Total and mutated EGFR quantification in cell-free DNA from non-small cell lung cancer patients detects tumor heterogeneity and presents prognostic value

< h3 class= " a-plus-plus " > Abstract < /h3 > < p class= " a-plus-plus " > Mutation analysis of epidermal growth factor receptor (EGFR) gene is essential for treatment selection in non-small cell lung cancer (NSCLC). Analysis is usually performed in tumor samples. We evaluated the clinical utility of < em class= " a-plus-plus " > EGFR < /em > analysis in plasma cell-free DNA (cfDNA) from patients under treatment with EGFR inhibitors. We selected 36 patients with NSCLC and < em class= " a-plus-plus " > EGFR < /em > -activating mutations. Blood samples were collected at baseline and during treatment with EGFR inhibitors. Wild-type < em class= " a-plus-plus " > EGFR < /em > , L858R, delE746-A750, and T790M mutations were quantified in cfDNA by droplet digital PCR. Stage IV patients had higher total circulating < em class= " a-plus-plus " > EGFR < /em > copy levels than stage I (3523 vs. 1003 copies/mL; < em class= " a-plus-plus " > p < /em >   & lt;  0.01). There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; < em class= " a-plus-plus " > p < /em >  = 0.001). In 34 % of advanced NSCLC patients, we detected mutations in cfDNA not previously detected in tumor samples and double mutations in 17 %. Patients with baseline total < em class= " a-plus-plus " > EGFR < /em > copy levels above the median presented decreased overall survival (OS) (341 vs. 870  days, < em class= " a-plus-p...

Source: Tumor Biology - July 28, 2016 Category: Cancer & Oncology Source Type: research