bluuebunny/crossref_metadata_2025_split huggingface dataset:
Looking to possible predictive factors of primary resistance to abiraterone acetate (AA) and enzalutamide (ENZ) in pretreated patients (pts) with castration-resistant prostate cancer (CRPC).
Authors: Caffo Orazio , Veccia Antonello , Maines Francesca , Bonetta Alberto , Spizzo Gilbert , Galligioni Enzo 
Published: February 2017

248 Background: Abiraterone acetate (AA) and enzalutamide (ENZ) are new generation hormonal agents (NHA) which demonstrated a survival gain in patients (pts) with castration-resistant prostate cancer (CRPC) pre-treated with docetaxel. Although all patients eventually became resistant to these NHAs, some of them show primary resistance, defined as an early progression within the first 3 months, which leads to an early treatment interruption. In the present analysis we have tried to identify which factor, if any, may predict primary resistance to AA and ENZ. Methods: We evaluated a consecutive series of 57 pts, treated in our hospital in two successive named patient programs conducted in our hospital to allow pre-treated CRPC patients to receive NHAs before their approval in Italy: 26 received AA (1,000 mg po + prednisone 10 mg po daily) and 31 ENZ (160 mg po daily). For each pt we have recorded the pre- and post-NHA clinical history, the treatment details and outcomes. We have also assessed the ability of a series of 24 selected clinical factors to predict NHAs resistance, through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: Among the 24 factors, the presence of pain at baseline, high baseline lactate dehydrogenase levels and prostate-specific antigen (PSA) levels after one month of treatment were predictive of primary NHA resistance at the univariate analysis. However, only PSA levels were confirmed at the multivariate analysis [exp(beta) 0.115; p = 0.007], as patients failing to achieve a 50% or more reduction in baseline PSA levels, were more likely to show primary NHA resistance (48% vs. 15%). Conclusions: Our results suggest that PSA trend may represent a simple and rapid method of identifying patients with primary resistance to NHAs, so patients failing to achieve a 50% or more reduction within the first month of treatment should undergo intensive investigations, to verify whether they have primary resistance to NHAs. These data should be confirmed in a larger patient population.
Incidence of patient-reported urinary incontinence after stereotactic body radiation therapy for clinically localized prostate cancer.
Authors: Chen Leonard N. , Woo Jennifer Ai-Lian , Bhagat Aditi , Moures Rudy A. , Kim Joy S. , Yung Thomas M. , Collins Brian Timothy , Suy Simeng , Lynch John H. , Dritschilo Anatoly , Collins Sean P. 
Published: February 2017

254 Background: Urinary incontinence (UI) following prostate radiotherapy is a rare toxicity that adversely affects a patient’s quality of life. The potential for hypofractionated radiotherapy to increase the risk of UI was investigated. This study sought to evaluate the incidence and severity of UI following stereotactic body radiation therapy (SBRT) for prostate cancer. Methods: Between February 2008 and August 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT at Georgetown University Hospital. Patients were treated to 35 to 36.25Gy in five fractions delivered with the CyberKnife (Accuray). UI was defined as self-reported involuntary urine loss and was assessed via the UI domain of the Expanded Prostate Index Composite (EPIC)-26 at baseline and at months 1, 3, 6, 9, 12, 18, and 24. EPIC scores range from 0 to 100 with lower values representing worsening incontinence. The minimally important difference (MID) was defined as a change of one-half standard deviation from the baseline. Results: The median age was 66 with a median prostate volume of 38 cc. The median follow-up was 3.2 years. Baseline UI was common with 22.0%, 26.2%, and 3.3% of patients reporting leaking, dribbling and pad usage, respectively. At two year post treatment, 31.1%, 34.7%, and 7.1% of patients reported some degree of incontinence based on leaking, dribbling and pad usage, respectively. Average EPIC UI domain scores showed a slow decline over the first two years following treatment. At two year post treatment, the median decreased from a baseline of 92.1 to 88.0. This change was statistically (p < 0.001) but not clinically significant (MID=6.7). The proportion of men feeling that their UI was a moderate to big problem increased from 1% at baseline to 6% at two years post treatment. Conclusions: SBRT for clinically localized prostate cancer was well tolerated with UI rates comparable to conventionally fractionated radiotherapy and brachytherapy. Greater than 90% of men who were pad-free prior to treatment remained pad-free two years following treatment. Less than 10% of men felt posttreatment UI was a moderate to big problem.
Real-world corticosteroid utilization in prostate cancer patients treated with two new oral agents.
Authors: Lafeuille Marie-Helene , Grittner Amanda M. , Lefebvre Patrick , Ellis Lorie , McKenzie R. Scott 
Published: February 2017

265 Background: Two oral agents have recently been approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC): abiraterone acetate (AA) combined with prednisone (P) for treatment of patients with mCRPC and enzalutamide (ENZ) for patients with mCRPC previously treated with docetaxel. Although corticosteroid (CS) co-administration is not required in ENZ prescribing information, 48% of ENZ-treated patients receive CS according to a large phase III clinical trial. To date, real world CS utilization patterns in AA- and ENZ-treated patients has not been reported. Methods: ProMetis Lx administrative claims data covering multiple health plans were used to identify patients with ≥1 PC diagnosis (ICD-9 185, V10.46) during ≥6 months of claims activity before the first AA or ENZ claim (index date). The proportion of patients receiving CS (identified by NDC codes) during AA or ENZ treatment (observation period-defined as first to end of last AA or ENZ prescription) was reported using descriptive statistics. Additionally, dosing and medication possession ratio (MPR) were calculated for the subset of patients receiving P. Results: A total of 3,228 AA-treated and 675 ENZ-treated PC patients were identified. Baseline comorbidities patterns were similar between treatment groups for hypertension (AA 55%, ENZ 56%), diabetes (25% both groups), and cardiovascular disease (28% both groups). The mean (SD) observation period for AA-treated patients was 142 (133) days and for ENZ-treated patients was 74 (46) days. CS use, P dose and P MPR are described in the following table. Conclusions: CS use was common in PC patients prior to and during treatment with AA and ENZ. While this data set may underreport CS use, patterns of CS use are consistent with clinical trial data. Further research based on data with longer follow-up and additional observational datasets is warranted. [Table: see text]
The management of adenocarcinoma of the prostate in rural Georgia: A population-based analysis.
Authors: Hall William A. , Nickleach Dana , Switchenko Jeffrey M. , Lipscomb Joseph , Goodman Michael , Ward Kevin C. , Gillespie Theresa Wicklin 
Published: February 2017

273 Background: The management of adenocarcinoma of the prostate (ACP) in minority populations and in the rural setting remains understudied. We conducted a population-based analysis exploring the management of ACP in rural Georgia. Methods: All cases of ACP diagnosed from 2001 to 2003 in a rural, 33-county, Southwest Georgia region were included. Data were obtained for all patients through direct medical record abstraction. Patient characteristics were described and associated with three specific outcomes: receipt of therapy, initiation of planned therapy, and completion of radiation therapy (RT) when initiated. Results: One thousand eighty seven patients were available for the analysis; median patient age was 69, and 44% of the patients were African American (AA). A total of 804 patients underwent a course of definitive therapy or elected to pursue regular active surveillance (AS). Of the patients 8.9% underwent radical prostatectomy (RP) alone, 3.1% RP and external beam radiation therapy (EBRT), 30.2 % EBRT alone, 10.8% brachytherapy (BT) alone, and 44.5% combination EBRT and BT; 2.5 % of patients underwent AS. Hormone therapy (HT) was used in 43.8% of all patients available for analysis. In a multivariable analysis conducted for the entire patient cohort, not being married (OR 0.60, 95% CI 0.42-0.85, p=0.004), lack of insurance (OR 0.32, 95% CI 0.16-0.61, p=0.008), and older age (OR 0.93, 95% CI 0.91-0.95, p<0.001) were all independently associated with not receiving definitive therapy. Race was not significantly related to receipt of definitive therapy. The full course of EBRT was successfully completed as planned in 98.4% of patients. Conclusions: Amongst those patients undergoing therapy for ACP in rural Georgia, a combination of BT and EBRT was the most common treatment modality. In contrast to recent studies, we found that race was not a significant predictor of receipt of care in Southwest Georgia. In this rural setting, EBRT was associated with extremely high rates of treatment completion. Despite the geographic and socioeconomic challenges associated with rural residency, our population-based study demonstrates that EBRT is a common treatment modality, with high patient compliance, even when used in a rural setting.
ODM-201 and the CNS: A clinical perspective.
Authors: Shore Neal D. , Bono Petri , Massard Christophe , Snapir Amir , Sarapohja Toni , Fizazi Karim 
Published: February 2017

275^ Background: ODM-201 is a potent, new generation androgen receptor inhibitor with activity in preclinical in vivo and in vitro studies. ODM-201 shows negligible penetration into the rat brain at pharmacological doses. In the phase I/II study with 134 patients with progressive castration-resistant prostate cancer (CRPC) (the ARADES study) patients with a history, or risk, of a seizure were not excluded. We reviewed the ARADES safety database to assess potential seizure or seizure-related adverse events (AEs). Methods: The following AE terminology was reviewed: seizure, syncope, presyncope, loss of consciousness, depressed level of consciousness, encephalopathy, and transient ischemic attack, hallucinations, vasovagal syndrome, falls and fall-related injuries, nonpathologic fractures, urinary or fecal incontinence, tonic-clonic activity, abnormal EEGs. We further reviewed medical histories and use of anti-seizure medications, as well as medications that could lower the seizure threshold and identified any seizure or seizure like condition as an AE. Results: Twenty one percent of the patients had concomitant medications indicated for epilepsy or other seizure-related disorders. Twelve patients had one or more of the above listed AE. None of the patients experienced seizures or related disorders while receiving ODM-201; one seizure event was reported to occur 27 days after stopping treatment. There were five fall events, one syncope, one presyncope, and four urinary incontinence cases - all interpreted by the investigators as not related to ODM-201 treatment and not leading to treatment discontinuation. Careful evaluation of these cases suggested that these events were unlikely to be related to seizure. Conclusions: ODM-201 has negligible brain entrance in nonclinical models. Treatment with ODM-201 was not linked with CNS-related events in patients in this trial. These preliminary findings suggest minimal CNS safety concerns. Clinical trial information: NTC01317641, NTC01429064.
The effect of cell cycle progression (CCP) score on treatment decisions in prostate cancer: Results of an ongoing registry trial.
Authors: Kar Ashok J. , Scholz Mark Creamer , Fegan Jeffrey E. , Crawford E. David , Scardino Peter T. , Kaldate Rajesh R. , Brawer Michael K. 
Published: February 2017

277 Background: Improved prognostic markers that provide individual patient risk stratification are a pressing need in prostate cancer. The CCP signature test (Prolaris, Myriad Genetic Laboratories, Inc.) is a novel prognostic assay that has been validated in multiple cohorts and provides accurate risk of prostate cancer-specific disease progression and disease specific mortality risk when combined with standard clinicopathologic parameters. This study evaluated clinicians’ judgment regarding the clinical utility of the CCP test in a prospective registry. Methods: Clinicians ordering the CCP signature test commercially were asked to complete a survey regarding their treatment recommendations before and after they received the CCP test result. In addition, clinicians were asked how influential the CCP test result was in making therapeutic decisions on a 5 point scale (0=None, 5=Very High). Results: Currently, 368 patients have been enrolled and 47 clinicians have completed surveys on the influence of the CCP signature test in 58 cases. In five additional surveys, the therapeutic decision was undecided pre-test, post-test or both. In 77% of cases [95% CI: 65%-86%], there was a change recorded between the therapy initially planned and the therapy actually selected. The table shows the change in intended therapeutic burden from pre-CCP test to post-CCP test. In 30 of 58 cases [52%; 95% CI 39%-64%], clinicians indicated they would reduce the intended therapeutic burden post-CCP test. The CCP signature test influenced treatment selection to a ‘High’ or ‘Very High’ degree in 37 men (62%) and had “Low” or “No” influence in only 3% of cases. Conclusions: Based on the judgment of ordering physicians, the CCP score appears to add meaningful new information to risk assessment for localized prostate cancer patients. Test results led to major changes in treatment decisions with a significant increase in conservative management options, including active surveillance or watchful waiting. [Table: see text]
Biochemical outcome of small volume or insignificant prostate cancer treated with radical prostatectomy.
Authors: Hashimoto Yasuhiro , Okamoto Akiko , Imai Atsushi , Yamamoto Hayato , Hatakeyama Shingo , Yoneyama Takahiro , Koie Takuya , Ohyama Chikara 
Published: February 2017

279 Background: We examined biochemical outcome of small volume prostate cancers (<0.5 cc, SVCa), and insignificant prostate cancers (<0.5 cc and Gleason scores <7, InsigCa) treated with radical prostatectomy. Methods: Between April 2000 and May 2011, 609 patients with prostate cancer were treated with radical prostatectomy in Hirosaki University Graduate School of Medicine. Of these, 237 were excluded from analysis because of pre-operative adjuvant treatment. The remaining 372 patients were eligible in the present study. Along with the routine pathological assessment, tumor volume (TV) was assessed in all patients. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) levels of greater than 0.2ng/ml. Results: The median age was 68 (48 to 78) and median pre-treatment PSA was 7.50 ng/ml.Average follow up period was 45.9 month. Mean tumor volume (TV) was 2.16 cc. We investigated 372 patients and found SVCa (<0.5 cc) in 60 patients (16.3%), and InsigCa in 14 patients (3.7%). The five year BCR-free survival rate for TV greater than or equal to 0.5 group and SVCa was 67.3% and 87.1% respectively. A significant difference was seen in the log-rank test between the two groups ( p=0.008). We could not identify BCR in InsigCa patients. Conclusions: Despite the limited number of cases, in our study InsigCa were clinically insignificant but in SVCa group 12.9% patients developed PSA failure after radical prostatectomy. SVCa is not identical to InsigCa. Therefore new biomarker is needed to examine what the prognostic relevance is of SVCa.
The prevalence of vasomotor and psychological symptoms in prostate cancer patients receiving hormonal therapy: Results from a single-institution experience.
Authors: Challapalli Amarnath , Saleem Waqar , Gjafa Ernese , Laniado Marc , Stanbridge Bente , Hellawell Giles , Mangar Stephen 
Published: February 2017

283 Background: Hormonal therapy is an important therapeutic modality in both early and metastatic prostate cancer. Whilst the long term effects of androgen deprivation (AD) have been extensively studied, little attention has focussed on assessing short-term vasomotor and psychological effects and the resulting impact of quality of life (QoL) in prostate cancer, relying on data mainly extrapolated from breast cancer patients. This prospective study sought to assess these effects and identify any predictive factors. Methods: Data from 200 consecutive prostate cancer patients were collected from January 2010 to August 2013. A self-reported questionnaire was employed to objectively assess a variety of vasomotor and psychological symptoms, graded from 1 no toxicity, 2 mild, 3 moderate to 4 severe toxicity. Other parameters including height, weight, Body Surface Area (BSA), Body Mass Index (BMI), duration and type of hormonal therapy were also recorded. Results: 181 patients were fully evaluable, with a median age of 75 (IQR 70.5-80). 166 received an LHRH analogue,11 maximum androgen blockade, and 4 received anti-androgens only. 33 (18.2%) of patients reported no toxicity, with 76 (42%), 55 (30%) and 17 (9.4%) experiencing mild, moderate and severe (debilitating) symptoms respectively. The commonest debilitating symptoms were vasomotor: drenching sweats (82%), and hot flashes (82%), which usually coexisted, and less commonly psychological: sleep disturbances (18%) and tiredness (12%). Age (median: 77 vs. 74 yrs), weight (median: 79.8 vs. 84.4), and BMI (median: 26.6 vs. 28.3) significantly predicted between those with grade 1/2 and grade 3/4 symptoms, (p=0.0007, 0.02, 0.02). A non-significant trend was observed with increasing duration of hormonal treatment and toxicity (median: 5, 7, 9.5 and 12 months for Grade 1-4, respectively, p=0.07). Conclusions: The short term side-effect profile of hormonal therapy for prostate cancer is generally favourable, though debilitating predominantly vasomotor symptoms can occur in a significant minority of cases. Increasing age, weight, and BMI may be predictive of toxicity.
Somatic genomic alterations in urothelial cancer: Results of the Cancer Genome Atlas (TCGA) bladder cancer (BC) analysis.
Authors: Rosenberg Jonathan E. , Kim Jaegil , Cherniack Andrew , Sougnez Carrie , Meyerson Matthew , Getz Gad , Weinstein John N. , Lerner Seth P. , Kwiatkowski David J. ,   The Cancer Genome Atlas Research Network Bladder Cancer Project
Published: February 2017

285 Background: We report here an integrated analysis of mutation and somatic copy number alterations (SCNAs) in 131 BCs to provide a comprehensive landscape of molecular alterations. Methods: Exon capture, whole exome sequencing (WES), and SNP arrays were performed on 131 MIBCs with no prior chemotherapy treatment, analyzed using the Cancer Genome Atlas Firehose Pipeline, and validated using orthogonal methods. Significantly mutated genes (SMGs) were determined by MutSig v1.5. Recurrent SCNAs were identified via GISTIC 2.0. Consensus non-negative matrix factorization (CNMF) was used to identify SCNA and SMG clusters. Results: 32 genes showed statistically significant levels of recurrent somatic mutation. Known druggable SMGs included FGFR3 (12%), PIK3CA (20%), TSC1 (8%), and ERBB3 (11%). CDKN1A (14%), ERCC2 (12%), RXRA (9%), ELF3 (8%), KLF5 (8%), FOXQ1 (5%), RHOB (5%), PAIP1 (5%), and BTG2 (5%) were not previously reported as SMGs in any other TCGA cancer type. Truncating mutations in 4 SMGs involved in epigenetic regulation (MLL2, ARID1A, KDM6A, and EP300) were significantly enriched. Clustering of both SMGs and focal SNCAs in 125 samples identified three distinct groups. Group A is highly enriched in focal SCNAs in several genes, as well as mutations in MLL2. Group B is enriched in papillary histology, loss of CDKN2A, and alterations in FGFR3. Group C has TP53 mutations, enrichment with RB1 mutations, and amplifications of E2F3 and CCNE1. There were no statistically significant associations between smoking status and the mutational spectrum, frequency of mutation in any SMG, focal SCNAs, or CNMF subtype. Conclusions: Analyses identified potential therapeutic targets in 69% of BCs, including 42% with targets in the PI3K/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Clustering reveals 3 groups with differences in pattern of genomic alteration suggesting the possibility of different pathogenic mechanisms of BC development. Epigenetic regulatory genes were more frequently mutated in urothelial carcinoma than in any common cancer studied to date, suggesting the future possibility of targeted therapy for chromatin abnormalities.
Quality of transurethral resection in patients with bladder cancer: A process-outcomes link.
Authors: Ballon-Landa Eric Christian , Chamie Karim , Bassett Jeffrey C. , Daskivich Timothy J. , Leventhal Meryl , Deapen Dennis , Litwin Mark S. 
Published: February 2017

292 Background: Detrusor muscle at diagnostic transurethral resection of a bladder tumor (TURBT) is often used as a surrogate of resection quality. We examined whether surgical and pathologic quality at the time of initial resection was associated with improved cancer-specific survival among subjects diagnosed with non-muscle-invasive bladder cancer. Methods: We retrospectively reviewed the operative and pathology reports of all individuals ≥18 years of age within the Los Angeles SEER registry, with an incident diagnosis of urothelial non-muscle-invasive bladder cancer between 2004-2005. We recorded patient age, gender, race, marital status, socioeconomic status, insurance type, institution type, surgeon and pathologist volume, tumor stage and grade, detrusor muscle presence/mention, and vital status. After adjusting for confounding using competing-risks regression analysis, we determined whether surgical and pathologic quality was associated with cancer-specific survival. Results: We identified 1,865 patients, 335 urologists, and 278 pathologists. Muscle was reported as present in 972 (52.1%), reported as absent in 564 (30.2%), and was not mentioned in 329 (17.7%) of the initial pathology reports. The incidence of detrusor muscle sampling did not differ according to grade or stage. However, bladder cancer death was more likely with higher stage disease (Tis: HR=5.00, 95% CI 2.38-10.50; T1: HR=5.44, 95% CI 3.00-9.88) and lower quality staging (muscle absent: HR=1.50, CI 1.00-2.27; muscle not mentioned: HR=2.01, CI 1.14-3.56). This pattern was enhanced among those with high-grade disease. For this group, the 5-year cancer-specific mortality was 8.0%, 13.0%, and 21.5% when muscle was present, absent, or not mentioned, respectively. Conclusions: Nearly half of all diagnostic TURBTs do not include muscle. This omission is associated with increased mortality, particularly in high-grade disease—yet few of these patients undergo treatment to correct this error. Because urologists cannot discern between high- or low-grade disease, we contend that all patients with bladder cancer should undergo endoscopic resection with detrusor muscle sampling (and appropriate pathology reporting) at diagnosis.