Lung Sparing for SBRT with beam's-eye-view images and real time tumor tracking

描述(申请人提供)：在美国，死于肺癌的人数比前列腺癌、乳腺癌、结肠癌和直肠癌的总和还要多。据估计，2009年美国有187,000人被诊断为非小细胞肺癌(NSCLC)，其中超过37,000人出现局部或早期疾病。随着早期检测方法的改进和更广泛的传播，这一比例预计会增加。立体定向全身放射治疗(SBRT)为早期肺癌患者提供了良好的局部控制率(85%-95%)。然而，最近的一项II期研究发现，很大一部分患者出现了3级或更大的毒性反应，特别是那些有中央肿瘤的患者。研究表明，降低SBRT的切缘可以显著降低正常组织并发症的概率。随着SBRT日益成为早期、局限性非小细胞肺癌的首选治疗方法，减少其不良反应变得越来越重要。我们正在提出一种新的故障安全技术，以减少毒性，同时保持对不断增长的患者群体的局部控制。我们的假设是，在SBRT期间，使用射束眼视图(BEV)成像结合动态多叶准直器(DMLC)直接追踪肺肿瘤，将导致临床上有意义的正常组织保留。目前的方案是第一次使用先进的多模板无标记BEV跟踪算法来推导出用于DMLC交付的实时肿瘤位置。这种多模板无标记物创新的临床好处包括1)相关标志物的自动选择，2)变形、旋转和部分遮挡期间的连续跟踪，3)患者不需要额外的成像剂量，4)直接成像整个肿瘤，以及5)不需要侵入性基准植入和相关的不良反应。这比以前的技术有了很大的改进。治疗的优势将在临床条件下的拟人体模系统中进行实验量化。最终结果将是一个用于放射治疗的集成实时目标跟踪和动态递送系统，以及预期临床益处的量化。临床与DMLC跟踪的整合是一个具有挑战性的工程问题，在很大程度上对人类健康具有可衡量的积极影响。这个项目很好地体现了NIBIB支持物理科学和工程学研究和开发以改善人类健康的理想。 公共卫生相关性：该项目的目标是量化使用治疗性放射束跟踪早期肺肿瘤的潜在临床益处，以避免在治疗过程中过度照射健康组织。我们提出的方法是目前提出的最安全、侵入性最小的方法。如果被发现是成功的，该技术可以应用于其他解剖部位，为非常大量的癌症患者提供更好的结果。

DESCRIPTION (provided by applicant): More people in the U.S. die from lung cancer than from prostate, breast, colon and rectum cancers combined. Of the estimated 187,000 people in the U.S. who were diagnosed with non-small cell lung cancer (NSCLC) in 2009, over 37,000 of them presented with localized or early stage disease. This fraction is expected to grow as methods of early detection improve and become more widely disseminated. Stereotactic body radiation therapy (SBRT) has been shown to provide excellent local control (85%-95%) for early-stage lung cancer patients. However, a recent phase II study found Grade 3 or greater toxicities in a significant fraction of the patients, particularly those with centrally located tumors. Studies have shown that decreases in SBRT margins can significantly reduce the probability of normal tissue complications. As SBRT is increasingly becoming the therapy of choice for early-stage, localized non-small cell lung cancer, reducing the harmful side effects becomes increasingly important. We are proposing a novel failsafe technology to reduce toxicity while retaining local control for this growing population of patients. Our hypothesis is that tracking lung tumors directly during SBRT, using beam's-eye-view (BEV) imaging coupled with a dynamic multileaf collimator (DMLC), will lead to clinically significant normal tissue sparing. The current proposal is the first to employ an advanced multi- template marker-less BEV tracking algorithm to derive the real-time tumor location for DMLC delivery. Clinical benefits of the multi-template marker-less innovation include 1) automatic selection of relevant landmarks, 2) continuous tracking during deformations, rotations and partial obscurations, 3) no additional imaging dose to the patient, 4) direct imaging of the entire tumor, and 5) no need for invasive fiducial implantations and the associated adverse effects. This represents a substantial improvement over previous techniques. The therapeutic advantage will be quantified experimentally in an anthropomorphic phantom system under clinical conditions. The end result will be an integrated real-time target tracking and dynamic delivery system for radiation therapy as well as quantification of the anticipated clinical benefits. Clinical integration with the DMLC tracking is a challenging engineering problem with a measurable positive impact on human health on a large scale. This project represents well the ideals of the NIBIB to support research and development in the physical sciences and engineering for the improvement of human health. PUBLIC HEALTH RELEVANCE: The goal of this project is to quantify the potential clinical benefits of tracking early stage lung tumors with the therapeutic radiation beam in order to avoid over irradiation of healthy tissues during treatment. Our proposed method is the safest, least intrusive to have been proposed. If found to be successful, the technique could be applied to other anatomical sites, providing better outcomes for a very large number of cancer patients.