TY - JOUR
T1 - Actionable mutations in plasma cell-free DNA in patients with advanced cancers referred for experimental targeted therapies
AU - Janku, Filip
AU - Angenendt, Philipp
AU - Tsimberidou, Apostolia M.
AU - Fu, Siqing
AU - Naing, Aung
AU - Falchook, Gerald S.
AU - Hong, David S.
AU - Holley, Veronica R.
AU - Cabrilo, Goran
AU - Wheler, Jennifer J.
AU - Piha-Paul, Sarina A.
AU - Zinner, Ralph G.
AU - Bedikian, Agop Y.
AU - Overman, Michael J.
AU - Kee, Bryan K.
AU - Kim, Kevin B.
AU - Scott Kopetz, E.
AU - Luthra, Rajyalakshmi
AU - Diehl, Frank
AU - Meric-Bernstam, Funda
AU - Kurzrock, Razelle
PY - 2015
Y1 - 2015
N2 - Cell-free (cf) DNA in the plasma of cancer patients offers an easily obtainable source of biologic material for mutation analysis. Plasma samples from 157 patients with advanced cancers who progressed on systemic therapy were tested for 21 mutations in BRAF, EGFR, KRAS, and PIK3CA using the BEAMing method and results were compared to mutation analysis of archival tumor tissue from a CLIA-certified laboratory obtained as standard of care from diagnostic or therapeutic procedures. Results were concordant for archival tissue and plasma cfDNA in 91% cases for BRAF mutations (kappa = 0.75, 95% confidence interval [CI] 0.63 - 0.88), in 99% cases for EGFR mutations (kappa = 0.90, 95% CI 0.71- 1.00), in 83% cases for KRAS mutations (kappa = 0.67, 95% CI 0.54 - 0.80) and in 91% cases for PIK3CA mutations (kappa = 0.65, 95% CI 0.46 - 0.85). Patients (n = 41) with > 1% of KRAS mutant cfDNA had a shorter median survival compared to 20 patients with < /= 1% of KRAS mutant DNA (4.8 vs. 7.3 months, p = 0.008). Similarly, 67 patients with > 1% of mutant cfDNA (BRAF, EGFR, KRAS, or PIK3CA) had a shorter median survival compared to 33 patients with < /= 1% of mutant cfDNA (5.5 vs. 9.8 months, p = 0.001), which was confirmed in multivariable analysis.
AB - Cell-free (cf) DNA in the plasma of cancer patients offers an easily obtainable source of biologic material for mutation analysis. Plasma samples from 157 patients with advanced cancers who progressed on systemic therapy were tested for 21 mutations in BRAF, EGFR, KRAS, and PIK3CA using the BEAMing method and results were compared to mutation analysis of archival tumor tissue from a CLIA-certified laboratory obtained as standard of care from diagnostic or therapeutic procedures. Results were concordant for archival tissue and plasma cfDNA in 91% cases for BRAF mutations (kappa = 0.75, 95% confidence interval [CI] 0.63 - 0.88), in 99% cases for EGFR mutations (kappa = 0.90, 95% CI 0.71- 1.00), in 83% cases for KRAS mutations (kappa = 0.67, 95% CI 0.54 - 0.80) and in 91% cases for PIK3CA mutations (kappa = 0.65, 95% CI 0.46 - 0.85). Patients (n = 41) with > 1% of KRAS mutant cfDNA had a shorter median survival compared to 20 patients with < /= 1% of KRAS mutant DNA (4.8 vs. 7.3 months, p = 0.008). Similarly, 67 patients with > 1% of mutant cfDNA (BRAF, EGFR, KRAS, or PIK3CA) had a shorter median survival compared to 33 patients with < /= 1% of mutant cfDNA (5.5 vs. 9.8 months, p = 0.001), which was confirmed in multivariable analysis.
KW - BRAF
KW - Cell-free DNA
KW - EGFR
KW - KRAS
KW - PIK3CA
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U2 - 10.18632/oncotarget.3373
DO - 10.18632/oncotarget.3373
M3 - Article
C2 - 25980577
AN - SCOPUS:84930025659
SN - 1949-2553
VL - 6
SP - 12809
EP - 12821
JO - Oncotarget
JF - Oncotarget
IS - 14
ER -