Results
During the study period, 410 patients with salivary gland neoplasms underwent surgery. Of these, 108 patients with salivary gland malignancies met the inclusion criteria. The clinicopathological data are shown in Table 1.
The median age was 57 years and 63 (58.3%) patients were male. Twelve (11.1%) patients had had definitive tumour resection prior to referral to this centre, and all subsequently had a revision resection and/or neck dissection at our centre. Among patients with parotid malignancies, 35 (40.7%) underwent partial or superficial parotidectomy, 41 (47.6%) underwent total conservative parotidectomy, and 10 (11.7%) underwent radical parotidectomy with facial nerve sacrifice. In 75 (87.2%) patients, the facial nerve was preserved.
Neck dissection was performed in 56 (51.8%) patients. Among those with parotid tumours, 35 (32.4%) underwent neck dissection. Of these, 14 (16.3%) underwent level II-III/IV dissection. A further 4 also included level I and 17 also included level V. Ten (11.6%) patients underwent selective sampling of level II alone. 50% of the patients with submandibular gland malignancies underwent neck dissection. Of these, 60% had level I-III/IV clearance while 40% underwent level V dissection as well. Among the minor salivary gland tumours, 5 (41.7%) underwent neck dissection. Of these, 80% had level I-III dissection and 20% had level II-V dissection. In addition, one patient (11.1%) had level II sampling alone.
Histological subtypes encountered are shown in Table 2. Mucoepidermoid carcinoma was the commonest histology seen (22 (20.4%) patients). This was followed by adenoid cystic carcinoma and acinic cell carcinoma (15 (13.9%) each). 71.3% had a pT1-2 tumour and 31% had a pT3-4 tumour. 75% of patients undergoing neck dissection were pN0 and 25% had N-positive disease. ENE was present in 9.3% of all cases and 37% among N-positive patients. There was no significant difference in the incidence of ENE by tumour site (p = 0.91).
Thirty (27.8%) patients had resection margins that were negative (≥5 mm), 19 (17.6%) were close, and 59 (54.6%) were positive. Seventy-eight (72.2%) had either close or positive margins. When grouped by tumour grade, there was no difference in the incidence of close or positive margins (high grade, 72.7%; low grade, 71.4%). For survival analysis, we compared patients with close and negative margins to those with positive margins. 45.4% had close and negative margins and 54.6% had positive margins.
PNI was seen in 40 (37%) patients. On stratification by site, PNI was seen in 32.5% of parotid, 50% of submandibular and 58.3% of minor salivary gland malignancies (p = 0.063). PNI was identified in 80% of adenoid cystic carcinoma, 58.3% of adenocarcinoma, 50% of salivary duct carcinoma, 40% of squamous cell carcinoma and 35.7% of carcinoma ex pleomorphic adenoma. LVI was found in 20 (18.5%) patients and there was no significant difference by site (p = 0.52). A higher incidence of LVI was seen in carcinoma ex-pleomorphic adenoma (35.7%), poorly differentiated cancers (33.3%), adenocarcinoma (33.3%), and salivary duct carcinoma (33.3%). Fifty-six (51.9%) of all patients received adjuvant radiotherapy, while 6.5% received adjuvant chemoradiotherapy. 36.7% of patients with negative margins received adjuvant therapy, whereas 57.9% of those with close margins and 67.8% with positive margins received adjuvant therapy.
Survival outcomes are summarised in Table 1 and Figures 1 and 2. The mean and median follow-up were 46.2 and 36 months. Five-year OS was 81.7%. Mean and median OS for the cohort were 116.1 months (95% CI: 99.2-133) and 128 months (95% CI: 105.4-150.6) respectively. On univariate analysis, age >50 years, pT stage 3-4, higher tumour grade, PNI, advanced TNM stage (III-IV), and adjuvant chemoradiotherapy adversely affected OS. Patients who received adjuvant radiotherapy had a superior mean OS (122.0 months) compared to those not given adjuvant therapy (101.7 months) (p = 0.025). Those who received adjuvant chemoradiation had an inferior OS (67.2 months).
When we compared patients by TNM stage (I-II versus III-IV), we found that even in early-stage disease, adjuvant radiation therapy improved the median survival (123.8 versus 114 months). In higher TNM stages, patients receiving adjuvant radiation had superior overall survival (73.3 months) compared to those treated with adjuvant chemoradiation (67.2 months) or no adjuvant therapy (44.2 months). There were no deaths in patients with submandibular gland or other minor salivary gland tumours. Owing to a lack of events, assessment based on site stratification could not be performed.
Recurrence and distant metastases were noted in 18 patients: 8 had local recurrence, 2 had regional recurrence, and 8 developed distant metastases. Of these, 13 patients were alive with disease at last known follow-up. Overall in the entire cohort, 17 (XX%) patients had died (3 from the index cancer and 14 from other causes).
At five years, 73 (71%) patients were alive and disease-free. The mean and median DFS were 98.4 months (95% CI: 82.3-114.5 months) and 118 months (95% CI: 61.4-174.6 months) respectively. DFS was found to be significantly better in patients with age <50 years, early pT classification, no PNI or LVI, lower-grade tumours, and early TNM stage (Table 1). We compared patients with close and negative resection margins to those with positive margins. Although the former had a better DFS (118 months versus 73 months), this finding was not statistically significant. Multivariate analysis using logistic regression was attempted to assess the impact of various covariates on OS and DFS using the covariates found to be significant on univariate analysis (Table 3). None of the factors was found to affect OS or DFS in a statistically significant manner.