Assessment of a Radiomics-Based Computer-Aided Diagnosis Tool for Cancer Risk Stratification of Pulmonary Nodules

项目摘要/摘要 这份提案描述了一项以培训为目标的全面的5年指导式职业发展计划 成为领先的独立内科医生兼科学家的候选人专注于改善诊断 评价和处理肺结节(PNS)以优化胸癌的早期发现和治疗 尽量减少对病人不必要的伤害。候选人目前是博士后研究员， 宾夕法尼亚大学(宾夕法尼亚大学)主治肺病专家。这项提议是建立在金博士之前 流行病学和生物统计学方面的研究培训和胸部肿瘤学的临床经验。PNS是 通常由计算机断层扫描(CT)检测到。肺活检是一种高度侵入性的程序，需要 确诊，但有很大的风险和成本。因此，临床医生面临着PN的诊断挑战 在决定哪些患者应该接受活组织检查以及哪些患者应该接受活检时进行恶性肿瘤风险评估 通过重复成像进行监视。该项目的总体目标是解决目前 在PN评估的诊断过程中，通过评估临床实用性和 基于放射组学的计算机辅助诊断(CAD)工具的有效性。这项新技术综合了 来自原始CT成像数据的定量特征，人眼看不见，以前 候选人的团队展示了提高临床医生PN诊断准确性的能力。这个项目的目标将是 通过三个相辅相成的具体目标实现。在目标1中，将进行回溯性队列研究 为了使用净重分类指数确定基于CAD的风险分层策略的临床实用性， 决策曲线分析，以及相对效用曲线。在目标2中，一项试点的单中心务实随机临床试验 将进行试验以比较基于CAD的风险分层策略与常规策略的临床效果 适当处理PNS，定义为对恶性PNS进行活检或经验性治疗 良性PNS的监测。最后，在目标3中，基于CAD的风险分层战略的成本效益 将使用决策分析模型对新发现的PNS患者的模拟队列进行评估。 Kim博士概述了一项严格的培训计划，包括课程、技能获取(重点是临床实用 分析、临床试验设计、决策分析建模和成本效益分析)和专业 职业发展。为了实现这一愿景，他召集了一支杰出的、多学科的导师队伍，并 顾问团队，由他的主要导师，Anil Vachani博士领导，他是 宾夕法尼亚大学介入肺病学和胸部肿瘤学，副主任凯瑟琳·伦德尔博士 宾夕法尼亚大学癌症护理创新中心的研究主任。宾夕法尼亚大学提供了一个杰出的 为这项提议营造智慧、协作和支持的环境，使金博士成功 完成目标和培训计划，使他成为R01奖项的有竞争力的申请者，以执行 评估PN恶性风险分层策略的多中心比较有效性试验。

PROJECT SUMMARY/ABSTRACT This proposal describes a comprehensive 5-year mentored career development plan with the goal of training the candidate to become a leading independent physician-scientist focused on improving the diagnostic evaluation and management of pulmonary nodules (PNs) to optimize early detection of thoracic cancer and minimize unnecessary harms to patients. The candidate is currently a Post-Doctoral Research Fellow and Attending Pulmonologist at the University of Pennsylvania (Penn). The proposal builds upon Dr. Kim’s previous research training in epidemiology and biostatistics and clinical experience in thoracic oncology. PNs are commonly detected by computed tomography (CT). Lung biopsy, a highly invasive procedure, is required for a definitive diagnosis but carries significant risks and costs. Thus, clinicians face the diagnostic challenge of PN malignancy risk estimation when deciding which patients should undergo a biopsy, and which should be surveilled with repeat imaging. The overall goal of this project is to address the current inadequacy of estimating malignancy risk within the diagnostic process of PN evaluation by assessing the clinical utility and effectiveness of a radiomics-based computer-aided diagnosis (CAD) tool. This novel technology synthesizes quantitative features from raw CT imaging data invisible to the human eye and has been previously demonstrated by the candidate’s team to improve clinicians’ PN diagnostic accuracy. This project’s goal will be accomplished via three complementary specific aims. In Aim 1, a retrospective cohort study will be performed to determine the clinical utility of a CAD-based risk stratification strategy using net reclassification indices, decision curve analysis, and relative utility curves. In Aim 2, a pilot, single-center pragmatic randomized clinical trial will be conducted to compare the clinical effectiveness of a CAD-based risk stratification strategy to usual care for appropriate management of PNs, defined as biopsy or empiric treatment for malignant PNs and surveillance for benign PNs. Finally, in Aim 3, the cost-effectiveness of a CAD-based risk stratification strategy will be evaluated using decision analytic models for a simulated cohort of individuals with newly detected PNs. Dr. Kim has outlined a rigorous training plan of coursework, skills acquisition (with a focus on clinical utility analysis, clinical trial design, decision analytic modeling, and cost-effectiveness analysis), and professional career development. To realize this vision, he has assembled a distinguished, multidisciplinary mentorship and advisory team, led by his primary mentor, Dr. Anil Vachani, the Director of Clinical Research in the Section of Interventional Pulmonology and Thoracic Oncology at Penn, and co-mentor, Dr. Katharine Rendle, Deputy Director for Research at the Penn Center for Cancer Care Innovation. Penn provides an outstanding intellectual, collaborative, and supportive environment for this proposal, positioning Dr. Kim to successfully complete the aims and training plan so that he will be a competitive applicant for an R01 award to perform a multicenter comparative effectiveness trial assessing PN malignancy risk stratification strategies.