Development of a novel salivary gland cancer lymph node staging system

Abstract

Background: Current lymph node (LN) staging for salivary gland cancer (SGC) is extrapolated from mucosal head and neck squamous cell carcinoma. However, given its unique biology and clinical behavior, it is possible that a SGC-specific LN staging system would be more accurate.

Methods: Patients from the National Cancer Data Base with nonmetastatic SGC of the head and neck who were diagnosed from 2004 through 2013 and underwent surgical resection and neck dissection removing at least 10 LNs were included. Multivariable models were constructed to assess the association between survival and LN factors, including number of metastatic LNs, extranodal extension, LN size, and lower LN involvement.

Results: Overall, 4520 patients met the inclusion criteria. An increasing number of metastatic LNs was found to be strongly associated with worse survival without plateau. The risk of death increased more rapidly up to 4 LNs (hazard ratio, 1.34; 95% confidence interval, 1.27-1.41 [P < .001]), and was more gradual for additional LNs >4 (hazard ratio, 1.02; 95% confidence interval, 1.01-1.03 [P < .001]). LN size, extranodal extension, and lower LN involvement appeared to have no impact on survival when accounting for the number of metastatic LNs. Recursive partitioning analysis was used to create a novel SGC LN staging system in which N0 indicates 0 positive LNs, N1 indicates 1 to 2 positive LNs, N2 indicates 3 to 21 positive LNs, and N3 indicates ≥ 22 positive LNs. This system exhibited greater concordance than the current American Joint Committee on Cancer (eighth edition) system.

Conclusions: Quantitative LN burden is an important determinant of survival in patients with SGC. Use of this variable may improve SGC staging. Cancer 2018. © 2018 American Cancer Society.

Keywords: lymph nodes; neck dissection; salivary gland cancer; staging.

Figure 1

The adjusted hazard ratio of death as a non-linear function of A) number of positive lymph nodes, with 0 positive lymph nodes as a reference, and B) number of lymph nodes examined, with 10 lymph nodes examined as a reference, for patients with salivary gland cancer. The gray area represents the 95% confidence interval of the natural logarithm of the predicted hazard ratios. The black curve represents the smoothed restricted cubic spline plot of the natural logarithm of the predicted adjusted hazard ratio for survival versus number of lymph nodes. The black vertical lines represent the calculated change point of 4 positive lymph nodes and 33 lymph nodes examined, respectively, for the hazard of death as a function of lymph node number.

Figure 2

Defining a novel nodal staging system for salivary gland cancer in patients with determinable American Joint Commission on Cancer (AJCC) 8^th edition stage, using recursive partitioning analysis based on number of positive lymph nodes.

Figure 3

Kaplan-Meier estimates for the A) proposed and B) AJCC 8^th edition N classification systems in salivary gland cancers.

Figure 4

Kaplan-Meier estimates for the proposed composite stage grouping, based on the sum of the American Joint Commission on Cancer (AJCC) 8^th edition pathologic tumor classification and the proposed nodal classification. Patients with equal sums of these two classifications were grouped together (Stage I: T1N0, Stage II: T2N0/T1N1, Stage IIIA: T3N0/T2N1/T1N2, Stage IIIB: T3N1/T4N0/T2N2/T1N3, Stage IIIC: T4N1/T3N2/T2N3, Stage IVA: T4N2/T3N3, Stage IVB: T4N3).