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Objective: Estimate the prevalence of hearing loss and hearing assistance device use among older adults in the United States, and assess for associations with select social determinants of health (SDOH)., Study Design: Cross-sectional US population-based study using National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 (pre-pandemic) data., Setting: Non-institutionalized civilian adult US population., Methods: US adults aged ≥70 years who completed NHANES audiometry exams were included. Sample weights were applied to provide nationally representative prevalence estimates of hearing loss and hearing assistance device use. Logistic regression analyses assessed associations between SDOH and both hearing loss and hearing assistance device use., Results: The overall prevalence of hearing loss was 73.7%. Among those with nonprofound hearing loss, the prevalence of hearing assistance device use was 31.3%. Older individuals (odds ratio [OR], 6.3 [3.668-10.694] comparing ages 80+ versus 70-74 yr) and with lower education (OR, 3.8 [1.455-9.766] comparing

Background: Presence of positive biopsy margins in melanoma can provoke anxiety over potential disease progression from delays to surgical excision, but their impact on outcomes is unknown. We aimed to compare the presence of residual melanoma in the surgical excision specimen and survival between patients with negative, microscopically positive, and macroscopically positive biopsy margins., Methods: Patients with cutaneous melanoma who underwent surgical excision over a 13-year period were included. Biopsy characteristics, residual disease in the surgical specimen, and overall and recurrence-free survival were compared between patients with negative, microscopically positive (only scar visible), and macroscopically positive (visible remaining melanoma) biopsy margins., Results: Of 901 patients, 42.4%, 33.3%, and 24.3% had negative, microscopically positive, and macroscopically positive margins, respectively. The incidence of residual invasive melanoma in the surgical specimen varied (P < 0.001), occurring in 5.5%, 17.0%, and 74.9% of patients, respectively. Both microscopically and macroscopically positive margins were associated with residual disease (P < 0.001) but only the latter predicted worse overall (P = 0.013) and recurrence-free survival (P = 0.009). Kaplan-Meier estimated survival was comparable between those with negative and microscopically positive margins, but overall (P = 0.006) and recurrence-free survival (P = 0.004) were significantly worse in the macroscopically positive margin group. These patients had worse prognosis melanoma, with 33.8% being stage III disease, and 23.2% having positive sentinel lymph nodes., Conclusions: Patients and physicians may be reassured in the presence of microscopically positive biopsy margins which are not associated with worse survival, However, patients with macroscopically positive margins have poorer prognosis and should be treated within an acceptable time frame., (© 2024. Society of Surgical Oncology.)

Radiotherapy (RT) and transoral robotic surgery (TORS) are both curative-intent treatment options for oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report the final outcomes of the ORATOR trial comparing these modalities, 5 years after enrollment completion. We randomly assigned 68 patients with T1-2N0-2 OPSCC to RT (with chemotherapy if node-positive) versus TORS plus neck dissection (± adjuvant RT/chemoradiation). The primary end point was swallowing quality of life (QOL) assessed with the MD Anderson Dysphagia Inventory (MDADI). Secondary end points included overall and progression-free survival (OS, PFS), adverse events (AEs), and other QOL metrics. The primary end point has been previously reported (Nichols 2019). In this report, the median follow-up was 5.1 years (IQR, 5.0-5.3 years). MDADI total scores converged by 5 years and were not significantly different across the follow-up period ( P = .11). EORTC QLQ-C30 and H&N35 scores demonstrated differing profiles, including worse dry mouth in the RT arm ( P = .032) and worse pain in the TORS arm ( P = .002). Grade 2-5 AE rates did not differ between arms (91% [n = 31] v 97% [n = 33] respectively, P = .61), with more neutropenia and hearing loss in the RT arm, and more dysphagia and other pain in the TORS arm based on grades 2-5 (all P < .05). There were no differences in OS or PFS. In conclusion, toxicity and QOL profiles differ in some domains between RT and TORS, but oncologic outcomes were excellent in both arms. Choice of treatment should remain a shared decision between the patient and their providers.

Objectives: Necrotizing fasciitis (NF) of the head and neck is a critical condition, known for its severe impact and high mortality rates, often linked with diabetes, odontogenic infections, and immunosuppression. Observations from the University of Ottawa's Department of Otolaryngology - Head and Neck Surgery indicate an increase in NF cases since the COVID-19 pandemic began, suggesting a possible association between COVID-19 and NF. This study aims to assess the incidence of NF since the pandemic's onset and explore its association with COVID-19., Design: Conducted as a single-center retrospective review from January 1, 2015 to April 7, 2023, this study included patients aged over 18 years with histopathologic confirmation of NF, analyzing clinical risk factors, treatment, and outcomes. Patients were divided into pre- and post-COVID-19 groups for comparison., Results: Of 16 patients, 68.7% were in the post-COVID-19 group, with a notable increase in 2022. The most common risk factors were diabetes mellitus (43.8%) and history of odontogenic infection or extraction (31.3%). Only one patient (6.3%) presented with concomitant COVID-19 infection and NF. All patients underwent treatment with serial surgical debridement and intravenous antibiotics with mortality rates rising to 12.5% after the pandemic., Conclusions: Our study demonstrates an increased incidence of NF cases in our institution after the COVID-19 pandemic., Competing Interests: The authors have no competing interests to declare., (© 2024 The Authors.)

Purpose: To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT)., Methods: This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan-Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS., Results: Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm 3 . With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%-78.9%) and DFS was 53.6% (47.4%-60.6%). Increasing TV was associated (per cm 3 increase) with worse OS (HR, 1.01, 95% CI 1.00-1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00-1.02, p = 0.02)., Conclusions: Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy., (© 2023 Wiley Periodicals LLC.)

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence., Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins., Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023., Main Outcomes and Measures: Main outcomes were risk factors for local recurrence., Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group., Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Objectives: A risk-adjusted analysis was completed using data from the National Surgical Quality Improvement Program (NSQIP) to compare the rates of recurrent laryngeal nerve injury in thyroid surgery using traditional versus alternative sources of cautery (defined as Harmonic Scalpel © and LigaSure © )., Methods: A retrospective cohort study was completed using the NSQIP database on adult patients who underwent total thyroidectomy, subtotal thyroidectomy, or completion thyroidectomy between 2016 and 2018. The primary outcome measure was recurrent laryngeal nerve injury. The exposure variable was use of conventional or alternative sources of cautery. Multivariable linear and logistic regression analyses were performed to control for potentially confounding variables., Results: A total of 13,961 cases were analyzed; 9450 used alternative sources of cautery compared to 4511 where traditional cautery was used. There was no significant difference in rates of postoperative recurrent laryngeal nerve injury between the 2 sources of cautery compared., Conclusions: Risk of recurrent laryngeal nerve injury should not be a factor when choosing method of cautery for thyroid surgery. Therefore, other factors like cost-effectiveness can be considered., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Due to its relatively low incidence and limited prospective trials, current recommendations are guided by historical single-institution retrospective studies., Objective: To evaluate the overall survival (OS) of patients in Canada with head and neck MCC (HNMCC) according to American Joint Committee on Cancer 8th edition staging and treatment modalities., Design, Setting, and Participants: A retrospective cohort study of 400 patients with a diagnosis of HNMCC between July 1, 2000, and June 31, 2018, was conducted using the Pan-Canadian Merkel Cell Cancer Collaborative, a multicenter national registry of patients with MCC. Statistical analyses were performed from January to December 2022., Main Outcomes and Measures: The primary outcome was 5-year OS. Multivariable analysis using a Cox proportional hazards regression model was performed to identify factors associated with survival., Results: Between 2000 and 2018, 400 patients (234 men [58.5%]; mean [SD] age at diagnosis, 78.4 [10.5] years) with malignant neoplasms found in the face, scalp, neck, ear, eyelid, or lip received a diagnosis of HNMCC. At diagnosis, 188 patients (47.0%) had stage I disease. The most common treatment overall was surgery followed by radiotherapy (161 [40.3%]), although radiotherapy alone was most common for stage IV disease (15 of 23 [52.2%]). Five-year OS was 49.8% (95% CI, 40.7%-58.2%), 39.8% (95% CI, 26.2%-53.1%), 36.2% (95% CI, 25.2%-47.4%), and 18.5% (95% CI, 3.9%-41.5%) for stage I, II, III, and IV disease, respectively, and was highest among patients treated with surgery and radiotherapy (49.9% [95% CI, 39.9%-59.1%]). On multivariable analysis, patients treated with surgery and radiotherapy had greater OS compared with those treated with surgery alone (hazard ratio [HR], 0.76 [95% CI, 0.46-1.25]); however, this was not statistically significant. In comparison, patients who received no treatment had significantly worse OS (HR, 1.93 [95% CI, 1.26-2.96)]., Conclusions and Relevance: In this cohort study of the largest Canada-wide evaluation of HNMCC survival outcomes, stage and treatment modality were associated with survival. Multimodal treatment was associated with greater OS across all disease stages.

Importance: Oral cavity cancer often requires multidisciplinary management, subjecting patients to complex therapeutic trajectories. Prolonged treatment intervals in oral cavity cancer have been associated with poor oncological outcomes, but there has yet to be a study investigating treatment times in Canada., Objective: To report treatment delays for patients with oral cavity cancer in Canada and evaluate the outcomes of treatment delays on overall survival., Design, Setting, and Participants: This multicenter cohort study was performed at 8 Canadian academic centers from 2005 to 2019. Participants were patients with oral cavity cancer who underwent surgery and adjuvant radiation therapy. Analysis was performed in January 2023., Main Outcomes and Measures: Treatment intervals evaluated were surgery to initiation of postoperative radiation therapy interval (S-PORT) and radiation therapy interval (RTI). The exposure variables were prolonged intervals, respectively defined as index S-PORT greater than 42 days and RTI greater than 46 days. Patient demographics, Charlson Comorbidity Index, smoking status, alcohol status, and cancer staging were also considered. Univariate (log rank and Kaplan-Meier) and multivariate (Cox regression) analyses were performed to determine associations with overall survival (OS)., Results: Overall, 1368 patients were included; median (IQR) age at diagnosis was 61 (54-70) years, and 896 (65%) were men. Median (IQR) S-PORT was 56 (46-68) days, with 1093 (80%) patients waiting greater than 42 days, and median (IQR) RTI was 43 (41-47) days, with 353 (26%) patients having treatment time interval greater than 46 days. There were variations in treatment time intervals between institutions for S-PORT (institution with longest vs shortest median S-PORT, 64 days vs 48 days; η2 = 0.023) and RTI (institution with longest vs shortest median RTI, 44 days vs 40 days; η2 = 0.022). Median follow-up was 34 months. The 3-year OS was 68%. In univariate analysis, patients with prolonged S-PORT had worse survival at 3 years (66% vs 77%; odds ratio 1.75; 95% CI, 1.27-2.42), whereas prolonged RTI (67% vs 69%; odds ratio 1.06; 95% CI, 0.81-1.38) was not associated with OS. Other factors associated with OS were age, Charlson Comorbidity Index, alcohol status, T category, N category, and institution. In the multivariate model, prolonged S-PORT remained independently associated with OS (hazard ratio, 1.39; 95% CI, 1.07-1.80)., Conclusions and Relevance: In this multicenter cohort study of patients with oral cavity cancer requiring multimodal therapy, initiation of radiation therapy within 42 days from surgery was associated with improved survival. However, in Canada, only a minority completed S-PORT within the recommended time, whereas most had an appropriate RTI. An interinstitution variation existed in terms of treatment time intervals. Institutions should aim to identify reasons for delays in their respective centers, and efforts and resources should be directed toward achieving timely completion of S-PORT.

Background: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands., Methods: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution., Results: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins., Conclusions: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins., (© 2023 American Cancer Society.)

Importance: Despite the sizeable global burden of hearing loss, cochlear implants have poor penetrance among eligible hearing-impaired individuals. Identifying populations who may benefit from a cochlear implant but among whom penetrance is poor is an important aim in reducing the health-related and economic effects of hearing loss on both individuals and society., Objectives: To explore the association of socioeconomic status (SES) with cochlear implant candidacy and the decision to undergo cochlear implantation., Design, Setting, and Participants: This retrospective cohort study was performed in a tertiary academic center. All adult patients evaluated for cochlear implant candidacy from January 1, 1999, through December 31, 2022, were included in the analysis., Exposures: Household income quintile and rural or urban residence were used as proxies for SES based on zip code linkage to US Census and US Department of Agriculture data., Main Outcomes and Measures: Odds of cochlear implant candidacy and surgery., Results: A total of 754 individuals underwent candidacy evaluations and were included in the analysis (386 [51.2%] women; mean [SD] age, 64.0 [15.7] years). Of these, 693 (91.9%) were cochlear implant candidates, and 623 candidates (89.9%) underwent cochlear implantation. Multivariable analyses demonstrated that individuals in the highest income quintile had lower odds of cochlear implant candidacy compared with those in the lowest income quintile (odds ratio [OR], 0.26 [95% CI, 0.08-0.91]), and candidates in the highest income quintile had greater odds of undergoing cochlear implant surgery compared with those in the lowest quintile (OR, 2.59 [95% CI, 1.14-5.86]). Living in a small town or a micropolitan or rural area was associated with lower odds of undergoing cochlear implant surgery compared with living in a metropolitan core (OR, 0.18 [95% CI, 0.04-0.83]) after controlling for distance to the primary implant center., Conclusions and Relevance: The findings of this cohort study suggest that individuals with higher SES are less likely to qualify for a cochlear implant; however, those who qualify are more likely to undergo surgery compared with those with lower SES. These findings highlight a hearing health care disparity that should be addressed through further studies to guide population-based initiatives.

Background: The effects of the COVID-19 pandemic have been more pronounced for socially disadvantaged populations. We sought to determine how access to SARS-CoV-2 testing and the likelihood of testing positive for COVID-19 were associated with demographic factors, socioeconomic status (SES) and social determinants of health (SDH) in three Canadian provinces., Methods: An observational population-based cross-sectional study was conducted for the provinces of Ontario, Manitoba and New Brunswick between March 1, 2020 and April 27, 2021, using provincial health administrative data. After excluding residents of long-term care homes, those without current provincial health insurance and those who were tested for COVID-19 out of province, records from provincial healthcare administrative databases were reviewed for 16,900,661 healthcare users. Data was modelled separately for each province in accordance to a prespecified protocol and follow-up consultations among provincial statisticians and collaborators. We employed univariate and multivariate regression models to examine determinants of testing and test results., Results: After adjustment for other variables, female sex and urban residency were positively associated with testing, while female sex was negatively associated with test positivity. In New Brunswick and Ontario, individuals living in higher income areas were more likely to be tested, whereas in Manitoba higher income was negatively associated with both testing and positivity. High ethnocultural composition was associated with lower testing rates. Both high ethnocultural composition and high situational vulnerability increased the odds of testing positive for SARS-CoV-2., Discussion: We observed that multiple demographic, income and SDH factors were associated with SARS-CoV-2 testing and test positivity. Barriers to healthcare access identified in this study specifically relate to COVID-19 testing but may reflect broader inequities for certain at-risk groups., Competing Interests: The authors have declared that no completing interests exist., (Copyright: © 2023 Antonova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The aim of this study was to determine an optimal follow-up imaging surveillance strategy in terms of cost-effectiveness after resection of nonfunctioning pituitary adenomas with curative intent., Methods: An individual-level state-transition microsimulation model was used to simulate costs and outcomes associated with three postoperative imaging strategies over a lifetime time horizon: 1) annual MRI surveillance, 2) tapered MRI surveillance (annual surveillance for 5 years followed by surveillance every 2 years), and 3) personalized surveillance (annual surveillance for 5 years followed by surveillance every 2 years when MRI shows remnant disease/postoperative changes, and surveillance at 7, 10, and 15 years for disease-free MRI). Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually. Model outcomes included lifetime costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs)., Results: Under base case assumptions, annual surveillance yielded higher costs and lower health effects (QALYs) compared with the tapered and personalized surveillance strategies (dominated). Personalized surveillance demonstrated an additional 0.1 QALY at additional cost ($1298) compared with tapered surveillance (7.7 QALYs at a cost of $12,862). The ICER was $11,793/QALY. The optimal decision was most sensitive to the probability of postoperative changes on MRI after surgery and MRI cost. Accounting for parameter uncertainty, personalized surveillance had a higher probability of being a cost-effective surveillance option compared with the alternative strategies at 79%., Conclusions: Using standard cost-effectiveness thresholds in the US ($100,000/QALY), personalized surveillance that accounted for remnant disease or postoperative changes on MRI was cost-effective compared with alternative surveillance strategies.

Importance: The association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors., Objective: To evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study., Design, Setting, and Participants: This multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria., Exposures: Tumor volume as measured on diagnostic imaging by expert neuroradiologists., Main Outcomes and Measures: Primary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study., Results: The mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76)., Conclusions and Relevance: Increasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.

Context: Pituitary tumors are the third most common brain tumor and yet there is no standardization of the surveillance schedule and assessment modalities after transsphenoidal surgery., Evidence Acquisition: OVID, EMBASE and the Cochrane Library databases were systematically screened from database inception to March 5, 2020. Inclusion and exclusion criteria were designed to capture studies examining detection of pituitary adenoma recurrence in patients 18 years of age and older following surgical resection with curative intent., Evidence Synthesis: A total of 7936 abstracts were screened, with 812 articles reviewed in full text and 77 meeting inclusion criteria for data extraction. A pooled analysis demonstrated recurrence rates at 1 year, 5 years and 10 years for non-functioning pituitary adenomas (NFPA; N = 3533 participants) were 1%, 17%, and 33%, for prolactin-secreting adenomas (PSPA; N = 1295) were 6%, 21%, and 28%, and for growth-hormone pituitary adenomas (GHPA; N = 1257) were 3%, 8% and 13%, respectively. Rates of recurrence prior to 1 year were 0% for NFPA, 1-2% for PSPA and 0% for GHPA. The mean time to disease recurrence for NFPA, PSPA and GHPA were 4.25, 2.52 and 4.18 years, respectively., Conclusions: This comprehensive review of the literature quantified the recurrence rates for commonly observed pituitary adenomas after transsphenoidal surgical resection with curative intent. Our findings suggest that surveillance within 1 year may be of low yield. Further clinical trials and cohort studies investigating cost-effectiveness of surveillance schedules and impact on quality of life of patients under surveillance will provide further insight to optimize follow-up., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The objective of this study was to compare the cost-effectiveness of preoperative octreotide therapy followed by surgery versus the standard treatment modality for growth-hormone secreting pituitary adenomas, direct surgery (that is, surgery without preoperative treatment) from a public third-party payer perspective., Methods: We developed an individual-level state-transition microsimulation model to simulate costs and outcomes associated with preoperative octreotide therapy followed by surgery and direct surgery for patients with growth-hormone secreting pituitary adenomas. Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs [2020 United States (US) Dollars], quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs)., Results: Under base case assumptions, direct surgery was found to be the dominant strategy as it yielded lower costs and greater health effects (QALYs) compared to preoperative octreotide strategy in the second-order Monte Carlo microsimulation. The ICER was most sensitive to probability of remission following primary therapy and duration of preoperative octreotide therapy. Accounting for joint parameter uncertainty, direct surgery had a higher probability of demonstrating a cost-effective profile compared to preoperative octreotide treatment at 77% compared to 23%, respectively., Conclusions: Using standard benchmarks for cost-effectiveness in the US ($100,000/QALY), preoperative octreotide therapy followed by surgery may not be cost-effective compared to direct surgery for patients with growth-hormone secreting pituitary adenomas but the result is highly sensitive to initial treatment failure and duration of preoperative treatment., (© 2022. The Author(s).)

Background: Accurate and timely testing for SARS-CoV-2 in the pediatric population is crucial to control the COVID-19 pandemic; saliva testing has been proposed as a less invasive alternative to nasopharyngeal swabs. We sought to compare the detection of SARS-CoV-2 using saliva versus nasopharyngeal swab in the pediatric population, and to determine the optimum time of testing for SARS-CoV-2 using saliva., Methods: We conducted a longitudinal diagnostic study in Ottawa, Canada, from Jan. 19 to Mar. 26, 2021. Children aged 3-17 years were eligible if they exhibited symptoms of COVID-19, had been identified as a high-risk or close contact to someone confirmed positive for SARS-CoV-2 or had travelled outside Canada in the previous 14 days. Participants provided both nasopharyngeal swab and saliva samples. Saliva was collected using a self-collection kit (DNA Genotek, OM-505) or a sponge-based kit (DNA Genotek, ORE-100) if they could not provide a saliva sample into a tube., Results: Among 1580 paired nasopharyngeal and saliva tests, 60 paired samples were positive for SARS-CoV-2. Forty-four (73.3%) were concordant-positive results and 16 (26.6%) were discordant, among which 8 were positive only on nasopharyngeal swab and 8 were positive only on saliva testing. The sensitivity of saliva was 84.6% (95% confidence interval 71.9%-93.1%)., Interpretation: Salivary testing for SARS-CoV-2 in the pediatric population is less invasive and shows similar detection of SARS-CoV-2 to nasopharyngeal swabs. It may therefore provide a feasible alternative for diagnosis of SARS-CoV-2 infection in children., Competing Interests: Competing interests: Roger Zemek is a founding partner and minority shareholder of 360 Concussion Care. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Objective: To determine the persistence of human papillomavirus (HPV) infection following treatment of HPV-positive oropharyngeal squamous cell carcinoma (HPV + OPSCC)., Methods: A cross-sectional study was undertaken at The Ottawa Hospital (Ottawa, ON, Canada), a tertiary academic hospital and regional cancer center. Adult patients who were diagnosed with HPV + OPSCC between the years of 2014 and 2016 and treated with curative intent, and who were alive and willing to consent were eligible for inclusion. A saliva assay was used to test for the presence of HPV DNA in a random sample of patients. qPCR was used to amplify DNA from saliva samples., Results: Saliva samples were obtained from 69 patients previously treated with HPV + OPSCC. All patients had a minimum of 2 years of follow-up. 5 patients tested positive for HPV: 2 were positive for HPV-16, 2 for HPV-18, and 1 "other" HPV type. No patient in our study cohort had suffered recurrence post-treatment., Conclusions: This study is the first to demonstrate the prevalence of persistent oncogenic HPV DNA in saliva following treatment for HPV + OPSCC. This prevalence appears to be low, despite the fact that persistent HPV infection is a precursor for the development of HPV + OPSCC. This finding raises questions about what factors influence the clearance or persistence of HPV DNA in saliva after treatment for HPV + OPSCC, and may add to our understanding about the longitudinal effects of HPV infection in these cancers.

Background: Saliva sampling is a promising alternative to nasopharyngeal swabs for SARS-CoV-2 testing, but acceptability data is lacking. We characterize the acceptability of saliva sampling and nasopharyngeal swabs for primary decision makers and their children after experiencing both testing modalities., Methods: We administered a cross-sectional survey to participants aged 6-to-17 years and their primary decision makers at an Ottawa community COVID-19 testing centre in March 2021. Included were participants meeting local guidelines for testing. Excluded were those identified prior to participation as having inability to complete the consent, sampling, or survey process. Acceptability in multiple hypothetical scenarios was rated using a 5-point Likert scale. Pain was measured using the Faces Pain Scale-Revised (FPS-R). Preference for testing was assessed with direct binary questions., Results: 48 participants and 48 primary decision makers completed the survey. Nasopharyngeal swab acceptability differed between scenarios, ranging 79% [95%CI: 66, 88] to 100% [95%CI: 95, 100]; saliva sampling acceptability was similar across scenarios, ranging 92% [95%CI: 82, 97] to 98% [95%CI: 89, 99]. 58% of youth described significant pain with nasopharyngeal swabbing, versus none with saliva sampling. 90% of children prefer saliva sampling. 66% of primary decision makers would prefer nasopharyngeal swabbing if it were 10% more sensitive., Conclusion: Though youth prefer saliva sampling over nasopharyngeal swabs, primary decision makers present for testing remain highly accepting of both. Acceptance of nasopharyngeal swabs, however, varies with the testing indication and is influenced by perceived test accuracy. Understanding factors that influence sampling acceptance will inform more successful testing strategies., Competing Interests: The authors have declared that no competing interests exist.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown., Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC., Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up., Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings)., Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects., Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively)., Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes., Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Purpose: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking., Methods: We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial., Results: Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time ( P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years ( P = .015). Dry mouth scores were higher in RT patients over time ( P = .041)., Conclusion: On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355)., Competing Interests: Anthony C. NicholsResearch Funding: Novartis Canada Pharmaceuticals Inc (Inst) Eric BertheletResearch Funding: Eisai Eric WinquistConsulting or Advisory Role: Merck, Bayer, Eisai, Amgen, Roche, IpsenResearch Funding: Roche/Genentech (Inst), Merck (Inst), Pfizer (Inst), Eisai (Inst), Ayala Pharmaceuticals (Inst) David A. PalmaThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Employment: London Health Sciences Centre (LHSC)Patents, Royalties, Other Intellectual Property: US patent: a method for analyzing a three-dimensional computed tomography image, US patent application no. 61/896349 (not licensed, no commercial or financial impact)No other potential conflicts of interest were reported.

A retrospective risk-adjusted analysis was completed using data from the National Surgical Quality Improvement Program (NSQIP) to (1) compare the risks of post-operative hematoma for thyroid surgery using conventional cautery compared alternative energy devices (defined as LigaSure and Harmonic Scalpel), and (2) compare operative times for the same. The primary outcome variable was post-operative hematoma occurrence. The secondary outcome variable was operative time. The exposure variable was use of conventional or alternative sources of cautery. All adult patients who underwent a total thyroidectomy, subtotal thyroidectomy or completion thyroidectomy between 2016 and 2018 were included. Multivariable linear and logistic regression analyses were performed to control for potentially confounding variables. A total of 13,330 cases were analyzed; 4342 used conventional cautery, and 8988 used alternative sources. There was a statistically significant decrease in post-operative hematoma risk using alternative sources of cautery compared to conventional cautery (OR 0.75; 95% CI 0.58-0.98) (p = 0.04). Use of alternative sources of cautery added 4.95 min onto operative time (95% CI 2.45-7.45) which was statistically significant (p < 0.0001). After controlling for confounding variables, there was a statistically significant lower rate of post-operative hematoma in thyroidectomies performed using alternative sources of cautery compared to those performed with traditional hemostatic methods. Alternative sources of cautery increased operative time by 4.95 min., (© 2021. The Author(s).)

Objective: Patient-centered decision making is increasingly identified as a desirable component of medical care. To manage indeterminate thyroid nodules, patients are offered the options of surveillance, diagnostic hemithyroidectomy, or molecular testing. Our objective was to identify factors associated with decision making in this population., Study Design: This is a retrospective cross-sectional study of patients with Bethesda III and IV thyroid nodules., Setting: Multi-institutional., Methods: Factors of interest included age, sex, socioeconomic status (SES), nodule size, institution, attending surgeon, surgeon payment model, and hospital type. Our outcome of interest was the initial management decision made by patients., Results: A total of 956 patients were included. The majority of patients had Bethesda III nodules (n = 738, 77%). A total of 538 (56%) patients chose surgery, 413 (43%) chose surveillance, and 5 (1%) chose molecular testing. There was a significant variation in management decision based on attending surgeon (proportion of patients choosing surgery: 15%-83%; P ≤.0001). Fee-for-service surgeon payment models (odds ratio [OR], 1.657; 95% CI, 1.263-2.175; P < .001) and community hospital settings (OR, 1.529; 95% CI, 1.145-2.042; P < .001) were associated with the decision for surgery. Larger nodule size, younger patients, and Bethesda IV nodules were also associated with surgery., Conclusion: While it seems appropriate that larger nodules, younger age, and higher Bethesda class were associated with decision for surgery, we also identified attending surgeon, surgeon payment model, and hospital type as important factors. Given this, standardizing management discussions may improve patient-centered shared decision making., (© The Authors 2021.)

Background: Salivary detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been proposed as an alternative to nasopharyngeal or oropharyngeal swab testing. Our group previously published a study demonstrating that both testing methods identified SARS-CoV-2 using polymerase chain reaction (PCR)-based detection methodology. We therefore conducted a follow-up study using antibody testing to evaluate the accuracy of saliva versus swabs for COVID-19 detection and the durability of antibody response., Methods: Venous blood samples were collected from consenting participants and the presence of serum antibodies for SARS-CoV-2 was evaluated on a large, automated immunoassay platform by the Roche anti-SARS-CoV-2 qualitative assay (Roche Diagnostics, Laval Quebec). Individuals with a serum antibody cut-off index (COI) ≥ 1.0 were considered positive., Results: In asymptomatic and mildly symptomatic patients with a previously positive standard swab and/or saliva SARS-CoV-2 PCR-test, 42 demonstrated antibodies with 13 patients positive by swab alone, and 8 patients positive by saliva alone., Conclusions: Despite their status as 'current standard' for COVID-19 testing, these findings highlight limitations of PCR-based tests.

As melanoma is one of the leading cancers in average years of life lost per death from disease, screening and early diagnosis are imperative to decrease morbidity and mortality. Socioeconomic status (SES) has been shown to be associated with melanoma incidence. However, it is unclear if this association holds true in universal healthcare systems where screening, diagnostic, and treatment services are available to all patients. The objective of this systematic review was to evaluate the evidence on the association of SES and melanoma incidence in Canada. A comprehensive search of PubMed and EMBASE yielded 7 studies reporting on melanoma incidence or outcomes with respect to SES in Canada. High SES was associated with increased melanoma incidence across all studies, which encompassed all Canadian provinces, and time periods spanning from 1979 to 2012. Studies also reported an increasing incidence of melanoma over time. There were substantial discrepancies in melanoma incidence across Canadian provinces, after controlling for SES and demographic characteristics. Populations of lower SES and living within certain healthcare regions had increased risks of advanced melanoma at diagnosis. This review highlights the potential for inequities in access to care even within a universal healthcare system. Future research is needed to characterize specific risk factors within different patient groups and within the universal health system context in order to implement targeted strategies to lower melanoma incidence, morbidity, and mortality.

Objectives/hypothesis: Quality improvement (QI) initiatives emphasize a need for reduction in hospital length of stay (LOS). We sought to determine the impact of surgical site infections (SSIs) on LOS after complex head and neck surgery (HNS)., Study Design: Retrospective cohort analysis., Methods: An analysis of the American College of Surgeons National Surgical Quality Improvement Program was undertaken. All adult patients undergoing complex HNS from 2005 to 2016 were included in the analysis. Our main outcomes were SSI incidence and increase in hospital LOS attributable to SSI., Results: Of 4,014 patients identified, 16.5% developed SSI. History of smoking, diabetes, preoperative wound infection, contaminated or dirty wound classes, and prolonged operative time were found to significantly predict postoperative SSI. Adjusting for significant pre- and postoperative factors, SSI was associated with significantly increased LOS (hazard ratio = 0.486, 95% confidence interval: 0.419-0.522)., Conclusions: SSI following complex HNS is associated with significantly increased hospital LOS. This result supports the need for institutional QI strategies that target SSIs after head and neck procedures in an effort to provide the highest quality care at the lowest possible cost. Our analysis identifies risk factors that can allow identification of patients at high risk of SSI and prolonged hospitalization., Level of Evidence: 2b Laryngoscope, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Quality metrics are an increasingly important means of improving patient care. Variability in the number of lymph nodes removed during central compartment lymph node dissection (CCLND) at the time of thyroidectomy has not been studied., Study Design: A retrospective cohort study was performed using American College of Surgeons National Quality Improvement Program (ACS-NSQIP) data., Setting: Centers in North America and worldwide contributing data to ACS-NSQIP and performing thyroidectomy on adults in inpatient and outpatient settings were included., Subjects and Methods: Adult patients undergoing thyroidectomy with or without CCLND were included. Outcomes of interest were number of nodes removed during CCLND and risks of postoperative hypocalcemia., Results: In total, 6108 patients met inclusion criteria (1565 with CCLND). The median number of lymph nodes removed during CCLND was 2. There was no statistically significant association between postoperative hypocalcemia and CCNLD, regardless of number of nodes removed. However, we were underpowered to detect this association based on the overall low nodal yield of many CCLNDs performed., Conclusion: In many cases where CCLND is documented as part of thyroidectomy, very few lymph nodes are removed. Our ability to draw conclusions regarding the effect of CCLND on postoperative hypocalcemia is restricted due to the limited nature of many CCLNDs performed.

Background: Xerostomia is a common complication following radiation therapy for head and neck cancer (HNC), for which there is no single, universally accepted therapy. Coconut oil has been anecdotally suggested to provide relief for this complication. This study sought to examine the feasibility and effectiveness of coconut oil as a therapy for radiation-induced xerostomia., Methods: A feasibility study was performed among 30 patients with xerostomia subsequent to radiation for HNC. Coconut oil samples were provided along with a protocol for use over a 2-week period and the option to continue if they found it beneficial. Patients were also instructed to keep diaries to document their patterns of use. The Xerostomia-related Quality of Life Scale (XeQOLS) was administered at baseline and 3-month follow-up. Descriptive methods were used to summarize patterns of coconut oil use and paired t -tests were used to assess changes in XeQOLS scores over time., Results: The mean total duration of coconut oil use during the study period was 16 days (1-71). The average number of uses per day was 3 (1-5), with an average amount per use of 5 mL (1.2-8.5). Twelve patients (41.4%) continued coconut oil use beyond the advised period. There was no statistically significant difference in XeQOLS scores pre- and post-treatment. There were no adverse events during the study period., Conclusions: The use of coconut oil as a treatment strategy for xerostomia post-HNC radiation is feasible, inexpensive, and safe. This study demonstrates that there may be a group of HNC patients that benefit from its use., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Alexandra E. Quimby et al.)

Background: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches., Methods: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity., Discussion: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials., Trial Registration: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.

Objective: Alternative energy devices have become a popular alternative to conventional hemostasis in thyroid surgery. These devices have been shown to reduce operative time and thermal nerve injury. As hemostasis is paramount in thyroid surgery, we sought to examine the relative efficacy of 2 alternate energy devices compared to conventional hemostasis in preventing postoperative hematoma following total thyroidectomy., Data Sources: Ovid MEDLINE, EMBASE, PubMed, and Cochrane Central Register of Controlled Trials., Review Methods: A systematic literature search was performed for all relevant English-language studies published between 1946 and July 2018. Two authors independently extracted data and analyzed articles for quality using the National Institute of Health Quality Assessment Scale. Our primary outcome of interest was hematoma requiring reoperation., Results: A total of 348 studies were screened, with 23 meeting the inclusion criteria. We found no significant difference in postoperative hematoma rates using alternate energy devices compared to conventional hemostasis ( P = .370, .317). Network meta-analysis echoed the results of conventional meta-analysis, demonstrating no significant difference in hematoma rates., Conclusions: We found no significant difference in postoperative hematoma rates following total thyroidectomy for any indication with the use of alternate energy devices compared to conventional hemostatic techniques. This suggests that hematoma occurrence does not necessarily need to be considered when choosing between these hemostatic devices. This information may help guide surgeons' decisions regarding choice of hemostatic technique during thyroid surgery.

Objective: Identify socioeconomic predictors of stage at diagnosis of laryngeal cancer in the United States., Study Design: Retrospective analysis of the North American Association of Central Cancer Registries' Incidence Data-Cancers in North America Deluxe Analytic File for expanded races., Setting: All centers reporting to the US Centers for Disease Control and Prevention's National Program of Cancer Registries., Subjects and Methods: All cases of laryngeal cancer in adult patients from 2005 to 2013 were reviewed. Ordinal logistic regression models were used to evaluate odd ratios (ORs) for socioeconomic indicators potentially predictive of advancing American Joint Committee on Cancer stage at diagnosis., Results: A total of 72,472 patients were identified and included. Analysis revealed significant correlation between advanced stage at diagnosis and: Medicaid insurance, lack of insurance, female sex, older age, black race, and certain states of residence. The strongest predictor of advanced stage was lack of insurance (OR, 2.212; P < .001; 95% CI, 2.035-2.406). The strongest protective factor was residing in the state of Utah (OR, 0.571; P < .001; 95% CI, 0.536-0.609). Once adjusted for regional price and wage disparities, relative income was not a significant predictor of stage at presentation across multiple analyses., Conclusion: Multiple socioeconomic factors were predictive of severity of disease at presentation of laryngeal cancer in the United States. This study demonstrated that insurance type was strongly predictive, whereas relative income had surprisingly little influence.

Background: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment., Methods: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting., Findings: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS., Interpretation: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options., Funding: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Central giant cell granulomas are benign tumours of the mandible, presenting in children and young adults. Divided into non- and aggressive subtypes, the aggressive subtype is relatively rare and can occasionally progress rapidly, resulting in significant morbidity., Case Presentation: We present a case of an aggressive central giant cell granuloma (CGCG) in a six year-old female. The lesion originated in the right mandibular ramus and progressed rapidly to involve the condyle. Diagnosis was made using a combination of imaging and pathology. A timely en bloc resection of the hemi-mandible was performed with placement of a reconstructive titanium plate and condylar prosthesis., Conclusion: Our case demonstrates the importance of considering CGCG in the differential diagnosis of rapidly progressive mandibular lesions in the pediatric population. Prompt diagnosis and management can greatly improve long-term outcomes.

Objective: Evaluate serum C-reactive protein (CRP) in human papillomavirus (HPV)-positive oropharynx cancer as compared with HPV-negative oropharynx cancer and determine if CRP levels were associated with overall survival and/or recurrence-free survival., Study Design: Prospective cohort study., Setting: Tertiary care academic cancer center between 2007 and 2010., Subjects and Methods: Among patients with oropharynx cancer and confirmed HPV status, plasma CRP levels were measured with a high-sensitivity ELISA kit. Multivariable logistic regression analysis compared 4 categories of CRP (low, moderate, high, very high) between the HPV-positive and HPV-negative groups. Kaplan-Meier methods and Cox regression models were used to determine overall survival and recurrence-free survival by CRP level in both populations., Results: Between 113 HPV-positive and 110 HPV-negative patients, CRP levels were significantly higher in the HPV-positive group, but these levels did not demonstrate a statistically significant dose-response trend. Higher CRP levels were also associated with reduced overall survival ( P = .016) and recurrence-free survival ( P < .001) within the HPV-negative group in univariable analysis; in multivariate analysis, the comparisons were not significantly different. Within HPV-positive oropharynx cancer, CRP levels were not significantly associated with overall survival or recurrence-free survival in univariable or multivariable analyses., Conclusion: Circulating CRP was higher in HPV-positive versus HPV-negative oropharynx cancer. Among HPV-negative patients, higher CRP levels were associated with reduced survival.

Objective: Diagnosis of laryngeal cancer is dependent on awareness that persistent hoarseness needs to be investigated as well as access to an otolaryngologist. This study aimed to better classify and understand 3 factors that may lead to variability in stage at presentation of laryngeal cancer: (1) socioeconomic status (SES), (2) differences in access to health care by location of residence (rural vs urban or by province), and (3) access to an otolaryngologist (by otolaryngologists per capita)., Study Design: Registry-based multicenter cohort analysis., Setting: This was a national study across Canada, a country with a single-payer, universal health care system., Subjects: All persons 18 years or older who were diagnosed with laryngeal cancer from 2005 to 2013 inclusive were extracted from the Canadian Cancer Registry (CCR)., Methods: Ordered logistic regression was used to determine the effect of income, age, sex, province of residence, and rural vs urban residence on stage at presentation., Results: A total of 1550 cases were included (1280 males and 265 females). The stage at presentation was earlier in the highest income quintile (quintile 5) compared to the lower income quintiles (quintiles 1-4) (odds ratio [OR], 0.68; P < .05). There was a statistically significant difference in stage at presentation based on rural or urban residence within the highest income quintile (OR, 1.73; P < .005)., Conclusion: There is a relationship between SES and stage at presentation for laryngeal cancer even in the Canadian universal health care system.

Background: Tobacco smoking is the leading cause of cancer, preventable death, and disability. Smoking cessation can increase life expectancy by nearly a decade if achieved in the third or fourth decades of life. Various stop smoking interventions are available including pharmacotherapies, electronic cigarettes, behavioural support, and alternative therapies. This protocol outlines an evidence review which will evaluate the benefits and harms of stop smoking interventions in adults., Methods: The evidence review will consist of two stages. First, an overview of systematic reviews evaluating the benefits and harms of various stop smoking interventions delivered in or referred from the primary care setting will be conducted. The second stage will involve updating a systematic review on electronic cigarettes identified in the overview; randomized controlled trials will be considered for outcomes relating to benefits while randomized controlled trials, non-randomized controlled trials, and comparative observational studies will be considered for evaluating harms. Search strategies will be developed and peer-reviewed by medical information specialists. The search strategy for the updated review on e-cigarettes will be developed using that of the candidate systematic review. The MEDLINE®, PsycINFO, Embase, and the Cochrane Library electronic databases will be searched as of 2008 for the overview of reviews and from the last search date of the selected review for the updated review. Organizational websites and trial registries will be searched for unpublished or ongoing reviews/studies. Two reviewers will independently screen the title and abstracts of citations using the liberal accelerated method. Full-text screening will be performed independently by two reviewers. Extracted data will be verified by a second reviewer. Disagreements regarding full-text screening and data extraction will be resolved by consensus or third-party adjudication. The methodological quality of systematic reviews, risk of bias of randomized and non-randomized trials, and methodological quality of cohort studies will be evaluated using AMSTAR 2, the Cochrane risk of bias tool, and a modified version of the Scottish Intercollegiate Guidelines Network critical appraisal tool, respectively. The GRADE framework will be used to assess the quality of the evidence for outcomes., Discussion: The evidence review will evaluate the benefits and harms of various stop smoking interventions for adults. Findings will be used to inform a national tobacco cessation guideline by the Canadian Task Force on Preventive Health Care., Systematic Review Registration: PROSPERO (CRD42018099691, CRD42018099692).

Background: We sought to expand upon preliminary data suggesting that metformin confers a survival benefit to patients with head and neck squamous cell carcinoma (HNSCC)., Methods: A large-scale retrospective cohort study of all patients in Ontario diagnosed with squamous cancer of the larynx, hypopharynx, and nasopharynx between Dec 1st 2007 to Dec 1st 2012 was undertaken. The Institute for Clinical and Evaluative Sciences was accessed to obtain patient demographic, treatment and outcome information. We included patients on metformin at the time of diagnosis. Kaplan Meier methods and Cox Regression models were used., Results: Patients taking metformin at the time of diagnosis had a higher comorbid status but were otherwise similar to patients without metformin usage. Using multivariate analysis, neither overall survival nor disease specific survival was improved in patients on metformin (OS: HR 1.123, p = .338; DSS: HR 1.048, p = .792)., Conclusions: No survival advantage was observed in patients with HNSCC taking metformin at the time of diagnosis.

Objective: Controversy exists regarding the surgical management of cutaneous melanoma and the optimal timing of reconstruction. One approach to ensuring an oncologically sound outcome is a two-stage procedure, with reconstruction delayed for negative permanent section margins. Alternatively, a single-stage excision with immediate reconstruction is advantageous because it limits both resource use and patient morbidity from multiple procedures. We sought to examine available published data on the oncologic outcomes associated with immediate versus delayed reconstruction of cutaneous melanoma in the head and neck region., Methods: We performed a systematic review using EMBASE, Ovid MEDLINE, and PubMed. We examined all English-language studies reporting oncologic outcomes (positive margins and/or local recurrence rates) of single-stage or delayed reconstruction of cutaneous melanoma in the head and neck region. Our primary outcomes of interest were rates of positive margins requiring re-excision and rates of local recurrence. A total of 1,557 studies were screened by three independent reviewers., Results: Nine studies met inclusion criteria for final analysis. Two of the nine studies directly compared immediate versus delayed reconstruction and demonstrated lower rates of positive margins in the immediate reconstruction group (odds ratio 3.7, [95% CI 0. 79-17. 34])., Conclusion: There are a paucity of studies directly comparing oncologic outcomes associated with immediate versus delayed reconstruction following excision of head and neck cutaneous melanoma. Based on a limited amount of heterogeneous data, single-stage excision with immediate reconstruction may be an oncologically sound alternative to delayed reconstruction for head and neck cutaneous melanoma., Level of Evidence: 3a. Laryngoscope, 2566-2572, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Following publication of the original article [1], the authors reported an error in one of the author names. In this Correction the incorrect and correct author names are listed.

Background: Preclinical and early-phase clinical studies have suggested an oncoprotective role of statins in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to determine whether incidental statin use in patients with human papillomavirus (HPV)-negative HNSCC is predictive of improved oncologic outcomes., Methods: A retrospective cohort study of 1194 patients from the Ontario Cancer Registry diagnosed with HNSCC from 2007 to 2012 was performed using linked databases from the Institute for Clinical Evaluative Sciences. Overall survival (OS) and disease-specific survival (DSS) were compared between patients taking statins and controls., Results: Patients with statin exposure demonstrated improved OS (hazard ratio [HR] 0.758; P = .0011; 95% confidence interval [CI] 0.642-0.896), and DSS (HR 0.693; P = .0040; 95% CI 0.539-0.889) compared with those not on statins at the time of diagnosis., Conclusion: Incidental statin use at the time of diagnosis of HPV-negative squamous cell carcinoma (SCC) of the larynx, hypopharynx, and nasopharynx demonstrated improved OS and DSS., (© 2018 Wiley Periodicals, Inc.)

The viral-transforming proteins E6 and E7 make human papillomavirus-positive (HPV + ) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multifunctional CD8 + T-cell responses. Boosting with MG1-E6E7 significantly increased the magnitude of T-cell responses compared with mice treated with a priming vaccine alone (greater than 50 × 10 6 E7-specific CD8 + T cells per mouse was observed, representing a 39-fold mean increase in boosted animals). MG1-E6E7 vaccination in the HPV + murine model TC1 clears large tumors in a CD8 + -dependent manner and results in durable immunologic memory. MG1-Maraba can acutely alter the tumor microenvironment in vivo and exploit molecular hallmarks of HPV + cancer, as demonstrated by marked infection of HPV + patient tumor biopsies and is, therefore, ideally suited as an oncolytic treatment against clinical HPV + cancer. This approach has the potential to be directly translatable to human clinical oncology to tackle a variety of HPV-associated neoplasms that cause significant morbidity and mortality globally. Cancer Immunol Res; 5(10); 847-59. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF following total laryngectomy using a large multicenter data registry., Methods: Retrospective cohort analysis was performed using patients undergoing total laryngectomy in the ACS-NSQIP database for 2006-2014. Sub-analysis was performed based on reconstruction type. Outcome of interest was PCF development within 30 days., Results: Multivariate analysis of 971 patients was performed. Three variables showed statistical significance in predicting PCF: wound classification of 3 and 4 vs. 1-2 (OR 6.42 P < 0.0004 and OR 8.87, P < 0.0042), pre-operative transfusion of > 4 units of packed red blood cells (OR 6.28, P = 0.043), and free flap versus no flap reconstruction (OR 2.81, P = 0.008)., Conclusions: This study identifies important risk factors for development of PCF following total laryngectomy in a large, multi-institutional cohort of patients, thereby identifying a subset of patients at increased risk.

Objective: The purpose of this study was to perform a systematic review and meta-analysis to determine whether a difference exists in hematoma rates following thyroidectomy for any of the following subgroups of patients: Graves disease, toxic nodular goiter (TNG), and malignancy., Study Design: Systematic review and meta-analysis., Methods: A systematic literature search was performed for all relevant English and French language studies (1946-2015) using Ovid MEDLINE, EMBASE, and PubMed. Three authors independently extracted data and analyzed articles for quality using the Newcastle-Ottawa Quality Assessment Scale. Our primary outcome of interest was hematoma requiring re-operation., Results: A total of 301 studies were screened, with 11 studies meeting the inclusion criteria. The results of our analysis demonstrated that Graves disease is the only indication for thyroidectomy that appears to have an increased risk of postoperative hematoma formation, pooled odds ratio = 1.58 (1.09-2.31); P = 0.02. Malignancy and TNG did not demonstrate significantly higher rates of postoperative hematoma formation., Conclusion: This study demonstrates that of patients undergoing thyroidectomy, Graves disease is the only indication in which patients are at increased risk of postoperative hematoma formation. This information may help guide future decisions regarding the implementation of outpatient thyroidectomy., Level of Evidence: NA. Laryngoscope, 127:1483-1490, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: The objective of this study was to compare the cost-effectiveness of transoral robotic surgery (TORS) versus the standard treatment modality for oropharyngeal squamous cell carcinoma (OPSCC), radiation therapy (RT), in a subset of patients with early-stage OPSCC., Methods and Materials: We developed a microsimulation state-transition model associated with RT and TORS for patients with clinically staged T1N0M0 to T2N1M0 OPSCC. Transition probabilities, utilities, and costs for each health state were estimated from recently published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs (in 2014 US dollars), health benefits (quality-adjusted life-years [QALYs]), and cost-effectiveness ratios from a societal perspective., Results: Under base-case assumptions, TORS was associated with modest gains in QALYs. RT yielded 10.43 QALYs at a cost of $123,410 per patient, whereas TORS yielded 11.10 QALYs at a cost of $178,480. This resulted in an incremental cost-effectiveness ratio of $82,190/QALY gained. The incremental cost-effectiveness ratio was most sensitive to the need for adjuvant therapy, cost of late toxicity, age at diagnosis, disease state utilities, and discount rate. Accounting for joint parameter uncertainty, RT had a higher probability of demonstrating a cost-effective profile compared with TORS, at 54% compared with 46%., Conclusions: By use of standard benchmarks for cost-effectiveness in the United States, TORS may be a cost-effective alternative for the subset of patients with early-stage OPSCC but demonstrates considerable sensitivity to assumptions around quality of life., (Copyright © 2016. Published by Elsevier Inc.)

Background: Burkitt lymphoma is a high-grade B cell lymphoma which accounts for less than 1% of all adult cases of non-Hodgkin lymphoma. Rare instances of Burkitt lymphoma developing secondary to prior irradiation have been described in the literature., Case Presentation: We report a case of a 90-year-old white woman with a recent history of irradiation for Hodgkin lymphoma, who presented with primary Burkitt lymphoma of the supraglottic larynx. She underwent emergency awake tracheostomy with biopsy. A histopathological examination confirmed non-Hodgkin, B cell lymphoma of Burkitt type. Given her age and poor functional status, she underwent treatment with palliative radiotherapy., Conclusions: A literature review was performed to clarify the clinical characteristics of radiation-induced Burkitt lymphoma in the head and neck, as well as its diagnosis and management. The present case represents the second case of radiation-induced Burkitt lymphoma in the head and neck in the reported literature, and the first in the supraglottic larynx. It highlights the need to maintain a broad differential in the assessment of malignancies of the larynx, particularly in patients with a prior history of radiation treatment.

Thyroid cancer incidence is increasing, and with it, an increase in total thyroidectomy. There are limited studies comparing outcomes in total thyroidectomy performed in the inpatient versus outpatient setting.The objective of this study was to perform a comparative analysis of risk factors and outcomes of postoperative morbidity and mortality in total thyroidectomy performed as an inpatient versus outpatient surgery.Retrospective cohort study of data from the 2005 to 2014 multi-institutional, risk-adjusted American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. A multivariate regression model with corresponding odds ratios and 95% confidence intervals was used to determine 30-day morbidity and mortality after total thyroidectomies, and also risk factors of postoperative outcomes.From 2005 to 2014, 40,025 total thyroidectomies were performed (48.5% inpatient, 51.5% outpatient). The 30-day complication rate for all total thyroidectomies was 7.74%. Multivariate logistic regression analysis was performed to control for potential confounding variables. Preoperative factors that affected complications rates for inpatient thyroidectomies included: age ≥70, non-Caucasian race, dependent functional status, history of congestive heart failure, smoking history, bleeding disorder, wound infection, and preoperative sepsis (P < 0.05). In addition, preoperative factors affecting complications in thyroidectomy performed as an outpatient surgery included malignant thyroid pathology (P  0.05).We identified a subset of preoperative conditions that affect risk of complications after total thyroidectomy. Recommendations for patient selection for outpatient total thyroidectomies should be modified to account for pre-existing conditions that increase the risk of postoperative morbidity., Competing Interests: The authors report no conflicts of interest.