scholarly journals Risk factors of proteinuria in renal cell carcinoma patients treated with VEGF inhibitors: a secondary analysis of pooled clinical trial data

2016 ◽  
Vol 114 (12) ◽  
pp. 1313-1317 ◽  
Author(s):  
Michael J Sorich ◽  
Andrew Rowland ◽  
Ganessan Kichenadasse ◽  
Richard J Woodman ◽  
Arduino A Mangoni
2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15500-e15500
Author(s):  
Michael K.K. Wong ◽  
Eric Jonasch ◽  
Sumanta Kumar Pal ◽  
James E. Signorovitch ◽  
Peggy L. Lin ◽  
...  

e15500 Background: Current overall survival (OS) for metastatic renal cell carcinoma (mRCC) patients in clinical practice may differ from clinical trials. We aimed to identify and validate prognostic factors for OS in practice-based patients receiving 2nd-line everolimus (EVE), and to compare their OS vs. the RECORD-1 trial of EVE for mRCC. Methods: Two separate samples of oncologists/hematologists reviewed charts for patients initiating 2nd-line EVE between 2009 and 2011 following a 1st-line tyrosine kinase inhibitor (TKI). OS was defined as time from EVE initiation to death (censored at last follow-up). In the 1st sample of charts (the study sample), prognostic factors were identified via multivariable Cox proportional hazards models with stepwise selection. Prognostic factors considered included age, duration of mRCC and 1st-line treatment, metastatic sites, diabetes, histological subtype, ECOG and KPS score, and progression during 1st-line treatment. Model performance was assessed in the 2nd sample (the validation sample). Kaplan-Meier (KM) estimates for OS were compared between chart data and RECORD-1. Results: The study and validation samples included 220 and 97 patients, respectively. Significant prognostic factors were clear cell histology (hazard ratio (HR) = 2.9), KPS score <80% (HR = 2.9), duration of mRCC <1 year (HR = 2.7), progression on 1st-line TKI (HR = 2.2), and liver metastasis (HR = 1.9) (all P <.05). In the validation sample, KM estimates for 1-year OS were 90% for patients with 0-2 risk factors, 62% for patients with 3 risk factors, and 20% for patients with 4-5 risk factors (log-rank P <.001). OS estimates were consistent between both chart samples with 1-year OS probabilities of 67% and 68% and median OS of 19 and 23 months. In RECORD-1 1-year OS was 60% and median OS was 14.8 months (Motzer et al., 2010, Cancer). Conclusions: Prognostic factors for OS following 2nd-line EVE for mRCC in clinical practice were consistent with those previously identified in trial data. However, OS with 2nd-line EVE in clinical practice was longer than observed in trial data, and was not associated with type of 1st-line TKI.


2011 ◽  
Vol 18 (0) ◽  
Author(s):  
Sebastien J. Hotte ◽  
G.A. Bjarnason ◽  
D.Y.C. Heng ◽  
M.A.S. Jewett ◽  
A. Kapoor ◽  
...  

2020 ◽  
Vol 12 ◽  
pp. 175883592097711
Author(s):  
Xia Ran ◽  
Jinyuan Xiao ◽  
Yi Zhang ◽  
Huajing Teng ◽  
Fang Cheng ◽  
...  

Background: Intratumor heterogeneity (ITH) has been shown to be inversely associated with immune infiltration in several cancers including clear cell renal cell carcinoma (ccRCC), but it remains unclear whether ITH is associated with response to immunotherapy (e.g. PD-1 blockade) in ccRCC. Methods: We quantified ITH using mutant-allele tumor heterogeneity, investigated the association of ITH with immune parameters in patients with ccRCC ( n = 336) as well as those with papillary RCC (pRCC, n = 280) from The Cancer Genome Atlas, and validations were conducted in patients with ccRCC from an independent cohort ( n = 152). The relationship between ITH and response to anti-PD-1 immunotherapy was explored in patients with metastatic ccRCC from a clinical trial of anti-PD-1 therapy ( n = 35), and validated in three equal-size simulated data sets ( n = 60) generated by random sampling with replacement based on this clinical trial cohort. Results: In ccRCC, low ITH was associated with better survival, more reductions in tumor burden, and clinical benefit of anti-PD-1 immunotherapy through modulating immune activity involving more neoantigens, elevated expression of HLA class I genes, and higher abundance of dendritic cells. Furthermore, we found that the association between the level of ITH and response to PD-1 blockade was independent of the mutation status of PBRM1 and that integrating both factors performed better than the individual predictors in predicting the benefit of anti-PD-1 immunotherapy in ccRCC patients. In pRCC, increased immune activity was also observed in low- versus high-ITH tumors, including higher neoantigen counts, increased abundance of monocytes, and decreased expression of PD-L1 and PD-L2. Conclusions: ITH may be helpful in the identification of patients who could benefit from PD-1 blockade in ccRCC, and even in pRCC where no genomic metrics has been found to correlate with response to immune checkpoint inhibitors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yanqing Ma ◽  
Weijun Ma ◽  
Xiren Xu ◽  
Zheng Guan ◽  
Peipei Pang

AbstractThis study aimed to construct convention-radiomics CT nomogram containing conventional CT characteristics and radiomics signature for distinguishing fat-poor angiomyolipoma (fp-AML) from clear-cell renal cell carcinoma (ccRCC). 29 fp-AML and 110 ccRCC patients were enrolled and underwent CT examinations in this study. The radiomics-only logistic model was constructed with selected radiomics features by the analysis of variance (ANOVA)/Mann–Whitney (MW), correlation analysis, and Least Absolute Shrinkage and Selection Operator (LASSO), and the radiomics score (rad-score) was computed. The convention-radiomics logistic model based on independent conventional CT risk factors and rad-score was constructed for differentiating. Then the relevant nomogram was developed. Receiver operation characteristic (ROC) curves were calculated to quantify the accuracy for distinguishing. The rad-score of ccRCC was smaller than that of fp-AML. The convention-radioimics logistic model was constructed containing variables of enhancement pattern, VUP, and rad-score. To the entire cohort, the area under the curve (AUC) of convention-radiomics model (0.968 [95% CI 0.923–0.990]) was higher than that of radiomics-only model (0.958 [95% CI 0.910–0.985]). Our study indicated that convention-radiomics CT nomogram including conventional CT risk factors and radiomics signature exhibited better performance in distinguishing fp-AML from ccRCC.


2016 ◽  
Vol 24 (5) ◽  
pp. 829-836 ◽  
Author(s):  
Amol J. Ghia ◽  
Eric L. Chang ◽  
Andrew J. Bishop ◽  
Hubert Y. Pan ◽  
Nicholas S. Boehling ◽  
...  

OBJECTIVE The objective of this study was to compare fractionation schemes and outcomes of patients with renal cell carcinoma (RCC) treated in institutional prospective spinal stereotactic radiosurgery (SSRS) trials who did not previously undergo radiation treatment at the site of the SSRS. METHODS Patients enrolled in 2 separate institutional prospective protocols and treated with SSRS between 2002 and 2011 were included. A secondary analysis was performed on patients with previously nonirradiated RCC spinal metastases treated with either single-fraction (SF) or multifraction (MF) SSRS. RESULTS SSRS was performed in 47 spinal sites on 43 patients. The median age of the patients was 62 years (range 38–75 years). The most common histological subtype was clear cell (n = 30). Fifteen sites underwent surgery prior to the SSRS, with laminectomy the most common procedure performed (n = 10). All SF SSRS was delivered to a dose of 24 Gy (n = 21) while MF regiments were either 27 Gy in 3 fractions (n = 20) or 30 Gy in 5 fractions (n = 6). The median overall survival duration for the entire cohort was 22.8 months. The median local control (LC) for the entire cohort was 80.6 months with 1-year and 2-year actuarial LC rates of 82% and 68%, respectively. Single-fraction SSRS correlated with improved 1- and 2-year actuarial LC relative to MF SSRS (95% vs 71% and 86% vs 55%, respectively; p = 0.009). On competing risk analysis, SF SSRS showed superior LC to MF SSRS (subhazard ratio [SHR] 6.57, p = 0.014). On multivariate analysis for LC with tumor volume (p = 0.272), number of treated levels (p = 0.819), gross tumor volume (GTV) coverage (p = 0.225), and GTV minimum point dose (p = 0.97) as covariates, MF SSRS remained inferior to SF SSRS (SHR 5.26, p = 0.033) CONCLUSIONS SSRS offers durable LC for spinal metastases from RCC. Single-fraction SSRS is associated with improved LC over MF SSRS for previously nonirradiated RCC spinal metastases.


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