bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and outcomes of patients with prostate cancer and parenchymal brain metastases (PBM).
Authors: Bambury Richard Martin , Hatzoglou Vaios , Curtis Kristen Rebecca , Patel Gita V , Scher Howard I. , Young Robert J. , Morris Michael J. 
Published: February 2017

187 Background: Parenchymal brain metastases' (PBM's) are rare in prostate cancer (PCa), but the introduction of novel therapies that prolong life for metastatic disease has raised the possibility that the distribution of disease may be changing as patients live longer. In an effort to establish the clinical characteristics and outcomes of PBM as a comparator for future studies, we reviewed all cases at our institution over a 13 year period. Methods: Patients (pts) diagnosed with PBM at Memorial Sloan-Kettering Cancer Center between 2000 and 2010 were retrospectively identified by billing codes for prostate cancer, brain metastases, and no additional primary cancers. Additional cases since 2010 were manually collected prospectively. Direct extension of osseous skull metastases or leptomeningeal disease were not considered PBM. Demographic, clinical, and pathologic characteristics were recorded. Results: 5,474 pts with metastatic PCa and no other primary malignancy were identified of whom 21 had PBM. An additional four PBM cases were prospectively identified, for a total of 25 pts. Twenty two pts (88%) had prostate adenocarcinoma (adeno), of which 14 had Gleason 8 or more disease, 20 had castration resistant disease, and nine had prostate-specific antigen (PSA) less than 5ng/mL. The other three (12%) had atypical histologies (osteosarcoma, small cell carcinoma, and high grade neuroendocrine carcinoma). Median time from diagnosis of PCa to diagnosis of PBM was 3.7 years (range 0 to 19.8) and from discovery of metastatic PCa to PBM was 2.3 years (range 0 to 10). At the time of PBM diagnosis all pts had 1 or more additional site of disease - bone metastases in 20 (80%), lung in 13 (52%), liver in nine (36%). Treatments included whole brain RT in 10 (45%), surgery +/- RT in 8 (36%) and stereotactic RT in 2 (9%). Median overall survival from diagnosis of PBM was 4.3 months (0.7-18.1) in adeno pts compared with 0.7 months (0.7-1.0) in atypical histology pts. Only four pts (16%) survived 12 or more months. Conclusions: In this contemporary cohort, PBM cases were often associated with PCa of atypical histology, high Gleason grade, frequent visceral disease, and low PSA production. Survival was poor after diagnosis of PBM despite treatment. These data can be used as a comparator to track whether treatment with novel PCa therapies is altering the incidence and characteristics of CNS involvement.
The role of FSH in castration-induced adipogenesis and cardiovascular diseases: Highlighting differences between orchiectomy, GNRH agonists, and antagonists.
Authors: Pinthus Jehonathan H. , Hopmans Sarah , Werstuck Geoff , Duivenvoorden Wilhelmina CM 
Published: February 2017

191 Background: Androgen deprivation therapy (ADT) is associated with weight gain and development of the metabolic syndrome (MS). Different modes of ADT can achieve castration but with different affects on serum FSH levels. Inspired by the observation that adiposity accompanies the incremental increase in serum follicle stimulating hormone (FSH) levels in menopause, we hypothesized that gonadotrophin-releasing hormone (GnRH) antagonists which maximally inhibit FSH levels will associate with reduced adiposity and MS development compared to GNRH analogues and orchiectomy. Methods: In-vitro models of adipocyte differentiations were used to investigate FSH effects on lipid accumulation and expression of the rate limiting enzyme in this process-FAS. In-vivo models for adipogenesis and MS (LDL receptor KO mice) were used to investigate and compare the effects of orchiectomy (n=12), sham surgery (control, n=12), sham surgery plus GNRH antagonist (Degarelix, n=12) and sham surgery plus GNRH agonist (Enanton, n=12). Mice were also manipulated by two nutritional conditions (normal/high fat diet). Longitudinal weight gain (four month), visceral fat accumulation (CT measurements), fasting blood glucose, two hours glucose tolerance tests, serum triglycerides, FSH, LH, and testosterone levels were studied along with number and characteristics of aortic atherosclerotic plaques. Results: The lowest and highest serum FSH levels were recorded in mice treated with degarelix versus orchiectomy and significantly lower levels of FSH and LH in mice treated with degarelix versus enanthon were recorded. Mice treated with enantone gained significantly more weight and visceral fat compared to mice treated with degarelix. Significant lower levels of serum triglycerides and better response to glucose loading were recorded in mice treated with degarelix. Data on atherosclerotic plaques is currently processed and will be discussed, but preliminary analysis reveal lower plauque size in mice treated with degarelix. Conclusions: Usage of GNRH antagonists as ADT attenuates weight gain and development of the MS in preclinical models.
Urinary obstruction following stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer.
Authors: Arscott W. Tristram , Chen Leonard , Wilson Nathan , Bhagat Aditi , Kim Joy S. , Yung Thomas M. , Lei Siyuan , Collins Brian Timothy , Suy Simeng , Dritschilo Anatoly , Lynch John H. , Collins Sean P. 
Published: February 2017

196 Background: Obstructive urinary symptoms are common following prostate cancer treatment with radiation therapy. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT obstructive urinary symptoms would be more severe. This study sought to evaluate obstructive urinary symptoms and urinary retention requiring catheterization following SBRT for prostate cancer. Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital with a minimum of two years of follow-up were included in this study. Treatment was delivered using the CyberKnife with doses of 35 Gy to 36.25 Gy in five fractions. Urinary retention was recorded and scored using the CTCAE v.4. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at months 1, 3, 6, 9, and 12 and every six months thereafter. Results: Two hundred sixty nine patients at a median age of 69 received SBRT with a median follow-up of three years. Prior to treatment, 32.1% of patients utilized alpha-antagonists and 17.8% were dissatisfied with their urinary function. The two-year actuarial incidence rates of acute and late urinary retention greater than or equal to grade 2 were 39.5% and 41.4%. Alpha-antagonist utilization rose at one month (57.9%) and 18 months (48.0%) post-treatment. However, grade 3 urinary retention was low with four men (1.5%) requiring catheterization and/or transurethral resection of the prostate. A mean baseline IPSS obstructive symptom score of 3.6 significantly increased to 5.0 at one month (p < 0.0001), however returned to baseline at three months (p = 0.74). Late IPSS increases were common, but transient. The IPSS obstructive symptom score returned to baseline in 79.6% of patients by six months and 92.6% by two years. Dissatisfaction with urinary function declined to 14% by two years post treatment (p < 0.05). Conclusions: Treatment of prostate cancer with SBRT resulted in an acute increase in obstructive urinary symptoms, which peaked at one month post-treatment. However, the risk of acute urinary retention requiring catheterization was low. Obstructive urinary symptoms returned to baseline in the majority of patients by six months and in more than 90% by two years.
Results of subset analyses on overall survival (OS) from study CA184-043: Ipilimumab (Ipi) versus placebo (Pbo) in post-docetaxel metastatic castration-resistant prostate cancer (mCRPC).
Authors: Drake Charles G. , Kwon Eugene D. , Fizazi Karim , Bossi Alberto , van den Eertwegh Alfons JM , Logothetis Christopher , Scher Howard I. , Beer Tomasz M. , McHenry Brent , Liu David , Gerritsen Winald R. 
Published: February 2017

2 Background: The CA184-043 phase 3 study did not reach statistical significance for its primary endpoint of OS (HR=0.85, p=0.053). However, antitumor activity was observed in other efficacy endpoints, including progression-free survival. Prespecified subset analyses were performed to understand if any prognostic features may identify mCRPC patients (pts) more likely to benefit from Ipi treatment. Methods: 799 pts were randomized to receive a single dose of radiotherapy (RT) followed by either Ipi (N=399) or Pbo (N=400). Prespecified subset analyses based on Kaplan-Meier/Cox methodology were performed using known prognostic factors for OS in mCRPC. Results: Prespecified subset analyses suggested that Ipi may be more active in pts with favorable prognostic factors, including no visceral disease, alkaline phosphatase <1.5 ULN, and hemoglobin ≥11 g/dL (Table). The safety profile in this study was consistent with previous reports of Ipi. Conclusions: Based on these subset analyses, Ipi added to RT appears to have greater activity than RT alone in pts with a favorable prognostic profile. These results support continued investigation of Ipi in the ongoing CA184-095 study in chemotherapy-naive mCRPC pts. Clinical trial information: NCT00861614. [Table: see text]
Is there an anti-androgen withdrawal effect with enzalutamide?
Authors: Rodriguez-Vida Alejo , Bianchini Diletta , Hughes Simon , Lorente David , Crawley Danielle , Van Hemelrijck Mieke , Voskoboynik Mark , Chau Noan Minh , Rudman Sarah Maria , Powles Thomas , Payne Heather , De Bono Johann Sebastian , Chowdhury Simon 
Published: February 2017

200 Background: The second generation anti-androgen enzalutamide has demonstrated improved survival in patients with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. While an anti-androgen withdrawal effect has been reported for bicalutamide, flutamide, and other non-steroidal and steroidal anti-androgens, there is no published evidence of any withdrawal effect with enzalutamide. Methods: We retrospectively identified 30 consecutive patients with advanced prostate cancer who were treated with enzalutamide post-docetaxel at three London hospitals. All patients were withdrawn from enzalutamide due to clinical (73%), PSA (87%) and/or radiological progression (47%). Post-discontinuation prostate-specific antigen (PSA) results were available for all patients and were determined two-weekly for at least six weeks until starting further anti-cancer treatment. PSA withdrawal response was defined as a 50% decline in PSA from baseline, with a confirmed decrease after 3 weeks or more. Clinical tumor and patient characteristics were evaluated in relation to the withdrawal effects using multivariate logistic regression analyses. Results: Median age was 71 (range 54 to 87). The median follow-up was 5.4 months (range: 0.5 to 16.0 months). At enzalutamide initiation, ECOG performance status was 0 and 1 in 10% and 69% of patients, respectively. The most common metastatic sites were bone (87%), lymph nodes (68%), liver (17%), and lung (6%). Most patients (70%) had been on abiraterone previously and 11 patients (37%) had also received prior cabazitaxel. The median treatment duration with enzalutamide was 3.7 months. Only one patient (3%) had a confirmed PSA response of 50% or more after enzalutamide discontinuation and two patients (7%) had a confirmed PSA response between 30% and 50%. None of the clinical variables assessed in relation to withdrawal effects were found to be statistically significantly associated. Conclusions: This preliminary case series represents the first clinical evidence that enzalutamide may have an anti-androgen withdrawal effect in a minority of patients. These results warrant further prospective and controlled validation of a potential enzalutamide withdrawal effect and its clinical relevance in prostate cancer management.
The expression levels of microRNAs that have the androgen receptor in localized prostate cancer as a target.
Authors: Leite Katia Ramos Moreira , Florez Manuel Garcia , Reis Sabrina Thalita , Viana Nayara , Katz Betina S. , Dip Nelson , Silva Iran Amorin , Pontes Jr Jose , Srougi Miguel 
Published: February 2017

206 Background: Prostate cancer (PC) depends on the androgen activity being the androgen blockage the main treatment in the setting of metastatic disease. Mechanisms of resistance in metastatic tumors are not completely known. MicroRNAs (miRNA) are small non-coding molecules that have as canonical mechanism the negative control of gene expression promoting messenger RNA (mRNA) degradation or impairing protein translation. The role of miRNAs that have as target the AR are still unknown. Our objective is to study the expression profile of miRNAs that have AR as target in localized prostate cancer. Methods: The expression levels of miRNAs that have as target AR (miR9, 34a, 34c, 185, 130a, 299, 421, 371, 541) were studied using qRT-PCR in the surgical specimens of 83 patients that underwent radical prostatectomy to treat localized prostate cancer. The expression levels of miRNAs were correlated to Gleason score (GS), pre-operatory PSA, pathological stage and biochemical recurrence (PSA>0.2 ng/mL) in a mean follow up of 45.9 months. The mean age was 62.9, mean GS was 7.2, mean PSA was 7.93 ng/mL, and 42 (50.6%) patients were staged pT2. Twenty-four (28.9%) patients presented biochemical recurrence. Specimens of six patients submitted to open surgery to treat benign prostate hyperplasia (BPH) composed the control group. Results: The mean expression of AR was 1.63, being overexpressed in 59% of the cases. The mean expression levels of the nine studied miRNAs was miR9=3.06, miR34a=0.76, miR34c=1.14, miR185=1.65, miR130a=1.9, miR299=6.23, miR421=2.84, miR371=1.41, and miR541=0.93. The univariate analysis showed that pT2 tumors have higher expression of miR371(p=0.009). Conclusions: In localized PC the higher expression of miR371 is related with organ-confined disease. This miRNA could be important in the control of AR and the comprehension of its role in PC might bring alternatives to treat metastatic disease. Funded by FAPESP – 2012/50163-0.
Clinical outcomes of patients (pts) age 60 or younger treated with docetaxel (DOC) for castration-resistant prostate cancer (CRPC): Results of an Italian multicenter retrospective study (CYCLOP study).
Authors: Veccia Antonello , Ortega Cinzia , di Lorenzo Giuseppe , La Russa Francesca , Burgio Salvatore Luca , Facchini Gaetano , Messina Caterina , Sacco Cosimo , Spizzo Gilbert , Aieta Michele , Lodde Michele , Mansueto Giovanni , Zucali Paolo A. , D'Angelo Alessandro , Iacovelli Roberto , Massari Francesco , Morelli Franco , Procopio Giuseppe , Ruatta Fiorella , Caffo Orazio ,   CYCLOP Study Group
Published: February 2017

214 Background: Since prostate cancer is usually diagnosed in patients (pts) over age 60, castration-resistant prostate cancer (CRPC) is rarely observed in pts age 60 or younger. Despite the clinical outcomes of these pts are not clearly defined, there is a common feeling of a worse prognosis for pts with CRPC age 60 or younger. The present study is aimed to assess the clinical outcomes of this specific population. Methods: In this multicentric retrospective study, after Ethical Committee approval, we have reviewed the clinical records of all pts younger than 60 with CRPC from participating institutions, treated with docetaxel (DOC), both in clinical trials and in clinical practice. We recorded the pre- and post-DOC clinical history, the DOC treatment details and outcomes. Results: To date we have collected a consecutive series of 128 pts from 24 Italian hospitals. The median age was 57 (range 41 to 60). The median baseline prostate-specific antigen (PSA) was 85 ng/ml (range 1 to 3,020); 87% of the pts had bone metastases while 47%, 10%, and 13% showed nodal, liver and lung metastases, respectively. All but 12 pts received DOC with a 3 week standard schedule, the remaining being treated with a weekly schedule. A PSA reduction greater than 50% was observed in 61% of the pts; among the 86 pts with measurable disease who underwent a radiological re-evaluation at the treatment end, four and 13 pts achieved complete and partial response, respectively (response rate 20%). The main grade 3-4 toxicities were anemia (five pts), neutropenia (18 pts), febrile neutropenia (one pt), fatigue (five pts), peripheral neuropathy (three pts). The median progression-free survival (PFS) and overall survival (OS) were 7 months and 21 months, while the 1 year PFS and OS rates were 17.6% and 74.9%, respectively. Conclusions: Our data seems to not confirm that younger pts with CRPC have a worse prognosis compared to the older pts since their survival outcomes and response rate are similar to those observed in general population of pts wiht CRPC.
A safety study of trebananib (AMG 386) and abiraterone in metastatic castration-resistant prostate cancer.
Authors: Ojemuyiwa Michelle A. , Karzai Fatima H. , Shah Avani Atul , Theoret Marc Robert , Harold Nancy , Chun Guinevere , Couvillon Anna , Apolo Andrea Borghese , Price Douglas K. , Madan Ravi Amrit , Figg William Douglas , Gulley James L. , Dahut William L. 
Published: February 2017

218 Background: Trebananib is an angiopoietin1/2 antagonist peptibody. Androgens stimulate expression of VEGF via activation of hypoxia inducible factor-a (HIFa). Androgen deprivation therapy (ADT) is associated with lower HIF1a gene expression in prostate cancer tissue. Dual targeting of the androgen and angiogenic axis represents a potential synergistic anti-angiogenic therapeutic approach in metastatic castration resistant prostate cancer (mCRPC). In this preliminary safety study we hypothesize that trebananib in combination with abiraterone will have a favorable tolerability and efficacy profile. Methods: Patients with mCRPC were treated with abiraterone 1000mg daily and prednisone 5 mg twice daily. Trebananib was administered intravenously every week, in escalating doses from 15mg/kg to 30mg/kg on days 1, 8, 15, and 22 every 28-days. Results: A total of 9 patients were enrolled. Three of nine patients had prior chemotherapy. The median age was 63.8 (63-71yrs). No dose limiting toxicities were observed. The most common grade ≥ 2 toxicities included limb edema (3/9), hyperglycemia (1/9), gastrointestinal (2/9), fatigue (2/9), hypertension (1/9), confusion (1/9), weight gain (1/9) and insomnia (2/9). 5/9 of patients had an overall PSA decline of >30%. 8/9 patients were evaluable for response. Prior chemotherapy patients were on study for 1 and 3 months. No prior chemotherapy patients were treated for 1, 6, 9, 10, 10, and 17 months. Conclusions: Trebananib in combination with abiraterone is well tolerated and displayed an acceptable safety profile in patients with mCRPC. Based on this safety data a randomized phase II study randomizing chemotherapy-naïve mCRPC patients to either abiraterone/prednisone plus AMG 386 at 30mg/kg or abiraterone/prednisone is currently accruing at the NCI. Clinical trial information: NCIT01553188.
Clinical and biologic factors for immune response to sipuleucel-T (SipT) for metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Hepgur Mehmet Faith , Dorff Tanya B. , Brining Lucy , Cai Jie , Pinski Jacek K. , Reed Mary , Luther Michael , Chan Betty , Quinn David I. 
Published: February 2017

219 Background: SipT prolongs overall survival of men with asymptomatic or minimally symptomatic mCRPC. Recently, it has been demonstrated that SipT immune parameters correlate with survival. We prospectively collected biological and inflammatory markers as part of an audit to identify possible predictors of immune response in patients (pts) receiving SipT. Methods: Circulating tumor cells (CTC), PSA, prostatic acid phosphatase (PAP), albumin (Alb), hemoglobin (Hb), serum alkaline phosphatase (SAP), LDH, C-reactive protein (CRP) and β2-microglobulin (β2m) were evaluated in reference lab before SipT. Product parameters CD54, CD54 upregulation (UPREG) and total nucleated cells (TNC) were measured by Dendreon. These datasets were analyzed using Spearman coefficients for continuous variables and the Kruskal-Wallis test for categorical variables. Results: 92 pts who received SipT were included. Median age was 69 (48-90). 43% had Gleason 8-9. 42% had ECOG Performance Status (PS) 0, 44% PS 1, and 13% PS 2. 26% had received prior chemotherapy and 18% had used opioids. 84% had bone mets, 42% had lymphadenopathy, 12% had visceral mets. Of clinical factors only PS was inversely correlated with UPREG (p=0.014) and TNC (p= 0.023). Biomarkers which significantly correlated with SipT immune parameters are shown in the Table. Age, location of mets, prior chemotherapy or opioid use did not impact the immune response to SipT Conclusions: Better product parameters correlated with good ECOG PS, lower PSA and SAP, and higher Hgb and Alb, suggesting that SipT induces a greater immune response in men with lower disease burden. The correlation of increased CD54 count with lower CRP, a surrogate for IL-6 activity, warrants investigation. [Table: see text]
Impact of number of lines of therapy following docetaxel (D) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Sonpavde Guru , Bhor Menaka , Hennessy Daniel , Bhowmik Debajyoti , Shen Liji , Schnadig Ian D. 
Published: February 2017

223 Background: The impact of number of lines of therapy on outcomes following docetaxel (D) in metastatic castration-resistant prostate cancer (mCRPC) is unclear. We examined outcomes with cabazitaxel (C) and/or abiraterone acetate (A), following D during a period when all three therapies were available. We previously reported that most patients received only two of these three therapies. Among patients who received all three, DCA was administered more commonly and exhibited better overall survival (OS) than DAC after controlling for prognostic factors. Here, we report the impact of number of lines of therapy following D. Methods: A retrospective analysis of the U.S. Oncology network electronic health records (EHR) was conducted of post-D patients with mCRPC who received C and/or A from April 2011 to May 2012. Median OS was analyzed by Kaplan-Meier method. Cox proportional hazard models were used to evaluate impact on OS of number of therapies administered, age, Prostate Cancer Working Group (PCWG2) subtype, Charlson comorbidity index, prostate-specific antigen (PSA), alkaline phosphatase, hemoglobin, narcotic use, and treatment duration. Results: Multivariate analysis showed significantly lower mortality in the three-drug group compared to the two-drug group (HR 0.209 95% CI: 0.092-0.476, p<0.05). 113 patients received three drugs (DCA=77, DAC=36) and 237 received two drugs (DA=183, DC=54). The three-drug cohort was significantly younger than the two-drug group (median age 69 vs. 73). Other significant covariates (p<0.05) for mortality were narcotic use (HR 2.010 [1.240-3.259]), PSA (HR 1.014 [1.001-1.027] and alkaline phosphatase (HR 1.001 [1.000-1.001]. Conclusions: In men with mCRPC receiving C and/or A post-D, patients receiving all three therapies were younger and exhibited significantly better OS after controlling for clinical factors. In those receiving only two therapies, there appeared to be no difference in outcomes for second-line C versus A. Given the favorable impact of receiving all three therapies, more frequent administration of DCA in the three-drug group and better OS for DCA compared to DAC, we hypothesize that DCA may be a more optimal sequence. These results are exploratory and prospective validation is necessary.