Christelle Dufour1, Stephanie Foulon2,3, Anne Geoffray4, Julien Masliah-Planchon5, Dominique Figarella-Branger6, Valerie Bernier-Chastagner7, Laetitia Padovani8, Léa Guerrini-Rousseau1, Cecile Faure-Conter9, Celine Icher10, Anne-Isabelle Bertozzi11, Pierre Leblond12, Tasnime Akbaraly13, Franck Bourdeaut14, Nicolas André15,16, Celine Chappé17, Pascale Schneider18, Emilie De Carli19, Pascal Chastagner20, Claire Berger21, Julien Lejeune22, Christine Soler23, Natacha Entz-Werlé24, Marie-Bernadette Delisle25. 1. Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France. 2. Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France. 3. Oncostat U1018, Inserm, University Paris-Saclay, labeled Ligue Contre le Cancer, Villejuif, France. 4. Department of Pediatric Imaging, Fondation Lenval Children's Hospital, Nice, France. 5. INSERM U830, Laboratory of Translational Research in Pediatric Oncology, SIREDO Pediatric Oncology Center, Curie Institute, Paris, France. 6. Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, CHU Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France. 7. Department of Radiotherapy, Alexis Vautrin Cancer Center, Vandoeuvre-les-Nancy, France. 8. Department of Radiotherapy, CHU La Timone, AP-HM, Marseille, France. 9. Department of Pediatry, Institut d'Hématologie et d'Oncologie pédiatrique, Lyon, France. 10. Department of pediatrics, Bordeaux university hospital, Bordeaux, France. 11. Department of Pediatric Onco-hematology, CHU Toulouse, Toulouse, France. 12. Pediatric Oncology Unit, Oscar Lambret Comprehensive Cancer Center, Lille, France. 13. Department of Pediatric Hematology-Oncology, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France. 14. SIREDO Pediatric Oncology Center, Curie Institute, Paris, France. 15. Department of Pediatric Hematology and Oncology, La Timone Children's Hospital, Marseille, France. 16. SMARTc Unit, Centre de Recherche en Cancerologie de Marseille Inserm U1068 Aix Marseille Univ, MarseilleFrance. 17. Department of Pediatric Oncology, Rennes University Hospital, Rennes, France. 18. Pediatric Hemato-Oncology Department, University Hospital, Rouen, Rouen, France. 19. Department of Pediatric Oncology, University Hospital, Angers, France. 20. Department of Pediatric Oncology, Children's Hospital, Nancy, France. 21. Department of Pediatric Hematology and Oncology Unit, University Hospital of Saint-Étienne, Saint-Étienne, France. 22. Pediatric Onco-Hematology Unit, University Hospital of Tours, Tours, France. 23. Hematology Department, Hôpital l'Archet, CHU de Nice, Nice, France. 24. Pediatric Onco-Hematology Unit, CHU of Strasbourg, Strasbourg, France. 25. Departments of Pathology, Toulouse University Hospital, Toulouse III University, Toulouse, France.
Abstract
BACKGROUND: High-risk medulloblastoma is defined by the presence of metastatic disease and/or incomplete resection and/or unfavorable histopathology and/or tumors with MYC amplification. We aimed to assess the 3-year progression-free survival (PFS) and define the molecular characteristics associated with PFS in patients aged 5-19 years with newly diagnosed high-risk medulloblastoma treated according to the phase II trial PNET HR+5. METHODS: All children received postoperative induction chemotherapy (etoposide and carboplatin), followed by 2 high-dose thiotepa courses (600 mg/m2) with hematological stem cell support. At the latest 45 days after the last stem cell rescue, patients received risk-adapted craniospinal radiation therapy. Maintenance treatment with temozolomide was planned to start between 1-3 months after the end of radiotherapy. The primary endpoint was PFS. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy). RESULTS: Fifty-one patients (median age, 8 y; range, 5-19) were enrolled. The median follow-up was 7.1 years (range: 3.4-9.0). The 3 and 5-year PFS with their 95% confidence intervals (95% CI) were 78% (65-88) and 76% (63-86), and the 3 and 5-year OS were 84% (72-92) and 76% (63-86), respectively. Medulloblastoma subtype was a statistically significant prognostic factor (P-value = 0.039) with large-cell/anaplastic being of worse prognosis, as well as a molecular subgroup (P-value = 0.012) with sonic hedgehog (SHH) and group 3 being of worse prognosis than wingless (WNT) and group 4. Therapy was well tolerated. CONCLUSIONS: This treatment based on high-dose chemotherapy and conventional radiotherapy resulted in a high survival rate in children with newly diagnosed high-risk medulloblastoma.
BACKGROUND: High-risk medulloblastoma is defined by the presence of metastatic disease and/or incomplete resection and/or unfavorable histopathology and/or tumors with MYC amplification. We aimed to assess the 3-year progression-free survival (PFS) and define the molecular characteristics associated with PFS in patients aged 5-19 years with newly diagnosed high-risk medulloblastoma treated according to the phase II trial PNET HR+5. METHODS: All children received postoperative induction chemotherapy (etoposide and carboplatin), followed by 2 high-dose thiotepa courses (600 mg/m2) with hematological stem cell support. At the latest 45 days after the last stem cell rescue, patients received risk-adapted craniospinal radiation therapy. Maintenance treatment with temozolomide was planned to start between 1-3 months after the end of radiotherapy. The primary endpoint was PFS. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy). RESULTS: Fifty-one patients (median age, 8 y; range, 5-19) were enrolled. The median follow-up was 7.1 years (range: 3.4-9.0). The 3 and 5-year PFS with their 95% confidence intervals (95% CI) were 78% (65-88) and 76% (63-86), and the 3 and 5-year OS were 84% (72-92) and 76% (63-86), respectively. Medulloblastoma subtype was a statistically significant prognostic factor (P-value = 0.039) with large-cell/anaplastic being of worse prognosis, as well as a molecular subgroup (P-value = 0.012) with sonic hedgehog (SHH) and group 3 being of worse prognosis than wingless (WNT) and group 4. Therapy was well tolerated. CONCLUSIONS: This treatment based on high-dose chemotherapy and conventional radiotherapy resulted in a high survival rate in children with newly diagnosed high-risk medulloblastoma.
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