TY - JOUR
T1 - BRAF Mutation testing in cell-free DNA from the plasma of patients with advanced cancers using a rapid, automated molecular diagnostics system
AU - Janku, Filip
AU - Huang, Helen J.
AU - Claes, Bart
AU - Falchook, Gerald S.
AU - Fu, Siqing
AU - Hong, David
AU - Ramzanali, Nishma M.
AU - Nitti, Giovanni
AU - Cabrilo, Goran
AU - Tsimberidou, Apostolia M.
AU - Naing, Aung
AU - Piha-Paul, Sarina A.
AU - Wheler, Jennifer J.
AU - Karp, Daniel D.
AU - Holley, Veronica R.
AU - Zinner, Ralph G.
AU - Subbiah, Vivek
AU - Luthra, Rajyalakshmi
AU - Kopetz, Scott
AU - Overman, Michael J.
AU - Kee, Bryan K.
AU - Patel, Sapna
AU - Devogelaere, Benoit
AU - Sablon, Erwin
AU - Maertens, Geert
AU - Mills, Gordon B.
AU - Kurzrock, Razelle
AU - Meric-Bernstam, Funda
N1 - Publisher Copyright:
©2016 American Association for Cancer Research.
PY - 2016/6
Y1 - 2016/6
N2 - Cell-free (cf) DNA from plasma offers an easily obtainable material for BRAF mutation analysis for diagnostics and response monitoring. In this study, plasma-derived cfDNA samples from patients with progressing advanced cancers or malignant histiocytosis with known BRAFV600 status from formalin-fixed paraffinembedded (FFPE) tumors were tested using a prototype version of the Idylla BRAF Mutation Test, a fully integrated real-time PCRbased test with turnaround time about 90 minutes. Of 160 patients, BRAFV600 mutations were detected in 62 (39%) archival FFPE tumor samples and 47 (29%) plasma cfDNA samples. The two methods had overall agreement in 141 patients [88%; k, 0.74; SE, 0.06; 95% confidence interval (CI), 0.63-0.85]. Idylla had a sensitivity of 73% (95% CI, 0.60-0.83) and specificity of 98% (95% CI, 0.93-1.00). A higher percentage, but not concentration, of BRAFV600 cfDNA in the wild-type background (>2% vs. ≤ 2%) was associated with shorter overall survival (OS; P= 0.005) and in patients with BRAF mutations in the tissue, who were receiving BRAF/MEK inhibitors, shorter time to treatment failure (TTF; P = 0.001). Longitudinal monitoring demonstrated that decreasing levels of BRAFV600 cfDNA were associated with longer TTF (P= 0.045). In conclusion, testing for BRAFV600 mutations in plasma cfDNA using the Idylla BRAF Mutation Test has acceptable concordance with standard testing of tumor tissue. A higher percentage of mutant BRAFV600 in cfDNA corresponded with shorter OS and in patients receiving BRAF/MEK inhibitors also with shorter TTF.
AB - Cell-free (cf) DNA from plasma offers an easily obtainable material for BRAF mutation analysis for diagnostics and response monitoring. In this study, plasma-derived cfDNA samples from patients with progressing advanced cancers or malignant histiocytosis with known BRAFV600 status from formalin-fixed paraffinembedded (FFPE) tumors were tested using a prototype version of the Idylla BRAF Mutation Test, a fully integrated real-time PCRbased test with turnaround time about 90 minutes. Of 160 patients, BRAFV600 mutations were detected in 62 (39%) archival FFPE tumor samples and 47 (29%) plasma cfDNA samples. The two methods had overall agreement in 141 patients [88%; k, 0.74; SE, 0.06; 95% confidence interval (CI), 0.63-0.85]. Idylla had a sensitivity of 73% (95% CI, 0.60-0.83) and specificity of 98% (95% CI, 0.93-1.00). A higher percentage, but not concentration, of BRAFV600 cfDNA in the wild-type background (>2% vs. ≤ 2%) was associated with shorter overall survival (OS; P= 0.005) and in patients with BRAF mutations in the tissue, who were receiving BRAF/MEK inhibitors, shorter time to treatment failure (TTF; P = 0.001). Longitudinal monitoring demonstrated that decreasing levels of BRAFV600 cfDNA were associated with longer TTF (P= 0.045). In conclusion, testing for BRAFV600 mutations in plasma cfDNA using the Idylla BRAF Mutation Test has acceptable concordance with standard testing of tumor tissue. A higher percentage of mutant BRAFV600 in cfDNA corresponded with shorter OS and in patients receiving BRAF/MEK inhibitors also with shorter TTF.
UR - http://www.scopus.com/inward/record.url?scp=84971516426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84971516426&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-15-0712
DO - 10.1158/1535-7163.MCT-15-0712
M3 - Article
C2 - 27207774
AN - SCOPUS:84971516426
SN - 1535-7163
VL - 15
SP - 1397
EP - 1404
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 6
ER -