Nodal Metastasis Count and Oncologic Outcomes in Head and Neck Cancer: A Secondary Analysis of NRG/RTOG 9501, NRG/RTOG 0234, and EORTC 22931. International journal of radiation oncology, biology, physics Lu, D. J., Luu, M., Gay, C., Nguyen, A. T., Anderson, E. M., Bernier, J., Cooper, J. S., Harari, P. M., Torres-Saaverdra, P. A., Le, Q. T., Chen, M., Mallen-St Clair, J., Ho, A. S., Zumsteg, Z. S. 2022


Better understanding of the relationship between spread of head and neck squamous cell carcinoma (HNSCC) to regional lymph nodes (LN) and the frequency and manner of treatment failure should help design better treatment intensification strategies. In this study, we evaluate the relationship between recurrence patterns, mortality, and number of pathologically positive (+) LN in HNSCC in three prospective randomized controlled trials.Secondary analysis of 947 HNSCC patients enrolled on XXX (N=410), XXX (N=203), and XXX (N=334) undergoing surgery and post-operative radiation +/- systemic therapy.   Multivariable models were constructed for overall survival (OS), disease-free survival (DFS), local-regional relapse (LRR), and distant metastases (DM). Restricted cubic splines were used to model the nonlinear relationship between +LN and outcomes.In multivariable analysis, OS and DFS decreased with each +LN without plateau, most pronounced up to 5 (OS: hazard ratio [HR], 1.19 per +LN; 95% confidence interval [CI], 1.10-1.29; P<0.001; DFS: HR per +LN 1.17, 95% CI 1.08-1.26; P<0.001), and more gradually beyond this (OS: HR per +LN, 1.03; 95% CI, 1.01-1.05; P<0.001; DFS: HR per +LN, 1.03; 95% CI, 1.02-1.05; P<0.001). In contrast to LRR risk, which increased sharply up to 5 +LNs (HR per +LN, 1.25; 95% CI, 1.11-1.39, P<0.001) but plateaued beyond this (HR per +LN, 1.00; 95% CI, 0.967-1.04; P=0.91), DM risk increased continuously with increasing +LN (=5 +LN: HR per +LN, 1.14; 95% CI, 1.01-1.28; P=0.04; >5 +LN, HR per +LN, 1.05; 95% CI, 1.02-1.07; P=0.002).In high-risk resected HNSCC, increased mortality was associated with increased +LN count. LRR and DM risk both increased in parallel up to 5 +LN, but only DM continued to increase for further +LN increases. These differing recurrence patterns can help inform design of future treatments.

View details for DOI 10.1016/j.ijrobp.2022.03.033

View details for PubMedID 35395358