bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic utility of CCP score in men with prostate cancer after primary external beam radiation therapy.
Authors: Freedland Stephen J. , Gerber Leah , Reid Julia E. , Welbourn William , Tikishvili Eliso , Park Jimmy , Younus Adib , Gutin Alexander , Sangale Zaina , Lanchbury Jerry S. , Salama Joseph Kamel , Stone Steven 
Published: February 2017

47 Background: Accurate risk stratification improves decision making in localized prostate cancer. The CCP score, a prognostic RNA signature based on the average expression level of 31 cell cycle progression (CCP) genes, was developed to aid in this task. Previously, the CCP score was shown to be predictive of biochemical recurrence (BCR) after prostatectomy, and prostate cancer specific mortality in men undergoing observation. However, the value of CCP score in men undergoing primary electron beam radiation therapy (EBRT) was untested. Methods: The CCP score was derived retrospectively from the diagnostic biopsy of 141 patients treated with EBRT at the Durham VA medical Center. Inclusion criteria were disease diagnosis from 1991 to 2006 and available biopsy tissue. Approximately half of the cohort was African-American. Outcome was time from EBRT to BCR using Phoenix definition, and median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by CoxPH survival analysis and likelihood ratio tests. Results: Patient data were censored at 5-years of follow-up and 19 patients (13%) had BCR. The median CCP score was 0.12(IQR -0.43 to 0.66). In univariable analysis, CCP score was a significant prognostic variable (p-value = 0.0017). The hazard ratio (HR) for BCR was 2.55 (95% CI (1.43, 4.55)) for a one-unit increase in CCP score (equivalent to a doubling of gene expression). In a predefined multivariable analysis that included Gleason score, PSA, and percent positive cores, the HR for CCP changed only marginally and remained significant (HR per CCP unit 2.09 (95% CI (1.05, 4.18), p-value = 0.035), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. Further adjustment for hormonal therapy or radiation dose did not materially alter this association. The score was also associated with prostate cancer specific mortality. There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: In a cohort of men treated with EBRT, the CCP score was significantly associated with outcome and provided prognostic information beyond what was available from clinical parameters. If validated in a larger cohort, CCP score could be used to select high-risk men undergoing EBRT who may need combination therapy for their clinically localized prostate cancer.
Sarcomatoid renal cell carcinoma (SRCC): University of Nebraska Medical Center experience.
Authors: Tandra Pavankumar , Wang Jue , Loberiza Fausto R. , Hemstreet George P. , Krishnamurthy Jairam , Bhatt Vijaya Raj 
Published: February 2017

472 Background: Sarcomatoid differentiation is not a distinct histological entity and it can present in any of the subtypes of renal cell carcinoma (RCC). Although many studies were published in the literature about its aggressive clinical course, limited clinical data was available about its management and especially about the role of newer targeted therapies. At our institution, we looked at the prognostic factors in SRCC and the role of systemic therapy in its management. Methods: During the years of 1997 to 2012, we studied the records of over 400 patients diagnosed with RCC. Out of them, 43 were identified as having SRCC. Cox proportional hazards risk analysis was used to analyze the factors associated with the risk of mortality. Survival probability was estimated using Kaplan Meier method. Results: Median age at diagnosis was 58. Median tumor size was 9.75 cm. High Furhmans grades (III & IV) were seen in 67.44%. 68.29% patients presented with stage IV disease. 74.42 % patients had upfront nephrectomy. Of the systemic therapies given, 20.9% received cytokines, 16.2% received chemotherapy and 34.8% received target therapy. Probability of survival at 1 year was 50% (95% CI 33-65) and at 5 years was 24% (95% CI 10-41). Median time to progression was 13 months (95% CI 7 -23). Factors associated with risk of mortality were mainly the stage at diagnosis [HR 2.174, p = 0.0123, CI (1.184-3.992)], Nephrectomy [HR0.243, p = 0.0012, CI (0.104- 0.571)] and the use of target therapy [HR 0.313, p = 0.0070, CI (0.134-0.728)]. Conclusions: Our study confirmed that the SRCC is more aggressive than conventional RCC in its presentation and in its median time to progression. It responds poorly and unpredictably to systemic therapies. In our study, upfront nephrectomy and target therapy appeared to be independent predictors of survival. SRCC needs to be considered as a different disease entity and new treatment options need to be explored for this unfortunate subset of patients with kidney cancer.
Mortality following hip fractures in men with prostate cancer.
Authors: Van Hemelrijck Mieke , Garmo Hans , Michaelsson Karl , Thorstenson Andreas , Stattin Pär , Akre Olof , Holmberg Lars , Adolfsson Jan 
Published: February 2017

49 Background: Rapid loss of bone-mineral density is a known side-effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). Hip fractures are also independently associated with risk of mortality. To our knowledge few population-based observational studies have yet investigated the risk of dying following fractures among men with PCa. We aimed to assess skeletal-related events and mortality in more detail by specifically studying the link between hip fractures in PCa men and risk of death. Methods: PCBaSe Sweden 2.0 is based on the National Prostate Cancer Register and contains age and county matched men free of PCa. We selected all men (n=14,205) who had been hospitalized with a hip fracture, as registered in the National Patient Register, between 2006 and 2010. A total of 2300 were diagnosed with PCa before the hip fracture and 66% of them were treated with ADT. The main outcome was death as registered in the National Cause of Death Register. The risk of death was estimated using multivariate Cox Proportional Hazards regression analyses and standardized mortality ratios (SMRs) taking into account PCa risk category, history of fractures, civil status, Charlson Comorbidity Index, and treatment with bisphosphonates. Results: In the analysis for risk of death >90 days after a hip fracture, there was an increased risk of death among PCa men on ADT, especially those aged <84 years (e.g., HR at 3-6 months after hip fracture: 2.47 (95%CI: 1.85-3.30) compared to men free of PCa with a hip fracture). The SMRs showed that PCa men on ADT who got a hip fracture were seven times more likely to die than expected in the reference population of all men with PCa, whereas PCa men who were not on ADT and had a hip fracture were 13 times more likely to die than expected in this reference population. However, the absolute risk difference between men with and without a hip fracture was 30 per 1,000 person-years when evaluating the effect of a hip fracturing among men on ADT, whereas a hip fracture would cause an additional 20 per 1,000 person-years to die among PCa men without ADT as well as among men free of PCa. Conclusions: Our SMRs and absolute risk calculations show that hip fractures are more dangerous in PCa men treated with ADT than in PCa men without ADT or in men free of PCa.
Nomograms to predict late urinary toxicity after prostate cancer radiotherapy.
Authors: Mathieu Romain , Ospina Arango Juan David , Beckendorf Veronique , Delobel Jean Bernard , Messai Taha , Bossi Alberto , Le Prise Elisabeth , Guerif Stephane , Simon Jean-Marc , Dubray Bernard M. , Zhu Jian , Lagrange Jean-Leon , Pommier Pascal , Gnep Khemara , Acosta Oscar , de Crevoisier Renaud 
Published: February 2017

53 Background: Tools are needed to predict toxicity after prostate cancer treatment. The objective of the study was to analyze late urinary toxicity after prostate cancer radiotherapy (RT) by symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms. Methods: 965 patient received a median total dose of 70 Gy (range, 65-80 Gy) for localized prostate cancer, using different fractionations (2 or 2.5 Gy/day) and RT techniques. Medical history was recorded. Late urinary toxicity was assessed, prospectively in half of the patients, using the CTCAE v3 classification: urinary frequency, incontinence, bleeding and retention (dysuria). Patients or treatment related predictors of late urinary toxicity (> grade 2) were identified by Univariate and multivariate Cox regression models. Nomograms were built up and their performance were assessed. Results: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, urinary retention and urinary incontinence rates were: 15%, 10%, 5%, 3% and 1%, respectively. The 5-year (≥ grade 3) urinary toxicity rate was 3%. The following parameters significantly increased the 5 year risk of global urinary toxicity (≥ grade 2): anticoagulant treatment (RR=2.35), total dose (RR=1.09), age (RR=1.06), bladder D25 (RR=1.03) and maximum dose (RR=1.1). Urinary frequency was increased by the total dose (RR=1.07) and diabetes (RR=4). Hematuria was increased by anticoagulant treatment (RR=2.9). Urinary retention (dysuria) was increased by the total dose (RR=1.1). Corresponding nomograms and their calibration plots were generated. Conclusions: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.
Multidisciplinary care and management of very low-risk prostate cancer.
Authors: Aizer Ayal A. , Paly Jonathan J. , Zietman Anthony L. , Nguyen Paul Linh , Beard Clair , Rao Sandhya K. , Kaplan Irving D. , Niemierko Andrzej , Hirsch Michelle S. , Wu Chin-Lee , Olumi Aria F. , Michaelson M. Dror , D'Amico Anthony Victor , Efstathiou Jason Alexander 
Published: February 2017

55 Background: The National Comprehensive Cancer Network (NCCN) recommends active surveillance (AS) as the primary management option for patients with very low-risk prostate cancer (VLRPC) and an expected survival of <20 years. Factors associated with selection of AS are therefore of clinical importance. We hypothesized that care at a multidisciplinary clinic (MC), where multiple physicians simultaneously review each case, will be associated with increased rates of AS in men with VLRPC, including those with limited life expectancy. Methods: Of 630 patients with low-risk prostate cancer managed at one of three tertiary care centers in Boston, MA in 2009, 274 (43.5%) had VLRPC. Patients were either seen by one or more individual providers in sequential visits (N=178) or at an MC (N=96), in which concurrent consultation with two or more of the following specialties was obtained: urology, medical oncology, and radiation oncology. Results: Patients seen at an MC were more likely to select AS than those seen by individual providers (64% vs 30%, p<.001), an association which remained significant on multivariable logistic regression (OR=4.16, p<.001), see Table. When the analysis was limited to patients with an expected survival of <20 years based on the 2007 Social Security Life Table, this association remained highly significant (OR=5.19, p<.001). Conclusions: Multidisciplinary care is strongly associated with selection of AS, adherence to NCCN guidelines, and minimization of over-treatment in patients with VLRPC. [Table: see text]
Evaluation of PTEN status in circulating tumor cells (CTCs) and matched tumor tissue from patients with castrate-resistant prostate cancer (CRPC).
Authors: Punnoose Elizabeth , Tucker Eric , Marrinucci Dena , Amler Lukas C. , Koeppen Hartmut , Patel Premal H. , Yan Yibing , Riisnaes Ruth , Attard Gerhardt , De Bono Johann Sebastian 
Published: February 2017

62 Background: PTEN loss occurs frequently in prostate cancer and may trigger progression to CRPC through activation of the PI3K/AKT pathway. A blood-based assay that determines PTEN status in CRPC patients could enable informed treatment decisions such as the use of a PI3K-targeted therapy. We evaluated PTEN status in archived tissue, metastatic bone biopsies, and CTCs from CRPC patients. Here we report the results of PTEN evaluation in CTCs from 42 CRPC patients and matched tissue from 6 patients with more underway. Methods: Nucleated cells from CRPC patient blood were plated onto glass slides and subjected to IF staining and CTC identification by high-speed fluorescent scanners at Epic Sciences. CTCs were identified as CK+/CD45- cells with intact DAPI nuclei, and samples with ≥5 CTCs per 2 slides (74%) were then tested for PTEN by FISH. Partial loss was defined as a decrease in PTEN copies (PTEN < CEP10) and total loss as zero PTEN copies. PTEN IHC in tissue was stained using CST clone 138G6 and H-scores ≤ 200 counted as loss. Results: Partial or total loss of PTEN by FISH was observed in 15 of 31 patients (48%) by CTC analysis. Changes in ploidy were frequently observed and broad heterogeneity seen both within and between patients. Weighted across patients, the most frequently observed abnormal genotypes in CTCs were 2 CEP10/0 PTEN (total loss, diploid, 5.8%), 3 CEP10/0 PTEN (total loss, triploid, 4.5%), and 3 CEP10/3 PTEN (PTEN-normal, triploid, 4.2%). These genotypes were not observed in over 1,000 white blood cells evaluated evenly across 31 patients, demonstrating that cells identified as CTCs on the Epic platform show malignant features not observed in normal cells. PTEN loss was detected by IHC in 6 of 8 (75%) archived patient samples and 7 of 8 (87%) of matched bone biopsies. Where CTCs were available (6 cases), PTEN status was correctly determined as lost in 4 cases, normal in 1 case and borderline in one case. Conclusions: Our results illustrate the high percentage of PTEN loss in CRPC patients and the potential for using CTCs as a non-invasive, real-time biopsy to determine a patient’s PTEN status. PTEN status will be determined using these assays in an upcoming AKT inhibitor Phase II trial.
Sentinel lymph node in prostate carcinoma: Methodology, feasibility, surgical, and oncological consequences: A prospective study about 93 patients.
Authors: Soler Claude , Perraud Yves , Gremillet Eric , Armand Corine , Geissler Benjamin , Steiner Aline , Levigne Frederic 
Published: February 2017

69 Background: There are few studies in the field of prostatic sentinel lymph node (SLN) procedure: in the literature at the most 10 publications are found. However the interest of urological surgeons is growing fast. We want to evaluate the rate of SLN SPECT-CT detection, the rate of SLN involvement, and the incidence of the SLN biopsy on the surgical and oncological management of patients. Methods: 93 patients with prostate cancer were included (gleason 6-9). All patients were elected for a radical laparoscopic prostatectomy. Nanocis* was intratumorally injected, guided by transrectal ultrosonography. 2 injections 0.6 ml in each lobe of the prostate were performed. Patient underwent planar imaging and SPECT-CT 2 hours after injections. Surgery was performed 18 hours after. Results: A lymphatic pelvic drainage was seen in 95,6 % (89/93) by SPECT-CT (external or internal iliac arteries areas). For 27 patients lymphatic drainage was on the right side, for 24 patients it was on the left side, for the 37 remaining patients migration was bilateral. The radioguided lymphadenectomy was assisted by a laparoscopic gamma-probe (Clerad, France), the SLN detection rate was 97.7% (87/89); the average number of resected radioactive nodes was 1.6 (range 1 to 5). By all the ways, a limited pelvic lymph node dissection was performed (including external iliac to common iliac arteries areas) in all 93 cases. An SLN involvement was found in 6 cases (5/87= 5.75%); in these 6 cases and in the 81 cases without SLN involvement, no metastatic involvement was found in the other lymph nodes, as well as in the 6 patients for which no SLN could be selectively resected (4 with no drainage seen and 2 not detected intra-operatively although visualized on lymphoscintigraphy). Conclusions: The low rate of lymphatic involvement is not surprising considering the Gleason score range 6 to 9 (low metastatic risk). So, the preliminary results are very attractive, especially for these patients that could have been falsely considered as N0. Our study is still in progress, and if these results are confirmed on a larger scale, then SLN procedure could be considered in the routine management of low risk prostatic carcinomas.
ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).
Authors: Smith Matthew Raymond , Antonarakis Emmanuel S. , Ryan Charles J. , Berry William R. , Shore Neal , Liu Glenn , Alumkal Joshi J. , Higano Celestia S. , Maneval Edna Chow , Rathkopf Dana E. 
Published: February 2017

7 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here. Methods: All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks. Results: Forty-seven patients were enrolled between November 2011 and May 2012. The median age was 71 years (range 51 to 88) and at baseline, patients presented with ECOG performance status 0 (77%), Gleason Score 8-10 (32%), and median PSA of 10.7 ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 20 weeks, three patients discontinued the study. The most common treatment-related adverse events (AE) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). The incidence of Grade 3 AEs was 6.4%, and no seizures have been observed to date. The 12-week PSA response was 91% and the time to PSA progression has not been reached. Conclusions: In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates. Clinical trial information: NCT01171898.
Population-based impact on overall survival (OS) after the introduction of docetaxel as standard therapy for metastatic castration resistant prostate cancer (CRPC).
Authors: Zielinski Robert Richard , Tyldesley Scott , Chi Kim N. 
Published: February 2017

77 Background: Docetaxel (DOC) was the first systemic therapy to improve OS (Hazard Ratio (HR) = 0.79) for patients (pts) with CRPC and a standard therapy since 2004. Because of the potential for severe toxicity with DOC, its use has been subject to pt selection. Even with this selective use, we sought to determine whether the introduction of docetaxel has improved OS at a population level. Methods: We performed aretrospective review of all CRPC pts treated with palliative radiotherapy (PRT) to bone metastases in the province of British Columbia, Canada. The pre-docetaxel cohort (pre-D) received PRT from 1998-2001. The docetaxel-era cohort (post-D)received PRT from 2006-2009. Time of first PRT to bone was used to select pts at a similar point in their disease state (i.e., onset of bone pain). Mortality and cause of death was attained from public registries. OS was calculated from time of first PRT using the Kaplan-Meier method and compared using the log-rank test. Results: Comparative baseline characteristics for the 1876 patients split into the pre-D (n=919) and post-D (n=957) eras were: metastatic at diagnosis 30% vs. 33% (p = 0.09), median age at PRT 75.5 vs. 76.7 years (p=0.04), time from diagnosis to PRT 3.9 vs. 3.1 years (p = 0.31), received DOC 7% vs. 37% (p < 0.0001). Median OS from time of first PRT was 7.5 months (m) vs. 10.3 m (HR: 0.79, 95% Confidence Interval 0.70 – 0.89, p < 0.0001) in the pre-D and post-D cohorts respectively. Within the post-D cohort, the median OS from time of RT was longer in pts receiving DOC at 13.9 m vs. 7.4 m for pts not receiving DOC (p=0.004). Conclusions: In this population based analysis, the introduction of DOC as a standard of care was associated with a significant improvement in OS even though DOC penetrance was <50%. This demonstrates for the first time the generalizability of the TAX-327 study results to the population at large. Even as the therapeutic landscape for CRPC evolves with the introduction of new agents that improve OS with favourable toxicity profiles, these data support the continued use of DOC in appropriately selected patients.
Sequencing of cabazitaxel and abiraterone acetate following docetaxel in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Schnadig Ian D. , Bhor Menaka , Vogelzang Nicholas J. , Hennessy Daniel , Nicacio Leonardo V. , Berry William R. , Hutson Thomas E. , Fleming Mark T. , Cowey C. Lance , Saravanan Shanmugapriya , Dhanda Rahul , Sonpavde Guru 
Published: February 2017

79 Background: Following docetaxel (D), treatment options for mCRPC include cabazitaxel (CBZ), abiraterone acetate (AA), and enzalutamide. With the introduction of new agents, optimal sequencing is undefined. We evaluated the prevalence of sequencing of AA and CBZ following D in a large community-based cohort to develop a hypothesis for the most optimal sequence. Methods: A retrospective analysis of treatment patterns using the MSH iKnowMed EHR was conducted. Post-D mCRPC patients receiving CBZ and/or AA at full EHR sites with ≥2 visits were included; clinical trial patients excluded. CBZ utilization between Jun’10 and May’12 and sequencing of CBZ or/and AA from Apr’11 and May’12 (when both drugs were available) were examined. OS, time to treatment failure (TTF), and demographics analyses are ongoing. Results: 667 evaluable patients were identified. Overall CBZ (n=359 pts/2 y) utilization declined between Jun’10-May’11 (n=232) and Jun’11-May’12 (n=127). From Apr’11 to May’12: overall AA (n=465 pts/y) utilization increased between Mar-May’11 (n=73) to Jun-Aug’11 (n=164) and subsequently decreased (n=57) from Mar-May’12. Between Apr’11-May’12, 130 patients received both CBZ and AA. More men (P<0.001) received D→CBZ→AA (n=88, 67.7%) compared with D→AA→CBZ (n=42, 32.3%). Median age of patients receiving both CBZ and AA was 67 (44-89) y and their median baseline PSA (111 evaluable) was 84.3 (0.4-7672.2) ng/mL. Conclusions: AA was administered more frequently than CBZ in post-D mCRPC patients. However, the sequence of D→CBZ→AA was more prevalent than D→AA→CBZ in this large community-based cohort. Until predictive biomarkers and outcomes with respective sequences are identified, delivery of all active agents according to patient-specific clinical factors should probably be considered. [Table: see text]