bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of testosterone deficiency or manipulation on prostate cancer.
Authors: Yassin Aksam , Yassin Dany-Jan , Hammerer Peter 
Published: February 2017

229 Background: There is controversy over whether testosterone replacement therapy is a risk factor for prostate cancer. Herein, we evaluate whether testosterone deficiency (TD), testosterone replacement therapy (TRT) or 5-alpha reductase inhibitor (5-ARI) therapy affect the risk of prostate cancer. Methods: Data were collected from 224 male patients who had an indication for prostate biopsy: Prostate specific antigen (PSA) greater than 4, PSA-Velocity >=0.75 in a year, hypogonadism with PSA >=1.5, positive digital rectal exam (DRE) and/or positive Transrectal Ultrasonography (TRUS) finding. Each patient was then subjected to a TRUS-guided 10 core prostate biopsy. Results: 25% (3 out of 12) of the patients on TRT were found to have prostate cancer via biopsy and 32.1% (68 out of 212) of patients who did not receive TRT were found to have prostate cancer; insignificant with p = 0.757. Seventeen our of 76 (22.4%) of the patients on 5-ARI treatment were found to have prostate cancer and 36.5% (54 out of 148) of the patients who did not receive 5-ARI were found to have prostate cancer; significant with p = 0.03. There was no significant statistical difference in Gleason grades among patients who were on TRT, no TRT, on 5-ARI and no 5-ARI. Conclusions: Our data suggest that TRT is not associated with increased risk of prevalence or Gleason grade of prostate cancer. 5-ARI therapy is associated with lower prevalence of prostate cancer but with no relationship to Gleason grade.
Triweekly docetaxel versus biweekly docetaxel as a treatment for advanced castration resistant prostate cancer: Quality of life analysis.
Authors: Kellokumpu-Lehtinen Pirkko-Liisa Irmeli , Harmenberg Ulrika , Hervonen Petteri , Joensuu Timo K. , McDermott Raymond S. , Ginman Claes , Luukkaa Marjaana , Nyandoto Paul , Hemminki Akseli , Nilsson Sten , McCaffrey John , Asola Raija , Turpeenniemi Hujanen Taina , Laestadius Fredrik , Tasmuth Tiina , Sandberg Katinka , Keane Maccon M. , Lehtinen Ilari , Luukkaala Tiina , Joensuu Heikki ,   The Prosty Study Group
Published: February 2017

23 Background: Bi-weekly docetaxel (T) with prednisone improved progression free survival and overall survival when compared with the standard tri-weekly T as first-line treatment for advanced castration resistant prostate cancer (CRPC) (Lancet Oncol. 2013;14:117-124). We report here the quality of life (QoL) results of this prospective randomized trial. Methods: Three hundred and forty-six patients were randomly allocated centrally to receive intravenous therapy T of either 75 mg/m² d1 q3 wks (the triweekly arm) or 50 mg/m² d1 and d 14, q4 wks (the biweekly arm) (identifier NCT00255606). Prednisone (10 mg/d) was administered orally in both groups. The baseline patients characteristics were well balanced between the groups with respect to the performance status, mean age (69, range 45 to 87 vs. 68, range 46 to 85), and median serum prostate-specific antigen (PSA) content (109 µg/L, range 11 to 1,230 vs. 116 µg/L, range 12 to 1,870). Quality of life (QoL), the frequency and severity of symptoms including pain were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) version 4.0 questionnaire. Results: The baseline (QoL) of both treatment groups was compared to QoL after six months of the treatment within each treatment group and between groups. Changes in fatigue, symptoms of pain and nausea, and the overall performance status did not differ between the groups. There were statistically significant differences in overall quality of life values (p=0.010) and discomforting pain values (p=0.028) favoring the bi-weekly treatment arm. Conclusions: Bi-weekly T is better tolerated than the tri-weekly standard T. Following the results from the clinical outcome and the QoL outcome in the PROSTY trial we would recommend the use of bi-weekly docetaxel as first line treatment of CRPC Clinical trial information: NCT00255606.
The natural history of bone metastases in castrate-resistant prostate cancer.
Authors: Pell Robert James , Harland Stephen John 
Published: February 2017

239 Background: Previous authorities have commented on the lack of data regarding overall prevalence of Skeletal-Related Events (SREs) in Castrate Resistant Prostate Cancer (CRPC) in patients who have not received therapy for SRE prevention. We describe a cohort of 129 patients followed to death. Methods: 129 patients treated with palliative chemotherapy for CRPC at University College Hospital London between 01/01/2006 and 31/12/2010 had retrospective collection of data concerning date of prostate cancer diagnosis, date of CRPC, date of death, date of bone metastasis development, radiotherapy treatment, pathological fracture, bone surgery, and spinal cord compression up until 01/06/2013. Results: Median age at castrate resistant prostate cancer development was 70 years. Overall median time from prostate cancer diagnosis to establishment of castrate-resistant state was 33 months (range 5-223). Median time from castrate-resistant state to death was 23 months (0-99). Only 9/129 patients failed to develop bone metastases. A total of 162 palliative radiotherapy treatments were given to 74 patients. Only 10 radiotherapy treatments occurred prior to the development of castrate-resistant disease, the remaining 152 all occurred after castrate-resistance occurred. Symptomatic pathological fracture occurred 28 times in 22 (17%) patients. One or more surgical interventions for bone disease were carried out in 23 (18%) patients. 27 (21%) patients were treated for spinal cord compression. In total, 352 skeletal-related events occurred in 89 patients. Conclusions: Important skeletal-related events occurred in 69% of patients with mCRPC. It is possible that incomplete follow-up in clinical trials of agents such as bisphosphonates considerably under estimate the effect of the investigational agent. The frequency of pathological long bone fracture suggests current measures to detect prefracture and intervene are inadequate. [Table: see text]
A multicenter phase I study of cabazitaxel (Cbz), mitoxantrone (Mito), and prednisone (Pred) (CAMP) for chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Aggarwal Rahul Raj , Weinberg Vivian K. , Ryan Charles J. , Harzstark Andrea , Bryce Alan H. , Derleth Christina Louise , Lowe Kimberly , Small Eric Jay 
Published: February 2017

243 Background: Cbz/pred extends survival in mCRPC patients (pts) following docetaxel and first-line studies comparing Cbz to docetaxel are ongoing. Mito/pred also has anti-tumor activity in mCRPC and a non-overlapping mechanism of action and toxicity profile with Cbz. A multicenter phase I trial was initiated through the DOD PCCTC to establish the maximally tolerated dose (MTD) of the combination of Cbz, Mito, and Pred. Methods: Chemotherapy (chemo)-naive pts with mCRPC were enrolled in an accelerated titration design. The primary objective was to determine the MTD of CAMP; secondary objectives included assessing PSA and objective response rates and duration of response. Starting dose of Cbz was 25 mg/m2 (the currently approved single-agent dose) and Mito 4 mg/m2, administered on day 1 of a 21-day cycle. Mito was escalated by 2 mg/m2 per dose level. Pred 5 mg BID and pegfilgrastim were administered with each cycle. Results: 9 pts were enrolled (dose level I, N = 1; dose level II, N = 1; dose level III, N = 3; dose level IV N = 4). The median age was 67 (range 55-81) and the median baseline PSA was 82.3 (range 20.4-791.2). There were 2 DLTs observed at dose level IV (Cbz 25 mg/m2 + mito 10 mg/m2), both grade 4 sepsis. The most common grade 3 adverse events were hematologic (neutropenia, n = 5; febrile neutropenia, n = 2, thrombocytopenia, n = 2). 6 of 9 pts remain on study (range 2.2 - 10.5+ months). Maximal PSA declines from baseline > 50% have been observed in 4/7 (57%) evaluable pts to date. 2 of 4 pts with measurable disease have experienced partial responses and a third has had a minor response after 4 cycles of chemo. The median progression-free survival and duration of response have not been reached. Conclusions: The approved single-agent dosage of Mito (12 mg/m2) could not be safely reached in combination with Cbz 25 mg/m2. Pre-planned evaluation of an alternate dosing strategy combining Mito with Cbz 20 mg/m2, which has demonstrated activity in mCRPC and potentially less hematologic toxicity, is underway. Preliminary efficacy data are encouraging but additional follow-up and further study of the treatment combination is required. Clinical trial information: NCT01594918.
Increase in bone scan index during abiraterone treatment in relation to reduced survival in mCRPC patients.
Authors: Reza Mariana , Bjartell Anders , Ohlsson Mattias , Edenbrandt Lars , Tragardh Elin 
Published: February 2017

244 Background: Abiraterone acetate (AA) is one of several new treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). It has showed to prolong survival in patients who had disease progression after chemotherapy. An objective biomarker that is associated with improvement in survival would be of value in the management of patients under AA treatment, for example in decisions to continue or change treatment. Bone Scan Index (BSI) is a measurement that reflects the tumor burden in bone as a percent of the total skeletal mass. The purpose of this study was to evaluate BSI as a response biomarker in mCRPC patients on treatment with AA. Methods: We retrospectively studied a consecutive series of 28 mCRPC patients who received AA following disease progression after chemotherapy. All patients had undergone whole-body bone scan before and during AA treatment. Baseline and follow-up BSI data was obtained using the automated quantification software EXINI Bonebsi(EXINI Diagnostics AB, Sweden). Data on prostate-specific antigen (PSA) and survival were collected from the medical records. Cox proportional-hazards regression models and Kaplan-Meier estimates of the survival function were used to investigate the association between changes in BSI and PSA from baseline to follow-up and survival. Discrimination between prognostic variables was assessed using the concordance index (C-index). Results: Patients with an increase in BSI of at least 0.2 (n=15) had a worse one-year survival (36%) than those with improvement or stable disease (BSI change <0.2) (96%) (p< 0.006). Both follow-up BSI and the BSI change from baseline to follow-up showed higher C-index (0.80) than the corresponding PSA values (0.73 and 0.75). Conclusions: Increase in BSI is significantly associated with reduced survival in mCRPC patients under AA treatment following disease progression after chemotherapy. Calculation of BSI could be a valuable tool for treatment response evaluation as a complement to the traditional methods. [Table: see text]
Prospective phase I/II trial of dose-painting prostate brachytherapy guided by cancer-specific ultrasound-based tissue-type imaging (TTI).
Authors: Ennis Ronald D. , Trichter Frieda , Saigal Kunal , Quinn Stuart A. , Feleppa Ernest J. 
Published: February 2017

246 Background: Standard treatments treat the entire prostate gland uniformly, while focal treatments target only the dominant tumor. We propose an alternative approach wherein tumor areas are treated with an escalated dose of radiation while the remainder of the prostate with dose de-escalation. Tissue-type images (TTIs), which identify intraprostatic tumors via ultrasound spectral analysis, were used to identify tumors. Methods: 14 low risk patients were enrolled. TTIs and standard B-mode ultrasound images were generated and fused intraoperatively. Based on TTIs, plans were developed to deliver 200% prescription dose to the tumors and 100% to the prostate. Doses above 100% to non-tumor regions were minimized and standard normal tissue constraints were respected. Results: 12 patients were successfully treated. Technical problems occurred in the first patient and another received a standard implant due to discordance of TTIs with MRI and biopsy findings. One patient passed away soon after the procedure of unrelated cause. A total of 28 tumors were identified in these 12 patients (median 2 tumors/patient, range 1-4). Mean tumor volume was 0.72cc (range 0.03cc -4.07cc). Tumor dose was significantly higher in TTI-based plans, with mean tumor V200%: TTI vs. standard 97% vs. 48%, p<0.05. Modest dose reduction of the whole prostate was also achieved. Median follow-up was 25.7 months (range 21.3-48 months). A low incidence of grade 2 toxicities and no grade 3-4 toxicities were seen (Table). Two patients experienced a biochemical failure per the nadir+2 definition, both failures are attributable to PSA bounce (PSA down to 1.0 and 0.59 at 42 and 30 mos., respectively). Post-treatment biopsies have been performed on 5/11 patients (4 refused), with 2 patients with pending biopsies. 4/5 available biopsies are negative, with 1 patient having a small focus of residual cancer. Conclusions: Dose-painting prostate brachytherapy is technically feasible. This tumor-directed approach, more rational than uniform whole gland treatments, offers the promise of excellent cancer control, low toxicity and low risk of re-treatment. Clinical trial information: NCT01227642. [Table: see text]
The difference in implantation quality between loose seed and variable spacing strand seeds in the field of prostate brachytherapy.
Authors: Grégoire Pigné , Grégoire Pigné , Ronan Tanguy , Julien Ribouton , Ruffion Alain , Chapet Olivier 
Published: February 2017

252 Background: Concordance between intraoperative and postoperative dosimetry is a well-known marker of implant quality in prostate brachytherapy. The aim of the study was to evaluate if the use of variable distance strand seeds allows an improvement in the quality of the post implantation dosimetry. Methods: Before December 2010, an iodine 125 loose-seed technique was used for prostate brachytherapy. Since this date, patients have been treated with new variable distance strand seeds (ProLink; Bard). Post implant dosimetry was compared to intraoperative dosimetry in 30 patients treated with loose seeds and 29 patients treated with strand seeds. The prescribed dose was 145Gy. Variations of dosimetric parameters were used to set the two techniques against one another: prostate V100 and D90 and rectum V145 and V160. Results: There was a significant difference between intraoperative and postoperative V100 and D90 for all 59 patients: V100 preop-postop: mean 6,65% +/- SD 4,5; D90 preop-postop: 18,73Gy +/- SD 15 (p<0,0001). This dosimetric difference between pre and post-operative dosimetry is more important using loose seeds brachytherapy: V100 preop-postop: 9,5% +/- SD 4,1 vs 3,7% +/- SD 2,7 for loose seeds and strand seeds respectively (p<0,0001), and D90 preop-postop: 27,9Gy +/-SD 13,6 vs 9,2Gy +/- SD 9,7 for loose seeds and strand seeds respectively (p<0,0001). For V145 rectum and V160 rectum, dosimetric difference wasn't significant: V145 rectum preop-postop: -0,9% +/- SD 1,4 with stranded seeds vs. -1,6% +/- SD 2,1 with loose seeds (p=0,14) and V160 rectum pre-postop: -0,5% +/- SD 0,8 with strand seeds vs. -0,5% +/- SD 0,8 with loose seeds (p=0,16). Conclusions: Stranded seeds implantation increases the quality of implantation by reducing the dosimetric difference (V100 and D90) between intra and post-operative dosimetry to a maximum of 6% and 7% vs. more than 20% with loose seed implantation. Moreover, this technique doesn’t seem to modify the risk of rectal toxicity. This achievement in implantation and dosimetric quality might lead to a gain in clinical results.
Safety and clinical outcome of a cohort of patients (pts) with castration resistant prostate cancer (CRPC) treated with abiraterone acetate (AA) in a named patient program (NPP): Updated results of a retrospective study from an Italian cooperative group.
Authors: Caffo Orazio , Fratino Lucia , Lo Re Giovanni , Basso Umberto , D'Angelo Alessandro , Donini Maddalena , Santini Daniele , Procopio Giuseppe , Massari Francesco , Gasparro Donatello , Verderame Francesco , Sacco Cosimo , Messina Caterina , Iacovelli Roberto , Zustovich Fable , Vicario Giovanni , Fraccon Anna Paola , Conteduca Vincenza , Maines Francesca , De Giorgi Ugo 
Published: February 2017

253 Background: Abiraterone acetate (AA) provided a survival advantage compared to placebo in patients (pts) with castration resistant prostate cancer (CRPC) who had received docetaxel (de Bono JS et al, NEJM 2011). The present retrospective study is aimed to assess safety and clinical outcome in an unselected CRPC population which received AA in a named patient program (NPP). Methods: We retrospectively reviewed the clinical records of all pts treated with AA for CRPC by NPP in our institutions. All pts have been previously treated with a docetaxel-based first-line chemotherapy and received the standard AA dose of 1,000 mg daily plus prednisone 10 mg daily. For each pt we recorded the pre- and post-AA clinical history, the AA treatment details toxicities and clinical outcomes. Results: To date we have collected a consecutive series of 245 pts from 18 Italian hospitals. The median age was 73 (range 45 to 91). The median baseline prostate-specific antigen (PSA) level was 100 ng/ml (range 0.33->100.000); 79% of the pts had bone metastases, while nodal, lung and liver metastases were observed in 52%, 9%, and 7% of the pts, respectively. The median duration of AA treatment was 5 months (range, 1 to 26). Grade 3 to 4 toxicities were anemia (11 pts), fatigue (nine pts), bone pain (four pts), constipation (two pts), thrombocytopenia (two pts), nausea (one pt), diarrhea (one pt), dyspnea (one pt), edema (one pt), hypertension (one pt), hyperbilirubinemia (one pt), and hypokaliemia (one pt). A PSA reduction of more than 50% was observed in 50.9% of the pts. The median progression-free survival (PFS) and overall survival (OS) were 6 months and 15 months, respectively; the 1 year PFS and OS rates were 24.3% and 56.9%, respectively. Conclusions: Our results have confirmed the safety and efficacy of AA in an unselected population of pts with pre-treated CRPC outside clinical trials and provided further support concerning the good safety profile of the drug.
Characteristics and outcome of octogenarian versus young patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) treated with ketoconazole.
Authors: Sinibaldi Victoria J. , Dadon-Nachum Michal , Gottfried Maya , Maimon Natalie , Dovrish Zamir , Peer Avivit , Neumann Avivit , Sella Avishay , Kovel Svetlana , Carducci Michael Anthony , Eisenberger Mario A. , Kejzman Daniel 
Published: February 2017

256 Background: Standard treatment options for patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) include docetaxel based chemotherapy, abiraterone, and radium 223. Octogenarian pts (age 80 and older) are often considered to be unfit for chemotherapy. However, recommendations for their management is limited by the paucity of clinical trials data in this population. In countries where abiraterone in the pre-chemotherapy setting has not been approved yet, or for pts who can’t afford it, the CYP 17 inhibitor ketoconazole is used as an alternative advanced hormonal tx. We aimed to study baseline characteristics and outcome of octogenarian versus young (age 60 or younger) pts with mCRPC treated with ketoconazole. Methods: We performed an international multicenter retrospective study of pts with mCRPC, who were treated with ketoconazole at four centers across two different countries. We compared baseline characteristics and outcome of octogenarian versus young pts. The effect of very old age on prostate-specific antigen (PSA) response, progression free survival (PFS), and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chi-square test and partial likelihood test from Cox model. Results: Between 2004 and 2013, 35 octogenarians (median age 83) and 33 young pts with (median age 57) mCRPC were treated with ketoconazole. The groups were balanced regarding the following baseline clinicopathologic characteristics: extent of disease (limited-axial skeleton and/or nodal versus extensive-appendicular skeleton and/or visceral), combined gleason score, pre-treatment risk category (Keizman, Oncologist 2012; based on pre-tx neutrophil to lymphocyte ratio/prostate-specific antigen doubling time, and prior response to ADT), pain intensity, ECOG performance status, alkaline phosphatase level, hemoglobin level, PSA level. In octogenarian versus young pts, PSA response (greater than or equal to 50% decline from baseline) was 40% versus 61% (OR 3.5, p=0.04), median PFS 7 versus 8 months (HR 0.91, p=0.44), and median OS 31 versus 36 months (HR 0.66, p=0.31). Conclusions: In very old vs young mCRPC patients treated with ketoconazole, PSA response was lower. Baseline clinicopathologic characteristics, PFS, and OS were not significantly different between the groups.
Efficacy of new agents on advanced castration-refractory prostate cancer with RAPID progression.
Authors: Wu Shenhong 
Published: February 2017

257 Background: Five new agents with diverse mechanisms of action have been shown to improve overall survival for patients with advanced castration-refractory prostate cancer (CRPC). Because of a heterogeneity in cancer growth and proliferation, it is not clear whether these agents are effective in patients with rapid progressive disease. Therefore, we conducted a systematic review and meta-analysis of published randomized controlled clinical trials (RCTs) to assess the effect of these new agents on three month progression and mortality. Methods: Databases from PUBMED, the Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until June, 2013 were searched to identify relevant studies. Early progression was defined as progressive disease or death at three months after the initiation of clinical trial. Eligible studies included prospective RCTs in which a new agent was compared to a control in metastatic CRPC patients. Summary incidences of three month progression or mortality, relative risk (RR), and 95% confidence interval (CI) were calculated based on the heterogeneity of included studies. Results: A total of 5,895 patients (new agents: 3,623, control: 2,272) with CRPC from seven RCTs were included for analysis. The new therapy significantly reduced the risk of mortality in the overall patient population (HR=0.69, 95% CI: 0.64-0.74) without significant variation among different agents (P=0.82). The new therapy also reduced the risk of three month mortality (RR=0.76, 95% CI: 0.60-0.97, P=0.027). However, significant risk reduction was only seen for enzalutamide (RR=0.54, 95% CI: 0.31-0.94; P=0.03). In addition, the new therapy reduced the risk of three month progression (RR=0.61, 95% CI: 0.46-0.81, P=0.001). The risk varied among these agents (P<0.001), with significant risk reduction seen for enzalutamide (RR=0.47, 95% CI: 0.21-0.54), abiraterone (RR=0.57, 95%CI: 0.35-0.97), and cabazitaxel (RR=0.80, 95% CI: 0.72-0.89), but not for Sipuleucel-T (RR=1.10, 95% CI: 0.21-5.76). Conclusions: The new agents may have a differential impact on the outcome of CRPC with rapid progression.