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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-SBIB-V (56))
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Vikram, Bhadrasain
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Northwestern University at Chicago
Schools of Medicine
United States
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