bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum testosterone level and overall survival in first-line abiraterone and enzalutamide for metastatic castration-resistant prostate cancer patients.
Authors: Vilbert Maysa Tamara Silveira , Cesca Marcelle Goldner , Pandolfi Natasha Carvalho , Calsavara Vinicius Fernando , Uchôa Bruno Cezar de Mendonça , de Andrade Poliana , Coelho Ricardo Lima , Corassa Marcelo , Rinck Jose A. , Dettino Aldo A. , Oliveira Thiago Bueno 
Published: May 2020

e17545 Background: Androgen receptor-targeted agents Abiraterone and Enzalutamide (Abi/Ez) prolonged overall survival in metastatic castration resistant prostate cancer (mCRPC). Patients with very-low serum testosterone levels seem to have less benefit from these therapies as well as more aggressive prostate cancer. Methods: A retrospective observational cohort study was conducted to evaluate whether a serum testosterone measured at time of start first-line therapy with Abi/Ez is related to overall survival (OS) and time-to-treatment failure (TTF) in mCRPC patients. Kaplan-Meier survival estimates and Cox-regression models were used for time-to-event analyses. The best cut-off for testosterone was defined using Log-rank statistics (Lausen and Schumacher). X² test and Mann-Whitney U-test were applied to compare categorical and continuous variables, respectively. Logistic regression was used to assess characteristics related to serum testosterone levels. Statistical significance was fixed at 0.05. Results: From May 2012 to February 2017, 100 patients were assessed. Median follow-up was 27.8 months (range 2.23 to 68.26). Pts with a high testosterone level ( > 28.2; n = 20) achieved a significantly higher OS (median 66.0 vs 31.9 mo, testosterone > 28.2 HR: 0.206, 95% CI 0.074 to 0.571, p = 0.002) and TTF (median 30.6 vs 11.8 mo, testosterone > 28.2 HR: 0.408, 95%CI 0.219 to 0.762, p = 0.005) than pts with a low serum testosterone level ( < 28.2; n = 80), regardless of receiving therapy with either Abi (n = 69) or Ez (n = 31). Pts with a higher testosterone level were younger (median 67.7 vs 73.6 years; p = 0.026), had a higher body mass index (BMI) (28.5 vs 25.9, p = 0.023) and a lower PSA at start Abi/Ez (12 vs 26, p = 0.031) than pts with lower values. Age (OR 0.93, 95%CI 0.8 to 0.9, p = 0.021), BMI (OR 1.21, 95%CI 1.1 to 1.4, p = 0.006) and baseline PSA (OR 1.2, 95%CI 1.03 to 1.4, p = 0.020) were significantly associated with testosterone > 28.2. After 4 months of Abi/Ez treatment, PSA decrease > 50% of baseline was seen more frequently in high testosterone levels group than in low testosterone levels pts (90% vs 57.5% of pts, respectively, p = 0.007). Conclusions: Pts with high levels of testosterone ( > 28.2) achieved a better OS and TTF when treated with Abi/Ez in first-line mCRPC than those with low levels. Testosterone can be considered a prognostic and predictive biomarker in this scenario, and could be used in treatment decision for this population.
Retzius-sparing robotic-assisted laparoscopic radical prostatectomy: Racial considerations for 250 consecutive cases.
Authors: Madi Rabii , Sayyid Rashid K. , Sherwood Dalton , Klaassen Zachary William Abraham 
Published: May 2020

e17546 Background: To report the functional and oncologic outcomes of a cohort of 250 consecutive prostate cancer patients undergoing a Retzius-sparing approach and to assess for racial differences in continence outcomes. Methods: This was a prospective, single-center, case series of 250 consecutive prostate cancer patients who underwent a Retzius-sparing robotic assisted laparoscopic radical prostatectomy by a single surgeon between May 2015 and April 2019.Our primary objective was to describe post-operative continence outcomes of patients undergoing this technique. Results: Median follow up was 24.0 months [Interquartile range (IQR) 18.0-30.0 months]. Median age and body mass index were 62.0 years (IQR 57.0-67.0) and 29.0 kg/m 2 (IQR 26.0-33.0), respectively. Median PSA was 8.22 ng/ml (IQR 5.74-13.31). 84.8% of patients were intermediate or high-risk pre-operatively. 96.0% had Gleason Score 7 or worse disease on final pathologic analysis. Positive margin incidence was 18.1% and 44.4% in patients with pT2 and pT3 disease, respectively. Immediate continence (i.e. continence achieved within one moth post-operatively) was achieved in 45.0% of patients. One-year continence rate was 92.0%. Caucasian patients experienced earlier return of continence (77% versus 65% at 3 months) compared to African American patients. IPSS scores gradually improved from 8.0 pre-operatively to 4.0 one year later. Median PSA level was 0.01 ng/ml (IQR 0.01-9.01) post-operatively. Conclusions: Retzius-sparing robotic assisted laparoscopic radical prostatectomy is an oncologically safe surgical technique with excellent short and long-term continence outcomes.
Radium 223 treatment in metastatic prostate cancer: Exploring use of clinical factors for prognostication in routine practice.
Authors: Vengalil Salil , Bee Paula , Beetham Dawn , Bhana Rajanee , Joseph Shibu , Dainty Stephen , Seedhouse Ian , El-Helw Loaie 
Published: May 2020

e17550 Background: Skeletal metastases are seen in over 90% of metastatic castrate resistant prostate cancer (mCRPC) patients during the course of their disease and is a major cause for significant morbidity and mortality in them. Radium 223 (Ra-223) is a bone seeking calcium mimetic alpha emitter that has demonstrated significant improvement in survival and reduction in skeletal related events (ALSYMPCA trial). Ra-223 treatment was well tolerated and showed benefit before or after chemotherapy. In this study we aimed to assess efficacy of Ra-223 in mCRPC patients treated in our centre and their survival in relation to some common clinical variables that may assist patient selection in routine clinical practice. Methods: We conducted a retrospective audit of mCRPC patients treated with Ra-223 from June 2015 – December 2019. We analysed treatment outcomes and use of Haemoglobin (Hb), Albumin (Alb) and Alkaline Phosphatase (ALP) as potential prognostic factors. Results: There were 46 patients in total with a median age of 76 years (range; 56-90) and 26% were ≥80 years of age. The median follow-up was 10 months (range; 2-38 months). Median baseline PSA was 103.7 (range; 7.2 - 2534) and median baseline ALP was 188 U/L (range; 51 - 2262). Ra-223 was given as 1st or 2nd line treatment in 65% of our patients. Median number of cycles of Ra-223 administered was 4 and 41% of patients completed 6 cycles of treatment. Biochemical response (drop in PSA > 50%) was only seen in 11% of patients but good response in ALP levels (drop in ALP > 50%) was seen in 35%. Median overall survival (OS) was 10 months. Median OS for patients who received Ra-223 as 1st or 2nd line vs subsequent line was 13 and 8.5 months respectively. Median OS for patients with Haemoglobin (Hb) ≥12gm/dl) and lower Hb were 11 and 7 months respectively. Patients with normal albumin at baseline had median OS of 15 months compared to 6 months for those with low albumin. Favourable prognostic group patients (Normal Hb, Normal albumin at baseline and normal ALP after treatment) had a median OS of 31 months compared to 9 months for those in less favourable group. Patients who completed at least 5 cycles had a better survival (13 vs 8.5 months). Fractures were reported in 3 patients (6.5%). Conclusions: Ra-223 treated patients in our centre had a reasonable survival despite having a larger proportion of elderly population compared to the registration trial. Ra-223 treatment seems to be more effective when given at earlier lines in mCRPC setting. Pre-treatment Albumin lower than normal seems to be a predictor for poor overall survival.
Artificial intelligence assisted bone lesion detection and classification in computed tomography scans of prostate cancer patients.
Authors: Masoudi Samira , Mehralivand Sherif , Harmon Stephanie , Walker Stephanie , Pinto Peter A. , Wood Bradford J. , Citrin Deborah E. , Karzai Fatima , Gulley James L. , Madan Ravi Amrit , Dahut William L. , Choyke Peter L. , Turkbey Baris 
Published: May 2020

e17567 Background: Patients diagnosed with prostate cancer undergo computed tomography (CT) for pretreatment staging to rule out bone metastases. However, detection and classification of bone lesions on CT is challenging and subject to inter-reader variability. We present a cascaded deep learning algorithm for automatic detection and classification of bone lesions on staging CT in patients diagnosed with prostate cancer. Methods: CT scans from 56 patients with histopathologically proven prostate cancer were included. An expert radiologist annotated the extent of individual bone lesions (N = 4217) and labelled all regions as either benign or malignant. All scans were anonymized and normalized at the patient-level prior to training. Our method can be described as a two-stage framework, 1) A detection algorithm: Inspired by Yolo-v3 detection method, we designed a network with a backbone of darknet-53 pretrained on Coco dataset and four final scaling blocks to compensate for wide range of lesion diameters, 2) A classification algorithm: we formed a binary classifier based on ResNet-50 pretrained using the ImageNet dataset. We used a train/validation split equal to 90%/10% for this study. To facilitate the learning process, horizontal flipping, relative zooming and mean weighted averaging were used for data augmentation in stage 1. Instead, the classification algorithm took advantage of synthesized patches generated by Deep Convolutional Generative Adversarial Network (DC-GAN) for augmentation. Results: We could achieve a real-time (~120ms per slice) performance on our validation set with a median penalty of 0.3(0.02-0.78) false positives per true positive within each patient. Overall performance of our detection algorithm was 81% sensitivity and 86% positive predictive value. In stage 2, we obtained an accuracy of 89% for correct classification of benign from malignant bone lesions with no augmentation which was improved to 91% when we incorporated the augmented data for training. Conclusions: Our 2-stage algorithm sequentially detects and classifies bone lesions on CT of prostate cancer patients with a significant performance. To further improve our results and for generalizability we are accruing more data from different centers. Eventually, with greater dataset, both algorithms will be cascaded and trained as a whole unit to become one single tool for fully automatic detection and classification which serves as an aid for radiologists who read the staging CTs.
Single nucleotide polymorphisms (SNPs) as predictors of efficacy of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Rivera Daniel Herrero , Duran Ignacio , Marcos Kovandzic Laura , Puente Javier , Mellado Begona , Grande Enrique , Virizuela Juan Antonio , Rodriguez-Moreno Juan Francisco , Azueta Ainara , Alonso Buznego Lucia Andrea , Luque Raquel , Garrigos Carmen 
Published: May 2020

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.
Prognostic implications of gene amplifications identified by circulating tumor DNA (ctDNA) analysis in metastatic prostate cancer (mPC).
Authors: Dincman Toros , Giordano Antonio , Li Hong , Gourdin Theodore Stewart , Drusbosky Leylah , Howe Philip , Lilly Michael B. 
Published: May 2020

e17594 Background: mPC is a dynamic disease that confers a poor prognosis- particularly in the metastatic castration-resistant prostate cancer (mCRPC) setting. Analysis of ctDNA provides an opportunity to identify and monitor somatic alterations (SAs) in a patient’s treatment course. However, how certain SAs can inform disease management is not fully characterized. We evaluated whether the presence of specific gene amplifications (GAs) and changes in plasma copy number (PCN) are associated with disease features and prognosis. Methods: This is a retrospective study of mPC patients seen at the Hollings Cancer Center between 2015-2019 who underwent ctDNA profiling using Guardant360 (Guardant Health Inc). Guardant360 identifies SAs and GAs of select genes by NGS. Descriptive statistics were used to summarize baseline patient characteristics. The chi-square test and odds ratio (OR) were used to evaluate associations between clinical factors and GAs. The Kaplan-Meier method was used to estimate OS from either the date of GA detection or the initiation of systemic therapy. Results: 130 men with mPC were identified as having ≥1 GA. The presence of liver and/or lung metastases were associated with GAs of BRAF (OR 2.5; 95%CI 1.1-5.8, p < 0.05) , CDK6 (OR 2.3; 95%CI 1.4-8.0, p < 0.01) , PI3KCA (OR 4.4; 95%CI 1.8-10.7, p < 0.01) , and FGFR1 (OR 3.1; 95%CI 1.1-9.0, p = 0.038). These GAs were also associated with having ≥2 concurrent GAs (p < 0.01 for each gene). From this cohort, survival analyses were completed on 59 patients with mCRPC. Men with only 1 GA, compared to men with ≥2 GAs, had improved median survival (mo.) from date of initial GA(s) detection (16.5 vs 9.4, p < 0.01) or therapy initiation (16.0 vs 9.0, p < 0.01). Among men with mCRPC, AR and/or MYC GA, median survival improved in men who had reduction in AR or MYC PCN during therapy compared to men without a PCN decrease (25.1 vs 15.9 p < 0.01). Conclusions: Patients with mPC who had liver and/or lung metastases were associated with having specific GAs in BRAF, CDK6, PI3KCA, and FGFR1. Notably, the presence of liver or lung metastases was not associated with AR GA. In mCRPC, patients with ≥2 GAs had decreased OS compared to men with one GA. Having an increased number of GAs is likely reflective of greater chromosomal instability and be associated with more aggressive disease. Our study reveals serial monitoring of AR and MYC PCN during therapy demonstrated reduced OS in patients without PCN reduction. This supports the use of serial ctDNA monitoring of PCN to inform therapeutic response and prognosis.
Genomic alterations associated with the progression from castration-sensitive to castration-resistant metastatic prostate cancer based on machine learning analysis of cell-free DNA genomic profile.
Authors: Lin Edwin , Hahn Andrew W. , Nussenzveig Roberto , Wesolowski Sergiusz , Maughan Benjamin Louis , McFarland Taylor Ryan , Rathi Nityam , Sartor A. Oliver , Sonpavde Guru , Swami Umang , Kohli Manish , Rich Thereasa A. , Yandell Mark , Agarwal Neeraj 
Published: May 2020

e17596 Background: Metastatic castration-sensitive prostate cancer (mCSPC) eventually progresses to metastatic castration-resistant prostate cancer (mCRPC), which has few treatment options and carries a poor prognosis. We hypothesize that there are specific genomic alterations (GAs) associated with the progression from mCSPC to mCRPC. Methods: Patients (Pts) with mCSPC and mCRPC undergoing next-generation sequencing of cell-free DNA by a CLIA certified lab (G360, Guardant Health Inc., Redwood City, CA) as a part of routine care were retrospectively identified. Principal components analysis, an unsupervised ML algorithm, was used for data exploration and visualization. A combination of feature selection and supervised machine learning classification algorithms were used to identify genes associated with mCRPC. Gene Ontology enrichment analysis was used to identify pathways enriched for mCRPC-associated GAs. Patterns of mCRPC-associated GAs at a gene- and pathway-level were identified by Bayesian networks fitted using an exact structure learning algorithm. Results: 154 Pts with mCSPC and 187 Pts with mCRPC were included. A set of 16 GAs that robustly distinguished mCRPC from mCSPC (PPV = 94%, specificity = 91%) using supervised machine learning algorithms. These GAs, primarily amplifications, corresponded to AR, MAPK signaling, PI3K signaling, G1/S cell cycle, and receptor tyrosine kinases (RTKs). Positive statistical dependencies were observed between genes in these pathways. At a pathway-level, the presence of G1/S GAs in mCRPC samples increased the likelihood of harboring GAs in RTK, MAPK, and PI3K signaling. Limitations: The retrospective nature of our study means that unknown exposures could act as confounding variables, however this is representative of real-world clinical settings. Although the strength of this study is inclusion of clinically annotated patient samples, the limitation is that patients with mCSPC and mCRPC were unmatched. Conclusions: These results provide evidence that progression from mCSPC to mCRPC is associated with stereotyped concomitant gain-of-function in the RTK, PI3K, MAPK, and G1/S pathways in addition to AR. Upon external validation, these hypothesis generating data may warrant further investigation into combinatorial therapies that target these pathways.
Prostate specific antigen testing as disease surveillance and monitoring five years after definitive therapy for localized prostate cancer.
Authors: Asiri Ibrahim M. , Cobran Ewan Kemar 
Published: May 2020

e17602 Background: The National Comprehensive Cancer Network, in 2007, recommends prostate specific antigen (PSA) testing every 6-12 months for the first 5 years following definitive treatment for localized prostate cancer. We compared guideline-concordant PSA testing, as disease surveillance and monitoring, in African-American (AA) and Caucasian (CA) men 5-years after definitive therapy. Methods: A total of 19,377 CA and 1,995 AA men from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database diagnosed with prostate cancer and received definitive treatments from 2007 through 2016 were included. Multivariate log-binomial regression model were used to examine the effect of demographic and clinical characteristics on the likelihood of not receiving at least one PSA surveillance test annually for the first 5 years following definitive treatment. Results: Overall, receipt of surveillance testing and monitoring was high, with 97% of CA men and 94% of AA men receiving at least one test the first year after treatment and approximately 81% of CA men and 77% of AA men receiving at least one test in the fifth year after treatment. Risk of not receiving a test in AA men declined with time compared to CA men, in the first year (Relative Risk [RR], 1.68, 95% CI, 1.37-2.07) and the fifth year (RR, 1.07, 95% CI, 0.98-1.18) since treatment. Further, non-married men and men with intermediate risk had a higher risk of not receiving a surveillance test. Conclusions: Most men received guideline-concordant PSA testing 5-years after definitive therapy. The decline in PSA surveillance overtime reflects the need for continued long-term survivorship care planning and coordination. [Table: see text]
Outcomes of statin use in veterans with prostate cancer: A retrospective single-center experience.
Authors: Warnecke Brian , Garza Juan , Datta Paromita , Hung Annie , Mader Michael , Wangjam Tamna 
Published: May 2020

e17612 Background: Prostate cancer is the most common cancer in men in the United States. Death in prostate cancer patients is often reported to be non-prostate cancer related, attributed to other medical conditions. As prostate cancer is associated with a prolonged survival, care of these patients includes optimizing other co-morbidities, such as cardiovascular disease. There are multiple reports and epidemiological studies of statins decreasing the risk, progression, and overall mortality of prostate cancer. Previously we had gathered data on 300 patients diagnosed with prostate cancer at the VA in San Antonio. The results indicated that using statins has a statistically significant positive effect at delaying death by prostate cancer, with a p-value of 0.018. We have updated our results with the addition of 105 patients. Methods: This is a retrospective observational study with chart review of 405 patients diagnosed with prostate cancer from 1995 to 2010, in a VA Hospital in San Antonio, Texas. Variables included age of diagnosis, statin use, type of statin (1st, 2nd, or 3rd generation), dose of statin (6 levels of dosage were identified), length of statin use, time followed in months (from time of diagnosis to either death or the end of the study period), death, and cause of death. The Cox proportional hazards regression model was used to estimate the hazard function, with age at diagnosis used as a covariate. Primary end point was death by prostate cancer (33 patients) and secondary end points- death by any cancer (71 patients), and death by all causes (205 patients). Results: The hazard ratio for use of statins at least 6 months was 0.56, with 95% confidence limits of 0.41 to 1.13, and a p-value of 0.118, indicating no statistically significant effect of statin usage and delay in death by prostate cancer. Secondary endpoint of death by all causes was significantly affected by statins, while death by any cancer showed no significant effect. The study was unable to conclude if the type of statin, dose of statin or the length of statin use had a significant effect in reaching the different end points. Conclusions: The addition of 105 more patients to this study has changed our previous statistically significant primary endpoint results.Concomitant statin use may not help prevent death from prostate cancer or death from any cancer, but may help prevent death from all causes. This updated primary endpoint data conflicts with multiple prior epidemiological studies and raises questions on the impact of statin usage on men with prostate cancer.