Medulloblastoma

Medulloblastoma occurs mainly in young children, with a small number of teenager and younger adults being diagnosed. Trials and treatment protocols were developed for children, so these often need to be adapted for older patients as the chemotherapy is often not tolerable. Patients often present with obstructive hydrocephalus due to the location of the tumour in the posterior fossa- often treated with endoscopic third ventriculostomy (we try to avoid shunts to avoid seeding into the peritoneum).

Treatment is based on complete resection of the primary site, craniospinal radiotherapy (if >=3 years) and chemotherapy.

In recent years the molecular subtyping of medulloblastoma has generated at least 5 different subtypes, wiht different prognoses, though currently, except WNT group, there are no different treatment options developed for each group. Trials are just starting in USA for SHH group to be treated with a SHH inhibitor, so we will await the results of this with interest.

Until recently, MB was considered as standard risk and high risk (anaplasia/large cell, metastatic, residual disease <1.5cm2, and later the addition of myc/n-myc- amplification). The new PNET-5 trial divides standard risk into low risk (WNT subgroup with no mets and <16 years old- determined by B-catenin mutation) and average risk (rest). Low risk groups are trialing a lower dose of craniospinal RT and standard risk is trialing different concomittant and adjuvant chemotherapy compared to the prior standard of "packer" regime.

Treatment of high risk MB is controversial. There are several different regimes recommended worldwide, with non-being shown to be clearly the best. Within Bristol, we use the Jakacki regime, based on the large phase 2 study, though the paediatric team have a new trial just opening which uses hyperfractionated radiotherapy. The Jakacki regime is being tested by COG in USA in a phase 3 study, but the final results have not yet been published.

Teaching Session

teaching session on the treatment of metastatic medulloblastoma, from Dr Cameron, 2020

Pathology- molecular subtypes

Molecular Classification of Medulloblastoma
Noriyuki Kijima, and Yonehiro Kanemura
Neurol Med Chir (Tokyo) 56, 687–697, 2016

Review (including easy to read overview) of the new 4 grupings in MB (WNT/SHH/group3/group4)

Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study
dward C Schwalbe, Janet C Lindsey, Sirintra Nakjang, Stephen Crosier, Amanda J Smith, Debbie Hicks, Gholamreza Rafiee, Rebecca M Hill, Alice Iliasova, Thomas Stone, Barry Pizer, Antony Michalski, Abhijit Joshi, Stephen B Wharton, Thomas S Jacques, Simon Bailey, Daniel Williamson, Steven C Clifford
Lancet Oncol 2017; 18: 958–71

New molecular classification for Medulloblastoma- now 7 prognostic groups suggested (WNT, SHH-infant and child, Group 3- LR and HR, Group 4-LR and HR)

Papers/trial protocols- treatment for low/average risk MB

AN INTERNATIONAL PROSPECTIVE STUDY ON CLINICALLY STANDARD-RISK MEDULLOBLASTOMA IN CHILDREN OLDER THAN 3 TO 5 YEARS WITH LOW-RISK BIOLOGICAL PROFILE (PNET 5 MB - LR) OR AVERAGE-RISK BIOLOGICAL PROFILE (PNET 5 MB -SR)
SIOPE
2015 version

Current trial protocol for low and standard risk MB (info on the RT protocol below)

Radiotherapy guidelines for the PNET-5 study
SIOPE
2018

Papers- treatment for high risk MB

Outcome of Children With Metastatic Medulloblastoma Treated With Carboplatin During Craniospinal Radiotherapy: A Children’s Oncology Group Phase I/II Study
Regina I. Jakacki, Peter C. Burger, Tianni Zhou, Emiko J. Holmes, Mehmet Kocak, Arzu Onar, Joel Goldwein, Minesh Mehta, Roger J. Packer, Nancy Tarbell, Charles Fitz, Gilbert Vezina, Joanne Hilden, and Ian F. Pollack
JCO 2012 VOLUME 30 NUMBER 21 JULY 20

Basis of the current protocol for high risk (including metastatic) medulloblastoma and what was classified as "supratentorial PNET". This phase II study has the largest multicentre study with the best results. Uses post surgery RT with concomittant vincristine and carboplatin and adjuvant cisplatin, vincristine and cyclophasphamide.

Jakacki Regime: Current UHBW protocol for high risk medulloblastoma
UHBW
current protocol in 2020