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


OBJECTIVE
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.


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.
Sozzi
Gabriella
G
Department of Experimental Oncology, Molecular Cytogenetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. gabriella.sozzi@istitutotumori.mi.it
Roz
Luca
L
Conte
Davide
D
Mariani
Luigi
L
Andriani
Francesca
F
Lo Vullo
Salvatore
S
Verri
Carla
C
Pastorino
Ugo
U
D000368:Aged; D019540:Area Under Curve; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed / Q000379:methods
D004273:DNA, Neoplasm