History of Medulloblastoma Research

(Adapted from Brain Tumour Magazine with permission. Contents researched by SickKids physicians Dr. Vijay Ramaswamy and Dr. Eric Bouffet.)


EACH year medulloblastoma affects five children in every one million, one of the most common malignant brain tumours in children.

This timeline illustrates the most important breakthroughs and advances in the knowledge and management of medulloblastoma and highlights the remarkable progress clinicians and researchers have made over the years.

With recent advances in molecular and genomic technologies, the landscape of medulloblastoma is changing. We can expect the treatment of this disease to see further important changes in the next decades.



Using integrated genomics, multiple global studies show that medulloblastoma is actually comprised of 12 distinct molecular subtypes, including two key clinically relevant infant medulloblastoma groups.


International team of researchers discovers previously ascribed clinical risk factors associated with surgery are far less important than previously throught once accounting for molecular subgroup.


Global consensus statement redefines risk stratification of medulloblastoma (Ramaswamy et al, Acta Neuropathological, 2016).


Several multi-centre studies in North America and Europe initiated evaluating de-escalation therapies for WNT Medulloblastoma due to the excellent prognosis in this sub-group offering the possibility that this subset of patients could be cured with less neurocognitive and neuroendocrine sequelae.


A study of recurrent medulloblastoma reveals that subgroup affiliation is stable at recurrence, and that Group 3 and 4 medulloblastoma frequently recur in the metastatic compartment. This suggests that progress in improving outcomes for these two subgroups must focus on treatment of the metastatic compartment.


  1. Results of the SIOP-PNET4 randomized study that assessed the role of hyperfractionated craniospinal radiation (HFRT). In this trial, HFRT was not superior to standard radiation, which therefore remains standard of care in medulloblastoma.
  2. A cross-species genomic study reveals that in disseminated medulloblastoma, the metastatic compartment is distinct from the primary tumour in both human and mouse medulloblastoma.


Multiple genomic and next-generation sequencing studies reveal that medulloblastoma is a heterogeneous tumour comprising of at least four distinct molecular variants (WNT, SHH, Group 3, Group 4).


Single case report of an adult treated with the smoothened inhibitor GDC-0449 reveals a dramatic but transient response, leading to several clinical trials of smoothened inhibition.


Genomic analysis of medulloblastoma reveals multiple molecular subgroups of medulloblastoma. This is the first study to suggest the existence of distinct molecular variants of medulloblastoma.

Multicentre studies initiated by the Children’s Cancer Group (CCG9961) and St. Jude’s (SJMB96) of reduced dose craniospinal irradiation followed by cisplatin-based adjuvant chemotherapy for average risk medulloblastoma patients showed five-year survivals of over 80%.


  1. Nuclear beta-catenin identified as a marker of excellent prognosis in medulloblastoma, and is later shown to be a defining feature of the Wingless (WNT) subgroup of medulloblastoma.
  2. A German study reveals that a high proportion of infants with desmoplastic histology can be successfully treated with chemotherapy only.


First whole genomic analysis of embryonal tumours published by Pomeroy et al in Nature showing that medulloblastoma is distinct from other embryonal tumours of the central nervous system, in particular atypical/teratoid rhabdoid tumours and CNS-PNET. This study also showed that classic histology medulloblastoma has distinct profiles from desmoplastic histology.


Results of CCG9892, a pilot study that shows an excellent five-year survival rate in children with average risk medulloblastoma treated with reduced dose radiation and chemotherapy combining cisplatin/CCNU/vincristine.


First evidence that deletion of the Patched1 gene is responsible for medulloblastoma formation in mice. This represents the first transgenic model of medulloblastoma.


A Pediatric Oncology Group (POG) study evaluating chemotherapy only approaches for infants (Baby-POG) is published suggesting that a small proportion of infants could be cured without radiation therapy.


Introduction of the MRI scan of the spine in the staging of medulloblastoma (up to that time, spinal staging was performed with myelogram). This dramatically improved the ability to detect metastases and allowed more robust identification of high risk patients with metastatic dissemination.


Several studies show significant neurocognitive impairment in children treated with standard doses of craniospinal irradiation, specifically young children. Approaches to reduce craniospinal irradiation using adjuvant chemotherapy are initiated. However, the SIOP 2 trial concluded that dose reduction was not safe.


First International Society of Paediatric Oncology (SIOP) and Children’s Cancer Study Group (CCG) randomised trials with similar design (radiation +/- chemotherapy) that suggest a benefit for chemotherapy in a subset of patients.


Staging system proposed by C.H. Chang. This staging system was developed in the pre-CT scan era and is based on size and invasiveness of the tumour at surgery (T stage) and evidence of spread outside the posterior fossa (M stage).


First comprehensive study of craniospinal irradiation for medulloblastoma leading to three-year survival of over 50%. This showed for the first time that a combination of surgery and craniospinal irradiation could lead to cure and that medulloblastoma was not necessarily a fatal disease.


  1. First attempt at x-ray therapy (roentgen therapy) by Percival Bailey and Harvey Cushing. They found that a subset of patients at autopsy in fact had no evidence of medulloblastoma, rather radiation necrosis. Led other groups to explore radiation therapy as a treatment after surgery.
  2. Harvey Cushing described medulloblastoma and performed the initial surgeries. It was realized very quickly that after surgery, the tumour returns in all cases.