Advantages and Challenges of Using ctDNA NGS to Assess the Presence of Minimal Residual Disease (MRD) in Solid Tumors

SIMPLE SUMMARY: Minimal residual disease (MRD) represents a status of the disease which is assumed to still be present in the body until it is clinically observed by radiology. At this time point, the tumor relapse is present and a new clinical decision should be taken. However, there is currently no official biomarker which can efficiently predict a relapse after a curative-intent surgery or treatment. This unmet clinical need would benefit from such a biomarker as it would help guiding the decision on adjuvant therapy. The possibility to use the liquid biopsy technology in order to measure non-invasive circulating tumor DNA (ctDNA) in the patient’s blood opens a new avenue to the establishment of this biomarker. In this review we summarize the current knowledge on ctDNA detection by NGS as a tool to assess the presence of MRD as well as the clinical trials focusing on the clinical utility of the method. ABSTRACT: The ability to detect minimal residual disease (MRD) after a curative-intent surgery or treatment is of paramount importance, because it offers the possibility to help guide the clinical decisions related adjuvant therapy. Thus, the earlier MRD is detected, the earlier potentially beneficial treatment can be proposed to patients who might need it. Liquid biopsies, and in particular the next-generation sequencing of circulating tumor DNA (ctDNA) in the blood, have been the focus of an increasing amount of research in the past years. The ctDNA detection at advanced cancer stages is practicable for several solid tumors, and complements molecular information on acquired therapy resistance. In the context of MRD, it is by definition more challenging to detect ctDNA, but it is technically achievable and provides information on treatment response and probability of relapse significantly earlier than standard imaging methods. The clinical benefit of implementing this new technique in the routine is being tested in interventional clinical trials at the moment. We propose here an update of the current use of ctDNA detection by NGS as a tool to assess the presence of MRD and improve adjuvant treatment of solid tumors. We also discuss the main limitations and medium-term perspectives of this process in the clinic.