Impact of the First Generation of Children’s Oncology Group Clinical Trials on Clinical Practice for Wilms Tumor

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  • 1 Division of Oncology, Center for Cancer and Blood Disorders, Children’s National Hospital and the Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC;
  • | 2 Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, Massachusetts;
  • | 3 Pediatric Hematology/Oncology, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada;
  • | 4 eviCore healthcare, Bluffton, South Carolina;
  • | 5 Department of Pediatric Surgery, University of Michigan, CS Mott Children’s Hospital, Ann Arbor, Michigan;
  • | 6 Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas;
  • | 7 Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio;
  • | 8 Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas;
  • | 9 Department of Radiology, Children’s Healthcare of Atlanta, Atlanta, Georgia;
  • | 10 Department of Radiation Oncology, Northwestern University School of Medicine, Chicago, Illinois;
  • | 11 Children’s Oncology Group and Division of Biostatistics, University of Southern California, Los Angeles, California;
  • | 12 Department of Pathology, Northwestern University Feinberg School of Medicine, and the Robert H. Lurie Cancer Center, Chicago, Illinois;
  • | 13 Department of Pediatrics, University of Alberta Hospital, Edmonton, Alberta, Canada; and
  • | 14 Division of Pediatric Hematology/Oncology, IWK Health Centre, Halifax, Nova Scotia, Canada.
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Refinements in surgery, radiation therapy, and chemotherapy since the mid-20th century have resulted in a survival rate exceeding 90% for patients with Wilms tumor (WT). Although this figure is remarkable, a significant proportion of patients continue to have event-free survival (EFS) estimates of <75%, and nearly 25% of survivors experience severe chronic medical conditions. The first-generation Children’s Oncology Group (COG) renal tumor trials (AREN ‘0’), which opened to enrollment in 2006, focused on augmenting treatment regimens for WT subgroups with predicted EFS <75% to 80%, including those with the adverse prognostic marker of combined loss of heterozygosity (LOH) at chromosomes 1p/16q, pulmonary metastasis with incomplete lung nodule response after 6 weeks of chemotherapy, bilateral disease, and anaplastic histology. Conversely, therapy was reduced for patient subgroups with good outcomes and potential for long-term toxicity, such as those with lung metastasis with complete lung nodule response after 6 weeks of chemotherapy. This article summarizes the key findings of the first-generation COG renal tumor studies and their implications for clinical practice.

Submitted March 8, 2021; final revision received May 28, 2021; accepted for publication June 9, 2021.

Disclosures: The authors have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in this article or their competitors.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Funding: Research reported in this publication was supported by the NCI of the NIH under award numbers CA180886, CA180899, CA098543, CA098413, and CA114766.

Correspondence: Jeffrey S. Dome, MD, PhD, Division of Oncology, Center for Cancer and Blood Disorders, Children’s National Hospital, 111 Michigan Avenue NW, Washington, DC 20010. Email: jdome@childrensnational.org
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