Cardiac Sparing Whole Lung IMRT in Children and Young Adults with Lung Metastases

患有肺转移的儿童和年轻人的心脏保留全肺 IMRT

• 批准号: 8129405
• 负责人: John Andrew Kalapurakal
• 金额: $ 38.28万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8129405
• 关键词: Acute; Adoption; Aftercare; British; Cancer Survivor; Cardiac; Cardiac Death; Cardiovascular Diseases; Chest; Child; Child Care; Childhood Cancer Survivor Study; Clinical; Clinical Protocols; Clinical Research; Congestive Heart Failure; Data; Diagnosis; Dose; Enrollment; Ensure; Ewings sarcoma; Feedback; Frequencies; Goals; Heart; Heart Atrium; Hot Spot; Image; Incidence; Institutes; Intensity-Modulated Radiotherapy; Liver; Low Dose Radiation; Lung; Methods; Morbidity - disease rate; Myocardial Infarction; National Wilms' Tumor Study Group; Neoplasm Metastasis; Nephroblastoma; Normal tissue morphology; Organ; Patients; Quality Control; Radiation; Relapse; Relative Risks; Reporting; Research Personnel; Rhabdomyosarcoma; Risk; Second Primary Neoplasms; Survivors; Techniques; Thyroid Gland; Time; Universities; X-Ray Computed Tomography; base; chemotherapy; childhood cancer survivor; density; dosimetry; experience; improved; irradiation; lung volume; meetings; mortality; novel; quality assurance; standard of care; treatment planning; young adult

DESCRIPTION (provided by applicant): Whole lung Irradiation (WLI) (AP-PA technique) is considered the standard of care for most patients with lung metastases from Wilms tumor, Ewing Sarcoma and rhabdomyosarcoma. Several studies have shown increased cardiac complications after WLI and chemotherapy. The National Wilms Tumor Study Group (NWTSG) showed that the 20 year frequency of congestive heart failure (CHF) was 4.4% after diagnosis and 17.4% after treatment for relapsed Wilms tumor. The Childhood Cancer Survivor Study (CCSS) noted that cardiac exposure of > 15Gy increased the risk of CHF and myocardial infarction by 2-6 times compared to non- irradiated survivors. The Institute Gustave Roussy reported that the 20 year incidence of CHF was 18% after >3.7Gy to the heart and 9% for lower doses. A recent French-British cancer survivors study showed that the relative risk of cardiac deaths was 12.5 after 5 -14.9Gy and 25.1 for > 15Gy dose to the heart. Along with second malignancies, cardiovascular disease is the leading cause of morbidity and mortality >20 years after diagnosis in childhood cancer survivors (NWTSG and CCSS). In an effort to reduce the heart dose received during WLI, investigators from Northwestern University (NU) examined a new method of delivering WLI using cardiac-sparing whole lung IMRT (WL-IMRT). WL-IMRT and standard WLI (SLRT) treatment plans were performed on chest CT scans of 22 children and young adults using 3D lung volumes (10 patients) and 4D lung volumes (12 patients). Radiation doses to the lungs, heart chambers, thyroid gland and liver from WL- IMRT and SLRT plans were compared. WL-IMRT delivered significantly lower doses of radiation to both atria and ventricles compared to SLRT. There were two additional advantages for WL-IMRT: 1) significantly improved dose coverage of 4D lung volumes compared to SLRT that was performed with 3D lung volumes and 2) significantly improved dose conformality with fewer hot spots in the lungs compared to SLRT that was performed without lung density correction. The proposed multi-institutional clinical protocol will examine the clinical feasibility of WL-IMRT in 20 patients. The normal tissue contouring, IMRT technique, treatment planning and dosimetry analysis will be performed similar to that reported in the Northwestern experience. The Quality Assurance Review Center (QARC) will facilitate pre-treatment image-based central quality review of all treatment data and provide prompt feedback for implementation before beginning actual treatment. This will ensure a uniform approach to the application of this novel treatment. The goals of this study are to demonstrate the feasibility of delivering WL-IMRT and to prospectively determine its dosimetric advantages compared to SLRT. This study will also determine the short-term efficacy and acute tolerance of WL-IMRT. This clinical study is the first to examine the feasibility of WL-IMRT and it has the potential to promote the adoption of a new standard for care for children with lung metastases. PUBLIC HEALTH RELEVANCE: Whole lung Irradiation (WLI) (AP-PA technique), the present standard of care for most patients with lung metastases from Wilms tumor, Ewing Sarcoma and rhabdomyosarcoma has been shown to cause increased cardiac complications. Preliminary dosimetry data with a new cardiac-sparing whole lung IMRT (WL-IMRT) technique has shown significant reduction in radiation doses to the heart compared to standard WLI. This multi-institutional study will examine the clinical feasibility of WL-IMRT and could help establish WL-IMRT as the new standard for these patients.

描述（由申请人提供）：全肺照射 (WLI)（AP-PA 技术）被认为是大多数患有肾母细胞瘤、尤文肉瘤和横纹肌肉瘤肺转移患者的标准治疗方法。多项研究表明 WLI 和化疗后心脏并发症增加。国家肾母细胞瘤研究组 (NWTSG) 表明，复发性肾母细胞瘤确诊后 20 年充血性心力衰竭 (CHF) 发生率为 4.4%，治疗后为 17.4%。儿童癌症幸存者研究 (CCSS) 指出，与未受辐射的幸存者相比，> 15Gy 的心脏暴露会使 CHF 和心肌梗死的风险增加 2-6 倍。 Gustave Roussy 研究所报告称，心脏接受 >3.7Gy 照射后，20 年 CHF 发病率为 18%，而接受较低剂量照射则为 9%。最近的一项法国-英国癌症幸存者研究表明，心脏接受 5 -14.9Gy 剂量后，心脏死亡的相对风险为 12.5，> 15Gy 心脏剂量为 25.1。与第二恶性肿瘤一样，心血管疾病是儿童癌症幸存者（NWTSG 和 CCSS）诊断后 20 年以上发病和死亡的主要原因。为了减少 WLI 期间心脏接受的剂量，西北大学 (NU) 的研究人员研究了一种使用保留心脏的全肺调强放射治疗 (WL-IMRT) 来提供 WLI 的新方法。使用 3D 肺体积（10 名患者）和 4D 肺体积（12 名患者）对 22 名儿童和年轻人进行胸部 CT 扫描，执行 WL-IMRT 和标准 WLI (SLRT) 治疗计划。比较了 WL-IMRT 和 SLRT 计划对肺、心室、甲状腺和肝脏的辐射剂量。与 SLRT 相比，WL-IMRT 向心房和心室传递的辐射剂量明显较低。 WL-IMRT 还有两个额外优势：1) 与使用 3D 肺体积进行的 SLRT 相比，显着改善了 4D 肺体积的剂量覆盖范围；2) 与进行 SLRT 相比，显着改善了剂量适形性，肺部热点更少无需肺密度校正。拟议的多机构临床方案将在 20 名患者中检验 WL-IMRT 的临床可行性。正常组织轮廓、IMRT 技术、治疗计划和剂量分析的执行方式与西北大学经验中报告的类似。质量保证审查中心（QARC）将促进对所有治疗数据进行治疗前基于图像的中央质量审查，并在开始实际治疗之前提供及时的实施反馈。这将确保采用统一的方法来应用这种新型治疗方法。本研究的目的是证明 WL-IMRT 的可行性，并前瞻性地确定其与 SLRT 相比的剂量学优势。这项研究还将确定 WL-IMRT 的短期疗效和急性耐受性。这项临床研究是第一个检验 WL-IMRT 可行性的临床研究，它有可能促进采用新的肺转移儿童护理标准。 公共卫生相关性：全肺照射 (WLI)（AP-PA 技术）是目前大多数患有肾母细胞瘤、尤文肉瘤和横纹肌肉瘤肺转移患者的护理标准，已被证明会导致心脏并发症增加。新型保心脏全肺调强放射治疗 (WL-IMRT) 技术的初步剂量测定数据显示，与标准 WLI 相比，心脏辐射剂量显着降低。这项多机构研究将检验 WL-IMRT 的临床可行性，并有助于将 WL-IMRT 确立为这些患者的新标准。