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. 2018 Apr;22(3):1513-1521.
doi: 10.1007/s00784-017-2247-3. Epub 2017 Oct 17.

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma

Wei-Chin Chang  1   2 , Chun-Shu Lin  3 , Cheng-Yu Yang  2 , Chih-Kung Lin  4 , Yuan-Wu Chen  5   6   7
Affiliations

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma

Wei-Chin Chang et al. Clin Oral Investig. 2018 Apr.

Abstract

Objectives: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals.

Material and methods: We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method.

Results: Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004).

Conclusions: Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis.

Clinical relevance: LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Keywords: Betel nut; Lymph node density; Oral squamous cell carcinoma; Prognostic factor.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All the patients provided informed consent and the Ethical Committee of the Tri-Service General Hospital (Taipei, Taiwan) approved the retrospective study (institutional review board protocol no: I-105-05-049).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
The lymph node density value is significantly different between the three histopathologic nodal stages (p < 0.001)
Fig. 2
Fig. 2
The receiver operating characteristic (ROC) curve for the LND value for overall survival of patients with pathologic-positive results. The red solid line indicates an LND value of 0.08 and the red dotted line indicates an LND value of 0.05. The Youden index (YI), for an LND value of 0.08 is 1.324 and for an LND value of 0.05, the YI is 1.184. The LND value of 0.05 is the optimal cutoff value since the sensitivity is much higher than for an LND of 0.08. (AUC, area under the curve)
Fig. 3
Fig. 3
Kaplan-Meier plots for stratification by group of (a) 5-year survival and (b) 5-year disease-free survival. In group A, the LND is 0; in group B, the LND is 0 to 0.05; and in group C, the LND is ≥ 0.05
Fig. 4
Fig. 4
The 5-year overall survival and disease-free survival rates as analyzed by the Kaplan-Meier method in patients with positive histologic lymph nodes: (a, b) based on tumor-node metastasis (TNM) lymph node classification; (c, d) based on lymph node density (LND) model with the cutoff point of 0.05
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