Monitoring of RAS mutant clones in plasma of patients with RAS mutant metastatic colorectal cancer

A Fernández Montes,A Cousillas,E Aranda,A Vivancos,E Élez,P González,N Martínez,J C Méndez,M Covela,B Graña,J De La Cámara

doi:10.1007/s12094-021-02767-7

Abstract

PurposeSome patients with histologically confirmed primary mCRC and mutated RAS reported undetectable RAS mutant clones in plasma after receiving anti-VEGF treatment. The aim was to prospectively assess it with its potential therapeutic implications.MethodsRAS mutant genes in solid biopsy (before first-line treatment: FOLFOX/CAPOX + bevacizumab) were compared in liquid biopsy (before second-line treatment: panitumumab + FOLFIRI), using Idylla™ system. Discordant results between solid/liquid biopsies were assessed by the next-generation sequencing (NGS) test (solid/liquid biopsies).ResultsTwenty-three patients were assessed (seven had RAS mutant discrepancies between solid/liquid biopsies). The NGS test confirmed that 3/23 (13%) patients had undetectable RAS mutant clones in liquid biopsy and 3/23 (13%) presented discrepancies in solid biopsy (Idylla™ system vs. NGS test).ConclusionThirteen percentage of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment. However, some discrepancies between solid and liquid biopsies have been observed. These results suggest a need to improve accuracy of RAS analyses, especially in solid biopsies.

Highlights

Assessment of RAS mutations is crucial to guide treatment decisions in clinical practice
Circulating cell-free tumor DNA that originates from the currently present tumor has the same genetic and epigenetic alterations, which are related to tumor development, progression, and treatment resistance [2,3,4]
The analysis of cell-free tumor DNA (ctDNA) so-called as a “liquid biopsy” has been proposed as an alternative to the invasive techniques for obtaining tumor samples

Summary

Introduction

Assessment of RAS mutations is crucial to guide treatment decisions in clinical practice. CtDNA is more accurate than circulating tumor cells in respect of tumor burden and can be used as both a prognostic and diagnostic biomarker. The analysis of ctDNA so-called as a “liquid biopsy” has been proposed as an alternative to the invasive techniques for obtaining tumor samples. This liquid biopsy enables minimally invasive monitoring of tumor evolution over, and could provide current genetic information before initiate second-line treatment [2,3,4]

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Discussion

Conclusion