bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosimetric predictors of sexual function decline following LDR brachytherapy for prostate cancer (PCa).
Authors: Mian Omar Y , Robertson Scott P. , Narang Amol , Aggarwal Sameer , Bae Hee Joon , Gergis Carol , McNutt Todd R. , Tran Phuoc T. , DeWeese Theodore L. , Song Danny 
Published: February 2017

113 Background: Conventional dosimetric standards for implant quality do not adequately predict patient reported QoL measures following prostate brachytherapy. We used a dynamic learning knowledgebase (Oncospace) to explore relationships between dose and patient-reported outcomes. Methods: Patient reported quality of life outcomes were prospectively collected for 366 patients with stage cT1-T2 PCa over a 10 year interval. Patients received Pd-103 seed implantation under real-time ultrasound guidance, and completed a QoL instrument (IIEF-5) prior to treatment and at follow-up. Multivariate risk models were used to evaluate dose/toxicity relationships and the Oncospace learning environment generated prediction models using granular dose volume relationships. Results: Median follow-up was 36 months (SD 28.5). In the cohort, 23.7% (n = 87) received combined brachytherapy and EBRT; 14.7% (n = 54) had received prior androgen suppression therapy. Sexual QoL data at minimum of 2 years was available in 141 men. The mean decrement in sexual function per the IIEF-5 instrument was 3.76 points (SD 10.3), with 17.0% of men reporting a decrement of 10 points or greater. There was no significant association with prior androgen suppression (p = 0.20) or combined EBRT use (p = 0.69). DVH curves were queried and dichotomized according to stable sexual function vs significant decline ( > 10) at 2 years post-implant. A logistic regression model was used to generate probability surface maps of volumetric dose effects on outcomes. Logistic regression revealed a correlation between dose to the cavernosal nerves and total SHIM score throughout the high dose region of the DVH curve (p < 0.05). No similar dose/volume correlation with sexual function emerged for structures. Conclusions: Granular dose/volume and toxicity correlation using the Oncospace learning environment exposed a statistically significant relationship between volumetric dose to the cavernosal nerves and sexual function decline in patients undergoing LDR brachytheramarpy. Minimization of dose to the cavernosal nerves may preserve sexual function after permanent prostate seed brachytherapy.
Does prostate inflammation on a negative prostate biopsy vary by race? Results from the REDUCE study.
Authors: Vidal Adriana , Howard Lauren , Moreira Daniel , Castro Ramiro , Andriole Gerald L. , Taioli Emanuela , Freedland Stephen J. 
Published: February 2017

116 Background: Prostateinflammation is linked with prostate cancer. However, whether prostate inflammation varies by race is unclear. Methods: We analyzed baseline acute and chronic prostate inflammation by race in REDUCE. REDUCE was a 4-year, multicenter, placebo-controlled study where all men received a single, negative prostate biopsy within 6 months prior to enrollment. Among 8,046 men who met the inclusion criteria, we included those with data on baseline biopsy prostate inflammation, acute/chronic or none, determined by central pathology. Logistic regression was used to compare prostate inflammation by race, and models were adjusted for demographic and clinical features. Results: Of the 8,046 men, 7,326 were white (91.1%), 184 (2.3%) black, 132 (1.6%) Asian, 323 (4.0%) Hispanic, and 81(1%) unknown. Seventy eight percent of men had chronic and 15% had acute prostate inflammation. Men with chronic inflammation were older (p<0.001), while men with acute inflammation were younger (p<0.001) compared to men with none prostate inflammation. Both acute and chronic inflammation was associated with lower PSA (all p≤0.0001), smaller prostate volume (all p≤0.0001) and geographic region (all p≤0.006). On crude analysis, compared to whites, Asian men were two times more likely to have acute prostate inflammation (OR=1.92, 95%CI: 1.29-2.85, p=0.001), whereas the associations with Hispanic and black race were not significant (all p≥0.39). However, on multivariable analysis, black men were 36% less likely to have acute prostate inflammation (OR=0.64, 95%CI: 0.41-0.99, p=0.04), whereas the likelihood of having acute prostate inflammation remained high in Asians (OR=1.85, 95%CI: 1.25-2.85, p=0.004). No associations by race were found with chronic prostate inflammation. Conclusions: Given that at the population level, black race is a high risk factor for PC and Asian men have lower risk of PC, these data indicate that the presence of acute inflammation in a negative prostate biopsy could be an indication of future PC risk. Further studies to confirm these findings are needed. Clinical trial information: NCT00056407.
Utility of PCA3 and TMPRSS2:ERG urinary biomarkers in African American men undergoing prostate biopsy.
Authors: Feibus Allison H. , Sartor A. Oliver , Moparty Krishnarao , Kattan Michael W. , Chagin Kevin M. , Ledet Elisa M. , Levy Justin , Lee Benjamin , Thomas Raju , Silberstein Jonathan L. 
Published: February 2017

126 Background: To determine the performance characteristics of urinary PCA3 andTMPRSS2:ERG (T2:ERG) in a racially diverse group of men. Methods: Following IRB approval, from 2013-2015, post digital rectal exam (DRE) urine was prospectively collected in patients without known prostate cancer (PCa), prior to biopsy. PCA3 and T2:ERG RNA copies were quantified and normalized to PSA mRNA copies using Progensa assay (Hologic, San Diego, CA). Prediction models for PCa and high-grade PCa were created using standard of care (SOC) variables (age, race, family history of PCa, prior prostate biopsy and abnormal DRE) plus PSA. Decision Curve Analysis was performed to compare the net benefit of using SOC, plus PSA, with the addition of PCA3 and T2:ERG. Results: Of 304 patients, 182 (60%) were AA; 139(46%) were diagnosed with PCa (69% AA). PCA3 and T2:ERG scores were greater in men with PCa, ≥ 3 cores, ≥ 33.3% cores, > 50% involvement of greatest biopsy core and Epstein significant PCa (p-values < 0.04). PCA3 added to the SOC plus PSA model for the detection of any PCa in the overall cohort (0.747 vs 0.677; p < 0.0001), in AA only (0.711 vs 0.638; p = 0.0002) and non-AA (0.781 vs 0.732; p = 0.0016). PCA3 added to the model for the prediction of high-grade PCa for the overall cohort (0.804 vs 0.78; p = 0.0002) and AA only (0.759 vs 0.717; p = 0.0003) but not non-AA. Decision curve analysis demonstrated significant net benefit with the addition of PCA3 compared with SOC plus PSA. For AA, T2:ERG did not improve concordance statistics for the detection any or high-grade PCa. Conclusions: For AA, urinary PCA3 improves the ability to predict the presence of any and high-grade PCa. However for this population, T2:ERG urinary assay does not add significantly to standard detection and risk stratification tools.
Ability of an epigenetic assay to identify anterior prostate tumors based on a negative 12-core biopsy.
Authors: Morgan Todd Matthew , Salami Simpa Samuel , Wei John Thomas , Palapattu Ganesh S. , Gursky Amy , Van Criekinge Wim , Van Neste Leander , Mehra Rohit 
Published: February 2017

131 Background: There is increasing awareness that anterior-predominant prostate cancers (PCa) are poorly sampled by 12-core transrectal ultrasound-guided (TRUS) prostate biopsies. Approximately one-fifth of all prostate tumors occur in this area, and many are high grade and extend beyond the prostatic capsule. An epigenetic assay, detecting PCa-specific DNA-methylation of GSTP1, RASSF1 and APC has shown to be a significant predictor for the presence of PCa in histopathologically cancer-negative biopsies through a cancer-associated field effect. It is currently unknown whether the field effect from an anterior-predominant cancer may be detected in standard posteriorly-directed sextant biopsy specimens. Methods: Seven patients with at least one prior negative TRUS biopsy were subsequently diagnosed with anterior-only PCa based on a transperineal mapping template prostate biopsy (MTPB). Three patients were diagnosed with low-grade Gleason score (GS) 6 tumors and four patients with GS ≥7 tumors. The outcome of the MTPB was compared with the result of the epigenetic test performed on the prior cancer-negative TRUS biopsy. Results: MTPB included a median of 68 cores (IQR 53-76). A total of 6 patients (86%) were methylation-positive at initial biopsy, suggesting that the field effect from these anterior-predominant cancers extends to the region of TRUS biopsy sampling. No methylation was found for one patient with only one GS6 positive core at MTPB and a tumor volume of 4%. Methylation intensities were higher for patients with GS ≥7 compared to those with GS6. A logistic regression model combining these intensities with traditional risk factors (PSA, age, TRUS-biopsy pathology and DRE) indicated higher risk scores for high-grade tumors. Conclusions: Aberrant DNA-methylation patterns are present in normal-appearing tissue from TRUS biopsy of patients with anteriorly located tumors. Although a small study, this is a unique cohort that underwent extensive sampling at re-biopsy demonstrating the presence of an anterior-predominant tumor. These results indicate that an epigenetic assay may be valuable even in patients with negative posteriorly-directed TRUS biopsies to detected anterior-predominant PCa.
Evaluation of MRI/TRUS fusion targeted biopsy versus 12-Core standard biopsy with pre-biopsy 1.5 Tesla multi-parametric MRI for diagnosis of prostate cancer in a community cancer center.
Authors: Bandyk Mark Gregory 
Published: February 2017

139 Background: Academic centers report the magnetic resonance imaging (MRI)/ transrectal ultrasound (TRUS) fusion biopsy increases detection of high−risk and high Gleason score (GS) prostate cancer (CaP) as compared to standard 12−core biopsy among men for suspected CaP. This prospective trial evaluated the utility and benefits of performing MRI/TRUS fusion biopsy in a community cancer center. Methods: Men suspected of CaP underwent prostate multi−parametric magnetic resonance imaging (mpMRI) using a 1.5 tesla GE 450W GEMS magnet with a 32 channel phased anterior array coil to identify suspicious regions for prostate cancer. Regions were graded with Prostate Imaging Reporting and Data System (PI−RADS V2.0) by a single radiologist (5 years of experience). Men underwent concurrent MRI/TRUS fusion targeted and 12−core standard biopsies using an image guided fusion system. This prospective trial evaluated 79 men for number of positive biopsies by GS, biopsy technique and cohort (biopsy naïve, prior negative biopsy and CaP under surveillance). McNemar test was used for statistical analysis. Results: Study group included 79 men (mean age 66 years) with mean PSA 8.25 ng/mL. Cancer detection rate (CDR) and GS for the entire cohort by biopsy technique were determined. Overall, target biopsy (TB) diagnosed more GS ≥ 7 versus the 12−core standard biopsy (SB) (26 vs 18) and less GS6 (13 vs 21) (p = 0.057). Exact agreement was demonstrated in 66% of cases between TB and SB for GS ≥ 7, GS6 and no cancer. SB found cancers in 11 men missed by the TB, but 73% of these cancers were low grade GS6. TB of higher PI−RADS category lesions found more and higher grade cancers: 73% PI−RAD 5, GS ≥ 7; 80% PI−RAD 4, GS > 6; and 73% PI−RAD 3 were benign. In the biopsy naïve group (32 men), TB detected more GS ≥ 7 than SB (19 vs 13) (p = 0.11). Conclusions: Utilizing a mpMRI with a 1.5 tesla magnet and no endorectal coil, these encouraging preliminary results suggest MRI/TRUS fusion biopsy can be validated in the community for CaP detection. Results support a new paradigm in CaP detection utilizing pre−biopsy mpMRI and targeting higher PI−RADS lesions possibly eliminating SB.
Imaging characteristics of patients with prostate cancer with favorable 17-gene genomic prostate score on 3T multiparametric prostate MRI.
Authors: Katz Aaron , Liu Corinne , Kosinski Kaitlin E. 
Published: February 2017

14 Background: Our practice utilizes a biopsy-based 17 gene test that is clinically validated as a predictor of favorable pathology and used to guide use of active surveillance for men with very low, low, and intermediate risk prostate cancer. The purpose of this study was to evaluate the imaging characteristics and PIRADS score of prostate cancer patients with a Genomic Prostate Score (GPS) indicating favorable pathology. Methods: 300 consecutive 3T Multiparametric Prostate MRI (MP-MRI) were identified from March 26, 2012, to June 29, 2015. Thirty patients (age 44-84 years) with GPS scores indicating favorable pathology were included in the study. Prostate Imaging Reporting and Data System (PIRADS) scores were assigned to each MP-MRI. MRI index lesions were defined as discrete hypointense T2 signal with at least one anatomically corresponding abnormal functional MRI parameter (diffusion weighted and dynamic contrast-enhanced images). The MRI examinations were evaluated for number and laterality of MRI index lesions and in relation to biopsy pathology findings after the MP-MRI was performed. Results: Out of 30 MP-MRI, 7 (23.3%) PIRADS 5, 10 (33.3%) PIRADS 4, 10 (33.3%) PIRADS 3, 1 (3.3%) PIRADS 2, and 2 (6.7%) PIRADS 1. Thirteen (43%) had bilateral MRI index lesions. Twenty-six (87%) MP-MRI had 1-3 MRI index lesions, 2 (7%) had 4-6 MRI index lesions and 2 (7%) had no index lesions. Six (20%) patients underwent curative treatment. Four (13.3%) patients underwent a transrectal ultrasound guided targeted biopsy and one underwent a prostatectomy after the MP-MRI. One harbored Gleason 7 with a PIRADS 1, 2 harbored Gleason 7 with PIRADS 5, and two were benign with PIRADS scores of 3 and 4. Conclusions: Patients with prostate cancer with a GPS score indicating favorable pathology had PIRADS scores ranging from 5 to 1, with the majority indicating either high or very high likelihood of harboring clinically significant cancer. This may imply that MP-MRI should continue to play an important role in stratifying patients with prostate cancer, even in those with favorable pathology. A study with a larger sample size and biopsy results after the initial MP-MRI to look for tumor upgrading is needed.
Prediction of postoperative histology in patients with prostate cancer using preoperative Ga-68-PSMA-PET/CT.
Authors: Boegemann Martin , Semjonow Axel , Breyholz Hans-Joerg , Schrader Andres Jan , Krabbe Laura-Maria , Weckesser Matthias , Schaefers Michael , Barth Peter J. , Huss Sebastian , Rahbar Kambiz 
Published: February 2017

144 Background: Recently developed 68Ga labeled prostate specific membrane antigen (PSMA) ligands were introduced as diagnostic tools to detect prostate cancer (PCa), PCa relapse and metastases with high accuracy. In this study we assessed the usability of preoperative PSMA-PET/CT information on congruency of spread of PCA compared with postoperative PCa-maps derived from radical prostatectomy (RPE) specimens. Methods: We referred 6 patients with biopsy proven high risk PCa to PSMA-PET/CT prior to RPE. Whole body PET/CT (Biograph mCT with 128 slice CT, Siemens) was performed 62±8 minutes after injection of 160±31 MBq [68Ga]-PSMA-HBED-CC (DKFZ-Ga-PSMA-11) as described by routine acquisition protocol. After RPE, prostate specimens were processed in the local pathology department. Topographical analysis of extension of PCa was reconstructed from representative slides on a schematic diagram resulting in a PCa-map of the prostate. After aligning the cutting planes of the PSMA-PET/CT to the PCa-map we defined 20 segments of the prostate and the seminal vesicles. We measured the maximum standard uptake value (SUV) of PSMA activity of the respective segments and compared the concordance of PSMA-positive and -negative areas with those of PCa and no PCa on the PCa-maps. We calculated sensitivity, specificity, positive and negative likelihood ratios (LR) taking available segments into account. Results: 106/112 segments were analyzed. 8 segments were excluded due to spillover of PSMA-activity in bladder urine. All but 3 segments with no PCa on the PCa-maps showed no uptake in PSMA-PET/CT (Specificity = 92%). The sensitivity of PSMA-PET/CT for showing PCa areas was equally 92%. The positive and negative LR for PSMA-PET/CT detecting or ruling out PCa was 11.5 and 0.09, respectively. Conclusions: This preliminary proof of concept study shows that prediction of later pathologic results in RPE-specimens could be estimated by preoperative PSMA-PET/CT. With optimized acquisition protocols it may be possible to improve our preliminary results. Perspectively PSMA-PET/CT may be helpful for identifying PCa suspicious lesions prior to prostate biopsy and support decision making prior to RPE or radiation therapy.
Evaluation of the clinical advantage of endo-rectal balloons (ERBs) for prostate treatments.
Authors: Barton Sarah J , Stratford Julia , Brand Douglas , Thompson Catherine , Taylor Cathy , Logue John P. , Wylie James , Coyle Catherine , McWilliam Alan , Choudhury Ananya 
Published: February 2017

148 Background: The challenge of prostate and rectal motion during radiotherapy has been firmly established, both these problems are exacerbated by rectal instability. A number of different mechanical methods have been explored to see if the rectum can be stabilised. This study aimed to establish whether there is a clinical advantage in the use of ERB’s for the treatment of prostate patients, assessing inter-fractional prostate stability and dose to the rectum. Methods: This planning study was based on 10 patients with 2 sets of CT and Cone beam CT (CBCT) data with and without an ERB in situ. The ERB was a 100cc air filled RectalPro balloon. CBCT scan with and without the ERB were taken on the same day. The scans were contoured and planned using pinnacle version 9.8 with rotational arc therapy to a dose of 60Gy in 20 fractions, for an Elekta Agility treatment unit. An assumption was made that the prostate stability was directly related to the rectal stability. Based on this assumption, comparisons of the rectal position and dose on the CBCT verses the respective CBCT were made. The rectal DVH on the plans for the ERB verses no ERB were compared and a two-tailed T-test was used for statistical analysis of all comparisons. Results: Positional analysis demonstrated 12% improvement in the dice coefficient similarity score of the rectum for the ERB (P=0.0003). This only correlated to a significant improvement in the AP movement at mid prostate for the ERBs (P=0.031). The ERB position was seen to be influenced by the angle of insertion. Removal of the CBCT data from the 4 ERBs with largest deviations in insertion angle significantly reduced the inter-fractional movement seen with the ERBs. The lower rectal doses showed an improvement of around 8% for the ERB group, although for the 57Gy dose was 2.5% better with no-ERB as shown in the Table. Conclusions: There is a clinical and statistical benefit in the dose reduction for the rectal wall in the use of ERB’s for prostate radiotherapy. Although the ERB position needs to be confirmed with IGRT to remove the potential for inter-fractional positional error. [Table: see text]
Effect of caloric restriction on the efficacy of radiation in both hormone-sensitive and hormone-resistant prostate cancers.
Authors: Schiewer Matthew Joseph , Gitman Robert Scott , Trabulsi Edouard John , DeAngelis Taziana , Kelly William Kevin , Gomella Leonard G. , Knudsen Karen E. , Dicker Adam , Simone Nicole Lynn 
Published: February 2017

16 Background: Locally advanced prostate cancers (LAPC) are aggressive, have poor prognosis, and are associated with high recurrence rates and conversion to castrate resistance. The molecular underpinnings of LAPC are being investigated to identify novel therapeutics. Animal models have shown that caloric restriction (CR) can potentially prevent the initiation of prostate cancer. We propose that CR may be used as a novel therapeutic intervention to enhance outcomes of radiation treatment by altering the molecular profile of prostate tumors. Methods: To assess the effect of CR with radiation in vivo, 6 week old male nude mice were injected with LNCaP (hormone sensitive, N = 60) or PC3 (hormone refractory, N = 60) tumor cells. Once tumors were palpable, mice were randomized to be treated with one of 4 conditions: ad libitum (AL) diet, 8Gy of radiation (RT), 30% reduction in caloric intake (CR), or CR+RT. Results: After PC3 tumor injection, compared with AL, the mice had a 22% reduction in tumor size with radiation, 77% with CR (p < 0.01) and an 80% reduction with CR+RT (p < 0.01). After LNCaP tumor injection, compared with ad libitum, the mice had a 49% reduction in tumor size with CR and a 55% reduction with CR+RT (p < 0.01). Tissue evaluation of mice treated with CR or CR+RT from both the LNCaP and PC3 models revealed decreased proliferation via Ki-67 and increased apoptosis with cleaved caspase-3 levels. Furthermore we establish significant changes of the pro-inflammatory IGF-1R pathway hypothesized to play in intricate roll in prostate cancer; down regulation of serum IGF-1R, IRS-1, PI3K, pAKT, and IGF-1:IGF-BP3. Conclusions: For the first time, we have shown that the efficacy of radiation can be increased by decreasing calories by 30% in both hormone-sensitive and hormone-refractory prostate cancer models. Future clinical trials should consider the innovative use of CR to augment standard cancer therapy as it has the potential to change the biology of tumors and enhance the opportunity for clinical benefit.
Do patients and physicians perceive PSA screening discussions the same?
Authors: Talcott James Austin , Aharonoff Gina , Bezuhly Maureen , Osborne Michael P. 
Published: February 2017

160 Background: Shared decision making is recommended for prostate-specific antigen (PSA) screening. We are performing a prospective randomized trial of educational interventions to improve screening compliance at an urban academic medical center. We hypothesize that patient and provider characteristics providers will affect compliance. We report the first results for PSA screening. Methods: In a cluster-randomized trial of educational supports for providers, we are recruiting an age- and sex-stratified sample of 216 patients aged 30 to 89 years undergoing an annual physical examination, 18 patients of each of 12 primary care physicians at two affiliated hospitals. Screening guideline format (color-coding) and academic detailing were randomly assigned in a 2 x 2 design. Surveys occurred immediately post-encounter to record recollections of screening discussions, recommendations and plans. Results: We report on the first 44 of 108 planned male participants. Most were white (77%), had a college degree (83%), and currently married (59%). When providers reported a PSA discussion, 13% of patients disagreed, while 23% of patients disagreed when their provider reported a PSA discussion. Discrepancies also occurred on additional elements of informed decision-making (data not shown). Reports also disagreed on physician recommendations: 2 of 8 patients (25%) disagreed with the physician’s report of recommending screening and 6 of 12 patients (50%) disagreed with the physician’s report of not recommending it. Half of patients (49%) reported distress at getting PSA results, but only 5% reported “a lot” of distress. Over half (58%) reported that PSA testing protected against prostate cancer “a lot.” No physician reported recommending PSA testing to men under age 50 or over age 70, but 1 of 6 men under 50 and 3 of 3 men over 70 reported that their physician had recommended testing. Conclusions: In a highly educated population of men and physicians surveyed immediately after their encounter, reports of whether PSA screening had occurred, the information that had been discussed and the recommendation had important discrepancies. Important differences may exist between patients and physicians in perceptions of PSA screening discussions. Clinical trial information: NCT02430948.