bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of new systemic therapies on overall survival (OS) of patients (pts) with metastatic castration resistant prostate cancer (mCRPC) in a hospital-based registry.
Authors: Francini Edoardo , Gray Kathryn P. , Shaw Grace , Evan Carolyn , Hamid Anis , Perry Caitlin E , Kantoff Philip W. , Taplin Mary-Ellen , Sweeney Christopher 
Published: February 2018

203 Background: From 2004 to 2009, mCRPC treatment options were limited to docetaxel (D), mitoxantrone, first generation anti-androgens (AA), estrogens, steroids, and ketoconazole, with only D showing OS benefit. Since 2010, five new therapies prolonged OS and were approved for mCRPC: sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, and radium 223. We sought to assess the aggregate impact of new therapies on OS. Methods: We used the DFCI CRIS database to identify cohorts of pts who developed mCRPC between 2004-2007 (cohort A) and 2010-2013 (cohort B). Therapies for mCRPC in each cohort were annotated. Given the median follow-up (FU) was 10.6 years (yrs) in cohort A and 4.6 yrs in cohort B, we evaluated OS, defined as time from mCRPC per PCWG3 criteria to death from all causes or last follow-up visit within 5 yrs (truncated OS). Kaplan-Meier method estimated the time to events distribution with median (95% CI). Cox proportional hazards model evaluated effects of treatment groups on disease outcomes with estimates of hazard ratio (95% CI). Results: Of the 583 pts identified, 317 (54%) were in cohort A and 266 (46%) in cohort B. Pts in cohort B had a significantly longer median OS (p<0.001), a 5-yr OS of 26% vs. 10%, and a 31% reduced risk of death compared to cohort A (HR=0.69; 95% CI, 0.57-0.83) (see Table). On multivariable analysis, adjusting for prior local Rx, ECOG PS, and the number of agents received, longer OS is confirmed associated with cohort B vs. A and also with ECOG PS status 0 vs. 1, number of agents received 5-12 vs. ≤3. Conclusions: Using the DFCI prostate cancer database, therapies approved for mCRPC since 2010 showed a modest impact on OS, with a median improvement of 6 months. There was a more substantial effect on long term survivors with 2.6 fold increase of 5-yr OS. [Table: see text]
Onset and maintenance of testosterone suppression in four pivotal trials of subcutaneously administered leuprolide acetate formulated with in-situ forming polymeric delivery technology.
Authors: Twardowski Przemyslaw , McLane John A. , Atkinson Stuart , Boldt-Houle Debbie , Sartor A. Oliver 
Published: February 2018

205 Background: Subcutaneously administered leuprolide acetate (SC-LA) formulated with in-situ forming polymeric delivery technology has demonstrated efficacy in suppressing testosterone (T) levels to achieve and maintain medical castration in patients with advanced prostate cancer (PCa). Increasing evidence suggests that reaching and sustaining the lowest T possible is desirable and correlated with disease specific survival. Data was pooled from four pivotal trials to determine the onset and maintenance of T levels at or lower than castration with SC-LA treatment. Methods: Eugonadal PCa patients received either 7.5 (6 doses), 22.5, 30, 45 mg (2 doses each) injections of SC-LA lasting 1, 3, 4, or 6 months, respectively, in 4 open-label, fixed-dose, pivotal trials. Serum T levels were assessed at screening, baseline (Day 0), and at least once per week throughout the studies. Target T levels were 50, 20, and 10ng/dL. The time when T crossed target level was extrapolated using the following formula: (target T – post-target T) / (pre-target T – post-target T) x (post-target date – pre-target date) = estimated days between crossing target T and post-target measurement Results: In the pooled population (N=437), median onset of T ≤50, ≤20, and ≤10ng/dL were 21 days, 28 days, and 35 days, respectively. Once the target T level was achieved, the mean proportion of time that patients maintained T suppression below each target level was 100% for T≤50 ng/dL, 94-99% for T≤20ng/dL, and 66-85% for T≤10ng/dL (Table). Conclusions: SC-LA achieved rapid onset of T≤50ng/dL in 3 weeks, T≤20ng/dL in 4 weeks, and T≤10ng/dL in 5 weeks. SC-LA maintained consistently low T levels, with over 66%, 95%, and 100% of the treatment period remaining below 10, 20, and 50 ng/dL respectively. This T suppression profile may have relevance for improved patient survival and extended time to disease progression. [Table: see text]
Safety and efficacy of abiraterone acetate (AA) in patients aged 75 or more with metastatic castration-resistant prostate cancer (mCRPC) in both pre-chemotherapy or post-chemotherapy settings: Real-life experience from thirteen Italian centers.
Authors: Sirotova Zuzana , Courthod Giulia , Tartarone Alfredo , Caffo Orazio , Maines Francesca , Bertuccelli Maurizio , Morelli Franco , Numico Gianmauro , Guglielmini Pamela , Fornarini Giuseppe , Prati Veronica , Palesandro Erica , Ortega Cinzia , Mosca Alessandra , Miraglia Stefania , Perrone Valentina , Fea Elena , Allegrini Giacomo , Mozzicafreddo Alessandro , Schena Marina 
Published: February 2018

209 Background: Prostate cancer affects mainly elderly patients (pts) that have different comorbidities. AA is a selective androgen synthesis inhibitor that showed the efficacy in either chemotherapy (CT) naive pts or those pretreated with docetaxel. Its oral administration and good tolerability make it a manegeable treatment for elderly mCRPC pts. Methods: We collected retrospectively data regarding mCRPC pts aged ≥75 years treated with AA in 13 Italian Centers since April 2013. The median age was 79 years (r. 75-90) with 48% of pts being octagerians. Post CT pts had more extensive disease, higher baseline PSA and ECOG PS. Nearly all the pts had comorbidities, the most frequent being hypertension present in 146 pts (58%), 43 pts (17%) had diabetes type II. We evaluated duration of the AA treatment, overall response rate (ORR), 50% PSA decline, time to progression (TTP) and overall survival (OS). We reported all toxicities observed. Results: A total of 252 pts ,147 pre treated with docetaxel and 105 chemo naive, were included. Median duration of treatment with AA was 8,6 months in post CT and 11,5 in CT naive pts. ORR was 35,3% in pre docetaxel and 27,4% in post docetaxel group. 64 pts (65%) and 51 pts (46%) obtained 50% PSA reduction in pre and post docetaxel group, respectively. Median TTP was 8,6 in post docetaxel and 11,9 in CT naive pts. We observed a median OS of 13,8 months in post CT group while for CT naive pts data were not yet mature. AA was well tolerated with only 8 pts (3,2%) who discontinued treatment due to toxicity, while in 4 pts (1,6%) temporary dose reductions were performed. The most frequent G3 toxicities were hypertension and liver toxicity with 4 pts (1,6%) and 5 pts (2%), respectively. After progressing on AA, 85 pts (34%) received at least one subsequent treatment. 40 pts (15,9%) are still on treatment with AA. Conclusions: Even if almost all the pts reported comorbidities at AA start and 72 pts (28,6%) had PS ECOG 2, only a small proportion of them discontinued the treatment due to toxicity confirming that AA is well tolerated and efficient treatment also for elderly patients.
Functional outcome and quality of life in patients undergoing salvage radical prostatectomy (SRPE).
Authors: Pfister David , Pullankavumkal Jasmin , Haidl Friederike , Zugor Vahudin , Kohl Tobias , Porres-Knoblauch Daniel , Heidenreich Axel 
Published: February 2018

212 Background: Salvage radical prostatectomy is one option for patients with locally recurrent disease with proven long term oncologic control. There are concerns about worse functional results due to fibrotic tissue after radiotherapy and patients are treated with palliative systemic androgendreptivation. We retrospectively analyzed continence and quality of life in patients undergoing SRPE. Methods: After biopsy proven local recurrent prostate cancer 138 patients were offered SRPE and extended lymphadenectomy. Continence and quality of life had been collected before 6 and 12 months after surgery. Validated questionaires with ICIQ and EORTC qlq 30 had been used. Results: Präoperatively at 6 monts and 12 months the feed back was available in 93, 84 and 82 patients respectively. Präoperatively there was no or mild incontinence in 38(40.8%), moderate in 33 (35.5%) and strong incontinence in 22 (23.7%) of the patients. There is a significant decrease in the rate of continence after 6 and 12 months to no or mild in 19 (23.1%), moderate in 19 (23.2%) and strong incontinence in 44 (53.7%) of the patients. In 5 patients an artifitial sphinkter was implanted. Quality of life did not change significantly before and 12 months after surgery. Median value of Question 30 was 6 and five respectively. Conclusions: Patients need to be informed about a worse functional outcome and the potential need for further surgical interventions as artificial sphinkter implantion compared to primary radical prostatectomy. Quality of life seems to be affected only moderatly. Nevertheless there is already a rather high rate of any incontinence before surgery that needs to be taken into account.
68-Ga-PSMA-PET in the diagnosis of local recurrent disease after radiotherapy in patients with prostate cancer.
Authors: Pfister David , Schmidt Matthias , Kohl Tobias , Porres-Knoblauch Daniel , Heidenreich Axel 
Published: February 2018

213 Background: For planning salvage procedures in recurrent prostate cancer accurate diagnostic tools are needed. Till now in patients suspicious for isolated local recurrent cancer invasive biopsy was needed. 68-Ga-PSMA-PET is frequently used to identify even small metastatic deposits. We analyzed the diagnostic value to identify local recurrence in patients after radiotherapy undergoing salvage radical prostatectomy, sRPE. Methods: We retrospectively reviewed patients undergoing sRPE with 68-Ga-PSMA-PET as preoperative staging. All patients underwent sRPE and extended lymph node dissection. Sensitivity, Specificity, pos and neg predictive value had been calculated per patient and per prostate lobe. Results: 37 patients with preoperative 68-Ga-PSMA-PEt could be identified. In all but one at least in one lobe PSMA staining could be identified. Mean tumor volume per prostate lobe was 6.22 (0.1-24)ml. Sensitivity, Specificity, neg and pos predictive value per lobe is 80%, 75%, 32% and 96%. Sensitivity to identify cancer recurrence per person irrespective of the side is 95% with a pos predictive value of 100%. Conclusions: 68-Ga-PSMA-PET seems to have a very high diagnistic value to identify local recurrence after radiotherapy. After validation of our experience an invasive biopsy to proof cancer recurrence might be spared.
Myeloid and plasmacytoid dendritic cell vaccinations for castration-resistant prostate cancer patients.
Authors: Westdorp Harm , van Oort Inge M. , Creemers Jeroen H.A. , Schreibelt Gerty , Mehra Niven , de Goede Anna L. , Hulsbergen-Van De Kaa Christina , Figdor Carl G. , Witjes Alfred , Aarntzen Erik H.J.G. , Mus Roel D.M. , Gotthardt Martin , Barentsz Jelle O. , De Vries Jolanda , Gerritsen Winald R. 
Published: February 2018

219 Background: Immunotherapy has limited applicability in the treatment for CRPC patients (pts). An advantageous effect of immune stimulation in CRPC pts was shown by sipuleucel-T, a dendritic cell (DC)-based vaccine. Vaccination (Vac) strategies using myeloid and plasmacytoid DC (mDC and pDC) may improve immunological and clinical outcome of CRPC pts. Methods: In this randomised phase II trial, 21 HLA-A*02.01 positive chemo-naive CRPC pts received maximally 3 cycles of 3 Vac consisting of mDC, pDC or combined mDC + pDC, loaded with tumour-associated antigens (MUC1, NY-ESO-1, and MAGE-C2). Radiological responses were assessed on 68Ga-PSMA PET-CT scan for RECIST 1.1, iron oxide-enhanced MRI scan of lymph nodes and MRI bones. Primary endpoint is the immunological response after DC Vac. Secondary endpoints are safety, feasibility, PSA responses, radiological PFS and OS. Results: All vaccine types were well tolerated, 14 out of 21 pts had grade 1-2 toxicity. There was no grade 3-4 toxicity observed. After 6 months, no radiological disease progression was observed in 62% (13 out of 21 pts). At 12 months follow-up, 45% of patients (5 out of 11) showed stable disease. Mean radiological PFS was 6.1 months (95% CI: 3.7-8.6). No difference between the groups was observed. One patient had a partial radiological response and a significant drop in PSA level from 120 ng/ml to 3.4 ng/ml. Radiological stable pts showed preVac a PSA doubling time of 6.9 months (95% CI: 3.8-10.1), at 6 months after randomisation this was 13.1 months (95% CI: 4.9-21.2). Over a median follow-up period of 12.0 months, median OS was not reached. Primary immunological outcome will be presented. Conclusions: Myeloid and plasmacytoid DC Vac is feasible and safe in early CRPC pts, with preliminary results hinting at possible clinical efficacy. This warrants further study. Clinical trial information: NCT02692976.
Detection of germline deleterious mutations in prostate cancer patients with use of a validated 30-gene sequencing assay.
Authors: Vlachostergios Panagiotis J. , Molina Ana M. , Beltran Himisha , Nanus David M. , Tagawa Scott T. 
Published: February 2018

223 Background: Germline DNA repair gene alterations in men with metastatic prostate cancer (PC) unselected for family history of malignancy occur in a greater frequency compared to localized PC and the general population. We hypothesized that assessing heritable alterations in a broader panel of high-susceptibility genes, may be relevant for detecting familial associations with other cancers in PC patients. Methods: We examined a cohort of 52 PC patients (median age 60, range 45-80) with histologically confirmed PC (17 localized, 35 metastatic). Germline DNA was isolated from blood lymphocytes or buccal swabs, and targeted next-generation sequencing was conducted with use of a previously validated panel of 30 genes associated with an elevated risk for common cancers (Color Genomics). As a reference for gene aberration frequencies we used the Exome Aggregation Consortium (ExAC) database. Results: The majority of patients (48/52, 92%) had a positive family history of cancer in any relative. Nine deleterious pathogenic mutations were identified in germline DNA samples from 8/52 (15%) patients, affecting the following genes: APC (n = 2, 3.8%), BRCA2 (n = 2, 3.8%), CHEK2 (n = 3, 5.7%), ATM (n = 1, 1.9%), RAD51D (n = 1, 1.9%). APC mutations were significantly more frequent in our cohort compared to the ExAC database (0.3%, p < 0.001). The frequency of DNA repair gene alterations (7/52, 13.5%) was also significantly higher compared to the ExAC database (0.3%, p < 0.001). The median overall survival (OS) between patients with and without germline gene alterations was similar (81.5 versus 74 months, respectively). The presence of heritable gene alterations from the 30-gene panel was significantly more frequent in patients with a positive family history of any cancer (p < 0.001) or prostate, breast, ovarian cancer (p = 0.001) in a first degree relative. Conclusions: The use of a targeted panel of high-susceptibility cancer-associated genes in PC not only confirms the enrichment of germline mutations in men with PC. It can also reveal associations of PC with other cancers which may portend implications for treatment and prognosis.
Dexamethasone in pretreated men with metastatic castration-resistant prostate cancer (mCRPC): A prospective study.
Authors: Baciarello Giulia , Hamilou Zineb , Chebib Ralph , Albiges Laurence , Fuerea Alina , Loriot Yohann , Massard Christophe , Colomba Emeline , Di Palma Mario , Escudier Bernard , Fizazi Karim 
Published: February 2018

239 Background: Corticosteroids have demonstrated activity in men with mCRPC. Previous data suggested that dexamethasone (D) can induce PSA responses when introduced after progression in mCRPC men receiving AR axis targeted drugs and/or prednisone (P). Methods: We prospectively tested P to D switch or D addition at PSA progression in 43 men with mCRPC with PSA progression and stable clinical disease. Baseline characteristics of the patients, time to castration resistance (TTCRPC), response to previous treatment, PSA response during D 0.5 mg/day and biochemical progression-free-survival (bPFS) after D initiation were recorded. Results were assessed using the Fisher’s exact test to compare variables. Results: Data from 43 patients were prospectively collected: 29 (67%) had been treated with abiraterone (AA) + P, 11 (26%) with enzalutamide (ENZ) and 3 (7%) with other treatments. At progression, 27 patients (63%) switched from P to D while continuing AA, 9 (21%) stopped their treatment and began D alone and 7 (21%) received D added to ENZ. Median age was 75 (70-79.5) and median bPFS with previous treatment was 17 months (6.75-22.25). After D initiation, 28% of patients had a PSA decrease ≥ 30% and the median bPFS was 4 months (2-6). The median bPFS was non-statistically different in patients with previous response to AR axis targeted drugs ≥ 6 months (4 [2-6] vs 1 [1-2] months; p-value = 1) and in those with TTCRPC ≥12 months (4 months [2-7.5] vs. 2 [1.5-2]; p-value = 0.3). Eleven patients (26%) had a bPFS ≥ 6 months and 5 (12%) had a bPFS ≥ 12 months. All long D responders (bPFS ≥ 6 months) had a TTCRPC ≥ 12 months, 10/11 patients had a previous PFS ≥ 6 months on AA or ENZ. None of the 2 patients (4.6%) with primary resistance to AA, responded to switch from P to D. Conclusions: D alone or in combination with previous AR axis targeted agents has activity in mCRPC men, with long responders observed amongst those with previous long response to ADT or to next generation AR axis targeting.
Overall survival and immune responses with sipuleucel-T and enzalutamide: STRIDE study.
Authors: Petrylak Daniel Peter , Drake Charles G. , Pieczonka Christopher Michael , Corman John M. , Garcia Jorge A. , Dunshee Curtis , Van Mouwerik Tim , Tyler Robert C. , Chang Nancy N. , Quinn David 
Published: February 2018

246 Background: STRIDE (NCT01981122) is the first study comparing concurrent (con) vs sequential (seq) enzalutamide (enz) with sipuleucel-T (sip-T) in patients (pts) with metastatic castration-resistant prostate cancer. Pts were followed until death or for 3 years. Methods: Fifty-two pts were randomized 1:1 to 3 sip-T infusions and enz started 2 wks before (n = 25, con) or 10 wks after (n = 27, seq) sip-T. Enz was continued for 52 wks or until disease progression (DP)/toxicity. Time to clinical outcomes was estimated by Kaplan-Meier analysis. Results: Median age (years): con 66; seq 72 (p = 0.01). Baseline characteristics and laboratory values were similar between arms. K-M estimated median follow up: 40.2 months. Clinical trial information: NCT01981122. Conclusions: Long-term follow-up suggests sip-T+enz is well-tolerated with no new safety concerns. Though not powered for such, con vs seq rx did not result in differences in OS or DP; differences in PSA responses cannot be excluded. Larger studies could better evaluate the clinical impact of combining immunotherapy with hormonal agents.[Table: see text]
Prognostic value of chromogranin-a (CGA) compared to circulating tumor cells (CTCs) in metastatic castration resistant prostate cancer (mCRPC).
Authors: Giridhar Karthik , Sanhueza Cristobal T. , Hillman David W. , Alkhateeb Hassan , Carlson Rachel , Tan Winston , Quevedo Fernando , Pagliaro Lance C. , Costello Brian Addis , Kohli Manish 
Published: February 2018

249 Background: Serum CGA has been identified as a candidate prognostic biomarker for mCRPC. In a two cohort study, we compared the prognostic value of serum CGA with a validated CTC assay. Methods: In the discovery cohort (DC), blood samples were collected from 256 men with mCRPC. In an independent validation cohort (VC), 92 men with mCRPC were enrolled in a biospecimen collection study. In both cohorts, men receiving proton pump inhibitors and those with non-castrate levels of testosterone ( > 50ng/dl) were excluded. Serum CGA was measured in a homogeneous automated immunofluorescent assay using time-resolved amplified cryptate emission. In the VC, CTC enumeration was performed using the FDA cleared CELLSEARCH CTC test prior to treatment with abiraterone acetate/ prednisone. Cox proportional hazard regression and Kaplan-Meier analysis were performed for associations with elevated CGA (above reference range), unfavorable (≥ 5) CTCs, and overall survival (OS). Results: In the DC, 200 men were eligible for analysis. The median age was 72 years (yrs), 81/200 pts had a Gleason score (GS) ≥ 8, 34/200 had an elevated CGA. At a median follow up of 2.2 yrs, 156/200 were deceased. In the subset of men with GS ≥ 8, elevated CGA was associated with shorter OS [hazard ratio (HR) 2.19, p = 0.017]. In the VC, 71 men were eligible for analysis. The median age was 71 yrs, 36/71 tumors were GS ≥ 8, 31/71 pts had an elevated CGA, 26/66 had unfavorable CTCs (≥ 5). At a median follow up of 1.8 yrs, 31/71 were deceased. Elevated CGA (HR 1.91, p = 0.043) and unfavorable CTC counts (HR 2.97, p = 0.0012) were adversely associated with OS. In the high GS group, both CTCs and CGA had the same area under the curve (AUC) of 0.72. Pts with elevated CTC and CGA had the poorest OS (HR 3.76, p = 0.008). Conclusions: Elevated serum CGA was negatively associated with OS in men with mCRPC. Serum CGA represents a prognostic biomarker that may complement CTC enumeration. Clinical trial information: NCT#01953640.
Continuous infusion fluorouracil (5FU) in heavily pre-treated mCRPC patients.
Authors: Manogue Charlotte , Moses Marcus Marie , Lewis Brian E. , Sartor A. Oliver 
Published: February 2018

257 Background: Pts with mCRPC resistant to novel hormones (abi/enza), and taxane chemotherapy are challenging. Extensive pre-treatment typically poses an issue for clinical trials, and there is no consensus regarding how to manage patients who no longer respond to conventional therapies but maintain a good performance status. Methods: 13 mCRPC pts were treated with 5FU at 200mg/m2 continuous infusion as a novel treatment option for those with heavily pretreated mCRPC. Data was retrospectively collected at Tulane Cancer Center for patient treatment history, and laboratory parameters. Results: All treated patients had prior exposure to an average of 8.7 lines of treatment. 5FU was used as median 8th line therapy. All pts had extensive bony disease and 6 had liver involvement. Median PSA at start of treatment was 356 ng/dL. 5 pts progressed within a month of initiation of therapy, and 2 pts did not respond. 8 (61%) patients had treatment for >1 month with 6 having >30% PSA reduction, 4 with a >50% PSA reduction and 2 with a >90% PSA reduction (Table). Median time on therapy was 4.5 months with 2 patients remaining on treatment for >6 months despite multiple pretreatments and far advanced disease. 5FU was well tolerated with improvement in both performance status and symptoms in several patients. Conclusions: Continuous 5FU is active in select highly pretreated pts and targets folate metabolism via inhibition of thymidylate synthase. It is one of the few chemotherapies that can be administered with little myelosuppression, an important issue in far-advanced pts. Prostate specific membrane antigen (PSMA) expression is upregulated in CRPC, especially after abi/enza treatment. PSMA hydrolyzes polyglutamated folates and functions as a folate transporter; its over-expression stimulates both folate transport and prostate cancer cell line growth. We hypothesize that 5FU, functioning as an anti-folate, antagonizes the downstream effects of PSMA over-expression. PSA data for pts on treatment > 1 month. [Table: see text]