A Multi-Institute Survivorship Study of Patients Living with Advanced Cancer Who Have Had Durable Response to Immune Checkpoint Inhibitors

摘要 免疫检查点抑制剂(ICIS)已经显著改变了许多类型的癌症的治疗格局 过去十年中的晚期恶性肿瘤。相当大比例的晚期癌症患者源于 ICIS带来的持久好处，并实现比以前更长的无进展生存期或缓解期 有可能。然而，我们仍然对ICI治疗的持久反应和症状的决定因素知之甚少。 这一不断增长的患者群体的轨迹和生存需求。因此，我们建议进行一项多研究所的研究。 有两个姐妹队列的晚期癌症患者。首先，仅有EHR数据的回溯性队列将 包括8,860名接受ICI治疗的晚期疾病患者，包括所有癌症类型 2014-2022年的基础免疫治疗。这一大群人将使我们能够识别和研究持久的应答者 ICIS，定义为对ICI治疗取得部分或完全反应并存活至少一年的患者 ICI治疗开始后。其次，未来的队列将招募并积极跟踪估计1200人 晚期肺癌、肾癌和黑色素瘤ICI治疗持久有效的患者 使用ICIS治疗的三种最常见的癌症。临床和患者报告的结果数据将在以下位置收集 基线和随访期间每隔6个月进行一次。这一前瞻性队列将使我们能够研究长期生存 以及对ICIS有持久反应的患者的生理和心理社会症状轨迹，并确定 预测ICI长期生存和常见副作用的临床和可改变的行为因素 治疗。在这些分析中确定的预测因素将在直接队列中独立验证，a 由研究小组领导的关于ICI治疗中种族差异的大型正在进行的研究。我们的具体目标是： 1.在回溯性的EHR数据队列中，1a)确定了耐久的患者比例 对脑梗塞治疗的反应(部分/完全应答和自首次脑梗塞治疗后1年存活的≥)和图表 他们的生存轨迹；1b)确定ICI治疗持久反应的临床预测因素；1c)。在 独立的直接队列，验证ICI治疗持久反应的临床预测因素。 2.在前瞻性队列中，2a)确定患者的长期生存和身体的纵向轨迹 以及ICI治疗后的心理社会症状；2b)调查长期生存与 使用多维预测因子进行ICI治疗的常见副作用；2c)。在独立的直接 队列，验证持久反应患者的生存和常见副作用的预测因素。 我们的研究结果将提供急需的数据，为新的循证干预提供依据 作为下一步优化生存护理并延长和提高成长者生活质量的战略 因ICI治疗而被诊断为晚期癌症的幸存者人数。

ABSTRACT Immune checkpoint inhibitors (ICIs) have markedly transformed the therapeutic landscape for many types of advanced malignancies over the past decade. A sizable proportion of patients with advanced cancer derive durable benefits from ICIs and achieve longer periods of progression-free survival or remission than previously possible. Yet we still know little about the determinants of durable response to ICI treatment and the symptom trajectory and survivorship needs of this growing patient population. We thus propose a multi-institute study with two sister cohorts of patients living with advanced cancers. First, a retrospective EHR data-only cohort will include 8,860 patients with advanced disease, inclusive of all cancer types, who have been treated with ICI- based immunotherapy in 2014-2022. This large cohort will allow us to identify and study durable responders to ICIs, defined as patients who achieve partial or complete response to ICI treatment and live at least one year after ICI treatment initiation. Second, a prospective cohort will enroll and actively follow an estimated 1,200 patients with durable response to ICI treatment for advanced lung cancer, kidney cancer, and melanoma, the three most common cancers treated with ICIs. Clinical and patient-reported outcome data will be collected at baseline and every 6 months during follow up. This prospective cohort will allow us to study long-term survival and physical and psychosocial symptom trajectories in patients with durable response to ICIs, and to identify clinical and modifiable behavioral factors predictive of long-term survival and common side effects of ICI treatment. The predictors identified in these analyses will be independently validated in the DiRECT Cohort, a large ongoing study of racial disparities in ICI treatment led by the study team. Our Specific Aims are: 1. In the retrospective EHR data-only cohort, 1a) Determine the proportion of patients who had durable response to ICI treatment (partial/complete response and alive ≥1 year since initial ICI treatment) and chart their survival trajectory; 1b) Identify clinical predictors for durable response to ICI treatment; 1c). In the independent DiRECT Cohort, validate the clinical predictors for durable response to ICI treatment. 2. In the prospective cohort, 2a) Identify long-term survival and longitudinal trajectories of patients' physical and psychosocial symptoms after ICI treatment; 2b) Investigate the relationships of long-term survival and common side effects from ICI treatment with multidimensional predictors; 2c). In the independent DiRECT Cohort, validate the predictors for survival and common side effects in patients with durable response. Findings from our study will provide much-needed data that can inform new evidence-based intervention strategies as the next step to optimize survivorship care and extend and improve quality of life for the growing population of survivors living after a diagnosis of advanced cancer due to ICI treatment.