bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of time to metastasis on survival in treatment-naïve prostate cancer patients.
Authors: Akamatsu Shusuke , Lynch Kenny , Black Peter , Gleave Martin , Goldenberg Larry , Chi Kim N. , So Alan 
Published: February 2017

212 Background: With the emergence of novel therapies, the treatment of advanced prostate cancer has evolved. However, patients eventually succumb to their metastatic disease. Nonetheless, little is known about the impact of time to metastasis on survival. To further expand on this, we separated metastatic prostate cancer patients into three groups according to the timing of metastasis and analyzed their survival. Methods: From 2008 to 2013, 157 CRPC patients were identified in our database. Of those, 92 with metastasis and sufficient data were analysed. The patients were classified into three groups according to the timing of metastasis. There were 35 de novo –M (metastasis within three months of initial diagnosis), 26 CSPC-M (initially metastasis free, metastasis found more than 6 months prior to CRPC), and 31 CRPC-M (metastasis found within 6 months of becoming CRPC, or after becoming CRPC). Patient characteristics were analyzed, and survival was calculated. Results: Median follow up were 2.2, 9.6, and 11.8 years for de novo-M, CSPC-M, and CRPC-M. 85 and 84 % in the CSPC-M and CRPC-M respectively had local therapies by surgery and/or radiation. The types of local therapies were similar between the groups. Mean time to PSA recurrence after intial therapy were 3.5 and 2.2 years for CSPC-M and CRPC-M, and median time to metastasis were 4.4 and 11.4 years respectively. Treatments after CRPC included Abiraterone, Enzalutamide, and Docetaxel, and the use of these agents were similar between the groups. Median time to CRPC were 1.4, 6.2, and 8.6 years, and median overall survival after diagnosis were 3.7, 12.3, and 15.8 years for de novo-M, CSPC-M, and CRPC-M. Conclusions: The overall survival and time to CRPC were significantly shorter in de novo-M. Although there was a marked difference in time to metastasis between CSPC-M and CRPC-M, there was no statistically significant difference in overall survival. Either treated with hormone therapy before or after emergence of metastasis, survival of more than 10 years after initial diagnosis is possible.
Metabolic syndrome in castration-resistant prostate cancer patients treated with abiraterone.
Authors: Conteduca Vincenza , Caffo Orazio , Derosa Lisa , Veccia Antonello , Petracci Elisabetta , Chiuri Vincenzo Emanuele , Santoni Matteo , Santini Daniele , Fratino Lucia , Maines Francesca , Testoni Sara , De Giorgi Ugo 
Published: February 2017

213 Background: The presence and the impact of metabolic syndrome (MS) in castration-resistant prostate cancer (CRPC) men treated with novel hormonal therapies, as abiraterone, has not still been studied. The study aims to assess the impact of MS on progression free survival (PFS) and overall survival (OS) from time starting abiraterone. Methods: We retrospectively evaluated a consecutive series of metastatic CRPC patients treated with abiraterone after docetaxel failure. MS, as defined by modified Adult Treatment Panel (ATP) III criteria, was assessed at the time of initiation of abiraterone, during treatment and follow-up. Cox regression model was used to evaluate the role of MS on the two end-points. Results: One hundred seventy eight patients had sufficient data to assess the presence of MS. Mean age (± SD) at start of abiraterone was 74.0 ± 7.7 years. Seventy out of 178 patients (39.5%) met MS criteria at baseline, before abiraterone initiation, whereas for eleven patients this occurred during treatment. Median PFS was equal to 5 months for patients with MS versus 9 months for those without MS. Patients with MS had a 2-fold increased risk of progression or death for all causes than patients without MS (HR=1.9, 95% CI [1.3-2.7], P<0.001). Median OS was 16 months and 22 months in patients with and without MS, respectively. After adjusting for covariates, MS resulted not significantly associated to OS (HR=1.2, 95% CI [0.8-1.9], P=0.340). Conclusions: MS may represent a complication of patients treated with abiraterone. The presence of MS appears to be a risk factor for shorter PFS in patients with CRPC treated with abiraterone, even if it does not show any impact on OS, so it needs a further prospective evaluation.
A multidisciplinary clinic to mitigate the impact of androgen deprivation therapy in prostate cancer: A pilot study.
Authors: Aggarwal Rahul Raj , Rodvelt Tammy J. , Rabow Michael W. , Macaire Greta , Fedric Regan , Cortese-Jimenez Geronima , Small Eric Jay 
Published: February 2017

218 Background: Androgen deprivation therapy (ADT) increases the risk of numerous metabolic toxicities, including weight and body fat gain, insulin resistance, and osteoporosis. Many of these toxicities can be mitigated with lifestyle changes and monitoring of cardiovascular and diabetes risk factors, however, these are not routinely implemented in clinical practice. We designed a pilot study to evaluate whether a structured multidisciplinary (multi-D) clinic can lessen the metabolic impact of ADT. Methods: Patients who started ADT within the past 6 months were enrolled in the year-long multi-D clinic consisting of monthly face-to-face visits and individualized counseling from registered dietitian, certified exercise physiologist, and symptom management specialist, and assessment of weight, body mass index, percent body fat, fasting glucose, lipids, and hemoglobin A1c on an every 3 month schedule. The primary endpoint for this pilot study was the patient adherence rate to the clinic visit schedule, with a targeted goal of greater than 80%. Secondary endpoints included maximal percent change from baseline in metabolic parameters as outlined above. Results: 22 patients were enrolled between November 2013 and May 2014. Participation in the multi-D clinic was high, with a 95% adherence rate to the clinic schedule. The mean maximal percent change from baseline in metabolic parameters is shown below in the Table. Conclusions: Conducting a multi-D clinic for men receiving ADT was feasible, with an adherence rate of over 90%. The metabolic impact of ADT during the 12-month clinic participation was minimal and compares favorably to historical controls, but may be due to selection bias. A randomized phase 2 study comparing multi-D clinic to usual standard of care is ongoing to validate these findings. [Table: see text]
Androgen deprivation therapy (ADT) and cardiovascular (CV) risk: Analysis of German Statutory Health Insurance (SHI) data.
Authors: Ruessel Christoph , Guthoff-Hagen Susanne , Donatz Verena 
Published: February 2017

219 Background: ADT is an established part of the guideline-oriented therapy of prostate cancer (PCa). Concerns regarding increased CV risks associated with ADT were raised by the FDA in 2010. Results from a pooled data-analysis of six prospective randomised trials suggest a lower number of CVevents in patients treated with the GnRH antagonist Degarelix compared with GnRH agonist treated patients with preexisting cardiovascular disease [Albertsen P. et al: Eur Urol 2014; 65: 565-73]. Objective: Can SHI data confirm the observation that the risk for CVevents varies depending on the substance used for ADT. Methods: Retrospective data sets of 4 Mio assured people from SHI funds from the years 2009-2012 were analysed to identify PCa patients treated with ADT, GnRH agonists and GnRH antagonists, respectively. An age-adjusted reference group with 1.1 Mio non-PCa persons was identified in the data sets. Results: 44.166 patients suffering from PCa were identified. Of those 10.611 patients were treated with ADT. 10.554 with GnRH agonists and 132 with GnRH antagonists, respectively. An increased prevalence for relevant baseline CV diseases was observed in ADT treated patients compared to the Non-PCa reference group (diabetes mellitus: 28.66% vs 17.43%.; CAD: 35.77% vs 15.70%; Heart failure: 27.54% vs 9.64%). The rate of heart attack and stroke (CVevents) after treatment begin with ADT was determined: 2.37% in the reference group, 5.9% in the PCa group, 7.8% in the ADT group, 2.3% in the GnRH antagonist group. All CVevents in GnRH antagonist group occurred in high risk patients, only. The urologist examined and reported the state of CV risk for 25% of the PCa patients, only. Urologists examine and treat statistically significantly more patients with a combination of PCa and CVevents than general practitioners (30 vs. 5 per year/per physician). Conclusions: This retrospective analysis confirms the hypothesis that the risk of CVevents varies by using different ADT. The risk might be lower by using GnRH antagonists. A close collaboration of urologists, general practitioners and cardiologists is therefore recommended in the management of PCa patients.
Patient-reported gastrointestinal and genitourinary toxicity after prostate cancer treatment: A comparison between radiotherapy including pelvic nodes and prostate-only radiotherapy.
Authors: Fransson Per , Olofsson Sebastian , Widmark Anders , Thellenberg Karlsson Camilla 
Published: February 2017

22 Background: To evaluate side effects of radiotherapy (RT) including the pelvic nodes in patients with prostate cancer. Methods: 143 patients with high risk prostate cancer (Pca) receiving whole pelvic radiotherapy (WPRT) was matched to a group of 142 patients receiving RT towards the prostate and seminal vesicles only (PORT). Both groups were given 78 Gy towards the prostate and 50 Gy towards the seminal vesicles. The WPRT group also received 50 Gy towards the pelvic nodes. WPRT was given with intensity modulated RT or volumetric modulated arc therapy technique and the group treated towards the prostate and seminal vesicles only was treated with 3-dimensional conformal RT. Gastrointestinal (GI) and genitourinary (GU) side effects were evaluated with patient-reported questionnaires and with the RTOG scale, scored by treating physician, at baseline and one-year after RT. Results: Overall the side effects were mild. At one-year follow up there were significant differences regarding morning urgency, mucus- and blood in stool between the two groups (Table 1). The WPRT group expressed lesser complications in all of these cases. In the RTOG GU and GI scores there were no differences between the groups. About 20% had RTOG grade 2 GU score and 2%/1% had RTOG grade 3 score in the PORT and WPRT groups, respectively. The numbers for RTOG grade 2 GI scores were 11% and 5% in the PORT and WPRT groups, respectively. None of the groups reported RTOG grade 3 GI symptoms. Conclusions: Whole pelvic RT can be done with a very satisfying profile of side effects. Sometimes even lesser gastrointestinal reported side effects are seen with the newer techniques compared to prostate only radiotherapy with older techniques. [Table: see text]
Association of baseline perineural invasion with shorter time to progression in men with prostate cancer undergoing active surveillance: Results from the REDEEM study.
Authors: Moreira Daniel M. , Fleshner Neil Eric , Freedland Stephen J. 
Published: February 2017

23 Background: Perineural invasion (PNI) on prostate cancer (PC) biopsies has been associated with disease upgrading among those undergoing radical prostatectomy. However, the clinical significance of PNI in men on active surveillance (AS) has been evaluated by a limited number of studies. Thus, we sought to evaluate the association of PNI with time to clinical and pathological progression in men with PC on AS. Methods: Retrospective analysis of 289 men 48 to 82 years old on AS for low-risk PC (T1c-T2a), Gleason ≤6, ≤3 positive cores, ≤50% of any core involved, prostate-specific antigen (PSA) ≤11ng/ml, life expectancy >5 years and follow-up data in the REduction by Dutasteride of clinical progression Events in Expectant Management study. Progression was divided in pathological (>3 positive cores, >50% core involvement or Gleason >6 in a repeat biopsy) or therapeutic (any treatment for PC) or both. Time to progression was analyzed with Kaplan-Meier plots, log-rank tests and Cox model adjusting for age, PSA density, percent cores involved, maximum core involvement and treatment. Results: A total of 11 (4%) patients had PNI on baseline biopsy. PNI was associated with higher tumor length and maximum core involvement (all P<0.05). PNI was not associated with patient’s age, race, PSA levels or density, percent or number of positive cores. After a median follow-up of 37 months, 125 (43%) patients developed progression. Of these, 95 (76%) patients had pathological and 30 (24%) had therapeutic progression. In univariable analysis, patients with baseline PNI had a shorter time to overall and pathological progression (HR=2.62, 95%CI=1.31-5.23, P=0.006 and HR=2.42, 95%CI=1.03-5.66, P=0.041, respectively). Similar results were obtained in multivariable analysis for overall and pathological progression (HR=2.26, 95%CI=1.10-4.68, P=0.028 and HR=2.13, 95%CI=0.88-5.13, P=0.092, respectively). Conclusions: Among patients with PC on AS, PNI is independently associated with shorter time to progression. Thus, PNI may be used to help select patients for AS and stratify them according to the risk of disease progression.
Correlation of baseline serum testosterone (T) and serum prostate-specific antigen (PSA) at 7 months (7 mo PSA) in patients (pts) with new hormone sensitive metastatic prostate cancer (mHSPC) treated with continuous androgen deprivation therapy (cADT).
Authors: Buckley Tyler Howard , Patel Shiven B. , Tantravahi Srinivas Kiran , Batten Julia A. , Stenehjem David D. , Alex Anitha , Agarwal Neeraj 
Published: February 2017

231 Background: Based on data from > 1,000 men with new mHSPC undergoing ADT in the SWOG-9346 study, a failure to achieve a 7 mo PSA of ≤4 ng/mL, is a powerful negative predictor of survival (Hussain et al., JCO 2006). Following baseline clinical variables predicted lack of achieving 7 mo PSA ≤ 4.0 ng/mL: increased age, PSA, and bone pain, poor performance status, and Gleason sum ≥ 8. We hypothesized that the baseline serum T is also an independent predictor of 7 mo PSA. Methods: Eligible pts were identified from an institutional database. The association of baseline clinical and disease characteristics with 7 mo PSA were analyzed using multivariate regression model (Table). Results: 54 pts were eligible for inclusion. 44% achieved undetectable 7 mo PSA, and 25% had a 7 mo PSA ≥ 4 ng/mL suggesting a representative population, similar to that in the SWOG-9346 study. Significant association between covariates and 7 mo PSA was observed (Prob > F = 0.0107; R2 = 0.404). Baseline serum T and PSA were independent predictors of 7 mo PSA. Baseline serum T, as a continuous variable, showed negative correlation with 7 mo PSA, while baseline PSA showed a positive correlation (Table). Conclusions: Baseline serum T independently predicts 7 mo PSA. Pts with new mHSPC with lower baseline T may have improved outcomes with deeper androgen blockade with ADT along with a 17,20-lyase and 17-alpha-hydroxylase inhibitor or a second generation androgen receptor inhibitor at the time of induction. Data need further validation in a larger cohort. [Table: see text]
Cabozantinib (C) plus docetaxel (D) and prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Karzai Fatima , Madan Ravi Amrit , Theoret Marc Robert , Arlen Philip M. , Dawson Nancy Ann , Rosner Inger L. , McLeod David G. , Wright John Joseph , Cordes Lisa M , Couvillon Anna , Chun Guinevere , Harold Nancy , Steinberg Seth M. , Trepel Jane B. , Price Douglas K. , Gulley James L. , Figg William Douglas , Dahut William L. 
Published: February 2017

235 Background: Docetaxel (D) improves overall survival in metastatic castrate-resistant prostate cancer (mCRPC), but benefits remain short-lived. Clinical data suggests patients (pts) with mCRPC treated with anti-androgen therapy like abiraterone (AA) or enzalutamide (ENZA) have decreased responses to subsequent therapy due to cross-resistance in the androgen pathway targeted by D, AA, or ENZA(van Soest et al, Eur J Cancer 49:18, 2013). Combining D with other agents, like cabozantinib (C), could target different cellular signaling pathways potentially minimizing tumor resistance. Methods: D naive pts receive 75 mg/m2 IV on day 1 of a 21 day cycle, and prednisone (P) 5 mg po q12 hours with C at 3 dose levels: 20, 40, or 60 mg po daily until maximum tolerated dose (MTD) is defined. In phase 2, pts who have progressed on AA or ENZA, enroll on a randomized 2 arm cohort comparing D plus C to D alone. Results: 20 pts have been accrued; 4 at 20 mg C, 8 at 40 mg C, and 7 at 60 mg C. On phase 2, 1 pt is randomized to D alone. Median age is 68 (44-84 yrs). Median baseline PSA is 94.7 (0.01-754.1 ng/mL). Gleason score is 9 (7-10). Median cycles is 9.5 (1-33). 8 pts have bone only disease, 12 pts have bone and soft tissue disease. Common grade 2 and grade 3 adverse events possibly related to C: hand/foot syndrome (4/16), oral mucositis (4/16), hypophosphatemia (4/16), and fatigue (3/16). The MTD of C is 40 mg daily with D. 15 pts were previously treated with AA or ENZA. In 13 patients previously treated with AA, median PFS has not been reached, with a median potential follow up of 12.4 months. Six month PFS is 77.8% and 9 month PFS is 60.5%. Conclusions: D plus P may have limited benefits after disease progression on AA as seen in 3 retrospective analyses demonstrating a median PFS survival of 4.6 months or less (Mezynski J, et al. Ann Oncol 23;11, 2012) (Aggarwal R, et al. Clin Genitourin Cancer 12;5, 2014) (Schweizer MT, et al. Eur Urol 66;4, 2014). PFS results seen in this trial compare favorably to previously published data of treatment with D after AA in mCRPC, suggesting the addition of C to D may help overcome acquired resistance. Further randomized trials will determine if C in combination with D will enhance clinical outcomes. Clinical trial information: NCT01683994.
A novel biomarker signature to predict aggressive disease in African-American men with prostate cancer.
Authors: Yamoah Kosj , Johnson Michael Hiroshi , Choeurng Voleak , Yousefi Kasra , Haddad Zaid , Den Robert Benjamin , Lal Priti , Feldman Michael D , Dicker Adam , Klein Eric A. , Davicioni Elai , Rebbeck Timothy R. , Schaeffer Edward M. 
Published: February 2017

24 Background: Numerous studies have reported a significantly higher incidence of PCa and/or adverse pathological features associated with African-American men compared to European-American men. Less however is known about the genomic disparities that exist between these two groups. In this report we compared the race-specific expression of biomarkers linked to PCa pathogenesis in a matched cohort of AA and EA men. Methods: PCa data from AA and EA patients were analyzed from four medical centers. Cases were matched based on CAPRA-S within each institution for a total sample size of 300 (121-AA; 179-EA). The distribution of mRNA expression levels of 20 validated biomarkers associated with PCa initiation and progression was compared by race using a false-discovery-rate adjusted Mann-Whitney U, and logistic regression models. Conditional logistic regression models were used to evaluate the interaction between race and biomarker expression for predicting pathologic T3 PCa. Results: Of 20 biomarkers interrogated, 6 showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include TMPRSS2-ERG (p<0.001), AMACR (p<0.001), SPINK1 (p=0.005), AR (p=0.018), SRD5A2 (p=0.005), and GSTP1 (p=0.021). Dysregulation of MYCBP (p=0.043) increases risk of pT3 disease in AA but decreases the risk in EA men, while the reverse is true for AMACR (p=0.013), TMPRSS2-ERG (p=0.026), FOXP1 (p=0.016), and GSTP1 (p=0.032). Loss-of-function mutation for tumor suppressors PTEN (p=0.046), TP53 (p=0.042), and RB1 (p=0.027), and dysregulation of AR (p=0.015), EZH2 (p=0.043), NKX3-1 (p=0.024), SRD5A2 (p=0.032), and SPOP (p=0.032) increased risk of pT3 disease for both AA and EA men. Conclusions: We have identified a subset of PCa biomarkers that predict risk of clinico-pathologic outcomes in a race-dependent manner. These biomarkers may in part explain the biological contribution to racial disparity in PCa outcomes between EA and AA men.
Androgen Receptor Modulation Optimized for Response in Splice Variant (ARMOR3-SV): Randomized, open-label, multicenter, controlled study of galeterone versus enzalutamide (enz) in men expressing AR-V7 splice variant (SV), metastatic castrate resistant prostate cancer (mCRPC).
Authors: Roberts Jennifer , Dhillon Reena , Dransfield Daniel T. , Mamlouk Khalid Kevin , Ferrante Karen J. 
Published: February 2017

259 Background: Recent data showed that mCRPC patients (pts) with the androgen receptor (AR) SV AR-V7, a truncated form of the AR that lacks the ligand-binding domain and remains a constitutively active transcription factor, had worse clinical outcomes than patients without AR-V7 (Antonarakis et al, NEJM 2014; Efstathiou et al, ASCO 2014; Bambury et al, ESMO 2014). Galeterone, a small molecule, disrupts AR signaling via selective inhibition of CYP17 lyase, competitively inhibits androgen binding to AR, and degrades AR protein. In preclinical models, it demonstrated activity against many AR aberrations, including AR-V7, ARv567es, AR-T878A, and AR-F876L. Given the encouraging results in pts with AR C-terminal loss in the phase 2 ARMOR2 trial (Taplin et al, ESMO 2014), further research is warranted. Methods: ARMOR3-SV is a global, phase 3, randomized, open-label, multicenter, controlled study of galeterone vs enz in men expressing AR-V7 SV–mCRPC. Among other enrollment criteria, eligible pts must have the AR-V7 splice variant, be on GnRH therapy or have had a bilateral orchiectomy with testosterone <50 ng/dL. Approximately <170 pts will be randomized to receive once-daily oral therapy with galeterone 2550 mg or enz 160 mg. The primary endpoint is radiographic progression-free survival. Secondary endpoints include overall survival, time to cytotoxic therapy, and skeletal related events. Pts will be followed until radiographic disease progression as assessed by an independent, blinded radiologic review. Post-progression anticancer interventions will be collected and pts will be followed until death or study termination. Results: Because AR-V7 status must be determined for enrollment, the availability of a validated, accurate, rapid, quantitative, and universally applicable assay performed in a central CLIA-certified laboratory is critical to the trial. Conclusions: Choice of assay to identify and select mCRPC pts harboring AR-V7 is key to enrollment strategy for ARMOR3-SV. The study is expected begin in the first half of 2015.