bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol metabolism and prostate cancer-specific mortality.
Authors: Stopsack Konrad Hermann , Sinnott Jennifer A. , Cerhan James Robert , Mucci Lorelei A. , Rider Jennifer R. 
Published: February 2017

12 Background: Cholesterol is needed in prostate cancer cells for cell proliferation and for androgen biosynthesis. Cholesterol-lowering statin drug use is associated with a lower risk of total and advanced prostate cancer and lower prostate cancer-specific mortality (PCSM). We hypothesized that tumor expression of cholesterol synthesis enzymes, transporters and regulators is associated with PCSM. Methods: We studied mRNA expression of 43 cholesterol metabolism genes in surgical specimens from 249 participants in the Health Professionals' Follow-up Study diagnosed with prostate cancer between 1986 and 2004. We included 81 cases of lethal prostate cancer and 168 indolent cases who survived >8 years without metastases. After multivariate dimensionality reduction for the synthesis, transport and regulator pathways using principal components analysis, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. We adjusted for age, year of diagnosis, body mass index, smoking status, family history, multivitamin use, high serum cholesterol and cholesterol-lowering drug use. Results: Reflecting the impact of the synthesis pathway and of the regulator pathway, respectively, the expression of squalene epoxidase (SQLE) and low-density lipoprotein receptor (LDLR) were significantly associated with lethal cancer in opposing directions. Compared to men with the mean level of SQLE expression, men with SQLE expression >1 standard deviation (SD) above the mean were 15.4 times more likely to have lethal cancer (95% CI: 3.31–71.53). For LDLR, expression >1 SD above the mean was associated with 96% lower odds of lethal cancer (95% CI: 0.01–0.70). Higher SQLE expression and lower LDLR expression were associated with higher Gleason grades (Fisher's test, p < 0.001 and p = 0.036, respectively) and were also predictive of PCSM independently from grade and tumor stage. Conclusions: These results suggest that the local cholesterol metabolism of the prostate tumor is tightly linked with mortality. Lethal cancers have higher activity of the second rate-controlling enzyme of cholesterol synthesis and are less dependent on cholesterol uptake.
Standard versus saturation biopsy before primary focal cryosurgery of the prostate: Does it matter?
Authors: Pak Jamie Sungmin , Cheetham Philippa J. , Katz Aaron , Wenske Sven 
Published: February 2017

123 Background: Primary focal cryosurgery (PFC) has emerged as a viable option for local therapy in prostate cancer (PCa), most suitable for patients with clinical stage T1c-T3 disease of any tumor grade in whom potency is not of primary concern and who are not suitable for radical prostatectomy or radiation therapy. Success of 5-year biochemical recurrence (BCR)-free survival, depending on criteria, ranges from 60% to 90% in the literature. We hypothesize that saturation biopsy before PFC leads to lower rates of BCR compared to standard 12-core biopsy. Methods: We compiled a consecutive series of patients who underwent PFC at our institution for localized PCa. Parameters including demographics, PSA levels, and Gleason scores before primary treatment and at time of recurrence were assessed. Biochemical failure was defined by both Phoenix (PD) and Stuttgart (SD) definitions. Chi-square analysis was performed to compare outcomes. Results: One hundred and forty-seven patients underwent PFC at our institution between August 2000 and January 2014. Forty-five patients were excluded due to incomplete follow-up data and/or missing biopsy information. Median follow-up was 40.3 months (0.8-116, IQR 41). Conclusions: Zero of the six patients who underwent a saturation biopsy before PFC experienced biochemical failure or progression. This in contrast to those who underwent a standard 12-core biopsy before PFC, of which 19% experienced biochemical failure by PD and 26% by SD, and 6% underwent progression. This may be due to more informed selection for local therapy and more comprehensive assessment of the extent of tumor for treatment planning. Though these differences were not statistically significant in our study, we believe that our results lay the groundwork for a larger study to assess differences in outcomes after PFC depending on the extent of biopsy before treatment. [Table: see text]
Prostate brachytherapy implant quality on biochemical control.
Authors: Muller Don , Monsour Paul 
Published: February 2017

128 Background: prostate brachytherapy at our institution was analyzed for implant quality on biochemical control. Methods: We treated 368 patients with clinically localized prostate cancer. All patients underwent 1 month CT based dosimetric analysis. Follow up data was available on 289 patients with a minimum follow up of 5 years. Gleason score was 6 in 80% (n=233), and 7 in 20% (n=56). Clinical stage was T1c in 90% of cases (n=260), T2a was 8% (n=23), T2b was <1% (n=3), T2c was < 1% (n=2). The initial prostate-specific antigen was < 10 ng/ml in 95% (n=274), 10.1-20 ng/ml in 5% (15).Patients with low risk disease ( clinical stage T1c, Gleason score 6 with a PSA < 10 ng/ml) n=228. Patients with intermediate risk disease Gleason 7 adenocarcinoma or with a PSA> 10 ng/ml < 20 ng/ml )n= 61. All patients were treated with I (125). All patients underwent a 1-month CT-based dosimetric analysis. The implant dose was defined as the dose delivered to 90% of the prostate volume on post implant dosimetry (D(90)). Results: At minimum follow up of 5 years overall freedom from biochemical failure was 91.4%. For Gleason grade 6 freedom from biochemical failure was 95%. For Gleason grade 7 freedom from biochemical failure was 77%. Based on PSA freedom from biochemical failure for PSA <10 ng/ml at diagnosis was 92 % and for PSA >10 ng/ml and <20 ng/ml was 80%. In patients with low risk disease ( clinical stage T1c, Gleason 6 adenocarcinoma with a PSA < 10ng/ml) the freedom from biochemical failure was 94%. In patients with intermediate risk disease (Gleason 7 adenocarcinoma or with a PSA >10 ng/ml <20 ng/ml ) freedom from biochemical failure was 84%. Patients with optimal dose implants n=264 freedom from biochemical failure was 95%. Patients with suboptimal dose implants n=25 freedom from biochemical failure was 52% Conclusions: With a minimum follow up of 5 years our data support the use of implant alone in low risk prostate cancer patients with a freedom from biochemical failure of 94%. Our data also shows the importance of implant quality in achieving optimal out comes.
Use of multiparametric MRI of prostate in active surveillance cohort of patients with localized prostate cancer in large urology group setting.
Authors: Kronhaus Richard , Telonis Dimitios , Pieczonka Christopher Michael , Williams Howard , Albala David , Mouraviev Vladimir , Buckingham Scott 
Published: February 2017

129 Background: The aim of this study was to determine the feasibility of using mpMRI to monitor/reclassify patients with low grade Prostate Cancer (PCa) undergoing Active Surveillance in a large urology practice. Methods: This is a retrospective study reviewing the records of 28 total patients following active surveillance (AS) protocol. All patients have been diagnosed with biopsy proven prostate cancer (PCa) and have undergone at least one mpMRI as a means of surveillance. The median total PSA of the group at time of diagnosis was 5.93 ng/ml and the mean age of the group was 64 years old. Between the 28 patients, 38 mpMRI tests were conducted, consisting of T2-weighted, diffusion weighted, and dynamic contrast enhanced MRI. Targeted ‘cognitive’ TRUS-MRI guided biopsy was used to locate progression of the PCa and help to determine whether a patient should stay on AS versus choosing more aggressive, definitive treatment. Confirmatory random biopsy was also used to determine overall sensitivity and specificity of the mpMRI conducted for suspicious regions of interest (ROI). Results: The sensitivity and specificity for the group was 65% and 92% respectively. The positive predictive value for the group was 94% while the negative predictive value was 55%. mpMRI was able to detect all clinically significant cancers except in one case. It did not detect some small size lesions (≤5.5mm) of Gleason score 6 that did not have a relevant clinical value. In five of the 28 cases (18%), patients fit the criteria for reclassification (Gleason ≥7, ≥ 3 new positive cores) out of the AS group. Four of these five patients exhibited clear progression of PCa on mpMRI and elected for more aggressive definitive treatment . The progression of cancer in the fifth patient was not seen on mpMRI but only after biopsy. This patient elected to stay in AS because of his advanced age. Conclusions: Despite the limitation of small sample size, mpMRI can be used as an effective diagnostic tool in the AS cohort of a community practice. It can facilitate early detection and progression of suspicious lesion(s) towards clinically significant PCa, thus triggering the start of more aggressive treatment.
Active surveillance outcomes among a cohort of county hospital patients.
Authors: Wood Erika L. , Canfield Steven 
Published: February 2017

136 Background: The standard of care for managing localized prostate cancer includes offering patients active surveillance. With the 10-year prostate cancer specific survival between 96-100% for both low and low-intermediate risk patients, active surveillance has proven to be a safe and effective option. Most studies have examined cohorts of patients within a tertiary referral center but data is sparse on county hospital patients, where health insurance coverage among other concerns pose barriers for patients to receive consistent medical care. We were interested in how active surveillance was performing amongst a cohort of county hospital based patients. Methods: A retrospective chart review was conducted on fifty patients placed on active surveillance for low and low-intermediate risk prostate cancer (by D’Amico criteria) between July 1, 2007 and August 1, 2013. Overall and cause-specific survival were the main outcome measures. Data was also collected on loss to follow-up rates. Results: In the cohort, the mean age at diagnosis was 62.2, mean body mass index was 28.0, most were African American or Hispanic (50% and 46%, respectively) and the majority had low-risk disease (84%). The median length of follow-up after diagnosis was 22 months. Nearly half of patients stopped active surveillance (44%), the most common reason being reclassification of their disease after second biopsy. All patients who were reclassified received definitive treatment with the exception of one patient who was lost to follow-up. Cause-specific and overall mortality were both 100% in this cohort. Nearly a quarter of patients (22%) were lost to follow-up (either had less than 12 months of surveillance following diagnosis or had not presented to clinic within the last 12 months). Conclusions: High rates of loss to follow-up present a significant challenge to managing localized prostate cancer with active surveillance in a county hospital population. In this small cohort, active surveillance appears to be a safe and effective management option for localized prostate cancer, yet undetected disease progression remains a significant concern.
Impact of crossover and baseline prognostic factors on overall survival (OS) with abiraterone acetate (AA) in the COU-AA-302 final analysis.
Authors: Ryan Charles J. , Smith Matthew Raymond , Fizazi Karim , Saad Fred , Sternberg Cora N. , Logothetis Christopher , Small Eric Jay , Carles Joan , Flaig Thomas W. , Taplin Mary-Ellen , Higano Celestia S. , De Souza Paul L. , De Bono Johann Sebastian , Griffin Thomas W. , De Porre Peter , Park Youn Choi , Li Jinhui , Kheoh Thian San , Molina Arturo , Rathkopf Dana E. 
Published: February 2017

142 Background: AA + prednisone (P) significantly increased OS, time to opiate use, and was well tolerated at the COU-AA-302 final analysis. Here we further characterize OS benefit adjusting for crossover therapy and for baseline prognostic factors. Methods: Patients (N = 1,088) were randomized 1:1 to receive AA (1 g) + P (5 mg po BID) vs P. Co-primary end points were radiographic progression-free survival and OS. Median time to events with 95% CI was estimated using the Kaplan-Meier method. Stratified log-rank test was used to test the difference in treatment effect. Adjustment for crossover utilized the iterative parameter estimate (IPE) and impact of baseline prognostic factors was examined via the multivariate Cox proportional hazard model. Results: With a median follow-up of 49.2 months and 741 deaths (96% of required), AA + P significantly reduced the risk of death vs P (19%) and prolonged median OS (34.7 vs 30.3 months) (Table). 44% of patients initially receiving P alone subsequently received AA + P as crossover per protocol (17%) or as subsequent therapy (27%). IPE adjustment resulted in a 26% reduction in the risk of death (Table). By multivariate analysis, AA + P treatment led to a 21% reduction in the risk of death; baseline prostate-specific antigen (PSA), lactate dehydrogenase (LDH), hemoglobin, alkaline phosphatase (ALP), bone metastases, and age were significant OS prognostic factors (Table). Conclusions: AA + P yielded a statistically significant improvement in OS. Greater improvement in OS was observed after adjusting for the 44% of patients originally on P who ultimately received AA + P. Adjusting for baseline prognostic factors also demonstrated an AA + P OS benefit. Clinical trial information: NCT00887198. [Table: see text]
Increase in higher risk prostate cancer cases following new screening recommendation by the US Preventive Services Task Force (USPSTF).
Authors: Hall Matthew David , Schultheiss Timothy E. , Farino Ginamarie , Wong Jeffrey Y.C. 
Published: February 2017

143 Background: In 2011, the USPSTF issued a draft recommendation that PSA not be used for prostate cancer screening in men irrespective of age. Here we present early measures of the potential consequences of this recommendation. Methods: Data on men diagnosed with prostate cancer from January, 2005 through June, 2013 were extracted from the National Oncology Data Alliance (Elekta/IMPAC Medical Systems, Inc., Sunnyvale, CA). This proprietary database of merged tumor registries captures newly diagnosed cancer cases at more than 150 hospitals in the United States. Data were available through 2013 compared to 2011 in Surveillance, Epidemiology, and End Results (SEER). The data in the NODA are identical to the data sent to state tumor registries and SEER in regions that participate in SEER. Date of diagnosis, age, race, T stage, Gleason score, and PSA were collected. Patients were classified into their respective National Comprehensive Cancer Network (NCCN) risk group. Data were available and analyzed for 87,562 men. Frequencies were examined by date of diagnosis, grouped in six-month intervals. Trends were assessed using linear regression. Results: From 2005 to 2011, the percentage of men with PSA>10 decreased gradually. From 2011 to 2013, the percentage increased by 3.0% per year (p<0.0004). The fraction of men with age ≥75 years to present with PSA>10 increased by nearly double the rate for men of all ages from 2011 to 2013. No significant trends in Gleason score were observed; the frequency of men with higher T stages generally decreased over the entire period without a notable change after 2011. The percentage of men with intermediate or higher risk cancer was stable at 70-73% prior to 2011, but rose by 2.9 % per year after 2011 (p<0.003) without evidence of a plateau. Conclusions: The proportion of men diagnosed with intermediate or higher risk cancer increased by nearly 6% from 2011 to 2013. Given an estimated 233,000 new prostate cancers in 2014, approximately 14,000 men per year will shift from low risk into a higher risk disease group. Our findings suggest an increase in the fraction of men diagnosed with higher risk prostate cancer after 2011.
A phase IIb trial of docetaxel concurrent with radiotherapy plus hormotherapy versus radio hormonotherapy in high-risk localized prostate cancer (QRT SOGUG trial): Preliminary report for design, tolerance, and toxicity.
Authors: Carles Joan , Gallardo Diaz Enrique , Domenech Montserrat , Font Albert , Bellmunt Joaquim , Mellado Begoña , Suárez Cristina , Bonfill Teresa , Saez M Isabel , Guix Marta , Mendez Maria Jose , Maroto Pablo , de Portugal Teresa , Figols Mariona , Luque Raquel , Aldabo Ramon , Morales Rafael , Bonet Marta , Maldonado Xavier , Foro Palmira 
Published: February 2017

15 Background: Docetaxel improves survival in patients (pts) with metastatic hormonosensitive prostate cancer (PC) and castration-resistant prostate cancer. The objective of this phase IIb trial was to assess the activity of low dose docetaxel concurrent with radiotherapy plus standard hormonal treatment in pts with high risk localized CaP. Methods: High-risk localized CaP was defined by ≥ 1 of the following criteria: T3-T4, Gleason score (GS) ≥ 8, PSA > 20 ng/mL, pN+. Pts were randomly assigned to either arm A (LH-RH analogs every 3 months for 3 years and radiotherapy 73.8 Gy [1.8 Gy x 41 fractions] or 74 Gy [2Gy x 37 fractions]) or arm B (LH-RH analogs every 3 months for 3 years, radiotherapy and concurrent weekly docetaxel at 20 mg/m2 for 9 weeks). Chemotherapy was started one week before of radiotherapy. Primary endpoint was PSA relapse according to the Phoenix definition. The planned number of pts was 130 to detect a 15% difference with a power of 80% and an alpha of 0.05 (two-sided). Results: From 12/2008 to 9/2012, 130 pts were accrued (Arm A: 64, Arm B: 66). Median age was 68 years (61-73). Patients had T3-T4 (82.6%), GS ≥ 8 (76.3%), PSA > 20 ng/mL (26.9%) and pN+ (18.9%). All characteristics were well-balanced between arms. Median dose of radiotherapy was 74 Gy (72–74.8) in arm A, and 73.8 Gy ( 72-75.6) in arm B. 75.7% of pts received the planned 9 treatments of docetaxel and median number of cycles delivered per patient was 9. After a median follow-up of 29.6 months (9.6-40.2), most common grade 1/2 toxicities (arm A and arm B) were: cystitis ( 12.5% vs 8.3%), diarrhea (35.9% vs 70%), proctitis (12.5% vs 13.3%), rectal tenesmus (3.1% vs 23.3%), asthenia (23.4% vs 61.6%) and dysuria ( 28.1% vs 30.0%). Toxicity G3/G4 diarrhea was reported in 8.3% of pts in arm B and 0% in arm A. G3/G4 lymphopenia occurred less often in arm A than in arm B (3.1% vs 23.3%). %). There was no toxicity-related death. Conclusions: The QRT SOGUG phase IIb trial met its accrual target and shows that concurrent weekly docetaxel can be administered with standard doses of radiotherapy and without increasing toxicity profile. Clinical trial information: 2008-003554-14.
A genomic classifier to improve prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy.
Authors: Klein Eric A. , Yousefi Kasra , Haddad Zaid , Choeurng Voleak , Buerki Christine , Stephenson Andrew J. , Li Jianbo , Kattan Michael W. , Magi-Galluzzi Cristina , Davicioni Elai 
Published: February 2017

154 Background: Surgery is a standard first line therapy for most intermediate-high risk men diagnosed with prostate cancer. While clinical factors such as tumor grade, stage and prostate specific antigen (PSA) are currently used to identify patients at risk of cancer recurrence, novel biomarkers that can improve risk stratification and distinguish local from systemic recurrence are needed. The Decipher Genomic Classifier (GC) is a validated model for predicting men at risk of metastasis. We evaluated its performance in predicting metastatic disease within 5 years after surgery (rapid metastasis, RM) in an independent cohort. Methods: Tumors and clinicopathologic data were obtained from a cohort of 2,641 RP patients treated between 1987-2008 at Cleveland Clinic. The final study cohort consisted of 15 RM patients and 154 patients as non-RM controls who met the following criteria: 1) preoperative PSA>20 ng/mL, stage pT3 or margin positive, or Gleason score ≥8; 2) pathologic node negative; 3) undetectable post-RP PSA; 4) no neoadjuvant or adjuvant therapy; and 5) minimum 5 year follow-up for the controls. Results: RM patients developed metastasis with a median of 2.3 (IQR: 0.8-5) years. In multivariable analysis, GC was a significant predictor of RM (OR=1.48, p=0.018) after adjusting for clinical risk factors. GC had the highest c-index, 0.77, compared to the Stephenson model (c-index 0.75) and CAPRA-S (c-index 0.72) as well as a panel of previously reported prostate cancer biomarkers unrelated to GC. Integration of GC into the Stephenson nomogram increased the c-index from 0.75 (95% CI: 0.65-0.85) to 0.79 (95% CI: 0.68-0.89). Conclusions: GC was independently validated as a genomic metastasis signature for predicting RM in a cohort of high-risk men treated with RP and managed conservatively without any adjuvant therapy. Integration of GC into clinical nomograms led to improvement in prediction of RM. GC may further allow identification of men most at risk for metastatic progression who should be considered for multimodal therapy or inclusion in clinical trials.
External validation of multiparametric MRI and fusion-guided prostate biopsy: A matched cohort analysis.
Authors: Abboud Steven F. , Rastinehad Ardeshir , George Arvin Koruthu , Frye Thomas P , Ho Richard , Shakir Nabeel Ahmad , Chelluri Raju , Fascelli Michele , Walton-Diaz Annerleim , Sankineni Sandeep , Turkbey Baris , Choyke Peter L. , Merino Maria J , Pinto Peter A. 
Published: February 2017

155 Background: MRI/US fusion-guided biopsy has been shown to improve the detection of clinically significant prostate cancer (PCa). As adoption of this novel technology expands, the reproducibility of outcomes from expert centers becomes essential. The objective of our study was to validate the comprehensive NCI experience of multiparametric MRI and fusion-guided biopsy (FB) with an external, independent, matched cohort of patients. Methods: We compared 1,003 patients enrolled from August 2007 through February 2014 in a prospective trial comparing systematic 12-core biopsy (SB) to FB at the NCI to 256 patients that underwent an identical procedure at Long Island-Jewish Hospital (LIJH) from February 2012 to June 2014. Patients from LIJH were matched 1:1 for age, PSA, and MRI suspicion score to a corresponding cohort of NCI patients. Clinically-significant (CS) disease was defined as a Gleason score of ≥4+3 in any biopsy core. Results: The overall cancer detection rate was 564/1,003 (56%) of NCI patients and 167/256 (65%) of LIJH patients. In the matched cohort analysis, cancer detection rate (CDR) by FB between cohorts was 52% NCI vs. 54% LIJH (p=0.67). Both cohorts demonstrated a similar rates of upgrading by FB compared to SB, 29% NCI vs. 23% LIJH (p=0.42). This trend applied to patients that upgraded to CS disease by FB, 12.7% NCI vs. 12.6% LIJH (p=0.42) (Table). Conclusions: The improved detection of clinically-significant cancer by mpMRI and FB is reproducible in the hands of an experienced multi-disciplinary team. Our results suggest that with appropriate training in the interpretation of mpMRI and performance of FB, dissemination of this technology can render equivalent outcomes. [Table: see text]