bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiandrogen withdrawal (AAWD) in patients (pts) with prostate cancer (PCa): Retrospective analysis of data from the South Australian Prostate Cancer Clinical Outcome Collaborative (SA-PCCOC).
Authors: Vatandoust Sina , Kichenadasse Ganessan , O'Callaghan Michael E , Kopsaftis Tina , Walsh Scott , Borg Martin , Karapetis Christos Stelios , Moretti Kim L 
Published: February 2017

240 Background: In 15-30% of pts with metastatic PCa who progress on Maximal Androgen Blockade (MAB), withdrawal of the antiandrogen agent (AAWD) and continuing the LHRH agonist alone, leads to PSA decreases of ≥50% and prolonged progression free survival. Here we describe patient and disease characteristics, treatment history and outcomes of pts who have been managed with AAWD. Methods: Data were obtained from SA-PCCOC (a longitudinal, observational registry of biopsy-proven PCa cases, throughout the Australian state of South Australia since 1998). Proportions were compared using a Chi squared test. A multivariable model used competing risks (Fine and Gray) and Cox proportional Hazards models to assess overall survival and Prostate cancer specific mortality (PCSM). Survival was calculated from the date of rising PSA for patients on LHRH and AA. Results: 140 pts were found to have MAB. Of these, 31(22.1%) had AAWD. In the AAWD group, median age was 81y (51-95). Age at diagnosis, Gleason score at biopsy and diagnostic PSA were not significantly different amongst the two groups. Treatment PSA was significantly lower in the AAWD group (20.55 (range 0.6-9,995) vs 50.50 (range 0.95-4378) p= 0.02). There was a significant association of AAWD with PCSM (sHR 0.35, 95% CI 0.16-0.76; p = 0.008). Also significant in the model was prior time on hormones (sHR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). There was also a significant association of AAWD with overall survival (HR 0.22, 95% CI 0.10-0.46; p <0.001). Again, prior time on hormones was also significant (HR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). Multivariate analysis was performed on data from 80 pts (60 pts omitted due to missing data). Conclusions: Pts in whom AAWD was used were older and had lower treatment PSA. In this small cohort, AAWD was associated with both reduced PCSM and overall risk of death. The time spent on MAB also appeared to be significant. This retrospective observational study may be subject to confounding, however the observation warrants further investigation in larger cohorts and in a prospective setting.
The impact of patient characteristics on voiding symptoms, irritative symptoms, and sexual function, following stereotactic body radiotherapy for prostate cancer.
Authors: Rana Zaker Hamid , Hong Robert , McRae Donald , Bernstein Gregory , Mordkin Robert , Nasr Nadim Munir 
Published: February 2017

245 Background: Urinary symptoms and sexual dysfunction are the two most common complaints following prostate radiotherapy. There is limited clinical data evaluating the impact of baseline patient characteristics on response to hypofractionated treatment. This study sought to evaluate how patient age and prostate size affects voiding symptoms, irritative symptoms, and sexual function, following stereotactic body radiotherapy (SBRT). Methods: This retrospective analysis includes 102 non-metastatic patients treated with SBRT at a single institution between May 2008 and September 2014. The course of radiotherapy consisted of 36.25 Gy (range 35–40) over 5 daily fractions. International Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) were recorded at baseline, 1, 3, 6, 9, 12, 18, 24, and 36 months after treatment. Results: Median patient age was 68 years old (range 47-88) and median prostate volume was 43 cc (range 18.7-170.7). Baseline IPSS irritative score, IPSS voiding score, and SHIM score were 5.34, 5.42, and 13.55. A statistically significant increase in voiding (7.02), irritative (7.21), and decrease in SHIM score (11.77) was observed after one month (p < .05). The IPSS irritative score and IPSS voiding scores returned to baseline in >90% of patients by 9 months and SHIM scores returned to baseline in >90% of patients by 2 years. Prostate size ≤ 50 cc showed higher baseline IPSS voiding and irritative resolution rates after 3 months (p < .05). Conclusions: While an increase in IPSS irritative score, and a decrease in SHIM score initially occurred, all symptoms return to baseline within three years. Age did not affect urinary or sexual dysfunction following radiotherapy. Patients with smaller prostate volumes had significantly better voiding and irritative outcomes when compared to larger volumes.
International survey of androgen deprivation therapy (ADT) for non-metastatic prostate cancer in 19 countries.
Authors: Liede Alexander , Hallett David , Hope Kirsty , Graham Alex , Arellano Jorge , Shahinian Vahakn B. 
Published: February 2017

248 Background: ADT is commonly used for non-metastatic (M0) prostate cancer (PC) patients as primary therapy for high risk disease, adjuvant therapy together with radiation, or for recurrence after initial local therapy. Intermittent androgen deprivation (IAD) is a more recently developed alternative strategy for providing ADT that is thought to potentially reduce adverse effects, but little is known about practice patterns relating to it. We aimed to describe factors related to physicians' ADT use and modality for M0 PC patients. Methods: A 45-minute online survey was completed by urologists and oncologists from 19 countries with high or increasing prevalence of M0 PC. Respondents were responsible for treatment decisions for M0 PC, and had ≥10 patients on ADT. ADT comprises gonadotropin agonist (GnRH) treatment or bilateral orchiectomy. Results: 441 physicians completed the survey representing 98,689 PC patients under their care, of which 76,386 (77%) had M0 PC. Of M0-PC patients, 38% received ADT (37% GnRH, 2% orchiectomy); among patients on GnRH, 48% received continuous ADT (≥6 months [mos]), 25% IAD, and 26% <6 mos (table). Highest rates of ADT were reported among oncologists (62%) and in Eastern Europe (68%). PSA levels (65%), Gleason score (52%), and treatment guidelines (48%) were the most common reasons for continuous ADT whereas PSA levels (54%), patient request (48%), and patient age (38%) were cited most frequently as the reason for IAD. Conclusions: This international comparison showed that ADT modalities are commonly used in the treatment of M0 PC patients, and that the decision to use ADT is influenced by high risk criteria (PSA and Gleason) and treatment guidelines. IAD use is prevalent and often driven by patient choice and PSA levels. [Table: see text]
Feasibility analysis of pathology and genetic yield from a prospective trial of tissue biopsies in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Jimenez Rafael E. , Sicotte Hugues , Barman Poulami , Sinnwell Jason P. , Eiken Patrick W , Atwell Thomas D , McMenomy Brendan P , Tan Winston , Wu Kevin , Bryce Alan Haruo , Ho Thai Huu , Pitot Henry Clement , Quevedo Fernando , Costello Brian Addis , Dronca Roxana Stefania , Moynihan Timothy J. , Wang Liewei , Qin Rui , Carlson Rachel , Kohli Manish 
Published: February 2017

249 Background: Evaluating tumor specific pathologic and genetic profiles in mCRPC stage is difficult due to the limited availability of mCRPC tissue. We describe findings from a prospective cohort study performed to obtain concomitant histopathology and genetic information in mCRPC. Methods: Patients with mCRPC initiating abiraterone acetate therapy underwent 2 serial (3 months apart) metastatic (met) site needle core biopsies (NCB1/2). Bone lesions were biopsied using 11-13G core needles and 18G core biopsy devices were used for non-osseous masses. Up to 4 cores were obtained at each biopsy with the 1st core (S1) sent for DNA sequencing, the 2nd (S2) for RNA sequencing, and the 3rd/4th (X3, X4) submitted for xenograft implantation. From each, 1-2 mm segments were separated and formalin-fixed for histopathologic examination (HPE). Results: A total of 54 patients, enrolled between June 2013 and July 2014, underwent 94 NCB (54 NCB1, 40 NCB2), rendering a total of 259 samples (94 S1; 75 S2; 59 X3 and 31 X4) of which 85 (32%) were positive (pos) for tumor by HPE. Positivity for tumor in S1, S2, X3, and X4 cores was 42%, 33%, 22%, and 19%, respectively. At least one core pos for met tumor was observed in 62% NCB1 and 52% NCB2 (overall 52/94; 56%). Met sites biopsied include bone (71), lymph nodes (18), liver (3), penile (1) and pelvic (1) soft tissues. HPE revealed met adenocarcinoma in 44/52, and poorly differentiated carcinoma in 8/52. Gleason grade applied to the met ranged from 3+4 to 5+5. 45/85 pos samples (53%) had > 50% tumor cellularity. Pos NCB in bone lesions was observed in 23/71 (32%), compared to 17/23 (73%) of non-bone sites (p=.0004). 85 S1 samples yielded DNA material, of which 66 (77%) had ≥10% tumoral DNA. 24 cases with negative HPE had ≥10% tumoral DNA; 7 cases with pos HPE had <10 tumoral DNA. In all, 76/94 (81%) NCB yielded tumor material either by HPE or DNA analysis. Conclusions: NCB of mCRPC is feasible and provides adequate tissue for pursuing HPE and sequencing studies. HPE of extracted material correlates with DNA sequencing data and provides complementary information on tumor features. Bone lesions yield significantly less tumoral material than non-osseous sites.
Optimal sequencing of docetaxel and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Maughan Benjamin Louis , Suzman Daniel L. , Nadal Rosa , Bassi Sunakshi , Schweizer Michael Thomas , Antonarakis Emmanuel S. 
Published: February 2017

252 Background: Currently there are multiple agents approved for the treatment of mCRPC based on prolongation of life. However, it is unclear what the optimal sequencing of these therapies is to maximize clinical benefit and survival. Here, we aimed to compare clinical outcomes among men with mCRPC who received docetaxel first followed immediately by abiraterone (doce-to-abi) or the opposite sequence (abi-to-doce). Only men that were treated with sequential therapy using these two agents (i.e. without intervening treatments) were included. Methods: A retrospective review of consecutive mCRPC patients treated at Johns Hopkins was conducted. A combined PFS (PFS = PFS1 + PFS2) was the primary endpoint, measured from the start of the first therapy (i.e. doce or abi) until the time of clinical/radiographic progression on the subsequent therapy (i.e. abi or doce). Overall survival (OS) from the start of the first therapy until death was the main secondary endpoint. Multivariable regressions were performed to determine whether one sequence was better than the other (doce-to-abi versus abi-to-doce) after adjusting for a number of baseline patient and treatment characteristics. Results: In total, 86 patients were identified that met our study criteria: 53 men received doce-to-abi and 33 men received abi-to-doce. PFS was longer in the doce-to-abi cohort: median 19.1 (95% CI 13.0–27.4) mo versus 10.4 (95% CI 9.1–11.5) mo (HR 2.6, 95% CI 1.5 – 4.5). OS was also superior in the doce-to-abi cohort: median 30.3 (95% CI 25.4–44.3) mo compared to 18.2 (95% CI 14.1–21.1) mo (HR 2.3, 95% CI 1.2 – 4.1). In multivariable analyses, superior outcomes were still observed in the doce-to-abi group with respect to PFS (HR 2.77, 95% CI 1.5–5.0, P=0.0008) and OS (HR 2.8, 95% CI 1.5–5.3, P=0.0016) after adjusting for Gleason score, baseline PSA and ECOG status at study initiation. Conclusions: This hypothesis-generating study seems to suggest superior PFS and OS in men with mCRPC receiving doce followed by abi (rather than the opposite sequence). These findings are in alignment with the results of the CHAARTED trial supporting earlier docetaxel use, but require prospective validation.
Cyberknife stereotactic radiotherapy for isolated nodal recurrence of prostate cancer.
Authors: Detti Beatrice , Bonomo Pierluigi , Giacomelli Irene , Cappelli Sabrina , Poggesi Linda , Franceschini Davide , Baki Muhammed Ali Muhammed , Carini Marco , Giulio Nicita , Serni Sergio , Baldazzi Valentina , Lucia Di Brina , Mancuso Anna , Eleonora Monteleone Pasquetti , Carta Giulio Alberto , Muntoni Cristina , Ciabatti Cinzia , Livi Lorenzo 
Published: February 2017

257 Background: We report a preliminary clinical experience in stereotactic body radiation therapy (SBRT) delivered using Cyberknife for isolated nodal metastases from prostate cancer. Methods: Between November 2011 and December 2013, 30 patients (39 lesions) were treated with SRT for recurrent prostate cancer with isolated nodal metastases. Prescribed doses and schedules of fractionation varied according to site of disease, ranging from 24 Gy in 1 fraction to 36 Gy in 3 fractions. Most commonly used schedules were 30 Gy in 3 fractions and 36 in Gy in 3 fractions on alternating days. Biochemical response, acute and late toxicity were analyzed. Results: At a median follow-up of 12 months (range: 2-24.9), reduction of PSA ≥ 50% was observed in 18 cases, reduction < 50% was observed in 7, while PSA was stable in 1 case and raised in 8 cases. At the time of analysis, among the 30 patients treated, 2 were dead for systemic disease; 12 patients experienced a relapse of disease in other sites and were treated with HT and salvage chemotherapy. Sixteen patients were still free of disease. In 24 cases, imaging evaluation three months after treatment was available. No in field recurrence was detected, CR was detected in three cases, PR in 14 and SD in 8 patients. The treatment with Cyberknife was well tolerated: one patient experienced G2 acute genitourinary toxicity. Late toxicity was evaluated in patients with more than 3 months of follow up and only one complained G1 proctitis. We did not observe any acute or late severe toxicity (≥G3). Conclusions: Our experience shows that SRT with Cyberknife for isolated nodal relapse from prostate cancer is a safe treatment, with promising results in terms of efficacy.
Dynamic changes of alkaline phosphatase as surrogate for best clinical benefit and overall survival during very early abiraterone therapy compared to PSA-changes in bone metastatic castration resistant prostate cancer.
Authors: Boegemann Martin , Mikah Phillip , Eminaga Okyaz , Herrmann Edwin , Papavassilis Philipp Marius , Hinkelammert Reemt , Semjonow Axel , Schrader Andres Jan , Krabbe Laura-Maria 
Published: February 2017

260 Background: Significant progress in treatment of metastatic castration resistant prostate cancer (mCRPC) has been made. Biomarkers to tailor therapy are scarce. To facilitate decision-making we evaluated dynamic changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and prostate specific antigen (PSA) under Abiraterone acetate (AA). ALP-Bouncing can be observed during very early AA-therapy. Methods: Men with bone mCRPC (bmCRPC) on AA 12/2009-01/2014 were analyzed. Dynamic ALP-, LDH- and PSA-changes were analyzed as predictors of best clinical benefit (BCB) and overall survival (OS) with logistic-regression, Cox-regression and Kaplan-Meier-analysis. Results: 39 pre- and 45 post-chemotherapy patients with median follow up of 14.0 months were analyzed. In univariate analysis failure of PSA-reduction ≥50% (PSA-red≥50%) and failure of ALP-Bouncing were the strongest predictors of progressive disease (p=0.003 and 0.021). Rising ALP at 12 weeks (ALP12), no PSA-red≥50% and no ALP-Bouncing were strongest predictors of poor OS, (all p<0.001). Kaplan-Meier-analysis showed worse OS for ALP12, no PSA-red≥50% and no ALP-Bouncing (p<0.001). In subgroup-analysis of oligosymptomatic patients all parameters remained significant predictors of poor OS, no PSA-red≥50% and ALP12 being the strongest (p<0.001). In multivariate analysis PSA-red≥50% remained independent predictor of OS for the whole cohort and for the oligosymptomatic subgroup (p=0.014). No patient with ALP-Bouncing had PD for BCB. Patients with ALP12 had no further benefit of AA. Conclusions: Dynamic changes of ALP, LDH and PSA during AA-therapy are associated with BCB and OS in bmCRPC. ALP-Bouncing occurring earlier than PSA-changes and rising ALP12 under AA may help to decide whether to discontinue AA.
Prostate cancer prognosis via integrative and co-localized glandular morphometry and immunofluorescent protein biomarker expression.
Authors: Donovan Michael J. , Khan Faisal M , Scott Richard , Fernandez Gerardo , Cordon-Cardo Carlos 
Published: February 2017

262 Background: Quantitative image analysis of both the prostate needle biopsy (PNB) and the radical prostatectomy sample (RPS) have proven to be robust and predictive for prostate cancer (PCa) prognosis. While metrics assessing morphology and protein biomarker expression separately have been published in prognostic risk prediction models, we sought to determine the performance of novel approaches which combine protein biomarker expression with the morphometry of the gland wherein they express. In order to assess robustness, we evaluated these metrics in both PNB and RPS cohorts. Methods: Novel quantitative biometric features were derived from computerized analysis of morphology and immunofluorescent (IF) biomarker expression in PCa images. A Bayesian probabilistic approach to co-locate and quantify IF biomarker expression within various glandular sub-types was developed. This permitted differentiable analysis of PCa biomarkers such as androgen receptor (AR) in high and low Gleason grade glands of the same patient. Performance in predicting significant clinical disease progression (including metastasis and death-of-disease) was assessed via the concordance index (CI). Performance was evaluated independently in a cohort of 326 PNB samples (median 8-year follow up) and a cohort of 373 RPS (median 5-year follow up). Results: In a univariate analysis, previously published glandular morphology features had a CI of 0.68 (PNB) and 0.76 (RPS). Quantitative AR had a CI of 0.67 (PB) and 0.72 (RPS). Novel metrics of integrative co-localization resulted in a significant increase in prognostic accuracy; CIs of 0.72 (PNB) and 0.83 (RPS). These features separately assessed AR expression depending on the multiple glandular sub-types within the tumor sample. Conclusions: Integrating quantitative image analysis of morphology and IF biomarker expression in the PNB and RPS outperformed previous quantitative metrics. Such robust and reproducible metrics may prove beneficial in improving risk stratification models for future treatment decision making.
Incidence of abiraterone acetate withdrawal response measured by PSA declines.
Authors: Chowdry Rajasree Pia , Lewis Brian E. , Ledet Elisa M. , Silberstein Jonathan L. , Sartor A. Oliver 
Published: February 2017

280 Background: The anti-androgen withdrawal effect is a well-described phenomenon occurring in patients with castrate resistant prostate cancer (CRPC) after discontinuing anti-androgen therapy. There is limited data on withdrawal responses after newer hormonal therapies such as Abiraterone Acetate (AA). Discontinuation of AA may lead to PSA declines but the frequency remains unclear. The goal of our study was to assess the incidence and duration of PSA decreases after stopping AA. Methods: We reviewed 51 patients with CRPC who had discontinued AA therapy at a single institution (6/2009-6/2014). PSA values were assessed before, during, and after stopping AA therapy. Response was defined as >50% PSA decline post-AA stoppage, with no additional therapy added. Results: From 51 patients treated with AA, only 22 (43%) were eligible for withdrawal response evaluation. A total of 29 patients (57%) were changed to alternate therapies too soon for withdrawal response evaluation. Of the 22 evaluable patients, AA withdrawal was seen in 2 patients (9%). The first patient had a 72% reduction in PSA upon discontinuation of AA, with PSA dropping from 330 (ng/mL) to 93 over 16 days. Previously administered dexamethasone was continued. He had been on AA therapy for 12 months. Time to next treatment was only 1 month so PFS was not ascertainable. The second patient had a 60% reduction in PSA after simultaneously discontinuing both AA and prednisone. His PSA declined from 25.1 to 9.9 over 2 months. He had received only 2 prior months of AA and prednisone and had a clear PSA rise during this therapy. PFS after AA and prednisone discontinuation was 3 months. Time to next treatment was 6 months. Neither patient who responded to AA withdrawal had a prior bicalutamide withdrawal response. Conclusions: PSA response to AA withdrawal is a known, but poorly understood phenomenon that occurs in a subset of patients. Larger studies with longer follow-up are needed to define the incidence of this observation. The potential role of glucocorticoids in this process needs additional elucidation.
Safety and efficacy of 2-weekly cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Clement-Zhao Alice , Auvray Marie , Verret Benjamin , Vano Yann Alexandre , Angelergues Antoine , Oudard Stephane 
Published: February 2017

284 Background: Cabazitaxel (C) administered on a 3-weekly dose schedule has shown a survival benefit in mCRPC patients (pts) pre-treated with docetaxel (D) with concerns about toxicity. We sought to evaluate safety and efficacy of a 2-weekly C schedule. Methods: At the EGP hospital from November 2013 to September 2014, 26 mCRPC pts for whom C was indicated (previously treated with D) received C 16 mg/m² on days 1 and 15 of a 4 weeks-cycle plus daily 10 mg prednisone, until completion of 6 cycles, disease progression, unacceptable toxicity or death. We analyzed safety with toxicity grade ≥ 3 and efficacy, including PSA response, time to biochemical progression (TTBP), radiological progression-free survival (rPFS) and overall survival (OS). Results: 26 pts received C in a 2-weekly schedule; full data are available for 20 pts. Median age was 66.5 years, 34.6% of pts were >70 years; 30.8% had ECOG PS 2; 47.8% had Gleason ≥ 8; 53.8% had lymph node metastases; 96.2% had bone metastases; none had lung or liver metastases. Median D cycles previously received were 6; respectively 80% and 88.4% of pts had received ≥ 2 hormonal manipulations and abiraterone acetate (AA). Median baseline hemoglobin was 12.2 g/dL, median PSA 104.6 ng/mL; 42.9% of pts had ALP ≥ 1.5N, 33.3% had LDH ≥ 1.5N. 4 pts (15%) had grade 1 thrombocytopenia at baseline, 1 (3.8%) had grade 4, reflecting diffuse bone marrow involvement. All pts received G-CSF in primary prophylaxis. Median number of C administration was 7, only 4 pts stopped C because of toxicity (2 for asthenia, 1 for febrile neutroepnia, 1 for thrombocytopenia). Toxicities grade ≥3 were: anemia 33.3%; thrombocytopenia 30%; neutropenia 23.8%; febrile neutropenia 5% (1 pt); no grade ≥3 diarrhea was observed. 45% (9 pts) achieved ≥30% PSA response and 30% (6 pts) ≥50% PSA response. Clinical, biological or radiological response occurred in 50% (10 pts). Median TTBP and rPFS were 3.0 months (2.2-3.6) and 4.2 months (2.8-7.4) respectively. Median OS was not reached at the time of data collection. Conclusions: 2-weekly 16 mg/m² C schedule has a manageable toxicity profile in heavily D and AA pretreated mCRPC pts, and warrants controlled prospective evaluation compared to the standard 3-weekly C schedule.