Assessment of cardiotoxicity in Immunity Checkpoint Blockers and other cancer therapies

背景：肺癌是世界范围内癌症死亡的主要原因，非小细胞肺癌 癌症(NSCLC)占所有肺癌病例的85%。酪氨酸治疗非小细胞肺癌的研究进展 激酶抑制剂(TKI)和免疫检查点阻滞剂(ICB)可提高存活率。然而，在那里 与新的癌症疗法相关的心脏毒性可能会导致早产，这是一个日益令人担忧的问题 幸存者中的发病率。不幸的是，心脏毒性造成的心脏损害通常直到 表现为急性或慢性心血管事件。 意义/影响：鉴于它们在改善癌症预后方面的临床有效性和潜在的 在VA患者中扩大使用，迫切需要更好地了解 临床使用TKI和ICB引起的心血管毒性。从这个过程中获得的信息 试点研究将使进行大规模的基于人群的研究，以确定临床表现 心脏毒性，量化随时间推移相关心血管疾病的发生率，确定 与特定治疗、持续时间和剂量相关的心脏毒性，并探索可能起作用的生物标志物 作为潜在心脏损伤的早期预警信号。研究结果也可能有助于心脏毒性的研究。 与其他癌症疗法和其他类型的癌症有关。 创新：癌症相关心脏毒性的人群研究面临的一个重大挑战是缺乏 在反映真实临床的观察性数据源中识别心脏毒性的有效算法 跨多个机构开展业务。因此，开发和验证量化和 监测接受替代疗法的患者的心血管事件将有助于以人群为基础 研究癌症治疗对幸存者的长期影响，并协助长期监测 新的癌症疗法以补充临床试验数据。在退伍军人事务部进行这项研究的好处包括 通过退伍军人管理局接受护理的大量退伍军人，所有VHA的临床细节可用 通过退伍军人信息学和计算基础设施(Vinci)在全国范围内为患者提供 NLP算法先前被验证可以从VA病历的临床记录中提取超声心动图结果。 我们将把试点分析集中在非小细胞肺癌患者身上，因为之前关于心脏毒性的研究有限。 非小细胞肺癌患者。 具体目标：这项初步研究将开发和验证心血管事件的可操作性定义 展示心脏毒性的潜在临床表现，以促进未来对心脏毒性的研究 与ICB和TKI相关联，采用基于人口的框架。具体目标是：1)开发和验证 一种用于识别非小细胞肺癌患者心血管事件的结构化算法 ICI、TKI或化疗；以及2)量化心血管事件的发生率，总体和时间框架 (早期效应与晚期效应)，以及特定的心脏状况。 方法：该研究将使用2014-2019年在退伍军人事务部接受非小细胞肺癌治疗的患者的数据 并将合并三个数据源：1)关于患者接触、诊断、程序、 和药物；2)电子病历中常规可用的数据，如实验室测试和生命体征；以及3) 超声心动图测试结果存储在将使用自然语言查询的非结构化临床记录中 处理(NLP)算法。心血管事件的定义将在抽样和抽象中进行验证 医疗记录，并用于开发心脏毒性发生率和类型的试点数据，供后续的IIR使用。 实施/下一步：最终，这项试点研究将在#年开发和验证心脏毒性指标 接受非小细胞肺癌治疗的患者可以跨多个临床实践使用，以促进未来 对有心脏毒性风险的癌症患者的趋势、预防和结果进行调查。

Background: Lung cancer is a leading cause of death from cancer death worldwide, and non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Advances in NSCLC treatment using tyrosine kinase inhibitors (TKI) and immunity checkpoint blockers (ICB) have led to improved survival. However, there is a growing concern that cardiotoxicity associated with novel cancer therapies may lead to premature morbidity among survivors. Unfortunately, heart damage due to cardiotoxicity is often not recognized until manifested through acute or chronic cardiovascular events. Significance/Impact: Given their proven clinical efficacy in improving cancer outcomes and potential for expanded use in VA patients, there is an urgent need to better understand the risk and impacts of cardiovascular toxicity associated with use of TKI and ICB in clinical practice. The information gained from this pilot study will enable the conduct of large-scale population-based studies to identify clinical manifestations of cardiotoxicity, quantify the incidence of related cardiovascular disease over time, identify risk factors for cardiotoxicity associated with specific treatments, duration, and dose, and explore biomarkers that may serve as early warning signals of potential heart damage. Results may also facilitate research into cardiotoxicity associated with other cancer therapies and other types of cancer. Innovation: A significant challenge to population-based studies of cancer-related cardiotoxicity is the lack of validated algorithms to identify cardiotoxicity in observational data sources that reflect real-world clinical practice across multiple institutions. Therefore, developing and validating algorithms for quantifying and monitoring cardiovascular events in patients receiving alternative therapies would facilitate population-based research on the long-term effects of cancer treatments among survivors, and assist in long-term surveillance of novel cancer therapies to supplement clinical trial data. Benefits of conducting this research in the VA include the large number of veterans who receive care through the VA, the availability of clinical detail for all VHA patients nationwide through the VA Informatics and Computing Infrastructure (VINCI), and the availability of an NLP algorithm previously validated to extract echocardiogram results from clinical notes in VA medical records. We will focus our pilot analysis on patients with NSCLC due to the limited prior research on cardiotoxicity in patients with NSCLC. Specific Aims: This pilot study will develop and validate operational definitions of cardiovascular events representing potential clinical manifestations of cardiotoxicity to facilitate future investigations into cardiotoxicity associated with ICB and TKI using a population-based framework. Specific Aims are: 1) Develop and validate a structured algorithm for identifying cardiovascular events in patients who initiate NSCLC cancer therapy with ICI, TKI, or chemotherapy; and 2) Quantify the incidence of cardiovascular events, overall and by time frame (early versus late effects), and specific cardiac conditions. Methods: The study will use data for patients undergoing treatment for NSCLC in the VA during 2014-2019 and will incorporate three data sources: 1) administrative data on patient encounters, diagnoses, procedures, and medications; 2) data routinely available in EMR such as laboratory tests and vital signs; and 3) echocardiogram test results stored in unstructured clinical notes that will be queried using a natural language processing (NLP) algorithm. Definitions of cardiovascular events will be validated in sampled and abstracted medical records, and used to develop pilot data on cardiotoxicity incidence and type for a subsequent IIR. Implementation/Next Steps: Ultimately, this pilot study will develop and validate indicators of cardiotoxicity in patients undergoing NSCLC therapy that can be used across multiple clinical practices to facilitate future investigations into trends, prevention, and outcomes of patients with cancer who are at risk of cardiotoxicity.