Minor salivary gland tumors of the head and neck-Memorial Sloan Kettering experience: Incidence and outcomes by site and histological type.

BACKGROUND: Minor salivary gland carcinomas of the head and neck are rare cancers with variable clinical behavior. This study explored the incidence, pathology, clinical behavior, and factors predictive of outcomes in a large cohort of patients treated at Memorial Sloan Kettering Cancer Center over a 30-year period (1985-2015). METHODS: Clinical, pathological, treatment, and outcome data were collected. Unadjusted and adjusted hazard ratios for each variable were calculated with univariate and multivariable Cox regression for survival and recurrence outcomes. RESULTS: Four hundred fifty patients were included: 55% were female, 56% were younger than 60 years, and the median follow-up was 74 months (range, 1-364 months). The most common site was the oral cavity with 305 tumors (68%), which was followed by the oropharynx with 96 (21%), the sinonasal cavity with 38 (8%), the trachea with 7 (2%), and the larynx with 4 (1%). The most common histological types were mucoepidermoid carcinoma (180 tumors [40%]), adenoid cystic carcinoma (141 tumors [31%]), and polymorphous low-grade adenocarcinoma (54 tumors [12%]). The 5-year predicted overall survival rate was 86%, and the disease-specific survival rate was 94% at 5 years. Pathology and tumor stage were significant variables on multivariate analysis for overall survival, disease-specific survival, recurrence-free survival, local recurrence-free survival, regional recurrence-free survival, and distant recurrence-free survival. CONCLUSIONS: American Joint Committee on Cancer stage and pathology were the most predictive variables across all outcomes. Tumor site, postoperative radiotherapy, and margin status were not statistically significant variables after tumor stage and pathology were controlled for in most outcomes.

Postoperative iodine-125 interstitial brachytherapy for the early stages of minor salivary gland carcinomas of the lip and buccal mucosa with positive or close margins.

BACKGROUND: The purpose of this study was to present our preliminary exploration of safety and efficacy of postoperative low-dose-rate brachytherapy for the early clinical stages of minor salivary gland carcinomas of the lip and buccal mucosa. METHODS: Twenty-seven patients with the early stages of minor salivary gland carcinomas of the lip and buccal mucosa received postoperative 125 I seed interstitial brachytherapy from March 2005 to May 2015. Actuarial likelihood estimates for local control, overall survival, and disease-free survival were calculated by Kaplan-Meier method. RESULTS: The actuarial 3-year, 5-year, and 10-year local control rates were 94.7%, 82.9%, and 82.9%, respectively. The actuarial 3-year, 5-year, and 10-year overall survival rates were 93.3%, 93.3%, and 77.8%, respectively. No patient experienced toxicity above grade 2. CONCLUSION: Postoperative 125 I seed interstitial brachytherapy is an alternative to radical surgery for early stages of minor salivary gland carcinomas of the lip and buccal mucosa, which offers satisfactory cosmetic and functional outcomes. © 2017 Wiley Periodicals, Inc. Head Neck 39: 572-577, 2017.

Radiation therapy in the treatment of minor salivary gland tumors.

PURPOSE: Minor salivary gland cancers are rare and account for roughly 2% to 3% of all head and neck tumors. This is a retrospective review in a modern cohort of patients treated for this rare cancer with surgery and adjuvant radiation therapy. MATERIALS AND METHODS: Between February 1990 and December 2010, 98 patients with cancer of the minor salivary glands were identified and treated at a single institution. The median radiation dose was 63 Gy. Outcomes assessed included local control (LC), locoregional control (LRC), and overall survival (OS). Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 3.0. Competing-risk analysis using the Gray test was performed, with death as the competing risk. OS was calculated by the Kaplan-Meier method. RESULTS: With a median follow-up of 7.3 years, the 5- and 10-year LC and LRC rates were 87.9% and 83%, and 80.5% and 73.7%, respectively. Higher T stage and adenocarcinoma histology were the significant negative prognostic factors for both LC and LRC. Freedom from distant metastasis at 5 and 10 years were 83% and 63%, respectively. The median OS was 19.6 years. Overall, no grade 4 or 5 toxicities occurred, and 20% of the cohort experienced an acute grade 3 toxicity, and 6% with a grade 3 late toxicity. CONCLUSIONS: In a modern cohort treated with surgery and radiotherapy, excellent outcomes can be achieved with lower toxicity rates compared with older published series.

Relapsing high grade mucoepidermoid carcinoma. Long-lasting complete response following reirradiation and EGFR blockade.

BACKGROUND AND PURPOSE: The treatment strategy for inoperable recurrent mucoepidermoid carcinoma (MEC) is not well established. Here, we present a case of a relapsed high grade MEC of the salivary glands of the hard palate that was successfully treated with a reirradiation (re-RT) and cetuximab, an antibody against epidermal growth factor receptor (EGFR). CASE REPORT: Twelve years after resection and adjuvant radiotherapy for high grade MEC of the salivary glands, a patient presented with inoperable recurrent disease. She received another 59.4 Gy. In addition, 400 mg/m(2) cetuximab was administered in the first week, followed by six additional weekly courses at 250 mg/m(2). RESULTS: Treatment was well tolerated. The patient is doing well and continuous radiological complete response (CR) is documented for 25 months after completion of the combined treatment. CONCLUSION: Combined re-RT and targeted inhibition of EGFR with cetuximab may be a valuable therapeutic strategy in patients with recurrent localized high grade MEC who are not candidates for radical surgery.

Reducing xerostomia after chemo-IMRT for head-and-neck cancer: beyond sparing the parotid glands.

PURPOSE: To assess whether, in addition to sparing the parotid glands (PGs), xerostomia after chemotherapy plus intensity-modulated radiotherapy (chemo-IMRT) for head-and-neck cancer is affected by reducing the dose to the other salivary glands. PATIENTS AND METHODS: In a prospective study, 78 patients with Stage III-IV oropharynx/nasopharynx cancer underwent chemo-IMRT, with the aim of sparing the parts of the bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) outside the target (when contralateral level I was not a target). Before therapy and periodically for 24 months, validated patient-reported xerostomia questionnaire (XQ) scores and observer-graded xerostomia scores were recorded. Also, the stimulated and unstimulated saliva was measured selectively from each of the PGs and SMGs. The mean OC doses served as surrogates of minor salivary gland dysfunction. Regression models assessed the XQ and observer-graded xerostomia predictors. RESULTS: Statistically significant predictors of the XQ score on univariate analysis included the OC, PG, and SMG mean doses and the baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. The OC, PG, and SMG mean doses were moderately intercorrelated (r = 0.47-0.55). On multivariate analyses, after adjusting for the PG and SMG doses, the OC mean dose (p < .0001), interval from RT (p < .0001), and stimulated PG saliva (p < .0025) were significant predictors of the XQ scores and the OC mean dose and time for observer-graded xerostomia. Although scatter plots showed no thresholds, an OC mean dose of <40 Gy and contralateral SMG mean dose of <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy points. CONCLUSION: The PG, SMG, and OC mean doses were significant predictors of both patient-reported and observer-rated xerostomia after chemo-IMRT, with OC doses remaining significant after adjusting for the PG and SMG doses. These results support efforts to spare all the salivary glands by IMRT, beyond the PGs alone.

A prospective study of salivary gland function in lymphoma patients receiving head and neck irradiation.

PURPOSE: To determine the radiation dose-response relationship on salivary dysfunction and quality of life (QOL) over time in patients with lymphoma receiving radiation therapy (RT) to the head and neck (H&N). METHODS AND MATERIALS: We conducted a prospective study on salivary-gland function in lymphoma patients receiving RT to the H&N. Fifteen patients were enrolled on the study. Dose-volume histograms and mean doses to the salivary glands were generated. Radiation-related toxicities and H&N-specific QOL were assessed before treatment and at prespecified time points posttreatment. Factors predicting a decrement in QOL were explored using Fisher's exact test. RESULTS: During RT, 47% of patients experienced Grade >or= 2 acute toxicity of the salivary gland, mucous membrane, or both. QOL scores improved over time, but up to one third of patients continued to have persistent oral symptoms at 2 years. At 6 months, a mean dose to at least one of the parotids of > 31 Gy was significantly associated with persistent dry mouth (100% vs. 17%, p = 0.02) and sticky saliva (100% vs. 25%, p = 0.04); a mean dose of > 11 Gy to the minor salivary glands was significantly associated with persistent sticky saliva (100% vs. 25%, p = 0.04), although the difference was no longer significant at 1 year. CONCLUSIONS: Limiting the mean parotid dose to

Minor gland saliva flow rate and proteins in subjects with hyposalivation due to Sjogren's syndrome and radiation therapy.

In this study, the secretion rate and IgA, albumin and lactoferrin concentrations in minor labial and buccal gland saliva were investigated in individuals with hyposalivation due to primary Sjogren's syndrome (pSS; 10 subjects) or head and neck radiation therapy (RT; 10 subjects) and in their matched controls. Whole saliva was similarly examined. The minor gland saliva flow was measured using the Periotron method. IgA, albumin and lactoferrin concentrations were analysed by ELISA techniques. A general finding was that the flow rate and protein concentrations were lower in labial than in buccal gland saliva. In both hyposalivation groups, the labial minor gland saliva secretion rate was lowered compared to their respective controls. The buccal gland saliva flow rate was significantly reduced in the RT group only. IgA and albumin concentrations were not different from the controls in the labial secretions. The concentration of lactoferrin was increased in the RT group. In buccal saliva, the concentrations of all proteins examined but pSS IgA, were increased compared to the controls. Reduced flow rate and increased protein concentrations were seen for whole saliva where the lactoferrin concentration was higher in RT than in pSS subjects. Thus, our findings suggested that minor gland saliva flow rate and protein concentrations are affected in RT and pSS subjects and to highest extent in the former.

Effect of 24 hours light on circadian rhythms of secretory enzymes and morphology of rat von Ebner's glands.

Von Ebner's glands of the rat are minor salivary serous glands in the posterior portion of the tongue. They secrete two digestive enzymes, lingual lipase and amylase. In this investigation, circadian rhythm in feeding was established under a normal 12 h light/12 h dark cycle, with the rats eating primarily during the dark period. At lights on, the size of the acinar cells and the area of the inclusive secretory granules, and the amount of digestive enzyme activity (lingual lipase and amylase) remaining in the gland was significantly less than in the mid-afternoon, after very little daylight food consumption. However, after 7 days of continuous light the circadian rhythm was altered: the food consumption during the normal night-time hours (5 p.m. to 8 a.m.) went from 88% of total 24 h food consumption to 45%, and during normal daylight hours (8 a.m. to 5 p.m.) from 12% to 55%. These changes were correlated with histometric findings of a near reversal of the areas of acinar cells and secretory granules of a.m. and p.m. samples under continuous light. Lingual lipase activity in the glands went from 35% under 12 h light to 61% under continuous light in the a.m. and from 65% to 39% in the p.m. Amylase activity also showed nearly a reversal in activity remaining in the gland, from 36% at 12 h light to 58% at 24 h light in the a.m. and 64% to 41% for the p.m. samples. These results indicate that the von Ebner's glands of the rat have a circadian rhythm of secretion and storage of secretory proteins that is subject to light entrainment similar to that seen in other exocrine glands such as the parotid and pancreas.

Radiation-induced hyposalivation and its treatment with oral pilocarpine.

OBJECTIVE: The aim of this study was to determine the effects of radiation on the secretion of saliva from mucous salivary glands in comparison with serous salivary glands. STUDY DESIGN: The minor salivary glands of the palate were used as an example of mucous glands, while the parotid glands were used as an example of a serous secretion organ. Serial flow rate measurements of the parotid and palatal glands were taken over a period of approximately 9 months in 13 patients who suffered from malignancies of the head and neck region. Twelve patients consented to take part in a second study in which salivary flow was stimulated by oral pilocarpine before and at the conclusion of radiotherapy and 7 months later. Complaints and symptoms were recorded at each time of measurement. RESULTS: After radiotherapy, the secretory performance of the parotid glands dropped off rapidly and irreversibly. Salivary secretion from the palatal glands was not totally diminished as a result of radiation. Clinical complaints and histologic findings indicate a serious alteration of the tissues irradiated; however, residual secretion from the remaining parenchyma of the mucous glands still remains. Pilocarpine produced a clinically significant increase of salivary flow from the palatal glands before and 7 months after radiation. Secretory performance of the parotid glands could not be sufficiently increased by stimulation with pilocarpine after radiotherapy. Clinical side effects and risks for the treatment of symptomatic postradiation xerostomia with pilocarpine were minimal. CONCLUSIONS: These findings emphasize the greater resistance and recoverability of the mucous secreting minor palatal glands in comparison with the serous secreting parotid glands. They also indicate the significant postradiation ability of the mucous secreting glands to be stimulated by pilocarpine.

Structural and cytochemical modifications in the lingual glands of the newborn chicken irradiated with He-Ne laser.

Despite the increasing and successful use of laser in Medicine and Odontology, the possible iatrogenic and otherwise deleterious side effects of this radiation remain mostly unknown. In previous studies, it was shown that both the embryonic and the post-hatched chicken constitute reliable experimental models for this type of studies. Hence, the purpose of the present work was to analyze the structural and cytochemical alterations of the lingual glands of the newborn chicken irradiated with low energy He-Ne laser. This laser produced regressive structural changes of the glands towards the embryonic stage as well as hyperplasia of the reserve glandular basal cells. Furthermore, a decrease in the glycoprotein content and a rise in the sulphated glycosaminoglycans were also found. These results corroborate the pathogenic effects of the He-Ne- laser on the experimental model employed and, at the same time, emphasize the importance of considering, regarding clinical applications, possible previous neoplastic alterations as well as adverse reactions which might appear once laser therapy has been installed.