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Original Investigation
January 2019

Association Between Lymph Node Ratio and Recurrence and Survival Outcomes in Patients With Oral Cavity Cancer

Author Affiliations
  • 1Department of Radiation Oncology, University of Colorado Denver, Aurora
  • 2Department of Health Systems, Management and Policy, University of Colorado Cancer Center, Aurora
  • 3Department of Otolaryngology and Head and Neck Surgery, University of Colorado Denver, Aurora
  • 4Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California
  • 5Department of Pathology, University of Colorado Denver, Aurora
  • 6Division of Medical Oncology, University of Colorado Denver, Aurora
JAMA Otolaryngol Head Neck Surg. 2019;145(1):53-61. doi:10.1001/jamaoto.2018.2974
Key Points

Question  What is the prognostic association between lymph node ratio and tumor recurrence and survival outcomes of oral cavity squamous cell carcinoma and how does it relate to other histopathologic prognostic factors?

Findings  In this single-institution study of 149 patients with oral cavity cancer who received upfront surgery, lymph node ratio was the strongest independent prognostic factor for overall, disease-free, and distant metastasis–free survivals, regardless of neck dissection or postoperative adjuvant therapy status. Lymph node ratio was also found to correlate significantly with other adverse pathologic features.

Meaning  Lymph node ratio may have implications for risk stratification and treatment intensification in patients with oral cavity squamous cell carcinoma.


Importance  Oral cavity squamous cell carcinoma (OCSCC) is associated with often-delayed clinical diagnosis, poor prognosis, and expensive therapeutic approaches. Prognostic accuracy is important in improving treatment outcomes of patients with this disease.

Objectives  To assess lymph node ratio (LNR) and other factors in estimating response to treatment and provide prognostic information helpful for clinical decision making.

Design, Setting, and Participants  A retrospective cohort study was conducted from January 1, 2000, to December 31, 2015, at an academic hospital in Denver, Colorado. Participants included 149 patients with primary OCSCC who received curative-intent surgery and/or postoperative adjuvant therapies. Analysis was performed from December 8, 2017, to August 15, 2018.

Main Outcomes and Measures  Overall survival (OS), disease-free survival (DFS), locoregional disease-free survival (LRDFS), and distant metastasis–free survival (DMDFS) adjusted for known prognostic risk factors, as well as correlation of LNR with other histopathologic prognostic factors.

Results  Of the 149 patients included in analysis, 105 were men (70.5%); the median age at diagnosis was 59 years (range, 28-88 years). Using the Kaplan-Meier method, the 5-year survival estimates for OS rate was 40.4% (95% CI, 31.3%-49.3%); DFS, 48.6% (95% CI, 38.6%-58.0%); LRDFS, 57.7% (95% CI, 46.6%-67.2%); and DMDFS, 74.7% (95% CI, 65.1%-82.0%). The median follow-up was 20 months for all patients and 34.5 months (range, 0-137 months) for surviving patients. Nonwhite race (hazard ratio [HR], 2.15; 95% CI, 1.22-3.81), T3-T4 category (HR, 1.99; 95% CI, 1.18-3.35), and LNR greater than 10% (HR, 2.71; 95% CI, 1.39-5.27) were associated with poorer OS. Nonwhite patients also had higher risk of locoregional failures (HR, 2.47; 95% CI, 1.28-4.79), whereas women were more likely to have distant metastasis (HR, 2.55; 95% CI, 1.14-5.71). Floor-of-mouth subsite had fewer locoregional recurrences than did other subsites (HR, 0.45, 95% CI, 0.21-0.99). An LNR greater than 10% independently was associated with worse OS (HR, 2.71; 95% CI, 1.39-5.27), DFS (HR, 2.48; 95% CI, 1.18-5.22), and DMDFS (HR, 6.05; 95% CI, 1.54-23.71). The LNR was associated with N-stage (Cramer V, 0.69; 95% CI, 0.58-0.78), extracapsular extension (Cramer V, 0.55; 95% CI, 0.44-0.66), lymphovascular invasion (Cramer V, 0.46; 95% CI, 0.27-0.61); number of excised lymph nodes (Cramer V, 0.24; 95% CI, 0.06-0.37), margin (Cramer V, 0.22; 95% CI, 0.05-0.38), and tumor thickness combined with depth of invasion (Cramer V, 0.25; 95% CI, 0.05-0.38).

Conclusions and Relevance  Locoregional treatment failure remained the predominant pattern of failure. An advanced pathologic stage and nonwhite race were found to be associated with worse outcomes. The findings from this study suggest that LNR is the most robust prognostic factor and appears to have implications for risk stratification in this disease.