bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective study of 68Ga-RM2 PET/MRI in patients with biochemically recurrent prostate cancer and negative conventional imaging.
Authors: Baratto Lucia , Song Hong , Duan Heying , Mari Aparici Carina , Davidzon Guido , Moradi Farshad , Srinivas Sandy , Iagaru Andrei 
Published: May 2020

e17536 Background: 68Ga-RM2 is a synthetic bombesin receptor antagonist targeting gastrin-releasing peptide receptors (GRPr) that are overexpressed in several human tumors, including prostate cancer (PC). Methods: We enrolled 114 men with BCR PC, 45-83-year-old (mean±SD: 68.2±7.0). Imaging started at 40-89 minutes (mean±SD: 51.3±9.2 after injection of 113.8-152.6 MBq (mean±SD: 140.7±6.4) of 68Ga-RM2 using a time-of-flight (TOF)-enabled simultaneous positron emission tomography (PET) / magnetic resonance imaging (MRI) scanner. Twenty-four and 23 patients also underwent 68Ga-PSMA11 and 18F-DCFPyL PET/CT, respectively. Results: All patients had rising PSA and negative conventional imaging prior to enrollment. 68Ga-RM2 PET identified recurrent PC in 78 of the 114 participants, while the simultaneous MRI was positive for PC in 45 of the 103 patients. Positivity rate of 68Ga-RM2 PET was: 31.8% for PSA < 0.5 ng/dl ( n= 22), 60% for PSA 0.5 – 1.0 ng/dl ( n= 15), 64.7% for PSA 1.0 – 2.0 ng/dl ( n= 17), 81.8% for PSA 2.0 – 5.0 ng/dl ( n= 22) and 87.2% for PSA > 5.0 ng/dl ( n= 38). PSA velocity values were 1.9±2.7 ng/ml/year (range: 0-9.1) in patients with negative PET scans and 5.8±9 ng/ml/year (range: 0.2-45.4) in patients with positive PET scans ( P: 0.01). Twenty-eight and 34 lesions were detected by 68Ga-RM2 PET and 68Ga-PSMA11 PET, respectively, while 25 lesions in 13 patients were identified by both radio-pharmaceuticals. The mean SUVmax ranged 1.6-51.2 (mean±SD:14.7±12.5) for PSMA and ranged 2.5-52.5 (mean±SD: 10.7±11.6) for RM2 ( P= 0.096). Three lesions in 2 patients were RM2-avid only (all lymph nodes) and 9 lesions in 7 patients were PSMA avid only (7 lymph nodes, 1 skeletal and 1 lung nodule). 32 and 48 lesions were detected by 68Ga-RM2 PET and 18F-DCFPyL PET, respectively. 28 lesions in 12 patients were identified by both radio-pharmaceuticals. The mean SUVmax ranged 1.7-79.3 (mean±SD: 22.2±23) for DCFPyL and ranged 1.7-46.8 (mean±SD: 7±9.2) for RM2 (P < 0.01). Four lesions in 2 patients were RM2 avid only (1 adrenal and 3 skeletal); 17 lesions in 6 patients were DCFPyL avid only (7 lymph nodes, 9 skeletal and 1 prostate). Conclusions: 68Ga-RM2 may identify higher risk patients given the highly statistically significant difference PSA velocity values between patients with negative and positive scans and may be a complementary radiopharmaceutical to the PSMA-targeting tracers to ultimately allow for personalized medicine. Clinical trial information: NCT02624518 .
Treatment of metastatic castration sensitive prostate cancer (mCSPC) by disease volume: A systematic review and a meta-analysis.
Authors: Sipra Qurat Ul Ain Riaz , Riaz Irbaz Bin , Asghar Noureen , Siddiqi Rabbia , Hwang Steven R , Husnain Muhammad , Adil Shahroz , Raina Ammad , Maheswari Deepa , Babiker Hani M. , Murad M. Hassan , Singh Parminder , Bryce Alan Haruo 
Published: May 2020

e17539 Background: Chemotherapy with Docetaxel (D) or androgen pathway inhibition (API) with Abiraterone Acetate plus prednisone (AAP), Aplautamide(APA) and Enzalutamide(E) are acceptable, FDA approved treatment options for mCSPC. It is not clear whether the magnitude of benefit varies by the choice of initial agent [chemotherapy vs API] or by volume of disease [High vs Low]. Data is now available from all registration trials by volume status and motivated this analysis to inform initial treatment choice in mCSPC. Methods: We systematically searched MEDLINE(Ovid), Embase, and Scopus for randomized controlled trials of chemotherapy(D) or APIs (AAP, APA, ENZ) that had available hazard ratios (HRs) for overall survival (OS) and Progression Free Survival (PFS) according to patient’s volume of disease. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled overall survival HR and 95% CI by chemotherapy and APIs and by high volume(HVD) and low volume(LVD) using a random effect model, and tested for heterogeneity to assess the null hypothesis that no difference in the survival advantage exists by choice of initial agent and volume of disease. Results: Of 4456 studies identified in our search, there were 8 eligible randomized controlled trials that were included in the analysis. Both D and APIs significantly improved PFS [HR 0.48; 0.45-0.51] and OS [0.72; 0.64-0.81] when added to ADT, however the latter was associated with significantly higher improvement in PFS( P < 0.01) and OS (P = 0.03). In patients treated with D, patients with HVD derive significantly more benefit as compared to LVD( P = 0.046) and patients treated with APIs both HVD and LVD patients derive similar benefit( P = 0.80) (Table). Conclusions: mCSPC patients derive higher magnitude of survival benefit when treated with APIs as compared to D; however, D may be preferred in HVD patients. [Table: see text]
Completion time in prostate cancer treated with proton beam therapy: Do interruptions matter?
Authors: Hasan Shaakir , Rosen Lane , Tsai Henry , Sinesi Christopher , Laramore George E , Mishra Mark V. , Simone Charles B. , Gorovets Daniel 
Published: May 2020

e17553 Background: The association between completion time of proton therapy(PT) in prostate cancer and biochemical control is unknown. Methods: We queried the multi-institutional, prospectively collected, proton collaborative group registry for prostate cases treated definitively with PT. Kaplan meier methodology was used for biochemical failure free (bFF) rates and multivariable regression analyses (MVA) were used to identify correlates of treatment interruptions (TI) and bF. Results: After exclusion, 2794 men with 693 low, 869 favorable intermediate, 627 unfavorable intermediate, and 605 high risk prostate cancers had available data. The median age was 68 years(40-92), 90% were white and 8% were black. Androgen deprivation therapy (ADT) was given to 676 patients, 312 treatments were hypofractionated, and median EQD2 dose = 75(74-86) GyE1.5. Kaplan-meier median follow-up was 79 months. In total 900 patients (32%) had at least one TI. Shorter treatments (HR = 0.95 per day, P < 0.01) and high risk (HR = 0.72, P < 0.04) cases were less likely to have Tis on MVA. There was no difference in 5-year bFF rate with (92.7) and without (93.1%) TIs. In a subset of only high risk patients treated with ADT (n = 385), the 5-year bFF was 83% without TIs and 75% with TIs (HR = 2.10, P = 0.06). This discrepancy was significant with multivariable binomial regression (HR = 2.36, P = 0.03), and the bF difference was greatest when > 5 treatment days were missed per receiver operating characteristic curve. Conclusions: Largely, there was no correlation between TIs and bF in prostate cancer treated with PT, however completion time may play a more significant role in high risk disease.
Randomized multicenter open-label trial of GT0918 (proxalutamide) in patients with mCRPC that progressed on abiraterone or enzalutamide.
Authors: Vogelzang Nicholas J. , Rezazadeh Kalebasty Arash , Levin Richard , Malik Zulfiqar A. , Ross Ashley , Bolemon Britt Haley , Gabrail Nashat Y. , Zhang Phoebe , Zhou Karl 
Published: May 2020

e17578 Background: Both abiraterone and enzalutamide have been approved for the treatment of mCRPC. GT0918 (proxalutamide) is a novel second-generation androgen receptor (AR) antagonist binding directly to the androgen receptor, impairing nuclear translocation and decreasing AR protein expression. This phase II portion of the Ph I/II study is being conducted to further evaluate safety and tolerability of GT0918 at 400 mg or 500 mg daily dosing. Methods: All eligible mCRPC pts with progressive disease based on rising prostate-specific antigen (PSA) or/and imaging while on either abiraterone or enzalutamide, but not both. One line of prior chemotherapy was allowed. Pts (n = 60) will be randomized to GT0918 either 400 mg or 500 mg po once daily for 6 months. The primary endpoint is safety and tolerability. Secondary endpoints are PSA reduction at 12 weeks, % radiographic progression at 6-month, time to imaging progression, and exploratory biomarker CTC & cf-DNA/RNA. PSA is assessed every 4 wks and tumor imaging is done every 12 wks. Results: 56 pts were screened June 2019 to January 15, 2020 and 40 pts were randomized to receive GT0918 either 400 mg or 500 mg po daily. 22 pts (55%) had enzalutamide as prior therapy and 18 pts (45%) had abiraterone as prior therapy. 17 pts (43%) had one or more lines of chemotherapy. The median age was 72 years (range 53-89) and median baseline PSA was 162 ng/mL (0.3-4195). 10 pts had 1 cycle or less of study drug due to rapid PSA progression, AEs and/or withdrawal of consent. The most common treatment-related AEs were fatigue (48%), loss of appetite/anorexia (25%), nausea (20%), lower leg extremity edema (18%), constipation (15%), weight loss (13%), vomiting (10%), and headache (8%). 8 pts (6 in 500 mg vs. 2 in 400 mg) required dose reduction due to AE. No seizures have been observed. As Jan 30, 2020, 3 pts (8%) and 8 pts (20%) had PSA reduction at 12 weeks and 4 weeks, respectively, but no 50% PSA reduction was observed. 2 pts (5%) received study drug treatment over 24 weeks and 10 pts (25%) received study drug over 16 weeks based on stable disease (SD) on imaging. Conclusions: GT0918 administrated orally once a day is well tolerated and first 40-pts taking GT0918 show some anti-tumor activities. Dose of 400 mg po daily is recommended for GT 0918 for further clinical trials. Clinical trial information: NCT03899467 .
A prospective trial of 68Ga-PSMA and 18F-FDG PET/CT in nonmetastatic prostate cancer patients with an early PSA progression during castration.
Authors: Wang Beihe , Chang Liu , Wei Yu , Meng Jin , Zhang Yingjian , Gan Hualei , Xu Xiaoping , Wan Fangning , Pan Jian , Ma Xuejun , Hu Silong , Freedland Stephen J. , Song Shaoli , Ye Dingwei , Zhu Yao 
Published: May 2020

e17579 Background: To evaluate tumor heterogeneity and burden in nonmetastatic prostate cancer patients with an early PSA progression during castration by 68Ga-PSMA and 18F-FDG PET/CT. Methods: The trial prospectively included 37 patients who had an early PSA progression (≤2ng/ml) during castration, and high-risk (PSADT ≤10 months) nonmetastatic disease by conventional imaging. All patients underwent both 68Ga-PSMA and 18F-FDG PET/CT. Lesions were classified into PSMA-dominant lesions (PSMA+/FDG- and PSMA+/FDG+) and PSMA-/FDG+ lesions according to the tracer uptake status. The primary endpoint was the prevalence of PSMA-/FDG+ disease. Results: All patients were treated with RP (median duration of castration = 23 months). The median PSA at imaging was 0.57ng/ml. Overall, 114 lesions were detected in 29 of the 37 patients. A high prevalence (73%) of N+/M+ disease was observed. Of the 114 lesions, 81 were PSMA-dominant and 33 were PSMA-/FDG+. Per patient level, 9 men (24%, 95%CI: 10%-39%) showed at least one new PSMA-/FDG+ lesions. A short PSADT ( P= 0.009, OR = 8.000) were associated with PSMA-dominant disease, while a high Gleason grade group ( P= 0.022, OR = 13.091) with PSMA-/FDG+ disease. 19 patients (51%) with 51 lesions could be enrolled for oligometastases-directed therapy including 10 PSMA-/FDG+ lesions. Among different disease stages, PSMA-/FDG+ disease was rarely detected in the hormone-sensitive cohort, but frequently found in the castration-resistant cohort. Conclusions: Using 68Ga-PSMA and 18F-FDG PET, we observed a high prevalence of N+/M+ disease and a significant proportion of PSMA-/FDG+ disease in patients with an early PSA progression during castration. (ChiCTR 1900022634). Clinical trial information: 1900022634 . [Table: see text]
Real-world experience with sipuleucel-T (Sip-T) in Asian men with castrate-resistant prostate cancer (CRPC).
Authors: Zhang Jingsong , Liu Ming , Pan Jiahua , Wei Xiao X. , Harmon Matthew , Azzolina John , Flanders Scott 
Published: May 2020

e17588 Background: Clinical trials of sip-T predominately included white men (over 90%). Previously we explored outcomes with sip-T in white and black patients (pts) (Kantoff PW, NEJM 2010; Sartor AO, ASCO 2019, #5035). In this retrospective analysis of data from electronic medical record and practice management systems, we explored the hypothesis that Asian and white pts who receive sip-T for CRPC exhibit similar overall survival. Methods: Data came from > 100 US community urology practices, predominantly large urology group practice associations. White and Asian pts were matched based on 5 criteria: sip-T treatment year; treatment pattern for oral and sip-T; metastatic site (Bone v. Nodal v. Visceral); prostate-specific antigen (PSA) within 10%; and age at treatment. Parameters retrieved include those listed in the table. Overall survival (OS) was analyzed using Kaplan Meier (KM) methodology with Cox Proportional Hazards Modelling used to generate the hazard ratio (HR) with Asians as the reference. Descriptive summary statistics were generated for other parameters. Results: The analysis identified 102 white and 77 Asian pts; treatment ranged from 2012 to 2019 with 60% receiving sip-T after 2016, impacting the ability to examine long-term outcomes. Characteristics of the 2 groups were broadly similar, although more Asians had Gleason scores ≥8 than whites (Table). In the KM analysis, most pts were censored. While the KM survival curves separate around month 25, favoring Asian pts, the difference is not significant (HR, 0.69 [95% CI: 0.4, 1.4]; P = 0.277). Conclusions: These real-world data do not show a significant difference in OS between Asian and white men. Both groups exhibited relatively low median PSAs near 5 ng/mL, an observation correlated with longer OS in previous studies. [Table: see text]
Effects of age on outcomes in men receiving treatment for metastatic castration-resistant prostate cancer (mCRPC): Analysis of Medicare fee for service (FFS) claims data.
Authors: Dorff Tanya B. , McKay Rana R. , Olsson Carl A. , Fitch Kate , Flanders Scott , Higano Celestia S. 
Published: May 2020

e17590 Background: Because elderly patients may exhibit differences in immune activation, we evaluated outcomes in men receiving first line treatment for mCRPC with sip-T or oral agents (ie, abiraterone acetate or enzalutamide) by age. Methods: Claims data from the 2013-2017 Centers for Medicare and Medicaid Services Fee for Service 100% Medicare Identifiable Database for Parts A, B and D were examined. We evaluated with index dates in 2014 and 3 years of follow-up. Patients were categorized by age (Table) and agent use as per Healthcare Common Procedure Coding System codes and National Drug Codes. First line use of sip-T vs oral agents was examined as was any line use of sip-T vs oral agents (without sip-T). Kaplan-Meier methodology was used to assess survival with Cox proportional hazards regression modelling used to calculate hazard ratios (HR). Results: Mean ages of men receiving sip-T and orals were 76 and 78 years, respectively. Most (84%) were white. Regardless of line of use, the risk of death among men receiving sip-T was lower than the risk in men receiving orals, except in men over 90 years old (Table). Conclusions: Based on these claims data, benefits of sip-T use were evident across all ages except for the men 90+ years old with decreasing differences between agents with increasing age, as would be expected. While the oral agents may be perceived as more convenient, greater survival with sip-T suggests that clinicians should consider use of sip-T therapy for mCRPC, irrespective of age. [Table: see text]
Fracture risk and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) sequentially treated with abiraterone acetate (AA) and radium-223 (RA223).
Authors: Caffo Orazio , Frantellizzi Viviana , Tucci Marcello , Galli Luca , Monari Fabio , Baldari Sergio , Masini Cristina , Bortolus Roberto , Facchini Gaetano , Alongi Pierpaolo , Zichi Clizia , Biasco Elisa , Fanti Stefano , Pignata Salvatore , Filice Angelina , Borsatti Eugenio , Rossetti Sabrina , Spada Massimiliano , Cortesi Enrico , De Vincentis Giuseppe 
Published: May 2020

e17593 Background: The increased incidence of bone fractures found in pts who received the AA-RA223 combination compared to those treated with AA alone in the ERA223 trial led to restrictive recommendations by the European Medicines Agency which limited the use of RA223 to pts who have received at least two previous treatments for mCRPC or who cannot receive any other treatment. Moreover, clinicians started to debate the risk of RA223-related fractures associated with the sequential administration of AA and RA223. The aim of this retrospective study was to assess the safety of administering RA223 to pts who have progressed during AA treatment mainly in terms of the rate of skeletal fractures. Methods: We retrospectively reviewed the records of mCRPC pts who received RA223 after progressing during an AA treatment line in everyday clinical practice in ten Italian Hospitals. Results: We reviewed data of a consecutive series of 94 mCRPC pts. Most of the pts (85.1%) received RA223 as second- or third-line treatment and had a Soloway score 2 or 3 (90%). RA223 treatment was well-tolerated: there were only four cases of grade 3 anemia, two case of grade 3 leukopenia, and one case of grade 3 neutropenia. The overall fracture rate of 2.1%: one fracture was recorded during the course of RA223 treatment, and one was recorded one month after its end. The fractures both occurred at metastatic sites in pts who were not treated with antiresorptive agents. Median overall survival (OS) from RA223 start was more than 14 mos and the pts who received Ra223 in second line (which is not allowed today in Europe) had the same median OS as those who received this agent in later lines. Conclusions: The findings of this study showed that the treatment with RA223 as subsequent treatment line after AA was active and safe with a very low risk of a fracture. The OS outcomes indicated that the administration of RA223 in early treatment lines is not detrimental, even after AA. Thus the present observational report makes a valuable contribution to the current debate concerning the risks and benefits of including RA223 in the therapeutic algorithm.
Identification of actionable BRAF mutations and their genomic associations in advanced prostate cancer.
Authors: Cittolin Santos Giordano Fabricio , Prophet Malshundria , Gourdin Theodore Stewart , Drusbosky Leylah , Ledet Elisa Marie , Sartor A. Oliver , Sonpavde Guru , Lilly Michael B. 
Published: May 2020

e17597 Background: Circulating tumor DNA (ctDNA) can be used to identify mutations and amplifications in patients with prostate cancer (PC). Identification of actionable mutations in BRAF may allow the use of targeted therapeutics not typically used in prostate cancer. Methods: We analyzed a ctDNA-based genomic profile database (Guardant Health) with 2274 unique advanced-stage patients, and a tissue-based genomic database (TCGA) with 3178 unique patients (73% locoregional, 27% metastatic). We compared the frequency and types of BRAF anomalies found in those datasets. We calculated the odds ratio of observing other genetic anomalies based on the BRAF mutation and amplification status. Finally, we utilized Principal Component Analysis (PCA) to study the utility of BRAF as a discriminator in identifying genetic subtypes of PC. Results: BRAF missense mutations in PC were found in 3.34% of the 2274 patients in the ctDNA cohort and in 1.1% of the 3178 patients in the TCGA cohort. Variants of Uncertain Significance (VUS) mutations were more commonly identified by ctDNA (53.8% of all mutations) vs TCGA (16.1% of all mutations). Biologically-significant mutations of all classes (I, II, III) were found in both datasets. BRAF mutations were mainly non-V600E and most mutations were clonal. Significant mutations common to both the ctDNA and TCGA cohorts include K601E, G469A, D594G, V600E, G466E, G446R, Q257K, I300V and R271H. Mutations unique to either ctDNA or TCGA datasets were found as well. BRAF mutations are highly associated with additional mutations in CDKN2A, TERT, and KRAS, as well as amplifications of CCNE1, KRAS, CDK6 (p < 0.01). BRAF amplifications are highly associated with multiple other gene amplifications, and with AR mutations (p < 0.01). Tumors with BRAF mutations and with BRAF amplifications are genetically distinct, and PCA indicates that BRAF status accounts for a significant amount of the difference. We described two patients that were treated with MEK targeted therapy with treatment response. Conclusions: 1. The use of ctDNA-based genomic analysis identified BRAF anomalies with a higher frequency than tissue-based techniques, but this is mostly due to higher numbers of VUS mutants found with ctDNA. Biologically significant BRAF mutations are mostly clonal and non-V600E mutations. 2. BRAF mutations and amplifications are associated with other specific gene anomalies. 3. ctDNA is a useful tool for identifying the genomic profile of PC in the clinical setting. 4. PC subjects with BRAF mutations identified by ctDNA may respond to MEK inhibitor therapy.
The impact of complications after diagnostic biopsy on repeat biopsy in men: Results from the Prostate Cancer Research International: Active surveillance (PRIAS-JAPAN) study.
Authors: Tohi Yoichiro , Kato Takuma , Matsumoto Ryuji , Shinohara Nobuo , Yokomizo Akira , Mitsuzuka Koji , Nakamura Masaki , Kume Haruki , Sugimoto Mikio 
Published: May 2020

e17616 Background: Active surveillance(AS) is the strategy to avoid the overtreatment for favorable prostate cancer. For safer AS protocol execution, repeat protocol biopsy is essential in evaluating cancer aggressiveness accurately. However, some men on AS refuse repeat protocol biopsy because of burdens on biopsy. We aimed to assess the complications of prostate biopsy and the impact of complications after diagnostic biopsy on repeat protocol biopsy from the analysis Japanese cohort forming part of the Prostate cancer Research International: Active surveillance (PRIAS) study. Methods: PRIAS-JAPAN started in January 2010, 39 institutions are participating in this study. Men are prospectively followed and repeat protocol biopsy are planned at 1 year and 4 years thereafter, or if prostate specific antigen-doubling time is < 10 years. Data was collected on the complications such as infection, hematuria, hematospermia, pain, and antibiotics, and approach of biopsy, retrospectively. We compared the complications in diagnostic biopsy between repeat biopsy acceptance group and repeat biopsy non-acceptance group at 1 year. Results: From 2010 to 2018, 862 men with low-risk prostate cancer were prospectively enrolled in PRIAS-JAPAN. 794 men (92%) actually proceeded to protocol at 1 year. Of the 794 men, repeat protocol biopsy non-acceptance rate at 1 year was 18.4%(146 men). According to differences in the complications of diagnostic biopsy, hematuria(p = 0.003) and pain(p < 0.001) rate were significantly higher in repeat biopsy non-acceptance group, but infection(p = 0.105) and hematospermia(p = 0.224). Approach of biopsy(p = 0.651) was not different in two groups. Conclusions: Hematuria and pain in diagnostic biopsy were significantly more frequent in repeat biopsy non-acceptance group. Our study supports the importance of adequate explanation and management of the complications at biopsy to improve the rate of protocol biopsy acceptance. [Table: see text]