Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research

Abstract

Background: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.

Methods: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.

Results: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.

Conclusion: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Figure 1

Five-year overall survival and disease-specific survival rates calculated using the Kaplan–Meier method in patients with positive neck nodes. (A and B) Using TNM nodal classification (P<0.001); (C and D) using LND with a cutoff point of 0.07 (P<0.001). An analysis using LND separation point of 0.066 (based on the bootstrapping analysis) yielded similar results.

Figure 2

Five-year (A) local control, (B) locoregional control and (C) distant metastasis failure and (D) disease-free survival rates calculated by the Kaplan–Meier method in patients with positive neck nodes. The LND model had a cutoff point of 0.07 (P<0.001). Similar results were retrieved using LND cutoff point of 0.066.

Figure 3

(A–D) Kaplan–Meier curves of overall and disease-specific survival according to the treatment modality. The difference in survival rate was assessed by the log-rank test.

Figure 4

The ability of LND to distinguish between low-risk and high-risk patients within individual pN subgroups. Kaplan–Meier curves of overall and disease-specific survival in a subgroup of patients with pN1 nodal classification (A and C) and pN2 nodal classification (B and D). LND reliably distinguished between patients in each subgroup with a low risk and those with a high risk for treatment failure (P<0.05).