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In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT).OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison.In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P0.001). Distant control was 97%, 87%, 68% (P0.001) and overall survival was 75%, 53% and 39% (P0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b.When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

OBJECTIVES/HYPOTHESIS The ideal strategy in the treatment of mucosal melanoma of the head and neck (MMHN) remains unclear. Our objective was to evaluate the importance of surgical margins, radiotherapy, and systemic therapy in MMHN. STUDY DESIGN Retrospective Single Institutional Review. METHODS Retrospective review of patients with MMHN treated at a tertiary care oncology center between 1999 and 2016. RESULTS Seventy-six patients were included, 60 of whom were treated with curative intent. Negative or close margins compared with positive margins were associated with higher 3-year overall survival (OS) (62% vs. 29% vs. 13% P = .012), disease-free survival (33% vs. 29% vs. 4% P = .003), and distant control (48% vs. 29% vs. 22% P = .039). Cases with pre-/postoperative radiotherapy had a marginally higher locoregional control versus without (69% vs. 59%, P = .117). Immunotherapy for recurrent and/or metastatic disease was associated with an increase in 3-year OS (15% vs. 3% P = .01). CONCLUSION Achieving negative surgical margins is relevant in disease control. Despite small sample size, our data suggest that radiotherapy may enhance surgical outcomes. Immunotherapy has therapeutic benefit. LEVEL OF EVIDENCE 3 Laryngoscope, 131:2269-2276, 2021.

Background: Active surveillance (AS) of small, low-risk papillary thyroid cancers (PTCs) is increasingly being considered. There is limited understanding of why individuals with low-risk PTC may choose AS over traditional surgical management. Methods: We present a mixed-methods analysis of a prospective observational real-life decision-making study regarding the choice of thyroidectomy or AS for management of localized, low-risk PTCs

Highlights • Hyperfractionated RT with augmented dose provides durable enhanced disease control. • Late toxicity is unchanged with higher optimal doses using smaller fraction sizes. • Hyperfractionation improves overall survival but mortality profile evolves over time. • Altered fractionation should avoid unnecessary RT protraction to maximize control. • Excessive acceleration should be avoided to minimize severe normal tissue sequelae., Purpose/objective(s) To examine the therapeutic ratio and mortality profile over time in a radiotherapy randomized trial in stage III-IV larynx/pharynx cancer with long-term follow-up. Materials/methods From 1988 to 1995, 331 cases were randomized to either hyperfractionated (HF) (58 Gy/40 fractions, twice daily) or conventional (CF) (51 Gy/20 fractions, once daily) radiotherapy. Overall survival (OS), locoregional (LRC), distant control (DC), ≥Grade 3 late toxicity (LT), and relative mortality risk profile over time were compared between both arms. Results Median follow-up was 13.6 years. HF had a 10% improved OS at 5-years (40% vs 30%, p = 0.04), but the benefit diminished to 3% at 10-years (21% vs 18%). A trend towards higher LRC with HF remained (5-year: 49% vs 40%; 10-year: 49% vs 39%, p = 0.05). DC rates were unchanged (5-year: 87% vs 85%; 10-year: 87 vs 84%, p = 0.56). LT rates were similar (HF vs CF: 5-year: 9% vs 12%; 10-year: 11% vs 14%, p = 0.27). Multivariable analysis confirmed that HF reduced mortality risk by 31% [HR 0.69 (0.55–0.88), p

PURPOSE: Lymphomas often present a diagnostic challenge, and for some a delay in diagnosis can negatively influence outcomes of therapy. We established a nurse practitioner–led lymphoma rapid diagnosis clinic (LRDC) with the goal of reducing wait times to definitive diagnosis. We examined the initial 30-month experience of the LRDC, and results were compared with time periods before implementation of the clinic to determine program impact. METHODS: All patients referred to LRDC with suspicion of lymphoma from June 1, 2015 to Nov 30, 2017 were evaluated. Time from initial consultation to diagnosis was compared with patients diagnosed at our center with lymphoma in 2008 and 2012. Patient symptoms and relevant laboratory/imaging findings were collected to identify patterns of presentation and predictive factors for benign diagnoses. RESULTS: Of the 126 patients evaluated, 66 (52%) had confirmation of lymphoma diagnosis. Median time to lymphoma diagnosis was 16 days for patients assessed in LRDC and 28 days for historical controls ( P < .001). By univariable analysis, lymph node size greater than 3.4 cm and presence of mediastinal or abdominal adenopathy increased the likelihood of a diagnosis of malignancy, whereas younger age, being a nonsmoker, and prior rheumatologic condition were associated with a nonmalignant diagnosis. In multivariable analysis, lymph node size, age, and prior rheumatologic diagnosis remained significant. CONCLUSION: Establishing a nurse practitioner–led LRDC was effective in shortening time to diagnosis of lymphoma. Younger age, smaller lymph node size, and prior rheumatologic disorder reduced the likelihood of a cancer diagnosis in our patient population.

OBJECTIVES/HYPOTHESIS Sarcopenia is a hallmark of aging and its identification may help predict adverse postoperative events in patients undergoing head and neck surgery. The study objective was to assess the relationship between sarcopenia and postoperative complications and length of stay in patients undergoing major head and neck cancer surgery. STUDY DESIGN Prospective cohort study. METHODS A prospective cohort study was performed of patients 50 years and older undergoing major head and neck surgery. Sarcopenia was defined as low muscle mass (determined by neck muscle cross-sectional imaging) with either low muscle strength (grip strength) or low muscle performance (timed walk test). Logistic regression was applied on binary outcomes, and linear regression was used for log-transformed length of hospital stay (LOS). Univariate and multivariate analyses were performed. RESULTS Of the 251 patients enrolled, pre-sarcopenia was present in 34.9% (n = 87) and sarcopenia in 15.6% (n = 39) of patients. Patients with sarcopenia were more likely to be older (P = .001), female (P = .001), have a lower body mass index (P = .001), and lower preoperative hemoglobin (P

It is unclear whether postoperative wound infections after head and neck cancer surgery are associated with cancer progression.Patients undergoing surgery for oral cancer from 1998 to 2011 were reviewed. Univariable analyses and multivariable were performed. Propensity scores were used to create matched cohorts for infection and non-infection groups. Neutrophil-to-lymphocyte ratios (NLR) were determined prior to surgery and at the time of infection.Of 551 patients with oral cancer treated with surgery, 98 developed wound infections (18%). Tumor factors associated with wound infections included higher T and N category, extranodal extension, depth of invasion, lymphovascular and perineural invasion (p 0.02 for all). On univariable analysis, wound infection was a predictor for recurrence free survival (p 0.001), locoregional control (p = 0.01), and distant control (p 0.001). Wound infection was not a predictor of overall survival (p = 0.88), recurrence free survival (p = 0.17), locoregional control (p = 0.79) or distant control (p = 0.18) on multivariable analysis. Using a propensity score matched cohort of 83 patients with and without infection, wound infection was not associated with recurrence free survival (p = 0.21), overall survival (p = 0.71), and locoregional control (p = 0.84), although there was a trend towards increased distant metastases (p = 0.10). Patients with wound infection had a greater preoperative NLR as well as a greater rise in the NLR after surgery, but these were not associated with survival or recurrence.Patients with wound infections have more adverse pathologic features. However, wound infection was not associated with poorer cancer outcomes although a trend towards increased distant metastases should be investigated.

Purpose/objective(s) Local control (LC) of head and neck (HN) soft tissue sarcoma (STS) is generally lower than the > 90% rate expected in extremity STS. We report outcomes of high-risk adult HN STS [defined as requiring surgery and radiotherapy (RT) after joint in-person assessment by a HN surgeon and radiation oncologist with expertise in sarcoma management] using pre-operative (Pre-op) RT to reduce target volumes adjacent to optic or other vulnerable anatomy. Materials/methods A prospective series of newly diagnosed adult HN STS patients who underwent Pre-op RT between 1989-2019 was analyzed. Angiosarcoma, fibromatosis, and embryonal/alveolar rhabdomyosarcoma were not included due to natural history requiring different management paradigms; other histologies were excluded due to the anticipated favorable control rates in these subtypes (i.e., dermatofibrosarcoma protuberans, HN sinonasal solitary fibrous tumor/hemangiopericytoma). Actuarial rates of LC, distant control (DC), and overall survival (OS) were analyzed by resection margin status. Important wound complications, defined according to a published randomized trial evaluating Pre-op RT in extremity STS, were also reported. Results Eligibility comprised 59 cases arising from neck/supraclavicular (n = 23), sinonasal (n = 16), oral (n = 11), parapharyngeal (n = 7), and scalp (n = 2) regions. UICC/AJCC TNM-8 cT-categories were: T1 (n = 10), T2 (n = 20), T3 (n = 20), and T4 (n = 9). Neoadjuvant chemotherapy was given to 3 patients (2 rhabdomyosarcomas and 1 synovial sarcoma). Pre-op RT included: 50 Gy in 25 fractions over 5 weeks (n = 53) or 60 Gy in 30 fractions over 6 weeks (n = 6). Median interval from pre-op RT to surgery was 7.3 weeks (range: 2.9-19.6). Four patients (6.7%) had wound complications considered important according to the defined criteria. One healed following flap debridement and the remainder only required conservative management. Resection margins were grossly positive (gross+) in 4 (7%), microscopically positive (micro+) in 16 (27%), and negative in 39 (68%) patients. Six received a post-op boost of 10 Gy in 5 fractions (1 for micro+ and 5 for Conclusion HN STS patients requiring combined modality local management with moderate dose Pre-op RT in a sarcoma-focused multidisciplinary clinic setting have excellent LC and functional outcomes that parallel extremity cases, but with less wound complications. Micro+ margins without postop boost RT does not seem to compromise LC when managed within a collaborative environment.

Purpose/Objective(s) Only 9% of adult Rhabdomyosarcomas (RMS) present with primary disease in the head and neck (HNRMS), often as a paranasal mass with proptosis, orbital and skull base invasion, and a prodigious risk of regional node involvement and distant metastatic dissemination to unusual locations in the young adult with the embryonal/alveolar (E/A) subtype. E/A-RMS respond rapidly to chemotherapy and radiotherapy (RT) and management is extrapolated from the pediatric experience where prognosis is better but treatment imperatives differ. We report on adults with HNRMS treated over 3 decades. Materials/Methods We reviewed adult patients treated from 1984 – 2017 via chart review and a prospectively maintained database from 1989 onward. RMS were categorized as embryonal/alveolar (E/A) or pleomorphic (P). Standard management was as follows: E/A-RMS were treated with neoadjuvant chemotherapy, definitive chemoradiotherapy (CRT), and then maintenance chemotherapy. Chemotherapy regimens included VAC and VAC/IE, with VC given concurrently with RT. P-RMS were treated with surgery +/- RT. IMRT was adopted from 2005 onward. Results Fifty-eight patients met inclusion criteria; median age was 32 years. Seventy-six percent of tumors (n = 45) were parameningeal and 45% (n = 26) were > 5cm. Of 45 patients with M0 disease treated with curative intent, 33 (73%) had E/A-RMS and 12 (27%) had P-RMS. All E/A-RMS patients received definitive RT with either 66 Gy or 70 Gy in 2 Gy per fraction, except 2 who had surgery for diagnostic purposes. Involved nodal regions were treated with radical dose RT and elective nodal RT was routinely delivered. In the IMRT-era, patients with primary disease in the nasopharynx or paranasal sinuses were treated with bilateral neck RT, while patients with well lateralized primary disease were generally treated with ipsilateral neck RT. Pre-IMRT, out of 23 patients with initial M0 E/A-RMS, 12 (52%) had a loco-regional recurrence. Post-IMRT, out of 10 patients with initial MO disease, only 1 (10%) had a local recurrence; this patient achieved a complete clinical response despite a 3-week interruption after 48 Gy due to local toxicity, but experienced an in-field local recurrence 45 months later that resulted in death. Locoregional control was statistically superior in the IMRT era as compared to pre-IMRT (Fisher's exact test, P = 0.049). Overall, distant metastasis was the predominant mode of treatment failure (n = 17/33, 52%). Conclusion In our experience, the rate of locoregional control for adult E/A-HNRMS following definitive CRT using IMRT is excellent. As such CRT should be considered the treatment of choice in this population to avoid extensive surgery including craniofacial resection and orbital exenteration, which would be needed for many of these patients but has functional and cosmetic consequence; it would also interrupt ongoing maintenance chemotherapy which has proven survival benefit. In contrast P-RMS is distinct and requires surgery +/- RT.

Made available in DSpace on 2020-12-12T01:55:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Canada Foundation for Innovation Ontario Institute for Cancer Research Canada Research Chairs Prognostic biomarkers for recurrence of Oral Squamous Cell Carcinoma (OSCC) are urgently needed. We aimed to independently validate a 4-gene expression signature (MMP1, COL4A1, P4HA2, THBS2) predictive of OSCC recurrence risk. Gene expression was measured using Nanostring nCounter® in 245 histologically normal surgical resection margins from 62 patients. Association between risk scores for individual patients and recurrence was assessed by Kaplan-Meier analysis. Signature performance was quantified by concordance index (CI), hazard ratio (HR) and the area under receiver operating characteristics (AUC). Risk scores for recurrence were significantly higher than recurrence-free patients (p = 9.58e-7, Welch’s t-test). A solid performance of the 4-gene signature was determined: CI = 0.64, HR = 3.38 (p = 1.4E-4; log-rank test), AUC = 0.71. We showed that three margins per patient are sufficient to preserve predictive performance (CI = 0.65; HR = 2.92; p = 2.94e-3; AUC = 0.71). Association between the predicted risk scores and recurrence was assessed and showed HR = 2.44 (p = 9.6E-3; log-rank test, N = 62). Signature performance analysis was repeated using an optimized threshold (70th percentile of risks), resulting in HR = 3.38 (p = 1.4E-4; log-rank test, N = 62). The 4-gene signature was validated as predictive of recurrence risk in an independent cohort of patients with resected OSCC and histologically negative margins, and is potentially applicable for clinical decision making on adjuvant treatment and disease monitoring. São Paulo State University UNESP Faculty of Medicine Department of Surgery and Orthopedics Krembil Research Institute University Health Network Department of Clinical Pathology Sunnybrook Health Sciences Centre Princess Margaret Cancer Centre University Health Network Brazilian Institute for Cancer Control Department of Pathology Toronto General Hospital University Health Network Departments of Medical Biophysics University of Toronto Department of Computer Science University of Toronto Institute of Neuroimmunology Slovak Academy of Sciences Clinical Laboratory Genetics Genome Diagnostics University Health Network Department of Laboratory Medicine and Pathobiology The University of Toronto São Paulo State University UNESP Faculty of Medicine Department of Surgery and Orthopedics

IntroductionAdvanced oral cancer and its ensuing treatment engenders significant morbidity and mortality. Patients are often elderly with significant comorbidities. Toxicities associated with surgical resection can be devastating and they are often highlighted by patients as impactful. Given the potential for suboptimal oncological and functional outcomes in this vulnerable patient population, promotion and performance of shared decision making (SDM) is crucial.Decision aids (DAs) are useful instruments for facilitating the SDM process by presenting patients with up-to-date evidence regarding risks, benefits and the possible postoperative course. Importantly, DAs also help elicit and clarify patient values and preferences. The use of DAs in cancer treatment has been shown to reduce decisional conflict and increase SDM. No DAs for oral cavity cancer have yet been developed.This study endeavours to answer the question: Is there a patient or surgeon driven need for development and implementation of a DA for adult patients considering major surgery for oral cancer?Methods and analysisThis study is the first step in a multiphase investigation of SDM during major head and neck surgery. It is a multi-institutional convergent parallel mixed-methods needs assessment study. Patients and surgeon dyads will be recruited to complete questionnaires related to their perception of the SDM process (nine-item Shared Decision-Making Questionnaire, SDM-Q-9 and SDM-Q-Doc) and to take part in semistructured interviews. Patients will also complete questionnaires examining decisional self-efficacy (Ottawa Decision Self-Efficacy Scale) and decisional conflict (Decisional Conflict Scale). Questionnaires will be completed at time of recruitment and will be used to assess the current level of SDM, self-efficacy and conflict in this setting. Thematic analysis will be used to analyse transcripts of interviews. Quantitative and qualitative components of the study will be integrated through triangulation, with matrix developed to promote visualisation of the data.Ethics and DisseminationThis study has been approved by the research ethics boards of the Nova Scotia Health Authority (Halifax, Nova Scotia) and the University Health Network (Toronto, Ontario). Dissemination to clinicians will be through traditional approaches and creation of a head and neck cancer SDM website. Dissemination to patients will include a section within the website, patient advocacy groups and postings within clinical environments.

Objective The aim of this study is to determine if Hyams grade may help predict which patients with esthesioneuroblastoma (ENB) tumors are likely to develop regional recurrences, and to determine the impact of tumor extent on regional failure in ENB patients without evidence of nodal disease at presentation. Design The study was designed as a retrospective review for ENB patients. Settings The study was prepared at tertiary care academic center for ENB patients. Participants Patients with ENB were included in the study. Main Outcome Measures Oncologic outcomes (5-year regional and locoregional control (LRC) and overall survival) in patients with Hyams low grade versus high grade. Oncologic outcomes based on radiographic disease extent. Results A total of 43 patients were included. Total 25 patients (58%) had Hyams low-grade tumor, and 18 (42%) had high-grade tumor. Of the 34 patients without regional disease at presentation, 8 (24%) were treated with elective nodal radiation. There were no statistically significant differences in 5-year regional control in the Hyams low-grade versus high-grade groups (78 vs. 89%; p = 0.4). The 5-year LRC rates in patients with low grade versus high grade were 73 versus 89% (p = 0.6). The 5-year overall survival rates in patients with low-grade versus high-grade tumors were 86 versus 63% (p = 0.1). Radiographic extension of disease into the olfactory groove, olfactory nerve, dura, and periorbita were statistically associated with decreased 5-year overall survival (5-year OS 49 vs. 91% [p = 0.04], 49 vs. 91% [p = 0.04], 44 vs. 92% [p = 0.02], and 44 vs. 80% [p = 0.04], respectively). Conclusion ENBs are associated with a risk of regional failure. The current analysis suggests that Hyams low-grade and high-grade malignancies have comparable rates of early and delayed regional recurrences, although small sample size may limit our conclusions.

Background In the wake of the coronavirus disease 2019 (COVID‐19) pandemic, access to surgical care for patients with head and neck cancer (HNC) is limited and unpredictable. Determining which patients should be prioritized is inherently subjective and difficult to assess. The authors have proposed an algorithm to fairly and consistently triage patients and mitigate the risk of adverse outcomes. Methods Two separate expert panels, a consensus panel (11 participants) and a validation panel (15 participants), were constructed among international HNC surgeons. Using a modified Delphi process and RAND Corporation/University of California at Los Angeles methodology with 4 consensus rounds and 2 meetings, groupings of high‐priority, intermediate‐priority, and low‐priority indications for surgery were established and subdivided. A point‐based scoring algorithm was developed, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN‐HN). Agreement was measured during consensus and for algorithm scoring using the Krippendorff alpha. Rankings from the algorithm were compared with expert rankings of 12 case vignettes using the Spearman rank correlation coefficient. Results A total of 62 indications for surgical priority were rated. Weights for each indication ranged from −4 to +4 (scale range; −17 to 20). The response rate for the validation exercise was 100%. The SPARTAN‐HN demonstrated excellent agreement and correlation with expert rankings (Krippendorff alpha, .91 [95% CI, 0.88‐0.93]; and rho, 0.81 [95% CI, 0.45‐0.95]). Conclusions The SPARTAN‐HN surgical prioritization algorithm consistently stratifies patients requiring HNC surgical care in the COVID‐19 era. Formal evaluation and implementation are required. Lay Summary Many countries have enacted strict rules regarding the use of hospital resources during the coronavirus disease 2019 (COVID‐19) pandemic. Facing delays in surgery, patients may experience worse functional outcomes, stage migration, and eventual inoperability.Treatment prioritization tools have shown benefit in helping to triage patients equitably with minimal provider cognitive burden.The current study sought to develop what to the authors' knowledge is the first cancer–specific surgical prioritization tool for use in the COVID‐19 era, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN‐HN). This algorithm consistently stratifies patients requiring head and neck cancer surgery in the COVID‐19 era and provides evidence for the initial uptake of the SPARTAN‐HN., To the authors' knowledge, the Surgical Prioritization and Ranking Tool and Navigation Aid for Head and Neck Cancer (SPARTAN‐HN) is the first cancer surgery–specific prioritization tool for use during the coronavirus disease 2019 (COVID‐19) pandemic. The SPARTAN‐HN algorithm is reliable and valid for the stratification of patients with head and neck cancer who require urgent cancer care in resource‐restricted practice environments.

With the COVID-19 pandemic, there has been significant changes and challenges in the management of oncology patients. One of the major strategies to reduce transmission of the virus between patients and healthcare workers is deferral of follow-up visits. However, deferral may not be possible in total laryngectomy patients. Urgent procedures may be necessary to prevent complications related to ill-fitting tracheoesophageal puncture (TEP) voice prostheses, such as aspiration or loss of voicing. In this paper, we describe the Princess Margaret Cancer Center’s approach to managing this unique patient population.

Optimal management of tracheal stenosis depends on identifying causative factors. Risk factors include high tracheostomy, cricothyroidotomy, prolonged intubation, and proximal migration of an endotracheal tube cuff. Management ranges from conservative observation to endoscopic procedures or open surgical resections. The goal of surgical repair is an adequate airway, decannulation, and normal laryngeal function. For early stage disease, management of refractory conditions is via endoscopic procedures. An understanding of the respiratory function of the glottis and subglottis is essential when an optimum functional reconstruction of the glottic/subglottic area is considered. In this article we discuss different airway assessments and surgical management techniques.

Importance Pharyngocutaneous fistula (PCF) results in an inflammatory reaction, but its association with the rate of locoregional and distant control, disease-free survival, and overall survival in laryngeal cancer remains uncertain. Objective To determine if pharyngocutaneous fistula after salvage laryngectomy is associated with locoregional and distant control, disease-free survival, and/or overall survival. Design, Setting, and Participants A multicenter collaborative retrospective cohort study conducted at 5 centers in Canada and the US of 550 patients who underwent salvage laryngectomy for recurrent laryngeal cancer from January 1, 2000, to December 31, 2014. The median follow-up time was 5.7 years (range, 0-18 years). Main Outcomes and Measures Outcomes examined included locoregional and distant control, disease-free survival, and overall survival. Fine and Gray competing risk regression and Cox-proportional hazard regression models were used for outcomes. Competing risks and the Kaplan-Meier methods were used to estimate outcomes at 3 years and 5 years. Results In all, 550 patients (mean [SD] age, 64 [10.4] years; men, 465 [85%]) met inclusion criteria. Pharyngocutaneous fistula occurred in 127 patients (23%). The difference in locoregional control between the group of patients with PCF (75%) and the non–PCF (72%) group was 3% (95% CI, −6% to 12%). The difference in overall survival between the group with PCF (44%) and the non–PCF group (52%) was 8% (95% CI, −2% to 20%). The difference in disease-free survival between PCF and non–PCF groups was 6% (95% CI, −4% to 16%). In the multivariable model, patients with PCF were at a 2-fold higher rate of distant metastases (hazard ratio, 2.00; 95% CI, 1.22 to 3.27). Distant control was reduced in those with PCF, a 13% (95% CI, 3% to 21%) difference in 5-year distant control. Conclusions and Relevance This multicenter retrospective cohort study found that development of PCF after salvage laryngectomy is associated with an increased risk for the development of distant metastases.

Background The purpose of this study was to compare the clinicoradiologic characteristics of human papillomavirus (HPV)-related (HPV-positive) and HPV-unrelated (HPV-negative) oropharyngeal carcinoma (OPC). Methods Primary tumor and lymph node features of HPV-positive and HPV-negative OPCs from 2008 to 2013 were compared on pretreatment CT/MRI. Intrarater/interrater concordance was assessed. Multivariable analyses identified factors associated with HPV-positivity to be used in nomogram construction. Results Compared to HPV-negative (n = 194), HPV-positive (n = 488) tumors were more exophytic (73% vs 63%; p = .02) with well-defined border (58% vs 47%; p = .033) and smaller axial dimensions; lymph node involvement predominated (89% vs 69%; p < .001) with cystic appearance (45% vs 32%; p = .009) but similar topography. Intrarater/interrater concordance varied (fair to excellent). Nomograms combining clinical (age, sex, smoking pack-years, subsite, T/N classification) and/or radiologic (nonnecrotic tumor and cystic lymph node) features were used to weigh the likelihood of HPV-driven tumors (area under the curve [AUC] = 0.84). Conclusion HPV-positive OPC has different radiologic tumor (exophytic/well-defined border/smaller axial dimension) and lymph node (cystic) features but similar lymph node topography.

Background Given the dramatic changes in global head and neck cancer epidemiology, the purpose of this study was to present the findings of our investigation on patterns of head and neck cancer incidence/survival within the province of Ontario, Canada. Methods Temporal variations in age/sex adjusted incidence and survival were analyzed for all incident head and neck cancer cases (n = 20 781) managed within Ontario from 1993-2010. Results From 1993-2010, the incidence of oropharyngeal (average annual percentage change [AAPC] 4.56%; P

Background Practice variability exists for the extent of neck dissection undertaken for papillary thyroid carcinoma (PTC) metastatic to the lateral neck nodes, with disagreement over routine level V dissection. Methods We performed a retrospective medical record review of PTC patients with lateral neck nodal metastases treated at University Health Network from 2000 to 2012. Predictive factors for regional neck recurrence, including extent of initial neck dissection, were analyzed using Cox regression. Results Out of 204 neck dissections in 178 patients, 110 (54%) underwent selective and 94 (46%) had comprehensive dissection including level Vb. Mean follow-up was 6.3 years (SD). Significant predictors of regional failure were the total number of suspicious nodes on preoperative imaging (p = 0.029), largest positive node on initial neck dissection (p

Background The primary purpose of this study was to examine whether angiosarcoma outcomes differ for the scalp and face. Methods We conducted a retrospective outcomes analysis of 50 patients with cutaneous angiosarcoma treated by curative intent identified from the Princess Margaret Cancer Centre Registry (from 1958 to 2014). Results Median survival was 26 months (95% confidence interval [CI], 17.6-34.6) and median follow-up 29 months. For the scalp and face, respectively, the 5-year locoregional control rate was 9% and 53% (p = .04); the recurrence-free survival (RFS) rate was 5% and 27% (p = .017); and the overall survival (OS) rate was 9% and 26% (p = .017). Scalp lesions were larger, more likely to be multifocal, and presented more rapidly once noticed. In multivariate Cox proportional hazards analysis, scalp location was independently prognostic for mortality (hazard ratio [HR], 2.10; 95% CI, 1.03-4.28; p = .04). Conclusion Scalp angiosarcoma has worse survival than angiosarcoma of the face. Scalp angiosarcoma tends to be larger at presentation, which may be because it is not noticed until more advanced. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1205-1211, 2017.

Gene-expression classifiers (GEC) and genetic mutation panels (GMP) have been shown to improve preoperative diagnostic evaluations of indeterminate thyroid nodules. Despite the improvement, uncertainty regarding the proper management exists. Patient preferences may better inform the management of these indeterminate thyroid nodules. Hypothetical scenarios were administered to two groups of patients: those with previous FNA-confirmed indeterminate thyroid nodules (Group A, n = 50) and those presenting to a general otolaryngology clinic for other reasons (Group B, n = 50). We evaluated patient preferences for surgery, observation and the use of molecular tests while varying the risk of malignancy, cost and diagnostic properties of the tests. The mean threshold for choosing surgery over observation was a 38.6% risk of malignancy on FNA. When offered either GEC, GMP or both (with their inherent imperfect diagnostic properties) in addition to the indeterminate FNA, 85.0% of respondents picked at least one of the molecular tests over either observation or surgery if the test(s) were free of charge. However, only 51.7% of respondents chose at least one of the tests when asked to pay the current cost of the test(s) (p

OBJECTIVES To evaluate whether frailty and functional measures are predictors of perioperative complications and length of hospital stay (LOS) in patients undergoing head and neck cancer surgery. STUDY DESIGN Prospective study. METHODS Patients 50 years and older undergoing major head and neck cancer surgery between 2011 and 2015 preoperatively completed Fried's Frailty Index, Barthel Index, Lawton-Brody questionnaire and Vulnerable Elders Survey-13. Primary outcome measures were postoperative complications and LOS, which were analyzed using multivariable logistic and linear regression models. RESULTS There were 274 patients recruited (105 aged 50-64 and 169 aged 65 and older). Of these, 119, 132, and 23 were defined as non-frail, pre-frail, and frail, respectively. Frailty score and functional measures were not predictors of overall complications. In multivariable models, frailty score (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.04-1.78, P = .025) was a predictor of medical complications and Clavien-Dindo Grade III and higher complications independent of age and comorbidity. Higher frailty score (β = 1.07; 95% CI, 1.02-1.12, P = .0025) and less independence on the Lawton Brody (β = -0.08; 95% CI, -0.11 to -0.05, P

OBJECTIVES/HYPOTHESIS Identify predictors of decannulation failure after cricotracheal resection (CTR) and thyrotracheal anastomosis (TTA) in patients with subglottic stenosis (SGS). STUDY DESIGN Retrospective cohort study. METHODS Charts of patients undergoing CTR and TTA for SGS at the University Health Network, Toronto, Ontario, Canada between 1988 and 2017 were reviewed. Patient, pathology, treatment, and outcome data were collected. The end points for statistical analysis were development of restenosis and permanent tracheostomy. RESULTS One hundred fourteen patients (n = 114) were eligible for inclusion in this review. The mean age at primary resection was 46.9 years, 95 (83%) were females, and 19 (17%) were males. The rate of restenosis and permanent tracheostomy was 13% and 5%, respectively. Sixty-two patients (54%) underwent a CTR and TTA, and 52 patients (46%) underwent a CTR, laryngofissure, and TTA. Traumatic stenosis (odds ratio [OR] = 10.3, P = .017), longer T-tube duration (OR = 1.2, P = .011), combined glottic/subglottic stenosis (OR = 10.47, P = .010), start of the stenosis at the vocal cords (OR = 6.6, P = .029), postoperative minor complications (OR = 13.6, P = .028), and need for repeat surgery (OR = 44.1, P

OBJECTIVES/HYPOTHESIS To describe initial presentations and idiosyncrasies in establishing the diagnosis for human papillomavirus-related (HPV(+) ) compared to HPV-unrelated (HPV(-) ) oropharyngeal carcinoma (OPC). STUDY DESIGN A single institution retrospective series derived from an institutional prospectively compiled database supplemented by chart review. METHODS We reviewed consecutive OPC patients referred to an academic tertiary cancer center from 2009 to 2011. HPV status was evaluated by p16 staining. Signs/symptoms and procedures to establish diagnosis were recorded independently by two abstractors blinded to the HPV status during data retrieval. Initial presentations (signs/symptoms), interval, and the procedures to establish the diagnosis were compared between HPV(+) and HPV(-) OPC. RESULTS The most common initial presentation was an asymptomatic nodal mass for HPV(+) patients (n = 208; 69% vs. 29%, P 12 months) from onset of signs/symptoms to diagnosis was observed in 18 (9%) HPV(+) versus three (3%) HPV(-) patients (P = .058). More HPV(+) patients required repeated (≥2) biopsy procedures (56% vs. 10%, P < .001). Misattribution to other disease occurred in eight (4%) HPV(+) patients (seven were mistaken as having a "branchial cleft cyst" when there were cystic lymph nodes and one as having a "lymphoma") compared to none in HPV(-) . CONCLUSIONS About two-thirds of HPV(+) patients present with an asymptomatic neck mass and often require multiple biopsy procedures to establish the diagnosis. Idiosyncrasies in appreciating the diagnostic setting (cystic lymph node, misattribution to other entities, or submucosal location of the tumor) or patient-related factors could delay the diagnosis of HPV(+) OPC. LEVEL OF EVIDENCE 4 Laryngoscope, 126:2270-2275, 2016.

Background The purpose of this study was to measure adherence rates to guideline-recommended process measures in patients with head and neck cancer. Methods A total of 5720 patients who underwent surgery for head and neck cancer in Ontario between 1993 and 2010 were identified from administrative databases. Adherence to 4 guideline-recommended processes of care was measured and stratified by hospital and physician case volume. Results Seventy-two percent of patients received preoperative head and neck imaging, 83% received preoperative chest imaging, 58% received preoperative multidisciplinary consultation, and 77% had appropriate follow-up visits. Higher surgeon and hospital surgical volumes were associated with higher adherence rates. Conclusion Adherence rates to guideline-recommended processes of care in the surgical management of patients with head and neck cancer in Ontario were moderate and should be improved. Although adherence rates seem proportional to surgical volume, even the highest volume centers have room to improve. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Background The purpose of this study was to determine the clinical outcomes of T4 laryngeal cancers. Methods T4 laryngeal cancers treated with curative intent from January 2003 to December 2010 were analyzed. Outcomes were evaluated in both primary radiotherapy (+/− chemotherapy) (RT/CRT) and primary surgery cohorts. Results Among the 65 primary RT/CRT and 42 primary surgery patients included, median follow-up was 4.4 years. There was a trend for improved locoregional control with surgery (74% vs 88%; p = .08). In the RT/CRT group the 3-year laryngectomy-free survival was 67%. The 2-year gastrostomy dependency rate was 23% with RT/CRT versus 6% with primary surgery (p = .07). Overall survival (OS) at 3 years was significantly lower in the RT/CRT versus primary surgery group (41% vs 70%; p < .01). Conclusion Laryngeal preservation is achieved in over two thirds of patients with primary RT/CRT. Patients with low volume minimal cartilage involvement T4 disease may be best suited to RT/CRT. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).

Importance Clinicians should understand the prevalence of depression and decision regret in patients with head and neck cancer and whether these factors differ with age or frailty. Objectives To assess whether age and frailty are associated with preoperative and/or worsening postoperative depression and postoperative decision regret in patients undergoing major head and neck surgery and to identify additional factors associated with depression and decision regret. Design, Setting, and Participants This prospective cohort study was conducted at a single institution, with patients aged 50 years or older undergoing major head and neck surgery recruited from December 1, 2011, to April 30, 2014. Statistical analysis was performed from July 1, 2018, to June 30, 2019. Main Outcomes and Measures Frailty, functional, and geriatric depression assessments were completed before surgery and 3, 6, and 12 months after surgery. Decision regret assessment was completed 6 months after surgery. The prevalence of depression and decision regret was determined by age group. Change in depression over time was compared between age groups using a linear-effects model. Variables potentially associated with moderate to severe depression and decision regret were analyzed using a logistic regression model. Results The study included 274 patients (68 women and 206 men; mean [SD] age, 67.8 [9.5] years). Of these, 105 (38.3%) were 50 to 64 years of age and 169 (61.7%) were 65 years or older. The rate of preoperative moderate to severe depression was 9.6% (21 of 219), with no difference between younger and older adult cohorts. For both age groups, depression scores increased in the postoperative period from baseline to 6 months. At 12 months, there was a difference in depression scores between the younger and older adult cohort (4.8 [4.6] vs 3.1 [3.6]). A higher preoperative Fried Frailty Index score (odds ratio, 2.58 [95% CI, 1.63-4.06]) was associated with preoperative moderate to severe depression. For all patients, the mean Decision Regret Scale score was 18.2 (range, 0-95), and 26.7% of patients (48 of 180) had moderate to severe regret. There was no difference in Decision Regret Scale scores between younger and older patients. Preoperative depression but not frailty is associated with postoperative moderate to severe decision regret (odds ratio, 1.17 [95% CI, 1.06-1.28]). Conclusions and Relevance In this cohort study, there was no difference based on age in the prevalence of moderate to severe depression or decision regret. A higher preoperative frailty score was associated with depression but not decision regret. Preoperative depression was the only factor associated with moderate to severe decision regret on multivariate analysis. Understanding the prevalence of and factors associated with moderate to severe depression and decision regret may aid in identifying patients who would benefit from more extensive preoperative counseling and preoperative and postoperative multispecialty assessment and treatment.

Introduction Low-risk papillary thyroid cancer (PTC) is increasingly being diagnosed throughout the world; yet the mortality risk is low compared with other malignancies. Traditional management includes thyroid surgery, sometimes followed by radioactive iodine and thyroid hormone treatment. Active surveillance (AS) has been proposed as a means to reduce overtreatment of PTC. AS involves close disease follow-up, with the intention to intervene if the disease progresses, or on patient request. Methods and analysis This is a multiphase prospective observational study. In the first phase of this study, consenting eligible adults with low-risk PTC, that is

(1) To estimate the prevalence of radiographically positive Retro-Pharyngeal Lymph Nodes (RPLN) in unknown primary carcinoma of the head and neck and (2) to determine the prognostic implications of radiographically positive RPLN and other radiographic features (3) to identify patients at low risk for retropharyngeal metastasis.The medical records of all 68 eligible patients treated at the Princess Margaret Cancer Centre between 2000 and 2014 were retrospectively reviewed for demographic, clinical, pathologic, and radiologic data. Radiologic data included: RPLN, extra capsular spread (ECS), neck staging and cystic/necrotic or matted neck nodes. LRR, DR, DFS and OS were estimated using the competing risk methods and the Kaplan-Meier method.Seven patients had concerning RPLN (10.3%). Forty-four patients were p16 positive (65%). RPLN status did not have any effect on LRR, DFS, DR and OS. Radiological ECS and p16 (neg.) status were found to be significant predictors of LRR (p = 0.023; p = 0.014). Matted nodes, radiological ECS and p16 (neg.) status were found to be significant predictors of DFS (p = 0.012; p 0.001; p = 0.014). Matted nodes and radiological ECS were found to be significant predictors of OS (p = 0.017; p = 0.0036). Only radiological ECS was found to be a significant predictor of distant recurrence (p = 0.0066).10% of CUP patients will harbor radiological positive RPLN. A large proportion of CUP patients are positive for p16. Radiologic features such as ECS and matted nodes can predict worse outcomes.

To evaluate the accuracy and prognostication of the presence of radiologic extranodal extension (rENE) versus pathologic extranodal extension (pENE) in patients with oral cavity squamous cell carcinoma (OSCC).A retrospective review was conducted for all newly diagnosed OSCC patients who underwent neck dissection in our institution from 2010 to 2015 with available records of preoperative computed tomography or magnetic resonance imaging. Two head and neck neuroradiologists reviewed the presence of rENE (defined as ill-defined lymph node borders) on imaging independently, being blinded regarding the pathology report. The impact of the imaging-surgery interval, imaging modalities, and intrarater and interrater concordance of rENE was assessed. The diagnostic accuracy of rENE versus pENE was evaluated. Overall survival (OS) was compared between those with and without rENE. Multivariate analysis evaluated the prognostic value of rENE.Among the 508 patients, rENE and pENE were identified in 57 and 121 cases, respectively. The diagnostic accuracy of rENE versus pENE was identical (73%) for cases with the imaging-surgery interval ≤4 weeks (n = 276) and 4 to 8 weeks (n = 207) but lower (48%) for those8 weeks (n = 25). Computed tomography displayed higher accuracy on rENE assessment versus magnetic resonance imaging (80% vs 63%, P = .011). Interrater and intrarater concordance (n = 93) was good (κ = 0.79) and excellent (κ = 0.94), respectively. Excluding the 25 cases with a8 weeks imaging-surgery interval, the sensitivity, specificity, positive predictive value, and negative predictive value of rENE versus pENE in the remaining 483 cases were 52%, 96%, 93%, and 66%, respectively. Patients with rENE (n = 55) had inferior OS versus those without rENE (n = 202), and both had lower OS than node-negative (n = 226) patients (3-year OS: 31% vs 68% vs 81%, P.001). Multivariate analysis, adjusted for age, T category, N category, and performance status, confirmed the prognostic value of rENE for OS (hazard ratio 3.3, 95% confidence interval 2.4-5.3, P.001).This large cohort study shows a high specificity but low sensitivity of rENE for pENE. Similar to pENE, the presence of rENE is associated with reduced survival in OSCC.

Background The purpose of this study was to evaluate the individual and combined relationship of comorbidity and performance status (PS) on head and neck squamous cell carcinoma (HNSCC) survival. Methods Six hundred patients with HNSCC were prospectively recruited. Comorbidity and PS were measured using the Charlson Comorbidity Index (CCI) and the Eastern Cooperative Oncology Group (ECOG) Scale. Outcomes were overall survival (OS) and cancer-specific survival (CSS). Results A total of 48.3% of the patients had at least 1 comorbidity, and 42.3% had impaired PS at baseline. There was no correlation between CCI and ECOG (Spearman's ρ = 0.033; p = .42). In multivariate analysis, CCI score was significantly associated with OS (p = .01). ECOG was not associated with OS, but seems to act as an effect modifier in the association between comorbidity and OS. CCI and ECOG were not associated with CSS. Conclusion CCI and ECOG scores both provide prognostic information in predicting OS in HNSCC, but a significant association with CSS was not observed. © 2015 Wiley Periodicals, Inc. Head Neck 38: 736–742, 2016

Background Adult laryngotracheal reconstruction for airway stenosis and after oncologic ablation can be extremely challenging. Methods Patients with the above conditions not amenable to or refractory to conventional treatments were offered specialized reconstruction by wrapping a contoured costal cartilage graft with a vascularized microvascular carrier. All constructs were lined with buccal mucosa grafts. Decannulation rates, quality of life questionnaires, and pulmonary function tests were performed and analyzed. Results Eleven patients underwent this procedure, 6 for stenosis and 5 for laryngotracheal oncologic defects. Ten patients were successfully decannulated after the procedure (91%). Median time to decannulation was 4 months. At mean follow-up of 76 months, all evaluated patients had a serviceable voice, tolerated a normal diet, and had minimal subjective shortness of breath. Conclusion Vascularized composite autograft can be successfully used to treat severe subglottic stenosis or reconstruct large laryngotracheal defects not amenable to or refractory to conventional treatments. © 2014 Wiley Periodicals, Inc. Head Neck 38: 253–259, 2016

Human papillomavirus (HPV) is responsible for a subset of mucosal head and neck cancer (mainly in oropharynx) as well as benign lesions such as recurrent respiratory papillomatosis. HPV-related (HPV+) head and neck cancer mainly arises from the oropharynx and has much lower prevalence in the oral cavity, larynx, hypopharynx, and larynx. Epidemiological studies show the incidence of HPV-related (HPV+) oropharyngeal cancer (OPC) rising in many countries in the world. Currently there are no established screening tools to facilitate early-diagnosed HPV+ OPC. HPV+ OPC has a unique clinical behavior that contrasts traditional HPV– patients. HPV+ OPC patients often present as an “unknown primary” with enlarged cervical lymph nodes. Delayed diagnosis may occur due to patient-related factors as well as clinician-related factors, such as unfamiliarity with potential initial presentations of HPV+ OPC, resulting in delayed referral from the family doctor to otolaryngologists and/or technical challenges in obtaining tissue or misdiagnosis by the otolaryngologist. An HPV+-specific TNM staging system will be included in the upcoming 8th edition UICC/AJCC TNM classification. HPV+ OPC has a remarkably good outcome in the low-risk group, and there is a strong likelihood that we are overtreating this subset using treatments designed for traditional HPV– OPC. A risk-stratified treatment algorithm is currently under testing. Counseling HPV+ patients is important to dispel stigmata and myths about this newly identified fast rising disease entity.

Despite improvements in surgical technique and technology, hardware complications occur relatively frequently. This study analyzes hardware complications in patients undergoing oromandibular reconstruction using scapular (SFF) or fibular (FFF) free flaps.Retrospective data for 178 patients was obtained (1999-2014) at University Hospital Network (Toronto, Canada). Univariable and multivariable analyses were performed to identify risk factors for hardware complications.Patients with FFF reconstruction (n=129) had significantly more hardware complications than those with SFF (n=49) (16% vs. 2%;p=0.01). Surgical site infection (SSI) (OR=7.05; p0.01), defect type (OR=2.63; p0.01) and flap (OR=0.12; p=0.01) were significant predictors of hardware complications on univariable analysis. Flap type (OR=0.12; p=0.04) was an independent predictor of plate complication after adjusting for SSI. A subgroup analysis suggested a trend towards fewer hardware complications with SFF stratified by mandibular defect type.Scapular free flaps are associated with a lower rate of hardware-related complications in oromandibular reconstruction.

Background Plate-related complications following head and neck cancer ablation and reconstruction remains a challenging problem often requiring further management and reconstructive surgeries. We aim to identify an association between surgical site infections (SSI) and plate exposure. Methods A retrospective study between 1997 and 2014 was performed to study the association between postoperative SSI and plate exposures. Eligible patients included those with a history of oral squamous cell carcinoma who underwent surgical resection, neck dissection, and free tissue reconstruction. Demographic and treatment related information was collected. SSI were classified based on CDC definition and previously published literature. Univariable analysis on demographic factors, smoking history, diabetes, radiation, surgical and hardware related factors; while multivariable analysis on SSI, plate height, segmental mandibulectomy defects and radiation were conducted such as using cox proportional hazard models. Results Three hundred sixty-five patients were identified and included in our study. The mean age of the study group was 59.2 (+/−13.8), with a predominance of male patients (61.9%). 10.7% of our patient cohort had diabetes, and another 63.8% had post-operative radiation therapy. Patients with SSI were more likely to have plate exposure (25 vs. 6.4%, p

Objective Skull base tumors are associated with quality of life (QOL) changes. A qualitative case-study approach may help better understand patients' experiences. Methods A total of 34 skull base surgery patients were selected into focus groups using a criterion-based maximum variation sampling strategy from a sampling frame of 138 patients. Eight groups were organized based on a factorial design of surgical approach (endoscopic/pen) and tumor location (anterior/central). Data were analyzed using a conceptual framework. Qualitative analysis was performed on focus group transcripts to identify major themes and determine if surgical approach or tumor location had differential effects on QOL. Concepts were quantitatively tallied from written workbooks. Results The 34 participants (19 men, 15 women; mean age: 48 years, standard deviation: 14 years) had mixed reactions to their diagnosis ranging from relief to fear. Participants reported physical and nonphysical changes in QOL with some variation in physical complaints by tumor location. Several major themes emerged from the analysis. Skull base tumors are associated with fear and frustration, loss of physical senses and self-identity, social isolation, and coping mechanisms. Conclusions Skull base surgery may impact patients' lives. Qualitative study of patient experiences can provide rich information to better understand this disease.

Objectives/Hypothesis The importance of reporting and grading surgical complications is central to quality improvement in head and neck surgery. The purpose of this study is to assess the interobserver reliability, content validity, and construct validity of the Clavien-Dindo classification system for use in grading complications related to head and neck surgery. Study Design 1 and 2. Methods Hypothetical cases of common head and neck surgical complications, along with a brief questionnaire, were responded to by 81 residents, fellows, and head and neck surgeons for grading to assess the interobserver reliability of the Clavien-Dindo system. Construct validity was assessed with the a priori hypothesis that increasing complication grade resulted in an increased length of hospital stay. Results Interobserver reliability scores for the complication grading scenarios ranged mostly from moderate to high. The grading system was well received by the respondents, but specific concerns were raised regarding utility in head and neck surgery. Construct validity was confirmed as hospital length of stay was statistically related to complication grade (P = .002) Conclusion Reporting of complications is critical to quality improvement in surgical practice. Currently, the Clavien-Dindo complication grading scale system is a useful tool for grading head and neck surgery complications; however, the development of a grading scale customized to head and neck surgery may be beneficial in the future. Level of Evidence N/A. Laryngoscope, 124:2726–2731, 2014

Background In this cross-sectional study, the sensibility, test-retest reliability, and validity of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire were assessed in patients who underwent neck dissection. Methods Sensibility was assessed with a questionnaire. Test-retest reliability was performed with completion of the DASH questionnaire 2 weeks after initial completion; validity, by evaluating differences in scores between patients undergoing different types of neck dissections and correlating DASH scores with Neck Dissection Impairment Index (NDII) scores. Results The DASH questionnaire met sensibility criteria. For test-retest reliability analysis, the intraclass coefficient was 0.91. The DASH questionnaire showed differences between patients who underwent accessory nerve-sacrifice and nerve-sparing neck dissection. DASH questionnaire scores strongly correlated with NDII scores (r = -0.86). Conclusion Although this study provides preliminary data on some psychometric properties of the DASH questionnaire in patients who have undergone a neck dissection, further assessment of responsiveness and other properties are required. © 2014 Wiley Periodicals, Inc. Head Neck 37: 234-242, 2015

Background The purpose of this study was to compare outcomes between human papillomavirus (HPV)-related versus -unrelated head and neck cancer after pathological positive planned neck dissection. Methods Positive planned neck dissection for head and neck cancers from 1998 to 2010 were included in this study. Outcomes after planned neck dissection were compared between HPV-related versus -unrelated cohorts. Multivariate analysis identified survival predictors. Results HPV-related head and neck cancer (n = 32) had better 5-year overall survival (48% vs 27%; p = .021), marginally lower second malignancy (7% vs 16%; p = .13), but similar local, regional, and distant control (87% vs 89%; 94% vs 89%; 62% vs 58%, respectively) versus HPV unrelated (n = 38). HPV status conferred reduced risk of death (hazard ratio [HR], 0.5; p = .038) after adjusting for age, smoking, and initial T and N classifications. Conclusion This study reveals that positive planned neck dissection for HPV-related head and neck cancer represents a biologic unfavorable subset of the HPV population with unsatisfactory survival attributable to distant metastasis. The longer survival compared to the HPV-unrelated counterpart is likely related to a marginally lower second malignancy rather than better disease control. © 2014 Wiley Periodicals, Inc. Head Neck 37: 946–952, 2015

Objectives/Hypothesis We aimed to assess whether surgeon and/or institution resection volume predicts long-term overall survival in head and neck cancer in a publicly funded healthcare system. Study Design Population-based retrospective cohort study. Methods Head and neck cancer patients in Ontario, Canada, who underwent a resection confirmed by both hospital-level and physician-level administrative data between 1993 and 2010, comprised our cohort (N = 5,720). Physician and hospital volumes were calculated based on number of cases performed in the year prior by the physician and at an institution performing each case, respectively. A multilevel hierarchical Cox regression model was used to estimate the effect on overall survival of each 25 increase in procedure volume. Results A crude model without patient or treatment characteristics demonstrated that both surgeon volume (hazard ratio [HR]: 0.927, 95% confidence interval [CI]: 0.879-0.978, P = .006) and hospital volume (HR: 0.980, 95% CI: 0.970-0.991, P = .0003) were associated with improved overall survival. After controlling for clustering and patient/treatment covariates, hospital volume (HR: 0.976, 95% CI: 0.955-0.997, P = .02), but not physician volume (HR: 1.042, 95% CI: 0.941-1.155, P = .43), remained a statistically significant predictor of overall survival. This translates into a 2.4% decrease in the HR for every 25 additional cases performed at an institution. Conclusions Both high-volume surgeons and hospitals are predictors of better overall survival in head and neck cancer patients. However, the effect is largely explained by hospital volume. This benefit, at the institution level, could potentially be explained by important processes of care that contribute to overall survival. Level of Evidence 4 Laryngoscope, 124:2081–2088, 2014

To evaluate a newly developed noninvasive ambulatory, quantitative polymerase chain reaction (Q-PCR) Epstein-Barr virus (EBV) DNA detection and screening system (NP Screen™) for nasopharyngeal carcinoma (NPC).Correlation of the nasopharyngeal epithelial EBV-DNA levels and clinical findings by nasopharyngoscopy and final pathologic diagnosis of NPC with biopsy.Multicenter ENT/Oncology clinics in Hong Kong (Radiation Oncology Clinic at the Queen Elizabeth Hospital and Radiation Oncology Clinic and Head and Neck Clinic, Queen Mary Hospital, University of Hong Kong) and in Toronto, Canada (the Otolaryngology-Head and Neck Clinic at the Rouge Valley Health System and 2 large ENT practices in Toronto).A single-use trans-oral brush was used for rapid, nontraumatic nasopharyngeal (NP) epithelial cells DNA harvest in 600 Chinese patients, combined with a preservation and shipping kit for remote, real-time Q-PCR EBV DNA determinations.All 600 patients had NP brushings using NP Screen in an ambulatory environment, and no adverse events or complications were recorded. A final 578 patients were included with sufficient amount of DNA for completion of the Q-PCR assay. Of these 578 patients, 94 were confirmed positive for NPC histologically. The study yielded a sensitivity of 98.9%, specificity of 99.3%, positive predictive value (PPV) of 96.9%, and negative predictive value (NPP) of 99.7% for NP Screen in detecting NPC. Endoscopy had a sensitivity of 94%, specificity 97.1%, PPV 85%, and NPP 98.9%.The trans-oral brushing system fulfills the characteristics of a noninvasive, sensitive, specific detection method suitable for routine, large-scale ambulatory NPC risk assessment for high-risk NPC populations.

Purpose: Deregulation of miRNAs is associated with almost all human malignancies. Human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) has a significantly more favorable outcome compared with HPV-negative OPCs; however, the underlying mechanisms are not well understood. Hence, the objectives of this study were to determine whether miRNA expression differed as a function of HPV status and to assess whether such miRNAs provide prognostic value beyond HPV status. Methods: Global miRNA profilings were conducted on 88 formalin-fixed and paraffin-embedded (FFPE) OPC biopsies (p16-positive: 56; p16-negative: 32), wherein the expression levels of 365 miRNAs plus 3 endogenous controls were simultaneously measured using quantitative real-time (qRT)-PCR. Seven FFPE specimens of histologically normal tonsils were used as controls. Results: Overall, 224 miRNAs were expressed in more than 80% of the investigated samples, with 128 (57%) being significantly differentially expressed between tumor versus normal tissues (P < 0.05). Upregulated miR-20b, miR-9, and miR-9* were significantly associated with HPV/p16-status. Three miRNA sets were significantly associated with overall survival (miR-107, miR-151, miR-492; P = 0.0002), disease-free survival (miR-20b, miR-107, miR-151, miR-182, miR-361; P = 0.0001), and distant metastasis (miR-151, miR-152, miR-324-5p, miR-361, miR492; P = 0.0087), which retained significance even after adjusting for p16 status. The associated biologic functions of these miRNAs include immune surveillance, treatment resistance, invasion, and metastasis. Conclusion: We have identified several miRNAs, which associate with HPV status in OPC; furthermore, three candidate prognostic sets of miRNAs seem to correlate with clinical outcome, independent of p16 status. Furthermore, evaluations will offer biologic insights into the mechanisms underlying the differences between HPV-positive versus HPV-negative OPC. Clin Cancer Res; 19(8); 2154–62. ©2013 AACR.

Objectives/Hypothesis Hard palate and maxillary alveolus are two commonly grouped oral cavity subsites due to their anatomic contiguity and oncologic disease behavior. Few studies have been conducted investigating clinical presentation, staging, prevalence of cervical metastases, and outcomes in this population. The primary objective of this study was to analyze predictors of disease-free survival (DFS) in surgically treated patients, particularly as it relates to the role of neck dissection. Study Design Cohort study with planned data collection. Methods This cohort study used planned data collection over 15 years (1994–2008) at a large tertiary care cancer center to study all patients presenting with squamous cell carcinoma of the maxillary alveolus and hard palate treated surgically. Univariate and multivariate Cox regression analyses were used to identify predictors of DFS. Results Ninety-seven patients met the inclusion criteria (54 male, 56%). The majority of patients (54, 56%) presented with locally advanced disease (cT3, cT4). Occult nodal metastases were noted in 26% (17 of 65) of patients clinically staged as N0. The 3-year DFS was 70% (95% confidence interval = 59%–78%) with a median time to failure of 1.1 years (range = 0.3–9.7 years). Cox regression multivariate model demonstrated that advanced pathologic T stage, hard palate tumor site, and poorly differentiated tumor grade were each independent predictors of DFS. Conclusions A significant portion of the patients with hard palate and maxillary alveolus tumors harbor occult cervical metastases. Elective neck dissection in the high-risk patients may potentially be beneficial in providing more accurate staging and improving DFS. Level of Evidence 2b. Laryngoscope, 123:2453–2458, 2013