scholarly journals 69P Outcomes with durvalumab and savolitinib in metastatic papillary renal cancer (mPRC) according to international metastatic renal cell carcinoma database consortium (IMDC) risk groups

2020 ◽  
Vol 31 ◽  
pp. S1446
Author(s):  
J. Choy ◽  
C. Suarez Rodriguez ◽  
J. Larkin ◽  
P. Patel ◽  
B. Perez Valderrama ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cancer ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Risk Groups

scholarly journals Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups

2016 ◽  
Vol 4 (10) ◽  
pp. 820-822 ◽  
Author(s):  
Guillermo de Velasco ◽  
Diana Miao ◽  
Martin H. Voss ◽  
A. Ari Hakimi ◽  
James J. Hsieh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Risk Groups ◽  
Mutational Load ◽  
Immune Parameters ◽  
Carcinoma Risk

scholarly journals Nomogram Predicting Survival to Assist Decision-Making of Metastasectomy in Patients With Metastatic Renal Cell Carcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Kan Wu ◽  
Zhihong Liu ◽  
Yanxiang Shao ◽  
Xiang Li
Keyword(s):  
Renal Cell Carcinoma ◽  
Decision Tree ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Risk Groups ◽  
Low Risk ◽  
Patient Stratification ◽  
Decision Tree Analysis ◽  
Tree Analysis

The survival benefit of metastasectomy (MSX) in patients with metastatic renal cell carcinoma (mRCC) remains unclear. A reliable model to predict an individuals’ risk of cancer-specific mortality (CSM) and to identify optimal candidates for MSX is needed. We identified 2,911 mRCC patients who underwent cytoreductive nephrectomy from the Surveillance, Epidemiology, and End Results database (2010–2015). Based on the Fine and Gray competing risks analyses, we created a nomogram to predict the survival of mRCC patients. Decision tree analysis was useful for patient stratification. The impact of MSX was assessed among three different subgroups. Overall, 579 (19.9%) cases underwent MSX. In the entire patients, the 1-, 2-, and 3-year cumulative incidence of CSM were 32.8, 47.2, and 57.9%, respectively. MSX was significantly associated with improved survival (hazard ratio [HR] = 0.875, 95% confidence interval [CI] 0.773–0.991; P = 0.015). Based on risk scores, patients were divided into three risk groups using decision tree analysis. In the low-risk group, MSX was significantly associated with a 12.8% risk reduction of 3-year CSM (HR = 0.689, 95% CI 0.507–0.938; P = 0.008), while MSX was not associated with survival in intermediate- and high-risk groups. We proposed a novel nomogram and patient stratification approach to identify suitable patients for MSX. The newly identified patient subgroup with a low-risk of CSM might benefit more from aggressive surgery. These results should be further validated and improved by the prospective trials.

Sunitinib in patients with metastatic renal cell carcinoma: Clinical outcome according to IMDC risk group.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4584-4584
Author(s):  
Brian I. Rini ◽  
Thomas E. Hutson ◽  
Robert A. Figlin ◽  
Mariajose Lechuga ◽  
Olga Valota ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Retrospective Analysis ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Risk Group ◽  
Risk Groups ◽  
Phase Iii ◽  
Poor Risk ◽  
Phase Iii Study

4584 Background: In a phase III study (NCT00083889), treatment-naïve patients (pts) with metastatic renal cell carcinoma (mRCC) of all prognostic risk groups were treated with sunitinib or interferon-α (IFN-α). Since sunitinib has become the reference standard of care and serves as the comparator in multiple randomized trials sometimes restricted to prespecified risk groups, a retrospective analysis of outcome according to prognostic group from the phase III study was performed. Methods: Investigator-assessed efficacy data were analyzed for pts based on risk group (International mRCC Database Consortium [IMDC] criteria). The objective was to determine objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) benchmarks by risk group. Results: Of sunitinib-treated pts, 134 were favorable, 205 were intermediate, and 34 were poor risk. The median sunitinib treatment duration/median number of cycles was 16.7 mo/12 cycles, 11.0 mo/8 cycles and 2.6 mo/2.0 cycles for favorable-, intermediate-, and poor-risk pts, respectively. ORR, PFS, and OS benchmarks for sunitinib-treated pts are shown in the Table. In sunitinib-treated intermediate-risk pts with 1 vs 2 risk factors, respectively: ORR was 43.3% vs 40.8%, mPFS (95% confidence interval [95% CI]) was 11.2 (9.7–13.6) vs 8.5 (5.6–10.7) mo, and mOS (95% CI) was 28.2 (23.0–not estimable) vs 16.3 (13.2–19.4) mo. Conclusions: This retrospective analysis provides ORR, PFS, and OS benchmarks for current and future clinical trial interpretation in mRCC pts with different prognostic risk treated with sunitinib. [Table: see text]

Genomic alterations to refine prognostication of patients with metastatic renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 626-626 ◽  
Author(s):  
Dominick Bosse ◽  
Wanling Xie ◽  
Aly-Khan A. Lalani ◽  
Guillermo de Velasco ◽  
Martin Henner Voss ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Kinase Inhibitors ◽  
Cox Regression ◽  
Risk Groups ◽  
Genomic Alterations ◽  
Endothelial Growth Factor

626 Background: The IMDC risk score is a valid and simple tool to prognosticate patients (pts) with metastatic renal cell carcinoma (mRCC). Some non-VHL common genomic alterations may be associated with outcomes. We therefore assessed the prognostic value of most commonly mutated genes in mRCC beside VHL overall, and within IMDC risk groups. Methods: We identified patients treated at Dana-Farber Cancer Institute (n = 65) or part of TCGA (n = 33) who had genomic data available and were treated with first line vascular endothelial growth factor tyrosine kinase inhibitors. Information on genomic alterations (GA) focused on PBRM1, BAP1, SETD2, KDM5C and TP53 was extracted. Cox regression was performed to assess the association of each GA with overall survival (OS), adjusting for IMDC risk groups and age. Results: Overall, 98 pts were identified. 96/98 pts had clear-cell histology. Pts distribution by IMDC risk groups was: 7% good, 58% intermediate, 27% poor and 8% unknown. Mutation rates were 27% PBRM1, 17% BAP1, 29% SETD2, 9% KDM5C and 8% TP53. In multivariable models, there was an association between GA and worse OS for BAP1 and BAP1 or TP53 combined (Table). When stratified by IMDC risk groups, GA in BAP1 or TP53 was associated with shorter median OS in poor risk pts [12.1 mo (95%CI 8.3- 24.0) v. 27.6 mo (95%CI 18.9- 53.4), aHR 4.64 (95%CI 1.32-16.4), p = 0.017] and a trend toward worse median OS in intermediate risk pts [20.5 mo (95%CI 7.4-54.6) v. 36.3 mo (95%CI 21.1, NR), aHR 2.11 (95%CI 0.94-4.74)] compared to pts without GA in BAP1 or TP53. Too few death events were observed in good risk pts to assess the prognostic value of GA in BAP1 or TP53. Conclusions: GA in BAP1 or TP53 are prognostic in mRCC and further discriminate pts with distinct outcomes within IMDC risk groups. Validation in larger dataset is ongoing. [Table: see text]

Comparative effectiveness of first-line immune checkpoint inhibitors plus tyrosine kinase inhibitors according to IMDC risk groups in metastatic renal cell carcinoma: a meta-analysis

Immunotherapy ◽  
2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Matteo Santoni ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Risk Groups ◽  
Risk Patients

Aim: Immune checkpoint inhibitor (ICI)-based combinations have become the new standard of primary systemic treatment for metastatic renal cell carcinoma patients. We performed a meta-analysis aimed at evaluating ICIs plus tyrosine kinase inhibitors (TKIs) combinations across International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups. Materials & methods: All the relevant randomized clinical trials were retrieved through Cochrane library, PubMed/Med and EMBASE; three Phase III randomized clinical trials were included. Results: ICI–TKI combinations significantly decreased the risk of death in IMDC poor- and intermediate-risk patients. Conversely, a nonstatistically significant benefit was observed in favorable-risk patients. Conclusion: Our results suggest that IMDC poor-risk patients benefit most from ICI–TKI combinations, while a proportion of metastatic renal cell carcinoma patients could respond to targeted agent monotherapy.

scholarly journals The clinical significance of routine risk categorization in metastatic renal cell carcinoma and its impact on treatment decision-making: a systematic review

2020 ◽  
Vol 16 (34) ◽  
pp. 2879-2896
Author(s):  
Shouki Bazarbashi ◽  
Abdullah Alsharm ◽  
Faisal Azam ◽  
Hazem El Ashry ◽  
Jamal Zekri
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Cancer Center ◽  
Eligibility Criteria

Aim: To analyze responses to first-line metastatic renal cell carcinoma (mRCC) treatment stratified by risk criteria. Patients & methods: Clinical trials and observational studies of patients aged ≥18 years, published January 2005–May 2019, were identified via Ovid from MEDLINE, EMBASE, the Cochrane Central Trials Register and the Cochrane Database of Systematic Reviews. Data extracted included progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Results: 47/1269 articles met eligibility criteria. Most studies stratified patients by International Metastatic RCC Database Consortium (n = 19) or Memorial Sloan Kettering Cancer Center (n = 21). PFS, OS and ORR varied according to risk group. Conclusion: Pembrolizumab + axitinib, ipilimumab + nivolumab and avelumab + axitinib were most effective across all risk groups. Favorable-risk patients benefit from sunitinib treatment.

scholarly journals Survival Outcomes and Tumor IMP3 Expression in Patients with Sarcomatoid Metastatic Renal Cell Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Srinivas K. Tantravahi ◽  
Daniel Albertson ◽  
Archana M. Agarwal ◽  
Sowmya Ravulapati ◽  
Austin Poole ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Small Sample Size ◽  
Mtor Inhibitors ◽  
Risk Groups ◽  
Small Sample ◽  
Cancer Center ◽  
Survival Outcomes

Metastatic renal cell carcinoma with sarcomatoid histology (SmRCC) is associated with poor survival. No data is available from randomized trials on the efficacy of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors in SmRCC. We identified SmRCC patients from a single institutional database. To identify predictive and prognostic biomarkers, immunohistochemistry (IHC) analysis was performed on the tumor samples for downstream targets of VEGF and mTOR pathways. Survival outcomes were stratified by IHC analysis, extent of sarcomatoid component, Memorial Sloan-Kettering Cancer Center (MSKCC), and Heng risk criteria. Twenty-seven patients with SmRCC were included. First line therapy included targeted therapy (n=19), immunotherapy (n=4), cytotoxic chemotherapy (n=1), and no treatment (n=3). Median OS was 8.2 months (95% CI 3.8–14.2 months). Median survival in months, based on MSKCC and Heng risk groups, was favorable 89.3 versus 84.5, intermediate 9.5 versus 12.7, and poor 3.9 versus 5.1. None of the IHC markers predicted outcomes of treatment with VEGF or mTOR inhibitors. Only tumor IMP3 expression was associated with inferior OS, although not statistically significant (IMP3 negative 14.2 versus IMP3 positive 4.9 months; HR 0.46, 95% CI 0.16–1.21;P=0.12). The study was limited by small sample size.

scholarly journals Candidate Gene and MicroRNA Biomarkers of Metastatic Renal Cell Carcinoma (MRCC) Response to Sunitinib

2022 ◽  
Author(s):  
qiwei yang ◽  
wei yang ◽  
yijun tian ◽  
da xu ◽  
chuanmin chu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Renal Cancer ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Differentially Expressed ◽  
Sphingolipid Metabolism ◽  
Microrna Target ◽  
Metastatic Renal Cancer

Abstract Backgrounds: The incidence of renal cancer is relatively insidious, and some patients have been metastatic renal cancer at the initial visit. Sunitinib is the first-line systemic therapy for patients with metastatic renal cell carcinoma, however, there is scant analysis of its effect on genes and microRNAs.Methods: In this study, 8 differentially expressed microRNAs and 112 differentially expressed genes were designated by analyzing mRNA and microRNA data sets and weighted correlation network analysis (WGCNA).Results: NIPSNAP1 gene showed the most co-expression with other genes. Through the intersection of the microRNA target gene with our differentially expressed genes, we got 26 genes. KEGG and GO analysis showed that these genes were predominantly concentrated in Pathways in cancer, Sphingolipid metabolism and Glycosaminoglycan degradation. After we set the 26 genes and gene of WGCNA do intersection, received six genes, respectively is NIPSNAP1, SDC4, TBC1D9, NEU1, STK40 and PLAUR. Conclusion: Through subsequent cell, molecular and flow cytometry experiments, we found the PLAUR would play a crucial role in renal cell carcinoma (RCC) resistant to sunitinib, which will be available for new ideas to forecast sunitinib resistance and reverse sunitinib resistance.

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