850 results on '"Robert G. Uzzo"'
Search Results
2. Human Gut Mycobiome and Fungal Community Interaction: The Unknown Musketeer in the Chemotherapy Response Status in Bladder Cancer
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Laura Bukavina, Megan Prunty, Ilaha Isali, Adam Calaway, Rashida Ginwala, Mohit Sindhani, Mahmoud Ghannoum, Kirtishri Mishra, Alexander Kutikov, Robert G. Uzzo, Lee E. Ponsky, and Philip H. Abbosh
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Mycobiome ,Bladder cancer ,Urothelial cancer ,Microbiome ,Diseases of the genitourinary system. Urology ,RC870-923 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Until recently, the properties of microbiome and mycobiome in humans and its relevance to disease have largely been unexplored. While the interest of microbiome and malignancy over the past few years have burgeoned with advent of new technologies, no research describing the composition of mycobiome in bladder cancer has been done. Deciphering of the metagenome and its aggregate genetic information can be used to understand the functional properties and relationships between the bacteria, fungi, and cancer. Objective: The aim of this project is to characterize the compositional range of the normal versus bladder cancer mycobiome of the gut. Design, setting, and participants: An internal transcribed spacer (ITS) survey of 52 fecal samples was performed to evaluate the gut mycobiome differences between noncancer controls and bladder cancer patients. Outcome measurements and statistical analysis: Our study evaluated the differences in mycobiome among patients with bladder cancer, versus matched controls. Our secondary analysis evaluated compositional differences in the gut as a function of response status with neoadjuvant chemotherapy. Data demultiplexing and classification were performed using the QIIME v.1.1.1.1 platform. The Ion Torrent–generated fungal ITS sequence data were processed using QIIME (v.1.9.1), and the reads were demultiplexed, quality filtered, and clustered into operation taxonomic units using default parameters. Alpha and beta diversity were computed and plotted in Phyloseq, principal coordinate analysis was performed on Bray-Curtis dissimilarity indices, and a one-way permutational multivariate analysis of variance was used to test for significant differences between cohorts. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to infer functional categories associated with taxonomic composition. Results and limitations: We found distinctive mycobiome differences between control group (n = 32) and bladder cancer (n = 29) gut flora, and identified an increasing abundance of Tremellales, Hypocreales, and Dothideales. Significant differences in alpha and beta diversity were present between the groups (control vs bladder; p = 0.002), noting distinct compositions within each cohort. A subgroup analysis by sex and neoadjuvant chemotherapy status did not show any further differences in mycobiome composition and diversity. Our results indicate that the gut mycobiome may modulate tumor response to preoperative chemotherapy in bladder cancer patients. We propose that patients with a “favorable” mycobiome composition (eg, high diversity, and low abundance of Agaricomycetes and Saccharomycetes) may have enhanced systemic immune response to chemotherapy through antigen presentation. Conclusions: Our study is the first to characterize the enteric mycobiome in patients with bladder cancer and describe complex ecological network alterations, indicating complex bacteria-fungi interactions, particularly highlighted among patients with complete neoadjuvant chemotherapy response. Patient summary: Our study has demonstrated that the composition of stool mycobiome (fungal inhabitants of the gastrointestinal tract) in patients with bladder cancer is different from that in noncancer individuals. Furthermore, when evaluating how patients respond to chemotherapy given prior to their surgery, our study noted significant differences between patients who responded and those who did not.
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- 2022
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3. PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth
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Weijia Cai, Liya Su, Lili Liao, Zongzhi Z. Liu, Lauren Langbein, Essel Dulaimi, Joseph R. Testa, Robert G. Uzzo, Zhijiu Zhong, Wei Jiang, Qin Yan, Qing Zhang, and Haifeng Yang
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Science - Abstract
Acetylation of p53 is critical for its transcriptional activity and its tumour suppressive function. Here, the authors show that PBRM1 is a reader protein for p53′s C-terminal domain acetylation on lysine 382 through its bromodomain 4 and that mutations in this domain leads to compromised tumour suppressive function and renal tumour growth.
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- 2019
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4. Combination of serum histidine and plasma tryptophan as a potential biomarker to detect clear cell renal cell carcinoma
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Hyung-Ok Lee, Robert G. Uzzo, Debra Kister, and Warren D. Kruger
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Kidney cancer ,Biomarker ,Serum ,Plasma ,Amino acids ,Medicine - Abstract
Abstract Background In previous work, we showed that serum-free amino acid (SFAA) profiles were different between kidney cancer patients and age and sex matched controls. The goals of the current study are to: (1) confirm our initial observation on an independent sample set; (2) examine if there were similar differences in plasma-free amino acids (PFAA); and (3) determine if removal of tumors changed SFAA and PFAA profiles. Methods SFAA and PFAA profiles were measured in 484 samples taken from 124 healthy controls and 56 clear cell renal cell carcinoma (ccRCC) patients both before and after resection of renal tumors. Results SFAA and PFAA profiles taken from identical blood samples were remarkably different, with the mean individual amino acid concentrations being 40% less in plasma compared to serum. Both SFAA and PFAA profiles differed significantly between ccRCC patients and controls, but the individual amino acids that differed the most, and the direction of the changes, were quite different between the two blood components. Removal of the tumor had almost no effect on either the SFAA or PFAA profiles. A logistic regression model using serum histidine and plasma tryptophan correctly classified 85.5% of control and 84.7% of case samples. Conclusions Our findings show that that tumor mass is not directly linked to alterations in blood amino acid levels, and that a combination of serum histidine and plasma tryptophan may be useful as a biomarker to detect ccRCC.
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- 2017
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5. Biology is Destiny: A Case of Adrenocortical Carcinoma Diagnosed and Resected at Inception in a Patient Under Close Surveillance for Lung Cancer
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Benjamin Miron, Benjamin T. Ristau, Jeffrey J. Tomaszewski, Josh Jones, Bart Milestone, Yu-Ning Wong, Robert G. Uzzo, Donna Edmondson, Walter Scott, and Alexander Kutikov
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Adrenocortical carcinoma ,Adrenal cancer ,Incidental adrenal mass ,Incidentaloma ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Adrenocortical carcinoma (ACC) is a rare malignancy that is generally associated with a poor prognosis whose existence dictates the management of incidental renal masses. We report a case of ACC diagnosed and treated at its apparent inception in a patient undergoing close surveillance imaging of a prior malignancy. Despite timely detection and resection of a localized ACC this patient rapidly progressed to systemic disease. This case highlights the rapid growth kinetics of ACC and puts into perspective the challenges associated with the established treatment paradigm for patients diagnosed with an adrenal mass.
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- 2016
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6. The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma
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Reza Mehrazin, Essel Dulaimi, Robert G. Uzzo, Karthik Devarjan, Jianming Pei, Marc C. Smaldone, Alexander Kutikov, Joseph R. Testa, and Tahseen Al-Saleem
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Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Background: The proto-oncogene c-MYC , located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. Results: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method ( n = 11) or CMA ( n = 7). Gain of 8q was associated with higher T stage ( p < 0.001), grade ( p < 0.001), nodal involvement ( p = 0.005), and distant metastasis ( p < 0.001). No association between gain of 8q and age ( p = 0.23), sex ( p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83–18.34, p < 0.001] and 3.31-fold (95% CI, 1.56–7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto-oncogene c-MYC , which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.
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- 2018
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7. Heterogeneity and renal mass biopsy: a review of its role and reliability
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Jeffrey J. Tomaszewski, Robert G. Uzzo, and Marc C. Smaldone
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Renal cell carcinoma (RCC) ,renal mass biopsy (RMB) ,tumor heterogeneity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Increased abdominal imaging has led to an increase in the detection of the incidental small renal mass (SRM). With increasing recognition that the malignant potential of SRMs is heterogeneous, ranging from benign (15%-20%) to aggressive (20%), enthusiasm for more conservative management strategies in the elderly and infirmed, such as active surveillance (AS), have grown considerably. As the management of the SRM evolves to incorporate ablative techniques and AS for low risk disease, the role of renal mass biopsy (RMB) to help guide individualized therapy is evolving. Historically, the role of RMB was limited to the evaluation of suspected metastatic disease, renal abscess, or lymphoma. However, in the contemporary era, the role of biopsy has grown, most notably to identify patients who harbor benign lesions and for whom treatment, particularly the elderly or frail, may be avoided. When performing a RMB to guide initial clinical decision making for small, localized tumors, the most relevant questions are often relegated to proof of malignancy and documentation (if possible) of grade. However, significant intratumoral heterogeneity has been identified in clear cell renal cell carcinoma (ccRCC) that may lead to an underestimation of the genetic complexity of a tumor when single-biopsy procedures are used. Heterogeneous genomic landscapes and branched parallel evolution of ccRCCs with spatially separated subclones creates an illusion of clonal dominance when assessed by single biopsies and raises important questions regarding how tumors can be optimally sampled and whether future evolutionary tumor branches might be predictable and ultimately targetable. This work raises profound questions concerning the genetic landscape of cancer and how tumor heterogeneity may affect, and possibly confound, targeted diagnostic and therapeutic interventions. In this review, we discuss the current role of RMB, the implications of tumor heterogeneity on diagnostic accuracy, and highlight promising future directions.
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- 2014
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8. Long-Term Results of a Phase 3 Randomized Prospective Trial of Erectile Tissue-Sparing Intensity-Modulated Radiation Therapy for Men With Clinically Localized Prostate Cancer
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Eddie Zhang, Karen J. Ruth, Mark K. Buyyounouski, Robert A. Price, Robert G. Uzzo, Mark L. Sobczak, Alan Pollack, J. Karen Wong, David Y.T. Chen, Mark A. Hallman, Richard E. Greenberg, Deborah Watkins-Bruner, Tahseen Al-Saleem, and Eric M. Horwitz
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Cancer Research ,Radiation ,Oncology ,Radiology, Nuclear Medicine and imaging - Published
- 2023
9. Pathological and Clinical Outcomes in a Large Surveillance and Intervention Cohort of Radiographically Cystic Renal Masses
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Randall A. Lee, Robert G. Uzzo, Jordan Anaokar, Ashanth Thomas, Shuanzeng Wei, Benjamin T. Ristau, Andrew McIntosh, Matthew Lee, David Y. T. Chen, Richard E. Greenberg, Rosalia Viterbo, Marc C. Smaldone, Andres Correa, Jared Schober, Kevin Ginsburg, Laura Bukavina, Diana Magee, Nicole Uzzo, Phyllis Parkansky, Karen Ruth, and Alexander Kutikov
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Urology - Published
- 2023
10. Oncologic Outcomes of cT1 and cT2 Micropapillary Variant Compared with cT1 and cT2 Conventional Urothelial Carcinoma Treated with Radical Cystectomy
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Kevin B. Ginsburg, Jared P. Schober, Laura Bukavina, Nicole Murray, Akhil A. Chandra, David Y. T. Chen, Richard E. Greenberg, Rosalia Viterbo, Robert G. Uzzo, Marc C. Smaldone, Alexander Kutikov, and Andres F. Correa
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Urology - Published
- 2022
11. Impact of Variant Histology on Oncological Outcomes in Upper Tract Urothelial Carcinoma: Results from the ROBUUST Collaborative Group
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Antoin Douglawi, Alireza Ghoreifi, Umberto Carbonara, Wesley Yip, Robert G. Uzzo, Vitaly Margulis, Matteo Ferro, Ottavio De Cobelli, Zhenjie Wu, Giuseppe Simone, Riccardo Mastroianni, Koon H. Rha, Daniel D. Eun, Adam C. Reese, James R. Porter, Ithaar Derweesh, Reza Mehrazin, Giuseppe Rosiello, Riccardo Tellini, Marcus Jamil, Alexander Kenigsberg, Jason M. Farrow, William P. Schrock, Giovanni Cacciamani, Abhishek Srivastava, Amit S. Bhattu, Alexandre Mottrie, Mark L. Gonzalgo, Chandru P. Sundaram, Firas Abdollah, Andrea Minervini, Riccardo Autorino, and Hooman Djaladat
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Oncology ,Urology - Published
- 2023
12. Computer-Generated R.E.N.A.L. Nephrometry Scores Yield Comparable Predictive Results to Those of Human-Expert Scores in Predicting Oncologic and Perioperative Outcomes
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Nicholas Heller, Resha Tejpaul, Fabian Isensee, Tarik Benidir, Martin Hofmann, P. Blake, Zachary Rengal, Keenan Moore, Niranjan Sathianathen, Arveen Adith Kalapara, J. Rosenberg, Sarah Chan, Edward Walczak, Alexander Kutikov, Robert G. Uzzo, Diego Aguilar Palacios, Erick M. Remer, Steven C. Campbell, Nikolaos Papanikolopoulos, and Christopher J. Weight
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Necrosis ,Artificial Intelligence ,Computers ,Urology ,Humans ,Female ,Middle Aged ,Nephrectomy ,Article ,Kidney Neoplasms ,Retrospective Studies - Abstract
We sought to automate R.E.N.A.L. (for radius, exophytic/endophytic, nearness of tumor to collecting system, anterior/posterior, location relative to polar line) nephrometry scoring of preoperative computerized tomography scans and create an artificial intelligence-generated score (AI-score). Subsequently, we aimed to evaluate its ability to predict meaningful oncologic and perioperative outcomes as compared to expert human-generated nephrometry scores (H-scores).A total of 300 patients with preoperative computerized tomography were identified from a cohort of 544 consecutive patients undergoing surgical extirpation for suspected renal cancer at a single institution. A deep neural network approach was used to automatically segment kidneys and tumors, and geometric algorithms were developed to estimate components of R.E.N.A.L. nephrometry score. Tumors were independently scored by medical personnel blinded to AI-scores. AI- and H-score agreement was assessed using Lin's concordance correlation and their predictive abilities for both oncologic and perioperative outcomes were assessed using areas under the curve.Median age was 60 years (IQE 51-68), and 40% were female. Median tumor size was 4.2 cm and 91.3% had malignant tumors, including 27%, 37% and 24% with high stage, grade and necrosis, respectively. There was significant agreement between H-scores and AI-scores (Lin's ⍴=0.59). Both AI- and H-scores similarly predicted meaningful oncologic outcomes (p0.001) including presence of malignancy, necrosis, and high-grade and -stage disease (p0.003). They also predicted surgical approach (p0.004) and specific perioperative outcomes (p0.05).Fully automated AI-generated R.E.N.A.L. scores are comparable to human-generated R.E.N.A.L. scores and predict a wide variety of meaningful patient-centered outcomes. This unambiguous artificial intelligence-based scoring is intended to facilitate wider adoption of the R.E.N.A.L. score.
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- 2023
13. Perspectives on the Role of Biopsy for Management of T1 Renal Masses: Survey Results From Two Regional Quality Improvement Collaboratives
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Zachary J. Prebay, Amit Patel, Anna Johnson, Tae Kim, Claudette Fonshell, Jay D. Raman, Serge Ginzburg, Robert G. Uzzo, Craig G. Rogers, and Brian R. Lane
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Biopsy ,Urology ,Humans ,Kidney ,Nephrectomy ,Quality Improvement ,Kidney Neoplasms - Abstract
To understand perspectives on renal mass biopsy, a survey was distributed to urologists in the Michigan Urological Surgery Improvement Collaborative and Pennsylvania Urologic Regional Collaborative. Renal mass biopsy (RMB) may reduce treatment of benign renal neoplasms; however, utilization varies widely.Michigan Urological Surgery Improvement Collaborative and Pennsylvania Urologic Regional Collaborative are two quality improvement collaboratives that include a "real-world" collection of urologists from academic- and community-based settings. A 12-item survey assessing current RMB utilization, patient- and tumor-specific factors, adverse events, impact on management, and simulated patient scenarios was distributed. Responses are reported using descriptive statistics.Many responders (n = 54) indicated using RMB in less than 25% of cT1a (59%) and cT1b (85%) tumors. The most important patient-specific factors on the decision to recommend RMB were possible metastasis to the kidney (94%), patient comorbidity as a risk factor for active treatment (89%), and patient age (81%). The most important tumor-specific factors were the presence of bilateral tumors (81%), tumor size (70%) and perceived potential of performing nephron-sparing surgery (67%). Ten responders (19%) noted barriers to RMB in their practice, 23 (43%) recalled experiences with complications or poor outcomes, and 43 (80%) reported experiences where the results of RMB altered management. When presented with simulated patients, few urologists (9%-20%) recommended RMB in younger patients with any sized mass. Recommendations varied based on patient age, comorbidity, and tumor size.Understanding perspectives on RMB usage is essential prior to implementing quality improvement efforts. Most urologists participating in two statewide collaboratives infrequently recommend RMB. Optimizing RMB utilization may help reduce unnecessary treatments.
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- 2022
14. The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis
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Pooja Ghatalia, Elizabeth A. Handorf, Daniel M. Geynisman, Mengying Deng, Matthew R. Zibelman, Philip Abbosh, Fern Anari, Richard E. Greenberg, Rosalia Viterbo, David Chen, Marc C. Smaldone, Alexander Kutikov, and Robert G. Uzzo
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Urology ,Humans ,Cytoreduction Surgical Procedures ,Carcinoma, Renal Cell ,Nephrectomy ,Kidney Neoplasms ,Article ,Retrospective Studies - Abstract
The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was challenged by the results of the CARMENA trial. Here we evaluate the role of CN in mRCC patients, including those receiving modern therapies.We included patients with synchronous mRCC between 2011-2020 from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic therapy alone, CN followed by systemic therapy (up-front CN [uCN]) and systemic therapy followed by CN (deferred CN [dCN]). The primary outcome was median overall survival (mOS) in patients receiving systemic therapy alone vs uCN. Secondary outcome was overall survival in patients receiving uCN vs dCN. First-treatment, landmark and time-varying covariate analyses were conducted to overcome immortal time bias. Weighted Kaplan-Meier curves, log-rank tests and Cox proportional hazards regressions were used to assess the effect of therapy on survival.Of 1,910 patients with mRCC, 972 (57%) received systemic therapy, 605 (32%) received uCN, 142 (8%) dCN and 191 (10%) CN alone; 433 (23%) patients received immunotherapy-based therapy. The adjusted mOS was significantly improved in first-treatment, landmark and time-varying covariate analysis (mOS 26.6 vs 14.6 months, 36.3 vs 21.1 months and 26.1 vs 12.2 months, respectively) in patients undergoing CN. Among patients receiving CN and systemic therapy, the timing of systemic therapy relative to CN was not significantly related to overall survival (HR=1.0, 95% CI 0.76-1.32, p=0.99).Our findings support an oncologic role for CN in select mRCC patients. In patients receiving both CN and systemic therapy, the survival benefit compared to systemic alone was similar for up-front and deferred CN.
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- 2022
15. Supplementary Figure 1 from PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection
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Kerry S. Campbell, Tahseen Al-Saleem, Essel Dulaimi, Samuel Litwin, Robert G. Uzzo, Gary R. Hudes, Elizabeth R. Plimack, Mowafaq Jillab, and Alexander W. MacFarlane
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PDF file - 4006K, Myeloid cell gating strategy. The myeloid cell gating strategy used in these experiments is shown with representative data from a healthy control donor. A. Forward scatter area and height were used to exclude aggregates and clusters of cells. B. Dead cells were excluded by propidium iodode staining. C. CD45+ Leukocytes were divided into lymphocyte and myeloid gates based on side scatter. D. T cells and NK cells were excluded from the myeloid cell analysis by CD3 and CD56 expression. E. Cells that express neither CD14 nor CD16 were excluded from the myeloid analysis (mostly B cells at this point in the gating). F. Myeloid cells were sub-gated into Classical Monocytes (CD14bright CD16-), Intermediate Monocytes (CD14bright CD16dim), Non-classical Monocytes (CD14dim CD16dim), CD14bright CD16bright myeloid cells, and Neutrophils (CD14dim CD16bright). Note that most of the neutrophils were removed along with the erythrocytes during gradient centrifugation on Lympoprep).
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- 2023
16. Supplementary Figure 3 from PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection
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Kerry S. Campbell, Tahseen Al-Saleem, Essel Dulaimi, Samuel Litwin, Robert G. Uzzo, Gary R. Hudes, Elizabeth R. Plimack, Mowafaq Jillab, and Alexander W. MacFarlane
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PDF file - 471K, Correlation between PD-1 expression and CD69 expression on T cells in pre-operative blood samples. Correlation of PD-1 expression on T cells (x-axis) to CD69 expression T cells (y-axis) is shown. A vertical line marks the median PD-1 expression on and the median CD69 expression is marked by a horizontal line. Statistical significance was calculated by a Spearman correlation. A least squares linear fit is shown as a thick black line.
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- 2023
17. Supplementary Figure 2 from PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection
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Kerry S. Campbell, Tahseen Al-Saleem, Essel Dulaimi, Samuel Litwin, Robert G. Uzzo, Gary R. Hudes, Elizabeth R. Plimack, Mowafaq Jillab, and Alexander W. MacFarlane
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PDF file - 5296K, Lymphocyte gating strategy. A. Leukocytes were gated as described in Supplemental Figure 1. B. T Cells were identified as CD3+ lymphocytes and NK cells as (CD3- CD56+) lymphocytes. C. T cells were sub-divided by CD4 and CD8 expression. D. CD8+ T cells were divided into subsets of Naive (CD45RA+ CD62L+), Effector (CD45RA+ CD62L-), Central Memory (CD45RA- CD62L+), and Effector Memory (CD45RA- CD62L-). E. CD4+ T Cells were sub-divided as for CD8+ T cells. F. B cells were identified as CD19+ lymphocytes. G. NK Cells were further divided into CD56bright and CD56dim phenotypes. H. B Cells were sub-divided into Naive (CD20+ CD27-), Memory (CD20+ CD27+), and plasmacytoid (CD20- CD27+). Fully differentiated plasma cells fall outside these gates because they are CD45-.
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- 2023
18. Supplementary Figure 4 from PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection
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Kerry S. Campbell, Tahseen Al-Saleem, Essel Dulaimi, Samuel Litwin, Robert G. Uzzo, Gary R. Hudes, Elizabeth R. Plimack, Mowafaq Jillab, and Alexander W. MacFarlane
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PDF file - 3477K, Effect of surgery on cellular activation markers. Pre-surgical (time point zero) and post-surgical (at designated weeks after surgery) measurements on the same patients are connected by a line and the statistical significance is calculated by a paired Wilcoxon rank-sum test. Data points from stage 4 patients are marked with black filled diamonds and the data from the single stage 3 patient is shown in grey. Sub-panels are as follows: A) CD69 on T Cells (CD3+ CD45+ CD56-), B) Perforin in CD8+ T Cells, C) Granzyme B in CD8+ T Cells, D) Perforin in CD4+ T Cells, E) Granzyme B in CD56dim NK Cells, F) Perforin in CD56dim NK Cells.
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- 2023
19. Supplementary Tables 1 - 3 from PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection
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Kerry S. Campbell, Tahseen Al-Saleem, Essel Dulaimi, Samuel Litwin, Robert G. Uzzo, Gary R. Hudes, Elizabeth R. Plimack, Mowafaq Jillab, and Alexander W. MacFarlane
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PDF file - 79K, Supplemental Table S1. Donor Characteristics. Supplemental Table S2. Antibody staining panel. Supplemental Table S3. Specific immune parameters analyzed.
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- 2023
20. Data from PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection
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Kerry S. Campbell, Tahseen Al-Saleem, Essel Dulaimi, Samuel Litwin, Robert G. Uzzo, Gary R. Hudes, Elizabeth R. Plimack, Mowafaq Jillab, and Alexander W. MacFarlane
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Programmed death-1 (PD-1) receptor is an inhibitory receptor on hematopoietic cells that can negatively regulate immune responses, particularly responses to tumors, which often upregulate PD-1 ligands. PD-1/PD-1 ligand blocking antibodies can reverse the inhibition and show significant therapeutic promise in treating renal cell carcinoma (RCC), lung cancer, and melanoma. While PD-1 expression on tumor-infiltrating lymphocytes has been associated with poor outcome in RCC, we sought to define immune cell biomarkers, including PD-1, on peripheral blood mononuclear cells (PBMC) that could predict disease progression of RCC patients before and after nephrectomy. We analyzed expression of numerous immune cell markers on fresh PBMCs from 90 RCC patients preoperatively and 25 age-matched healthy controls by 10-color flow cytometry. Postoperative blood samples were also analyzed from 23 members of the RCC patient cohort. The most striking phenotypic immune biomarker in RCC patients was a significant increase in PD-1 expression on certain PBMCs in a subset of patients. Increased PD-1 expression on CD14bright myelomonocytic cells, effector T cells, and natural killer (NK) cells correlated to disease stage, and expression was significantly reduced on all cell types soon after surgical resection of the primary tumor. The results indicate that PD-1 expression on fresh peripheral blood leukocytes may provide a useful indicator of RCC disease progression. Furthermore, measuring PD-1 levels in peripheral blood may assist in identifying patients likely to respond to PD-1 blocking antibodies, and these therapies may be most effective before and immediately after surgical resection of the primary tumor, when PD-1 expression is most prominent. Cancer Immunol Res; 2(4); 320–31. ©2013 AACR.
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- 2023
21. Table S1 from Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma
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Christopher G. Wood, Charles A. Nicolette, Irina Y. Tcherepanova, Joe Horvatinovich, Marcus S. Norris, Ana Plachco, Alicia Gamble, Mark DeBenedette, Gennady Bratslavsky, William Lowrance, Daniel Vaena, Anil Kapoor, Viraj Master, David Y.T. Chen, Scott S. Tykodi, Robert G. Uzzo, Nizar M. Tannir, and Robert A. Figlin
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subsequent standard of care treaments
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- 2023
22. Figure 1S from Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma
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Christopher G. Wood, Charles A. Nicolette, Irina Y. Tcherepanova, Joe Horvatinovich, Marcus S. Norris, Ana Plachco, Alicia Gamble, Mark DeBenedette, Gennady Bratslavsky, William Lowrance, Daniel Vaena, Anil Kapoor, Viraj Master, David Y.T. Chen, Scott S. Tykodi, Robert G. Uzzo, Nizar M. Tannir, and Robert A. Figlin
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Consort diagram
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- 2023
23. Supplementary figure 1 legend from Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma
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Christopher G. Wood, Charles A. Nicolette, Irina Y. Tcherepanova, Joe Horvatinovich, Marcus S. Norris, Ana Plachco, Alicia Gamble, Mark DeBenedette, Gennady Bratslavsky, William Lowrance, Daniel Vaena, Anil Kapoor, Viraj Master, David Y.T. Chen, Scott S. Tykodi, Robert G. Uzzo, Nizar M. Tannir, and Robert A. Figlin
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supplementary figure 1 legend
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- 2023
24. Supplementary Tables 1-2 from Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer among High-Risk Men Enrolled in Prostate Cancer Early Detection
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Veda N. Giri, Timothy R. Rebbeck, Rosalia Viterbo, David Y.T. Chen, Robert G. Uzzo, Laura Gross, Eric Ross, Fang Zhu, and Lucinda Hughes
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PDF file - 95K
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- 2023
25. Data from Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results from ASSURE, ECOG 2805
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Robert S. DiPaola, George Wilding, Janice J. Dutcher, Michael B. Atkins, Christopher G. Wood, Lori Wood, Michael Jewett, Christopher J. Kane, Robert G. Uzzo, Keith T. Flaherty, Bonnie Ky, Judith Manola, and Naomi B. Haas
- Abstract
Purpose: Sunitinib and sorafenib are used widely in the treatment of renal cell carcinoma (RCC). These agents are associated with a significant incidence of cardiovascular (CV) dysfunction and left ventricular ejection fraction (LVEF) declines, observed largely in the metastatic setting. However, in the adjuvant population, the CV effects of these agents remain unknown. We prospectively defined the incidence of cardiotoxicity among resected, high-risk RCC patients treated with these agents.Experimental Design: Sunitinib, sorafenib, or placebo was administered for up to 12 months in patients with high-risk, resected RCC. LVEF was measured by multigated acquisition (MUGA) scans at standard intervals. Additional CV adverse events were reported according to NCI Common Terminology Criteria for Adverse Events (CTCAE).Results: Among 1,943 patients randomized, 1,599 had at least 1 post-baseline MUGA. Within 6 months, 21 patients (1.3%) experienced a cardiac event, defined as an LVEF decline from baseline that was >15% and below the institutional lower limit of normal. Nine of 513 patients (1.8%) were on sunitinib, 7 of 508 (1.4%) on sorafenib, and 5 of 578 (0.9%) on placebo (P = 0.28 and 0.56 comparing sunitinib and sorafenib to placebo, respectively). With dose interruption or adjustment, 16 of the 21 recovered their LVEF to >50%. The incidence of symptomatic heart failure, arrhythmia, or myocardial ischemia did not differ among groups.Conclusions: In the adjuvant setting, we prospectively define low incidence of cardiotoxicity with sunitinib and sorafenib. These findings may be related to close CV monitoring, or potentially to fewer CV comorbidities in our nonmetastatic population. Clin Cancer Res; 21(18); 4048–54. ©2015 AACR.
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- 2023
26. Data from Angiogenic Factor and Cytokine Analysis among Patients Treated with Adjuvant VEGFR TKIs in Resected Renal Cell Carcinoma
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Rupal S. Bhatt, Robert S. DiPaola, Janice P. Dutcher, Robert G. Uzzo, Keith Flaherty, Naomi B. Haas, Michael B. Atkins, David F. McDermott, Daniel Tamasauskas, Andrea J. Bullock, Judith Manola, Maneka Puligandla, and Wenxin Xu
- Abstract
Purpose:The use of VEGFR TKIs for the adjuvant treatment of renal cell carcinoma (RCC) remains controversial. We investigated the effects of adjuvant VEGFR TKIs on circulating cytokines in the ECOG-ACRIN 2805 (ASSURE) trial.Experimental Design:Patients with resected high-risk RCC were randomized to sunitinib, sorafenib, or placebo. Plasma from 413 patients was analyzed from post-nephrectomy baseline, 4 weeks, and 6 weeks after treatment initiation. Mixed effects and Cox proportional hazards models were used to test for changes in circulating cytokines and associations between disease-free survival (DFS) and cytokine levels.Results:VEGF and PlGF increased after 4 weeks on sunitinib or sorafenib (P < 0.0001 for both) and returned to baseline at 6 weeks on sunitinib (corresponding to the break in the sunitinib schedule) but not sorafenib (which was administered continuously). sFLT-1 decreased after 4 weeks on sunitinib and 6 weeks on sorafenib (P < 0.0001). sVEGFR-2 decreased after both 4 and 6 weeks of treatment on sunitinib or sorafenib (P < 0.0001). Patients receiving placebo had no significant changes in cytokine levels. CXCL10 was elevated at 4 and 6 weeks on sunitinib and sorafenib but not on placebo. Higher baseline CXCL10 was associated with worse DFS (HR 1.41 per log increase in CXCL10, Bonferroni-adjusted P = 0.003). This remained significant after adjustment for T-stage, Fuhrman grade, and ECOG performance status.Conclusions:Among patients treated with adjuvant VEGFR TKIs for RCC, drug–host interactions mediate changes in circulating cytokines. Elevated baseline CXCL10 was associated with worse DFS. Studies to understand functional consequences of these changes are under way.
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- 2023
27. Supplementary Figure from Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results from ASSURE, ECOG 2805
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Robert S. DiPaola, George Wilding, Janice J. Dutcher, Michael B. Atkins, Christopher G. Wood, Lori Wood, Michael Jewett, Christopher J. Kane, Robert G. Uzzo, Keith T. Flaherty, Bonnie Ky, Judith Manola, and Naomi B. Haas
- Abstract
Supplementary Figure: Consort diagram of patients participating in cardiac sub study
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- 2023
28. Supplemental Figure S1 from Plasma KIM-1 Is Associated with Recurrence Risk after Nephrectomy for Localized Renal Cell Carcinoma: A Trial of the ECOG-ACRIN Research Group (E2805)
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Rupal S. Bhatt, Venkata Sabbisetti, Robert S. DiPaola, Janice P. Dutcher, Robert G. Uzzo, Keith T. Flaherty, Naomi B. Haas, Brian Halbert, Mäneka Puligandla, and Wenxin Xu
- Abstract
Distribution of baseline KIM-1 values
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- 2023
29. Data from Plasma KIM-1 Is Associated with Recurrence Risk after Nephrectomy for Localized Renal Cell Carcinoma: A Trial of the ECOG-ACRIN Research Group (E2805)
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Rupal S. Bhatt, Venkata Sabbisetti, Robert S. DiPaola, Janice P. Dutcher, Robert G. Uzzo, Keith T. Flaherty, Naomi B. Haas, Brian Halbert, Mäneka Puligandla, and Wenxin Xu
- Abstract
Purpose:No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy.Experimental Design:The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4–12 weeks after nephrectomy. Lognormal accelerated failure time models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS).Results:Plasma from 418 patients was analyzed. Higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T stage, N stage, and tumor histology [survival time ratio 0.56 for 75th vs. 25th percentile of KIM-1; 95% confidence interval (CI), 0.42–0.73; P < 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (Pinteraction = 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43, P = 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40, P = 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse OS after multivariable adjustment (survival time ratio 0.71 for 75th vs. 25th percentile of KIM-1; 95% CI, 0.56–0.91; P < 0.001).Conclusions:Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.
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- 2023
30. Data from Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer among High-Risk Men Enrolled in Prostate Cancer Early Detection
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Veda N. Giri, Timothy R. Rebbeck, Rosalia Viterbo, David Y.T. Chen, Robert G. Uzzo, Laura Gross, Eric Ross, Fang Zhu, and Lucinda Hughes
- Abstract
Background: Men with familial prostate cancer and African American men are at risk for developing prostate cancer at younger ages. Genetic markers predicting early-onset prostate cancer may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset prostate cancer in a longitudinal cohort of high-risk men enrolled in prostate cancer early detection with significant African American participation.Methods: Eligibility criteria include ages 35 to 69 with a family history of prostate cancer or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped. Cox models were used to evaluate time to prostate cancer diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by genotype. Harrell's concordance index was used to evaluate predictive accuracy for prostate cancer by PSA and genetic markers.Results: Four hundred and sixty participants with complete data and ≥1 follow-up visit were included. Fifty-six percent were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to prostate cancer diagnosis (P = 0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When combined with PSA, rs6983561 improved predictive accuracy for prostate cancer compared with PSA alone among African American men (PSA = 0.57 vs. PSA + rs6983561 = 0.75, P = 0.03).Conclusions: Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing prostate cancer risk assessment. Further study is warranted to validate these findings.Impact: Genetic markers of early-onset prostate cancer have potential to refine and personalize prostate cancer early detection for high-risk men. Cancer Epidemiol Biomarkers Prev; 21(1); 53–60. ©2011 AACR.
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- 2023
31. Tables S1, S2, S3, S4, S5. Figures S1, S2. from Angiogenic Factor and Cytokine Analysis among Patients Treated with Adjuvant VEGFR TKIs in Resected Renal Cell Carcinoma
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Rupal S. Bhatt, Robert S. DiPaola, Janice P. Dutcher, Robert G. Uzzo, Keith Flaherty, Naomi B. Haas, Michael B. Atkins, David F. McDermott, Daniel Tamasauskas, Andrea J. Bullock, Judith Manola, Maneka Puligandla, and Wenxin Xu
- Abstract
Supplemental Table 1: Catalog numbers for MSD assays Supplemental Figure 1: Hazard ratio for CXCL10 and DFS by treatment arm Supplemental Figure 2: Assessment of log-linearity for relationship between IP-10 and recurrence risk Supplemental Table 2: Median changes in cytokines at weeks 4 and 6 Supplemental Table 3: Relationship between on-treatment cytokine levels and DFS Supplemental Table 4: Subset analysis for cytokine changes among patients who did not recur Supplemental Table 5: Evaluation for interaction effects between treatment arm and the association between baseline CXCL10 and DFS
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- 2023
32. Data from Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma
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Christopher G. Wood, Charles A. Nicolette, Irina Y. Tcherepanova, Joe Horvatinovich, Marcus S. Norris, Ana Plachco, Alicia Gamble, Mark DeBenedette, Gennady Bratslavsky, William Lowrance, Daniel Vaena, Anil Kapoor, Viraj Master, David Y.T. Chen, Scott S. Tykodi, Robert G. Uzzo, Nizar M. Tannir, and Robert A. Figlin
- Abstract
Purpose:Rocapuldencel-T is an autologous immunotherapy prepared from mature monocyte-derived dendritic cells (DC), coelectroporated with amplified tumor RNA plus CD40L RNA. This pivotal phase III trial was initiated to investigate the safety and efficacy of a combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with metastatic renal cell carcinoma (mRCC).Patients and Methods:Patients received either Rocapuldencel-T plus standard of care (SOC) or SOC treatment alone. The primary objective compared overall survival (OS) between groups. Secondary objectives included safety assessments, progression-free survival (PFS), and tumor responses based on RECIST 1.1 criteria. Exploratory analyses included immunologic assessments and correlates with OS.Results:Between 2013 and 2016, 462 patients were randomized 2:1, 307 to the combination group and 155 to the SOC group. Median OS in the combination group was 27.7 months [95% confidence interval (CI) 23.0–35.9] and 32.4 months (95% CI, 22.5–) in the SOC group HR of 1.10 (95% CI, 0.83–1.40). PFS was 6.0 months and 7.83 months for the combination and SOC groups, respectively [HR = 1.15 (95% CI, 0.92–1.44)]. The ORR was 42.7% (95% CI, 37.1–48.4) for the combination group and 39.4% (95% CI, 31.6–47.5) for the SOC group. Median follow up was 29 months (0.4–47.7 months). On the basis of the lack of clinical efficacy, the ADAPT trial was terminated on February 17, 2017. Immune responses were detected in 70% of patients treated with Rocapuldencel-T, and the magnitude of the immune response positively correlated with OS. In addition, we report the survival-predictive value of measuring IL-12 produced by the DC vaccine and the observation that high baseline numbers of T regulatory cells are associated with improved outcomes in DC-treated patients, but are associated with poor outcomes in patients receiving SOC treatment. No serious adverse events attributed to the study medication have been reported to date.Conclusions:Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immunotherapy, IL-12 produced by the DC vaccine and higher numbers of T regulatory cells present in the peripheral blood of patients with advanced RCC.
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- 2023
33. Supplementary Tables 1-5, Figures 1-3 from Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results from ASSURE, ECOG 2805
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Robert S. DiPaola, George Wilding, Janice J. Dutcher, Michael B. Atkins, Christopher G. Wood, Lori Wood, Michael Jewett, Christopher J. Kane, Robert G. Uzzo, Keith T. Flaherty, Bonnie Ky, Judith Manola, and Naomi B. Haas
- Abstract
Supplementary Tables 1-5, Figures 1-3. Supplemental Table 1: Events per person-year of follow-up Supplemental Table 2: Event rates among patients randomized to sorafenib or sunitinib who started at reduced vs. full dose Supplemental Table 3a. Event rates among patients who did or did not discontinue treatment due to adverse events, and among patients with ECOG PS 0 vs. 1 Supplemental Table 3b: Baseline LVEF and change in LVEF among patients who did or did not discontinue treatment due to adverse events Supplemental Table 4: Relationship among treatment duration, baseline LVEF by MUGA, and probability of an event by any definition Supplemental Table 5: Relationship among treatment duration, baseline LVEF by MUGA, and probability of an event by the definition "Per Protocol Including Other" Supplemental Figure 1: Relationship among baseline LVEF by MUGA, treatment duration, and event status, where event is defined by any of the criteria Supplemental Figure 2: Relationship among baseline LVEF by MUGA, treatment duration, and event status, where event is defined as a decline in LVEF of 16% or more to below the lower limit of normal, or a grade 3 or higher cardiac adverse event Supplemental Figure 3: Algorithm for management of study drug-induced hypertension
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- 2023
34. Appendix from Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma
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Christopher G. Wood, Charles A. Nicolette, Irina Y. Tcherepanova, Joe Horvatinovich, Marcus S. Norris, Ana Plachco, Alicia Gamble, Mark DeBenedette, Gennady Bratslavsky, William Lowrance, Daniel Vaena, Anil Kapoor, Viraj Master, David Y.T. Chen, Scott S. Tykodi, Robert G. Uzzo, Nizar M. Tannir, and Robert A. Figlin
- Abstract
ADAPT study group and participating centers
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- 2023
35. Supplemental Table S1 from Plasma KIM-1 Is Associated with Recurrence Risk after Nephrectomy for Localized Renal Cell Carcinoma: A Trial of the ECOG-ACRIN Research Group (E2805)
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Rupal S. Bhatt, Venkata Sabbisetti, Robert S. DiPaola, Janice P. Dutcher, Robert G. Uzzo, Keith T. Flaherty, Naomi B. Haas, Brian Halbert, Mäneka Puligandla, and Wenxin Xu
- Abstract
Sensitivity analysis AFT model for DFS with imputation of KIM-1 levels below lower limit of detection (9.1 pg/mL)
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- 2023
36. Supplementary Legend S1 from Identification of Novel Target Genes by an Epigenetic Reactivation Screen of Renal Cancer
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Paul Cairns, Robert G. Uzzo, Tahseen Al-Saleem, Amanda M. Hoffman, Essel Dulaimi, and Inmaculada Ibanez de Caceres
- Abstract
Supplementary Legend S1 from Identification of Novel Target Genes by an Epigenetic Reactivation Screen of Renal Cancer
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- 2023
37. Data from Identification of Novel Target Genes by an Epigenetic Reactivation Screen of Renal Cancer
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Paul Cairns, Robert G. Uzzo, Tahseen Al-Saleem, Amanda M. Hoffman, Essel Dulaimi, and Inmaculada Ibanez de Caceres
- Abstract
Aberrant promoter hypermethylation is a common mechanism for inactivation of tumor suppressor genes in cancer cells. To generate a global profile of genes silenced by hypermethylation in renal cell cancer (RCC), we did an expression microarray-based analysis of genes reactivated in the 786-0, ACHN, HRC51, and HRC59 RCC lines after treatment with the demethylating drug 5-aza-2 deoxycytidine and histone deacetylation inhibiting drug trichostatin A. Between 111 to 170 genes were found to have at least 3-fold up-regulation of expression after treatment in each cell line. To establish the specificity of the screen for identification of genes, epigenetically silenced in cancer cells, we validated a subset of 12 up-regulated genes. Three genes (IGFBP1, IGFBP3, and COL1A1) showed promoter methylation in tumor DNA but were unmethylated in normal cell DNA. One gene (GDF15) was methylated in normal cells but more densely methylated in tumor cells. One gene (PLAU) showed cancer cell–specific methylation that did not correlate well with expression status. The remaining seven genes had unmethylated promoters, although at least one of these genes (TGM2) may be regulated by RASSF1A, which was methylated in the RCC lines. Thus, we were able to show that up-regulation of at least 6 of the 12 genes examined was due to epigenetic reactivation. The IGFBP1, IGFBP3, and COL1A1 gene promoter regions were found to be frequently methylated in primary renal cell tumors, and further study will provide insight into the biology of the disease and facilitate translational studies in renal cancer. (Cancer Res 2006; 66(10): 5021-8)
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- 2023
38. Supplementary Figure S1 from Identification of Novel Target Genes by an Epigenetic Reactivation Screen of Renal Cancer
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Paul Cairns, Robert G. Uzzo, Tahseen Al-Saleem, Amanda M. Hoffman, Essel Dulaimi, and Inmaculada Ibanez de Caceres
- Abstract
Supplementary Figure S1 from Identification of Novel Target Genes by an Epigenetic Reactivation Screen of Renal Cancer
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- 2023
39. Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine
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Rebecca M. Shulman, David S. Weinberg, Eric A. Ross, Karen Ruth, Glenn F. Rall, Anthony J. Olszanski, James Helstrom, Michael J. Hall, Julia Judd, David Y.T. Chen, Robert G. Uzzo, Timothy P. Dougherty, Riley Williams, Daniel M. Geynisman, Carolyn Y. Fang, Richard I. Fisher, Marshall Strother, Erica Huelsmann, Sunil Adige, Peter D. Whooley, Kevin Zarrabi, Brinda Gupta, Pritish Iyer, Melissa McShane, Hilario Yankey, Charles T. Lee, Nina Burbure, Lauren E. Laderman, Julie Giurintano, Samuel Reiss, and Eric M. Horwitz
- Subjects
COVID-19 Vaccines ,Oncology ,SARS-CoV-2 ,Neoplasms ,COVID-19 ,Humans ,Prospective Studies ,RNA, Messenger ,BNT162 Vaccine ,Article - Abstract
Background: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. Patients and Methods: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. Results: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. Conclusions: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.
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- 2022
40. A Preoperative Nomogram to Predict Renal Function Insufficiency for Cisplatin-based Adjuvant Chemotherapy Following Minimally Invasive Radical Nephroureterectomy (ROBUUST Collaborative Group)
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James E Steward, Linhui Wang, Georgi Guruli, Daniel Eun, Mark L. Gonzalgo, Riccardo Tellini, Alessandro Veccia, Robert G. Uzzo, Amit S Bhattu, Ahmad Almujalhem, Alexander Mottrie, Qi Chen, Hooman Djaladat, Riccardo Autorino, Andrea Minervini, Alireza Ghoreifi, Ithaar Derweesh, Alyssa Danno, Giuseppe Simone, Antoin Douglawi, James R. Porter, Vitaly Margulis, Elio Mazzone, Zhenjie Wu, Ali Al-Qathani, Fady Ghali, Giovanni Cacciamani, Koon Ho Rha, Matteo Ferro, Reza Mehrazin, Aeen Asghar, Andrea Mari, Chandru P. Sundaram, Firas Abdollah, Jamil Marcus, and Abhishek Srivastava
- Subjects
medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Renal function ,Kidney ,Nephrectomy ,Nephroureterectomy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Retrospective Studies ,Chemotherapy ,Framingham Risk Score ,business.industry ,Hazard ratio ,Area under the curve ,Nomogram ,Nomograms ,Regimen ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Cisplatin ,business ,Body mass index - Abstract
Background Postoperative renal function impairment represents a main limitation for delivering adjuvant chemotherapy after radical nephroureterectomy (RNU). Objective To create a model predicting renal function decline after minimally invasive RNU. Design, setting, and participants A total of 490 patients with nonmetastatic UTUC who underwent minimally invasive RNU were identified from a collaborative database including 17 institutions worldwide (February 2006 to March 2020). Renal function insufficiency for cisplatin-based regimen was defined as estimated glomerular filtration rate (eGFR) 50 ml/min/1.73 m2 (n = 361) were geographically divided into a training set (n = 226) and an independent external validation set (n = 135) for further analysis. Outcome measurements and statistical analysis Using transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines, a nomogram to predict postoperative eGFR Results and limitations The model that incorporated age, body mass index, preoperative eGFR, and hydroureteronephrosis was developed with an area under the curve of 0.771, which was confirmed to be 0.773 in the external validation set. The calibration curve demonstrated good agreement. Besides, the model was converted into a risk score with a cutoff value of 0.583, and the difference between the low- and high-risk groups both in overall death risk (hazard ratio [HR]: 4.59, p Conclusions A nomogram incorporating immediately available clinical variables can accurately predict renal insufficiency for cisplatin-based adjuvant chemotherapy after minimally invasive RNU and may serve as a tool facilitating patient selection. Patient summary We have developed a model for the prediction of renal function loss after radical nephroureterectomy to facilitate patient selection for perioperative chemotherapy.
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- 2022
41. Impact of COVID-19 on Initial Management and Evaluation of Prostate Cancer
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Jay D. Raman, Serge Ginzburg, Andres F. Correa, Edouard J. Trabulsi, Adam C. Reese, Bruce L. Jacobs, John Danella, Laurence Belkoff, Kaynaat Syed, Jeffery Tomaszewski, Adrien N. Bernstein, Thomas J. Guzzo, Elizabeth Handorf, Ruchika Talwar, Marc C. Smaldone, Robert G. Uzzo, and Eric A. Singer
- Subjects
medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Prostatectomy ,Urology ,medicine.medical_treatment ,Cancer ,medicine.disease ,Prostate cancer ,Health care ,Pandemic ,medicine ,business ,Intensive care medicine - Abstract
Introduction:The COVID-19 pandemic starkly affected all aspects of health care, forcing many to divert resources towards emergent patient needs while decreasing emphasis on routine cancer c...
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- 2021
42. Examining the Effect of PARP-1 Inhibitors on Transcriptional Activity of Androgen Receptor in Prostate Cancer Cells
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Peter Makhov, Rushaniya Fazliyeva, Antonio Tufano, Robert G. Uzzo, and Vladimir M. Kolenko
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- 2022
43. Examining the Effect of PARP-1 Inhibitors on Transcriptional Activity of Androgen Receptor in Prostate Cancer Cells
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Peter, Makhov, Rushaniya, Fazliyeva, Antonio, Tufano, Robert G, Uzzo, and Vladimir M, Kolenko
- Abstract
Since the early 1940s, androgen ablation has been the cornerstone of treatment for prostate cancer (PC). Importantly, androgen receptor (AR) signaling is vital not only for the initiation of PC, which is initially androgen-dependent, but also for castration-resistant disease. Recent studies demonstrated clear promise of the poly(ADP-ribose) polymerase 1 (PARP-1) inhibitors for targeting prostate cancer cells harboring mutations in DNA damage-repair genes. In addition, it has been established that PARP-1 inhibition suppresses growth of AR-positive prostate cancer cells in cell and animal models. Thus, prostate cancer represents a particularly promising disease site for targeting PARP-1, given that both DNA repair and AR-mediated transcription depend on PARP-1 function. Here, we describe the development and use of cell-based assay to evaluate the impact of PARP-1 inhibitors on the AR signaling in prostate cancer cells.
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- 2022
44. Adjuvant therapy in patients with sarcomatoid renal cell carcinoma: post hoc analysis from Eastern Cooperative Oncology Group‐American College of Radiology Imaging Network (ECOG‐ACRIN) E2805
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Michael R. Pins, Robert S. DiPaola, Robert G. Uzzo, Janice P. Dutcher, Jose A. Karam, Naomi B. Haas, Surena F. Matin, Christopher G. Wood, Maneka Puligandla, Christopher J. Kane, Michael A.S. Jewett, Se Eun Kim, and Keith T. Flaherty
- Subjects
Sorafenib ,medicine.medical_specialty ,business.industry ,Sunitinib ,Urology ,Hazard ratio ,urologic and male genital diseases ,medicine.disease ,Placebo ,Gastroenterology ,female genital diseases and pregnancy complications ,Clinical trial ,Internal medicine ,Post-hoc analysis ,medicine ,Adjuvant therapy ,business ,Kidney cancer ,medicine.drug - Abstract
OBJECTIVES To study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805. PATIENTS AND METHODS The original trial (E2805) was a randomised, double-blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805. RESULTS A total of 171 patients (8.8%) had sarcomatoid features. Of these, 52 patients received sunitinib, 58 received sorafenib, and 61 received placebo. Most patients were pT3-4 (71.1%, 63.7%, and 70.5%, respectively); 17.3%, 19.0%, and 27.9% had pathologically positive lymph nodes; and 59.6%, 62.1%, and 62.3% of the patients were University of California Los Angeles (UCLA) Integrated Staging System (UISS) very-high risk. In 49% of patients with subsequent development of metastatic disease, recurrence occurred in the lung, followed by 30% in the lymph nodes, and 13% in the liver. There was a high local recurrence rate in the renal bed (16%, 29%, and 18%, respectively). The 5-year disease-free survival (DFS) rates were 33.6%, 36.0%, and 27.8%, for sunitinib, sorafenib and placebo, respectively (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.45-1.20 for sunitinib vs placebo, and HR 0.82, 95% CI 0.53-1.28 for sorafenib vs placebo). CONCLUSIONS Adjuvant therapy with sunitinib or sorafenib did not show an improvement in DFS or OS in patients with sRCC.
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- 2021
45. Preventing Prostate Biopsy Complications: to Augment or to Swab?
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Mark Mann, Kanata Syed, Jay D. Raman, Timothy M. Han, Robert G. Uzzo, Thomas J. Guzzo, John Danella, Lydia Glick, Sage Vincent, Eric A. Singer, Jeffrey J. Tomaszweski, Marc Smaldone, Bruce L. Jacobs, Adam C. Reese, Edouard J. Trabulsi, Leonard G. Gomella, Serge Ginzburg, Thomas Lanchoney, and Danielle Squadron
- Subjects
Image-Guided Biopsy ,Male ,medicine.medical_specialty ,Prostate biopsy ,medicine.drug_class ,Urology ,Antibiotics ,030232 urology & nephrology ,Risk Assessment ,Sepsis ,03 medical and health sciences ,Prostate cancer ,Postoperative Complications ,0302 clinical medicine ,Prostate ,Internal medicine ,Biopsy ,medicine ,Humans ,Antibiotic prophylaxis ,Ultrasonography, Interventional ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Rectum ,Bacterial Infections ,Odds ratio ,Antibiotic Prophylaxis ,medicine.disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business - Abstract
To use data from a large, prospectively- acquired regional collaborative database to compare the risk of infectious complications associated with three American Urologic Association- recommended antibiotic prophylaxis pathways, including culture-directed or augmented antibiotics, following prostate biopsy.Data on prostate biopsies and outcomes were collected from the Pennsylvania Urologic Regional Collaborative, a regional quality collaborative working to improve the diagnosis and treatment of prostate cancer. Patients were categorized as receiving one of three prophylaxis pathways: culture-directed, augmented, or provider-discretion. Infectious complications included fever, urinary tract infections or sepsis within one month of biopsy. Odds ratios of infectious complication by pathway were determined, and univariate and multivariate analyses of patient and biopsy characteristics were performed.11,940 biopsies were included, 120 of which resulted in infectious outcomes. Of the total biopsies, 3246 used "culture-directed", 1446 used "augmented" and 7207 used "provider-discretion" prophylaxis. Compared to provider-discretion, the culture-directed pathway had 84% less chance of any infectious outcome (OR= 0.159, 95% CI = [0.074, 0.344], P0.001). There was no difference in infectious complications between augmented and provider-discretion pathways.The culture-directed pathway for transrectal prostate biopsy resulted in significantly fewer infectious complications compared to other prophylaxis strategies. Tailoring antibiotics addresses antibiotic-resistant bacteria and reduces future risk of resistance. These findings make a strong case for incorporating culture-directed antibiotic prophylaxis into clinical practice guidelines to reduce infection following prostate biopsies.
- Published
- 2021
46. Risk Factors for Intravesical Recurrence after Minimally Invasive Nephroureterectomy for Upper Tract Urothelial Cancer (ROBUUST Collaboration)
- Author
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Jamil Marcus, James R. Porter, Giuseppe Rosiello, Reza Mehrazin, Koon Ho Rha, Daniel Eun, Riccardo Autorino, Mark L. Gonzalgo, Chandru P. Sundaram, Rollin Say, Matteo Ferro, Firas Abdollah, Hooman Djaladat, Amit S Bhattu, Andrew B. Katims, Alessandro Veccia, Alireza Ghoreifi, Vitaly Margulis, Adam C. Reese, Andrea Minervini, Alex Mottrie, Laura C. Kidd, Robert G. Uzzo, Riccardo Tellini, Giuseppe Simone, Andrea Mari, Margaret Meagher, Ithaar Derweesh, Alyssa Danno, and Zhenjie Wu
- Subjects
Male ,medicine.medical_specialty ,Biopsy ,Urology ,Urinary Bladder ,Kidney ,Nephroureterectomy ,Disease-Free Survival ,Neoplasm Seeding ,Ureter ,Robotic Surgical Procedures ,Risk Factors ,Ureteroscopy ,medicine ,Humans ,Urothelial cancer ,Ureteral neoplasm ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Urothelial carcinoma ,Carcinoma, Transitional Cell ,Urinary bladder ,medicine.diagnostic_test ,Ureteral Neoplasms ,business.industry ,Margins of Excision ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,Upper tract ,Female ,business ,Follow-Up Studies - Abstract
Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) has an incidence of approximately 20%-50%. Studies to date have been composed of mixed treatment cohorts-open, laparoscopic and robotic. The objective of this study is to assess clinicopathological risk factors for intravesical recurrence after RNU for UTUC in a completely minimally invasive cohort.We performed a multicenter, retrospective analysis of 485 patients with UTUC without prior or concurrent bladder cancer who underwent robotic or laparoscopic RNU. Patients were selected from an international cohort of 17 institutions across the United States, Europe and Asia. Univariate and multiple Cox regression models were used to identify risk factors for bladder recurrence.A total of 485 (396 robotic, 89 laparoscopic) patients were included in analysis. Overall, 110 (22.7%) of patients developed IVR. The average time to recurrence was 15.2 months (SD 15.5 months). Hypertension was a significant risk factor on multiple regression (HR 1.99, CI 1.06; 3.71, p=0.030). Diagnostic ureteroscopic biopsy incurred a 50% higher chance of developing IVR (HR 1.49, CI 1.00; 2.20, p=0.048). Treatment specific risk factors included positive surgical margins (HR 3.36, CI 1.36; 8.33, p=0.009) and transurethral resection for bladder cuff management (HR 2.73, CI 1.10; 6.76, p=0.031).IVR after minimally invasive RNU for UTUC is a relatively common event. Risk factors include a ureteroscopic biopsy, transurethral resection of the bladder cuff, and positive surgical margins. When possible, avoidance of transurethral resection of the bladder cuff and alternative strategies for obtaining biopsy tissue sample should be considered.
- Published
- 2021
47. Papillary Renal Neoplasm With Reverse Polarity Is Often Cystic
- Author
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Tahseen Al-Saleem, Alexander Kutikov, Robert G. Uzzo, Jianming Pei, Essel Dulaimi, Joseph R. Testa, Jacqueline Talarchek, Shuanzeng Wei, Douglas B. Flieder, and Arthur S. Patchefsky
- Subjects
Pathology ,medicine.medical_specialty ,Psammoma body ,business.industry ,Cystic Change ,medicine.disease ,medicine.disease_cause ,Pathology and Forensic Medicine ,Renal neoplasm ,Cystic Neoplasm ,Hemosiderin ,Eosinophilic ,medicine ,Surgery ,KRAS ,Anatomy ,Trisomy ,business - Abstract
Papillary renal neoplasm with reverse polarity (PRNRP) is a newly proposed entity with distinct histology and frequent KRAS mutations. To date, 93 cases of PRNRPs have been reported. In this study, we present 7 new cases of PRNRP and review the literature. Most of the pathologic features in our 7 cases are similar to those previously reported cases. However, all 7 of our cases showed at least partial cystic changes, which was not stressed in prior studies. Single-nucleotide polymorphism-microarray based chromosomal analysis demonstrated no trisomy or other alteration of chromosomes 7 or 17; and no loss or other alteration of chromosome Y was detected in all 7 cases. Next-generation sequencing detected KRAS missense mutations in 4 of 7 cases. No fusion genes were detected. In summary, PRNRP is a small, well-circumscribed often encapsulated and cystic neoplasm with loose papillary formations. Cuboidal tumor cells always have eosinophilic cytoplasm and nuclei located at the pole opposite the basement membrane with a low World Health Organization (WHO)/International Society of Urologic Pathologists (ISUP) nuclear grade. The fibrovascular cores can be hyalinized or edematous. Macrophage aggregates and intracellular hemosiderin are uncommon, and no psammoma bodies or necrosis should be seen. Immunophenotypically, this tumor is always positive for CK7 and GATA3, and negative for CD117 and vimentin. CD10 and AMACR can be positive, but often weakly and focally. PRNRP often has KRAS mutations, however, only 32% of cases have chromosomal abnormalities in chromosomes 7, 17, and Y. No recurrences, metastases, or tumor-related deaths have been reported following complete resection.
- Published
- 2021
48. Renal Mass and Localized Renal Cancer: Evaluation, Management, and Follow-Up: AUA Guideline: Part I
- Author
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Robert G. Uzzo, Jose A. Karam, Steven C. Campbell, Peter E. Clark, Lesley Souter, and Sam S. Chang
- Subjects
Ablation Techniques ,Counseling ,medicine.medical_specialty ,Evidence-Based Medicine ,Adult patients ,medicine.diagnostic_test ,business.industry ,Urology ,medicine.medical_treatment ,Thermal ablation ,Cancer ,Antineoplastic Agents ,Guideline ,medicine.disease ,Nephrectomy ,Kidney Neoplasms ,Biopsy ,medicine ,Renal mass ,Humans ,business ,Kidney cancer - Abstract
This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article.Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.
- Published
- 2021
49. Prescribing Trends in Post-operative Pain Management After Urologic Surgery: A Quality Care Investigation for Healthcare Providers
- Author
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Serge Ginzburg, Philip Abbosh, Robert G. Uzzo, Erin Ohmann, Eric Ghiraldi, Steven Sterious, Justin I. Friedlander, Jay Simhan, Matthew Nitti, Jeffrey L. Ellis, and Joshua A. Cohn
- Subjects
Male ,medicine.medical_specialty ,Narcotic ,Health Personnel ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Specialty ,Quality care ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Pain Management ,Urologic surgery ,Practice Patterns, Physicians' ,Pain, Postoperative ,business.industry ,Public health ,Middle Aged ,Quality Improvement ,Patient Discharge ,United States ,Analgesics, Opioid ,Opioid ,030220 oncology & carcinogenesis ,Emergency medicine ,Morphine ,Urologic Surgical Procedures ,Female ,business ,Healthcare providers ,Needs Assessment ,medicine.drug - Abstract
To assess prescribing and refilling trends of narcotics in postoperative urology patients at our institution. Although the opioid epidemic remains a public health threat, no series has assessed prescribing patterns across urologic surgery disciplines following discharge.All urologic surgeries were retrospectively reviewed from May 2017-April 2018. Demographics, comorbidities, and postoperative pain management strategies were analyzed. Narcotics usage following surgery were reported in total morphine equivalents (TME). Opioid refill rate was characterized by medical specialty and stratified by urologic discipline.817 cases were reviewed. Mean age and TME at discharge was 57±15.6 years and 35.43±19.5 mg, respectively. 13.6% (mean age 55±15.9) received a narcotic refill following discharge (mean TME/refill 37.7±28.9 mg). A higher proportion of patients with a pre-operative opioid prescription received a refill compared to opioid naïve patients (38.2% vs 21.6%, P.01). Refill rate did not differ between urologic subspecialties (P = .3). Urologists were only responsible for 20.4% of all refills filled, despite all patients continuing follow-up with their surgeon. Procedures with the highest rates of post-operative refills were in oncology, male reconstruction/trauma and endourology. Patients with a history of chronic pain (OR 1.9, CI 1.1-3.3) preoperative narcotic prescription (OR 1.6, CI 1.0-2.6), and higher ASA score (OR 1.8, CI 1.6-2.8) were more likely to obtain a postoperative opioid prescription refill.Approximately 1 in 7 postoperative urology patients receive a postoperative narcotics refill; however, nearly two-thirds receive refills exclusively from non-urologic providers. Attempts to avoid overprescribing of postoperative narcotics need to account for both surgeon and nonsurgeon sources of opioid refills.
- Published
- 2021
50. Long Term Results of a Phase III Randomized Prospective Trial of Erectile Tissue Sparing IMRT for Men with Clinically Localized Prostate Cancer
- Author
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Eddie, Zhang, Karen J, Ruth, Mark K, Buyyounouski, Robert A, Price, Robert G, Uzzo, Mark L, Sobczak, Alan, Pollack, J Karen, Wong, David Y T, Chen, Mark A, Hallman, Richard E, Greenberg, Deborah, Watkins-Bruner, Tahseen, Al-Saleem, and Eric M, Horwitz
- Abstract
To determine if limiting the doses delivered to the penile bulb (PB) and corporal bodies (CB) with IMRT preserves erectile function compared to standard IMRT in men with prostate cancer.117 patients with low-intermediate risk, clinical T1a-T2c prostate adenocarcinoma were enrolled to a single-institution, prospective, single blind, phase III randomized trial. All received definitive IMRT to 74-80 Gy in 37-40 fractions and standard IMRT (s-IMRT) or erectile tissue sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the PB and CB to ≤ 15 Gy and ≤ 7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function (IIEF) and PDE5 medication records.62 patients received ETS-IMRT and 54 received s-IMRT; 1 patient did not receive radiation therapy. Prior to treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, p=0.53). Of 85 evaluable patients with IIEF and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (p=0.86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (p=0.54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-yr 91.8% vs 90.7%, respectively, p=0.77) with a median follow-up of 7.4 years. There were no differences in acute or late GI or GU toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, though power was limited by attrition and unplanned dosimetric crossover.Erectile tissue sparing IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited.
- Published
- 2022
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