David Sefrioui1, Nasrin Sarafan-Vasseur2, Ludivine Beaussire3, Marina Baretti4, Alice Gangloff5, France Blanchard6, Florian Clatot7, Jean-Christophe Sabourin8, Richard Sesboüé2, Thierry Frebourg2, Pierre Michel9, Frédéric Di Fiore10. 1. Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France. Electronic address: david.sefrioui@chu-rouen.fr. 2. EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France. 3. Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France; Cancer Center, Humanitas Cinical and Research Center, Rozzano, Milano, Italy; Department of Pathology, Rouen University Hospital, Rouen Cedex, France; Department of Medical Oncology, Centre Henri Becquerel, Rouen Cedex 1, France. 4. Cancer Center, Humanitas Cinical and Research Center, Rozzano, Milano, Italy. 5. Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France. 6. EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Department of Pathology, Rouen University Hospital, Rouen Cedex, France. 7. EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Department of Medical Oncology, Centre Henri Becquerel, Rouen Cedex 1, France. 8. EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France; Department of Pathology, Rouen University Hospital, Rouen Cedex, France. 9. Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France. 10. Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen Cedex, France; EquIpe de Recherche Onco-Normande (IRON), Rouen University Hospital, Rouen Cedex, France; Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen Cedex, France; Department of Medical Oncology, Centre Henri Becquerel, Rouen Cedex 1, France.
Abstract
BACKGROUND: The detection of circulating DNA is considered a promising strategy in cancer patients. Digital PCR has emerged as a sensitive method able to quantify both circulating free and tumour DNA. AIM: The aim of this study was to prospectively evaluate the clinical value of a chip-based digital PCR for the detection of circulating DNA. METHODS: Digital PCR was used in 34 metastatic colorectal cancer patients to detect and quantify circulating free and tumour DNA based on K-ras mutational status. Clinical outcomes were analyzed according to circulating DNA measurements. RESULTS: Digital PCR yielded a detection rate of 69% for circulating tumour DNA. The median concentrations of circulating free and tumour DNA were 20 and 6.8 ng/mL, respectively, with significant correlation between both biomarkers (p<0.001). Median overall survival was 4.8 months in patients with high circulating free DNA (>75% quartile) versus not reached in patients with a low level (<25% quartile) (p=0.029). Moreover, median overall survival was significantly decreased in patients with detectable circulating tumour DNA compared to those without (respectively 11.8 months versus not reached, p=0.04). CONCLUSIONS: Chip-based digital PCR is a simple and non-invasive method allowing the efficient detection of circulating DNA. Our results highlight that levels of these circulating markers may have a potential prognostic value.
BACKGROUND: The detection of circulating DNA is considered a promising strategy in cancerpatients. Digital PCR has emerged as a sensitive method able to quantify both circulating free and tumour DNA. AIM: The aim of this study was to prospectively evaluate the clinical value of a chip-based digital PCR for the detection of circulating DNA. METHODS: Digital PCR was used in 34 metastatic colorectal cancerpatients to detect and quantify circulating free and tumour DNA based on K-ras mutational status. Clinical outcomes were analyzed according to circulating DNA measurements. RESULTS: Digital PCR yielded a detection rate of 69% for circulating tumour DNA. The median concentrations of circulating free and tumour DNA were 20 and 6.8 ng/mL, respectively, with significant correlation between both biomarkers (p<0.001). Median overall survival was 4.8 months in patients with high circulating free DNA (>75% quartile) versus not reached in patients with a low level (<25% quartile) (p=0.029). Moreover, median overall survival was significantly decreased in patients with detectable circulating tumour DNA compared to those without (respectively 11.8 months versus not reached, p=0.04). CONCLUSIONS: Chip-based digital PCR is a simple and non-invasive method allowing the efficient detection of circulating DNA. Our results highlight that levels of these circulating markers may have a potential prognostic value.
Authors: Karen-Lise G Spindler; Anders K Boysen; Niels Pallisgård; Julia S Johansen; Josep Tabernero; Morten M Sørensen; Benny V Jensen; Torben F Hansen; David Sefrioui; Rikke F Andersen; Ivan Brandslund; Anders Jakobsen Journal: Oncologist Date: 2017-08-04
Authors: Louise B Callesen; Julian Hamfjord; Anders K Boysen; Niels Pallisgaard; Tormod K Guren; Elin H Kure; Karen-Lise G Spindler Journal: Br J Cancer Date: 2022-04-19 Impact factor: 9.075