Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Tumour Genomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Ann Oncol. 2022 Apr;33(4):395-405. doi: 10.1016/j.annonc.2022.01.008. Epub 2022 Jan 25.
Large randomized trials have demonstrated that lung cancer (LC) screening with low-dose computed tomography (LDCT) reduces LC mortality in heavy smokers. We previously showed in the MILD screening trial that the combination of a prespecified circulating microRNA (miRNA) signature classifier (MSC) and LDCT improves the accuracy of LDCT alone. The primary aim of the prospective BioMILD study was to assess the additional value of the blood MSC assay at the time of baseline LDCT with the goal of personalizing LC screening intervals.
The study enrolled 4119 volunteers from January 2013 to March 2016, with a median follow-up of 5.3 years. Baseline LDCT and miRNAs stratified participants into four groups: CT-/MSC- (n = 2664; 64.7%); CT-/MSC+ (n = 800; 19.4%); CT+/MSC- (n = 446; 10.8%); and CT+/MSC+ (n = 209; 5.1%). As per the protocol, those in the CT-/MSC- and CT-/MSC+ groups were allocated to LDCT repeat at 3-year and 1-year intervals; CT+ participants were allocated for 1-year or earlier intervals on the basis of LDCT features independent of MSC results.
CT+ participants had a 15.8-fold higher 4-year LC incidence than CT- participants (95% confidence interval 10.34-24.05), and MSC+ participants had a 2.0-fold higher 4-year LC incidence than MSC- participants (95% confidence interval 1.40-2.90); there was no evidence that the MSC effect differed between CT+ and CT- participants. LC incidence at 4 years was 0.8% in CT-/MSC-, 1.1% in CT-/MSC+, 10.8% in CT+/MSC-, and 20.1% in CT+/MSC+ participants. LC mortality rates at 5 years in the four risk groups were 0.5 in CT-/MSC-, 1.5 in CT-/MSC+, 4.2 in CT+/MSC-, and 10.1 in CT+/MSC+.
The combined use of LDCT and blood miRNAs at baseline predicts individual LC incidence and mortality, with a major effect of MSC for LDCT-positive individuals. These findings may have important implications in personalizing screening intervals.
多项大型随机试验已证实，低剂量计算机断层扫描（LDCT）肺癌（LC）筛查可降低重度吸烟者的 LC 死亡率。我们之前在 MILD 筛查试验中表明，预先指定的循环 microRNA（miRNA）特征分类器（MSC）与 LDCT 的结合可提高 LDCT 的准确性。前瞻性 BioMILD 研究的主要目的是评估基线 LDCT 时血液 MSC 检测的附加价值，目标是使 LC 筛查间隔个体化。
该研究于 2013 年 1 月至 2016 年 3 月期间招募了 4119 名志愿者，中位随访时间为 5.3 年。基线 LDCT 和 miRNA 将参与者分为四组：CT-/MSC-（n=2664；64.7%）；CT-/MSC+（n=800；19.4%）；CT+/MSC-（n=446；10.8%）和 CT+/MSC+（n=209；5.1%）。根据方案，CT-/MSC-和 CT-/MSC+组的参与者被分配在 3 年和 1 年后进行 LDCT 重复检查；CT+的参与者根据 LDCT 特征而不是 MSC 结果被分配进行 1 年或更早的间隔检查。
CT+参与者的 4 年 LC 发生率比 CT-参与者高 15.8 倍（95%置信区间 10.34-24.05），MSC+参与者的 4 年 LC 发生率比 MSC-参与者高 2.0 倍（95%置信区间 1.40-2.90）；没有证据表明 MSC 效应在 CT+和 CT-参与者之间存在差异。4 年时的 LC 发生率分别为 CT-/MSC-组为 0.8%，CT-/MSC+组为 1.1%，CT+/MSC-组为 10.8%，CT+/MSC+组为 20.1%。在 4 个风险组中，5 年时的 LC 死亡率分别为 CT-/MSC-组为 0.5%，CT-/MSC+组为 1.5%，CT+/MSC-组为 4.2%，CT+/MSC+组为 10.1%。
LDCT 和基线时血液 miRNA 的联合使用可预测个体 LC 的发病率和死亡率，MSC 对 LDCT 阳性个体的影响较大。这些发现可能对个体化筛查间隔具有重要意义。
