A clinicopathological study and prognostic factor analysis of 177 salivary duct carcinoma patients from The Netherlands

Abstract

Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in-situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and-to a lesser extent-HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting.

Keywords: ErbB-2; androgen receptors; fluorescence; immunohistochemistry; in situ hybridization; prognosis; receptor; salivary duct carcinoma; salivary gland neoplasms; survival.

Figure 1

Consort diagram of inclusion of SDC patients. PALGA is the Nationwide Network and Registry of Histo‐ and Cytopathology in the Netherlands.

Figure 2

Tumor‐positive lymph nodes are plotted against the total number of lymph nodes during neck dissection (number of patients = 126). The dark blue line represents the line at which all resected lymph nodes would have been tumor positive. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Patterns of disease recurrence. (a) Breakdown of local and regional recurrences and distant metastases in 87 patients with a recurrence. The numbers in the circles represent the absolute number of patients with local and regional recurrences and the presence of distant metastases. Patients with primarily metastatic disease are not included in this figure. (b) Localization of distant metastases sorted by percentage of presence in 84 patients with distant metastases. Patients with primarily metastatic disease were included in this figure. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Kaplan–Meier curves for overall survival (OS), disease‐free survival (DFS) and distant metastasis free survival (DMFS) based on data of 177 SDC patients. (a) Kaplan–Meier curve for OS based on data of 177 SDC patients. Estimated median OS was 51 months (95% CI 40–61 months). (b) Kaplan–Meier curves for DFS based on data of 177 SDC patients. Estimated median DFS was 23 months (95% CI 18–27 months). (c) Kaplan–Meier curve of DMFS based on data of 177 SDC patients. Estimated median DMFS was 26 months (95% CI 20–34 months). [Color figure can be viewed at http://wileyonlinelibrary.com]