bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the AJCC staging system (7th edition) in Asian patients with localized prostate cancer undergoing radical radiotherapy.
Authors: Wong M. , Yip C. , Hou X. , Tan P. , Huang H. , Chowbay B. , Lau W. , Tan T. , Tan M. , Wong F. 
Published: February 2017

112 Background: The epidemiology of prostate cancer (PCa) varies widely internationally. Although prostate cancer is usually regarded as uncommon in Asia, dramatic rises in recent years have resulted in it being ranking third by incidence in Singapore. Conventional prognostic parameters derived from Western populations have been integrated into systems such as the new AJCC seventh edition staging system, the validity of which is unclear in Asia. We thus sought to validate its performance, alongside other prognostic factors in a large Asian series of radiotherapy patients. Methods: A retrospective review of 404 consecutive Singaporean patients receiving radical radiotherapy between 1997 and 2005 at the National Cancer Centre was performed. The primary outcome was biochemical relapse free survival (BRFS), defined by the Phoenix criteria. Prognostic risk groups were defined using AJCC seventh edition. Univariate analysis (UVA) and multivariate analysis (MVA) was performed for other putative risk factors: age, race, Gleason score, prognostic risk grouping, tumour classification, radiation delivery technique, radiotherapy dose, hormonal therapy (HT) and initial PSA. Results: Median age was 69; median BRFS was 55 months with 71 biochemical relapses. 4 risk factors showed univariate association with BRFS: AJCC risk groups (p=0.038), T-stage (p=0.018), RT dose (p=0.025) and initial PSA value (p=0.013) with AJCC risk groups and initial PSA value remaining significant after MVA ( Table ). Harrell's c-index for AJCC risk grouping was 0.56, with no significant difference seen in outcomes between AJCC risk group II and III. Conclusions: Our results validate the new AJCC seventh edition prostate cancer prognostic risk grouping in an Asian radiotherapy population for the first time; the actual association however is relatively weak possibly due to differences in biology, screening or epidemiology. [Table: see text] No significant financial relationships to disclose.
Does increasing number of core biopsies change the results of needle biospy in prostate cancer?
Authors: Farhat M. H. , Dabaja A. , Agarwal P. 
Published: February 2017

113 Background: The superiority of extended sampling of the prostate compared to standard sextant biopsy in predicting the final Gleason score has been controversial. In the literature, sextant biopsies have a match rate between 28–68% and an upgrading rate of 25–57%. Consequently, multiple studies recommend that extended biopsies should be the standard of care. This study examines the effect of greater core biopsy number on upgrading GS and predicting surgical pathology. Methods: Prostate biopsies of 984 patients who underwent RP between 2001 and 2008 were retrospectively reviewed. The GS of the biopsies was compared to the pathological specimens using the Chi-square test. Further adjusted comparison was performed using logistic regression. A clinical significant upgrade was defined as increase of the total GS or the primary GS. Results: The majority of the upgrading occurred in biopsy Gleason 3+3 and 3+4 cases. Upgrading was seen in 35.1% of patients with 6 cores or less, 34.5% with 7–12 cores, and 45.5% with 13+ cores (p=0.061). Number of cores, BMI, or prostate size did not affect upgrading, while perineural invasion, cancer volume on a biopsy, and D'Amico risk criteria increased the likelihood of upgrading. Conclusions: The extended core biopsy does not seem to correlate with higher gleason score or to better predict the final pathologic gleason score compared to standard sextant biopsies in prostate cancer. D'Amico risk factors, perineural invasion, and cancer volume can be viewed as risk factors for upgrading especially in GS 3+3. No significant financial relationships to disclose.
Nomograms to predict 3-year biochemical recurrence after robotic-assisted laparoscopic radical prostatectomy based on preoperative and perioperative variables of 774 patients.
Authors: Sooriakumaran P. , John M. , Srivastava A. , El-Douaihy Y. , Grover S. , Bhagat D. , Rajan S. , Leung R. , Tewari A. 
Published: February 2017

115 Background: Predictors of biochemical recurrence after robotic-assisted laparoscopic radical prostatectomy (RALP) are not well reported in the literature. We wanted to investigate preoperative predictors as well as the influence of nerve sparing and positive surgical margin status on 3-year biochemical recurrence. Methods: 774 patients with at least 3 year follow up had undergone RALP by a single surgeon at our institution. Biochemcial recurrence was defined as a postoperative PSA >0.2 ng/ml. Multivariable logistic regression models were used to develop the biochemical recurrence predictive nomograms: nomogram 1- age, BMI, PSA density, clinical stage, biopsy Gleason, percent positive cores, perineural invasion; nomogram 2- age, BMI, PSA density, clinical stage, biopsy Gleason, percent positive cores, perineural invasion, nerve sparing, positive surgical margins (none, unifocal, or multifocal). The predictive accuracy of the models was assessed in terms of discrimination and calibration. Results: Both nomograms discriminated well between patients that recurred and those that did not (bootstrap corrected c-indices of 0.766 and 0.806 for nomograms 1 and 2 respectively). Nomogram 1 was well calibrated, but nomogram 2 over- predicted the probability of biochemical recurrence in patients at >30% risk. Conclusions: Our nomogram based on age, BMI, PSA density, clinical stage, biopsy Gleason, percent positive cores, and perineural invasion on preoperative biopsy has a good predictive ability to differentiate between RALP-treated patients that biochemically recur by 3 years from those that do not. Adding nerve sparing and surgical margin status further improved discriminatory ability but at the expense of over-prediction for patients at high risk. These nomograms may be used to guide the use of nerve sparing and the management of positive margins in men undergoing RALP for clinically localized prostate cancer. No significant financial relationships to disclose.
Phase III study of the efficacy and safety of zibotentan (ZD4054) in patients with bone metastatic castration-resistant prostate cancer (CRPC).
Authors: Nelson J. B. , Fizazi K. , Miller K. , Higano C. S. , Moul J. W. , Morris T. , McIntosh S. , Pemberton K. , Gleave M. E. 
Published: February 2017

117 Background: Endothelin-1 and the endothelin A (ETA) receptor have been implicated in prostate cancer progression in bone. Zibotentan, a specific ETA receptor antagonist, had a promising signal for prolonged overall survival (OS) in a phase II study of patients with CRPC and bone metastases who were pain free or mildly symptomatic for pain. The aim of this phase III study was to confirm the efficacy and safety of zibotentan in a similar but larger population. Methods: Patients with CRPC and bone metastases were randomized 1:1 to zibotentan 10 mg/day po or placebo, plus standard of care including chemotherapy. The primary endpoint was OS. Secondary endpoints included times to pain progression, chemotherapy use, new bone metastases, and safety. Efficacy endpoints were analyzed using a log-rank test. At least 263 deaths were required for formal analysis. If the true hazard ratio (HR) for zibotentan versus placebo was 0.67, the analysis would have 90% power to demonstrate a statistically significant effect in OS at the 5% level. Results: A total of 594 patients were randomized (299 to zibotentan; 295 to placebo). Baseline group demographics were similar. Mean age was ∼71 yrs, and 64% were Caucasian. Although median OS was longer in zibotentan-treated patients than those receiving placebo (median 24.5 vs 22.5 months), the difference did not reach significance (HR [95.2% confidence interval]; 0.87 [0.69–1.10]: P=0.240). No significant differences were observed for any secondary endpoints. The most commonly reported AEs in the zibotentan group, peripheral edema and headache, were consistent with the pharmacologic action of zibotentan as a vasodilator. Cardiac failure events, actively solicited following a phase II signal, were higher in the zibotentan group (any grade, 5.7%; Common Terminology Criteria for Adverse Events [CTCAE] grade ≥3, 3.0%) than placebo (any grade, 1.7%; CTCAE grade ≥3, 1.0%), but were manageable and reversible. Conclusions: In this placebo-controlled phase III trial treatment with zibotentan 10 mg/day did not lead to a significant improvement in OS in patients with CRPC and bone metastases. Zibotentan had an acceptable safety profile. [Table: see text]
Correlation of 11c-choline PET-CT with time to treatment and disease-specific survival in men with recurrent prostate cancer after radical prostatectomy.
Authors: Breeuwsma A. J. , Pruim J. , Leliveld A. M. , Dierckx R. A. , de Jong I. J. 
Published: February 2017

123 Background: Restaging with PET-CT in biochemical recurrent prostate cancer after prostatectomy shows a higher frequency of (false) negative cases compared to restaging after EBRT. It is uncertain if this reflects low volume of disease and/or low grade as biopsies fail to prove recurrent cancer in 50% of cases. We followed the clinical course of men with recurrent prostate cancer (PCa) after radical prostatectomy and investigated treatment and survival. PET-CT data were correlated with clinical data, PSA kinetics and disease specific and overall survival. We also studied relative survival comparing an age matched group from the Central Dutch Statistical Office (CBS). Methods: 64 patients underwent 11C-Choline PET-CT on PSA relapse. All patients were initially treated with radical prostectomy and reached PSA nadir of <0.1ng/mL. Recurrent disease was defined as PSA <0.4ng/mL after nadir. Patients were either treated with watchful waiting, adjuvant radiotherapy and/ or androgen deprivation therapy based on individual assesments by the treating urologists. Chi-square, log-rank and Mann-Whitney-U tests were used to study this population Results: The 64 patients had median PSA of 1.4ng/mL. Median follow-up period of patients was 50 (6–124) months. Ten patients died during the course of follow-up of which 5 due to metastasized PCa. No significant differences were seen in age, time to recurrence, total PSA at recurrence and PET-CT results. Patients with abnormal PET had higher PSAVel (median 3.09 ng/mL/yr vs 10.17, p= 0.002) and and shorter PSADT (med 4.83 mo vs 0.53, p= 0.016). Median time to treatment was significantly lower in the PET-CT negative group. Age of patients at death from the whole group did not differ from the age of death in an age matched group. Disease specific survival was significantly higher in the PET-CT negative group (p0.05). Conclusions: A negative 11C-Choline PET-CT correlated with a higher disease specific survival and a lower treatment rate. Overall survival of the group was equal to the age matched cohort. No significant financial relationships to disclose.
Phase II study of XL184 in a cohort of patients (pts) with castration-resistant prostate cancer (CRPC) and measurable soft tissue disease.
Authors: Smith D. C. , Smith M. R. , Small E. J. , Sweeney C. , Kurzrock R. , Gordon M. S. , Vogelzang N. J. , Scheffold C. , Ballinger M. D. , Hussain M. 
Published: February 2017

127 Background: XL184 is an oral, potent inhibitor of MET and VEGFR2. MET pathway activation promotes tumor growth, invasion and metastasis. Overexpression of MET and/or its ligand HGF are associated with prostate cancer metastasis. In preclinical studies, androgen ablation upregulates MET signaling. Preliminary data from the open label Lead-in Stage of an ongoing adaptive design phase II randomized discontinuation trial are presented. Methods: Eligible pts had CRPC, measurable disease with or without bone metastasis, and disease progression on ≤1 prior non-hormonal systemic treatment. XL184 was administered orally for 12 weeks (wks). Tumor (RECIST) and bone scan response (complete or partial resolution) were assessed every 6 wks. Primary endpoint is objective response rate at wk 12. Pts with SD at wk 12 will enter a placebo-controlled randomized phase. Results: As of 10/4/10, 72 pts have been enrolled. Median time on study was 50 days (range, 6+-350+ days). Median age was 69 yrs; 45% of pts were docetaxel-pretreated. All pts had measurable disease, including 69% with visceral metastases. To date, there are 24 response evaluable pts, defined as enrolled ≥12 wks prior to data cutoff. 5/24 (21%) pts had a partial response (≥30% reduction) in measurable disease with 3 responses confirmed at 12 wks and 2 unconfirmed responses ongoing. 6/24 (25%) had PSA declines of ≥50%. 13 of 15 (87%) pts with known bone metastases had either complete or partial resolution of lesions on bone scan. Bone scan responses were associated with investigator-reported improvement in bone pain in 11/15 (73%) with pain at baseline. Effects on osteoclast and osteoblast activity were observed: plasma C-telopeptide declined ≥50% in 8/12 (66%) pts and serum total alkaline phosphatase (tALP) declined ≥50% in 5/8 (63%) pts with bone metastases and baseline elevated tALP. The most common AEs ≥Grade 3 severity (related) were fatigue (10%), diarrhea (3%) and elevated AST (3%). Conclusions: XL184 results in tumor responses, partial or complete resolution of lesions on bone scan, and symptom relief in pts with metastatic CRPC, including those pretreated with docetaxel. XL184 also decreased biomarkers of both osteoblast and osteoclast activity. [Table: see text]
Antitumor activity of MDV3100 in pre- and post-docetaxel advanced prostate cancer: Long-term follow-up of a phase I/II study.
Authors: Higano C. S. , Beer T. M. , Taplin M. , Efstathiou E. , Anand A. , Hirmand M. , Fleisher M. , Scher H. I. ,   Prostate Cancer Clinical Trials Consortium
Published: February 2017

134 Background: MDV3100 is a novel androgen receptor (AR) antagonist selected for potent AR activity and devoid of partial agonist effects. A preliminary report of the phase I/II study described anti-tumor activity and adverse events (Scher HI et al. Lancet. 2010;375:1437). This abstract provides long-term follow-up on time to PSA and radiographic progression in this trial. Methods: Patients (pts) with progressive castration resistant prostate cancer (CRPC) were enrolled in sequential cohorts of 3-6 pts at MDV3100 doses of 30, 60, 150, 240, 360, 480 and 600 mg/day. Once the tolerability of a dose was established, enrollment was expanded at doses ≥60 mg/day to include approximately 12 chemotherapy naïve (naïve) pts and 12 pts previously treated with docetaxel (post-chemo) per cohort. Results: 140 pts were enrolled of which 18 (13%) pts continue on active treatment (16 naive and 2 post-chemo). The median time on treatment is 51 weeks for naïve and 17 weeks for post-chemo groups. Median time on treatment for the 18 patients still on study is 131 weeks. The median time to PSA progression, defined per-protocol as a ≥25% increase in PSA from baseline, was not met for naïve and was 33 weeks for post-chemo groups. Median time to PSA progression by Prostate Cancer Clinical Trials Working Group 2 criteria was 41 weeks for naïve and 20 weeks for post-chemo groups. Median time to radiographic progression was 56 weeks for naive and 24 weeks for post-chemo groups. Circulating tumor cell counts available for 128 of 140 pts showed 91% (70/77) with favorable pre-treatment counts (<5 cells/7.5 mL blood) remaining favorable post-treatment, while 49% (25/51) converted from unfavorable pre-treatment to favorable post-treatment. Conclusions: MDV3100 demonstrates durable anti-tumor activity in pts with CRPC both before and after chemotherapy. Based on these promising results MDV3100 is currently being evaluated in two global phase III studies in pts with metastatic CRPC, the AFFIRM study in pts previously treated with docetaxel and the PREVAIL study in chemotherapy-naïve pts who have progressed on androgen deprivation therapy. [Table: see text]
Subsequent treatment with APC8015F and its effect on survival in the control arm of phase III sipuleucel-t studies.
Authors: George D. J. , Nabhan C. , Gomella L. G. , Whitmore J. B. , Frohlich M. W. 
Published: February 2017

139 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for metastatic castrate resistant prostate cancer. Methods: After disease progression, subjects in the control arms of 3 randomized controlled sipuleucel-T trials were offered 3 infusions of APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control generation. Results: Of 249 control subjects, 165 (66.3%) received APC8015F; the median time from randomization to first infusion was 5.2 months (range 1.8 to 33.1), median time from objective disease progression to first APC8015F infusion was 2.2 months (range 0.5 to 14.6), and 145 subjects (87.9%) received all 3 infusions. The frequency of infusional toxicities was increased following APC8015F relative to control infusion, but was slightly lower than following sipuleucel-T. APC8015F-treated subjects (n=155) had improved post-progression survival relative to untreated controls (n=61) (HR=0.52 [95%CI 0.37, 0.73] p=0.0001, log rank test, unadjusted Cox regression); however, APC8015F-treated subjects had more favorable prognostic features than untreated controls. A Cox regression analysis adjusting for baseline PSA and LDH demonstrated that APC8015F therapy remained a predictor of survival in control subjects (HR=0.56 [95%CI 0.40, 0.80]; p=0.001). A Cox regression model adjusting for age, PSA, LDH and post-randomization docetaxel use (yes/no), also showed a significant effect for salvage treatment among control subjects (HR=0.55 [95%CI 0.39, 0.78] p<0.001). Examination of APC8015F product characteristics demonstrated that cumulative CD54 upregulation was associated with survival following first infusion in subjects who progressed and received APC8015F (p=0.03), consistent with previous reports of correlations between sipuleucel-T product parameters and overall survival. Conclusions: Although confounded with measured and unmeasured factors influencing outcome, these analyses suggest that post-progression treatment with APC8015F may have extended the survival of subjects in the control arms of these studies. [Table: see text]
Intraprostatic vaccine administration in patients with locally recurrent prostate cancer.
Authors: Heery C. , Pinto P. A. , Schlom J. , Tsang K. Y. , Madan R. A. , Poole D. , Vergati M. , Walter Rodriguez B. , Merino M. , Gulley J. L. 
Published: February 2017

141 Background: PSA-TRICOM is a cancer vaccine consisting of recombinant poxviruses with transgenes for PSA and 3 T cell costimulatory molecules (TRICOM). A multicenter randomized vector controlled phase II study showed an 8.5 month improvement in median survival in men with metastatic CRPC. Preclinical studies showed intratumoral administration of TRICOM vaccines may improve anti-tumor outcomes. This study was intended to show safety of intraprostatic (i.p.) vaccine administration. 2° goals included immunologic and tumor response. Methods: 21 pts were enrolled with locally recurrent prostate cancer after radiation into 5 cohorts and received initial vaccination with s.c. recombinant vaccinia (rV)-PSA-TRICOM and booster i.p. recombinant fowlpox (rF)-PSA-TRICOM. Cohorts 3-5 also received i.p. rF-GM-CSF. Cohort 5 received concurrent s.c. and i.p. boosters. Priming was given on day 1, and boosters were given on days 29, 57, and 85. Pts had pre- and post-treatment prostate biopsies. Tumor infiltrate was evaluated when adequate tissue was available. PBMCs were analyzed by ELISPOT for response to PSA and 3-color flow cytometry to characterize regulatory T cells (Treg) or effector T cells. Treg suppression function was assayed by suppression of the CD4+ effector T cell proliferation. Results: Only 1 grade 3 toxicity occurred, a transient fever. Most common grade 2 adverse events for all doses were fever (14.5%) and injection-site reactions (21%). 15 of 21 pts had stable or improved PSA on study, and 16 of 21 pts had stable or improved PSA doubling time. Post-vaccination, 4 of 8 evaluable pts had immunological response by ELISPOT assay and 11 of 15 pts had decreased (n=8) or stable (n=3) Treg function. A paired t-test of 13 biopsies pre- and post- vaccination showed significant increases in immune infiltrates within tumors after vaccination. CD4+ cells increased from 1.3 → 13.1/high power field (hpf). CD8+ cells rose from 6.4 → 14/hpf. Conclusions: I.p. administration of PSA-TRICOM is safe, feasible and can generate a substantial immunologic response. Improved PSA kinetics and intense post-vaccination immune infiltrates were seen in the majority of pts. Trials of i.p. PSA-TRICOM examining clinical endpoints are warranted. No significant financial relationships to disclose.
Neoadjuvant trial of sunitinib malate and androgen ablation (ADT) in patients with localized prostate cancer (PCa) at high risk for recurrence.
Authors: Zurita A. J. , Ward J. F. , Araujo J. C. , Pettaway C. A. , Dieringer P. , Wang X. , Troncoso P. , Logothetis C. 
Published: February 2017

143 Background: Presurgical ADT does not improve long-term outcomes in patients (pts) with high-risk localized PCa. Since the VEGF and PDGF signaling pathways have been implicated in PCa progression, and ADT results in endothelial cell apoptosis in the prostate by a VEGF-mediated mechanism, we hypothesized that combined treatment with sunitinib malate (SU), an oral inhibitor of the tyrosine kinases of VEGFR and PDGFR, might improve the efficacy of ADT in this pt population. Methods: Pts with no radiological evidence of metastases and either PCa ≥ clinical (c)T3 disease or Gleason grade 8-10 or serum prostate-specific antigen (PSA) ≥ 20 ng/mL or cT2b-c and Gleason 7 and PSA ≥10 ng/mL (AJCC, 1992), received i.m. leuprolide and oral SU for three 30-day cycles followed by surgery. SU was administered continuously at 37.5 mg daily (25 mg daily in the initial 6 pts). The primary endpoint of this phase II trial was rate of pathologic complete response (pCR). Secondary endpoints included safety and time to progression (TTP). Unresectable pelvic nodal disease, confirmed post-operative PSA ≥ 0.2 ng/mL, or administration of post-operative radiation or ADT, defined treatment failure. Results: Forty-four pts completed accrual, with a median age of 58 years (range 47-72); 34 Caucasian, 5 African-American, 4 Hispanic, and 1 Indian. High-risk criteria included cT3 (24/44), Gleason 8-10 (30/44), PSA ≥ 20 ng/mL (16/44). Two men were ineligible/declined therapy and one postponed surgery. No grade 4 toxicities or related discontinuations were observed. Thirty-five pts completed 3 months on 37.5 mg daily SU plus ADT and surgery with no unexpected complications. Of these, 2 pts experienced a pCR. Twenty (57%) pts have failed treatment or died, with a median TTP 27 months (95% CI: 12 – not estimable). The median follow-up of the remaining event-free pts is 35 months (range 23-41). Conclusions: The 3-months preoperative combination of SU and ADT is safe and well tolerated in pts with high-risk primary PCa. We observed 2 complete remissions in 35 patients. Ongoing characterization of molecular changes in the epithelial and stromal compartments will help understand the mechanisms of SU activity in PCa. [Table: see text]