Jonas E Adolph1, Gudrun Fleischhack1, Ruth Mikasch1, Julia Zeller1, Monika Warmuth-Metz2, Brigitte Bison2, Martin Mynarek3, Stefan Rutkowski3, Ulrich Schüller3, Katja von Hoff4, Denise Obrecht3, Torsten Pietsch5, Stefan M Pfister6,7,8, Kristian W Pajtler6,7,8, Olaf Witt6,7,8, Hendrik Witt6,7,8, Rolf-Dieter Kortmann9, Beate Timmermann10, Jürgen Krauß2, Michael C Frühwald11, Andreas Faldum12, Robert Kwiecien12, Udo Bode5, Stephan Tippelt1. 1. Department of Pediatrics III, University Hospital of Essen, Essen, Germany. 2. Institute of Diagnostic and Interventional Neuroradiology and Neurosurgical Clinic, University Hospital Wuerzburg, Wuerzburg, Germany. 3. Department of Pediatric Hematology and Oncology, Center for Obstetrics and Pediatrics and Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 4. Department of Pediatric Oncology and Hematology, Charité University Medicine Berlin, Berlin, Germany. 5. Institute of Neuropathology, DGNN Brain Tumor Reference Center and Department of Pediatric Hematology and Oncology, University Hospital of Bonn, Bonn, Germany. 6. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 7. Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg, Germany. 8. Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany. 9. Department of Radio-Oncology, University Leipzig, Leipzig, Germany. 10. Department of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen, Essen, Germany. 11. University Children's Hospital Augsburg, Swabian Children's Cancer Center, Augsburg, Germany. 12. Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.
Abstract
BACKGROUND: Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results. METHODS: Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas. RESULTS: Fifty-three patients with a median age of 6.9 years (1.25-25.4) at first recurrence and a median follow-up time of 36 months (2-115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9-120.1) vs. 95 (CI: 20.7-169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7-31.3) vs. 7 (CI: 0-15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%. CONCLUSION: The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).
BACKGROUND: Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results. METHODS: Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas. RESULTS: Fifty-three patients with a median age of 6.9 years (1.25-25.4) at first recurrence and a median follow-up time of 36 months (2-115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9-120.1) vs. 95 (CI: 20.7-169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7-31.3) vs. 7 (CI: 0-15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%. CONCLUSION: The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (>6 months) mediated by TMZ occurred in a small number of cases (14.3%).
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