4590 - Circulating-free DNA analysis from long-term surviving metastatic colorectal cancer patients undergoing surgery for resectable disease.

Background

Liquid biopsies (LB) allow monitoring of genetically different and co-occurring cancer cell clones. In metastatic colorectal cancer (mCRC), circulating-free DNA (cfDNA) can be relevant for monitoring treatment and identification of molecular alterations resulting in disease relapse often earlier than radiological examinations.

Methods

Patients with mCRC at diagnosis and treated with chemotherapy (CT) in combination with antibodies (bevacizumab, cetuximab or panitumumab) before undergoing surgery for resectable disease were included. LB were collected before therapy start, every four weeks during treatment, within ten days of radiological disease evaluation, at radiological relapse and until two months after progression. Next generation sequencing based on plasma samples was performed (testing for mutations and copy number variations covering 77 genes).

Results

From February 2016 to October 2018, 14 patients having surgery after first line treatment were included herein; median follow-up was 21.5 months. Five of them had RAS wild-type disease and received CT plus anti-EGFR treatment, while nine RAS mutated mCRC patients received bevacizumab. Disease relapse happened in seven cases, with subsequent death in three cases. In six out of seven cases, gene alterations were already detected in the pre-operative cfDNA. In the seven cases without disease relapse, gene variants were detected even after the surgery in two patients despite receiving radical resection. Median number of gene variants was two. Beside the well-established mutations in TP53 gene, both APC and ROS1 gene mutations were frequent, while further evaluations are required for the other variants detected.

Conclusions

Evaluation of cfDNA mutations in LB from mCRC may be a useful tool for monitoring clinical response and predict treatment outcome. Moreover, this molecular analysis can help to subgroup patients with regard to risk of relapse after radical surgery. Indeed, cfDNA mutations present before surgery seem to be an indication for a higher risk of post-surgery disease relapse.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

MEDeA Onlus.

Disclosure

All authors have declared no conflicts of interest.