Clinical Utility of Biomarkers Driven Management of Indeterminate Pulmonary Nodules

项目总结 此应用程序的目标是测试生物标记物知情方法的临床实用价值，以评估和 不明原因肺结节(IPN)的管理。这项研究旨在解决这一主要问题和 鉴于美国和国外对肺癌筛查的采用和普遍存在的需求，需求仍未得到满足 偶然发现的IPN的发生。我们已经开发并在外部队列中验证了高敏感性 HS-Cyfra 21-1生物标记物分析和定量成像特征共同改善了目前的非 对IPN的侵入性评估。在这项建议中，我们假设一个结合临床的预测模型 变量、hs-Cyfra 21-1血清浓度和定量成像特征将通过以下方式显示临床应用 减少昂贵和侵入性的程序，同时缩短诊断时间。为了检验这一假设，我们建议 具体目标如下：首先，我们将测试生物标记物信息策略的临床效用。 IPN治疗的种类随机临床试验。我们将招收440名具有中等风险IPN的个人(10- 70%的癌症风险)，目标是减少侵入性手术的数量和时间 诊断。在控制臂中，参与者将遵循护理标准，而在干预臂中，参与者将 生物标志物结果，以肺癌检测后的概率表示，将提供给提供者和参与者 向结核管理部门通报。第二，进一步确定新的候选生物标志物 风险分层，我们将应用评估候选人的工作流程，并验证最佳候选人进入 在一组预期收集的样本中，评估了 回顾盲法(探头设计)，我们将测试诊断准确率的提高。 基于Mayo风险模型的肺癌中度风险IPN患者的候选生物标记物。一个 雅培实验室的血液生物标记物签名将单独进行测试，并与经过验证的 放射组学评分，以确定它们是否共同对至少20%的中等风险患者(10%-70%)进行了重新分类 仅在Mayo风险模型上分为风险较低(10%)或风险较高(70%)组。我们将确定 最佳且最具成本效益的Mayo模型+生物标志物组合或序列 综合方案网络管理中的决策门槛。在本项目结束时，我们将：a)演示 首次使用生物标记物知情方法管理IPN，并获得了额外的 一项更大规模的后续随机多中心试验的结果数据，b)验证了增量诊断 用于IPN管理的新的候选生物标志物的准确性，以及c)开辟了快速 测试最有效的组合(S)考生。

PROJECT SUMMARY The goal of this application is to test the clinical utility of a biomarker-informed approach to the evaluation and management of indeterminate pulmonary nodules (IPNs). The study is designed to address this major and growing unmet need given the adoption of lung cancer screening in the US and abroad and the common occurrence of incidentally identified IPNs. We have developed and validated in external cohorts a high sensitivity hs-CYFRA 21-1 biomarker assay and quantitative imaging features that together improve the current non- invasive assessment of IPNs. In this proposal we hypothesize that a prediction model that integrates clinical variables, hs-CYFRA 21-1 serum concentration, and quantitative imaging signature will show clinical utility by reducing costly and invasive procedures while shortening time to diagnosis. To test this hypothesis, we propose the following specific aims: First, we will test the clinical utility of a biomarker-informed strategy in a first of its kind randomized clinical trial of IPN management. We will enroll 440 individuals with intermediate risk IPNs (10- 70% risk for cancer) at four institutions with the goal of reducing the number of invasive procedures and time to diagnosis. In the control arm, participants will follow the standard of care and in the intervention arm the biomarker results, expressed as a post-test probability for lung cancer, will be given to providers and participants to inform nodule management. Second, to further our work in identifying new candidate biomarkers for better risk stratification, we will apply a workflow for evaluation of candidates and validate the best candidates for entry into a similar future trial to that proposed in Aim 1. In a set of prospectively collected specimens, evaluated retrospectively in a blinded fashion (ProBE design), we will test the improvement in diagnostic accuracy of candidate biomarkers in patients with IPNs of intermediate risk for lung cancer based on the Mayo risk model. A blood biomarker signature from Abbott laboratories will be tested alone and in combination with a validated radiomics score to determine if together they reclassify at least 20% of those at intermediate risk (10-70%) based on the Mayo risk model alone into either a lower risk (<10%) or higher risk (>70%) group. We will determine the optimal and most cost-effective Mayo model + biomarker combination or sequence needed to achieve the critical decision thresholds in the management of IPNs. At the end of this project, we will have: a) demonstrated for the first time the clinical utility of a biomarker informed approach to IPN management and acquired additional outcomes data for a larger follow-on randomized multicenter trial, b) validated the incremental diagnostic accuracy of new candidate biomarkers for the management of IPNs, and c) opened a new avenue for rapid testing of the most effective combination(s) of candidates.