bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major histocompatibility complex class I (MHC 1) expression in clear cell renal cell carcinoma: Correlation with clinical outcome.
Authors: Master Viraj A. , Holzman Sarah , Pollack Brian , Osunkoya Adeboya O. 
Published: February 2017

541 Background: Most patients with clear cell renal cell carcinoma (ccRCC) initially present with localized disease but a fraction subsequently develop metastases. Current predictive models of ccRCC recurrence are imperfect, suggesting a need for additional predictors. Metastatic ccRCC may be modulated by the immune system, suggesting that the immune system plays a role in tumor progression. Major histocompatibility complex class I (MHC I) expression on tumor cells is critical for immune system recognition. Here, we analyzed MHC I expression in ccRCC and its correlation with clinical outcomes. Methods: ccRCC patients who underwent radical nephrectomy with a ≥4 years of follow-up, without T4 disease or metastasis at presentation were included. All slides were re-reviewed by a single Urologic Pathologist and blocks with tumor and adjacent renal parenchyma were selected for each case for immunohistochemical staining for MHC I . Whole slide scanning and automated image analysis was used; representative areas of tumor and normal kidney were selected and averaged with Aperio image analysis software (positive pixel count v. 9). Unpaired t-test and one-way ANOVA were performed in GraphPad Prism. Results: 34 patients were analyzed. Fuhrman nuclear grades (FNG) were: FNG 2 10/34 (29%), FNG 3 20/34 (59%) and FNG 4 4/34 (11%). Although there was no correlation with FNG and MHC1 (ANOVA, p=0.800), patients who were alive at follow up had increased MHCI expression (80.1% average positivity score) than those who died (53% average positivity score; t-test, p<0.0001). Patients living with recurrence had increased MHCI expression (81.3% positivity score) compared to those who succumbed to their disease (53.2% positivity score; t-test, p<0.0001). Conclusions: MHCI expression may be an important prognostic factor in ccRCC for recurrence free survival, and also for prognosis of those patients with recurrence. This is the first study to show that increased MHCI expression is a favorable prognostic indicator in metastatic ccRCC. These results suggest that MHCI expression plays an important role in tumor-host immune system interaction of ccRCC and merits further study.
Results from the seminal vesicle sparing prostatectomy trial.
Authors: Gilbert Scott Michael , Dunn Rodney , Montgomery Jeffrey Scott , Miller David , Skolarus Ted A. , Weizer Alon , Wood David Peter , Hollenbeck Brent K. 
Published: February 2017

55 Background: Prostate cancer accounts for greater than 200,000 cases each year. Although cancer control is generally favorable with treatment, side effects are common. Among men treated with surgery, nerve-sparing prostatectomy is associated with lower rates of incontinence and erectile dysfunction. Seminal vesicle sparing (SVS) may further limit damage to the neurovascular tissue surrounding the prostate. Although some surgeons practice SVS, evidence supporting its use is lacking. We implemented a randomized control trial to determine if SVS is associated with better functional outcomes compared to non-SVS prostatectomy. Methods: 140 men with early-stage (T1c/T2N0M0, Gleason score <= 7) prostate cancer and adequate erectile function (IIEF >= 21) were enrolled in the Seminal Vesicle Sparing Prostatectomy Trial (NCT01825642) and randomized to either SVS or non-SVS prostatectomy between 2006 and 2011. The Expanded Prostate Cancer Index Composite (EPIC) was used to assess quality of life outcomes following surgery. Results: 71 and 69 men were enrolled in the SVS and non-SVS arms, respectively. The predominant surgical approach was robotic assisted prostatectomy (>97% in both arms). Men in the SVS arm were slightly younger (56 vs 58 years, p = 0.02); however, there were no significant differences in other clinical or demographic factors. There were no cases of seminal vesicle invasion. PSA recurrence was noted in 3 patients (1 in SVS group and 2 in non-SVS group). At 12 months postoperatively, sexual (76 vs 75) and urinary incontinence (92 vs 94) scores were similar among SVS and non-SVS patients (both p > 0.2). Conclusions: Recovery of urinary and sexual function was common among men undergoing SVS or non-SVS prostatectomy. SVS did not negatively impact cancer control, but was not associated with enhanced recovery of sexual or urinary function, perhaps due to the high level of recovery of the control arm. Clinical trial information: NCT01825642. [Table: see text]
Using MRI/ultrasound fusion biopsy to detect clinically significant prostate cancer in the African American population.
Authors: George Arvin , Rais-Bahrami Soroush , Rothwax Jason , Siddiqui Minhaj , Stamatakis Lambros , Su Daniel , Okoro Chinonyerem , Raskolnikov Dima , Shakir Nabeel , Walton-Diaz Annerleim , Turkbey Baris , Choyke Peter L. , Wood Bradford J. , Merino Maria , Pinto Peter A. 
Published: February 2017

57 Background: African-American (AA) men are at greater risk for prostate cancer (CaP) and experience increased prostate cancer-specific mortality. We aimed to determine racial disparities in CaP incidence, pathology, and anatomy identified on MRI/US fusion biopsy. Methods: Patients who underwent MP-MRI with targeted MRI/US fusion biopsy at our institution between May 2007 and June 2013 were reviewed. AA patients undergoing fusion biopsy were matched by age and PSA with a Caucasian cohort at a 1:2 ratio. MRI and pathologic parameters including lesion location, number of lesions, and Gleason score. Bivariate comparisons were made with the Student’s t-test and Χ2 analysis. Results: 822 patients had MRI/US fusion biopsy. 127 AA men were paired with a matched cohort of 254 Caucasians. Mean age was 60.2 and 61.4 years and mean PSA was 11.6 and 10.7ng/ml in AAs and Caucasians, respectively. We identified significantly more AA with CaP (49.6% vs 37.4%, p=0.03; Table). AAs also had higher grade disease (Gleason 7-10) versus white men (20.5% vs. 11.8%, p=0.04). Additionally, the diagnostic yield for the AA cohort was significantly higher per sampled lesion (37.5% vs 24.5%, p<0.01), despite no significant differences in % core involvement of the highest risk lesion between the groups. While there was no significant difference in presence of anterior lesions between the groups (15.7% vs 12.9%, p=NS), anterior lesions equally represented the highest risk lesions in both cohorts. Conclusions: MRI/US Fusion-guided biopsy demonstrates increased diagonostic yield/incidence of CaP and higher risk disease in the AA population in an age and PSA matched cohort of Caucasian patients. [Table: see text]
Enzalutamide monotherapy: Extended follow-up of a phase II study in hormone-naive prostate cancer patients.
Authors: Tombal Bertrand , Borre Michael , Rathenborg Per , Werbrouck Patrick , Van Poppel Hendrik , Heidenreich Axel , Iversen Peter , Braeckman Johan , Heracek Jiri , Baskin-Bey Edwina , Ouatas Taoufik , Perabo Frank , Phung De , Smith Matthew R. 
Published: February 2017

62 Background: The efficacy and safety of enzalutamide (ENZA) monotherapy was assessed in hormone-naive men with prostate cancer (PC; any stage) eligible for androgen-deprivation therapy (ADT). The primary end point of prostate-specific antigen (PSA) response rate (80% or more decline), assessed at 25 weeks (wks), was 92.5% with a median (range) maximum decrease of –99% (–100, –86.5) (Tombal et al. ASCO-GU 2013). Here we present data from the extended follow-up at 49 wks. Methods: In an open-label, single-arm phase II study, men age 18 or older with histologically confirmed PC requiring ADT, non-castrate testosterone (8 nmol/L or more), PSA 2 ng/mL or more at screening and a life expectancy of 12 months or more, received 160 mg ENZA once daily (NCT01302041). Treatment continued until disease progression or unacceptable toxicity. Secondary end points included changes in endocrine levels, metabolic parameters, bone mineral density (BMD), quality of life, and safety. Results: Sixty seven men were enrolled. Median (range) age was 73 (48 to 86); 38.8% had prior metastases; 35.8% and 23.94% had undergone prior prostatectomy and radiotherapy, respectively. Fifty nine men continued treatment beyond wk 25, and 54 completed wk 49. PSA response rate (80% or more reduction from baseline) at wk 49 was 80.6%, with a median (range) maximum decrease of –100% (–100, –86.5). Luteinizing hormone and testosterone were increased from baseline to wk 49 by 215.2% and 101.7%, respectively. Mean changes from baseline for metabolic outcomes at wk 49 were: +5.02% (total cholesterol), +8.86% (triglycerides), –3.54% (HbA1c), and +19.72% (HOMA-IR). Total body BMD was maintained at 49 wks (–0.30% from baseline). The most frequently reported treatment-emergent adverse events (AEs) were gynecomastia (47.8%) and fatigue (38.8%). Seven men had serious AEs, none of which were drug related. Data on patient reported outcomes will be presented. Conclusions: ENZA monotherapy was associated with significant PSA reductions after 49 wks of treatment in men with hormone-naive PC. Endocrine changes and AEs were consistent with potent AR inhibition. Outcomes for all end points at 49 wks were consistent with those reported at 25 wks. Clinical trial information: NCT01302041.
Using whole-genome sequencing to implicate the androgen receptor as the predominant driver of DNA breakpoints and fusion events in prostate cancer.
Authors: Corcoran Niall , Macintyre Geoff , Hong Matthew , Slogget Clare , Naeem Haroon , Cmero Marek , Pedersen John , Haviv Izhak , Ryan Andrew , Phal Pramit , Costello Anthony , Hovens Christopher 
Published: February 2017

67 Background: Structural rearrangements in cancers genomes have the potential to disrupt normal gene function and result in a selective growth advantage, either by inactivating tumour suppressors or creating novel gene fusions with oncogenic gain-of-function. Specific fusion genes identified to date are found in particular tumor types rather than being present in all cancers suggesting there are tissue-specific mechanisms underlying these events. The most well-known fusion event in prostate cancer is TMPRSS2-ERG. Recent studies have suggested that androgen receptor may play a role in the formation of TMPRSS2-ERG fusions, bringing the two loci in close proximity in the nucleus and facilitating DNA strand break and repair along with AR associated enzymes. Methods: To explore this mechanism more comprehensively, we performed whole-genome sequencing of 14 prostate cancers from seven patients as well as paired whole blood controls. Results: Across the cancer genomes we identified approximately 4,500 high confidence DNA breakpoints and found that a large proportion of these breakpoints were in close proximity to curated androgen receptor binding sites. Furthermore, when we examined breakpoints in 11 other cancers from the TCGA and ICGC projects, we identified a similar association with androgen (and estrogen) receptor binding sites specifically in hormone-dependent tumour types, suggesting a role for steroid hormone receptors in the formation of cancer driving structural rearrangements. In addition, in at least one patient, the formation of a novel gene fusion contributed directly to the lethal evolution of his tumour. Conclusions: These data suggest that the androgen receptor drives genome wide breakpoints and novel fusion events in prostate cancer.
Metabolic response by choline positron emission tomography (cPET) to enzalutamide (ENZ) in castration-resistant prostate cancer (CRPC) patients (pts): Preliminary results of a monoinstitutional prospective study.
Authors: Maines Francesca , Caffo Orazio , Donner Davide , Veccia Antonello , Chierichetti Franca , Galligioni Enzo 
Published: February 2017

76 Background: ENZ is a new generation hormone therapy, able to produce a survival improvement in CRPC pts pre-treated with docetaxel. In Italy, ENZ is not approved yet for the daily clinical practice but until few months ago it was available through a named patient programme (NPP). Since in our Hospital CRPC pts are regularly assessed by cPET to evaluate the treatment response, so pts treated with ENZ were monitored in the same way. Methods: Eligible pts received ENZ at the standard dose of 160 mg po daily until progression. The cPET was performed at baseline, at the 3rd treatment month and thereafter every 4 mos. For each cPET we recorded the median of the maximum standard uptake values (SUVmax) of the 5 most choline-avid region of interest (ROI) and the overall number of ROIs with SUVmax > 2.5. A progressive disease (PD) was defined as the increase ≥ 30% of median SUVmax or the appearance of at least two new ROIs; a partial response (PR) as the reduction ≤ 30% of median SUVmax compared to the baseline; otherwise we considered the disease as stable (SD). Results: Out of the 31 CRPC pts treated with ENZ in our hospital from 09/12 to 03/13, 28 had complete cPET data for evaluation. The baseline median SUVmax of all evaluable pts was 10.82. At 3 mos the median SUVmax decreased to 9.30 (7 PR, 12 SD, 9 PD). Among the 19 pts evauable at 7 mos, the median SUVmax was 7.15 (8 PR, 9 SD, 2 PD). The correlation between the best metabolic response and the prostate specific antigen (PSA) response is showed in the Table. Conclusions: Our preliminary data showed a good concordance between the cPET response and biochemical response in either responding or progressing pts, while most of the pts with stable metabolic parameters showed a good PSA reduction. This is to our knowledge the first report concerning the metabolic response to ENZ and its correlation to PSA response. Further studies are required to define the role and use of cPET in monitoring the treatment efficacy in pts receiving ENZ. [Table: see text]
Evaluation of the prostate health index (phi) as a novel biomarker in active surveillance of prostate cancer.
Authors: Eichholz Andrew , McCarthy Frank , Dennis Nening , Thomas Karen , Howlett Tim , Iqbal Jhangir , Amin Jan , Tan Mildred , Singhera Mausam , Selvadurai Elizabeth , Huddart Robert Anthony , Dearnaley David Paul , Parker Chris 
Published: February 2017

81 Background: Phi is calculated from serum PSA, free/total (f/t) PSA and [-2]proPSA using the Beckman Coulter assay kit, and has been approved for use in patient selection for diagnostic prostate biopsy. We hypothesized that phi might also predict outcome of active surveillance. Methods: From 2002, we have done a prospective cohort study of active surveillance for men with T1/2, Gleason <= 3+4, PSA < 15ng/ml prostate cancer. Serum was banked at baseline. Monitoring included 6 monthly PSA and 2-yearly repeat biopsy. Treatment was indicated for PSA velocity > 1ng/ml/yr or Gleason >= 4+3 on repeat biopsy. We analyzed baseline phi with respect to time to treatment. A multivariate model was fitted using total PSA, PSA velocity, PSA density, Gleason score, % biopsy cores positive, T stage, and maximum % cancer in any biopsy core. The fit of this model was then compared with the addition of % f/t PSA and phi. Results: 370 patients were evaluable with a median follow-up of 5 years. The table shows the association between baseline phiand time to treatment. On multivariate analysis, the model with % f/t PSA was a significant improvement over base model (change in fit 41.1, p<0.001), and the model with % f/t PSA and phi was a significantly better fit than % f/t PSA alone (change in fit 11.1, p=0.001). Conclusions: In men with favorable risk prostate cancer, phi at diagnosis was a significant predictor of the outcome of active surveillance. The data require validation, but suggest that active surveillance is particularly attractive to men with a low phi. [Table: see text]
Transcriptome-wide analysis of matched biopsy and prostatectomy to measure genomic classifiers of prostate cancer progression and field effect.
Authors: Knudsen Beatrice , Simko Jeffry P. , Lam Lucia L.C. , Erho Nicholas , Sierocinski Thomas , Tenggara-Hunter Imelda , Wellman Hugh , Davicioni Elai , Chan June M. , Carroll Peter , Kim Hyung Lae , Cooperberg Matthew R. 
Published: February 2017

85 Background: Active surveillance (AS) allows patients with localized prostate cancer to delay and even avoid treatments that carry risk of significant side-effects. However, biomarkers are needed to more accurately risk-stratify patients and enhance acceptance of AS. Challenges with biomarkers measured from needle biopsy specimen that need to be address include limited material, tumor and specimen heterogeneity and fragmentation of RNA. Methods: A total of 23 patients with matched formalin-fixed paraffin-embedded (FFPE) biopsy and radical prostatectomy (RP) specimens were identified at University of California, San Francisco and Cedar Sinai. For each patient, samples were taken from tumor, non-neoplastic tissue adjacent to tumor (NAT) and non-neoplastic tissue contralateral to tumor (NCT) from both biopsy and RP specimens. RNA expression was measured in 130 samples using the 1.4 million feature Affymetrix Human Exon 1.0 ST arrays. Results: From 1 mm cylindrical cores punched from FFPE blocks, sufficient RNA was extracted for the assay from 63 out of 69 (91%) biopsy specimens and 69 out of 69 (100%) RP specimens. Median RNA yield from biopsies was lower than RP specimens but a similar quantity and quality of cDNA was amplified from the 100 ng RNA required for the assay. RNA from 62/63 (98%) of the biopsy specimens and 68/69 (99%) of the RP specimens generated expression data that passed quality control. Genomic classifiers (GC) predicting metastasis (GC1) and presence of high Gleason grade tumor (GC2) were highly correlated between matched biopsy and RP specimens with R=0.74 (p=0.0003) and R=0.63 (p=0.004), respectively. For GC2, matched tumor and NAT from RP had a higher correlation (R=0.57, p=0.0045) than matched tumor and NCT (R=0.10, p=0.67). There was no relationship between percentage of stromal contamination in the biopsy and the GC scores for either classifier, R=0.02 (p=0.91) and R=-0.16 (p=0.28) respectively. Conclusions: RNA expression levels can be measured in FFPE needle biopsy on a genome-wide scale with similar data quality compared to RP specimens. GC scores from biopsies and RP samples correlate well, are robust to stromal contamination, and are present in adjacent non-neoplastic tissue.
Stereotactic body radiosurgery versus intensity modulated radiotherapy for prostate cancer: Comparison of toxicity.
Authors: Yu James B. , Cramer Laura D. , Herrin Jeph , Soulos Pamela R. , Potosky Arnold L. , Gross Cary 
Published: February 2017

89 Background: Stereotactic body radiosurgery (SBRT) is a recent innovation in the treatment of prostate cancer that has begun to disseminate into national practice. Comparative studies have yet to be performed and little is known about the cost to Medicare or difference in toxicity between SBRT and intensity modulated radiation therapy (IMRT). Methods: We performed a retrospective study using a national sample of all Medicare beneficiaries age 66 or older who received SBRT or IMRT as primary treatment for prostate cancer during 2008 through 2011. Each SBRT patient was matched to two IMRT patients with similar follow-up (6, 12, or 24 months) and clinical and demographic characteristics. Cost of treatment was calculated for matched patients with six months of follow-up. We assessed toxicity by searching Medicare claims for procedure or diagnosis codes indicative of treatment related toxicity. We used a random effects model to compare the likelihood of genitourinary (GU), gastrointestinal (GI), and other toxicity from 0 to 6, 0 to 12, and 0 to 24 months after the initiation of SBRT or IMRT treatment. Results: The study sample consisted of 1,335 SBRT patients matched to 2,670 IMRT patients. The mean cost of SBRT was $11,668 compared to $15,838 for IMRT. At all follow-up points, SBRT patients were significantly more likely to experience GU toxicity. In the first six months after treatment initiation, 15.6% of SBRT versus 12.6% of IMRT patients had claim indicative of a GU complication (p=.009). In the first 12 months, 27.1% of SBRT versus 23.2% of IMRT had a GU complication (p=.014). Finally, from 0-24 months, 43.9% of SBRT versus 36.3% of IMRT had a GU complication (p=.001). The higher rate of GU toxicity after SBRT was largely due to an increase in urethral strictures and bladder outlet obstructions and urinary incontinence or obstruction. Conclusions: In this retrospective observational study, while SBRT was associated with lower costs, there was a greater rate of urinary obstructive toxicity for patients undergoing SBRT compared to IMRT at all time points studied. Whether this increased rate of complication is offset by a higher cure rate or lower cost should be the subject of further study.
Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.
Authors: Zhao Bo , Garcia Jorge A. , Gilligan Timothy D. , Rini Brian I. , Dreicer Robert 
Published: February 2017

99 Background: Studies have shown activity of Abiraterone acetate (AA) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior ketoconazole. Prostate-specific antigen (PSA) response to AA in relation to previous PSA response to ketoconazole was investigated. Methods: A retrospective analysis was conducted to determine the clinical activity of AA in men with CRPC who have received prior ketoconazole therapy at our institution. Time to PSA progression (PSA TTP) was defined by PCWG2 criteria, a PSA reduction of 50% or more was considered as PSA response. Results: Thirty four pts were identified. Nineteen pts (56%) had previous PSA responses on ketoconazole, with a median PSA TTP of 11 months (95% confidence interval [CI] 6.8-19.9). Subsequently, 11 of 34 (33%) of pts achieved a PSA response on AA, with a median PSA TTP of 6 months (95% CI 4.9-9.5). Among the 19 pts having a PSA response on ketoconazole, only four (21%) pts subsequently had PSA response to AA. Two of these pts had transient PSA response with PSA TTP less than 3 months on kKetoconazole, one patient discontinued Ketoconazole due to side effects, one patient had intermittent non-castrate testosterone levels. In contrast, 7 of 15 (46.7%) pts without prior PSA response to ketoconazole subsequently achieved PSA response on AA (p=0.11). Of note, PSA reduction of less than 50% on AA was observed in 9 of 34 pts (26%), which was associated with a longer median PSA TTP compared to pts who had PSA-progressive disease (5.9 months [95% CI 3.5-7.3] vs.1.5 months [95% CI 1.0-3.5], p=0.028). Five of these nine patients had a prior PSA response to ketoconazole but required drug discontinuation for reasons other than disease progression. Conclusions: PSA response to prior ketoconazole therapy is associated with lower PSA response rate to subsequent AA. The observation suggests that there is a biologically distinct subset of patients who are ketoconazole-resistant but abiraterone-sensitive, the underlying mechanism needs to be further investigated.