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 老年人蒽环类药物化疗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）分析目前的 心脏保护用途和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， 临床研究和卫生政策研究塔夫茨医疗中心，培训计划的基础上， 候选人先前的临床和研究经验，以发展1）设计 使用大型管理数据库进行有影响力的心脏肿瘤学结局研究; 2）肿瘤学 临床试验设计; 3）定性和决策分析研究方法。每年在 在美国，超过40，000名65岁及以上的人被诊断患有淋巴瘤， 含蒽环类药物的方案被推荐为大多数 淋巴瘤亚型而蒽环类化疗药物有助于诱发淋巴瘤 缓解，他们也增加了心力衰竭（HF）的风险。这些影响在老年人中恶化 因为年龄是非癌症和癌症人群中HF的潜在风险因素。 然而，即使在毒性风险高的老年患者中， 与更糟糕的结果相关。因此，更好地预测和预防蒽环类抗生素的策略 心脏毒性，以改善老年淋巴瘤患者的预后。小 在主要为非淋巴瘤人群中进行的随机试验已经确定了几个有希望的 在接受蒽环类药物治疗的患者中预防HF的策略;然而， 由于缺乏足够的证据， 在新诊断的淋巴瘤成人中预防HF。这项建议的目的是 推进蒽环类药物心脏毒性预测和预防的科学：1）开发 以及在患有新诊断的淋巴瘤的老年个体中验证HF风险预测模型; 2)确定目前在实践中使用的心脏保护策略，以及3）引出 患者和提供者对心脏保护的治疗偏好。这项研究将导致 为提高蒽环类药物心脏毒性预防的认识，提供初步数据， 在淋巴瘤高危人群中进行心脏保护的研究，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.