bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and age specific differences in localized and metastatic prostate cancer incidence: 1988-2013.
Authors: Dall'Era Marc , deVere White Ralph , Rodgriguez Danielle , Cress Rosemary Donaldson 
Published: March 2017

211 Background: The United States Preventive Services Task Force (USPSTF) recommended against routine PSA based prostate cancer screening in all men in 2012. This led to dramatic reductions in screening and rates of localized disease across all clinical risk groups. We sought to study the impact of this on rates of metastatic disease, specifically by patient race and age. Methods: We analyzed new prostate cancer incidence by stage at diagnosis between 1988-2013 within the Cancer Registry of Greater California. We further stratified cases by four major race/ethnicity groups (non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and non-Hispanic Asian/PI (API)) and age. Incidence rates were calculated and compared per 100,000 and age-adjusted to the 2000 US Standard Population. Joinpoint regression was used to detect changes in incidence and to calculate the average percent change (APC). Results: Adjusted rates of remote prostate cancer incidence for NHW men increased slightly in the most recent decade (+0.28%) after steady declines in previous years with the inflection point occurring in 2002, however this was not statistically significant. In contrast, incidence of remote prostate cancer continued to decline for NHB (-2.73%), Hispanic (-2.04%), and API (-1.45%) men. The greatest increase of +1.1% a year since 2002 was observed for NHW men under age 65. The incidence of localized prostate cancer declined for all race/ethnicity groups over the most recent time period and also declined in all age groups. After remaining relatively flat since 1992, incidence of localized prostate cancer among NHW men declined by over 8% per year starting in 2007 compared with a more gradual decline of -3.52% a year since 2000 for NHB, and more recent declines of -14.41% and -16.64% for Hispanic and API men, respectively. Incidence of regional stage cancer also declined in all groups, but less dramatically. Conclusions: Incidence rates of newly metastatic prostate cancer have not significantly changed since PSA screening declined in the US although we noted a slight upward trend primarily for younger, white men since 2002.
Real-world outcomes in first-line treatment of metastatic castration-resistant prostate cancer (mCRPC): The prostate cancer registry.
Authors: Chowdhury Simon , Birtle Alison J. , Bjartell Anders , Costa Luis , Feyerabend Susan , Galli Luca , Kalinka-Warzocha Ewa , Kramer Gero , Lumen Nicolaas , Maroto Pablo , Matveev Vsevolod B. , Paiss Thomas , Pisconti Salvatore , Spaeth Dominique , Antoni Laurent , Klumper Edwin , Wapenaar Robert , Van Den Berg Erik , Lee Emma 
Published: March 2017

212 Background: The Prostate Cancer Registry is the first prospective, international observational study in mCRPC documenting characteristics and management in routine clinical practice, independent of treatment used. The study began in June 2013 enrolling > 3000 mCRPC patients (pts) followed for ≤ 3 years. Methods: Source-verified data were collected from men with documented mCRPC initiating a new mCRPC treatment or in surveillance. A history of disease progression despite surgical or chemical ADT was confirmed in all pts. This interim analysis reports baseline characteristics, treatments and outcomes in pts with no prior mCRPC treatment. To evaluate comparative effectiveness between treatments, propensity scoring (PS) methods were used to reduce effects of confounding. Results: Of 1906 evaluable pts with ≥ 12-month follow-up, the most commonly initiated first-line mCPRC treatments (n ≥ 50) were abiraterone acetate + prednisone (AA, n = 472), enzalutamide (ENZ, n = 98) or docetaxel (DOC, n = 382). Baseline characteristics, time to progression (TTP) and prostate-specific antigen (PSA) response ( ≥ 50% decrease within 6 months) are shown in the table below. Conclusions: In this real-world study, pts receiving DOC as their first mCRPC treatment had more severe disease at entry and a trend for shorter TTP vs androgen inhibitors. TTP results are consistent with those in randomised clinical trials for AA and ENZ. Clinical trial information: NCT02236637. [Table: see text]
Evaluation of treatment patterns and costs for patients with prostate cancer and bone metastases.
Authors: Valdarrama Adriana , Yao Jianying , Wen Lonnie Kent 
Published: March 2017

215 Background: To describe treatment patterns and costs of care associated with the use of FDA-approved agents for metastatic castrate-resistant prostate cancer (mCRPC). Methods: Two large integrated claims databases (MarketScan, PharMetrics) were used to identify males ≥ 18 years old diagnosed and treated for prostate cancer (ICD9 = 185.xx or 233.4) with bone metastases (ICD9 = 198.5) from 06/2013 to 09/2014. Patients were required to be continuously enrolled ≥ 6 months pre- and post-initiation of treatment with abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, radium-223, or sipuleucel-T. Results: There were 953 and 565 patients meeting all inclusion criteria in each database, with a median follow-up time of 18 and 14 months, respectively. Mean age was 69 to 71 years. Prior to mCRPC treatment initiation, 14.0% to 18.2% of patients received radiation therapy, 36.1% to 40.0% denosumab, 16.5% to 16.8% zoledronic acid, and 0.2% to 0.8% pamidronate. Across both databases, abiraterone was most commonly received agent across all lines of therapy, except fourth line (Table 1). The median cost per patient per month during the post-index period was $10,292 to $10,916 in the each database, respectively, compared to $2,643 to $2,742 per patient per month during the 6-month pre-index period. Conclusions: Patients were treated mainly with abiraterone across most lines of care, with bone-targeted therapy being used in < 3% of patients. Median costs per patient per month increased approximately ~$8,000 over this period. [Table: see text]
Relationship between smoking, prognostic factors, and outcomes in patient (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving sipuleucel-T (sip-T): Preliminary analysis of the PROCEED registry.
Authors: Armstrong Andrew J. , Higano Celestia S. , Sartor Oliver , Penson David F. , Vogelzang Nicholas J. , Dakhil Shaker R. , Pieczonka Christopher Michael , Vacirca Jeffrey L. , Tutrone Ronald F. , Nordquist Luke T. , Chang Nancy N. , Cooperberg Matthew R. 
Published: March 2017

216 Background: Smoking is associated with poor treatment outcomes after definitive therapy for PC (Steinberger 2015 BJU Int; Joshu 2011 JNCI). However, there is a paucity of data on the effects of active smoking on pts with mCRPC. The PROCEED registry provides an opportunity to evaluate differences in disease characteristics and outcomes by smoking status in men receiving sip-T, an FDA-approved, autologous cellular immunotherapy for asymptomatic or minimally symptomatic mCRPC. Methods: Enrolled pts with mCRPC who never smoked (NS) or were current smokers (CS) were evaluated.Pt characteristics, time to first anticancer intervention (tACI; measured from last sip-T infusion to first ACI; agents: abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223), PC-specific survival, and OS were assessed. Results: Of 1956 enrolled pts with known smoking status, 904 were NS, 179 were CS; 873 were former smokers and not included in this analysis. Compared with NS, CS were younger, had lower BMI (p < 0.001), higher hemoglobin (Hgb; p < 0.001), lower lactate dehydrogenase (LDH; p = 0.05), and shorter time between PC diagnosis and first sip-T infusion (p = 0.01). Fewer CS pts had Gleason score < 8 (p = 0.2) and prior radical prostatectomy (p = 0.07). CS and NS did not differ in pattern or extent of metastatic disease spread. CS was associated with shorter OS, PC-specific survival, and tACI (Table). Conclusions: CS were younger at enrollment and had shorter OS, PC-specific survival, and tACI. Higher Hgb in CS likely reflects reduced plasma volume and/or increased red cell production. A multivariate analysis of prognostic factors for survival outcomes including smoking status in mCRPC is planned. However, active smoking represents a possible modifiable risk factor in the mCRPC setting. Clinical trial information: NCT01306890. [Table: see text]
Patient expectations from systemic treatment of metastatic prostate cancer (mPC).
Authors: Moses Kelvin A. , Penson David F. , Du Liping , Ahmed Ivy , Morgans Alicia Katherine 
Published: March 2017

218 Background: Multiple systemic therapies prolong the survival of men with mPC, but the disease remains incurable. High-quality treatment decisions require an informed understanding of the purpose of treatment and expected risks and benefits, particularly because cancer patients may accept otherwise unacceptable treatment if they believe there is a ≥ 1% chance of cure. Reconciling patient expectations with expected outcomes of providers is necessary to prevent treatment with toxic therapies that patients would refuse if cure were not possible. We assessed patient expectations from treatment among men receiving systemic therapy for mPC. Methods: Between 6/1/15 and 9/29/16, men with mPC completed surveys defining expectations of cure from their current mPC treatment. We used frequencies and relative frequencies to describe expectations, and proportional odds models with robust standard errors to assess the association between expectations, optimism, clinical characteristics, and sociodemographic factors. Results: Among 96 men completing surveys, 32 (33%) reported that cure was at least a little likely (8% very likely, 14% somewhat likely, and 11% a little likely). Higher optimism scores were associated with higher expectations of cure (adjusted OR 2.5, 95% CI 1.3-4.8 for most versus least optimistic), and non-white race was associated with lower expectations of cure as compared with white patients (adjusted OR 0.08, 95% CI 0.02 – 0.3). Report of excellent or good overall health was associated with greater odds of expecting cure than report of fair or poor health (adjusted OR 13, 95% CI 1.3 – 125). Marital status and age were not associated with expectations. Conclusions: Up to 1/3 of men with mPC receive treatment with an expectation that it may cure their cancer. Men with greater optimism and better reported health status have greater odds of expecting cure. Actions to align patient and physician expectations are necessary to adequately counsel patients and avoid overtreatment with toxic therapies.
Exploring optimal sequence of abiraterone and enzalutamide in patients with castration-resistant prostate cancer: The Kyoto-Baltimore collaboration.
Authors: Terada Naoki , Maughan Benjamin Louis , Akamatsu Shusuke , Kobayashi Takashi , Yamasaki Toshinari , Inoue Takahiro , Kamba Tomomi , Ogawa Osamu , Antonarakis Emmanuel S. 
Published: March 2017

219 Background: Abiraterone (ABI) and enzalutamide (ENZA) are novel hormonal treatments for castration-resistant prostate cancer (CRPC) used before and after docetaxel (DTX) chemotherapy. We aimed to evaluate and compare the efficacy of sequential treatment with ABI followed by ENZA or vice versa in patients with CRPC, using combined data from two institutions. Methods: We retrospectively evaluated data on 352 consecutive patients who had received both ABI and ENZA for CRPC at Kyoto University Hospital and at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. Using Kaplan-Meier analysis and log-rank tests, we compared PSA progression-free survival (PSA-PFS) and overall survival (OS) in patients treated with sequential ABI-to-ENZA versus ENZA-to-ABI without intervening therapies. Results: The number of patients receiving ABI-to-ENZA and ENZA-to-ABI were 163 (pre-DTX: 116, post-DTX: 47) and 189 (pre-DTX: 85, post-DTX: 104), respectively. The > 50% PSA response rates to ABI and ENZA were 47% and 52% in the first-line CRPC setting, and were 9% and 29% in the second-line setting. In the pre-DTX population, median PSA-PFS was not significantly different between ABI (median: 194 days) and ENZA (median: 126 days) in the first-line setting (p = 0.411), but there was an advantage favoring ENZA (median: 91 days) compared to ABI (median: 55 days) in the second-line setting (p = 0.008). Furthermore, the combined PSA-PFS was significantly longer in the ABI-to-ENZA sequence (median: 455 days) than in the ENZA-to-ABI sequence (median: 296 days) (p < 0.001). There was no statistical difference in OS between the two sequences (p = 0.598). Conclusions: The ABI-to-ENZA sequence may have more favorable efficacy in terms of combined PSA-PFS than the ENZA-to-ABI sequence, although no differences in OS were observed. This may possibly be attributable to higher PSA response rates and longer PSA-PFS to second-line ENZA compared to ABI (i.e., ENZA retains activity after ABI but not vice versa).
Accuracy of 68Ga-PSMA-PET/CT for patient selection for lymphadenectomy in addition to salvage radical prostatectomy in locally recurrent prostate cancer after primary radiotherapy.
Authors: Pfister David , Heidegger Isabel , Verburg Frederik , Porres-Knoblauch Daniel , Heidenreich Axel 
Published: March 2017

229 Background: Salvage radical prostatectomy, sRPE, is an option for patients in locally recurrent prostate cancer with curative intent. Patients with low PSA at time of salvage treatment and initially low-risk disease have a favourable outcome whereas locally advanced and lymph node positive patients do not. Imaging studies could be beneficial for patient selection of lymph node dissection in addition to sRPE. Here we show first results of the diagnostic accuracy of PSMA-PET/CT in this setting. Methods: We reviewed 87 patients with sRPE and PSMA-PET/CT prior to surgery. In all patients an extended sRPE with an extended lymphnode dissection including the internal, external iliac artery, fossa obturatoria as well as the A iliaca communis to the ureteral crossing, was performed. For diagnostic accuracy Sensitivity, Specifity, pos. and neg. predictive value was calculated per person and per lymph node. Results: 11 patients had a PSMA PET/CT prior to surgery. All scans showed positive results in the prostate but only one showed a positive lymph node. A total of 141 lymph nodes were dissected (median 13,5; 8-29 per patient). Pathological analysis showed 6 lymph nodes with a metastasis in 4 patients. No positive lymph node was identified correctly by PSMA PET/CT. Specificity and negative predictive value per patient / per lymph node were high with 85% / 99% and 60% / 95.7%, respectively. As no patient or lesion was identified correctly sensitivity and pos. predictive value could not be calculated. Accuracy was 55% / 95.7%. Conclusions: In this small patient group PSMA PET/CT has an insufficient per-patient accuracy for patient selection of lymph node dissection in addition to sRPE. For patient selection clinical data including primary risk profile and PSA kinetics prior to surgery are still more useful for this purpose.
Imaging metastatic prostate cancer with 18F-DCFBC PET/CT (DCFBC) and 18F-NaF PET/CT (NaF).
Authors: Fakhrejahani Farhad , Lindenberg Maria Liza , Bargvall Ethan S. , Mena Esther , Turkbey Baris , Adler Stephen , Gulley James L. , Madan Ravi Amrit , Pomper Martin G. , Dahut William L. , Choyke Peter L. 
Published: March 2017

231 Background: Conventional imaging of advanced prostate cancer (computerized tomography and nuclear bone scintigraphy) is limited and indicates a need for a more specific molecular imaging probe. DCFBC is a radiolabeled PET agent that binds with high affinity to prostate specific membrane antigen (PSMA), which is overexpressed in almost all prostate cancers and through whole-body non-invasive functional imaging, may provide new information on the expression of PSMA. We compare the uptake of DCFBC in bone with respect to NaF PET/CT in metastatic prostate cancer patients. DCFBC has added capability to detect soft tissue metastasis whereas NaF is confined to secondary effects of bone disease. Methods: Subjects with known or suspected prostate cancer metastasis underwent DCFBC PET/CT imaging performed at 1 hour and 2 hours after IV bolus injection of 8 mCi of DCFBC. Patients also underwent a whole body NaF PET/CT scan within 3 weeks of DCFBC PET/CT to assess for bone metastases. Patients received 3 mCi of NaF IV bolus and then were imaged 1hour post injection. PSA levels and antiandrogen therapy status were obtained at the time of DCFBC imaging. Results: Fifteen patients have been preliminarily analyzed. PSA ranged from < .01 to 4379 ng/mL. NaF identified bone lesions in 10 patients but matching focal DCFBC uptake was only seen in 3 patients. DCFBC additionally showed lymph node metastasis in 1of these 3 patient. There were 5 patients without focal abnormal bone uptake on NaF or DCFBC. In this group, 4 of 5 patients had focal DCFBC uptake in lymph nodes or soft tissue lesions. Ten patients were on some form of androgen deprivation therapy (ADT). For those on ADT, 7 of 10 patients had positive findings on NaF, compared to 2 of 10 patients on DCFBC. Conclusions: DCFBC uptake in bone metastasis does not routinely correspond to focal NaF uptake which could be due to distinct mechanisms of tracer uptake and tumor biology. There is an inverse association in focal bone findings when comparing each tracer on antiandrogen therapy. Through whole-body non-invasive functional imaging and further study, DCFBC may prove useful in characterizing prostate cancer based on PSMA expression. Clinical trial information: NCT02190279.
Treatment sequencing of abiraterone and enzalutamide in patients with mCRPC.
Authors: Feibus Allison H. , Vasudevamurthy Ashwin , Guccione Jeffrey R. , Ledet Elisa M. , Cotogno Patrick , Manogue Charlotte , Ernst Emma M. , Lewis Brian E. , Silberstein Jonathan L. , Sartor Oliver 
Published: March 2017

233 Background: Abiraterone (Abi) and Enzalutamide (Enza) are among the treatment modalities available for treating metastatic castrate-resistant prostate cancer (mCRPC). This study aimed to analyze the efficacy of Abi and Enza as direct sequential treatments for patients with mCRPC. Methods: A single institution retrospective review was performed on 66 patients, in which 52 (79%) of the patients received Enza following Abi. The primary outcome measure was PSA response (50% PSA decline). Patients treated with taxanes between Abi and Enza were excluded from these analyses. Results: In patients treated first with Abi and second with Enza (n = 52), 35/52 (67%) responded initially to Abi. Following PSA progression or lack of initial response, all 52 patients were then treated with Enza, and 15/52 (29%) responded. Of the 17 patients that did not initially respond to Abi, 9 (53%) patients had a PSA response to Enza, in which 5/9 had a PSA decline ≥ 50%. 14 patients had a PSA decline ≥ 50% on initial Abi only (no PSA declines at all were noted post-Abi) and 3/14 responded to Enza. The median duration on the 1st drug was 294 days; median duration on the 2nd drug was 89 days. Conclusions: Additional investigation is needed for clinicians to understand better the cross resistance of Abi and Enza in mCRPC patients. [Table: see text]
Risk factors for metastatic prostate cancer: A sentinel event case series.
Authors: Paller Channing Judith , Cole Alexander , Partin Alan W. , Carducci Michael Anthony , Kanerak Norma 
Published: March 2017

235 Background: After 25 years of declines in late stage prostate cancer (PCa), evidence is mounting that an increasing fraction of men may present with metastatic disease, well after they might have been treated with local therapy. Identification of modifiable risk factors may allow for systems-level interventions to reduce delayed diagnoses. Methods: We performed an in-depth case series analysis of 15 patients who presented with metastatic disease at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center using root cause analysis, a tool commonly employed to understand the root cause of dangerous adverse events. Results: Key factors in late diagnosis include lack of insurance, lack of routine PSA testing, comorbidities, reluctance of patients to follow up actionable PSA as well as aggressive disease. Three patients had aggressive disease that would likely not have been discovered at an early stage regardless screening. However, analysis of the remaining 12 patients illuminated how health system factors led to missing important diagnostic information might have led to diagnosis of PCa at an earlier stage. Conclusions: These cases emphasize the need for systems-based approaches to early diagnosis of prostate cancer, which may prevent men from missing the opportunity to cure prostate cancer at an early stage. These results show how one might target PCa screening recommendations to more fully reflect key risk factors such as race and family history.
A personalized medicine approach to identifying dysregulated epigenetic enzymes in the development of castrate-resistant prostate cancer.
Authors: Jarrard David Frazier , Lee Jin-Hee , Boersma Melissa , Yang Bing , Damaschke Nathan Alan , Corey Eva , Denu John M 
Published: March 2017

237 Background: Recent advances in proteomic and chromatin immunoprecipitation tools have been crucial in studying cancer epigenetics but the ability to measure directly the enzyme activities of dysregulated histone-modifiers is lacking. We utilize a novel approach to identify altered histone-modifying enzymes in the progression from hormone sensitive (HS) to castrate-resistant prostate cancer (CRPC) progression. Methods: We developed, validated and utilized a high-throughput peptide microarray assay to identify altered histone lysine (de)acetylation activity in tumor lysates. Functional assays, novel HS and CRPC human tumor arrays and xenografts were utilized to confirm these findings. Results: This microarray-based activity assay revealed up-regulated histone acetyltransferase (HAT) activity against specific histone H3 sites in a castrate-resistant CR cell line compared to its hormone-sensitive (HS) isogenic counterpart. NAD+-dependent deacetylation assays revealed down-regulated Sirtuin activity in validated CR lines. Levels of acetyltransferases GCN5, PCAF, CBP and p300 were unchanged between matched HS and CR cell lines. However, auto-acetylation of p300 at K1499, a modification known to enhance HAT activity and a target of deacetylation by SIRT2, was highly elevated in CR cells. Among all 7 Sirtuins, only SIRT2 and SIRT3 protein levels were reduced in CR lines. Interrogation of HS and matched CR xenograft lines reveals that H3K18 hyperacetylation, increased p300 activity, and decreased SIRT2 expression are associated with progression to CR in 8/12 (66%). Tissue microarray analysis revealed that hyperacetylation of H3K18 is a feature of CRPC. Inhibition of p300 results in lower H3K18ac levels and increased expression of androgen receptor. Conclusions: This novel microarray approach provides a method to identify commonly dysregulated chromatin enzymes during progression providing a personalized therapeutic strategy to direct available drugs to target enzymes. Reduced SIRT2 expression and increased p300 activity lead to a concerted mechanism of hyperacetylation at specific histone lysine sites (H3K9, H3K14, and H3K18)