bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stability of white blood cell counts following standard radiation approaches for high-risk adenocarcinoma of the prostate: Implications for combination therapy.
Authors: Finkelstein Steven E. , Myslicki Francisco A. , Salenius Sharon , Mantz Constantine , Shore Neal , Fernandez Eduardo , DeVries Todd , Sims Robert Brownell 
Published: February 2017

201 Background: Traditional wisdom has suggested that under some circumstances radiation therapy may be immunosuppressive, thus obviating effective combination approaches with immunotherapy. Our purpose was to test whether standard radiation therapy for high-risk prostate cancer are immune modulating, thereby prohibiting potential combination with cellular based immunotherapies such as sipuleucel-T. Methods: Retrospective analysis of complete blood count with differential (CBC) data was performed on 26 patients with high-risk adenocarcinoma of the prostate undergoing external beam radiation therapy between January 2008 and November 2010. CBC data were collected prior to radiation therapy and at up to 4 time points thereafter, and compared to normal ranges from an outside reference lab (WBC 3,800-10,700/μL; ALC 910-4,280/μL). Results: The median age was 73 (range 62-86), and 16 patients were on concurrent androgen deprivation therapy. Patients received intensity modulated, dose-escalated external beam radiotherapy. Baseline and subsequent median white blood counts (WBC) and absolute lymphocyte counts (ALC) remained within the normal ranges. In the clinically relevant time frame of <3 months following radiation therapy where sipuleucel-T could be considered, the WBC and ALC were 5,350 and 970, respectively. The median WBC and ALC then gradually increased to 5,800 and 1,250, respectively, at 6-12 months post radiation therapy. Conclusions: These data suggest that in the setting of external beam radiation approaches for high-risk adenocarcinoma of the prostate, no significant changes in either WBC or ALC were observed. The hematologic status in these patients remained stable, suggesting that combination radiation / cellular based immunotherapy approaches are feasible. Further analysis is warranted to test the potential of novel immunotherapeutic agents with radiation therapy. [Table: see text]
Health services utilization differences between patients with metastatic (M1) and nonmetastatic (M0) prostate cancer (PCa).
Authors: Yong Candice , Onukwugha Ebere , Mullins C. Daniel , Seal Brian S. , Hussain Arif 
Published: February 2017

203 Background: Metastatic (M1) disease is diagnosed in up to 5% of PCa patients, but there is limited information about the differences in health services utilization between stage IV M1 and stage IV M0 patients in the one year leading up to and following diagnosis. Methods: We analyzed patients aged 66 or older from the linked Surveillance, Epidemiology, and End Results & Medicare (SEER-Medicare) database. Patients with incident stage IV PCa diagnosed between 2005 and 2007 were identified and followed until one year post-diagnosis. Health services utilization measures included skilled nursing facility (SNF) stay, hospice stay, hospitalization, use of walking aid, wheelchair, and oxygen. We calculated the proportion of M1 and M0 patients utilizing each health service in the year before and after diagnosis. Results: Application of inclusion criteria resulted in 3,379 patients, of which 671 (19.9%) had M0 and 2,708 (80.1%) had M1 disease. The mean (median) age of the sample was 78 (77) years. The increase in the percentage of patients with SNF stay from the year prior to diagnosis to the year post-diagnosis was much larger in the M1 population (M0: 2.1% to 8.7%; M1: 5.2% to 23.6%). The proportion of M1 patients with hospice stay increased from 0.1% in the year prior to diagnosis to 21.1% in the year post-diagnosis, compared to an increase from 0% to 5.1% in the M0 population. Compared to M0 patients, M1 patients also exhibited greater increases in oxygen use (M0: 5.3% to 6.6%; M1: 6.5% to 12.6%), walking aid use (M0: 3.4% to 4.3%; M1: 3.5% to 10.6%), and wheelchair use (M0: 1.8% to 4.5%; M1: 4.1% to 11.4%) in the year following diagnosis. However, the increase in hospitalization in the year following diagnosis was lower in the M1 population (M0: 17.9% to 76.9%; M1: 24.4% to 66.6%). Conclusions: Among stage IV PCa patients, health services utilization is generally higher for M1 patients than M0 patients in the one year following diagnosis. However, hospitalization is lower among M1 patients compared to M0 patients in the one year following diagnosis. The finding that more than 20% of M1 patients had SNF and hospice stays in the one year following diagnosis suggests that M1 PCa is associated with substantial disease burden.
Effect of dutasteride on tumor proliferation during the regrowth phase of intermittent androgen ablation therapy in men with advanced prostate cancer.
Authors: Shevrin Daniel H. , MacVicar Gary R. , Kuzel Timothy , Stadler Walter Michael , Jovanovic Borko , Kaul Karen , Wang Zhou 
Published: February 2017

21 Background: We have previously shown in an animal model of IAAT that blocking testosterone (T) to DHT by a 5α-reductase inhibitor (5ARI) has a more significant effect on tumor growth in a "regressed" prostate, ie previously treated with AAT, than in an "intact" prostate. It was also observed that 5ARI significantly inhibited tumor proliferation, but only early in the regrowth phase. A randomized phase II trial was done in which dut or placebo was given during the regrowth phase and a prostate biopsy was done to measure tumor proliferation. Methods: Eligible patients (pts) had metastatic, castrate-sensitive prostate cancer and had an intact prostate (no previous surgery or XRT). Treatment consisted of AAT for 8 months. Responding pts were randomized to receive dut (0.5 mg daily) or placebo during the regrowth phase. When serum T normalized, pts underwent a research biopsy of the prostate and then were resumed on AAT. Responding pts were then crossed-over to receive dut or placebo during the second regrowth phase. When T normalized, a second research biopsy was done and the pts resumed AAT. PSA levels were measured monthly to determine PSA doubling time (PSADT). Tumor proliferation was measured by Ki-67 index. Statistical analysis was by students t-test. Results: 21 pts were enrolled onto the study. 16 pts were randomized to dut vs placebo and 11 pts underwent prostate biopsies. Dut resulted in significant inhibition of tumor proliferation as measured by Ki-67 index compared to placebo (3.65 ± 1.7 vs 8.5 ± 2.3, p=0.001). PSADT during the regrowth phase was similar between the 2 groups. Dut was well tolerated without significant toxicities. Conclusions: The clincial observation of an early inhibitory effect of 5ARI on tumor proliferation during regrowth of a regressed (treated) prostate is novel and was similar to that observed in our animal xenograft model of IAAT. This suggests that using a 5ARI during the regrowth phase of IAAT and using T normalization as the trigger for resumption of AAT may result in improved efficacy of this treatment. This study was supported in part by NIH Grant P50 CA90386 (Prostate SPORE). Clinical trial information: NCT00668642.
Effect of simultaneous blockade of androgen and estrogen receptors on prostate cancer: In vivo study.
Authors: Nunez-Nateras Rafael , Ferrigni Erin N. , Gades Naomi M. , Castle Erik P. 
Published: February 2017

214 Background: In our preliminary in vitro studies, we have demonstrated evidence of enhanced apoptosis and inhibition of cellular proliferation in both hormone sensitive and castrate resistant prostate cancer (PCa) cell lines using a combination of an antiandrogen (Bicalutamide) and a selective estrogen receptor modulator (Raloxifene). The aim of this study was to study the effect of the administration of these two drugs in in vivo models of castrate resistant PCa. Methods: In vivo model consisted on NCr Nude: Mice bearing s.c. human prostate (PC3 cell line) xenografts. Based on the treatment received, mice were divided into 5 groups as follows: Group 1: No drugs (control); Group 2: Bicalutamide 50mg; Group 3: Raloxifene 60 mg; Group 4: Combined administration of Bicalutamide 50 mg and Raloxifene 60 mg; Group 5 Combined administration of Bicalutamide 150 mg and Raloxifene 120 mg. A total of 10 mice where included in each group. All drugs dosages were converted to their equivalent in the mice. Drugs were administered by gavage technique to the mice once per day for a total of 14 days. Results: As expected, Bicalutamide administered alone causes minimal inhibition without reaching statistical significance (Group 2: 0.34 g Vs Group 1: 0.40 g; p=0.073). Although Raloxifene causes some marked growth inhibition, its effect is not statistically significant (Group 3: 0.31 Vs Group 1: 0.40 g; p=0.062). Bicalutamide and Raloxifene, when administered in combination, induced prominent growth inhibition in PC3 tumors when compared to the control group (Group 4: 0.26 g Vs Group 1: 0.40 g; p=0.038). Growth inhibition is significantly more evident when the drugs dosages are increased (Group 5: 0.17 g Vs Group 1: 0.40 g; p=0.024). Conclusions: The simultaneous administration of Bicalutamide and Raloxifene appears to have a synergistic effect on tumor growth inhibition in PC3 xenografts. The pathway(s) responsible for this observation may be independent of the androgen receptor as PC3 cells are AR negative and still affected by the combination over the drugs administered alone. Research is warranted to identify these potential pathways.
Prognostic value of serum androgens, by ultrasensitive assay, in metastatic castration-resistant prostate cancer (mCRPC): Phase III trial data.
Authors: Ryan Charles J. , Molina Arturo , Li Jinhui , Kheoh Thian San , Small Eric Jay , Haqq Christopher M. , Grant Russell P , De Bono Johann Sebastian , Scher Howard I. 
Published: February 2017

22 Background: Serum testosterone (T) and precursors, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A4), may be prognostic of overall survival (OS) by identifying patients (pts) with varying dependency on androgen. To test this hypothesis, we investigated the relationship between the distribution of serum androgen concentrations measured by ultrasensitive mass spectrometric assays with OS, in pts with mCRPC treated in COU-AA-301, a randomized phase III study of abiraterone acetate (AA)(1000mg) plus prednisone (P) vs P. Methods: Pts were stratified by ECOG PS (0-1 vs 2), pain (present vs absent), prior chemotherapy regimens (1 vs 2), and type of progression (PSA only vs radiographic). Eligibility required baseline T ≤50 ng/dL. In a post hoc exploratory analysis, the effect of baseline serum androgen levels (T, DHEAS, A4) on OS (95% CI, months), stratified by quartiles of each androgen was determined. T, DHEAS, and A4 serum levels were measured using novel liquid-liquid extraction 1D or 2D-LC/tandem mass spectrometry ((LC)-LC-MS/MS) assays. Univariate and multivariate analyses using the Cox proportional hazards regression model were performed. Results: Baseline T levels were available from 97% of pts (93% with baseline T ≤15 ng/dL). Median OS increased in a step-wise fashion per T quartile, regardless of treatment (p<0.0001) (Table). Similar results were observed for DHEAS and A4. A positive association was observed in the multivariate analysis adjusted for treatment, other androgens, and lab parameters (LDH, HGB, ALKP, PSA; all p<0.0001). In AA and P-treated pts, respectively, the hazard ratio for OS (95% CI) comparing pts with baseline T above and below baseline median was 0.64 (0.53-0.77; p<0.0001) and 0.51 (0.39-0.67; p=0.0004). Conclusions: Baseline serum androgen concentrations as measured by an ultrasensitive mass spectrometric assay may be prognostic of OS in mCRPC pts and bear consideration as a stratification variable in phase III studies. Clinical trial information: NCT00638690. [Table: see text]
Cell-free DNA as a prognostic marker for response to taxan-based chemotherapy in patients with prostate cancer (CaP).
Authors: Kienel Alexandra , Porres Daniel , Piper Charlotte , van Erps Thomas , Heidenreich Axel , Pfister David J. K. P. 
Published: February 2017

228 Background: PSA is of limited value for predicting response to chemotherapy in castration resistant CaP patients. Nevertheless there is no better biological marker to control therapy response. cfDNA showed significant results in prostae cancer diagnostics and predicting recurrence after radical prostatectomy. We analyzed for the first time the role of cfDNA in castration resistant CaP predicting response to chemotherapy. Methods: We analyzed cfDNA isolated from an EDTA blood sample from 58 patients taken before initiating a first or second-line taxan based chemotherapy. 54 (93,1%), 8 (13,8%) and 3 (5.1%) of the patients had bone, lymph node or parenchymatous metastases respectively. Patients were selected according to PSA response after at least 3 cycles of chemotherapy to 30% (A), 50% (B) and 80% (C) decrease under chemotherapy. The concentration of cfDNA at the beginning of the therapy was correlated to PSA resonse at the end of the treatment. Results: Mean PSA and cfDNA concentration at therapy initiation was 391 (0,1-2663)ng/ml and 32,5 (8,93-136,63)ng/ml. In group A there was a trend of higher cfDNA concentration in the patients not achieving a PSA decrease of at least 30% (24,6ng/ml versus 35.5ng/ml) not reaching statistical significance (p=0,078). Conclusions: Patients with PSA decrease of less than 30% and PSA progression under chemotherapy have the poorest outcome. cfDNA is easy to investigate and is probably of importance to distinguish patients profiting from chemotherapy in a palliative setting. These data should be validated in a larger patient cohort.
Paradoxical significance of endorectal MRI (erMRI) response to neoadjuvant chemotherapy in patients with high-risk localized prostate cancer (HRLPC).
Authors: Galsky Matt D. , Xie Wanling , Nakabayashi Mari , Ross Robert W. , Fennessy Fiona M. , Tempany Clare M. , Choueiri Toni K. , Khine Krystal , Kantoff Philip W. , Taplin Mary-Ellen , Oh William K. 
Published: February 2017

23 Background: Intermediate endpoints are desirable to expedite the integration of perioperative systemic therapy in HRLPC. erMRI response has been utilized as an endpoint in neoadjuvant trials but has not been correlated with clinical outcomes. Methods: Data were pooled from two trials exploring neoadjuvant chemotherapy in HRLPC. Trial 1 explored docetaxel for 6 months and Trial 2 explored docetaxel plus bevacizumab for 4.5 months, both prior to radical prostatectomy (RP). erMRI was done at baseline and end of chemotherapy. erMRI response was categorized as PR (>50% decline in largest lesion), MR (25%-50% decline), or no response. PSA response was defined as >50% decline in PSA compared to baseline. Multivariable Cox regression was undertaken to evaluate the association between clinical parameters and biochemical recurrence (BCR). Results: Trial 1 enrolled 19 patients and Trial 2 enrolled 41 patients. Among the 60 evaluable patients in the combined analysis, 20 (33%) achieved a PSA response, 16 (27%) achieved an erMRI PR, and 24 (40%) achieved an erMRI MR. Median follow-up was 4.2 years and 33 of 53 evaluable (62%) patients developed BCR. Median time to BCR from RP was 26.2 months (95% CI 12.5-53.2 mos). The multivariable model is shown in the Table. Conclusions: Response by erMRI does not correlate with decreased likelihood of BCR in patients with HRLPC treated with neoadjuvant docetaxel and may be associated with inferior outcomes. While speculative, this unexpected result could potentially be explained by a higher likelihood of erMRI response in more highly proliferative tumors. These data do not support the use of erMRI response as an endpoint in neoadjuvant chemotherapy trials. [Table: see text]
Phase II trial of acai juice product in biochemically recurrent prostate cancer.
Authors: Kessler Elizabeth Riley , Su Lih-Jen , Yang Xiaoping , Lu Xian , Morales Diana , Anduha Mary , Chronister Nicole , Wacker Michael , Flaig Thomas W. , Glode L. Michael , Lam Elaine Tat 
Published: February 2017

230 Background: There are conflicting data as to the benefit of treating patients with biochemically recurrent prostate cancer (PCa). Plant derivatives, called “nutraceuticals” such as grape seed extract or milk thistle, have been studied as therapies for PCa based on their purported anti-inflammatory and anti-oxidant properties and low toxicities. Acai is a fruit rich in bioflavinoids shown to induce apoptosis in preclinical studies of PCa, leukemia and esophageal cancer. Anecdotal experience of two patients with falling prostate specific antigen (PSA) values while consuming acai juice prompted us to evaluate its efficacy in a clinical trial. Methods: This was a phase II Simon two-stage open-label single-arm single-institution study of the efficacy of Acai Juice Product in asymptomatic PCa patients with a rising PSA. Eligibility included lack of current hormone therapy, hormone sensitivity, and a PSA doubling time of >4 weeks. Patients consumed 2 oz of Acai Juice Product twice daily for 30 weeks, with a primary endpoint of PSA response. Secondary endpoints included PSA doubling time, PSA velocity, and duration of PSA response. Progression was defined as a rise of 25% from baseline PSA with absolute rise of 2ng/dL. Results: 21 patients were enrolled in the first stage of the trial. Median baseline PSA was 2.74 (range 0.38-36.88). Eighteen patients have completed therapy with 1 PSA response. In the one responder, the patient entered with a doubling time of 4 months and a PSA of 12.57, which was 2.15 at 36 weeks suggesting a prolonged and continued response. PSA either decreased or doubling time prolonged from baseline in 18 patients. PSA velocity was a negative rate of change per month in 4 patients. Conclusions: Acai juice did not produce enough PSA responses in this patient population to proceed beyond the first stage of this trial. However, PSA doubling time did slow in 85.7% of patients, and the one observed PSA response was sustained over at least 36 weeks at the time of data cutoff. Thus, we will analyze potential cellular signals through an M30 Apotosense ELISA assay and Human Cytokine 10-plex panel on patient samples with data available for presentation at the meeting. Clinical trial information: NCT01521949.
Utilization of local salvage therapy after primary radiotherapy for prostate cancer.
Authors: Tran Henry , Kwok Jaime , Pickles Tom , Tyldesley Scott , Black Peter C. 
Published: February 2017

231 Background: Early biochemical detection and subsequent slow progression of recurrent prostate cancer after primary radiotherapy permit the delivery of potentially curative local salvage therapy (LST). Several LST options are available, including cryotherapy, brachytherapy (BT), and radical prostatectomy (RP). We studied the rates at which patients are offered, and receive LST after failure of primary radiotherapy. Methods: Patients with localized prostate cancer who received primary radiotherapy with curative intent between 1999-2000 were identified in the British Columbia radiotherapy database. Data on clinicopathologic features, primary therapy, PSA kinetics, and salvage therapy were collected retrospectively. We excluded patients with T4 tumors, PSA >40, or age >72 years at time of primary therapy. Biochemical recurrence (BCR) was defined by the Phoenix criteria. Patients were also deemed radiation failures if salvage therapy was started without meeting criteria for BCR. Results: Out of 1785 patients treated with radiation, 1067 met the inclusion criteria. Of these, 257 experienced BCR. Five patients received LST (3 RP, 2 BT). LST was considered in 11 other patients, but 2 were not referred for urologic opinion, and 9 declined intervention. 60 patients were considered ineligible for LST: 43 due to suspected metastasis and 17 due to other comorbidities. LST was unlikely to be offered to 80 patients due to age >75 at time of BCR. 59 additional patients appeared to be eligible for LST but there was no evidence that it was considered in the medical record. ADT was started within 12 months of BCR in 118 patients, and after at least one year of observation in another 66. Conclusions: Few patients were considered for LST in the study period, and only 5 received it. This review of practice patterns reveals a lack of uniform monitoring and treatment strategies in this challenging patient population, and indicates a need for more collaboration between all treating physicians, as well as with tertiary care centers.
Experimental therapy of PC-3 and DU-145 human androgen-independent prostate cancers with targeted cytotoxic analog of somatostatin AN-162.
Authors: Rick Ferenc , Abi-Chaker Andrew , Szalontay Luca , Block Norman L. , Halmos Gabor , Schally Andrew V. 
Published: February 2017

236 Background: Management of castration-resistant prostate cancer (CRPC) is challenging because of limitations in efficacy of current therapies. Somatostatin receptors are expressed in human CRPC. Here we tested targeted somatostatin AN-162 analog consisting of doxorubicin (DOX) conjugated to octapeptide RC-121, acting as a carrier, in human androgen-independent prostate cancer cell lines in vitro and in vivo. Methods: Expression of mRNA for the five subtypes of the somatostatin receptor in PC-3 and DU-145 human prostate cancer cell lines was evaluated by RT-PCR. Somatostatin receptor binding was measured with radioligand assays. The effect of AN-162 and DOX on the viability of PC-3 and DU-145 cells was assessed by MTS assay. Nude mice bearing PC-3 and DU-145 tumors were randomized to 5 groups (control, AN-162, DOX, somatostatin analog RC-160 as a control, and DOX + RC-160). Treatment consisted i.v. injections of AN-162, DOX, RC-160, DOX + RC-160, or vehicle once a week for 4 weeks. Tumor volume was measured every week; the study lasted 28 days. The doses of AN-162 were equivalent to 1.45 mg/kg DOX (2.5 μmol/kg). Results: The PC-3 and DU-145 cell lines were positive for the five subtypes of the somatostatin receptor. AN-162 and DOX (0.10–10 µM) inhibited the proliferation of PC-3 and DU-145 prostate cancer cells in a dose-dependent manner. AN-162 exerted a stronger inhibition of proliferation than DOX alone, but in vitro the difference was not significant. In vivo, AN-162 significantly inhibited growth of both tumor models’ compared with the controls and the groups given equimolar doses of doxorubicin, RC-160, or doxorubicin unconjugated to RC-160. Conclusions: Our work demonstrates potent inhibitory effects of AN-162 on somatostatin receptor positive androgen-independent prostate cancers, which were greater than any of the components of AN-162. The mechanisms of action of targeted cytotoxic analog of somatostatin AN-162 in CRPC should be explored. Our findings suggest the possible use of AN-162 in patients with CRPC.