Medulloblastomas: update on a heterogeneous disease

Medulloblastoma is the main primitive neuroectodermal tumour of the posterior fossa in childhood. The classical therapeutic approach consists of surgical resection, followed by craniospinal irradiation. Because of the good overall survival (75%), the main recent research efforts focus on refining the most relevant prognostic stratification and in decreasing the long-term sequelae.

Thanks to the better understanding of the heterogeneity of medulloblastomas, clinical, histological and biological markers have been clearly identified and allow risk-adapted strategies. A subset of tumours of early childhood (<3-5 years), frequently associated with a Sonic Hedgehog signalling, might be cured without irradiation. In older children, several trials have demonstrated the safety of reduced craniospinal irradiation in standard risk tumours. Furthermore, the evidence of an excellent prognosis associated with a subset of tumours characterized by an activation of the WNT pathway leads to forthcoming de-escalating strategies. Reducing long-term sequelae also relies on new surgical approaches aiming at reducing the cerebellar injuries. Tremendous efforts have also been made in defining the most adapted irradiation doses and fields. Intensity-modulated radiotherapy and proton beam therapy might also influence the long-term neurological and endocrine defects of the patients.

Histological and biological characteristics clearly define various prognostic groups within medulloblastomas; confirming the overall good outcome and reducing long-term sequelae are the main focus of current clinical trials.