Prediction of watchful waiting in newly diagnosed metastatic clear cell renal cell carcinoma patients with a good or intermediate prognosis.

5079 Background: In metastatic clear cell renal cell carcinoma (mccRCC), the number of International Metastatic Database Consortium (IMDC) risk factors plus metastatic sites may identify patients with rapid or slow disease progression in a period of watchful waiting (WW) (median WW of 8.4 vs 22.2 months; Rini et al. Lancet Oncol. 2016). We aimed to validate this and prospectively assess the added value of baseline PET with [18F]FDG and [89Zr]Zr-DFO-girentuximab to predict the WW-period in the multicenter IMaging PAtients for Cancer drug selecTion (IMPACT)-RCC cohort study. (NCT02228954). Methods: Between February 2015 and March 2018, 40 treatment-naïve mccRCC patients with a good (n=13) or intermediate prognosis (n=25) according to IMDC, were enrolled. Following baseline CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab-PET, CT scans (RECIST1.1) were acquired at 2, 4, 6, 9, 12 months and thereafter every 4 months. Primary endpoint was time to radiological and/or clinical disease progression, requiring systemic treatment. Patients were assigned to a favorable (<2 IMDC risk factors and <3 metastatic sites) or unfavorable for WW-group (all others; Rini et al). Maximum standardized uptake values (SUVmax) were measured in PET-positive lesions measuring ≥10mm, or 15mm in lymph nodes. High and low-uptake groups were defined based on median geometric mean (gm) SUVmax across patients. A one-sided test was used to validate observations by Rini et al; other tests were two-sided. Results: The median WW-period was 9.3 months in the unfavorable WW-group (n=19) vs 20.4 months in the favorable WW-group (n=21) (HR 1.89 95%CI 0.94-3.89; p=0.037), confirming observations of Rini et al. Patients with high [18F]FDG uptake had a median WW-period of 8.5 months compared to 25.2 months in the low-uptake group (HR 4.08 95%CI 1.89-9.28; p=0.0002). Patients with high [89Zr]Zr-DFO-girentuximab uptake had a median WW-period of 10.7 versus 16.4 months in the low-uptake group (HR 1.37; 95%CI 0.69-2.76; p=0.37). [18F]FDG uptake groups improved a Cox-model for WW based on the prognostic groups of Rini et al (p=0.0015); [89Zr]Zr-DFO-girentuximab did not (p=0.98). Conclusions: The IMPACT-RCC study validated the observations by Rini et al. and shows that adding baseline [18F]FDG PET further improves the prediction of the duration of the WW-period in mccRCC patients. Clinical trial information: NCT02228954 .

Download Full-text

A convention-radiomics CT nomogram for differentiating fat-poor angiomyolipoma from clear cell renal cell carcinoma

Scientific Reports ◽

10.1038/s41598-021-84244-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yanqing Ma ◽

Weijun Ma ◽

Xiren Xu ◽

Zheng Guan ◽

Peipei Pang

Keyword(s):

Risk Factors ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Logistic Model ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Entire Cohort ◽

Conventional Ct ◽

Radiomics Signature

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.

Download Full-text

MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

BioMed Research International ◽

10.1155/2015/192406 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Brian Shuch ◽

Ryan Falbo ◽

Fabio Parisi ◽

Adebowale Adeniran ◽

Yuval Kluger ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Predictive Biomarkers ◽

Cell Renal Cell Carcinoma ◽

Primary Tumors ◽

Distant Tissue ◽

Significant Expression ◽

Metastatic Sites

Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available.Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1). MET expression weakly correlated between primary and matched metastatic sites (R=0.5) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39).Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

Download Full-text

Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with pazopanib after disease progression with other targeted therapies

European Journal of Cancer ◽

10.1016/j.ejca.2013.06.003 ◽

2013 ◽

Vol 49 (15) ◽

pp. 3169-3175 ◽

Cited By ~ 24

Author(s):

M.R. Matrana ◽

C. Duran ◽

A. Shetty ◽

L. Xiao ◽

B.J. Atkinson ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Disease Progression ◽

Targeted Therapies ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma

Download Full-text

Abstract 1493: Specific miRNA signatures characterize different metastatic sites in clear cell renal cell carcinoma

10.1158/1538-7445.am2014-1493 ◽

2014 ◽

Author(s):

Joana Heinzelmann ◽

Franzsika Stolzenbach ◽

Robert Schneeweiss ◽

Ulrike Wickmann ◽

Sophie Baumgart ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Metastatic Sites

Download Full-text

GFOD1 and peejar are promising markers for clear-cell renal cell carcinoma disease progression

Oncotarget ◽

10.18632/oncotarget.9379 ◽

2016 ◽

Vol 7 (25) ◽

pp. 38004-38009 ◽

Cited By ~ 2

Author(s):

Xiao-rong Wu ◽

Yong-hui Chen ◽

Wei Chen ◽

Wen Kong ◽

Ji-wei Huang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Disease Progression ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma

Download Full-text

Abstract 2340: Differences in risk factors for molecular subtypes of clear cell renal cell carcinoma in a case-control study

10.1158/1538-7445.am2020-2340 ◽

2020 ◽

Author(s):

Mark P. Purdue ◽

Jongeun Rhee ◽

Lee Moore ◽

Xiaohua Gao ◽

Xuezheng Sun ◽

...

Keyword(s):

Risk Factors ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Case Control Study ◽

Clear Cell ◽

Molecular Subtypes ◽

Case Control ◽

Cell Renal Cell Carcinoma ◽

Control Study

Download Full-text

The genomic landscape of metastatic non-clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.474 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 474-474 ◽

Cited By ~ 1

Author(s):

Maria Isabel Carlo ◽

Nabeela Khan ◽

Yingbei Chen ◽

James Hsieh ◽

A. Ari Hakimi ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Mtor Inhibitors ◽

Driver Gene ◽

Cell Renal Cell Carcinoma ◽

Primary Tumors ◽

Targeted Next Generation Sequencing ◽

Metastatic Sites

474 Background: Non-clear cell renal cell carcinoma (nccRCC) encompasses about 20% of RCC cases and includes a number of subtypes that vary clinically and molecularly. Compared to ccRCC, these tumors have more limited sensitivity to conventional anti-VEGF agents and mTOR inhibitors, and there is clear need for better therapies. Analysis of genomic alterations in potentially targetable pathways may lead to novel therapeutic development strategies. Methods: We retrospectively analyzed tumors from 112 patients with metastatic nccRCC with targeted next-generation sequencing (NGS) across a panel of >340 cancer-relevant genes. Matched tumor and normal was used to facilitate somatic calling. We report on recurrent alterations observed for nccRCC variants. Results: Median age was 53 years (range 12-77), 67% were male; 47% presented with metastatic disease and 53% with localized disease that later metastasized. NGS was performed on tissue from primary tumors (57%) or metastatic sites (43%). Subtype classifications included unclassified (44%), papillary (21%), chromophobe (13%), translocation (12%), and other (9%). The most frequently altered genes by subtype are included in table. 36% of unclassified or papillary tumors had a mutation in a putative driver gene amenable to targeted therapies, including MET, NOTCH1, SMARCB1, TSC1, TSC2, PIK3CA, and FGFR3. 3 chromophobe tumors and 1 translocation tumor had a mutation in a potentially targetable pathway. Conclusions: The mutation profiles of metastatic nccRCC vary by papillary, chromophobe, and translocation subtype, with unclassified tumors most approximating papillary subtype. Unclassified and papillary subtypes harbor frequent mutations in potentially targetable pathways that merit further investigation. [Table: see text]

Download Full-text

Phenotypic differences in tumor-associated macrophages between metastatic and primary sites of clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.105 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 105-105

Author(s):

Yuji Miura ◽

Takanobu Motoshima ◽

Nanako Wakigami ◽

Natsuki Kusada ◽

Toshikazu Okaneya ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

M2 Macrophages ◽

Cell Renal Cell Carcinoma ◽

Paired Samples ◽

Metastatic Lesions ◽

Metastatic Sites

105 Background: Tumor-associated macrophages (TAMs) are one of the key contributors to the tumor microenvironment and are phenotypically differentiated into M1 and M2 macrophages. M1 macrophages stimulate anti-tumor immune responses, whereas M2 macrophages promote immunosuppression and are associated with tumor progression in clear cell renal cell carcinoma (ccRCC). However, little information is available regarding the difference in TAM polarization between primary and metastatic lesions of ccRCC. Methods: We collected paired samples of primary and matched metastatic sites from the first recurrence in 41 metastatic ccRCC patients. Immunohistochemistry (IHC) for Iba1, which is a common pan-macrophage marker, and CD163 and CD204, which are considered to be M2 macrophage markers, was performed on all paired samples. Results: Thirty-three paired primary and metastatic samples were available for IHC assessment in this analysis. The most common metastatic sites were lung (N = 26, 78.8 %) and lymph node (N = 3, 9.1 %). The mean (± standard deviation) cell density of Iba1+ TAMs was higher in metastatic lesions than in primary lesions (756 ± 267 mm2 vs. 581 ± 155 mm2, P = 0.0012). By contrast, the ratio of CD163+ and CD204+ to Iba1+ TAMs was significantly lower in metastatic lesions than in primary lesions (0.76 ± 0.30 vs. 0.90 ± 0.24, P = 0.0067 and 0.39 ± 0.27 vs. 0.67 ± 0.29, P = 0.0001, respectively). The median overall survival of patients with high- vs. low-density Iba1+, CD163+, and CD204+ TAMs in metastatic lesions was 120 vs. 92 months (log-rank P = 0.67), 120 vs. 58 months (log-rank P = 0.056), and 120 vs. 92 months (log-rank P = 0.35), respectively. Conclusions: TAMs in the metastatic lesions of ccRCC polarized towards an M1-like phenotype, although the total number of TAMs was greater in metastatic compared with primary lesions. The cell density of Iba1+, CD163+, and CD204+ TAMs in metastatic sites was not associated with overall survival in patients with ccRCC.

Download Full-text