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Treatment of Anaplastic Histology Wilms' Tumor: Results From the Fifth National Wilms' Tumor Study

Jeffrey S. Dome, Cecilia A. Cotton, Elizabeth J. Perlman, Norman E. Breslow, John A. Kalapurakal, Michael L. Ritchey, Paul E. Grundy, Marcio Malogolowkin, J. Bruce Beckwith, Robert C. Shamberger, Gerald M. Haase, Max J. Coppes, Peter Coccia, Morris Kletzel, Robert M. Weetman, Milton Donaldson, Roger M. Macklis, Daniel M. Green

From the Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN; Department of Biostatistics, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Pathology, Loma Linda University, Loma Linda; Department of Pediatrics, Los Angeles Children's Hospital; Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA; Department of Radiation Oncology, Robert H. Lurie Cancer Center, Northwestern University; Departments of Pathology and Laboratory Medicine, and Pediatrics, Children's Memorial Medical Center, Chicago; Department of Pediatrics, School of Medicine, Northwestern University, Evanston, IL; Department of Pediatric Surgery, University of Texas at Houston Health Science Center, Houston, TX; Department of Surgery, Children's Hospital; Department of Surgery, Harvard Medical School, Boston, MA; Department of Pediatric Surgery, Denver Children's Hospital, Denver, CO; Departments of Pediatrics and Oncology, Cross Cancer Institute and the University of Alberta, Edmonton; Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada; Department of Pediatrics, School of Medicine, University of Nebraska, Omaha, NE; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN; Department of Pediatrics, Cooper Hospital, Camden, NJ; Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH; Department of Pediatrics, Roswell Park Cancer Institute; and the School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY.

Address reprint requests to Jeffrey S. Dome, MD, Department of Hematology/Oncology, St Jude Children's Research Hospital, 332 N Lauderdale St, D5048C, Memphis, TN 38105; e-mail: jeff.dome{at}stjude.org

Purpose An objective of the fifth National Wilms' Tumor Study (NWTS-5) was to evaluate the efficacy of treatment regimens for anaplastic histology Wilms' tumor (AH).

Patients and Methods Prospective single-arm studies were conducted. Patients with stage I AH were treated with vincristine and dactinomycin for 18 weeks. Patients with stages II to IV diffuse AH were treated with vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks plus flank/abdominal radiation.

Results A total of 2,596 patients with Wilms' tumor were enrolled onto NWTS-5, of whom 281 (10.8%) had AH. Four-year event-free survival (EFS) and overall survival (OS) estimates for assessable patients with stage I AH (n = 29) were 69.5% (95% CI, 46.9 to 84.0) and 82.6% (95% CI, 63.1 to 92.4). In comparison, 4-year EFS and OS estimates for patients with stage I favorable histology (FH; n = 473) were 92.4% (95% CI, 89.5 to 94.5) and 98.3% (95% CI, 96.4 to 99.2). Four-year EFS estimates for patients who underwent immediate nephrectomy with stages II (n = 23), III (n = 43), and IV (n = 15) diffuse AH were 82.6% (95% CI, 60.1 to 93.1), 64.7% (95% CI, 48.3 to 77.7), and 33.3% (95% CI, 12.2 to 56.4), respectively. OS was similar to EFS for these groups. There were no local recurrences among patients with stage II AH. Four-year EFS and OS estimates for patients with bilateral AH (n = 29) were 43.8% (95% CI, 24.2 to 61.8) and 55.2% (95% CI, 34.8 to 71.7), respectively.

Conclusion The prognosis for patients with stage I AH is worse than that for patients with stage I FH. Novel treatment strategies are needed to improve outcomes for patients with AH, especially those with stage III to V disease.

Supported by National Institutes of Health Grant No. CA-42326.

Presented at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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