In an analysis from the single-institution phase III SJMB03 trial reported in the Journal of Clinical Oncology, Acharya et al found that increasing radiation doses to the corpus callosum, frontal white matter, and hippocampus were associated with neurocognitive impairment in pediatric patients undergoing radiation therapy for medulloblastoma.
Study Details
The study involved data from 124 patients aged 3 to 21 years enrolled in the SJMB03 trial at St. Jude Children’s Research Hospital. Radiotherapy consisted of a craniospinal dose of 23.4 Gy for average-risk patients and 36 to 39.6 Gy for high-risk patients, with a boost dose of 55.8 Gy to the tumor bed. Patients underwent neurocognitive testing at baseline and annually for 5 years. The current analysis assessed performance on tests of associative memory and working memory as well as composite processing speed and perceptual processing speed.
Key Findings
The median follow-up for neurocognitive outcomes was 5 years.
Mean right and left hippocampal radiotherapy doses were significantly associated with decline over time in associative memory in patients without posterior fossa syndrome (both P < .05).
Mean corpus callosum (genu, body, and splenium) and frontal white matter radiotherapy doses were significantly associated with declines over time in both composite processing speed and perceptual processing speed (all P < .05).
The hippocampus median dose-volume histogram was shifted to the right for patients with a decline in associative memory (P ≤ .001 for both right and left hippocampus). The corpus callosum and frontal white matter median dose-volume histograms were shifted to the right for patients with a decline in composite processing speed and perceptual speed (all P ≤ .025).
The odds of decline in associative memory increased by 23% to 26% for every 1-Gy increase in mean hippocampal radiotherapy dose. The odds of a decline in composite processing speed and perceptual speed increased by 10% to 15% and 8% to 12%, respectively, for every 1-Gy increase in mean corpus callosum or frontal white matter radiotherapy dose.
The investigators concluded, “Increasing radiotherapy dose to the corpus callosum or frontal white matter and hippocampus is associated with worse performance on tests of processing speed and associative memory, respectively. Brain substructure–informed radiotherapy planning may mitigate neurocognitive impairment.”
Sahaja Acharya, MD, of the Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a 2020 Conquer Cancer-Genentech BioOncology Women Who Conquer Cancer Career Development Award, American Lebanese Syrian Associated Charities, and National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
