Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, PR China; Department of Radiation Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, PR China.
Department of Radiation Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, PR China.
Radiother Oncol. 2019 Mar;132:178-187. doi: 10.1016/j.radonc.2018.10.018. Epub 2018 Nov 14.
To evaluate the effect of radiotherapy interruption (RTI) in patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT).
A total of 7826 patients using the well-established big-data intelligence platform were identified. Computer-generated random numbers were used to assign these patients into a training cohort (n = 3913 patients) and an internal validation cohort (n = 3913 patients). RTI was defined as the difference between radiation treatment time and planned radiation time (assuming a Monday start). Survival analysis was performed using the Kaplan-Meier method for survival, and log-rank test to evaluate difference. Optimal RTI threshold was identified using the recursive partitioning analyses (RPAs). Multivariate analysis was performed using the Weibull model. The primary endpoint was overall survival (OS).
The optimal threshold of RTI with respect to OS in the training cohort was 6.5 d based on RPAs. Therefore, a uniform threshold of 7 d (<7 vs. ≥7 d) was selected to classify both training and validation cohorts into high and low RTI groups for survival analysis. RTI of ≥7 d showed significant detrimental effects on OS in both training (5-y OS, 82.4% vs 86.5%; P = 0.001) and validation cohorts (5-y OS, 85.2% vs 86.7%; P = 0.013) than those patients with RTI of <7 d. Consistent with results of the univariate analysis, RTI of ≥7 d was found to be an independent unfavorable prognostic factor for OS in both training (HR, 1.49; 95% CI, 1.14-1.95; P = 0.003) and validation cohort (HR, 1.37; 95% CI, 1.07-1.65; P = 0.031). Subgroup analysis showed that RTI of ≥7 d had significant adverse effects on prognosis of NPC patients receiving IMRT, regardless of TNM stage and chemotherapy (P < 0.05 for all).
In the IMRT era, RTI independently influences survival. Raising RTI ≥ 7 d was consistently unfavorable for NPC survival. Medical practitioners must remind patients on the importance of minimizing RT interruptions.
评估接受调强放疗（IMRT）的鼻咽癌（NPC）患者放疗中断（RTI）的效果。
使用成熟的大数据智能平台共确定了 7826 例患者。使用计算机生成的随机数将这些患者分配到训练队列（n=3913 例）和内部验证队列（n=3913 例）。RTI 定义为放射治疗时间与计划放射时间（假设周一开始）之间的差异。采用 Kaplan-Meier 方法进行生存分析，对数秩检验评估差异。采用递归分区分析（RPA）确定最佳 RTI 阈值。使用威布尔模型进行多变量分析。主要终点是总生存（OS）。
基于 RPA，训练队列中与 OS 相关的最佳 RTI 阈值为 6.5d。因此，选择 7d（<7 与≥7d）的统一阈值将训练和验证队列分类为高和低 RTI 组，以进行生存分析。RTI≥7d 与训练队列（5 年 OS，82.4%比 86.5%；P=0.001）和验证队列（5 年 OS，85.2%比 86.7%；P=0.013）的 OS 均有显著的不利影响。与单变量分析结果一致，RTI≥7d 是训练队列中 OS 的独立不良预后因素（HR，1.49；95%CI，1.14-1.95；P=0.003）和验证队列（HR，1.37；95%CI，1.07-1.65；P=0.031）。亚组分析表明，RTI≥7d 对接受 IMRT 的 NPC 患者的预后有显著的不良影响，与 TNM 分期和化疗无关（均 P<0.05）。
在 IMRT 时代，RTI 独立影响生存。RTI≥7d 不利于 NPC 患者的生存。医务人员必须提醒患者尽量减少 RT 中断的重要性。
