Effective Predictor Factors for Lymph Node Metastasis and Survival in Patients with Betel Nut-Related Oral Squamous Cell Carcinoma

Abstract

Background: The Ministry of Health and Welfare has reported oral cancer to be one of the most prevalent malignant cancers; it has the third highest incidence rate of all cancers and is the fifth leading cause of death among men in Taiwan. Lymph node metastasis in oral cancer usually has a low survival rate, with no significant improvement in the past 30 years. Therefore, a more effective survival predictor is warranted. Many cancer studies have revealed that monitoring tumor thickness and lymph node density, in addition to tumor, node, and metastasis (TNM) stages, can provide more accurate predictions. Methods: This retrospective study analyzed data from 612 patients with oral cancer who had the habit of chewing betel nuts. The study focused on tumor thickness, lymph node density, and the regional distribution of lymph node metastasis to determine their effectiveness as predictors. Results: The results revealed that a tumor thickness of 6 mm indicated cervical lymph node metastasis and was the optimal cutoff point for overall survival. The optimal cutoff value for lymph node density was 0.04. Patients with a tumor thickness of >6 mm and a lymph node density of >0.04 had significantly lower overall survival rates. Additionally, patients with >1 lymph node metastasis level and lower cervical metastasis exhibited a relatively worse prognosis. Conclusions: Therefore, in addition to TNM staging, tumor thickness, lymph node density, and metastasis level are suitable as parameters for predictors that can be used as references for adjuvant therapies for better therapeutic effects.

Keywords: lymph node density; lymph node metastasis level; oral cancer; survival rate; tumor thickness.

Figure 1

(A) The receiver operating characteristic curve for the tumor thickness value. The tumor thickness value of 6 mm is the optimal cutoff value. (B) The receiver operating characteristic curve for the lymph node density ratio. The lymph node density ratio of 0.04 is the optimal cutoff value.

Figure 2

(A) Correlation distributions between tumor thickness and lymph node metastasis for cancers of all anatomic sites. (B,C) Correlation distributions between tumor thickness and lymph node metastasis for cancers of different anatomic sites.

Figure 3

(A) Kaplan–Meier survival rate curve; comparison between patients with a tumor thickness of >6 mm and ≤6 mm, where patients with a tumor thickness of >6 mm demonstrated poorer overall survival (p < 0.001). (B) Patients with lymph node metastasis and tumor thickness of >6 mm demonstrated poorer overall survival rates after including tumor thickness in survival rate analysis (p = 0.006).

Figure 4

(A,B) Correlation distribution diagram between patients with lymph node metastasis and lymph node density. Lymph node metastasis cases are divided into pN1, pN2, and pN3 stages. Correlation distribution diagram between lymph node metastasis stage and lymph node density.

Figure 5

(A) Kaplan–Meier survival rate curve; comparison between patients with lymph node density of >0.04 and ≤0.04, where patients with a lymph node density of >0.04 exhibited poorer overall survival (p < 0.001). (B) Patients with lymph node metastasis and lymph node density of >0.04 demonstrated a poorer overall survival rate after including lymph node density in survival rate analysis (p < 0.001). (C) Patients in the pN1 stage with a lymph node density of >0.04 exhibited poorer overall survival rates; we divided the patients with lymph node metastasis into the pN1, pN2, and pN3 groups and included lymph node density into the survival rate analysis of patients with different lymph node metastasis stages (p < 0.001). No significant difference was found between patients with pN2 and those with pN3.

Figure 6

(A) Kaplan–Meier lymph node metastasis level distribution curve and overall survival rate. The results revealed poor overall survival rates, regardless of lymph node metastasis level (p < 0.001). (B) Further analysis revealed that patients with lymph node metastasis in lower cervical level (level VI–V) (p < 0.001) demonstrated poorer survival rates.

Figure 7

(A) After including both lymph node density and tumor thickness for survival rate analysis, patients with a lymph node density of >0.04 and tumor thickness of >6 mm demonstrated poorer overall survival rates (p = 0.005). (B) Linear regression was utilized to examine the correlation between the overall survival rate and the two parameters of tumor thickness and lymph node density (p = 0.0053).