bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of previous nephrectomy on clinical outcome of metastatic renal carcinoma treated with immune-oncology (I-O):A real-world study on behalf of Meet-URO group (MeetUro-7b).
Authors: Stellato Marco , Santini Daniele , De Giorgi Ugo , Verzoni Elena , Casadei Chiara , Fornarini Giuseppe , Maruzzo Marco , Napolitano Andrea , Sbrana Andrea , Di Lorenzo Giuseppe , Soraru' Mariella , Naglieri Emanuele , Buti Sebastiano , De Vivo Rocco , Vignani Francesca , Mucciarini Claudia , Grillone Francesco , Roviello Giandomenico , Pignata Sandro , Procopio Giuseppe 
Published: May 2020

e17088 Background: Immuno-oncology (IO) treatment demonstrated to improve Overall Survival (OS) in metastatic renal cell carcinoma (mRCC). The prognostic impact of previous citoreductive nephrectomy (CN) and radical nephrectomy with curative intent in patients (pts) treated with IO is not well defined. Methods: 229 eligible pts, with a least one radiological assessment of response according to the RECIST 1:1 criteria, were retrospectively collected from 16 Italian referral centers. Baseline characteristics, outcome data including progression-free survival (PFS) and OS were collected. Kaplan-Meier method and log-rank test were performed to compare PFS and OS between groups. Results: 153(66.8%) pts received IO as second line, 61(26.6%) as third line and 15(6.6%) pts as further line. 54 pts (23.6%) were good risk, 144(62.9%) were intermediate and 31(13.5%) were poor risk according to IMDC score. 189(82.5%) pts underwent nephrectomy (of them 72(32.4%) pts had synchronous metastatic disease and underwent CN), while 40(17.4%) pts did not. Nephrectomy was performed before IO treatment. ECOG PS, at the beginning of IO, was 0 for 167 pts (72.9%), the other 62 (27.1%) had ECOG PS 1 or 2. At a median follow up time of 17.5 months (mo), 13 (5.7%) pts are still in treatment while 216 (94.3%) experienced progression. 81 (35.3%) pts were treated after IO progression with mTOR and VEGFR inhibitors. 63 (27.5%) pts continued IO beyond progression. G3-G4 iAE were reported in 46 pts (20%). Median IO-PFS was 4.5 months in pts who did not undergo nephrectomy and 2.9 mo in pts who did (HR log rank 0.713, 95%CI 0.4788 to 1.063; p= 0.0582). Median IO-OS was 18.4 mo in pts who underwent nephrectomy and 10.3 mo in pts who did not (HR log rank 1.915, 95%CI 1.118 to 3.281; p= 0.0024). The difference in OS was irrespective of the IMDC criteria and the lines of treatment. Conclusions: In our real world experience, in mRCC pts treated with IO, previous nephrectomy was associated with a better outcome in terms of OS with all the limitations of a retrospective collection.
Underrepresentation of genitourinary cancers in studies of venous thromboembolism (VTE) prophylaxis.
Authors: Perlmutt Max S , Rose Tracy L , Kumar Vaibhav , Milowsky Matthew I. 
Published: May 2020

e17115 Background: Significant advances in the management of VTE in cancer have led to a recent ASCO clinical practice update for VTE prophylaxis and treatment in patients with cancer. Genitourinary (GU) cancers (including bladder, kidney, prostate, testicular) have a high incidence of VTE, but also frequent bleeding complications, and it is not clear if patients with GU cancers are adequately represented in studies of VTE prophylaxis. We sought to determine the frequency of inclusion of patients with GU cancers in prospective studies of VTE prophylaxis. Methods: A systematic review of the literature using MEDLINE (inception to January 2020) was conducted. We included randomized controlled trials that compared thromboprophylaxis to placebo or best supportive care in patients with an established diagnosis of cancer. Observational studies, case series, and case reports were excluded. The primary outcome was proportion of patients with GU malignancies included within the trials. Results: A total of 137 articles were identified under the original search and 7 underwent full text review. A total of 6066 patients were included in 7 thromboprophylaxis trials, of which only 119 (2.0%) had a defined GU malignancy (Table). Given the heterogeneity of the GU cancers represented in each study, and the small numbers of patients included with GU cancers, a patient-level meta-analysis among GU patients in this population was not performed. Conclusions: In spite of the high risk for VTE in GU cancers, in particular bladder and testicular cancer, GU cancers are underrepresented in prospective randomized trials investigating VTE prophylaxis. To ensure appropriate decision making for each individual patient, future prospective trials must ensure adequate representation of patients with GU cancers to better understand the potential role for VTE prophylaxis in this high-risk population.[Table: see text]
Changes in ki-67 and cleaved caspase-3 (CC3) with short term androgen deprivation therapy (ADT) prior to prostatectomy as part of a trial in intermediate and high-risk prostate cancer (PC).
Authors: Vargas Pivato de Almeida Daniel , Chen Ying-Bei , Autio Karen A. , Carver Brett Stewart , Slovin Susan F. , Danila Daniel Costin , Scher Howard I. , Touijer Karim A. , Rathkopf Dana E. 
Published: May 2020

e17502 Background: Ki-67 and CC3 are markers of cellular proliferation and apoptosis and have been associated with prognosis in localized PC. Testosterone suppression promotes a time-dependent modulation of these indices. We explored changes in Ki-67 and CC3 at different timepoints in a pilot trial using short-term ADT prior to radical prostatectomy (RP). Methods: Pts with intermediate and high-risk localized PC were randomized to receive a single dose of neoadjuvant degarelix (240 mg SC) either 4 ± 1 days (Cohort A) or 7 ± 1 days (Cohort B) prior to RP. Anatomically matched tumor foci from the pre-treatment diagnostic biopsy and the prostatectomy specimens were assessed by immunohistochemistry (IHC) for Ki-67, CC3, and PTEN expression. Results: 32 pts were randomized: 15 to Cohort A and 17 to Cohort B. Ki-67 and CC3 expression in the pre- and post-treatment samples for both cohorts are summarized in the table. A significant reduction in Ki-67 and increase in CC3 expression occurred in both cohorts (all p-values < 0.05). No difference was found when the absolute difference of Ki-67 expression was compared between Cohort A and Cohort B (p = 0.7). A significant reduction of Ki-67 and increase in CC3 expression occurred in pts independent of PTEN status. Conclusions: A reduction of Ki-67 and an increase in CC3 expression was achieved in both cohorts following a single dose of degarelix within 1 week of RP. Although loss of PTEN has been associated with androgen-independent progression, reduction of proliferation and increase in apoptosis levels were achieved independent of PTEN status in this small cohort. Further analyses are ongoing to correlate the pathologic findings with clinical outcomes. Clinical trial information: NCT01542021 . [Table: see text]
Development of a circulating tumor cell-based RNA classifier for patients with castration-resistant prostate cancer: CTC-PCS/PAM50.
Authors: Teng Pai-Chi , Jan Yu Jen , Kim Minhyung , Chen Jie-Fu , Yoon Junhee , Wang Jasmine Jiemei , Chen Pin-Jung , Yao Nu , Lee Yi-Te , Lozano Amber , Gadilov Ruslan , Freeman Michael , You Sungyong , Tseng Hsian-Rong , Posadas Edwin Melencio 
Published: May 2020

e17509 Background: Genomic profiling has strongly impacted the contemporary understanding of prostate cancer (PCa). Clinical trials are now testing the utility of genomic classifiers such as the PCS (You, Ca Res 2016) and PAM50 (Zhao, JAMA Onc 2017) systems to optimize therapy selection. As contemporary tissue is not always readily available, especially in metastatic, castration-resistant PCa (mCRPC), a blood-based test would be better suited for assessing patients and predicting treatment response. Methods: The CTC-RNA assay combines the Thermoresponsive (TR)-NanoVelcro system with the NanoString nCounter platform. This allows for CTC purification and RNA analysis. Using a novel bioinformatics approach that accounts for differences in background signals between tissue and blood, we reconstructed the PCS and PAM50 panels to recapitulate both classifiers in this blood-based assay. A weighted Z-score and nearest centroid classifier were used to calculate gene expression and to assign PCS and PAM50 subtypes. Performance of the revised signatures and CTC-RNA assay was benchmarked on simulated spiked-blood specimens. An initial clinical test was performed using clinically annotated, banked blood specimens within the Translational Oncology Program Blood and Biospecimen Bank. Results: CTC-RNA profiles of C4-2B AR signaling inhibitor (ARSI)-resistant sublines were compared to parental C4-2B. C4-2B ARSI-resistant cells had significantly higher PCS1 Z scores, PCS1 probability, and basal probability compared to the parental C4-2B cells. Blood samples from 34 mCRPC patients prior to initiation of therapy with ARSIs (abiraterone, enzalutamide, or apalutamide) were then analyzed. Samples were classified as PCS1 (n = 3), PCS2 (n = 20), and PCS3 (n = 11); luminal A (n = 12), luminal B (n = 11), and basal (n = 11). The biochemical progression-free survival (bPFS) on ARSI and overall survival (OS) for PCS1/Basal vs. other are shown in the table. Conclusions: The CTC-RNA assay is capable of generating luminal-basal classifications such as those in the PCS and PAM50 systems. Given early data of these classifiers and their potential to guide therapeutic decisions, this approach may be useful as an alternative to biopsy to facilitate such decisions. Larger prospective studies will be needed to confirm and validate its clinical utility. [Table: see text]
Landscape of somatic DNA damage repair (DDR) gene mutations in genitourinary cancer in China.
Authors: Yang Kaiwei , Tang Qi , Mi Yue , Yu Wei , Song Yi , Zhang Yanrui , Wang Huina , Lou Feng , Cao Shanbo , He Zhisong 
Published: May 2020

e17516 Background: DDR gene alterations(GAs) are prevalent in cancer and play key roles in tumorigenesis, progression and therapeutic response. However, the molecular profile of DDR in genitourinary cancer is still lacking in Asian. In this study, we assessed DDR GAs for better understanding therapeutic implications. Methods: Patients(pts) diagnosed with genitourinary cancer were enrolled. Tumors and plasma samples were collected for next-generation sequencing with Acornmed panel(2.0 Mbp) containing 808 cancer-related genes, including 34 DDR genes(Jonathan, et al.). OncoKB and COSMIC were used to identify GAs status including deleterious, unknown significance, and wild type(wt). Results: A total of 140 pts were enrolled with 56 pts of prostate cancer(PC), 55 pts of renal cell cancer(RCC) and 29 pts of urothelial cancer(UC). Metastatic diseases were accounted for 33.5%. A total of 127 tumor tissues and 109 baseline plasma samples were collected, including 96 matched tissue/plasma samples. A total of 109 pts(77.9%) harbored at least one GA in DDR pathway. UC carried the most DDR GAs(93.1 %), followed by PC(75%) and RCC(72.7%). After stratifying GA status, the most commonly deleterious GAs were ATM(n = 5); FANCA(n = 4); ERCC2, BRCA1, ATR, CHEK2(n = 2 each); MSH6, ERCC4, BRCA2, PALB2(n = 1 each).Tumor mutation burden(TMB) was significantly different among pts with deleterious, unknown significance and wt in PC(Mean: 17.8 vs 9.065 vs 4.468; p = 0.0003). Notably, DDR GAs were more likely to present in pts with metastatic disease(80.95% vs 62.50%), deleterious DDR GAs as well(14.29% vs 8.33%). Conclusions: DDR pathways are frequently altered in genitourinary cancer, especially UC in China. DDR GAs were significantly associated with higher TMB in PC. A higher prevalence was identified in metastatic disease. Comprehensive genomic profiling of DDR GAs highlights the clinical and therapeutic implication. Further exploration of the deleterious nature and alterations of unknown significance are required. [Table: see text]
Impact of socioeconomic disparities on upstaging for prostate cancer: A national cancer database analysis.
Authors: Patel Sagar , Worrilow William Mills , Trufan Sally Jeanne , Beano Hamza Mustafa , Kearns James T. , Riggs Stephen Boyd 
Published: May 2020

e17526 Background: Recent data suggest that socioeconomic disparities impact the outcome of oncologic disease. This retrospective analysis investigates the role of socioeconomic variables on clinical to pathologic staging of prostate cancer (PC). Methods: 455,773 males with stage 1-3 adenocarcinoma of prostate who underwent surgical intervention (96% radical prostatectomy) were extracted from the National Cancer Database from 2004-2016. Patients were stratified into age groups based on American Urologic Association PSA screening recommendations ( < 40, 40-54, 55-69, > 70 years). Changes from clinical to pathological staging were the primary outcomes. Demographics, income level, education status and distance to treatment facility ( < 12.5, 12.5-49.9, > 50 miles) were analyzed using Chi-square and logistic regression to find upstaging predictors. Results: Rates of stage changes are summarized in Table. Increased distance ( > 50 vs < 12.5 mi) was associated with upstaging in all age groups (40-54: OR 1.10 95%CI 1.05-1.16; 55-69: OR 1.20 95%CI 1.18-1.23; > 70: OR 1.42 95%CI 1.35-1.50) except for < 40 years (OR 1.15, 95%CI 0.60-2.21). Other predictors of upstaging included black or other race compared to white (OR 1.06 95%CI 1.04-1.09 and OR 1.10 95% CI 1.06-1.14, respectively) and in men with government insurance vs private insurance (OR 1.19 95%CI 1.17-1.21). Lower risk of upstaging was seen for those who were not insured vs private insurance (OR 0.70 95%CI 0.67-0.73), lived in areas with the highest vs lowest high school education rate (OR 0.95, 95%CI 0.92-0.98), or lived in the lowest vs highest income areas (OR 0.93, 95%CI 0.90-0.96). Conclusions: Socioeconomic disparities directly impact the outcome for prostate cancer. Our study suggests age, distance from treatment facility, and race are associated with a greater risk for clinical to pathologic upstaging. Investigation should continue to better understand at-risk populations. [Table: see text]
Tumor subtypes associated with prostate cancer (PCa) both as first and second primary tumors: A registry-based analysis.
Authors: Wellen Andrew , Peace David J. 
Published: May 2020

e17528 Background: First primary tumors (FPT) generally are associated with decreased survival and, thus, reduced risk of second primary tumors (SPT). A greater than expected incidence of SPT may indicate causal factors shared in common with a particular FPT, especially if the converse also is observed, i.e. if incidence is also greater than expected when tumor sequence is reversed. We analyzed the Surveillance, Epidemiology, and End Results (SEER) cancer registry to identify tumors with higher than expected incidence in relation to PCa, both as FPT and SPT. Methods: We searched the SEER18 cancer database covering 18 geographical regions of the U.S. from 2000 to 2016. SEER*Stat software v.8.3.6 was used to calculate standardized incidence ratios (SIR) of various SPT after defined FPT. SIR compare the incidence of a particular cancer within subsets of the registry population as a ratio to the expected incidence from a comparable matched group derived from the general population. 813,712 men with prostatic FPT (1° PCa) were included in the analysis for SIR of any SPT, while 2,554,835 men with any FPT were included in the analysis for SIR of prostatic SPT (2° PCa). Results were stratified by race and latency. Reciprocal SIR (1° PCa; 2° PCa) for values with p < 0.05 are reported. Results: Aggregate analysis of all tumors demonstrated lower than expected SIR for SPT, both for any SPT after 1° PCa and for 2° PCa after any FPT (0.69; 0.53). By contrast, six tumor subtypes – small intestine (1.17; 1.19), melanoma (1.05; 1.23), bladder (1.14; 2.02), kidney (1.22; 1.36), thyroid (1.27; 1.36), and chronic myelogenous leukemia (1.10; 1.15) – had bidirectionally increased secondary SIR in relation to PCa. The reciprocal increases were detected across racial subgroups for bladder, kidney and thyroid cancers. SIR tended to be highest in the early post-FPT period (2-11 mo.) with significant increases for bladder (1.49; 6.75), kidney (2.66; 1.87), and thyroid (1.61; 1.65) cancers. These three tumor types retained bidirectional increases in relation to PCa over intermediate latencies (12-119 mo.), but not beyond 120 mo. Conclusions: Overall, FPT were associated with lower than expected incidence of SPT, most likely as a result of shortened life expectancy. However, several tumors were identified that 1). occurred with higher than expected incidence after 1° PCa and 2). were associated with higher than expected incidence of 2° PCa. Further examination of the relationship of these tumors with PCa may identify mutual intrinsic or extrinsic factors that contribute to tumor development.
Epidemiological profile of patients diagnosed with prostate cancer at Muriaé Cancer Hospital, Minas Gerais, Brazil.
Authors: Freitas Carla Simone Moreira de , Soares Aleida Nazareth 
Published: May 2020

e17530 Background: Prostate cancer (CP) is one of the most common malignant neoplasms among men with high prevalence worldwide. In Brazil, in 2019, 582,000 new cases of cancer were estimated, 282,000 in women and 300,000 in men, 75% are prostate cancer in individuals over 65 years of age (BRASIL, 2019). The occurrence of CP has specific risk factors, such as advanced age (over 65 years), genetic predisposition (patients with a family history of prostate cancer, between 35 and 40 years of age) and ethnicity (mostly blacks). Mortality due to this neoplasm is considered relatively low compared to other types of cancers, which partly reflects a good prognosis.The objective of this study is to describe the epidemiological profile of prostate cancer patients treated in an Muriae Cancer hospital in Minas Gerais - Brazil. Methods: Descriptive cross-sectional study conducted between 1997 and 2019 with 4,395 patients diagnosed with CP, living in the region and adjacencies, 4,175 (95%) assisted by the Unified Health System (SUS). Results: Patients from Minas Gerais-Brazil, cities of microregions and rural areas, the most prevalent age group was between 61-70 years of age with 1769 cases (40.25%), 3476 (79.1%) with low schooling, 3156 (71.82%) with per capita family income less than 0.5 minimum wages, and in regarding profession, the majority 541 (58.05%) is retired and rural workers 148 (15.88%); 1933 (44%) alcohol users, 2021 (46%) smokers and 1626 (37%) with a report of a family history of cancer. As for ethnicity, 1943 (44.23%) were black. Nutritional status 3845 (87.49) were eutrophic. The mean time between diagnosis and treatment was 51 months. PSA levels were 1ng/ml to 10 ng/ml (39%), from 10 ng/ml to 28 ng/ml (21%), from 28 ng/ml to 70 ng/ml (9%) and from 70 ng/ml to 200 ng/ml (6%) and > 200 ng/ml (5%); altered tests 1845 (42%), PSA elevation 1538 (35%), obstructive symptoms 965 (5%), dysuria 579 (3%) and pain 579 (3%). The majority (50.41%) with stage II, stage III (18.10%) and IV (9%), highlighting that in 1997 the percentage of advanced stages (III and IV) was 47% and in 2019 it decreased to 18%, due to earlier diagnoses. Conclusions: The analyzed data allowed to characterize the epidemiological and sociodemographic profile of patients treated in Muriaé Cancer hospital, Brazil, contributing to decision-making regarding the treatment provided to this population.
Early PSA decline as a predictor of progression in patients with metastatic castration-naïve prostate cancer (mCNPC) treated with abiraterone acetate and prednisone (AA/P).
Authors: Barata Pedro C. , Sheng Iris Yeong- Fung , Fallah Jaleh , Gupta Ruby , Li Hong , Allman Kimberly D. , Martin Allison , Ornstein Moshe Chaim , Gilligan Timothy D. , Rini Brian I. , Garcia Jorge A. 
Published: May 2020

e17542 Background: Treatment intensification with androgen deprivation therapy (ADT) plus AA/P is a standard of care in patients with metastatic castration naïve prostate cancer (mCNPC). Despite initial responses, nearly all men will eventually progress to castration resistant disease (CRPC). Early changes in PSA while on ADT plus AA/P has significant clinical and therapeutic implications for mCNPC patients, yet limited data is available. We aimed to assess PSA patterns while on therapy with ADT plus AA/P and time to CRPC. Methods: mCNPC patients treated with ADT plus AA/P between June 2017 and February 2019 at the Cleveland Clinic, were included. The primary objective was to describe patterns of PSA change evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months from AA/P initiation. Other endpoints of interest included PSA progression by PCWG3 and CRPC-free survival at 12 and 18 months. Results: A total of 130 patients, 82% Caucasian, median age 69 years, with 50% with de-novo mCNPC, 47% high-volume (60.8% Gleason score ≥8, 16.2% visceral disease, and 53.8%had ≥3 bony lesions) were included. Half of the patients achieved undetectable PSA ( < 0.03) while on therapy. The median time to PSA < 0.03 was 13.1 months (95%CI, 7.6-NE). The greatest PSA reduction occurred at the first 3 months (80%, p < 0.0001), changes after 3 months were small, (4% from 3 to 6 months, p < 0.0001; 3% from 6 to 9 months, p < 0.0001) and not significant from 9 to 12 months. The 12 and 18-months mCRPC-free survival after initiation of ADT plus AA/P was 88.1% and 81.3%, respectively. A PSA > 0.2 at 3 months was associated with a shorter time to mCRPC (p = 0.002). Similarly, a PSA reduction < 98% at 3 months was associated with worse outcomes (12 mo CRPC survival 68.0% vs. 94.9%, respectively; p < 0.001). Conclusions: In this data set, timing and depth of serologic response predicted the early development of CRPC in patients receiving ADT plus AA/P. Further validation is ongoing using data from large randomized clinical trials.