translational research. 1617P. CLINICAL INTEREST OF DIGITAL PCR FOR ROUTINE. DETECTION OF CIRCULATING DNA IN METASTATIC. COLORECTAL ...
Annals of Oncology 25 (Supplement 4): iv546–iv563, 2014 doi:10.1093/annonc/mdu358.48
translational research 1617P
CLINICAL INTEREST OF DIGITAL PCR FOR ROUTINE DETECTION OF CIRCULATING DNA IN METASTATIC COLORECTAL CANCER
D. Sefrioui1, C. Vasseur2, R. Sesboué2, F. Blanchard3, A. Gangloff1, M. Baretti4, L. Beaussire2, F. Clatot5, C. Dolfus3, J. Sabourin3, P. Michel1, T. Frebourg2, F. Di Fiore6 1 Digestive Oncology Unit, C.H.U. Charles Nicolle, Rouen, FRANCE 2 U1079, Rouen University, Rouen, FRANCE 3 Department of Pathology, C.H.U. Charles Nicolle, Rouen, FRANCE 4 Cancer Center, Humanitas Clinical and Research Center, Rozzano, ITALY 5 Medical Oncology Department, Centre Henri Becquerel, Rouen, FRANCE 6 Digestive Oncology Unit, CHU Hôpitaux de Rouen-Charles Nicolle, Rouen, FRANCE
abstracts
Aim: Liquid biopsy based on circulating DNA is considered as a promising issue in cancer patients to assess key somatic alterations involved in disease progression or in treatment sensitivity. However, the clinical relevance of sensitive detection methods such as Digital PCR remains to be established. The aim was to evaluate the clinical interest of Digital PCR in circulating DNA detection including cell-free (cfDNA) and circulating tumour (ctDNA) DNA in patients treated for a metastatic colorectal cancer (MCRC).
Methods: A prospective single-center study was conducted from April to July 2013 in 34 patients treated for a MCRC. DNA was extracted from 1 mL of plasma using the QIAamp ® kit Circulating Nucleic Acid. ctDNA was detected and quantified (fragments per mL of plasma) by Digital PCR (Digital 3D ™ QuantStudio ®, Life Technologies) from KRAS mutations identified in the primary tumor. cfDNA was also quantified by Digital PCR and expressed in ng/mL of plasma. Response to chemotherapy and survival were analyzed according to both cfDNA and ctDNA. cfDNA was integrated as a dichotomized covariate (above versus below 75% percentile) for response and overall survival (OS) analysis. Results: The mean cfDNA concentration was 106 ng/mL (range, 3-1443 ng/mL). KRAS mutations were identified in tumour from 16/34 patients (c.34G>T, n=1; c.35G>A, n=8; c.35G>C, n=3; c.35G>T, n=2; c.38G>A, n=2) with a sensitivity and specificity for ctDNA detection of 63% (10/16) and 100% (0/18), respectively. The mean level of ctDNA was 21972 fragments/mL (range, 136 and 308,000). There was a significant correlation between cfDNA and ctDNA (ρ=0.993, p
