bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urban-rural kidney cancer disparities: The role of health literacy, cancer literacy, smoking status, and urinary bother.
Authors: Su Christina , Linnenbringer Erin , Dynda Danuta , Delfino Kristin , Lyons Sarah , Kim Sharon , Alanee Shaheen , McVary Kevin 
Published: June 2022

e16513 Background: Kidney cancer (KCa) does not currently have efficacious screening methods, therefore targeting modifiable risk factors is a strong approach to primary prevention. Prior research from our group identified a significant difference in KCa incidence and mortality between the urban and rural populations in Illinois, but the reason(s) for this geographic variation were unclear. The objective of this pilot study was to investigate KCa-relevant knowledge and health behaviors in order to explain our observed urban-rural differences in KCa incidence and mortality, and to inform approaches to KCa prevention. Methods: A convenience sample was surveyed from five study sites between June 2016 and February 2018. These included 207 urban and 53 rural patients presenting at urology and primary care clinics. Four outcome measures related to KCa were assessed using validated measures: 1) health literacy, 2) cancer health literacy, 3) smoking status and knowledge of its association with KCa, and 4) degree of bother caused by urologic symptoms. Multivariate logistic regression models were used to examine these outcome measures between the two populations. Smoking history, personal and family history of cancer, and socio-demographic characteristics were controlled for in the analysis. Results: The overall model for predicting health literacy was significant (Wald Pvalue = 0.0269). When accounting for all covariates, rural versus urban residence was not a significant predictor of adequate health literacy (p = 0.4871). However, participants with higher levels of education (p = 0.0005), higher household income (p = 0.0395), and participants who were female (p = 0.0104) were all more likely to have adequate vs. low health literacy. We did not identify a statistically significant difference in cancer health literacy, knowledge of smoking as a KCa risk factor, or measurement of urinary bother between urban and rural residents in this population. Conclusions: The analyses revealed significant differences in health literacy by education, income, and gender, but not by geographic location. While there were no statistically significant geographical differences found in three of our four domains, this may have been attributed to the low proportion of rural-residing clinic patients recruited in this study. With potential limitations of using RUCA as a measure of rurality, future work is needed to better reach this population and validate results to understand the disparity of improving KCa outcomes in rural areas.
PBRM1 genomic alterations as a predictive biomarker to immune checkpoint inhibitors (ICI) and/or anti-angiogenic therapies (anti-VEGF) in metastatic renal cell carcinoma (mRCC): A systematic review and meta-analysis.
Authors: Ghiglione Lucio , Fernandez-Mañas Laia , Ferrer-Mileo Laura , Aversa Caterina , Garcia de Herreros Marta , Laguna Juan Carlos , Gorria Teresa , Marin Mercedes , Jiménez Natalia , Prat Aleix , Maurel Joan , Mellado Begona , Reig Oscar 
Published: June 2022

e16515 Background: Combination therapy with ICI and anti-VEGF has become the standard first-line (1L) therapy for metastatic clear cell RCC (mccRCC). However, about 25% of patients (pts) are long responders to anti-VEGF monotherapy. PBRM1 genomic alterations (ga) are present in around 40% mccRCC pts and contradictory results have been reported about its role as a predictive biomarker. We performed a systemic review and meta-analysis to assess the role of PBRM1 ga as a predictive biomarker of response to ICI, anti-VEGF, or its combination. Methods: A systematic review of PubMed, EMBASE, Cochrane, and Web of Science databases was performed (February 2022) to identify studies involving mRCC pts who received systemic therapy and had PBRM1 status and clinical outcomes reported. Study design, baseline characteristics, treatment data, and hazard ratios (HRs) with 95% confidence intervals (CI) for each clinical outcome were extracted. HRs were combined across studies using a random effect model. The primary endpoint was to correlate PBRM1 status with progression-free survival (PFS) to anti-VEGF, ICI, or its combination. Results: The systematic review included 12 out of 892 publications (n = 6528 pts), 98% (n = 6372) mccRCC; 3297 pts (51%) treated with anti-VEGF monotherapy, 1574 (24%) ICI (PD-L1 (n = 1019, 65%) or CTLA4 + anti PD-L1 (n = 555, 35%)), 997 pts (15%) anti-VEGF + ICI, and 660 pts (10%) with other therapies (e.g., mTORi or INF). PBRM1 status was assessed by NGS in 3841 pts (59%) and detected in 1595 (41%). Nine out of 12 publications were considered for the meta-analysis; excluding those with duplicated pts or lack of information. Six studies (n = 2593 pts) evaluated PBRM1 status in first-line (1L) therapies, including anti-VEGF in monotherapy (n = 1487, 57%) and ICI (n = 1106, 43%; combined w/anti-VEGF (n = 773), w/CTL4 (n = 262) or in monotherapy (n = 71)). In 1L setting, PBRM1 ga pts had longer PFS under monotherapy with anti-VEGF ( PBRM1 ga 44%; HR = 0.74 (95% CI, 0.62 - 0.88), p < 0.01) but not under ICI ( PBRM1 ga = 42%; HR = 1 (95% CI, 0.85 - 1.17), p = 0.38) nor ICI + anti-VEGF treatment ( PBRM1 ga = 33.5%; HR = 0.93 (95% CI, 0.73 - 1.18), p = 0.56). Two studies evaluated PBRM1 status in second line (2L) ICI-treated mRCC pts (n = 517 pts). PBRM1 ga pts had longer PFS under ICI in 2L ( PBRM1 ga = 36%, HR = 0.64 (95% CI, 0.49 - 0.83), p = 0.0007). Conclusions: mRCC pts with PBRM1 ga showed longer PFS to 1L anti-VEGF and 2L ICI therapy, supporting its role as a predictive biomarker. Anti-VEGF + ICI combination de-escalation strategies merits further investigation in PBRM1 ga mRCC patients.
Efficacy and toxicity of antibody-drug conjugates (ADCs) in the treatment of metastatic urothelial cancer (mUC): A systematic review.
Authors: Padua Tiago Costa de , Malena Greta , Moschini Marco , Martini Alberto , Marandino Laura , Raggi Daniele , Briganti Alberto , Montorsi Francesco , Necchi Andrea 
Published: June 2022

e16536 Background: mUC is an aggressive disease with limited overall survival. Recently, immunotherapy with checkpoint inhibitors (ICI) has dramatically improved outcomes but with limited response rates and overall survival. ADC were designed with the intent to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells by linking cytotoxins to mAbs and have emerged as a new option of treatment with promising results. We aimed to realize a systematic review of efficacy, treatment-related AEs (trAEs) and impact on quality of life of ADC in mUC. Methods: A systematic review of the literature has been performed in January 2022 using Pubmed and Embase database according to the Preferred Reported Items for Systematic Reviews and Meta-analyses (PRISMA) statement. After excluding review, duplicate and non-relevant articles, 10 clinical trials were included in the analysis. The search method involved querying for the terms bladder carcinoma or urothelial carcinoma with any of the following: enfortumab vedotin (EV), sacituzumab govitecan (SG), antibody-drug conjugate. Only prospective clinical trials were included. Results: The systematic review yielded 1103 records using MEDLINE (741 records) and EMBASE (362 records). Ultimately, 9 phase 1, 2 or 3 clinical trials with 1355 patients were selected for inclusion and 4 drugs were identified: Enfortumab vedotin (EV), sacituzumab govitecan (SG), an anti-HER2 compound (RC48-ADC), and an anti- SLITRK6 drug (ASG-15ME). Efficacy outcomes are presented in table 1. Phase 2 trials have reported promising response rates in mUC and one randomized phase 3 trial showed the superiority of EV vedotin over CT after failure to platinum-based CT and ICI with improvement in overall survival. TRAEs of any grade occurred in more than 90% of patients in phase 2 or 3 trials, with high rates of discontinuation (table 2). TRAEs of special interest related to EV were rash, neuropathy, and hyperglycemia. SG is associated with diarrhea and hematologic toxicity. Data from phase 2 and 3 trials of EV suggest no impact on quality of life and an improvement in some parameters. Conclusions: ACDs represent a very promising new option for the treatment of mUC. A phase 3 trial confirmed the superiority of EV over CT after platinum and IO failure. A high incidence of potential adverse events was observed in phase 2 and 3 trials, including rash, neutropenia, hematologic toxicity, and neuropathy. Practitioners’ oncologists should be aware of potential adverse events and optimal management. Quality of life is preserved during the treatment with EV.
Molecular mechanism in urothelial carcinoma with FGFR3 mutation.
Authors: Liu Huanhuan , Zhang Yanrui , Lou Feng , Cao Shanbo , Wang Huina 
Published: June 2022

e16548 Background: Specific genomic alterations in the FGFR (fibroblast growth factor receptor) family are well-known to be characteristic driver events of urothelial carcinoma and is a therapeutic target. However, molecular mechanism differences of urothelial carcinoma (UC) stratified by the FGFR mutation status has not yet been described. Methods: Patients diagnosed with UC were enrolled in the study. Tumor tissue and matching blood were sequenced by next-generation sequencing (NGS) techniques with Acornmed panel with 808 cancer-related genes. Results: A total of 368 patients with UC were enrolled including 75 patients with FGFR2/3 mutation and 293 patients with FGFR2/3 wildtype. In FGFR2/3 mutation cohorts, the five most frequently mutated genes were FGFR2/3 (100%), KMT2D (56%), KMT2C (35%), CREBBP (32%) and FAT1 (31%). For FGFR2/3 wildtype cohorts, the five most frequently mutated genes were TP53 (46%), KMT2D (41%), BRD4 (23%), ARID1A (15%), and KMT2C (14%). 87 frequently mutated genes were significant difference between FGFR2/3 mutation and FGFR2/3 wildtype cohorts, such as KMT2D, KMT2C, STAG2, CREBBP and FAT1, excluding the FGFR2/3 gene. Signature 1 for spontaneous deamination of 5−methylcytosine and signature 22 for exposure to aristolochic acid (AA) existed in both cohorts. Although there were APOBEC Cytidine Deaminase signatures in both groups, they were projected to different COSMIC signatures (signature 2 and 13, respectively). Signature 10 for defects in polymerase POLE (4.81%) were only observed in the FGFR2/3 mutation cohorts. In the FGFR2/3 mutation cohorts, mutated genes were mainly enriched in the cancer pathway, PI3K-Akt signaling pathway, and Ras signaling pathway. However, in the FGFR2/3 wildtype cohorts, the primary pathways included the cancer pathway, PI3K-Akt signaling pathway, and Rap1 signaling pathway. Conclusions: There were characterized the genomic differences and similarities, stratified by the TP53 status, which may reflect the UC patients with TP53 mutation harbored specific molecular mechanism.
Clinical utility of urine tumor DNA in bladder cancer patients.
Authors: Hu Hailong , Niu Yuanjie , Wang HaiTao , Guo Zhaoxia , Liu Huanhuan , Shen Chong , Da La , Zhao Gangjian , Wang Lili , Wu Zhouliang , Zhang Zhe , Cao Shanbo , Lou Feng , Wang Huina 
Published: June 2022

e16560 Background: Concordance between tumor DNA (tDNA) and urine tumor DNA (utDNA) profiles using paired samples was analyzed. Genomic analysis of utDNA and tDNA showed a high consistency, indicating that urine is an optional sample for noninvasive detection and response evaluation of bladder cancer (BC). Methods: Methods and results data were analyzed from an ongoing study, collecting all cases from Second Hospital Affiliated to Tianjin Medical University. Cases with pathologically confirmed BC and matching tissue/urine/whole blood before treatments were recruited. In 85 patients, 48 with paired samples were enrolled in this analysis after excluding 37 paired samples failed in sample QC or sample collection. WES (Whole Exome Sequence) was applied to tDNA and paired white blood cell (WBC) DNA. An Acornmed 808-Gene panel was applied to utDNA and paired WBC DNA. Somatic events, including SNV (single nucleotide variant), InDel (insertion and deletion) of hot genes were analyzed. Consistency of tDNA and utDNA were identified and analyzed in the intersection set between the two chips, and tDNA profiling was used as the“golden standard”. Results: Among 48 patients, 24(50.0%) were MIBC, 21(43.8%) were NMIBC and 41 (81.5%) were male. With neoadjuvant therapy, 23(47.9%) are identified as responders (CR or PR), 7(14.6%) identified as non-responders (SD or PD), 18(37.5%) are still following up. Overall, 75.4% (214/284) tDNA mutations were found in utDNA, and 75.1% (214/285) utDNA mutations were found in tDNA. The top20 genes’ mutation landscape of utDNA highly resembled that of tDNA. The top20 genes could cover 97.9% (47/48) tissue samples and 89.6% (43/48) urine samples. Also, top20 mutated genes showed a strong correlation between tDNA and utDNA(r = 0.7371, p = 0.0002). TP53, KMT2D, ARIDA1A, CREBBP, ERBB2, ERCC2 and KDM6A are the most frequent abnormalities captured in tDNA and utDNA. Interestingly, we also found that the consistency of top20 genes in responders (n = 23, r = 0.7015, p = 0.0006) are higher than non-responders (n = 7, r = 0.4118, p = 0.1853). As a consequence, 70.1% (157/224), 61.8% (21/34) tDNA mutations were found in utDNA, and 72.0% (157/218), 25.0% (21/84) utDNA mutations were found in tDNA in responders and in non-responders, respectively. Conclusions: In brief, utDNA was robustly consistent and highly associated with tDNA, with 61.8%̃75.4% tDNA variations detected in utDNA target sequecing by acornmed 808 panel. The consistency would be higher if TERT promoter included in WES panel. While in non-responders, only 25.0% utDNA mutations were found in tDNA, indicating a spatial and temporal tumor heterogeneity. Our data provided initial prospective evidence on further developing urine as an optional sample for noninvasive detection and response evaluation of BC. The large prospective cohort study is still ongoing.
A systematic review of racial disparities in enrollment into clinical trials and clinical outcomes in men with metastatic prostate cancer.
Authors: Lawal Oluwadolapo D , Shui Irene M , Ghate Sameer 
Published: June 2022

e17028 Background: Men of African ancestry have a disproportionately higher incidence of prostate cancer than Caucasians. Yet, men of African ancestry have historically been underrepresented in clinical trials for metastatic prostate cancer (MPC). Further, differences in the magnitude of clinical benefit from treatment by race have been reported. The objective of this study was to assess the racial disparities in clinical trial enrollment of men with MPC and the magnitude of difference in clinical benefit between men of African ancestry and Caucasians with MPC. Methods: A systematic review of MEDLINE was conducted to identify studies published between January 2001 to May 2021. We included: (a) studies that enrolled adults with metastatic castration-resistant prostate cancer (mCRPC) or metastatic hormone sensitive prostate cancer; (b) clinical trials with complete race-stratified frequencies for enrolled subjects; or (c) clinical trials or observational studies that reported race-stratified subgroup analyses or adjusted effect estimates for efficacy/effectiveness outcomes. Outcome measures included overall survival (OS) and progression-free survival (PFS). Results: Of 2,140 retrieved articles, 39 studies involving 39,181 subjects met eligibility criteria. The majority of the studies (n = 35) enrolled mCRPC subjects. Of the 39 studies, 24 were clinical trials and 15 were observational studies. Twenty-one studies enrolled only patients in the US while 18 were multinational studies. Of the 15,761 subjects enrolled in clinical trials, 1750 (11.1%) were men of African ancestry and 12,321 (78.1%) Caucasian. The median (interquartile range) enrollment rate of men of African ancestry in clinical trials was 5.7% (2.3%, 10.1%). Of the 39 eligible studies, 15 reported race-stratified clinical outcomes. Three studies compared men of African ancestry vs Caucasians, 2 men of African ancestry vs non-African ancestry, 3 Caucasian vs others or vice-versa. The remaining 7 studies reported separate estimates on survival by race. All 5 studies comparing men of African ancestry versus other racial groups were conducted in mCRPC subjects. No difference in survival risks by race was observed in the 3 studies that compared men of African ancestry vs Caucasian (HR: 1.09 [0.77, 1.53], 0.68 [0.36, 1.29] and 1.05 [0.97, 1.14]). HRs of 0.90 [0.52, 1.57] and 0.76 [0.61, 0.95] were reported in the 2 studies comparing OS in men of African ancestry vs non-African ancestry. No studies reported a significant increased risk of death by race. Conclusions: Overall, men of African ancestry were largely underrepresented in MPC clinical trials. Concerted efforts are needed to increase the enrollment of this at-risk population in future clinical trial programs. Additional studies are needed to confirm the absence of differences in survival by race in real-life settings.
Impact of PSMA-targeted PET/CT in the clinical management of men with advanced prostate cancer.
Authors: Tucker Matthew D , Chen Yu-Wei , Yasin Hesham Abdallah , Ancell Kristin Kathleen , Barocas Daniel Ari , Beckermann Katy , Chang Sam S. , Davis Nancy B. , Jessop Aaron , Kaiser Elizabeth , Kirschner Austin Noah , Kluwe Christien Alexandre , Luckenbaugh Amy , Moses Kelvin A. , Penson David F. , Sherer Philip , Smelser Woodson , Wallace Deborah , Schaffer Kerry , Rini Brian I. 
Published: June 2022

e17053 Background: 18F-DCFPyL (piflufolastat F 18) is a PSMA-targeted agent FDA-approved for PET imaging in men with prostate cancer. Given the recent availability for clinical use, we sought to evaluate the impact and potential changes in management after the incorporation of 18F-DCFPyL (PyL) PET/CT at an academic medical center. Methods: We reviewed the first 100 PyL PET/CT scans performed at the Vanderbilt-Ingram Cancer Center for men with prostate adenocarcinoma. Patient demographics, treatment history, and prior imaging results were recorded, along with PyL PET results, most recent PSA, and clinical management plans. Management changes were designated as change in systemic therapy, radiation, or surgery and were determined by two independent reviewers with a third reviewer for any discordant cases. Results: There were 100 men included with PyL PET scans dating from 9/1/21 to 12/31/21. The median age was 69 years, 76% of patients were white and 13% were black. The median Gleason sum at diagnosis was 7 (4+3), 55% of men had prior prostatectomy, and 38% had prior radiation to the prostate/pelvis. The median PSA prior to PyL PET scan was 1.86 (IQR 0.53-9.95 ng/mL), 32% of men had previous ADT exposure, and 15% were on ADT at the time of PyL PET scan. The clinical setting prior to PyL PET scan was initial staging 22%, biochemical recurrence 59%, m1HSPC 14%, m0CRPC 2%, and m1CRPC 3%. There were 16 patients who had a prior 18F-fluciclovine within six months of PyL PET; of these 69% (11/16) had additional disease on PyL PET not previously identified. Activity in lymph nodes was observed in 48%, bone 37%, visceral sites 3%, prostate/prostate bed 46%, and 15% had no PSMA-avid disease. Clinical staging was altered after the PyL PET scan in 55% of patients, with the most common change being from BCR to m1HSPC (40/55). Clinical management was altered in 59% of cases: systemic therapy 38%, radiation planning 46%, and surgical planning 6% (Table). Conclusions: Clinical management was affected in 59% of cases after implementation of PyL PET in this retrospective, single center review. Given the rapid adoption of PSMA-targeted PET imaging agents, further studies are needed to evaluate the clinical impact of subsequent changes to management planning, as well as to develop multidisciplinary consensus statements and protocols to guide management.[Table: see text]
Exploring the accuracy of multiparametric MRI in prostate cancer staging: An institutional retrospective study.
Authors: Denisenko Andrew , Mico Vasil , McPartland Connor , Clark Cassra B , Shumaker Andrew , Gomella Patrick H. , Izes Joseph , Mann Mark Jonathan , Trabulsi Edouard John , Mark James Ryan , Lallas Costas D. , Gomella Leonard G. , Chandrasekar Thenappan 
Published: June 2022

e17056 Background: Multiparametric Magnetic Resonance Imaging (mpMRI) has been increasingly utilized in prostate cancer (PCa) diagnosis and staging. While there is Level 1 data supporting MRI utility in identifying clinically significant PCa and guiding PCa diagnosis, there is little data on its ability to predict surgical outcomes and its utility as a staging study. We aimed to evaluate the accuracy of mpMRI in predicting common surgical pathology outcomes in patients who underwent radical prostatectomy (RP). Methods: Men who underwent either open radical prostatectomy (ORP) or robotic assisted laparoscopic prostatectomy (RALP) for prostate adenocarcinoma from January-December 2021 at a single tertiary level care academic medical center were identified. Chart review for relevant patient demographics, mpMRI related variables and final surgical pathology was completed. In patients who had pre-operative mpMRI, we evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of mpMRI in predicting relevant surgical outcomes, including presence of pT2N0 organ confined disease (OCD), extracapsular extension (ECE), seminal vesicle invasion (SVI), lymph node involvement (LNI), and bladder neck invasion (BNI). Results: 168 eligible patients were identified in a 12-month period. The mean age was 63.5±6.24 years and mean Prostate Specific Antigen (PSA) was 11.4±23.7, with 166 (98.8%) patients undergoing RALP and 115 (68.5%) having pre-operative mpMRI. Median GGG was 2 in both MRI and CT subsets (p = 0.580), and patients who had pre-op MRI were more likely to have higher PSA (12.7 ±28.1 vs 8.38± 6.32, p = 0.073) and clinically node positive disease (p < 0.001) than those with CT. However, there was no significant difference in final surgical pathology or positive surgical margin rates between these two groups. On subset analysis of the MRI subset, Table summarizes the sensitivity, specificity, PPV, and NPV of pre-op MRI to predict OCD, ECE, SVI, LNI, and BNI. While specificity of pre-op MRI was adequate for all outcomes (89.1-100%), sensitivity (2.9-49.2%), PPV (40-100%), and NPV (56.3-94.3%) were poor. Conclusions: At present, pre-op MRI of the prostate does not appear to be accurate in its ability to predict important pathologic outcomes at the time of radical prostatectomy and should be used cautiously as a local staging tool. More work is needed before MRI can be used as a reliable staging tool for PCa.[Table: see text]