The median age for the cohort was 44 years (range, 13–76years), with the male (n =1279)-to-female (n =473) ratio of 2.7:1. The median maximal axial diameter was 19mm( range: 5mm-89mm). The number of patients with N1, N2 and N3 were 837, 597 and 315 respectively. Furthermore, 768 patients were with ENE, and 825patients were with rENE.The detail was shown in Table-1.
Survival and pattern of failure
The median follow-up for the whole was 124 months and 72 patients (4%) were lost to follow after 3- to 91- months. By the last follow-up date, distant metastasis occurred in 221 patients (12.6%) and became the most common pattern of failure. Among these with distant metastasis, 156 patients were with single organ metastasis and 65 patients were with multiple organs metastasis. The bone was the most common metastatic site, then was the lung and the liver.The 10-years DMFS rate was 86.5%.
A total of 161 patients developed local and/or regional failure including 119 patients with local failure only, 38 patients with regional failure only and 4 patients with both of them. The 10-years LRFS , RRFS and PFS rates were 92.6%,97.4% and 78.6%, respectively.
A total of 347 patients died. Among these, 188 patients (188/347,54.2%) died from the distant metastasis, 104 patients (104/347,29.9%) died from the local+/-regional failure, 14 patients (14/347,4.0%) died from radiation-related complications, 18 patients (18/347,5.2%)died from other malignant tumors , 8 patients (8/347, 2.3%) died from the internal medication and 15 patients(15/347,4.3%) died unknown causes. The 10-years OS and DSS rates were 79.8% and 80.8%. The detail was shown in Table-2.
Univariate and multivariate analysis
The results of univariate analysis show that the factors of LDH, the nodal number, CNN, rENE, T stage and clinical stage were identified as a significant prognostic factor for LRFS, DMFS, PFS and DSS, and N stage was also identified as a significant prognostic factor for DMFS, PFS and DSS(Table-1).
Consistent with the results of univariate analysis, multivariate analysis also show that the factors of CNN, rENE, T stage and N stage were significant prognostic factor for DMFS, PFS and DSS，however the clinical stage and the nodal number were not independent prognostic factors. The 10-year DSS, DMFS and PFS for patients with CNN were poor than those without CNN, with 70.8% vs 88.6%, 80.8% vs 91.9%, 68.7% vs 86.2% (Figure-2). The 10-year DSS, DMFS and PFS for patients with rENE were also significantly poor than those without rENE, with 71.7% vs 86.7%, 79.8% vs 90.1%, 70.1% vs 86.0%(Figure-3).
The factors of T stage, LDH and CNN were associated with the LRFS, and the N stage and CNN were associated with the RRFS .The detail of the multivariate analysis was seen in Table-3.
Establishment of nomograms model for DSS with or with nodal feature
Firstly, we built a nomogram (Nomogram A) to predict the 5-, 10-year DSS rate only based on independent prognostic factors of gender, age, LDH, T stage and N stage. Then with the combinations of the ENE and CNN, a new nomogram (Nomogram B) was bulit to predict the 5-, 10-year DSS rate. Each variable has a corresponding score according to the point scale, and the total score is achieved by calculating the score of each variable. Next, by mapping the total score on the probability scale, the 5-, 10-year DSS rate probabilities could be estimated(Figure-4) .
A calibration curve showed good agreement between prediction and observation in the probability of 5-,10-year DSS. In Figure-5, the y-axes are observed DSS estimated by the Kaplan-Meier method, and the x-axes are predicted DSS calculated by the nomogram, and the solid lines represent the ideal reference line for which predicted survival corresponds with actual DSS. The C-index of nomogram B was 0.708 (95% CI = 0.681 to 0.733), which was higher than the C-index s of nomogram A of 0.676 (95% CI = 0.649 to 0.703).The results indicated that nomogram B displayed better accuracy in predicting recurrence compared with Nomogram A.