Prognostic impact of lymph node involvement and loss of heterozygosity of 1p or 16q in stage III favorable histology Wilms tumor: A report from Children's Oncology Group Studies AREN03B2 and AREN0532

Nicholas Evageliou, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Lindsay A. Renfro, Division of Biostatistics, University of Southern California and Children's Oncology Group, Monrovia, California, USA.
James Geller, Division of Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Elizabeth Perlman, Department of Pathology and Laboratory Medicine, The Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
John Kalapurakal, Department of Radiation Oncology, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
Arnold Paulino, Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas, USA.
David Dix, Division of Oncology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
Meryle J. Eklund, Department of Radiology, Medical University of South Carolina, Charleston, South Carolina, USA.
Andrew J. Murphy, Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Rodrigo L. Romao, Departments of Surgery and Urology, IWK Health, Dalhousie University, Halifax, Nova Scotia, Canada.
Peter F. Ehrlich, Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Carly R. Varela, Division of Oncology, Children's National Hospital, Washington, District of Columbia, USA.
Kelly Vallance, Division of Hematology and Oncology, Cook Children's Hospital, Fort Worth, Texas, USA.
Conrad V. Fernandez, Department of Pediatrics, IWK Health Centre and Dalhousie University, Halifax, Nova Scotia, Canada.
Jeffrey S. Dome, Division of Oncology, Children's National Hospital, Washington, District of Columbia, USA.
Elizabeth A. Mullen, Dana-Farber/Boston Children's Blood Disorders and Cancer Center, Boston, Massachusetts, USA.

Document Type

Journal Article

Publication Date

10-30-2023

Journal

Cancer

DOI

10.1002/cncr.35084

Keywords

Wilms tumor; lymph node positivity; risk stratification; tumor genetics

Abstract

INTRODUCTION: The prognostic impact of positive lymph nodes (LN+) and/or singular loss of heterozygosity (LOH) of 1p or 16q were assessed in children with stage III favorable histology Wilms tumor (FHWT) enrolled on AREN0532 or AREN03B2 alone. PATIENTS AND METHODS: A total of 635 stage III FHWT vincristine/dactinomycin/doxorubicin (DD4A)-treated patients met inclusion criteria. Event-free survival (EFS) and overall survival are reported overall and by LN sampling, LN status, LOH 1p, LOH 16q, and a combination of LN status and singular LOH. Patients with unknown or positive combined LOH of 1p and 16q status and AREN03B2-only patients with unknown outcomes or treatment other than DD4A were excluded. RESULTS: EFS did not differ by study, supporting pooling. Lack of LN sampling (hazard ratio [HR], 2.12; p = .0037), LN positivity (HR, 2.78; p = .0002), LOH 1p (HR, 2.18; p = .0067), and LOH 16q (HR, 1.72; p = .042) were associated with worse EFS. Compared with patients with both LN- and LOH-, those with negative nodes but positive LOH 1p or 16q and those with LN+ but LOH- for 1p or 16q had significantly worse EFS (HR, 3.05 and 3.57, respectively). Patients positive for both LN and LOH had the worst EFS (HR, 6.33; overall group factor, p < .0001). CONCLUSION: Findings confirm LN+ status as an adverse prognostic factor amplified by presence of singular LOH 1p or 16q, supporting study of intensified therapy for patients with LN+ in combination with singular LOH in a prospective clinical trial.

Department

Pediatrics

Link to Full Text

Share

COinS