Molecular analysis may allow noninvasive monitoring in lung cancer

Using isolated circulating tumor cells from 27 patients with non–small-cell lung cancer, researchers were able to detect the mutations of the epidermal growth factor receptor gene, meaning it may be possible to conduct noninvasive serial monitoring of tumor genotypes during treatment.

Researchers at several institutions in Boston used a newly developed microfluidic device to capture highly purified circulating tumor cells. They conducted EGFR mutational analysis on DNA recovered from the tumor cells using allele-specific polymerase-chain reaction amplification.

The researchers isolated circulating tumor cells in all patients, with a median number of 74 cells per milliliter. They found the EGFR activating mutation in 92% of patients.

The study team also found low levels of the T790M mutation, which is associated with drug resistance, in a small number of cells in 10 of 26 patients. The presence of T790M in pretreatment tumor biopsy specimens was associated with a lowered PFS — 7.7 months compared with 16.5 months for patients without the mutation (HR=11.5; 95% CI, 2.94-45.1).

In a related editorial, Joan H. Schiller, MD, division director of hematology/oncology at the University of Texas-Southwestern Medical Center in Dallas, questioned whether the CTC-chip used in the study could consistently isolate enough viable cells of sufficient purity to identify treatment effects, and whether the technique would allow for analysis of pathways other than EGFR.

“Moreover, this study represents a proof of principle, and the ease with which this approach can be used by others remains to be determined,” she wrote. “That said the capture and analysis of circulating tumor cells from patients with lung cancer represents a new diagnostic approach that may bring us closer to an era of individualized medicine.” – by Jason Harris

N Engl J Med. 2008;doi:10.1056/NEJMoa0800668.