bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors that affect survival outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223.
Authors: Al-Ezzi Esmail Mutahar , Alqaisi Husam , Picardo Sarah , Iafolla Marco , Sridhar Srikala S. , Sacher Adrian G. , Fallah-Rad Nazanin , Catton Charles , Warde Padraig , Hamilton Robert James , Fleshner Neil Eric , Zlotta Alexandre , Hansen Aaron Richard 
Published: February 2020

225 Background: Radium-223 (Ra-223) improved overall survival (OS) in men with mCRPC with predominantly bone metastases. We analyzed their survival outcomes to identify factors associated with prognosis for men treated with Ra-223. Methods: This was a retrospective study of men with mCRPC at Princess Margaret Cancer Centre treated with Ra-223. Demographics, disease characteristics, number of bone metastasis [ < 6, 6-20, > 20], laboratory results, number of Ra-223 doses, systemic treatment lines after radium-223, use of bone protecting agents (BPA) and survival outcomes were collected. OS and progression-free survival (PFS) were estimated by Kaplan-Meier (log-rank) analysis. Uni- (UVA) and multi-variate (MVA) analysis (Cox-regression) were used to evaluate patient and disease characteristics, number of Ra-223 doses and overall survival. Results: 114 men received Ra-223 between May 2015 and May 2018 with median age 75 years (range 53-93). Median radium doses was 5 (68 [59.6%] received > 4 doses, 46 [40.4%] received ≤4 doses). Median baseline ALP 113.5 U/L (31-1121), median baseline Hb 118 g/L (69-153), median baseline PSA 70.2 ug/L (0.15-5275), median LDH 242 UL (82-1426). 58% had 6-20 bone metastases and 28% had > 20 bone metastases. The median OS and PFS for men who received ≤4 doses vs > 4 doses was 4.56 vs 19.8 months (HR = 8.4; 95%CI: 4.861-14.62; p≤ 0.0001) and 2.9 vs 7.45 months (HR = 4.6; 95%CI: 2.837 to 7.537; p≤ 0.0001) respectively. The baseline median ALP was (154 vs 98; p = 0.03) for men who received ≤4 doses vs > 4 doses Ra-223. On UVA, ECOG 0-1 (HR = 0.33; p = 0.0003), baseline PSA < 70 ug/L (HR = 0.51; p = 0.0023), LDH < 250 U/L (HR 0.55; p = 0.0082), Hb > 120 g/L(HR 0.46; p = 0.0004), ALP < 150 U/l(HR 0.38; p ≤ 0.0001) and receipt of subsequent treatment after Ra-223 (HR = 0.33; p < 0.0001) were associated with improved OS. On MVA, receipt of subsequent treatment, administration > 4 cycles of Ra-223 and baseline ALP < 150 U/L were associated with improved OS. Conclusions: Men who receive > 4 cycles of Ra-223 have significantly better OS than those who receive ≤4 doses. Baseline ALP was independently associated with better OS and could be used to identify patients most likely to benefit from Ra-223.
Review of the real-world prevalence of mHSPC, nmCRPC, mCRPC, and gene alterations associated with HRR in prostate cancer (PC).
Authors: Shore Neal D. , Oliver Louisa , Shui Irene , Gayle Alicia , Wong On Yee , Kim Jeri , Payne Sarah , Ghate Sameer R. 
Published: February 2020

229 Background: The clinical journey of PC is evolving rapidly. New hormonal agents (NHA) have demonstrated clinical efficacy in metastatic hormone sensitive prostate cancer (mHSPC), non-metastatic castrate-resistant prostate cancer (nmCRPC) and metastatic castrate-resistant prostate cancer (mCRPC). A shift in the treatment landscape considering precision medicine, recently supported by the phase III PROFOUND study, suggests updates to the currently limited clinical guideline recommendations for genomic testing. Better understanding of the patient pathway and respective proportion of patients to support patient care is needed. The objective of this SLR was to summarize published literature on the prevalence of mHSPC, nmCRPC, mCRPC and HRR gene alterations. Methods: An SLR was conducted across nine databases in OVID to capture English language studies published 01/2009–05/2019 on global epidemiology and clinical practice trends for mHSPC, nmCRPC, mCRPC and HRRm. 4,732 papers were identified which were systematically screened for inclusion. Grey literature searches included 10 conference proceedings from 2014–2019. Results: In total, 244 observational publications met the inclusion criteria - 4 studies reported the prevalence of mCRPC, 3 on nmCRPC and 0 on mHSPC. From these, the estimated prevalence of mCRPC and nmCRPC is 1.6–2.1 and 1.1–2.1 per 100 PC cases, respectively. HRRm were investigated in 13 publications with next generation sequencing of tissue and blood samples being reported as the most frequent method. Of the HRR gene alterations examined, BRCA2 were found to have the highest prevalence with a range of 4.5–9.3 and 1.1–15.1 per 100 overall PC cases for germline and somatic gene alterations, respectively. Other prevalent HRR gene alterations included germline ATM, BRCA1 and CHEK2. Conclusions: Limited data are available evaluating the prevalence of mHSPC, nmCRPC and mCRPC required to quantify the burden of these populations suggesting a lag in the published literature following updates to US treatment guidelines. Our review also shows that HRR gene alterations, specifically BRCA2, are prevalent in PC consistent with recently published data on PROFOUND population.
Late dosing of luteinizing hormone-releasing hormone agonists (LHRH) and testosterone (T) levels >20 ng/dL in prostate cancer (PCa).
Authors: Twardowski Przemyslaw , Atkinson Stuart , Boldt-Houle Deborah , Sartor A. Oliver 
Published: February 2020

31 Background: LHRH agonists are the most frequently used drugs for the delivery of androgen deprivation therapy (ADT) for PCa. Evidence suggests achieving and sustaining T levels ≤20 ng/dL with ADT is desirable and correlates with improved disease-specific survival in advanced PCa patients. However, T levels may rise above castration level (50 ng/dL) between injections, especially if a subsequent dose is delayed. Increase in prostate-specific antigen (PSA) level on ADT may represent true disease progression to castration resistant PCa, or may be a result of late ADT dosing and inadequate T suppression. Current study evaluated timeliness of LHRH agonist dosing, subsequent rate of T breakthroughs and frequency of T/PSA testing prior to dosing in PCa patients. Methods: A retrospective review of electronic medical records and associated claims data (1/1/07-6/30/16) of LHRH agonist injections (n=85,030) evaluated the frequency of late dosing (defined as occurring after day 32, 97, 128, 194 for 1-, 3-, 4-, 6-month formulations, respectively), T tests >20 ng/dL and frequency of T/PSA tests prior to dosing. Results: 26.9% of injections were late: 14.4% were ≤1 week late, 3.1% were between 1-2 weeks late and 9.4% were >2 weeks late. 43% of T values exceeded 20 ng/dL for late injections; while only 21% exceeded this level for early/on-time injections. 83% of LHRH injections had a PSA value drawn prior to dosing; however, only 13% had a similarly timed T assessment. Conclusions: Overall, >25% of injections were late. For late injections, the proportion of T tests with T >20 ng/dL was higher compared to when the dosing was early/on-time. Late injections correlated with ineffective T suppression (>20 ng/dL) over 40% of the time. For all injections, T levels were not monitored as frequently as PSA levels. Considering the potential clinical benefits of maintaining effective T suppression throughout the course of ADT, clinicians should ensure treatments are delivered within approved dosing instructions, routinely monitor T levels and consider prescribing treatments with proven efficacy through the dosing interval to maintain T ≤20 ng/dL.
Transperineal prostate biopsies without antibiotic prophylaxis: Safety evaluation of the first 65 patients.
Authors: Kohl Tobias , Schuster Kai-Peter , Lang Konrad , Blanckenberg Alexandra , Kuru Timur H. , Zumbé Jürgen , Porres Daniel 
Published: February 2020

355 Background: There is an ongoing trend towards perineal prostate biopsies for the detection of prostate cancer. For many reasons the issue of antibiotic prophylaxis in prostate biopsies is becoming more important, especially with quinolone antibiotics being excluded from this indication and an increasing antibiotic resistance. Considering that the perineal biopsy is a sterile procedure, not giving antibiotics for prophylaxis seems to be an alluring approach. Methods: At the General Hospital Leverkusen, transperineal (TP) MRI TRUS fusion biopsies are performed using the Ginsburg Protocol with a template and software-guided approach in general anesthesia. Patients received single dose antibiotics (Ciprofloxacine 500 mg) two hours prior to surgery from Jan 2019 to Aug 2019 (group 1). Starting in Sep 2019, no antibiotics were used for prophylaxis (group 2). Surgical disinfection using Povidone-iodine was performed ahead of every procedure. In this study, postoperative infection rates were assessed. Patients were followed up by telephone interview at least two weeks after biopsy and were asked about the need for postoperative antibiotics to treat regular UTI, fever, prostatitis or for readmission to other hospitals. Results: A total of 180 TP biopsies were performed with a median of 22 cores (min 18, max 28). Out of 115 cases with antibiotic prophylaxis, no patient was readmitted to the hospital due to infection or fever. Group 2 included 65 patients. No one was readmitted with fever or prostatitis. At the time of abstract admission 45 out of 65 patients in this group were followed up by telephone interview. None needed antibiotics and none was readmitted to a hospital elsewhere. Conclusions: The study shows an infection rate of 0 % for perineal prostate biopsies with or without antibiotic prophylaxis. The results argue in favor of perineal prostate biopsies and challenge the dogma of prostate biopsies needing an antibiotic prophylaxis irrespective of the approach. However, a larger prospective multicenter study should be initiated to ensure patient safety.
WATChmAN: A randomized trial of virtual surveillance versus standard in-person care for clinical stage I testicular cancer.
Authors: Hamilton Robert James , Landoni Lauren , Kuhathaas Kopika , Chung Peter W. M. , Bedard Philippe L. , Warde Padraig Richard , Hansen Aaron Richard , Truong Tran , Hahn Ezra , Jewett Michael A.S. 
Published: February 2020

396 Background: Most guidelines recommend active surveillance (AS) as initial management for stage I testis cancer (TC). AS entails blood work and imaging at regular intervals requiring multiple clinic visits spanning 5 years. This can be time-consuming, difficult to adhere to, dissatisfying and costly for patients and health care systems. We innovated a secure online platform, WATChmAN (Web-based virtuAl Testicular CANcer clinic) allowing asynchronous communication between patients, results, and physician team. Methods: We are conducting an RCT (NCT03360994) where patients with stage I TC on AS are randomized to virtual care (WATChmAN), or standard in-person care. Primary endpoint is safety: examining loss-to-follow-up and compliance with AS schedules, incidence of relapse, delays in detection of relapse, and burden of relapse. Non-compliance represents a) patient-derived delay in visit; or b) follow-up visit with incomplete testing. Secondary endpoints include: patient/physician satisfaction and cost savings. Results: At present, 102 of a planned 144 patients are enrolled: 51 to virtual care, and 51 to standard in-person care. More patients in the virtual arm have been compliant with AS schedules (89% vs 73%) with shorter median compliance delays (12 vs. 14 days). To date, 10 patients have relapsed: 6 virtual (11.8%) and 4 standard (7.8%). Median time to relapse was shorter for the virtual arm (8 vs. 9.5 months), with no difference in burden of disease at relapse. Response rates to 6-month surveys were 90% and 59% for virtual and standard arms respectively. When asked if satisfied with their care, on the virtual arm 67% reported “extremely satisfied”, and 33% “satisfied” compared to 50% and 45% for the standard arm. When WATChmAN patients were asked if the application is able to provide the same excellence of care as in-person appointments, 82% reported “strongly agree” or “agree”. Conclusions: Interim results suggest virtual care in stage I TC is feasible and safe with improvements in patient satisfaction. Through semi-structured interviews and cost-effectiveness analyses, we anticipate more insight into virtual care. This may serve as a potential model for virtual care for other cancers. Clinical trial information: NCT03360994.
Prevalence and clinical impact of BRCA1/2 mutations in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Martinez Chanza Nieves , Tkint De Roodenbeke Marie , Desmyter Laurence , Wilkin Francoise , Badoer Cindy , Vandernoot Isabelle , Smits Guillaume , Accarain Anna Ayako , Sideris Spyridon , Gil Thierry , Awada Ahmad , Roumeguere Thierry Andre , Hamid Anis 
Published: February 2020

44 Background: Somatic BRCA gene mutations ( sBRCAm) have been identified in a significant proportion of patients (pts) with castration resistant PC (CRPC), with mixed data regarding effect on CRPC therapies. However, the prevalence and clinical significance in mHSPC are not well characterized. Methods: Sequencing of primary tumor for sBRCA1/2 was performed in unselected pts with de novo mHSPC. We assessed the association of sBRCAm on time to CRPC (TTCRPC) and overall survival (OS) from diagnosis using Kaplan-Meier method, as well as PSA response (50% fall from baseline). Associations were evaluated using a Cox regression model with multivariable analyses adjusting for docetaxel use. Results: We identified 69 pts with de novo mHSPC, of whom 7 (10%) harbored a pathogenic sBRCA2m. Median age at diagnosis was 66 years. The majority were classified as high volume disease (n=54; 84%) with Gleason 9-10 grade (n=40; 61%). Therapies in the HSPC setting included ADT alone (n=29, 42%), ADT + Docetaxel (n=35, 51%), and ADT + Docetaxel + Abiraterone (n=5, 7%). Only 1 s BRCA2m case compared to 39 wild-type pts were treated with docetaxel. PSA response was achieved in 65 (96%) and PSA £ 0.2 ng/ml at 7 mos in 20 (31%) pts, without significant association with BRCA status ( p=0.13 and p=0.66, respectively). At a median FU of 29 mos, CRPC occurred in 44 (64%) pts with a median TTCRPC of 24 mos. TTCRP was numerically shorter for non-mutated pts compared to sBRCAm (22 vs. 40 mos, HR 0.5, p=0.23); there was no significant association with docetaxel use. In multivariate analyses, there was no significant association between sBRCAm and TTCRPC (HR 0.43, p=0.175). Median OS was 74 mos without any difference according to BRCA status ( p=0.30) nor docetaxel use ( p=0.14). Conclusions: In this real-world study of routine s BRCA1/2 assessment, we found a 10% prevalence in de novo mHSPC. Time to CRPC trended longer in the sBRCAm population despite less use of docetaxel, indicating that pts with sBRCAm appear to have at least similar outcomes with standard mHSPC therapies. Larger datasets correlating genomics with outcomes in this subset of pts are warranted.
Secondary analysis of PURE-01: Role of FDG-PET/CT in evaluating lymph node involvement of patients with muscle invasive bladder cancer (MIBC) receiving neoadjuvant pembrolizumab and radical cystectomy (RC).
Authors: Marandino Laura , Capozza Antonella , Briganti Alberto , Raggi Daniele , Farè Elena , Pederzoli Filippo , Gallina Andrea , Bandini Marco , Capitanio Umberto , Bianchi Marco , Gandaglia Giorgio , Fossati Nicola , Giannatempo Patrizia , Seregni Ettore , Salonia Andrea , Montorsi Francesco , Alessi Alessandra , Necchi Andrea 
Published: February 2020

445 Background: FDG-PET/CT has limited utility in clinical N0 (cN0) patients (pts) with MIBC who receive neoadjuvant chemotherapy and RC or RC alone (Dason, AUA19). Methods: In PURE-01 (NCT02736266), 3 courses of 200 mg pembrolizumab, q3 weeks, were administered prior to RC. Pts were assessed with thorax-abdomen CT scan and with PET/CT scan during screening and before RC. Imaging review and analysis was internally performed. For each pt with lymph node (LN) increased uptake in abdomino-pelvic area, the SUVmax and the short-axis size of the most intense LN were recorded. All pts underwent extended pelvic LN dissection (LND) with packeted node submission. Results: From 02/17 to 06/2019, 103 total evaluable pts (206 PET/TC scans) were enrolled ad treated. Six pts (5.8%) had LN uptake at baseline PET/CT: mean SUVmax=2.75; mean short axis: 6.2 mm. Eight pts (7.8%) had LN uptake at PET/CT post-pembrolizumab: mean SUVmax=4.21; mean short axis: 7.2mm. The rate of pathologic LN positive (pN+) disease was 15.5% (16 pts). The performance of post-pembrolizumab PET/CT in predicting pN+ disease is indicated in the Table. In total, 4/6 pts (66.7%) with baseline FDG uptake revealed as pN+ vs 12/97 (12.4%) with no baseline FDG uptakes (p=0.005). A total of 39 pts (37.9%) developed inflammatory FDG-uptakes post-pembrolizumab in several target organs/regions: top 5 sites were thyroid (N=21, 61.8%), stomach and mediastinum (13 pts each, 12.6%), lung (N=10, 9.7%), other lymph nodes (N=4, 3.9%). These changes were clinically evident (signs/symptoms or laboratory changes) in 15 pts (38.5%). Conclusions: Criteria for eligibility of cN0 pts to single-agent neoadjuvant pembrolizumab trials may be enhanced with PET/CT use. Three cycles of pembrolizumab determined profound inflammatory changes, whose long-term impact on safety is still to be determined. Clinical trial information: NCT02736266 . [Table: see text]
Vefora, GETUG-AFU V06 study: Randomized multicenter phase II/III trial of fractionated cisplatin (CI)/gemcitabine (G) or carboplatin (CA)/g in patients (pts) with advanced urothelial cancer (UC) with impaired renal function (IRF)—Results of a planned interim analysis.
Authors: Mourey Loic , Flechon Aude , Tosi Diego , Abadie Lacourtoisie Sophie , Joly Florence , Guillot Aline , Loriot Yohann , Dauba Jerome , Roubaud Guilhem , Rolland Frederic , Abraham Christine , Gauthier Hélène , Barthelemy Philippe , Gravis Gwenaelle , Nénan-Le Ficher Soazig , Cabarrou Bastien , Filleron Thomas 
Published: February 2020

461 Background: Standard treatment for advanced UC is chemotherapy (CT) combining CI and G. 70% of pts with UC are over 65 and 40% of them are unfit for CI because of IRF or comorbidities. CA replaces frequently CI, when creatinine clearance (Cr Cl) is < 60 ml/min according to Cockroft and Gault formula (CGF). However, CA tends to show a lower efficacy than CI, due to decreased dose intensity of CT. Methods: We performed a multicentre randomized phase II/III study in order to compare the activity and safety of a CT regimen with fractionated CI or CA for advanced UC in 1st line setting among pts unfit for standard CT because of IRF (40 ≤ Cr Cl ≤ 60ml/min) according to CGF. We report here the results of the interim analysis of phase II. Treatment: Arm A: CA AUC4,5 D1+ G 1000 mg/m² D1, [D1 = D21]; Arm B: fractionated CI 35 mg/m² D1D8 + G 1000 mg/m² D1D8, [D1 = D21] The co-primary objectives of the phase II were to evaluate activity (non-progression (RECIST V1.1) at (D21 C6)) and safety defined by the absence during treatment of: IRF: Cr Cl <35 mL/min or deterioration of Cr Cl >20%; delayed CT (≥ 2 weeks); decrease twice G dose on day 1 for: NCI CTC grade III or IV non-hematologic toxicity; hematologic toxicity; A two-stage Bryant and Day design was used. Results: A planned first step analysis was performed after randomization of 25 and 21 pts from April 2015 to January 2018. 23 and 19 of them were evaluable (resp. Arm A/B). 8 failures were reported for safety reason in experimental arm B, 7 for renal toxicity. Conclusions: According to our pre planned first step analysis, the trial met criteria for excessive toxicity in experimental arm (fractionated CI), predominantly renal toxicity. The study was therefore definitely stopped. Survival results will be available at the meeting. Clinical trial information: NCT02240017 . [Table: see text]
Sarcomatoid urothelial carcinoma (SUC): A single-institution experience of oncologic outcomes and recurrence patterns.
Authors: Diamantopoulos Leonidas Nikolaos , Sekar Rishi Robert , Khaki Ali Raza , Winters Brian , Vakar-Lopez Funda , Tretiakova Maria S. , Gore John L. , Schade George R. , Psutka Sarah P. , Hsieh Andrew Caleb , Lee John Kyung , Yezefski Todd , Schweizer Michael Thomas , Cheng Heather H. , Yu Evan Y. , Lin Daniel W. , Montgomery Robert B. , Grivas Petros , Wright Jonathan L. 
Published: February 2020

465 Background: SUC is a rare histology with aggressive behavior. We evaluated outcomes and recurrence patterns of patients (pts) with SUC, in comparison with conventional urothelial carcinoma (CUC). Methods: We retrospectively assessed our radical cystectomy (RC) database to identify pts with cT2-4 SUC (any %) or CUC, at RC or transurethral resection specimens. Clinicopathologic/treatment data were captured and compared with t and χ2 tests, as appropriate. Overall survival (OS; diagnosis to death) and recurrence-free survival (RFS; RC to recurrence or death) were estimated (KM method). Significant factors in univariable (UVA) Cox regression for OS were included in multivariable analysis (MVA). Results: We identified 38 consecutive pts with cT2-4 SUC and 287 with CUC (2003-2018); 17 (45%) and 162 (56%) received neoadjuvant chemotherapy (NAC). The primary non-mesenchymal component was urothelial in all SUC cases. SUC had higher rates of pT3/4 (66% vs. 35%, p < .001) but comparable rates of pN+ disease (26% vs. 20%, p = .38). Complete response (ypT0N0) after NAC was lower for SUC (6% vs. 35%, p = .02). Median follow-up was 73.6 months (95%CI 62.6 – 84.7). Median RFS and OS was inferior among pts with SUC (9.4 vs 109.8 months, p < .001, 19.7 vs. 130.4 months, p < .001 respectively). On MVA, SUC was independently associated with worse OS ( Table). Of 17 (45%) pts with SUC who recurred post-RC, 5 presented with abdomino-pelvic cystic masses, with an average time to recurrence < 5 months. Conclusions: SUC was associated with high rates of extravesical spread at RC and worse NAC response, RFS and OS, vs. CUC. Development of abdomino-pelvic fluid collections should raise suspicion of recurrence among pts with this histology. [Table: see text]