Impact of the radiotherapy rhythm on prognosis in nasopharyngeal carcinoma

The role of chronoradiobiology in nasopharyngeal carcinoma (NPC) has not been fully elucidated. We sought to investigate the impact of radiotherapy rhythm on the survival outcomes of individuals to explore a chronomodulated radiation strategy to improve prognosis of NPC. A cohort comprising non-metastatic NPC patients subjected to intensity-modulated radiotherapy at Fujian Cancer Hospital between Jan. 2016 and Dec. 2019 was assembled. Rhythmic fluctuation of radiotherapy (RFRT) was quantified based on the temporal distribution of radiation delivery. Cox proportional hazard model was performed to explore the impact of radiotherapy rhythm on all-cause mortality. The maximally selected rank statistics method was employed to discern an optimal cutoff. Sensitivity analyses were conducted to ensure the robustness of observed associations. Our analysis encompassed 2245 patients, with a median follow-up duration of 55 months, during which 315 individuals succumbed. Multivariate Cox regression analysis unveiled a significant correlation between prolonged RFRT and heightened mortality risk in NPC patients (HR, 1.17, 95% CI, 1.07-1.27, <i>p</i> &lt; .001), a relationship robust to comprehensive adjustment for confounding variables. A cutoff value of 3 h was selected for potential clinical application, beyond which patients exhibited markedly poorer survival outcomes. Subgroup analyses consistently underscored the directional consistency of observed effects. Our study sheds light on the potential advantages of scheduling radiotherapy sessions at consistent times. These findings have implications for optimizing radiotherapy schedules and warrant further investigation into personalized chronotherapy approaches in NPC management.时间放射生物学（chronoradiobiology）在鼻咽癌（nasopharyngeal carcinoma, NPC）中的作用尚未完全阐明。本研究旨在探讨放射治疗节律对患者生存结局的影响，以期探索时间调控放射治疗策略以改善鼻咽癌患者的预后。本研究纳入2016年1月至2019年12月期间于福建肿瘤医院接受调强放射治疗（intensity-modulated radiotherapy）的非转移性鼻咽癌患者，组建了回顾性队列。本研究基于放射递送的时间分布，量化了放射治疗节律波动（rhythmic fluctuation of radiotherapy, RFRT）。采用Cox比例风险模型探讨放射治疗节律对全因死亡率的影响，并通过最大选择秩和统计法（maximally selected rank statistics method）确定最优截断值。此外，开展敏感性分析以验证所观察到的关联的稳健性。本研究共纳入2245例患者，中位随访时间为55个月，期间共有315例患者死亡。多因素Cox回归分析显示，延长的放射治疗节律波动与鼻咽癌患者的死亡风险升高显著相关（风险比HR=1.17，95%置信区间CI:1.07~1.27，p<0.001），且该关联在对混杂变量进行全面校正后依然稳健。亚组分析亦证实所观察到的效应方向具有一致性。本研究阐明了固定时间安排放射治疗疗程的潜在优势，上述研究结果为优化放射治疗方案提供了参考，并有望在鼻咽癌治疗中进一步探索个体化时间治疗（chronotherapy）策略。