bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of ARV7 in Asian metastatic castrate-resistant prostate cancer (mCRPC) patients using multiple detection platforms.
Authors: Chan Johan , Ong Whee Sze , Ng Quan Sing , Toh Chee-Keong , Rajasekaran Tanujaa , Tan Wan Ling , Tan Hui Shan , Tan Min-Han , Lim Kiat Hon , Lee Yifang , Wong Siew Wei , Wong Alvin SC , Saad Marniza Bte , Ng Chi-Fai , Chansriwong Phichai , Horie Shigeo , Kanesvaran Ravindran 
Published: February 2020

245 Background: The presence of AR-V7 in metastatic castrate resistant prostate cancer (mCRPC) men has been associated with worse outcome in men initiated on 2nd generation androgen receptor signalling inhibitors (ARSI) in the Caucasian population. A multinational study was conducted to investigate this in the Asian population. Methods: mCRPC patients were recruited prospectively across 5 countries. Blood samples were collected and processed from patients with progressive disease immediately before the initiation of a new treatment and at progression. AR-V7 detection were performed using 3 methods: CTC enrichment followed by automated immunofluorescent staining (Clearbridge [CB]), CTC enrichment followed by reverse-transcription PCR analysis (IBN), and the AdnaTest Prostate Cancer(Adna) platform for CTC analysis and detection. Only blood samples collected in Singapore underwent all 3 methods of detecting AR-V7. Comparison of AR-V7 prevalence using the 3 detection methods were done on patients with the AdnaTest platform as gold standard. We examined associations between AR-V7 status and PSA response rates, PSA progression free survival and overall survival(OS). Results: 102 patients were recruited. 72 patients had ARSi while 30 patients had chemotherapy. 66 patients were included for the comparison of AR-V7 detection methods. AR-V7 prevalence rate was 14.3% (95% CI 4.8-30.3), 21.6% (95% CI 12.9-32.7) and 33.7% (95% CI 24.6-43.8) based on Adna, CB and IBN respectively. Concordance between Adna and CB was 75% while Adna and IBN was 68%. AR-V7- patients had a trend towards higher PSA response, lower risk of PSA progression as compared to AR-V7+ patients. AR-V7- patients had a significantly lower risk of death as compared to AR-V7+ patients detected by Adna and IBN platforms but not the CB platform. The association between ARV7 status and outcomes did not vary when compared across treatment groups. Conclusions: AR-V7 positivity in Asian mCRPC patients is consistent with the data reported in Western populations with lower PSA response rates, PSA progression free survival and OS. This data suggest that ARV7 is more likely a prognostic than a predictive biomarker. Clinical trial information: 2015/2797.
Association of PI-RADS categories and PSA density with active surveillance progression in patients with prostate cancer.
Authors: Wang Alex Z. , O'Connor Luke P. , Yerram Nitin , Zeng Johnathan , Mehralivand Sherif , Harmon Stephanie , Gurram Sandeep , Chalfin Heather , Telfer Siobhan , Lebastchi Amir H. , Ahdoot Michael , Gomella Patrick H. , Merino Maria J. , Turkbey Baris , Wood Bradford J. , Choyke Peter L. , Pinto Peter A. 
Published: February 2020

293 Background: Active surveillance (AS) is now considered a well-accepted alternative for low-favorable intermediate risk prostate cancer over definitive therapy. Few studies have incorporated the use of multi-parametric MRI (mpMRI) into the treatment paradigm. In this study we investigate imaging findings that are predictive of a patient dropping off AS. Methods: Our institutional database was queried for all patients who met criteria for active surveillance from 11/2003 to 5/2017. Criteria for inclusion included ≥ 2 mpMRIs, ≥ 2 prostate biopsies, and a diagnosis of Gleason Grade group (GG) 1 or higher. Patients were excluded if they received any other therapy for the treatment of their prostate cancer such as radiation, chemotherapy, focal therapy, or immunologic therapy. Patient demographics, mpMRI, biopsy and most recent follow-up data were recorded. Factors, including PSA density (PSAD), PSA, lesion size, and PI-RADS category, associated with AS progression were evaluated in Cox Proportional Hazards Model. Results: An analysis of a total of 212 patients were performed during the study time interval. 88 patients were dropped from AS during this time and of those patients the median amount of time before removal was 4.70 years (range, 0.7-10.5). On univariable analysis, PI-RADS category (HR, 1.302 for every increase in 1 unit of the PI-RADS category; 95% CI, 1.046-1.62, p = 0.01) and PSAD (HR, 4.98 for every increase in 0.001 ng/mL/cc; 95% CI, 2.127-11.66; p < 0.001) were found to be associated with being removed from AS. On multivariable analysis, both PI-RADS score (HR, 1.281 for every increase in 1 unit of the PI-RADS category; 95% CI, 1.025-1.6; p = 0.003) and PSAD (HR, 4.188 for every increase in 0.001 ng/mL/cc; 95% CI, 1.640-10.7; p < 0.001) remained associated with being removed from AS. Conclusions: PI-RADS categories and PSAD predict the risk of a patient to drop off active surveillance. AS. Patients with these criteria should be considered high risk in any current AS protocol.[Table: see text]
A randomized phase II study of apalutamide (APA), androgen deprivation therapy (ADT), or APA + ADT in patients (pts) with biochemically relapsed (BCR) prostate cancer (PC).
Authors: Aggarwal Rahul Raj , Alumkal Joshi J. , Szmulewitz Russell Zelig , Higano Celestia S. , Bryce Alan Haruo , Lopez-Gitlitz Angela , McCarthy Sharon Anne , Miladinovic Branko , McQuarrie Kelly , Thomas Shibu , Small Eric Jay 
Published: February 2020

320 Background: While there is no standard therapy for BCR PC following local therapy, intermittent ADT is widely used. We evaluated utility of APA alone, ADT (luteinizing hormone–releasing hormone agonist [LHRHa]) alone, or APA + LHRHa in ADT-naïve BCR PC pts. Methods: Pts with BCR PC after primary definitive local therapy and prostate-specific antigen (PSA) doubling time (PSADT) ≤ 12 mo were randomized 1:1:1 to open-label 240 mg APA daily, LHRHa alone, or APA + LHRHa for 12 mo, followed by a 12-mo observation period off therapy. Pts were stratified by PSADT (< 6 vs 6-12 mo) and age (≤ 70 vs > 70 y). Primary end point: mean change from baseline (BL) in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy-Prostate total score at 12 mo. Secondary end points included PSA nadir < 0.2 ng/mL by 7 mo, time to PSA progression (TTPpsa), and time to testosterone (T) recovery. Results: 90 pts (APA, n = 29; LHRHa, n = 30; APA + LHRHa, n = 31) were treated for median of 12 mo with similar distribution of BL characteristics across groups: 67% age ≤ 70 y; 67% PSADT < 6 mo. There was no significant difference in HRQoL in APA vs LHRHa at 12 mo, or between LHRHa vs APA + LHRHa groups. At median follow-up of 30-33 mo, TTPpsa in APA, LHRHa, and APA + LHRHa groups was 26 mo, 31 mo, and 36 mo, respectively. Compared to LHRHa alone, APA + LHRHa resulted in a trend toward improved TTPpsa (HR [95% CI] 0.56 [0.23-1.36], p = 0.196), and APA alone resulted in a trend for shorter TTPpsa (HR 1.09 [0.49-2.43], p = 0.824). PSA nadir < 0.2 ng/mL was reached in 89%, 89%, and 97% in APA, LHRHa, and APA + LHRHa pts. Median time to T recovery was similar in LHRHa and APA + LHRHa groups (23 mo vs 24 mo). Grade 3-4 adverse events (AEs) occurred in 17% of APA, 14% of LHRHa, and 29% of APA + LHRHa pts. The only grade 3-4 AE reported in > 1 pt per group was hypertension (APA, 3%; LHRHa, 0; APA + LHRHa, 13%). Conclusions: Addition of APA to LHRHa resulted in a trend for longer TTPpsa and a higher proportion of pts achieving optimal PSA nadir without significant difference in HRQoL or time to T recovery. Observed AEs were consistent with known safety profiles. Results support further evaluation of APA + LHRHa for a specified duration in BCR PC. Clinical trial information: NCT01790126.
Biochemical relapse in very high-risk prostate cancer after radical prostatectomy and DC-vaccine loaded with tumor RNA, hTERT, and survivin.
Authors: Lilleby Wolfgang , Tryggestad Anne Merete , Bigalke Iris , Brennhovd Bjørn , Axcrona Karol , Josefsen Dag , Axcrona Ulrika , Kvalheim Gunnar , Dueland Svein 
Published: February 2020

324 Background: Patients with very high-risk prostate cancer (VHR-PC) features experience worse outcome after radical prostatectomy. This study was designed to assess biochemical failure and toxicity of adjuvant dendritic cells vaccine (DCV) in prostate cancer patients who are at greatest risk for cancer progression. Methods: Twenty patients with pathological stage pT2 - pT3b and Gleason score 7B-10, pN0, pN+ or pNx were enrolled into the approved study DC-005. The primary end point was clinical failure. Ten patients were tested for disseminated tumor cells (DTCs) to the bone marrow before inclusion to the study. Three patients out of 10 patients had positive DTCs detection in bone marrow. The mean age of the cohort was 63 years (SD 6.9 years), and three patients had postsurgical pN1 status. Eighteen patients had two or more high-risk factors (ISUP grade 5, T3- stage and or PSA > 20 ng/mL). Autologous dendritic cells were transfected with mRNA for hTERT, survivin and tumor mRNA. The DCV product was applied intradermally after curative intended surgery once per week the first months, then once per months the first year, thereafter every 3 months for two years or until biochemical progression (PSA relapse cut-off ≥ 0.3). Results: After 5 years follow-up (FU) 62% (12/20 patients) had not biochemically progressed and with a median FU of 69 months all patients included in the study are alive. Five patients were treated with salvage and one patient with adjuvant radiation treatment, three patients received limited ADT, and three patients are on first line ADT, none of those eight patients have experienced castration resistant prostate cancer. The toxicity was mild with no serious adverse event related to DCV. Conclusions: Adjuvant DCV mitigates the time to biochemical progression. These results appear favorably compared to historical controls in VHR-PC. The clinical outcomes of this study warrants a future enlarged clinical trial. Clinical trial information: NCT01197625.
Adjuvant docetaxel for high-risk localized prostate cancer: Update of NRG Oncology/RTOG 0521.
Authors: Sandler Howard M. , Karrison Theodore , Sartor A. Oliver , Gomella Leonard G. , Amin Mahul B. , Purdy James , Michalski Jeff M. , Garzotto Mark , Pervez Nadeem , Balogh Alexander G. , Rodrigues George , Souhami Luis , Reaume M. Neil , Williams Scott , Hannan Raquibul , Jones Christopher U. , Horwitz Eric M. , Rodgers Joseph P. , Feng Felix Y , Rosenthal Seth A. 
Published: February 2020

333 Background: High-risk, localized prostate cancer has a poor prognosis. We hypothesized that adj docetaxel (D) and prednisone and long-term (24 mos) androgen suppression (AS) and radiation therapy (RT) would improve overall survival (OS) and tested this in NRG/RTOG 0521. Results with med follow-up of 5.7 yrs were reported (JCO 37:1159, 2019), showing a benefit of D (HR=0.69, 90% CI: 0.49-0.97, 1-sided p=0.034). Med follow-up is now 10.4 yrs and we report updated results for OS and metastasis (DM). Methods: NRG/RTOG 0521 opened 12/05 and closed 8/09 with targeted accrual of 600 and designed to detect a HR of 0.49, based on improvement in 4-yr OS from 86 to 93%. With 0.05 1-sided type I error and 90% power >78 deaths were required. Pts were stratified by predefined risk groups. Group 1: Gl 9-10, any T; Group 2: Gl 8, PSA<20, T≥T2; Group 3: Gl 8, PSA≥20, any T; Group 4: Gl 7, PSA≥20, any T. maxPSA ≤150. RT dose was 75.6 Gy. Chemo consisted of 6, 21-day cycles of D starting 28 days after RT. Results: Of 612 accrued, 563 were eligible/available for analysis. By risk group 1-4, there were 297, 116, 64, and 86 pts. Med PSA 15 ng/mL. 10-yr OS rates were 64% [95% CI: 58-70%] for AS+RT and 69% [95% CI: 63-75%] for AS+RT+CT (HR = 0.89, 90% CI: 0.70, 1.13, 1-sided p=0.22). However there was evidence of non-proportional hazards (Grambsch-Therneau test, p=0.016). Thus survival was alternatively evaluated with restricted mean survival time (RMST). The difference in RMST at 10 yrs was 0.42 yrs (90% CI: 0.07-0.77, 2-sided p=0.048). Cumulative incidence of DM at 10 yrs was 22% [95% CI: 17-27%] for AS+RT and 20% [95% CI: 15-25%] for AS+RT+CT (2-sided log-rank p=0.29). At 10 years most deaths occurred in risk group 1: 62 in AS+RT and 50 in AS+RT+CT (HR= 0.93, 95% CI: 0.66-1.32, 2-sided log-rank p=0.16). There was no new related Grade 5 toxicity. Conclusions: OS findings, reported after follow-up of 5.7 yrs, demonstrated a small beneficial effect of adding D to AS and RT. With longer follow-up the benefit of D remains, but the HR varies over time and the OS curves have converged. Support: U10CA180868 (NRG Operations), U10CA180822 (NRG SDMC), U24CA180803 (IROC) from the NCI and Sanofi-Synthelabo Int. Clinical trial information: NCT00288080.
Fraction genome altered (FGA) to regulate both cell autonomous and non-cell autonomous functions in prostate cancer and its effect on prostate cancer aggressiveness.
Authors: Chakraborty Goutam , Ghosh Arnab , Nandakumar Subhiksha , Armenia Joshua , Mazzu Ying Zhang , Atiq Mohammad Omar , Lee Gwo-Shu Mary , Mucci Lorelei A. , Merghoub Taha , Wolchok Jedd D. , Kantoff Philip W. 
Published: February 2020

347 Background: Our ability to distinguish lethal from non-lethal forms of prostate cancer (PC) is limited. Given prostate tumors’ genetic heterogeneity, is it unlikely that a single somatic variant is prognostic. Herein we investigated fraction of genome altered (FGA; percentage of copy number altered chromosome regions out of measured regions; cBioportal) and tumor mutational count (TMC; number of mutational events per case) harbored by the primary tumor as two tumor-specific factors posited to influence disease aggressiveness or responsiveness to certain therapeutic agents. Methods: We used the TCGA data (n= 490 primary PC) and MSKCC-IMPACT (n=717, Zehir et al 2017) PC datasets to analyze the correlation between FGA and TMC in PC. GSEA was performed with transcriptomes used to identify signaling pathways associated with these two measures. We then categorized 490 primary PC patients from TCGA dataset into 4 groups based on FGA and TMC levels (based on the median values) to assess associations with outcomes. Results: Primary PC patients who harbor FGAhighTMClow exhibited shorter disease-free survival (High Risk). We observed attenuation of the androgen signaling pathway and induction of cell proliferation pathways associated with this aggressive form of disease. We used results from CIBERSORT algorithm and deep learning methods of TCGA data and observed that quantities of tumor infiltrating lymphocytes was higher in the FGAhighTMClow group (p=0.038). However, we also observed significantly reduced immune effector signaling-pathway signaling in this high-risk FGAhighTMClow group suggesting the presence of immune-suppressive networks in primary disease associated with a high risk of progression. Conclusions: A greater understanding of molecular features of aggressive primary PC (FGA/TMC) will be important in developing management strategies. Based on our preliminary analyses, we hypothesize that patients whose primary PC harbors FGAhighTMClow have a higher likelihood of aggressive disease due to their impact on PC cell proliferation and dedifferentiation (cell autonomous), and subdued immune responses (non-cell-autonomous).
The prevalence of cardiovascular disease and its risk factors among prostate cancer patients treated with and without androgen deprivation.
Authors: Pinthus Jehonathan H. , Shayegan Bobby , Klotz Laurence , Siemens D. Robert , Luke Patrick P. , Niazi Tamim , Fradet Vincent , Fradet Yves , Duceppe Emmanuelle , Lavallee Luke , Mousavi Negareh , Hamilton Robert James , Brown Ian , Chin Joseph , Gopaul Darin , Violette Philippe , Davis Margot , Mian Rajibul , Karampatos Sarah , Leong Darryl ,   RADICAL-PC Investigators
Published: February 2020

364 Background: Cardiovascular disease (CVD) is the second most common cause of death in prostate cancer (PC) patients, yet the prevalence of CVD and its risk factors have been incompletely described in this population. Androgen deprivation therapy (ADT) is a risk factor for CVD. The objective of this study were to describe the CVD characteristics and risk factors in PC patients and the relationship between CVD risk and how ADT is used in real-world practice. Methods: RADICAL-PC (Role of Androgen Deprivation Therapy in CArdiovascular Disease – A Longitudinal Prostate Cancer Study) is an ongoing prospective cohort study. We recruited 2395 consecutive men (mean age 68 years) with newly diagnosed PC or with a plan to prescribe ADT for the first time. Cardiovascular risk was estimated by calculating Framingham risk scores. A Framingham score >17 (corresponding with a predicted 10-year CVD risk of >30%) was considered high-risk. Multivariable logistic regression was performed with ADT use as the outcome variable and CVD risk factors as the exposures of interest. Results: The prevalence of known CVD for the entire cohort was 22% and 35% had a Framingham risk score >17. Most participants (58%) were current or former smokers; 16% had diabetes; 45% had hypertension and 23% had high blood pressure but had not received a diagnosis of hypertension; 31% were obese (BMI ≥30kg/m2); 24% had low levels of physical activity. There was a positive relationship between each major cardiovascular risk factor and the use of ADT. However, after adjustment for age, education, alcohol use, BMI and time from PC diagnosis to eligibility assessment, these associations were significantly attenuated. Participants in whom ADT was planned had higher Framingham risk scores than those not intending to receive ADT. This risk was abolished after adjustment for confounders. Conclusions: One in three men with PC is at high cardiovascular risk. Men receiving ADT are a priori at higher CVD risk than PC patients whose treatment strategy does not include ADT. These differences are explained by confounding factors. Clinical trial information: NCT03127631.
Utilization of androgen deprivation therapy (ADT) and stereotactic body radiation therapy (SBRT) for localized prostate cancer (PC) in the United States (US).
Authors: Royce Trevor Joseph , Switchenko Jeffrey M. , Zhang Chao , Spratt Daniel Eidelberg , Chen Ronald C. , Jani Ashesh B. , Patel Sagar Anil 
Published: February 2020

370 Background: Randomized trials have demonstrated improved survival with the addition of ADT to conventionally fractionated radiotherapy (RT) for men with unfavorable intermediate risk (UIR) and high-risk (HR) prostate cancer (PC). The benefit of ADT with SBRT is unknown. The purpose of this study is to examine ADT utilization with SBRT in the US. Methods: Men > 40 years old with localized PC treated with external beam RT for curative intent between 2004-2015 were analyzed from the National Cancer Database. Patients who received brachytherapy, surgery, or lacked ADT or risk stratification data were excluded. A total of 7,559 men treated with SBRT (≥5Gy/fraction; ≤5 fractions; dose ≥25Gy) versus 133,825 men treated with moderate or conventional RT (≤3Gy/fraction; dose ≥60Gy) were included. Patients were stratified by risk: low (LR), favorable intermediate (FIR), UIR, and HR using NCCN criteria. Differences between RT and SBRT were determined via Chi-square test. Results: Among all PC treated with RT, SBRT use increased from 2004 to 2015 across risk groups – overall: 0.9% to 10.3%; LR: 0.9% to 21.6%; FIR: 1.1% to 13.7%; UIR: 0.6% to 10.8%; HR: 0.8% to 2.8%; p < 0.001. Among all PC treated with RT, ADT use declined from 2004 to 2015 for LR (22.8% to 5.5%), FIR (51.7% to 40.0%), UIR (53.4% to 49.5%), but not HR (78.9% to 84.2%); p < 0.001. Patients with EBRT were more likely to receive ADT compared to those with SBRT across risk groups (Table). Conclusions: The majority of patients receiving SBRT for UIR and HR disease in the US do not receive concurrent ADT, despite national guideline recommendations and the lack of level 1 evidence to support this practice pattern. The omission of ADT may result in inferior oncologic outcomes, and randomized trials are needed to establish the safety of omitting ADT with SBRT for higher risk PC.[Table: see text]
Evaluation of the oncologic benefit of adjunctive surgery at time of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Authors: Nestler Tim , Paffenholz Pia , Pfister David , Hiester Andreas , Nini Alessandro , Albers Peter , Heidenreich Axel 
Published: February 2020

388 Background: PC-RPLND for advanced nonseminomatous germ cell tumors aims to resect all remaining metastatic tissue. The resection of adjacent visceral or vascular organs is commonly performed to achieving complete resection of the residual masses. However, the frequency of metastatic involvement of those organs with teratoma or vital cancer is currently unknown. Methods: We reviewed a cohort of 1181 patients who underwent PC-RPLND between 2008 and 2018 as a 2-center study and identified 235 (20%) cases of adjunctive surgery during PC-RPLND. We analysed the pathohistological presence of germ cell tumor elements in the resected organs: viable tumor (V), teratoma (T) or necrosis / fibrosis (N). Surgery associated complications were reported according to the Clavien-Dindo classification. Outcomes of subgroups were compared by using log-rank test. Results: V, T, N was present in 51 (21%), 91 (39%) and 93 (40%) of all patients with adjunct resected organs. In 235 patients, 316 adjunct organs were resected with 64 (27%) of these patients receiving a resection of multiple organs. The kidney was the most often resected organ (n = 74; V: 27% T: 39% N: 34%), followed by V. Cava (n = 66; V: 24% T: 36%, N: 40%) and partial liver resections (n = 48; V: 15%, T: 31%, N: 54%). Intraoperative complications occurred in 21% of patients (VT 32% vs N 17%, p = 0.021). Postoperative complications occurred in 35% of which 22% were Clavien Grad III-V showing no significant differences between VTN p = 0.093. 27% of all patients suffered from a relapse during a median follow-up of 22 months [0-180]. Patients with T or V in the resected specimens had a significantly reduced 5-year RFS compared to patients with only N (39%, 81%, p < 0.001). Conclusions: This study shows for the first time that 40% of all resections of adjunct organs are oncologically unnecessary due to the presence of N only in the pathological specimens. In case of doubt we propose an organ safe procedure with multiple intraoperative frozen section to avoiding oncologically unnecessary adjunctive surgeries especially nephrectomies and vascular resections. Additionally, a more accurate presurgical workup is required to spare patients with N from PC-RPLND.