Ardalan Ebrahimi1, Ruta Gupta2, Peter Luk2, Tsu-Hui Hubert Low3, Lachlan McDowell4, Matthew J R Magarey5, Paul N Smith6, Diana M Perriman6, Klaus-Martin Schulte6, Michael Veness7, Sandro V Porceddu8, Jonathan R Clark9. 1. Medical School, College of Health and Medicine, Australian National University, Canberra, Australia; Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Department of Head and Neck Surgery, The Canberra Hospital, Canberra, Australia. Electronic address: ardalan@specialistheadandneck.com. 2. Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, Australia; Sydney Medical School, The University of Sydney, Sydney, Australia. 3. Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, Sydney, Australia. 4. Department of Radiation Oncology, Peter MacCallum Cancer Centre, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia. 5. Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 6. Medical School, College of Health and Medicine, Australian National University, Canberra, Australia. 7. Sydney Medical School, The University of Sydney, Sydney, Australia; Department of Radiation Oncology, Westmead Hospital, Sydney, Australia. 8. Faculty of Medicine, The University of Queensland, Brisbane, Australia; Radiation Oncology Department, Princess Alexandria Hospital, Brisbane, Australia. 9. Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, Sydney, Australia; Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Sydney, Australia.
Abstract
OBJECTIVES: We aimed to determine if the number of nodal metastases is an independent predictor of survival in HNcSCC, whether it provides additional prognostic information to the AJCC N and TNM stage and identify optimal cut-points for risk stratification. MATERIALS AND METHODS: Retrospective multi-institutional cohort study of patients with parotid and/or cervical nodal metastases from HNcSCC treated with curative intent by surgery ± adjuvant therapy. The impact of number of nodal metastases on disease-specific and overall survival was assessed using multivariate Cox regression. Optimal cut-points for prognostic discrimination modelled using the AIC, BIC, C-index and PVE. RESULTS: The study cohort included 1128 patients, with 962 (85.3%) males, median age of 72.9 years (range: 18-100 years) and median follow-up 3.4 years. Adjuvant radiotherapy was administered to 946 (83.9%) patients. Based on objective measures of model performance, number of nodal metastases was classified as 1-2 (N = 816), 3-4 (N = 162) and ≥5 (N = 150) nodes. In multivariate analyses, the risk of disease-specific mortality progressively increased with 3-4 nodes (HR, 1.58; 95% CI: 1.03-2.42; p = 0.036) and ≥5 nodes (HR, 2.91; 95% CI: 1.99-4.25; p < 0.001) with similar results for all-cause mortality. This simple categorical variable provided superior prognostic information to the TNM stage. CONCLUSION: Increasing number of nodal metastases is an independent predictor of mortality in HNcSCC, with categorization as 1-2, 3-4 and ≥5 nodes optimizing risk stratification and providing superior prognostic information to TNM stage. These findings may aid in the development of future staging systems as well as identification of high-risk patients in clinical trials.
OBJECTIVES: We aimed to determine if the number of nodal metastases is an independent predictor of survival in HNcSCC, whether it provides additional prognostic information to the AJCC N and TNM stage and identify optimal cut-points for risk stratification. MATERIALS AND METHODS: Retrospective multi-institutional cohort study of patients with parotid and/or cervical nodal metastases from HNcSCC treated with curative intent by surgery ± adjuvant therapy. The impact of number of nodal metastases on disease-specific and overall survival was assessed using multivariate Cox regression. Optimal cut-points for prognostic discrimination modelled using the AIC, BIC, C-index and PVE. RESULTS: The study cohort included 1128 patients, with 962 (85.3%) males, median age of 72.9 years (range: 18-100 years) and median follow-up 3.4 years. Adjuvant radiotherapy was administered to 946 (83.9%) patients. Based on objective measures of model performance, number of nodal metastases was classified as 1-2 (N = 816), 3-4 (N = 162) and ≥5 (N = 150) nodes. In multivariate analyses, the risk of disease-specific mortality progressively increased with 3-4 nodes (HR, 1.58; 95% CI: 1.03-2.42; p = 0.036) and ≥5 nodes (HR, 2.91; 95% CI: 1.99-4.25; p < 0.001) with similar results for all-cause mortality. This simple categorical variable provided superior prognostic information to the TNM stage. CONCLUSION: Increasing number of nodal metastases is an independent predictor of mortality in HNcSCC, with categorization as 1-2, 3-4 and ≥5 nodes optimizing risk stratification and providing superior prognostic information to TNM stage. These findings may aid in the development of future staging systems as well as identification of high-risk patients in clinical trials.