Negative lymph node count is a significant prognostic factor in patient with stage IV gastric cancer after palliative gastrectomy

Abstract

Negative lymph node (NLN) count has been validated as a protective predictor in various cancers after radical resection. However, the prognostic value of NLN count in the setting of stage IV gastric cancer patients who have received palliative resection has not been investigated. Surveillance, Epidemiology, and End Results Program (SEER)-registered gastric cancer patients were used for analysis in this study. Kaplan-Meier survival curves and multivariate Cox proportional hazards model were used to assess the risk factors for patients' survivals. The results showed that NLN count and N stage were independently prognostic factors in patients with stage IV gastric cancer after palliative surgery (P< 0.001). X-tile plots identified 2 and 11 as the optimal cutoff values to divide the patients into high, middle and low risk subsets in term of cause-specific survival (CSS). And NLN count was proved to be an independently prognostic factor in multivariate Cox analysis (P< 0.001). The risk score of NLN counts demonstrated that the plot of hazard ratios (HRs) for NLN counts sharply increased when the number of NLN counts decreased. Collectively, our present study revealed that NLN count was an independent prognostic predictor in stage IV gastric cancer after palliative resection. Standard lymph node dissection, such as D2 lymphadectomy maybe still necessary during palliative resection for patients with metastatic gastric cancer.

Keywords: gastric cancer; negative lymph node; palliative resection; prognostic factor; survival analysis.

Figure 1. The flow chart of eligible patient selection in the present study

Surveillance, Epidemiology, and End Results (SEER)database collects incidence and survival data of gastric cancer from population-based cancer registries covering 28 percent of US population. Refer to the section of Patients’ Characteristics for study inclusion criteria.

Figure 2. Cutoff value for NLN counts calculated using the X-tile program

The X-tile program was utilized to calculate the optimal cutoff value for the negative lymph node (NLN) count. The entire population was divided into the training and validation sets based on the patient survival data. X-tile plots of training sets are shown in the upper-left quartile, with plots of the matched validation set in the small long strip (on the bottom X-axis). The black dot in the validation set represents the exact cutoff value for the NLN count (A) The entire cohort was divided into low (blue), middle (grey), and high (pink) NLN count groups based on the cutoff value (2 and 11), as shown in the histogram (B) Kaplan-Meier plots were generated based on the cutoff values (χ²= 77.318, P< 0.001) (C).

Figure 3. The risk score of NLN counts

The risk score of negative lymph node (NLN) counts was built using the linear combination of NLN counts with the estimated regression coefficients. Distribution of death and survival status of the patients was shown. It showed that the plot of hazard ratios (HRs) for NLN counts increased sharply when the number of NLN counts decreased.

Figure 4. Clinical significance of NLN counts on patients’ survival stratified by N stage

Subpopulation analysis of the prognostic value of negative lymph node (NLN) counts on patients’ survival according to N stage. For pN0 patients, χ2=10.615, P= 0.005 (A) For pN1 stage, χ2= 3.362, P= 0.186 (B) For pN2 stage, χ2= 26.503, P< 0.001 (C) For pN3 stage, χ2 = 22.509, P < 0.001 (D) It showed that the protective (more favorable) effect of higher NLN counts on patients’ 5-year cause-specific survival (CSS).