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.
在低剂量计算机断层扫描（LDCT）肺癌筛查中，总血浆游离DNA（cfDNA）的作用尚不明确。我们假设cfDNA可能有助于区分LDCT观察到的恶性与良性结节。本研究对ITALUNG试验中137名受试者的基线cfDNA进行了测量，其中包括29名筛查发现的肺癌患者（17例为流行性肺癌，12例为偶发性肺癌）以及108名良性结节受试者。将基线cfDNA区分恶性与良性结节的预测能力与初次LDCT（iLDCT）时的Lung-RADS分类及Brock评分进行比较。流行性肺癌患者既表现出恶性结节具有良好鉴别性的影像学特征（17例中有16例被归类为Lung-RADS 4级），又显示出cfDNA显著升高（平均18.8 ng/mL）。在偶发性肺癌患者中，iLDCT检测到的恶性结节平均直径和Brock评分与良性结节无显著差异。然而，75%（9/12）的偶发性肺癌患者基线cfDNA≥3.15 ng/mL，而良性结节患者中这一比例仅为34%（37/108）（p=0.006）。此外，基线cfDNA与通过体积倍增时间测量的肿瘤生长速度存在相关性（p=0.001）。综上所述，升高的基线cfDNA可能有助于在LDCT筛查中区分恶性与良性结节受试者。
Baseline Cell-Free DNA Can Predict Malignancy of Nodules Observed in the ITALUNG Screening Trial
肿瘤(癌症)患者之家