Strategy to minimize radiation burden in infants and high-risk medulloblastoma using intrathecal methotrexate and high-dose chemotherapy: A prospective registry study in Japan.

Abstract

Most childhood medulloblastoma (MB) cases are curable using multimodal treatment, including craniospinal irradiation (CSI). However, late effects are a serious problem for survivors. This prospective registry study evaluated Japanese patients to determine whether a reduced radiation dose was feasible. Patients with MB were classified as an infant group (<3 years old) and a high-risk (HR) group (≥3 years old with metastasis). The HR group received intrathecal methotrexate (IT-MTX) and high-dose chemotherapy (HDC) using thiotepa and melphalan, as well as concomitant radiotherapy with a recommended CSI dose of 18Gy and a total local dose of 50Gy. Radiotherapy was only considered for infants if residual tumors were present after the HDC. Between 1997 and 2006, we identified 28 HR patients (M1: 9, M2/3: 19) and 17 infant patients (M0: 11, M1: 3, M2/3: 3). During the median follow-up of 9.4 years for the entire HR group, the 5-year progression-free survival (PFS) rate was 82.1±7.2% and the 5-year overall survival (OS) rate was 85.7±6.6%. Subanalyses of the patients who received the recommended treatment revealed that the 5-year PFS and OS rates were both 90.5±6.4%. In the infant group, the 5-year PFS rate was 52.9±12.1% and the 5-year OS rate was 51.8±12.4%. There were no serious adverse events associated with the IT-MTX and HDC treatments. Intensified chemotherapy using HDC and IT-MTX might allow for a reduced prophylactic radiation dose in patients with MB with metastases. Further studies are needed to validate these findings.