Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small cell lung cancer reduces hippocampal atrophy compared to conventional PCI.



High quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated 4 months (57 HAPCI patients and 46 PCI patients) and 12 months (28 HAPCI patients and 27 PCI patients) after (HA-)PCI. We additionally studied multimodal indices of brain injury. Memory was assessed with the Hopkins Verbal Learning Test Revised (HVLT-R).


HA-PCI reduced hippocampal atrophy at 4 months (1.8% for HA-PCI and 3.0% for PCI) and at 12 months (3.0% for HA-PCI and 5.8% for PCI). Both HA-PCI and PCI were associated with considerable reductions of gray matter and normal appearing white matter, increases of white matter hyperintensities and brain aging. There were no significant associations between hippocampal atrophy and memory.


Reducing radiation dose to the hippocampus with hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is proposed to prevent cognitive decline. It has, however, not been investigated whether hippocampal atrophy is actually mitigated by this approach. Here, we determined whether HA-PCI reduces hippocampal atrophy. Additionally we evaluated neurotoxicity of (HA-)PCI to other brain regions. Finally, we evaluated associations of hippocampal atrophy and brain neurotoxicity with memory decline.


HA-PCI reduces hippocampal atrophy at 4 and 12 months compared to regular PCI. Both types of radiotherapy are associated with considerable brain injury. We did not find evidence for excessive brain injury after HA-PCI relative to PCI. Hippocampal atrophy was not associated with memory decline in this population as measured with HVLT-R. The usefulness of HA-PCI is still subject to debate.

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  • Publication date 31-05-2022

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