To the best of our knowledge, this is the largest US series to date of patients with malignant tumors of the sinonasal tract treated with endoscopic resection. Our results suggest that, in well-selected patients and with appropriate use of adjuvant therapy, endoscopic resection of sinonasal cancer results in acceptable oncologic outcomes.

IMPORTANCE Large patient cohorts are necessary to validate the efficacy of transoral robotic surgery (TORS) in the management of head and neck cancer. OBJECTIVES To review oncologic outcomes of TORS from a large multi-institutional collaboration and to identify predictors of disease recurrence and disease-specific mortality. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of records from 410 patients undergoing TORS for laryngeal and pharyngeal cancers from January 1, 2007, through December 31, 2012, was performed. Pertinent data were obtained from 11 participating medical institutions. INTERVENTIONS Select patients received radiation therapy and/or chemotherapy before or after TORS. MAIN OUTCOMES AND MEASURES Locoregional control, disease-specific survival, and overall survival were calculated. We used Kaplan-Meier survival analysis with log-rank testing to evaluate individual variable association with these outcomes, followed by multivariate analysis with Cox proportional hazards regression modeling to identify independent predictors. RESULTS Of the 410 patients treated with TORS in this study, 364 (88.8%) had oropharyngeal cancer. Of these 364 patients, information about post-operative adjuvant therapy was known about 338: 106 (31.3) received radiation therapy alone, and 72 (21.3%) received radiation therapy with concurrent chemotherapy. Neck dissection was performed in 323 patients (78.8%). Mean follow-up time was 20 months. Local, regional, and distant recurrence occurred in 18 (4.4%), 15 (3.7%), and 10 (2.4%) of 410 patients, respectively. Seventeen (4.1%) died of disease, and 13 (3.2%) died of other causes. The 2-year locoregional control rate was 91.8% (95% CI, 87.6%-94.7%), disease-specific survival 94.5% (95% CI, 90.6%-96.8%), and overall survival 91% (95% CI, 86.5%-94.0%). Multivariate analysis identified improved survival among women (P = .05) and for patients with tumors arising in tonsil (P = .01). Smoking was associated with worse overall all-cause mortality (P = .01). Although advanced age and tobacco use were associated with locoregional recurrence and disease-specific survival, they, as well as tumor stage and other adverse histopathologic features, did not remain significant on multivariate analysis. CONCLUSIONS AND RELEVANCE This large, multi-institutional study supports the role of TORS within the multidisciplinary treatment paradigm for the treatment of head and neck cancer, especially for patients with oropharyngeal cancer. Favorable oncologic outcomes have been found across institutions. Ongoing comparative clinical trials funded by the National Cancer Institute will further evaluate the role of robotic surgery for patients with head and neck cancers.

OBJECTIVE Summarize functional outcomes after transoral robotic surgery (TORS) ± adjuvant therapy for oropharyngeal cancer (OPC). STUDY DESIGN A systematic review was conducted. The MEDLINE database was searched (MeSH terms: transoral robotic surgery, pharyngeal neoplasms, oropharyngeal neoplasms). METHODS Peer-reviewed human subject papers published through December, 2013 were included. Exclusion criteria were: 1) case report design (n<10), 2) review article, or 3) technical, animal or cadaver studies. Functional outcomes extracted included feeding tube dependence, swallow examination findings, speech ratings, velopharyngeal insufficiency, pneumonia, and oral intake measures. RESULTS Twelve papers comprising 441 patients with OPC treated with TORS ± adjuvant therapy were included. Feeding tube rates were the most commonly reported functional outcome. Excluding prophylactic placement, 18% to 39% of patients required gastrostomy placement, typically during adjuvant therapy. Chronic gastrostomy dependence ranged from 0% to 7% (mean follow-up: 11–26 months), regardless of disease stage. Composite MD Anderson Dysphagia Inventory (MDADI) scores ranged from 65.2 to 78 (89 patients, 3 series, mean follow-up: 12–13 months). Videofluoroscopic swallowing studies were not systematically reported. Incidence of postoperative pneumonia was 0% to 7%. Predictors of swallowing function included baseline function, T-stage, N-stage, tongue base primary tumors, and adjuvant chemoradiation. Rates of transient hypernasality were 4% to 9%. A single study suggested dose-dependent effects of adjuvant therapy (none, radiation alone, chemoradiation) on diet scores at 6- and 12-months. CONCLUSIONS Crude endpoints of functional recovery after TORS ± adjuvant therapy suggest promising swallowing outcomes, depending on the functional measure reported.

Head and neck squamous cell carcinoma (HNSCC) remains a significant public health problem, accounting for over 5% of all cancer-related deaths, and these deaths primarily result from metastatic disease. The molecular processes involved in HNSCC pathogenesis and progression are poorly understood, and here we present experimental evidence for a direct role of the cell surface receptor tyrosine kinase, TrkB, in HNSCC tumor progression. Using immunohistochemical analysis and transcriptional profiling of archival HNSCC tumor specimens, we found that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF), are expresses in greater than 50% of human HNSCC tumors, but not in normal upper aerodigestive tract (UADT) epithelia. Studies with HNSCC cell lines reveal that in vitro stimulation with BDNF, the ligand for TrkB, upregulates the migration and invasion of HNSCC cells, and both transient and stable suppressions of TrkB result in significant abrogation of constitutive and ligand-mediated migration and invasion. Furthermore, enforced over-expression of TrkB results in altered expression of molecular mediators of epithelial-to-mesenchymal transition (EMT), including downregulation of E-cadherin and upregulation of Twist. Using an in vivo mouse model of HNSCC, we were able to show that downregulation of TrkB suppresses tumor growth. These results directly implicate TrkB in EMT and the invasive behavior of HNSCC, and correlate with the in vivo overexpression of TrkB in human HNSCC. Taken together, these data suggest that the TrkB receptor may be a critical component in the multi-step tumor progression of HNSCC, and may be an attractive target for much needed new therapies for this disease.

BACKGROUND: Sinonasal mucosal melanoma is a rare disease associated with a very poor prognosis. Because most of the series extend retrospectively several decades, we sought to determine prognostic factors and outcomes with recent treatment modalities. METHODS: A retrospective chart review of 58 patients treated for sinonasal melanoma at a tertiary cancer center between 1993 and 2004. The patients were retrospectively staged according to the sinonasal American Joint Committee on Cancer (AJCC) staging system. Demographic, clinical and pathological parameters were identified and correlated with outcomes. RESULTS: There were 35 males and 23 females with a median age of 63 years; 56 patients were treated surgically and 33 received radiation therapy. According to Ballantyne's clinical staging system, 88% of the patients presented with stage I (local) disease. Classification by the AJCC staging classified yielded 27% of the patients with T1, 33% with T2, 21% with T3, and 19% with T4. T-stage and the degree of tumor pigmentation were associated with a worse survival (P ¼ .0096 and P ¼ .018, respectively), while pseudopapillary architecture was associated with a higher locoregional failure (P ¼ .0144). Postoperative radiation therapy improved locoregional control when a total dose greater than 54 Gy was used (P ¼ .0215), but did not affect overall survival. CONCLUSIONS: Tumor stage according to sinonasal AJCC staging system is an effective outcome predictor and should be the staging system of choice. Postoperative radiation therapy improves locoregional control when a higher dose and standard fractionations are used. Histological features such as pigmentation and pseudopapillary architecture are associated with worse outcome. Cancer 2010;116:2215-23.