bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate MRI/ultrasound fusion and biopsy yield.
Authors: Margolis Daniel , Kumar Dinesh , Macairan Maria Luz , Narayanan Ram , Natarajan Shyam , Gandhi Nishant , Shaw Gregory , Marks Leonard S. 
Published: February 2017

206 Background: MRI has been shown useful for identifying targets after negative biopsy. We purport to show the advantage of realtime fusion of MRI data with ultrasound for initial or repeat TRUS biopsy compared with sextant biopsy. Methods: An IRB-approved prospective study of 57 consecutive men with diffusion weighted imaging and dynamic contrast enhanced (DCE) perfusion in addition to T2-weighted imaging on a Siemens Magnetom 3.0 T Trio using an external phased array coil had targets chosen based on decreased T2 signal with abnormally restricted diffusion or abnormal DCE by a uroradiologist with 6 years experience in prostate imaging, followed by ultrasound-guided biopsies using MR/ultrasound fusion software (Artemis, Eigen) in addition to standard 12-core sextant biopsies. Results: In 56 patients, 101 suspicious areas were identified by MRI; 28 positive targets were found in 22 men, including 19 Gleason 3+3 (68%), 8 Gleason 3+4 (29%), and one with HGPIN (3%). In 28 patients, neither targets nor systematic cores were positive, and in one patient no targets were identified. Positive cores were found in 12 patients only on targets only including 6 Gleason 3+4. One patient was “upstaged;” the target was Gleason 3+4 whereas the positive systematic cores were Gleason 3+3. In 8 patients the Gleason score of systematic and targeted cores was identical, 2 Gleason 3+4 and 6 Gleason 3+3. In 7 patients systematic cores were Gleason 3+3 with negative targets, all less than 4 mm and less than 25 percent of the core. Fisher exact test showed a trend to significance, p = 0.06 for any cancer identified, and p = 0.03 for Gleason 3+4 disease. Conclusions: The improved accuracy of MRI-TRUS fusion biopsies may be able to replace systematic biopsies, avoiding the discomfort and risks associated, and improve diagnostic yield, and improve confidence for patients with a small amount of low-grade cancer who opt for active surveillance.
TNF-α deficiency as protection against sickness behavior related to external beam radiation of the pelvis in mice.
Authors: Chennupati Sravana K , Siddiqui Faisal A , McDonald Tasha L. , Thomas Charles R. , Hung Arthur , Wood Lisa J 
Published: February 2017

208 Background: Prostate cancer patients undergoing localized external beam radiation therapy (EBRT), experience significant fatigue during treatment, which can affect physical functioning and QOL. We hypothesize that cancer treatment related fatigue (CTRF) is the same as sickness behavior caused, in part, by increases in TNF-α. Our previous data demonstrate that pelvic EBRT induces systemic increases in TNF-α and a decline in voluntary wheel running activity (VWRA) , an objective measure of sickness in mice. A specific aim of this study was to determine the requirement of EBRT for TNF-α for the induction of sickness behavior. Methods: Daily VWRA was monitored in male WT (n=10) and TNF-α−/− (n=10) anesthetized mice undergoing pelvic EBRT at 4.6 Gy/fraction, 5 days per week for 15 fractions for a total dose of 69 Gy [4.6 X 15 = 69, not 70]. Control WT (n=10) and TNF-α−/− (n= 10) mice underwent anesthesia followed by sham EBRT. The effect of treatment on weight and food intake was also determined by calculating change in weight and daily food intake during treatment. A 2 x 2 repeated measure analysis of covariance ANCOVA was used to determine whether there was a significant interaction between treatment group (EBRT or Control) and genotype (WT or TNF-α−/−) on voluntary wheel running activity controlling for baseline differences in this variable. Similarly a 2 x 2 ANOVA was used to determine whether there was a drug x genotype interaction between change in body weight or food intake. Results: There was a significant effect of EBRT on VWRA (p< 0.001), food intake (p0.002), and weight (p<0.001). We did not however observe a significant interaction between EBRT and genotype in VWRA (p= 0.756), food intake (p=0.654), or weight (p= 0.450). Conclusions: Targeting TNF-α using specific cytokine blocking agents has been suggested as a potential strategy for preventing or managing EBRT related fatigue. Although our prior data support that localized EBRT to the pelvis may induce TNF-α and sickness behavior in mice, our latest data do not support a direct role for this cytokine in mediating these effects.
Inhibition of 3β-hydroxysteroid dehydrogenase by abiraterone as a rationale for dose escalation in castration-resistant prostate cancer.
Authors: Sharifi Nima , Li Rui , Evaul Kristen , Sharma Kamalesh , Auchus Richard J 
Published: February 2017

209 Background: Treatment with abiraterone acetate (abi) increases the survival of men with castration-resistant prostate cancer (CRPC). Resistance to abi invariably occurs, probably due in part to up-regulation of steroidogenic enzymes and/or other mechanisms that sustain the synthesis of dihydrotestosterone (DHT), which raises the possibility of reversing resistance by concomitant inhibition of other required steroidogenic enzymes. The 1000 mg daily abi dose was selected for the phase III trials despite the absence of dose-limiting toxicities at higher doses. Based on the 3β-hydroxyl, Δ5-structure, we hypothesized that abi also inhibits 3β-hydroxysteroid dehydrogenase/isomerase (3βHSD), which is absolutely required for the intratumoral synthesis of DHT in CRPC, regardless of origins or routes of synthesis. Methods: We tested if abi inhibits recombinant 3βHSD2 activity in vitro or endogenous 3βHSD activity in LNCaP and LAPC4 cells, including conversion of [3H]-dehydroepiandrosterone (DHEA) to androstenedione (AD), androgen receptor (AR) nuclear translocation, expression of AR-responsive genes, and LAPC4 xenograft growth in orchiectomized mice supplemented with DHEA. Results: Abi has a mixed inhibition pattern of 3βHSD2 in vitro, blocks the conversion from DHEA to AD and DHT with an IC50 of < 1 µM in CRPC cell lines, inhibits AR nuclear translocation and expression of TMPRSS2, and decreases CRPC xenograft growth in DHEA-supplemented mice. Conclusions: Abi blocks 3βHSD enzymatic activity, synthesis of AD and DHT, inhibits the AR-response, and suppresses growth of CRPC cells at concentrations that are clinically achievable. Variable abi inhibition of 3βHSD might account in part for the heterogeneous clinical response to abi. More importantly, 3βHSD inhibition with abi might be clinically harnessed to reverse resistance to CYP17A1 inhibition at the standard dose by dose-escalation, or simply by administration with food to increase drug exposure.
Use of total illness burden index for prostate cancer (TIBI-CaP) to predict nonprostate cancer morbidity.
Authors: Liss Michael Andre , Osann Kathryn , Moskowitz Ross , Kaplan Adam , Billimek John , Greenfield Sheldon , Dash Atreya 
Published: February 2017

215 Background: Comorbidities significantly influence how physicians approach the treatment of prostate cancer and should be evaluated prior to the prostate biopsy. The Total Illness Burden Index for Prostate Cancer (TIBI-CaP) patient questionnaire and Charlson Comorbidity Index (CCI) usually calculated by the physician, may provide information on competing risks but have not been compared prospectively. Methods: A prospective observational cohort study was performed of 133 participants prior to obtaining a transrectal ultrasound guided prostate biopsy. Eleven patients had incomplete data or missing follow-up; therefore, a total of 122 (92%) patients were retained for a mean of 21 months (range 4 – 31 months). The TIBI-CaP and CCI scores were compared between subgroups defined by non-elective hospital admission, elective surgery, non-prostate malignancy and survival status using t-tests. Results: Patients averaged 64.5 years at enrollment. One patient died in the study from a metastatic sarcoma. The overall hospital admission rate was 17% (21/122), most commonly from cardiovascular or pulmonary complications. Forty-six men (38%) were diagnosed with cancer on the prostate biopsy. The most common treatments were prostatectomy (39%), active surveillance (26%), or external beam radiation therapy (20%). Twenty-three percent (28/122) had elective surgery and 5% (6/122) were diagnosed with a non-prostate malignancy. Mean TIBI-CaP scores were higher in men who were admitted to the hospital (5.1 vs. 3.5, p=0.03), had elective surgery (4.8 vs. 3.4, p=0.05) or non-prostate cancer (5.5 vs 3.7, p=0.17). No significant differences were observed in CCI scores In stepwise logistic regression, a TIBI-CaP score > 5.0 was associated with 3.5 times higher risk for hospital admission (95% CI: 1.3–10.0, p=0.02). Conclusions: The patient-reported measure of comorbidity (TIBI-CaP) identified patients at high risk for non-elective hospital admission over at 20 month average follow up period and may aid medical decision making specifically in the prostate biopsy population better than that of the Charlson Comorbidity Index.
Active surveillance for low-risk prostate cancer: Practice across Europe.
Authors: Azmi Aini , Dillon Ruth , Marignol Laure , Borghesi Simona , Dunne Mary , Power Richard , O'Neill Brian 
Published: February 2017

217 Background: Active surveillance (AS) is a recognized treatment option for patients with low-risk prostate cancer (PCa). We carried out a web-based survey to evaluate how AS is practiced by European urologists and to review criteria for patient selection, follow up and indications for intervention. Methods: 2959 potential participants were identified via various European urological association databases and invited via email to complete an online survey consisting of 19 questions. Only urologists practising in an EU country were eligible to participate. Results: 226 urologists participated in the survey corresponding to a response rate of 8%. None of the 19 questions were answered by all urologists, therefore results exclude the missing data. 220 (97%) urologists offer AS. 48% (n=103/216) and 24% (n=53/216) urologists offer AS within the context of an official protocol or clinical trial respectively. The most used factors in selecting patients are Gleeson score (GS) ≤3+3=6 (n=174/202, 86%) and PSA ≤10ng/ml (n=171/200, 85%). 48% (n=96/201) only include patients with ≤2 cores positive while 18% (n=37/201) include those with <50% positive biopsy cores. 41% urologists (n=82/202) only include patients with a clinical stage ≤T1cN0M0. MRI pelvis is performed as a baseline investigation by only 28% (n=57/200). All responding urologists (n=194) use serial PSA to follow up their patients. 89% (n=172/194) carry out serial DRE while 83% (n=161/194) perform repeated prostate biopsy. Re-biopsy is performed within the first year of AS by 77% of urologists (n=131/171). Only 8% (n=15/193) use serial MRI pelvis to monitor their patients. The follow up intensity also varies widely. GS progression was the most frequently cited trigger for intervention (n=168/192, 87%) followed by PSA doubling time of ≤3 years (n=115/192, 60%). Conclusions: Several internationally published guidelines on PCa treatment have recommended AS as a therapeutic option for patients with low-risk PCa. However presently there is a lack of consensus on an optimal AS protocol. This survey shows the wide variation in the practice of AS across Europe and highlights the need for patients to be included in clinical trials to enable an evidence-based guideline to be established.
Bowel and bladder toxicity patterns in patients with prostate cancer treated with proton beam versus intensity-modulated radiation therapy.
Authors: Gray Phillip J. , Paly Jonathan J. , Sanda Martin G. , Sandler Howard Mark , Michalski Jeff M. , Talcott James Austin , Coen John , Shipley William U. , Zietman Anthony L. , Bekelman Justin E. , Efstathiou Jason Alexander ,   The PROST-QA Consortium
Published: February 2017

22 Background: Limited data exist comparing contemporary technologies in the treatment of prostate cancer. Proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT) are both accepted ways of delivering high-dose radiation. We evaluated patient-reported quality of life (QOL) outcomes from two modern prospective cohorts treated with either PBT or IMRT. Methods: QOL data for 153 patients treated with IMRT and collected by the PROST-QA consortium using the Expanded Prostate Cancer Index Composite instrument were compared to data for 95 patients treated on protocol between 2004 and 2008 at the Massachusetts General Hospital with PBT using the Prostate Cancer Symptoms Index instrument. Mean score changes from baseline were compared using the Satterthwaite t-test. Clinically meaningful decline was defined as a score drop exceeding half the standard deviation of the baseline value. Results: Both cohorts had a similar distribution of Gleason score and baseline PSA though the IMRT cohort was older (median age 69 vs. 64, p<.0001). Treatment dose range was 75.6-79.2 Gy for IMRT and 74-82 CGE for PBT. Neither group received hormonal therapy. By 3 months after treatment there was a significant worsening in the bowel domain for the IMRT but not PBT cohort (15.9 point reduction vs. 1.5, p<.0001) which normalized by 12 months. Post-treatment scores were also lower in the urinary irritation domain (13.8 point reduction vs. 5.5, p<.0001) and in the urinary incontinence domain (7.3 point reduction vs. 1.5, p=.002) for IMRT but were similar by 24 months. All immediate post-treatment score changes in the IMRT but not PBT cohort were clinically meaningful. A steady decline in the sexual function domain was seen in both groups but the difference was not significant. Conclusions: In this non-randomized comparison using two validated QOL instruments measuring similar domains, PBT appears to be associated with lower gastrointestinal and urinary toxicity early after treatment with similar late outcomes. While subject to selection bias, these preliminary data suggest transient differences in toxicity patterns underscoring the rationale for a randomized controlled trial.
Effects of 6 months of abiraterone acetate (AA) on muscle and adipose mass in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Brondfield Samuel Craig , Weinberg Vivian K. , Koepfgen Kathryn M. , Molina Arturo , Ryan Charles J. , Small Eric Jay , Harzstark Andrea Lynne 
Published: February 2017

222 Background: AA, an inhibitor of androgen biosynthesis, has been shown to prolong overall survival in patients with mCRPC who have previously been treated with chemotherapy. Androgen deprivation therapy (ADT) has been shown to result in muscle wasting in prostate cancer pts. The effects of AA on progression of muscle and fat wasting have not been characterized. We evaluated whether 6 months of AA therapy altered total skeletal muscle mass or adipose mass. Methods: 10 sequential pts who responded to AA therapy for at least 6 months and had available computed tomography (CT) scans were retrospectively selected from the phase I-II COU-AA-002 study. CT image analysis was used to quantify change from baseline in total skeletal muscle and adipose tissue after 6 months of AA treatment. Skeletal muscle and adipose tissue cross-sectional area were calculated at the L3 level using Slice-O-Matic software V4.3. Previously published regression models were used to estimate fat-free mass, fat mass and skeletal muscle mass. Paired t-tests were performed to determine the change in measurements. Results: At baseline, 7 of 10 pts were overweight or obese (body mass index [BMI] > 25 kg/m2), and none were underweight. Advanced muscle wasting (sarcopenia, previously defined as the ratio of skeletal muscle cross-sectional area at L3 level to height < 52.4 cm2/m2) was present at baseline and 6 months in 9 of 10 pts. Over 6 months of AA treatment, pts lost an average of 1.9 kg ± 1.9 kg (p = 0.13). Mean changes (kg) (±standard deviation) in total skeletal muscle mass (−0.80 ± 1.71, p = 0.18) and total non-adipose mass (−1.44 ± 3.09, p = 0.17) were not significant. A significant decrease in total adipose mass (−0.61 ± 0.84, p = 0.048) was observed. Conclusions: Sarcopenia is prevalent in pts with mCRPC. AA was not related to significantly worsening sarcopenia or overall weight loss during the first 6 months of treatment; however, this may reflect a relatively short duration of therapy and/or small sample size. A significant loss of adipose tissue was observed, which is unexpected given the known effects of ADT, which increases adipose mass. Evaluation of additional AA treated patients is ongoing.
Final analysis: A multicenter phase I study of EMD 525797 (DI17E6), a novel humanized monoclonal antibody to human αv integrins, in progressive castrate-resistant prostate cancer with bone metastases after chemotherapy.
Authors: Wirth Manfred , Heidenreich Axel , Gschwend Jürgen E. , Gil Thierry , Zastrow Stefan , Laniado Michael , Zuehlsdorf Michael , Gerloff Joachim , Uhl Wolfgang , Lannert Heinrich 
Published: February 2017

231 Background: EMD 525797 is a humanized monoclonal IgG2 antibody specifically targeting αv integrins involved in tumor progression. Methods: The safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of EMD 525797 were assessed in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts). 24 pts (43–80 years) were treated with IV infusions of 250, 500, 1000, or 1500 mg EMD 525797 given over 1 h and received 3 doses (weeks 1, 3, and 5) before response assessment at the end of week 6. Pts without progressive disease could receive further doses every 2 weeks. Dose-limiting toxicities (DLTs) were assessed over the first 6 weeks and safety was monitored until 4 weeks after the last administration of EMD 525797. Results: Final analysis showed that 13 of 24 pts had a longer exposure time than expected (≥84 d): 7 pts had exposure times ≥126 d, 3 pts ≥280 d and 1 pt received EMD 525797 for 534 d (Table). All pts experienced adverse events (AEs), and in 11 pts AEs were considered related to EMD 525797. 4 pts had generalized pruritus, erythema, or rash and 3 pts experienced fatigue, mucosal inflammation, or peripheral edema, but no pt had administration site reactions. Changes in clinical lab values were consistent with basic disease. No DLTs occurred. EMD 525797 showed a dose-dependent, nonlinear PK profile in line with a target-mediated drug disposition. Pt 1 and 2 of the 500 mg cohort had a marked decrease in prostate specific antigen. Pt 1 also had primary tumor shrinkage and normalization of lymph node size. These pts had long-term anti-integrin treatment (297 and 534 d, respectively). Both patients showed additional pain relief. Conclusions: EMD 525797 showed clinical activity in mCPRC pts in salvage setting, pain relief, and tumor regression. EMD 525797 is well tolerated without any premedication and did not show clinically relevant dose-related changes in the safety parameters assessed. [Table: see text]
Three-dimensional ultrasound-based spectroscopic imaging for the detection of prostate cancer.
Authors: Chung Hans T. , Sofrani Ervis , Papanicolau Naum , Sugar Linda , Morton Gerard , Yaffe Martin , Nam Robert , Czarnota Gregory J. 
Published: February 2017

234 Background: The objective of this translational research was to investigate the use of real-time novel three-dimension, quantitative ultrasound-based spectroscopic imaging of the prostate as a means of cancer detection. Methods: Fourteen patients with T2-3 prostate cancer underwent a 6–9 MHz trans-rectal ultrasound scan of the prostate prior to radical prostatectomy. Equally spaced axial ultrasound images (0.5 cm separation) corresponding elasticity and spectroscopy data were collected in each patient. Colour-coded spectroscopic parametric maps of 0-Mhz intercept (0-Mhz), mid-band fit (MBF) and slope of line of best fit (slope) were generated indicating where the disease in the prostate gland is hypothetically located. Quantitative data (% volume of cancer over the prostate gland) were compared to whole-mount radical prostatectomy histopathology maps to determine the sensitivity and accuracy in parametrically delineating prostate cancer. Results: Representative data indicate spectral changes were associated with the presence of co-incident disease as located on correlative histopathology whole mount sections. Of the 14 patients enrolled, 7 have been analyzed and presented here. The mean % difference between 0-MHz and MBF, with H&E, was 14% (SD 38%) and 21% (SD 24%), respectively. Gross areas of disease were readily visualized in ultrasound parametric maps and corresponded to a maximum 10dB decrease in 0-MHz or MBF. Parametric maps generated from the spectral slope offered no discrimination of disease. There were differences in scatterer size estimates and scatter concentration estimates between putative disease areas and the remaining tissue. Conclusions: Initial results suggest that there is good correlation between spectroscopic maps with disease on whole-mount specimens. This method may ultimately permit ultrasound-guided targeted biopsies to improve detection rates and non-invasive assessment of disease for radiotherapy planning.
Health care cost in hormone-naive and hormonally pretreated patients with prostate cancer treated with degarelix.
Authors: Wolff Johannes , Tolle Alexander , Gedamke Michael 
Published: February 2017

240 Background: Degarelix, is a GnRH-antagonist, which is used in the treatment of prostate cancer since 2009. We performed a non-interventional study (NIS) with prostate cancer (PCA) patients treated routinely with degarelix. This NIS focused on pharmaco-economical data, quality of life as well as efficacy and safety in patients receiving degarelix as first or second line therapy. Methods: In the interims analysis of this ongoing NIS, data from 279 out of 670 PCA-patients treated with degarelix were included. The included cohort reflects advanced PCA patients (age: 72 years, PSA: 15.8 ng/ml (median values)).Testosterone and PSA values, quality of life and pharmaco-economical data were collected at baseline, 1, 3, 6, 9 and 12 months. Quality of life was assessed by EQ-5D. Pharmaco-economical data included direct costs for physicians, drugs, hospital, emergency treatment and others. Results: Treatment costs in hormon-naïve patients treated with degarelix were lower than in the hormonally pre-treated patients. Direct costs for six month were 498,- € for hormone naïve patients treated with degarelix in contrast to 1436,- € for hormonally pre-treated patients. As expected there was a marked difference in the PSA-decline between hormone-naïve patients and hormonally pre-treated patients. Hormone-naïve patients experienced a sharp median decrease in PSA by 80.7% (n=116) at month 1. This decline remained stable in 98.7% of the patients after one year. Median PSA reduction was significantly different (p=0.013) between hormone-naïve and pre-treated patients. Furthermore treatment of degarelix improved quality of life by 14% at one year compared to baseline. Testosterone was suppressed to a median of 0.2 ng/ml from month 1 to 12. Safety results mirrored the results of clinical trials. Conclusions: First-line treatment with degarelix was supported by a marked difference in health care costs between hormone naïve and pre-treated prostate cancer patients, who received degarelix. As expected a pronounced difference in the PSA-decrease in hormone naïve and pre-treated patients was seen. However a distinct quality of life improvement was noted in all patients.