bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of clinical and pathologic criteria in neuroendocrine and aggressive variant prostate cancer.
Authors: Karir Beerinder S. , Vlachostergios Panagiotis J. , Christos Paul J. , Febles Victor RA , Pinto-Chengot Kavya , Molina Ana M. , Nanus David M. , Beltran Himisha , Tagawa Scott T. 
Published: February 2017

268 Background: Various clinical and pathologic criteria have been proposed to identify neuroendocrine (NE) or aggressive variant (AV) prostate cancer (PC). We assessed the prognostic value of clinical parameters in a single-institution cohort. Methods: An IRB-approved database was screened for clinical and/or pathologic criteria (Table 1) for NE/AV PC. Patients with advanced CRPC not meeting any of the criteria served as contemporary controls. Overall survival (OS) for each group was assessed using Kaplan-Meier method and comparisons with log-rank test. Results: 249 men were identified, median age 71.5 (45.1-90.8 years). 145 patients met at least 1 criterion suggestive of NE/AV PC, whereas 104 were CRPC only. Median OS for each subgroup, the combined NE/AV PC group, and the CRPC cohort are provided in Table 1. OS for NE/AV PC vs. CRPC cohort was 25.4 vs 33 months (p = 0.26). Patients with parenchymal brain metastasis had the worst survival of 5.2 mo [95%CI 2.1, 8.3]. On multivariate analysis, bulky high-grade disease in prostate/pelvis carried the highest risk of death (HR 1.71 [1.07, 2.74; p = 0.02]). Conclusions: A number of clinical and pathologic criteria have been used to define NE/AV PC for clinical practice or trial enrollment. Some criteria are associated with a shorter survival than others. Additional studies are warranted to further define both prognostic and molecularly defined subgroups. [Table: see text]
Impact of prior definitive therapy on survival outcomes in men with new hormone sensitive metastatic prostate cancer (mHSPC).
Authors: Alex Anitha , Stenehjem David D. , Twardowski Przemyslaw , Cheng Heather H. , Buckley Tyler Howard , Gill David , Patel Shiven B. , Vaishampayan Ulka N. , Agarwal Neeraj 
Published: February 2017

269 Background: In mHSPC, treating the primary tumor may have a biologic effect on the metastatic sites, and definitive therapy in this setting has been hypothesized to delay disease progression and even death. Outcomes with prior definitive therapy in this setting have not been reported. Methods: In this multicenter study, men with new mHSPC, starting androgen deprivation therapy (ADT) were included. Index date was the day of starting ADT. Kaplan-Meier and Cox proportional hazard methods assessed time to castrate resistance (CRPC) and overall survival (OS) in those with or without prior definitive therapy. Variables significant at P < 0.05 were included in the final models. Results: A total of 235 men with mHSPC were included (median age ~ 67 yrs). Prior definitive therapy was performed in 64 men (27%). Results are presented in the table. Conclusions: Definitive treatment was associated with improved time to CRPC and OS in univariate analysis; however, when combined with other prognostic factors the significance was not maintained. Analysis of a larger data set is warranted to fully assess the role of prior definitive therapy in mHSPC. [Table: see text]
Patient reported outcomes in NRG Oncology/RTOG 0938, evaluating two ultrahypofractionated regimens (UHR) for prostate cancer (CaP).
Authors: Lukka Himanshu , Pugh Stephanie L. , Bruner Deborah , Bahary Jean-Paul , Lawton Colleen Anne , Efstathiou Jason A. , Kudchadker Rajat , Ponsky Lee Evan , Seaward Samantha A. , Dayes Ian S. , Gopaul Darindra , Michalski Jeff M. , Delouya Guila , Kaplan Irving D. , Horwitz Eric M. , Roach Mack , Pinover Wayne , Beyer David , Sandler Howard M. , Kachnic Lisa A. 
Published: February 2017

27 Background: The considerable interest in short UHR 5-12 fractions(fr) in management of CaP is based on potential radiobiological advantages, patient convenience & resource allocation benefits. Prior to comparison with standard RT regimens (SRTR), a study was undertaken whose primary objective was to demonstrate that 1-year health-related quality of life (HRQOL) for at least one UHR arm was not significantly lower than baseline as measured by the Bowel & Urinary domains EPIC instrument(EPIC B&U). Secondary objectives included acute & late GI & GU toxicity. Methods: RTOG 0938 is a randomized phase II study of CaP patients(pts), (Gleason score 2-6, stage T1-2a & PSA < 10 ng/mL) receiving 36.25 Gy (5 fr of 7.25 Gy in 2 wks), or 51.6 Gy (12 fr of 4.3 Gy in 2.5 wks). Pts were stratified according to RT technique – Cyberknife vs IMRT/VMAT or protons. A change in EPIC bowel domain score (baseline to 1-year) > 5 points & in EPIC urinary domain score > 2 points were felt to be clinically significant. The frequency for > 5 point change in bowel score (FREQE-B) in ≤ 35% of pts was considered acceptable, with the frequency ≥ 55% unacceptable. Similarly, the frequency for > 2 point change in urinary score (FREQE-U) in ≤ 40% was considered acceptable, with the frequency ≥ 60% unacceptable. A sample size of 156 pts was needed for 95% power with one-sided significance level of 0.025 to preserve an overall level of 0.05. Results: 240 pts were enrolled to ensure adequacy of data for analysis. The compliance for HRQOL completion was good ( > 80%). The 1 year FREQE-B for 5 fr was 23.5% (p < 0.001) & 12 fr was 23.1% (p < 0.001). The 1 year FREQE-U for 5 fr was 35.3% (p < 0.001) & 12 fr was 34.7% (p < 0.001). Conclusions: This study confirms that based on changes in EPIC B&U (baseline to 1-year), acute & late toxicity, both the 5 & 12 fr regimens are well tolerated. These UHR need to be compared to current SRTR in the context of a RCT with efficacy & toxicity endpoints. Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, UG1CA189867 from the National Cancer Institute (NCI). Clinical trial information: NCT01434290. [Table: see text]
Clinical differences between African-Americans (AA) and Caucasians (CA) with and without family history (FH) of prostate cancer.
Authors: Garvey Cathryn E. , Cotogno Patrick , Ernst Emma M. , Ledet Elisa M. , Sartor A. Oliver 
Published: February 2017

279 Background: Prostate cancer is one of the most common adult malignancies. Two well characterized risk factors for prostate cancer (PCa) are family history (FH) and race. The goal of this study was to distinguish the influence of family history and race with regards to clinically relevant covariates. Methods: In this single-institution study, 497 PCa patients from Tulane Hospital were clinically annotated and FH was evaluated. FH was defined as having ≥ 1 first degree relative affected with PCa and/or ≥ 2 affected second or third degree relatives. There were 147 AA and 350 CA patients; 66 AA and 120 CA reported PCa FH. The following clinical factors were documented: age and PSA at diagnosis (dx), Gleason score (biopsy or radical prostatectomy), and presence of metastasis (at any time). Chi-square, ANOVA, and odds ratio tests were performed to identify potential clinical correlates with regard to FH and race. Results: Results indicate that race and FH are not independent (p = 0.0266), where AAs were 1.5 times more likely to have a FH of PCa than CAs (95% CI 1.0543-2.3133). On average, men with a FH of PCa were younger at dx (p = 0.0063). FH significantly impacted age at dx for AAs (p = 0.036) but not CAs. No difference in age of dx was detected between race. FH of PCa did not influence PSA at dx in either CA (6.5, 1.2-681) or AA (19.2, 1.7-500) men, however race did (p = 0.004). CAs with FH of PCa were more likely to be diagnosed with low or intermediate risk PCa (Gleason score ≤ 7, p = 0.03). Gleason scores were not significantly different between races. Overall, FH did not influence metastasis. Although, AAs (n = 19) were 1.61 times more likely to develop metastatic disease compared to CA men. Conclusions: For AAs, FH lowered age at dx but did not have influence on development of metastatic disease, Gleason score or PSA. For CAs, Gleason score was lower in men with a FH. Overall AAs, as compared to CAs had more metastatic disease and higher PSAs at dx. Continuing to track clinical differences between AAs and CAs with a FH of PCa may provide additional insights into underlying racial and clinical disparities.
The role of adjuvant radiotherapy in pathologically node positive prostate cancer.
Authors: Jegadeesh Naresh , Liu Yuan , Zhang Chao , Zhong Jim , Gillespie Theresa Wicklin , Kucuk Omer , Rossi Peter John , Master Viraj A. , Alemozaffar Mehrdad , Jani Ashesh B. 
Published: February 2017

28 Background: The postoperative management of prostate cancer with regional lymph nodal involvement (LNI) is controversial. Prospective evidence to guide the role of radiotherapy (RT) in this setting does not exist. Randomized studies demonstrate an improvement in disease-related outcomes with adjuvant RT in high-risk patients without LNI following prostatectomy (RP). Retrospective evidence supports the selective use of RT with LNI following extended pelvic lymph node dissection. It is unclear if this experience is generalizable to practice in the United States where extended dissection is uncommon. We sought to identify patients with LNI who may derive a survival benefit following adjuvant RT. Methods: The National Cancer Data Base was queried for M0 patients with prostate adenocarcinoma who underwent RP with pathologic LNI. Adjvuant RT was defined as delivered within 6 months following RP. Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching (PSM) was employed to further reduce treatment selection bias. Results: 7,902 patients diagnosed between 2003-2011 were eligible for analysis; 1,439 (18.2%) received RT. RT was more frequently employed in patients with lower Charlson-Deyo Comorbidity Score, higher T stage, <5 nodes examined, ≥50% nodal positivity ratio, Gleason 8-10, ≥20 PSA, positive surgical margin, and <65 years of age (all p < 0.05). Five year OS was 87.6% vs. 85% in those receiving RT vs. not (p = 0.075). With androgen deprivation (ADT) (n = 3,265), 5-year OS was 87.2% vs. 82.7% in those receiving RT vs. not (p = 0.004). In multivariable analysis, the use of RT was independently associated with improved OS (HR 0.73, 95% CI 0.59-0.89, p = 0.002). 894 remained in each cohort following PSM. In this analysis, RT remained associated with OS (HR 0.66, 95% CI 0.51-0.85, p = 0.002). Conclusions: Adjuvant RT was associated with improved OS following RP in patients with LNI in this large generalizable retrospective analysis. This effect appears stronger in those receiving ADT. This series is the largest describing adjuvant RT in this population. In the absence of prospective evidence, these results may help guide therapy in this setting.
Copy number variations in AR-associated and DNA repair genes from plasma cell-free DNA of metastatic CRPC patients.
Authors: Gambhira Ratish , Ledet Elisa M. , Dotiwala Aryeneesh , Mandal Diptasri , Sartor A. Oliver 
Published: February 2017

281 Background: Cell-free DNA (cfDNA) present in the plasma of advanced cancer patients can reflect tumor related genetic alterations. Recent data suggests copy number variations (CNVs) in AR-associated and DNA repair pathway genes play a potential role in prostate cancer progression. Here, we performed sequencing of cfDNA from 13 mCRPC patients to evaluate its potential in elucidating tumor related genetic variations. The long-term goal of our project is to correlate cfDNA derived genetic alterations with prostate cancer progression and/or therapeutic resistance/responses. Methods: cfDNA was isolated from 13 advanced mCRPC patient plasma samples using the Qiagen circulating nucleic acid kit. 100ng of cfDNA was utilized for library construction; and the libraries were paired-end sequenced on the Illumina HiSeq 2000. The resulting data was analyzed using the GATK best practices bioinformatics pipeline and the visualized using the SNP & Variation Suite v8.x. Results: The bioanalyzer profiles of cfDNA derived from mCRPC patients is highly fragmented with an average fragment size of 306-605bp. Although, several CNVs were found across the genome, we focused analysis on CNVs related to AR associated and DNA repair genes. Our preliminary analysis of cfDNA, despite low sequencing depth, shows full or partial amplifications in AR (13/13), and other genes including FOXA1, NCOR1, NCOR2 and/or PIK3CA (7/13) and NCOR2 (10/13). For DNA repair genes partial/full amplifications were present in BRAC1, BRAC2, ATM, CDK12, MLH1 and/or MSH2 (7/13). Deletions are less reliably detected in the highly fragmented cfDNA. The majority of these CNVs have been reported in the WGS studies from metastatic CRPC tissue derived genomic DNA (cBioPortal). We are currently validating cfDNA genomic alterations by comparing it to germ line DNA derived via qPCR. Conclusions: Our preliminary study indicates that AR and DNA repair related genetic alterations could be found in the cfDNA derived from metastatic CRPC patients. This warrants more detailed examination of these cfDNA genetic alterations for identifying clinically relevant issues in mCRPC patients.
Association of changing prostate-specific antigen (PSA) levels on repeat testing with lower risk for Gleason Score (GS) ≥ 7 prostate cancer.
Authors: Nordström Tobias , Adolfsson Jan , Gronberg Henrik , Eklund Martin 
Published: February 2017

284 Background: PSA levels are often verified before recommending a prostate biopsy because of the variability of PSA, We used data from the STHLM3 trial to assess the value of a second PSA test taken prior to biopsy. Methods: STHLM3 is a prospective and population-based prostate cancer diagnostic study performed in Stockholm, Sweden, 2013-2015. 1686 men in STHLM3 with a PSA value 3-10 ng/ml performed a second PSA test within 8 weeks of the first test and then underwent prostate biopsy. We compared proportions of cancer detected in men with stable PSA levels (2nd PSA within +/-10% of 1stPSA) to men whose PSA levels increased or decreased at least 10%, respectively. Results: Men with GS ≥ 7 cancer in the biopsy had more stable PSA than men with benign biopsies; the median change was 13.7% (inter-quartile range (IQR) 6.1-26.9) in men with benign biopsies, 13.0% (IQR 6.1-25.6) in men with GS ≤ 6 tumors and 8.2% (IQR 4.5-16.7) in men with GS ≥ 7 tumors. The average risk of having GS ≥ 7 cancer was 15.4% (95% CI 13.7 – 17.1) after the first test (i.e. the entire cohort), 21.6% (95% CI 18.6 – 24.6) in men with stable PSA levels compared with 13.5% (95% CI 10.2 – 16.7) and 9.0% (95% CI 6.6 – 11.4) if PSA levels increased or decreased at least 10%, respectively. There were no significant differences in risk of GS ≤ 6 tumor for men with stable PSA compared to men with increasing/decreasing PSA. Conclusions: As previously shown, the risk of prostate cancer decreases if a repeat PSA test shows decreasing levels. We show that this effect mainly affect GS ≥ 7 tumors, and that the risk of prostate cancer also decreases with increasing PSA values. Our findings need validation, but suggest that PSA is more stable in men with GS ≥ 7 cancer, whereas elevated but fluctuating PSA levels to a higher degree are caused by other processes (e.g. inflammation). Use of decision tools could aid incorporation of complex information such as repeat PSA values in diagnostics.
Evaluation of response to enzalutamide (E) consecutively after disease progression on abiraterone/prednisone (AP) and potential predictors of response.
Authors: Emamekhoo Hamid , Elson Paul , Grivas Petros , Shomali William , Edwin Natasha Catherine , Rini Brian I. , Garcia Jorge A. 
Published: February 2017

294 Background: Efficacy data of E immediately after AP failure in castrate resistant prostate cancer (CRPC) is limited. Although clinical cross-resistant has been observed, the optimal sequence of these agents is not defined. Specific patient pt) characteristics on AP could be useful in selecting appropriate pts for subsequent therapy with E. Methods: We retrospectively reviewed records of 40 pts with CRPC treated at the Cleveland Clinic with E immediately after disease progression on AP. We evaluated clinical / pathological features that could predict subsequent response or lack thereof to E. For this exploratory analysis, best % change in PSA (%Ch-PSA) was used as indicator of treatment response. Results: Median age at E initiation was 69 (58-81), median time from diagnosis to AP initiation was 6.1 years (0.9-16.3). Median PSA was 30.9ng/mL (1.5-1680) at the time of AP initiation and 66.9ng/mL (2.52-3130) at E initiation. 30/40 and 35/40 pts had bone metastasis at AP and E initiation, respectively. Prior treatments to AP included Ketoconazole (45%), Docetaxel (35%). Median time to PSA progression on AP was 9.6 m (0.5-49.6) and 2.3 m (1.8-3.1) on subsequent E. 26/39 pts on AP achieved PSA decline >25%; among these 20 had >50% PSA decline. Similarly, 13 and 8 pts receiving subsequent E achieved >25% and >50% PSA decline, respectively. 10/40 pts did not have PSA response with either agent. 4 pts had PSA decline > 50% on both agents. There was no significant correlation between %Ch-PSA on E and %Ch-PSA on AP, pre-E PSA, time to PSA progression on AP, or time from diagnosis to AP. Longer interval between AP and E initiation was associated with better outcome on E (p=.03). Prior treatment to AP did not predict subsequent response to E. Conclusions: Except for the association between longer interval between AP and E initiation with PSA response on subsequent E, other clinicopathological factors did not predict response to consecutive E in this cohort of pts. Identifying clinical and/or molecular factors predictive of response to AP and E in this setting is of critical importance. Ongoing randomized prospective studies will help determine the optimal treatment sequencing in men with CRPC.
Interrogating metastatic prostate cancer treatment switch decisions.
Authors: Lorente David , Ravi Praful , Mehra Niven , Pezaro Carmel Jo , Omlin Aurelius Gabriel , Miranda Miguel , Payne Heather , Hall Emma , Terstappen Leon W M M , Ijzerman Maarten J , De Bono Johann S. 
Published: February 2017

296 Background: Increased availability of treatment options in CRPC requires improved biomarkers to optimize decision making for therapeutic sequencing. Despite evidence for the value of CTCs in assessing prognosis and response to treatment, their use in clinical practice is not widely implemented. Clinicians rely on PCWG2 criteria based on PSA, clinical and radiological criteria although these are only inconsistently used in clinical practice. We evaluated the trends for clinical decision-making by physicians treating CRPC. Methods: An online questionnaire was distributed to physicians treating PC from the UK, Switzerland and Australia. Questions on clinical practice, familiarity with progression criteria, use of CTCs and clinical-decision making were formulated. Results: 111 participants replied. Most (84.7%) were oncologists treating ≥ 50 patients per year (65.3%). Although only 39.6% usually used PCWG2 in clinical practice, 74.5% considered PSA, bone scans and CT to be useful for monitoring disease. 55.6% considered PSA to be an important biomarker. A minority were able to identify PSA (41.4%) and bone scan (39.4%) progression criteria by PCWG2. On average, more physicians discontinued cabazitaxel (28%) than docetaxel (10.4%) before cycle 4. Similar number of cycles were given to bone only disease compared to RECIST evaluable patients. Clinical progression was most important for switching treatment for most physicians (90.5%), followed by RECIST (71.6%), bone scan (47.7%), CTC (23.2%) and PSA (21.1%). The main challenge associated with the use of CTCs was the access to technology (84.7%). Most respondents (92%) would not stop therapy with rising PSA but falling CTC counts; most (88.8%) would not stop with declining PSA but rising CTCs. Although 50% acknowledged the prognostic value of CTCs, only 33% would use them to guide decision-making. Conclusions: A significant number of physicians discontinue treatment before 12 weeks. Most physicians rely on clinical progression for decision-making. Knowledge of PCWG2 response and progression criteria is generally suboptimal. Greater physician awareness, access to technology and further evidence and will be required for the implementation of CTCs as a routine biomarker in CRPC.
Regular aspirin use and the risk of lethal prostate cancer in the Physicians' Health Study.
Authors: Allard Christopher Brian , Downer Mary K , Preston Mark A , Gaziano J. Michael , Stampfer Meir J. , Mucci Lorelei A. , Batista Julie 
Published: February 2017

306 Background: Aspirin exerts chemopreventive effects against several malignancies. An inverse association between regular aspirin intake and advanced prostate cancer is suggested by previous reports, but potential effects on lethal prostate cancer have not been characterized. Methods: The study population comprised 22,071 male physicians enrolled in the prospective Physicians' Health Study followed from 1982-2009. We evaluated the relationship between regular aspirin intake ( > 3 tablets per week) and lethal prostate cancer (metastases or prostate cancer death). Secondary outcomes included the incidence of total, high-grade (Gleason 8-10), and advanced (T3b-T4 or N1 or M1) cancers. Cox proportional hazards models estimated age- and multivariate-adjusted hazard ratios (HR) for the incidence of primary and secondary outcomes and survival among participants with prostate cancer. Results: Over 27 years of follow-up (533,261 person-years), 3,183 men were diagnosed with prostate cancer, of whom 402 developed lethal disease. Decreased multivariate-adjusted risks of lethal prostate cancer were observed for regular aspirin users (HR: 0.67, 95%CI: 0.55-0.82). Recent regular use (within 12 months) was protective, with effects diminishing with time since last regular use (p for trend = 0.007). Among men with prostate cancer, regular aspirin use after diagnosis was associated with decreased prostate cancer mortality (HR: 0.79, 95%CI: 0.64-0.98), whereas pre-diagnostic use did not confer a measurable benefit. Regular aspirin use was not significantly associated with the incidence of total, high-grade, or advanced cancers. Conclusions: Regular aspirin use was associated with a decreased risk of lethal prostate cancer in this cohort of American physicians. An inhibitory effect of regular aspirin use on prostate cancer progression is suggested.