Blood microRNA testing in participants with suspicious low-dose CT findings: follow-up of the BioMILD lung cancer screening trial

IF 13.6 Q1 HEALTH CARE SCIENCES & SERVICES Lancet Regional Health-Europe Pub Date : 2024-09-16 DOI:10.1016/j.lanepe.2024.101070

Mattia Boeri , Federica Sabia , Roberta E. Ledda , Maurizio Balbi , Paola Suatoni , Miriam Segale , Anna Zanghì , Anna Cantarutti , Luigi Rolli , Camilla Valsecchi , Giovanni Corrao , Alfonso Marchianò , Ugo Pastorino , Gabriella Sozzi

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Abstract

Background

The proper management of suspicious radiologic findings is crucial to optimize the effectiveness of low-dose computed tomography (LDCT) lung cancer screening trials. In the BioMILD study, we evaluated the utility of combining a plasma 24-microRNA signature classifier (MSC) and LDCT to define the individual risk and personalize screening strategies. Here we aim to assess the utility of repeated MSC testing during annual screening rounds in 1024 participants with suspicious LDCT findings.

Methods

The primary outcome was two-year lung cancer incidence in relation to MSC test results, reported as relative risk (RR) with 95% confidence interval (CI). Lung cancer incidence and mortality were estimated using extended Cox models for time-dependent covariates, yielding the respective hazard ratios (HR). Clinicaltrials.gov ID: NCT02247453.

Findings

With a median follow-up of 8.5 years, the full study set included 1403 indeterminate LDCT (CTind) and 584 positive LDCT (CT+) results. A lung cancer RR increase in MSC+ compared to MSC- participants was observed in both the CTind (RR: 2.5; 95% CI: 1.4–4.32) and CT+ (RR: 2.6; 95% CI: 1.81–3.74) groups and was maintained when considering stage I or resectable tumors only. A 98% negative predictive value in CTind/MSC− and a 30% positive predictive value in CT+/MSC+ lesions were recorded. At seven years’ follow-up, MSC+ participants had a cumulative HR of 4.4 (95% CI: 3.0–6.4) for lung cancer incidence and of 8.1 (95% CI: 2.7–24.5) for lung cancer mortality.

Interpretation

Our study shows that MSC can be reliably performed during LDCT screening rounds to increase the accuracy of lung cancer risk and mortality prediction and supports its clinical utility in the management of LDCT findings of uncertain malignancy.

Funding

Italian Association for Cancer Research; Italian Ministry of Health; Horizon2020; National Cancer Institute (NCI); Gensignia LifeScience.

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对低剂量 CT 检查结果可疑的参与者进行血液 microRNA 检测：BioMILD 肺癌筛查试验的后续研究

背景对可疑的放射学发现进行适当处理对于优化低剂量计算机断层扫描（LDCT）肺癌筛查试验的效果至关重要。在 BioMILD 研究中，我们评估了结合血浆 24 微RNA 特征分类器（MSC）和 LDCT 来确定个体风险和个性化筛查策略的效用。方法主要结果是与 MSC 检测结果相关的两年肺癌发病率，以相对风险 (RR) 和 95% 置信区间 (CI) 的形式报告。肺癌发病率和死亡率采用时间依赖性协变量的扩展 Cox 模型进行估算，得出各自的危险比 (HR)。Clinicaltrials.gov ID：NCT02247453.研究结果中位随访时间为 8.5 年，整套研究包括 1403 项不确定的 LDCT (CTind) 结果和 584 项阳性 LDCT (CT+) 结果。在CTind组（RR：2.5；95% CI：1.4-4.32）和CT+组（RR：2.6；95% CI：1.81-3.74）中均观察到，与MSC-参试者相比，MSC+参试者的肺癌RR增加了，而且在仅考虑I期或可切除肿瘤时，这种增加仍保持不变。CTind/MSC-病变的阴性预测值为98%，CT+/MSC+病变的阳性预测值为30%。在七年的随访中，MSC+参与者的肺癌发病率累积HR为4.4（95% CI：3.0-6.4），肺癌死亡率累积HR为8.1（95% CI：2.7-24.5）。释义我们的研究表明，MSC可以在LDCT筛查中可靠地进行，以提高肺癌风险和死亡率预测的准确性，并支持其在处理LDCT发现的不确定恶性肿瘤中的临床实用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lancet Regional Health-Europe Multiple-

CiteScore

19.90

自引率

1.40%

发文量

260

审稿时长

9 weeks

期刊介绍： The Lancet Regional Health – Europe, a gold open access journal, is part of The Lancet's global effort to promote healthcare quality and accessibility worldwide. It focuses on advancing clinical practice and health policy in the European region to enhance health outcomes. The journal publishes high-quality original research advocating changes in clinical practice and health policy. It also includes reviews, commentaries, and opinion pieces on regional health topics, such as infection and disease prevention, healthy aging, and reducing health disparities.