Proton Therapy to Reduce Heart Damage for Lung Cancer Patients

项目摘要/摘要 胸部放射治疗与心脏损伤之间的关系已经通过 对乳腺癌和霍奇金淋巴瘤心脏疾病患者的长期研究成为 这类患者的主要非癌症死因。这两种疾病的临床治疗都是 经过调整，通过简单的屏蔽和技术进步将心脏辐射暴露降至最低。对于患有以下疾病的患者 局部晚期肺癌，意味着心脏正后方的纵隔淋巴结 已经与癌症有关，在治疗过程中避免心脏暴露是极其困难的，因为 肿瘤的物理位置。然而，由于假设，对这个问题的关注很少 辐射引起的心脏损伤只对存活超过5年的患者有问题。 他们的诊断。这排除了绝大多数肺癌患者，因为他们与目前的 护理标准估计为18-24个月。这种假设认为辐射只会导致晚期- 最近出现的心脏问题受到了质疑。最近的一项第三阶段研究表明，穷人 肺癌患者的存活率可能反映了无意中接触到的心脏组织的数量 治疗过程中的辐射，可能会导致过早死亡。我们最近完成了一项随机试验 比较了质子和光子对肺癌患者的影响，发现质子治疗可以显著 减少对心脏的有害辐射。然而，我们还没有调查是否将辐射减少到 心脏损害减少了，心脏暴露的减少也不能转化为改善 肺癌患者的存活率。受损的心脏组织释放心肌肌钙蛋白T(TnT)，用于 广泛用于诊断和监测乳房化疗和放疗后的心脏损害 癌症或淋巴瘤。受损的心脏组织也可以通过PET扫描进行可视化和量化。在这 建议，我们将确定通过质子治疗减少心脏辐射暴露是否真的可以减少 肺癌患者辐射所致心脏损害。我们还将确定减少的心脏损伤 将提高这些患者的存活率。这两个目标都将通过使用高度敏感的 心脏TnT的测定及其PET图像的变化 完成随机临床试验。我们还将调查某些心脏结构是否对 通过利用已实施的治疗计划的详细剂量测定进行辐射。虽然这项提议存在风险 质子辐射不会对心脏有益，它还具有显著的临床应用潜力。 影响，因为它可能导致改变实践的结果。

PROJECT SUMMARY/ABSTRACT The relationship between radiation therapy to the thorax and heart damage has been established through long-term studies of patients with breast cancer and Hodgkin lymphoma as cardiac disease became the primary non-cancer cause of death among such patients. Clinical treatments for both diseases have been adjusted to minimize radiation heart exposure by simple shielding and technical advances. For patients with locally advanced lung cancer, meaning that the mediastinal lymph nodes directly behind the heart are already involved with cancer, it is extremely difficult to avoid heart exposure during treatment owing to the physical location of the tumor. Yet little attention has been paid to this problem because of the assumption that radiation-induced cardiac damage is problematic only for patients who live longer than 5 years after their diagnosis. This excludes the vast majority of lung cancer patients, as their longevity with the current standard of care is estimated in the range of 18-24 months. This assumption that radiation causes only late- onset cardiac problems has been recently called into question. A recent phase III study suggested that poor survival rates of lung cancer patients may reflect the amount of heart tissue that is inadvertently exposed to radiation during treatment, which may cause premature death. We recently completed a randomized trial comparing protons and photons for lung cancer patients and found that proton therapy can significantly reduce unwanted radiation to the heart. However, we have not investigated if the reduction of radiation to the heart has reduced heart damage, nor if the reduction in heart exposure can translate to improved survival in patients with lung cancer. Damaged heart tissue releases cardiac troponin T (TnT), which is used widely in cardiology to diagnose and monitor heart damage after chemotherapy and radiation for breast cancer or lymphoma. Damaged heart tissue can also be visualized and quantified by PET scans. In this proposal, we will determine if reduced heart exposure to radiation by proton therapy can indeed reduce heart damage due to radiation in lung cancer patients. We will also determine if the reduced heart damage will improve the survival of these patients. Both of these goals will be analyzed by using a highly sensitive assay for cardiac TnT and the changes on the PET images from samples collected during the course of a completed randomized clinical trial. We will also investigate if certain heart structures are more sensitive to radiation by leveraging detailed dosimetry of implemented treatment plans. While this proposal carries risk that no cardiac benefit will be found after proton radiation, it also carries the potential of significant clinical impact as it could lead to practice-changing findings.