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: 8272529
• 负责人: John Andrew Kalapurakal
• 金额: $ 32.55万
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8272529
• 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.

描述(申请人提供)：全肺照射(AP-PA技术)被认为是大多数Wilms瘤、尤文肉瘤和横纹肌肉瘤肺转移患者的标准护理。一些研究表明，WLI和化疗后心脏并发症增加。美国国家肾母细胞瘤研究组(NWTSG)的研究显示，肾母细胞瘤复发后20年充血性心力衰竭(CHF)的发生率为4.4%，治疗后为17.4%。儿童癌症存活者研究(CCSS)指出，与未接受辐射的幸存者相比，心脏照射15Gy会增加心力衰竭和心肌梗死的风险2-6倍。古斯塔夫·鲁西研究所报告说，心脏3.7Gy20年后心力衰竭的发生率为18%，而低剂量的CHF发生率为9%。最近法国和英国的一项癌症幸存者研究表明，心脏接受5-14.9Gy射线照射后心脏死亡的相对风险为12.5，而接受15Gy射线照射心脏的相对死亡风险为25.1。与第二种恶性肿瘤一样，心血管疾病是儿童癌症幸存者确诊20年后发病率和死亡率的主要原因(NWTSG和CCSS)。为了减少WLI期间接受的心脏剂量，来自西北大学(NU)的研究人员研究了一种使用保留心脏的全肺调强放疗(WL-IMRT)来传递WLI的新方法。对22例儿童和青壮年胸部CT扫描采用三维肺体积(10例)和四维肺体积(12例)进行WL-IMRT和标准WLI(SLRT)治疗计划。比较WL-IMRT和SLRT计划对肺、心腔、甲状腺和肝脏的辐射剂量。与SLRT相比，WL-IMRT对心房和脑室的放射剂量显著降低。WL-IMRT还有两个额外的优点：1)与3D肺体积的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，肺内的剂量一致性显著提高，肺部热点较少。拟议的多机构临床方案将在20名患者中检查WL-IMRT的临床可行性。正常组织轮廓、调强放射治疗技术、治疗计划和剂量学分析将与西北经验中报道的相似。质量保证审查中心(QARC)将促进所有治疗数据的基于图像的治疗前中央质量审查，并在开始实际治疗之前为实施提供及时的反馈。这将确保对这一新疗法的应用采取统一的方法。这项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。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次检验WL-IMRT的可行性，它有可能促进采用一种新的肺转移瘤儿童护理标准。

项目成果

Cardiac-Sparing Whole Lung IMRT in Patients With Pediatric Tumors and Lung Metastasis: Final Report of a Prospective Multicenter Clinical Trial.

儿科肿瘤患者和肺转移患者的心脏比较整个肺IMRT：一项前瞻性多中心临床试验的最终报告。

• DOI: 10.1016/j.ijrobp.2018.08.034
• 发表时间: 2019-01-01
• 期刊: International journal of radiation oncology, biology, physics
• 作者: Kalapurakal JA;Gopalakrishnan M;Walterhouse DO;Rigsby CK;Rademaker A;Helenowski I;Kessel S;Morano K;Laurie F;Ulin K;Esiashvili N;Katzenstein H;Marcus K;Followill DS;Wolden SL;Mahajan A;Fitzgerald TJ
• 通讯作者: Fitzgerald TJ