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Salvage Therapy for Childhood Medulloblastoma: A Single Center Experience

  • Michelle M. Kameda-Smith (a1) (a2) (a3), Alick Wang (a3), Noora Abdulhadi (a4), Rebecca Voth (a3), Anjali Sergeant (a3), Arjuna Maharaj (a3), David Bakhshinyan (a2), Ashley A. Adile (a2), Akshat M. Pai (a3), Olufemi Ajani (a1) (a5) (a3), Blake Yarascavitch (a1) (a5) (a3), M. Cheryl Alyman (a3), JoAnn Duckworth (a3), M. Constantine Samaan (a3), Forough Farrokhyar (a4) (a3), Sheila K. Singh (a1) (a5) (a2) (a3), Adam Fleming (a5) (a3) and on behalf of the Pediatric Brain Tumour Study Group (a6)...

Abstract:

Introduction: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. Methods: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. Results: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. Conclusion: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

Traitement de sauvetage dans le cas du médulloblastome chez l’enfant : une expérience menée au sein d’un établissement hospitalier. Introduction: Les enfants chez qui l’on a diagnostiqué un médulloblastome réfractaire à un traitement initial ou qui sont victimes d’une récidive présentent d’habitude des pronostics de guérison vraiment défavorables. Bien qu’il existe des traitements basés sur des essais cliniques de phases I et II, ces traitements ont tendance à produire des taux notables de morbidité et de mortalité. Méthodes: Nous avons ainsi mené à l’Université McMaster une analyse rétrospective des dossiers d’enfants chez qui l’on avait diagnostiqué entre 2002 et 2015 une récidive de médulloblastome. Résultats: La réapparition de cette maladie chez 10 patients a provoqué un phénomène de diffusion leptoméningée, trois d’entre eux étant victimes d’une récidive locale. Sur ces 10 jeunes patients, la maladie a progressé de façon importante : ces enfants ont alors été transférés aux soins palliatifs. Quant aux autres 10 enfants, ils ont subi un certain type de traitement de sauvetage (des résections chirurgicales, de la radiothérapie, de la chimiothérapie), que ce soit de façon exclusive ou en variant les combinaisons possibles. Sur les 13 enfants réfractaires à un traitement initial ou victimes d’une récidive, 4 sont toujours en vie, leur suivi médian ayant été de 38,5 mois (75,5 mois). Sur les 8 patients pour qui on a pu obtenir des données moléculaires, aucun de ceux qui étaient atteints d’un médulloblastome du sous-type Wnt n’a connu de récidive. Conclusion: Les médulloblastomes qui réapparaissent après une période de guérison complète présentent un pronostic de guérison défavorable. Leur taux de survie globale est en effet de 18,2 % au cours d’une période de 5 ans, et ce, même après avoir bénéficié d’un traitement de sauvetage. Ajoutons aussi que le type de traitement initial reçu, la disponibilité des traitements ainsi que la tolérance à l’égard des traitements de sauvetage proposés a entraîné une grande hétérogénéité dans le traitement de ces jeunes patients victimes d’une récidive.

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Corresponding author

Correspondence to: Michelle Kameda-Smith, PGY3 Neurosurgery Resident (McMaster University), Surgeon Scientist Program PhD Candidate, Laboratory of Dr. Sheila K. Singh, Medulloblastoma Stem Cell Research Program, McMaster SCC-RI, MDCL 5061, 1280 Main St. W., Hamilton, ON, Canada, L8S 4K1. Email: michelle.kameda@medportal.ca

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The abstract of this paper has been presented at the Society of Neurooncology meeting November 2017, AANS/CNS Pediatrics in December 2017 and Canadian Federation of Neurological Sciences (CNSF) in June 2018.

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References

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