febrero 2021

Development and Validation of a Clinical Prognostic Model Based on Immune-Related Genes Expressed in Clear Cell Renal Cell Carcinoma

Ren S, Wang W, Shen H, et al.
Front Oncol. 2020 Aug 28;10:1496.
DOI: 10.3389/fonc.2020.01496

Abstract

Background

Clear cell renal cell carcinoma (ccRCC) is the most frequent and terminal subtype of RCC. Reliable markers associated with the immune response are not available to predict the prognosis of patients with ccRCC. We exploited the extensive number of ccRCC samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repository to perform a comprehensive analysis of immune-related genes (IRGs).

Methods

Based on TCGA data, we incorporated IRGs and their expression profiles of 72 normal and 539 ccRCC samples. Univariate Cox analysis was used to evaluate the relationship between overall survival (OS) and IRGs expression. The Lasso Cox regression model identified prognostic genes used to establish a clinical immune prognostic model. The TF-IRG network was used to study the potential molecular mechanisms of action and properties of ccRCC-specific IRGs. Multivariate Cox analysis established a clinical prognostic model of IRGs.

Results

We found a significant correlation among 15 differentially expressed IRGs with the OS of patients with ccRCC. Gene function enrichment analysis showed that these IRGs are significantly associated with response to receptor ligand activity. Lasso Cox regression analysis identified 10 genes with the greatest prognostic value. A clinical prognostic model based on six IRGs, which performed well for predicting prognosis, revealed significant associations of patients’ survival with age, sex, stage, tumor, node, and metastasis. Moreover, these findings reflect the infiltration of tumors by various immune cells.

Conclusions

We identified six clinically significant IRGs and incorporated them into a clinical prognostic model with great significance for monitoring and predicting prognosis of ccRCC.

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Cytoreductive Nephrectomy in Patients Presenting With Advanced Disease: Have We Finally Answered the Question?

Shapiro DD, Westerman ME, Karam JA, et al.
Cancer J. Sep/Oct 2020;26(5):382-389.
DOI: 10.1097/PPO.0000000000000470.

Abstract

Determining the appropriate patients for cytoreductive nephrectomy (CN) has evolved with the integration of more effective systemic therapies for patients with metastatic renal cell carcinoma (mRCC). While previously considered to be first-line therapy for mRCC, CN has not demonstrated a significant survival advantage over systemic therapy in more recent randomized trials when compared with targeted therapy. Conversely, multiple observational studies demonstrate a therapeutic benefit for CN. This review synthesizes the current literature regarding patient selection for CN and further evaluates the role of CN in the current era of immune checkpoint inhibitor therapy. With careful patient selection, CN maintains an important role in the management of mRCC patients.

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Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE)

McKay RR, McGregor BA, Xie W, et al.
J Clin Oncol. 2020 Oct 27;JCO2002295.
DOI: 10.1200/JCO.20.02295

Abstract

Purpose

In this phase II response-adaptive trial, we investigated the rational application of immune checkpoint blockade in renal cell carcinoma (RCC; ClinicalTrials.gov identifier: NCT03203473).

Methods

We enrolled patients with metastatic RCC with no prior checkpoint inhibitor exposure. All patients received nivolumab alone with subsequent arm allocation based on response. Patients with a confirmed partial response (PR) or complete response (CR) within 6 months discontinued nivolumab and were observed (arm A). Patients with stable disease or progressive disease (PD) after no more than 6 months of nivolumab received two doses of ipilimumab (arm B). The primary endpoints were the proportion of patients with PR/CR at 1 year after nivolumab discontinuation (arm A) and proportion of nivolumab nonresponders who converted to PR/CR after ipilimumab (arm B).

Results

Overall, 83 patients initiated treatment, of whom 96% had clear-cell histology, 51% were treatment naïve, and 67% had intermediate/poor-risk disease. Median follow-up was 19.5 months. Within 6 months, induction nivolumab resulted in a confirmed PR in 12% of patients (n = 10). Fourteen patients were not allocated to a study arm (seven because of toxicity, seven because of PD). Twelve patients (14%) were allocated to arm A and discontinued nivolumab, of whom five (42%; 90% CI, 18% to 68%) remained off nivolumab at ≥ 1 year. Of 57 patients (69%) allocated to arm B, two patients converted to a confirmed PR (4%; 90% CI, 1% to 11%), and no CRs were observed.

Conclusions

In this study, nivolumab followed by two doses of ipilimumab resulted in no CRs and a low PR/CR conversion. The number of patients evaluated for nivolumab discontinuation was too small to assess the value of this approach. Currently, our data do not support a response-adaptive strategy for checkpoint blockade in advanced RCC.

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