Circulating Cell-Free DNA Levels in Patients with Metastatic Renal Cell Carcinoma

Abstract

Background: Limited data about biomarkers are available to predict the outcomes of targeted therapy in metastatic renal cell carcinoma (mRCC). Circulating cell-free DNA (CFD) is elevated in various cancers. Patients and Methods: We performed a prospective study of patients with mRCC who received targeted therapy in the Soroka Medical Center between 2013 and 2015. CFD levels were measured using a simple fluorometric assay. Blood samples for CFD were collected before treatment and at weeks 1, 4, 12, 18, and 24 of treatment. The normal cut-off level of CFD was defined as 800 ng/ml. The association of CFD with objective response, progression-free survival (PFS), and overall survival was tested, with adjustment for known confounding risk factors. Results: A total of 23 patients were included; 18 were treated with first-line therapy and 5 with second- and third-line therapies. Patients with normal pretreatment CFD level had a better PFS versus patients with increased levels (p = 0.023). In multivariate analysis, factors associated with PFS were pretreatment CFD levels (p = 0.020) and Heng risk (p = 0.006). Conclusions: Elevated pretreatment CFD levels measured using a simple fluorometric assay may be associated with a worse PFS in patients with mRCC. A larger prospective study is warranted in order to validate our observation.

Circulating Cell-Free DNA in Renal Cell Carcinoma: The New Era of Precision Medicine

“…Few studies have explored the role of cfDNA in monitoring therapeutic efficacy in mRCC [ 61 , 69 , 70 , 89 ]. A report by Fang et al on patients with mRCC showed a correlation between higher levels of plasma cfDNA and poor response to sorafenib [ 61 ].…”

Targeting Circulating SINEs and LINEs with DNase I Provides Metastases Inhibition in Experimental Tumor Models

“…Nowadays, several measurements of cfDNA characteristics are used in cancer patient liquid biopsies: SNP analysis of proto-oncogenes and onco-suppressors, changes in the pattern of DNA methylation, and the abundance of oncogene fragments and other specific fragments of tumor-derived DNA microsatellites, tandem repeats, and mobile genetic elements. [1][2][3] Although attempts have been made to use cfDNAs as indicators of cancer development, based on the content of specific DNA sequences in the blood, the low sensitivity of cfDNA measurement methods, and failure to apply developed markers for early-stage tumor development, has significantly limited the clinical application of this analysis. 4,5 On the other hand, increases in microsatellite content, tandem repeats, and mobile genetic elements are commonly detected in the early stages of cancer, both in experimental tumor models and patients, causing researchers to consider these sequences as potential markers for prognosis, as well as factors in disease progression and cure.…”

Systematic Review and STARD Scoring of Renal Cell Carcinoma Circulating Diagnostic Biomarker Manuscripts

“…Cell-free DNA is shed from apoptotic and necrotic cells into the blood stream ( 66 ). Since its first identification in cancer patients ( 67 ), it has been investigated as both a diagnostic ( 68 , 69 ) and prognostic cancer ( 70 , 71 ) biomarker in RCC and other cancers ( 72–75 ). However, cell-free DNA is not yet clinically validated in RCC.…”