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

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.

Clinical Validity of Circulating Tumor DNA as Prognostic and Predictive Marker for Personalized Colorectal Cancer Patient Management

“…CtDNA analysis enables the non-invasive and real-time assessment of tumor burden and mutant signatures in cancer patients, which may be used for residual disease, recurrence and tumor progression detection. For implementation into clinical routine, clinically relevant positive ctDNA signals at low levels must clearly be verified as being tumor-specific without interference from analytical measurement noise (technical artefact) or clonal hematopoiesis (biological artefact) [35]. Hence, clinicians need a defined cutoff for true tumor-specific ctDNA positivity.…”

Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma

“…We found a discrepancy in mutation comparisons between gDNA (FFPE samples) and ctDNA (liquid biopsies), which may lead to false-negative and false-positive results in ctDNA analysis. This is related to technical and biological factors ( 45 ). As the total number of genomic copies in the plasma volume of a sample is very limited, the number of specific variants of interest is also very limited.…”

Circulating Tumor DNA-Based Genomic Profiling Assays in Adult Solid Tumors for Precision Oncology: Recent Advancements and Future Challenges

“…Technical and biological factors which account for the generation of false-positive and falsenegative results may contribute to the discordance observed. These factors remain the key limitations and challenges for the routine use of ctDNA profiling in clinical settings [17,101]. Furthermore, the lack of comprehensive guidelines to recommend the usage of ctDNA CGP also restricts its clinical use.…”