Enhancing Understanding of Harms and Benefits of Cardiac Monitoring During Breast Cancer Therapy

增强对乳腺癌治疗期间心脏监测的危害和益处的了解

• 批准号: 9979796
• 负责人: Anthony Francis Yu
• 金额: $ 17.64万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9979796
• 关键词: Address; Adherence; Adjuvant; Adult; Adverse effects; Anthracycline; Breast Cancer Patient; Breast Cancer Treatment; Breast Cancer therapy; Cancer Survivor; Cardiac; Cardiac Death; Cardiomyopathies; Cardiotoxicity; Cardiovascular system; Clinical; Clinical Investigator; Clinical Trials; Cost Savings; Detection; ERBB2 gene; Echocardiography; Enrollment; Ensure; Event; Foundations; Frequencies; Future; Goals; Guidelines; Health; Health Care Costs; Health Expenditures; Heart; Heart failure; Institution; Interruption; Intervention; Investigation; Knowledge; Lead; Left Ventricular Ejection Fraction; Life; Malignant Neoplasms; Mentors; Mentorship; Methods; Modeling; Monitor; Morbidity - disease rate; National Comprehensive Cancer Network; New York Heart Association Class III/IV; Newly Diagnosed; Observational Study; Oncology; Outcome; Paclitaxel; Participant; Patient-Focused Outcomes; Patients; Positive Test Result; Prevention strategy; Prospective Studies; Recommendation; Recording of previous events; Regimen; Reporting; Research; Research Design; Retrospective Studies; Retrospective cohort study; Risk; Safety; Savings; Scientist; Structure; Supervision; Testing; Training; Trastuzumab; Treatment-Related Cancer; United States Food and Drug Administration; Variant; Woman; Work; base; cancer therapy; cardiovascular risk factor; career; career development; chemotherapy; clinical practice; cost; economic impact; evidence base; evidence based guidelines; experience; health care service utilization; improved; malignant breast neoplasm; member; mortality; multidisciplinary; phase 2 study; primary outcome; prospective; response; safety and feasibility; skills; survivorship; treatment duration; trend

PROJECT SUMMARY/ABSTRACT Dr. Yu, an adult cardiologist at Memorial Sloan Kettering (MSK) with advanced training in echocardiography, has demonstrated a strong commitment to developing a career as a clinical investigator in cardio-oncology. His long-term goal is to lead efforts to develop evidence-based strategies for the prevention, detection, and management of cancer therapy-associated cardiotoxicity in order to mitigate the competing cardiovascular causes of morbidity and mortality in cancer survivors. The career development and training plans outlined in this application have been tailored to provide Dr. Yu with the necessary skills, structured mentoring, and research experience to meet his long-term research and career goals and ensure a successful transition to independence as a clinician scientist. Members of a multidisciplinary mentorship team comprised of nationally recognized leaders in survivorship, cardio-oncology, and health outcomes are committed to providing close supervision and guidance to Dr. Yu in achieving all of the career development, training, and research objectives of this proposal. The overall objective of the scientific aspect of this proposal is to better understand the harms and benefits associated with cardiac monitoring during trastuzumab therapy. Cardiotoxicity is a well recognized adverse effect of trastuzumab therapy used to treat HER2-positive breast cancer. Clinical guidelines for cardiac monitoring during trastuzumab therapy recommend routine serial assessments of left ventricular ejection fraction (LVEF). However, evidence to support this one-size-fits-all recommendation for all patients treated with trastuzumab is lacking, particularly given the growing trend in the use of non-anthracycline trastuzumab-based regimens with safer cardiotoxicity risk profiles. There is also the potential harm that false- positive results or clinically insignificant LVEF declines detected during routine cardiac monitoring will unnecessarily lead to interruption or early termination of curative and life-saving breast cancer therapy and result in worse cancer outcomes. The central hypothesis is that a strategy of limited cardiac monitoring among women with a low cardiovascular risk profile and treated with a non-anthracycline trastuzumab-based regimen will be safe and less costly. Dr. Yu will address this central hypothesis using two distinct and complementary approaches. In Aim 1, he will capitalize on existing variations in the frequency of cardiac monitoring observed at MSK to retrospectively examine the association between adherence to cardiac monitoring guidelines and cardiotoxicity events. In Aim 2, acknowledging the limitations of a retrospective study design, he will prospectively evaluate the safety and feasibility of a limited cardiac monitoring strategy in patients treated with a non-anthracycline trastuzumab-based regimen. In Aim 3, he will estimate the healthcare utilization and costs associated with guideline-based versus limited cardiac monitoring strategies. The knowledge gained on the harms and benefits of cardiac monitoring will lay the groundwork to develop evidence-based recommendations for cardiac monitoring during breast cancer therapy.

项目摘要/摘要 Yu博士是纪念斯隆·凯特林（MSK）的成人心脏病专家，并在超声心动图上进行了高级培训， 已经表现出致力于发展为心脏肿瘤学临床研究者职业的坚定承诺。他的 长期目标是领导努力制定基于证据的策略，以预防，检测和 管理癌症治疗相关的心脏毒性，以减轻竞争性心血管 癌症幸存者的发病率和死亡率的原因。概述的职业发展和培训计划 该应用程序是针对Yu博士提供必要技能，结构化指导和 研究经验，以实现他的长期研究和职业目标，并确保成功过渡到 独立作为临床科学家。由全国性的多学科指导团队的成员 幸存，心脏肿瘤和健康成果的公认领导者致力于提供关闭 对Yu博士的监督和指导，以实现所有职业发展，培训和研究 该提议的目标。该提案科学方面的总体目标是更好地理解 曲妥珠单抗治疗期间与心脏监测相关的危害和益处。心脏毒性是一口井 公认的曲妥珠单抗治疗的不良影响用于治疗HER2阳性乳腺癌。临床 曲妥珠单抗治疗期间心脏监测指南建议左侧的常规系列评估 心室射血分数（LVEF）。但是，支持所有人的证据支持所有人 缺乏接受曲妥珠单抗治疗的患者 基于曲妥珠单抗的方案，具有更安全的心脏毒性风险特征。还有可能的危害 在常规心脏监测期间检测到的积极结果或临床上微不足道的LVEF下降将会 不必要地导致治愈和挽救生命的乳腺癌疗法的中断或早期终止 导致癌症结果较差。中心假设是一种有限的心脏监测策略 心血管风险较低的妇女，并接受了非抗trastuzumab疗法的治疗 将是安全的，成本较低。 Yu博士将使用两个不同的互补和补充来解决这一中心假设 方法。在AIM 1中，他将利用观察到的心脏监测频率的现有变化 在MSK回顾性地检查遵守心脏监测准则与 心脏毒性事件。在AIM 2中，承认回顾性研究设计的局限性，他将 预期评估患者患者的心脏监测策略有限的安全性和可行性 一种基于曲妥珠单抗的非人类环境方案。在AIM 3中，他将估计医疗保健利用和成本 与基于准则的和有限的心脏监测策略相关。在 心脏监测的危害和益处将为开发基于证据的建议奠定基础 用于乳腺癌治疗期间的心脏监测。