BT as compared to RP (4.1 vs. 7.2 years, P < 0.001), there was a trend toward an increased risk of PCSM (18 vs. 9 deaths: AHR, 2.30; 95% CI, 0.95–5.58; P = 0.07) for men treated with BT. Conclusions: The risk of PCSM among men with low-risk PC was not significantly different following RP or BT, however there may be a reduced risk of PCSM after RP as compared to BT in men with intermediate-risk PC. [Table: see text] No significant financial relationships to disclose.
Factors associated with vertebral fractures in men treated with androgen-deprivation therapy (ADT) for prostate cancer.
Authors: Saylor P. J. , Hancock M. L. , Barnette G. , Steiner M. S. , Morton R. A. , Smith M. R. 
Published: February 2017

205 Background: Fragility fractures are common among men and have the potential to cause considerable morbidity and mortality. Androgen deprivation therapy (ADT) for prostate cancer causes accelerated loss of bone mineral density (BMD) and is associated with increased risk for fractures. We evaluated clinical risk factors associated with fracture among men receiving ADT and at elevated risk for fracture due to age and/or BMD. Methods: Analysis included men receiving ongoing ADT for prostate cancer and enrolled in a phase III fracture prevention trial. All men were either age ≥ 70 years or had low BMD (T-score < −1.5 for the lumbar spine or total hip). We analyzed baseline demographic and laboratory characteristics of those with and without vertebral fractures at the time of study entry. Given that the trial enrolled patients who were age < 70 only if BMD was low, we conducted additional analyses confined to the portion of the cohort that was age ≥ 70. Results: A total of 162 of the 1,244 subjects (13.0%) had a vertebral fracture at baseline. Two factors were significantly associated with prevalent fractures: white race (p = 0.028 when compared with non-white race) and osteoporosis (p = 0.002 for osteoporosis at any site; p = 0.053 for osteoporosis at the spine; p = 0.002 for osteoporosis at the hip). Lower BMD was also significantly associated with fractures when analyzed as a continuous variable. Factors not associated with fractures included age, country of residence, ADT duration at baseline, ADT mode, body mass index, testosterone, estradiol, C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase, and osteocalcin. Results were similar in analyses limited to men ≥ 70 years old (n = 1,002). Conclusions: Vertebral fractures cause substantial morbidity and mortality among men treated with ADT for prostate cancer. In this study of men receiving ADT, white race and low BMD were significantly associated with vertebral fractures. These observations should inform the assessment of fracture risk in this vulnerable population. [Table: see text]
Development of leptomeningeal carcinomatosis (LC) in advanced prostate cancer patients: Characteristics of six cases in a single institution.
Authors: Sperlich C. , Fontaine A. , Ayllon J. , Van Campenhout I. 
Published: February 2017

218 Background: In the past months, we have noticed an increasing number of leptomeningeal carcinomatosis (LC) in patients known for advanced prostate cancer (PC). This complication has only been reported in a few patients. Methods: We identified and reviewed the charts of all patients known for advanced PC who later developed LC. We report their characteristics as well as survival. Results: Between March 2009 and April 2010, we identified 6 patients known for advanced PC that showed evidence of LC (median time from diagnosis of prostate cancer to development of LC, 55.8 months). Disease was already metastatic to other sites in all of them, and all had previously showed evidence of castrate refractory prostate cancer (CRPC). All patients maintained LHRH agonist therapy and were treated with prednisone once they showed evidence of CRPC. Most had also been treated with docetaxel (n=5), zoledronic acid (n=4; the remaining 2 patients received either zoledronic acid or denosumab as part of a protocol) and/or other (dasatinib/placebo as part of a protocol, n=1; sunitinib as part of a protocol, n=1). LC was diagnosed a median of 21.2 months after evidence of CRPC, based on clinical findings (cranial nerve[s] involvement [n=6] and nausea and/or ataxia [n=2]) and magnetic resonance imaging (MRI). 2 patients underwent lumbar puncture (negative results). Treatment administered for LC included dexamethasone (n=1), radiation therapy (n=1), or both (n=2). Two patients with poor performance status did not receive any treatment. All patients assessable for response (n=3) showed a partial improvement in their symptoms, but not complete resolution. Median overall survival from development of CRPC and from diagnosis of LC is 23.9 months and 2.7 months, respectively. Conclusions: LC is a newly described site of metastasis in patients with advanced CRPC. It is associated with a late onset and a very poor prognosis. [Table: see text]
Pathohistologic findings in patients with nonseminomatous germ cell tumors (NSGCT) who undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for small tumors.
Authors: Pfister D. J. , Busch J. , Winter C. , Schmelz H. U. , Dieckmann K. , Albers P. , Schrader M. , Heidenreich A. 
Published: February 2017

224 Background: The current guidelines recommend the resection of all visible residual tumors in NSGCT after a cisplatin based chemotherapy. There are controversial data concerning the necessity of PC-RPLND in patients with residual tumours less than one centimetre in diameter. The aim of our study was to evaluate the pathological findings in a modern series with regard of the residual tumour size. Methods: A retrospective analysis of the patient's charts was performed including patients who underwent PC-RPLND between 1989 and 2010. Of 408 patients 330 had a NSGCT, 78 patients had a pure seminoma or a primary extragonadal germ cell cancer and were excluded from analysis. The tumour size at the time of surgery was available in 261 patients in the remaining 69 pateints no preopretive data with regard to the tumour size were recorded in the radiology reports. Due to the location of the residual tumour a median laparotomy, a thoracoabdominal approach was used. In one center a laparoscopic approach was preferred. Results: Mean tumour diameter was 4.7 (0 to 32) cm. The patients were stratified in three groups: group 1 n=28 (RT<=1cm), group 2 n=23 (RT>1<=1.5cm) and group 3 n=209 (RT>1.5cm). The histological specimens contained teratoma in 21.4%, 39.1%, 44.5% respectively, viable cancer in 10.7%, 17.4% and 22% respectively, and fibrosis/necrosis in 64.3%, 52.2% and 37.8% respectively in the three grpups respectively. Conclusions: The finding of both teratoma and viable cancer decreases with decreasing sizes of the residual tumour. Nevertheless lesions <= than 1 cm still harbour a significant pathohistology in one third of the patients. As a consequence PC-RPLND must not be omitted even in small RT. No significant financial relationships to disclose.