Proton Therapy to Reduce Heart Damage for Lung Cancer Patients

项目总结/摘要 胸部放射治疗和心脏损伤之间的关系已经通过以下研究建立起来： 随着心脏病成为乳腺癌和霍奇金淋巴瘤患者的长期研究 这类患者的主要非癌症死亡原因。这两种疾病的临床治疗方法 通过简单的屏蔽和技术进步调整以最大限度地减少辐射心脏暴露。患者 局部晚期肺癌，这意味着心脏后面的纵隔淋巴结 已经与癌症有关，在治疗期间避免心脏暴露是非常困难的， 肿瘤的物理位置。然而，很少有人注意到这个问题，因为假设 辐射引起的心脏损伤只对那些在辐射后存活超过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，因为他们的寿命与目前 护理标准估计为18-24个月。假设辐射只会导致晚期- 心脏问题的发作最近受到了质疑。最近的一项III期研究表明， 肺癌患者的存活率可能反映了无意中暴露于 治疗过程中的辐射，可能导致过早死亡。我们最近完成了一项随机试验 比较质子和光子对肺癌患者的治疗，发现质子治疗可以显著地 减少对心脏的有害辐射。然而，我们还没有调查是否减少辐射， 心脏已经减少了心脏损伤，如果心脏暴露的减少可以转化为改善， 肺癌患者的生存率。受损的心脏组织释放心肌肌钙蛋白T（TnT）， 广泛应用于心脏病学，诊断和监测乳腺癌化疗和放疗后的心脏损伤 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，我们将确定是否减少心脏暴露于辐射的质子治疗确实可以减少 肺癌患者因辐射而导致的心脏损伤。我们还将确定减少的心脏损伤 将提高这些患者的生存率。这两个目标都将通过使用高度敏感的 心脏TnT的测定和在PET图像上的变化，这些图像来自在治疗过程中收集的样本。 完成随机临床试验。我们还将研究某些心脏结构是否对 通过利用实施的治疗计划的详细剂量测定进行辐射。虽然这一提议有风险， 质子辐射后不会发现心脏益处，但它也具有重要的临床应用潜力。 影响，因为它可能导致实践改变的结果。

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.