Research has identified a whole chromosomal signature that allows non-wingless (WNT)/non-sonic hedgehog (SHH) medulloblastoma patients normally classified as standard-risk to be categorised into favourable-risk and high-risk categories.
The International Society of Paediatric Oncology (SIOP) HIT-SIOP PNET 4 trial recruited patients aged 4-21 years with medulloblastoma in 120 treatment institutions in seven European countries to investigate the efficacy of hyperfractionated versus standard radiotherapy in standard risk medulloblastoma. A retrospective analysis of tumour samples from patients in the HIT-SIOP PNET 4 trial has now been published in the Lancet Oncology.
A novel whole chromosomal aberration signature associated with increased ploidy and multiple non-random whole chromosomal aberrations was identified in 38 (42%) of 91 samples from patients with non-WNT/non-SHH medulloblastoma. Biomarkers associated with this whole chromosomal aberration signature (at least two of chromosome 7 gain, chromosome 8 loss, and chromosome 11 loss) predicted favourable prognosis.
The study authors say patients with non-WNT/non-SHH tumours with the genetic signature and patients with SHH-TP53wild-type tumours should be considered for therapy de-escalation in future biomarker-driven, risk-adapted clinical trials. The remaining subgroups of patients with high-risk medulloblastoma might benefit from more intensive therapies, they add.