Mutation and methylation analysis of circulating tumor DNA can be used for follow-up of metastatic colorectal cancer patients

Improvements in follow-up methods of metastatic colorectal cancer patients during treatment are warranted to ensure response to therapy. The potential of circulating tumor DNA ( ctDNA) for follow-up was investigated using methylation and mutation analyses in different blood samples collected during treatment. Our results corresponded to the results of radiographic evaluation, and therefore the analysis of ctDNA is valuable to complement current follow-up methods. Background: Targeted therapies, although contributing to survival improvement in metastatic colorectal cancer ( mCRC), are expensive and may cause adverse effects. Therefore, confirming that patients are responding to these therapies is extremely important. Currently, follow-up is performed using radiographic evaluation, which has its limitations. Liquid biopsies, reflecting real-time tumor characteristics, hold great potential in monitoring tumor disease. Patients and Methods: Blood samples were collected at different time points during treatment of 24 mCRC patients. Mutation and NPY methylation picoliter droplet-based digital PCR ( ddPCR) assays were performed on circulating DNA to investigate whether these assays can be used for disease monitoring. Results: The results of the mutation and methylation assays were correlated with each other and corresponded with the results of radiographic evaluation. There was a steep decrease in circulating tumor DNA levels immediately after treatment initiation. Furthermore, circulating tumor DNA levels were increased in progressive samples and were undetectable in patients undergoing curative surgery. Conclusion: This prospective study showed that tumor-specific mutation and NPY methylation ddPCR assays performed on circulating DNA can be used for the follow-up of mCRC patients during treatment and could complement current follow-up methods. The analysis of NPY methylation is promising, as it has the additional advantage that no prior knowledge of tumor mutations is needed. (C) 2018 Elsevier Inc. All rights reserved.

Jaar van publicatie:2018