摘要:
Purpose/Objective(s) Current pathologic lymph node (LN) staging for head and neck squamous cell carcinomas (HNSCC) is based on LN size, laterality, and presence of extracapsular extension. However, some retrospective registry and single institution studies have suggested that the number of positive (+) LNs is the dominant nodal factor driving survival in HNSCC. Given the limitations of these datasets, it is unclear whether number of +LNs increases mortality through increased locoregional recurrence (LRR), distant metastases (DM), or both. In this study, we evaluate the prognostic value of number of +LNs in HNSCC using an international cohort of patients enrolled on three prospective randomized controlled trials (RCTs). Materials/Methods Secondary analysis was performed of RTOG 9501, RTOG 0234, and EORTC 22931, 3 prospective RCTs of patients undergoing surgery followed by post-operative radiation (RT) with or without systemic therapy. Univariate and multivariable models with restricted cubic splines were constructed to evaluate the association between number of +LNs and overall survival (OS), disease-free survival (DFS), LRR, and DM. Competing risks analysis was used for LRR and DM. Non-linear restricted cubic splines were used to model the relationship between +LN number and outcomes. Results Overall, 947 patients were included in this secondary analysis. OS independently decreased with increasing number of +LNs without plateau, which was most pronounced up to a change point of 5 +LNs (hazard ratio [HR], 1.19 per LN; 95% confidence interval [CI], 1.10–1.29; P < 0.001). Mortality risk continued to increase after 5 +LNs, but more slowly (HR per LN, 1.03; 95% CI, 1.01–1.05; P < 0.001). Similarly, DFS decreased sharply up to 5 LNs (HR per LN, 1.19; 95% CI, 1.1–1.29; P < 0.001), and more gradually beyond this (HR per LN, 1.03; 95% CI, 1.01–1.05; P < 0.001). DM displayed similar behavior to OS and DFS, with risk increasing sharply with each +LN up to 5 (HR per LN, 1.14; 9