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J Clin Oncol. 2018 Jun 1;36(16):1564-1570. doi: 10.1200/JCO.2017.77.1931. Epub 2018 Apr 16.

Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children's Oncology Group AREN0533 Study.

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David B. Dix, British Columbia Children's Hospital, Vancouver, British Columbia; Paul E. Grundy, University of Alberta, Edmonton, Alberta; Conrad V. Fernandez, Dalhousie University, Halifax, Nova Scotia, Canada; Nita L. Seibel, National Cancer Institute, Bethesda, MD; Yueh-Yun Chi, University of Florida, Gainesville, FL; Geetika Khanna, Washington University School of Medicine, St Louis, MO; Eric Gratias, University of Tennessee College of Medicine Chattanooga, Chattanooga, TN; James R. Anderson, Merck Research Laboratories, North Wales, PA; Elizabeth A. Mullen, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA; James I. Geller, Cincinnati Children's Hospital Medical Center, Cincinnati; Julie M. Gastier-Foster and Elizabeth Wagner, Nationwide Children's Hospital; Julie M. Gastier-Foster, The Ohio State University College of Medicine, Columbus, OH; John A. Kalapurakal, Lurie Comprehensive Cancer Centre of Northwestern University; Elizabeth J. Perlman, Ann and Robert H. Lurie Children's Hospital, Chicago, IL; Arnold C. Paulino, MD Anderson Cancer Center, Houston, TX; Peter F. Ehrlich, University of Michigan, Ann Arbor, MI; Marcio Malogolowkin, University of California at Davis Comprehensive Cancer Center, Sacramento, CA; Jeffrey S. Dome, George Washington University School of Medicine and Health Sciences, Washington, DC; on behalf of the AREN0533 Study Committee.


Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% ( P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% ( P < .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P < .001) and 84.0% (95% CI, 79.4% to 88.6%; P < .001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.

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