Evaluation of blood MSI burden dynamics to trace immune checkpoint inhibitor therapy efficacy through the course of treatment

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality globally. The standard methods for assessing MSI and dMMR are polymerase chain reaction (PCR) and 4-antibody immunohistochemistry (IHC). In clinical practice, limitations of MSI/dMMR testing include false negative or false positive results in cases when the sample quality is suboptimal, as well as variable concordance between the two methods. Furthermore, IHC can yield inconclusive results, such as the loss of only one protein. Next-generation sequencing (NGS) is an emerging approach that allows to expand the range of analyzed markers. NGS allows to dynamically monitor tumor variability through the analysis of mutations in circulating tumor DNA (ctDNA). NGS-based analysis of liquid biopsy (LB) has several advantages, as it allows to evaluate the dynamics of tumor variability, as well as monitor the response to therapy. Analysis of serial liquid biopsy (LB) samples has been found to be a promising approach for the monitoring of tumor dynamics in the course of therapy for patients with colorectal cancer (CRC). We describe outcomes of the first nine patients enrolled in the study by using GeneMind GenoLab M sequencer, the results provide the rationale for further validation of bMSI as a predictive biomarker of ICI in MSI-positive patients.

Read           Download