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

 描述(由申请人提供)：可疑的筛查发现的肺结节给患者及其提供者带来了巨大的挑战。护理标准在预测a)良性疾病的恶性和b)懒惰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(活组织检查与随访)是合理的，每一种策略都会带来巨大的后果，包括癌症的治愈、手术过程中的死亡风险或因不早期干预疾病而死亡的风险。这项应用将重点放在早期肺腺癌的行为上，而不是区分良恶性结节。我们召集了一个独特的多学科专家小组，以独创性的方式解决这个问题。我们将为组织(ADC新鲜冰冻组织、血液)和图像建立一个回顾和前瞻性的资料库，从中我们将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/流行病学的集成将使我们能够在肿瘤内部和内部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行为的集成模型，验证对循环DNA的新的基因组分子测试，并提出前瞻性研究，最终基于这些预测提供不同的干预措施，即手术、手术和非手术、辅助免疫或化疗和非辅助治疗，从而减少过度治疗，最终提高治愈率和降低医疗成本。

 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.