Baseline Cell-Free DNA Can Predict Malignancy of Nodules Observed in the ITALUNG Screening Trial.

Simple Summary: We investigated whether the baseline plasma cell-free DNA might help to differentiate malignant nodules from benign lesions observed in screening low-dose computed tomography (LDCT) examinations. Plasma cell-free DNA was determined before the first LDCT in 137 participants in the ITALUNG trial, including 29 with screen-detected malignant nodules (17 prevalent and 12 incident) and 108 with benign nodules. In subjects with prevalent lung cancers (LC), the radiological characteristics well differentiated the malignant nodule, and the cell-free DNA was markedly increased. A total of 75% of subjects with incident LC showed a baseline cell-free DNA ≥ 3.15 ng/mL, compared to 34% of subjects with benign nodules (p = 0.006). Moreover, the cell-free DNA correlated (p = 0.001) with the tumor growth measured with nodular volume doubling time. The baseline plasma cell-free DNA is an independent, potentially useful biomarker in the LC screening process and should be further investigated. The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects of the ITALUNG trial, including 29 subjects with screen-detected LC (17 prevalent and 12 incident) and 108 subjects with benign nodules. The predictive capability of baseline cfDNA to differentiate malignant and benign nodules was compared to that of Lung-RADS classification and Brock score at initial LDCT (iLDCT). Subjects with prevalent LC showed both well-discriminating radiological characteristics of the malignant nodule (16 of 17 were classified as Lung-RADS 4) and markedly increased cfDNA (mean 18.8 ng/mL). The mean diameters and Brock scores of malignant nodules at iLDCT in subjects who were diagnosed with incident LC were not different from those of benign nodules. However, 75% (9/12) of subjects with incident LC showed a baseline cfDNA ≥ 3.15 ng/mL, compared to 34% (37/108) of subjects with benign nodules (p = 0.006). Moreover, baseline cfDNA was correlated (p = 0.001) with tumor growth, measured with volume doubling time. In conclusion, increased baseline cfDNA may help to differentiate subjects with malignant and benign nodules at LDCT. [ABSTRACT FROM AUTHOR]