Benefits and Harms of Lung Cancer Screening in HIV Infection

描述(申请人提供)：肺癌是最常见的非艾滋病定义癌症(NADC)，也是艾滋病毒感染者(HIV+)中NADC死亡的主要来源。艾滋病毒携带者患肺癌的负担更大，因为吸烟率较高，加上与艾滋病毒相关的独立疾病增加了患肺癌的风险。不幸的是，大多数肺癌在临床上被诊断为晚期，并且有15%的5年生存率。迫切需要更早的检测战略，以提高艾滋病毒携带者中的肺癌死亡率。国家肺部筛查试验(NLST)最近证实，低剂量筛查胸部计算机断层扫描(CT)导致高危、未感染艾滋病毒(HIV-)的吸烟者的肺癌死亡率降低20%。因此，国家综合癌症网络现在建议对高危吸烟者进行肺癌筛查。将NLST的结果外推到HIV+个体是具有挑战性的。在这个老龄化的人口中，肺癌风险和负担的增加将使艾滋病毒+者成为优秀的筛查对象。然而，艾滋病毒携带者也会经历相当多的多发病，并可能因相互竞争的风险而有更高的死亡率。因此，如何将NLST结果应用于HIV+患者尚不清楚，因为一些患者可能活不到足够长的时间，无法获得筛查的好处。此外，艾滋病毒携带者由于既往肺部疾病和免疫功能受损，CT扫描可能更有可能出现假阳性。因此，与相当常见的良性结节的工作相关的发病率可能会很高。鉴于在不久的将来，仅针对HIV+患者进行随机对照试验的可能性很小，我们建议开发一个数学模型来估计筛查的潜在好处，确定合适的筛查候选者， 并确定最佳的筛查方案。由于筛查CT的医疗保健负担可能很大，我们将首先通过分析CT扫描的结果和一项大型队列研究的数据，确定在HIV阳性个体中进行筛查胸部CT扫描所产生的临床后果。然后，我们将构建一个模型来评估肺癌筛查对HIV+人群死亡率的影响；我们将把该模型及其结果与我们在NCI资助的癌症干预和监测建模网络(CISNET)中的合作者产生的结果进行比较。在基本病例分析之后，我们将考虑在不同的HIV+人群中进行筛查，竞争原因导致的死亡率，以及筛查的最佳方案和年龄。建议的分析将提供相关的、临床上有用的结果，为艾滋病毒+患者的护理提供信息。研究结果还将为正在制定肺癌筛查国家指南的政策制定者提供信息，并将在肺癌筛查传播过程的早期解决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.