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
Received 14 October 2009; received in revised form 28 January 2010; accepted 30 January 2010. published online 24 February 2010. Corrected Proof
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.
aDepartment of Medicine, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India
bDivision of Molecular Oncology, Institute of Cytology and Preventive Oncology, I-7, Sector-39, Noida, Uttar Pardesh 201301, India
cDr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi (North Campus), Delhi 110007, India
Corresponding author at: 4083 A, Teaching Block-4th Floor, Department of Medicine, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India. Tel.: +91 11 26593676; fax: +91 11 26588641.
ABSTRACT
ng/mL, which was significantly higher than the controls (74.0 (±19.8)