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

描述（由申请人提供）：全肺照射（WLI） （AP-PA技术）被认为是大多数Wilms肿瘤、Ewing肉瘤和横纹肌肉瘤肺转移患者的标准治疗方法。一些研究表明，WLI和化疗后心脏并发症增加。国家肾母细胞瘤研究小组（NWTSG）显示，复发肾母细胞瘤诊断后20年的充血性心力衰竭（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，与未接受放疗的幸存者相比，心脏暴露于bbb15gy的患者患CHF和心肌梗死的风险增加了2-6倍。Gustave Roussy研究所报告说，在向心脏注射3.7Gy剂量后，20年的CHF发病率为18%，较低剂量为9%。最近一项法国-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，而接受5 - 15Gy剂量后心脏死亡的相对风险为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年发病率和死亡率的主要原因。为了减少WLI期间接受的心脏剂量，西北大学（NU）的研究人员研究了一种使用保心全肺IMRT （WL-IMRT）递送WLI的新方法。采用3D肺容积（10例）和4D肺容积（12例）对22例儿童和青年进行胸部CT扫描，采用WL-IMRT和标准WLI （SLRT）治疗方案。比较WL- IMRT和SLRT方案对肺、心室、甲状腺和肝脏的辐射剂量。与SLRT相比，WL-IMRT对心房和心室的辐射剂量显著降低。WL-IMRT还有两个额外的优势：1)与3D肺体积进行的SLRT相比，4D肺体积的剂量覆盖率显著提高；2)与未进行肺密度校正的SLRT相比，剂量一致性显著提高，肺部热点减少。拟议的多机构临床方案将在20例患者中检查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将执行与西北经验报告相似。质量保证审查中心（QARC）将促进治疗前基于图像的所有治疗数据的中央质量审查，并在开始实际治疗前为实施提供及时反馈。这将确保采用统一的方法来应用这种新的治疗方法。本研究的目的是证明提供WL-IMRT的可行性，并前瞻性地确定其与SLRT相比的剂量学优势。本研究还将确定WL-IMRT的短期疗效和急性耐受性。这项临床研究首次探讨了WL-IMRT的可行性，并有可能促进采用一种新的肺转移儿童治疗标准。

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.