Frank Berthold1, Carolina Rosswog2,3, Holger Christiansen4, Michael Frühwald5, Nadine Hemstedt2,3, Thomas Klingebiel6, Birgit Fröhlich7, Freimut H Schilling8, Irene Schmid9, Thorsten Simon1, Barbara Hero1, Matthias Fischer2,3, Angela Ernst10. 1. Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany. 2. Department of Experimental Pediatric Oncology, University of Cologne, Cologne, Germany. 3. Center for Molecular Medicine, Medical Faculty, University of Cologne, Cologne, Germany. 4. Department of Pediatric Oncology and Hematology, University of Leipzig, Leipzig, Germany. 5. Swabian Children's Cancer Center, Children's Hospital, University Hospital Augsburg, Augsburg, Germany. 6. Department of Children and Adolescents, University Hospital, Goethe University Frankfurt (Main), Frankfurt, Germany. 7. Department of Pediatric Oncology and Hematology, University of Munster, Munster, Germany. 8. Department of Pediatric Oncology and Hematology, Olgahospital Stuttgart, Stuttgart, Germany. 9. Department of Pediatric Hematology and Oncology and Hematology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany. 10. Institute of Medical Statistics and Computational Biology, University of Cologne, Cologne, Germany.
Abstract
INTRODUCTION: The survival of children with stage 4(M) neuroblastoma without MYCN amplification and below the age of 18 months is considered better than the still dismal outcome of older high-risk neuroblastoma patients. This study analyzes the impact of clinical and molecular characteristics on the long-term outcome. PATIENTS AND METHODS: Clinical presentation, survival, and recurrence patterns of patients enrolled onto trials NB90, NB97, and NB2004 were retrospectively analyzed. Gene expression signatures based on RNA microarrays (TH10) were investigated if tumor material was available. RESULTS: Between 1990 and 2015, 177 patients with stage 4(M) MYCN nonamplified neuroblastoma aged less than 18 months at diagnosis were eligible. After a median follow-up of 9.7 years (IQR 5.0, 13.4), the proportions of 10-year event-free survival (EFS) and overall survival (OS) were 73% (95% confidence interval [CI] 67-79%) and 86% (95% CI 80-92%), respectively. Of the 27 neuroblastoma recurrences, 44% occurred in more than one site. Four additional patients presented histologically mature ganglioneuroma at recurrence. Six patients developed a secondary malignancy. The secondary 5-year EFS and OS of the 27 patients with neuroblastoma recurrence were 44% and 59%, respectively. TH10 gene expression signature was not prognostically predictive in the investigated subcohort. CONCLUSION: The outcome of patients with stage 4(M) neuroblastoma aged less than 18 months is favorable when treated with high-risk or otherwise intensive therapy. The development of secondary malignancies and the potential of maturation to ganglioneuroma call for a controlled stepwise reduction of treatment intensity.
INTRODUCTION: The survival of children with stage 4(M) neuroblastoma without MYCN amplification and below the age of 18 months is considered better than the still dismal outcome of older high-risk neuroblastoma patients. This study analyzes the impact of clinical and molecular characteristics on the long-term outcome. PATIENTS AND METHODS: Clinical presentation, survival, and recurrence patterns of patients enrolled onto trials NB90, NB97, and NB2004 were retrospectively analyzed. Gene expression signatures based on RNA microarrays (TH10) were investigated if tumor material was available. RESULTS: Between 1990 and 2015, 177 patients with stage 4(M) MYCN nonamplified neuroblastoma aged less than 18 months at diagnosis were eligible. After a median follow-up of 9.7 years (IQR 5.0, 13.4), the proportions of 10-year event-free survival (EFS) and overall survival (OS) were 73% (95% confidence interval [CI] 67-79%) and 86% (95% CI 80-92%), respectively. Of the 27 neuroblastoma recurrences, 44% occurred in more than one site. Four additional patients presented histologically mature ganglioneuroma at recurrence. Six patients developed a secondary malignancy. The secondary 5-year EFS and OS of the 27 patients with neuroblastoma recurrence were 44% and 59%, respectively. TH10 gene expression signature was not prognostically predictive in the investigated subcohort. CONCLUSION: The outcome of patients with stage 4(M) neuroblastoma aged less than 18 months is favorable when treated with high-risk or otherwise intensive therapy. The development of secondary malignancies and the potential of maturation to ganglioneuroma call for a controlled stepwise reduction of treatment intensity.
Authors: Wei-Ling Liang; Xiao-Fan Ye; Gong Zhong; Jian-Jun Chen; Kang-Lin Dai; Ka Leung Daniel Cheuk; Shu Mo; Bo-Shen Wang; Chun-Yu Li; Xuan-Zhu Jiang; Zhi-Yuan Xu; Li Zhou; Irene Chan; Jian-Liang Chen; Patrick Chu; Pui Wah Pamela Lee; Chi Fung Godfrey Chan Journal: Zhongguo Dang Dai Er Ke Za Zhi Date: 2022-07-15