Biologyarticle2026-09-17

Impact of post‐chemotherapy classification on outcomes in stage III and IV unilateral favorable histology Wilms tumor: Pooled data from Children’s Oncology Group AREN0532, AREN0533, and AREN03B2 studies

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Abstract

Abstract Background Improvements in therapy for patients with favorable histology Wilms tumor (FHWT) have relied on refinement of risk stratification for therapeutic assignment through identification of favorable and unfavorable prognostic factors. Although well established in International Society of Pediatric Oncology‐Renal Tumor Study Group protocols, the Children’s Oncology Group (COG) has not historically used post‐chemotherapy histology (PCH) to guide therapy. This study examines whether outcomes are associated with PCH classification in the COG treatment context. Methods The authors identified 2386 patients with stage III or IV FHWT enrolled on AREN0532, AREN0533, or AREN03B2‐only from 2006 to 2019. Inclusion criteria included delayed nephrectomy more than 5 and fewer than 16 weeks after initial biopsy, treatment on or as per protocol with DD4A or Regimen M, and known PCH classification and outcome. Results Of 352 included patients, 45 (12.7%) were classified as low risk (LR), 287 (81.5%) as intermediate risk (IR), and 20 (5.6%) as high risk (HR). PCH classification was significantly prognostic for event‐free survival (EFS) ( p < .0001) and overall survival (OS) ( p < .0001). Four‐year EFS for LR, IR, and HR groups was 93% (95% CI, 86%–100%), 85% (95% CI, 81%–89%), and 53% (95% CI, 35%–81%); 4‐year OS was 96% (95% CI, 90%–100%), 93% (95% CI, 89%–96%), and 62% (95% CI, 44%–89%). Compared with LR or IR, EFS and OS were significantly lower for HR, regardless of stage or treatment. Conclusion PCH is a significant prognostic factor in unilateral FHWT treated on COG regimens, strongly supporting its incorporation into therapeutic stratification in prospective COG trials.

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View paper (DOI)OpenAlexCancerPublished 2026-09-17

Authors: Nicholas F. Evageliou, Lindsay A. Renfro, Kelly Vallance, Carly R. Varela, Daniel J. Benedetti, Nicholas G. Cost, Peter F. Ehrlich, J KALAPURAKAL, Geetika Khanna, Jennifer H. Aldrink, Richard D. Glick, Michael V. Ortiz, Lauren Parsons, Arnold C. Paulino, Maddy Artunduaga, Ethan A. Smith, David Dix, Conrad V. Fernandez, Jeffrey S. Dome, James I. Geller, Elizabeth A. Mullen

Institutions: Northwestern University, University of Colorado Denver, University of California San Diego, Dalhousie University, Johnson & Johnson (United States), Nationwide Children's Hospital, Cincinnati Children's Hospital Medical Center, Children's Hospital of Philadelphia, Children's Healthcare of Atlanta, University of Michigan, University of Southern California, Cohen Children's Medical Center, The University of Texas MD Anderson Cancer Center, George Washington University, BC Children's Hospital, Southwestern Medical Center, The University of Texas Southwestern Medical Center, George Washington University Hospital, Children's National, Memorial Sloan Kettering Cancer Center, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Vanderbilt University Medical Center, Cook Children's Medical Center, Children's Hospital Colorado, Center for Cancer and Blood Disorders, Children's Oncology Group, Children's Hospital of Wisconsin