Cellular, molecular and quantitative imaging analysis of screening-detected lung adenocarcinoma

筛查发现的肺腺癌的细胞、分子和定量成像分析

• 批准号: 9338192
• 负责人: PIERRE P. MASSION
• 金额: $ 72.76万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-24 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9338192
• 关键词: Academic Medical Centers; Adenocarcinoma; Adjuvant; Adjuvant Therapy; Aggressive behavior; Area; Behavior; Benign; Bioinformatics; Biological; Biological Markers; Biometry; Biopsy; Blood; Cancer Biology; Cancer Center; Cells; Cellular biology; Cessation of life; Clinical; Clinical Data; Clinical Management; Collaborations; Country; DNA analysis; Data; Data Element; Databases; Discrimination; Disease; Early Detection Research Network; Environment; Epidemiology; Fertilization; Freezing; Funding; Future; Genes; Genomics; Goals; Health Care Costs; Heterogeneity; Image; Image Analysis; Indolent; Institution; Inter-tumoral heterogeneity; Intervention; Investigation; Laboratories; Light; Lung Adenocarcinoma; Lung nodule; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measurement; Medical center; Modeling; Molecular; Molecular Analysis; Morbidity - disease rate; Natural History; Nodule; Operative Surgical Procedures; Pathology; Patients; Phenotype; Positioning Attribute; Procedures; Prospective Studies; Proteomics; Provider; Pulmonology; Research; Research Personnel; Resected; Risk; Science; Solid; Standardization; Technology; Testing; Tissues; Work; base; cancer cell; cancer risk; cellular imaging; chemotherapy; circulating DNA; circulating biomarkers; cohort; design; follow-up; functional genomics; high throughput screening; improved; interdisciplinary approach; low-dose spiral CT; lung cancer screening; molecular imaging; molecular marker; molecular/cellular imaging; multidisciplinary; new technology; novel; phenotypic biomarker; predictive modeling; programs; prospective; public health relevance; quantitative imaging; repository; screening; single cell analysis; standard of care; synergism; tumor; tumor DNA; tumor heterogeneity; tumor microenvironment

 DESCRIPTION (provided by applicant): Suspicious screening-detected lung nodules present a formidable challenge to patients and their providers. The standard of care lacks accuracy in predicting a) malignancy from benign disease and b) indolent vs aggressive behavior. The answer to these questions justifies diametrically opposed strategies (biopsy vs follow up) each of which carries huge consequences including cure of the cancer, risk of death during a procedure or risk of dying from not intervening early in the disease. This application will focus o the behavior of early stage adenocarcinoma of the lung and not on the distinction between benign from malignant nodules. We assembled a unique multidisciplinary group of experts to tackle this problem in an original way. We will develop a retrospective and a prospective repository for both tissue (ADC fresh frozen tissues, blood) and images from which we will derive detailed quantitative structural imaging analysis, targeted genomic analysis and single cell analysis to interrogate the functional genomics of these tumors. The integration of this multidimensional data imaging/molecular/cellular/epidemiology will allow us to identify and validate cellular and molecular determinants of tumor behavior in the context of their inter- and intra-tumor heterogeneity. With these results, we will be able to build integrated models of ADC behavior, validate a new genomic molecular test on circulating DNA and propose prospective studies that would eventually offer a different intervention based on these predictions i.e. surgery, vs no surgery, adjuvant immuno- or chemotherapy vs no adjuvant therapy and therefore reduce overtreatment and ultimately increase the rate of cure and reduce healthcare cost.

 描述（由申请人提供）：可疑筛查检测到的肺结节对患者及其提供者提出了严峻的挑战。标准治疗在预测a）恶性肿瘤与良性疾病以及B）惰性与攻击性行为方面缺乏准确性。这些问题的答案证明了截然相反的策略（活检与随访），每一种策略都带来了巨大的后果，包括癌症的治愈，手术期间的死亡风险或因疾病早期不干预而死亡的风险。该应用将关注早期肺腺癌的行为，而不是良性结节与恶性结节之间的区别。我们组建了一个独特的多学科专家小组，以独创的方式解决这个问题。我们将开发一个回顾性和前瞻性的组织（ADC新鲜冷冻组织，血液）和图像库，我们将从中获得详细的定量结构成像分析，靶向基因组分析和单细胞分析，以询问这些肿瘤的功能基因组学。这种多维数据成像/分子/细胞/流行病学的整合将使我们能够在肿瘤间和肿瘤内异质性的背景下识别和验证肿瘤行为的细胞和分子决定因素。有了这些结果，我们将能够建立ADC行为的综合模型，验证循环DNA的新基因组分子检测，并提出前瞻性研究，最终根据这些预测提供不同的干预措施，即手术与非手术，辅助免疫或化疗与非辅助治疗，从而减少过度治疗，最终提高治愈率并降低医疗成本。