Plasma DNA quantification in lung cancer computed tomography screening: five-year results of a prospective study

Am J Respir Crit Care Med. 2009 Jan 1;179(1):69-74. doi: 10.1164/rccm.200807-1068OC. Epub 2008 Sep 11.


Rationale: Free circulating plasma DNA has emerged as a potential biomarker for early lung cancer detection. In a previous case-control study we have shown that high levels of plasma DNA are a strong risk factor for lung cancer.

Objectives: To assess the diagnostic performance and prognostic value of plasma DNA levels in a cohort of 1,035 heavy smokers monitored by annual spiral computed tomography (CT) for 5 years.

Methods: Plasma DNA levels were determined through real-time quantitative PCR at baseline and at time of lung cancer diagnosis. Screening performance of the assay was calculated through the area under the receiver-operating characteristic curve (AUC-ROC). Kaplan-Meier analyses were computed for association with prognosis.

Measurements and main results: Median baseline concentration of plasma DNA was not different in individuals who developed CT-detected lung cancers in the 5-year period (n = 38) versus cancer-free control subjects (AUC-ROC, 0.496; P = 0.9330), and only slightly higher at the time of cancer diagnosis (AUC-ROC, 0.607; P = 0.0369). At surgery, plasma DNA was higher in tumors detected at baseline (AUC-ROC, 0.80; P < 0.0001) and in Stage II to IV tumors detected during the first 2 years of screening (AUC-ROC, 0.87; P < 0.0001). A longitudinal study of plasma DNA levels showed increased values approaching to lung cancer diagnosis (P = 0.0010). Higher plasma DNA was significantly associated with poorer 5-year survival (P = 0.0066).

Conclusions: Baseline assessment of plasma DNA level does not improve the accuracy of lung cancer screening by spiral CT in heavy smokers. Higher levels of plasma DNA at surgery might represent a risk factor for aggressive disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Area Under Curve
  • DNA, Neoplasm / blood*
  • Female
  • Humans
  • Lung Neoplasms / blood*
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Prospective Studies
  • ROC Curve
  • Survival Analysis
  • Tomography, X-Ray Computed / methods


  • DNA, Neoplasm