Comparative-Effectiveness of Pretreatment Lung Cancer Nodal Staging

摘要 我们的目标是减少诊断和治疗错误，提高存活率，增加对肺部的护理价值 通过提高我们选择受益于前处理淋巴结活检的患者的能力，我们可以为癌症患者提供更多的治疗机会。 准确确定癌症是否已扩散到淋巴结以及扩散的程度(这一过程称为 结节分期)对于适当的治疗选择至关重要。筹划不足可能会导致遗漏 化疗或不必要的手术。分期过长可能导致不必要的化疗和遗漏 做手术。诊断和治疗错误会对存活率产生负面影响。这些错误通常发生在使用 单独用于结节分期的成像。活组织检查可以减少出错的机会，但也可能导致罕见的生命- 危险的不良事件。每次活检的费用约为5,000美元。实践指南建议有选择地执行 当影像表现提示结节病变时进行活检。然而，全国的活检率还不到 他们应该是什么样子。此外，有25倍的设施级别的差异不能用获得护理的机会来解释，病例- 混合，或临床医生或设施的特点。这些发现，以及潜在的低水平证据 指南建议，对淋巴结的适应症提出了真正的临床和科学不确定性 活组织检查。我们进行了一项初步研究，以更好地了解指南建议如何选择患者 用于活检，并了解到符合指南的结节分期选择所有患有真正结节病的患者进行 活检和三分之二无真正结节病变的患者进行活检。此外，我们还开发了和 验证了基于风险的替代节点分段战略，该战略使用预测模型进行分层和选择 患者进行淋巴结活检。初步数据显示，它能识别几乎所有有真正结节的患者 疾病进行活检，但选择较少无结节真结节病变的患者进行活检。然而， 淋巴活检的选择策略与患者预后之间的关系尚不清楚。我们 假设与指南一致的结节分期与较高的5年生存率相关 与指南不一致的结节分期(目标I)，基于风险的结节分期等同于指南- 在生存率方面的一致性结节分期，但在较低的活检相关不良事件和 医疗保健支出(AIM II)。验证这些假设将需要大约4,000名患者；因此，试验不是 目前是可行的。我们将利用癌症研究网络创建一个新的肺癌患者队列 基础设施使用观察性、比较有效性研究设计和高级 回归技术和机器学习，以最大限度地减少混淆。此外，我们将使用患者级别 来自该队列的数据作为我们将开发的比较有效性模拟模型中的模型输入 开展目标二.这项研究的结果将导致：1)制定和测试执行战略 旨在增加与指南一致的结节分期，2)针对结节的替代指南建议 分期，和/或3)比较不同节点分期策略之间的结果的正当性试验。

ABSTRACT Our goal is to reduce diagnostic and treatment errors, improve survival, and increase the value of care for lung cancer patients by improving our ability to select patients who benefit from a pretreatment lymph node biopsy. Accurately determining whether cancer has spread to lymph nodes and the extent of spread (a process called nodal staging) is critical for appropriate treatment selection. Understaging can lead to omission of chemotherapy or unnecessary surgery. Overstaging can lead to unnecessary chemotherapy and omission of surgery. Diagnostic and treatment errors negatively impact survival. These errors commonly occur when using imaging alone for nodal staging. A biopsy can reduce the chances of error, but it can also result in rare, life- threatening adverse events. Each biopsy costs ~$5,000. Practice guidelines recommend selectively performing a biopsy when imaging findings suggest nodal disease. However, national biopsy rates are less than half of what they should be. Moreover, there is 25-fold facility-level variability not explained by access to care, case- mix, or clinician or facility characteristics. These findings, along with the low levels of evidence underlying guideline recommendations, suggest true clinical and scientific uncertainty over the indications for lymph node biopsy. We conducted a pilot study to better understand how well guideline recommendations select patients for biopsy and learned that guideline-concordant nodal staging selects all patients with true nodal disease for biopsy and two-thirds of patients without true nodal disease for biopsy. Additionally, we developed and validated an alternative risk-based nodal staging strategy that uses a prediction model to stratify and select patients for lymph node biopsy. Preliminary data show that it identifies nearly all patients with true nodal disease for biopsy but selects fewer patients without nodal true nodal disease for biopsy. However, the relationship between selection strategies for lymph node biopsy and patient outcomes remains unknown. We hypothesize that guideline-concordant nodal staging is associated with higher 5-year survival rates compared with guideline-discordant nodal staging (Aim I) and that risk-based nodal staging is equivalent to guideline- concordant nodal staging in terms of survival but superior in terms of lower biopsy-related adverse events and healthcare expenditures (Aim II). Testing these hypotheses will require ~4,000 patients; therefore, a trial is not feasible at this time. We will create a novel cohort of lung cancer patients using the Cancer Research Network infrastructure to conduct Aim I using an observational, comparative-effectiveness study design with advanced regression techniques and machine learning to minimize confounding. Additionally, we will use patient-level data from this cohort as model inputs in a comparative-effectiveness simulation model that we will develop to conduct Aim II. Findings from this study will lead to: 1) developing and testing implementation strategies designed to increase guideline-concordant nodal staging, 2) alternative guideline recommendations for nodal staging, and/or 3) justifying trials comparing outcomes between different nodal staging strategies.