bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of the 17-gene genomic prostate score test in men with prostate cancer (PCa) managed with active surveillance (AS): Results from the Canary Prostate Active Surveillance Study (PASS).
Authors: Lin Daniel W. , Zheng Yingye , McKenney Jesse , Brown Marshall , Lu Ruixiao , Crager Michael , Boyer Hilary , Brooks James D. , Dash Atreya , Fabrizio Michael , Gleave Martin , Liss Michael A. , Morgan Todd Matthew , Thompson Ian M , Wagner Andrew , Tsiatis Athanasios , Pingatore Andrea , Lawrence H. Jeffrey , Nelson Peter S , Newcomb Lisa F 
Published: March 2019

262 Background: The 17-gene Genomic Prostate Score (GPS) test (scale 0-100) predicts adverse surgical pathology (AP) and recurrence in newly diagnosed low- and intermediate-risk PCa. Studies of the predictive value of the GPS test in men initially managed with AS are limited. Methods: Diagnostic biopsy tissue was obtained from 634 men enrolled at 8 sites in PASS. Time to AP (Gleason Grade Group (GG) ≥3, ≥pT3a, or N1) in men who underwent radical prostatectomy (RP) was the primary endpoint. All diagnostic biopsies and RP specimens were centrally reviewed. Multivariate regression models for interval censored data were used to evaluate the association between time to AP and GPS. Inverse probability of censoring weighting was applied to adjust for informative censoring. Association between GPS and time to Gleason score upgrade on surveillance biopsy was also evaluated using a Cox Proportional Hazards model. Results: GPS results were obtained for 432 men (median follow-up 4.6 [IQR: 2.9-6.2] years); 374 and 58 with GG 1 or 2 cancer, respectively; median PSA density (PSAD) was 0.11 [IQR: 0.08-0.15]; 101 men underwent RP with central pathology after a median of 2.1 [IQR: 1.3-4.3] years surveillance, and 52 (52%) men undergoing RP had AP. 167 men upgraded at a subsequent biopsy. No clinico-pathologic covariates were significantly associated with AP other than PSAD. GPS was significantly associated with time to AP (hazards ratio [HR]/20 GPS units: 1.96 [95% CI = 1.17-4.28]; p = 0.030), when adjusted for diagnostic GG, or for dichotomous PSAD ( < vs ≥ 0.15; HR: 1.83, 95% CI = 1.04-3.62; p = 0.046). GPS was not significantly associated with AP (HR: 1.61, 95% CI = 0.87-2.98; p = 0.12) when adjusted for continuous PSAD. No association, either univariable or multivariable, was observed between GPS and subsequent biopsy upgrade. Conclusions: In a cohort of men on AS, GPS was associated with time to AP when adjusted for diagnostic GG or dichotomous PSAD. GPS was not associated with surveillance biopsy GG upgrading or AP at surgery after adjustment for continuous PSAD, although a trend was seen for AP, suggesting an association may be seen in a larger study.
Alkaline phosphatase (ALP) value at diagnosis of CRPC and response to primary androgen deprivation therapy may predict metastasis in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Authors: Keiichiro Mori , Kimura Takahiro , Egawa Shin 
Published: March 2019

294 Background: Numerous therapeutic options are available for metastatic castration-resistant prostate cancer (mCRPC). However, current therapeutic options remain inadequate for non-metastatic CRPC (nmCRPC); furthermore, there is a paucity of clear evidence to show who may be targeted for aggressive therapy among nmCRPC patients. Therefore, the objective of this retrospective study was to explore predictors of metastasis in patients with nmCRPC and to identify a subpopulation of nmCRPC patients who may benefit from aggressive therapy. Methods: A total of 115 patients with CRPC who had no metastasis at the time of diagnosis of CRPC were included in this retrospective study. All patients were treated at Jikei University Hospital. The primary outcome measure was metastasis-free survival (MFS) from the time of diagnosis of CRPC. Predictors of MFS were also explored with a multivariate Cox model. Results: The median observation period after diagnosis of CRPC in these patients was 30 months. Kaplan-Meier analysis revealed a median MFS of 76 months in these patients. Multivariate analysis demonstrated that low ALP values at diagnosis of CRPC and favorable response to primary androgen deprivation therapy (ADT) were significant predictors of longer MFS ( P = 0.011, and 0.031, respectively). Conclusions: Study results suggest that high ALP values at diagnosis of CRPC and poor response to primary ADT may predict metastasis in patients with nmCRPC. Further prospective studies will be required in more patients to confirm our findings. Univariate/multivariate analysis of factors contributing to MFS in nmCRPC patients. [Table: see text]
Next generation sequencing of primary prostate cancer tumors to reveal potentially actionable opportunities for clinical management: The UNC experience.
Authors: Crona Daniel James , Drier Anthony , Zhu Jing Daisy , Bell Emily Fox , Sketch Margaret Rose , Garrett Amy , Mitchell Khalis , Tomlins Scott A , Dees Elizabeth Claire , Godley Paul Alphonso , Dunn Mary , Rose Tracy L , Basch Ethan M. , Milowsky Matthew I. , Whang Young E. 
Published: March 2019

305 Background: The Strata trial (NCT03061305) is a multi-institutional precision oncology collaboration structured as an observational protocol that aims to match patients to genomically-guided therapies. Methods: Selected University of North Carolina (UNC) metastatic prostate cancer (mPC) patients were enrolled on this IRB-approved study. Formalin fixed paraffin-embedded primary tumor specimens, without matched germline controls, were sent for targeted next generation sequencing (NGS) to detect actionable variants, including: mutations in 87 genes, copy number variations in 31 genes, and gene fusions in 46 gene drivers. mPC-related genes of particular interest included: AR, ATM, BRCA1/2, ERG, MSH2, MSH6, PTEN, RB1, and TP53. Results: Of the 92 cases sequenced, 5 [5%] failed testing. Of the 87 mPC patients (median age 69 years [47-86]) enrolled: 53 [61%] were white, 28 [32%] were black, 1 [1%] was Asian, and 5 [6%] declined to be identified. NGS data revealed 106 variants in 27 genes: 62 patients (71%) had at least one variant, 21 (24%) had 2 variants, 7 (8%) had 3 variants, and 4 (3%) had 4 variants. Among the 62 patients with at least 1 identified variant, TMPRSS2-ERG fusion occurred most frequently (50%), followed by TP53 (40%), and PTEN (16%). 6% of all sequenced patients had variants in DNA damage repair genes including ATM (3%), BRCA2 (2%) and MSH2 (1%). One patient had a SLC45A3-ERG fusion combined with PTEN deep deletion, which has been associated with a more aggressive phenotype. One patient with a microsatellite-instability high tumor was treated with pembrolizumab. Conclusions: The UNC experience shows that a high proportion of primary prostate cancer tumors from mPC patients have genomic variants, and one patient was treated based on these data. Limited actionability may reflect the landscape of currently FDA approved mPC treatments, and available clinical trials. It may also be due to a short follow-up, and these data could inform treatment planning upon progression.
The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.
Authors: Cem Onal , Sedef Ali Murat , KOse Fatih , Oymak Ezgi , Guler Ozan Cem , Sumbul Ahmet Taner , Aksoy Sercan , Akkus Yildrim Berna , Besen Ali Ayberk , Mullaoglu Sadik , Mertsoylu Huseyin , Ozyigit Gokhan 
Published: March 2019

308 Background: The aim of this study is to evaluate the prognostic implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and after 4 and 12 weeks of treatment with abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively evaluated 102 mCRPC treated with abiraterone either pre- or post-chemotherapy between November 2012 and October 2017 in three institutions. We calculated NLR and PLR at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks. Fifty patients (49%) were treated with abiraterone post-docetaxel, and 52 patients (51%) received abiraterone pre-chemotherapy. Based on receiver operating characteristic analysis, patients were stratified as low NLR ( < 3.1) or high NLR (≥ 3.1), and low PLR ( < 163) or high PLR (≥ 163). The cutoff for anemia was < 12g/dL. Results: Median follow-up times for patients overall and for those who survived were 24.0 months (range, 0.3 – 54.9 months) and 25.5 months (range, 2.8 – 54.9 months), respectively. The median time of abiraterone treatment was 8.1 months (range, 2.4 – 40.1 months). The median overall survival (OS) was 20.8 months (interquartile range: 17.3–24.4). In univariate analysis, NLR, PLR, PSA response, and low hemoglobin (Hgb) were found significantly predictive of OS and progression-free survival (PFS). In multivariate analysis, declines in NLR and PSA of ≥ 90% emerged as significant independent predictors of OS and PFS. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. Patients with baseline Hgb > 12 g/dL had significantly longer median OS compared with patients with Hgb ≤ 12 g/dL; however, the significance of Hgb was lost at 12 weeks. Conclusions: NLR and PSA response to abiraterone was a significant predictor of OS and PFS in mCRPC patients treated with abiraterone delivered either pre- or post-chemotherapy. Furthermore, persistent increase in NLR during abiraterone has prognostic value for OS in patients with mCRPC.
Questioning the status quo: Should Gleason 3+3=6 PCa be considered a “negative core” for pre-RP risk nomograms?
Authors: Leong Joon Yau , Chandrasekar Thenappan , Tham Elwin , Teplitsky Seth , Trabulsi Edouard John , Gomella Leonard G. , Lallas Costas D. 
Published: March 2019

31 Background: Current pre-radical prostatectomy (RP) nomograms predicting RP pathology do not differentiate between Gleason 6 prostate cancer (Gl6 PCa) and clinically significant Gleason 7-10 PCa. As such, use of these nomograms can be problematic. We assess the impact of excluding Gl6 PCa on nomogram and RP outcomes. Methods: Utilizing a prospectively maintained database, all men who underwent prostate biopsy (PBx) prior to RP were identified. Each patient was assessed using the MSKCC Kattan and Briganti nomogram using the following iterations: 1) “Original” [ORIG] (all available core data) and 2) "Selective” [SEL] (only cores Gleason score ≥7). Nomogram outcomes (risk of LNI, ECE, SVI, and OCD), were compared across iterations and stratified based on pre-RP risk classification (3+3 [low], 3+4, 4+3, 8-10 [high]). Clinically significant impact on management [CSIM] was defined as a change in risk of LNI above or below 2% (Δ2) or 5% (Δ5), based on current guidelines recommendations for PLND. Nomogram outcomes were validated using RP pathology. Results: 1118 men met inclusion criteria. Using the Kattan nomogram, when compared to actual RP pathology, the SEL iteration was a better predictor of LNI, ECE and OCD than the ORIG iteration, but not SVI. Using the Briganti nomogram, the SEL iteration was a better predictor of LNI. As for CSIM, the greatest impact was on men with Gl7 PCa. In the 359 Gl 3+4 patients, Δ2 was 3.9-28.13% and Δ5 was 12.81-17.27%. In the 184 Gl 4+3 patients, Δ2 was 0% and Δ5 was 7.61-11.41%. In all cases, the change favored decreased need for PLND. Conclusions: As Gleason 3+3=6 PCa is increasingly being considered an insignificant prostate cancer, its inclusion in established pre-RP nomograms becomes problematic. We find that excluding Gl6 PCa cores from these nomograms can reduce the need to complete a PLND at the time of RP, and more importantly, may better reflect the true extent of cancer. [Table: see text]
Clinical drivers for imaging testing in nonmetastatic castration-resistant prostate cancer: May they be optimized?—Data of “IDENTIFICA” study.
Authors: Useros RodrÃguez Eduardo , Juárez Álvaro , Carballido Rodríguez Joaquín , Rubio Jose , Rodríguez Antolín Alfredo , Amores Bermúdez Francisco Javier , Medina González Antonio , Rodrigo Miguel , Moreno Jiménez Juan , Vázquez Fernando , Muñoz del Toro Jacobo , Garcia Angela , Cózar Olmo José Manuel 
Published: March 2019

318 Background: Metastases (M+) detection is a critical event in non-metastatic castration-resistant prostate cancer (nmCRPC), as it entails a change in PC management and is a potential surrogate for survival at this stage. PSA doubling time (PSA-DT) has been described as a prognostic factor to develop M+. However, there could be other relevant factors to raise suspicion of progression in nmCRPC patients. The “IDENTIFICA” study tries to describe disease characteristics and clinical drivers that make physicians suspect the presence of M+ in nmCRPC patients in clinical practice in Spain. Methods: Observational, transversal, multicenter study. nmCRPC patients with physician’s suspiction of M+ were selected. Imaging tests to rule out metastases were requested; clinical drivers were described, along with clinical data related to prostate cancer (PC). Results: 197 nmCRPC patients were recruited (Jan-Jun 2018). Median age was 81.3 years. Median time from the onset of androgen deprivation therapy (ADT) to CRPC was 5.1 years (IQR: 2.5-8.2). ADT was the first PC treatment for 64.4% of , while 41.2% went through a curative-intent treatment. Median PSA-DT at CRPC diagnosis was 7.5 months. Time from PC diagnosis to CRPC was influenced by Gleason score at diagnosis ( p=0.001), primary curative intent treatment ( p<0.001), and PSA-DT at CRPC diagnosis ( p=0.04). Most important clinical drivers leading physicians to request imaging were PSA value, PSA-DT and PC guidelines recommendations. M+ were detected in 23 patients (16.5%). In the multivariate analysis, there was a statistically significant relation between positive imaging and time on ADT (OR 1.16; 95% CI 1.018-1.325; p=0.026) and time on CRPC status (OR 1.55; 95% CI 1.038-2.302; p=0.032). In this interim analysis, PSA and PSA-DT seemed not to be statistically related to M+ appearance. Conclusions: PSA and PSA-DT seem to be the most influential drivers to request imaging tests during follow-up of nmCRPC patients. Time on ADT and time on CRPC status could be relevant factors for M+ detection and phycisians should be aware of them and not just PSA or PSADT to properly ask for imaging tests.
Genetic testing patterns for homologous recombination repair (HRR) alterations in patients with metastatic prostate cancer (mPC): An assessment at the University of Rochester (UR).
Authors: Schaffer Kerry , Kyi Kaitlin , Lustig Carol , Sahasrabudhe Deepak M. , Shayne Michelle , Baran Andrea M , Fung Chunkit 
Published: March 2019

322 Background: Germline and somatic HRR alterations are present in 12% and 20% of patients with mPC, respectively, and can have treatment implications. NCCN guidelines recommend offering genetic testing for patients with mPC. This study examines genetic testing patterns in patients with mPC at UR. Methods: We conducted a retrospective study of all patients (n = 240) with mPC who saw medical oncology at UR from 10/1/2017 to 4/1/2018. We abstracted the following data from medical records: patient demographics, mPC characteristics, types of genetic testing, and clinically significant (CS) HRR alterations as defined by Myriad, Ambry, and Foundation One. To compare characteristics of patients who had genetic testing to those who did not, we used non-parametric Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables. Results: The median age at mPC diagnosis was 71 years (range: 42-93 years), 86.3% were white, and 35% had mPC at initial diagnosis. 64 patients (26.7%) were offered genetic testing and 40 patients (16.7%) completed germline (n = 12), somatic (n = 21), or both germline and somatic genetic testing (n = 7). Median time from diagnosis of mPC to germline and somatic genetic testing were 9 months and 35 months, respectively. Among the 24 patients who were offered, but did not have testing, the reasons were: patients’ refusal (n = 10), death/hospice care (n = 7), insurance issue (n = 3), patient’s preference to have somatic testing at disease progression (n = 3), and missed genetic counseling visit (n = 1). Compared to patients who did not have genetic testing, those who had testing were younger at the time of mPC diagnosis (63.5 vs 73.0 years; p < 0.0001). CS HRR alterations were identified in 8 of 40 patients tested (20%): somatic HRR alterations include BRCA2 (n = 2), ATM (n = 1), CDK 12 (n = 1), and C HEK2 (n = 1); germline HRR alterations include BRCA2 (n = 2) and CHEK2 (n = 1). Conclusions: We report that approximately one-fourth of patients with mPC at UR had genetic testing offered, with a 20% prevalence of HRR alterations in those tested. Future research should develop strategies to address barriers to genetic testing.
Multidimensional flow characterization of circulating immune cells in cisplatin-resistant metastatic urothelial cancer (mUC) patients (pts) treated with pembrolizumab (P) with or without acalabrutinib (acala).
Authors: Zhang Tian , Staats Janet S. , Chan Cliburn , Alva Ajjai Shivaram , O'Donnell Peter H. , Harrison Michael Roger , Batich Kristen A , Munugalavadla Veerendra , George Daniel J. , Weinhold Kent J. 
Published: March 2019

357 Background: Immunotherapy checkpoint inhibitors (ICIs) are now standard treatments (txs) in mUC, with response rates ranging 15-25%. A phase 2 randomized study (NCT02351739) treated 75 pts with mUC with either P or PA. We profiled peripheral blood mononuclear cells (PBMCs) to understand changes on tx. Methods: Comprehensive immune profiling of PBMCs was performed at baseline, weeks (wk) 4, 7, and 10. The Wilcoxon rank sum (WRS) test was used to compare tx arms, as well as pts with complete and partial response (CR/PR) vs disease progression (PD). Using the Benjamini-Hochberg (BH) method, results were deemed significant if they had false discovery rate (FDR) of 0.1 or less. Results: Clinical responses did not differ between tx arms (Zhang T et al, ESMO, 2017). The majority of patients showed largest immune changes from baseline at wk7. Comparing P vs PA pts, the PA group had statistically significant increases in PD-L1+ monocytes; CD8 T cells expressing: CD39, CTLA-4, ICOS, PD-1, TIM3, HLA-DR, Ki67, CD39/HLA-DR, CD39/Ki67, and PD-1/TIM-3; and exhausted (CD28-) CD8 T cells expressing ICOS and PD-L1 (Table). Comparing CR/PR vs PD pts, Treg subsets expressing CCR4/HLA-DR and CD39/HLA-DR were significant by WRS but not FDR criteria. Conclusions: From this extensive, exploratory, non-functional flow analysis of PBMCs, PA may potentiate immune changes of PD-L1+ monocytes and CD8+ T cell subsets. Increasing activated peripheral Tregs in CR/PR pts in either arm may indicate marginalization of Tregs from the tumor microenvironment. [Table: see text]
Re-examining an old trend: The association of human papillomavirus and bladder cancer.
Authors: Reinstatler Lael Suzanne , Shee Kevin , Stensland Kristian D. , Dagrosa Lawrence , Seigne John D. , Sverrisson Einar F. 
Published: March 2019

362 Background: The Human Papilloma Virus (HPV) is a recognized carcinogenic factor. Previous studies have shown a possible association between HPV and bladder cancer, however HPV serology has not been reported. In this study, we assessed the correlation between bladder cancer and HPV positive serology. Methods: Using NHANES, a large nationally-representative population-based survey, we gathered clinical and demographic data on all patients with a diagnosis of bladder cancer over from 2007-2010 and analyzed their HPV serology status. We assessed the effects of positive serologic results for HPV18, HPV16, HPV11, and HPV6 on the rates of bladder cancer diagnosis. Results: Over the four-year period there was a weighted population of 155,650,000 Americans. The prevalence of HPV positive serology was as follows: HPV18–5.5%, HPV16–13.2%, HPV11–6.4%, HPV6–17.4%. There were 443,948 bladder cancer cases. Among cases there was a higher prevalence of male gender (80% vs. 53%, p = 0.0056), Caucasian race (93% vs. 66%, p = 0.001), and HPV6 positive serology (18.1% vs. 17.6%, p = 0.0005). There was no difference among the other three HPV types. On logistic regression controlling for race, gender, and smoking status, increasing body weight (OR 1.01, p < 0.0001) and HPV6 positivity (OR 1.9, p < 0.0001) were associated with increased odds of bladder cancer diagnosis while HPV11 positivity (OR 0.23, p < 0.0001) was associated with a decreased odds of bladder cancer diagnosis. Conclusions: Prior research has shown that there is a relationship between HPV and bladder cancer, but this relationship has previously been incompletely defined. In this large, nationally representative database, we describe a significant association of HPV6 positive serology with a diagnosis of bladder cancer. This finding is striking and might affect future investigation into the pathophysiologic basis of this relationship.
Circulating tumor cell (CTC) enumeration in patients (pts) with metastatic genitourinary (mGU) tumors treated in a phase I study of cabozantinib and nivolumab (CaboNivo) +/- ipilimumab (CaboNivoIpi).
Authors: Hu Zishuo , Mortazavi Amir , Pal Sumanta K. , Lara Primo , Mayer Tina M. , Steinberg Seth M , Mayfield Christian , Graap Katherine , Mallek Marissa , Costello Rene , Diaz Carlos , Schonhoft Joseph , Wang Yipeng , Dittamore Ryan , Chu Lincy , Trepel Jane B , Bottaro Donald P. , Apolo Andrea B. 
Published: March 2019

379 Background: CTCs may serve as biomarkers for clinical outcomes in GU tumor pts. We examined the association between baseline CTC enumeration, change in CTC enumeration post treatment, progression-free-survival, overall survival and response to therapy with combination CaboNivo or CaboNivoIpi. Methods: 128 samples from 52 pts with mGU tumors treated with CaboNivo (38 pts) or CaboNivoIpi (14 pts) were drawn at baseline, cycle (C) 2 Day (D) 1, and C3D1 and processed with Epic Sciences platform. CTCs were defined as cytokeratin (CK)+, CD45-, distinct morphology, intact nucleus. PD-L1 expression was assessed. Results: From 07/20/2016-09/01/2018, 52 pts were treated for metastatic [urothelial carcinoma (UC) N = 33; UC plasmacytoid N = 1; clear cell renal cell carcinoma N = 4; bladder adenocarcinoma (BAC) N = 8; bladder squamous cell carcinoma N = 2; bladder small cell carcinoma N = 2; renal medullary carcinoma N = 2]. Median age was 61.5 years (range 20-82); 35 (67%) were male; N = 37(71%) had visceral involvement, N = 15(29%) had liver involvement, N = 11(21%) had bone involvement. CTCs were found in the peripheral blood of 39 (75%) pts, 1 pt (BAC) had PDL1+ CTCs at baseline. Median CTC/mL at C1D1, C2D1, C3D1, were 0.5 (0-357.1), 0.4 (0-71.8), and 0.75 (0-18), respectively. Median (lower and upper quartile) CTCs in pts with complete or partial responses (responders) vs stable or progressive disease (non-responders) were: 0.0 (0 to 5.40) vs 0.7 (0 to 2.5) at baseline; -0.35 (-3.65 to 0) vs 0 (-2 to 1.7) change from baseline to C2D1; and 0 (-5.4 to 0.5) vs 0 (-0.9 to 0.65) change from baseline to C3D1 (all p > 0.15). CTC counts of > 2 and > 4 at C2D1 were potentially associated with shorter OS (p = 0.071 and p = 0.045 without adjustment for multiple cutoffs for evaluation). PFS results exhibited similar trends. Conclusions: CTC were detected in pts with mGU tumors treated with CaboNivo and CaboNivoIpi. CTC values were lower in responders than in non-responders. On treatment lower CTCs were associated with better clinical outcomes. Ongoing analyses with the CTCs include cell morphology and heterogeneity, single cell genomics, and T-cell populations.