Optimizing Personalized Screening and Diagnostic Decisions for Lung Cancer Based on Dynamic Risk Assessment and Life Expectancy

基于动态风险评估和预期寿命优化肺癌的个性化筛查和诊断决策

• 批准号: 10644014
• 负责人: Iakovos Toumazis
• 金额: $ 61.52万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644014
• 关键词: Address; Age; Age Years; Anxiety; Benign; Biopsy; Blood; Cancer Etiology; Cancer Patient; Cessation of life; Data; Data Management Resources; Decision Making; Decision Modeling; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Dose; Early Diagnosis; Effectiveness; Eligibility Determination; Ensure; Exclusion; Family; Guidelines; Health Benefit; Histology; Individual; Intervention; Knowledge; Life Expectancy; Lung; Lung CAT Scan; Lung diseases; Lung nodule; Malignant Neoplasms; Malignant neoplasm of lung; Modality; Modeling; Morbidity - disease rate; Natural History; Nodule; PET/CT scan; Patients; Population; Population Group; Process; Race; Radiation exposure; Recommendation; Recording of previous events; Relaxation; Reporting; Research; Resources; Risk; Risk Assessment; Risk Factors; Schedule; Secondary Cancer Prevention; Smoke; Smoker; Smoking; Smoking History; Specific qualifier value; Testing; Time Management; United States; United States Preventative Services Task Force; Update; blood-based biomarker; cancer diagnosis; cancer risk; compare effectiveness; cost; cost effective; cost effectiveness; cost-effectiveness evaluation; diagnostic biomarker; diagnostic strategy; effectiveness evaluation; emotional distress; high risk; improved; low dose computed tomography; lung cancer prevention; lung cancer screening; models and simulation; mortality; mortality risk; non-smoking; personalized diagnostics; personalized management; personalized screening; programs; psychological distress; randomized, clinical trials; risk mitigation; risk prediction model; screening; screening guidelines; screening program; sex; smoking cessation; smoking exposure; standardize guidelines

Project Summary/Abstract Lung cancer is the leading cause of cancer related deaths in the United States and worldwide. Most patients are diagnosed with advanced stage disease for which available treatment interventions offer minimal survival benefit. Early detection through screening is vital to achieve cure and minimize lung cancer morbidity and mortality. Low- dose computed tomography (LDCT) has become the standard lung cancer screening modality based on data from randomized clinical trials. In 2021, the US Preventive Services Task Force (USPSTF) relaxed its lung cancer screening eligibility criteria (based on age and smoking history) providing coverage to younger and lighter smokers. Even though the eligibility expansion is expected to enhance benefits in specific population groups, many newly eligible individuals would have low lung cancer risk making it less likely to benefit from screening, but will be subject to potential harms such as false-positive findings and risks from invasive diagnostic procedures, emotional and psychological distress, and cost. Thus, it is imperative to accurately identify individuals that are likely to benefit from screening. Management of indeterminate findings is challenging, given the high rates of benign nodules detected by LDCT. Existing lung cancer screening and diagnostic guidelines ignore important risk-factors, whereas promising risk prediction models assessing screening eligibility of individuals and malignancy of indeterminate findings omit life-expectancy and remain underutilized. This research aims to develop individualized, dynamic risk-based screening and diagnostic strategies through stochastic, dynamic decision models. This project leverages the individualizEd luNG cAncer screeninG dEcisions (ENGAGE) framework – a previously developed and validated framework – that offers individualized screening decisions by dynamically assessing the risk and life expectancy of ever-smoked individuals. We will expand the current version of ENGAGE, which is based on age, sex, and smoking history, to incorporate non-smoking risk factors including race, family history and history of pulmonary disease among others, into the decision-making process. We will develop microsimulation models to simulate the progression of pulmonary nodules and overlay a partially observable Markov decision process to optimize the diagnostic management of pulmonary nodules at the patient level, based on a risk assessment for the nodule’s malignancy and information collected from serial LDCT, biopsy, PET/CT or a diagnostic blood-based biomarker. We will integrate the diagnostic module into ENGAGE to derive state-of-the-art individualized screening and diagnostic recommendations, and compare the effectiveness, efficiency, and cost-effectiveness of the updated ENGAGE framework against current practice. This project presents a new direction in lung cancer screening research paving the road towards individualized secondary cancer prevention. The expansion of the ENGAGE framework to facilitate a personalized risk-based program that integrates smoking and non-smoking risk factors, along with life expectancy, will form the basis for the development of optimal, cost-effective lung cancer screening guidelines tailored to individuals.

项目总结/摘要 肺癌是美国和全世界癌症相关死亡的主要原因。大多数患者 诊断为晚期疾病，可用的治疗干预措施提供最小的生存益处。 通过筛查进行早期发现对于实现治愈和最大限度地降低肺癌发病率和死亡率至关重要。低- 剂量计算机断层扫描（LDCT）已成为标准的肺癌筛查模式， 来自随机临床试验。2021年，美国预防服务工作组（USPSTF）放松了对肺 癌症筛查资格标准（基于年龄和吸烟史），为年龄较小和体重较轻的人提供覆盖 吸烟者。尽管扩大资格预计将增加特定人口群体的福利， 许多新合格的个体将具有低肺癌风险使得其不太可能从筛查中获益， 但会受到潜在的伤害，如假阳性结果和侵入性诊断的风险 程序、情绪和心理困扰以及费用。因此，必须准确识别 可能从筛查中受益的人。鉴于不确定结果的管理具有挑战性， LDCT检出良性结节率高。现有的肺癌筛查和诊断指南 忽视重要的风险因素，而有前途的风险预测模型评估筛查资格 个体和不确定结果的恶性肿瘤忽略了预期寿命，仍然没有得到充分利用。 本研究旨在通过以下方法开发个性化的、动态的基于风险的筛查和诊断策略： 随机动态决策模型该项目利用个性化的癌症筛查决策 （ENGAGE）框架-一个先前开发和验证的框架-提供个性化筛选 通过动态评估吸烟者的风险和预期寿命来做出决策。我们将扩大 目前版本的ENGAGE，基于年龄、性别和吸烟史，纳入非吸烟风险 包括种族、家族史和肺病史等因素， 过程我们将开发微观模拟模型来模拟肺结节的进展和覆盖 一个部分可观察的马尔可夫决策过程，以优化肺结节的诊断管理， 根据结节恶性程度的风险评估和从系列研究中收集的信息， LDCT、活检、PET/CT或诊断性血液生物标志物。我们将把诊断模块集成到 参与制定最先进的个体化筛查和诊断建议，并比较 更新后的ENGAGE框架与当前实践的有效性、效率和成本效益。 该项目为肺癌筛查研究提供了一个新的方向， 癌症的二级预防。扩展ENGAGE框架，以促进基于风险的个性化 一项将吸烟和不吸烟的危险因素与预期寿命沿着整合的计划，将成为以下方面的基础： 制定适合个人的最佳、具有成本效益的肺癌筛查指南。