bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of localized prostate cancer during the Covid-19 pandemic at a multidisciplinary cancer center in New York City, New York.
Authors: Wood Andrew , Shpeen Benjamin , Lee Jeffrey , Snyder Rose , Xu Yiqing , Kotamarti Srinath , Teper Ervin , Lubin Marc , Silver David , Becker Kevin Douglas , Meghal Trishala , Schulman Ariel 
Published: March 2021

213 Background: In March 2020, the coronavirus disease (COVID-19) spread across New York City. All non-emergent medical care was delayed, and healthcare resources were redirected to COVID-19 patients. Physicians managing prostate cancer faced unprecedented decisions to balance risks of the pandemic against risks of cancer progression. Here we review management of localized prostate cancer at an Urban Cancer Center in New York City during the height of the pandemic. Methods: We examined men with newly diagnosed, localized prostate cancer seen in initial consultation by Urology or Radiation Oncology between January 1 and June 30, 2020 (COVID-19 cohort). We reviewed cancer management, as well as the impact of the pandemic on treatment choice and patterns of care. Chi square and t-test analyses were performed to compare the COVID-19 cohort to a similar cohort managed before the pandemic from July 1, 2019 to December 31, 2019 (pre-COVID-19 cohort). Results: We identified 75 men in the COVID-19 cohort. NCCN risk profile: 20% low risk, 53.4% intermediate, and 26.7% high. During the height of the pandemic, there was 7 week pause in both new radiation therapy (RT) and radical prostatectomy. 11 patients continued previous RT, 1 of which developed a symptomatic covid infection and required a 2 week pause in treatment. During the operating room restart, 11 patients underwent radical prostatectomy including 8 with unfavorable-intermediate or high-risk disease. No surgical patients acquired COVID-19. Compared to the pre-COVID-19 cohort, the COVID-19 cohort had longer time from initial visit to treatment (92.1 days vs 71.0 days, p = 0.045) and a larger percentage of patients who were seen but did not return for management (25.3% vs 14%, p = 0.044). Conclusions: Our cancer center had a coordinated, 7-week cessation in primary RT and surgery for prostate cancer during the height of the COVID-19 pandemic. There were no severe COVID-19 infections among patients finishing RT, or the first cohort of men having surgery during the restart of treatments, suggesting that localized prostate cancer treatments can be safely delivered in the event of a second wave. We identified a substantial number of men who were seen, but did not return for management, highlighting a cohort who need to be reintegrated into the healthcare system. [Table: see text]
Impact of active surveillance for prostate cancer on the risk of depression and anxiety: Patient-reported outcomes (PROs) from the Vican Prospective Cohort.
Authors: Pignot Geraldine , Touzani Rajae , Marino Patricia , Walz Jochen , Rybikowski Stanislas , Maubon Thomas , Salem Naji , Mancini Julien , Gravis Gwenaelle , Bendiane Marc Karim , Bouhnik Anne Deborah 
Published: March 2021

220 Background: Active surveillance (AS) is an option for low-risk localized prostate cancer and its use is on the rise due to the good long-term oncologic results. However, its impact on the quality of live of patients, particularly in terms of anxiety and emotional responses related to cancer is poorly evaluated. Methods: The french VICAN cohort is a representative sample of 4174 patients treated for cancer and survivors after 5 years. Patient-reported Outcomes (PROs) were collected prospectively by self-questionnaires on quality of live (SF-12) and treatments side effects. Among the 447 patients with prostate cancer, patients managed by active surveillance (AS), radiotherapy (RT), or radical prostatectomy (RP), for localized T1-T2 N0 M0 cancer with a Gleason score < 8 were selected. Data regarding depressive symptoms and percieved anxiety were analysed comparatively. Results: A total of 301 patients were included, among whom 68 (22.6%) managed by AS, 170 (56.5%) treated by RP and 63 (20.9%) treated with RT. Patients treated with AS had a lower clinical stage (p = 0.04) compared with patients in RP and RT groups. Regarding the impact on the quality of live, there was no significant difference in terms of depressive symptoms (no depressive symptoms reported for 82.4% of patients in the AS group vs 88.8% in RP and 74.6% in RT, p = 0.468) or percieved anxiety (no anxiety reported in 63.3% of cases in the AS group vs 71.2% in RP and 66.6% in RT, p = 0.214). Conclusions: Patients managed by AS for localized prostate cancer do not report more depressive symptoms or anxiety than patients treated with curative treatment (RP or RT). This confirms the importance of offering this therapeutic option if the histopathological criteria allow it and if the patient is compliant.
The BARCODE1 pilot study targeting men with increased genetic risk of developing prostate cancer: Examining the feasibility of a community-based screening program using polygenic risk score to target screening.
Authors: McHugh Jana Kathlyn , Benafif Sarah , ni Raghallaigh Holly , Bancroft Elizabeth , Kote-Jarai Zsofia , Eeles Ros A. ,   Barcode1 Study Team
Published: March 2021

227 Background: A significant proportion of Prostate cancer (PrCa) risk is attributable to heritable risk factors of which only a minority are high risk Mendelian traits. A greater proportion of PrCa is due to the combined effect of multiple low risk variants. There have been approximately 170 single nucleotide polymorphisms (SNPs) identified that are associated with PrCa risk in Europeans. Although each of these confer a low to moderate risk of PrCa, the cumulative risk (polygenic risk score, PRS) of increasing numbers of these risk alleles may confer a substantial relative risk. In PrCa genetic profiling, using PRS, could be used to target population screening to those at highest risk. BARCODE1 is the first study to prospectively review the use of a genetic profile in PrCa screening in the general population in the UK. Methods: Our study invited healthy males aged 55-69 to participate through their Primary Care physicians. Collection kits were mailed to retrieve saliva samples. Genotyping was carried out after DNA extraction using a study specific assay and the PRS was calculated for each participant using the sum of weighted alleles for 130 risk loci. Prostate MRI and Biopsy were then offered to men in the top 10% of the genetic risk profile. Results: 1434 men were invited by letter to participate. The uptake was 26%, of whom 87% of men were eligible for inclusion. Following DNA extraction, genotyping, and quality control checks, data were available for 297 men. 25 participants had PRS in the top 10% and were invited for screening; 19 underwent a prostate MRI, and 18 went on to have a systematic (+/- targeted prostate biopsy. There were 7 diagnoses of PrCa (38.9%). The cancers detected were low-risk and are being managed with Active Surveillance (AS). Results of the first year of follow up will be presented and an update of the main study which aims to recruit 5000 men. Conclusions: The BARCODE1 pilot has shown the feasibility of this population-based study, with an overall uptake of 26% and a cancer incidence of nearly 40%. We have identified approximately 70 Primary care providers who have contributed to the transition to the full BARCODE1 study, which will aim to recruit 5,000 men. The BARCODE1 study results will be important in defining the role of PRS genetic profiling in targeted PrCa population screening. Clinical trial information: IRAS257684.
Risk of urinary morbidity associated with photoselective vaporization of the prostate (PVP) in prostate cancer patients undergoing a combined radiotherapy regimen consisting of dynamic adaptive radiotherapy (DART) and brachytherapy boost.
Authors: Dattoli Michael J. , Kaminski Joseph M , Lawrence Gregory , Kaplon Daniel 
Published: March 2021

231 Background: Recent studies have shown PVPs to be associated with diminished perioperative and postoperative complications compared to transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). This is the first study to evaluate the timing of PVP intervention and post-treatment morbidity related to a combined regimen of DART and Pd-103 brachytherapy for treatment of prostate cancer. Methods: Between 12/05 and 04/20, 51 consecutive patients underwent Greenlight Laser (GLL) or Olympus Plasma Button (OPB) PVP after DART (median dose: 45 Gy) and before Pd-103 brachytherapy (median dose: 90 Gy). 27 patients received GLL PVP and 24 patients received OPB PVP. Peripheral seed loading designs were utilized to achieve optimal urethral sparing. The time from DART to PVP ranged from 1 to 81 days (median: 18 days). For 12 patients, the interval between DART and PVP was ≤7 days. The time from PVP to seed implant ranged from 0 to 55 days (median: 18 days). For 13 patients, the interval between PVP and implant was ≤7 days. American Urological Association (AUA) symptom scores were compiled prior to PVP and on the last post-brachytherapy follow-up. Post-implant follow-up ranged from 6 months to 15 years (median: 6.4 years). Results: No patient experienced post-implant urinary retention or incontinence. Morbidity was limited to RTOG grade 1-2 symptoms, with the exception of one patient who experienced protracted dysuria, which was identified to be secondary to a pre-existing prostate anomaly (steep urethral curvature). Only that patient required dilation for urethral stricture. AUA scores improved or remained the same in 43 of 51 patients. Only 1 patient of the remaining 8 experienced an increase in AUA > 8 points. Conclusions: In our experience, there have been remarkably few adverse urinary sequelae following Pd-103 implantation in patients with prior PVP and DART. In contrast to TURPs, PVPs are safe even with short intervals between DART and brachytherapy. Based upon these results, pre-implant PVP is preferred, rather than PVPs or TURPs in the post-implant setting.
Investigation of a 22-gene genomic classifier (GC) for risk stratification and molecular subtyping in an Asian prostate cancer (PCa) cohort.
Authors: Yee Wei Loong Sherman , Woo Wai Yee , Sim Adelene , Low Kar Perng , Meng Alice , Tan Janice Ser Huey , Tuan Jeffrey , Tan Terence WK , Wang Michael Lian Chek , Tay Kae-Jack , Cheng Christopher , Yeong Joe Poh Sheng , Liu Yang , Lee Lui Shiong , Kanesvaran Ravindran , Tan Michael Chien Sheng , Davicioni Elai , Khor Li Yan , Chua Melvin Lee Kiang 
Published: March 2021

249 Background: A 22-gene GC has been proposed to refine risk stratification of localized PCa by conventional NCCN criteria, and this may potentially influence treatment recommendations. Nonetheless, majority of studies looking at the utility of GC were conducted in White and non-White men from Western cohorts. We therefore investigated the association of GC with NCCN risk groups (RG) in an Asian PCa cohort. Additionally, we examined for inter-racial differences in molecular subtyping between Asian and White/non-White PCa. Methods: GC (Decipher Biosciences Inc., CA) was performed on diagnostic biopsies of men who were treated with radiotherapy +/- hormonal therapy at a single institution (N = 75). ISUP Gleason’s grade (GG) and tumor cellularity were reviewed by an expert GU pathologist. RNA was extracted from 2 x 2.0-mm tumor cores using Qiagen AllPrep DNA/RNA FFPE Kit (Qiagen, Germany) and gene expression was performed on Affymetrix Human Exon 1.0 ST Array (ThermoFischer, CA). PAM50 molecular subtyping was derived using the DecipherGRID database. Results: We profiled 80 tumors from 75 patients, comprising of 18 (24.0%), 9 (12.0%), 21 (28.0%), and 19 (25.3%) NCCN low-/favorable intermediate-, unfavorable intermediate-, high- and very high-RG, respectively; of note, 8 (10.7%) patients had regional/metastatic disease at diagnosis. Using the GC, 27 (33.8%), 14 (17.5%) and 39 (48.8%) were classified as low- (<0.45), intermediate- (0.45-0.6) and high-RG, respectively (>0.6). When stratified using a three-tier clinico-genomic (CG) classification system (Spratt et al. 2017), 6 of 21 (28.6%) NCCN-defined high-risk and 4 of 19 (21.1%) very high-risk patients were downgraded to CG-defined intermediate-/low-risk, while 2 of 27 (7.4%) NCCN low-/intermediate-risk patients were in fact upgraded to CG high-risk. Next, we interrogated the PAM50 basal-luminal signature in our cohort. Interestingly, when matched to White (N = 5762) and non-White (N = 155) for NCCN RG, ISUP GG and age, we observed a high proportion of basal subtype (62.7%) in Asians, which contrasted the prevalence observed in White (16.7%) and non-White (15.9%) North American patients (Chi-sq P <0.001). Conclusions: Here, we demonstrated the utility of the 22-gene GC for refining the NCCN risk stratification in a largest Asian PCa dataset to-date. An unexpectedly high proportion of PAM50 basal-subtype was observed, suggesting race-specific differences of the tumor transcriptome.
Immunohistochemical evaluation of glutaminase expression in prostate adenocarcinoma and correlation with clinicopathologic parameters.
Authors: Myint Zin , Hensley Patrick J. , James Andrew Callaway , Wang Peng , Strup Stephen , Yan Donglin , St Clair William H. , DiPaola Robert S. , Allison Derek B. 
Published: March 2021

251 Background: Glutaminolysis plays a significant role in the metabolic reprogramming of cancer cell growth and proliferation. Glutaminase (GLS1), the rate-limiting enzyme of the glutamine pathway, is frequently dysregulated in cancer. High GLS1 expression is reported in colorectal and breast cancers and has been found to correlate with the tumor stage and disease progression. Furthermore, a new orally bioavailable glutaminase inhibitor (CB-839) is in early phase clinical trials in select tumors. The purpose of this study is to investigate the status of GLS1 expression in prostate cancer (PCa) and to correlate expression levels with clinicopathologic parameters. Methods: Radical prostatectomy samples from 154 patients with prostate adenocarcinoma were retrospectively reviewed and used to evaluate GLS1 expression by immunohistochemistry (IHC). The IHC expression score was calculated by multiplying the intensity of the stain by the proportion of cells staining; cases were then segmented into negative, low, or high expression groups. In addition, 41 samples of benign prostate tissue were used as a control. Associations between GLS1 levels and clinicopathologic parameters were analyzed by Pearson’s chi-squared and Log-rank tests. Results: GLS1 expression in the benign controls were negative, low, and high in 59%, 41%, 0% of cases, respectively, compared to 53%, 21.5%, 25.5%, respectively, in PCa (p < 0.003). Most PCa patients were age < 60 (55.8%), white (78.6%), stage T2 (52.9%), node negative (80.5%), Grade Group 3 (44%), and non-smokers (63.6%). There was no difference between GLS1 expression and age, race, Gleason score, stage, node status, and smoking status by univariate analysis. The median biochemical-progression free survival for negative, low, and high expression was 10, 9, and 10 years, respectively (p = 0.7). Conclusions: In our study, PCa samples were more likely to have GLS1 expression compared to benign controls. Although GLS1 expression did not appear to be a prognostic marker, our cohort was enriched for cases with localized disease and low-to-intermediate grade PCa. As a result, future studies are warranted to evaluate the expression levels in high grade and advanced PCa cases to determine a role for prognostic and or therapeutic implication to justify future preclinical studies with CB-839.
The effect of maximum tumor diameter on disease control in intermediate and high-risk prostate cancer patients treated with brachytherapy boost.
Authors: Parsons Matthew , Hutten Ryan , Khouri Ashley , Tward Alexander , Morrell Glen , Peterson John Stuart , Cannon Donald Maurice , Lloyd Shane , Johnson Skyler B 
Published: March 2021

252 Background: Larger maximum tumor diameter (MTD) has been associated with worse prostate cancer outcomes for those undergoing surgery as well as salvage radiation. MTD is also an important consideration for patients weighing active surveillance. However, the impact of MTD in intermediate and high-risk prostate cancer treated with external beam radiotherapy (EBRT) and brachytherapy boost is unknown. We set out to evaluate MTD of the dominant nodule on MRI as a prognostic factor in patients treated with EBRT and brachytherapy boost for localized prostate cancer. Methods: Patients with prostate cancer treated with EBRT and brachytherapy boost were identified from an institutional database. In patients with a pretreatment MRI, data on MTD were retrospectively collected. Clinical data including age, ADT use, pretreatment PSA, International Society of Urologic Pathology (ISUP) group, clinical T-stage, and presence of adverse pathology on imaging (either seminal vesicle invasion or extraprostatic extension) were also collected. Multivariable and univariable cox proportional hazards models for biochemical failure (BF) and distant metastasis (DM) were produced in patients with MTD grouped by receiver operating characteristic (ROC) cutpoint. Cumulative hazard functions for BF and DM were compared with log-rank test and stratified by ISUP group. Results: Of 191 patients treated with EBRT and brachytherapy boost, 113 had pretreatment MRI and available MTD measurement. Median follow up was 40 months (interquartile range 23-66 months) and median MTD was 17 mm (interquartile range 13-22mm). Increasing MTD was associated with higher T stage and increased ADT use. ROC cutpoint optimization identified MTD of 24mm to be the optimal cut-point for both BF and DM. On univariate log-rank analysis, patients with MTD > 24mm had higher 5-year BF (31% vs 4%, p = 0.004) and DM (21% vs 4%, p = 0.002) than those with MTD≤24. Stepwise multivariable cox model for BF (P = 0.130, HR 1.08, 95% CI 0.98-1.21) and DM (P = 0.115, HR 1.09, 95% CI 0.98-1.23), MTD did not demonstrate statistical significance when controlling for clinical t-stage, adverse pathologic features on imaging, ISUP group, and ADT use. However, in patients with ISUP group 4-5 disease, MTD > 24 was independently associated with increased risk of DM (P = 0.032, HR 1.18, 95% CI 1.01-1.37). Conclusions: This is the first study to evaluate MTD on MRI as a prognostic factor in the setting of brachytherapy boost. These results demonstrate that for patients treated with EBRT and brachytherapy boost, MTD is independently associated with risk for metastasis in patients with ISUP grade 4 and 5 disease. Although these results require further validation, this suggests a possible role for MTD as a factor in risk assessment models and clinical decision-making.
Single-cell analysis of cellular state heterogeneity in human localized prostate cancer.
Authors: Song Hanbing , Weinstein Hannah N.W. , Allegakoen Paul , Wadsworth Marc , Xie Jamie , Yang Heiko , Feng Felix Y , Carroll Peter R. , Wang Bruce , Cooperberg Matthew R. , Shalek Alex , Huang Franklin W. 
Published: March 2021

254 Background: Prostate cancer is the second most common malignancy in men worldwide. The development of cancer from prostate tissue involves complex interactions of tumor cells with surrounding epithelial and stromal cells and can occur multifocally, suggesting that prostate epithelial cells may undergo cellular state transitions towards carcinogenesis. Previous studies on localized prostate cancer molecular changes have focused on unsorted bulk tissue samples, leaving a gap in our understanding of the cellular heterogeneity in the tumor microenvironment. Single-cell analyses of tumor specimens have the potential to reveal, at unprecedented resolution, cellular composition, as well as instructive intercellular interactions. Methods: To characterize the localized prostate cancer tumor microenvironment, we performed single-cell RNA-sequencing (scRNA-seq) on prostate biopsies, radical prostatectomy specimens, and matched patient-derived organoids from localized prostate cancer patients. Results: Within prostate epithelial cells, we identified a population of club cells that may act as progenitor cells. Furthermore, we uncovered luminal-like epithelial cellular states augmented in androgen signaling across basal and club cell populations. By classifying tumor cells based on ERG expression status, we found that ERG- tumor cells, in contrast to ERG+ cells, share transcriptomic heterogeneity with surrounding luminal epithelial cells and are associated with common stromal and immune microenvironment responses. These results suggest that specific immune niches may arise based on TMPRSS2-ERG fusion status. Finally, we generated prostate epithelial organoids derived from matched localized prostate cancer patients and characterized their transcriptomic profiles by scRNA-seq. These patient-derived organoids recapitulated tumor-associated epithelial cell states but also harbored distinct cell types and states from their parent tissues. Conclusions: Our data from localized prostate cancer specimens and organoids provide diagnostically relevant insights and will help advance our understanding of the cancer cellular states associated with prostate carcinogenesis.
Stage at presentation and oncologic outcomes for agent orange exposed and non-exposed United States veterans diagnosed with prostate cancer.
Authors: Tward Alexander , Tward Jonathan David 
Published: March 2021

259 Background: Exposure of Vietnam War Veterans to the defoliant Agent Orange (AO) has been linked to increased tumor stage of Veterans diagnosed with prostate cancer. However, information on the effect of exposure to treatment outcomes is lacking. The goal of this study was to evaluate oncologic outcomes in Veterans based on AO exposure history, accounting for known prognostic covariates not previously studied. Methods: United States military Veterans diagnosed with prostate adenocarcinoma born between the years 1930-1956 were identified from a large professionally curated institutional database. Evaluable patients had to have known AO exposure status, age, NCCN risk group, Charlson comorbidity score, smoking status, and whether initial therapy was surgical, radiation, or systemic. Risk of death, metastasis, and progression stratified by the type of initial therapy received was analyzed using Cox regression. Results: There were 70 AO exposed and 561 non-exposed Veterans identified, with a median follow-up of 10.0 years. AO exposure Veterans (AOeV) were significantly younger (64.0 versus 65.7 years, p=0.013) at diagnosis and presented at more advanced stages (e.g. Stage 4: 14.3% versus 2.5%) than non-exposed Veterans (non-AOeV). There was no difference for overall survival (HR=0.86, p=0.576, metastasis-free survival (HR=1.5, p=0.212), or progression-free survival (HR=0.67, p 0.060) between AOeV versus non-AOeV in analyses stratified by treatment received accounting for other prognostic covariates. Cigarette smoking was associated with a 2- 3-fold increased risk of death over those who quit or never smoked. Conclusions: Although AOeV do present at younger age and higher clinical stages than non-AOeV, the oncologic outcomes after accounting for treatments received and other prognostic covariates are similar. The implication is that AOeV are more likely to be recommended multimodality or systemic therapies at presentation.