bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of degarelix prior to radiation on prostatic tissue androgens.
Authors: Montgomery Robert B. , Russell Kenneth J. , Liao Jay Justin , Ellis William J , Cheng Heather H. , Yu Evan Y. , Mostaghel Elahe A. 
Published: February 2018

103 Background: Optimizing androgen suppression may provide better treatment outcomes for localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation (ADT) with definitive radiotherapy in men with locally advanced or high-grade disease. LHRH agonist (LHRHa) is most commonly used. The LHRH antagonist degarelix may provide more robust androgen suppression. The impact on tissue androgens following use of degarelix prior to radiation has not been reported. We examined the impact on androgens in serum and tissue after 12 weeks of degarelix in this phase II study. Methods: A prospective, phase II study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent degarelix with radiation. Prostate biopsies were obtained at the time of fiducial placement before radiotherapy. Serum and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Needle biopsies from a separate analysis of untreated men or those receiving LHRHa prior to prostatectomy were used as tissue androgen level controls. Results: 16 men with intermediate (4) and high-risk (12) PCa received study therapy. 14 men completed degarelix and planned radiation to 77.4-81 Gy. Serum and tissue androgens after 12 weeks of therapy are compared to untreated control and LHRHa treated patients (12 weeks). Serum levels of dihydrotestosterone (DHT) and testosterone were similarly suppressed by LHRHa or degarelix compared to untreated controls, without statistically significant differences. Degarelix provided statistically greater reduction in androsterone than LHRHa. Conclusions: In this phase II study degarelix and LHRHa achieved similar serum and tissue androgen levels at 12 weeks; however, there was a greater suppression of tissue androsterone with degarelix. The clinical significance of this difference remains uncertain. Clinical trial information: NCT01731912. [Table: see text]
Improving risk-stratification of localized prostate cancer in a prospective active surveillance cohort.
Authors: Gregg Justin , Reichard Chad A. , Wang Xuemei , Chapin Brian Francis , Pisters Louis L. , Pettaway Curtis Alvin , Ward John Francis , Achim Mary F. , Choi Seungtaek , Kuban Deborah A. , Davis John W. , Kim Jeri 
Published: February 2018

104 Background: Prospective active surveillance (AS) studies in men with low- and intermediate-risk prostate cancer (PCa) have demonstrated feasibility, but no consensus supports an optimal monitoring scheme. To expand our findings on AS disease reclassification, we examined predictors of disease reclassification in a prospective single-institution AS study. Methods: Men with localized PCa diagnosed within 6 months (mos) of AS enrollment were stratified into four groups: group 1 (Gr 1) was defined by a Gleason score (GS) ≤6 (3+3), one positive (pos) core ( < 3 mm), and a prostate-specific antigen (PSA) level < 4 ng/mL (adjusted by prostate size); Gr IIa by GS 6, one pos core, and either tumor length ≥3 mm or PSA ≥4 ng/mL; Gr IIb by GS6, > one pos core, and any PSA level or tumor length; Gr IIc by GS7, > one pos core or any PSA. Monitoring included PSA and digital rectal exam every 6 mo. Biopsy (BX) was repeated at 1 year and then on a predetermined BX scheme. Patients with reclassified disease (upgrading, increase in pos cores and/or tumor length) were offered treatment. Cox proportional hazards modeling was used to determine the association of baseline clinicopathologic parameters with time to reclassification. Results: Between 2006 and 2015, 803 patients met criteria for inclusion: Gr I, 242; Gr IIa, 67; Gr IIb, 376; Gr IIc, 118. Median age was 64 years (range, 36–83), 662 (82.4%) were white, 703 (87.5%) had cT1c disease, 687 (85.6%) had GS 6, and median PSA level was 4.2 ng/mL (range 0.2–34). At a median follow-up of 2.9 years, 249 (31.0%) men had disease reclassification and 258 (32.1%) left AS to pursue curative treatment. Overall, 82% of reclassifications occurred within 3 years of study enrollment. Stratification to group IIb/IIc was significantly associated with time to reclassification compared to Gr I/IIa (HR 2.13, 95 CI 1.63-2.80, p < 0.001) while CAPRA score did not show a significant difference (p = 0.27). Conclusions: Grouping patients on characteristics including tumor length and pos core number may improve risk stratification in localized PCa. Risk-based surveillance protocols merit further evaluation. Clinical trial information: NCT00490763.
Phase II trial of 6 months ADT/abiraterone acetate plus prednisone (AAP) and definitive radiotherapy (AbiRT) for men with intermediate to high risk localized prostate cancer.
Authors: Koontz Bridget F. , Hoffman Karen E. , Healy Patrick , George Daniel J. , Harrison Michael Roger , Zhang Tian , Lee W. Robert , Berry William R. , Pugh Thomas J , Corn Paul Gettys , Bratt LuEllen , Shobe Kellie , Thornburg Blair , Allen Donna M. , Brummer Katie , Tojong Beth , Hobbs Bridget , Halabi Susan , Armstrong Andrew J. 
Published: February 2018

11 Background: Combined external beam radiotherapy (RT) and androgen deprivation therapy (ADT) improves survival over RT alone for high risk prostate cancer (PC). Long-term ADT use, currently recommended for high risk PC, also increases toxicity. Recent data suggests synergistic efficacy with the addition of abiraterone acetate plus prednisone (AAP) to RT/ADT. Potent androgen blockade may provide biochemical control with short-term ADT course in men with aggressive but localized PC. Methods: This was a two center prospective phase 2 single arm clinical trial within the Department of Defense PCCTC (NCT01717053). Eligibility included 2+ intermediate or 1 high NCCN risk factors and no metastatic disease. Men received 6 months of ADT concurrently with 1000mg AA/5mg P daily and 78 Gy RT to prostate/SV. Primary endpoint was PSA < 0.1 ng/ml at 1 year. Secondary objectives included BPFS, PSA nadir, testosterone recovery, toxicity, and patient-reported QOL. Results: We enrolled 37 men (82% white, 18% black) with intermediate to high risk localized PC; 33 completed course of treatment (4 patients halted early for personal preference (N = 2), planned prostatectomy, or renal artery stenosis). Median age was 66 years; 46% Gleason 8-10, 40% Gleason 4+3 = 7, 62% T1c. Median follow-up is 23 months. Regimen was well tolerated with 12 (32%) G3 toxicities (10 hypertension, 2 hyperglycemia, 1 hypokalemia); no G4-5 or unexpected toxicities were observed. At 12 months from enrollment, PSA remained at undetectable levels in 52% of men. Testosterone recovery to normal lab value occurred in 12 (62%) at 12 months. In those patients, 20 (95%) and 21 (100%) remained with PSA under 0.5 and 1.0 ng/ml, respectively. No patient has failed by Phoenix definition to date. 1 year EPIC QOL had median summary scores above 90 for incontinence, urinary, bowel, hormonal, and satisfaction. Sexual summary score fell from median of 46 at baseline to 26 at 1 year. Conclusions: In men with high risk intermediate or limited high risk PC, utilizing short-term ADT/AAP with definitive RT shows 1) high rate of testosterone recovery and good quality of life and 2) excellent PSA control at 1 and 2 years. Clinical trial information: NCT01717053.
National trends in the management of patients with positive surgical margins at the time of radical prostatectomy.
Authors: Ghabili Kamyar , Nguyen Kevin , Hsiang Walter , Syed Jamil , Suarez-Sarmiento Alfredo , Shuch Brian M. , Park Henry Soo-Min , Yu James B. , Leapman Michael 
Published: February 2018

111 Background: The optimal management approach for patients with positive surgical margins (PSM) at radical prostatectomy (RP) has not been definitively assessed. To better understand contemporary patterns of care, we sought to examine time trends and determinants of adjuvant therapy in a large national sample of men with prostate cancer (PCa) treated with RP. Methods: We queried the National Cancer Database (NCDB) to identify men with clinically-localized PCa diagnosed from 2010 to 2014 who had PSM at RP performed as initial primary definitive treatment. We used descriptive statistics to examine subsequent management strategies, assessed as no adjuvant therapy as part of the initial planned course of management, receipt of adjuvant radiation therapy (RT), and receipt of adjuvant RT in combination with androgen deprivation therapy (ADT). Binary logistic regression models were constructed to identify patient, tumor, and facility features associated with receipt of adjuvant therapy. Results: During the study period, we identified 44,523 patients with PSM. Of those, 5,179 (11.6%) men received any adjuvant RT (+/- ADT), while only 1,380 (3%) received adjuvant RT with ADT. Use of adjuvant RT did not change over the study period ( p= 0.61). On multivariable analysis men of uninsured status (p = 0.003), Medicaid insurance (p = 0.001), and patients treated in non-academic facilities (p < 0.001) were more likely to receive adjuvant RT. In addition, use of adjuvant RT was associated with higher pre-treatment PSA (p < 0.001), pathologic stage (p < 0.001) and Gleason grade group (p < 0.001), decreasing distance from the treatment center (p < 0.001), and shorter duration between diagnosis and RP (p < 0.001). Receipt of adjuvant ADT with RT was associated with clinical and pathologic features; however, not with sociodemographic factors. Conclusions: The majority of patients experiencing PSM at RP did not receive adjuvant RT, and rates of adjuvant therapy have remained stable over time. In addition to adverse clinical and pathologic features, sociodemographic and facility factors were significantly associated with receipt of adjuvant RT; however, the addition of ADT appears largely driven by disease characteristics.
Are all biopsies created equal? comparison of extended sextant prostate biopsies performed with and without MRI-TRUS fusion biopsy system.
Authors: Hale Graham R. , Bloom Jonathan , Sabarwal Vikram , Gold Samuel , Rayn Kareem , Wood Brad J. , Turkbey Baris , Pinto Peter A. , Hwang Tyler 
Published: February 2018

117 Background: Extended sextant systematic prostate biopsies have the inherent risk of under-sampling prostate cancer. Fusion guided multiparametric magnetic resonance imaging (mpMRI) biopsies have been employed to better represent the disease and guide treatment. We sought to determine if due to heightened suspicion of cancer and/or visualization of mpMRI there were any discrepancies between systematic biopsies done with a Fusion System as compared to those done without (TRUS alone). Methods: From a prospectively collected database, we performed a review collecting age, race, clinical stage, PSA, and time until repeat systematic biopsy as part of fusion guided biopsy (IB). We also collected pathology results reported as Gleason Score (GS), for both the patients’ OB and our IB. Patients were stratified into groups based on time between OB and IB/fusion biopsy ( < 6 months, < 1 year and < 2 years). Results: 69 patients with a previous OB underwent combined fusion and IB within our designated time intervals. Cancer detection rates between the OB and IB results were similar at 6 months, 1 year and 2 years (80 vs 90%, 87.5 vs 87.5% and 65 vs 69%). Detection rates of GS ≥ 3+4 were higher with IB within 12 months compared with IB from 12-24 months (72.7 vs 40.9%, p = 0.03 OR 3.85 (1.09-13.66). Of the patients who were upgraded (n = 24), 54.2% (n = 13) went from benign pathology to a diagnosis of prostate adenocarcinoma. Of all OB GS 3+3 (n = 31), 29% were restaged to higher risk disease on IB. Rates of IB upgrading were similar within 6 months, 1 year and 2 year, 40%, 33.33% and 31.91%). Patients who were upgraded on IB compared to those who were not upgraded were of similar age (67.0 ± 6.53 vs 66.50 ± 6.47), race (17.4% African-American vs 13%), PSA (7.60 ± 5.61 vs 7.50 ± 4.39) and prostate volume on MRI (51.30 ± 26.87 vs 59.26 ± 38.52). Conclusions: A systematic biopsy at our referral center during a mpMRI fusion biopsy was over 3.5 times more likely to detect GS ≥ 3+4 when done within 1 year of the outside biopsy. There continued to be a risk, 34.7% overall, of disease upgrading in all time periods. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH
The association between physician trust and prostate specific antigen screening: Implications for shared decision making.
Authors: Klaassen Zachary William Abraham , Wallis Christopher J.D. , Goldberg Hanan , Chandrasekar Thenappan , Fleshner Neil Eric , Finelli Antonio , Kulkarni Girish S. , Satkunasivam Raj 
Published: February 2018

13 Background: Most cancer organizations recommend shared decision making for PSA screening, a process relying on a trusting relationship between patient and physician. The objective of this study was to assess the degree to which an individual’s trust in cancer information from their physician compared to internet-based information impacts the likelihood of receiving PSA-screening. Methods: This was a cross-sectional study (2011-2014) of the Health Information National Trends Survey (HINTS), a survey of people living in the US. The primary exposure was degree of trust in cancer information from participant’s physician (CIP). The secondary exposure was degree of trust in cancer information from the internet (CII). The primary outcome was patient-reported receipt of PSA-screening. The Cochran-Armitage test was used to identify significant trends in the primary outcome, across levels of trust. A multivariable logistic regression model assessed the association between CIP and CII with PSA-screening, adjusted for a priori covariates. Results: Among 5069 eligible respondents, 3,606 (71.1%) reported trusting CIP ‘a lot’, 1,186 (23.4%) ‘some’, 219 (4.3%) ‘a little’, and 58 (1.1%) ‘not at all’. 2,655 (52.4%) men received PSA-screening. The degree of trust in CIP was strongly associated with the likelihood of receiving PSA-screening: among men who reported ‘a lot’ of trust, 54.9% underwent screening, 48.6% ‘some’ trust, 38.4% ‘a little’ trust, and 27.6% among men ‘not at all’ trusting their physician (trend p < 0.0001). The degree to which men trusted CII was also associated with having received PSA-screening (p = 0.005), albeit with an insignificant trend (p = 0.07). After multivariable adjustment, these significant results persisted for degree of CIP trust (vs ‘a lot’: ‘some’ OR 0.80, 95%CI 0.66-0.97; ‘a little’ OR 0.61, 95%CI 0.41-0.90; ‘not at all’ OR 0.33, 95%CI 0.15-0.73), but not for trust in CII. Conclusions: The level of trust an individual has in their physician is strongly associated with undergoing PSA-screening. As rationale implementation of PSA screening requires shared decision-making, the level of physician trust has implications for dissemination of PSA-screening guidelines.
How many cores are needed to detect clinically significant prostate cancer on targeted MRI-ultrasound fusion biopsy?
Authors: Lu Amanda , Ghabili Kamyar , Nguyen Kevin , Leapman Michael , Sprenkle Preston 
Published: February 2018

134 Background: The optimal number of MRI-US fusion biopsy cores to adequately sample regions of interest (ROI) remains unknown. To better understand the optimal approach to lesion targeting, we aimed to examine the cancer detection rate based on sequential number of cores obtained. Methods: Of 744 patients undergoing MRI-US fusion biopsy between 2012 and 2016 at our institution, we identified 628 men with targets on multi-parametric MRI (mpMRI) who underwent targeted and systematic fusion biopsy using the Artemis platform for clinical suspicion (n=465) or known history of PCa (n=163). mpMRI studies were reviewed by genitourinary radiologists using a 3-tiered Likert scale and PI-RADS classification schema. Biopsy was performed by two urologists performing a high volume of fusion biopsies (PS and RD). Cores were taken sequentially from each ROI with an even distribution. The primary outcome was the proportion of high-grade (Gleason ≥3+4) cancers missed on a 2-core lesion biopsy. Results: We biopsied 1,233 ROI with a median of 5 cores (IQR 3-5) from each ROI. A total of 581 ROI (47%) were positive for any Gleason grade PCa, in 380 (61%) patients. On a per-lesion basis, 84% of any Gleason score cancers were detected with a two-core biopsy and 77% of Gleason ≥3+4 tumors. Cancer detection rates improved with increasing number of cores (Table 1). For any Gleason grade PCa, additional cores beyond 5 cores had no significance. For G≥3+4 cancer, there was no significance with additional sampling from 3 to 4 cores, but improved detection from 3 to 5 cores (P<0.05). For PI-RADs 4 and 5 lesions, additional sampling up to 4 cores significantly improves G≥3+4 detection, while for PI-RADs 1-3 lesions sampling up to 2 cores improves detection. Conclusions: On a per-lesion basis, sampling two cores of mpMRI-evident lesions at the time of fusion biopsy misses nearly one-quarter of clinically significant PCa that would be detected on additional sampling. [Table: see text]
Normal Tissue Complication Probability (NTCP) model for erectile dysfunction (ED) following external beam radiotherapy (RT) for prostate cancer.
Authors: Murray Julia , Griffin Clare , Hall Emma , Dean Jamie , Syndikus Isabel , Staffurth John , Mayles Helen , Gulliford Sarah , Dearnaley David P. 
Published: February 2018

135 Background: ED remains a common toxicity of prostate RT despite technological advances. Penile bulb (PB) dose has been proposed as a predictor of ED post RT. The main objective of this study was to develop NTCP models for ED. Methods: 162 men treated within the CHHiP IGRT substudy (CRUK/06/16) had baseline clinical data, PB dosimetric data & evaluation of ED using EPIC-26 at least 3 years post RT. Planning CT and reference dose distributions were imported into analysis software (VODCA, MSS GmbH) and PB retrospectively contoured by one clinician. The defined endpoint (severe ED) was a standardised average value of 0-33 for EPIC-26 sexual domain. Predictive models of ED were generated using PB dose in EQD2 (α/β ratio = 3Gy) & clinical data (age, diabetes, hypertension, NCCN risk group, baseline PSA, hormone therapy, IGRT, margin size, PB volume). Multivariate logistic regression method using resampling methods was applied to select model order and parameters. Models were fitted using logistic regression of the form Probability = eA(x)/1+eA(x), where A(x) = constant + sum of (variables * associated regression coefficients). Model performance was evaluated through area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow (HL) goodness-of-fit test. Results: 101/162 (62%) men had severe ED with statistically significant difference in PB max and mean dose between those patients with or without severe ED (max: 61.8Gy vs 43Gy & mean: 27.4Gy vs 14Gy respectively; p = 0.001). In the univariate analyses, age, diabetes, risk group, PB mean and max doses were significantly associated with EPIC calculated severe ED. The optimal NTCP model (AUC 0.78; CI 0.71-0.86: p for HL = 0.75) for EPIC calculated severe ED included age, PB mean dose and diabetes where A(x) = -10.13+(0.14*age)+(0.03*PB mean dose)+(2.88 if diabetic). A comparable model using clinician completed outcomes will be reported. Conclusions: This study provides the first known clinical prediction model for ED including PB dose, with good model performance. The determined predictors for the NTCP model of severe ED in this cohort were PB mean dose, age & diabetes. External validation of this model is desirable. Clinical trial information: 97182923.
What is the accuracy of multi-parametric magnetic resonance imaging in predicting adverse pathology in patients undergoing radical prostatectomy?
Authors: Rai Samarpit , Dervishi Adnan , O'Bryan Brittany Ewing , FitzGibbon Thomas Michael , Knoll Paul , Nguyen Kristy Doan , Ankem Murali , Messer Jamie Christopher 
Published: February 2018

139 Background: Few studies have examined the accuracy of preoperative multi-parametric magnetic resonance imaging (MP-MRI) in predicting adverse pathological features in patients undergoing radical prostatectomy (RP) for localized prostate cancer (PCa). Methods: We retrospectively analyzed the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of preoperative MP-MRI for adverse pathologic features [extracapsular extension (ECE), seminal vesicle invasion (SVI), lymph node involvement (LNI) and high Gleason score) on postoperative pathologic staging after RP in 30 patients with localized PCa . Results: The median age and preoperative PSA were 62.5 years and 8.5 ng/mL, respectively.17 patients had ECE, 5 had SVI, 5 had LNI, and 15 had high risk Gleason score (4+3, tertiary pattern 5, 4+4 or higher). The sensitivity, specificity, PPV and NPV of MP-MRI for ECE was 64.71% (95%CI 38.33 - 65.79), 92.31% (95% CI 63.97 - 99.81), 91.67% (95% CI 61.52 - 99.79), and 66.67% (95% CI 40.89 - 86.96) respectively. For the detection of SVI on MP-MRI, the sensitivity, specificity, PPV, and NPV were 60% (95% CI 14.66 - 94.73), 96% (95% CI 76.95 - 99.90), 75% (95% CI 19.41 - 99.37), and 92.31% (95% CI 74.87 - 99.05) respectively. For the detection of LNI, the sensitivity of MP-MRI was 100% (95% CI 47.82 - 100), specificity was 96% (95% CI 79.65 - 99.90), PPV was 83.33% (95% CI 35.88 - 99.58), NPV was 100% (95% CI 85.75 - 100). For detection of of high risk Gleason score the sensitivity of MP-MRI was 94.44% (95% CI 72.71 - 99.86), specificity was 66.67% (95% CI 34.89 - 90.08), PPV was 80.95% (95% CI 58.09 - 94.55), and NPV was 88.89% (95% CI 51.75 - 99.72). Conclusions: MP-MRI has a reasonable sensitivity, specificity, and NPV for the preoperative detection of adverse pathologic features at prostatectomy. This could provide assistance in the selection of patients appropriate for Active Surveillance as well as in the preoperative counseling regarding multimodality treatment for PCa.