Efficacy of circulating plasma DNA as a diagnostic tool for advanced non-small cell lung cancer and its predictive utility for survival and response to chemotherapy

Abstract 

Background

Increased presence of circulating DNA has been reported in lung cancer. However, the utility of circulating DNA as a diagnostic and prognostic marker and in assessing therapeutic efficacy is yet to be realized.

Methods

Circulating plasma DNA levels were quantified in 100 patients with non-small cell lung cancer and 100 age-matched controls. Forty-two patients received platinum-based chemotherapy for a minimum of three cycles after which response was assessed by computed tomography. Association of circulating plasma DNA levels with lactate dehydrogenase (LDH) levels, leukocyte counts, response to therapy and survival was determined.

Results

The mean (±SD) plasma level of circulating DNA in lung cancer patients was 122.7 (±47.4)ng/mL, which was significantly higher than the controls (74.0 (±19.8)ng/mL; p<0.001). At 95% specificity, circulating plasma DNA levels detected lung cancer with a sensitivity of 52% at a cut-off of 104.5ng/mL. Circulating plasma DNA levels significantly correlated with higher LDH levels, but not with leukocyte counts or any of the prognostic factors. There was no significant difference in pre-treatment circulating plasma DNA levels between responders and non-responders to chemotherapy. However, circulating plasma DNA levels were significantly higher in patients with progressive disease as compared to patients with partial remission or stable disease.

Conclusions

In our opinion, circulating DNA can serve as a diagnostic tool, especially if combined with other more sensitive tumor markers or imaging modalities. Further, circulating DNA may predict therapeutic efficacy which may help in better management of cancer patients.

Keywords: Non-small cell lung cancer, Sensitivity, Specificity, Diagnosis, Prognosis, Survival