scholarly journals Identification of a 6-Gene Signature Associated with Resistance to Tyrosine Kinase Inhibitors: Prognosis for Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 26 ◽  
Author(s):  
Qinke Li ◽  
Wenbo Yang ◽  
Maoqing Lu ◽  
Ronggui Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Gene Signature ◽  
Cell Renal Cell Carcinoma

Prognostic and predictive role of intra-tumoral CXCR1 expression in patients receiving tyrosine kinase inhibitors for metastatic clear-cell renal cell carcinoma

2021 ◽  
pp. 205141582110122
Author(s):  
Sridhar Panaiyadiyan ◽  
Brusabhanu Nayak ◽  
Prabhjot Singh ◽  
Seema Kaushal ◽  
Subhradip Karmakar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

Objective: We aimed to evaluate the role of intra-tumoral CXCR1 expression in predicting prognosis and treatment response in metastatic clear-cell renal cell carcinoma patients receiving tyrosine kinase inhibitors. Materials and methods: Patients with metastatic clear-cell renal cell carcinoma presented between February 2018–December 2019 were studied for the CXCR1 expression in tumor tissues before starting tyrosine kinase inhibitors. Primary outcome measure was progression-free survival. Secondary outcome measures included overall survival and prediction of treatment response. Results: The study included 35 patients with a mean age of 53.6±9.6 years. At a mean follow-up of 12.2±4.1 months, 17 (48.6%) patients had disease progression including eight (22.9%) deaths. Patients with high CXCR1 expression, compared to those with low CXCR1 expression, had a significantly shorter 12-month progression-free survival (35.4% vs 77.9%, p=0.01) and an insignificant impact on 12-month overall survival. The CXCR1 expression scores significantly differed between patients with progressive and nonprogressive disease (20.1 vs 15.1, p=0.01) and patients with high CXCR1 expression had a reduced benefit from tyrosine kinase inhibitors. The multivariate Cox regression analysis showed CXCR1 expression as a significant predictor of progression-free survival. Conclusion: High intra-tumoral CXCR1 expression before tyrosine kinase inhibitors can be an independent prognostic factor for progression-free survival and predictor of reduced benefit in patients with metastatic clear-cell renal cell carcinoma. Level of evidence: Level 2b.

scholarly journals Predictive value of De Ritis ratio in metastatic renal cell carcinoma treated with tyrosine-kinase inhibitors

2021 ◽  
Author(s):  
Florian Janisch ◽  
Thomas Klotzbücher ◽  
Phillip Marks ◽  
Christina Kienapfel ◽  
Christian P. Meyer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cox Regression ◽  
Clear Cell ◽  
Multivariable Analyses

Abstract Background Predictive markers can help tailor treatment to the individual in metastatic renal cell carcinoma (mRCC). De Ritis ratio (DRR) is associated with oncologic outcomes in various solid tumors. Objective To assess the value of DRR in prognosticating survival in mRCC patients treated with tyrosine-kinase inhibitors (TKI). Methods Overall, 220 mRCC patients treated with TKI first-line therapy were analyzed. An optimal cut-off point for DRR was determined with Youden’s J. We used multiple strata for DRR, performed descriptive, Kaplan–Meier and multivariable Cox-regression analyses to assess associations of DRR with progression-free (PFS) and overall survival (OS). Results Patients above the optimal cut-off point for DRR of ≥ 1.58 had fewer liver metastases (p = 0.01). There was no difference in PFS (p > 0.05) between DRR groups. DRR above the median of 1.08 (HR 1.42; p = 0.03), DRR ≥ 1.1(HR 1.44; p = 0.02), ≥ 1.8 (HR 1.56; p = 0.03), ≥ 1.9 (HR 1.59; p = 0.02) and ≥ 2.0 (HR 1.63; p = 0.047) were associated with worse OS. These associations did not remain after multivariable adjustment. In the intermediate MSKCC group, DRR was associated with inferior OS at cut-offs ≥ 1.0 (HR 1.78; p = 0.02), ≥ 1.1 (HR 1.81; p = 0.01) and above median (HR 1.88; p = 0.007) in multivariable analyses. In patients with clear-cell histology, DRR above median (HR 1.54; p = 0.029) and DRR ≥ 1.1 (HR 1.53; p = 0.029) were associated with OS in multivariable analyses. Conclusion There was no independent association between DRR and survival of mRCC patients treated with TKI in the entire cohort. However, OS of patients with intermediate risk and clear-cell histology were affected by DRR. DRR could be used for tailored decision-making in these subgroups.

Are tyrosine kinase inhibitors fit for purpose in the treatment of metastatic papillary renal cell carcinoma?

2021 ◽  
pp. 205141582098766
Author(s):  
Joshua Hemmant ◽  
Karyee Chow
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Level Of Evidence ◽  
Weak Evidence

Renal cell carcinoma encompasses a range of histological subtypes. The treatment of metastatic disease in this context remains challenging. Papillary renal cell carcinoma is the second most common subtype and forms a significant subsection of non-clear cell renal cell carcinoma. Tyrosine kinase inhibitors form a significant part of the treatment of this largely incurable disease; however, outcomes tend to be poor. The aim of this article is to scrutinise whether these treatments are evidence-based in their use for metastatic papillary renal cell carcinoma and if good outcomes are reported. A literature review was made using PubMed of major prospective and retrospective studies. The European Association of Urology and European Society of Medical Oncology have both published guidance suggesting sunitinib should be offered first line in the treatment of metastatic papillary renal cell carcinoma. This, however, is based upon weak evidence produced by the ASPEN trial, although this did not discriminate between non-clear cell subtypes and results in further studies were modest. The National Institute for Care and Health Excellence has recently published new guidelines for the use of cabozantinib, which has shown evidence of improved progression-free survival and overall response rates compared with sunitinib. Unfortunately, many of the relevant studies did not specifically assess these treatments in patients solely with papillary renal cell carcinoma and had modest overall success. There is weak evidence that tyrosine kinase inhibitors give significant benefit in those patients with metastatic papillary renal cell carcinoma. Level of evidence: 2a

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