Impact of Pulmonary Tumor Burden in Favorable Histology Wilms Tumor Outcomes: A Report From the Children's Oncology Group Study AREN0533

David B. Dix, British Columbia Children's Hospital, Vancouver, BC, Canada.
Geetika Khanna, Children's Healthcare of Atlanta, Atlanta, GA.
Lindsay A. Renfro, University of Southern California and Children's Oncology Group, Los Angeles, CA.
Ian C. Tfirn, University of Southern California and Children's Oncology Group, Los Angeles, CA.
Ethan A. Smith, Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Maddy Artunduaga, UT Southwestern/Simmons Cancer Center, Dallas, TX.
Meryle J. Eklund, Medical University of South Carolina, Charleston, SC.
Jesse K. Sandberg, Lucile Packard Children's Hospital Stanford University, Palo Alto, CA.
Lauren N. Parsons, Children's Hospital of Wisconsin, Milwaukee, WI.
John A. Kalapurakal, Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, IL.
Peter F. Ehrlich, C S Mott Children's Hospital, Ann Arbor, MI.
Jennifer H. Aldrink, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH.
Richard D. Glick, Cohen Children's Medical Center, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY.
Daniel J. Benedetti, Vanderbilt University Medical Center, Nashville, TN.
Conrad V. Fernandez, IWK Health Centre, Dalhousie University, Halifax, NS, Canada.
Jeffrey S. Dome, Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC.
Elizabeth A. Mullen, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA.
James I. Geller, Peckham Center for Cancer and Blood Disorders, Rady Children's Hospital, San Diego, CA.

Document Type

Journal Article

Publication Date

11-12-2025

Journal

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

DOI

10.1200/JCO-25-00532

Abstract

PURPOSE: Children with favorable histology Wilms tumor (FHWT) with pulmonary metastases have inferior outcomes compared with those with localized disease. We evaluated the impact of pulmonary tumor burden within subgroups of similarly treated children with stage IV FHWT. METHODS: Children with FHWT with pulmonary-only metastasis enrolled in AREN0533 were included. Lung nodule response assessment, by chest computed tomography after two cycles of vincristine/dactinomycin/doxorubicin (Regimen DD-4A) chemotherapy, identified rapid complete responses (RCRs) and slow incomplete pulmonary nodule responses (SIRs). Event-free survival (EFS) and overall survival (OS) were compared by number and size of pulmonary metastases within two cohorts: (1) RCR treated with additional DD-4A without lung radiation therapy (RT) and (2) SIR treated with the original three drugs plus cyclophosphamide/etoposide (Regimen M) with lung RT. The multivariable Cox proportional hazards model for EFS and OS stratified by treatment assessed the impact of the number and size of pulmonary metastases adjusted for tumor 1q gain. RESULTS: AREN0533 enrolled 288 children with stage IV pulmonary-only metastases, of whom 251 met inclusion criteria for outcome analyses. In the RCR cohort (n = 105), EFS and OS were not significantly different based on the number of lung metastases, whereas size of pulmonary metastases was significantly associated with EFS (P = .022), but not OS. In the SIR cohort (n = 146), EFS and OS did not differ by the number or size of lung metastases. In multivariable models, neither number nor size of lung metastases was significantly associated with EFS or OS although 1q gain was significant (EFS P = .0015; OS P = .039) after adjustment for these factors. CONCLUSION: 1q gain is a superior prognostic indicator to pulmonary tumor burden in patients with FHWT with pulmonary-only metastasis.

Department

Pediatrics

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