Determining the optimal cutoff point for lymph node density and its impact on overall survival in children with Wilms’ tumor

Abstract

Zhenyu Pan,1–3,* Qingting Bu,4,* Haisheng You,5 Jin Yang,1,2 Qingqing Liu,1,2 Jun Lyu1,2 1Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China; 3Department of Pharmacy, The Affiliated Children Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Genetics, Northwest Women’s and Children’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 5Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Objective: 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.Methods: 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.Results: 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 (P=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 (P=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; P=0.035). Smooth curve fitting suggested that the risk of mortality tended to be ascending with the increase in LND in general.Conclusion: 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. Keywords: Wilms’ tumor, lymph node density, cutoff point, survival 

Keywords

• Wilms’ tumor
• lymph node density
• children
• cutoff point
• survival