166 results on '"Brian Shuch"'
Search Results
2. Fumarate hydratase variant prevalence and manifestations among individuals receiving germline testing
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Eric Lu, Shantao Li, Kathryn E. Hatchell, Heather R. Christofk, Blake R. Wilde, Brian Shuch, Keith Nykamp, Shirin Zavoshi, Liying Zhang, Sarah M. Nielsen, Karen Ouyang, Edward D. Esplin, and Paul C. Boutros
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Oncology ,Cancer Research ,Kidney Disease ,Skin Neoplasms ,Fumarase deficiency ,urologic and male genital diseases ,Germline ,Fumarate Hydratase ,Renal cell carcinoma ,Prevalence ,kidney neoplasms ,2.1 Biological and endogenous factors ,Aetiology ,Cancer ,education.field_of_study ,medicine.diagnostic_test ,Penetrance ,Kidney Neoplasms ,Hereditary ,Uterine Neoplasms ,Public Health and Health Services ,Female ,hereditary leiomyomatosis and renal cell cancer ,fumarate hydratase ,medicine.medical_specialty ,Oncology and Carcinogenesis ,Population ,Article ,genetic testing ,Cancer syndrome ,Clinical Research ,Neoplastic Syndromes, Hereditary ,Leiomyomatosis ,Internal medicine ,Genetics ,medicine ,Humans ,Neoplastic Syndromes ,Oncology & Carcinogenesis ,education ,Carcinoma, Renal Cell ,Germ-Line Mutation ,Genetic testing ,business.industry ,Carcinoma ,Renal Cell ,medicine.disease ,Germ Cells ,business - Abstract
BackgroundGermline variants in fumarate hydratase (FH) are associated with autosomal dominant (AD) hereditary leiomyomatosis and renal cell cancer (HLRCC) and autosomal recessive (AR) fumarase deficiency (FMRD). The prevalence and cancer penetrance across different FH variants remain unclear.MethodsA database containing 120,061 records from individuals undergoing cancer germline testing was obtained. FH variants were classified into 3 categories: AD HLRCC variants, AR FMRD variants, and variants of unknown significance (VUSs). Individuals with variants from these categories were compared with those with negative genetic testing.ResultsFH variants were detected in 1.3% of individuals (AD HLRCC, 0.3%; AR FMRD, 0.4%; VUS, 0.6%). The rate of AD HLRCC variants discovered among reportedly asymptomatic individuals without a clear indication for HLRCC testing was 1 in 2668 (0.04%). In comparison with those with negative genetic testing, the renal cell carcinoma (RCC) prevalence was elevated with AD HLRCC variants (17.0% vs 4.5%; P 
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- 2021
3. Sequencing of Renal Mass Biopsy and Ablation: Results from the National Cancer Database
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Xiaoyan Wang, Andrew T. Lenis, Brian Shuch, and Annemarie Uhlig
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Urology ,medicine.medical_treatment ,Thermal ablation ,Cancer ,urologic and male genital diseases ,Ablation ,medicine.disease ,Renal cell carcinoma ,Biopsy ,medicine ,Renal mass ,Radiology ,business - Abstract
Introduction:We assessed current utilization and sequencing of renal mass biopsy (RMB) and thermal ablation for renal cell carcinoma (RCC) patients in the United States.Methods:The 2004–201...
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- 2021
4. Role of Imaging in Renal Cell Carcinoma: A Multidisciplinary Perspective
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Asser Abou Elkassem, Joseph I. Clark, Sandeep Vaidya, Alexander V. Louie, Andrew J. Gunn, Anca-Ligia Grosu, Shankar Siva, Molly E. DeWitt-Foy, Robert Abouassaly, Andrew D. Smith, Simon S. Lo, and Brian Shuch
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Kidney ,medicine.medical_specialty ,Percutaneous ,business.industry ,medicine.medical_treatment ,Cancer ,Immunotherapy ,urologic and male genital diseases ,medicine.disease ,Embolization, Therapeutic ,Magnetic Resonance Imaging ,Kidney Neoplasms ,Targeted therapy ,medicine.anatomical_structure ,Renal capsule ,Renal cell carcinoma ,medicine ,Medical imaging ,Humans ,Radiology, Nuclear Medicine and imaging ,Radiology ,business ,Carcinoma, Renal Cell - Abstract
With the expansion in cross-sectional imaging over the past few decades, there has been an increase in the number of incidentally detected renal masses and an increase in the incidence of renal cell carcinomas (RCCs). The complete characterization of an indeterminate renal mass on CT or MR images is challenging, and the authors provide a critical review of the best imaging methods and essential, important, and optional reporting elements used to describe the indeterminate renal mass. While surgical staging remains the standard of care for RCC, the role of renal mass CT or MRI in staging RCC is reviewed, specifically with reference to areas that may be overlooked at imaging such as detection of invasion through the renal capsule or perirenal (Gerota) fascia. Treatment options for localized RCC are expanding, and a multidisciplinary group of experts presents an overview of the role of advanced medical imaging in surgery, percutaneous ablation, transarterial embolization, active surveillance, and stereotactic body radiation therapy. Finally, the arsenal of treatments for advanced renal cancer continues to grow to improve response to therapy while limiting treatment side effects. Imaging findings are important in deciding the best treatment options and to monitor response to therapy. However, evaluating response has increased in complexity. The unique imaging findings associated with antiangiogenic targeted therapy and immunotherapy are discussed. An invited commentary by Remer is available online. Online supplemental material is available for this article. ©RSNA, 2021.
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- 2021
5. HIF2 Inhibition for von-Hippel Lindau Associated Kidney Cancer: Will Urology Lead or Follow?
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Brian Shuch
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medicine.medical_specialty ,von Hippel-Lindau Disease ,business.industry ,Urology ,Von hippel lindau ,medicine.disease ,Kidney Neoplasms ,Oncology ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Humans ,business ,Kidney cancer - Published
- 2021
6. Distinguishing Benign Renal Tumors with an Oncocytic Gene Expression (ONEX) Classifier
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Peter A. Humphrey, Jamil Syed, Brian Shuch, Peter G. Schulam, Paul C. Boutros, Patrick McGillivray, Neil Mendhiratta, Kevin A. Nguyen, Aydin Pooli, Adebowale J. Adeniran, and Daiki Ueno
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Adenoma ,Oncology ,medicine.medical_specialty ,Renal oncocytoma ,Kidney Disease ,Urology ,Clinical Sciences ,Chromophobe Renal Cell Carcinoma ,Renal and urogenital ,030232 urology & nephrology ,Gene Expression ,Chromophobe renal cell carcinoma ,urologic and male genital diseases ,Benign tumor ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Internal medicine ,Diagnosis ,Gene expression ,Genetics ,medicine ,Adenoma, Oxyphilic ,Humans ,Carcinoma, Renal Cell ,Cancer ,Molecular biomarkers ,screening and diagnosis ,business.industry ,Tumor classification ,Oxyphilic ,Carcinoma ,Renal Cell ,RNA expression ,Urology & Nephrology ,medicine.disease ,Kidney Neoplasms ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,030220 oncology & carcinogenesis ,Differential ,Cohort ,business ,Kidney cancer ,Classifier (UML) - Abstract
Renal oncocytoma (RO) accounts for 5% of renal cancers and generally behaves as a benign tumor with favorable long-term prognosis. It is difficult to confidently distinguish between benign RO and other renal malignancies, particularly chromophobe renal cell carcinoma (chRCC). Therefore, RO is often managed aggressively with surgery. We sought to identify molecular biomarkers to distinguish RO from chRCC and other malignant renal cancer mimics. In a 44-patient discovery cohort, we identified a significant differential abundance of nine genes in RO relative to chRCC. These genes were used to train a classifier to distinguish RO from chRCC in an independent 57-patient cohort. The trained classifier was then validated in five independent cohorts comprising 89 total patients. This nine-gene classifier trained on the basis of differential gene expression showed 93% sensitivity and 98% specificity for distinguishing RO from chRCC across the pooled validation cohorts, with a c-statistic of 0.978. This tool may be a useful adjunct to other diagnostic modalities to decrease the diagnostic and management uncertainty associated with small renal masses and to enable clinicians to recommend more confidently less aggressive management for some tumors. PATIENT SUMMARY: Renal oncocytoma is generally a benign form of kidney cancer that does not necessarily require surgical removal. However, it is difficult to distinguish renal oncocytoma from other more aggressive forms of kidney cancer, so it is treated most commonly with surgery. We built a classification tool based on the RNA levels of nine genes that may help avoid these surgeries by reliably distinguishing renal oncocytoma from other forms of kidney cancer.
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- 2021
7. The Role of Opioids and Their Receptors in Urological Malignancy: A Review
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Karim Chamie, Vishnukamal Golla, Wayne Brisbane, Patrick M Lec, Brian Shuch, Isla P. Garraway, Robert E. Reiter, and Andrew T. Lenis
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Male ,Urologic Neoplasms ,Carcinogenesis ,business.industry ,Urology ,Urinary Bladder ,Prostate ,Cancer Pain ,Kidney ,Malignancy ,medicine.disease ,Bioinformatics ,Disease-Free Survival ,Analgesics, Opioid ,Cell Movement ,Receptors, Opioid ,Humans ,Pain Management ,Medicine ,Neoplasm Invasiveness ,Perioperative Period ,business ,Receptor ,Cell Proliferation ,Opiate alkaloid - Abstract
We reviewed the literature surrounding the role of opioids and their receptors in urological malignancy. Recent studies have suggested clinically significant effects of agonism or antagonism of opioid receptors on cancer related outcomes and tumorigenesis. The focus of these efforts has centered on nonurological malignancies. However, a compelling body of evidence is growing in the fields of prostate, bladder and kidney cancer.A systematic review of English language articles published through 2020 was conducted with key phrases related to kidney, bladder or prostate cancer, and opioids or narcotics. A total of 837 unique records were identified, of which 49 were selected for full text review and 33 were included in the qualitative analysis. Eight records were identified via citation review and 1 study was recently presented at a national meeting.Retrospective reviews suggest poorer disease specific and recurrence-free survival with increased perioperative opioid administration in patients undergoing prostate or bladder cancer surgery. However, the data are controversial. Kappa opioid receptors are implicated in both proliferation and inhibition of prostate cancer cell growth across in vitro studies, with a proposed interaction with the androgen cascade. Similarly opioid growth factor receptor is highly expressed in prostate cancer cells and repressed by androgens. Prostate cancer tissue stains more intensely for the mu opioid receptor, and patients with higher expression have poorer oncologic outcomes. Opioid agonism in vitro induces urothelial cell carcinoma proliferation, migration and invasion, with possible additional influence from interactions with the bradykinin b2 receptor. Agonism of the mu, kappa and delta opioid receptors induces renal cell carcinoma tumorigenesis, possibly via upregulation of survivin. Meanwhile, opioid growth factor receptor agonism has the opposite effect in renal cell carcinoma.Evidence surrounding the role of opioids and their receptors in urological malignancy is provocative and should serve as an impetus for further investigation.
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- 2020
8. Fear of Cancer Recurrence in Patients With Localized Renal Cell Carcinoma
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Pavlos Msaouel, Michael Staehler, Errol J. Philip, Sumanta K. Pal, Dena Battle, Cristiane Decat Bergerot, Eric Jonasch, Adeola Esther Bamgboje, Ithaar Derweesh, Brian Shuch, Paulo Gustavo Bergerot, Allan Ben Smith, and Adam P. Stern
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cancer recurrence ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Renal cell carcinoma ,Internal medicine ,medicine ,Humans ,In patient ,Child ,Carcinoma, Renal Cell ,Oncology (nursing) ,business.industry ,Health Policy ,Cancer ,Fear ,medicine.disease ,Kidney Neoplasms ,Distress ,030104 developmental biology ,Child, Preschool ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,Neoplasm Recurrence, Local ,business - Abstract
PURPOSE: Patients with cancer commonly report distress and fear of cancer recurrence (FCR) impacting quality of life and clinical outcomes. This study aims to test the association between emotional well-being and clinical characteristics of survivors with localized renal cell carcinoma (RCC). MATERIALS AND METHODS: Survivors with localized RCC were invited to participate in this study through social media by the Kidney Cancer Research Alliance. Participants self-reported clinical characteristics, distress (Distress Thermometer), and FCR (Fear of Cancer Recurrence-7). Ordinal regression was used to test the association between emotional well-being and patient characteristics. RESULTS: A total of 412 survivors were included in this analysis. Participants were mostly female (79.4%) and well educated (58.3%), with a median age of 54 years (range, 30-80 years) and median time since diagnosis of 17.5 months. More than one half were diagnosed with stage I disease (56.1%). Most patients (62.3%) had a clear understanding of their diagnosis. A high prevalence of moderate to severe distress (67.0%) and FCR (54.9%) was reported across all survivors of RCC. Higher FCR was associated with female gender, younger age, and lack of understanding of their diagnosis ( P = .001), whereas more recent diagnosis was associated with higher distress levels ( P = .01). CONCLUSION: Our findings suggest that FCR is a common problem that is persistent after therapy and that certain individuals, including female and younger patients, may be at particular risk of experiencing clinically relevant FCR.
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- 2020
9. Transcriptomics in RCC
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Paul C. Boutros, Joseph Brito, Jamil Syed, Brian Shuch, and Aydin Pooli
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Microarray ,Angiogenesis ,Urology ,Clinical Decision-Making ,Population ,030232 urology & nephrology ,Computational biology ,Kidney ,Nephrectomy ,Risk Assessment ,Transcriptome ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Immune infiltration ,Renal cell carcinoma ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Adjuvant therapy ,Humans ,RNA-Seq ,education ,Carcinoma, Renal Cell ,Clinical Trials as Topic ,education.field_of_study ,business.industry ,Computational Biology ,Prognosis ,medicine.disease ,Kidney Neoplasms ,Progression-Free Survival ,Gene Expression Regulation, Neoplastic ,Oncology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,business ,Kidney cancer - Abstract
Improvements in chemistry, molecular biology, genetics, and bioinformatics have allowed broad use of transcriptomic profiling. Understanding the population of ribonucleic acid (RNA) transcripts can provide important clinical information relevant to kidney cancer care. This includes a better understanding of kidney cancer subtype and distinct clusters within these categories. RNA-sequencing (RNA-seq) is typically done on a region within the tumor, which represents thousands to millions of heterogeneous cells and various components of the microenvironment. Computational tools can deconvolute these populations to provide insight into the microenvironment. Specific signatures of hypoxia, proliferation, angiogenesis and immune infiltration can predict response and survival. Prognostic signatures can risk stratify tumors to aid in identification of patients who might derive benefit from adjuvant therapy. As the cost of sequencing continues to decline and improved bioinformatic tools are developed, the barriers to clinical use of transcriptomic data continue to crumble. Here we review the current literature around the use of transcriptomics in kidney cancer diagnosis and management.
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- 2020
10. NCCN Guidelines Insights: Kidney Cancer, Version 1.2021
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Brittany McCreery, Bryan Lewis, Naomi B. Haas, Lakshminarayanan Nandagopal, Mary A. Dwyer, Angela D. Motter, Christos Kyriakopoulos, Ajjai Alva, Maria I. Carlo, Phillip M. Pierorazio, M. Dror Michaelson, Sundhar Ramalingam, Brandon Manley, Clayton Lau, Lee Ponsky, Eric Jonasch, Neeraj Agarwal, David C. Madoff, Elizabeth R. Plimack, Bradley G. Somer, Jeffrey A. Sosman, Robert J. Motzer, Amir Mortazavi, Steven L. Hancock, Shawna L. Boyle, Elaine T. Lam, Ithaar Derweesh, Brian Shuch, Katy Beckermann, Arpita Desai, Saby George, Brian A. Costello, Zachary L. Smith, John L. Gore, and Toni K. Choueiri
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,MEDLINE ,Treatment options ,urologic and male genital diseases ,medicine.disease ,Systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,Carcinoma ,Medicine ,030212 general & internal medicine ,business ,Intensive care medicine ,Stage iv ,Kidney cancer ,Genetic testing - Abstract
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.
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- 2020
11. Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer
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Brian Shuch, Mark Gerstein, Patrick McGillivray, Shantao Li, Harvey A. Risch, and Ranjit S. Bindra
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Adult ,Male ,Oncology ,Heterozygote ,Cancer Research ,medicine.medical_specialty ,Skin Neoplasms ,Population ,Kidney ,Article ,Fumarate Hydratase ,Cancer syndrome ,03 medical and health sciences ,0302 clinical medicine ,Germline mutation ,Gene Frequency ,Neoplastic Syndromes, Hereditary ,Risk Factors ,Leiomyomatosis ,Internal medicine ,Humans ,Medicine ,Exome ,Genetic Predisposition to Disease ,030212 general & internal medicine ,education ,Allele frequency ,Germ-Line Mutation ,education.field_of_study ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Penetrance ,Kidney Neoplasms ,030220 oncology & carcinogenesis ,Uterine Neoplasms ,Female ,business ,Kidney cancer - Abstract
BACKGROUND: Hereditary leiomyomatosis and renal cancer (HLRCC) is a cancer syndrome associated with a germline mutation in fumarate hydratase (FH). The syndrome is associated with cutaneous and uterine leiomyomas, and some patients develop a lethal form of kidney cancer. This study provides estimates for the FH carrier frequency and kidney cancer penetrance. METHODS: Data sets containing sequencing data for the FH gene were used: the 1000 Genomes Project (1000GP) and the Exome Aggregation Consortium (ExAC). Alterations in the FH gene were characterized on the basis of different variant risk tiers: 1) ClinVar annotated variants, 2) loss-of-function alterations, and 3) highly impactful missense alterations. The cumulative incidence of FH alterations overall and by different world populations was evaluated in 1000GP and ExAC. A lifetime penetrance of HLRCC kidney cancer risk was generated with 3 estimates of the annual incidence. RESULTS: The overall allele frequencies of tier 1 to 3 FH alterations in the ExAC and 1000GP data sets were 2.54 × 10(–3) (1 in 393) and 1.20 × 10(–3) (1 in 835), respectively. There were differences in the allele frequencies of FH alterations between world populations. Based on various estimates of the percentage of kidney cancers with FH alterations, the lifetime kidney cancer penetrance for carrier estimate 3 in ExAC was 1.7% to 5.8%. CONCLUSIONS: FH alterations are common and are carried by approximately 1 in 1000 individuals according to the more conservative estimates. The lifetime kidney cancer penetrance appears lower than previously estimated. Although databases are not population cohorts, they provide a useful quantitative estimate of rare variants with low penetrance.
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- 2020
12. High WHO/ISUP Grade and Unfavorable Architecture, Rather Than Typing of Papillary Renal Cell Carcinoma, May Be Associated With Worse Prognosis
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Chen Yang, Adebowale J. Adeniran, Peter A. Humphrey, Brian Shuch, and Harriet M. Kluger
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,030232 urology & nephrology ,Risk Assessment ,Gastroenterology ,Disease-Free Survival ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Carcinoma ,Humans ,Medicine ,Child ,Carcinoma, Renal Cell ,Grading (tumors) ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Univariate analysis ,business.industry ,Proportional hazards model ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,Confidence interval ,030220 oncology & carcinogenesis ,Predictive value of tests ,Disease Progression ,Female ,Surgery ,Neoplasm Grading ,Anatomy ,business - Abstract
Conflicting data have been published on the prognostic significance of histologic parameters in papillary renal cell carcinoma (PRCC). We conducted a comprehensive evaluation of clinical and histologic parameters in PRCC in nephrectomies and their impact on prognosis, with an emphasis on World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade, tumor architecture (solid, micropapillary, and hobnail), and PRCC type. A total of 185 PRCC cases were evaluated, 117 (63.2%) type 1, 45 (24.3%) type 2, and 11 (5.9%) mixed type 1 and type 2. Using WHO/ISUP grading criteria, PRCCs were graded as follows: 6 (3.2%) grade 1; 116 (62.7%) grade 2; 61 (33.0%) grade 3; and 2 (1.1%) grade 4. The solid architecture was present in 3 cases (1.6%) and comprised 10%, 10%, and 30% of the tumor area. Micropapillary architecture was present in 10 cases (5.4%), ranging from 5% to 30% of the tumor (mean=11%; median=10%). Hobnail architecture was seen in 9 cases (4.9%), with mean percentage of 23% (median=15%; range: 5% to 50%) involvement of tumor area. Parameters associated with worse disease-free survival (DFS) and overall survival (OS) in the univariate analysis included WHO/ISUP grade, pathologic stage, tumor size, and solid, micropapillary, or hobnail architecture (P
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- 2020
13. Genetic Testing in Kidney Cancer Patients: Who, When, and How?
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Brian Shuch and Sandy T. Lui
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Adult ,medicine.medical_specialty ,Urology ,030232 urology & nephrology ,Risk Assessment ,Germline ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Mass Screening ,Genetic Predisposition to Disease ,Genetic Testing ,Clinical care ,Patient summary ,Intensive care medicine ,Carcinoma, Renal Cell ,Germ-Line Mutation ,Genetic testing ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Penetrance ,Kidney Neoplasms ,Pedigree ,030220 oncology & carcinogenesis ,business ,Risk assessment ,Kidney cancer - Abstract
There are more than a dozen recognized hereditary forms of kidney cancer. While classic syndromic forms are readily recognizable, more recently described conditions are subtler because of lower penetrance. Adequate counseling and implementation of risk assessment before or after management are important aspects of clinical care. Germline testing to assess hereditary risk has rapidly evolved thanks to multigene panel testing, which can be performed quickly and at relatively low cost. This review discusses what is known about germline risk assessment, namely which individuals should be tested and when and how, and covers many of the uncertainties around this process. Patient summary More than a dozen genes have been linked to predisposition to kidney cancer. We review genetic testing in terms of who should be tested and when and how the testing should be carried out. Results from genetic tests can help in tailoring screening and surgical management and in selecting the most suitable chemotherapy.
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- 2019
14. Harnessing the Genomic Landscape of the Small Renal Mass to Guide Clinical Management
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Karim Bensalah, Andrew W. Silagy, Börje Ljungberg, A. Ari Hakimi, Brian Shuch, Brandon J. Manley, Axel Bex, Alejandro Sanchez, and Jose A. Karam
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Male ,Biopsy ,Cost-Benefit Analysis ,Urology ,030232 urology & nephrology ,Genomics ,Context (language use) ,Disease ,Bioinformatics ,Nephrectomy ,Risk Assessment ,Article ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Renal mass ,medicine ,Humans ,Precision Medicine ,Carcinoma, Renal Cell ,Neoplasm Staging ,Tumor size ,business.industry ,Disease Management ,Reproducibility of Results ,Prognosis ,medicine.disease ,Kidney Neoplasms ,030220 oncology & carcinogenesis ,Female ,business ,Kidney cancer ,Evidence synthesis - Abstract
CONTEXT: Small renal masses (SRMs; tumors
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- 2019
15. Genetic Risk Assessment for Hereditary Renal Cell Carcinoma: Clinical Consensus Statement
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Adam R. Metwalli, Gennady Bratslavsky, James Brugarolas, Othon Iliopoulos, Alexander Kutikov, Anhyo Jeong, W. Kimryn Rathmell, Khaled S. Hafez, Mark W. Ball, Bruce H. Lee, Ronald S. Boris, Michael A.S. Jewett, Dena Battle, Katherine L. Nathanson, W. Marston Linehan, Eric A. Singer, Lindsay Middleton, Ramaprasad Srinivasan, Gloria Morris, Michael Daneshvar, Mary B. Daly, Michael J. Hall, Vivek Narayan, Maria I. Carlo, A. Ari Hakimi, Eric Jonasch, Christina Karamboulas, Brian Shuch, Neil Mendhiratta, Elizabeth P. Henske, Colette Hyatt, Ulka N. Vaishampayan, Phillip M. Pierorazio, and Sumanta K. Pal
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Cancer Research ,medicine.medical_specialty ,Consensus ,medicine.diagnostic_test ,business.industry ,Statement (logic) ,Genetic counseling ,urologic and male genital diseases ,medicine.disease ,Risk Assessment ,Article ,Kidney Neoplasms ,Uniform consensus ,Oncology ,Family medicine ,Medicine ,Humans ,Genetic Testing ,Family history ,Genetic risk ,business ,Risk assessment ,Kidney cancer ,Carcinoma, Renal Cell ,Genetic testing - Abstract
Background Although renal cell carcinoma (RCC) is believed to have a strong hereditary component, there is a paucity of published guidelines for genetic risk assessment. A panel of experts was convened to gauge current opinions. Methods A North American multidisciplinary panel with expertise in hereditary RCC, including urologists, medical oncologists, clinical geneticists, genetic counselors, and patient advocates, was convened. Before the summit, a modified Delphi methodology was used to generate, review, and curate a set of consensus questions regarding RCC genetic risk assessment. Uniform consensus was defined as ≥85% agreement on particular questions. Results Thirty-three panelists, including urologists (n = 13), medical oncologists (n = 12), genetic counselors and clinical geneticists (n = 6), and patient advocates (n = 2), reviewed 53 curated consensus questions. Uniform consensus was achieved on 30 statements in specific areas that addressed for whom, what, when, and how genetic testing should be performed. Topics of consensus included the family history criteria, which should trigger further assessment, the need for risk assessment in those with bilateral or multifocal disease and/or specific histology, the utility of multigene panel testing, and acceptance of clinician-based counseling and testing by those who have experience with hereditary RCC. Conclusions In the first ever consensus panel on RCC genetic risk assessment, 30 consensus statements were reached. Areas that require further research and discussion were also identified, with a second future meeting planned. This consensus statement may provide further guidance for clinicians when considering RCC genetic risk assessment. Lay summary The contribution of germline genetics to the development of renal cell carcinoma (RCC) has long been recognized. However, there is a paucity of guidelines to define how and when genetic risk assessment should be performed for patients with known or suspected hereditary RCC. Without guidelines, clinicians struggle to define who requires further evaluation, when risk assessment or testing should be done, which genes should be considered, and how counseling and/or testing should be performed. To this end, a multidisciplinary panel of national experts was convened to gauge current opinion on genetic risk assessment in RCC and to enumerate a set of recommendations to guide clinicians when evaluating individuals with suspected hereditary kidney cancer.
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- 2021
16. Renal Cell Carcinoma Associated with Germline Mutations in the Krebs Cycle
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Eric Lu, Brian Shuch, and Alexandra Drakaki
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Germline mutation ,business.industry ,Renal cell carcinoma ,Cancer research ,Medicine ,urologic and male genital diseases ,business ,medicine.disease ,The Krebs Cycle - Abstract
Germline mutations in the fumarate hydratase (FH) and succinate dehydrogenase (SDH) genes lead to hereditary leiomyomatosis and RCC (HLRCC) and hereditary paraganglioma and pheochromocytoma, respectively. The renal cell carcinomas that arise in these conditions are characterized by dysregulated Krebs cycles, accumulation of oncometabolites, downstream changes in gene expression, and epigenetic modifications that carry unique therapeutic implications. In this review, we evaluate the current literature on these tumors, including the epidemiology, clinical course, screening guidelines, and management of localized and metastatic disease.
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- 2021
17. The Association Between the Affordable Care Act and Insurance Status, Stage and Treatment in Patients with Testicular Cancer
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Michael S. Leapman, Xuesong Han, Ahmedin Jemal, James B. Yu, Kevin A. Nguyen, Cary P. Gross, Walter Hsiang, Henry Park, Brian Shuch, and Amy J. Davidoff
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medicine.medical_specialty ,business.industry ,Urology ,030232 urology & nephrology ,Disease ,medicine.disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Insurance status ,Family medicine ,Patient Protection and Affordable Care Act ,Health insurance ,Medicine ,In patient ,sense organs ,Stage (cooking) ,business ,skin and connective tissue diseases ,Medicaid ,Testicular cancer - Abstract
PURPOSE: We aimed to determine whether insurance expansions implemented through the Affordable Care Act (ACA) were associated with changes in coverage status, disease stage, and treatment of younger adults with testicular germ cell tumors (GCT). MATERIALS AND METHODS: We identified men aged 18–64 diagnosed with testicular GCTs between 2010 and 2015 in the National Cancer Data Base. We defined time periods as: pre-ACA (2010–2013) and post-ACA (2014–2015) and used difference-in-differences (DID) modeling to examine associations between state Medicaid expansion status and changes in insurance, stage at diagnosis, and treatment. RESULTS: Following the ACA, the proportion of patients with any health insurance increased 3.7% (95% CI 3–4.5) in Medicaid expansion states and 3.0% (95% CI 1.5–4.5) in non-expansion states, mainly by gaining Medicaid and private insurance, respectively. The largest increases occurred in low-income patients, where Medicaid expansion was associated with an adjusted increase of 14.5 percentage points (95% CI 7.2–21.8) in Medicaid coverage following the ACA. We did not observe reductions in late-stage diagnoses during the observation period. Changes in the proportion of patients receiving chemotherapy or radiation for advanced-stage cancers were ongoing prior to the ACA and differed between expansion and non-expansion states, limiting assessment of ACA-related effects on individual treatments. CONCLUSIONS: Post-ACA, the proportion of newly diagnosed testicular cancer patients with health insurance increased, with the largest effects seen among lowest income individuals. Our findings that changes in practice preceded the ACA and differed by expansion status highlight the need for caution in assessing the legislation’s impact.
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- 2021
18. Considerations for the Next Clinical Trial Evaluating the Role of Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma
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Edward M. Messing, Catherine M. Tangen, Eddie Mayerson, Hyung L. Kim, Primo N. Lara, Brian Shuch, and Ulka N. Vaishampayan
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Oncology ,medicine.medical_specialty ,Urology ,Immune checkpoint inhibitors ,medicine.medical_treatment ,030232 urology & nephrology ,Nephrectomy ,Article ,Targeted therapy ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,Sunitinib ,medicine ,Humans ,Cytoreductive nephrectomy ,Carcinoma, Renal Cell ,Protein Kinase Inhibitors ,Randomized Controlled Trials as Topic ,business.industry ,Cytoreduction Surgical Procedures ,Immunotherapy ,medicine.disease ,Ipilimumab ,Survival Analysis ,Kidney Neoplasms ,Clinical trial ,Nivolumab ,Clinical Trials, Phase III as Topic ,030220 oncology & carcinogenesis ,business - Abstract
Trials SWOG 8949 and EORTC 30947 had the same eligibility criteria and established the role of cytoreductive nephrectomy for metastatic renal cell carcinoma. The more recently published CARMENA trial calls into question the need for cytoreductive nephrectomy. A systematic comparison of CARMENA and SWOG 8949 suggests that cytoreductive nephrectomy may be beneficial for patients receiving immunotherapy but not targeted therapy. The approval of immune checkpoint inhibitors for previously untreated metastatic renal cell carcinoma underlines the need for another randomized phase 3 trial of cytoreductive nephrectomy for patients receiving powerful modern immunotherapies.
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- 2019
19. Inherited kidney cancer syndromes
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Brian Shuch and Mark W. Ball
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Urology ,030232 urology & nephrology ,Clinical manifestation ,Bioinformatics ,Systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,Neoplastic Syndromes, Hereditary ,medicine ,Genetic predisposition ,Humans ,Mass Screening ,Genetic Predisposition to Disease ,Genetic Testing ,Carcinoma, Renal Cell ,Genetic testing ,Kidney ,medicine.diagnostic_test ,business.industry ,High-Throughput Nucleotide Sequencing ,medicine.disease ,Penetrance ,Kidney Neoplasms ,Natural history ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,business ,Kidney cancer - Abstract
PURPOSE OF REVIEW To describe current paradigms for genetic testing, screening, and treatment of patients with inherited kidney cancer syndromes. RECENT FINDINGS We describe various new aspects of hereditary kidney cancer. Recent data now support that hereditary kidney cancer may account for 5-8% of kidney cancers diagnosed. Methods of testing have evolved including the introduction of multigene next-generation sequencing panels. We continue to learn more about the natural history and management of classic hereditary cancer syndromes. New emerging conditions with lower kidney cancer penetrance have been recognized adding the growing list of syndromes associated with kidney cancer development. The surgical management strategies of enucleation remain however systemic therapy options are being explored both for localized and advanced settings. SUMMARY Genetic predisposition to kidney cancer is likely more common than once thought. Knowledge of clinical manifestation and genetic testing strategies are needed to properly identify and treat patient and their families.
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- 2019
20. Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription
- Author
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Yang Yang-Hartwich, Huamao Liang, Tobias M.P. Hartwich, Sarah L Cady, Kay Yi Chong, Daiki Ueno, Francesca Garofalo, Oluwagbemisola Madarikan, Brian Shuch, Cheng-Hsiu Tsai, Min Kang, and Nicholas Pitruzzello
- Subjects
STAT3 Transcription Factor ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,Transcription, Genetic ,Lactams, Macrocyclic ,Tumor initiation ,Hsp90 inhibitor ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Benzoquinones ,medicine ,Humans ,HSP90 Heat-Shock Proteins ,Phosphorylation ,Promoter Regions, Genetic ,STAT3 ,Transcription factor ,Ovarian Neoplasms ,Pharmacology ,biology ,Chemistry ,Twist-Related Protein 1 ,Nuclear Proteins ,Nasopharyngeal Neoplasms ,medicine.disease ,Kidney Neoplasms ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Drug Resistance, Neoplasm ,Tissue Array Analysis ,Tumor progression ,Cancer cell ,biology.protein ,Cancer research ,STAT protein ,Molecular Medicine ,Female ,030217 neurology & neurosurgery - Abstract
Molecular chaperone heat shock protein 90 (HSP90) is involved in oncogenic signaling pathways including epithelial-mesenchymal transition (EMT), a key process in tumor initiation, progression, metastasis, and chemoresistance. The molecular mechanisms underlying the involvement of HSP90 in EMT are still under investigation. In this study, we identified a previously unrecognized role of HSP90 in cooperating with signal transducer and activator of transcription 3 (STAT3) to regulate TWIST1 transcription in cancer cells. The HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin suppressed TWIST1 mRNA expression and promoter activity in epithelial ovarian cancer, renal clear cell cancer, and nasopharyngeal cancer cell lines. The interactions between HSP90 and transcription factors were visualized in cancer cell lines and tumor tissues using proximity ligation assays. Our findings reveal that HSP90 promotes the binding of STAT3 to the TWIST1 promoter, leading to the transcription of TWIST1. The inhibition of HSP90 downregulates STAT3 activity and TWIST1 transcription, thereby suppressing EMT and potentially inhibiting tumor progression, metastasis, and chemoresistance in different types of cancers. SIGNIFICANCE STATEMENT: Our study provides new evidence that HSP90 promotes EMT through enhancing TWIST1 transcription, which can be suppressed by HSP90 inhibitors. The HSP90 inhibitor inhibits EMT, thus potentially slowing down tumor growth, invasion, dissemination, metastasis, and drug resistance. These findings will hopefully pave the way for new therapeutic opportunities to target EMT and metastasis using HSP90 inhibitors.
- Published
- 2019
21. Active Surveillance Versus Nephron-Sparing Surgery for a Bosniak IIF or III Renal Cyst: A Cost-Effectiveness Analysis
- Author
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Kelly Cox, Reza Sirous, J Daniel Carson, Xu Zhang, Asser Abou Elkassem, Erick M. Remer, Rupan Sanyal, Brian C. Allen, Andrew D. Smith, and Brian Shuch
- Subjects
Male ,medicine.medical_specialty ,genetic structures ,Cost-Benefit Analysis ,urologic and male genital diseases ,Nephrectomy ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Life Expectancy ,Postoperative Complications ,0302 clinical medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,Cyst ,Watchful Waiting ,integumentary system ,business.industry ,IIf ,General Medicine ,Cost-effectiveness analysis ,Kidney Diseases, Cystic ,Middle Aged ,medicine.disease ,Markov Chains ,Surgery ,Renal cysts ,030220 oncology & carcinogenesis ,Female ,Quality-Adjusted Life Years ,Nephron sparing surgery ,business - Abstract
The objective of our study was to evaluate the cost-effectiveness of active surveillance (AS) versus nephron-sparing surgery (NSS) in patients with a Bosniak IIF or III renal cyst.Markov models were developed to estimate life expectancy and lifetime costs for 60-year-old patients with a Bosniak IIF or III renal cyst (the reference cases) managed by AS versus NSS. The models incorporated the malignancy rates, reclassification rates during follow-up, treatment effectiveness, complications and costs, and short- and long-term outcomes. An incremental cost-effectiveness analysis was performed to identify management preference under an assumed $75,000 per quality-adjusted life-year (QALY) societal willingness-to-pay threshold, using data from studies in the literature and the 2015 Medicare Physician Fee Schedule. The effects of key parameters were addressed in a multiway sensitivity analysis.The prevalence of malignancy for Bosniak IIF and III renal cysts was 26% (25/96) and 52% (542/1046). Under base case assumptions for Bosniak IIF cysts, the incremental cost-effectiveness ratio of NSS relative to AS was $731,309 per QALY for women, exceeding the assumed societal willingness-to-pay threshold, and AS outperformed NSS for both life expectancy and cost for men. For Bosniak III cysts, AS yielded greater life expectancy (24.8 and 19.4 more days) and lower lifetime costs (cost difference of $12,128 and $11,901) than NSS for men and women, indicating dominance of AS over NSS. Superiority of AS held true in sensitivity analyses for men 46 years old or older and women 57 years old or older even when all parameters were set to favor NSS.AS is more cost-effective than NSS for patients with a Bosniak IIF or III renal cyst.
- Published
- 2019
22. Determinants of Active Surveillance in Patients With Small Renal Masses
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Alfredo Suarez-Sarmiento, Michael S. Leapman, Jamil Syed, Kevin A. Nguyen, Oriyomi Alimi, Adam Nolte, Aaron J. Perecman, Brian Shuch, Kamyar Ghabili, Walter Hsiang, and Amanda J. Lu
- Subjects
Male ,medicine.medical_specialty ,Multivariate analysis ,Urology ,030232 urology & nephrology ,MEDLINE ,Logistic regression ,National cohort ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,In patient ,Watchful Waiting ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Tumor size ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,Tumor Burden ,030220 oncology & carcinogenesis ,Cohort ,Female ,business - Abstract
To evaluate trends in the utilization of active surveillance (AS) in a nationally representative cancer database. AS has been increasingly recognized as an effective strategy for patients with small renal masses but little is known about national usage patterns.We identified patients with clinical T1a renal masses within the National Cancer Database in 2010 through 2014. Patients were classified according to initial management strategy received including AS, surgery, ablation, or other treatment. We characterized time trends in the use of AS vs definitive therapy and examined clinical and socio-demographic determinants of AS among patients with small renal masses using multivariable logistic regression models.We identified 59,189 patients who satisfied the inclusion criteria. Of the total cohort, 1733 (2.9%) individuals received initial management with AS, while 57,456 (97.1%) received definitive treatment. Surveillance rates remained below 5% in all years. On multivariate analysis, patient age (OR: 1.08, 95% CI 1.08-1.09), smaller tumor size of2 cm vs ≥2 cm (OR: 2.43, 95% CI: 2.20-2.7, P.0001), management at an academic center vs community center (OR: 2.05, 95% CI: 1.83-2.29), and African American vs Caucasian race (OR: 1.56, 95% CI:1.35-1.80) were independently associated with use of AS as initial management.In a representative national cohort of patients with small renal masses, we observed clinical and facility-level differences in the utilization of active surveillance in patients with T1a renal masses. Further investigation is warranted to better understand the forces underlying initial management decisions for patients with small renal masses.
- Published
- 2019
23. Risk factors for metachronous bilateral renal cell carcinoma: A Surveillance, Epidemiology, and End Results analysis
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Theodore R. Holford, Kevin A. Nguyen, Jamil Syed, Brian Shuch, and Jonathan N. Hofmann
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Cancer Research ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Disease ,urologic and male genital diseases ,medicine.disease ,Confidence interval ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,Internal medicine ,Epidemiology ,Surveillance, Epidemiology, and End Results ,Medicine ,Cumulative incidence ,030212 general & internal medicine ,business - Abstract
Background Patients treated for renal cell carcinoma (RCC) may be diagnosed with a metachronous, contralateral tumor. We evaluated the risks of contralateral tumor development using the Surveillance, Epidemiology, and End Results database. Methods Among RCC patients, we identified those with a metachronous, contralateral RCC diagnosed ≥1 year after primary diagnosis. We performed a competing risks analysis to evaluate associations between clinicopathologic factors and metachronous, bilateral RCC. Cumulative incidence and standardized incidence ratios (SIRs) were calculated. Results There were 80,403 cases of RCC identified, with a median follow-up of 8.3 years; of these, 1063 (1.3%) developed metachronous, contralateral RCC (median of 6 years after diagnosis). The cumulative incidence at 10, 20, and 30 years of follow-up was 1.5%, 3.1%, and 4.7%, respectively. An increased risk was observed among men (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.20-1.55), blacks (HR, 2.00; 95% CI, 1.71-2.33), and those with papillary histology (HR, 1.72; 95% CI, 1.41-2.10). Risk of metachronous disease decreased with increasing age at primary diagnosis (HR per 1-year increase, 0.97; 95% CI, 0.96-0.97). The SIRs were highest among those diagnosed at a younger age and remained elevated even after extended follow-up (>10 years). Conclusions Our findings suggest that the cumulative incidence of metachronous, contralateral RCC may be higher than previously reported. Younger age, black race, papillary histology, and male sex increase the risk of metachronous, contralateral RCC development. The high SIRs seen in all demographic groups may support a rationale for lifelong surveillance, especially in high-risk subgroups with early disease onset.
- Published
- 2018
24. Novel Liquid Biomarkers and Innovative Imaging for Kidney Cancer Diagnosis: What Can Be Implemented in Our Practice Today? A Systematic Review of the Literature
- Author
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Riccardo Campi, Antonio Finelli, Axel Bex, Michael Staehler, Brian Shuch, Saeed Dabestani, Umberto Capitanio, Grant D. Stewart, Markus A. Kuczyk, and Börje Ljungberg
- Subjects
medicine.medical_specialty ,Urology ,Urinary system ,030232 urology & nephrology ,MEDLINE ,Context (language use) ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Epidemiology ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Carcinoma, Renal Cell ,Retrospective Studies ,business.industry ,Gold standard (test) ,medicine.disease ,Kidney Neoplasms ,Clinical trial ,Oncology ,030220 oncology & carcinogenesis ,Surgery ,Radiology ,business ,Kidney cancer ,Biomarkers - Abstract
Context The epidemiological signature of renal cell carcinoma (RCC) during the past decades is explained by overdetection and overtreatment of indolent cancers; furthermore, a non-negligible proportion of patients undergoing surgery for suspected RCC harbour benign renal tumours. As the gold standard for RCC diagnosis remains histopathological analysis of surgical or biopsy specimens, implementation of noninvasive diagnostic strategies to discriminate between benign and malignant renal masses is an urgent unmet need. Objective To systematically review novel liquid biomarkers and imaging modalities for RCC diagnosis. Evidence acquisition A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42020190773) using the MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUADAS 2 tool. Evidence synthesis Overall, 15 studies (six on biomarkers and nine on imaging) and eight clinical trials were included. None of the biomarkers or imaging modalities has been validated or shown to have a distinct clinical value for RCC. Specific combinations of urinary cell-free and exosomal miRNAs, urinary miR-15a, and specific panels of urinary metabolites assessed by metabolomics appear promising. In addition, machine/deep learning algorithms and radiomics applied to cross-sectional images may have potential to improve RCC diagnosis. Most studies are limited by the retrospective design, size, and lack of external validation. Conclusions Liquid biomarkers or imaging modalities are not ready for integration in the clinic and further well-designed studies must validate preliminary findings and explore utility in clinical decision-making. Patient summary We provide a comprehensive overview of the currently available biomarkers (measured in blood or urine) and novel imaging tests (other than conventional imaging) to discriminate kidney cancer from benign renal masses in a noninvasive fashion. None of the biomarkers or imaging modalities studied was validated or added clinical value; therefore, none of them can be implemented in the clinic. However, these approaches appear to be promising for improving the diagnosis of kidney cancer in the future.
- Published
- 2020
25. PD11-11 SURVEILLANCE AND COMMUNICATION OF SURGICAL RESULTS IN LOCALIZED RENAL CELL CARCINOMA, RESULTS FROM A LARGE INTERNATIONAL PATIENT SURVEY
- Author
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Michael Staehler, Cristiane Decat Bergerot, Ithaar Derweesh, Brian Shuch, Dena Battle, and Adam P. Stern
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Surgical resection ,Surgical results ,medicine.medical_specialty ,Standard of care ,business.industry ,Urology ,urologic and male genital diseases ,medicine.disease ,female genital diseases and pregnancy complications ,Renal cell carcinoma ,Medicine ,Patient survey ,Radiology ,business ,neoplasms - Abstract
INTRODUCTION AND OBJECTIVE:Surgical resection remains the standard of care for localized Renal Cell Carcinoma (RCC). Approximately 75 percent of RCC patients will be diagnosed with localized diseas...
- Published
- 2020
26. Obesity and renal cell carcinoma risk by histologic subtype: A nested case-control study and meta-analysis
- Author
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Jonathan N. Hofmann, Douglas A. Corley, Mark P. Purdue, Catherine L. Callahan, Brian Shuch, Wei K. Zhao, and Wong Ho Chow
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Epidemiology ,030232 urology & nephrology ,Chromophobe cell ,California ,Article ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Renal cell carcinoma ,Internal medicine ,Odds Ratio ,medicine ,Humans ,Obesity ,Risk factor ,Carcinoma, Renal Cell ,Aged ,business.industry ,Not Otherwise Specified ,Case-control study ,Odds ratio ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,Logistic Models ,Case-Control Studies ,030220 oncology & carcinogenesis ,Relative risk ,Nested case-control study ,Female ,business - Abstract
Background Although obesity is an established risk factor for renal cell carcinoma (RCC), it is unclear whether this relationship varies across histologic subtypes. Methods We conducted a nested case-control study within the Kaiser Permanente Northern California (KPNC) health care network, and meta-analysis combining our results with those of previously published studies. Our KPNC study included 685 RCC cases [421 clear cell; 65 papillary; 24 chromophobe; 35 other; 141 not otherwise specified (NOS)] and 4266 controls. Subtype-specific odds ratios (ORs) and 95% confidence intervals (CIs) for categories of body mass index (BMI) and were computed from the case-control data using polytomous logistic regression. Findings from this and other relevant studies were combined by meta-analysis using a random effects model. Results In the KPNC study, obesity (BMI ≥ 30 kg/m2) was associated with clear cell RCC (OR 1.5, 95% CI 1.1–2.1) and chromophobe RCC (OR 2.5, 95%CI 0.8–8.1), but not with papillary RCC (OR 1.0, 95% CI 0.5–1.9). In meta-analysis including three additional studies, a similar pattern of summary relative risks (SRR) for obesity was observed across subtypes (clear cell: SRR 1.8, 95% CI 1.5–2.2; chromophobe: SRR 2.2, 95% CI 1.3–3.7; papillary, SRR 1.2, 95% CI 0.8–1.6). Conclusions These findings support the hypothesis that histologic subtypes of RCC possess distinct etiologic pathways, with obesity important for the development of clear cell and, possibly, chromophobe RCC, but not papillary RCC.
- Published
- 2018
27. Genomic heterogeneity and the small renal mass
- Author
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Marta Boeke, Yuval Kluger, Harriet M. Kluger, Daiki Ueno, Brian Shuch, Garrett M. Dancik, Kevin A. Nguyen, Zongzhi Liu, Adebowale J. Adeniran, Zuoquan Xie, Jamil Syed, Peter A. Humphrey, and Patrick McGillivray
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,DNA Copy Number Variations ,medicine.medical_treatment ,030232 urology & nephrology ,Biology ,Nephrectomy ,Article ,Genetic Heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Gene expression ,Biopsy ,Biomarkers, Tumor ,genomics ,medicine ,Carcinoma ,Humans ,biopsy ,Carcinoma, Renal Cell ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,Genome, Human ,Genetic heterogeneity ,Biopsy, Needle ,Cell Cycle ,active surveillance ,kidney cancer ,Cancer ,Middle Aged ,medicine.disease ,RCC ,Phenotype ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Clear cell renal cell carcinoma ,Editorial ,030220 oncology & carcinogenesis ,Female - Abstract
Purpose: Tumor heterogeneity may represent a barrier to preoperative genomic characterization by needle biopsy in clear cell renal cell carcinoma (ccRCC). The extent of heterogeneity in small renal tumors remains unknown. Therefore, we set out to evaluate heterogeneity in resected large and small renal tumors. Experimental Design: We conducted a study from 2013 to 2016 that evaluated 47 consecutive ccRCC tumors resected during radical or partial nephrectomy. Cases were designated as small (7 cm) tumors. Each tumor had three regions sampled. Copy-number variation (CNV) was assessed and gene expression analysis was performed to characterize the clear-cell A and B (ccA/ccB) profile and the cell-cycle progression (CCP) score. Genomic heterogeneity between three regions was evaluated using CNV subclonal events, regional expression profiles, and correlation between gene expression. Results: Twenty-three small and 24 large tumors were analyzed. Total CNVs and subclonal CNVs events were less frequent in small tumors (P < 0.001). Significant gene expression heterogeneity was observed for both CCP scores and ccA/ccB classifications. Larger tumors had more variance in CCP scores (P = 0.026). The distribution of ccA/ccB differed between small and large tumors with mixed ccA/ccB tumors occurring more frequently in the larger tumors (P = 0.024). Analysis of five mixed tumors (with both ccA/ccB regions) demonstrated the more aggressive ccB phenotype had greater CNV events (P = 0.014). Conclusions: Small renal tumors have much less genomic complexity and fewer subclonal events. Pretreatment genomic characterization with single-needle biopsy in small tumors may be useful to assess biologic potential and may influence therapy. Clin Cancer Res; 24(17); 4137–44. ©2018 AACR.
- Published
- 2018
28. Understanding racial disparities in renal cell carcinoma incidence: Estimates of population attributable risk in two U.S. populations
- Author
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Nathaniel Rothman, Douglas A. Corley, Mark P. Purdue, Brian Shuch, Wong Ho Chow, Wei K. Zhao, Barry I. Graubard, Catherine L. Callahan, Kendra Schwartz, Julie J. Ruterbusch, Jonathan N. Hofmann, and Debra T. Silverman
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Michigan ,Comorbidity ,Article ,California ,White People ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Renal cell carcinoma ,Risk Factors ,Epidemiology ,medicine ,Prevalence ,Electronic Health Records ,Humans ,030212 general & internal medicine ,Obesity ,Healthcare Disparities ,Carcinoma, Renal Cell ,Aged ,Chicago ,business.industry ,Incidence (epidemiology) ,Incidence ,Smoking ,Health Status Disparities ,Middle Aged ,medicine.disease ,Confidence interval ,Kidney Neoplasms ,Black or African American ,Oncology ,030220 oncology & carcinogenesis ,Case-Control Studies ,Attributable risk ,Hypertension ,Female ,business ,Kidney cancer ,Demography ,Kidney disease - Abstract
PURPOSE: Renal cell carcinoma (RCC) incidence is higher among black than white Americans. The reasons for this disparity remain unclear. METHODS: We calculated race- and sex-specific population attributable risk percentages (PAR%) and their 95% confidence intervals (CI) for hypertension and chronic kidney disease (CKD) among black and white subjects ≥50 years of age from the US Kidney Cancer Study (USKC; 965 cases, 953 controls), a case-control study in Chicago and Detroit, and a nested case-control study in the Kaiser Permanente Northern California health care network (KPNC; 2,162 cases, 21,484 controls). We also estimated PAR% for other modifiable RCC risk factors (cigarette smoking, obesity) in USKC. RESULTS: In USKC, the PAR% for hypertension was 50% (95%CI 24-77%) and 44% (95%CI 25-64%) among black women and men, respectively; and 29% (95%CI 13-44%) and 27% (95%CI 14-39%) for white women and men, respectively. In KPNC, the hypertension PAR% was 40% (95%CI 18-62%) and 23% (95%CI 2-44%) among black women and men, and 27% (95%CI 20-35%) and 19% (95%CI 14-24%) among white women and men, respectively. The PAR% for CKD in both studies ranged from 7-10% for black women and men but was negligible (
- Published
- 2019
29. Genetic testing for hereditary prostate cancer: Current status and limitations
- Author
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Michael S. Leapman, Jun Tu Zhen, Neeraj Agarwal, Kevin A. Nguyen, Xavier Llor, Brian Shuch, Erin Hofstatter, Jamil Syed, and Karina L. Brierley
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Genetic counseling ,MLH1 ,Polymorphism, Single Nucleotide ,Olaparib ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,CHEK2 ,Germ-Line Mutation ,Genetic testing ,BRCA2 Protein ,medicine.diagnostic_test ,BRCA1 Protein ,business.industry ,Prostatic Neoplasms ,Cancer ,medicine.disease ,Neoplasm Proteins ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,business - Abstract
A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. These include breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively), mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and ataxia telangiectasia mutated (ATM). Currently, there are no uniform guidelines on the definition of hereditary prostate cancer and genetic testing. With the advent of next-generation sequencing, which is capable of testing multiple genes simultaneously, and the approval of olaparib for BRCA1/BRCA2 or ATM-mutated, metastatic, castrate-resistant prostate cancer, it is being recognized that the results of genetic testing have an impact on therapeutic strategies. In this review, the authors examine the role of genetic counseling and testing, the challenges of insurance coverage for testing, the available germline and somatic testing panels, and the complexity of each testing method and its implications. Cancer 2018. © 2018 American Cancer Society.
- Published
- 2018
30. Analysis of mutation, selection, and epistasis: an informed approach to cancer clinical trials
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Brian Shuch, Jeffrey P. Townsend, Jon F Wilkins, and Vincent L. Cannataro
- Subjects
0301 basic medicine ,epistasis ,Mutation rate ,Natural selection ,Cancer ,natural selection ,Computational biology ,Biology ,medicine.disease ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,Oncology ,Drug development ,Mutation (genetic algorithm) ,Research Perspective ,evolution ,medicine ,Epistasis ,cancer ,mutation ,Selection (genetic algorithm) - Abstract
Currently, drug development efforts and clinical trials to test them are often prioritized by targeting genes with high frequencies of somatic variants among tumors. However, differences in oncogenic mutation rate-not necessarily the effect the variant has on tumor growth-contribute enormously to somatic variant frequency. We argue that decoupling the contributions of mutation and cancer lineage selection to the frequency of somatic variants among tumors is critical to understanding-and predicting-the therapeutic potential of different interventions. To provide an indicator of that strength of selection and therapeutic potential, the frequency at which we observe a given variant across patients must be modulated by our expectation given the mutation rate and target size to provide an indicator of that strength of selection and therapeutic potential. Additionally, antagonistic and synergistic epistasis among mutations also impacts the potential therapeutic benefit of targeted drug development. Quantitative approaches should be fostered that use the known genetic architectures of cancer types, decouple mutation rate, and provide rigorous guidance regarding investment in targeted drug development. By integrating evolutionary principles and detailed mechanistic knowledge into those approaches, we can maximize our ability to identify those targeted therapies most likely to yield substantial clinical benefit.
- Published
- 2018
31. 68Ga-FAPI-46 and 18F-FDG PET/CT in a patient with immune-related thyroiditis induced by immune checkpoint inhibitors
- Author
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Jeremie Calais, Sandy T. Liu, Shadfar Bahri, Johannes Czernin, Masatoshi Hotta, Matthias R. Benz, Andrei Gafita, Ida Sonni, Brian Shuch, and Run Yu
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Immune checkpoint inhibitors ,General Medicine ,medicine.disease ,Thyroiditis ,Text mining ,Immune system ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Fdg pet ct ,business - Published
- 2021
32. Advances in the Characterization of Clear Cell Papillary Renal Cell Carcinoma: Identifying the Sheep in Wolf’s Clothing
- Author
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Pauline Filippou, Sarah P. Psutka, and Brian Shuch
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,Urology ,MEDLINE ,medicine ,Clear cell papillary renal cell carcinoma ,medicine.disease ,business - Published
- 2021
33. Leukocyte telomere length and renal cell carcinoma survival in two studies
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Mark P. Purdue, Jonathan N. Hofmann, Qing Lan, Richard M. Cawthon, Catherine L. Callahan, Wong Ho Chow, Barry I. Graubard, Nathaniel Rothman, Brian Shuch, Andrea A. Baccarelli, Kendra Schwartz, and Julie J. Ruterbusch
- Subjects
Male ,0301 basic medicine ,Oncology ,renal cell carcinoma ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Epidemiology ,survival ,03 medical and health sciences ,0302 clinical medicine ,blood ,Renal cell carcinoma ,Internal medicine ,Biomarkers, Tumor ,Leukocytes ,telomere length ,Carcinoma ,Humans ,Medicine ,Carcinoma, Renal Cell ,Survival rate ,Telomere Shortening ,Aged ,Ovarian Neoplasms ,business.industry ,Proportional hazards model ,Hazard ratio ,Case-control study ,Prostatic Neoplasms ,kidney cancer ,Middle Aged ,Telomere ,Prognosis ,medicine.disease ,Kidney Neoplasms ,Confidence interval ,Survival Rate ,030104 developmental biology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,Colorectal Neoplasms ,business ,Kidney cancer - Abstract
Background: Leukocyte telomere length (LTL) is a potential biomarker of cancer prognosis; however, evidence for renal cell carcinoma (RCC) is inconsistent. Methods: We investigated LTL and RCC-specific survival among 684 cases from the US kidney cancer study (USKC) and 241 cases from the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO). Leukocyte telomere length was measured by quantitative polymerase chain reaction, and hazard ratios (HRs) and 95% confidence intervals (CIs) computed using multivariable Cox models. Results: Short LTL was associated with poorer disease-specific survival in both USKC (lowest vs highest quartile: HR: 2.3, 95% CI: 1.2–4.4; P for trend=0.02) and PLCO (HR: 2.4, 95% CI: 1.0–5.4; P=0.04). Among USKC cases, the association was strongest for stage-I RCC (HR: 5.5, 95% CI: 1.6–19.0; P=0.006). Conclusions: Our findings suggest that shorter LTL is an independent marker of poor RCC prognosis, particularly for stage-I disease.
- Published
- 2017
34. Transforming the Perioperative Treatment Paradigm in Non-Metastatic RCC—A Possible Path Forward
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Daniel J. George, Primo N. Lara, Rupal S. Bhatt, E.M. Van Allen, David F. McDermott, Charles G. Drake, Michael A.S. Jewett, Daniel Y.C. Heng, Judith Manola, Maneka Puligandla, Lauren C. Harshman, Sabina Signoretti, David Cella, Toni K. Choueiri, D. Michaelson, Rajan T. Gupta, Naomi B. Haas, Michael A. Carducci, Anil Kapoor, Mohammad E. Allaf, and Brian Shuch
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,PD-1 blockade ,Review ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,adjuvant ,Renal cell carcinoma ,law ,Internal medicine ,medicine ,Adjuvant therapy ,Clinical endpoint ,nephrectomy ,PROSPER RCC ,recurrence-free survival ,priming ,EA8143 ,nivolumab ,business.industry ,neoadjuvant ,Perioperative ,medicine.disease ,Nephrectomy ,Surgery ,Clinical trial ,030104 developmental biology ,Nephrology ,030220 oncology & carcinogenesis ,Nivolumab ,business - Abstract
In 2017, there is no adjuvant systemic therapy proven to increase overall survival in non-metastatic renal cell carcinoma (RCC). The anti-PD-1 antibody nivolumab improves overall survival in metastatic treatment refractory RCC and is generally tolerable. Mouse solid tumor models have revealed a benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivolumab in RCC patients have shown preliminary feasibility and safety with no surgical delays or complications. The recently opened PROSPER RCC trial (A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy; EA8143) will examine if the addition of perioperative nivolumab to radical or partial nephrectomy can improve clinical outcomes in patients with high risk localized and locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in non-metastatic RCC, we are executing a three-pronged, multidisciplinary approach of presurgical priming with nivolumab followed by resection and adjuvant PD-1 blockade. We plan to enroll 766 patients with clinical stage ≥T2 or node positive M0 RCC of any histology in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. The investigational arm will receive two doses of nivolumab 240 mg IV prior to surgery followed by adjuvant nivolumab for 9 months. The control arm will undergo the current standard of care: surgical resection followed by observation. Patients are stratified by clinical T stage, node positivity, and histology. The trial is powered to detect a 14.4% absolute benefit in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 years (HR = 0.70). The study is also powered to detect a significant overall survival benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the impact of the baseline immune milieu and changes after neoadjuvant priming on clinical outcomes.
- Published
- 2017
35. Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology
- Author
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Elizabeth R. Plimack, Guru Sonpavde, Clayton Lau, Jeffrey A. Sosman, Thomas Olencki, Phillip M. Pierorazio, Rashmi Kumar, Thomas H. Gallagher, Won Kim, Ithaar Derweesh, Brian Shuch, Steven L. Hancock, Christos Kyriakopoulos, Chad A. LaGrange, Michael R. Harrison, Neeraj Agarwal, M. Dror Michaelson, Mary A. Dwyer, William P Bro, Toni K. Choueiri, Bruce G. Redman, Robert J. Motzer, John L. Gore, Brad Somer, Brian A. Costello, Eric Jonasch, Sam S. Chang, Sam B. Bhayani, Elaine T. Lam, and Mayer Fishman
- Subjects
medicine.medical_specialty ,030232 urology & nephrology ,MEDLINE ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Multidisciplinary approach ,Interim ,medicine ,Humans ,Disease management (health) ,Intensive care medicine ,Continuous evolution ,Neoplasm Staging ,business.industry ,Disease Management ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Kidney Neoplasms ,Clinical Practice ,Oncology ,030220 oncology & carcinogenesis ,Retreatment ,business ,Kidney cancer ,Renal carcinoma - Abstract
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.
- Published
- 2017
36. Ablative Therapies for Early Stage Kidney Cancer and the Evolving Role of the Urologist
- Author
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Joshua A. Halpern, Jim C. Hu, Aaron A. Laviana, Brian Shuch, Hung-Jui Tan, and Andrew T. Lenis
- Subjects
medicine.medical_specialty ,Percutaneous ,business.industry ,Ablation Techniques ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Ablation ,medicine.disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Ablative case ,Epidemiology ,Carcinoma ,Medicine ,Stage (cooking) ,business ,Kidney cancer - Abstract
Introduction The modern treatment paradigms for early stage kidney cancer include ablative therapies. Unlike surgical ablation, percutaneous ablation uses a radiographic platform, potentially altering the role of the urologist. We compared surgical and percutaneous ablation regarding treatment processes and outcomes. Methods Using SEER (Surveillance, Epidemiology and End Results)-Medicare data, we identified subjects undergoing surgical or percutaneous ablation between 2006 and 2009 for stage I kidney cancer. We evaluated outcomes relating to 30-day complications, unplanned hospital admissions, long-term survival and mortality. Adjusting for patient characteristics, we compared processes and outcomes according to ablation approach using generalized estimating equations and Cox proportional hazard models, respectively. Results We identified 376 subjects (45.8%) treated with surgical ablation and 444 (54.1%) treated with percutaneous ablation. Use of percutaneous ablation increased substantially during the study period. Compared to surgical ablation, percutaneous ablation was applied more often in the outpatient setting (71.2% vs 2.4%, p Conclusions Percutaneous ablation has become the most common ablative modality for early stage kidney cancer. Although percutaneous ablation carries a more favorable safety profile, posttreatment morbidity occurs with some frequency, highlighting the need for continued urologist engagement.
- Published
- 2017
37. MP50-20 CLINICAL CONSENSUS STATEMENT
- Author
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Anhyo Jeong, Neil Mendhiratta, Gennady Bratslavsky, Ramaprasad Srinivasan, Eric Jonasch, Michael Daneshvar, Brian Shuch, and Othon Iliopoulos
- Subjects
medicine.medical_specialty ,business.industry ,Statement (logic) ,Urology ,Medicine ,Genetic risk ,business ,Intensive care medicine ,medicine.disease ,Kidney cancer - Published
- 2020
38. Adverse Histopathologic Characteristics in Small Clear Cell Renal Cell Carcinomas Have Negative Impact on Prognosis: A Study of 631 Cases With Clinical Follow-up
- Author
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Maria F. Serrano, Chen Yang, Peter A. Humphrey, Adebowale J. Adeniran, Cayce Nawaf, Robin T. Vollmer, Adam S. Kibel, and Brian Shuch
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Cell ,030232 urology & nephrology ,urologic and male genital diseases ,Malignancy ,Nephrectomy ,Risk Assessment ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine ,Carcinoma ,Humans ,Carcinoma, Renal Cell ,Aged ,Retrospective Studies ,Aged, 80 and over ,Tumor size ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,Tumor Burden ,Clear cell renal cell carcinoma ,Editorial Commentary ,medicine.anatomical_structure ,Treatment Outcome ,030220 oncology & carcinogenesis ,Surgery ,Female ,Anatomy ,business ,Clear cell ,Follow-Up Studies - Abstract
Tumor size has been used for decision making in the management of patients with renal masses. Active surveillance in selected patients is now increasingly common in tumors ≤4 cm in size. Clear cell renal cell carcinoma (CCRCC) is the most common type of renal malignancy. Adverse histopathologic characteristics that correlate with worse prognosis have been described in CCRCCs. The aim of our study was to determine the frequency and extent of adverse histopathologic characteristics in CCRCCs ≤4 cm and their association with patient outcome. A search of a single institution for nephrectomies performed for CCRCC identified 631 consecutive cases. Cases were reviewed for the following morphologic features: high nuclear grade, necrosis, lymphovascular invasion, and rhabdoid or sarcomatoid histology. Relationships between the variables were examined by Kruskal-Wallis test, Wilcoxon test, χ test, and logistic regression. We found adverse tumor histopathologic characteristics were significantly related to size: In CCRCCs4 versus ≤4 cm, there were more high nuclear grade (45% vs. 15%, P0.01), necrosis (46% vs. 21%, P0.01), and lymphovascular invasion (17% vs. 3%, P0.01). Although adverse histologic features are less commonly seen in CCRCCs ≤4 cm, their presence was associated with lower disease-free survival (P0.01). Adverse histopathologic characteristics in CCRCCs ≤4 cm correlated with worse prognosis and identification of these features through needle core biopsy examination may guide clinical management, especially in patients for whom active surveillance is considered.
- Published
- 2019
39. Brain Metastasis From Renal-Cell Carcinoma: An Institutional Study
- Author
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Jamil Syed, Kamyar Ghabili, Michael E. Hurwitz, Sandy T. Liu, Kevin A. Nguyen, Alfredo Suarez-Sarmiento, Veronica Chiang, Michelle Cheng, Harriet M. Kluger, Brian Shuch, and Adam Nolte
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Urology ,030232 urology & nephrology ,urologic and male genital diseases ,Systemic therapy ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,medicine ,Carcinoma ,Humans ,Cumulative incidence ,Carcinoma, Renal Cell ,Aged ,Retrospective Studies ,business.industry ,Brain Neoplasms ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,female genital diseases and pregnancy complications ,Kidney Neoplasms ,Clinical trial ,030220 oncology & carcinogenesis ,Clear cell carcinoma ,Female ,medicine.symptom ,business ,Brain metastasis - Abstract
Background Brain metastases (BM) are frequently observed in advanced renal-cell carcinoma (RCC). Historically these individuals have been excluded from clinical trials, but recently, with better local control, many can receive aggressive therapy after treatment. We evaluate our single-institution experience over various treatment eras. Patients and Methods Patients undergoing evaluation for RCC BM from 2001 to 2018 were identified from our institutional database. Clinical notes, demographics, comorbidities, histology, central nervous system (CNS) treatments, systemic therapy, and outcomes were reviewed. Overall survival (OS) and CNS recurrence-free survival (RFS) were evaluated by the Kaplan-Meier method. Cumulative incidence was evaluated using a competing risk model. Results We identified 158 patients with RCC BM, of whom 94.4% had clear-cell RCC, and 90.6% had extracranial metastases at diagnosis. Of these patients, 94 (60%) developed RCC BM over time, while 46 (29.1%) had RCC BM at initial presentation. Clinical symptoms were noted in 81.9% of patients. The median OS after diagnosis of RCC BM was 8.4 months, with a 3-year OS of 28.2%. The median CNS RFS was 8.5 months overall; however, those with one and more than one lesion had median CNS RFS of 12.4 and 6 months, respectively (P Conclusion The majority of RCC patients with BM are symptomatic and had prior metastatic disease that progressed to the brain. Those with a solitary RCC BM are less likely to develop CNS recurrence after local therapy and are ideal candidates for enrollment onto clinical trials.
- Published
- 2019
40. The future of perioperative therapy in advanced renal cell carcinoma: how can we PROSPER?
- Author
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M.D. Michaelson, Walter M. Stadler, Suzanne Cole, Anil Kapoor, Robert S. Svatek, Lynne I. Wagner, Naomi B. Haas, Hiten D. Patel, Scott E. Eggener, Eric A. Singer, Sabina Signoretti, David Cella, Maneka Puligandla, Michael A. Carducci, Mohamad E. Allaf, Primo N. Lara, David F. McDermott, Viraj A. Master, Charles G. Drake, Lauren C. Harshman, Deborah Maskens, Bradley C. Leibovich, Brian Shuch, Daniel Y.C. Heng, Toni K. Choueiri, and Rajan T. Gupta
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Clinical Trial Protocol ,medicine.medical_treatment ,Nephrectomy ,Perioperative Care ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Clinical Protocols ,Renal cell carcinoma ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Molecular Targeted Therapy ,Carcinoma, Renal Cell ,Neoadjuvant therapy ,Neoplasm Staging ,business.industry ,General Medicine ,Perioperative ,medicine.disease ,Combined Modality Therapy ,Kidney Neoplasms ,Neoadjuvant Therapy ,Clinical trial ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Disease Susceptibility ,Nivolumab ,business ,Kidney cancer ,Adjuvant - Abstract
Patients with high-risk renal cell carcinoma (RCC) experience high rates of recurrence despite definitive surgical resection. Recent trials of adjuvant tyrosine kinase inhibitor therapy have provided conflicting efficacy results at the cost of significant adverse events. PD-1 blockade via monoclonal antibodies has emerged as an effective disease-modifying treatment for metastatic RCC. There is emerging data across other solid tumors of the potential efficacy of neoadjuvant PD-1 blockade, and preclinical evidence supporting a neoadjuvant over adjuvant approach. PROSPER RCC is a Phase III, randomized trial evaluating whether perioperative nivolumab increases recurrence-free survival in patients with high-risk RCC undergoing nephrectomy. The neoadjuvant component, intended to prime the immune system for enhanced efficacy, distinguishes PROSPER from other purely adjuvant studies and permits highly clinically relevant translational studies.
- Published
- 2019
41. Development of a 2-dimensional atlas of the human kidney with imaging mass cytometry
- Author
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Lloyd G. Cantley, Brian Shuch, Judith A. Kliegel, Nikhil Singh, Zachary M. Avigan, Ruth R. Montgomery, and Gilbert W. Moeckel
- Subjects
0301 basic medicine ,Nephrology ,Adult ,Male ,Models, Anatomic ,medicine.medical_specialty ,Cell type ,Pathology ,Concurrent analysis ,Biology ,Kidney ,Antibodies ,Machine Learning ,03 medical and health sciences ,0302 clinical medicine ,Atlases as Topic ,Internal medicine ,medicine ,Humans ,Mass cytometry ,Aged ,Image Cytometry ,medicine.diagnostic_test ,Reproducibility of Results ,Human kidney ,General Medicine ,Baseline data ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Renal biopsy ,Kidney disease - Abstract
An incomplete understanding of the biology of the human kidney, including the relative abundances of and interactions between intrinsic and immune cells, has long constrained the development of therapies for kidney disease. The small amount of tissue obtained by renal biopsy has previously limited the ability to use patient samples for discovery purposes. Imaging mass cytometry (IMC) is an ideal technology for quantitative interrogation of scarce samples, permitting concurrent analysis of more than 40 markers on a single tissue section. Using a validated panel of metal-conjugated antibodies designed to confer unique signatures on the structural and infiltrating cells comprising the human kidney, we performed simultaneous multiplexed imaging with IMC in 23 channels on 16 histopathologically normal human samples. We devised a machine-learning pipeline (Kidney-MAPPS) to perform single-cell segmentation, phenotyping, and quantification, thus creating a spatially preserved quantitative atlas of the normal human kidney. These data define selected baseline renal cell types, respective numbers, organization, and variability. We demonstrate the utility of IMC coupled to Kidney-MAPPS to qualitatively and quantitatively distinguish individual cell types and reveal expected as well as potentially novel abnormalities in diseased versus normal tissue. Our studies define a critical baseline data set for future quantitative analysis of human kidney disease.
- Published
- 2019
42. Familial Kidney Cancer: Implications of New Syndromes and Molecular Insights
- Author
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Ying-Bei Chen, Victor E. Reuter, A. Ari Hakimi, Gennady Bratslavsky, James Brugarolas, Kenneth Offit, Maria J. Merino, Maria I. Carlo, W. Marston Linehan, Jonathan A. Coleman, Brian Shuch, Eamonn R. Maher, Grant D. Stewart, Stewart, Grant [0000-0003-3188-9140], Maher, Eamonn [0000-0002-6226-6918], and Apollo - University of Cambridge Repository
- Subjects
Skin Neoplasms ,von Hippel-Lindau Disease ,Urology ,Genetic counseling ,030232 urology & nephrology ,Hereditary Papillary Renal Cell Carcinoma ,Context (language use) ,urologic and male genital diseases ,Bioinformatics ,Birt–Hogg–Dubé syndrome ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Neoplastic Syndromes, Hereditary ,Tuberous Sclerosis ,Leiomyomatosis ,Medicine ,Humans ,Carcinoma, Renal Cell ,Genetic counselling ,business.industry ,Birt-Hogg-Dubé syndrome ,Cancer ,Hereditary papillary renal cell carcinoma ,Kidney cancer ,Syndrome ,medicine.disease ,Hereditary cancer ,Hereditary leiomyomatosis renal cell carcinoma ,Tuberous sclerosis complex ,030220 oncology & carcinogenesis ,Uterine Neoplasms ,Hereditary leiomyomatosis and renal cell carcinoma ,business - Abstract
Context Hereditary cases account for about 5% of all cases of renal cell carcinoma (RCC). With advances in next-generation sequencing, several new hereditary syndromes have been described in the last few years. Objective To review and summarise the recent preclinical and clinical literature in hereditary renal cancer. Evidence acquisition A systematic review of the literature was performed in November 2018 using PubMed and OMIM databases, with an emphasis on kidney cancer, genetics and genomics, clinical criteria, and management. Evidence synthesis Several autosomal dominant hereditary RCC syndromes have been described, including those related to germline pathogenic variants in VHL, MET, FH, TSC1/TSC2, FLCN, SDHA/B/C/D, BAP1, CDC73, and MITF. Clinical spectrum of SDH, BAP1, and MITF is still being defined, although these appear to be associated with a lower incidence of RCC. FH and likely BAP1 RCC are associated with more aggressive disease. Preclinical and clinical studies show that using systemic therapy that exploits specific genetic pathways is a promising strategy. Conclusions There are several well-described hereditary RCC syndromes, as well as recently identified ones, for which the full clinical spectrum is yet to be defined. In the new era of precision medicine, identification of these syndromes may play an important role in management and systemic treatment selection. Patient summary This review covers updates in the diagnosis and management of familial kidney cancer syndromes. We describe updates in testing and management of the most common syndromes such as von Hippel-Lindau, and hereditary leiomyomatosis and renal cell carcinoma. We also provide insights into recently described familial kidney cancer syndromes.
- Published
- 2019
43. MP29-16 THE ASSOCIATION BETWEEN THE AFFORDABLE CARE ACT, INSURANCE STATUS, AND TREATMENT AMONG PATIENTS WITH TESTICULAR CANCER
- Author
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Amy J. Davidoff, Ahmedin Jemal, Michael S. Leapman, Henry Park, Walter Hsiang, Brian Shuch, James B. Yu, Cary P. Gross, and Kevin A. Nguyen
- Subjects
medicine.medical_specialty ,business.industry ,Urology ,Family medicine ,Insurance status ,Health insurance ,Medicine ,Young adult ,business ,Association (psychology) ,medicine.disease ,Testicular cancer - Abstract
INTRODUCTION AND OBJECTIVES:Young adults are historically the least likely to have health insurance in the United States. We aimed to investigate whether implementation of key provisions of the Aff...
- Published
- 2019
44. MP14-03 THE UCLA HISTO-GENETIC RISK CLASSIFICATION (U-HGRC) TO PREDICT OUTCOMES OF LOCALIZED CLEAR-CELL RENAL CELL CARCINOMA
- Author
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Nils Kroeger, Allan J. Pantuck, Cedric Lebacle, Aydin Pooli, Erika L. Wood, Karim Chamie, Alexandra Drakaki, Grace-Hyun Kim, Izak Faiena, Nagesh Rao, Brian Shuch, Sandy T. Liu, and Arie S. Belldegrun
- Subjects
Oncology ,Clear cell renal cell carcinoma ,medicine.medical_specialty ,business.industry ,Urology ,Internal medicine ,medicine ,Genetic risk ,medicine.disease ,business - Published
- 2019
45. Telemedicine-Based Perioperative Management of Pheochromocytoma in a Patient With Von Hippel Lindau Disease: A Case Report
- Author
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Lucas Cusumano, Run Yu, Timothy Donahue, Brian Shuch, Catharina Alapag, Nirav Kamdar, and Dane Saksa
- Subjects
medicine.medical_specialty ,Telemedicine ,von Hippel-Lindau Disease ,endocrine system diseases ,medicine.medical_treatment ,Adrenal Gland Neoplasms ,Pheochromocytoma ,Pancreaticoduodenectomy ,Resection ,Pregnancy ,medicine ,Humans ,Von Hippel–Lindau disease ,neoplasms ,Remote management ,Perioperative management ,business.industry ,General surgery ,General Medicine ,medicine.disease ,Secure messaging ,Female ,business - Abstract
We present the case of a young woman with Von Hippel Lindau (VHL) disease who underwent a combined pheochromocytoma resection along with pancreaticoduodenectomy. Her preoperative management, including effective alpha-blockade, was conducted remotely via telemedicine video visits, patient-entered vital sign data, and secure messaging between provider and patient. Similar remote management was undertaken before a subsequent pheochromocytoma resection while the patient was pregnant, and both surgeries had positive outcomes. This represents the first time that telemedicine and mobile health monitoring have been successfully used for preoperative alpha-blockade in a high-acuity patient before a complex multivisceral surgery.
- Published
- 2021
46. Vascular Endothelial Growth Factor Receptor–Targeted Therapy in Succinate Dehydrogenase C Kidney Cancer
- Author
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Christopher J. Ricketts, Maria J. Merino, Nnenaya Q. Agochukwu, Rabindra Gautam, Ramaparasad Srinivasan, Cathy D. Vocke, Brian Shuch, and W. Marston Linehan
- Subjects
Cancer Research ,Indoles ,medicine.medical_treatment ,Vascular Endothelial Growth Factor Receptor ,030232 urology & nephrology ,Antineoplastic Agents ,Article ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Sunitinib ,medicine ,Humans ,Pyrroles ,Molecular Targeted Therapy ,Carcinoma, Renal Cell ,Protein Kinase Inhibitors ,Germ-Line Mutation ,Vascular Endothelial Growth Factor Receptor-1 ,biology ,business.industry ,Succinate dehydrogenase ,Membrane Proteins ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Kidney Neoplasms ,Pedigree ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Female ,business ,Kidney cancer - Published
- 2016
47. Hereditary Renal Cell Carcinoma Syndromes
- Author
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Brian Shuch, Peter A. Humphrey, and Adebowale J. Adeniran
- Subjects
Pathology ,medicine.medical_specialty ,Heredity ,Cell ,urologic and male genital diseases ,medicine.disease_cause ,Pathology and Forensic Medicine ,Neoplastic Syndromes, Hereditary ,Predictive Value of Tests ,Biomarkers, Tumor ,Carcinoma ,medicine ,Humans ,Genetic Predisposition to Disease ,Carcinoma, Renal Cell ,Pathological ,business.industry ,Prognosis ,medicine.disease ,Kidney Neoplasms ,Pedigree ,Phenotype ,medicine.anatomical_structure ,Renal pathology ,Surgery ,Anatomy ,Age of onset ,business ,Carcinogenesis ,Kidney cancer - Abstract
Renal cell carcinomas associated with syndromes of a heritable nature account for about 4% of all renal cell carcinomas. They are characterized by an earlier age of onset, and are often multicentric and bilateral. Some of these patients may fit into well-characterized kidney cancer syndromes, while many more may have a genetic component that is not fully recognized or understood. The presence of extrarenal clinical features may suggest a specific renal tumor susceptibility syndrome. Moreover, each syndrome is associated with specific renal pathology findings. Recognition of individuals and families with a high risk of renal neoplasia is important so that surveillance for renal tumors may be initiated. This manuscript reviews the clinical, pathological, and molecular features of hereditary renal cell carcinoma syndromes with emphasis on the morphologic features of these tumors and the molecular mechanisms of hereditary renal tumorigenesis.
- Published
- 2015
48. Current Treatment Landscape of Advanced Papillary Renal Cancer
- Author
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Neeraj Agarwal, Brian Shuch, and Andrew W. Hahn
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,MEDLINE ,Cancer ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Carcinoma ,Current (fluid) ,business - Published
- 2017
49. Minimally invasive partial nephrectomy versus percutaneous cryoablation for stage Ia renal cell carcinoma: A cost-effectiveness analysis
- Author
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Kevin Kim, Xiao Wu, Brian Shuch, and Johannes Uhlig
- Subjects
Cancer Research ,medicine.medical_specialty ,Percutaneous cryoablation ,business.industry ,medicine.medical_treatment ,Urology ,Cost-effectiveness analysis ,medicine.disease ,Nephrectomy ,Oncology ,Renal cell carcinoma ,medicine ,Treatment strategy ,Stage (cooking) ,business - Abstract
e17066 Background: Minimally invasive partial nephrectomy (PN) and percutaneous cryoablation (Cryo) are treatment strategies for renal cell carcinoma (RCC). The purpose of this study is to assess the cost-effectiveness of PN and Cryo for stage Ia RCC. Methods: A decision-analysis model was constructed over 5 years from a health care sector’s perspective using TreeAge Pro Suite 2019 (TreeAge Software LLC, Cambridge, MA). The two evaluated strategies were PN and Cryo. The model incorporated the clinical course of stage Ia RCC after either treatment, including costs and quality of life associated with major complications, imaging surveillance (based on 2014 National Comprehensive Cancer Network guidelines), local and metastatic recurrences, and cancer-specific mortality. All clinical parameters were derived from the literature. A willingness-to-pay threshold of $100,000/quality adjusted life year (QALY) was used. 1 QALY is equivalent to 1 year of life in perfect health. Outcomes were measured by incremental effectiveness ratio. Base case calculations, Monte Carlo Simulations with 10,000 iterations using bootstrapping for parameters from their distributions, and multiple sensitivity analyses were performed. Results: Five-year local recurrence-free, metastasis-free, and cancer-specific survival from recent literature were 97.7% versus 95.9% ( p = 0.18), 98.0% versus 100% ( p = 0.14), 99.3% versus 100% % ( p = 0.7) for PN and Cryo. PN and Cryo yielded similar health benefits of 3.63 QALY and 3.64 QALY. Overall costs were $26,343 and $19,346 for PN and Cryo. A total of 89.28% of the 10,000 simulations showed higher cost-effectiveness of Cryo than PN. One-way sensitivity analyses varying long-term outcomes after Cryo while keeping outcomes after PN constant, revealed that Cryo is more cost-effective than PN when its local recurrence risk is < 3.94% per year (18.2% over 5 years), metastasis risk is < 1.51% per year (7.33% over 5 years), or cancer-specific mortality risk is < 0.96% per year (4.7% over 5 years). PN is more cost-effective if Cryo local recurrence risk is 3.5% higher than PN per year, when the metastasis risk is 1.1% higher than PN per year, or when its cancer-specific mortality is more than 0.9% higher than PN per year. Cryo is more cost-effective than PN if its cost is not more than $1,000 higher than PN. Conclusions: Our study showed that Cryo is more cost-effective than PN for stage Ia RCC patients with comparable effectiveness at a lower cost, based on multiple probabilistic and deterministic sensitivity analyses.
- Published
- 2020
50. Clinically advanced renal cell carcinoma (RCC) and renal sarcoma (RSC) in young patients: A comprehensive genomic profiling (CGP) study
- Author
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Gennady Bratslavsky, Andrea Necchi, Amanda Hemmerich, Oleg Shapiro, Eric Allan Severson, Brian M. Alexander, Joseph M. Jacob, Natalie Danziger, Alexa B. Schrock, Venkataprasanth P. Reddy, Brian Shuch, Erik A. Williams, Jonathan Keith Killian, Julia A. Elvin, Petros Grivas, Jo-Anne Vergilio, Shakti H. Ramkissoon, Mehdi Mollapour, Jeffrey S. Ross, and Kimberly McGregor
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Genomic profiling ,biology ,business.industry ,medicine.disease ,Renal Sarcoma ,Renal cell carcinoma ,Internal medicine ,medicine ,biology.protein ,In patient ,Chromatin structure remodeling (RSC) complex ,business - Abstract
5066 Background: We queried whether the landscape of genomic alterations (GA) would differ in patients with metastatic RCC under 40 years of age (under40) and patients 40 years of age or older (over40). Methods: FFPE tissues from 2,128 clinically advanced RCC and 25 RSC underwent hybrid-capture based CGP to evaluate all classes of GA. Samples were classified at time of sequencing as the following RCC subtypes: clear cell (ccRCC), papillary (papRCC), chromophobe (chrRCC), medullary (medRCC), collecting duct (cdRC), sarcomatoid (sarcRCC) and NOS (nosRCC). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA. Tumor cell PD-L1 expression was determined by IHC (Dako 22C3). Results: The male preponderance increased in the over40 patients. The GA/tumor increased in the over40 cohorts except for medRCC. Similarly, TMB was consistently higher in over40 groups. MSI high status was virtually absent. PD-L1 expression, available only in small subsets, was generally absent although 44% high positive staining in sarcRCC was noteworthy. Differences in GA in under40 vs over40 RCC were seen and included increased PBRM1 and SETD2 GA in over40 vs under40 ccRCC; increased C DKN2A/B and TERT and decreased FH GA in over40 vs under40 papRCC; increased TP53 and decreased VHL, BAP1, SETD2 and PTEN in over40 vs under40 chrRCC; increased TP53, PTEN and TERT GA with decreased NF2 GA in over40 vs under 40 sarcRCC; and increased TP53, VHL and TERT in over40 vs under40 nosRCC. Changes in GA in under40 vs over40 medRCC, cdRCC and RSC were noted but insufficient cases prevented further evaluation. Conclusions: When separately evaluated by under/over 40 years of age, CGP of clinically advanced RCC demonstrates differences in genomic landscapes with over40 cases featuring increasing male preponderance, higher GA/tumor, higher TMB and increases in a variety of GA. These findings may play important roles in the planning of future clinical trials designed to personalize the treatment of metastatic RCC. [Table: see text]
- Published
- 2020
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