Beyond the well-established case for hippocampal sparing, are there other brain regions that are associated with neurocognitive effects? This ESTRO CNS focus group systematic review of 28 studies (mostly small, single-center, and heterogeneous in cognitive testing) synthesizes what's known about regional radiosensitivity. Memory was the most consistently affected domain, with the strongest dose–effect link to the hippocampus. Signals also emerged for the temporal lobes, thalamus, amygdala, cerebellum, and corpus callosum. These were implicated in effects on various neurocognitive measures. MRI diffusion imaging and perfusion changes pointed toward distributed network injury rather than isolated effects on the hippocampus or other brain regions. Despite these associations, there were no clear dose constraints for non-hippocampal structures that could be used for treatment planning, and further prospective studies are needed. Hippocampal sparing during WBRT (validated by RTOG 0933 and NRG CC001) remains the only neuroprotective strategy supported by randomized data. | Turcas, Radiother Oncol 2026
