Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: A report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5


Daniel J. Benedetti, Division of Hematology/Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Carly R. Varela, Division of Hematology and Oncology, Pediatric Specialists of Virginia, Inova Fairfax Hospital, Fairfax, Virginia, USA.
Lindsay A. Renfro, Division of Biostatistics, University of Southern California, Los Angeles, California, USA.
Brett Tornwall, Glaukos Corp., San Clemente, California, USA.
David B. Dix, Division of Oncology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
Peter F. Ehrlich, Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Richard D. Glick, Division of Pediatric Surgery, Zucker School of Medicine at Hofstra/Northwell, Cohen Children's Medical Center, New Hyde Park, New York, USA.
John Kalapurakal, Department of Radiation Oncology, Northwestern University, Chicago, Illinois, USA.
Elizabeth Perlman, Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Eric Gratias, eviCore Healthcare, Bluffton, South Carolina, USA.
Nita L. Seibel, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
James I. Geller, Division of Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Geetika Khanna, Department of Radiology & Imaging Sciences, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Marcio Malogolowkin, Division of Pediatric Hematology-Oncology, UC Davis Comprehensive Cancer Center, Sacramento, California, USA.
Paul Grundy, Division of Immunology, Hematology, Oncology, Palliative Care and Environmental Interactions, University of Alberta, Edmonton, Alberta, Canada.
Conrad V. Fernandez, Division of Pediatric Hematology/Oncology, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
Jeffrey S. Dome, Division of Oncology, Children's National Hospital and the George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Elizabeth A. Mullen, Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts, USA.

Document Type

Journal Article

Publication Date







Wilms tumor; extrapulmonary metastases; metastatic Wilms


BACKGROUND: Patients with stage IV favorable histology Wilms tumor (FHWT) with extrapulmonary metastases (EPM) constitute a small subset of patients with FHWT. Because of their rarity and heterogeneity, optimal FHWT treatment is not well understood. Children's Oncology Group protocol AREN0533 assigned patients with FHWT and EPM to intensified chemotherapy, regimen M, after initial DD-4A chemotherapy. To improve understanding of prognostic factors and best therapies, experiences of patients with EPM on AREN0533, as well as on protocols AREN03B2 and NWTS-5, were reviewed. METHODS: Combined outcomes for patients with EPM from NWTS-5, AREN0533, and AREN03B2 were determined. Those treated on AREN0533 were compared with those treated on NWTS-5. Prognostic factors were explored in the pooled cohort. RESULTS: Forty-seven patients with FHWT with EPM enrolled on AREN0533, 37 enrolled on NWTS-5, and 64 were followed only on AREN03B2. The pooled cohort of all 148 patients demonstrated a 4-year event-free survival (EFS) of 77.3% (95% CI, 70.8-84.4) and 4-year overall survival of 88.9% (95% CI, 83.9-94.2). Four-year EFS of patients with EPM treated on AREN0533 was 76.0% (95% CI, 64.6-89.4) vs 64.9% (95% CI, 51.7-82.2) on NWTS-5; hazard ratio, 0.64, p = .26; no difference in overall survival was observed. Increasing linear age and slow incomplete lung response were associated with worse EFS in a pooled cohort. CONCLUSIONS: Outcomes for patients with EPM are among the lowest for children with FHWT. Further trials with standardized surgical and radiation treatment to metastatic sites, and prospectively collected biologic and treatment details are needed. CLINICAL TRIAL REGISTRATION: Clinical identifiers: NCT00379340, NCT00898365, and NCT00002611.