bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world evidence in patient-related outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate plus prednisone (AA+P).
Authors: Gotto Geoffrey , Fradet Vincent , Drachenberg Darrel , Sabbagh Robert , Rendon Ricardo A. , Shayegan Bobby , Danielson Brita Lavender , Casey Richard , Chan Katherine , Camacho Fernando , Zardan Anousheh , Hew Huong , Feifer Andrew 
Published: February 2018

196 Background: Oral androgen biosynthesis inhibitor, abiraterone acetate plus prednisone (AA+P), has shown to improve survival and patient-related outcomes (PROs) in clinical trials. The COSMiC study (Canadian Observational Study in Metastatic Cancer of the Prostate; ClinicalTrials.gov: NCT02364531) set out to prospectively amass real-world data on mCRPC patients (pts) managed with AA+P in communities within Canada. Here, we report the interim analysis of their PROs. Methods: At planned data cutoff in Sept 2017 after a median follow-up of 33.8 months, 264 pts were enrolled in 39 sites across Canada. Their FACT-P (Functional Assessment of Cancer Therapy – Prostate) and MoCA (Montreal Cognitive Assessment) were evaluated at baseline as well as at weeks 12, 24, 48 and 72 after AA+P initiation. A 10-point decrease denotes clinically significant degradation in FACT-P and a total MoCA score of > = 26 is considered normal. Descriptive analysis was utilized with continuous variables. Changes from baseline were summarized using mean (SD). Results: At a median age of 77 among 264 pts, 230, 185, 110 and 63 pts were available for analysis at their week 12, 24, 48, and 72 assessments respectively. The mean baseline FACT-P total score was 111.2 (19.44) with a < 3-point absolute change from baseline at subsequent assessments, denoting no clinically significant change in functional status over time. The mean baseline MoCA score was 25.2 (4.50), yet all subsequent assessments scored above 26 and a mean absolute change from baseline of < 1, showing an absence of cognitive decline over time. PSA value was available for 221 pts, 64.3% (142/221) and 34.4% (76/221) achieved a PSA decline of > 50% and 90% respectively. All-grade treatment-related adverse events were reported in 63 pts, with 11% who have had AA+P discontinuation or interruption. Conclusions: COSMiC represents the largest Canadian mCRPC cohort treated with AA+P with real world prospective evaluation of PROs. This data demonstrated the maintenance in quality of life and cognitive status over the course of the study, and underscores the importance of PRO utilization in this complex patient population. Clinical trial information: NCT02364531.
Transcriptomic heterogeneity of androgen receptor activity in primary prostate cancer: Identification and characterization of a low AR-active subclass.
Authors: Spratt Daniel Eidelberg , Alshalalfa Mohammed , Weiner Adam , Fishbane Nick , Mehra Rohit , Walter Rayford , Erho Nicholas , Dicker Adam , Freedland Stephen J. , Karnes Jeffrey , Glass Andrew , Weinmann Sheila , Davicioni Elai , Ross Ashley , Den Robert Benjamin , Feng Felix Y , Schaeffer Edward M. 
Published: February 2018

2 Background: Significant genomic diversity exists in the androgen receptor ( AR) and its activity (AR-A) in mCRPC. In localized prostate cancer, the biologic, prognostic, and therapeutic clinical implications of AR-A heterogeneity have yet to be interrogated Methods: Genome-wide expression profiles of FFPE RP or biopsy tumor samples were evaluated from a prospective registry cohort (n = 5,239, NCT02609269) and six retrospective institutional cohorts (n = 1,170). AR-A was calculated based on expression of 9 targets of AR.. Results: Utilizing 6,409 localized prostate adenocarcinomas with full transcriptomic data, we found there was marked inter-individual transcriptomic diversity in AR and AR-A expression, and weak correlation between them (r = 0.08 to 0.36 based on cohort), in contrast to mCRPC that has a strong correlation between AR and AR-A expression (r = 0.76). Additionally, serum PSA had no correlation to intratumoral AR-A (r = 0.06). Unsupervised hierarchical clustering identified a distinct subclass of low AR-A prostate tumors, which had increased markers of immunogenicity (decreased T-regs and MDSCs, and increased CD3 effector T-cells), increased neuroendocrine marker expression ( NCAM1, ENO2, and SCG2), and decreased DNA repair pathway expression (all p < 0.001). Clinically, low AR-A tumors had more rapid development of metastatic disease in three independent cohorts, were more prone to develop resistance to hormonal therapy and develop CRPC, and were found at an increased frequency in African-American men. Interrogating in vitro drug sensitivity analyses utilizing the NCI-60 panel, low AR-A tumors appear more sensitive to platinum chemotherapy and PARP inhibition, and less sensitive to hormone therapy and taxanes. Conclusions: The diversity in AR-signaling in localized prostate cancer represents important biological heterogeneity that is both prognostic and predictive of treatment response. These findings are provocative in that low AR-A tumors may be more susceptible to immunotherapy, PARP inhibition, platinum chemotherapy, and/or radiotherapy. Patients with low AR-A tumors warrant dedicated biomarker enhanced clinical trials.
Individual and joint effect of postdiagnostic metformin and statin use on prostate cancer mortality among patients with high-risk prostate cancer.
Authors: Lu-Yao Grace L. , E Jian-Yu , Lin Yong , Rebbeck Timothy , Lu Shou-En , Kelly William Kevin , D'Amico Anthony Victor , Stein Mark N. , Zhang Lanjing , Kim Isaac , Demissie Kitaw , Ferrari Anna C. , Tan Xiang-Lin 
Published: February 2018

202 Background: Metformin and statin together may delay prostate cancer (CaP) metastasis. However, the joint effects on CaP mortality remain unknown. This study is to quantify individual and joint effects of post diagnostic statin and metformin use on CaP mortality in survivors with high-risk CaP. Methods: This population-based study includes patients identified from the SEER database linked with Medicare files diagnosed with high-risk CaP (T category ≥T2c or prostate specific antigen level ≥20 or Gleason score ≥8) in 2008-2011. Comparators did not have documented use of statin or metformin. Hazard ratios (HR) and 95% were calculated using a time-varying Cox proportional hazard model with competing causes of death. Results: Based on 12,700 patients, post-diagnostic use of statin and metformin was associated with a substantial reduction in CaP mortality (Table), with more pronounced effects in patients with obesity (HR=0.32) or M1 disease (HR=0.54). Effects of statins vary widely by brand, with atorvastatin being associated with the largest reduction in CaP mortality (HR=0.18, 95% 0.07-0.50). Conclusions: CaP mortality was substantially lower in post-diagnostic users of statin with high-risk CaP within 6 years of follow-up. Synergistic effect of statin and metformin was observed in M1 disease only. Randomized trials are warrant to confirm the findings.[Table: see text]
Nadir testosterone (T) following in-situ polymer delivered, subcutaneously administered leuprolide acetate in men with prostate cancer (PCa).
Authors: Twardowski Przemyslaw , McLane John A. , Atkinson Stuart , Boldt-Houle Debbie , Tagawa Scott T. 
Published: February 2018

204 Background: Achieving and maintaining T suppression to castration level is the cornerstone of androgen deprivation therapy (ADT) for advanced PCa. Modern assay methodology found median T level after surgical castration to be 15ng/dL; the 2016 European Association of Urology guidelines define castration as T < 20ng/dL. Additionally, reaching nadir T < 20ng/dL is correlated with improved duration of response to ADT, time to progression or disease-specific survival (Klotz 2015), and prognosis for overall survival (Kamada 2015). To examine the effectiveness of in-situ polymer-delivered, subcutaneously-administered leuprolide acetate (SC-LA) on T suppression, nadir T was evaluated in 4 pivotal trials. Methods: Eugonadal patients with advanced PCa were treated with either 7.5 (6 doses), 22.5, 30, or 45mg (2 doses each) SC-LA lasting 1, 3, 4, or 6 months, respectively in 4 open-label, fixed-dose, pivotal trials. Serum T levels were evaluated byradioimmunoassay. T was measured 2-4 times on day 0 and once on days 1, 3, 7, and every week until the next dose, and repeated until end of study. The 45mg group had an additional measurement on day 2. LA was measured on days 0, 4, 7, 14, 21, 28, 35, 42, 49, and 56 post-injection. Nadir T was the lowest value obtained in the entire trial. Results: Across the SC-LA formulations, median LA levels were consistently between 0.1-1ng/mL from week 2 until the end of study. When pooled, 90-96% of patients achieved T≤20ng/dL by week 6 and 90-97% maintained T≤20ng/dL from weeks 6-24. Pooled analysis (n = 437) showed 99%, 97%, 91%, and 80% of patients reached nadir T≤20ng/dL, ≤10ng/dL, ≤5ng/dL, and ≤3ng/dL respectively with a median nadir T≤3 ng/dL. When comparing across all doses, > 88% of patients reached nadir T≤5ng/dL. Conclusions: Across all doses, SC-LA achieves consistent and prolonged serum LA drug delivery above 0.1ng/mL and provides favorable T suppression < 20ng/dL, which may be attributed to the in-situ forming polymeric delivery system. Multiple T measurements throughout the study confirmed that 91% of PCa patients achieved low nadir T≤5ng/dL, which may have implications for extending progression-free survival and duration of response to ADT.
Proportion of biochemically-recurrent prostate cancer patients with durable undetectable PSA after short-course androgen deprivation therapy.
Authors: Lim Daniel M. , Gulati Roman , Aleshin-Guendel Serge , Cheng Heather H. , Gawne Agnes M. , Wingate Jonathan T. , Etzioni Ruth Douglas , Yu Evan Y. 
Published: February 2018

207 Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate specific antigen (PSA) levels as a marker of efficacy. The proportion of patients and clinical relevance of those with a prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6–12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥ 0.2 ng/mL and no radiographically detectable metastasis. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death from any cause were evaluated by log-rank tests. Results: After ineligibility exclusions, data were abstracted from 93 patients. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were n=23/93 (24.7%; 95% CI 16.4–34.8%; P<0.001) and n=14/93 (15.1%; 95% CI 8.5–24.0%; P<0.001), respectively. Proportions of patients with undetectable PSA 12 and 24 months after testosterone recovery ≥ 50 ng/dL were n=16/65 (24.6%; 95% CI 14.8-36.9%) and n=10/65 (15.4%; 95% CI 7.6-26.5%), respectively. Being 1 year older at diagnosis was associated with an 11.5% (95% CI 3.1–21.9%; P=0.01) increase in the odds of having a detectable PSA after controlling for PSA at diagnosis, Gleason sum and time from initial therapy to BCR. Detectable PSA was associated with increased risk of metastasis (P=0.006) with marginal evidence of association with death from any cause (P=0.07). Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. Additional analysis is needed to demonstrate the clinical value of this measure as a surrogate for prostate cancer outcomes and for consideration as a trial endpoint.
Prostate-specific membrane antigen (PSMA) PET-CT imaging in the investigation and management of biochemical recurrence in prostate cancer.
Authors: Keane Fergus , Ged Yasser , Greally Megan , Maher Michael A. , O'Malley Kieran , McCaffrey John 
Published: February 2018

208 Background: It is estimated that within ten years of primary treatment for prostate cancer up to 40% of patients post radical prostatectomy, and up to 50% of patients post radiotherapy will develop disease recurrence. While monitoring of PSA levels is informative of biochemical recurrence, it may precede radiologically detectable recurrence by months to years, and cannot differentiate local/regional recurrence from systemic disease. This represents a management dilemma for treating physicians. The incorporation of PET probes targeting prostate-specific membrane antigen (PSMA) for prostate cancer shows promise for improving the management of patients with prostate cancer, when used alongside existing imaging techniques, like CT, MRI and bone scans. Methods: Retrospective review of all patients referred from our institution for PSMA imaging was carried out. Baseline clinical features were determined and we analyzed impact of PSMA imaging on management outcomes and survival data. Results: 33 patients referred for 68Ga-PSMA-PET imaging were identified. Median age at diagnosis was 65 years (51 -75). The indication for referral in all patients was biochemical recurrence in the absence of radiological evidence of disease by CT imaging and bone scan. Median PSA at time of referral for PSMA scan was 7.3ug/L (1.4ug/L to 87.7ug/L). 100% of patients (n = 33) were upstaged following PSMA imaging, and 30% (n = 10) had more than one site of metastatic disease identified. Most common sites of metastasis were lymph node and bone. Median number of sites of metastatic disease identified by PSMA imaging was one. These results led to a change in management for 96% patients (n = 32). All patients at the time of this review are alive with a median follow up of 13 months, and median progression-free survival of 11 months. Conclusions: PSMA PET-CT directly led to an alteration in the treatment of the majority of patients in this study. This real world data reflects the growing role of PSMA imaging in influencing clinical decisions for prostate cancer patients with biochemical recurrence. Prospective data from randomized studies are awaited to further validate the role of PSMA PET-CT in this patient cohort.
68-Ga-PSMA-PET in lymph node staging in PSA recurrent prostate cancer-does the primary influence the result?
Authors: Pfister David , Kohl Tobias , Porres-Knoblauch Daniel , Haidl Friederike , Heidenreich Axel 
Published: February 2018

210 Background: Prostate cancer is the most common cancer in western countries. 68Ga PSMA-PET is the most accurate tool to detect lymph node metastases even at low PSA values. Salvage lymph node dissection prolongs biochemical recurrent free survival, whereas salvage radical prostatectomy has the potential to achieve long term tumor control at least in node negative disease. We compared the diagnostic value of 68Ga-PSMA PET in patients with biochemical recurrence after radical prostatectomy an salvage radiotherapy (Group1) and in patients with local recurrence after radiotherapy (Group2) to evaluate the influence of the primary. Methods: We retrospectively reviewed 57 and 31 patients in Group I and II respectively. In Group I a salvage lymph node dissection was performed on the side of the positive PSMA-staining. In Group II an extended pelvic lymph node dissection was performed in addiction to a salvage radical prostatectomy. Sensitivity, Specificity, posisive and negative predictive value as well as accuracy of PSMA-PET was calculated per lesion. Results: A total of 649 (2-32) and 515 (3-29) lymph nodes had been dissected. In 39 (68%) and 11(35,5%) at least one positive lymph node could be found. Mean diameter of the metastases was 0,81 (0,1-2,6)cm and 0,8(0,1-2) cm respectively. Sensitivity, Specificity, pos and neg. predicitve value as well as accuracy in Group I and two are 85, 96, 77, 98, 94,6 and 40, 100, 100, 98, 97,6%. Conclusions: In salvage surgeries in PCA good diagnostic tools to identify lymph node metastases are mandatory. With the primary in situ there is a significant reduced sensitivity of only 40% to identify positive nodes. The specific role of the primary tumor is not yet known.
Value of bone scan index for predicting overall survival among patients treated with radium-223 for bone metastatic castration-resistant prostate cancer.
Authors: Yoneyama Shuko , Miyoshi Yasuhide , Tsutsumi Sohgo , Kawahara Takashi , Hattori Yusuke , Yokomizo Yumiko , Hayashi Narihiko , Yao Masahiro , Uemura Hiroji 
Published: February 2018

216 Background: The objective of this study was to evaluate the bone scan index (BSI) as a prognostic biomarker for overall survival (OS) among patients treated with radium-223 (Ra-223) for bone metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 42 men who had been treated with Ra-223 for bone metastatic CRPC between 2012 and 2017 and investigated correlations between the baseline clinical factors of age, time to CRPC, previous use of docetaxel, PSA, Gleason score, alkaline phosphatase (ALP), and BSI and OS by multivariate analysis using the Cox proportional hazard model. We also analyzed the correlations between OS and absolute BSI value or BSI change from baseline after 12 weeks of treatment. Continuous variables were classified as dichotomous. Results: The median age, PSA, and time to CRPC were 75.5 years, 42.8 ng/mL, and 11.2 months, respectively. The median observation period was 11.7 months. Twenty-five (59.5 %) of the 42 patients had completed six cycles of Ra-223 treatment. Twenty-two patients (52.4 %) had died, including 20 (47.6 %) of cancer, by the time of analysis. The median OS in the entire cohort was 20.7 months. Multivariate analysis also showed that only BSI (≥1.5 vs. < 1.5, HR 3.72, 95% CI 1.17–11.79, p = 0.026) was significantly correlated with OS. The BSI had decreased in 16 (51.6%) of the 31 patients who had undergone bone scans after 12 weeks of treatment . Multivariate analysis showed that absolute BSI value after 12 weeks treatment was significantly correlated with OS (BSI (≥2.0 vs. < 2.0%, HR 13.07, 95% CI 2.61–65.53, p = 0.002). No correlation was found between BSI change from baseline after 12 weeks and OS. Conclusions: According to multivariate analysis, both baseline BSI and PSA were significant prognostic factors for OS among men treated with Ra-223. Absolute BSI value after 12 weeks of Ra-223 treatment was also found to be an independent prognostic factor for OS.
Neuropsychiatric adverse events of enzalutamide and abiraterone acetate: Meta-analysis of randomized clinical trials with real world reporting patterns from EudraVigilance.
Authors: Moreno Perez Maria Paola , Sanchez Iznaola Miguel , Garcia Angela , Muñoz del Toro Jacobo , Casariego Joaquin , Robinson Paul , Parra Rafael 
Published: February 2018

217 Background: Androgen deprivation is associated with cognitive decline and mood changes. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are oral hormonal agents for the treatment of metastatic castration resistant prostate cancer (mCPRC); both target the androgen signaling pathway. Meta-analysis for individual neuropsychiatric adverse effects (NAEs) associated with these drugs has not been available in the literature. Methods: Following the methodology presented by Ruiz et al. a further meta-analysis was performed to estimate the pooled Relative Risk (RR) of NAEs for AAP and ENZ. A complementary analysis of the EudraVigilance database was performed to explore the consistency of the real world adverse drug reactions (ADR) reporting pattern with the meta-analysis. Results: The meta-analysis results indicate that patients treated with ENZ had a statistically significant higher risk of restless leg syndrome (RLS), anxiety, headache and insomnia vs control. Both AAP and ENZ showed significant increased risk for falls vs control. The Proportional Reporting Ratio (PRR) of ADRs reported in Eudra is higher with ENZ than with AAP for all the variables analyzed. Conclusions: NAEs studied are more prevalent with ENZ vs placebo than AAP vs prednisone plus placebo. Reporting trend in Eudra is consistent with this results. [Table: see text]
Multiparametric MRI-based intraprostatic tumor volume delineation in localized prostate cancer.
Authors: Lee Joon Kyu , Liu Chang , Elshaikh Mohamed A. , Wen Ning 
Published: February 2018

22 Background: Multiparametric MR imaging (mpMRI) has shown promising results in the diagnosis and localization of prostate cancer. Furthermore, mpMRI may play an important role in identifying a suitable target volume for intraprostatic radiotherapy boost. We sought to investigate the level of correlation between dominant tumor foci contoured on various mpMRI sequences. Methods: mpMRI data from 18 patients with MR-guided biopsy-proven prostate cancer were obtained from the SPIE-AAPM-NCI Prostate MR Classification Challenge. Each case consisted of T2-weighted, apparent diffusion coefficient (ADC), and ktrans images computed from dynamic contrast-enhanced sequences. All image sets were rigidly co-registered, and the dominant tumor foci were identified and contoured for each MRI sequence. Hausdorff distance (HD), mean distance to agreement (MDA), and Dice and Jaccard coefficients were calculated between the contours for each pair of MRI sequences (i.e., T2 vs. ADC, T2 vs. ktrans, and ADC vs. ktrans). The Pearson correlation coefficient (PCC) was also obtained for Dice and Jaccard between these image pairs. Results: The dominant tumor foci were located in the peripheral zone, transition zone, and anterior fibromuscular stroma in 5 (28%), 7 (39%), and 6 (33%) patients, respectively. Mean tumor volumes in the T2-weighted, ADC, and ktrans sequences were 2.71 +/- 2.74 mL, 2.71 +/- 2.67 mL, and 2.21 +/- 1.86 mL, respectively. Mean HD and MDA were lowest (4.34 +/- 1.52 mm and 1.00 +/- 0.52 mm) and Dice and Jaccard coefficients highest (0.74 +/- 0.12 and 0.60 +/- 0.15) for T2 vs. ADC. The PCC for Dice was 0.15 between T2 vs. ADC and T2 vs. ktrans, 0.37 between T2 vs. ADC and ADC vs. ktrans, and 0.62 between T2 vs. ktrans and ADC vs. ktrans, and similar values were obtained for Jaccard (0.12, 0.32, and 0.67, respectively). Four patients were excluded in the PCC calculation as no vascular permeability was visible in the ktrans maps. Conclusions: This analysis suggests that T2-weighted and ADC sequences have high correlation in identifying a suitable intraprostatic radiotherapy boost volume for localized prostate cancer. Furthermore, ktrans maps may provide additional information for tumor volume delineation.