Modeling Best Approaches for Cardiovascular Disease Prevention in Cancer Survivors

模拟癌症幸存者心血管疾病预防的最佳方法

基本信息

批准号：
10608446
负责人：
Chung Yin Kong
金额：
$ 71.3万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10608446
关键词：
Affect Aspirin Atherosclerosis Attenuated Biochemical Breast Calcium Calibration Cancer Model Cancer Survivor Cardiovascular Diseases Cardiovascular system Cause of Death Cessation of life Clinical Trials Cost Effectiveness Analysis Data Decision Making Development Disease Outcome General Population Genetic Genetic Risk Goals Guidelines High Prevalence Hyperlipidemia Hypertension Incidence Life Lipids Lung Malignant Neoplasms Methods Modeling Morbidity - disease rate Natural History Outcome Patients Population Population Heterogeneity Populations at Risk Prevention strategy Preventive care Primary Prevention Prostate Quality of life Quality-Adjusted Life Years Radiation therapy Randomized, Controlled Trials Recommendation Recurrence Recurrent Malignant Neoplasm Regional Disease Risk Risk Factors Risk Reduction Source Stratification Survivors Testing Treatment-Related Cancer United States Woman cancer recurrence cancer risk cancer therapy cardiovascular disorder prevention cardiovascular disorder risk chemotherapy chest computed tomography cohort comorbidity comparative effectiveness computed tomography screening coronary calcium scoring cost effectiveness data harmonization effectiveness evaluation ethnic minority genetic risk factor improved in silico innovation low dose computed tomography men models and simulation mortality multi-ethnic novel polygenic risk score population based racial minority sex simulation targeted treatment

项目摘要

PROJECT SUMMARY The overall goal of this proposal is to identify optimal strategies for primary prevention of cardiovascular disease (CVD) for survivors of breast (BC), prostate (PC) and lung (LC) cancer. All together, there are >6 million BC, PC and LC survivors in the US. While cancer is a major source of morbidity and mortality, the majority of BC and PC as well as many early-stage LC survivors die of comorbidities, particularly CVD. Cancer survivors have increased rates of both CVD risk factors as well as CVD itself, and CVD is the leading cause of death among BC and PC survivors. Among LC survivors, CVD-related deaths account for ~30% of mortality; this proportion is higher among the growing number identified with early-stage LC. In the general population, primary prevention with lipid-lowering agents (i.e., statins) and aspirin is highly effective for decreasing CVD incidence and mortality, but these guidelines for primary CVD prevention cannot be extrapolated to cancer survivors. Approaches for CVD prevention in cancer survivors need to consider traditional risk factors (including genetic risks) for CVD as well as CVD risk from certain cancer treatments. Additionally, competing risks from cancer recurrence or comorbidities may limit the long-term benefits of primary CVD prevention. Finally, the cancer itself, cancer treatment-related complications, and a higher prevalence of comorbidities can negatively impact quality-of-life and attenuate the absolute improvement in quality-adjusted life expectancy and the cost effectiveness (CE) of primary CVD prevention. Lack of specific data applicable to cancer survivors has profound negative impact, resulting in worse cardiovascular outcomes. It is unlikely that randomized controlled trials (RCT) assessing the benefits of CVD preventive strategies for cancer survivors will be ever conducted. Thus, there is an urgent need to use alternative methods to optimize preventive care recommendations for this growing population. We propose using simulation modeling, an approach complementary to clinical trials, to assess the harms, benefits, and CE of CVD prevention in diverse populations of cancer survivors. The Specific Aims are to: (1) Develop an Integrated Multi-Ethnic Cancer model (IMEC) to incorporate the development, progression, and outcomes of CVD among a diverse population of BC, PC and LC survivors; (2) Identify BC survivors who will benefit from and determine the CE of primary CVD prevention; (3) Determine effectiveness and CE of primary CVD prevention in PC survivors; and (4) Determine the most effective and CE CVD prevention strategies for LC survivors. To achieve these Aims, we will use data from several large, diverse and nationally representative, population-based cancer and cardiovascular cohorts to create, calibrate, and validate IMEC (Aim 1). Then, we will use the model to test our hypothesis by conducting in-silico RCTs (Aims 2-4). Our study is innovative in using state-of-the-art modeling methods and novel data harmonization, statistical and simulation approaches to optimize the use of CVD preventive strategies in cancer survivors. The results will have direct implications for the management of large numbers of survivors and guide patient decision-making.

项目概要该提案的总体目标是确定心血管疾病一级预防的最佳策略乳腺癌 (BC)、前列腺癌 (PC) 和肺癌 (LC) 幸存者的疾病 (CVD)。总共有 >6 个美国有 100 万 BC、PC 和 LC 幸存者。虽然癌症是发病率和死亡率的一个主要来源，大多数 BC 和 PC 以及许多早期 LC 幸存者死于合并症，特别是 CVD。癌症幸存者的 CVD 危险因素以及 CVD 本身的发生率均有所增加，而 CVD 是导致 CVD 的主要原因 BC 和 PC 幸存者的死亡。在 LC 幸存者中，CVD 相关死亡约占死亡率的 30%；在越来越多的早期 LC 患者中，这一比例更高。在一般人群中，使用降脂药（即他汀类药物）和阿司匹林进行一级预防对于减少心血管疾病非常有效发病率和死亡率，但这些 CVD 一级预防指南不能推广到癌症幸存者。癌症幸存者的 CVD 预防方法需要考虑传统危险因素 CVD 的风险（包括遗传风险）以及某些癌症治疗带来的 CVD 风险。此外，竞争癌症复发或合并症的风险可能会限制心血管疾病一级预防的长期益处。最后，癌症本身、癌症治疗相关的并发症以及较高的合并症患病率可以对生活质量产生负面影响并削弱质量调整预期寿命的绝对改善 CVD 初级预防的成本效益（CE）。缺乏适用于癌症幸存者的具体数据深远的负面影响，导致更糟糕的心血管结果。随机对照不太可能将进行评估 CVD 预防策略对癌症幸存者的益处的试验（RCT）。因此，迫切需要使用替代方法来优化该疾病的预防保健建议人口不断增长。我们建议使用模拟建模，这是一种补充临床试验的方法，评估不同癌症幸存者人群中 CVD 预防的危害、益处和 CE。具体目标是： (1) 开发综合多种族癌症模型 (IMEC)，以纳入以下发展：不同人群的 BC、PC 和 LC 幸存者中 CVD 的进展和结果； (2) 识别BC 将受益于并确定 CVD 初级预防的 CE 的幸存者； (3) 确定有效性 PC 幸存者的 CVD 初级预防的 CE； (4) 确定最有效的 CE CVD LC 幸存者的预防策略。为了实现这些目标，我们将使用来自多个大型、多样化和具有全国代表性、基于人群的癌症和心血管队列来创建、校准和验证 IMEC（目标 1）。然后，我们将使用该模型通过进行计算机随机对照试验（目标 2-4）来检验我们的假设。我们的该研究在使用最先进的建模方法和新颖的数据协调、统计和模拟方法优化癌症幸存者的 CVD 预防策略的使用。结果将对大量幸存者的管理有直接影响并指导患者决策。