Improving emergency care and outcomes of immune-related adverse events: The immune-related emergency disposition index (IrEDi)

摘要 我们响应特别关注的通知：紧急情况下的研究，并将在压缩的基础上 重大肿瘤学急诊研究网络(关注)。对于许多癌症患者来说，免疫检查- 点抑制药(ICPI)可以挽救生命。然而，来自ICPI的免疫相关不良事件(IrAE)可以 使人虚弱，可能很快变得严重，甚至是致命的。通常情况下，irAE会催生对Emer的访问- 急诊部(ED)。因此，及早认识到并决定承认、遵守或释放这些许可证- 来自急诊室的数据可能是癌症患者发病率和死亡率的关键。急诊临床医生通常会让他们的 在患者出现急救后2-6小时内作出处置决定(入院、观察或出院)。 然而，irAEs在ED中尤其具有挑战性，因为它的表现不典型，缺乏经典的 症状，在急诊室就诊期间诊断测试的延迟，以及急诊室设置的快节奏。 目前，还没有一个足够大的ED数据源，包括临床、生物、实验室和成像 数据将允许开发一种工具，指导早期识别和适当的ED分发- 潜在的irAEs患者的位置。因此，我们建议利用多站点协作 在4个受关注的ED中(MD Anderson癌症中心、俄亥俄州立大学、西北大学和 加州大学圣地亚哥分校)在不同的州，达到以下目的：1)发展概率 [免疫相关应急处置指数(Iredi)]模型对ED患者的ICPI进行危险分层 性情。我们将利用我们现有的数据(n=~2000)，即在3个月内接受ICPI的独特ED患者 在4个研究站点进行为期数月的ED报告。我们假设宿主免疫反应是 在ED遭遇期间可获得的炎症/免疫生物标记物和irAEs的发展将促进 证明入院、观察或出院的预测，以及传统因素，即EPIDE- 生物学因素(年龄、种族/民族)、生物学因素(性别、体重指数)、癌症(类型、分期/转移)和治疗-- 血管紧张素转换酶相关变量(ICPI分类、单一治疗与联合治疗、剂量/持续时间)和临床状态 (合并症、先前存在的自身免疫性疾病、生命体征、实验室结果、影像研究结果)；以及2) 使用前瞻性数据验证Iredi，并确定Iredi的预测效度。我们将进行一次专业- 对接受ICPI的ED癌症患者进行了前瞻性队列研究，共从4个地点招募了1500名患者，时间超过3个月. 一年期间。急诊室研究的一个常见局限性是，患者可能会接受多个急诊室的护理。因此，我们 将在30天内进行跟进电话，以评估急诊科的复诊或住院情况。我们假设艾瑞迪开发了- AIM 1的OPED具有较高的灵敏度(≥90%)和较高的特异度(≥90%)来预测合适的ED值。 职位(入院、观察或出院)如果我们的目标实现了，Iredi将是第一个风险 分层工具源于大量种族/民族和地理上不同的癌症患者。 我们未来的目标是验证Iredi在普通急诊室的有效性，以改善ICPI上癌症患者的紧急护理。

ABSTRACT We respond to Notice of Special Interest: Research in the Emergency Setting, and will build upon the Compre- hensive Oncologic Emergency Research Network (CONCERN). For many cancer patients, Immune Check- point Inhibitors (ICPIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICPIs can be debilitating, and can quickly become severe, or even be fatal. Often irAEs will precipitate visits to the emer- gency department (ED). Therefore, early recognition and the decision to admit, observe or discharge these pa- tients from the ED can be key to a cancer patient’s morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe or discharge) within 2-6 hours from their patient’s ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the absence of classic symptoms, delayed availability of diagnostic tests during the ED encounter, and the fast pace in the ED setting. At present, there is no single sufficiently large ED data source with clinical, biological, laboratory, and imaging data that will allow for the development of a tool that will guide early recognition and appropriate ED dispo- sition of patients with potential irAEs. Therefore, we propose to capitalize on a multi-site collaboration among 4 CONCERN EDs (MD Anderson Cancer Center, Ohio State University, Northwestern University and University of California San Diego) in different States, to achieve the following aims: 1) To develop a probability model [the Immune-related Emergency Disposition Index (IrEDi)] to risk stratify ED patients on ICPIs for ED disposition. We will leverage our existing data (n=~2000) of unique ED patients who received ICPIs within 3 months of ED presentation at the 4 research sites. We hypothesize that host immune response underlie the development of irAEs and that inflammation/immune biomarkers available during the ED encounter will im- prove the prediction of Hospital admission; Observation; or Discharge, along with traditional factors, i.e. epide- miological factors (age, race/ethnicity), biological factors (sex, BMI), cancer (type, stage/metastases) and treat- ment-related variables (class of ICPI, monotherapy versus combination, dose/duration), and clinical status (comorbidities, preexisting autoimmune diseases, vital signs, laboratory results, imaging study results); and 2) To validate IrEDi using prospective data and determine the predictive validity of irEDi. We will conduct a pro- spective cohort study of ED cancer patients who had received ICPIs, recruiting 1500 total from 4 sites over a 3- year period. A common limitation of ED studies is that patients may receive care from multiple EDs. Thus, we will conduct follow-up calls in 30 days to assess ED revisits or hospitalization. We hypothesize that IrEDi devel- oped in aim 1 will have high sensitivity (≥90%) and high specificity (≥90%) for predicting appropriate ED dispo- sition (hospital admission, observation, or discharge). If our aims are achieved, the IrEDi will be the first risk stratification tool derived from a large racial/ethnically and geographically diverse population of cancer patients. Our future goal is to validate irEDi in general EDs to improve emergency care of cancer patients on ICPIs.