Li Yunpeng, Liang Jiahui, Fu Gui, Pan Jie, He Haoqiang, Li Jing, Chen Shishi, Deng Aner, Tang Linquan, Mai Haiqiang, Lv Xiaofei
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.
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.
Radiother Oncol. 2025 Aug;209:110997. doi: 10.1016/j.radonc.2025.110997. Epub 2025 Jun 21.
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.
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.
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.
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.
放射性海马萎缩是鼻咽癌（NPC）患者放疗（RT）后神经功能障碍的关键因素；然而，其动态模式和潜在的微观结构损伤特征尚不清楚。
在这项前瞻性研究中，我们纵向分析了193例NPC患者（发现队列158例，验证队列35例）和20例健康对照。基于结构和多壳扩散磁共振成像，采用重复测量协方差分析、广义相加混合模型和偏相关分析来研究海马体积、微观结构指标的纵向演变及其关系。采用自助增强最小绝对收缩和选择算子以及多变量逻辑回归来选择放疗后1年海马萎缩的关键危险因素。使用正常组织并发症概率模型和剂量反应分析来进一步研究放疗对海马萎缩的影响。
NPC患者双侧海马在放疗后的急性期迅速萎缩，随后各期体积保持稳定，这与颞叶不同。海马微观结构损伤主要表现在急性期，且与放疗后海马萎缩相关。D是放疗后1年海马萎缩最强的预测剂量学因素。对于接受新辅助化疗（NCT）的NPC患者，发生海马萎缩概率为50%时的耐受剂量为44.26 Gy，低于未接受NCT的NPC患者的55.06 Gy。
NPC患者放疗后1年内观察到非线性早期快速海马萎缩，这与微观结构损伤有关。了解海马耐受剂量并合理使用化疗药物可能有助于优化放疗计划并保留海马体积。
