Lymph node density as prognostic variable in oral cancer: Systematic review and meta-analysis

Abstract

Introduction Lymph node ratio(LNR) has recently emerged as an independent prognostic factor in various centre-based studies for oral squamous cell carcinoma(OSCC). However, a range of cut-off values were suggested. A meta-analysis was conducted to evaluate the prognostic effects of LNR as well as to investigate cut-off value. Materials & Methods Electronic search on Pubmed, Embase and Cochrane library and manual search were performed for studies up to January 2018. The outcomes were overall survival(OS), disease specific survival(DSS), disease free survival(DFS), local recurrence free survival(LF), locoregional disease free survival(LRF), and distant metastasis disease free survival(DM). Results and Conclusion 19 studies were included. Total number of patients was 14254 (range 19 – 3958). The included studies were published between 2009 and 2017. Two studies were multicentre, eight studies were conducted in Asian countries, and the remaining nine studies were carried out in non-Asian countries. One study was prospective, and rest were retrospective. The reported follow-up varied from 20.9 to 79 months. Data was grouped into Group A (pN+) and Group B (pN- and pN+). In the meta-analysis, higher LNR was significantly associated with shorter OS in both groups (A = HR 1.902; 95%CI: 1.453-2.488, B= HR 2.76; 95%CI: 2.13-3.59), DSS (A = HR 1.728; 95%CI: 1.159-2.579; B= HR 2.83; 95%CI: 1.8-4.44), DFS (A = HR 2.27; 95%CI: 1.74-2.96; B= HR 2.01; 95%CI: 1.44-2.82), and LRF in B (HR 5.013; 95%CI: 3.584-7.011). All cut-off values suggested by the studies included in the meta-analysis were shown to be significant and there was no evidence of a second significant value. In Group A, the lowest LNR cut-off value is 0.05 with OS and DFS as endpoints. In Group B, the lowest cut-off LNR are 0.025 and 0.05 with OS and LRF as endpoints respectively. Given that Group A is a subset of Group B, we proposed 0.025 to be considered for OS in both groups. Based on our results, LNR was shown to be an independent prognostic factor in OSCC and may be considered in future oncologic staging systems.