Prevention of Anthracycline Chemotherapy Cardiotoxicity

该提案提出了一个为期五年的研究职业发展计划，重点关注 老年人危及生命的蒽环类化疗心脏毒性的预测和预防 成人淋巴瘤患者通过：1) 改进的预测工具，2) 分析当前 心脏保护的使用以及 3) 确定患者和提供者的治疗偏好。的 候选人是塔夫茨大学医学院的助理教授 塔夫茨医学中心心脏病科心脏肿瘤学项目主任。 在大卫·肯特博士和苏珊·帕森斯博士的指导下，研究所的研究人员 塔夫茨医学中心的临床研究和卫生政策研究，培训计划建立在 候选人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影响力的心脏肿瘤学结果研究； 2）肿瘤学 临床试验设计和3）定性和决策分析研究方法。每年在 美国有超过 40,000 名 65 岁及以上的人被诊断患有淋巴瘤 含蒽环类药物的治疗方案被推荐作为大多数患者的一线治疗 淋巴瘤亚型。虽然蒽环类化疗药物有助于诱发淋巴瘤 缓解后，它们还会增加心力衰竭（HF）的风险。这些影响在老年人中更为严重 成人，因为年龄是非癌症和癌症人群中心力衰竭的一个潜在危险因素。 然而，即使对于具有高毒性风险的老年患者，省略蒽环类药物也可能会产生不良影响。 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 需要心脏毒性来改善老年淋巴瘤患者的预后。小号 主要针对非淋巴瘤人群的随机试验已经确定了一些有希望的药物 接受蒽环类药物治疗的患者预防心力衰竭的策略；然而，无论是临床实践 由于证据不足，FDA 指南也不认可这些疗法中的任何一种 预防新诊断的成人淋巴瘤患者的心力衰竭。该提案的目的是 通过以下方式推进蒽环类药物心脏毒性预测和预防的科学：1) 开发 在新诊断淋巴瘤的老年人中验证心力衰竭风险预测模型； 2) 确定目前在实践中使用哪些心脏保护策略，以及 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 为提高对蒽环类药物心脏毒性预防的认识，为预防蒽环类药物心脏毒性提供初步数据 对患有淋巴瘤的高危个体进行心脏保护研究，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.