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The fluctuation of the freight rates is an important source of risk for all participants in the tanker shipping markets including ship-owners, charterers, traders, hedge funds, banks, etc. This study examines the freight rate risk involved in the most popular clean tanker route and the most popular dirty tanker route using historical prices from April 2008 to September 2015 for the routes TC5 and TD7 which are further divided into an in-sample period from 24 April 2008 to 7 November 2013, to estimate the coefficients and an out-of-sample period from 8 November 2013 to 2 September 2015, to measure the day to day Value at Risk performance. The analysis of the historical returns of both spot and future prices reveals historical distributions with high peaks and fat tails. The establishment of a risk management method that could capture these distribution characteristics is of paramount importance. For the quantification of the risk, the Value at Risk approach is applied. More specifically, a range of parametric (multiple GARCH family) and non-parametric (i.e. historical simulation) Value at Risk models are applied on the returns of both TC5 and TC7 spot and one and three months future markets. The results suggest substantial freight rate risk at both routes. The backtesting of the Value at Risk models is applied in two stages, firstly by the means of statistical accuracy of the results and secondly by the means of economic accuracy, in order to track down the best VAR models in the case of our research. According to the results, the simple GARCH and non-parametric models are proposed for risk management purposes, for both spot and future markets. The results are consistent for both long and short positions. According to the results, simple GARCH non-parametric models perform better in risk management, for both spot and futures markets. The results are consistent for both long and short positions.

Use of videos of surgical and medical techniques for educational purposes has grown over the last years. To our knowledge, there is no validated tool to specifically assess the quality of these types of videos. Our goal was to create an evaluation tool and study its intrarater and interrater reliability and its acceptability. We named our tool UM-OSCAARS (Université de Montréal Objective and Structured Checklist for Assessment of Audiovisual Recordings of Surgeries/techniques).UM-OSCAARS is a grid containing 10 criteria, each of which is graded on an ordinal Likert-type scale of 1 to 5 points. We tested the grid with the help of 4 voluntary otolaryngology - head and neck surgery specialists who individually viewed 10 preselected videos. The evaluators graded each criterion for each video. To evaluate intrarater reliability, the evaluation took place in 2 different phases separated by 4 weeks. Interrater reliability was assessed by comparing the 4 topranked videos of each evaluator.There was almost-perfect agreement among the evaluators regarding the 4 videos that received the highest scores from the evaluators, demonstrating that the tool has excellent interrater reliability. There was excellent test-retest correlation, demonstrating the tool's intrarater reliability.The UM-OSCAARS has proven to be reliable and acceptable to use, but its validity needs to be more thoroughly assessed. We hope this tool will lead to an improvement in the quality of technical videos used for educational purposes.Au fil des ans, l’utilisation de vidéos pour l’enseignement de techniques chirurgicales et médicales s’est répandue. À notre connaissance, il n’existe aucun outil pour évaluer spécifiquement la qualité de ces types de vidéos. Notre objectif était de créer un outil d’évaluation et d’analyser sa fiabilité interévaluateurs et son acceptabilité. Notre outil a pour nom UM-OSCAARS (Université de Montréal Objective and Structured Checklist for Assessment of Audiovisual Recordings of Surgeries/Techniques).L’outil UM-OSCAARS est une grille qui contient 10 critères; chacun est noté sur une échelle de type Likert de 1 à 5 points. Nous avons testé la grille avec l’aide de 4 volontaires, spécialistes en otorhinolaryngologie/chirurgie de la tête et du cou, qui ont visionné 10 vidéos présélectionnées. Les évaluateurs ont noté chacun des critères pour chaque vidéo. Afin de vérifier la fiabilité interévaluateurs, l’évaluation s’est déroulée en 2 phases, à 4 semaines d’intervalle. La fiabilité interévaluateurs a été mesurée en comparant les 4 vidéos les mieux cotées par chaque évaluateur.La concordance a été quasi parfaite entre les évaluateurs pour les 4 vidéos qu’ils ont les mieux cotées, ce qui montre que l’outil a une excellente fiabilité interévaluateurs. La corrélation test–retest a été excellente, ce qui démontre la fiabilité interévaluateurs de l’outil.L’outil UM-OSCAARS et son utilisation se sont révélés fiables et acceptables, mais il faut évaluer davantage sa validité. Nous espérons que cet outil permettra d’améliorer la qualité des vidéos techniques destinées à l’enseignement.

Purpose To assess cancer control and patient-reported outcomes (PROs) after de-intensified intensity-modulated radiotherapy (IMRT) in lateralized p16-associated oropharyngeal cancer (p16-OPC). Methods Lateralized p16-OPC treated with radiotherapy and concurrent Carboplatin/5-fluorouracil between 2011 and 2014 were enrolled. De-intensified IMRT consisted in elective neck dose of 43.2 Gy/24 fractions and omission of contralateral retropharyngeal/level IV nodes. PROs were assessed using the EORTC QLC-C30 and QLQ-HN35 scales. Results Twenty-nine patients were included. Median follow-up was 44 months. As per AJCC 7th Ed, 7%, 83% and 10% of patients had stage III, IVa and IVb. 5-year locoregional control and overall survival rates were 100% and 100%, respectively. Rates of acute were 52% and 35%, respectively. At 2 years post-treatment, 50% and 14% of patients had grade 1 xerostomia and dysgueusia, respectively. Most PROs scores returned to baseline within 8 months post-treatment. Conclusion De-intensified IMRT was associated with excellent cancer outcomes, and rapid recovery of PROs in lateralized p16-OPC.

Using a Bootstrap Malmquist Productivity Index approach, this paper investigates productivity changes of 24 high capitalization firms, listed in the London Stock Exchange over the period from 2009 to 2016. In the aftermath of the global financial crisis, we find evidence of technological and technical efficiency variations for our sample of industrial firms. Specifically, we show that, on average, only 26.2% of the examined firms managed to perform a positive increase in their Total Factor Productivity for the investigated period. There is an apparent deterioration in the technological efficiency for all firms, enhancing the view that these companies avoided investing in new technologies. However, in general, an improvement of technical efficiency is observed, meaning that firms improve the allocation of their available inputs in the production process.

Background The radial forearm free flap (RFFF) is the most commonly used flap for defects of the oral cavity. The facial artery musculomucosal (FAMM) is a safe and effective method to reconstruct medium sized defects of the oral cavity. No comparison exists between the FAMM flap and RFFF. Methods 1) Retrospective chart review from 2007 to 2016. 2) Cost difference analysis. Results Thirteen FAMM flap cases and 18 RFFF met inclusion criteria. The FAMM flap showed a tendency to lower rates of return to the operating room (p = 0.065) as well as lower rates of complications not requiring return to the OR with 1 complication in 1 patient as opposed to 10 patients with 15 complications (p = 0.008). Also, FAMM flap had shorter operative times compared to the RFFF group (7.2HR and 8.9 HR respectively, p = 0.002). The average operative room related costs for a FAMM flap were 6510 CAD vs 10,703 CAD for RFFF (p p > 0.05). Conclusion The FAMM flap can be used for reconstruction of medium-size defects of the oral cavity with functional outcomes similar to the RFFF while decreasing the associated costs and morbidity. Graphical Abstract

BACKGROUND Optical coherence tomography (OCT) is a noninvasive imaging modality that may reproduce the microarchitecture of tissues in real-time. This study examines whether OCT can render distinct images of thyroid, parathyroid glands, adipose tissue, and lymph nodes in both healthy and pathological states. METHODS Twenty-seven patients undergoing thyroidectomy, parathyroidectomy, and/or neck dissection for thyroid cancer were recruited prospectively for imaging prior to histopathological analysis. RESULTS Based on 122 imaged specimens, qualitative OCT descriptions were derived for healthy thyroid, parathyroid gland, adipose tissue, and lymph node. The frequencies at which distinguishing features were present for each tissue type were 88%, 83%, 100%, and 82%. OCT appearance of pathological specimens were also described. CONCLUSIONS Healthy neck tissues have distinct OCT appearances, which could facilitate parathyroid identification during thyroidectomies. However, images of parathyroid adenomas could be confused with those of lymph nodes, and benign and malignant thyroid nodules could not be differentiated.

Objective The present review focuses on comparative studies of reconstruction with free flaps (FF) versus pedicled flaps (PF) after oncologic resection. Method A systematic review was developed in compliance with PRISMA guidelines and performed using the Pubmed, Medline, EMBASE, Amed and Biosis databases. Results A total of 30 articles were included. FF are associated with a longer operative time, a higher cost and a higher incidence of postoperative revisions compared to PF. FF are associated with a longer stay at the intensive care unit than the supraclavicular artery island flap (SCAIF) and with a more extended hospital stay compared to the submental island flap (SMIF). FF are associated with fewer infections and necrosis compared to the pectoralis major myocutaneous flap (PMMF). Conclusion The comparison of both type of flaps is limited by the inherent design of the studies included. In sum, FF seem superior to the PMMF for several outcomes. SMIF and SCAIF compare favorably to FF for some specific indications achieving similar outcomes at a lower cost.

The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway has previously been demonstrated in metastatic head and neck squamous cell carcinoma (HNSCC). Stereotactic Body Radiotherapy (SBRT) aims at ablating metastatic lesions and may play a synergistic role with immunotherapy. The purpose of this study is to assess the safety and efficacy of triple treatment combination (TTC) consisting of the administration of durvalumab and tremelimumab in combination with SBRT in metastatic HNSCC. This is a phase I/II single arm study that will include 35 patients with 2–10 extracranial metastatic lesions. Patients will receive durvalumab (1500 mg IV every 4 weeks (Q4W)) and tremelimumab (75 mg IV Q4W for a total of 4 doses) until progression, unacceptable toxicity or patient withdrawal. SBRT to 2–5 metastases will be administered between cycles 2 and 3 of immunotherapy. The safety of the treatment combination will be evaluated through assessment of TTC-related toxicities, defined as grade 3–5 toxicities based on Common Terminology Criteria for Adverse Events (v 4.03), occurring within 6 weeks from SBRT start, and that are definitely, probably or possibly related to the combination of all treatments. We hypothesize that dual targeting of PD-L1 and CTLA-4 pathways combined with SBRT will lead to

Background The objective was to develop an assessment tool to evaluate residents' competency for neck dissection and provide preliminary evidence of feasibility, reliability, and validity. Methods Six surgeons developed a neck dissection assessment tool using a modified Delphi method and evaluated 58 neck dissections from six junior and six senior otolaryngology residents. Results The assessment tool uses a double checklist: a previously validated global rating scale (GRS) and a task-specific checklist (TSC). Use of the instrument appeared feasible and the average scores on the GRS and TSC differed significantly between junior and senior residents. The Pearson correlation coefficient between both checklists was 0.87. Intraclass correlation (ICC) for inter-rater reliability was 0.69 for the GRS, and 0.80 for the TSC. Conclusion This study provides preliminary evidence of feasibility, reliability, and validity for the first neck dissection assessment tool and provides a foundation for further psychometric analysis and research.

Germline single nucleotide polymorphisms in the promoter region of the DCBLD1 gene are associated with non-smoking cases of both non-small cell lung carcinoma (NSCLC) and human papillomavirus-negative head and neck cancer. However the clinical relevance and function of DCBLD1 remain unclear. This multicenter retrospective study was designed to evaluate the prognostic value and function of DCBLD1 in the four main solid cancers: NSCLC, invasive breast carcinoma, colorectal adenocarcinoma and prostate adenocarcinoma. We included the following cohorts: GSE81089 NSCLC, METABRIC invasive breast carcinoma, GSE14333 colorectal adenocarcinoma, GSE70770 prostate adenocarcinoma and The Cancer Genome Atlas (TCGA) Firehose Legacy cohorts of all four cancers. DCBLD1 gene expression was associated with a worse overall survival in multivariate analyses for both NSCLC cohorts (TCGA: P = 0.03 and GSE81089: P = 0.04) and both invasive breast carcinoma cohorts (TCGA: P = 0.02 and METABRIC: P DCBLD1 expression showed an upregulation of the integrin signaling pathway in comparison to those with low DCBLD1 expression in the TCGA NSCLC cohort (FDR = 5.16 × 10–14) and TCGA invasive breast carcinoma cohort (FDR = 1.94 × 10–05).

Genetic factors behind the increasing incidence of human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC) in young non-smokers are suspected, but have not been identified. Recently, rs6942067, a single nucleotide polymorphism (SNP) located upstream of the DCBLD1 gene, was found associated with non-smoking lung adenocarcinoma. To validate if this SNP is also implicated in HNSCC, participants of The Cancer Genome Atlas HNSCC cohort were investigated for rs6942067 status, associated DCBLD1 expression, and clinical characteristics. Occurrence of the rs6942067 GG genotype is significantly higher in young and in HPV negative non-smoking HNSCC than in other HNSCC. Additionally, rs6942067 GG is associated with higher DCBLD1 expression in HNSCC and patients with high DCBLD1 expression have a worse overall survival at three years, both in univariate and multivariate analysis. Furthermore, high DCBLD1 expression is associated with activation of the integrin signaling pathway and its phosphorylation with EGFR and MET. Collectively, these findings suggest that DCBLD1 plays a critical role in HNSCC and demonstrate an association between rs6942067 and clinical characteristics of young age and HPV negative non-smoking status in HNSCC patients.

Objective To compare the surgical and functional outcomes between two harvesting techniques for the inferiorly based facial artery musculomucosal (FAMM) flap for oral cavity and oropharynx reconstructions. Methods Multicenter retrospective chart review. Results We reviewed 55 cases of FAMM flap, including 29 traditional cases and 26 performed using the modified harvesting method. The overall rate of surgical re-intervention in the traditional group was 31% (n = 9 of 29) and 15% (n = 4 of 26) in the modified group (P = 0.196). The specific re-intervention rate for pedicle sectioning was 27% (n = 8 of 29) in the traditional group versus 0% (n = 0 of 26) in the modified group. The overall rate of complications was 21%. Nine out of 10 dentate patients in the traditional group and four out of five in the modified group needed tooth extraction. There was no difference between the two groups in terms of tracheostomy duration (P = 0.338) and time to first oral intake (P = 0.629). Speech and feeding outcomes were similar among groups (P = 0.922; P = 0.700, respectively). Dental rehabilitation was achieved in 67% and 78% of patients in the traditional and modified groups, respectively. Conclusion The FAMM flap offers a low morbidity approach to reconstruct the oral cavity. The modified approach to harvesting the flap is a safe and effective technique, with similar functional results and equally low morbidity profile as the traditional technique. It has the added advantage of lower rates of secondary surgical interventions. Level of evidence 4. Laryngoscope, 1802-1805, 2018.

Background Perioperative practices in thyroid surgery vary from one specialty, institution, or country to the next. We evaluated the preoperative, intraoperative, and postoperative practices of thyroid surgeons focusing on preoperative ultrasound, vocal cord evaluation, wound drains, and hospitalization duration, among others. Methods A survey was sent to 7 different otolaryngology and endocrine/general surgery associations. Results There were 965 respondents from 52 countries. Surgeon-performed ultrasound is practiced by more than one third of respondents. Otolaryngologists perform preoperative and postoperative vocal cord evaluation more often than endocrine/general surgeons (p < .001). Sixty percent of respondents either never place drains or place drains

Genomic analyses of head and neck squamous cell carcinoma (HNSCC) have highlighted alterations in the phosphatidylinositol 3-kinase (PI3K) signaling pathway, presenting a therapeutic target for multiple ongoing clinical trials with PI3K or PI3K/MTOR inhibitors. However, these inhibitors can potentially increase autophagy in HNSCC and indirectly support cancer cell survival. Here, we sought to understand the relationship between the PI3K signaling pathway and autophagy during their dual inhibition in a panel of HNSCC cell lines. We used acridine orange staining, immunoblotting, and tandem sensor Red Fluorescent Protein- Green Fluorescent Protein-, microtubule-associated protein 1 light chain 3 beta (RFP-GFP-LC3B) expression analysis to show that PI3K inhibitors increase autophagosomes in HNSCC cells, but that chloroquine treatment effectively inhibits the autophagy that is induced by PI3K inhibitors. Using the Bliss independence model, we determined that the combination of chloroquine with PI3K inhibitors works in synergy to decrease cancer cell proliferation, independent of the PIK3CA status of the cell line. Our results indicate that a strategy focusing on autophagy inhibition enhances the efficacy of therapeutics already in clinical trials. Our results suggest a broader application for this combination therapy that can be promptly translated to in vivo studies.

Summary Purpose To report outcomes and predictive factors of overall survival, hospitalization and treatment completion rates in elderly patients with locally advanced head and neck cancer treated with concurrent chemoradiotherapy (CRT). Material and methods A retrospective analysis of patients aged 70 years or older treated with concurrent CRT for locally advanced head and neck cancer was conducted. Univariate and multivariate analysis as well as competing risk survival analysis were used to determine predictors of mortality. Logistic regression was used to predict for hospitalization and treatment completion rates. Results In total, 129 patients were included. Median follow-up was 27 months (range: 1.7–125 months). Completion rate of combined CRT was 84%. Actuarial OS and DSS at 4 years were 56% and 75%. Hospitalization rate was 36%. On multivariate analysis, a Karnofsky performance status (KPS) ⩽80 was predictive of mortality. Using competing risks, KPS ⩽80 and weight loss >5% were predictive of cancer mortality whereas Charlson score ⩾3 was predictive of mortality due to other causes. On logistic regression, patients with abnormal renal function and lower body mass index were more likely to be hospitalized during their treatment course. Charlson score and chemotherapy regimen were predictive of treatment completion. Conclusion Concurrent CRT may be a feasible treatment option for healthier older patients at the cost of high hospitalization rates. Pre-treatment factors linked to physiological age such as KPS ⩽80, Charlson score ⩾3, abnormal renal function should be considered at the time of treatment decision.

Background The aim of the study was to evaluate the oncological and functional outcomes with transoral laser microsurgery (TOLM) of patients with early glottic cancer. Methods We have prospectively evaluated patients treated with TOLM for Tis, T1 or T2 glottic squamous cell carcinoma. Evaluation of oncological outcomes, and voice and functional outcomes was assessed using voice-handicap index 10 (VHI-10) and performance status scale for head & neck cancer patients (PSS-H&N). Predictors of poor voice quality were evaluated using Student’s t-test. Results Thirty patients were included, with 17.7 months mean follow-up. There were no cases of locoregional recurrence. Twelve patients (40%) were considered as having a problematic voice outcome. Four subjects out of 30 (13.3%) had significant problems with understandability of speech. Significant differences (P < 0.05) in VHI-10 score were found with tumor stage and partial resection of the ventricular fold. Conclusions We report excellent oncological and functional outcomes in early glottic cancer treated with TOLM, with advanced tumors and partial resection of the ventricular fold as a surrogate predicting worse voice outcomes.

The aim of this study is to evaluate the additional costs associated with calcium monitoring and treatment as well as evaluate the incidence and predictors of postthyroidectomy hypocalcemia. Methods. This case-control study involved thyroidectomy and completion thyroidectomy patients operated on between January 2012 and August 2013. Cases were defined as requiring calcitriol supplementation, and controls did not require supplementation. Patient (age, sex), nodule (cytology, pathology), surgical data (neck dissection, parathyroid identification, and reimplantation), and hospital stay (days hospitalized in total and after drain removal) were compared. Comparisons were made using t-tests and chi-square tests with an alpha of 0.05. The estimated cost associated with the extended stay was then compared with the cost of supplementation. Results. A total of 191 patients were evaluated (61 cases and 130 controls). Predictors of hypocalcemia include female age, neck dissection, and parathyroid reimplantation. Hypocalcemic patients were hospitalized for a longer period of time after drain removal (2.5 versus 0.8 days, P<0.001), and hospitalization costs after neck drain removal were higher in this group as well (8,367.32$ versus 2,534.32$, P<0.001). Conclusion. Postoperative hypocalcemia incurs significant additional health care costs at both the local and health care system levels.

The first objective of this study was to identify work-related musculoskeletal symptoms and determine their prevalence in the practice of Otolaryngology and Head and Neck surgery in Canada. The second objective was to establish potential associations between those musculoskeletal symptoms and variables related to demographic status of the surgeons, their workload and work ergonomics. This study was designed as a Canadian census on work-related musculoskeletal symptoms amongst Otolaryngologist and Head and Neck surgeons. The census was a self-administered electronic survey. It was distributed to all Otolaryngologists and Head and Neck surgeons members of either the Canadian Society of Otolaryngology-Head and Neck Surgery or the Association of Oto-rhinolaryngology-Head and Neck Surgery of Quebec. The questionnaire contained three sections: demographic and workload-related data, identification of work-related musculoskeletal symptoms and evaluation of working ergonomics. The response rate was 23%. Ninety seven percent (97%) of respondents experienced some physical symptom in one or many regions of their body. Seventy-four percents (74%) of respondents noted an exacerbation of their musculoskeletal symptoms by work. Musculoskeletal symptoms limited the daily activities of 45% of respondents while 23% think that their occupational longevity will be diminished by these limitations. The prevalence of work-related musculoskeletal disorders is high among otolaryngologists and its impact on the surgeon's personal and professional life is high. There is a need to improve ergonomics in the clinical and operative room settings and to educate surgeons on ergonomic principles.

The aim of this study is to identify clinical factors that are predictive of depression and quality of life (QOL) among long-term survivors of head and neck squamous cell carcinoma and to develop predictive scores using these factors.Cohort studyTertiary referral center.A total of 209 posttreatment (median follow-up, 38.7 months) head and neck cancer patients were prospectively evaluated using the Hospital Anxiety Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, and the EORTC Quality of Life Questionnaire Head and Neck 35, and pretreatment patient-related, tumor-related, and treatment-related predictors were identified using chart review. Bivariate (χ(2) and t test) and multivariate (linear regression) analyses were used to construct predictive models.Significant pretreatment predictors of depression were identified on multivariate analysis as smoking at diagnosis,14 alcoholic drinks per week, T3 or T4 status, and3 medications (P.001). Two or more of these factors yielded an 82.3% sensitivity in detecting significant depressive symptoms (defined as a HADS cutoff score of 5). Significant predictors of fatigue, global health/QOL, social contact, speech, pain, swallowing, and xerostomia were also identified.Pretreatment predictors of long-term depression and QOL have been defined using multivariate models, and an easily applicable predictive score of long-term depression is proposed. Potential eventual clinical applications include prophylactic intervention in at-risk patients.

Background. HPV is a positive prognostic factor in HNSCC. We studied the prevalence and prognostic impact of HPV on survival parameters and treatment toxicity in patients with locally advanced HNSCC treated with concomitant chemoradiation therapy.Methods. Data on efficacy and toxicity were available for 560 patients. HPV was detected by PCR. Analysis was performed using Kaplan-Meier survival curves, Fisher’s test for categorical data, and log-rank statistics for failure times.Results. Median follow-up was 4.7 years. DNA extraction was successful in 255 cases. HPV prevalence was 68.6%, and 53.3% for HPV 16. For HPV+ and HPV−, median LRC was 8.9 and 2.2 years (P=0.0002), median DFS was 8.9 and 2.1 years (P=0.0014), and median OS was 8.9 and 3.1 years (P=0.0002). Survival was different based on HPV genotype, stage, treatment period, and chemotherapy regimen. COX adjusted analysis for T, N, age, and treatment remained significant (P=0.004).Conclusions. Oropharyngeal cancer is increasingly linked to HPV. This study confirms that HPV status is associated with improved prognosis among H&N cancer patients receiving CRT and should be a stratification factor for clinical trials including H&N cases. Toxicity of CRT is not modified for the HPV population.

Level II neck dissection is a commonly performed procedure in head and neck surgery. It carries the risk of injury to the spinal accessory nerve (SAN) and the internal jugular vein (IJV). Injury to any of these structures leads to increased intraoperative and postoperative complications and morbidity. Knowledge of the anatomic relation and possible variations from the norm is vital to decrease the morbidity of this frequently practiced procedure. This report describes 2 rare variations of the relation of the SAN to the IJV: 1) the IJV splitting with SAN passage through the IJV window and 2) the IJV splitting without SAN passage through the IJV window. Preoperative imaging and the pertinent literature regarding the variability in the relations of these structures are reviewed.

To evaluate the oncologic and functional outcomes of partial laryngeal surgery (PLS) using transoral laser microsurgery (TLM) and supracricoid laryngectomy (SCL) in patients with intermediate-stage laryngeal squamous cell carcinoma (LSCC).Historical cohort study.Single tertiary care center.Retrospective review of oncologic and functional outcomes in intermediate-stage (T2-3/N0-1, stage II and III) LSCC patients who underwent TLM or SCL from 1998 to 2010.Sixty patients were included, of whom 28 (47%) underwent TLM and 32 (53%) underwent SCL. For the entire cohort, 2- and 5-year probabilities were 86.2% (95% confidence interval [CI], 73.0%-93.2%) and 72.9% (95% CI, 52.4%-85.6%), respectively, for overall survival (OS) and 79.3% (95% CI, 65.6%-88.0%) and 62.4% (95% CI, 41.9%-77.4%), respectively, for recurrence-free survival (RFS). There was no difference between the TLM and SCL cohorts in OS (P = .542) or RFS (P = .483). More than 75% of patients avoided adjuvant therapy. Communication Scale and Functional Outcome Swallowing Scale scores at median follow-up of 33 months were 2 or better in 97% and 91% of patients, respectively, reflecting functional voice and swallowing postoperatively. Eighty-eight percent of patients retained a functional larynx.PLS provides excellent oncologic and functional outcomes for intermediate-stage LSCC and should be considered an alternative to chemoradiation or total laryngectomy in selected patients.

Purpose To determine the effectiveness and rate of complications of intensity-modulated radiotherapy (IMRT) in the treatment of cervical lymph node metastases from unknown primary cancer. Methods and Materials Between February 2005 and November 2008, 25 patients with an unknown primary cancer underwent IMRT, with a median radiation dose of 70 Gy. The bilateral neck and ipsilateral putative pharyngeal mucosa were included in the target volume. All patients had squamous cell carcinoma, except for 1 patient who had adenosquamous differentiation. They were all treated with curative intent. Of the 25 included patients, 20 were men and 5 were women, with a median age of 54 years. Of these patients, 3 had Stage III, 18 had Stage IVa, and 4 had Stage IVb. Of the 25 patients, 18 (72%) received platinum-based chemotherapy in a combined-modality setting. Neck dissection was reserved for residual disease after definitive IMRT. Overall survival, disease-free survival, and locoregional control were calculated using the Kaplan-Meier method. Results With a median follow-up of 38 months, the overall survival, disease-free survival, and locoregional control rates were all 100% at 3 years. No occurrence of primary cancer was observed during the follow-up period. The reported rates of xerostomia reduced with the interval from the completion of treatment. Nine patients (36%) reported Grade 2 or greater xerostomia at 6 months, and only 2 (8%) of them reported the same grade of salivary function toxicity after 24 months of follow-up. Conclusion In our institution, IMRT for unknown primary cancer has provided good overall and disease-free survival in all the patients with an acceptable rate of complications. IMRT allowed us to address the bilateral neck and ipsilateral putative pharyngeal mucosa with minimal late salivary function toxicity. The use of concurrent chemotherapy and IMRT for more advanced disease led to good clinical results with reasonable toxicities.

In patients with laryngeal cancer, pretreatment diagnosis of cartilage invasion often warrants a surgical or a bimodal treatment. Controversy exists on whether laryngeal cartilage sclerosis on computed tomography (CT) scan is a sign of tumor invasion. Our objective is to evaluate locoregional, laryngectomy-free, disease-specific, and overall survival in patients with laryngeal cancer with or without laryngeal cartilage sclerosis treated with primary radiation therapy.Historical cohort study.Tertiary referral university center.All laryngeal cancer patients treated with primary radiation therapy between 2002 and 2007 were included. Patients with and without laryngeal cartilage sclerosis on CT scan were identified. Patient, tumor, and treatment data were collected. Univariate and multivariate analyses were conducted using Kaplan-Meier survival analyses and Cox proportional-hazards regression.One hundred eleven patients were included for analysis. Seventy-nine patients were classified as T1 or T2, and 32 patients were classified as T3 or T4. Twenty-three percent of patients had any laryngeal cartilage sclerosis, and 77% of patients had no sclerosis. On univariate and multivariate analyses, there was no statistically significant difference between patients with or without sclerosis. Results did not vary when studying each cartilage separately.Laryngeal cancer patients with cartilage sclerosis on CT scan do not have significantly different survival than patients without sclerosis. Validation of these results prospectively is warranted.

Angiogenesis is a necessary process for tumor progression and is driven through molecular interactions between cancer cells and neighboring vascular endothelial cells. The primary mediators of angiogenesis are the vascular endothelial growth factors and their respective receptors on endothelial cells. There are several U.S. Food and Drug Administration–approved anti-angiogenic agents in clinical use. In head and neck cancer there are clinical trials assessing the efficacy of anti-angiogenic agents in combination with chemoradiation therapy. Although the aforementioned growth factors and receptors have been traditionally viewed as anti-angiogenic targets, there are concomitant efforts to understand the role these molecules play within the tumor cells. In this review, we first discuss the biology of angiogenic proteins and the targeting of angiogenic molecules for cancer treatment. We summarize the current clinical trials of anti-angiogenic therapies in head and neck squamous cell carcinoma. Finally, the additional role these molecules play in tumor progression independent of angiogenesis is discussed. © 2010 Wiley Periodicals, Inc. Head Neck, 2011

Complications following free tissue transfer have been well established in the literature. Common and rare causes of free flap failure must be addressed by the treating surgeon when microvascular patency is threatened. With the evolution and prevalence of microsurgery, ‘rare’ causes of free flap failure will become increasingly frequent. A high index of suspicion must be established in patients with multiple failed operative interventions. A case of recurrent free flap failure secondary to heparin-induced thrombocytopenia is presented in a patient with a history of squamous cell carcinoma of the floor of the mouth, and a long-standing history of alcohol and tobacco consumption.

Objectives:To determine whether the fibula free flap is the most frequently used osteocutaneous flap for mandible reconstruction, and whether it provides quality of life, depression and anxiety advantages.Methods:A systematic review of the public Medline database was conducted. Thirteen patients who underwent mandibular reconstruction at our hospital centre completed questionnaires to evaluate quality of life, depression and anxiety outcomes.Results:The most frequently used free flaps are those of the fibula (n = 982), radial forearm (n = 201), iliac crest (n = 113), subscapular system (n = 50) and rib–serratus (n = 7). In our patient population, there was a trend towards a better quality of life in those with a fibula free flap. However, patients in this group were significantly younger than patients with other flap types (p = 0.025). Patients with a subscapular system free flap were more depressed (p = 0.031); however, they had large through-and-through defects.Conclusion:The flap used most frequently in the literature is the fibula free flap. Comparative quality of life data are lacking, and homogeneous populations should be used to reach significant conclusions.

Human papillomavirus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) have been shown to have a significantly better prognosis and response to current treatment modalities. Current guidelines recommend systematic HPV-DNA and/or p16 testing on HNSCCs, although treatment approach should not be directed by test results. The objectives of this study were to (1) assess whether HPV-DNA and/or p16 status are systematically evaluated across North American otolaryngologists-head and neck surgeons and (2) whether the status is used to direct treatment approach.A 15-question online survey was sent to three associations: the Association of Oto-rhino-laryngology-Head and Neck Surgery of Quebec, the Canadian Society of Otolaryngology-Head and Neck Surgery, and the American Head and Neck Society.Sixty-seven percent of respondents systematically test for HPV-DNA and/or p16 on HNSCC sites, while 58.3% report using test results to direct treatment for oropharyngeal cancers. A lack of official guidelines was the primary reason (81.8%) physicians did not use test results to direct treatment. Academic centre physicians (83.3%) and physicians with ⩾50% oncologic practice (87.6%) were more likely to test for HPV-DNA and/or p16 in HNSCC compared to non-academic centre physicians (39.7%) and physicians with50% oncologic practices (51.4%) (p0.001). Cost of the tests (69.2%), lack of relevance (46.1%) and time constraints (30.8%) were the primary reasons HPV-DNA and/or p16 were not tested.The majority of North American respondents in this survey systematically test for HPV-DNA and/or p16 in HNSCC sites, and most indicate that test results influence their treatment approach for oropharyngeal cancers.

Objectives:1) Evaluate systematic testing of human papillomavirus (HPV) and p16 status on head and neck cancer in North America. 2) Assess if HPV or p16 status is used to influence treatment in this population.Methods:An online survey was sent to three professional associations: the American Head & Neck Society, the Canadian Society of Otolaryngology, and the Quebec Association of Otolaryngology. Inclusion criteria were physicians practicing in North America. Incomplete surveys were disregarded. Chi-square analyses were conducted.Results:There was a response rate of 20% with a total of 216 complete responses. Most respondents were otolaryngologists (196; 90.7%), English-speaking (178; 82.4%), and practicing in an academic setting (138; 63.9%). Routine HPV or p16 testing was performed by 146 respondents for the oropharynx, 69 for oral cavity, and 44 for other subsites. Most physicians (113; 77.4%) test for both HPV and p16, while 58.3% indicated that HPV/p16 status influences their treatment approach for o...

Objective: 1) To identify and evaluate patient-reported quality of life (QOL) questionnaires used in studies of oral and oropharyngeal cancer. 2) To provide information on the trends of use of each questionnaire according to language, country of origin, publication date, and type of treatment.Method: Systematic review of the English-language literature. A search using the Medical Subject Headings (MeSH) queries (“Oropharyngeal Neoplasms” OR “Mouth Neoplasms”) AND “Quality of Life” was carried out by using a publicly available MEDLINE interface (PubMed). A total of 371 articles were identified and reviewed. We identified all English-language studies of oral or oropharyngeal cancer patients that measure QOL using a patient-reported questionnaire. Exclusion criteria are review article, comment, non-English-language study, wrong disease, and absence of quality of life measure.Results: Identified questionnaires will be summarized. Each instrument will be compared against the standards for health outcome instru...

Objective: 1) To evaluate p16 status as a predictor of quality of life (QOL) in oral and oropharyngeal squamous cell carcinoma (OSCC). 2) To identify independent predictive factors of QOL in OSCC.Methods: 1) We conducted a cross-sectional study on 156 OSCC patients. Patients were evaluated using 3 validated QOL questionnaires (EORTC QLQ-C30, EORTC QLQ-HN35, HADS). HPV status was determined using p16 status on immunohistochemistry staining on paraffin blocks. Using chi-square and t test analyses, we identified the value of p16 as a predictor of QOL. 2) Patient factors, tumor factors, risk factors, and treatment factors were then identified on medical record review. Bivariate analyses identified predictors of QOL, and multivariate regression analyses identified factors with independent significance.Results: QOL data were collected for 156 patients. Mean and median follow-up times were 63.2 and 35.0 months. Pretreatment tumor p16 status was available for 88 patients. Pretreatment p16 status did not significa...

There are over 30,000 new cases of head and neck squamous cell carcinoma (HNSCC) each year. Despite recent advances, the overall survival of HNSCC patients has remained unchanged in the past 30 years. Patients with recurrent or metastatic cancer have a poorer prognosis and a decreased overall survival. Surgical resection of these cancers often leads to severe permanent cosmetic deformities and functional deficits. Therefore, there is a critical need for more effective agents to treat HNSCC. The epidermal growth factor receptor (EGFR) has shown significant potential as a therapeutic target in solid malignancies, including those of the head and neck. Dys-regulation of EGFR contributes to HNSCC progression. EGFR is overexpressed in approximately 90% of HNSCC tumor specimens where increased expression is correlated with poor clinical outcome.1 Antitumor effects have been observed upon inhibition of the EGFR tyrosine kinase in both in vitro and in vivo models. Among the various approaches to EGFR inhibition, cetuximab (Erbitux, IMC-C225), a chimeric monoclonal antibody against EGFR, has been the most studied.2,3 The 2006 study reported by Bonner et al,3 which examined the efficacy of cetuximab when combined with radiotherapy in patients with locoregionally advanced head and neck cancer, led to the FDA approval of cetuximab for HNSCC. There have been parallel developments with targeted therapies that inhibit angiogenesis. A key regulator of angiogenesis is vascular endothelial growth factor (VEGF), which is secreted by tumor cells in hypoxic conditions. After VEGF is secreted, it binds its receptors (VEGFR1–3) on endothelial cells, leading to endothelial cell proliferation and tumor angiogenesis.4 Beva-cizumab (Avastin, Genentech), a recombinant human monoclonal antibody to VEGF, has been studied in many cancers and has been FDA-approved in colorectal and breast carcinomas.5 Inhibition of EGFR and/or VEGFR has individually shown promise as an anticancer strategy; thus, it is not surprising that the concomitant inhibition of both targets has been proposed as an anticancer therapy.6–8 Tonra et al6 showed that combined treatment with cetuximab and DC101, a humanized monoclonal antibody to VEGFR-2, had more significant antitumor effects in xenografts of colon and pancreatic cancer than each agent alone. AEE788, a small-molecule tyrosine kinase inhibitor (TKI) with dual specificity against EGFR and VEGFR, proved to be an effective therapeutic strategy in a murine oral cancer model.7 Bevacizumab in combination with erlotinib (a small-molecule inhibitor of the EGFR tyrosine kinase) has been studied in phase I/II clinical trials involving patients with recurrent HNSCC. Vokes et al9,10 showed that this combination treatment resulted in a response rate of approximately 70% of patients enrolled. A novel small-molecule TKI, vandetanib, ZD6474 (Astra-Zeneca, Macclesfield, UK), is an oral dual inhibitor of both EGFR and VEGFR developed by AstraZeneca.11 In non-small cell lung cancer, vandetanib showed promising results when used in combination with docetaxel, a anti-mitotic chemotherapy drug.12 Additionally, vandetanib is in an ongoing open-label phase I study in combination with radiation therapy with or without cisplatin for untreated, unresected, locally advanced HNSCC.13 The antitumor effects of EGFR inhibition on HNSCC have been well documented. It has also been observed in vitro that inhibition of EGFR on tumor cells decreases production of VEGF by tumor cells.8 Consistent with this observation, EGFR inhibitors such as gefitinib and cetuximab have shown antiangiogenic properties when used in vivo.14 In several cancer types, signal transducer and activator of transcription 3 (STAT3) has been shown to mediate VEGF production.15,16 STAT3 mediates intracellular signaling pathways in tumor cells that are downstream of EGFR via activation of STAT3 target genes including VEGF.17 It has been demonstrated that EGFR inhibition decreases STAT3 activity and that in vitro suppression of STAT3, in breast and cervical cancers, decreases VEGF production.16,18 Therefore, it is our hypothesis that EGFR inhibition in HNSCC using vandetanib will result in antitumor effects in vitro and in vivo, and these effects are mediated by the activation of STAT3. We hypothesize that the anti-tumor effects of EGFR inhibition will be exerted, in part, through the downregulation of STAT3 and the STAT3 target gene, VEGF. We also anticipate that the decreased production of VEGF will potentiate the effects of direct VEGFR inhibition on the tumor endothelium. HNSCC tumor cells express significant levels of EGFR, but VEGFR expression is limited primarily to the endothelium. Although the specificity of vandetanib to VEGFR is approximately 10-fold greater than that of EGFR, we hypothesized that vandetanib will still have a significant antitumor effect on HNSCC due to the high EGFR expression.19 In this study, we demonstrate that vandetanib exerts significant in vitro and in vivo antitumor effects via inhibition of the EGFR pathway.

Objectives To determine the efficacy of combined positron emission tomography–computed tomography (PET-CT) in identifying recurrent thyroid cancer and to elucidate its role in the clinical management of thyroid carcinoma. Design Retrospective study. Setting Tertiary care referral academic center. Patients One hundred twenty-four patients with previously treated thyroid carcinoma who underwent PET-CT. Main Outcome Measures PET-CT images were correlated with clinicopathologic information. The influence of PET-CT findings on disease status determination and the treatment plan was evaluated. Results Among 121 patients undergoing iodine I 131 ( 131 I) imaging (an 131 I image was unavailable for 3 patients), 80.6% had negative findings on 131 I imaging before undergoing PET-CT. Among 75 patients who had positive findings on PET-CT, 71 were true positive results. Among 49 patients who had negative findings on PET-CT, 32 were true negative results. Therefore, PET-CT demonstrated a sensitivity of 80.7%, specificity of 88.9%, positive predictive value of 94.7%, and negative predictive value of 65.3%. A significant difference was noted in the mean serum thyroglobulin levels between patients with positive vs negative PET-CT findings (192.1 vs 15.0 ng/mL, P = .01) (to convert thyroglobulin level to micrograms per liter, multiply by 1.0). Overall, distant metastases were detected in 20.2% of patients using PET-CT. There was an alteration of the treatment plan in 28.2% of patients as a result of added PET-CT information, and 21.0% of patients underwent additional surgery. Conclusions PET-CT is usually performed in patients with thyroid cancer having elevated thyroglobulin levels but non- 131 I–avid tumors and has high diagnostic accuracy for identifying local, regional, and distant metastases. Additional information from PET-CT in patients with 131 I-negative and thyroglobulin-positive tumors frequently guides the clinical management of recurrent thyroid carcinoma.

v Neck dissections were then performed on all patients and histopathological results were used as gold standard Characteristics N % Mean age (y) 56 Sex M 14 82 F 3 17 Primary tumour site Oropharynx 12 71 Oral cavity 5 29 T stage T1 4 24 T2 5 29 T3 4 24 T4 4 24 N stage N1 2 12 N2 10 59 N3 5 29 Chemotherapy Carbo/ 5FU 10 59 Cisplatin 7 31 Number of cycles 2 8 47 3 9 53 Neck dissection Selective 10 59 Modified radical 4 24 Radical 1 6 Unknown 2 12

5574 Background: HPV has recently been recognised as a good prognostic factor in head and neck (H&N) cancer. However, most of the data is derived from randomised trials with different treatment opt...