Benefits and Harms of Lung Cancer Screening in HIV Infection

描述（由申请人提供）：肺癌是最常见的非艾滋病定义癌症（NADC），也是HIV感染（HIV+）个体中NADC死亡率的主要来源。由于吸烟率较高，加上与艾滋病毒相关的独立肺癌风险增加，艾滋病毒阳性者患肺癌的负担更大。不幸的是，大多数肺癌在临床上被诊断为晚期，5年生存率<15%。迫切需要采取早期检测战略，以降低艾滋病毒阳性者的肺癌死亡率。国家肺筛查试验（NLST）最近表明，低剂量筛查胸部计算机断层扫描（CT）导致高风险，HIV未感染（HIV-）吸烟者肺癌死亡率降低20%。因此，国家综合癌症网络现在建议高危吸烟者进行肺癌筛查。将NLST的结果外推到HIV+个体具有挑战性。在这一老龄化人口中，肺癌的风险和负担增加，这将使艾滋病毒阳性者成为筛查的最佳候选人。然而，艾滋病毒阳性者也经历了相当多的多重死亡，并可能因相互竞争的风险而死亡率更高。因此，如何将NLST的结果应用于HIV阳性者尚不清楚，因为一些患者可能无法存活足够长的时间以获得筛查的益处。此外，艾滋病毒阳性者可能更有可能由于先前的肺部疾病和免疫功能低下而出现假阳性CT扫描。因此，与良性结节的检查相关的发病率可能是显著的，良性结节是相当常见的。考虑到在不久的将来不太可能进行仅限于HIV+患者的RCT，我们建议开发一个数学模型，以估计筛查的潜在益处，确定合适的筛查候选人， 并确定最佳筛选方案。由于CT筛查的卫生保健负担可能很大，我们将首先通过分析CT扫描结果和大型队列研究的数据，确定在HIV+个体中进行胸部CT筛查扫描的临床后果。然后，我们将构建一个模型来估计肺癌筛查对HIV+人群死亡率的影响;我们将把这个模型及其结果与我们的合作者在NCI-funded Cancer Intervention and Surveillance Modeling Network（CISNET）中生成的模型进行比较。在基础病例分析后，我们将考虑在不同的HIV+人群中进行筛查，竞争原因的死亡率以及筛查的最佳方案和年龄。拟议的分析准备提供相关的，临床上有用的结果，告知艾滋病毒+患者的护理。研究结果还将为正在制定国家肺癌筛查指南的决策者提供信息，并将在肺癌筛查传播过程的早期讨论筛查在艾滋病毒中的作用。

DESCRIPTION (provided by applicant): Lung cancer is the most common non-AIDS defining cancer (NADC) and leading source of NADC mortality amongst HIV infected (HIV+) individuals. HIV+ persons have a greater burden of lung cancer due to higher smoking rates combined with an independent HIV related increased risk of lung cancer. Unfortunately, most lung cancers are clinically diagnosed at an advanced stage and have 5-year survival rates <15%. Earlier detection strategies to improve lung cancer mortality among HIV+ persons are urgently needed. The National Lung Screening Trial (NLST) recently demonstrated that low-dose screening chest computed tomography (CT) led to a 20% reduction in lung cancer mortality among high-risk, HIV uninfected (HIV-) smokers. As a result, lung cancer screening is now recommended by the National Comprehensive Cancer Network for high-risk smokers. Extrapolating results of the NLST to HIV+ individuals is challenging. The increased risk and burden of lung cancer in this aging population would make HIV+ persons excellent candidates for screening. However, HIV+ persons also experience considerable multimorbidity and can have higher mortality from competing risks. Thus, how to apply results of the NLST to HIV+ persons is unclear, as some patients may not survive long enough to derive benefits of screening. Additionally, HIV+ persons may be more likely to have false positive CT scans due to prior lung disease and immunocompromise. Consequently, the morbidity associated with the work-up of benign nodules, which are quite common, could be significant. Given that an RCT limited to HIV+ patients is very unlikely in the near future, we propose to develop a mathematical model that estimates the potential benefits of screening, identifies the appropriate candidates for screening, and determines the best screening regimen. As the health care burden of screening CT can be substantial, we will first determine the clinical consequences that result from performing screening chest CT scans among HIV+ individuals by analyzing results of CT scans and data from a large cohort study. Then, we will construct a model to estimate the impact of lung cancer screening on mortality among HIV+ persons; we will compare this model and its results to one generated by our collaborators in the NCI-funded Cancer Intervention and Surveillance Modeling Network (CISNET). After base case analyses, we will consider screening in different HIV+ populations, mortality from competing causes, and the optimal regimen and age for screening. The analyses proposed are poised to provide relevant, clinically useful results to inform the care of HIV+ patients. The results will also inform policy makers who are in the process of developing national guidelines for lung cancer screening, and will address early in the process of dissemination of lung cancer screening the role for screening in HIV.