Quantification of Plasma Cell-Free DNA¹in Predicting Therapeutic Efficacy of Sorafenib on Metastatic Clear Cell Renal Cell Carcinoma

Abstract

Abstract. PURPOSE:The objective of this study is to determine whether or not plasma cfDNA levels can predict efficacy of sorafenib in patient with metastatic cRCC. MATERIALS AND METHODS: Plasma cfDNA levels were quantified by quantitative real-time PCR at six different time-points (before treatment, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 24 weeks) in 18 metastatic cRCC patients receiving sorafenib, as assessed by CT examination according to RECIST 1.1. RESULTS: A significantly lower plasma cfDNA level, measured from 8 weeks to 24 weeks, was found in patients with remission or stable disease than in those with progression. Higher levels in plasma cfDNA levels during the course of treatment indicated poor outcome. For predicting progression, a sensitivity of 66.7% was achieved at 100% specificity using cfDNA levels at 8 weeks. CONCLUSIONS: Monitoring of plasma cfDNA levels during the course of sorafenib therapy could identify metastatic cRCC patients who are likely to exhibit a poor response at an early stage.

CNAPS in Therapy Monitoring

“…In line with these results, cfDNA levels in human cancers decreased in patients with response to radiotherapy and showed stable or increasing values in progressive patients [54]. The results of this first study were later confirmed in patients with lung cancer undergoing chemotherapy [55][56][57], in patients with rectal cancer receiving neoadjuvant radiochemotherapy [58], in patients with ovarian cancer treated by chemotherapy [59,60] and in patients with renal cancer treated by tyrosine kinase inhibitors [61]. However, it has to be mentioned that some minor studies with lower numbers of patients reported no association between cfDNA kinetics and tumor relapse or treatment response [37,62].…”

Liquid biopsy: a step forward towards precision medicine in urologic malignancies

“…Higher cfDNA levels during the course of treatment also indicated poor prognosis [13]. Another study found that plasma cfDNA levels were elevated in metastatic RCC relative to localized disease and could predict postoperative recurrence with 91% sensitivity and 100% specificity [14].…”

A decade of pharmacogenomics research on tyrosine kinase inhibitors in metastatic renal cell cancer: a systematic review

“…Feng et al [62] showed that high levels of circulating cell-free DNA (cfDNA) were associated with a poor response to sorafenib in 18 Chinese mRCC patients. Aziz et al [63] reported that a high microvessel area was associated with a better response on sorafenib; smaller primary tumors were observed (P = 0.005) [63].…”