bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex vivo propagation and characterization of circulating tumor cell clusters from late stage prostate cancer patients.
Authors: Lim James , Ryan Charles J. , Adams Bruce , Hough Jeff , Chow Tianna 
Published: February 2017

314 Background: Cells shed by a tumor into the bloodstream upon metastasis present an opportunity to study the properties of these cells for biomarker discovery, drug development, and personalized therapy. Enrichment and expansion of circulating tumor cells (CTCs) in culture enables molecular characterization not readily available for rare cells. Here, we demonstrate the successful identification and culture of rare circulating tumor cell clusters from peripheral blood of metastatic castration resistant prostate cancer patients (mCRPC). Methods: The approach to isolate CTC clusters relies on nucleated cell enrichment via Ficoll-based centrifugation from 15 mL of peripheral blood. A collagen-based cell-binding substrate was used to capture cell clusters with preferential affinity for collagen (i.e. epithelial-like cells). Hypoxic and pressurized culturing conditions were used to maintain and propagate adhered CTC clusters. After 7 days in culture, immunofluorescence imaging, qPCR and/or mRNAseq were performed on CTC clusters that had formed colonies. Results: Blood samples processed within 3 hours from time of draw yielded a 25% success rate (4/16) for identifying PSMA+/EpCAM+/CD45- CTC colonies. Morphologically distinct CTC colonies cultivated at 1% oxygen and increased hydrostatic pressure (2 PSI) were positive for PSMA and EpCAM staining as observed via confocal microscopy, with individual colonies ranging from approximately 50 to 1000 in cell number. Colonies consistently revealed white blood cell contaminants (T-cells and dendritic cells, 10 to 30% of colony) that did not appear to perturb colony growth. CTC colonies were collected for qPCR analysis and mRNAseq via laser-capture microdissection and/or micropipetting. Genomic analysis revealed differential gene expression patterns between CTC colonies cultured from the same patient sample, with a subset expressing neuroendocrine like signatures (AURKA), stem cell markers (SOX2, OCT4), and immuno-oncology relevant markers (PD-L1, CTLA4). Conclusions: In conclusion, we show that viable CTCs are amenable to ex vivo culture, providing both functional and molecular insights into a sub-population of CTCs with propagating potential. The presence of T-cells and dendritic cells on CTC colonies warrants further investigation, and may provide unique insights into immune-tumor interactions. The culturing platform is currently being evaluated as a research tool for biomarker discovery and as a clinical tool for disease monitoring and treatment decision-making.
Treatment outcome of enzalutamide against castration resistant prostate cancer in Japanese cohort.
Authors: Shimomura Tatsuya 
Published: February 2017

318 Background: Enzalutamide (ENZ) is next generation anti androgen agent and prolonged survival both of before chemotherapy and after chemotherapy setting. In japan, it was approved to use against castration resistant prostate cancer (CRPC) from June 2014 and there is few report of treatment outcome of this agent in Asian countries. Prostate cancer is well known with the racial difference and then we investigated the outcome of enzalutamide in Japanese cohort. Methods: Total of 120 CRPC cases were introduced enzalutamide from June 2014 to July 2015 in our department and were investigated (before chemotherapy in 57 cases (group 1) and after chemotherapy in 62 cases (group 2) (One case was unknown)). We compared treatment outcome of these two groups and compared with AFFIRM and PREVAIL. Results: Comparing group 1, group 2 was younger in age, higher PSA, lower hemoglobin, higher ALP, higher LDH and higher CRP at starting ENZ. In terms of survival, OS of group 1 was better than group 2 (12 month survival rate were 0.95 and 0.58, respectively. p = 0.0088). However there was no significant difference in PSA response between Group 1 and 2 (Mean PSA decline was 51.7% and 50.1%, respectively. p = 7764). PSA response rate (PSARR) ≥ a50% was 57.8 % (group 1) and 58.1% (group 2)( p = 0.985). And PSARR ≥ a50% did not affect survival in both groups. (p = 0.1152 and 0.1288, respectively). When comparing group 1 with PREVAIL trial, survival rate was similar but PSA response was poorer. And when comparing group 2 with AFFIRM trial, survival rate was worse but PSA response was similar. Conclusions: Although this study was retrospective and follow up period was not long, we concluded that docetaxel treatment before enzalutamide affected survival rate, however that did not affect PSA response. And there were differences in outcome between this Japanese study and major randomized clinical trials (PREVAIL and AFFIRM).
High dose rate brachytherapy and external beam radiotherapy for local and locally advanced prostate cancer: Uni-institutional long term results.
Authors: Pellizzon Antonio Cassio Assis , Fogaroli Ricardo César , Silva Maria Leticia GOBO , Guedes Douglas , .Chen Michael , Gondim Guilhreme , Ramos Henderson 
Published: February 2017

319 Background: Dose-escalation is a determining factor that influences biochemical control (BC) of prostate cancer. High-dose rate brachytherapy (HDR) is one method for providing BC. Methods: Patients with histological diagnosis Gleason scored (GS), clinical stage T1 to T3a, no evidence of metastatic disease, prostate volume > 20cc < 60cc and initial PSA (PSAi) < 60 mg/ml treated from 1997 to 2005 with an Institutional Policy of treatment were evaluated. Results: There were 273 patients treated with this treatment combination at AC Camargo Cancer Center, Sao Paulo, Brazil. The median age and FU time were 64.7 and 10.3 years, respectively. Two hundred thirteen (78.0%) patients had FU longer than 5 years. Actuarial 10-year OS, CSS and BC were 89.8%, 63.6% and 71.8%, respectively. On univariate analyses GS < 7, clinical stage < T2b, low risk group (LR), absence adjuvant androgen deprivation (ADT), age > 65, PSAi < 10, localized EBRT and three dimensional HDR planning were associated with improved CSS and BC. PSAi and age were not favorable associated to BC. Multivariate Cox regression analyses confirmed LR, GS < 7, PSAi < 10, absence of ADT, age < 65 years as predictors of improved CSS and BC. For OS only LR was confirmed as predictive factor. Conclusions: The present data represents a unique single institution study at long FU for the given technique and the comparison with the current literature data confirms the excellent results achieved with this treatment combination.
Clinicians’ attitudes and preferences in choosing the first line drug for metastatic castration resistant prostate cancer (mCRPC): Preliminary results from a multicenter Italian study after the introduction of abiraterone acetate (AA) in the clinical practice.
Authors: Caffo Orazio , Ortega Cinzia , Sava Teodoro , Sacco Cosimo , Barni Sandro , Ermacora Paola , La Russa Francesca , Maines Francesca , Prati Veronica , Ruatta Fiorella , Veccia Antonello , Galligioni Enzo 
Published: February 2017

332 Background: For one decade, docetaxel (DOC) represented the only therapeutic option for mCRPC pts. Recently, AA and enzalutamide demonstrated a survival gain in first line setting. Lacking direct comparison with DOC and considering some differences in selection criteria of the pivotal trials, the choice between DOC and these hormonal agents, which have a quite different toxicity profile, is often driven by pts’ characteristics and feelings and by clinicians’ attitudes and preferences as well. To date, only AA is available in Italy, from September 2014, for the first line setting and the present study explores the attitudes and preferences of clinicians in choosing between DOC and AA. Methods: We retrospectively reviewed the clinical records of all mCRPC pts who received a first-line treatment in 5 Italian hospitals after the introduction of AA in the clinical practice. All pts were treated with AA 1,000 mg po + prednisone (PDN) 10 mg po daily or with DOC at the dose of 75 mg/sqm i.v. every three wks. For each pt we have recorded the pre-first line clinical history and the baseline characteristics. Results: From September 2014 to August 2015, we collected a consecutive series of 70 mCRPC pts: 49 received AA, 21 DOC. The median age was 74 yrs (range 46-90), 6% had visceral mets; 8% had a performance status 2; 47% had pain. Pts treated with AA were significantly older (75.8 vs 69.7 yrs; p = 0.002); received more previous hormone therapies (2.19 vs 1.76; p = 0.03), had a longer interval between first hormone therapy and the start of mCRPC first line (47.6 vs 21.2 mos; p = 0.01) and finally, were less frequently symptomatic (27% vs 67%; p = 0.02%). Conclusions: The present study is the first to explore the clinicians’ attitudes and preferences, in the routine clinical practice, in choosing the first line drug for mCRPC pts. From our preliminary data, it appears that some pts characteristics are important in driving the choice of the clinicians between AA and DOC. Data collection is ongoing in other Italian hospitals.
Management of metastatic prostate cancer patients in first line: Audit of real-life practices.
Authors: Turpin Anthony , Lemoine Laetitia , Berdah Jean François , Massard Christophe , Culine Stephane , Bauvin Eric , Penel Nicolas 
Published: February 2017

333 Background: Docetaxel and new hormonal therapies (NHT, abiraterone and enzalutamide) are both appropriate options in management of castration resistant prostate cancer (CRPCa) patients in first line therapy. There is no reliable guidance for choosing the best option. We have carried out an audit of real life practice among French physicians. Methods: We used an online software and built a questionnaire with 22 closed questions. With the help of French regional networks in Oncology and GETUG (Groupe d’étude des tumeurs urogénitales), this questionnaire has been sent to 481 physicians treating patients with CRPCa. All the answers were declarative, individual and, anonymized. The descriptive analysis was based on percentages and their 95% confidence intervals in the case of categorical variables, and the median and extreme values in the case of continuous variables. Results: From March to July 2015, 101 physicians (20,9%) completed the questionnaire: 49 medical oncologists, 29 radiation-oncologists, 21 urological surgeons and two other specialists from 22 French regions. The selection criteria for choosing docetaxel first were: presence of visceral metastases (78.2%), heavy tumour burden (68.3%), aggressive tumour disease (67.3%), short-term efficacy of the castration (65.4%). The selection criteria for the NHT were: long-term efficacy of castration (67.3%), higher age (67.3%), low tumour grade (56.4%) and absence of symptoms (53.5%). Under Docetaxel, 1st tumour re-assessment was done mainly after 3 (1-6) cycles, this assessment included PSA, thoraco-abdominopelvic CT and bone scintigraphy in respectively 96%, 68% and 58% of cases. Physicians assessed PSA level every cycle in 40.8% of cases and every 3 cycles in 41.8%. Under NHT, tumour reassessment was done mainly after 3 months of treatment (1-6) and included PSA, thoraco-abdominopelvic CT and bone scintigraphy, in respectively, 90%, 58%, and 62% of cases. Physicians assessed PSA level every 3 months in 50.5% of cases and monthly in 29.3%. Conclusions: This is the first descriptive study depicting real-life practice in French physicians treating CRPCa. Practices are heterogeneous. Guidelines for management of CRPCa are needed.
Prevalence of glucocorticoid use in prostate cancer patients.
Authors: Ellis Lorie , Behl Ajay , Xiao Yongling , Pilon Dominic , Lefebvre Patrick 
Published: February 2017

336 Background: The prevalence of glucocorticoid (GC) use increases with age consistent with age-acquired diseases such as chronic obstructive pulmonary and inflammatory conditions for which GCs are indicated. GCs are commonly used alone or in combination with other therapies for prostate cancer (PC), but studies of GC treatment patterns in treated and untreated PC patients (pts) have not been widely reported. This study aimed to describe the prevalence of GC use in PC. Methods: Patients with ≥ 2 PC diagnoses or ≥1 claim for a PC therapy and ≥ 12 months continuous eligibility between 1/2005 and 7/2014 were identified in Truven Health MarketScan databases. The index date for the treated cohort (i.e., pts receiving LHRH agonist, adrenal blocker, anti-androgen, chemotherapy, oral mCRPC therapy, surgery or radiation) was defined as the date of the most recent PC treatment. The index date for the untreated cohort (i.e., with PC diagnosis but without PC treatment) was defined as the most recent PC diagnosis date. GC use was summarized post-index, for treated and untreated PC pts using descriptive statistics. Baseline demographics and comorbidities were also reported. Results: A total of 321,113 eligible PC pts were identified. Of these, 223,953 (70%) were untreated and 97,160 (30%) pts were treated with a PC therapy. Untreated pts had a mean age of 68 years and a mean Quan-Charlson comorbidity index (CCI) of 1.7 and treated pts had a mean age of 71 years and a mean CCI of 1.8. Approximately 30% of untreated pts and 40% of treated pts received GCs during the observation period. Among treated pts, 70% of pts receiving chemotherapy and 88% of pts receiving oral mCRPC therapies (abiraterone and enzalutamide) had evidence of GC use. Median daily GC dose was 24 mg in untreated and 20 mg in treated PC pts. Median daily GC dose was 14mg in chemotherapy-treated pts and 10 mg in pts treated with oral mCRPC therapies. Conclusions: GC use is common in pts with PC, including in those not receiving PC therapies. Median daily GC dosages tended to be lower in pts treated with PC therapies than in those without PC therapies. GC use in PC pts may be related to non-PC comorbidities which should be made known to PC physicians.
Abiraterone acetate in metastatic castration-resistant prostate cancer after chemotherapy: A “real life” retrospective analysis of progression-free (PFS) and overall survival (OS) according to duration of androgen deprivation therapy.
Authors: Fabbri Maria Agnese , Marchetti Paolo , Cortesi Enrico , Santini Daniele , Gamucci Teresa , Angelini Francesco , Sperduti Isabella , Longo Flavia , Pellegrino Arianna , Milano Annalisa , Quadrini Silvia , Mancini ML , Primi Francesca , Nelli Fabrizio , Ratta Raffaele , Ruggeri Enzo 
Published: February 2017

337 Background: Abiraterone acetate (AA) is a potent, selective androgen (CYP17) biosynthesis inhibitor, which showed to improve overall survival in mCRPC pts progressing after docetaxel. Few data are available concerning the clinical outcome of AA treatment in mCRPC in terms of the duration of prior androgen deprivation therapy (ADT). In this retrospective analysis we assessed the PFS and OS in patients affected with mCRPC according to the duration of ADT. Methods: We retrospectively reviewed the clinical data of pts affected by mCRCP progressive after chemotherapy who received AA (1000 mg/d) plus prednisone (5 mg/twice daily). A total of 189 pts were included in the analysis, 71 received AA with ADT duration<12 months (Group A) and 118 received AA with ADT duration ≥ 12 months (Group B). Patient characteristics’ in the two treatment groups (A VS B) were: median age: 75 vs 69 years, Gleason score ≥7: 96% vs 92%; median PSA at AA start 47 (range 36-2130) vs 32 (range 85-2100), No of metastatic sites: 1 : 70% vs 75% ;bone only 50% vs 47%, visceral disease alone: 3% vs 5%; symptomatic disease : 58% vs 40% (p 0.02); median number of prior docetaxel courses: 6 in both groups; second-line cabazitaxel:14% in both groups, bisphosphonates concomitant treatment 66% vs 52.5% (p:0.21). No difference in radical prostatectomy or radiation therapy were evidenced Results: At a median follow-up of 8.5 months (range 1-51) the median progression-free survival (PFS) and the median overall survival (OS) were 10 months (95% CI: 7-13) and 26 months (95% CI: 17-35) respectively in all mCRPC. Group B patients had a statistically significant longer PFS (13 vs 7 months, p=0.009) and OS (28 vs 17 months, p=0.03 months). The median decrease in the PSA level > 50% was observed in 50 % of pts in both groups. AA was well tolerated and no relevant toxicity were observed Conclusions: This retrospective analysis showed a benefit in terms of PFS and OS in group B patients, our finding might be related to the best prognostic factors of patients in group B (less symptomatic).
Time to next line therapy after initiation of sipuleucel-T in metastatic castration-resistant prostate cancer patients.
Authors: Luu Dai , Goldstein Leanne , Twardowski Przemyslaw 
Published: February 2017

341 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for patients with symptomatic or minimally asymptomatic metastatic castration-resistant prostate cancer based on prolongation of overall survival. We sought to retrospectively analyze the type and time to next-line therapy after the initiation of Sipuleucel-T (Sip-T) in the era of multiple new other therapeutic compounds that became available since approval of Sip-T to better understand the context of utilization of this immunotherapy in the current era. Methods: We performed a retrospective analysis of 53 patients with metastatic prostate cancer (PC) who have been treated with Sip-T at The City of Hope Medical Center between September 2010 and April 2013 and subsequently received another therapy. Variables included age at Sip-T treatment, Karnofsky Performance Score (KPS), Gleason score at diagnosis, extent of metastatic disease (limited or extensive), and white blood cell (WBC) count pre and post (Sip-T). PSA was measured at six time points (3 pre and 3 post Sip-T) and these were analyzed using a mixed linear regression model. A Cox Proportional Hazard model was used to examine predictors of time in days to next therapy as a function of the above variables including mixed model slopes of PSA. Results: Kaplan – Meier estimated median time to next treatment among the 53 patients was 122 days (95% CI, 86-177 days) and was significantly predicted by slope of PSA from the mixed model (HR = 25.883, p < .0001), WBC post therapy (HR = 1.352, p = 0.0017), and age at Sip-T (HR = 1.044 p = 0.0492). KPS, Gleason score, pre Sip-T WBC, and the extent of metastatic disease were not predictive. Most patients had abiraterone acetate for next treatment (n = 32, 58.2%). Other treatments included docetaxel (n = 5, 9.1%), orteronel with prednisone or prednisone alone (n = 12, 21.8%), and others (n = 6, 10.9%). Conclusions: In our experience median time to subsequent therapies was shorter than reported in pivotal Phase III study. Shorter time to post-Sip-T therapy was associated with older age, higher levels of WBC post-Sip-T therapy and more rapid rate of increase in the PSA level.
Does abiraterone withdrawal syndrome (AWS) exist also in metastatic castration-resistant prostate cancer (mCRPC) first-line setting?
Authors: Maines Francesca , Caffo Orazio , Trentin Chiara , Veccia Antonello , Galligioni Enzo 
Published: February 2017

344 Background: AWS is a recently phenomenon observed in mCRPC patients (pts) characterized by a PSA reduction with or without objective response after abiraterone acetate (AA) discontinuation. This syndrome has clinical features similar to antiandrogen withdrawal syndrome and was described in pts who treated with AA in the post-docetaxel setting. At the best of our knowledge, to date AWS was never described in chemo-naïve mCRPC pts. Methods: We retrospectively reviewed clinical records of mCRPC pts treated with first-line AA at our Institution. All pts were treated with AA 1,000 mg + prednisone (PDN) 10 mg po daily; the treatment was continued until progression disease (PD) which required an imaging confirmation too. After PD, we also discontinued the PDN administration. For each pt we recorded pre and post-AA clinical history, treatment details and outcomes. AWS was defined by PSA reduction ≥ 25% compared to the AA-end values observed in the first month after AA stop. Results: From September 2014, eight pts received first-line AA and, to date, 6 patients (75%) who discontinued the treatment due to PD are evaluable for AWS occurrence. We observed an AWS in 2/6 (33.3%). The first patient, a 76 year-old man, who experienced a PD after 12 wks AA treatment, had a 69% reduction in PSA with PSA dropping from 60 ng/mL to 19.47 ng/mL after about 30 days from the discontinuation. The second patient, 83 years old, treated with AA for 12 weeks, had a reduction in PSA from 112.2 ng/mL to 55 ng/mL at one-month (51% reduction) and to 35.36 ng/mL at two months (68.5% reduction) after AA and PDN discontinuation; after 9 wks the AWS is still ongoing. Conclusions: Notwithstanding the limits of the small sample size, our data shows for the first time that AWS can be observed also in mCRPC patients receiving AA as first-line treatment. Larger observations are needed to establish frequency and clinical role of this phenomenon. Although pathogenetic mechanisms and predictive factors are still unclear, AWS may represent a possibility to delay the second line start for mCRPC pts.
To assess the clinical effect of radium 223 (Ra223) in patients with progressive symptomatic bone metastases on a background of metastatic castrate resistant prostate cancer (mCRPC).
Authors: Hague Christina J. , Fisher Charlotte , Wylie James , Choudhury Ananya , Elliot Tony , Tran Anna , Coyle Catherine , Conroy Ruth , Logue John P. 
Published: February 2017

347 Background: Ra223 is the first radiopharmaceutical shown in the ALSYMPCA trial to improve survival and achieve a tolerable safety profile in patients with symptomatic bone metastases. It remains unclear as to where Ra223 is best placed in the treatment pathway of CRPC. We assessed the effect of Ra223 in mCRPC in terms of biochemical and clinical response. Methods: Retrospective analysis of mCRPC patients treated with Ra223 via CDF between Dec 2013-May 2015. Clinical benefit assessed by pain response. Toxicities graded as per CTCAE V 4. Results: 58 patients, median follow up 11.6 (1.0-18.1) months. Median age 71 (54-84); median WHO PS 1 (0-2). 58 patients received 50kBq/kg, median number of cycles 5 (1-6). 43% and 33% completed 6 and 3 cycles respectively. Median number of previous treatments 3 (1-6). 52%, 17% and 5 % received prior Docetaxel, Bisphosphonates and Strontium respectively. Median time from radiotherapy for symptomatic bone metastases to initiation of Ra 223 was 433 days. Incidence of Grade (G) 3/ 4 events 5% ; 2% G3 anaemia, 3% G3 neutropenia and 0% G3 thrombocytopenia. No treatment related deaths. 5% developed a skeletal related event, mean time of development from completion of Ra223 was 218 days. Median PSA pre v post treatment was 225 and 418. Median ALP (Alkaline Phosphatase) pre v post treatment was 292 and 138. Median Hb (Haemoglobin) pre v post treatment was 118 and 103. 50% patients had a clinical response. Whilst no significant association was seen between clinical benefit and change in PSA (p 0.973) or ALP (p 0.455) across this cohort, a number of patients had a sharp increase in PSA and decrease in ALP with no clinical benefit and clinical benefit respectively. 36/58 (62%) are alive; 16/58 (44%) alive with progressive disease. Median PFS 7.23 months (95% c.i. 5.73, 7.93) and median OS 8.33 months ((95% c.i. 5.65-13.50). Conclusions: Ra223 is safe and effective in pre-treated mCRPC patients. PSA response is not clinically meaningful whereas ALP may be a useful adjunct in measuring response. The optimum sequence is yet to be defined but better selection and earlier use in patients with predominant bone only disease should be considered.