bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post docetaxel treatment for castration-resistant prostate cancer (CRPC): Does sequencing matter?
Authors: Malik Zafar I , Montazeri Amir H , Wong Helen , Eswarvee Chinnamani 
Published: March 2020

e15135 Background: Two phase 3 studies have demonstrated efficacy for cabazitaxel (CAB) and abiraterone (AB) post docetaxel (DT) for CRPC. Both studies show survival benefit in patients who have progressed during or shortly after DT. Currently there is no data to show which agent is superior. It may be possible that as these agents have different mechanisms of resistance and the benefits are additive. Currently no predicative markers are available to identify response to therapy or optimal sequencing. Both agents are available for prescription at our centre. In this study we investigated the number of patients who were able to receive both treatments sequentially and whether therapy sequencing matters. Methods: In this retrospective study, patients with CRPC treated with CAB or AB after DT between Jan2011- Jan 2012 were included. Baseline patient characteristics were recorded as well as treatments following progression. In particular patient numbers receiving both CAB & AB were recorded. Statistical analysis was performed using SPSS v18. Results: 42 consecutive patients post DT included, 24 CAB and 18 AB. Median follow up was 7.9 months for CAB and 2.5 months for AB. At analysis, 18 CAB patients and 9 AB patients had progressed. Of those who progressed following CAB, 13 received AB, 1 restarted Goserelin and 4 patients received best supportive care (BSC). 9 patients progressed on AB and none were able to receive CAB, 4 received BSC, 1 was treated with stilboestrol and 4 remained on AB despite progression. Conclusions: Our series provides insight into the sequencing of these agents in the real world. As these agents have different resistant mechanisms it is possible that the benefits may be additive .Our study suggests that if patients receive CAB as the first option, they are more likely to receive AB subsequently whilst the converse does not apply. At this time the series is not mature enough to determine if differences in sequencing will impact on survival benefit, however progression free survival and overall survival will be updated for the meeting. [Table: see text]
Survival in metastatic castration resistant prostate cancer (mCRPC) trial participants.
Authors: Pezaro Carmel Jo , Omlin Aurelius Gabriel , Mukherji Deborah , Bianchini Diletta , Sandhu Shahneen Kaur , Mulick Cassidy Amy , Maier Gal , Olmos David , Thompson Emilda , Attard Gerhardt , De Bono Johann Sebastian 
Published: March 2020

e15136 Background: Median overall survival (mOS) in patients (pts) with metastatic prostate cancer progressing despite castrate levels of testosterone (mCRPC) was 13-16 months (m) in the pre-docetaxel era. These data, obtained from clinical trials, were used to construct currently available prognostic nomograms. We hypothesise that these models no longer reflect survival. Pts and physicians urgently require updated prognostic data on which to base management decisions. Methods: Pts with mCRPC treated on phase I-III trials at our institution were identified and data retrospectively collected. Predicted survival by Halabi and Smaletz nomograms were compared to calculated survival using Kaplan-Meier analysis. Cox model multivariate (MV) analysis used variables at referral, including performance status (PS), Gleason (GS), prostate specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), hemoglobin (Hb), visceral disease and albumin. Results: 423 pts with CRPC treated between 2003 and 2011 were included. At diagnosis median age was 62 years (y; 41.8 – 82.7); 226 (53.4%) had metastatic disease. Median interval from diagnosis to CRPC was 2.7y (0.2 – 21.7). At referral 248 pts (58.6%) were chemotherapy-naïve. Halabi and Smaletz models predicted mOS in chemo-naïve pts of 21m and 18m respectively, however the observed mOS was 32m (95%CI 28 – 38). Survival from CRPC was 43m (CI 37 – 46) and 39m (CI 34 - 44) in pre- and post-chemo pts, respectively. Conclusions: Despite aggressive disease characteristics, our pts lived significantly longer than predicted by current nomograms. MV analysis confirmed the importance of several previously identified prognostic factors. Survival data from this large cohort of CRPC pts should encourage men considering clinical trial participation. Previously developed nomograms no longer accurately predict survival.
Effect of inhibition of Src and insulin/insulin-like growth factor-1 receptor (IR/IGF-1R) on tumor activity and bone turnover in prostate cancer (PCa) models in vivo relative to inhibition of either kinase alone.
Authors: Dayyani Farshid , Araujo John C. , Carboni Joan M. , Gottardis Marco M. , Trudel Geralyn Carol , Logothetis Christopher , Gallick Gary E. 
Published: March 2020

e15151 Background: Growth of prostate cancer (PCa) metastases relies on bidirectional interactions between the tumor and microenvironment.The Src family kinases (SFK) and insulin-like growth factor-1 receptor (IGF-1R) signaling axes are aberrantly activated in both PCa and the microenvironment of bone metastases. Dasatinib and BMS-754807 are small molecule inhibitors that target SFK and IGF-1R/IR, respectively. This study examined the in vitro and in vivo effects of BMS-754807 and dasatinib on PCa growth. Methods: Antitumor effects of both reagents were tested alone and in combination in vitro in PC3 and LNCaP cells, using proliferation and apoptosis assays. Signaling pathways were interrogated by western blots. Tumor growth in vivo was assessed by orthotopic and intratibial injection of PC3 cells and subcutaneous growth of primary human xenograft PCa-133b. Serum markers were measured by ELISA. Results: In vitro, dasatinib decreased proliferation and migration of PCa cells whereas BMS-754807 induced apoptosis. All observed anti-tumor effects were enhanced when dual blockade was used. IGF-1 induced phosphorylation of Akt1, but not Akt2, was partially inhibited by either drug alone and almost completely abrogated by the combination. Dasatinib and BMS-754807 inhibited in vivo orthotopic and intratibial tumor growth of PC3 cells more potently than either as a single agent alone with a corresponding decrease in bone turnover markers. Both drugs also exhibited synergism in primary human xenograft tumors. Potent target inhibition (p-Src, p-IGF-1R, p-Akt) by the drug combination was also demonstrated in xenografts. Conclusions: The combination of dasatinib and BMS-754807 may be a rational therapeutic approach in PCa by blocking both independent and complementary processes critical to tumor growth.
Modafinil for fatigue associated with docetaxel-based chemotherapy: A randomized controlled trial.
Authors: Hovey Elizabeth J. , De Souza Paul L. , Marx Gavin M. , Rapke Tal , Parente Phillip , Hill Andrew , Bonaventura Antonino , Michele Antonio , Craft Paul Stanley , Abdi Ehtesham A. , Lloyd Andrew R. 
Published: March 2020

e15152 Background: Docetaxel is the standard of care for castrate-resistant prostate cancer, but is associated with a high level of fatigue, limiting dosage and leading to premature withdrawal from therapy. Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel group study in patients with metastatic prostate or breast cancer suffering significant chemotherapy-related fatigue whilst undergoing docetaxel-based chemotherapy. Patients were enrolled at the start of their 3rdor subsequent cycles of docetaxel which was continued for up to four further cycles (defined here as ‘treatment periods’). Patients were randomized 2:1 to receive modafinil 200mg daily or placebo for 15 days during each treatment period. Fatigue was evaluated by the MD Anderson Symptom Inventory (MDASI). The primary endpoint was MDASI area under the curve (AUC) during the first 7 days of study medication for the first two treatment periods (possible range 0-70). Other validated tools were used to record disturbances in sleep, mood and functional status. Results: Eighty-three patients (65 with prostate cancer) were randomized and received at least one dose of study medication. The number of grade 3 or 4 adverse events (AEs) was 16/55 (29.1%) in the modafinil group and 5/28 (17.9%) in the placebo group. The toxicity profile was largely consistent with docetaxel-based chemotherapy and with previously reported AEs associated with modafinil use in the community; 11 AEs were possibly related to docetaxel; 1 to modafinil and 9 to neither treatment. Conclusions: Assessing and managing chemotherapy-related fatigue remains a major challenge. Despite not reaching the primary endpoint, there was a consistent trend towards improvement of chemotherapy-related fatigue in the modafinil arm. Further studies are needed to better address the significant symptom of docetaxel-related fatigue. Funding sanofi-aventis; Study ID NCT00917748. [Table: see text]
Potential predictors of fear of progression among long-term prostate cancer survivors: Do illness perceptions and family history matter?
Authors: Herkommer Kathleen , Hahn Astrid , Dinkel Andreas , Marten-Mittag Birgitt , Herschbach Peter , Gschwend Jürgen E. 
Published: March 2020

e15157 Background: Fear of illness progression (FoP) or recurrence is known to be one of the most prominent fears in patients with prostate cancer (PCa) even years after treatment. To improve detection of men at risk, possible predictors need to be discovered. So far, little is known about the influence of patients' illness perceptions (IP) and family history on dysfunctional FoP (dysFoP). Methods: A nationwide mail survey was sent out to a total of 6.305 men who had been treated with radical prostatectomy. Median time since diagnosis was 7.4 years. Patients were divided into 2 subgroups according to their family history: 68.9% (n=4.341) sporadic and 31.1% (n=1.964) familial (at least 1 first-degree relative with PCa). FoP was assessed with the short form of the Fear of Progression Questionnaire (FoP-Q-SF), IP were assessed with the Brief Illness Perception Questionnaire (B-IPQ). We also evaluated sociodemographic and clinical parameters and their influence on FoP. Results: Dysfunctional FoP was identified in 3.4% of all patients. Patients worried most about family, being dependent on others, and whether the children would also be diagnosed with PCa. Younger age, worse subjective economic situation, shorter time since diagnosis and disease progression were significantly associated with dysFoP (p<.01). IP and prevalence of dysFoP did not differ significantly between patients with sporadic and familial PCa, but familial PCa was associated with a higher mean level of FoP. IP explained a high amount of variance in FoP (R²=.435). Stronger perceptions of worry and negative emotions were significant predictors of FoP (p<.001). Furthermore, having at least one son (p=.004), time since diagnosis <5 years (p=.006) and worse subjective economic situation (p=.030) were predictive of dysFoP. Conclusions: In this study only a minority of patients reported dysFoP. The study findings suggest the importance of addressing IP, especially worries, negative emotions, and perceived consequences as key factors of FoP. Prevalence of dysFoP did not differ depending on family history, however patients with familial PCa showed higher mean levels of FoP.
Early results of prostate cancer radiation therapy at Korle Bu Teaching Hospital: An analysis with emphasis on research strategies to improve treatment delivery and outcomes among patients in Ghana.
Authors: Yamoah Kosj , Beecham Kwamena , Hegarty Sarah , Hyslop Terry , Showalter Timothy Norman , Yarney Joel 
Published: March 2020

e15163 Background: Although there is interest in racial disparities in prostate cancer outcomes among persons of African descent living in the United States there is scant data available regarding disease presentation and treatment response among black men living in Africa. In this study we evaluate disease presentation and early clinical outcomes among Ghanaian men with prostate cancer treated with external beam radiotherapy (EBRT). Methods: A total of 379 men with prostate cancer were referred to the National Center for Radiotherapy and Nuclear Medicine, Ghana, from January 2003 to December 2009. Data were collected regarding patient- and tumor-related factors such as age, prostate specific antigen (PSA), Gleason score, clinical stage, and use of hormonal therapy. For patients who received EBRT, freedom from biochemical failure (FFbF) was evaluated using Kaplan-Meier analysis. Results: The median age at diagnosis was 65 years. Of 379 patients referred for treatment 69.6% of all patients had initial PSA >20ng/ml, and the median iPSA was 39.0 ng/ml. A total of 128 men representing 33.8% of overall cohort were diagnosed with metastatic disease at time of referral. We identified 166 men treated with EBRT or brachytherapy +/- androgen depravation therapy (ADT), and an additional 139 men treated with ADT alone (including orchiectomy in 38 patients). The median EBRT dose was 70 Gy, in 2 Gy per fraction. Among all EBRT patients with at least 2 years of follow-up after treatment (n=52; median follow-up time: 38.9 months), 5-year actuarial FFbF was 65.1%: 67.0% for patients with PSA < 30.0 ng/mL and 63.2% for PSA ≥ 30.0 ng/mL [log-rank, p=0.586]. Conclusions: This is the largest series reporting on outcomes for prostate cancer treatment in West Africa. That one-third of patients presented with metastatic disease suggests potential need for earlier detection of prostate cancer to permit curative-intent local therapy. Data from this study will aid in the strategic development of a prostate cancer research roadmap in Ghana, with a focus on improving therapeutic approach as well as fostering a prudent allocation of scarce resources.
Actual total hospital costs of primary localized prostate cancer treatments analyzed by risk group.
Authors: Lavery Hugh J. , Levinson Adam W. , Phalen Adrien , Stone Nelson , Stock Richard , Sebrow Dov , Hobbs Adele , Samadi David B. 
Published: March 2020

e15164 Background: Radical prostatectomy (RP) and radiotherapy (RT) provide comparable HRQOL and oncologic outcomes of localized prostate cancer (PCa), yet no studies have evaluated their relative costs when investigated by risk group. We evaluated hospital costs associated with modern PCa therapies at a multidisciplinary program. Methods: Institutional billing data was queried for hospital patients from 2005 to 2009 with a primary admission for prostate cancer and primary procedure codes for RP, brachytherapy (BT), intensity modulated RT (IMRT) or combination treatment. All hospital costs related to the primary procedure were analyzed as assigned by the hospital. Costs were adjusted to 2009 USD and analyzed per patient and pretreatment D’Amico risk group. Results: 1969 localized PCa patients with a median age of 62 were identified with complete clinical information. There was a marked increase in the use of robotic-assisted laparoscopic prostatectomy (RALP) starting in 2007. The median total hospital costs for IMRT monotherapy ($16,673), BT+IMRT ($22,145) and RP+ adjuvant IMRT ($24,380) combination therapies were significantly higher than any other treatment type, although these patients had worse pathologic features. BT was the least expensive treatment with a total cost of $7,506, but was not routinely used as monotherapy for high-risk patients. The total cost of RALP ($7,676) was lower than open radical prostatectomy (RRP) ($8,991, p<0.001) and similar to laparoscopic radical prostatectomy (LRP) ($7,769).These trendsremained consistent when stratified by risk group (Table). Conclusions: In a high volume setting, RALP and BT are the least expensive modalities for treating low and intermediate risk PCa. For high risk patients, all forms of RP and IMRT alone were less expensive than combination therapy. [Table: see text]
Safety and feasibility of salvage robot-assisted radical prostatectomy for recurrent prostate cancer.
Authors: Abreu Andre Luis de Castro , Chauhan Sanket , Fairey Adrian Stuart , Camacho Ignacio , Goh Alvin , Park Daniel , Desai Mihir , Patel Vipul , Gill Inderbir S , Aron Monish 
Published: March 2020

e15171 Background: The safety and feasibility of salvage robot-assisted radical prostatectomy (sRARP) for recurrent prostate cancer is unclear. Herein we report short-term cancer control, functional, and perioperative outcomes in a multi-institutional cohort. Methods: Between July 2007 and October 2011, 38 consecutive men underwent sRARP for recurrent prostate cancer at the University of Southern California (n=14) or Global Robotics Institute (n=24). Failed primary therapy was varied (external beam radiotherapy [EBRT; n=14]; interstitial brachytherapy [IBT; n=11]; EBRT + IBT [n=5]; high-intensity focused ultrasound [n=3]; cryoablation [n=3]; other [n=2]). The main outcomes were immediate biochemical failure (IBF), positive surgical margins (PSM), urinary continence and erectile function at 3 months, and complications within 90 days of surgery. Immediate biochemical failure was defined as a PSA > 0.2 ng/ml. Urinary continence was defined as the use of no pads and erectile function was defined as a SHIM score > 21. Complications were classified and graded using the Clavien system. Results: The median age was 68 years (50-83 years) and median preoperative PSA was 4.1 ng/ml (0.4-15.2 ng/ml). Preoperative biopsy Gleason score was ≤6 (n=7), 7 (n=18), and ≥8 (n=12). All procedures were completed without the need for open conversion. No patient experienced an intra-operative complication. Median estimated blood loss was 100 ml (30-300 ml) and operative time was 1.5 h (1-6h). Median length of hospital stay was 1 day (1-7 days). The median duration of urethral catheterization was 12 days (4-48 days). IBF occurred in 9 (29%) patients and PSM occurred in 7 (18%) patients. Urinary continence and erectile function occurred in 9 (34%) and 0 patients, respectively. One or more postoperative complications occurred in 12 (31%) patients. Low grade (I-II) and high grade (III-IV) complications occurred in 8 (21%) and 4 (10%) patients, respectively. No patient died. Conclusions: Salvage robot-assisted radical prostatectomy is safe and feasible. Short-term cancer control and perioperative morbidity were acceptable; however, functional recovery was poor. To date, this is the largest series worldwide.
Provider mix and costs associated with treatment of patients with bone metastases secondary to prostate cancer.
Authors: Shermock Kenneth M. , Sullivan Sean D , Ramsey Scott David , Seal Brian S. 
Published: March 2020

e15175 Background: Treatment of patients with bone metastases secondary to prostate cancer can involve several provider types and combinations of chemotherapy, surgery, radiation, and pharmaceutical treatment. This study evaluated the combinations of provider types and associated treatment patterns for a cohort of patients with bone metastases secondary to prostate cancer. Methods: Continuously enrolled patients older than 20 years of age in the MarketScan database between January 2004 and December 2010 with evidence of bone metastases (ICD9 code 198.5 or treatment with zolderonic acid, pamidronate, or demosumab) were included. Inpatient and outpatient medical claims data were used to define provider combinations. Treatment patterns were determined from prescription fill/refill claims and procedure codes from inpatient and outpatient medical claims. Results: A total of 4,493 patients had evidence of bone metastases. A radiologist was involved in care for a vast majority (n=4,054, 90%). Less than half of the population, (n=1,751, 39%) had an oncologist actively involved in care. Most patients (n=2633, 59%) had both an urologist and a radiologist involved in their care. The most common combinations of providers were urologist and radiologist (n=998, 22%); urologist, radiologist, and surgeon (n=951, 21%), and urologist, radiologist, and oncologist (n=781, 17%). About 15% (n=684) of patients had a surgeon, urologist, oncologist, and radiologist involved in their care. Only approximately half (n=2,274, 51%) of the population had evidence of receiving radiation therapy, suggesting that the radiologist plays a diagnostic role for many patients. A vast majority of patient were prescribed hormone therapy (89%) and 76% were prescribed steroid agents (mostly glucocorticoids). Less than half of the population (n=1,838, 41%) received surgery related to their prostate cancer. Conclusions: There is significant variation in combinations of provider types and associated treatment patterns for patients who have bone metastases secondary to prostate cancer. Follow-up studies should examine optimal conditions for different provider mixes and treatment patterns.
Biochemical survival and morbidity of high-intensity focused ultrasound (HIFU) as a primary monotherapy for low-risk localized prostate cancer: Outcomes from the @-registry following the ENLIGHT trial inclusion criteria.
Authors: Robertson Cary N. , Ward John Francis , Crouzet Sebastien , Brown Stephen CW , Berge Victor , Chaussy Christian G , Ganzer Roman , Paulsau Antonello , Gelet Albert , Thueroff Stefan , Blana Andreas 
Published: March 2020

e15194 Background: Prostate Cancer (PCa) HIFU (Ablatherm, EDAP-TMS, Lyon, France) is currently under investigation in the US. This study reports biochemical, biopsy and morbidity outcomes for a population of low risk localized PCa patients meeting ENLIGHT FDA trial inclusion criteria. These data were accrued from European HIFU centers using an online HIFU database (@-Registry) . Methods: The patient’s selection criteria for this study were: low risk prostate cancer patients (T1c to T2a, PSA<10ng/ml, Gleason≤6), with a prostate A-P diameter and volume of <25mm and <40cc, and no pre-treatment hormone therapy. Kaplan-Meier analysis was performed to determine biochemical survival with failure defined as the Phoenix definition (PSA nadir+2). Morbidity data, need for salvage treatment and biopsy data were analyzed. Results: From 12 European centers, 358 men met the inclusion criteria. The baseline mean age, PSA and median Gleason sum were 69.7±6.4 years, 5.8±2.4 ng/ml and 6, respectively. Stage was 65.9% T1c and 34.1% T2a. Patients were followed for 6.6±3.1 years (range: 0.6 to 18 years). Median PSA nadir was 0.09 which was reached 13.9±10.7 weeks after HIFU. The salvage treatment rate was 8.7%, and the negative biopsy rate was 90.2% Actuarial BDFS at 5 and 10 years was 87% and 73% respectively. The morbidity data identified GradeI, II and III stress incontinence in 12.3%, 4.5% and 1.7% of the population, respectively. The Bladder Outlet Obstruction rate was 20.7% (urinary retention, urethral stenosis ). Urethro-rectal fistula was not observed. Conclusions: HIFU achieved good biochemical control at 10 years of follow-up for low riskPCa patients and negative biopsy rates were high. HIFU demonstrated an acceptable morbidity, especially with the lack of any serious events(specifically fistula). Bladder Outlet Obstruction was the most bothersome adverse event. HIFU appears as a valuable and safe therapy for long term low risk PCa treatment.