Post-radiation neurocognitive decline differs by medulloblastoma subtype
medwireNews: In children with medulloblastoma undergoing radiotherapy, neurocognitive outcomes vary depending on the molecular subtype of the disease, findings indicate.
The research, published in the Journal of Clinical Oncology, also shows that only specific subgroups derive a neurocognitive benefit from limiting radiation exposure.
Paediatric medulloblastoma patients can be classified into four distinct subtypes – namely wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4 – on the basis of the genomic profiles of the tumours, with varying responses to treatment and survival times, explain Donald Mabbott (Hospital for Sick Children, Toronto, Ontario, Canada) and team.
In this study comprising 121 medulloblastoma patients treated between 1991 and 2013, they found that neurocognitive outcomes also differed by subtype.
Following radiotherapy, all measures of neurocognitive functioning – including Full Scale IQ, verbal comprehension and working memory – declined comparably across the four subtypes. The only exception was processing speed, the post-radiation decline of which was significantly lower for SHH (n=28) than for Group 3 (n=25) patients.
The SHH subgroup also had a lower pre-therapy incidence of cerebellar mutism and motor deficits than the other subgroups, note the researchers who consider this to be “the most distinct subgroup”.
They suggest that inherent genetic features that modulate the response to radiation or the presence of mutations associated with radiotherapy resistance, such as TP53, could be responsible for the less pronounced decline in processing speed for the SHH subtype.
Mabbott et al also assessed the effects of reducing radiation exposure on neurocognitive functioning by subtype.
Patients in the WNT (n=17) and Group 4 (n=51) categories, that is, those most likely to undergo therapy de-escalation, were considered together owing to small numbers in the WNT subgroup. In these patients, use of low-dose craniospinal irradiation plus a tumour bed boost led to nonsignificant increases in all measures except processing speed, relative to all other radiotherapy options.
By contrast, limiting radiation intensity in SHH and Group 3 patients was not associated with favourable neurocognitive outcomes.
Although the findings need to be confirmed in larger, collaborative studies, the investigators conclude that their results “highlight the value of conducting subgroup-specific analyses, and can be used to inform novel biologically based treatment protocols for patients with medulloblastoma.”
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