This collection contains data from the Children’s Oncology Group (COG) Clinical Trial NCT00379340, “Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms Tumor, " Study Chair: David Dix, MD. It was sponsored by NCI and performed by the Children's Oncology Group under study number AREN0533. This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV favorable histology Wilms tumor. Select patient-level clinical data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/737.

Trial Description

Patients with stage IV favorable histology Wilms tumor (FHWT), the majority of whom have pulmonary metastases, have inferior outcomes compared with those with localized disease. Their treatment is also complicated by a risk of late effects, including cardiac dysfunction, lung toxicity, musculoskeletal and soft tissue defects, and second malignancies. The AREN0533 study applied two separate strategies for risk stratification for patients with Stage III and IV favorable histology Wilms tumor. The first is the identification of patients with pulmonary nodules who can be spared bilateral pulmonary irradiation. Patients with Stage IV favorable histology Wilms tumor have a 4-year event-free survival (EFS) of 75% with chemotherapy and irradiation to sites of metastatic disease (most frequently in the lungs). European investigators are able to spare 75% of their patients with pulmonary nodules from irradiation based on the initial response to chemotherapy. The response of the lung metastases to 6 weeks of chemotherapy consisting of vincristine, dactinomycin, and doxorubicin (Regimen DD-4A) was used to determine if radiation of lung nodules is needed. Patients who had complete disappearance of their lung metastases (or who had tissue confirmation that the nodules do not contain viable tumor) at the Week 6 evaluation were considered rapid responders and continued with DD-4A. Patients who did not have complete resolution of pulmonary nodules by Chest CT underwent pulmonary irradiation and were switched to Regimen M (DD-4A variation with dactinomycin and doxorubicin given on the same day plus cyclophosphamide and etoposide). Central radiology review of the chest CTs were performed on all Stage IV patients with lung metastases at study enrollment and at Week 6. The second risk stratification variable was the allelic loss of 1p and 16q. Patients with Stage III and IV favorable histology Wilms tumor with loss of heterozygosity (LOH) of both 1p and 16q have a 4-yr EFS of 65%. Patients with LOH of 1p and 16q were assigned to Regimen M in an attempt to improve the 4-year EFS of this group of patients to 84%.

Trial Outcomes

Results of the trial have been reported in the following publications:

• Dix DB, Seibel NL, Chi YY, Khanna G, Gratias E, Anderson JR, Mullen EA, Geller JI, Kalapurakal JA, Paulino AC, Perlman EJ, Ehrlich PF, Malogolowkin M, Gastier-Foster JM, Wagner E, Grundy PE, Fernandez CV, Dome JS. Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study. J Clin Oncol. 2018 Jun 1;36(16):1564-1570. doi: 10.1200/JCO.2017.77.1931. Epub 2018 Apr 16. PMID: 29659330; PMCID: PMC6075846.
• Dix, D. B., Fernandez, C. V., Chi, Y.-Y., Mullen, E. A., Geller, J. I., Gratias, E. J., Khanna, G., Kalapurakal, J. A., Perlman, E. J., Seibel, N. L., Ehrlich, P. F., Malogolowkin, M., Anderson, J., Gastier-Foster, J., Shamberger, R. C., Kim, Y., Grundy, P. E., & Dome, J. S. (2019). Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children’s Oncology Group AREN0532 and AREN0533 Study Report. In Journal of Clinical Oncology (Vol. 37, Issue 30, pp. 2769–2777). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.18.01972