Jihane Adelon1, Christelle Dufour2, Stéphanie Foulon3, Julien Masliah Planchon4, David Meyronnet5, Franck Bourdeaut6, Gilles Palenzuela7, Fanny Fouyssac8, Sandra Raimbault9, Emilie De Carli10, Sébastien Klein11, Anne Pagnier12, Anne-Isabelle Bertozzi13, Angélique Rome14, Audrey David15, Sylvie Chabaud16, Cécile Faure-Conter17. 1. Department of Pediatrics, Institut d'Hématologie et d'Oncologie pédiatrique, 1 Place Professeur Joseph Renaut, 69008, Lyon, France. jihane.adelon@gmail.com. 2. Department of Pediatric and Adolescent Oncology, Gustave Roussy Institute, Villejuif, France. 3. Biostatistics and Methodology Unit, Department of Clinical Research and Investigation, Gustave Roussy Institute, Villejuif, France. 4. INSERM U830, Laboratory of Translational Research in Pediatric Oncology, SIREDO Pediatric Oncology Center, Curie Institute, Paris, France. 5. Department of Neuropathology, Institut de Pathologie Est, Hospices civils de Lyon, Lyon, France. 6. SIREDO Pediatric Oncology Center, Curie Institute, Paris, France. 7. Department of Pediatric Hematology-Oncology, Centre Hospitalo-Universitaire de Montpellier, Montpellier, France. 8. Department of Pediatric Oncology, Children's Hospital, Nancy, France. 9. Pediatric Oncology Unit, Oscar Lambret Comprehensive Cancer Center, Lille, France. 10. Department of Pediatric Oncology, University Hospital, Angers, France. 11. Department of Pediatric Hematology-Oncology, University Hospital, Besançon, France. 12. Department of Pediatric Immunohematology and Oncology, University Hospital, Grenoble, France. 13. Department of Pediatric Onco-Hematology, CHU Toulouse, France. 14. Department of Pediatric Hematology and Oncology, La Timone Children's Hospital, Marseille, France. 15. Department of Pediatric Hematology and Oncology Unit, University Hospital of Saint-Étienne, Saint-Étienne, France. 16. Clinical Research and Innovation Department, Léon Bérard Cancer Centre, Biostatistics Unit, Lyon, France. 17. Department of Pediatrics, Institut d'Hématologie et d'Oncologie pédiatrique, 1 Place Professeur Joseph Renaut, 69008, Lyon, France.
Abstract
PURPOSE: High-risk medulloblastomas (HR-MB) may not respond to induction chemotherapy, with either post-induction stable (SD) or progressive disease (PD). There is no consensus regarding their optimal management. METHODS: A retrospective, multicentre study investigated patients with non-responder HR-MB treated according to the PNET HR + 5 protocol (NCT00936156) between 01/01/2009 and 31/12/2018. After two courses of etoposide and carboplatin (induction), patients with SD or PD were analyzed. Upon clinician's decision, the PNET HR + 5 protocol was either pursued with tandem high-dose chemotherapy (HDCT) and craniospinal irradiation (CSI) (continuation group) or it was modified (switched group). RESULTS: Forty-nine patients were identified. After induction, 37 patients had SD and 12 had PD. The outcomes were better for the SD group: the 5-y PFS and OS were 52% (95% CI 35-67) and 70% (95% CI 51-83), respectively, in the SD group while the 2-y PFS and OS were 17% (95% CI 3-41) and 25% (95% CI 6-50), respectively, in the PD group (p < 0.0001). The PNET HR + 5 strategy was pursued for 3 patients in the PD group, of whom only one survived. In the SD group, it was pursued for 24/37 patients whereas 13 patients received miscellaneous treatments including a 36 Gy CSI in 12 cases. Despite that continuation and switched group were well-balanced for factors impacting the outcomes, the latter were better in the continuation group than in the switched group: the 5-y PFS were 78% (95% CI 54-90) versus 0% (p < 0.001), and the 5-y OS were 78% (95% CI 54-90) versus 56% (95% CI 23-79) (p = 0.0618) respectively. In the SD group, multivariate analysis revealed that MYC amplification, molecular group 3, and a switched strategy were independent prognostic factors for progression. CONCLUSION: Patients with post-induction SD may benefit from HDCT and CSI, whereas patients with early PD will require new therapeutic approaches.
PURPOSE: High-risk medulloblastomas (HR-MB) may not respond to induction chemotherapy, with either post-induction stable (SD) or progressive disease (PD). There is no consensus regarding their optimal management. METHODS: A retrospective, multicentre study investigated patients with non-responder HR-MB treated according to the PNET HR + 5 protocol (NCT00936156) between 01/01/2009 and 31/12/2018. After two courses of etoposide and carboplatin (induction), patients with SD or PD were analyzed. Upon clinician's decision, the PNET HR + 5 protocol was either pursued with tandem high-dose chemotherapy (HDCT) and craniospinal irradiation (CSI) (continuation group) or it was modified (switched group). RESULTS: Forty-nine patients were identified. After induction, 37 patients had SD and 12 had PD. The outcomes were better for the SD group: the 5-y PFS and OS were 52% (95% CI 35-67) and 70% (95% CI 51-83), respectively, in the SD group while the 2-y PFS and OS were 17% (95% CI 3-41) and 25% (95% CI 6-50), respectively, in the PD group (p < 0.0001). The PNET HR + 5 strategy was pursued for 3 patients in the PD group, of whom only one survived. In the SD group, it was pursued for 24/37 patients whereas 13 patients received miscellaneous treatments including a 36 Gy CSI in 12 cases. Despite that continuation and switched group were well-balanced for factors impacting the outcomes, the latter were better in the continuation group than in the switched group: the 5-y PFS were 78% (95% CI 54-90) versus 0% (p < 0.001), and the 5-y OS were 78% (95% CI 54-90) versus 56% (95% CI 23-79) (p = 0.0618) respectively. In the SD group, multivariate analysis revealed that MYC amplification, molecular group 3, and a switched strategy were independent prognostic factors for progression. CONCLUSION: Patients with post-induction SD may benefit from HDCT and CSI, whereas patients with early PD will require new therapeutic approaches.
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