Peer Review Report For: Longitudinal Assessment of Neurocognitive Outcomes and Correlation with Limbic System Radiation Doses in Patients Undergoing Radiotherapy for Central Nervous System Tumours: A preliminary report [version 1; peer review: 1 approved]

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Background Radiation therapy (RT) for central nervous system (CNS) malignancies can result in neurocognitive decline, affecting quality of life. While hippocampal-sparing approaches are well documented, limited data exist on the impact of radiation dose to other cognitive structures. This prospective study evaluates domain-specific cognitive changes following RT and explores correlations with radiation dose to key brain regions. Methodology Twenty-five patients with primary CNS tumours undergoing focal radiotherapy, with or without concurrent chemotherapy, were enrolled. Neurocognitive function was assessed using the Addenbrooke’s Cognitive Examination III (ACE-III) tool, pre- and six months post-treatment. Radiation dose-volume histogram (DVH) data were analyzed for structures including the hippocampus, amygdala, cerebellum, and corpus callosum. Patients were stratified based on ACE-III score decline (≥3 points vs. <3 points), and dose-response correlations were examined. Results A statistically significant decline in mean ACE-III scores was observed post-treatment (pre: 89.48 ± 6.84 vs. post: 87.91 ± 6.29, p = 0.007). Attention, language, and fluency were the most affected domains. Patients with cognitive decline received higher radiation doses to all examined structures, with the corpus callosum showing the strongest association (mean dose in decline group: 35.91 Gy vs. 30.70 Gy; p = 0.440). However, no dose-response relationship reached statistical significance. Conclusion This study highlights early, domain-specific neurocognitive decline following focal RT for CNS tumours, with attention and language being most vulnerable. Corpus callosum dose emerged as a key correlate. These findings suggest the need to broaden neuroprotection strategies beyond the hippocampus and emphasize the value of incorporating routine neurocognitive assessment.

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