EFIRM-Liquid Biopsy (eLB): Ultrasensitive ctDNA and miRNA Detection for Early Assessment of Lung Cancer

EFIRM-液体活检 (eLB)：用于肺癌早期评估的超灵敏 ctDNA 和 miRNA 检测

• 批准号: 9982813
• 负责人: DENISE R. ABERLE
• 金额: $ 66.96万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-13 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982813
• 关键词: Address; Area; Attenuated; Benign; Biological; Biological Assay; Biological Markers; Biological Testing; Blood; Blood Volume; Blood specimen; Caliber; Cancer Biology; Cancer Detection; Categories; Characteristics; Classification; Clinical; Clinical Data; Clinical Management; Collaborations; Complement; DNA Sequence Alteration; Data Element; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Detection Research Network; Early Diagnosis; Eligibility Determination; Engineering; Epidermal Growth Factor Receptor; Evaluation; FDA approved; Goals; Image; Individual; Industrialization; Industry; Knowledge; Lung; Lung nodule; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measurement; Methods; MicroRNAs; Modeling; Molecular; Mutation; Nodule; Non-Small-Cell Lung Carcinoma; Pathologic; Pathologist; Patients; Penetration; Performance; Population; Prevalence; Procedures; Prospective cohort; Public Health; Publishing; ROC Curve; Research; Research Personnel; Risk; Scientist; Sensitivity and Specificity; Signal Transduction; Smoker; Specimen; Symptoms; System; Techniques; Technology; Testing; Thoracic Radiography; Time; Tissue Sample; Tumor Markers; Validation; X-Ray Computed Tomography; anticancer research; base; biomarker panel; blood-based biomarker; cancer diagnosis; cell type; circulating DNA; clinical material; clinical practice; clinical translation; comparative; computed tomography screening; electric field; high risk; industry partner; instrument; liquid biopsy; low dose computed tomography; lung basal segment; lung cancer screening; member; molecular marker; mortality; mutant; never smoker; non-smoker; novel; performance tests; peripheral blood; point of care; pre-clinical; preservation; prospective; quality assurance; screening; screening guidelines; seal; serial imaging; success; surveillance imaging; tool; tumor DNA

Project Summary/Abstract: Computed tomography (CT) is currently the most sensitive test for detecting preclinical lung cancer, which typically presents as an indeterminate pulmonary nodule (IPN). The success of CT for early detection was sealed by the National Lung Screening Trial, in which lung cancer mortality was reduced by 20% relative to chest radiography. However, in the NLST, the screen positivity rate was 24% and 96% of positive screens were false positive. Although these percentages have been partially attenuated by new screening guidelines, it is axiomatic that LDCT screening is highly sensitive for detecting lung cancer, but non-specific, and not without harms. Furthermore, more individuals, both smokers and non-smokers, are diagnosed outside of screening based on the finding of an indeterminate nodule. Methods are urgently needed to better differentiate between individuals with benign disease and those should undergo invasive diagnostic testing. Liquid biopsy has found its way into the cancer lexicon as a reference to tumor biomarkers within blood or other readily accessible biospecimens that reflect the presence and biology of cancer. This precompetitive collaboration brings together academic and industrial partners across the cancer spectrum to advance liquid biopsy technologies for early detection that are viable as clinical tools. Our partnership interleaves the expertise of lung cancer biologists, clinicians, and biostatisticians with industry engineers, converging on a novel liquid biopsy technology “EFIRM-Liquid biopsy (eLB)” that has already shown high sensitivity detecting circulating DNA mutations in patients with EGFR-mutant lung cancers. To address early lung cancer detection, our academic researchers will develop and validate independent assays for 10 DNA mutations commonly observed in lung cancer as well as introduce a 6-biomarker panel of miRNA to complement and strengthen the blood-based molecular signal of lung cancer. Our industry partners will convert these individual assays to a single array while preserving high sensitivity and specificity. With our clinician scientists, this integrated platform will be validated in patients with screen- or incidentally- detected lung nodules in the size ranges that are most diagnostically challenging. Our overall research proposition is that blood-based biomarkers using the eLB-Lung Cancer Detection Panel (eLB-LCDP) will inform the accurate and robust classification of nodules as benign or malignant. Beyond contributing molecular and technological expertise, standard operating procedures, and annotated clinical materials, we will compare eLB- LCDP with other lung cancer-associated liquid biopsy platforms to be developed in this and related NCI consortia to determine the highest performing biomarkers and platforms that should move to clinical translation, alone or in combination with models that include clinical and imaging variables acquired as part of patient management. Using this orthogonal, multiparametric interrogation approach, we hypothesize that the eLB-LCDP can achieve a classification performance area under the receiver operating characteristic curve (AUC) > 0.85 in near real- time clinical practice.

项目摘要/摘要： 计算机断层扫描（CT）目前是检测临床前肺癌的最敏感测试，该测试 通常以不确定的肺结核（IPN）表示。 CT在早期检测中的成功已密封 通过国家肺筛查试验，相对于胸部，肺癌死亡率降低了20％ 射线照相。但是，在NLST中，屏幕正率为24％，96％的正屏幕为假 尽管这些百分比已被新的筛查指南部分衰减，但它是公理的 该LDCT筛查对检测肺癌但非特异性且没有危害的筛查高度敏感。 此外，越来越多的人（吸烟者和非吸烟者）在筛查外被诊断 发现不确定的结节。迫切需要方法以更好地区分个体 良性疾病以及这些应进行诊断测试。液体活检已进入 癌症词典是对血液或其他容易获得的生物测量中的肿瘤生物标志物的参考 反映癌症的存在和生物学。这种预竞争的合作将学术和 癌症范围内的工业伙伴，以推动液体活检技术的早期检测 可行作为临床工具。我们的伙伴关系交织了肺癌生物学家，临床医生和 生物统计学家与行业工程师，融合了一种新型的液体活检技术“ Efrim-Liquid活检 （ELB）”已经显示出高灵敏度检测到EGFR突变患者的循环DNA突变 肺癌。为了解决早期肺癌检测，我们的学术研究人员将发展和验证 在肺癌中通常观察到的10种DNA突变的独立测定，并引入了6个生物标志物 miRNA面板以完成和增强肺癌的血液分子信号。我们的行业 合作伙伴将将这些个体测定法转换为单个数组，同时保留高灵敏度和特异性。 在我们的临床科学家中，该集成平台将在筛查或偶然的患者中得到验证 检测到最诊断挑战的大小范围的肺结节。我们的整体研究 命题是使用ELB肺癌检测面板（ELB-LCDP）的基于血液的生物标志物将告知 结节的准确性和鲁棒分类为良性或恶性。除了贡献分子和 技术专长，标准操作程序和注释的临床材料，我们将比较ELB- LCDP与其他与肺癌相关的液体活检平台以及相关的NCI联盟中开发 确定应单独转移到临床翻译的性能最高的生物标志物和平台 结合包括作为患者管理的一部分获得的临床和成像变量的模型。 使用这种正交的多参数审讯方法，我们假设ELB-LCDP可以实现 接收器操作特性曲线（AUC）下的分类性能区域> 0.85 时间临床实践。