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Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients

This study was designed to monitor circulating tumor DNA (ctDNA) levels during perioperative chemotherapy in patients with non-metastatic gastric adenocarcinoma. Plasma samples were prospectively collected in patients undergoing perioperative chemotherapy for non-metastatic gastric adenocarcinoma (e...

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Autores principales: Cabel, Luc, Decraene, Charles, Bieche, Ivan, Pierga, Jean-Yves, Bennamoun, Mostefa, Fuks, David, Ferraz, Jean-Marc, Lefevre, Marine, Baulande, Sylvain, Bernard, Virginie, Vacher, Sophie, Mariani, Pascale, Proudhon, Charlotte, Bidard, Francois-Clement, Louvet, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468548/
https://www.ncbi.nlm.nih.gov/pubmed/30901876
http://dx.doi.org/10.3390/cancers11030396
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author Cabel, Luc
Decraene, Charles
Bieche, Ivan
Pierga, Jean-Yves
Bennamoun, Mostefa
Fuks, David
Ferraz, Jean-Marc
Lefevre, Marine
Baulande, Sylvain
Bernard, Virginie
Vacher, Sophie
Mariani, Pascale
Proudhon, Charlotte
Bidard, Francois-Clement
Louvet, Christophe
author_facet Cabel, Luc
Decraene, Charles
Bieche, Ivan
Pierga, Jean-Yves
Bennamoun, Mostefa
Fuks, David
Ferraz, Jean-Marc
Lefevre, Marine
Baulande, Sylvain
Bernard, Virginie
Vacher, Sophie
Mariani, Pascale
Proudhon, Charlotte
Bidard, Francois-Clement
Louvet, Christophe
author_sort Cabel, Luc
collection PubMed
description This study was designed to monitor circulating tumor DNA (ctDNA) levels during perioperative chemotherapy in patients with non-metastatic gastric adenocarcinoma. Plasma samples were prospectively collected in patients undergoing perioperative chemotherapy for non-metastatic gastric adenocarcinoma (excluding T1N0) prior to the initiation of perioperative chemotherapy, before and after surgery (NCT02220556). In each patient, mutations retrieved by targeted next-generation sequencing (NGS) on tumor samples were then tracked in circulating cell-free DNA from 4 mL of plasma by droplet digital PCR. Thirty-two patients with a diagnosis of non-metastatic gastric adenocarcinoma were included. A trackable mutation was identified in the tumor in 20 patients, seven of whom experienced relapse during follow-up. ctDNA was detectable in four patients (N = 4/19, sensitivity: 21%; 95% confidence interval CI = 8.5–43%, no baseline plasma sample was available for one patient), with a median allelic frequency (MAF) of 1.6% (range: 0.8–2.3%). No patient with available plasma samples (N = 0/18) had detectable ctDNA levels before surgery. After surgery, one of the 13 patients with available plasma samples had a detectable ctDNA level with a low allelic frequency (0.7%); this patient experienced a very short-term distant relapse only 3 months after surgery. No ctDNA was detected after surgery in the other four patients with available plasma samples who experienced a later relapse (median = 14.4, range: 9.3–26 months). ctDNA monitoring during preoperative chemotherapy and after surgery does not appear to be a useful tool in clinical practice for non-metastatic gastric cancer to predict the efficacy of chemotherapy and subsequent relapse, essentially due to the poor sensitivity of ctDNA detection.
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spelling pubmed-64685482019-04-24 Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients Cabel, Luc Decraene, Charles Bieche, Ivan Pierga, Jean-Yves Bennamoun, Mostefa Fuks, David Ferraz, Jean-Marc Lefevre, Marine Baulande, Sylvain Bernard, Virginie Vacher, Sophie Mariani, Pascale Proudhon, Charlotte Bidard, Francois-Clement Louvet, Christophe Cancers (Basel) Article This study was designed to monitor circulating tumor DNA (ctDNA) levels during perioperative chemotherapy in patients with non-metastatic gastric adenocarcinoma. Plasma samples were prospectively collected in patients undergoing perioperative chemotherapy for non-metastatic gastric adenocarcinoma (excluding T1N0) prior to the initiation of perioperative chemotherapy, before and after surgery (NCT02220556). In each patient, mutations retrieved by targeted next-generation sequencing (NGS) on tumor samples were then tracked in circulating cell-free DNA from 4 mL of plasma by droplet digital PCR. Thirty-two patients with a diagnosis of non-metastatic gastric adenocarcinoma were included. A trackable mutation was identified in the tumor in 20 patients, seven of whom experienced relapse during follow-up. ctDNA was detectable in four patients (N = 4/19, sensitivity: 21%; 95% confidence interval CI = 8.5–43%, no baseline plasma sample was available for one patient), with a median allelic frequency (MAF) of 1.6% (range: 0.8–2.3%). No patient with available plasma samples (N = 0/18) had detectable ctDNA levels before surgery. After surgery, one of the 13 patients with available plasma samples had a detectable ctDNA level with a low allelic frequency (0.7%); this patient experienced a very short-term distant relapse only 3 months after surgery. No ctDNA was detected after surgery in the other four patients with available plasma samples who experienced a later relapse (median = 14.4, range: 9.3–26 months). ctDNA monitoring during preoperative chemotherapy and after surgery does not appear to be a useful tool in clinical practice for non-metastatic gastric cancer to predict the efficacy of chemotherapy and subsequent relapse, essentially due to the poor sensitivity of ctDNA detection. MDPI 2019-03-21 /pmc/articles/PMC6468548/ /pubmed/30901876 http://dx.doi.org/10.3390/cancers11030396 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cabel, Luc
Decraene, Charles
Bieche, Ivan
Pierga, Jean-Yves
Bennamoun, Mostefa
Fuks, David
Ferraz, Jean-Marc
Lefevre, Marine
Baulande, Sylvain
Bernard, Virginie
Vacher, Sophie
Mariani, Pascale
Proudhon, Charlotte
Bidard, Francois-Clement
Louvet, Christophe
Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients
title Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients
title_full Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients
title_fullStr Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients
title_full_unstemmed Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients
title_short Limited Sensitivity of Circulating Tumor DNA Detection by Droplet Digital PCR in Non-Metastatic Operable Gastric Cancer Patients
title_sort limited sensitivity of circulating tumor dna detection by droplet digital pcr in non-metastatic operable gastric cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468548/
https://www.ncbi.nlm.nih.gov/pubmed/30901876
http://dx.doi.org/10.3390/cancers11030396
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