scholarly journals Prognostic Factors in De Novo Metastatic Renal Cell Carcinoma: A Report From the Latin American Renal Cancer Group

2021 ◽  
pp. 671-685
Author(s):  
Diego Abreu ◽  
Gustavo Carvalhal ◽  
Guillermo Gueglio ◽  
Ignacio Tobia ◽  
Patricio Garcia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Latin American ◽  
Renal Cell ◽  
Cox Regression ◽  
De Novo ◽  
Risk Group ◽  
External Validation ◽  
Prognostic Information

PURPOSE To assess the effect of clinical and pathological variables on cancer-specific and overall survival (OS) in de novo metastatic patients from a collaborative of primarily Latin American countries. PATIENTS AND METHODS Of 4,060 patients with renal cell carcinoma diagnosed between 1990 and 2015, a total of 530 (14.5%) had metastasis at clinical presentation. Relationships between clinical and pathological parameters and treatment-related outcomes were analyzed by Cox regression and the log-rank method. RESULTS Of 530 patients, 184 (90.6%) had died of renal cell carcinoma. The median OS of the entire cohort was 24 months. American Society of Anesthesiology classification 3-4 (hazard ratio [HR]: 1.64), perirenal fat invasion (HR: 2.02), and ≥ 2 metastatic organ sites (HR: 2.19) were independent prognostic factors for 5-year OS in multivariable analyses. We created a risk group stratification with these variables: no adverse risk factors (favorable group), median OS not reached; one adverse factor (intermediate group), median OS 33 months (HR: 2.04); and two or three adverse factors (poor risk group), median OS 14 months (HR: 3.58). CONCLUSION Our study defines novel prognostic factors that are relevant to a Latin American cohort. With external validation, these easily discerned clinical variables can be used to offer prognostic information across low- and middle-income countries.

Subclassification of the intermediate-risk group in patients with advanced renal cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16537-e16537
Author(s):  
Maria Zapata-Garcia ◽  
Maria Zurera Berjaga ◽  
Alba Moratiel Pellitero ◽  
Marta Gascon Ruiz ◽  
Andrea Sesma Goñi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Risk Group ◽  
Intermediate Risk ◽  
First Line ◽  
Poor Risk ◽  
Prognosis Group

e16537 Background: Renal cell carcinoma (RCC) have low prevalence but it incidence is increasing. For a correct therapeutic approach, it is important to carry out a correct prognostic stratification. Several prognostication systems have been proposed. One of the most commonly used is the one developed by Heng. It is based on IMDC database. This classification includes six prognostic factors (hemoglobin, neutrohils, platelets, serum calcium, Karnosky Performance Status and time from diagnosis to initiaton treatment) to divide patients into three gorups. The relevance of IMDC prognostic criterio, in the era of immunotherapy, remains to be established. In the absence of alternative criteria, these prognostication system continue to be used. A great prognostic disparity has been observed in the intermediate prognosis group. This raises the need to divide this group into two. Thus, patients included in it would be better selected. Methods: Observational, single-center, retrospective study, based on a cohort of 107 patients with advanced RCC, recruited from January 2006 to December 2019. Main objective: Evaluate whether survival of patients with intermediate prognosis (treated with antiangiogenic in first-line) is different depending on the presence of one or two prognostic factors. Descriptive and survival analysis (OS and PFS) were performed. In addition, the influence of prognostic factors on OS and PFS were compared using the log-rank test and Cox regression. Results: In the overall population, median overall survival (OS) was 26.86 months (95% CI: 21.09-32.63) and median PFS was 18.41 months (95% CI: 14.02-22.79). Median OS were, in favorable-risk 42.24 months (95% CI: 29.62-54.62), in intermediate-risk 27,24 (95% CI: 19.44-35-03) and in poor-risk 8.00 (95% CI: 4.54-11.45). Median PFS were in favorable-risk 30.53 months (95% CI:20.92-40.13), in intermediate-risk 17,16 (95% CI:11.54-22.78) and poor-risk 6.13 (95% CI:3.02-9.25). Median OS and PFS, in patients with intermediate-risk, with a single risk factor were 33.79 (95% CI 23.17-44.41) and 20.97 months (95% CI 13.35-28.59), compared to 14.88 (95% CI 8.80-20.95) and 10.59 months (95% CI 4.87-16.32) in those with two risk factors. The results were statistically significant in OS (p = 0.01) and PFS (p = 0.037). Conclusions: The differences in median OS and PFS, within the intermediate prognosis group (1 or 2 RF), confirm the existence of two subgroups of patients. Patients with 1 RF are similar to those with favorable-risk. These results are important since, the presence of 1 or 2 RF, would condition the choice of TKIs as part of the first-line treatment combination. More studies are needed to better subclassify the intermediate risk group when optimizing the best treatments for each patient.

Prognostic biomarker exploration for patients with metastatic renal cell carcinoma receiving VEGFR TKI.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 491-491
Author(s):  
Inkeun Park ◽  
Yong Mee Cho ◽  
Jae-Lyun Lee ◽  
Jin-Hee Ahn ◽  
Dae Ho Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Risk Group ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Coagulative Necrosis ◽  
Prognostic Importance

491 Background: To verify the prognostic importance of selected tumor tissue biomarkers in metastatic renal cell carcinoma (mRCC) patients (pts), we performed immunohistochemical (IHC) staining in tumor sample and statistical analyses. Methods: The clinicopathological features, treatment, and outcome of mRCC pts treated with vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) between July 2006 and March 2011 at our center were reviewed. IHC staining for FGF base, FGFR1, 2, 3, and 4, HGF, PTEN, CAIX, pS6, HIF-1a, HIF-2a, IL-8, mTOR was done, and each specimen was scored based on the staining intensity and the percentage of positive cells. We performed univariate and multivariable analyses to verify prognostic factors for overall survival (OS). Results: We found 123 pts who met inclusion criteria. Most pts had clear cell carcinoma (107 pts, 87.0%). Fuhrman’s nuclear grade (NG) was 2 in 21 (17.1%), 3 in 49 (39.8%), and 4 in 52 (42.3%), respectively. Sarcomatoid change and coagulative necrosis were found in 51 pts and 58 pts. Using Heng’s criteria, 20 pts (16.3%), 87 (70.7%), and 16 (13.0%) belonged to favorable, intermediate, and poor risk group, respectively. First-line VEGFR TKIs prescribed were sunitinib (97 pts, 78.9%), sorafenib (23 pts, 18.7%), and pazopanib (3 pts, 2.4%). In univariate analysis, CAIX (less than 47.5% vs 47.5% or more, p=0.001), mTOR (20% or less vs more than 20%, p=0.0032), Heng risk group (good vs intermediate vs poor, p<0.001), sarcomatoid change (40% or less vs more than 40%, p<0.001), coagulative necrosis (20% or less vs more than 20%, p<0.001), Furhman NG (2 vs 3 vs 4, p=0.037) were statistically significant. In multivariable analysis, CAIX, Heng risk group, sarcomatoid change, and hyaline necrosis were identified as independent prognostic factors (Table). Conclusions: All investigated biomarkers but CAIX did not show prognostic importance for mRCC pts receiving VEGFR TKI. [Table: see text]

Outcomes and prognostic factors in metastatic renal cell carcinoma patients with brain metastases.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 289-289
Author(s):  
İzzet Dogan ◽  
Ayca Iribas ◽  
Nail Paksoy ◽  
Meltem Ekenel ◽  
Sezai Vatansever ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
De Novo ◽  
Brain Radiotherapy ◽  
Metastatic Sites

289 Background: The study aimed to evaluate the outcomes and prognostic factors in patients with brain metastatic renal cell carcinoma (bmRCC). Methods: The data of 322 patients with renal cell carcinoma, between 2012 and 2020, were retrospectively reviewed. The clinicopathological features and treatments of the patients with bmRCC were recorded. Overall survival (OS) and prognostic factors were evaluated with Kaplan-Meier analysis and Cox-regression analysis. Results: Forty (12.4%) of the patients had bmRCC. The median follow-up period was 7.3 months (range, 0.2-55.5). The male/female ratio was 2.3, and the median age at diagnosis was 62 years (range, 25-84). Seventeen (42.5%) of the patients were de-novo metastatic, and nine (22.5%) of the patients had brain metastases at presentation. The most common extracranial metastatic sites of the disease were lung (72.5%), bone (47.5%), lymph node (27.5%), and liver (12.5%). Twenty-four (60%) patients previously had received various therapies (tyrosine kinase inhibitor, checkpoint inhibitors, or palliative radiotherapy). After brain metastases developed, 92% of the patients received brain radiotherapy (whole-brain radiotherapy or stereotactic radiosurgery), and twenty-five (62.5%) patients received different therapies. Nine patient received sunitinib, nine patient pazopanib, five patient nivolumab, and two patient axitinib. A total of 32 (80%) patients died during the study period. The median OS was 8.8 months (range, 2.9-14.6) for all patients with bmRCC. Six months- and one-years overall survival ratios were 60% and 40%, respectively. In univariate analysis, the number of brain metastasis (p = 0.352), the localization of brain metastasis (p = 0.790), the longest size of brain metastasis (p = 0.454), the number of extracranial metastatic sites (p = 0.812), de-novo metastatic disease (p = 0.177), primary tumor localization (left or right) (p = 0.903), and tumor grade (p = 0.093) were not statistically significant factors on OS. However, age (p = 0.02), a history of nephrectomy (p < 0.001), receiving brain radiotherapy (p = 0.005), and type of treatment (p = 0.044) was statistically significant. Only, the effect of brain radiotherapy on OS (p = 0.011) was confirmed in multivariate analysis. Conclusions: The prognostic data of patients with bmRCC is limited. In this study, we observed that the prognosis of patients with bmRCC was poor. Despite a small number of patients, we detected that the effect of tyrosine kinase inhibitors and nivolumab was comparable, and receiving brain radiotherapy was a prognostic factor for OS.

scholarly journals The Immunoexpression of YAP1 and LATS1 Proteins in Clear Cell Renal Cell Carcinoma: Impact on Patients’ Survival

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
J. Godlewski ◽  
J. Kiezun ◽  
B. E. Krazinski ◽  
Z. Kozielec ◽  
P. M. Wierzbicki ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Cellular Localization ◽  
Cox Regression ◽  
Clear Cell ◽  
Rank Test ◽  
Cell Renal Cell Carcinoma

The aim of the study was to determine by immunohistochemistry cellular localization and immunoreactivity levels of YAP1 and LATS1 proteins in paired sections of tumor and unchanged renal tissues of 54 clear cell renal cell carcinoma (ccRCC) patients. Associations between clinical-pathological and overall survival (OS; median follow-up was 40.6 months) data of patients and YAP1 and LATS1 immunoreactivity were analyzed by uni- and multivariate Cox regression model and log-rank test. YAP1 immunoreactivity was found in the nuclei of tumor cells in 64.8% of ccRCC patients, whereas only 24.1% of tumors revealed cytoplasmic YAP1 expression. LATS1 immunoexpression was observed only in the cytoplasm of tumor cells in 59.3% of patients. LATS1 immunoreactivity in cancer cells negatively correlated with the size of primary tumor. The overall YAP1 immunoreactivity did not correlate with clinical-pathological data of patients. However, the subgroup of ccRCC patients who presented with cytoplasmic YAP1 immunoexpression had significantly shorter OS (median = 26.8 months) than patients without cytoplasmic YAP1 expression (median undefined). Multivariate Cox analysis revealed that increased cytoplasmic YAP1 (HR = 4.53) and decreased LATS1 immunoreactivity levels (HR = 0.90) were associated with worse prognosis, being independent prognostic factors. These results suggest that YAP1 and LATS1 can be considered as new prognostic factors in ccRCC.

Entry Bias: Order of Patient Entry Influences Outcome in Trials of Allogeneic Transplant for Renal Cell Carcinoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 269-269
Author(s):  
Andrew S. Artz ◽  
Masha Kocherginsky ◽  
Koen Van Besien
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Patient Selection ◽  
Renal Cell ◽  
Surrogate Marker ◽  
Cox Proportional Hazards ◽  
Patient Specific ◽  
Prognostic Information ◽  
Probability Of Response

Abstract Early trials evaluating nonmyeloablative allogeneic hematopoietic transplant (NST) for metastatic renal cell carcinoma (RCC) have reported widely discordant results. We performed a meta-analysis of the published literature to identify prognostic factors for NST. However, known RCC prognostic factors are not often detailed in these studies, hindering the identification of patient differences among studies. We explored the order of patient entry as a surrogate marker for patient selection, hypothesizing that patient selection, rather than treatment differences, accounted for early promising results. Patient specific data and adequate follow-up were available for 76 patients from six studies. The rank of patient entry on each individual trial was recorded as well as ≥ grade 2 acute graft-versus-host disease (aGVHD), recipient age, recipient sex, response (partial plus complete), and survival. Multivariable analyses for response and survival were modeled using logistic and cox proportional hazards regression, respectively. The mean overall response rate was 22/76 (29%), with responses across individual studies significantly varying from 0% to 57% P =.009 by Chi-square). Median Kaplan-Meier survival was 263 days. Neither age nor sex was significantly ( associated with response or survival. Acute GVHD occurred in 42% of individuals and correlated with response (OR=9.9, P =0.012) but not survival (HR=1.53, P=0.28). When adjusting by study, later patient entry rank reduced the probability of response (OR=0.30, P =0.007) and survival (HR=1.89, P =0.006). Alternatively, being among the first five patients enrolled in a given study relative to subsequent patients, increased the probability of response (OR=6.69, 95% CI 1.95–39.1, P=0.005), even when adjusting for aGVHD, and afforded a survival benefit (HR= 0.45, 95% CI 0.022 −0.92, P=0.028). The prognostic strength of patient entry rank strongly suggests “entry bias” in patient selection. This bias potentially accounts for the large variation in outcome among studies and for the promising results in early studies. Entry bias analysis offers a novel method to assess early phase trials for selection bias, when detailed individual prognostic information is lacking. Further study is warranted to determine to what extent, if any, entry bias occurs in other clinical trial settings. Figure Figure

scholarly journals A novel ferroptosis-related 12-gene signature predicts clinical prognosis and reveals immune relevancy in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Yingkai Hong ◽  
Mingen Lin ◽  
Dehua Ou ◽  
Zhuangkai Huang ◽  
Peilin Shen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Risk Group ◽  
Gene Signature ◽  
Cell Renal Cell Carcinoma ◽  
Prognostic Predictor

Abstract Background Clear cell renal cell carcinoma (ccRCC) is still highly aggressive and lethal even with various therapeutic approaches. As kidney is an iron-metabolism-related organ, exploring and assessing the clinical value of ferroptosis, an iron-dependent regulated cell death, is practical and significant. Methods Prognostic ferroptosis-related differentially expressed genes (DEGs) were identified from KIRC cohort in TCGA database, from which a prognostic signature was established using the Lasso-penalized Cox regression analysis. Each patient in the KIRC cohort and the E-MTAB-1980 cohort (from the ArrayExpress database) was assigned with a calculated signature-correlated risk score and categorized to be either in high- or low-risk group divided by the median risk score in the KIRC cohort. Then, the independent prognostic value of the signature was further assessed by Kaplan-Meier (K-M) survival, time-dependent receiver operating characteristic (ROC) and Cox regression analyses base on overall survival (OS) in both cohorts. Lastly, risk-related DEGs were identified in both cohorts and applied with the enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and immune infiltration. Results Within 60 ferroptosis-related genes, 32 prognostic DEGs were identified, from which we constructed a prognostic 12-gene signature including CARS1, HMGCR, CHAC1, GOT1, CD44, STEAP3, AKR1C1, CBS, DPP4, FANCD2, SLC1A5 and NCOA4. Patients in both cohorts were divided into high- and low-risk group which were visually distributed in two sets and with positive-risk-related mortality. The K-M survival and the ROC curves validated the signature as prognostic valuable with P <0.05 and area under the curve >0.7 in both cohorts, respectively. Multivariate Cox regression further confirmed the risk score as an independent prognostic predictor for OS. Commonly enriched term in GO and KEGG not only shown a highly iron correlation, but also, interesting, an immunity relevancy of 3 immune cells (macrophages, mast cells and regulatory T cell) and 1 immune-related function (antigen processing cell co-stimulation). Conclusion We established a novel 12 ferroptosis-related-gene signature which was proved as an independent prognostic predictor for OS and inferred as relating to tumor immunity in ccRCC, however, the underlying mechanism is still poorly characterized and needed further exploration.

scholarly journals Integrated Analysis to Identify a Redox-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-35
Author(s):  
Yue Wu ◽  
Xian Wei ◽  
Huan Feng ◽  
Bintao Hu ◽  
Bo Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Clear Cell ◽  
Risk Group ◽  
External Validation ◽  
Integrated Analysis ◽  
Prognostic Signature ◽  
Cell Renal Cell Carcinoma

The imbalance of the redox system has been shown to be closely related to the occurrence and progression of many cancers. However, the biological function and clinical significance of redox-related genes (RRGs) in clear cell renal cell carcinoma (ccRCC) are unclear. In our current study, we downloaded transcriptome data from The Cancer Genome Atlas (TCGA) database of ccRCC patients and identified the differential expression of RRGs in tumor and normal kidney tissues. Then, we identified a total of 344 differentially expressed RRGs, including 234 upregulated and 110 downregulated RRGs. Fourteen prognosis-related RRGs (ADAM8, CGN, EIF4EBP1, FOXM1, G6PC, HAMP, HTR2C, ITIH4, LTB4R, MMP3, PLG, PRKCG, SAA1, and VWF) were selected out, and a prognosis-related signature was constructed based on these RRGs. Survival analysis showed that overall survival was lower in the high-risk group than in the low-risk group. The area under the receiver operating characteristic curve of the risk score signature was 0.728 at three years and 0.759 at five years in the TCGA cohort and 0.804 at three years and 0.829 at five years in the E-MTAB-1980 cohort, showing good predictive performance. In addition, we explored the regulatory relationships of these RRGs with upstream miRNA, their biological functions and molecular mechanisms, and their relationship with immune cell infiltration. We also established a nomogram based on these prognostic RRGs and performed internal and external validation in the TCGA and E-MTAB-1980 cohorts, respectively, showing an accurate prediction of ccRCC prognosis. Moreover, a stratified analysis showed a significant correlation between the prognostic signature and ccRCC progression.

Evolving Principles of Surgical Management and Prognostic Factors for Outcome in Renal Cell Carcinoma

2006 ◽  
Vol 24 (35) ◽  
pp. 5565-5575 ◽  
Author(s):  
John S. Lam ◽  
Alberto Breda ◽  
Arie S. Belldegrun ◽  
Robert A. Figlin
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Surgical Management ◽  
Renal Cell ◽  
Surgical Techniques ◽  
Renal Tumors ◽  
Clinical Staging ◽  
Prognostic Information ◽  
Cross Sectional

The generally accepted principles for the surgical management of renal cell carcinoma (RCC) were first described more than 30 years ago. Since then, much has changed in the understanding of the basic biology and genetics of kidney cancer. Improvements in cross-sectional imaging has allowed for more accurate preoperative clinical staging of renal tumors, and the necessity of completing all the components of the radical nephrectomy have been questioned. Surgical techniques have also evolved, and technology has advanced to make possible new methods of managing renal tumors. The TNM staging system is currently the most extensively used system to provide prognostic information for RCC. However, data published in the last few years has led to significant controversies as to whether further revisions are needed and whether improvements can be made with the introduction of new, more accurate and predictive prognostic factors. Furthermore, the recent discovery of molecular tumor markers are expected to revolutionize the staging of RCC and lead to the development of new therapies based on molecular targeting. This review will examine the evolving principles in the surgical management of RCC as well as provide an update on current staging modalities and prognostic factors.

A Novel Ferroptosis-Related Lncrnas Signature for Prognosis Prediction in Patients with Papillary Renal Cell Carcinoma

2021 ◽  
Author(s):  
Meiling Jin ◽  
Diangeng Li
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Prognostic Signature

Abstract BackgroundPapillary renal cell carcinoma (PRCC) is a common renal cell carcinoma. Recent studies have reported that ferroptosis is involved in the occurrence and development of tumors. Long non-coding RNAs could be used as independent biomarkers for the diagnosis and prognosis of a variety of tumors, and many lncRNAs are related to the pathogenesis of PRCC. However, there are few studies on the ferroptosis-related lncRNAs of PRCC. This study aimed to establish ferroptosis-related lncRNAs prognostic signature in patients with PRCC.MethodsGene expression profile and clinical information of patients with PRCC were obtained from The Cancer Genome Atlas (TCGA) database. Lasso-Penalzed Cox regression and univariate Cox regression analysis were utilized for model construction. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Immune cell infiltration and immune function were compared between the high-risk and low-risk groups. Chemotherapy sensitivity analysis was also performed. ResultsWe constructed a prognostic signature consisted of 15 ferroptosis-related lncRNAs. The Kaplan-Meier curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the lncRNAs signature was 0.930, exhibiting robust prognostic capacity. The high-risk group had a greater degree of immune cell infiltration, such as B cells, T cell CD8, macrophages, NK cell, etc., compared with the low-risk group. There were significant differences in inflammation-promoting, parainflammation and Type I IFN reponse between the low-risk and high-risk groups. The expressions of immune checkpoints including CD80, IDO1, LAG3, etc. were significantly higher in high-risk group. Chemotherapy sensitivity analysis showed that MNX1-AS1, ZFAS1, MIR4435-2HG and ADAMTS9-AS1 were significantly correlated with the sensitivity of some chemotherapy drugs. ConclusionWe demonstrated that a ferroptosis-related lncRNAs prognostic signature could be a novel biomarker for PRCC. Our findings could provide a new insight for immune research and treatment strategies for patients with PRCC.

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