Optimizing the Approach to Identify Cancer-Associated Myositis

优化癌症相关肌炎的识别方法

• 批准号: 10685611
• 负责人: Christopher Mecoli
• 金额: $ 15.46万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10685611
• 关键词: 3-hydroxy-3-methylglutaryl-coenzyme A; Abdomen; Address; Age; Antibodies; Autoantibodies; Biological; Blood Tests; Cancer Detection; Cancer Patient; Characteristics; Chest; Clinical; Clinical Investigator; Control Groups; Cox Proportional Hazards Models; DNA Sequence Alteration; Data; Dermatomyositis; Detection; Development; Diagnosis; Diagnostic; Disease; Event; Foundations; Future; General Population; Goals; Guidelines; High-Risk Cancer; Idiopathic Inflammatory Myopathies; Image; Immune; Immunoprecipitation; Incidence; Knowledge acquisition; Malignant Neoplasms; Mediating; Methods; Modeling; Myopathy; Myositis; Nuclear Matrix-Associated Proteins; Onset of illness; Outcome; Oxidoreductase; Pathogenesis; Patients; Pelvis; Performance; Phenotype; Polymyositis; Positron-Emission Tomography; Predictive Value; Procedures; Radiation; Recommendation; Registries; Risk; Role; SEER Program; Scoring Method; Screening for cancer; Site; Specificity; Standardization; Subgroup; Symptoms; Testing; Time; Uncertainty; United States; Validation; Visit; Work; X-Ray Computed Tomography; cancer risk; cancer type; clinical decision-making; clinical phenotype; clinically relevant; cohort; evidence base; evidence based guidelines; experience; follow-up; high risk; high risk population; improved; insight; novel; patient subsets; predictive tools; prophylactic mastectomy; protein biomarkers; sex; skills; tool; transcriptional intermediary factor 1; tumor; tumor DNA

PROJECT SUMMARY Although the pathogenesis of idiopathic inflammatory myopathies (IIM) is largely unknown, data has emerged describing a relationship between cancer and IIM onset. In a subset of IIM patients, there exists an increased risk of cancer around the time of myositis onset, referred to as cancer-associated myositis (CAM). Several myositis-specific autoantibodies have proven useful in the clinical phenotyping of patients with IIM, including associating with cancer. However, which patients are at highest risk for developing cancer, the magnitude of the risk, the type of cancer, and the optimal cancer detection strategy are all unknown. Our preliminary data demonstrate that these myositis-specific autoantibodies can serve a useful role in the ability to define subgroups with regards to cancer risk as well as provide insight into the type of cancer a patient may be at highest risk for. Furthermore, we demonstrate that despite the widespread use of a large variety of cancer- screening tests employed by clinicians in the United States, not all tests have equal value in IIM patients. The proposed studies will utilize one of the largest cohorts of IIM patients in the world to define and validate autoantibodies associated with increased cancer risk and to assess their utility in quantifying the cancer risk at disease onset. In Aim 1 we will determine the risk of cancer-associated myositis relative to the general population in our cohort overall and in distinct autoantibody subgroups. We will demonstrate that the risk and type of cancer associated with IIM relative to the general population will vary based on the autoantibody the patient produces. Aim 2 will provide data on the usefulness of the current standard of cancer assessment that is performed in IIM patients, and generate an argument for a more selective, less harmful detection strategy. Lastly, in Aim 3 we will derive a predictive tool that will be used to inform clinical decision-making for optimal strategies to assess IIM patients for malignancy. This work will allow the development of a clinically relevant and evidence-based approach to cancer detection at IIM onset and establish the role for defining IIM patients by autoantibody subsets.

项目概要 尽管特发性炎症性肌病 (IIM) 的发病机制在很大程度上尚不清楚，但已有数据出现 描述癌症与 IIM 发病之间的关系。在 IIM 患者的子集中，存在增加的 肌炎发作期间患癌症的风险，称为癌症相关肌炎 (CAM)。一些 肌炎特异性自身抗体已被证明可用于 IIM 患者的临床表型分析，包括 与癌症有关。然而，哪些患者患癌症的风险最高，其严重程度 风险、癌症类型和最佳癌症检测策略都是未知的。我们的初步 数据表明，这些肌炎特异性自身抗体可以在定义肌炎的能力方面发挥有用的作用 关于癌症风险的亚组，并提供对患者可能患有的癌症类型的深入了解 的风险最高。此外，我们证明，尽管广泛使用多种癌症 - 根据美国临床医生采用的筛查测试，并非所有测试对 IIM 患者都具有相同的价值。这 拟议的研究将利用世界上最大的 IIM 患者队列之一来定义和验证 与癌症风险增加相关的自身抗体，并评估其在量化癌症风险方面的效用 疾病发作。在目标 1 中，我们将确定相对于一般人群的癌症相关肌炎的风险 在我们的总体队列和不同的自身抗体亚组中。我们将证明癌症的风险和类型 与一般人群相比，IIM 的相关性将根据患者产生的自身抗体而有所不同。 目标 2 将提供关于 IIM 中执行的当前癌症评估标准的有用性的数据 患者，并提出了一种更具选择性、危害性较小的检测策略的论据。最后，在目标 3 中，我们将 导出预测工具，用于为临床决策提供信息，以制定评估 IIM 的最佳策略 恶性肿瘤患者。这项工作将有助于开发一种临床相关且基于证据的 IIM 发病时癌症检测的方法，并确立通过自身抗体定义 IIM 患者的作用 子集。

项目成果

Perifollicular Hypopigmentation in Systemic Sclerosis: Associations With Clinical Features and Internal Organ Involvement.

• DOI: 10.3899/jrheum.210983
• 发表时间: 2022-05
• 期刊: JOURNAL OF RHEUMATOLOGY
• 影响因子: 3.9
• 作者: Chung, Melody P.;Mecoli, Christopher A.;Perin, Jamie;Richardson, Carrie;McMahan, Zsuzsanna H.
• 通讯作者: McMahan, Zsuzsanna H.