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: 10456340
• 负责人: DENISE R. ABERLE
• 金额: $ 64.72万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456340
• 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; detection platform; electric field; former smoker; high risk; industry partner; instrument; liquid biopsy; low dose computed tomography; lung basal segment; lung cancer cell; 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.

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