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.

NOTCH1 mutations have been reported to occur in 10 to 15% of head and neck squamous cell carcinomas (HNSCC). To determine the significance of these mutations, we embarked upon a comprehensive study of NOTCH signaling in a cohort of 44 HNSCC tumors and 25 normal mucosal samples through a set of expression, copy number, methylation and mutation analyses. Copy number increases were identified in NOTCH pathway genes including the NOTCH ligand JAG1. Gene set analysis defined a differential expression of the NOTCH signaling pathway in HNSCC relative to normal tissues. Analysis of individual pathway-related genes revealed overexpression of ligands JAG1 and JAG2 and receptor NOTCH3. In 32% of the HNSCC examined, activation of the downstream NOTCH effectors HES1/HEY1 was documented. Notably, exomic sequencing identified 5 novel inactivating NOTCH1 mutations in 4/37 of the tumors analyzed, with none of these tumors exhibiting HES1/HEY1 overexpression. Our results revealed a bimodal pattern of NOTCH pathway alterations in HNSCC, with a smaller subset exhibiting inactivating NOTCH1 receptors mutations but a larger subset exhibiting other NOTCH1 pathway alterations, including increases in expression or gene copy number of the receptor or ligands as well as downstream pathway activation. Our results imply that therapies that target the NOTCH pathway may be more widely suitable for HNSCC treatment than appreciated currently.

SUMMARY Human papillomavirus (HPV) is etiologically responsible for a distinct subset of head and neck squamous cell cancers (HNSCCs). HPV-positive HNSCCs (HPV-HNSCCs) most commonly arise from the oropharynx and are responsible for the increasing incidence of oropharyngeal SCC (OSCC) in the United States (US) and abroad. HPV-positive OSCC (HPV-OSCC) has a unique demographic and risk factor profile and tumor biology. HPV-OSCC patients tend to be white, younger, and have a higher cumulative exposure to sexual behaviors as compared with HPV-negative OSCC patients. HPV-positive tumor status also significantly improves survival, and is indeed the single strongest prognostic factor for OSCC. The mechanisms that underlie the improved prognosis conferred by HPV-positive disease are unknown. The purpose of this review is to describe the clinical impact of HPV status in HNSCC, particularly in OSCC, both in terms of the unique clinic-demographic profile and prognostic implications.

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Background More people are presenting with mild cognitive impairment (MCI), frequently a precursor to dementia but we do not know how to reduce deterioration. Aims To systematically review Randomised Controlled Trials (RCTs) evaluating effects of any intervention for MCI on cognitive, neuropsychiatric, functional, global outcomes, life quality, or incident dementia. Methods We reviewed the 41 studies fitting predetermined criteria, assessed validity using a checklist, calculated standardised outcomes, and prioritised primary outcome findings in placebo-controlled studies. Results The strongest evidence was that cholinesterase inhibitors did not reduce incident dementia. Cognition improved in single trials of: a heterogeneous psychological group intervention over 6 months; piribedil, a dopamine agonist over 3 months; and donepezil over 48 weeks. Nicotine improved attention over 6 months. There was equivocal evidence that Huannao Yicong improved cognition and social functioning. Conclusions There was no replicated evidence that any intervention was effective. Cholinesterase inhibitors and rofecoxib are ineffective in preventing dementia. Further good quality RCTs are necessary and preliminary evidence suggests these should include trials of psychological group interventions and piribedil.

Background Evidence suggests the incidence of oral tongue squamous cell carcinoma is increasing in young patients, many who have no history of tobacco use. Methods We clinically reviewed 89 oral tongue cancer patients. Exomic sequencing of tumor DNA from 6 non-smokers was performed and compared to previously sequenced cases. RNA from 20 tumors was evaluated by massively parallel sequencing to search for potentially oncogenic viruses. Results Non-smokers (53 of 89) were younger than smokers (36 of 89) mean 50.4 vs. 61.9 years, P<0.001), and appeared more likely to be female, (58.5% vs. 38.9%, P=0.069). Non-smokers had fewer TP53 mutations (P=0.02) than smokers. No tumor-associated viruses were detected. Conclusions The young age of non-smoker oral tongue cancer patients, and fewer TP53 mutations suggest a viral role in this disease. Our efforts to identify such a virus were unsuccessful. Further studies are warranted to elucidate the drivers of carcinogenesis in these patients.

IMPORTANCE Sarcopenia, or the loss of muscle mass, is associated with poor treatment outcomes in a variety of surgical fields. However, the association between sarcopenia and long-term survival in a broad cohort of patients with head and neck cancer (HNC) is unknown. OBJECTIVE To determine whether sarcopenia is associated with long-term survival in patients undergoing major head and neck surgery for HNC. DESIGN, SETTING, AND PARTICIPANTS A retrospective medical records review was conducted at a tertiary care academic hospital. Two hundred sixty patients undergoing major head and neck ablative procedures with cross-sectional abdominal imaging performed within 45 days prior to surgery were included in the analysis.