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博士是斯隆·凯特琳纪念医院(MSK)的一名成年心脏病专家，接受过高级超声心动图培训， 表现出坚定的承诺，致力于发展心脏肿瘤学临床研究员的职业生涯。他的 长期目标是领导努力制定以证据为基础的战略，以预防、检测和 癌症治疗相关心脏毒性的管理，以减轻竞争的心血管 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 这个应用程序为Yu博士提供了必要的技能、结构化的指导和 研究经验，以满足他的长期研究和职业目标，并确保成功过渡到 作为一名临床科学家的独立性。多学科指导小组成员，由国家 在生存、心脏肿瘤学和健康结局方面公认的领导者致力于提供 监督和指导Yu博士完成所有的职业发展、培训和研究 这项提案的目标。这项提议的科学方面的总体目标是更好地理解 曲妥珠单抗治疗期间心脏监测的危害和益处。心脏毒性是一口井 曲妥珠单抗治疗HER2阳性乳腺癌的公认副作用。临床 曲妥珠单抗治疗期间心脏监测指南建议常规系列评估左 左心室射血分数(LVEF)。然而，支持这一一刀切建议的证据 曲妥珠单抗治疗的患者很少，特别是考虑到非蒽环类药物的使用呈增长趋势。 基于曲妥珠单抗的方案具有更安全的心脏毒性风险概况。还有一个潜在的危害，那就是虚假- 在常规心脏监测中检测到的阳性结果或临床上不明显的LVEF下降将 不必要地导致治疗和挽救生命的乳腺癌治疗的中断或提前终止 会导致更糟糕的癌症结果。中心假设是有限的心脏监测策略 心血管风险较低的女性，接受非蒽环类药物曲妥珠单抗治疗 将是安全的，而且成本更低。Yu博士将用两个截然不同和互补的方法来阐述这一中心假设 接近了。在目标1中，他将利用观察到的心脏监测频率的现有变化 在MSK回顾检查遵守心脏监测指南和 心脏毒性事件。在目标2中，他承认回溯性研究设计的局限性，他将 前瞻性评价有限心脏监测策略在非心脏疾病患者治疗中的安全性和可行性 一种以曲妥珠单抗为基础的非蒽环类药物方案。在目标3中，他将估计医疗保健利用率和成本 与基于指南的心脏监测策略和有限的心脏监测策略相关。在此基础上获得的知识 心脏监测的危害和好处将为制定循证建议奠定基础 用于乳腺癌治疗期间的心脏监测。