Abstract 2298: Monitoring of circulating tumor DNA in non metastatic gastric cancer
Authors: Cabel Luc , Decraene Charles , Bieche Ivan , Pierga Jean-Yves , Bennamoun Mostefa , Fuks David , Ferraz Jean-Marc , Lefevre Marine , Baulande Sylvain , Bernard Virginie , Mariani Pascale , Cottu Paul , Proudhon Charlotte , Bidard François-clément , Louvet Christophe 
Published: August 2019

Introduction Perioperative chemotherapy significantly improves the survival of patients with non-metastatic gastric adenocarcinoma (GA), yet some patients develop local and/or distant relapse during follow-up. The present study was designed to monitor circulating tumor DNA (ctDNA) levels during perioperative chemotherapy in patients with a non-metastatic GA.

Patients and Methods As part of a prospective study (NCT02220556), plasma samples were prospectively collected in patients undergoing perioperative chemotherapy for non-metastatic GA. Plasma was collected prior to the initiation of perioperative chemotherapy, before surgery and after surgery. In each patient, mutations retrieved by panel NGS on tumor sample were then tracked in circulating cell-free DNA from 4ml of plasma by droplet digital PCR (ddPCR, Biorad). Circulating tumor DNA detection was correlated with the prospectively collected patient characteristics and outcome.

Results Thirty-two patients with a diagnosis of non-metastatic GA were included in this study from 06.2014 to 10.2016. Tumor panel sequencing retrieved a mutation deemed to be trackable in plasma for 20 patients, of which 7 experienced a relapse during follow-up (median follow-up: 26.4 months). Among the 19 plasma samples available prior to perioperative chemotherapy, ctDNA was detectable in four patients (N=4/19, sensitivity: 21%; 95%CI=[2.7-39%]), with a median allelic frequency of 1.6% (range=0.8-2.3%). ctDNA detection prior to perioperative chemotherapy was not correlated with any patient characteristic and had no significant prognostic effect. Before surgery, no patient with available plasma sample (N=0/18) had detectable ctDNA levels. After surgery, one patient (N=1/13) had detectable ctDNA level with a low allelic frequency (0.7%); that patient experienced a very short-term distant relapse only 3 months after surgery. The other four patients who experienced a relapse with available plasma sample after surgery had no ctDNA detected after surgery.

Conclusion This study is the first to report the ctDNA detection rate before and during perioperative chemotherapyfor non-metastatic GA. Despite the use of large volume of plasma, the detection rate at baseline was lower than expected, knowing that the same technical approach (tumor NGS followed by customized ddPCR on plasma) yielded a 75% detection rate in non-metastatic triple negative breast cancer (Riva et al, Clin Chem 2017). Mechanisms underlying this low detection rate are still to be characterized. In regards to ctDNA kinetic during therapy, preoperative chemotherapy was associated with a marked decrease of ctDNA levels - which became undetectable in all patients. Our data showed a very short lead time between rising ctDNA detection after curative surgery and the occurrence of a metastatic relapse, suggesting that postoperative ctDNA detection can uncover growing metastases.

Citation Format: Luc Cabel, Charles Decraene, Ivan Bieche, Jean-Yves Pierga, Mostefa Bennamoun, David Fuks, Jean-Marc Ferraz, Marine Lefevre, Sylvain Baulande, Virginie Bernard, Pascale Mariani, Paul Cottu, Charlotte Proudhon, François-clément Bidard, Christophe Louvet. Monitoring of circulating tumor DNA in non metastatic gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2298.