Prevention of Anthracycline Chemotherapy Cardiotoxicity

该提案提出了一项为期五年的研究职业发展计划，重点是 老年人应用蒽环类药物化疗后心脏毒性的预测和预防 成人淋巴瘤通过：1)改进的预测工具，2)电流分析 心脏保护使用和3)确定患者和提供者的治疗偏好。这个 候选人是塔夫茨大学医学院和医学院的助理教授 塔夫茨医学中心心内科心脏肿瘤科主任。 在大卫·肯特博士和苏珊·帕森斯博士的指导下， 塔夫茨医疗中心的临床研究和卫生政策研究，培训计划建立在 应聘者之前的临床和研究经验，以发展1)设计方面的专业知识 使用大型管理数据库进行有效的心脏肿瘤学结果研究；2)肿瘤学 临床试验设计；3)定性和决策分析研究方法。每一年， 在美国，超过4万名65岁及以上的人被诊断出患有淋巴瘤 大多数患者建议将含蒽环类药物作为一线治疗方案 淋巴瘤亚型。而蒽环类化疗药物有助于诱发淋巴瘤 在病情缓解的同时，它们还会增加心力衰竭(HF)的风险。这些影响在年龄较大的人中会恶化。 成人，因为在非癌症和癌症人群中，年龄都是心力衰竭的潜在危险因素。 然而，即使是在具有高毒性风险的老年患者中，也可能会遗漏蒽环类药物 与更糟糕的结果相关。因此，更好地预测和预防蒽环类药物的策略 心脏毒性是需要的，以改善老年淋巴瘤患者的预后。小的 在以非淋巴瘤为主的人群中进行的随机试验确定了几个有希望的 预防服用蒽环类药物患者发生心衰的策略；然而，这两种临床实践 指南和FDA都不认可这些疗法中的任何一种，因为证据不足 预防新近诊断的成人淋巴瘤患者的心力衰竭。这项建议的目的是 通过：1)发展：1)加强对蒽环类药物心脏毒性预测和预防的研究 并验证了新诊断为淋巴瘤的老年人的心力衰竭风险预测模型； 2)确定目前在实践中使用的心脏保护策略；3)引出 患者和提供者对心脏保护的治疗偏好。这项研究将引领 为提高对预防蒽环类药物心脏毒性的认识，为 淋巴瘤高危人群的心脏保护研究并为候选人提供 成为一名成功的独立调查员所需的技能和经验。

This proposal presents a five-year research career development program, focused on the prediction and prevention of life-threatening anthracycline chemotherapy cardiotoxicity in older adults with lymphoma through: 1) improved prediction tools, 2) analysis of current cardioprotection use and 3) ascertainment of patient and provider treatment preferences. The candidate is an Assistant Professor at Tufts University School of Medicine and the Medical Director of the Cardio-Oncology Program in the Division of Cardiology at Tufts Medical Center. Under the mentorship of Dr. David Kent and Dr. Susan Parsons, researchers in the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center, the training plan builds on the candidate's prior clinical and research experience to develop expertise in 1) designing impactful cardio-oncology outcomes studies using large administrative databases; 2) oncology clinical trial design and 3) qualitative and decision analytic research methods. Each year in the US, more than 40,000 individuals 65 years and older are diagnosed with lymphoma with anthracycline-containing regimens recommended as first-line treatment in the majority of lymphoma subtypes. While anthracycline chemotherapeutic agents help induce lymphoma remission, they also increase the risk of heart failure (HF). These effects are worsened in older adults, as age is a potent risk factor for HF in both non-cancer and cancer populations. However, omission of anthracyclines, even in elderly patients at high risk of toxicity, may be associated with worse outcomes. Thus, strategies to better predict and prevent anthracycline cardiotoxicity are needed to improve outcomes in older patients with lymphoma. Small randomized trials in predominately non-lymphoma populations have identified several promising strategies to prevent HF in patients receiving anthracyclines; however, neither clinical practice guidelines nor the FDA endorse any of these therapies due to insufficient evidence for the prevention of HF in newly diagnosed adults with lymphoma. The objective of this proposal is to advance the science of anthracycline cardiotoxicity prediction and prevention by: 1) developing and validating a HF risk prediction model in older individuals with newly diagnosed lymphoma; 2) determining which cardioprotective strategies are currently used in practice and 3)eliciting treatment preferences for cardioprotection from patients and providers. This research will lead to improved knowledge of anthracycline cardiotoxicity prevention, provide preliminary data for a study of cardioprotection in high-risk individuals with lymphoma and provide the candidate with the necessary skills and experience to become a successful independent investigator.