Evolution of Systemic Therapy in Medulloblastoma Including Irradiation-Sparing Approaches

Abstract

The management of medulloblastoma in children has dramatically changed over the past four decades, with the development of chemotherapy protocols aiming at improving survival and reducing long-term toxicities of high-dose craniospinal radiotherapy. While the staging and treatment of medulloblastoma were until recently based on the modified Chang’s system, recent advances in the molecular biology of medulloblastoma have revolutionized approaches in the management of this increasingly complex disease. The evolution of systemic therapies is described in this review.

Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma

“…Contemporary management for noninfantile MB [2,3,7] comprises maximal safe resection followed by postoperative risk-stratified adjuvant craniospinal irradiation (CSI) to a dose of 23.4-36 Gy/13-20 fractions plus boost irradiation of the tumour-bed to a dose of 18-30.6 Gy/10-17 fractions, resulting in a total primary site radiotherapy (RT) dose of 54 Gy/30 fractions. This is followed by 6-9 cycles of multiagent adjuvant systemic chemotherapy [2,3,8]. Traditionally, children over the age of 3 years at diagnosis with no/small residual tumour (<1.5 cm 2 ) and an absence of metastatic disease (M0) were classified as average risk for disease [9], with >80% long-term survival [10][11][12], while younger age (<3 years), large residual tumour (≥1.5 cm 2 ), and presence of leptomeningeal metastases (M+ disease) either alone or in combination were considered high-risk features [9], yielding much worse 5-year survival (30-60%) despite aggressive multimodality therapy [12,13].…”