Optimizing Lung Cancer Treatment in HIV Infected Persons

优化 HIV 感染者的肺癌治疗

基本信息

批准号：
9902377
负责人：
Keith Magnus Sigel
金额：
$ 53.33万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-13 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902377
关键词：
Adjuvant Chemotherapy Advisory Committees Age-Years Aging Antiviral Therapy Cancer Etiology Cancer Patient Cardiac Cause of Death Cessation of life Chemotherapy and/or radiation Chemotherapy-Oncologic Procedure Clinical Clinical Trials Data Databases Diagnosis Early treatment Excision Goals HIV Hepatic Kidney Kidney Diseases Knowledge Life Expectancy Lobectomy Localized Disease Lung Malignant Neoplasms Malignant neoplasm of lung Medicaid Medicare Modeling Modification Morbidity - disease rate Natural History Non-Small-Cell Lung Carcinoma Outcome Patients Persons Policies Population Postoperative Complications Preventive service Quality of life Radiation Randomized Controlled Trials Risk Screening for cancer Smoker Smoking Source Surgical complication Toxic effect Toxicity due to chemotherapy Treatment Effectiveness Treatment outcome Uncertainty Veterans base cancer therapy chemotherapy cohort comorbidity comparative comparative effectiveness computed tomography screening experience frailty functional status high risk improved innovation kidney dysfunction lung cancer screening mathematical model models and simulation mortality mortality risk older patient optimal treatments overtreatment population based public health priorities risk benefit ratio tetrahydrobiopterin treatment disparity tumor tumor behavior tumor progression virology

项目摘要

PROJECT SUMMARY The overall goal of this project is to improve the management of HIV infected (HIV+) lung cancer patients. Lung cancer is the leading cause of cancer death in older HIV+ patients. Up to 30% of lung cancer cases are diagnosed at a loco-regional stage (with expected increases due to the implementation of lung cancer screening in the HIV+ population), can be treated with a curative intent, and may experience relatively good long-term survival. Despite this, HIV+ lung cancer patients experience lung cancer treatment disparities and have poorer lung cancer outcomes. The risk/benefit ratio of cancer therapies can be substantially altered in HIV+ patients because of differences in treatment toxicity, tumor aggressiveness, functional status, life expectancy, and quality of life. Unfortunately, patients with comorbidities such as HIV are consistently excluded from randomized controlled trials (RCTs) generating an important gap in knowledge regarding their management. Lack of data relevant to HIV+ patients has profound negative impact including under treatment, increased morbidity, and decreased survival. Thus, optimizing the management of HIV+ lung cancer patients is a major public health priority. In this study, we will use simulation modeling, an approach complementary to RCTs, to determine the optimal treatment of early stage HIV+ lung cancer patients. The Specific Aims are to: 1) enhance and validate the Lung Cancer Policy Model (LCPM) to simulate the management and subsequent outcomes of HIV+ patients with loco-regional non-small cell lung cancer (NSCLC); 2) determine the optimal management for stage I NSCLC in HIV+ patients; 3) find the optimal indications for adjuvant chemotherapy for stage II-IIIA NSCLC in HIV+ patients; and 4) identify optimal management strategies for stage I-IIIA NSCLC in HIV+ patients with severe cardiac, pulmonary, renal or hepatic comorbidities. To achieve these Aims, we will use an enhanced version of the LCPM, a well-validated mathematical model of lung cancer progression. In Aim 1, we will use data from several population-based HIV+ cohorts to substantially enhance, calibrate, and validate the LCPM by incorporating an HIV natural history module, as well as HIV-specific parameter modifications for functional status, frailty, cancer treatments, complications of surgery and chemotherapy toxicity, outcomes, survival and quality of life. Then, we will assess the optimal management, in terms of reducing toxicity and maximizing survival and quality of life, of HIV+ patients with early stage lung cancer. Our study is innovative in providing HIV-specific cancer treatment guidance, as well as in applying modeling approaches mostly used to evaluate cancer screening, to the optimization of lung cancer therapies. The results of the study will directly inform the management of large numbers of HIV+ lung cancer patients, a vulnerable and understudied group that currently experience substantially worse outcomes.

项目概要该项目的总体目标是改善艾滋病毒感染（HIV+）肺癌患者的管理。肺癌是老年艾滋病病毒感染者癌症死亡的主要原因。高达 30% 的肺癌病例是在局部区域阶段诊断（由于实施肺癌计划，预计会增加） HIV+人群中的筛查），可以以治愈为目的进行治疗，并且可能会经历相对较好的治疗长期生存。尽管如此，艾滋病毒+肺癌患者仍会经历肺癌治疗差异，并且肺癌预后较差。癌症治疗的风险/效益比可以在以下方面发生显着改变： HIV+患者由于治疗毒性、肿瘤侵袭性、功能状态、生活的差异预期和生活质量。不幸的是，患有艾滋病毒等合并症的患者始终被排除在外随机对照试验 (RCT) 产生了关于其相关知识的重要差距管理。缺乏与 HIV+ 患者相关的数据会产生深远的负面影响，包括接受治疗、发病率增加，生存率下降。因此，优化 HIV+ 肺癌患者的管理是一项重要的公共卫生优先事项。在本研究中，我们将使用模拟建模，这是一种补充方法随机对照试验，以确定早期 HIV+ 肺癌患者的最佳治疗。具体目标是： 1）增强和验证肺癌政策模型（LCPM）以模拟管理和后续患有局部区域非小细胞肺癌 (NSCLC) 的 HIV + 患者的结局； 2）确定最优 HIV+ 患者 I 期 NSCLC 的管理； 3）寻找辅助化疗的最佳适应症 HIV+ 患者的 II-IIIA 期 NSCLC； 4) 确定 I-IIIA 期 NSCLC 的最佳管理策略患有严重心脏、肺部、肾脏或肝脏合并症的 HIV+ 患者。为了实现这些目标，我们将使用 LCPM 的增强版本，这是一种经过充分验证的肺癌进展数学模型。在目标 1，我们将使用来自几个基于人群的 HIV+ 队列的数据来大幅增强、校准和通过纳入 HIV 自然历史模块以及 HIV 特定参数来验证 LCPM 功能状态、虚弱、癌症治疗、手术和化疗并发症的改变毒性、结果、生存和生活质量。然后，我们将根据以下方面评估最佳管理：降低艾滋病毒+早期肺癌患者的毒性并最大限度地提高其生存率和生活质量。我们的该研究在提供艾滋病毒特异性癌症治疗指导以及应用模型方面具有创新性方法主要用于评估癌症筛查、优化肺癌治疗。结果该研究的结果将直接为大量艾滋病毒+肺癌患者的管理提供信息，这些患者是弱势群体以及目前尚未得到充分研究的群体，其结果要差得多。