scholarly journals Metastatic clear-cell renal cell carcinoma: Computed tomography texture analysis as predictive biomarkers of survival in patients treated with Nivolumab: NivoMics 01-Study

2020 ◽  
Vol 19 ◽  
pp. e1103-e1104
Author(s):  
Z-E. Khene ◽  
R. Kokorian ◽  
B. Peyronnet ◽  
J. Edeline ◽  
R. Decrevoisier ◽  
...  
2019 ◽  
Vol 18 ◽  
pp. 153303381987845 ◽  
Author(s):  
Chiara Marigliano ◽  
Stefano Badia ◽  
Davide Bellini ◽  
Marco Rengo ◽  
Damiano Caruso ◽  
...  

Purpose: A relevant challenge for the improvement of clear cell renal cell carcinoma management could derive from the identification of novel molecular biomarkers that could greatly improve the diagnosis, prognosis, and treatment choice of these neoplasms. In this study, we investigate whether quantitative parameters obtained from computed tomography texture analysis may correlate with the expression of selected oncogenic microRNAs. Methods: In a retrospective single-center study, multiphasic computed tomography examination (with arterial, portal, and urographic phases) was performed on 20 patients with clear cell renal cell carcinoma and computed tomography texture analysis parameters such as entropy, kurtosis, skewness, mean, and standard deviation of pixel distribution were measured using multiple filter settings. These quantitative data were correlated with the expression of selected microRNAs (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both the evaluations (microRNAs and computed tomography texture analysis) were performed on matched tumor and normal corticomedullar tissues of the same patients cohort. Results: In this pilot study, we evidenced that computed tomography texture analysis has robust parameters (eg, entropy, mean, standard deviation) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression was evidenced in tumor versus normal tissue. Interestingly, entropy and miR-21-5p show promising correlation in clear cell renal cell carcinoma opening to a radiogenomic strategy to improve clear cell renal cell carcinoma management. Conclusion: In this pilot study, a promising correlation between microRNAs and computed tomography texture analysis has been found in clear cell renal cell carcinoma. A clear cell renal cell carcinoma can benefit from noninvasive evaluation of texture parameters in adjunction to biopsy results. In particular, a promising correlation between entropy and miR-21-5p was found.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Brian Shuch ◽  
Ryan Falbo ◽  
Fabio Parisi ◽  
Adebowale Adeniran ◽  
Yuval Kluger ◽  
...  

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.


2018 ◽  
Vol 35 (2) ◽  
pp. 147-151
Author(s):  
Emily Rail ◽  
Janell Stormo

Clear cell renal cell carcinoma (RCC) is proposed to arise from the proximal convoluted tubules within the kidney. Diagnostic imaging plays a role in the detection of RCC. A case is presented of a clear cell RCC that was initially identified sonographically. Sonography detected and characterized the mass, which was further evaluated with computed tomography (CT) to obtain additional information, prior to a radical nephrectomy. The use of both CT and sonography led to proper diagnosis and treatment of this suspected tumor.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16070-e16070
Author(s):  
Jamal Zekri ◽  
Abdelrazak Meliti ◽  
Mohammed Abhas Baghdadi ◽  
Turki Sobahy ◽  
Saba Imtiaz

e16070 Background: The management of the clear cell renal cell carcinoma (cc-RCC) has evolved over the past decade. Clinical patients’ and tumor characteristics have a limited role in predicting the outcome of these patients. The search for reliable prognostic and predictive biomarkers should be pursued in particular during the current era of next generation sequencing (NGS) technology. Methods: Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimens of cc-RCC were sequenced using NGS and a customized gene panel testing for 72 tumor-related genes. High potential variants were defined by mutation effect (stop-loss, stop-gain, frame-shift substitutions or non-synonymous SNV) and class (pathogenic or likely pathogenic). Cases with identical variants were identified. Results: In total, all 47 cases had 69,052 variants, of which 20,453 were classified as high potential variants. Identical alterations in 15 genes were present in all samples. These genes are: MUC3A, MUC12, MUC7, SRRT, MUC2, MUC5AC, MUC5B, MUC22, MUC6, CR1, MUC4, MUC16, MUC19, MUC17 and MERTK. The numbers of identical and non-identical variants in these 15 genes were counted for each sample. Median number of variants was 377 and was selected as a cut off to define cases with high ( > 377) and low (≤377) variants number (HVN and LVN respectively). For the whole cohort, HVN was associated with shorter overall survival compared to LVN (Median 50 months vs. not reached; Log Rank P = 0.041). In the 11 patients who received anti-angiogenic tyrosine kinase inhibitors (TKIs), HVN was associated with a trend of shorter progression free survival (Median 5 vs. 10 months; Log Rank P = not significant). Conclusions: Alterations in SRRT, CR1, MERTK and MUCIN family genes are very common in RCC. HVN ( > 377) is associated with worse prognosis and may predict decreased benefit from anti-angiogenic TKIs.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4583-4583 ◽  
Author(s):  
Ronan Flippot ◽  
Bradley Alexander McGregor ◽  
Abdallah Flaifel ◽  
Kathryn P. Gray ◽  
Sabina Signoretti ◽  
...  

4583 Background: NccRCC and ccRCCsd are aggressive tumors associated with poor prognosis and response to therapy. Combination strategies co-targeting VEGF signaling and inhibitory immune checkpoints are highly active in clear-cell renal cell carcinoma, but data is lacking in NccRCC and ccRCCsd. We conducted a multicenter, open-label, single arm phase II trial of atezolizumab plus bevacizumab in NccRCC and ccRCCsd. Methods: Patients with NccRCC and ccRCCsd ( > 20% sarcomatoid differentiation), and ECOG performance status of 0-2 were eligible. Prior systemic treatment was allowed with the exception of prior PD-1/PD-L1-directed therapy. Atezolizumab 1200mg and bevacizumab 15mg/kg were administered every 3 weeks until progression, unacceptable toxicity, or patient withdrawal. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Exploratory biomarker analyses included PD-L1 expression on tumor (TC) and immune cells (IC), and spatial analysis of the immune infiltrate. Results: Sixty patients received at least 1 cycle of treatment, among whom 56 were evaluable for response (17 ccRCCsd and 39 NccRCC). ORR was 34% in the overall population, 53% in ccRCCsd and 26% in NccRCC. Median progression-free survival was 8.4 months (95%CI, 6.9-16.5). Baseline tumor tissue was available for 36 patients. TC PD-L1 expression ≥1% was associated with improved ORR (9/14, 64%) compared to patients with PD-L1 expression < 1% (4/20, 20%). Patients with TC PD-L1 expression ≥1% who experienced progressive disease as best response had shorter average distance between tumor cells and nearest neighboring immune cells at baseline. Further analysis of the immune tumor microenvironment on an expanded cohort, including IC PD-L1 expression and correlation with clinical outcomes, is ongoing and will be updated. Conclusions: The combination of atezolizumab plus bevacizumab is active in NccRCC and ccRCCsd. Candidate predictive biomarkers include PD-L1 expression in TC and topological analysis of the immune infiltrate. Clinical trial information: NCT02724878.


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