bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gaps in treatment amongst metastatic castration resistant prostate cancer (mCRPC) patients taking abiraterone acetate or enzalutamide.
Authors: Behl Ajay , Ellis Lorie , Pilon Dominic , Xiao Yongling , Lefebvre Patrick , Dawson Nancy Ann 
Published: February 2017

334 Background:Abiraterone acetate (ABI) and enzalutamide (ENZ) are novel oral therapies offering survival benefit to metastatic castration-resistant prostate cancer (mCRPC) patients. The efficacy of cancer treatments rely on patient consistency and adherence to recommended dosage regimens. Factors such as drug-drug interactions and intolerance or toxicities can result in patients or their providers reducing the drug dosage. This study aims to describe treatment discontinuation patterns observed for ABI and ENZ. Methods: The Truven Health MarketScan Research Databases were used to conduct a retrospective analysis of mCRPC patients initiated on ABI or ENZ (index date) between 10/01/2012 to 12/31/2014 with ≥6 months of continuous eligibility prior to index date and a PC diagnosis during the period of continuous eligibility. Patients were observed until loss to follow-up, or end of data availability. Kaplan-Meier (KM) survival curves were used to compare the rates of having a refill gap (i.e., ≥14 days, ≥30 days, or ≥60 days) in patients initiated on ABI or ENZ. Results: The table below summarizes the KM probabilities of having a refill gap among patients initiated on ABI or ENZ. Conclusions: Significantly higher rates of refill gaps ≥30 days and ≥ 60 days were observed for patients initiating ENZ as compared to ABI after 6 months of observation in this initial analysis. Additional research is needed to understand the reasons for gaps in treatment in patients treated with mCRPC therapies. [Table: see text]
Serum parathyroid hormone and calcium changes in metastatic castration resistant prostate cancer patients receiving enzalutamide in post-docetaxel setting.
Authors: Gernone Angela , Pappagallo Maria Nicla , Silvestris Francesco ,   Franco Silvestris
Published: February 2017

349 Background: Among novel hormonal therapeutic targets for post docetaxel mCRPC, Enzalutamide is an oral androgen-receptor blocker disrupting the androgen-receptor nuclear translocation that significantly increases the OS. In this study we evaluated the potential association of both PTH and Ca levels change in pts with mCRPC after the first Enzalutamide administration. Methods: Between 01 and 05/2015, 20 mCRPC pts relapsed after 2-3 prior lines of therapy (docetaxel, cabazitaxel, abiraterone) have been treated with Enzalutamide that was orally administered at 160 mg/day as continuous dosing. Patient characteristics included: median age 67 years (range 50-84), median baseline PSA 120 ng/ml (range 6-1200), median ECOG P S: 1 (range 0-2), Gleason score ≥ 7. In addition 80% of pts had ≥ 2 metastatic sites. Pretreatment baseline and follow up data including measurement of serum Ca and PTH levels (6.5-36.8 pg/ml), ALP, PSA and QoL parameters were evaluated through all lines of therapy. Pts with bone metastasis received zoledronic acid or denosumab with Ca and vitamin D supplementation. Results: In 18/20 pts with bone disease progression we recorded increased PTH levels and, contrarily, decreased Ca levels after 1 month of Enzalutamide despite vit. D and Ca supplementation. PTH levels remained unchanged after 3 months. In 2/20 pts without bone disease progression PTH ranged normal. All pts reported PSA response ≥ 50%, with improved QoL and are still on treatment since Enzalutamide is well tolerated. We did not find PTH change in bone mCRPC pts treated with prior therapy. Conclusions: Our study showed that increase in PTH levels and reduction in Ca levels and increase in PTH levels after 1 month of Enzalutamide treatment is associated with a dramatic reduction of PSA level. These data support a relationship between PTH and Ca changes in pts treated with Enzalutamide and, thus, their changes level may be adopted in clinical practice as surrogate to reflect the drug activity. No studies have evaluated the variations in serum PTH levels following Enzalutamide treatment and whether these early changes relate to the clinical outcome.
Metabolomics analysis of non-muscle invasive and muscle-invasive bladder cancer.
Authors: Sahu Divya , Lotan Yair , Wittman Bryan , Neri Bruce , Hansel Donna E. 
Published: February 2017

362 Background: Bladder cancer accounts for greater than 70,000 new cancer cases in the United States annually and an annual global incidence of more than 400,000 patients. Despite its high incidence, therapeutic options are limited both in early and late stage cancers and there is need for alternative, rational therapies in this population. Methods: We extensively analyzed benign urothelium, high-grade non-muscle invasive bladder cancer and advanced, muscle-invasive bladder cancer using global metabolomics profiling, coupled with publicly available data on transcriptomics of key enzymes, to determine pathways that may be suitable for future therapeutics development. Results: Categorical pathways globally dysregulated in cancer relative to benign urothelium included glucose, TCA cycle, lipid, amino acid and nucleotide pathways. Bladder cancers demonstrated Warburg metabolism, with elevated glucose utilization to drive glycolysis and sorbitol pathway intermediates. Elevated late TCA cycle intermediates, coupled with higher levels of amino acids and dipeptides, suggest the possibility of anaplerotic activity in bladder cancer as a mechanism to sustain energy production. Medium and long chain fatty acids were produced at the expense of dicarboxylic fatty acids. Muscle-invasive bladder cancers showed enhanced use of COX and LOX metabolomics pathways and a possible role for inflammation in regulating NAD+ synthesis in muscle-invasive bladder cancer. Transcriptomic profiling validated that the majority of metabolomics pathway alterations corresponded to gene expression changes of enzymes responsible for metabolite production. Conclusions: This study identifies multiple parallel metabolomics changes unique to non-muscle invasive and muscle-invasive bladder cancer that can be used to justify testing novel therapeutics targeting metabolomics pathways in bladder cancer.
COXEN prediction of antineoplastic drug sensitivity in bladder cancer patients.
Authors: Kothari Shalin , Gustafson Daniel , Killian Keith , Costello James , Edelman Daniel C. , Walling Jennifer , Meltzer Paul S. , Theodorescu Dan , Apolo Andrea B. 
Published: February 2017

365 Background: COXEN (Co-eXpression ExtrapolatioN) uses molecular profiles as a “rosetta stone” for translating drug sensitivities of one set of cancers into predictions for another completely independent set of cell lines or human tumors. The ability of COXEN to predict drug effectiveness in pts using tumor samples from in vitro assays is unique. Methods: We tested the predictive value of COXEN for standard chemotherapies in a cohort of bladder cancer pts. Total RNA was extracted from formalin fixed paraffin embedded (FFPE) tissue and converted to cDNA, amplified with Ovation FFPE WTA, and hybridized to a GeneChip Human Genome U133 Plus 2.0 array. Using gene expression data from 278 independent bladder tumors, COXEN scores were generated using bioinformatics models originally built using the NCI-60 cell line panel and a model building algorithm (MiPP). Gene expression data was processed to score 76 FDA approved antineoplastic drugs. Results: A total of 24 samples were tested (15 tumors with 1 sample and 9 tumors with 2 biological replicas (2 samples from the same tumor)) from 15 pts who received chemotherapy (median age 64 (41-74); 73% male; with muscle invasive bladder cancer (MIBC) (12/15, 80%) or metastatic bladder cancer (mBC) (3/15, 20%)). Response to therapy was confirmed by pathologic response in MIBC pts and radiologic response in mBC pts. Chemotherapies evaluated included: methotrexate/vinblastine/doxorubicin/cisplatin; gemcitabine/cisplatin; gemcitabine/carboplatin; and cisplatin/etoposide. COXEN accurately predicted antineoplastic drug sensitivity in 11/15 (73%) pts (75% MIBC and 67% mBC), of which 7/11 pts had 2 biological samples. However, only 3/7 (43%) biological replicas confirmed COXEN prediction. COXEN accurately predicted drug sensitivity in 9/10 (90%) pts with response and 2/5 (40%) pts with resistance to therapy. Conclusions: COXEN did well in predicting antineoplastic drug response for the majority of bladder cancer pts in this cohort. However, predictions from 2 samples within the same tumor were not always consistent, likely due to the expected tumor heterogeneity found in bladder cancer tumors. A prospective clinical trial in patients with mBC using COXEN to select next best therapy is in development.
Effects of interruptions of radiotherapy on outcomes of patients with prostate cancer.
Authors: Dong Yanqun , Li Tianyu , Churilla Thomas M. , Viterbo Rosalia , Sobczak Mark L. , Smaldone Marc C. , Chen David Y. T. , Uzzo Robert G. , Hallman Mark , Horwitz Eric M. 
Published: February 2017

37 Background: To evaluate if interruptions of radiotherapy have any effect on outcomes for men with localized prostate cancer (PCa) treated with definitive external beam radiation therapy (EBRT). Methods: We included men with localized PCa treated with definitive 3DCRT or IMRT of escalated dose (≥74 Gy in daily fraction of 2 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) between 1989 and 2013. Men receiving androgen deprivation therapy, or follow up <1 year were excluded. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of therapy, to account for the difference in total RT dose and planned RT duration. NTDR was analyzed for each NCCN risk group. Results: A total of 1,796 men including 861 low risk, 821 intermediate risk, and 114 high risk were included, with median follow up of 53.5 m (range 12 to 185.8 m). The median NTDR was 31% (range 23.1%-71.2%), translating to approximately 2 breaks (each break represents a missed treatment that would be made up in the end) for an 8-week RT with 5 treatments per week. The 75th percentile of NTDR was 33.3%, translating to approximately 4 breaks, which was used as the cutoff to compare the outcomes with NTDR ≥33.3% vs <33.3%. There were no significant differences in freedom from biochemical failure (FFBF), distant metastasis (DM), cancer-specific survival(CSS), or overall survival (OS) for men with NTDR ≥33.3% compared to NTDR<33.3% for each risk group (Table). Multivariable analyses including NTDR, age, race, Gleason score, T stage, and PSA were performed using the PHREG procedure. NTDR ≥33.3% was not significantly associated with increased hazard ratio for outcomes in each risk group compared to NTDR <33.3%. Conclusions: Interruptions of RT do not cause significant difference in outcomes in each risk group for men with localized PCa treated with definitive EBRT of escalated dose. [Table: see text]
A randomized trial comparing two different retention periods of intravesical pirarubicin instillation for intermediate risk non-muscule invasive bladder cancer (NMIBC) after transurethral resection.
Authors: Kasejima Yutaka , Takahashi Wataru , Kawano Yoshiaki , Yamaguchi Takahiro , Tanoue Ken-ichiro , Sakakida Hiroshi , Yatsuda Junji , Murakami Youji , Sugiyama Yutaka , Eto Masatoshi 
Published: February 2017

384 Background: Anthracyclines are recommended reagents for one immediate intravesical instillation after transurethral resection (TUR) and additional adjuvant instillation in intermediate risk NMIBC to reduce the risk of recurrence. Several studies have showed that Pirarubicin (THP), an anthracycline analogue, can rapidly penetrate tumor tissue after intravesical instillation. Therefore long instillation time (e.g. 120 min) may not be required for its prophylactic effect against recurrence without compromising its efficacy. Methods: This randomised, prospective, open-label trial intended to enroll 160 pts with primary NMIBC with intermediate risk based on EORTC criteria. Pts who seemed likely to be at intermediate risk were provisionally registered and then randomised into two groups with different intravesical THP retention times before TUR, (a) 30 min versus (b) 120 min. The registration was finally confirmed by pathology results of TUR. All registered pts received initial THP instillation within 24 hr after TUR and then intended to continue weekly repetitive THP instillation for a total of 9 treatments. Follow-up period is 4 years. Primary endpoint is change from baseline in quality of life measurements (e.g. OABSS and I-PSS), which were evaluated prior to each THP intravesical instillation. Secondary endpoint is recurrence-free survival. Results: 126 pts were enrolled for provisional registration. After excluding pts due to the result of pathology by TUR, 29 pts were assigned to group (a), and 26 pts to group (b). Although not statistically significant, there is a trend that group (a) is less prone to increase in OABSS after 3rd instillation compared to group (b). Log-rank test shows that there is no significant difference in recurrence-free survival between the groups during follow-up period (HR = 2.161, 95% C.I.: 0.4317-10.82, p= 0.3484). Conclusions: Shortening intravesical instillation period to 30 min has little effect on reducing the adverse effect of THP. However, it does not compromise the prophylactic effect on recurrence in intermediate risk NMIBC pts. Clinical trial information: UMIN000006861.
Outcomes of advanced urothelial carcinoma following discontinuation of programmed death (PD)-1 or PD-ligand (L)-1 inhibitors.
Authors: Sonpavde Guru , Pond Gregory Russell , Mullane Stephanie A. , Ramirez Ana Arlene , Vogelzang Nicholas J. , Necchi Andrea , Powles Thomas , Bellmunt Joaquim 
Published: February 2017

385 Background: The outcomes and therapy of advanced urothelial carcinoma (UC) patients (pts) following discontinuation of PD-1/PD-L1 inhibitors are unclear. We performed a retrospective analysis to examine the frequency of systemic therapy administered following PD-1/PD-L-1 inhibitors and outcomes in these pts. Methods: Data were collected from institutions for pts with advanced UC following prior PD-1/PD-L1 inhibitors as salvage therapy. Baseline demographics and therapy administered following prior check-point inhibitors was captured. Univariable Cox regression analyses examined clinical factors potentially associated with overall survival (OS) following check-point inhibitors. Results: Data from 62 pts were available from 4 institutions with capture of therapy and outcomes following checkpoint inhibitor immunotherapy. The median age was 65.5 years and 51 (82.3%) were male. The median duration of PD-1/PD-L1 inhibitors available from 55 pts was 64 days (range 7-669). Of these pts, 22 (35.5%) received post-PD1/PD-L1 pathway inhibitor therapy with a variety of chemotherapy (n = 16), chemobiologic combination (n = 1), biologic agents (n = 4) and immunotherapy (n = 1). The median time from last PD1/PD-L1 pathway inhibitor therapy to subsequent therapy was 58 days (range 14-242). The median OS of all pts following completion of PD-1/PD-L1 inhibitors was 149 days (95% CI: 75-359). Among pts who received some post-PD1/PD-L1 pathway inhibitor therapy, median OS was 182 days (95% CI: 121-372), and the median time to progression was 124 days (95% CI: 61-273) when examining from start of post-PD1/PD-L1 therapy. Among these 22 pts, the only significant baseline prognostic factor associated with OS was performance status. Conclusions: In this dataset, 35.5% of pts with advanced UC received subsequent systemic therapy following salvage therapy with PD1/PD-L1 inhibitors. Outcomes with subsequent therapy appear similar to historically observed outcomes in pts who had not received prior PD1/PD-L1 inhibitors. Further study of pts post-PD1/PD-L1 inhibitor therapy is warranted to identify factors associated with outcomes and potentially synergistic sequences.
Development of a PSA tracking system for patients wtih prostate cancer following definitive radiotherapy to enhance rural health.
Authors: Chang Michael G. , DeSotto Kristine , Taibi Paul , Troeschel Sandra 
Published: February 2017

39 Background: Patients with prostate cancer (PC) may benefit from early intervention when they experience relapse/recur. About 50% of our PC patients are rural and experience barriers to care due to distance, cost, and convenience. We sought to create a PSA tracking system with the Veterans Administration’s (VA) Electronic Medical Record (EMR) that would provide a remote way to monitor disease progression after definitive radiotherapy (XRT) by annual PSA testing alone. Methods: Using VA’s EMR, we developed a query tool to identify all patients ever treated at our center with XRT for prostate cancer who were alive, had not been seen in our clinic in more than a year, did not have metastatic disease, and had a rising PSA of at least 0.5 ng/ml above nadir, or who had no PSA drawn within 15 months. Results: Among roughly 50,000 unique patients in the McGuire VAMC EMR, we found 1,858 patients treated with XRT for PC more than 5 years ago between 1997 and 2015. Of these 1,190 were still alive and 455 had not been seen by our clinic in 400 days or more. Of these 455 patients, 159 patients had not had a PSA drawn within 15 months and/or their most recent PSA was more than 0.5 ng/ml above nadir, triggering a chart review followed by either a phone call, repeat testing, in person follow up visit, or removal from follow up monitoring if clinically indicated. 296 patients were receiving appropriate care outside of our clinic and had no sign of significant rise in PSA. An analysis by the VA showed annual savings of $60,360 per year in fuel costs by avoiding unnecessary visits. Conclusions: The VA’s robust EMR and a new query tool can identify patients with prostate cancer who are lost to follow up or who needed intervention from among thousands of patients in the EMR, improving quality while reducing cost and unnecessary time and travel for rural and all patients. More importantly, our tool could be modified to improve survival for all VA patients with prostate cancer by creating a VA-wide PSA failure detection system. The system would alert providers to any patient who may benefit from early salvage radiotherapy or hormonal therapy before their disease progresses beyond the therapeutic window of benefit.
Definitive radiotherapy in the management of node-positive bladder cancer: A National Cancer Data Base (NCDB) analysis.
Authors: Stokes William Allen , Rusthoven Chad G , Yeh Norman , Kavanagh Brian D. 
Published: February 2017

394 Background: The survival impact of definitive radiotherapy (RT) in lymph node positive (N+) non-metastatic (M0) bladder cancer is unclear, as reflected in the National Comprehensive Cancer Network (NCCN) guideline recommendation for chemotherapy (CT) with or without RT in this population. We conducted the present analysis of the NCDB to determine whether RT at a definitive dose would be associated with improved overall survival (OS) in patients with N+ bladder cancer. Methods: NCDB was queried for subjects diagnosed from 1998-2012 with cN1-3 M0 cancer of the urinary bladder who did not undergo cystectomy. Definitive RT included external beam radiotherapy to the pelvis or bladder regions to a cumulative dose of ≥ 54Gy (per NCCN guideline for gross nodal disease). Cox regression was used to assess the association of definitive RT with overall survival while controlling for patient-related, tumor-related, and treatment-related factors. Results: 3,298 N+ subjects not undergoing cystectomy were identified, of whom 840 (25.5%) received any RT and 392 (11.9%) received ≥ 54Gy. In the entire cohort, multivariate analysis adjusting for age, year, sex, race, location, income, comorbidity, histology, grade, T-stage, N-stage, and receipt of chemotherapy demonstrated an OS benefit (HR for death 0.69; 95%CI 0.59-0.82; p < 0.01) with cumulative RT dose ≥ 54Gy. On subgroup analysis, this OS benefit persisted both among the 1905 patients (331 receiving ≥ 54Gy) undergoing CT (HR 0.66; 95%CI 0.46-0.95; p = 0.02) and among the 1393 patients (61 receiving ≥ 54Gy) not undergoing CT (HR 0.67; 95%CI 0.55-0.82; p < 0.01). Conclusions: In the largest analysis to date of definitive radiotherapy for N+ bladder cancer, receipt of a definitive RT dose was associated with improved OS, irrespective of receipt of CT. Intermediate oncologic endpoints including locoregional control and disease-free survival were unavailable for analysis. With a minority of N+ subjects receiving any radiotherapy, this intervention appears to be underutilized among these patients.
Long-term outcomes after bladder-preserving combined-modality therapy for patients with muscle-invasive bladder cancer.
Authors: Giacalone Nicholas J , Clayman Rebecca Helen , Shipley William U. , Niemierko Andrzej , Heney Niall M. , Michaelson M Dror , McGovern Francis J. , Kaufman Donald S. , Zietman Anthony L. , Efstathiou Jason A. 
Published: February 2017

398 Background: Transurethral resection of bladder tumor (TURBT), chemotherapy (CT), and radiation therapy (RT) is an established treatment paradigm for muscle-invasive bladder cancer (MIBC). Herein we report long-term outcomes for MIBC patients treated with combined-modality therapy (CMT). Methods: We analyzed 465 patients with MIBC (cT2-T4a) treated on successive protocols at a single center between 1986 and 2012. Patients underwent TURBT followed by concurrent cisplatin-based chemoradiation (CRT). A subset of patients received neoadjuvant CT. Repeat cystoscopy was performed after 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64-65 Gy, while those with less than a CR or invasive recurrence were recommended to undergo salvage RC. Overall survival (OS) and disease-specific survival (DSS) were evaluated using Kaplan-Meier method and Cox proportional hazards regression. Results: Median follow-up was 4.8 years for all patients and 7.5 years for surviving patients. CR to induction CRT was achieved in 76% patients; 84% of patients with a complete TURBT achieved a CR vs. 59% with an incomplete TURBT, p< 0.001. When evaluated in four-year intervals, the CR rate improved from 64% in 1986-1990 to 96% in 2010-2012. Salvage RC was performed in 125 patients (27%), 55 for less than CR and 70 for superficial or invasive recurrence. Among patients with a CR, the 10-year actuarial rates for non-invasive, invasive, pelvic, and distant failure were 32%, 16%, 14%, and 29%, respectively. Median OS was 6.4 years. Five- and 10-year OS rates were 57% and 39% (T2 = 66%, 46%; T3-T4a = 41%, 26%), respectively. Five- and 10-year DSS rates were 66% and 59% (T2 = 75%, 66%; T3-T4a = 50%, 45%), respectively. In multivariate analyses, T2 disease (vs. T3-4; HR 0.55, 95%CI 0.40-0.76) and CR to induction therapy (HR 0.40, 95%CI 0.28-0.55) were significant predictors for improved OS. Age was not associated with DSS (HR 1.01, 95%CI 0.99-1.03). Conclusions: These data support the high rates of CR and bladder preservation in patients receiving CMT, and demonstrate long-term DSS similar to modern cystectomy series. CMT should be considered as an alternative treatment strategy for selected patients with MIBC.