High-risk Medulloblastoma—Balancing the High Stakes of Molecular Profiling to Enhance Treatment Responsivity
Mené entre 2007 et 2018 sur 261 patients pédiatriques atteints d'un médulloblastome à haut risque (âge médian : 8,6 ans ; 70 % de garçons), cet essai randomisé multicentrique de phase III évalue l'intérêt, du point de vue de la survie sans événement, d'ajouter du carboplatine pendant la radiothérapie craniospinale ou de l'isotrétinoïne pendant la chimiothérapie d'entretien
Children with high-risk medulloblastoma have relatively poor survival rates, with few studies demonstrating durable treatment responses, despite aggressive multimodality therapy. As such, improved therapy for high-risk medulloblastoma represents an urgent unmet clinical need in pediatric neuro-oncology. In this issue of JAMA Oncology, Leary et al describe the results of a phase 3 randomized clinical trial that meets that need. The addition of carboplatin to traditional high-risk therapy specifically benefited molecularly unfavorable patients with group 3 medulloblastoma, including those with metastatic disease. Over the past decade, research has helped to inform pathologic and molecular differences between the 4 noted subtypes: WNT, sonic hedgehog (SHH), group 3, and group 4. However, many challenges remain in widely implementing this therapy in patients who will benefit most. Despite multiple treatment options intent on influencing survival curves, in retrospective analyses, only WNT medulloblastoma, the least common subgroup, has shown high treatment responsivity and lower rates of recurrence. Historically, treatments for high-risk medulloblastoma given in addition to radiotherapy and surgery have ranged from use of standard DNA intercalator/alkylator-based chemotherapies to high-dose myeloablative chemotherapy requiring autologous stem-cell rescue to adjunctive biologic and/or immunologic therapies. Poor success in achieving statistically significant increases in survival within this high-risk group has necessitated intelligent consortium trials that evaluate treatment options based on pathologic, radiologic, and molecular classifications.
JAMA Oncology , éditorial, 2020