Proton Therapy to Reduce Heart Damage for Lung Cancer Patients

质子治疗可减少肺癌患者的心脏损伤

• 批准号: 10017671
• 负责人: ZHONGXING LIAO
• 金额: $ 17.62万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-17 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017671
• 关键词: 3-Dimensional; Accounting; Acute; Affect; Aftercare; Attention; Autonomic Dysfunction; Biological Assay; Biological Markers; Blood specimen; Breast Lymphoma; Cancer Patient; Cardiac; Cardiac Death; Cardiac Myocytes; Cardiology; Cardiotoxicity; Cause of Death; Cessation of life; Chemotherapy and/or radiation; Chest; Clinical; Clinical Treatment; Conformal Radiotherapy; Data; Dependence; Deposition; Development; Diagnosis; Diagnostic radiologic examination; Disease; Dose; Drops; Enrollment; Event; Exposure to; Future; General Hospitals; Goals; Heart; Heart Diseases; Heart Rate; Hodgkin Disease; Hypersensitivity; Image; Intensity modulated proton therapy; Intensity-Modulated Radiotherapy; Knowledge; Lead; Length; Location; Longevity; Longitudinal Studies; Lung; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of lung; Malignant neoplasm of thorax; Massachusetts; Measures; Mediastinal lymph node group; Modeling; Monitor; Non-Small-Cell Lung Carcinoma; Patient Selection; Patients; Pattern; Photons; Positron-Emission Tomography; Proton Radiation; Protons; Radiation; Radiation Oncologist; Radiation therapy; Randomized Clinical Trials; Rest; Risk; Roentgen Rays; Sampling; Serum; Structure; Survival Rate; System; Time; Tissues; Translating; Troponin T; Tumor Tissue; Work; cancer site; cardioprotection; clinical practice; comparative; cost; dosimetry; heart damage; high risk; improved; innovation; interest; irradiation; malignant breast neoplasm; myocardial damage; particle beam; phase 3 study; premature; prevent; prospective; proton therapy; radiation delivery; radiation effect; radiological imaging; randomized trial; standard of care; tool; treatment planning; trial comparing; tumor

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.

项目概要/摘要 胸部放射治疗与心脏损伤之间的关系已通过以下方法建立： 随着心脏病成为最常见的疾病，对乳腺癌和霍奇金淋巴瘤患者进行了长期研究 此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进行调整，以最大限度地减少心脏辐射暴露。对于患有以下疾病的患者 局部晚期肺癌，这意味着直接位于心脏后面的纵隔淋巴结 由于已经患有癌症，在治疗期间很难避免心脏暴露，因为 肿瘤的物理位置。然而，由于假设，这个问题很少受到关注 辐射引起的心脏损伤仅对术后存活超过 5 年的患者造成问题 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的水平相比 标准护理时间估计为 18-24 个月。这种辐射仅导致晚期的假设 心脏病发作最近受到质疑。最近的一项 III 期研究表明，贫困人口 肺癌患者的生存率可能反映了无意中暴露于的心脏组织的数量 治疗期间的辐射，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效果，发现质子治疗可以显着 减少对心脏的不必要的辐射。然而，我们还没有研究是否可以减少辐射 心脏已经减少了心脏损伤，而且心脏暴露的减少是否可以转化为改善 肺癌患者的生存率。受损的心脏组织会释放心肌肌钙蛋白 T (TnT)，用于 广泛应用于心脏病学，用于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。在这个 建议，我们将确定通过质子治疗减少心脏暴露于辐射是否确实可以减少 肺癌患者因辐射造成心脏损伤。我们还将确定心脏损伤是否减少 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分析器进行分析 心脏 TnT 测定以及在治疗过程中收集的样本 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来进行辐射。虽然这个提议存在风险 虽然质子辐射不会对心脏产生任何益处，但它也具有重要的临床潜力 影响，因为它可能导致改变实践的发现。