bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Gleason 9-10 prostate cancer with worse outcomes compared to Gleason 8 disease.
Authors: Tsao Che-Kai , Gray Kathryn P. , Nakabayashi Mari , Evan Caroline , Galsky Matt D. , Kantoff Philip W. , Oh William K. , Pomerantz Mark 
Published: February 2017

157 Background: Use of pathological Gleason score for risk stratification of localized prostate cancer is widely accepted. However, data are lacking regarding differences in presentation and outcome among those with Gleason 8-10 disease. Methods: Using the Dana-Farber Cancer Institute Prostate Clinical Research Information Systems database, we identified a cohort of patients with biopsy Gleason 8-10 disease who received definitive radical prostatectomy (RP) or radiation therapy (RT) (external beam or brachytherapy) for curative intent. The study endpoints, time to biochemical recurrence (BCR), time to metastatic disease (MD), and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to investigate the association of the study endpoints and Gleason score groups (8 vs. 9 and 10) adjusted for clinical and pathological factors including age, PSA at diagnosis, type of local therapy, and tumor stage. Results: We identified 848 patients who received either local definitive RT (n=411) or RP (n=437). Median follow-up from diagnosis was 5.3 years. Patient characteristics at diagnosis (race, age, and clinical stage) were similar between the two groups (Gleason 8 vs. Gleason 9-10). Patients with Gleason 9-10 disease were more likely to receive radiotherapy as primary local therapy (58% vs. 46%, p=0.001), and to receive hormonal therapy as a part of their definitive treatment course (64% vs. 48%, p<0.001). Patients with Gleason 9-10 disease had shorter time to BCR, time to MD, and a trend towards worse OS using multivariate analysis adjusted for significant clinical and pathological factors. (Detailed in table below). Conclusions: In our study, we found that patients with localized Gleason 9-10 disease who were treated with definitive therapy with curative intent had worse outcomes compared to patients with Gleason 8 disease. More aggressive, multimodality treatments may be indicated for men diagnosed with the highest Gleason grades. [Table: see text]
Overtreatment of low-risk prostate cancer in the United States: Incidence, cost, complications, and implications for the screening debate.
Authors: Aizer Ayal A. , Gu Xiangmei , Choueiri Toni K. , Martin Neil E. , Hu Jim C. , Nguyen Paul Linh 
Published: February 2017

161 Background: The National Comprehensive Cancer Network (NCCN) recommends active surveillance as the sole option for men with low-risk prostate cancer (LRPC) and a life expectancy <10 years. We sought to describe the incidence, risk factors, cost, and morbidity related to overtreatment of LRPC within the United States. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare Program to identify 11,744 men ≥66 years with LRPC diagnosed from 2004-2007. Expected survival was estimated using the 2007 Social Security Life Table and was increased and decreased by 50% in men in the upper and lower quartiles of comorbidity, respectively, as specified by the NCCN. Overtreatment was definitive treatment in men with LRPC and life expectancy <10 years. Costs were the amount paid by Medicare in the year following minus the year prior to diagnosis. Toxicities were defined as relevant Medicare diagnoses or interventions. Results: Of 3001 men with LRPC and a life expectancy <10 years, 2011 (67%) were treated definitively. On multivariable logistic regression, men overtreated for prostate cancer were more likely to be younger (p<.001), white (vs black, OR 1.44, 95% CI 1.03-2.02, p=.03), married (OR 1.30, 95% CI 1.05-1.61, p=.02), urban (trend, OR 1.40, 95% CI 0.98-2.00, p=.06), have higher Elixhauser comorbidity (p<.001), and have a higher clinical stage (T2 vs T1, OR 1.57, 95% CI 1.19-2.07, p=.001) and prostate-specific antigen level (OR 1.02, 95% CI 1.02-1.02, p<.001). Relative to expectant management, the mean added cost per definitive treatment was $15,308. When extrapolated nationally the cumulative net cost of overtreatment in men ≥66 years is $32 million per annum. Long-term urinary, erectile, and bowel toxicity occurred in 59.2% and 50.0%, 47.9% and 19.7%, and 7.1% and 17.8% of prostatectomy and radiation patients, respectively. Conclusions: Overtreatment of prostate cancer is partially driven by sociodemographic factors and occurs in a high percentage of men with LRPC and limited life expectancy, with marked impact on patient quality of life and health care costs. Efforts to enhance appropriate management of LRPC would reduce the harms associated with screening.
Effect of Wnt-1 induced signaling protein-2 (Wisp-2/CCN5) on angiogenesis and invasion in prostate cancer.
Authors: Hashimoto Yasunobu , Singh Rajendra , Lokeshwar Bal L. 
Published: February 2017

164 Background: The Wnt-Induced Signaling Protein-2 (Wisp-2/CCN5) is a secreted protein implicated in modification of extracellular matrix, invasion, and angiogenesis. The regulation of Wisp-2 and its function in CaP is poorly explored although it is highly expressed in advanced CaP cells. We discovered recently that a pro-inflammatory chemokine, Interleukin-8 (IL-8) strongly modulates Wisp2 expression in CaP cells. Since chronic inflammation is thought to be significant in CaP metastasis and IL-8 is a major effecter of inflammatory pathway, we investigated the physiological consequence of Wisp-2 modulation in CaP cells. Methods: Quantitative PCR was used to determine the expression of Wisp-2 mRNA and other mRNA in prostate epithelial and cancer cells. Wisp-2 mediated-VEGF secretion was determined by ELISA and endothelial tube formation assay using human vascular endothelial cells. Invasive activity and their attributes were determined using gelatin-zymography for matrix metalloproteinases (MMPs), Matrigel invasion assay and chemotaxis assay. Results: Wisp2 RNA was strongly expressed in two highly metastatic CaP cell lines, DU145 and PC-3 and moderately in less invasive LAPC4 and LNCaP cells. Constitutive autocrine expression or external addition of IL-8 increased Wisp-2 mRNA by ≥15.2 times in LNCaP, and 7.4 times in LAPC4 cells. Depleting Wisp-2 by RNA interference caused 82% reduction of Wisp2 in DU145, and 75% in PC-3. Depletion of Wisp2 did not affect cell proliferation in DU145 and PC3 but it reduced expression of VEGF mRNA by 64% in DU145 and 43% in PC3. Secreted VEGF protein in cultures of DU145 and PC-3 cells showed a decrease of 62% in DU145 and 30% in PC3. Condition medium of Wisp-2 depleted DU145 cell cultures showed 20% decrease in proliferation and vessel formation activity in HUVEC cells. Further, Wisp-2 depletion in DU145 cells resulted in significant decrease in chemoinvasion activity (28%) and secretion of MMP-9 (25%). Conclusions: These results show that Wisp2 is down stream effector of IL-8 and is an important modulator, affecting extracellular matrix to stimulate angiogenesis and invasiveness in CaP cells. Suppression of Wisp-2 in CaP may reduce their metastatic potential.
Specification and validation of prostate cancer quality-of-care e-measures in the Veterans Health Administration (VHA).
Authors: Shelton Jeremy B. , Skolarus Ted A. , Ryoo Joan Joonsun , Malin Jennifer , Antonio Anna Liza M. , He Ren , Saigal Christopher 
Published: February 2017

178 Background: Quality measures based on chart abstraction are the “gold-standard,” but the costs of measurement limit widespread adoption. Electronically specified measures (e-measures) promise a way forward, however the fidelity of electronic abstraction compared to chart abstraction is unknown. We sought to validate e-measure versions of VHA-developed prostate cancer quality of care measures. Methods: Quality measures were chart abstracted on 11,263 men in the VHA with incident prostate cancer in 2008. We identified and linked VHA cancer registry and administrative data for the same cohort. E-measures were specified iteratively and validated by comparing accuracy of measure denominators and numerators, and the overall pass rates to chart abstracted results. Results: 3 of 6 quality measures were successfully validated (Table). Conclusions: The VHA’s information technology infrastructure is sufficiently advanced to support valid e-measurement that is equivalent to that performed by chart abstraction, however data availability at this time limits the breadth of e-measurement as compared to chart abstraction. [Table: see text]
Use of microRNA signature to distinguish early from late biochemical failure in prostate cancer.
Authors: Lichner Zsuzsanna , Schaefer Annika , Saleh Carol , Nasser Aurfan , Boles Dina , Al-Haddad Sahar , Kupchak Peter , Dharsee Moyez , Nuin Paulo S. , Evans Kenneth R. , Jung Klaus , Stephan Carsten , Fleshner Neil Eric , Yousef George M. 
Published: February 2017

194 Background: With the introduction of PSA testing, the problem of over-treatment emerged in prostate cancer. Only a small subset of prostate cancer patients will require more intensive adjuvant therapy. There is currently no biomarker that can predict disease aggressiveness at the time of surgery. Methods: We analyzed miRNA expression in 41 patients (the discovery set) which were dichotomized into; 'high risk'- experienced biochemical failure within 24 months after radical prostatectomy (n=26) and 'low risk' who did not have biochemical failure for at least 35 months (n=15). The validation set consisted of 72 cases. Total RNA was isolated from FFPE cores. cDNA was prepared for each patients and expression miRNA expression was screened by qRT-PCR –based panel. miRNAs were ranked by non-parametric tests. Linear regression models were built to predict biochemical failure. We used TargetScan for miRNA target prediction. Targets were validated by transient transfection of synthetic miRNA precursors followed by qRT-PCR quantification of the targets. Proliferation was assessed by measuring cell viability. Results: We compared the expression of 754 mature human miRNAs in patients with ‘high’ or ‘low’ risk for biochemical failure. We identified 24 miRNAs that were differentially expressed between the risk groups. We developed three logistic regression models, based on the expression of 2-3 miRNAs (PPV=100% and NPV ranges 86.4-100%). We confirmed the differential expression on the study set and on a larger, independent set of PCa pateints. We also validated one model on an independent set of patients. Further, we show that transfection of miR-152 and miR-331-3p, featured in the logistic regression models, altered proliferation of PCa3 and DU145 cells. Target prediction indicated Erbb3 and Erbb2 as potential direct targets and their mRNA expression significantly reduced when miR-152 and miR-331-3p were overexpressed. Conclusions: Altered miR-331-3p and miR-152 expression represent a potential tool for assessing the risk of early biochemical failure. These miRNAs may act through the Erbb family to induce an alternative way of AR activation.
Utility of blood oxygen level dependent magnetic resonance imaging in the evaluation of tissue oxygenation patterns of prostate cancer.
Authors: Gayed Bishoy A. , Hallac Rami , Youssef Ramy F. , Francis Franto , Yuan Qing , Sims Robert , Ding Yao , Roehrborn Claus G , Mason Ralph , Raj Ganesh 
Published: February 2017

198 Background: Tumor hypoxia is associated with worse pathologic features and oncological outcomes. Blood Oxygen Level Dependent (BOLD) MRI evaluates changes in endogenous contrast generated by paramagnetic deoxy-hemoglobin to non-invasively evaluate tissue oxygenation. Prior attempts using carbogen-based (95%O2 + 5%CO2) imaging were limited by patient tolerance. We present the first-in-man evaluation of a novel oxygen breathing challenge technique to monitor tissue oxygenation with BOLD MRI in patients with prostate cancer. Methods: Following IRB approval, 10 patients with clinically localized prostate cancer scheduled for radical prostatectomy underwent preoperative imaging with a 3-Tesla MRI scanner. Images were acquired using a 6-element SENSE body transmit coil and endorectal receive coil. T2* signal intensity is dependent on the concentration of deoxy-hemoglobin. Signal intensity measurements were obtained at different time points. Shorter T2* times imply the presence of hypoxia. Dynamic T2* maps were acquired while subjects breathed air for 2 mins followed by oxygen (15 l/min). Results: 10 patients (median age: 59 years (range 48-73), median PSA 6.9 ng/ml (range 2.5-25), with prostate cancer (Gleason sum 6- 7, 8-9 in 7 and 3 patients respectively) underwent BOLD MRI within 3 weeks of definitive management with a robotic assisted laparoscopic prostatectomy. All patients tolerated BOLD MRI with oxygen challenge without difficulty. Evaluation of BOLD MRI revealed wide variation in T2* values within the prostates from a median of 14.7 ± .71 ms to 44.5 ± 3.3ms. Surrounding muscle T2* values were similar for all patients, indicating that heterogeneous values were specific to each patient’s prostate. Shorter T2* values were seen in Gleason 6-7 than Gleason 8- 9 cancers, indicating more hypoxic areas in these tumors. HIF-1α staining was strongly positive in all tumors. Conclusions: BOLD MRI with oxygen challenge is well tolerated in patients and is a feasible noninvasive technique to study tissue oxygenation in tumors. Differential oxygenation patterns of prostates appear to correlate with pathological features. Further testing is needed to validate these findings.
Impact of magnetic resonance imaging (MRI) in the local staging, risk group classification, and treatment of patients with prostate cancer with combination of high dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT).
Authors: Gomez-Iturriaga Alfonso , Casquero Francisco , Carvajal Claudia , Urresola Arantxa , Canteli Begona , Ezquerro Ana , Hortelano Eduardo , San Miguel Inigo , Cacicedo Jon , Llarena Roberto , Martinez-Indart Lorea , Espinosa Jose Maria , Minguez Pablo , Bilbao Pedro 
Published: February 2017

202 Background: To assess the impact of magnetic resonance imaging (MRI) staging for patients undergoing High Dose Rate (HDR) brachytherapy with external beam radiotherapy (EBRT). Methods: Fifty consecutive patients with intermediate risk and high risk prostate cancer underwent staging MRI. The MRI findings were used to guide stage-appropriate treatment recommendations, and to assist in the preplanning and optimization of the brachytherapy isodose distributions. Results: Median age of the patients was 71 years (range 58-78), median pre-treatment PSA was 10.15 ng/ml (3.3-66), median prostate volume was 35cc (14-58). Eighty-four percent of the patients were Gleason ≥ 7. Fifty-two percent had ≥ 50 of cores involved. Fifty four percent of patient’s PSA was ≥ 10 ng/ml. Pre-MRI staging was T1 in 70% of the patients, T2 in 30 %. Of the 50 patients staged by MRI, 70% were upstaged from the digital rectal examination-based clinical stage; 46% of cT1- T2 patients were upstaged to cT3. This upstaging changed the risk group in 56% of the patients while using the NCCN classification and in 24% when the D’Amico classification was used. The treatment reccomendation was modified in 26% and 20% of the patients using the NCCN and the D’Amico classification respectively. Conclusions: Staging MRI impacts in the assessment of the local staging, leading to changes in risk group classification and treatment decision in intermediate and high risk patients undergoing HDR brachytherapy and EBRT.
C35: A new prognostic tool and potential target in prostate cancer.
Authors: Kilari Deepak , Yao Jorge , Scosyrev Emelian , Evans Elizabeth E. , Sahasrabudhe Deepak M. 
Published: February 2017

212 Background: Identification and validation of biomarkers can help prognosticate patients and potentially serve as therapeutic targets. C35, a protein encoded by novel gene C17orf37 is located on 17q12 “the hotspot of cancer”. Dasgupta et al. (Oncogene 2009) noted higher expression of C35 in prostate cancer cell lines as compared to minimal expression in normal prostate cells. Furthermore, over expression of C35 enhanced motility and invasion. We hypothesized that C35 expression would correlate with other markers of aggressive clinical behavior and tested this by studying C35 expression in tissue microarrays (TMAs). Methods: TMAs were constructed using tissue samples obtained from normal organs including prostate, primary prostate cancers and prostate cancer from various metastatic sites. The TMAs had triplicates of each specimen which was then stained with rabbit polyclonal anti -C35 antibody. Each sample was scored based on the product of intensity (0-3) and distribution (0-4) of staining, with the maximum score being 12. A blinded review of the final scores and Gleason’s sum were independently conducted by a pathologist. Results: The C35 expression scores were higher in primary prostate cancer compared to benign prostate tissue. The average expression scores increased with increasing Gleason sum. Prostate cancer specimens from the metastatic sites had significantly lower expression scores when compared with the primary prostate cancer specimens. There was minimal to no expression in other normal organs. All these differences were statistically significant (p<0.001). The protein was predominantly cytosolic with membrane localization. Distributions of expression scores according to specimen type are summarized below. Conclusions: C35 expression directly correlates with Gleason sum, a validated prognostic marker. C35 may be a potential target for therapeutic agents. Further studies are needed to determine if increased expression of C35 in normal prostate can predict future development of prostate cancer. [Table: see text]
Diagnostic accuracy of PET scan in salvage lymph node resections in patients with prostate cancer (CaP).
Authors: Pfister David J. K. P. , Piper Charlotte , Porres Daniel , Klotz Theodor , Heidenreich Axel 
Published: February 2017

215 Background: PET-CT scans in patients with CaP are often used to identify either local recurrent disease or suspected lymph node metastases in early biochemical recurrent disease. The diagnostic accuracy is controversial. We want to show our experience of PET-CT and its diagnostic accuracy in salvage lymph node dissection. Methods: 21 patients treated with radical prostatectomy between 1997 and 2009 presented with PET-CT´s and biochemical recurrent disease and were treated by salvage lymph node dissection to prolong the time to either androgene deprivation or chemotherapy. Diagnostic accuracy was correlated per patient and per lymph nodes. Results: Mean PSA at time of lymph node dissection was 2,73 (0,4-8,4)ng/ml. 17 (81%) received prior radiotherapy and 6 (29%) received androgene deprivation. In total 203 lymph nodes were resected with 58 (29%) harbouring metastasis in 15 (71%) patients. This leads to a Sensitivity, Specifity, positive and negative predictive value of 69%, 12%, 76% and 88% concerning lymph node detection and 70%, 0%, 93% and 0% concerning the calculation per patient. At time of analysis follow-up was available in 5 patients with a biochemical recurrence free survival of 5 (3-12) months. Conclusions: The value of PET-CT in salvage lymph node dissection is under debate and must be questioned according to our results in this setting.
Patient-reported quality of life in men with TURP undergoing proton therapy for prostate cancer.
Authors: Lee Derek , Hoppe Bradford S. , Smith Tamara L. , Morris Christopher G. , Nichols Romaine Charles , Henderson Randal H. , Mendenhall William M. , Williams Christopher R. , Li Zuofeng , Mendenhall Nancy Price 
Published: February 2017

220 Background: We report on quality of life (QOL) and early toxicity following proton therapy (PT) among men with prostate cancer who underwent transurethral resection of the prostate (TURP) prior to treatment. Methods: Between 2006 and 2010, 1,540 patients were treated definitively with PT for prostate cancer at UFPTI and enrolled on a prospective IRB-approved outcomes protocol. One hundred of the men had received a TURP before PT. Baseline comorbidities, medications, expanded prostate index composite (EPIC) score, international prostate symptom score (IPSS), and CTCAE vs.3 toxicity assessment were collected prospectively. The Kaplan-Meier product limit method was used to estimate freedom from toxicity. Results: Men who had TURP prior to PT had lower EPIC scores at baseline and at all followup points for urinary function, urinary incontinence, and urinary summary (Table). The TURP group also had lower EPIC bowel bother, bowel function, and bowel summary at baseline, 6-month, and 1-year followup. EPIC urinary bother, urinary irritation/obstruction, and subscales did not show a statistically significant difference at baseline, but they did show lower scores for the TURP group at variable follow-up time points. The IPSS scores among the TURP group did not show a statistical difference from the non-TURP group, except at the 6-month follow-up time point. Toxicity assessment showed that the 2-year and 3-year cumulative incidence of grade 3 GU toxicity rate in the pretreatment TURP group were 14% and 18%, respectively. Conclusions: Pretreatment TURP was associated with both a high incidence of physician-assessed toxicity and inferior patient-reported QOL scores both before and after PT treatment. Studies investigating QOL and toxicity after specific prostate cancer therapies should stratify patients by pretreatment TURP. Longer follow-up and further evaluation of risk factors for grade 3 GU toxicity among this cohort are needed. [Table: see text]
Dosimetic quality and evolution of edema after prostate brachytherapy for small prostates: Implications for the use of newer isotopes.
Authors: Kovtun Konstantin , Wolfsberger Luciant D. , Niedermayr Thomas , Neubauer Emily , Murciano-Goroff Yonina R. , Beard Clair , D'Amico Anthony Victor , Martin Neil E. , Orio Peter F. , Nguyen Paul Linh 
Published: February 2017

232 Background: Prostate brachytherapy is often avoided in men with small prostate volumes (PV) due to concerns about suboptimal dosimetry. We characterized prostate swelling and dosimetry in patients with small PVs compared with large PVs. Methods: We studied twenty-five patients with PV <25 cc (range 15.1-24.8) and sixty-five patients with PV >=25 cc (range 25.0-66.2) who underwent brachytherapy. Gland size was based on the contoured volume on a 3D transrectal ultrasound before the procedure. Ultrasound-guided brachytherapy was performed under intra-operative planning with loose Iodine-125 seeds to a prescription dose of 145 Gy. Patients underwent CT and MRI scans on post-implant Days 1 and 30 for dosimetric study. MRI was used to contour the prostate and then fused with the CT for dosimetry. Results: Small PVs had greater Day 1 post-implant swelling than patients with large PVs (32.5% increase in volume vs. 23.7%, p=0.04) but Day 30 swelling was minimal and not significantly different (4.4% increase in volume vs. 1.6%, p=0.44) for small and large PVs respectively. Small PVs had greater seed and needle density at implant (p<0.001). Small PV patients had larger Day 1 hot spots in the prostate at (V150 = 59.6% vs. 53.0, p=0 .022) which resolved by Day 30 (V150 = 70.9% vs. 67.1, p=0.20). Rectal and urethral doses were nearly identical by Day 30 (Small PV RV100 = 0.32 cc, Large PV RV100 = 0.33 cc, p=0.99; small PV UV150 = 0.20, large PV UV150 = 0.20, p=0.91). Day 1 swelling created cold areas (rate D90>140 Gy = 88.0% and 90.6% for the small and large PV groups respectively, p=0.71), but day 30 dosimetry was excellent (rate D90>140 Gy = 100% for both groups). Conclusions: While smaller prostates have more immediate post-operative swelling, good Day 30 dosimetry can be achieved in small prostates, which makes them excellent candidates for treatment with I-125 seeds (t½ = 60 days). Due to the increased short-term swelling, small prostates may be suboptimal candidates for implants done with shorter half-life sources such as cesium-131 (t½ = 9.7 days), where the majority of the dose may be delivered to an edematous gland.