Abstract 4590
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.
Resources from the same session
3664 - Longitudinal changes in cell-free DNA (cfDNA) methylation levels identify early non-responders to treatment in advanced solid tumors
Presenter: Andrew Davis
Session: Poster Display session 3
Resources:
Abstract
3212 - Multigene panel testing results for hereditary breast cancer in 1325 individuals: implications for gene selection and considerations for guidelines.
Presenter: Georgios Tsaousis
Session: Poster Display session 3
Resources:
Abstract
2591 - PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Presenter: Julia Quintanilha
Session: Poster Display session 3
Resources:
Abstract
4377 - ERBB2 mRNA as a predictor in HER2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC) treated with HER2 blockade in combination with endocrine therapy (ET): a retrospective analysis of the ALTERNATIVE and SOLTI-PAMELA trials.
Presenter: Nuria Chic
Session: Poster Display session 3
Resources:
Abstract
3439 - Early on-treatment vs pre-treatment tumor transcriptomes as predictors of response to neoadjuvant therapy for HER2-positive inflammatory breast cancer
Presenter: Sonia Pernas
Session: Poster Display session 3
Resources:
Abstract
2512 - AXL expression predicts poor prognosis and lack of efficacy of anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC)
Presenter: Claudia Cardone
Session: Poster Display session 3
Resources:
Abstract
4061 - Prevalence of EGFR mutations and its correlation with Egyptian patients’ human kinetics (PEEK Study)
Presenter: Adel Ibrahim
Session: Poster Display session 3
Resources:
Abstract
2547 - Evaluation of tumor microenvironment identifies immune correlates of response to combination immunotherapy with margetuximab (M) and pembrolizumab (P) in HER2+ gastroesophageal adenocarcinoma (GEA)
Presenter: Sergio Rutella
Session: Poster Display session 3
Resources:
Abstract
4671 - Clinicopathological and molecular criteria assessment for the screening of hypermutated proficient mismatch repair (pMMR) colorectal cancers (CRC) with exonucleasic domain POLE (edPOLE) mutations (mt).
Presenter: Benoit Rousseau
Session: Poster Display session 3
Resources:
Abstract
3862 - Tumor mutation burden and microsatellite instability in colorectal cancer
Presenter: Francesca Fenizia
Session: Poster Display session 3
Resources:
Abstract