Maheswaran S et al. – Molecular analysis of circulating tumor cells from blood of NSCLC pts may serve to monitor changes in epithelial tumor genotypes during treatment Methods
Molecular characterization of circulating tumor cells as a strategy for noninvasive serial monitoring of tumor genotypes during treatment
Use of a microfluidic device with microposts coated with antibodies against epithelial cells to capture highly purified circulating tumor cells from blood of NSCLC pts
Allele-specific PCR amplification for epidermal growth factor receptor gene (EGFR) mutational analysis on circulating tumor cell DNA
Comparison of results with those from concurrently isolated free plasma DNA and from original tumor-biopsy specimens
Results
Isolation of circulating tumor cells from 27 metastatic NSCLC pts; median number, 74 cells/mL
Identification of expected EGFR-activating mutation in circulating tumor cells in 11 of 12 pts (92%) and in matched free plasma DNA in 4 of 12 pts (33%)
Detection of T790M mutation (conferring drug resistance), in circulating tumor cells from pts with EGFR mutations who received tyrosine kinase inhibitors
Correlation of the presence of T790M mutation with reduced progression-free survival (7.7 vs 16.5 mo)
Changes in number of captured cells: reduction associated with radiographic tumor response; increase associated with tumor progression and additional EGFR mutations in some cases