Abstract
PURPOSE: In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy. METHODS: Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies. RESULTS: LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease (P = .042), and 61.3% for patients with stage III/IV disease (P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%). CONCLUSION: Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2769-2777 |
| Number of pages | 9 |
| Journal | Journal of Clinical Oncology |
| Volume | 37 |
| Issue number | 30 |
| DOIs | |
| State | Published - 2019 |
Funding
Supported by Grants No. U10CA180886, U10CA180899, U10CA098543, U10CA098413, and U24CA114766 from the National Cancer Institute, National Institutes of Health, to support the Children’s 1British Columbia Children’s Hospital, Vancouver, British Columbia, Canada 2Dalhousie University, Halifax, Nova Scotia, Canada 3University of Florida, Gainesville, FL 4Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA 5Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 6University of Tennessee College of Medicine Chattanooga, Chattanooga, TN 7Washington University School of Medicine, St Louis, MO 8Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 9Ann and Robert H. Lurie Children’s Hospital, Chicago, IL 10National Cancer Institute, Bethesda, MD 11University of Michigan, Ann Arbor, MI 12University of California at Davis Comprehensive Cancer Center, Sacramento, CA 13Merck Research Laboratories, North Wales, PA 14Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, OH 15Boston Children’s Hospital and Harvard Medical School, Boston, MA 16Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada 17Children’s National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC Supported by Grants No. U10CA180886, U10CA180899, U10CA098543, U10CA098413, and U24CA114766 from the National Cancer Institute, National Institutes of Health, to support the Children's
ASJC Scopus subject areas
- Oncology
- Cancer Research
