bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of cabazitaxel and its relationship with predictors of poor response to second hormonal therapies (2d HT) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Oudard Stephane , Mercier Florence , Flechon Aude , Guillot Aline , Le Moulec Sylvestre , Gravis Gwenaelle , Beuzeboc Philippe , Massard Christophe , Fizazi Karim , De La Motte Rouge Thibault , Elaidi Reza-Thierry , Angelergues Antoine 
Published: February 2017

137 Background: Potential predictors of low response to 2d HT including new agents have been recently identified: high Gleason score, rapid progression with first androgen deprivation therapy (ADT), chemotherapy lines >1 and low baseline testosterone (T) levels. We evaluated the influence of these factors on the efficacy of cabazitaxel (C), a new taxane developed to overcome docetaxel (D) resistance. Methods: Records of 84 consecutive mCRPC pts (median 67 yrs) treated with C for disease progression on D or after D were retrospectively collected in 8 French centers. Baseline characteristics, disease history, PSA response, overall survival (OS) and radiological or clinical progression-free survival (PFS) were collected. Results: At C initiation, 84% of pts were ECOG 0-1, 59% had pain and 24% received ≥2 prior chemotherapy lines. Metastases were located in bone (93%), lymph nodes (49%) and visceral/soft tissues (9%). Gleason score was 8-10 in 47%, median time to progression with first ADT was 20 months and median T was 0.1 ng/ml. Median number of C cycles received was 6 (range 2-14). Efficacy of C was not influenced by Gleason score, response duration to first ADT, prior number of chemo lines, or baseline T (table). Main grade ≥ 3 toxicities were neutropenia (32%), anaemia (17%), thrombocytopenia (8%), diarrhoea (6%), and febrile neutropenia (5%). There was no grade ≥3 peripheral neuropathy and no toxic death. Conclusions: This retrospective study suggests that C is effective and shows an acceptable safety profile. Efficacy was not influenced by predictors of poor response to 2d HT (high Gleason, short response to first ADT, Number of chemo lines, low T levels). If these results are confirmed in further investigations, cabazitaxel could be proposed whatever the baseline characteristics of mCRPC pts. [Table: see text]
Hypofractionated radiotherapy (66Gy at 3Gy per fraction) for favorable-risk prostate cancer: Long-term outcomes.
Authors: Patel Nita , Faria Sergio , Cury Fabio L. , David Marc , Duclos Marie , Shenouda George , Souhami Luis 
Published: February 2017

141 Background: Hypofractionated radiotherapy (HypoRT) is increasingly being used to treat prostate cancer to take advantage of its likely low α/β ratio. There is limited experience in delivering a high biologically equivalent dose with HypoRT. We report long-term outcomes from patients treated with high-dose HypoRT. Methods: Patients with low and intermediate risk prostate cancer were treated using 3-dimensional conformal radiotherapy at a dose of 66Gy in 22 daily fractions of 3Gy without hormonal therapy. A uniform 7mm margin was created around the prostate for the planning target volume (PTV) and treatment was prescribed to the isocentre. Treatment was delivered using daily ultrasound image guided radiotherapy (IGRT). The CTCv3.0 was used to prospectively score toxicity. Biochemical failure was defined using the Phoenix criteria of nadir+2ng/ml. Results: A total of 129 patients were treated between November 2002 and December 2005. With a median follow-up of 90 months, the 5- and 8-year actuarial biochemical control rate was 97% and 92% respectively. The 5- and 8-year actuarial overall survival was 92% and 88% respectively. Only one patient died from prostate cancer at 92 months after treatment resulting in an 8-year actuarial cancer specific survival of 98%. Radiotherapy was well tolerated with 57% of patients experiencing no acute gastrointestinal (GI) or genitourinary (GU) toxicity. For late toxicity, the worst grade ≥2 rate for GI and GU toxicity was 27% and 33% respectively, but at the last follow-up the rate of grade ≥2 was only 1.5% for both GI and GU toxicity (Table). Conclusions: High dose HypoRT delivering 66 Gy in 22 fractions at 3Gy per fraction is a safe, effective and convenient modality of delivering radiotherapy to patients with favorable risk prostate cancer with excellent biochemical control rates and acceptable rates of acute and late GI and GU toxicity. [Table: see text]
A phase Ib trial of mushroom powder in biochemically recurrent, hormone-naive prostate cancer.
Authors: Twardowski Przemyslaw , Frankel Paul Henry , Pal Sumanta Kumar , Synold Timothy W. , Ruel Christopher , Junqueira Maribel , Nguyen Tina , Palomares Melanie R. , Tryon Pamela Renee , Chen Shiuan 
Published: February 2017

142 Background: Biochemically recurrent prostate cancer (PC) is a common presentation of relapse after primary local therapies. Strategies to delay disease progression and defer initiation of androgen deprivation therapy and associated side effects are needed. White button mushroom (WBM, Agaricus bisporus) extract suppresses prostate cancer tumor growth in animals, and prior human experience indicates favorable toxicity profile. Methods: Patients (pts) with rising PSA of ≥0.2 ng/mL after prostatectomy (RP) and/or radiation (RT) and no radiographic evidence of metastases were treated with WBM powder tablets at 4, 6, 8, 10, 12 and 14 grams po daily. Dose escalation was conducted in cohorts of 6 and continued as long as no more than 1 patient per cohort experienced dose limiting toxicity (DLT). Therapy continued until PSA increased by ≥100% and by ≥1 ng/mL, or clinically detectable metastases or unacceptable toxicity occurred. Primary objective was feasibility and toxicity, secondary objective was the effect of WBM on serum PSA and androgen levels. Results: Thirty six pts were treated. Median age was 68 (53-80).Thirty three pts (92%) had prior RP and all underwent previous RT. Median PSA was 1.9 (0.2-22.2). Mean compliance was 98.6 %. No DLT’s were encountered. The most common side effect was grade 1 abdominal bloating (39%); one patient experienced asymptomatic grade 3 hyponatremia. Overall PSA response rate was 11% (95% CI: 4%-27%). Two pts receiving 8 and 14 gm/day demonstrated a PSA complete response (CR), defined as a decline in PSA to undetectable levels that continues for 26 and 7 months respectively. Two pts, receiving 8 and 14 gm/day, experienced confirmed PSA partial responses (PR), defined as a ≥50% PSA decline on treatment. After 3 months of therapy 36% of pts (13/36) demonstrated some PSA decrease below baseline. No association between PSA response and serum testosterone, DHT or DHEA levels was observed. Median duration on therapy is 10.2 months (0.9 – 35.3). Ten pts remain on therapy. Conclusions: Therapy with WBM was well tolerated. Our data suggest that WBM intake results in durable decreases in PSA level in some patients with biochemically recurrent PC. Further studies to clarify mechanism of action are warranted. Clinical trial information: NCT00779168.
Quality-of-life outcomes for prostate cancer treatment in Australia.
Authors: Millar Jeremy L. , Evans Susan M. , Frydenberg Mark , Murphy Declan G. , Bolton Damien M. , Giles Graham G. , Davis Ian D. 
Published: February 2017

143 Background: We aimed to use a population based quality registry established in Australia, to review patient-reported health-related QOL after the diagnosis of Prostate Cancer (PCa). Methods: Prospective registry of men with PCa from statutory notifications to the canonical population-based cancer registry in Victoria. An "opt-off" mechanism used. Coverage expanded from 30%-80% of State population over time. Demographics and disease features, management, and outcomes from medical record; men phoned at 12 and 24 months (m), interviewed with script including SF12 and items from standard form (UCLA PCI) for specific QOL outcomes. Urinary, rectal, and sexual function bother (UB, RB, and SB) scores where analysed by univariate and multivariable modelling for relationship of these with presentation or management factors, adjusting for risk. Results: Men from 8/2008 - 2/2011; 1.9% of eligible opted out. Followed 1172 to 12 & 24 m. Median diagnosis age 65 yr; median PSA 6.8 ng/mL; 97.3% clinically localised with 47.7% having NCCN intermediate risk. 520 had treatment with Radical Prostatectomy (RP) (89 also with external beam-EBRT), 171 had EBRT (with or without HDR brachy), and 211 seed implant (SI). 226 had no treatment (NT) in the first 12 m. 52.5% managed in public hospitals, rest private. Univariate analysis: UB associated with management type, and hospital type, and RB and SB associated with these factors, as well as age and disease stage. On multivariate regression SB at 12 m was associated with increasing age (p=0.002) and radical treatment types (RP and EBRT/HDR, p<0.001 and 0.003 respectively)—except SI—compared to NT; RB was associated with SI (0.02) and EBRT/HDR (0.007) and treatment in a public hospital (0.006); and UB was associated with public hospital (<0.001). All associations at 12 m remained significant at 24 m. SF12 physical score had a positive association with RP vs NT (0.014), hospital type (0.001) and younger age. SF12 mental health also showed associations. Conclusions: A large scale registry in Australia assessing patient-reported quality of life outcomes after prostate cancer treatment shows patterns similar to that seen in North American reports.
Outcomes in elderly patients with metastatic castration-resistant prostate cancer (mCRPC) treated with the androgen receptor inhibitor enzalutamide: Results from the phase III AFFIRM trial.
Authors: Sternberg Cora N. , De Bono Johann Sebastian , Chi Kim N. , Fizazi Karim , Mulders Peter , Hirmand Mohammad , Forer David , Scher Howard I. 
Published: February 2017

16 Background: Enzalutamide (ENZA) inhibits multiple steps in the androgen receptor signaling pathway (Tran et al, Science. 2009;324:787). The phase III AFFIRM trial demonstrated that ENZA increased median overall survival (OS) by 4.8 months with a 37% reduction in the risk of death (P <0.001, HR 0.63) vs placebo (PBO) in post-docetaxel mCRPC patients (pts) (Scher et al, NEJM 2012; 367:1187). In a post-hoc analysis, the effect of ENZA on outcomes in elderly (≥ 75 yrs) vs younger (< 75 yrs) pts in the AFFIRM trial was assessed. Methods: The AFFIRM trial was a Phase III multinational, randomized, double-blind study in post-docetaxel mCRPC pts. Randomization was 2:1 to ENZA 160 mg/day or PBO, stratified by baseline ECOG performance status and mean pain score. Statistics are presented by age group (≥75, yrs <75 yrs) for efficacy outcomes of OS, radiographic progression-free survival (rPFS), and time to prostate-specific antigen (PSA) progression. Top line safety results are also presented for both age groups. Results: Elderly pts comprised 25% (199/800) of ENZA pts and 26% (104/399) of PBO pts. Improved outcomes with ENZA treatment were observed in both elderly and younger pts, with similar safety profiles in each age group. Conclusions: ENZA significantly improved outcomes in both elderly (≥ 75yrs) and younger pts (< 75yrs). Safety and tolerability findings were comparable between the two age groups. Clinical trial information: NCT00974311. [Table: see text]
Use of biopsy detail to identify subgroup risk in high-risk patients with prostate cancer.
Authors: Townsend Natasha C. , Buyyounouski Mark K. , Ruth Karen J. , Kutikov Alexander , Viterbo Rosalia , Sobczak Mark , White Terry , Horwitz Eric M. 
Published: February 2017

169 Background: High Risk (HR) prostate cancer (CaP) patients (pts) are a heterogeneous group. A recursive partitioning analysis (RPA) was performed to determine if tissue involvement could identify patients at risk for biochemical failure (BF). Methods: Between 1992-2009, 608 HR CaP pts with complete prostate biopsy detail data (% overall tissue involvement (%TI), GP45 (weighted average of %TI for Gleason Pattern 4 or 5), Gleason Score (GS)) underwent RT with/out ADT. Primary endpoint was freedom from biochemical failure (FFBF). RPA based on time to BF was used to determine cutpoints for each prognostic variable. Multivariable (MVA) RPAs were used to assess interactions of significant variables (p<0.05) from univariate analysis (UVA). Results: Median follow up for PSA measurement was 45 months (3-193 mo). UVA RPA revealed significant cutpoints for FFBF for Tstage (higher risk of BF(HRBF) for T2c,T3b,T3c,T4,Tx vs lower risk of BF(LRBF) for T1,T2a,T2b,T3a, (p<0.001)); GS(HRBF 3+4/5, 4+5 vs LRBF 2-6, 2+3/4, 5+3/4/5 (p=0.011); iPSA (LRBF ≤37 vs HRBF >37 ng/ml (p<0.001)); dose (HRBF ≤74.9 vs LRBF >74.9 Gy); RT type(LRBF IMRT vs HRBF 3D-CRT, p=0.032), %TI (LRBF ≤53% vs HRBF >53% (p<0.001)); GP45 (LRBF ≤33% vs HRBF >33%(p<0.001)). Overall, FFBF at 5 yr was 79.2% (95%CI 75.0-82.8). For MVA RPA, splits are same as UVA unless noted. MVA RPA excluding GP45 and %TI showed 5 groups (5 yr FFBF 45.9%, 66.8%, 74.2%, 84.2% and 89.5%; N 16, 195, 69, 20 and 308, respectively). Tstage, iPSA, GS and RT type had significant interactions, with highest risk group including PSA >44ng/ml, low Tstage and 3D-CRT, and lowest risk group including PSA ≤44 ng/ml, lower risk Tstage, and lower risk GS. Including %TI in the RPA, significant interactions were between %TI (2 splits), iPSA and GS (5 yr FFBF 50.0%, 62.5%, 71.9%, 80.4% and 92.7%; N 80, 24, 65, 233, and 206, respectively). Highest risk group included pts with %TI >53%; lowest risk included pts with %TI <17%, iPSA <40 ng/mL, and GS lower risk. Using GP45 instead of %TI, 3 groups were found: high GP45; low GP45 and iPSA ≥40; low GP45 and iPSA<40 ng/ml, (5 yr FFBF 58.9%, 67.7% and 85.5%; N 103, 63 and 442, respectively). Conclusions: Pts with > 53% TI, > 33% GP45 and iPSA > 40 ng/ml are at highest risk of failure, and should be considered for most aggressive treatment.
Effect of enzalutamide on health-related quality of life (HRQoL) in men with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel-based therapy: Results from the AFFIRM study.
Authors: Miller Kurt , Scher Howard I. , Fizazi Karim , Basch Ethan M. , Sternberg Cora N. , Hirmand Mohammad , Cella David , Ivanescu Cristina , Phung De , Spalding James Robert , Bui Cat N. , Holmstrom Stefan , De Bono Johann Sebastian 
Published: February 2017

17 Background: In the AFFIRM trial, enzalutamide (ENZ), an oral androgen receptor inhibitor, was superior to placebo (PBO) in overall survival (HR=0.63 [0.53, 0.75], p<0.001) [Scher et al. NEJM 2012;367:1187]. This analysis focuses on impact of ENZ on HRQoL. Methods: Men with mCRPC previously treated with docetaxel were randomized (2:1) to receive ENZ (160mg/day) or PBO. HRQoL was assessed at baseline (BL), weeks 13, 17, 21, 25 and every subsequent 12 weeks using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Patients with BL and ≥1 post-BL evaluable forms were included in this analysis. Change from BL in FACT-P scores over 25 weeks of treatment was analyzed using linear mixed models. HRQoL improvement/deterioration was defined as a 10-point or higher increase/decrease during the study compared to BL on the FACT-P total score. Results: The HRQoL analysis included 938 patients. Changes from BL in FACT-P total score and domains over 25 weeks of treatment were significantly smaller (less decline) with ENZ than PBO (Table). A greater percentage of patients on ENZ reported HRQoL improvement compared to PBO (42.2% vs 14.5%; p<0.001). Median time to first HRQoL deterioration was 9.0 months for ENZ and 3.7 months for PBO (p<0.001). Overall, 46.8% of patients on ENZ and 59.3% on PBO experienced HRQoL deterioration at some point while on treatment (p=0.001). Conclusions: Compared to PBO, therapy with ENZ yields significantly better HRQoL across all domains and delays deterioration. The extent of the HRQoL advantage, along with the previously established overall survival gain of ENZ over PBO, suggest that ENZ confers a significant and meaningful clinical benefit to men with mCRPC. [Table: see text]
Long-term outcomes of active surveillance for prostate cancer: 10 years later.
Authors: Buethe David D. , Russell Christopher , Yue Binglin , Lin Hui-Yi , Pow-Sang Julio M. 
Published: February 2017

170 Background: Prostate cancer (CaP) has exhibited a downward stage migration during the PSA era. Approximately 70% of those newly diagnosed with CaP, harbor tumors of low-risk. Such tumors often prove to be of low-volume and of clinical insignificance at time of radical prostatectomy (RP), suggesting over treatment and excessive exposure to the morbidity associated with definitive management. Over the last decade, active surveillance (AS) strategies have become a more accepted practice when addressing low-risk tumors. We present the long-term oncologic outcomes of patients placed on AS. Methods: An IRB approved retrospective chart review identified 114 patients placed on AS for their CaP between November of 1997 and November of 2000. Of those, 96 patients meet study inclusion criteria mandating a Gleason sum of < 7, tumor presence in < 4 sextets, and involvement of <50% of any single biopsy core. Eligible patients were surveyed by serum PSA , digital rectal exam, and surveillance transrectal ultrasound (TRUS)-guided biopsies at physician determined intervals. Results: At diagnosis, the mean age was 70.3 (SD±5.3) years with a mean PSA value of 8.2 (SD±8.2) ng/dL. Surveillance patterns approached acquisition of a PSA at a mean of 9 months and a TRUS-guided biopsy of the prostate every 1.5 years. The median total number of PSA’s and biopsies obtained while on surveillance were 6.0 (SD±5.72) and 3.5(SD±2.02), respectively. At a median follow-up of 134.8 months (95%CI: 114.5, 148.7), 52 (54%) of patients had been reclassified or demonstrated disease progression. The median progression-free and overall survival for the cohort were 68.7 (95%CI: 53.2, 97.3) months and 156.9 (95%CI: 139.9, 161.5) months, respectively. Only one prostate cancer specific mortality was identified. Conclusions: AS presents a reasonable management strategy option for low-risk prostate cancer in appropriately selected patients. However, treatment at time of disease progression did not improve survival. A significant percentage of men on AS are exposed to progression of their disease if alive beyond 10 years from their diagnosis.
Pathologic findings in additional prostatic and periprostatic tissue removed during radical prostatectomy.
Authors: Chen Henry , Kahnoski Richard J. , Lane Brian R. 
Published: February 2017

172 Background: Additional prostatic and periprostatic tissue (PPT) can be removed during radical prostatectomy (RP) when there is concern for incomplete removal of the entire prostate gland or residual extraprostatic extension of cancer. The presence of cancer in PPT during RP is largely unknown. We analyzed the rate of positive PPT findings during RP in a community-based health system to determine the yield of PPT resection to inform future clinical practice. Methods: Retrospective review of pathology reports from 976patients undergoing RP between 1998-2011 was performed. Demographic and pathologic data were collected in an IRB-approved database. Results: Of 976 RP, 267 patients (27%) had PPT excised (median: 1, range: 1-4). Median PSA was 5.0 (IQR: 3.9-7), clinical stage was T1c in 69%, and biopsy Gleason score was 6 or lower in 39%, 7 in 52% and 8 or higher in 9%. Pathologic stage was pT2 in 85%, T3 in 13%, and LN positive in 2.6%. Among 177 bladder neck biopsies, 31% contained benign prostate and 3.4% (n=6) had adenocarcinoma. Of 37 urethral biopsies, 46% contained benign prostate and 16% (n=6) had adenocarcinoma. Of 21 prostatic apical excisions, 86% contained benign prostate and 14% (n=3) contained adenocarcinoma. Of 35 excisions of suspected residual (or fragmented) prostate (posterior-lateral, median, base, capsule, pedicle), 94% contained prostate and 0% contained adenocarcinoma. No prostate tissue or cancer was present in 15 samples labeled as “periprostatic fat” and 9 “neurovascular bundle”. Conclusions: Complete excision of adenocarcinoma during RP remains the primary surgical objective. Clinical suspicion of incomplete excision of benign or cancer-containing prostate tissue may lead to removal of additional PPT samples. In this single-center study, prostate tissue was present in 45% of such samples overall, supporting this practice. However, cancer is rarely present in such samples (5.6% of cases with PPT removed, 1.5% of RP overall), with apical/urethral regions appearing to be at highest risk (~15% of samples).
Effect of PEDF on the in vivo antitumor activities of low-dose chemotherapy in CRPC.
Authors: Nelius Thomas , Cobos Everardo , Hirsch Jennifer , Filleur Stephanie 
Published: February 2017

173 Background: The development of metronomic/low dose administration of conventional chemotherapeutic drugs has shown great promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which is down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF may enhance the cytotoxicity effects of low dose docetaxel (DTX) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: PC3 and CL1 cell lines were genetically modified to stably express the fluorescent DsRed Express protein with PEDF. Resulting cells were characterized in vitro for PEDF expression by western blot and, for proliferation by growth curves and clone formation in matrigel. PEDF anti-tumor effects were assessed on established s.c. xenografts in mice treated with DTX (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1-PEDF or -control cells into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF expression inhibits the proliferation and induces the differentiation of CPRC cells in vitro, and decreases by 85% and 70% the development of s.c. PC3 and CL1 tumors, respectively. In the survival study, PEDF expression prolongs significantly (P=0.01; 95% confidence interval) the median survival of CL1 tumor-bearing mice (53±0.001 days versus 57±1). Furthermore, we demonstrated that PEDF enhances the cytotoxicity effects of low dose chemotherapy on established s.c. tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for PC3 and CL1) and prolongs significantly the survival of tumor-bearing mice undergoing low dose chemotherapy. Conclusions: These data reinforce the significance of PEDF as a potent target for the treatment of CRPC. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low dose chemotherapies.