Steve E Braunstein1, Wendy B London2, Susan G Kreissman3, Judith G Villablanca4, Andrew M Davidoff5, Kenneth DeSantes6, Robert P Castleberry7, Kevin Murray8, Lisa Diller9, Katherine Matthay10, Susan L Cohn11, Barry Shulkin12, Daniel von Allmen13, Marguerite T Parisi14, Collin Van Ryn15, Julie R Park6, Michael P La Quaglia16, Daphne A Haas-Kogan17. 1. Department of Radiation Oncology, University of California, San Francisco, California. 2. Department of Pediatric Oncology/Hematology, Biostatistics Division, Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, Massachusetts. 3. Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina. 4. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California. 5. Department of Surgery, Pediatrics Division, St. Jude's Children's Research Hospital, Memphis, Tennessee. 6. Department of Pediatrics, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin. 7. Department of Pediatrics, University of Alabama Medical Center, Tuscaloosa, Alabama. 8. Department of Pediatrics, University of Louisville, Louisville, Kentucky. 9. Department of Pediatric Oncology/Hematology, Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, Massachusetts. 10. Department of Pediatric Hematology-Oncology, University of California, San Francisco, California. 11. Department of Pediatrics, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois. 12. Department of Diagnostic Imaging, Pediatrics Division, St. Jude's Children's Research Hospital, Memphis, Tennessee. 13. Department of Pediatric Surgery, Cincinnati Children's Hospital, Cincinnati, Ohio. 14. Department of Radiology, University of Washington, Seattle Children's Hospital, Seattle, Washington. 15. Department of Biostatistics, University of Florida, Gainesville, Florida. 16. Department of Pediatric Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. 17. Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts.
Abstract
PURPOSE: Neuroblastoma is the most common extracranial solid pediatric malignancy, with poor outcomes in high-risk disease. Standard treatment approaches employ an increasing array of aggressive multimodal therapies, of which local control with surgery and radiotherapy remains a backbone; however, the benefit of broad regional nodal irradiation remains controversial. We analyzed centrally reviewed radiation therapy data from patients enrolled on COG A3973 to evaluate the impact of primary site irradiation and the extent of regional nodal coverage stratified by extent of surgical resection. METHODS:Three hundred thirty high-risk neuroblastoma patients with centrally reviewed radiotherapy plans were analyzed. Outcome was evaluated by the extent of nodal irradiation. For the 171 patients who also underwent surgery (centrally reviewed), outcome was likewise analyzed according to the extent of resection. Overall survival (OS), event-free survival (EFS), and cumulative incidence of local progression (CILP) were examined by Kaplan-Meier, log-rank test (EFS, OS), and Grey test (CILP). RESULTS: The five-year CILP, EFS, and OS for all 330 patients receiving radiotherapy on A3973 were 8.5% ± 1.5%, 47.2% ± 3.0%, and 59.7% ± 3.0%, respectively. There were no significant differences in outcomes based on the extent of lymph node irradiation regardless of the degree of surgical resection (< 90% or ≥90%). CONCLUSION: Although local control remains a significant component of treatment of high-risk neuroblastoma, our results suggest there is no benefit of extensive lymph node irradiation, irrespective of the extent of surgical resection preceding stem cell transplant.
RCT Entities:
PURPOSE:Neuroblastoma is the most common extracranial solid pediatric malignancy, with poor outcomes in high-risk disease. Standard treatment approaches employ an increasing array of aggressive multimodal therapies, of which local control with surgery and radiotherapy remains a backbone; however, the benefit of broad regional nodal irradiation remains controversial. We analyzed centrally reviewed radiation therapy data from patients enrolled on COG A3973 to evaluate the impact of primary site irradiation and the extent of regional nodal coverage stratified by extent of surgical resection. METHODS: Three hundred thirty high-risk neuroblastomapatients with centrally reviewed radiotherapy plans were analyzed. Outcome was evaluated by the extent of nodal irradiation. For the 171 patients who also underwent surgery (centrally reviewed), outcome was likewise analyzed according to the extent of resection. Overall survival (OS), event-free survival (EFS), and cumulative incidence of local progression (CILP) were examined by Kaplan-Meier, log-rank test (EFS, OS), and Grey test (CILP). RESULTS: The five-year CILP, EFS, and OS for all 330 patients receiving radiotherapy on A3973 were 8.5% ± 1.5%, 47.2% ± 3.0%, and 59.7% ± 3.0%, respectively. There were no significant differences in outcomes based on the extent of lymph node irradiation regardless of the degree of surgical resection (< 90% or ≥90%). CONCLUSION: Although local control remains a significant component of treatment of high-risk neuroblastoma, our results suggest there is no benefit of extensive lymph node irradiation, irrespective of the extent of surgical resection preceding stem cell transplant.
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