Pan Zhenyu, Bu Qingting, You Haisheng, Yang Jin, Liu Qingqing, Lyu Jun
Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China,
School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China,
Cancer Manag Res. 2019 Jan 15;11:759-766. doi: 10.2147/CMAR.S190138. eCollection 2019.
Previous studies showed that the lymph node density (LND) was a predictor of survival in Wilms' tumor (WT). However, the optimal LND cutoff point is controversial due to methodological shortcomings of previous studies, and no studies have shown the effect of LND on survival in children with WT. The purpose of this study was to remedy this situation.
We identified 376 children with WT. LND cutoff point was determined using the median value, the X-tile program, the survival-tree algorithm, and the time-dependent ROC curve analysis. Survival functions were estimated by the Kaplan-Meier method. We used Cox regression analysis to determine the impact of LND on survival. Smooth curve fitting between relative mortality risk and LND was performed.
The LND cutoff point was 0.44, 0.65, 0.65, and 0.64 according to the median value, the X-tile program, the survival-tree algorithm, and the time-dependent ROC curve analysis, respectively. The 5-, 10-, and 20-year overall survival rates were 86.9%, 86.9%, and 84.7%, respectively, in the <0.44 group and 81.3%, 80.3%, and 80.3%, respectively, in the ≥0.44 group. Survival did not differ significantly between the two groups (=0.185). The 5-, 10-, and 20-year overall survival rates were 87.8%, 87.8%, and 86.0%, respectively, in the < 0.65 or < 0.64 group and 76.5%, 75.1%, and 75.1%, respectively, in the ≥ 0.65 or ≥ 0.64 group. Children with the high LND had a significantly worse survival (=0.011) if 0.64 or 0.65 was used for the stratification. LND was a significant predictor for overall survival in the multivariate Cox regression analysis (HR =1.797; 95% CI, 1.043-3.097; =0.035). Smooth curve fitting suggested that the risk of mortality tended to be ascending with the increase in LND in general.
The three methods including the X-tile program, the survival-tree algorithm, and the time-dependent receiver operating characteristic (ROC) curve analysis are equivalent in their ability to stratify patients and clearly better than the median method. The results showed that the optimal LND cutoff point was around 0.65 and the LND was a reliable predictor of overall survival in children with WT.
既往研究表明，淋巴结密度（LND）是肾母细胞瘤（WT）生存的一个预测指标。然而，由于既往研究的方法学缺陷，最佳LND临界值存在争议，且尚无研究显示LND对WT患儿生存的影响。本研究的目的是纠正这种情况。
我们纳入了376例WT患儿。使用中位数、X-tile程序、生存树算法和时间依赖性ROC曲线分析来确定LND临界值。采用Kaplan-Meier法估计生存函数。我们使用Cox回归分析来确定LND对生存的影响。对相对死亡风险和LND之间进行平滑曲线拟合。
根据中位数、X-tile程序、生存树算法和时间依赖性ROC曲线分析，LND临界值分别为0.44、0.65、0.65和0.64。LND<0.44组的5年、10年和20年总生存率分别为86.9%、86.9%和84.7%，LND≥0.44组分别为81.3%、80.3%和80.3%。两组间生存率无显著差异（P=0.185）。LND<0.65或<0.64组的5年、10年和20年总生存率分别为87.8%、87.8%和86.0%，LND≥0.65或≥0.64组分别为76.5%、75.1%和75.1%。如果采用0.64或0.65进行分层，LND高的患儿生存率显著更差（P=0.011）。在多变量Cox回归分析中，LND是总生存的一个显著预测指标（HR=1.797；95%CI，1.043-3.097；P=0.035）。平滑曲线拟合表明，总体上死亡风险倾向于随LND的增加而上升。
包括X-tile程序、生存树算法和时间依赖性ROC曲线分析在内的三种方法在对患者分层的能力上相当，且明显优于中位数法。结果显示，最佳LND临界值约为0.65，且LND是WT患儿总生存的一个可靠预测指标。
