bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rates and determinants of prostatectomy in prostate cancer (PCa) patients with node-positive disease.
Authors: Sun Lova , Vapiwala Neha , Lee Daniel , Takvorian Samuel U , Haas Naomi B. , Vaughn David J. , Narayan Vivek 
Published: February 2020

362 Background: Consensus guidelines recommend that PCa patients with “regional risk” clinical node positive (cN1) disease undergo EBRT and ADT. However, many of these patients still undergo radical prostatectomy (RP), and the role of clinical node status in predicting benefit from RP is debated. Using National Cancer Database (NCDB), we sought to characterize the rates and determinants of initial RP for cN1 patients, and to assess the prognostic significance of clinical nodal stage for patients undergoing RP with pathologic node involvement (pN1). Methods: Among incident cases of nonmetastatic PCa within NCDB (2004-2012), we identified two cohorts: (1) patients with cN1 disease, and (2) patients with pN1 post-RP. For the cN1 cohort, factors associated with initial RP were evaluated using univariate logistic regression, and post-surgical pathologic staging and adjuvant therapies were described. For the pN1 cohort, multivariate Cox regression was used to compare overall survival (OS) by preoperative clinical stage (cN1 vs cN0). Results: Of 7787 patients with cN1 disease, 2166 underwent initial RP, with consistent annual rates (24-31%) over the study period. Factors independently associated with higher likelihood of RP included age ≤ 65 (HR 1.8), white race (HR 1.4), private insurance (HR 1.8), T stage ≥ T2C (HR 1.3), PSA ≤ 10 (HR 1.6), and Gleason score <8 (HR 1.4). Of cN1 patients who underwent RP, 84% were pN1 and 26% were pN0. 26% of these cN1/pN1 patients later received RT, 49% received ADT, and 20% received both. Separately, among 7396 PCa patients with pN1 disease after RP, 17% were initial cN1 and 83% were cN0. After adjustment for practice setting, patient, and disease variables, initial cN1 clinical stage was associated with significantly worse OS (HR = 1.2, p=0.04). Conclusions: The initial treatment of regional risk cN1 disease is highly variable, with approximately 1 in 4 patients undergoing initial prostatectomy, the vast majority of whom are confirmed pN1. Among all patients with pN1 disease, clinical nodal staging retains prognostic significance for OS. These findings underscore the utility of initial clinical staging when considering initial and adjuvant treatments for regional risk patients.
Adjuvant radiotherapy following radical prostatectomy for prostate cancer: A systematic review and meta-analysis.
Authors: Botrel Tobias Engel Ayer , Clark Otávio , Bretas Francisco Flávio Horta , Sadi Marcus V. , Ferreira Ubirajara , Paladini Luciano , Matheus Wagner Eduardo , Reis Rodolfo , Duraes Ronilson Oliveira , Pompeu Antônio Carlos Lima 
Published: February 2020

366 Background: To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing efficacy of adjuvant radiotherapy (AR) versus expectant management (EM) in men who undergo radical prostatectomy for localized prostate cancer (CaP). Methods: To perform this review and meta-analysis,several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. We included all the studies that compared AR versus EM after radical surgery for CaP. The primary endpoints analyzed were biochemical progression-free survival (bPFS), metastasis-free survival (MPFS), prostate cancer-specific survival (CSS), overall survival (OS) and side effects. The data extracted from the studies were combined by using the Hazard Ratio (HR) or Risk Ratio (RR) with their corresponding Confidence Intervals of 95% (CI95%). Results: Overall, 68 studies were identified and screened. The final analysis included 7 trials (EORTC 22911, SWOG 8794, ARO 96-02/AUO AP 09/95, RAVES, FINNISH, GETUG-AFU 17 and RADICALS-RT) comprising 4,221 patients. The bPFS was higher in patients who received AR (fixed effect: HR = 0.58, CI95% = 0.52 to 0.66; p < 0.00001) but with significant heterogeneity (Chi2 = 40.34, df = 6 (P < 0.00001); I2 = 85%). We performed a random-effect model analysis to better explore this heterogeneity: in this analysis, the result remained in favor of AR (random effect: HR = 0.64, CI95% = 0.45 to 0.90; p = 0.01). The MPFS also was higher in patients who received AR (HR = 0.77, CI95% = 0.65 to 0.91; p = 0.002). The CSS and OS were not statistically different in patients with or without adjuvant radiotherapy (HR = 0.79, CI95% = 0.47 to 1.32; p = 0.36 and HR = 0.92, CI95% = 0.77 to 1.11; p = 0.38, respectively). The incidence of adverse events (gastrointestinal and genitourinary) were higher in the AR group. Conclusions: This is the first meta-analysis including the seven available RCTs in the literature (the previous meta-analysis reviewed only three), comparing adjuvant radiotherapy versus expectant management following radical prostatectomy for CaP. Adjuvant radiotherapy statistically increased the bPFS and MPFS, but did not have an impact on the OS or CSS.
Long-term health-related quality-of-life outcomes in a racially diverse cohort of prostate cancer patients receiving retropubic versus robotic prostatectomy.
Authors: Conti Galen , Kuo Huai-Ching , Flores John Paul , Frankel Jason , Levie Katherine , Jung Nathan , Caumont Fernando , Brand Timothy C. , Musser John E. , Stroup Sean P. , Rice Kevin R. , Kallingal George , Porter Christopher , Rosner Inger L. , Cullen Jennifer 
Published: February 2020

37 Background: This study compared 5-year health-related quality of life (HRQoL) outcomes among prostate cancer (PCa) patients who underwent a robotic-assisted radical prostatectomy (RARP) versus a radical retropubic prostatectomy (RRP), with a focus on race-specific outcomes for Caucasian American (CA) compared to African American (AA) men. RARPs have almost replaced RRPs in recent years, with few long-term studies focused on HRQoL and race. Methods: A prospective cohort study of HRQoL was conducted on patients diagnosed with PCa from 2007 to 2017 and enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database. HRQoL was assessed with the EPIC instrument. Temporal changes in urinary and sexual-related quality of life domain scores were compared across surgery type (RARP versus RRP) at pre-treatment (“baseline”), 1-, 2-, 3-, 4-, and 5 years post-baseline. Longitudinal HRQoL patterns were modeled using generalized estimating equations (GEE), adjusting for baseline HRQoL and key clinical characteristics. Results: Of 497 PCa patients who met study inclusion criteria, 68% had RARP and 32% had RRP, with 22% AA men and 88% CA men. Baseline HRQoL domains were comparable across race and surgery type. In adjusted GEE analysis, no differences were noted between AA and CA patients. However, treatment-related differences were observed over time in urinary function (UF) and incontinence (UI) (p=0.02 and p=0.03, respectively), with lower HRQoL scores in RARP vs. RRP patients. Upon dual stratification by surgery type and race, the differences for UF and UI persisted (p=0.01 and p=0.03, respectively) with poorest outcomes observed, and similar trajectories of decline, for AA patients who received RARP. Conclusions: In this 10+ year prospective cohort study, AA patients receiving RARP had the poorest UF and UI outcomes which continued to decline for 5 years post treatment. In light of these findings, AA men considering RARP might benefit from discussions with their providers to set expectations regarding long-term urinary outcomes; though these decrements in HRQoL may be overshadowed by the minimally invasive nature of RARP.
Isotope selection and PSA failure in prostate seed implant: Experience with CS-131 in a community hospital system.
Authors: Booher Jacquelyn G. , Domenig Peter , Chuba Paul J. 
Published: February 2020

375 Background: A recent large single institutional study reported excellent long-term biochemical control and survival for Cs-131 prostate implant. This isotope has short half-life (9.7 days) with clinical advantages including shorter duration of symptoms. We previously showed Cs-131 dosimetry to be quantitatively similar to I-125 with improved homogeneity (mean percent V150 36% for I-125 versus 27% for Cs-131 (p < 0.0001). Our objective was to evaluate PSA failure rates and dosimetric outcomes in a multi-institutional community based setting. Methods: Within an IRB approved retrospective study, we compared outcomes for three groups of permanent prostate implant patients treated at Ascension Macomb Oakland, Ascension Saint John, and Ascension Providence Rochester Hospitals over a 10 year time interval. The comparison groups included isotopes Cs-131 (n = 66; t1/2 9.7 days), I-125 (n = 60; t1/2 60 days), and Pd-103 (n = 60; t1/2 17 days). Kaplan Meier estimates of PSA failure used the nadir plus 2 (Phoenix) definition. Results: Standard permanent implant doses employed were 145 Gy for I-125 monotherapy or 109 Gy for combination therapy. The dose for Cs-131 was 115 Gy for monotherapy and 85 Gy for combination therapy. For Pd-103, the doses employed were 125 Gy and 90 Gy for mono- and combination therapy, respectively. Median age at diagnosis was Cs-131; 69 (range 49-80), I-125; 71 (49-78), and Pd-103; 70 (60-82). Mean pretreatment PSA values were Cs-131 5.73 ng/ml, I-125 6.62 ng/ml, and for Pd-103 8.87 ng/ml. Median PSA follow up was 30 months and the median PSA value at 60 months was 0.11 ng/ml. There was excellent PSA control for all three groups of cases (p = NS), however with fewer failures using Cs-131. Conclusions: Permanent interstitial brachytherapy continues to be an attractive option for treatment early stage prostate cancer. Only a few large single institutional studies have examined PSA failure rates or dosimetric aspects of shorter half-life Cs-131 seed implants. This series confirms wide applicability of Cs-131 permanent prostate seed implant in the community hospital setting.
High-dimensional single cell-based immune profiling of the tumor immune microenvironment in prostate cancer.
Authors: Masetti Michela , Portale Federica , Carriero Roberta , Partini Bianca , Morina Nicolò , Ponzetta Andrea , Colombo Piergiuseppe , Elefante Maria Grazia , Saita Alberto , Lughezzani Giovanni , Buffi Nicolo' , Casale Paolo , Peano Clelia , Kunderfranco Paolo , Cibella Javier , Guazzoni Giorgio Ferruccio , Lazzeri Massimo , Di Mitri Diletta 
Published: February 2020

376 Background: Genetic lesions that drive prostate cancer (PCa) development are able to modify the immune response and tumor infiltrating immune subsets, resulting in tumor progression. We investigated the profile of the immune microenvironment in PCa by high dimensional single cell analysis. Methods: We conducted an immune profiling study based on integrated RNA single cell sequencing and multiparametric flow cytometry in order to dissect the immune landscape of PCa. CD45+ immune cells infiltrating tumoral and adjacent non tumoral tissues were isolated from patients with PCa who underwent software assisted fusion biopsy, based on MRI, and/or radical prostatectomy, and analyzed by single cell sequencing. The primary endpoint was to evaluate the effectiveness of single cell RNA sequencing on CD45+ cell sorted from tumoral and adjacent non-tumoral tissues. Secondary endpoint was the identification of tumor-driven immune changes in prostatic lesions. Results: The cohort consisted of 3 patients who underwent radical prostatectomy (RP) and 45 patients with positive prostate biopsy; the negative control was checked by pathological assessment. In patients who underwent RP the gene expression analysis identified a modulation in the abundance of several immune subsets infiltrating the tumoral tissue, when compared with the non tumoral, evident for Tumor associated macrophages (TAMs), Natural Killer cells (NK) and T regulatory cells. We then implemented a 22 parameters flow cytometry panel that we tested on fresh prostatic tissue and peripheral blood from positive PCa biopsies. We identified a subset of tumor infiltrating macrophages showing an altered gene expression profile when compared with macrophages infiltrating the non-tumoral tissue. Importantly we derived a genetic signature from this subset of tumoral TAMs that resulted to be associated with cancer progression. Conclusions: Our findings support the effectiveness of single cell RNA sequencing in the dissection of the immune landscape in PCa and identified immune changes in patients when comparing neoplastic tissue with non tumoral areas. Such data may be useful for understanding the role of immune system in PCa carcinogenesis.
Significance of distinct specifically enriched missense TP53 mutations in prostate cancer.
Authors: Vasilevskaya Irina , McCann Jennifer , McNair Christopher , Neupane Neermala Poudel , Gallagher Peter , Knudsen Karen E. 
Published: February 2020

377 Background: The most common TP53 alterations are missense mutations occurring in the DNA binding domain. The majority of missense p53 mutants (mut-p53) demonstrate oncogenic gain-of-function (GOF) abilities, irrespective of wild-type p53 presence, and thus contribute to a more aggressive disease. In prostate cancer (PCa), characterized by comparatively low overall mutational burden, TP53 is frequently mutated in both primary and advanced disease. Despite significant progress made in the field, detailed mechanisms of GOF in PCa remain undefined due to differing features of p53 mutants. Methods: Analysis of available datasets was performed to assess TP53 mutational status in PCa patient samples and its correlation with the clinical outcome. Using hormone therapy sensitive and CRPC cells, a panel of cell lines was generated to model the two most frequently occurring mutations in the presence or absence of wild-type TP53, as occurs clinically. CHIP-seq, gene expression arrays, and in vitro and in vivo biological assays were performed to interrogate the significance of mut-p53 in PCa. Results: In PCa, missense mutations are significantly associated with decreased progression-free and overall survival. In PCa patient samples these mutations most commonly occur at the R273 residue, demonstrating specific enrichment when compared to other cancers, with R273C alteration being the most frequent. Using our cell panel, CHIP-seq data revealed an expansion of the p53 cistrome upon expression of R273C and R273H mutants in a manner distinct from p53 stabilization in the presence of wt-p53. Moreover, analysis of the TP53 missense mutant-sensitive transcriptomes demonstrated differential gene expression between these mutants, related to the expression of wild-type TP53 in those cells. Finally, R273C and R273H p53 mutants elicited context dependent effects on canonical p53 functions, thereby modulating distinct downstream biological outcomes. Conclusions: These data expand our knowledge of the underlying mechanisms by which distinct gain-of-function p53 mutants affect prostate cancer, and can lead to identification of novel therapeutic targets to improve clinical outcomes in PCa patients harboring these mutations.
Consistency of patient versus investigator reporting of symptomatic adverse events (AEs) in international trials.
Authors: Chang Elaine , Gong Yutao , Weinstock Chana , Suzman Daniel L. , Ibrahim Amna , Beaver Julia A. , Kluetz Paul Gustav 
Published: February 2020

38 Background: FDA approved 3 androgen receptor inhibitors for nonmetastatic castration-resistant prostate cancer (nmCRPC) based on global randomized trials with control arms of placebo + ADT. Despite similar enrolled populations, grade 1 or higher investigator-reported, Common Terminology Criteria for Adverse Events (CTCAE)-graded fatigue ranged 11-25% in the placebo arms. We sought to characterize variability in investigator-reported, CTCAE-graded fatigue across geographic regions and compare this with the variability in patient-reported fatigue. Methods: Data from patients receiving ≥ 1 placebo dose were reviewed from control arms of 3 nmCRPC double-blind, placebo-controlled trials submitted to FDA. We determined worst grade clinician-reported (ClinRO) CTCAE fatigue, and most severe fatigue reported by patient-reported outcome (PRO) for each patient at any time during treatment or within 30 days of last dose in each trial by geographic region: North America/Western Europe (NAWE) versus rest of the world (ROW). We compared variability in fatigue rates to those of a more objective AE, CTCAE-defined anemia. Results: NAWE enrollment comprised 46-75% of placebo cohorts. Median age was comparable across trials and regions. ClinRO CTCAE fatigue was higher in NAWE (15-33%) compared to ROW (8-14%) in each of the 3 placebo cohorts (see Table). Rates of PRO fatigue varied by region (50-73% in NAWE compared to 42-59% in ROW), and the regional differential was present at baseline. Anemia rates were similar in NAWE and ROW in each trial ( < 5%) per CTCAE. Conclusions: CTCAE reporting of fatigue, a subjective symptom, was inconsistent across sites. Anemia, an objective AE, was more consistently reported. ROW investigators less frequently reported fatigue compared to NAWE investigators. Reasons for this are unclear, but could include cultural and language factors. PRO fatigue was relatively consistent across trials and regions. These results should be interpreted with caution, as we acknowledge the limitations of cross-trial comparison.[Table: see text]
Validation of the two best models to predict “benign” pathohistology in patients with advanced nonseminomatous germ cell tumors (NSGCT) undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Authors: Nestler Tim , Paffenholz Pia , Baeßler Bettina , Hellmich Martin , Hiester Andreas , Nini Alessandro , Pfister David , Albers Peter , Heidenreich Axel 
Published: February 2020

389 Background: The aim of our study is to validate and evaluate the two currently best performing prediction models (Vergouwe and Leao) for final pathohistology in NSGCT patients undergoing PC-RPLND and we introduce a new radiomics approach. Methods: We performed a retrospective analysis including 496 patients who underwent a PC-RPLND between 2008 and 2018 to validate the two prediction models using published formulas and thresholds. ROC were plotted and AUC was calculated. We determined the optimal cut point and used bootstrapping (1,000 replications) to estimate its variability. For radiomics, lymph nodes of 80 patients were identified on CT images, semiautomatically segmented with 93 radiographic features (pyRadiomics package). A linear support vector machine algorithm was applied to analyze reproducible radiomics features. A continuous reduction of features analyzed was performed using Random Forest algorithms and ROC analysis. Results: In our validation cohort, the Vergouwe model had a significantly better AUC compared to Leao model (0.749 [CI 0.706-0.792] vs. 0.689 [0.642-0.736], p=0.004) to predict benign histology. At a threshold of > 70% for the probability of benign disease, the Leao model would have avoided PC-RPLND in 8.6% with benign disease with an error rate of 5.6% for viable tumor. The Vergouwe model would avoid PC-RPLND in 23.4% with benign disease with an error rate of 12.7% for viable tumor/teratoma. Of the 93 radiomic features analyzed, 51 features were reproducible. Applying the trained algorithm on the training dataset resulted in an accuracy of 0.96 (93% sensitivity, 100% specificity, 100% PPV), on an independent validation cohort the accuracy was 0.81 (88% sensitivity, 72% specificity, 78% PPV). Conclusions: According to our data, the discriminatory accuracy of both models is not sufficient to safely select patients for surveillance strategy instead of PC-RPLND. The radiomics model is promising but needs prospective validation. Further studies including new biomarkers are needed to optimize the accuracy of potential prediction models.
Performance characteristics of 18F-Fluciclovine positron emission tomography/computed tomography prior to retroperitoneal lymph node dissection.
Authors: Meng Xiaosong , Woldu Solomon L. , Wong Daniel , Lafin John T. , Ghandour Rashed , Margulis Vitaly , Conyers Jesse , Xi Yin , Subramaniam Rathan M. , Bagrodia Aditya 
Published: February 2020

390 Background: There is no reliable way to differentiate between fibrosis/necrosis, teratoma, and viable germ cell tumor in patients receiving post-chemotherapy retroperitoneal lymph node dissection (RPLND) for non-seminomatous germ cell tumor (NSGCT). Functional imaging, including 18F-FDG positron emission tomography/computed tomography (PET/CT), has been disappointing. Due to the need for better imaging modalities, our prospective, pilot study aims to investigate the accuracy of 18F-Fluciclovine PET/CT in detecting residual tumor prior to RPLND. Methods: From Mar 18 – May 19, 10 eligible patients underwent pre-operative 18F-Fluciclovine PET/CT prior to undergoing bilateral full template RPLND or excision of mass (for one re-do retroperitoneal lymph node dissection) in a prospective phase II study. Correlation between PET/CT findings and pathology were evaluated on per patient level. Results: A total of 10 patients underwent 18F-Fluciclovine PET/CT prior to surgery. 9/10 patients received chemotherapy prior to RPLND. Correlation between 18F-Fluciclovine PET/CT and RPLND pathology was seen in 3/10 patients. 5/10 patients with negative anti-18F-FACBC PET/CT were found to have residual disease/teratoma on RPLND. Compared to the reference standard of RPLND, 18F-Fluciclovine PET/CT demonstrated 29% sensitivity and 33% specificity. Conclusions: Current management of NSGCT is heavily reliant on sub-optimal imaging modalities that are unable to accurately distinguish between post-chemotherapy necrosis/fibrosis versus residual disease and/or teratoma. Despite a different mechanism of action from 18F-FDG, 18F-Fluciclovine has low sensitivity and specificity for residual teratoma in the retroperitoneum. Clinical trial information: NCT03426865. [Table: see text]
Overcoming sociodemographic factors in the care of testicular cancer patients at a safety net hospital.
Authors: Chertack Nathan , Ghandour Rashed , Singla Nirmish , Freifeld Yuval N. , Hutchinson Ryan C. , Courtney Kevin Dale , Moore Joseph Allen , Aydin Ahmet , Margulis Vitaly , Lotan Yair , Woldu Solomon L. , Bagrodia Aditya 
Published: February 2020

398 Background: Optimal treatment of GCT in underserved populations is subject to barriers that are associated with worse clinical outcomes. We determine whether standardized treatment of GCT can overcome such sociodemographic factors limiting patient care. Methods: The records of all patients undergoing primary treatment for GCT were analyzed from both a public safety net hospital and an academic tertiary care center in the same metropolitan area. Patients at both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center and clinicopathologic features, practice patterns, and outcomes were analyzed. Results: 106 and 95 patients underwent initial treatment for GCT between 2006 and 2018 in the safety net hospital and tertiary care center, respectively. Safety net patients were younger (29 vs 33 years, p=0.005), more likely to be Hispanic (79% vs 11%), more likely to be uninsured (80% vs 12%, p<0.001), and present via the emergency department (76% vs 8%, p<0.001). They were more likely to have metastatic (stage II/III) disease (42% vs 26%, p=0.025). On multivariable analysis, presence of lymphovascular invasion (OR=0.30, p=0.008) and embryonal carcinoma component (OR=0.36, p=0.02) were associated with surveillance vs adjuvant treatment for Stage I patients; hospital setting was not (OR=0.67, p=0.55). For patients with Stage II/III NSGCT, there was no difference in performance of PC-RPLND at the safety net hospital vs tertiary care center (52% vs 64%, p=0.53). No difference in recurrence rates between cohorts (5% vs 6%, p=0.76) was observed. Conclusions: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCT; this may be overcome with integrated, standardized management of testicular cancer.