bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expectant management of veterans with early-stage prostate cancer.
Authors: Filson Christopher Paul , Shelton Jeremy B. , Tan Hung-Jui , Kwan Lorna , Skolarus Ted A. , Saigal Christopher , Litwin Mark S. 
Published: February 2017

13 Background: We evaluated the association between various factors and the use of expectant management (EM) among patients with prostate cancer treated in the Veterans Health Administration. Methods: We identified men diagnosed with prostate cancer in 2008. Outcome of interest was use of EM captured through an in-depth chart review. We fit multivariable regression models to examine associations between EM use and patient demographics, cancer severity, and facility characteristics. We then assessed regional variation across 52 facilities by generating predicted probabilities for receipt of EM. Results: Among our analytic cohort (n=6,540), 34% of men were treated expectantly. EM was more common among patients 75 and older (40% vs. 27% under 55 years, OR 2.57) and with low-risk tumors (49% vs. 20% high-risk, OR 5.35). There was no association between patient comorbidity and receipt of EM (p=0.90) (Table). There were also no significant associations between facility factors and receipt of EM (all p>0.05). Among ideal EM candidates, receipt of expectant management varied considerably across individual facilities (0 – 85%, p<0.001). Conclusions: Patient age and tumor risk were both more strongly associated with the use of expectant EM than patient comorbidity. Though its appears appropriate broadly, there was variation in EM between hospitals, apparently not attributable to facility factors. Research determining the basis of this variation—with a focus on providers—will be critical to help optimize prostate cancer treatment for veterans. [Table: see text]
Gleason <6 (G6) prostate cancer (PC) at radical prostatectomy (RP): Does a high-risk setting truly exist? A recursive partitioning analysis (RPA).
Authors: Smith Mark C , Russo James Kyle , Tracy Chad , Mitchell Darrion , Mott Sarah , Buatti John Michael , Watkins John Morgan 
Published: February 2017

132 Background: G6PC is associated with low rates of PSA failure (bF) after primary treatment. The present study seeks to determine whether a "high-risk" subpopulation of G6PC with lower PSA relapse-free survival (bRFS) may be identified within a large population of men with mature follow-up who underwent RP for curative-intent. Methods: Patients were retrospectively identified for inclusion by cT1-2 PC with PSA <30 at diagnosis, managed by RP alone, with final pathology demonstrating G6PC. Exclusion criteria were: pT3b or pN1, pre- or post-RP (adjuvant) radiotherapy (RT) or hormone therapy, or PSA follow-up (<12 months). The Kaplan-Meier method was employed for survival probability estimation. RPA by conditional inference analysis was applied to identify variables associated with bF. Results: From 2003-2009, 284 patients were eligible for this analysis. The median age was 60 yrs (range, 44-76), 233 (82%) were T1c, and median PSA was 5.3 (92% <10 ng/dL). The median biopsy to RP interval was 50 days (11-410, with 97% <180 days). Eighty patients (28%) had a positive margin (M+). At a median follow-up of 92.6 months (16.9-160.9, with 45% followed >8 years), 32 patients (11%) had bF, with estimated 5/8yr bRFS rates of 91%/89%. Univariate analysis identified M+, EPE, detectable initial post-RP PSA (at <26wks post-RP), longer biopsy to RP interval, and smaller RP specimen volume as significantly associated with bF, with M+ and longer biopsy to RP interval significant at multivariate analysis. RPA identified only M+ as a stratification factor, with 5/8yr bRFS estimates of 79/74% for M+ vs. 96/95% for M-. No other factors permitted further substratification of risk. Of note, 7 of 12 patients who underwent salvage RT alone remained disease-free at last follow-up, including 7 of 8 whose highest pre-salvage RT PSA was <0.6. Conclusions: G6PC managed by RP alone is generally associated with high rates of bRFS; however, in the M+ setting, irrespective of other clinical factors, early bF rates >20% are observed. Adjuvant RT should be considered in G6PC M+ cases; however, close surveillance with early salvage RT may be a reasonable alternative.
High-intensity focused ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: Predictors of disease response.
Authors: Dason Shawn , Allard Christopher Brian , Hoogenes Jen , Orovan William , Shayegan Bobby 
Published: February 2017

135 Background: Some patients with localized radio-recurrent prostate cancer (PCa) may have long-term recurrence-free (RFS) survival with salvage high-intensity focused ultrasound (HIFU). In this study, we describe our previously unreported oncologic outcomes and predictors of disease response after salvage HIFU. Methods: Participants were prospectively enrolled in this study from January 2005 to December 2014 if they had localized radio-recurrent prostate cancer. Participants had to meet both biochemical (PSA nadir+ 2ng/ml) and histologic (positive biopsy) definitions of recurrence. Study exclusion criteria included the receipt of prior salvage therapy, presence of metastastatic disease, and receipt of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the Ablatherm device (EDAP, France). The primary endpoint of this study was RFS, defined as a composite endpoint of PSA progression (PSA nadir + 2 ng/ml), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (undetectable PSA nadir, low TRUS biopsy grade, >3 TRUS biopsy cores positive, pre-HIFU PSA<4ng/ml, receipt of prior ADT and presence of pre-HIFU palpable disease). Survival analysis was performed on participants with a minimum of 1-year follow-up. Results: Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02 ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04 ng/ml. 2-year and 5-year RFS were 66.3% and 51.6% respectively. An undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). No participants developed a rectourethral fistula. Conclusions: Salvage HIFU allows for disease control in select patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.
Inclusion of corrected calcium and creatinine levels in a novel nomogram for prediction of pathologically localized prostate cancer.
Authors: Eminaga Okyaz , Alhamad Omran , Engelmann Udo , Wille Sebastian , Heidenreich Axel 
Published: February 2017

140 Background: The role of routine parameters in the prediction of organ-confined Prostate Cancer (oPCa) remains unclear. Methods: We conducted a retrospective study of 246 patients with PCa diagnosed on biopsy, who underwent radical prostatectomy with extended lymph node dissection. None of these patients received a neoadjuvant therapy. Gleason score (xGLS), percent of positive cores involved by PCa (pCores), results of transrectal evaluation (TRUS, DRE), prostate volume (PVol), albumin-corrected Calcium (Ca), Hemoglobin (Hb), Creatinine (Crea), PSA, and age at RPE were considered. Postoperative variables including Gleason score (pGLS), TNM stages were evaluated. These patients were divided according to disease advancement into pathologically localized (pT2) and advanced PCa (pT3/4 or pN1). A L2 penalized regression model including all preoperative parameters was evaluated to design a nomogram for oPCa prediction. Furthermore, the internal validation of the nomogram was performed using bootstrapping and cross-validations. The precision and accuracy of the novel nomogram were evaluated by using AUC, F-Score, Brier-Score and the classification accuracy (CA). Results: The lowest probability for pathologically localized PCa was found in patients having the following features: PSA > 20 ng/ml, detection of PCa in all cores, high Ca [1.21 fold over upper normal limit (ULN)] and Crea levels (2.27 fold over ULN), xGls > 7 and normal PVol. A nomogram for oPCa was developed including the following parameter: Crea, Ca, PSA, xGls, PVol, TRUS, pCores. The sensitivity and the specificity of the nomogram for prediction of pathologically localized PCa were 92.2% and 35.9%, respectively. AUC of 0.811, CA of 80.1%, F-Score 0.879, a precision of 84.0%. and Brier-Score of 0.2599 were calculated. The predicted probability of the novel nomogram was associated with higher accuracy for prediction of oPCa compared to those of Partin table and Kattan nomogram. Conclusions: Serum creatinine and corrected calcium are indpendent predictors of oPCa. The novel nomogram can predict oPCa with high precision and accuracy. However, an external validation of the novel nomogram is needed.
Intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT): A risk group with heterogeneous behavior.
Authors: Pérez de la Puente Constanza , Losco Federico , Chacon Carolina , Sade Juan Pablo , Giornelli Gonzalo H. , Chacon Matias , Chacon Reinaldo D. 
Published: February 2017

145 Background: In men with intermediate-risk prostate cancer (IR-PC) treated with low dose EBRT, the addition of androgen deprivation therapy (ADT) prolongs overall survival. Zumsteg proposes a subdivision for de IR-PC group: favorable or unfavorable. Purpose: retrospective evaluation of EBRT efficacy according to IR-PC subgroups (favorable or unfavorable). Methods: From the institutional radiotherapy department database, from 2000 to 2011, 95 men with IR-PC were identified and subdivided as follows: Favorable Risk (FR) – Gleason 3+4 or less and positive prostate biopsies (ppb) not exceeding 50% and only one intermediate-risk factor excluding 4+3; Unfavorable risk (UR) – Gleason 4+3 or at least 2 intermediate-risk factors or at least one intermediate risk factor and ppb >50%. Results: 95 patients were included in the analysis, mean FUP 6.2 years. 32.6% (31) had >50% ppb, 14.7% (14) had Gleason 4+3, 38.9% (37) had 2 intermediate-risk factors. 42.1% (40) were FR and 57.9% (55) were UR. Median EBRT dose: 79.8Gy. Only 25% of FR patients received some hormonal therapy treatment. There were no differences in time to Prostatic Specific Androgen (PSA) nadir (FR 12 vs UR 13 months; p= .50), biochemical relapse free survival (RFS) (FR 60 vs US 58 months; p= .80), or doubling time PSA (FR 12 vs UR 11 months; p= .19). Biochemical relapse (BR) and local relapse (LR) rates were lower for FR (BR: FR 27.5 vs UR 38.2%, p= .17; LR: FR 5 vs UR 14.5%, p= .40). Local RFS (FR 13.6 vs UR 9.6 years; p= .11) and distant RFS (FR 13.1 vs UR 12.4 years; p= .65) were longer for FR patients. Conclusions: Short course ADT is the standard treatment in IR-PC patients when EBRT is indicated, especially if they have UR features. In our study IR-PC group had heterogeneous outcomes and, in spite the study limitations, FR patients had a trend for better prognosis even with a very low use of ADT. If Favorable IR-PC patients may avoid ADT morbidity should be answered by a randomized trial.
Single institution, retrospective comparison of toxicity and outcome for static 5-field IMRT versus VMAT in the delivery of prostate and pelvic nodal irradiation in high-risk prostate cancer.
Authors: Turner Philip Geoffrey , Jain Suneil , Corey Gemma , Mitchell Darren M. , Tumelty Karen , Irvine Denise , Harney Jacqueline A. , Houghton Fionnuala , McAleese Jonathan , Shum Lin , Stewart David P. , O'Sullivan Joe M. 
Published: February 2017

147 Background: There is emerging evidence for the role of pelvic nodal irradiation in high-risk prostate cancer. We have assessed the toxicity rates and outcomes with 2 different radiotherapy techniques. Methods: The baseline disease metrics, toxicity and outcome data for men treated at our institution with prostate and pelvic nodal irradiation during a 2 year period were retrospectively collected. The radiotherapy technique, either 5-field IMRT or VMAT was recorded along with a single dose-level to indicate normal tissue exposure (V50 to bowel and rectum, that is the percentage of total organ receiving ≥ 50Gy). Results: 67 men with a median age of 64 years were identified; 83.6% were Gleason ≥ 8, 82.1% were ≥ T3a, 50.7% were N1, 4.5% were M1a/M1b. All had neoadjuvant and concurrent hormone therapy. All received 74Gy to prostate; 70.1% received 60Gy to pelvic nodes, 28.4% received 55Gy to pelvic nodes (1 patient received 56Gy). 55.2% were treated with static IMRT and 44.8% with VMAT with no significant difference in nodal dose received by static vs VMAT groups. Median follow up was 25 months. Analysis found V50 rectum was significantly lower in those treated with VMAT compared to static IMRT (48.5% vs 54.76% p = 0.001). Acute bowel toxicity rates (RTOG grade) were 80.6% grade < 2, 19.4% grade 2, nil > grade 2. Late bowel toxicity rates (RTOG grade) were 88% grade < 2, 12% grade 2, nil > grade 2. There was no significant difference in rates of acute or late bowel toxicity in groups treated with static IMRT vs VMAT. 13 patients (19.4%) underwent lower GI endoscopy during follow up, 9 had radiation proctitis. There was no significant difference in rates of endoscopy or proctitis for VMAT vs IMRT groups. 11.9% of patients developed biochemical failure during follow up. Rates of biochemical failure were not significantly different in groups separated by dose to pelvic nodes or radiotherapy technique. Conclusions: In a single institution, retrospective analysis, prostate and pelvic nodal irradiation is associated with acceptable rates of toxicity. Treatment with VMAT is associated with a significantly lower V50 rectum than that delivered by static IMRT.
MRI-US fusion targeted biopsy results in patients without history of prostate biopsy.
Authors: Nawaf Cayce , Rosoff James , Weinreb Jeffrey , Lu Amanda , Levi Angelique , Humphrey Peter , Schulam Peter , Sprenkle Preston 
Published: February 2017

150 Background: Results from 12-core template mapping biopsy (Mbx) and concurrent MRI-US fusion targeted biopsy (Tbx) were compared in 118 men without prior biopsy. Methods: Between 12/2012 and 06/2015, 374 men with an indication for prostate biopsy presented to our institution and underwent pre-biopsy mpMRI followed by 12-core standard trans-rectal mapping biopsy (Mbx) and MRI-Ultrasound fusion targeted biopsy (Tbx) of lesions identified on mpMRI. The combination of Mbx and Tbx, when both occurred, constitutes a fusion biopsy (Fbx). Men who underwent both Mbx with or without Tbx using the Artemis/Pro-Fuse system with no previous biopsy were included. Patients without a lesion on MRI underwent Mbx only. Maximum Gleason scores (GS) was assigned on a per patient basis with Mbx GS available for all patients in the cohort and Tbx GS available only for patients with a lesion visible on MP-MRI. Clinically significant (CS) was defined as GS ≥3+4. GS per patient was compared by chi-square and McNemar’s test. Results: 118 men met inclusion criteria (mean age=64.9, mean PSA=11.5). Prostate cancer was detected in 64 (54%) Fbx cases. Cancer detection rates for Mbx and Tbx were 54% and 57%, respectively. In patients where Fbx identified CS cancer, Tbx was more likely to have identified the cancer than Mbx (96% vs 72%; p < 0.001). Fewer GS 6 cancers were detected by Tbx (n=7) than by Mbx (n=25), and Tbx alone would have prevented the detection of 21 (18%) cases of GS 6 disease. Conversely, more GS≥ 7 (50% of men) was detected on Tbx than on Mbx (33% of men). In total, there were 16 patients (13.5%) that were missed or understaged by Tbx, but only 4 of these patients (3%) were GS≥ 7. In contrast, there were 19 (16%) patients that were missed or understaged by Mbx, but 17 (14%) of these 19 patients harbored GS≥ 7 disease. Conclusions: In biopsy-naive men who are suspected to have prostate cancer, Tbx provides improved detection of CS prostate cancer compared with Mbx while decreasing the detection of low-grade disease. Tbx alone in biopsy-naive men should be considered if missing 3% of CS disease is acceptable. [Table: see text]
Diagnostic capability of multiparametric MRI in patients with transrectal prostate biopsy.
Authors: Altamirano Jaime Antonio , Pinto Ivan Federico , Vilches Roberto Mauricio , Diaz Jorge Gonzalo , Sandoval Camilo , Vidal Alvaro Daniel , Canals Mauricio , Roman Cristobal , Rojas Alejandro , Quiroz Maria Jesus , Vega Andres 
Published: February 2017

155 Background: The prostatic multiparametric MRI (mpMRI) is the combination of anatomical imaging and functional sequences. Nowadays this technique is still being researched due to its positive published results. The objective of this study is to show our experience in the application of the mpMRI in patients, prior to the TRUS-guided biopsy, and the sensitivity and specificity of its measured parameters and their combination. Methods: Prospective cohort. MpMRI was indicated to patients prior to the TRUS-Guided biopsy. Diffusion, PIRADS, DCE and T2 parameters were observed on the MRIs, and the presence of cancer and Gleason score on the biopsy. Logistic regression test was performed with a 95% confidence interval. We assigned different values, depending of the importance of each factor, applying binominal regression. Results: We registered 73 patients with mpMRI prior to the TRUS-Guided Biopsy, and their results. The cancer detection rate was 60.27% (44 patients). The T2 signal had a sensibility of 81.82% and a specificity of 27.59%, ROC curve 0.54 (CI 0.44 – 0.64). The diffusion has a sensibility of 30% and a specificity of 85.19% with a ROC curve of 0.58 (CI 0.48-0.68). The DCE has a sensibility and specificity of 77.78% and 35.29% respectively, ROC curve of 0.57 (CI 0.42-0.71). By combining the T2, diffusion and DCE parameters, having 2 or more altered values, we obtained a sensibility of 84.62% with a 41.18% specificity, curve of 0.68 (CI 0.54-0.81). The sensitivity and specificity with a PIRADS score ≥ 3 was of 68.42 and 36.36% with a ROC curve of 0.56 (CI 0.36-0.76). With a PIRADS ≥ 4 the sensitivity and specificity was 57.89% and 54.55% respectively. The calculated measured score was assigned as 7 points for altered T2, 8 points for altered diffusion and 5 points for altered DCE. With a total value ≥ 12 the sensitivity of the score was 84.62% with a 41.18% sensitivity, ROC curve 0.68 (CI 0.54-0.81). Conclusions: The use of isolated mpMRI parameters have low performance, whereas this is greatly increased when used combined. The assigned weight of each parameter is a factor to consider and review on the existing scores.
Diagnostic capability of prostate multiparametric magnetic resonance in prediction of cancer and histological grade.
Authors: Altamirano Jaime Antonio , Pinto Ivan Federico , Quiroz Maria Jesus , Diaz Jorge Gonzalo , Canals Mauricio , Vilches Roberto Mauricio , Sandoval Camilo , Vidal Alvaro Daniel , Rojas Alejandro , Roman Cristobal 
Published: February 2017

161 Background: The prostatic multiparametric MRI (mpMRI) can enhance the performance of the prostate core biopsy to detect cancer. The objective of this study is to assess the capability of MpMRI to identify high- and intermediate-risk prostate cancer. Methods: Prospective cohort. MpMRI was performed to patients with TRUS-guided biopsy indication prior to the biopsy. Diffusion, PIRADS, DCE and T2 parameters were observed on the MRI, and the presence of cancer and Gleason score on the biopsy. The results were divided between no cancer, and presence of cancer Gleason 6 or higher. Logistic regression test was performed with a 95% confidence interval. We assigned different values, depending on the importance of each factor, applying binominal regression. Ordinal regression was then performed and Odds ratio calculated. Results: Seventy three patients met the described criteria. Cancer detection rate was 60.27% (44 patients). Seventeen of these patients were Gleason score six. The calculated score, gave 7 points for altered T2, 8 points for altered diffusion and 5 points for altered DCE. With a score of 12 points or more, the calculated sensibility was 84,62% and the specificity was 41.18%. The estimated OR was 1.15 [IC 1-1.38]. We calculated that having one altered parameter, had a probability between 0.17 and 0.25 of having intermediate and high-risk cancer. With more than one altered parameter, the probability was 0.37. One or more altered parameters gives a probability of having Gleason 6 score of 0.20 to 0.25. Conclusions: The MpMRI is a useful tool because it has high correlation with the histological grade, and it´s an excellent test for predicting high- and intermediate-risk prostate cancer when two or more parameters are altered. Based on this findings we strongly suggest TRUS-guided biopsy with an altered MpMRI.
Sipuleucel-T (sip-T)–induced proliferative CD8+ T-cell responses to immunizing and secondary antigens.
Authors: Antonarakis Emmanuel S. , Quinn David I. , Kibel Adam S. , Petrylak Daniel Peter , Chang Nancy N. , Cummings Crystal , Chinn Jason , Pufnock Jeff , Sheikh Nadeem Anwar , Drake Charles G. 
Published: February 2017

165 Background: Sip-T is an FDA-approved autologous immunotherapy for patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Sip-T is manufactured from peripheral blood mononuclear cells cultured with PA2024, a fusion antigen of prostatic acid phosphatase (PAP) conjugated to granulocyte macrophage-colony stimulating factor (GM-CSF). In sip-T–treated pts, T cell and antibody responses to PA2024 or PAP as well as antibody responses to secondary antigens (i.e., antigen spread) correlate with improved overall survival. To explore the biology of this relationship, we further characterized the T cell subpopulations involved in the cellular immune responses to sip-T. Methods: In vitro proliferative CD8+ (cytotoxic T lymphocyte) and CD4+ (T helper) T cell responses to PA2024 and PAP as well as to secondary antigens (PSA, LGALS3, and KRAS) were evaluated using flow cytometry on pt samples from two sip-T–containing clinical trials (STAND [NCT01431391] and STRIDE [NCT01981122]). Results: PA2024-specific CD8+ and CD4+ responses were observed beginning 2 weeks after the first sip-T infusion through week 26 in most evaluable pts. CD8+ and CD4+ responses to PAP were also observed, although the magnitude of this response (to a self-antigen) was smaller when compared with PA2024 responses. Most pts with CD8+ responses to PA2024 also had a CD4+ response, which occurred more frequently than CD8+ responses. Both CD8+ and CD4+ responses to secondary antigens were amplified after sip-T, and these CD8+ proliferative responses to secondary antigens were greater in magnitude compared with CD4+ responses. Conclusions: Here,we report the first evidence of antigen-specific CD8+ responses in pts receiving sip-T, indicating CD8+ T cell involvement in sip-T–mediated immune responses that occur in concert with the expected CD4+ T cell responses to soluble antigens (i.e., PA2024). These CD8+ responses were durable, lasting up to 26 weeks post–sip-T treatment. Importantly, responses to secondary antigens and in particular, CD8+ responses, were also amplified after sip-T treatment, suggesting that antigen spread could be resulting from sip-T–mediated tumor cell lysis. Clinical trial information: NCT01431391 and NCT01981122.