# Prognostic Value of Lymph Node Density in Lingual Squamous Cell Carcinoma
## 4 Discussion
### Relation to Similar Publications and Comparison between Terms of Agreement and Disagreement  
Most of the published studies on LND in carcinoma of the oral cavity include patients with OSCC. To our knowledge, the only multicenter studies performed to date, which provide the most consistent results, include cohorts of patients diagnosed with OSCC on whom cervical dissection was routinely performed in conjunction with tumor excision [12; 17].  
In both studies, LND is shown to be superior to the conventional N-staging system in predicting survival [12; 17].  
The main area of disagreement in the literature involves the establishment of the optimal cut-off point for stratifying patients according to LND. Multiple studies have used minimal \(p\)-values to identify a cut-off point for LND, leading to several threshold values ranging from 4.8% to 20% [18]. The largest study conducted to date by [PERSON] [12] applied time-dependent curve analysis for disease-specific survival (DSS) in selecting the cut-off point for LND, setting the cut-off point at 0.07. This study demonstrated in multivariate analysis that a DSS > 0.07 was an independent prognostic factor associated with worse OS and DFS. However, the study did not provide further information on the methods used to achieve their sample size and, in their analysis, they also achieved significance for staging based on N [12; 20]. [PERSON] [22] analyzed 1408 patients using a cut-off point of 0.088 based on time-dependent curve analysis for DFS, and reported that it was significant compared to N [12; 20].  
[PERSON] [17] analyzed in their multicenter study a cohort of 717 patients and categorized LND based on the median value (0.055). LND was also shown to be an independent prognostic factor in OS and DFS by uni- and multivariate analysis. Likewise, [PERSON] [14] used a cut-off point of 0.06 based on the median of the 386 patients included in their cohort, and concluded that LND reliably stratifies the risk of disease recurrence and survival in these patients. Therefore, the use of mean or median values to establish the cut-off point of the LND is not a reliable approach, since its value can deviate widely with small changes in the data or in the sample size [18; 20].  
Along a similar approach, [PERSON] [19] analyzed the comparability and universality of LND in the different anatomic locations included in OSCC, highlighting the need to develop specific treatment protocols for each anatomic sublocation, given the different treatment failure rates and clinical outcomes. In their study, they demonstrated that there is probably no universal cut-off point for LND, and that its assessment cannot constitute the only factor in the prognostic evaluation of patients with OSCC.  
Another area of disagreement in the literature is the inclusion or non-inclusion of pN0 patients in the analysis of the LND cut-off point. [PERSON] [18], in accordance with other previous studies, discussed in their study the need to exclude those patients with negative nodes from the LND analysis, as their inclusion could influence the estimation of the LND cut-off inappropriately. In their study, they confirmed the statistical significance of the association between LND > 14.3% and worse OS and DFS. Other studies, including both multicenter studies reviewed, confirm the statistical significance of the LND value taking into account pN0 patients, as they consider that LND is derived from N staging and therefore N0 lymph node metastasis should be taken into account when establishing the LND cut-off point [12; 17; 20].