Xue Gong, Hongjuan Zhao, M. Saar, D. Peehl, J. Brooks
Background: Clear cell renal cell carcinoma (ccRCC) is molecularly diverse and distinct molecular subtypes show different clinical outcomes. MicroRNAs (miRNAs) are essential components of gene regulatory networks and play a crucial role in progression of many cancer types including ccRCC. Objective: Identify prognostic miRNAs and determine the role of miR-22 in ccRCC. Methods: Hierarchical clustering was done in R using gene expression profiles of over 450 ccRCC cases in The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis was performed to identify prognostic miRNAs in the TCGA dataset. RNA-Seq was performed to identify miR-22 target genes in primary ccRCC cells and Matrigel invasion assay was performed to assess the effects of miR-22 overexpression on cell invasion. Results: Hierarchical clustering analysis using 2,621 prognostic genes previously identified by our group demonstrated that ccRCC patients with longer overall survival expressed lower levels of genes promoting proliferation or immune responses, while better maintaining gene expression associated with cortical differentiation and cell adhesion. Targets of 26 miRNAs were significantly enriched in the 2,621 prognostic genes and these miRNAs were prognostic by themselves. MiR-22 was associated with poor overall survival in the TCGA dataset. Overexpression of miR-22 promoted invasion of primary ccRCC cells in vitro and modulated transcriptional programs implicated in cancer progression including DNA repair, cell proliferation and invasion. Conclusions: Our results suggest that ccRCCs with differential clinical outcomes have distinct transcriptomes for which miRNAs could serve as master regulators. MiR-22, as a master regulator, promotes ccRCC progression at least in part by enhancing cell invasion.
{"title":"miR-22 Regulates Invasion, Gene Expression and Predicts Overall Survival in Patients with Clear Cell Renal Cell Carcinoma","authors":"Xue Gong, Hongjuan Zhao, M. Saar, D. Peehl, J. Brooks","doi":"10.3233/KCA-190051","DOIUrl":"https://doi.org/10.3233/KCA-190051","url":null,"abstract":"Background: Clear cell renal cell carcinoma (ccRCC) is molecularly diverse and distinct molecular subtypes show different clinical outcomes. MicroRNAs (miRNAs) are essential components of gene regulatory networks and play a crucial role in progression of many cancer types including ccRCC. Objective: Identify prognostic miRNAs and determine the role of miR-22 in ccRCC. Methods: Hierarchical clustering was done in R using gene expression profiles of over 450 ccRCC cases in The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis was performed to identify prognostic miRNAs in the TCGA dataset. RNA-Seq was performed to identify miR-22 target genes in primary ccRCC cells and Matrigel invasion assay was performed to assess the effects of miR-22 overexpression on cell invasion. Results: Hierarchical clustering analysis using 2,621 prognostic genes previously identified by our group demonstrated that ccRCC patients with longer overall survival expressed lower levels of genes promoting proliferation or immune responses, while better maintaining gene expression associated with cortical differentiation and cell adhesion. Targets of 26 miRNAs were significantly enriched in the 2,621 prognostic genes and these miRNAs were prognostic by themselves. MiR-22 was associated with poor overall survival in the TCGA dataset. Overexpression of miR-22 promoted invasion of primary ccRCC cells in vitro and modulated transcriptional programs implicated in cancer progression including DNA repair, cell proliferation and invasion. Conclusions: Our results suggest that ccRCCs with differential clinical outcomes have distinct transcriptomes for which miRNAs could serve as master regulators. MiR-22, as a master regulator, promotes ccRCC progression at least in part by enhancing cell invasion.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"3 1","pages":"119 - 132"},"PeriodicalIF":1.2,"publicationDate":"2019-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43761464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Synold, M. Plets, C. Tangen, E. Heath, G. Palapattu, P. Mack, M. Stein, M. Meng, P. Lara, N. Vogelzang, I. Thompson, C. Ryan
Background: S0931 is assessing recurrence-free survival in renal cell carcinoma (RCC) patients randomized to receive everolimus (EVE) versus placebo for one year following nephrectomy. Due to a higher than expected dropout rate, we assessed EVE trough levels in the adjuvant setting to evaluate the relationship between EVE exposure and probability of toxicity. Methods: Patients received 10 mg daily EVE for nine 6-week cycles. Pre-dose whole blood samples were collected pre-cycle 2 and pre-cycle 3 and analyzed for EVE. Patients with pre-cycle 2 and/or pre-cycle 3 EVE results were used in the analysis. Patients were segregated into quartiles (Q) based on EVE levels and logistic regression was used to model the most common adverse event outcomes using EVE trough as a predictor. Hazard and odds ratios were adjusted for age, BMI and performance status. Results: A total of 467 patients were included in this analysis. Quartiles normalized to an EVE dose of 10 mg/day were < 9.0, 9.0–12.9, 12.9–22.8, and > 22.8 ng/mL, respectively. EVE trough levels increased with increasing age (p < 0.001). Furthermore, EVE trough levels were higher in men than women (19.4 versus 15.4 ng/mL, p = 0.01). Risk of grade 2 + triglycerides was increased in Q2 and Q3 vs Q1 (OR = 2.08; p = 0.02 and OR = 2.63; p = 0.002). Risk of grade 2 + rash was increased in Q2 and Q4 vs Q1 (OR = 2.99; p = 0.01 and OR = 2.90; p = 0.02). There was also an increased risk of any grade 3 + tox in Q2 vs Q1 (OR = 1.71; p = 0.05). Conclusions: We identified significant gender and age-related differences in EVE trough levels in patients receiving adjuvant treatment for RCC. Furthermore, our analysis identified significant associations between EVE exposure and probability of toxicity.
背景:S0931正在评估肾细胞癌(RCC)患者在肾切除术后随机接受依维莫司(EVE)和安慰剂治疗一年的无复发生存率。由于退出率高于预期，我们评估了佐剂环境下EVE的低谷水平，以评估EVE暴露与毒性可能性之间的关系。方法:患者接受每日10mg EVE治疗，共9个6周周期。在第2周期和第3周期前采集给药前全血样本，分析EVE。第2周期前和/或第3周期前患者的EVE结果被用于分析。根据EVE水平将患者分为四分位数(Q)，并使用逻辑回归对最常见的不良事件结局进行建模，并使用EVE槽作为预测因子。危险比和优势比根据年龄、身体质量指数和表现状况进行调整。结果:共纳入467例患者。按EVE剂量10毫克/天归一化的四分位数分别为22.8纳克/毫升。EVE波谷水平随着年龄的增长而增加(p < 0.001)。此外，男性EVE波谷水平高于女性(19.4 ng/mL vs 15.4 ng/mL, p = 0.01)。与Q1相比，Q2和Q3的2 +级甘油三酯风险增加(OR = 2.08;p = 0.02, OR = 2.63;p = 0.002)。与Q1相比，Q2和Q4出现2 +级皮疹的风险增加(OR = 2.99;p = 0.01, OR = 2.90;p = 0.02)。Q2组与Q1组相比，任何3 +级毒性的风险也增加(OR = 1.71;p = 0.05)。结论:我们发现在接受RCC辅助治疗的患者中EVE谷水平存在显著的性别和年龄相关差异。此外，我们的分析确定了EVE暴露与毒性概率之间的显著关联。
{"title":"Everolimus Exposure as a Predictor of Toxicity in Renal Cell Cancer Patients in the Adjuvant Setting: Results of a Pharmacokinetic Analysis for SWOG S0931 (EVEREST), a Phase III Study (NCT01120249)","authors":"T. Synold, M. Plets, C. Tangen, E. Heath, G. Palapattu, P. Mack, M. Stein, M. Meng, P. Lara, N. Vogelzang, I. Thompson, C. Ryan","doi":"10.3233/KCA-180049","DOIUrl":"https://doi.org/10.3233/KCA-180049","url":null,"abstract":"Background: S0931 is assessing recurrence-free survival in renal cell carcinoma (RCC) patients randomized to receive everolimus (EVE) versus placebo for one year following nephrectomy. Due to a higher than expected dropout rate, we assessed EVE trough levels in the adjuvant setting to evaluate the relationship between EVE exposure and probability of toxicity. Methods: Patients received 10 mg daily EVE for nine 6-week cycles. Pre-dose whole blood samples were collected pre-cycle 2 and pre-cycle 3 and analyzed for EVE. Patients with pre-cycle 2 and/or pre-cycle 3 EVE results were used in the analysis. Patients were segregated into quartiles (Q) based on EVE levels and logistic regression was used to model the most common adverse event outcomes using EVE trough as a predictor. Hazard and odds ratios were adjusted for age, BMI and performance status. Results: A total of 467 patients were included in this analysis. Quartiles normalized to an EVE dose of 10 mg/day were < 9.0, 9.0–12.9, 12.9–22.8, and > 22.8 ng/mL, respectively. EVE trough levels increased with increasing age (p < 0.001). Furthermore, EVE trough levels were higher in men than women (19.4 versus 15.4 ng/mL, p = 0.01). Risk of grade 2 + triglycerides was increased in Q2 and Q3 vs Q1 (OR = 2.08; p = 0.02 and OR = 2.63; p = 0.002). Risk of grade 2 + rash was increased in Q2 and Q4 vs Q1 (OR = 2.99; p = 0.01 and OR = 2.90; p = 0.02). There was also an increased risk of any grade 3 + tox in Q2 vs Q1 (OR = 1.71; p = 0.05). Conclusions: We identified significant gender and age-related differences in EVE trough levels in patients receiving adjuvant treatment for RCC. Furthermore, our analysis identified significant associations between EVE exposure and probability of toxicity.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"3 1","pages":"111 - 118"},"PeriodicalIF":1.2,"publicationDate":"2019-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47744097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstracts from the Seventeenth International Kidney Cancer Symposium, 2nd-3rd November 2018, Miami, Florida","authors":"","doi":"10.3233/kca-189005","DOIUrl":"https://doi.org/10.3233/kca-189005","url":null,"abstract":"","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-189005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48397063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radiation therapy (RT) has traditionally been disregarded in the primary or adjuvant treatment of renal cell carcinoma (RCC), but recent advances have necessitated a re-examination of the role radiation therapy may be able to play. The advent of stereotactic ablative radiotherapy (SABR), which allows for targeting of disease with higher doses in a shorter window of time, may open up new avenues for RT’s role in the treatment of RCC, a cancer with a relatively low alpha/beta ratio. Thus, this review examines both the history and future of RT in the treatment of RCC with an aim to expand the discussion on treatment options for RCC.
{"title":"Radiation Therapy for Renal Cell Carcinoma","authors":"R. Choi, James B. Yu","doi":"10.3233/KCA-180040","DOIUrl":"https://doi.org/10.3233/KCA-180040","url":null,"abstract":"Radiation therapy (RT) has traditionally been disregarded in the primary or adjuvant treatment of renal cell carcinoma (RCC), but recent advances have necessitated a re-examination of the role radiation therapy may be able to play. The advent of stereotactic ablative radiotherapy (SABR), which allows for targeting of disease with higher doses in a shorter window of time, may open up new avenues for RT’s role in the treatment of RCC, a cancer with a relatively low alpha/beta ratio. Thus, this review examines both the history and future of RT in the treatment of RCC with an aim to expand the discussion on treatment options for RCC.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47831839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Luyo, L. Carril-Ajuria, F. Schutz, D. Castellano, G. Velasco
Long considered an immunogenic tumour, immunotherapy has been the cornerstone of systemic treatment in renal cell carcinoma (RCC) for decades. Since the introduction of interleukin 2 and interferon-alfa in the 80s to the more recently approved nivolumab (anti-PD-1) in second line setting. Moreover, on the basis that anti-CTLA-4 and anti-PD-1/PDL1 intrinsic mechanisms are different, double checkpoint inhibition was proposed to further improve anti-tumor immune response. The first trial to assess double checkpoint inhibition was the Checkmate 016 (nivolumab and ipilimumab), showing acceptable safety and promising antitumor activity that led to the first phase III trial with combination immunotherapy in RCC, the Checkmate 214. This trial showed superior overall survival and response rate of the combination immunotherapy (nivolumab and ipilimumab) versus sunitinib in intermediateand poorrisk advanced RCC, leading to its approval in this setting. Despite these advances, there is still room for improvement. In this sense, cytokines and T-cell costimulatory molecules are currently under investigation. This review summarizes the principles of immunotherapy and its role in RCC, provides an update on double checkpoint blockade and finally discusses the major challenges with double checkpoint blockade. 7
{"title":"Double Immune Checkpoint Blockade in Renal Cell Carcinoma","authors":"M. Luyo, L. Carril-Ajuria, F. Schutz, D. Castellano, G. Velasco","doi":"10.3233/KCA-190054","DOIUrl":"https://doi.org/10.3233/KCA-190054","url":null,"abstract":"Long considered an immunogenic tumour, immunotherapy has been the cornerstone of systemic treatment in renal cell carcinoma (RCC) for decades. Since the introduction of interleukin 2 and interferon-alfa in the 80s to the more recently approved nivolumab (anti-PD-1) in second line setting. Moreover, on the basis that anti-CTLA-4 and anti-PD-1/PDL1 intrinsic mechanisms are different, double checkpoint inhibition was proposed to further improve anti-tumor immune response. The first trial to assess double checkpoint inhibition was the Checkmate 016 (nivolumab and ipilimumab), showing acceptable safety and promising antitumor activity that led to the first phase III trial with combination immunotherapy in RCC, the Checkmate 214. This trial showed superior overall survival and response rate of the combination immunotherapy (nivolumab and ipilimumab) versus sunitinib in intermediateand poorrisk advanced RCC, leading to its approval in this setting. Despite these advances, there is still room for improvement. In this sense, cytokines and T-cell costimulatory molecules are currently under investigation. This review summarizes the principles of immunotherapy and its role in RCC, provides an update on double checkpoint blockade and finally discusses the major challenges with double checkpoint blockade. 7","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The advent of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs) a decade ago revolutionized the treatment paradigm in advanced metastatic clear cell renal cell carcinoma (RCC) with improved survival rates compared to the pre-TKI era. Monotherapy with VEGF TKIs has remained first-line. However, sequencing of different TKIs, mammalian target of rapamycin (mTOR) inhibitors, or immune checkpoint inhibitors (ICIs) has been the subject of controversy in the treatment landscape of metastatic RCC. First-line treatment further evolved with the approval of nivolumab plus ipilimumab in intermediateand poor-risk patients based on an overall survival (OS) benefit demonstrated in the CheckMate214 trial as well as a progression-free survival (PFS) benefit of cabozantinib in the CABOSUN trial. Optimal sequencing, patient selection, and understanding resistance pathways continue to be prominent concerns. Efforts to bypass resistance mechanisms have led to the study of combination therapies. Given enhancement of immune checkpoint inhibitor (ICI) T-cell mediated effects by VEGF-mediated immunosuppression, the combination of VEGF inhibitors and ICIs in treatment-naı̈ve locally advanced and metastatic RCC has shown promise. Available results of phase III trials utilizing these combinations are discussed herein.
{"title":"The Emerging Role of Combination Angiogenesis Inhibitors and Immune Checkpoint Inhibitors in the Treatment of Metastatic Renal Cell Cancer","authors":"A. Nizam, L. Rhea, Brinda Gupta, J. Aragon-Ching","doi":"10.3233/KCA-190050","DOIUrl":"https://doi.org/10.3233/KCA-190050","url":null,"abstract":"The advent of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs) a decade ago revolutionized the treatment paradigm in advanced metastatic clear cell renal cell carcinoma (RCC) with improved survival rates compared to the pre-TKI era. Monotherapy with VEGF TKIs has remained first-line. However, sequencing of different TKIs, mammalian target of rapamycin (mTOR) inhibitors, or immune checkpoint inhibitors (ICIs) has been the subject of controversy in the treatment landscape of metastatic RCC. First-line treatment further evolved with the approval of nivolumab plus ipilimumab in intermediateand poor-risk patients based on an overall survival (OS) benefit demonstrated in the CheckMate214 trial as well as a progression-free survival (PFS) benefit of cabozantinib in the CABOSUN trial. Optimal sequencing, patient selection, and understanding resistance pathways continue to be prominent concerns. Efforts to bypass resistance mechanisms have led to the study of combination therapies. Given enhancement of immune checkpoint inhibitor (ICI) T-cell mediated effects by VEGF-mediated immunosuppression, the combination of VEGF inhibitors and ICIs in treatment-naı̈ve locally advanced and metastatic RCC has shown promise. Available results of phase III trials utilizing these combinations are discussed herein.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Historically, tumor biopsies and clinical laboratory testing have been the gold standard for diagnosis and prognosis in metastatic renal cell carcinoma (mRCC). Genomic profiling in mRCC has traditionally been performed on tumor tissue; however, challenges and limitations in obtaining tissue biopsies led to the discovery of alternative biological specimens, namely circulating cell-free DNA (cfDNA). Rapidly evolving technologies, with increased sensitivity and specificity, have been used to query cfDNA in the clinical research setting. These investigations are rapidly establishing cfDNA and liquid biopsies as valuable complementary specimens to the gold standard, and in some instances surpassing these with unique insight into the contemporary genomic landscape and tumor heterogeneity. In this review, we will discuss recent research into the prognostic, diagnostic, and predictive utility of liquid biopsies in mRCC. We will explore their potential role in precision treatment of mRCC and conclude with what is needed in order to translate them to clinical practice.
{"title":"Cell-free Circulating Tumor DNA (ctDNA) in Metastatic Renal Cell Carcinoma (mRCC): Current Knowledge and Potential Uses","authors":"A. Hahn, R. Nussenzveig, B. Maughan, N. Agarwal","doi":"10.3233/KCA-180048","DOIUrl":"https://doi.org/10.3233/KCA-180048","url":null,"abstract":"Historically, tumor biopsies and clinical laboratory testing have been the gold standard for diagnosis and prognosis in metastatic renal cell carcinoma (mRCC). Genomic profiling in mRCC has traditionally been performed on tumor tissue; however, challenges and limitations in obtaining tissue biopsies led to the discovery of alternative biological specimens, namely circulating cell-free DNA (cfDNA). Rapidly evolving technologies, with increased sensitivity and specificity, have been used to query cfDNA in the clinical research setting. These investigations are rapidly establishing cfDNA and liquid biopsies as valuable complementary specimens to the gold standard, and in some instances surpassing these with unique insight into the contemporary genomic landscape and tumor heterogeneity. In this review, we will discuss recent research into the prognostic, diagnostic, and predictive utility of liquid biopsies in mRCC. We will explore their potential role in precision treatment of mRCC and conclude with what is needed in order to translate them to clinical practice.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70125975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Metastasectomy for advanced renal cell carcinoma has been practiced for over 80 years. However, there is uncertainty regarding the clinical benefit of this procedure and the optimum selection of appropriate patients. Materials and Methods: A systematic literature search was conducted according to the PRISMA statement to identify studies that reported outcomes in patients who underwent metastasectomy at any time. Primary endpoints were overall and disease-free survival. Radiation therapy studies were not included. Case reports and series with less than 20 patients were
{"title":"Metastasectomy in Advanced Renal Cell Carcinoma: A Systematic Review","authors":"Tala Achkar, J. Maranchie, L. Appleman","doi":"10.3233/KCA-180042","DOIUrl":"https://doi.org/10.3233/KCA-180042","url":null,"abstract":"Introduction: Metastasectomy for advanced renal cell carcinoma has been practiced for over 80 years. However, there is uncertainty regarding the clinical benefit of this procedure and the optimum selection of appropriate patients. Materials and Methods: A systematic literature search was conducted according to the PRISMA statement to identify studies that reported outcomes in patients who underwent metastasectomy at any time. Primary endpoints were overall and disease-free survival. Radiation therapy studies were not included. Case reports and series with less than 20 patients were","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-180042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70125914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. May, Anirudh Guduru, J.P. Fernelius, S. Raza, F. Davaro, S. Siddiqui, Z. Hamilton
Background: Renal masses can be surgically treated by partial nephrectomy (PN) or radical nephrectomy (RN); however, in 2009 guidelines recommended PN as the standard of care for cT1a renal masses. Objective: To evaluate national trends of surgically appropriate patients using the National Cancer Database (NCDB) for utilization of PN focusing on guideline release, evaluating underlying health disparity. Methods: We identified 99,035 patients from 2004–2015 that underwent surgical resection of cT1a renal masses. We evaluated treatment proportions over time of patients treated with PN or RN. Logistic regression was utilized for multivariable analysis. Results: PN increased from 40.2% in 2004 to 71.3% in 2015 (p < 0.001). Older patients were more likely to be treated with RN (OR 1.018, p < 0.001), as were those with Charlson score 2 or 3+ (OR 1.288 and 2.074, p < 0.001). Patients with lower income were more likely to be treated with RN (OR 1.186, p < 0.001) as were uninsured patients (OR 1.108, p = 0.018) and low volume centers (OR 1.063, p < 0.001). Females were more likely to undergo RN (OR 1.123, p < 0.001) as were black patients (OR 1.339, p < 0.001). While these demographic trends persisted after the release of the guidelines, all associations decreased except for Charlson score and race. Black patients became more likely to undergo RN (pre-guideline OR 1.248 vs post-guideline OR 1.474, p < 0.001). Patients treated with RN had worsened mortality (17.4% vs. 7.3%, p < 0.001). Conclusions: Although use of PN in surgically appropriate patients for cT1a renal masses has increased over time, 30% of patients underwent RN in 2015. Socioeconomic disparities affect treatment decisions and require additional research.
背景:肾肿块可以通过部分肾切除术(PN)或根治性肾切除术(RN)进行手术治疗;然而，在2009年的指南中推荐PN作为cT1a肾肿块的标准治疗。目的:利用国家癌症数据库(NCDB)评估全国手术适宜患者使用PN的趋势，重点关注指南发布，评估潜在的健康差异。方法:我们确定了2004-2015年间99,035例手术切除cT1a肾肿块的患者。我们评估了接受PN或RN治疗的患者随时间的治疗比例。采用Logistic回归进行多变量分析。结果:PN由2004年的40.2%上升至2015年的71.3% (p < 0.001)。老年患者更有可能接受RN治疗(OR 1.018, p < 0.001)， Charlson评分为2或3+的患者也是如此(OR 1.288和2.074,p < 0.001)。收入较低的患者更有可能接受RN治疗(OR 1.186, p < 0.001)，没有保险的患者(OR 1.108, p = 0.018)和低容量中心(OR 1.063, p < 0.001)。女性更容易发生RN (OR 1.123, p < 0.001)，黑人患者也同样如此(OR 1.339, p < 0.001)。虽然这些人口统计趋势在指南发布后仍然存在，但除了查尔森评分和种族外，所有关联都有所下降。黑人患者更有可能接受RN(指南前OR 1.248 vs指南后OR 1.474, p < 0.001)。接受RN治疗的患者死亡率加重(17.4% vs. 7.3%， p < 0.001)。结论:尽管随着时间的推移，适合手术的cT1a肾肿块患者使用PN的情况有所增加，但2015年仍有30%的患者接受了RN。社会经济差异影响治疗决策，需要进一步研究。
{"title":"Current Trends in Partial Nephrectomy After Guideline Release: Health Disparity for Small Renal Mass","authors":"A. May, Anirudh Guduru, J.P. Fernelius, S. Raza, F. Davaro, S. Siddiqui, Z. Hamilton","doi":"10.3233/kca-190066","DOIUrl":"https://doi.org/10.3233/kca-190066","url":null,"abstract":"Background: Renal masses can be surgically treated by partial nephrectomy (PN) or radical nephrectomy (RN); however, in 2009 guidelines recommended PN as the standard of care for cT1a renal masses. Objective: To evaluate national trends of surgically appropriate patients using the National Cancer Database (NCDB) for utilization of PN focusing on guideline release, evaluating underlying health disparity. Methods: We identified 99,035 patients from 2004–2015 that underwent surgical resection of cT1a renal masses. We evaluated treatment proportions over time of patients treated with PN or RN. Logistic regression was utilized for multivariable analysis. Results: PN increased from 40.2% in 2004 to 71.3% in 2015 (p < 0.001). Older patients were more likely to be treated with RN (OR 1.018, p < 0.001), as were those with Charlson score 2 or 3+ (OR 1.288 and 2.074, p < 0.001). Patients with lower income were more likely to be treated with RN (OR 1.186, p < 0.001) as were uninsured patients (OR 1.108, p = 0.018) and low volume centers (OR 1.063, p < 0.001). Females were more likely to undergo RN (OR 1.123, p < 0.001) as were black patients (OR 1.339, p < 0.001). While these demographic trends persisted after the release of the guidelines, all associations decreased except for Charlson score and race. Black patients became more likely to undergo RN (pre-guideline OR 1.248 vs post-guideline OR 1.474, p < 0.001). Patients treated with RN had worsened mortality (17.4% vs. 7.3%, p < 0.001). Conclusions: Although use of PN in surgically appropriate patients for cT1a renal masses has increased over time, 30% of patients underwent RN in 2015. Socioeconomic disparities affect treatment decisions and require additional research.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/kca-190066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Bruchbacher, Sebastian Nachbargauer, H. Fajkovic, M. Schmidinger
Background and objective: Sunitinib has been a standard treatment for patients with metastatic renal cell carcinoma (mRCC) since 2006. However, almost all patients will eventually progress. Besides well described mechanisms of primary or secondary resistance, insufficient drug exposure may lead to disease progression. The aim of this study was to identify patients in whom sunitinib dose escalation was performed and to analyse safety and efficacy of this strategy in clinical practice. Methods: A single-centre retrospective study on dose escalation in mRCC patients who were treated with sunitinib at the Medical University of Vienna between January 2011 and May 2016. Dose escalation was studied in patients who had either progressed (cohort 1: PD) or had stable disease with minor progression (cohort 2: SD). The primary endpoints were response rate before and after dose escalation, global progression free survival and overall survival. Secondary endpoints were treatment duration before and after dose escalation and toxicity. Results: Dose escalation up to 75 mg was offered in 21 out of 265 patients. Response rates before and after dose escalation were 42,8% and 23.8%, respectively. The median global PFS and OS were 15.60 and 32.95 months, respectively. The median treatment duration before and after dose escalation was 6.1 months (1.3–29.3 months) and 6.6 months (2.5–16.6 months). No new toxicities emerged under escalated dose and no grade 4 adverse events occurred. Conclusion: Sunitinib dose escalation may be a strategy in patients with few toxicities at the time point of progression.
{"title":"Sunitinib Dose Escalation in Metastatic Renal Cell Carcinoma","authors":"A. Bruchbacher, Sebastian Nachbargauer, H. Fajkovic, M. Schmidinger","doi":"10.3233/KCA-190055","DOIUrl":"https://doi.org/10.3233/KCA-190055","url":null,"abstract":"Background and objective: Sunitinib has been a standard treatment for patients with metastatic renal cell carcinoma (mRCC) since 2006. However, almost all patients will eventually progress. Besides well described mechanisms of primary or secondary resistance, insufficient drug exposure may lead to disease progression. The aim of this study was to identify patients in whom sunitinib dose escalation was performed and to analyse safety and efficacy of this strategy in clinical practice. Methods: A single-centre retrospective study on dose escalation in mRCC patients who were treated with sunitinib at the Medical University of Vienna between January 2011 and May 2016. Dose escalation was studied in patients who had either progressed (cohort 1: PD) or had stable disease with minor progression (cohort 2: SD). The primary endpoints were response rate before and after dose escalation, global progression free survival and overall survival. Secondary endpoints were treatment duration before and after dose escalation and toxicity. Results: Dose escalation up to 75 mg was offered in 21 out of 265 patients. Response rates before and after dose escalation were 42,8% and 23.8%, respectively. The median global PFS and OS were 15.60 and 32.95 months, respectively. The median treatment duration before and after dose escalation was 6.1 months (1.3–29.3 months) and 6.6 months (2.5–16.6 months). No new toxicities emerged under escalated dose and no grade 4 adverse events occurred. Conclusion: Sunitinib dose escalation may be a strategy in patients with few toxicities at the time point of progression.","PeriodicalId":17823,"journal":{"name":"Kidney Cancer","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/KCA-190055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70126355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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