Non-linear early rapid hippocampal atrophy and associated microstructural injury in patients with nasopharyngeal carcinoma after radiotherapy: Implications for hippocampal protection.

BACKGROUND

Radiation-induced hippocampal atrophy is a key contributor to neurological dysfunction in patients with nasopharyngeal carcinoma (NPCs) after radiotherapy (RT); however, its dynamic pattern and underlying microstructural injury characteristics are unclear.

METHODS

In this prospective study, we longitudinally analyzed 193 NPCs (158 in the discovery cohort and 35 in the validation cohort) and 20 healthy controls. Based on structural and multi-shell diffusion magnetic resonance imaging, repeated-measures analysis of covariance, generalized additive mixed model, and partial correlation analysis were used to study the longitudinal evolution of hippocampal volume, microstructural metrics, and their relationships. Bootstrap-enhanced least absolute shrinkage and selection operator and multivariate logistic regression were employed to select key risk factors of hippocampal atrophy 1 year after RT. The normal tissue complication probability model and dose-response analysis were used to further investigate the effect of RT on hippocampal atrophy.

RESULTS

The bilateral hippocampus of NPCs underwent rapid atrophy in the acute phase after RT, and the volumes remained stable during the subsequent phases, which differed from those of the temporal lobe. Hippocampal microstructural injury primarily manifests in the acute phase and is associated with hippocampal atrophy post-RT. D was the strongest predictive dosimetric factor for hippocampal atrophy 1 year after RT. For NPCs who had received neoadjuvant chemotherapy (NCT), the tolerance dose for a 50 % probability of developing hippocampal atrophy was 44.26 Gy, which was lower than the 55.06 Gy for NPCs who had not received NCT.

CONCLUSIONS

Nonlinear early rapid hippocampal atrophy was observed within 1 year post-RT in NPCs, which was associated with microstructural injuries. Understanding the hippocampus tolerance dose and rational use of chemotherapy drugs may help to optimize RT planning and preserve hippocampal volume.