Scientific article

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort

Published inJournal of clinical oncology, vol. 38, no. 18, p. 2028-2040
Publication date2020-06-20
First online date2020-04-24

Purpose: The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.

Patients and methods: From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia.

Results: Five years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012).

Conclusion: Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma.

  • Cerebellar Neoplasms / drug therapy
  • Cerebellar Neoplasms / mortality
  • Cerebellar Neoplasms / radiotherapy
  • Child, Preschool
  • Cranial Irradiation / adverse effects
  • DNA Methylation
  • Female
  • Humans
  • Infant
  • Male
  • Medulloblastoma / drug therapy
  • Medulloblastoma / mortality
  • Medulloblastoma / radiotherapy
  • Methotrexate / administration & dosage
  • Neuropsychological Tests
  • Prospective Studies
Citation (ISO format)
MYNAREK, Martin et al. Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort. In: Journal of clinical oncology, 2020, vol. 38, n° 18, p. 2028–2040. doi: 10.1200/JCO.19.03057
Main files (1)
Article (Published version)
Secondary files (2)
ISSN of the journal0732-183X

Technical informations

Creation10/15/2021 10:08:00 AM
First validation10/15/2021 10:08:00 AM
Update time03/16/2023 2:08:30 AM
Status update03/16/2023 2:08:26 AM
Last indexation02/12/2024 12:16:55 PM
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