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

Yunpeng Li; Jiahui Liang; Gui Fu; Jie Pan; Haoqiang He; Jing Li; Shishi Chen; Aner Deng; Linquan Tang; Haiqiang Mai; Xiaofei Lv

doi:10.1016/j.radonc.2025.110997

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

Radiother Oncol. 2025 Jun 21:209:110997. doi: 10.1016/j.radonc.2025.110997. Online ahead of print.

Authors

Yunpeng Li¹, Jiahui Liang¹, Gui Fu¹, Jie Pan¹, Haoqiang He¹, Jing Li¹, Shishi Chen¹, Aner Deng¹, Linquan Tang², Haiqiang Mai³, Xiaofei Lv⁴

Affiliations

¹ Department of Medical Imaging, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China.
² Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China. Electronic address: tanglq@sysucc.org.cn.
³ Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China. Electronic address: maihq@sysucc.org.cn.
⁴ Department of Medical Imaging, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China. Electronic address: lvxf@sysucc.org.cn.

PMID: 40550421
DOI: 10.1016/j.radonc.2025.110997

Abstract

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_max 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.

Keywords: Hippocampal atrophy; Microstructural injury; Nasopharyngeal carcinoma; Normal tissue complication probability model; Radiotherapy.