Baseline Characteristics and Outcomes
The data for around 100,000 EC patients were reviewed through SEER statistical software, but only the medical records of 13,491 patients were collected under the inclusion criteria. The 13,491 patients with EC were classified into two groups according to the random number method. The two groups were the training population (n=6698) and the validation population (n=6793).
The mean age of the total population was 66.70±11.12 years, and 10,776(79.9%) of the patients were male. The median size of tumors was 104.45±223.14 millimeters, and the average tumor size was 366.58±179.92. The proportions of white, black, and other races were 84.9%, 10.1%, 4.7%, respectively. Follow-up data revealed that 5,327(39.5%) of patients survived, and 8,164(60.5%) of patients had died. Average survival time was 11.31±11.35 months.
In the comparison of the results from the training population with that from the validation population, no significant differences were observed according to sex, age, tumor site, tumor size, the organ metastasis, numberPLN and NLN (Table 1).
The Parameters Identified in the Results of Cox Proportional HazardRegression Analysis
The univariate analysis revealed that sex, race, age, tumor site, tumor size, tumor length, pathological grade of tumor, AJCC stage, the post-operation treatment, the extent of esophageal tumor metastasis, and numberNLN were all independent prognostic factors. The result of the multivariate analysis demonstrated that numberPLN was also an independent prognostic factor in addition to the above parameters (Table 2).
The Modified N Stage Proposed in This Study
According to the results of the Cox proportional hazard model, the HR of PLN was 1.064, and the HR of NLN was 0.962. The distance between the HR of PLN and the statistical standard point (which was 1) was 0.064 (∆HPpositive), and the distance between the HR of NLN and the statistical point was 0.038 (∆HPnegative). The ratio of ∆HPpositive to ∆HPnegative (N ratio) was used as a coefficient to produce the re-adjusted number of PLN and NLN. `
The analysis result of the minimum P value method indicated that the following ranges for the modified N stage were an appropriate solution:
forN0 stage, the re-adjusted N ratio = 0；
for N1stage, the re-adjusted N ratio = (0-0.08];
for N2 stage, the range of rate was (0.08-0.63];
for N3,the re-adjusted N ratio (0.63,+¥]
In order to calculate the ratio of the re-adjusted number of PLN to NLN in special situations, the authors settled on the following two definitions of the ratio:
1) When numberPLN and NLN were both 0, the ratio of the readjusted number of PLN to NLN (re-adjusted N ratio) was defined as 0;
2) When one of numberPLN and numberNLN is 0, 0 was defined as 0.0001.
The Feasibility and Superiority of the Modified N Stage
A cross-validation study was performed on the modified N stage. The modified N stage was developed from the training population and validated using the validation population. The log-rank test indicated that significant survival differences were confirmed among the N1, N2 and N3 sub-groups of patients in the training population, and the survival difference could be replicated in the validation population using the Kaplan-Meier analysis (P< 0.05, Figure 1).
The survival analysis on all the patients using the method of N stage coming from AJCC tumor stage system, the log-rank test indicated that significant survival differences were confirmed among the N1, N2 and N3 sub-groups of all patients. Log-rank value of modified N stage is 304.7, the traditional AJCC N stage is 17.03, the K-M curve interval of modified N stage NI, N2, N3 is wider than the traditional AJCC N stage (Figure 2).
The comparison between the modified N stage and the AJCC N stage was performed using the ROC method. The result of ROC analysis revealed that the area under AJCC N stage curve was 0.934， and the area under modified N stage curve was 0.956 , which indicated that the modified N stage could represent the N stage of EC more accurately(Figure 3). The results show that the area under modified N stage curve was 0.956, the log-rank value was 304.7, which was greater than 0.934 of the area under AJCC N stage curve and log-rank value17.03 of AJCC N stage, and the K-M curve interval of modified N stage NI, N2, N3 is wider than the traditional AJCC N stage, it is considered that all the patients using the modified N stage method were relative accurate in predicting patients outcome compare with AJCC N stage.