Medulloblastoma: an Old Diagnosis with New Promises

Molecular subtyping in medulloblastoma (MB) has diagnostic and prognostic values which impact therapy. This paper provides guidance for the clinician caring for pediatric and adult patients with medulloblastoma in the modern era.

Medulloblastoma comprises four molecularly distinct subgroups: wingless activated (WNT), sonic hedgehog activated (SHH), group 3, and group 4. Risk stratification before and after the discovery of molecular subgroups aims at minimizing toxicity by reducing radiation and chemotherapy doses in low-risk patients while maintaining favorable overall survival (OS). The mainstay of newly diagnosed medulloblastoma treatment is surgery, radiation therapy, and chemotherapy, except for children under 6 years of age, where high-dose chemotherapy with autologous stem cell rescue is used to avoid or delay radiotherapy, preventing neurocognitive sequelae. Management of recurrent/refractory medulloblastoma remains a challenge with immunotherapy and small-molecule inhibitors forming the backbone of novel strategies. Recent innovations in medulloblastoma research allow us to better understand pathogenesis and molecular characteristics resulting in advanced risk stratification models, new therapeutic approaches, and overall improved survival and quality of life.