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决定性癌症（NADC），也是艾滋病毒感染者（HIV+）中NADC死亡率的主要来源。由于较高的吸烟率以及独立的与艾滋病毒相关的肺癌风险增加，艾滋病毒阳性患者有更大的肺癌负担。不幸的是，大多数肺癌在临床诊断为晚期，5年生存率<15%。迫切需要早期发现战略，以提高艾滋病毒阳性患者的肺癌死亡率。国家肺部筛查试验（NLST）最近表明，低剂量胸部计算机断层扫描（CT）筛查可使高风险、未感染艾滋病毒（HIV-）的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风险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。在这一老龄化人群中，肺癌风险和负担的增加将使艾滋病毒阳性患者成为筛查的优秀候选人。然而，艾滋病毒阳性患者也有相当多的发病率，并可能因竞争风险而具有更高的死亡率。因此，如何将NLST的结果应用于HIV+患者尚不清楚，因为一些患者可能无法存活足够长的时间来获得筛查的益处。此外，由于先前的肺部疾病和免疫功能低下，HIV阳性患者更有可能出现假阳性的CT扫描。因此，发病率相关的良性结节的工作，这是相当常见的，可能是显著的。考虑到在不久的将来不太可能局限于HIV+患者的随机对照试验，我们建议开发一个数学模型来估计筛查的潜在益处，确定合适的筛查候选者，

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.