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

Pediatr Blood Cancer. 2020 Jan;67(1):e28012. doi: 10.1002/pbc.28012. Epub 2019 Sep 22.

Abstract

Background: 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 and methods: 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 18 Gy and a total local dose of 50 Gy. Radiotherapy was only considered for infants if residual tumors were present after the HDC.

Results: 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.

Conclusion: 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.

Keywords: chemotherapy; craniospinal irradiation; intrathecal methotrexate; medulloblastoma; radiotherapy; thiotepa.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cerebellar Neoplasms / drug therapy*
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / radiotherapy
  • Child
  • Child, Preschool
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Cranial Irradiation
  • Cyclophosphamide / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Spinal
  • Male
  • Medulloblastoma / drug therapy*
  • Medulloblastoma / pathology
  • Medulloblastoma / radiotherapy
  • Melphalan / administration & dosage
  • Methotrexate / administration & dosage
  • Prognosis
  • Prospective Studies
  • Registries / statistics & numerical data*
  • Survival Rate

Substances

  • Etoposide
  • Cyclophosphamide
  • Cisplatin
  • Melphalan
  • Methotrexate