Comparative Effectiveness of Surgery vs Stereotactic Radiation Therapy for Stage I Lung Cancer

在美国，非小细胞肺癌（NSCLC）是癌症相关发病率和死亡率的主要原因。 随着越来越多地使用计算机断层扫描和肺癌筛查，肿瘤越来越多地被诊断为恶性肿瘤。 在第一阶段被检测到，这意味着治愈的可能性超过70%。手术一直是 I期NSCLC的传统治疗。然而，基于人口的研究表明， 立体定向放射治疗（SBRT）在过去的十年。回顾性研究比较手术和 SBRT，包括我们小组的几篇出版物，由于样本量相对较小，缺乏 患者报告的结局，以及关于合并症和癌症相关结局的稀疏信息。 因此，最近的一项系统性综述得出结论，“有必要对两种治疗方法进行大规模的比较， 前瞻性试验”。不幸的是，多项尝试比较手术和SBRT的随机对照试验 由于专业偏见和缺乏平衡感，未能积累和过早关闭。此外，委员会认为， 我们先前的工作已经证明，个体患者特征在治疗选择中是至关重要的。在 由于缺乏前瞻性比较研究，治疗分配主要由机构指导， 经验、回顾性数据和供应商意见。缺乏循证治疗分配的患者 I期肺癌的治疗仍然是一个关键的未满足的需求。为了解决这一知识上的根本差距，我们将 进行一项前瞻性、实用性、多中心队列研究，比较手术和SBRT的有效性 I期非小细胞肺癌这种务实的研究设计非常适合提供可操作的结果。 目的1：比较手术与立体定向体部放射治疗（SBRT）对 利益相关者选择临床I期肺癌患者的短期和长期结局。目标1a： 比较手术和SBRT之间的3年无病生存期（DFS）。我们将比较长期DFS 使用倾向评分匹配的队列。我们假设SBRT会导致更少更不严重的治疗- 相关并发症，而手术将导致更长的DFS。目的1b：比较患者报告的结局 (PRO)手术和SBRT的区别我们将在倾向匹配的队列中比较短期和长期PRO 使用患者报告结局测量信息系统。我们假设SBRT会导致 在更好的短期PRO与相当的长期PRO。 目的2：开发和验证个体患者治疗结局的预测模型， I期肺癌在接受手术或SBRT治疗I期的前瞻性患者队列中 在肺癌中，我们将使用回归技术预测个体患者的长期DFS和PRO。这些 将对模型进行验证，并将其作为基于网络的工具提供给I期NSCLC患者。我们的建议将 为肺癌的个性化治疗分配创建基准，并提供可操作的结果， 改善I期NSCLC患者的护理。

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related morbidity and mortality in the U.S. With the increasing use of computed tomography scans and lung cancer screening, tumors are increasingly being detected at stage I disease, conferring a greater than 70% likelihood of cure. Surgery has been the traditional treatment for stage I NSCLC. However, population-based studies demonstrate a rapid increase in stereotactic body radiation therapy (SBRT) over the past decade. Retrospective studies comparing surgery and SBRT, including several publications from our group, have been hampered by relatively small sample sizes, lack of patient reported outcomes, and sparse information on comorbidities and cancer-related outcomes. Consequently, a recent systematic review concluded, “there is a need to compare both treatments in large prospective trials”. Unfortunately, multiple attempted randomized controlled trials comparing surgery to SBRT have failed to accrue and closed prematurely due to specialty bias and perceived lack of equipoise. Furthermore, our previous work has demonstrated that individual patient characteristics are crucial in the choice of therapy. In the absence of prospective comparative studies, treatment allocation is largely directed by institutional experience, retrospective data, and provider opinion. The lack of evidence-based treatment allocation in patients with stage I lung cancer remains a critical unmet need. To address this fundamental gap in knowledge, we will perform a prospective, pragmatic, multi-center cohort study to compare the effectiveness of surgery and SBRT for stage I NSCLC. This pragmatic study design is ideally suited to provide actionable results. Aim 1: To compare the effectiveness of surgery versus stereotactic body radiation therapy (SBRT) on stakeholder selected short and long-term outcomes in patients with clinical stage I lung cancer. Aim 1a: To compare 3-year disease-free survival (DFS) between surgery and SBRT. We will compare long-term DFS using propensity score matched cohorts. We hypothesize that SBRT will lead to fewer and less severe treatment- related complications, while surgery will result in longer DFS. Aim 1b: To compare patient reported outcomes (PRO) between surgery and SBRT. We will compare short and long-term PRO in propensity-matched cohorts using the Patient Reported Outcomes Measurement Information System. We hypothesize that SBRT will result in better short-term PRO with equivalent long-term PRO. Aim 2: To develop and validate prediction models for treatment outcomes for an individual patient with stage I lung cancer. In prospectively assembled cohorts of patients undergoing surgery or SBRT for stage I lung cancer, we will predict long-term DFS and PRO for an individual patient using regression techniques. These models will be validated and presented as a web-based tool for patients with stage I NSCLC. Our proposal will create a benchmark for personalized treatment allocation in lung cancer and provide actionable results to improve care for Stage I NSCLC patients.