Evaluation of liquid biopsies for the follow-up of metastatic colorectal cancer patients during treatment.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide with a high morbidity and mortality. Although CRC can be cured in most cases when it is detected in its early stages, the treatment of patients with metastatic CRC (mCRC) still has its limitations. Accurate monitoring of tumor disease and appropriate tumor tissue for mutation-analysis before anti-EGFR therapy are lacking. Possible solutions can be found in liquid biopsies. During my PhD, a lot of time and effort has been put in starting up a clinical trial recruiting mCRC patients treated in first-line with targeted therapies. Blood samples are collected at four different time points during treatment for the isolation of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs). Our first pilot study on 24 patients has just been finished and reveals exciting results. We find out that it is possible to monitor tumor disease during treatment using mutation and methylation digital droplet PCR (ddPCR) assays on ctDNA and these results were also corresponding with the imaging results. We would like to confirm these results on an expanded study cohort where additional monthly blood samples are collected between time point 3 (first radiographic evaluation) and 4 (disease progression or curative surgery). In this way, we want to investigate whether it is possible to early detect progression, meaning before detection by radiographic evaluation. At this moment, we have the knowledge, the patients (n=40) and the motivation to perform these highly interesting experiments, we only need some extra time. In addition, some additional experiments should be performed on ctDNA of serum samples to make a clear comparison between plasma and serum samples. If our results would indicate that ctDNA isolated from serum samples follows the same trend as plasma samples during tumor disease monitoring, this will be the start of multiple liquid biopsy studies as a lot of serum samples are stored in the biobank of different hospitals. Lastly, we want to finish our study on CTCs. Up to now, we performed already expensive and time-consuming detection and isolation of CTCs. Unfortunately, we did not have the time yet to perform whole genome amplification and mutation detection. It would be very interesting to evaluate whether CTCs reveal the same or additional information compared to circulating DNA. In conclusion, liquid biopsies are promising tools in mCRC treatment. We managed to collect a very interesting patient cohort and showed already some exciting results. Unfortunately, due to lack of time, the majority of the samples has not yet been studied. Thanks to the acquired expertise so far, I believe that we can perform very interesting experiments with a minimal time investment (12 months) which enables me to successfully and proudly finish this PhD.

Keywords:COLORECTAL CANCER

Disciplines:Morphological sciences, Oncology