Treatment of Pulmonary Metastases in Children With Stage IV Nephroblastoma With Risk-Based Use of Pulmonary Radiotherapy Arnauld Verschuur, Harm Van Tinteren, Norbert Graf, Christophe Bergeron, Bengt Sandstedt, and Jan de Kraker Arnauld Verschuur, Hoˆ pital d’Enfants de La Timone, Marseille; Christophe Bergeron, Institut d’Hematologie- Oncologie Pe´ diatrique/Centre Le´on Be´ rard, Lyon, France; Arnauld Verschuur and Jan de Kraker, Academic Medical Centre, University of Amster- dam, Emma Children’s Hospital, Amsterdam; Harm Van Tinteren, Neth- erlands Cancer Institute, Amsterdam, the Netherlands; Norbert Graf, Univer- sity Hospital, Homburg, Germany; and Bengt Sandstedt, Karolinska Institutet, Astrid Lindgren Children’s Hospital, Stockholm, Sweden. Submitted March 9, 2011; accepted May 3, 2012; published online ahead of print at www.jco.org on August 27, 2012. Written on behalf of the International Society of Pediatric Oncology Renal Tumor Study Group. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Corresponding author: Arnauld Verschuur, MD, PhD, Department of Pediatric Oncology, Hoˆ pital d’Enfants de La Timone, 264, rue Saint Pierre, 13385 Marseille Cedex 5, France; e-mail: arnauld.verschuur@mail .ap-hm.fr. © 2012 by American Society of Clinical Oncology 0732-183X/12/3028-3533/$20.00 DOI: 10.1200/JCO.2011.35.8747 A B S T R A C T Purpose The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients. Patients and Methods Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remis- sion (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory. Results Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P  .001) and had larger tumor volumes compared with nonmetastatic patients (P  .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P  .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P  .001). Conclusion Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome. J Clin Oncol 30:3533-3539. © 2012 by American Society of Clinical Oncology INTRODUCTION Nephroblastoma is the most frequent renal tumor of childhood, with an incidence of seven patients diag- nosed per million children. 1 The current approach for treatment of nephroblastoma in the National Wilms’ Tumor Study Group (NWTS) is to perform surgery followed by risk-based chemotherapy. The treatment strategy according to the International Society of Pediatric Oncology (SIOP) consists of neoadjuvant chemotherapy, nephrectomy, postop- erative chemotherapy, and sometimes radiother- apy (RT). For the treatment of PM, different strategies have been adopted. In addition to the treatment for the renal tumor and the use of chemotherapy, some collaborative groups have advocated the routine use of pulmonary RT for metastases detected on con- ventional pulmonary x-ray, whereas other collabor- ative groups have adopted a strategy based on the response to a neoadjuvant three-drug regimen. In case of complete remission (CR) of the pulmonary lesions at the time of nephrectomy, this regimen is continued for 27 weeks. In case of persistent but resectable pulmonary nodules, metastasectomy is recommended. If no complete response can be obtained or in case of high-risk (HR) histology, chemotherapy is switched to a four-drug regimen followed by pulmonary RT in case of persisting nod- ules or HR histology. This strategy was adopted in JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 30  NUMBER 28  OCTOBER 1 2012 © 2012 by American Society of Clinical Oncology 3533 Downloaded from ascopubs.org by 34.239.171.13 on July 7, 2022 from 034.239.171.013 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.