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Clinical Trial
. 2023 Jan 5;25(1):167-176.
doi: 10.1093/neuonc/noac148.

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

Michiel B de Ruiter  1 , Paul F C Groot  2 , Sabine Deprez  3   4 , Pim Pullens  5 , Stefan Sunaert  3 , Dirk de Ruysscher  6 , Sanne B Schagen  1   7 , José Belderbos  8
Affiliations
Clinical Trial

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

Michiel B de Ruiter et al. Neuro Oncol. .

Abstract

Background: 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.

Methods: High-quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated for 4 months (57 HA-PCI patients and 46 PCI patients) and 12 months (28 HA-PCI 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).

Results: 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 in gray matter and normal-appearing white matter, increases in white matter hyperintensities, and brain aging. There were no significant associations between hippocampal atrophy and memory.

Conclusions: 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.

Keywords: brain aging; brain injury; hippocampal atrophy; hippocampal avoidance prophylactic cranial irradiation; memory.

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Figures

Fig. 1
Fig. 1
Study flowchart.
Fig. 2
Fig. 2
Time × Group analyses for 4-month follow-up and 4- and 12-month follow-up. For clarity, the figure shows percentage change compared to pre-(HA-)PCI baseline (BL) measurement. Statistics as shown in Table 2 were performed on raw data. Panel A shows the primary outcome measure, hippocampal volume. For accelerated aging (panel E), chronological aging is shown as a dotted line as a reference. See text for details.
See this image and copyright information in PMC

References

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