Management of malignant submandibular gland tumors: A 30-year experience from a single center.

OBJECTIVE: Owing to histologic heterogeneity, biological behavior, and rarity, recommendations for the treatment of malignant submandibular gland tumors (MSGT) are inconsistent. The aim of this study was to present a single-center experience in the treatment of MSGT with an emphasis on surgical treatment, including indication on elective neck dissection (END). STUDY DESIGN: Twenty-four MSGT were primary surgically treated (gland excision with neck dissection). Their records were retrospectively collected and analyzed. RESULTS: The most frequent histology was adenoid cystic carcinoma (41.6%), followed by mucoepidermoid carcinoma (25%) and carcinoma ex pleomorphic adenoma (16.7%). There were 18 elective and 6 therapeutic neck dissections. Histopathologic examination confirmed 29% (7/24) of positive neck dissection specimens. The Kaplan-Meier analysis presented rates of disease-specific survival, disease-free survival, and overall survival (OS) of 81%, 78%, and 52% at 5 years, respectively. Patients undergoing postoperative radiotherapy had significantly higher OS rates compared with patients treated with surgery alone (P = .0209). CONCLUSION: Results of this study suggest that END has questionable benefit in early stage MSGT. Elective selective neck dissection levels I-III is recommended in high-grade and advanced stage MSGT without evidence of multilevel lymphadenopathy.

Dose-volume derived nomogram as a reliable predictor of radiotherapy-induced hypothyroidism in head and neck cancer patients.

Background The aim of this study was to determine the possible predictive value of various dosimetric parameters on the development of hypothyroidism (HT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. Patients and methods This study included 156 patients with HNSCC who were treated with (chemo)radiotherapy in a primary or postoperative setting between August 2012 and September 2017. Dose-volume parameters as well as V10 toV70, D02 to D98, and the VS10 to VS70 were evaluated. The patients' hormone status was regularly assessed during follow-up. A nomogram (score) was constructed, and the Kaplan-Maier curves and Log-Rank test were used to demonstrate the difference in incidence of HT between cut-off values of specific variables. Results After a median follow-up of 23.0 (12.0-38.5) months, 70 (44.9%) patients developed HT. In univariate analysis, VS65, Dmin, V50, and total thyroid volume (TTV) had the highest accuracy in predicting HT. In a multivariate model, HT was associated with lower TTV (OR 0.31, 95% CI 0.11-0.87, P = 0.026) and Dmin (OR 9.83, 95% CI 1.89-108.08, P = 0.042). Hypothyroidism risk score (HRS) was constructed as a regression equation and comprised TTV and Dmin. HRS had an AUC of 0.709 (95% CI 0.627-0.791). HT occurred in 13 (20.0%) patients with a score < 7.1 and in 57 (62.6%) patients with a score > 7.1. Conclusions The dose volume parameters VS65, Dmin, V50, and TTV had the highest accuracy in predicting HT. The HRS may be a useful tool in detecting patients with high risk for radiation-induced hypothyroidism.

Elective neck dissection in adenoid cystic carcinoma of head and neck: yes or no? A systematic review.

PURPOSE: Adenoid cystic carcinoma of head and neck (AdCCHN) is salivary gland malignancy known for its slow progression accompanied with perineural invasion, rare lymphatic spread to the neck, high rate of local recurrence and delayed onset of distant metastases. While local recurrence and distant metastases are most common patterns of relapse and cause of death in AdCCHN, it has been debated whether lymph node involvement affects the course of the disease. The aim of this systematic review was to address this important issue and to recommend guidelines on clinically node-negative neck management in patients with AdCCHN. METHODS: A systematic review of the published literature on cases of elective neck dissection (END) among patients with AdCCHN was performed. RESULTS: This analysis included a total of 5767 AdCCHN patients with 2450 ENDs, ranging from 10 to 1190. Elective lymphadenectomy was employed in 42.5% of patients with AdCCHN (range 9.2-100%). The overall rate of occult neck metastases in patients with AdCCHN was reported to range between 0 and 43.7%, the average being 13.9%. CONCLUSIONS: If performed, END should be limited to levels I-III of the ipsilateral neck since occult metastases are exclusively located within these neck regions. Although END is associated with a prolonged regional recurrence-free period, it influence on final outcome or survival is still controversial. This review strongly supports conduction of prospective trials on indications, prognostic significance and extent of END in AdCCHN.

Cisplatin-based chemoradiotherapy vs. cetuximab-based bioradiotherapy for p16-positive oropharyngeal cancer: an updated meta-analysis including trials RTOG 1016 and De-ESCALaTE.

PURPOSE: Human papilloma virus (HPV)-associated oropharyngeal cancer (OPC) is a special entity among head and neck squamous cell carcinomas (HNSCCs). Given its favorable prognosis, one of the de-escalating strategies in the treatment of OPC includes the introduction of cetuximab (C225) instead of cisplatin (CDDP) in conjunction with radiotherapy. An updated meta-analysis of published studies has been performed, which directly compared the efficacy of CDDP vs. C225 given concurrently with radiotherapy as definitive treatment of p16-positive OPC. METHODS: A systematic literature search was performed for studies published between 2006 and 2018. A total of 1490 citations were obtained and 8 studies met inclusion criteria, with a total of 1665 patients. RESULTS: The data from seven studies were available for the analysis of 2-year overall survival (OS). Calculated pooled OR for CDDP-based chemoradiotherapy vs. C225-based bioradiotherapy, was 0.45 (P < 0.0001). The data from eight studies were available for the analysis of 2-year locoregional recurrence (LRR). Calculated pooled OR for CDDP-based chemoradiotherapy vs. C225-based bioradiotherapy was 0.35 (P < 0.0001). Patients receiving CDDP with irradiation had 2.2- and 2.9-fold decreased risk for death from any cause and LRR, respectively. CONCLUSIONS: For patients with HPV-positive OPC, radiotherapy plus C225 showed inferior OS and higher LRR rates compared with radiotherapy plus CDDP. CDDP-based chemoradiotherapy should remain standard of definitive treatment of p16-positive OPC.

Prognostic significance of bone morphogenetic protein 6 (BMP6) expression, clinical and pathological factors in clinically node-negative oral squamous cell carcinoma (OSCC).

Bone morphogenetic protein 6 (BMP6) has unique properties regarding structure and function in supporting bone formation during development and adult life. Despite its known role in various malignant tumors, the prognostic significance of BMP6 expression in oral squamous cell carcinoma (OSCC) remains unknown. The aim of the study was to investigate immunohistochemical expression of BMP6 in OSCC in correlation with clinical and pathological parameters, disease recurrence and survival. In addition, we investigated other parameters in order to identify prognosticators of neck metastases and final outcome. The study included 120 patients with clinically T1-3N0 OSCC who were primarily surgically treated between 2003 and 2008. There were 99 (82.5%) male and 21 (17.5%) female patients. The five-year disease-specific survival for the whole cohort was 79.7%. Tumors smaller than 2 cm in diameter showed higher incidence of strong BMP6 expression. No statistical correlation was observed between other clinico-pathological factors and BMP6 expression. Expression of BMP6 was not associated with disease recurrence and survival. BMP6 may not serve as prognosticator of final outcome or recurrence in clinically node-negative OSCC subjects. In multivariate analysis predictors of poorer survival were positive surgical margin, moderate tumor cell differentiation and pathological involvement of levels IV and/or V.

Outcomes for patients with second primary malignancy after primary surgical treatment for early-stage squamous cell carcinoma of the oral cavity.

BACKGROUND: The purpose of our article was to describe a tertiary center's experience with patients with primarily surgically treated early-stage intraoral cancer with a second primary malignancy confirmed during follow-up. METHODS: A total of 183 patients were primarily surgically treated for oral cancer between 2000 and 2004. Among these, 24 patients (13.1% (24/183)) met inclusion criteria. RESULTS: There were 22 men (91.7%) and 2 women (8.3%) with a median age of 59.5 years. Patients with head and neck cancer with a second primary malignancy had significantly higher survival compared to nonhead and neck cancer with a second primary malignancy. Patients with head and neck cancer with second primary malignancy were diagnosed during the period of 14 to 45 months (median 29 months), whereas nonhead and neck cancer with second primary malignancy occurred in a period of 7 to 46 months (median 19 months). CONCLUSION: This study highlights the importance of optimizing screening strategies for second primary malignancies. In order to improve the survival of patients with head and neck squamous cell carcinoma (HNSCC), effective programs of screening and/or chemoprevention of second primary malignancies are essential.

Predictive markers for delayed lymph node metastases and survival in early-stage oral squamous cell carcinoma.

BACKGROUND: The purpose of this study was to identify clinicopathological and immunohistochemical factors predicting delayed lymph node metastases and survival in early oral squamous cell carcinoma (OSCC). METHODS: The study included 85 consecutive patients with clinically T1 to T2N0 OSCC who were primarily surgically treated between 2000 and 2004. RESULTS: There were 68 men and 17 women (median age, 61 years; range, 34-82 years). Of all the patients, 25 (29.4%) developed delayed lymph node metastases within 3 to 42 months after treatment of the primary tumor. Multivariate logistic regression analysis identified poorly differentiated tumors, low laminin, and high fibronectin expression as prognosticators of delayed lymph node metastases. Cox's proportional hazards regression analysis demonstrated that moderately differentiated tumors and delayed lymph node metastases had predictive value regarding survival. CONCLUSION: Large prospective investigations with reproducibility and the clinical translatability of immunohistochemical methods are needed in order to provide new and effective therapeutic strategies in the future. © 2016 Wiley Periodicals, Inc. Head Neck 39: 694-701, 2017.

The prognostic significance of estrogen receptor ß in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world. Although multimodal and targeted therapy is now used in therapeutic procedures, the survival of patients with HNSCC has remained unchanged over the last 30 years. A number of studies have demonstrated that the increased expression of intranuclear ERß in breast, lung and colon cancer is a favorable prognostic marker associated with higher survival rates. However, the clinical significance of sex hormone receptors in HNSCC remains unclear. The current study aimed to assess the expression of ERß in HNSCC immunohistochemically and investigate any possible association between ERß expression, and clinical and histopathological factors, disease recurrence and patient survival. The present study included 174 patients (165 males and 9 females) with a median age of 60.8 years (range, 39-79) with HNSCC who were primary surgically treated between January 2000 and December 2006. Immunohistochemical reactions for ERß demonstrated that 73 patients (42%) exhibited positive ERß expression. Distribution of ERß status among different head and neck subsites indicated that >40% of all negative cases were located in laryngeal primaries, while incidence of other sublocalization within positive cases was similar and comparable (P=0.04). Furthermore, a correlation was observed between ERß immunopositivity and the survival of patients, with respect to the primary tumor site. Patients with ERß positive oropharyngeal cancer had a survival rate of 35.3% at 5-years compared with 25% for patients with negative expression. However, ERß status was not significantly correlated with any other clinical or histopathological parameter. After an average follow-up time of 38.5 months (range, 3-60 months), 54 patients (31.1%) had succumbed to disease recurrence while 50 (28.7%) succumbed to other causes. In conclusion, ERß positivity indicates improved survival of patients with oropharyngeal cancer. Further research is required in order to implement novel therapeutic strategies.

Adenoid cystic carcinoma of the head and neck: a single-institution's analysis of 45 consecutive cases over a 29-year period.

OBJECTIVE: A series of patients with head and neck adenoid cystic carcinoma (ACC) was studied with respect to treatment modalities, recurrence, survival and prognostic factors. STUDY DESIGN: Between August 1984 and December 2013, 45 patients with ACC of the head and neck who were primary surgically treated at our institution were retrospectively reviewed. RESULTS: Disease-specific survival (DSS) rates at 5, 10, and 15 years were 85%, 79.4%, and 65.7%, respectively. Tumors of the major salivary glands had a better DSS. Patients with ACC of the paranasal sinuses or nasal cavity had poorer survival compared with other head and neck subsites, although this correlation did not reach statistically significant level. DSS rates were 81.5% at 5 years, 70.5% at 10 years, and 31.3% at 15 years for patients with perineural invasion (PNI) compared with 88.9% for those patients who did not have PNI (P = .01). Follow-up ranged from 7 to 337 months (mean 129.4 months). CONCLUSIONS: ACC is a unique malignant salivary gland tumor associated with prolonged survival even in metastatic settings, which emphasizes the necessity for lifetime follow-up as well as more active oncologic treatment. In our study, survival was adversely affected by the primary tumor site and PNI.

Intraoral adenoid cystic carcinoma: is the presence of perineural invasion associated with the size of the primary tumour, local extension, surgical margins, distant metastases, and outcome?

Adenoid cystic carcinoma is the most common malignancy of the minor salivary glands, and its biological behaviour is characterised by slow and indolent growth; rare involvement of regional lymph nodes; a high propensity for perineural invasion; multiple or delayed recurrences, or both; and a high incidence of distant metastases. Our aim was to find out the relation between the presence of perineural invasion and these factors. Between 1 January 1984 and 1 May 2008, 26 cases of adenoid cystic carcinoma of the intraoral salivary glands, which had initially been treated surgically, were reviewed retrospectively. The most common site was the palate, and perineural invasion was reported in 13 of the 26 resected specimens. There was no significant association between it and the size of the primary tumour (OR=1.0; p=1.00), invasion of the surgical margins (OR=2.08; p=0.4), the presence of distant metastases (OR=3.43; p=0.197), or local control (p=0.76). It was exclusively present in patients with local extension, and was significantly associated with outcome (p=0.04). Resection with clear margins is the gold standard of care for patients with intraoral adenoid cystic carcinoma, and the role of adjuvant irradiation remains controversial. Given its paradoxical and complex biological behaviour, large studies with long term follow-up are needed to define the clinicopathological and immunohistochemical variables associated with outcome, as well as the optimal treatment.

Pleomorphic adenoma in ectopic salivary gland tissue in the neck.

A case of pleomorphic adenoma originating from ectopic salivary gland tissue (ESGT) of the upper neck is reported. A 34-year-old male patient was referred to our Department for a painless swelling in the right submandibular region. Preoperative evaluation (clinical examination, fine-needle aspiration cytology (FNAC) and imaging studies) was performed and the finding was that of pleomorphic adenoma in ESGT A modified "S" incision with extension to the submandibular region was performed and the tumour was extirpated. The histopathological report confirmed our initial diagnosis. No recurrence was obtained during a four-year follow-up period. Isolated neck mass may be overlooked as ectopic salivary gland tissue neoplasm (ESGTN). Proper preoperative assessment and optimal surgical treatment are the keys for successful management of these rare tumours. The distinction between metastatic lesion from a head and neck tumour and ESGTN may present considerable diagnostic problem. A review of the literature on ESGT and associated tumours with emphasis on clinical features, diagnosis and treatment is also presented.