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Background Transoral robotic surgery (TORS) is an emerging minimally invasive surgical treatment for residual, recurrent, and new primary head and neck cancers in previously irradiated fields, with limited evidence for its oncological effectiveness. Methods A retrospective observational cohort study of consecutive cases performed in 16 high-volume international centers before August 2018 was conducted (registered at clinicaltrials.gov [NCT04673929] as the RECUT study). Overall survival (OS), disease-free survival, disease-specific survivals (DSS), and local control (LC) were calculated using Kaplan-Meier estimates, with subgroups compared using log-rank tests and Cox proportional hazards modeling for multivariable analysis. Maximally selected rank statistics determined the cut point for closest surgical resection margin based on LC. Results Data for 278 eligible patients were analyzed, with median follow-up of 38.5 months. Two-year and 5-year outcomes were 69.0% and 62.2% for LC, 71.8% and 49.8% for OS, 47.2% and 35.7% for disease-free survival, and 78.7% and 59.1% for disease-specific survivals. The most discriminating margin cut point was 1.0 mm; the 2-year LC was 80.9% above and 54.2% below or equal to 1.0 mm. Increasing age, current smoking, primary tumor classification, and narrow surgical margins (≤1.0 mm) were statistically significantly associated with lower OS. Hemorrhage with return to theater was seen in 8.1% (n = 22 of 272), and 30-day mortality was 1.8% (n = 5 of 272). At 1 year, 10.8% (n = 21 of 195) used tracheostomies, 33.8% (n = 66 of 195) used gastrostomies, and 66.3% (n = 53 of 80) had maintained or improved normalcy of diet scores. Conclusions Data from international centers show TORS to treat head and neck cancers in previously irradiated fields yields favorable outcomes for LC and survival. Where feasible, TORS should be considered the preferred surgical treatment in the salvage setting.

Background: Traditional, trans-cervical thyroidectomy results in the presence of a neck scar, which has been shown to correlate with lower quality of life and lower patient satisfaction. Transoral thyroid surgery (TOTS) has been utilized as an alternative approach to avoid a cutaneous incision and scar by accessing the neck and thyroid through the oral cavity. This study was designed to evaluate patient preference through health-state utility scores for TOTS as compared to conventional trans-cervical thyroidectomy. Methods: In this cross-sectional study, patient preferences were elicited for TOTS and trans-cervical thyroidectomy with the use of an online survey. Respondents were asked to consider 4 hypothetical health scenarios involving thyroid surgery with varying approaches. Health-state utility scores were elicited using visual analog scale and standard gamble exercises. Results: Overall, 516 respondents completed the survey, of whom 261 (50.6%) were included for analysis, with a mean age of 41.5 years (SD 14.9 years), including 171 (65.5%) females. Health utility scores were similar for TOTS and conventional transcervical techniques. Statistically significant differences in the standard gamble utility score were noted for gender and ethnicity across all scenarios. Comparisons of visual analog score utilities were not statistically significant based on respondent demographics. Conclusion: Preferences for TOTS and trans-cervical thyroidectomy did not significantly differ in the current study. Females and white ethnicity indicated stronger preference for a TOTs approach compared to males and other ethnicities, respectively. Some literature suggests certain types of patients who might prefer minimally invasive thyroidectomy more so than other patients—in keeping with the current findings of this study.

Supplementary Figure from Tumor-Naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma

Supplementary Data from Tumor-Naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma

Purpose:Circulating tumor DNA (ctDNA) enables personalized treatment strategies in oncology by providing a noninvasive source of clinical biomarkers. In patients with low ctDNA abundance, tumor-naïve methods are needed to facilitate clinical implementation. Here, using locoregionally confined head and neck squamous cell carcinoma (HNSCC) as an example, we demonstrate tumor-naïve detection of ctDNA by simultaneous profiling of mutations and methylation.Experimental Design:We conducted CAncer Personalized Profiling by deep Sequencing (CAPP-seq) and cell-free Methylated DNA ImmunoPrecipitation and high-throughput sequencing (cfMeDIP-seq) for detection of ctDNA-derived somatic mutations and aberrant methylation, respectively. We analyzed 77 plasma samples from 30 patients with stage I–IVA human papillomavirus–negative HNSCC as well as plasma samples from 20 risk-matched healthy controls. In addition, we analyzed leukocytes from patients and controls.Results:CAPP-seq identified mutations in 20 of 30 patients at frequencies similar to that of The Tumor Genome Atlas (TCGA). Differential methylation analysis of cfMeDIP-seq profiles identified 941 ctDNA-derived hypermethylated regions enriched for CpG islands and HNSCC-specific methylation patterns. Both methods demonstrated an association between ctDNA abundance and shorter fragment lengths. In addition, mutation- and methylation-based ctDNA abundance was highly correlated (r > 0.85). Patients with detectable pretreatment ctDNA by both methods demonstrated significantly worse overall survival (HR = 7.5; P = 0.025) independent of clinical stage, with lack of ctDNA clearance post-treatment strongly correlating with recurrence. We further leveraged cfMeDIP-seq profiles to validate a prognostic signature identified from TCGA samples.Conclusions:Tumor-naïve detection of ctDNA by multimodal profiling may facilitate biomarker discovery and clinical use in low ctDNA abundance applications.

IMPORTANCE: Patient-derived xenografts (PDXs) offer the opportunity to identify patients with oral cavity squamous cell carcinoma (OSCC) who are at risk for recurrence and optimize clinical decision-making. OBJECTIVE: To develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, PDX models were generated from patients with OSCC treated with curative intent at Princess Margaret Cancer Centre (Toronto, Canada) between 2006 and 2018. The cohort included 288 patients (aged ≥18 years) with a new diagnosis of nonmetastatic (M0) OSCC whose tumor samples were available for engraftment under the skin of xenograft mice. Patients were scored as a nonengrafter if PDX formation did not occur within 6 months. Data analysis was performed between August 2006 and May 2018. INTERVENTIONS: All patients received up-front curative-intent surgery followed by either observation or postoperative radiation with or without concurrent chemotherapy based on institutional guidelines. MAIN OUTCOMES AND MEASURES: Main outcomes were LRF, DM, and overall survival (OS). Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups. RESULTS: Overall, 288 patients (mean [SD] age at diagnosis, 63.3 [12.3] years; 112 [39%] women and 176 [61%] men) with OSCC were analyzed. The MVA identified pT3-4, pathologic extranodal extension, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (hazard ratio [HR], 1.98; 95% CI, 1.24-3.18) and DM (HR, 2.64; 95% CI, 1.21-5.75) compared with nonengrafters. A prediction score based on the aforementioned variables identified patients at high risk and low risk for LRF (43.5% vs 26.5%), DM (38.2% vs 8.4%), and inferior OS (34% vs 66%) at 5 years. Additionally, rapid engraftment was shown to be similarly prognostic, with rapid engrafters demonstrating higher rates of relapse and poor OS. CONCLUSIONS: In this cohort study, a prediction score using OSCC PDX engraftment, in conjunction with pT3-4 and pathologic extranodal extension, was associated with improved prognostic utility of existing clinical models and predicted patients at risk for LRF, DM, and poor survival.

An international survey was conducted to investigate the preferences for completion lymph node dissection (CLND) in head and neck melanomas.A questionnaire was sent through the American Society of HeadNeck Surgery (AHNS) and Canadian Society of Otolaryngology-Head and Neck Surgery (CSO).Hundred and forty-nine surgeons completed the survey. Response rate was 6.3% and 9.7% from AHNS and CSO members, respectively. When presented the scenario of a 47-year-old male with a clinical T3bN0 cheek melanoma, with 1/1 positive sentinel lymph node (SLN) with nodal deposit2 mm, 72 of respondents (48.3%) would perform a CLND. Reasons for CLND included multiples positive SLN (64.1%), size of nodal deposits (54.2%), and perceived lack of compliance to follow-up (54.2%). Surgeons with access to immunotherapy treatment were less likely to recommend CLND (p = 0.025).Following SLN biopsy, nearly half of the surveyed head and neck surgeons would recommend CLND, which contrasts with the current melanoma practice patterns in other anatomic locations. However, compared with an earlier study in the literature it does seem that there has been a shift away from completion neck dissection. Further investigation into understanding practice variations is warranted.

Objectives/hypothesis Sonographic risk criteria may assist in further prognostication of indeterminate thyroid nodules (ITNs). Our aim was to determine whether sonographic criteria could further delineate the post-test probability of malignancy in ITNs. Study design Meta-analysis of diagnostic test accuracy. Methods A systematic review of Web of Science, MEDLINE, EMBASE, and CINAHL was performed from inception to April 15, 2021. Eligible studies included those which reported ultrasonographic evaluations with the American Thyroid Association (ATA) or the Thyroid Imaging Reporting and Data System (TIRADS) in adult patients with ITNs. ATA or TIRADS were scored as low (negative) or high (positive) malignancy risk using a previously validated binary classification. Primary outcomes included pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio for all sonographic criteria. Studies were appraised using Quality Assessment of Diagnostic Accuracy Studies and the data were pooled using bivariate random-effects models. Results Seventeen studies were included in the analysis. For Bethesda III, ATA had a specificity (0.90, 95% confidence interval (CI): 0.74-0.94), but a sensitivity of 0.52 (95% CI: 0.25-0.77). Conversely, K-TIRADS had the highest sensitivity (0.78, 95% CI: 0.62-0.89) with a specificity of 0.53 (95% CI: 0.31-0.74). Furthermore, American College of Radiology and EU TIRADS had specificities of 0.60 (95% CI: 0.36-0.80) and 0.81 (95% CI: 0.73-0.87) with sensitivities of 0.70 (95% CI: 0.37-0.90) and 0.38 (95% CI: 0.20-0.60), respectively. There were few studies with Bethesda IV nodules. Conclusions Though dependent on malignancy rates, Bethesda III nodules with low-suspicion TIRADS features may benefit from clinical observation, whereas nodules with high-suspicion ATA features may require molecular testing and/or surgery. Level of evidence NA Laryngoscope, 2021.

We recently described the development of the Neck Fibrosis Scale (NFS). In this submission, we confirm domain structure and validate a scoring system for the NFS.Prospective cross-sectional study.Between January 2020 and December 2021, 127 head and neck cancer patients with varying degrees of cutaneous neck fibrosis completed the original 15 item NFS. Exploratory factor analysis was used to identify optimal groupings with similar underlying factors. The association between the domains of the NFS and various measures of neck morbidity (i.e., construct validity) were assessed using gamma regression.Exploratory factor analysis confirmed 13 of the 15 items from the NFS mapped onto two factors, which were labelled 'physical' and 'emotional' domains. Of the remaining two items, 'energy' did not load uniquely onto one factor and was removed. 'Neck-swelling' did not load on either factor (loadings0.3) but was retained within the physical domain based on clinical importance. This resulted in a revised 14-item questionnaire. Internal consistency for these two domains was high (0.8, p 0.01). Both the physical and emotional domains of the revised NFS show strong correlation with the neck dissection impairment index and neck range of motion. The physical domain strongly correlated with neck elasticity (0.902 [95%CI 0.839-0.972], p 0.01). Patients receiving multimodal therapy had physical domain scores that were 31.6% [95% 13.9-51.8] higher (worse) than unimodal therapy patients.A domain structure and scoring strategy have been developed for the NFS. Future efforts should be directed toward an evaluation of responsiveness.NA Laryngoscope, 2022.

OBJECTIVES/HYPOTHESIS Despite considerable effort being dedicated to contouring reconstruction plates, there remains limited evidence demonstrating an association between contour and reconstructive outcomes. We sought to evaluate whether optimizing mandibular reconstruction plate contouring is associated with reduced postoperative hardware complications. STUDY DESIGN Retrospective cohort study. METHODS A cohort study was performed with adult patients (age ≥18 years) who underwent mandibulectomy and osseous free flap reconstruction following oncologic ablation at the University Health Network in Toronto, Canada, between January 1, 2003 and December 31, 2014. Patients with computed tomography scans performed within 1 year of reconstruction were included. Computer-based three-dimensional models were generated and used to calculate the mean plate-to-bone gap (mm). The primary outcome was plate exposure. Secondary outcome included a composite of plate exposure or intraoral dehiscence. Logistic regression models were fitted for each outcome accounting for other patient and surgical characteristics associated with the primary outcome. RESULTS Ninety-four patients met inclusion criteria, with a mean age of 60.4 (standard deviation [SD] 14.9). The mean follow-up time was 31.4 months (range 3-94). Reconstruction was performed with fibular (57%) and scapular free flaps (43%). In the multivariable model, small mean plate-to-bone gap (

Background The cost utility of image-guided surveillance using computed tomography (CT) and positron emission tomography (PET)-CT to planned postradiation neck dissection (PRND) was compared for the management of advanced nodal human papillomavirus-positive oropharyngeal cancer following chemoradiation. Methods A universal payer perspective was adopted. A Markov model was designed to simulate four treatment approaches with 3-month cycles over a lifetime horizon: 1) CT surveillance, 2) standard PET-CT surveillance, 3) a novel PET-CT approach with repeat PET at 6 months postchemoradiation for equivocal responders, and 4) PRND. Parameters including probabilities of CT nodal progression/resolution, PET avidity, recurrence, and survival were obtained from the literature. Costs were reported in 2019 Canadian dollars and utilities were expressed in quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. Results PET-CT surveillance dominated CT surveillance and PRND in the base case scenario, and the novel PET-CT approach was the most cost-effective strategy across a wide range of variables tested in one-way sensitivity analysis. On probabilistic sensitivity analysis, novel PET-CT surveillance was the most cost-effective strategy in 78.1% of model iterations at a willingness-to-pay of $50,000/QALYs. Novel PET-CT surveillance resulted in a 49% lower rate of neck dissection compared with traditional PET-CT, and yielded an incremental benefit of 0.14 QALYs with average cost savings of $1309. Conclusions Image-guided surveillance including PET-CT and CT are more cost effective than PRND. The novel PET-CT approach with repeat PET for equivocal responders was the dominant strategy and yielded both higher benefit and lower costs compared with standard PET-CT surveillance.

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 Tanning bed use is common among US adolescents, but is associated with increased melanoma risk. The decision to ban tanning bed use by adolescents should be made in consideration of the potential health benefits and costs. Methods The US population aged 14 to 17 years was modeled by microsimulation, which compared ban versus no ban strategies. Lifetime quality-adjusted life years (QALYs) and costs were estimated from a health care sector perspective and two societal perspectives: with and without the costs of policy enforcement and the economic losses of the indoor-tanning bed industry. Results Full adherence to the ban prevented 15,102 melanoma cases and 3299 recurrences among 17.1 million minors, saving $61in formal and informal health care costs per minor and providing an increase of 0.0002 QALYs. Despite the intervention costs of the ban and the economic losses to the indoor-tanning industry, banning was still the dominant strategy, with a savings of $12 per minor and $205.4 million among 17.1 million minors. Findings were robust against varying inspection costs and ban compliance, but were sensitive to lower excess risk of melanoma with early exposure to tanning beds. Conclusions A ban on tanning beds for minors potentially lowers costs and increases cost effectiveness. Even after accounting for the costs of implementing a ban, it may be considered cost effective. Even after accounting for the costs of implementing a ban and economic losses in the indoor-tanning industry, a tanning bed ban for US minors may be considered cost effective. A ban has the potential to reduce the number of melanoma cases while decreasing health care costs. Lay summary Previous meta-analyses have linked tanning bed use with an increased risk of melanoma, particularly with initial use at a young age. Yet, it remains unclear whether a ban of adolescents would be cost effective. Overall, a ban has the potential to reduce the number of melanoma cases while promoting a decrease in health care costs. Even after accounting for the costs of implementing a ban and the economic losses incurred by the indoor-tanning industry, a ban would be cost effective.

To describe the utilization pattern of head and neck (HN) surveillance imaging and explore the optimal strategy for radiologic "residual" lymph node (LN) surveillance following definitive (chemo)radiotherapy (RT/CRT) in human papillomavirus (HPV)+ oropharyngeal carcinoma (OPC).All HPV+ OPC patients who completed RT/CRT from 2012 to 2015 were included. Schedule and rationale for post-treatment HN-CT/MRI were recorded. Imaging findings and oncologic outcomes were evaluated.A total of 1036 scans in 412 patients were reviewed: 414 scans for first post-treatment response assessment and 622 scans for the following reasons: follow-up of radiologic "residual" LN(s) (293 scans/175 patients); local symptoms (227/146); other (17/16); unknown (85/66). Rate of scans with "unstated" reason varied significantly among clinicians (3-28%, p 0.001) and none of them yielded any positive imaging findings. First post-treatment scans identified 192 (47%) patients with radiologic "residual" LNs. Neck dissection (ND) was performed in 28 patients: 16 immediately (6/16 positive), 10 after one follow-up scan (2/10 positive), and 2 after 2nd follow-up scan (1/2 positive). Thirty patients had2 consecutive follow-up scans at 2-3-month intervals, and none showed subsequent imaging progression or regional failure.Pattern of HN imaging utilization for surveillance varied significantly among clinicians. Imaging surveillance reduces the need for ND. However, routine HN-CT/MR surveillance without clinical symptoms/signs does not demonstrate proven value in identifying locoregional failure or toxicity. Radiologic "residual" LNs without adverse features are common. If two subsequent follow-up scans demonstrate stable/regressing radiologic "residual" LNs, clinical surveillance without further imaging appears to be safe in this population.

Background In early oral cavity cancer, elective neck dissection (END) for the clinically node-negative (cN0) neck improves survival compared with observation. This paradigm has been challenged recently by the use of positron emission tomography-computed tomography (PET-CT) imaging in the cN0 neck. To inform this debate, we performed an economic evaluation comparing PET-CT-guided therapy with routine END in the cN0 neck. Methods Patients with T1-2N0 lateralized oral tongue cancer were analyzed. A Markov model over a 40-year time horizon simulated treatment, disease recurrence, and survival from a US health care payer perspective. Model parameters were derived from a review of the literature. Results The END strategy was dominant, with a cost savings of $1576.30 USD, an increase of 0.055 quality-adjusted life years (QALYs), a net monetary benefit of $4303 USD, and a 0.22 life-year advantage. END was sensitive to variation in cost and utilities in deterministic and probabilistic sensitivity analyses. PET-CT became the preferred strategy when decreasing occult nodal disease to 18% and increasing the negative predictive value (NPV) of PET-CT to 89% in 1-way sensitivity analyses. In probabilistic sensitivity analysis, assuming a cost effectiveness threshold of $50,000 USD/QALY, END was dominant in 64% of simulations and cost effective in 69.8%. Conclusion END is a cost-effective strategy compared with PET-CT in patients who have node-negative oral cancer. Although lower PET standardized uptake value thresholds would result in fewer false negatives and improved NPV, it is still uncertain that PET-CT would be cost effective, as this would likely result in more false positive tests.

OBJECTIVE. Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENE(mi)) and role of adjuvant concurrent chemoradiation (CRT) for ENE(mi) remain unclear. This study evaluates (1) the prognostic significance of ENE(mi) in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. STUDY DESIGN. Retrospective cohort study. SETTING. Commission on Cancer (CoC)–accredited facilities. METHODS. This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENE(mi) or no ENE who had undergone margin-negative surgery. The association of ENE(mi) with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENE(mi) receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. RESULTS. We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENE(mi). On multivariable analysis, ENE(mi) was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENE(mi) who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). CONCLUSION. For patients with HPV-negative HNSCC, pN+ with ENE(mi) is associated with worse OS than pN+ without ENE. However, for patients with ENE(mi), concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENE(mi) requires additional investigation.

Introduction Endoscopic endonasal approaches (EEAs) provide improved access and operative visualization for resection of pituitary adenomas. Although the technique has gained wide acceptance, there is a paucity of data regarding late recurrence. Objective We aim to assess long-term outcomes of patients with nonfunctioning pituitary adenomas (NFPAs) who underwent EEA. Methods We reviewed 269 patients operated on for an NFPA between 2005 and 2015. Clinical and radiologic factors including those potentially related to higher chances of recurrence were analyzed. Progression-free survival was analyzed using the Kaplan-Meier method, and univariate and multivariate survival were analyzed using a Cox regression model. Results The study included 269 patients. The gross total resection rate was 46.0% (n = 124) but cavernous sinus involvement was present in almost half the patients (n = 115). The probability of recurrence at 5 years and 10 years was 22.0% and 47.2%, respectively. The median time to recurrence was 10 years for patients without cavernous sinus involvement and 6 years for those with cavernous sinus involvement. Univariate and multivariate analysis showed that tumor size, cavernous sinus invasion, anterior skull base extensions, and residual tumor were significantly associated with recurrence. Conclusions Recurrence rate of NFPA remains high despite the better visualization offered by EEA, especially in those tumors involving the cavernous sinus and/or previously operated on. Repeat surgery is adequate for tumor debulking and decompression of the optic apparatus but is unlikely to achieve gross total resection if a successful previous EEA has been performed. Radiation therapy is an effective option for management of recurrent tumors.

ImportanceThe 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresTumor volume as measured on diagnostic imaging by expert neuroradiologists.Main Outcomes and MeasuresPrimary 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.ResultsThe 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 RelevanceIncreasing 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.

The study objective was to measure the prevalence and predictors of cognitive impairment (CI) and delirium. Adults undergoing major head and neck cancer surgery completed the Clock Draw Test to screen for CI, defined as a score of 0 or 1. Postoperative delirium was recorded. Predictors of delirium and length of stay were assessed by univariate logistic regression and the latter with multivariate linear regression. Overall 274 patients were included, of which 47% had a Clock Draw Test score of 0 or 1. Post-operative delirium occurred in 17 (6%). CI was a predictor of postoperative delirium (odds ratio, 3.9; 95% CI, 1.2-12; P = .02). Postoperative delirium was a predictor of increased length of stay (adjusted odds ratio, 1.30; 95% CI, 1.07-1.57; P = .0073) on multivariate regression while baseline Clock Draw Test result was not a predictor on univariate regression (P = .98). Screening for CI can help predict delirium and facilitate targeted interventions in the postoperative period.

Highlights • Definitive RT/CRT for OSCC achieved acceptable rate of locoregional control. • Definitive RT is a reasonable alternative treatment strategy if surgery is not possible. • cN2-3 is associated with poor distant control, DFS, and OS., Purpose To determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT). Methods All OSCC patients treated radically with IMRT (without primary surgery) between 2005–2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed. Results Among 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p

Background Being able to predict negative postoperative outcomes is important for helping select patients for treatment as well for informed decision‐making by patients. Frailty measures are often time and resource intensive to use as screening measures, whereas the Braden scale, a commonly used measure to assess patients at risk of developing pressure ulcers after surgery, may be a potential tool to predict postoperative complication rates and longer length of stay (LOS) in patients undergoing major head and neck cancer surgery. Methods A retrospective analysis of Braden scale scores was performed on a prospectively collected cohort of patients undergoing major head and neck surgery recruited between December 2011 and April 2014. The association of Braden scale score with the primary outcomes of complications and LOS was analyzed using logistic regression and linear regression models on univariate analysis (UVA), respectively. Multivariate analysis (MVA) was performed based on a backward stepwise selection algorithm. Results There were 232 patients with a mean (SD) Braden scale score of 14.9 (2.8) with a range from 9 to 23. The Braden scale (β = −.07 per point; 95% CI −0.09, −0.04, P, Being able to predict negative postoperative outcomes is important for helping select patients for treatment as well for informed decision‐making by patients. The Braden Scale, a commonly used measure to assess patients at risk of developing pressure ulcers after surgery, may be a potential tool to predict postoperative complication rates and longer length of stay in patients undergoing major head and neck cancer surgery. In the sample population the Braden scale did not demonstrate an ability to predict negative outcomes in head and neck surgery patients

We compare outcomes in two large-scale contemporaneously-treated HPV-positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemo-radiotherapy (RT/CRT). p16-confirmed HPV+ OPC treated between 2007-2015 at PMH and DAHANCA were identified. Locoregional failure (LRF), distant metastasis (DM), and overall survival (OS) were compared. Multivariable analysis (MVA) calculated adjusted-hazard-ratio (aHR) with 95% confidence interval (95% CI), adjusting for cohort, age, gender, performance status, smoking pack-years, T- and N-category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM-8 T-categories (T1-2:77% vs 56%), N-categories (N0-N1: 77% vs 67%), and stages (stage I: 63% vs 44% (all P < 0.001). PMH used standard-fractionation CRT in 69% (481) while 31% (220) received hypo-fractionated or moderately-accelerated RT-alone. All DAHANCA patients were treated with moderately-accelerated RT; 96% (1129) received Nimorazole (NIM) and 73% (856) concurrent weekly Cisplatin. DAHANCA had shorter overall-treatment-time (P < 0.001), lower gross tumor (66-68 vs 70 Gy) and elective neck (50 vs 56 Gy) doses. Median follow-up was 4.8 years. DAHANCA had higher 5-year LRF (13% vs 7%, aHR = 0.47 [0.34-0.67]), comparable DM (7% vs 12%, aHR = 1.32 [0.95-1.82]), but better OS (85% vs 80%, aHR = 1.30 [1.01-1.68]). CRT patients had a lower risk of LRF (aHR 0.56 [0.39-0.82]), DM (aHR 0.70 [0.50-1.00]) and death (aHR 0.39 [0.29-0.52]) vs RT-alone. We observed exemplary outcomes for two large-scale trans-Atlantic HPV+ OPC cohorts treated in a similar manner. Concurrent chemotherapy was a strong, independent prognostic factor for all endpoints. Our findings underscore the need for a very careful approach to de-intensification of treatment for this disease. This article is protected by copyright. All rights reserved.

To evaluate clinical outcome of low (G1), intermediate (G2), and high-(G3) grade mucoepidermoid carcinomas (MEC) of the parotid gland.Retrospective chart review including 212 patients. Clinicopathological data was statistically analyzed regarding grading, overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS).105 (49.5%) G1, 73 (34.5%) G2, and 34 (16%) G3 MEC were included and 56 (26.4%) patients presented with neck node metastases. The risk of occult nodal metastases was significantly associated with grading and increased from 9.2% in G1 to 26.7% and 27.8% in G2 and G3 tumors, respectively (p = 0.008). Elective periparotid and cervical lymph node dissection was performed in 170 (80.2%) and 70 (33%) patients, respectively. All patients with positive periparotid nodes when subjected to an additional neck dissection had associated cervical neck node involvement (p 0.001). Grading was an independent significant prognostic factor for OS (HR 4.05; 95%CI: 1.15-14.35; p = 0.030) and DSS (HR 17.35; 95%CI: 1.10-273.53; p = 0.043). In a subgroup analysis, elective neck dissection (END) was also significantly associated with a better DFS (p = 0.041) in neck node-negative G1 MECs.The risk of occult nodal metastasis in intermediate-grade MEC is as high as in high-grade MEC and that END in G1 tumors is associated with a prolonged DFS. Additionally, periparotid node involvement seems to be a predictor for positive neck node involvement. This study presents some preliminary data to consider END in clinically neck node negative patients with parotid MEC; however, larger series are needed.3 Laryngoscope, 2022.

Background Endoscopic endonasal approaches (EEAs) have been adopted as an alternative to standard transcranial approaches for olfactory groove meningiomas (OGMs). However, the relative cost-effectiveness remains controversial. Methods Cost-utility analysis from a societal perspective comparing EEA vs transcranial approaches for OGM was used in this study. Surgical treatment was modeled using decision analysis, and a Markov model was adopted over a 20-year horizon. Parameters were obtained from literature review. Costs were expressed in 2017 Canadian dollars. Results In the base case, EEA was cost-effective compared with transcranial surgery with an incremental cost-effectiveness ratio of $33 523 ($30 475 USD)/QALY. There was a 55% likelihood that EEA was cost-effective at a willingness-to-pay of $50 000/QALY. EEA remained cost-effective at a cerebrospinal fluid leak rate below 60%, gross total resection rate above 25%, and base cost less than $66 174 ($60 158 USD). Conclusion EEA may be a cost-effective alternative to transcranial approaches for selected OGM.

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

Contains fulltext : 220257.pdf (Publisher’s version ) (Closed access) The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

The COVID‐19 pandemic has profoundly disrupted head and neck cancer (HNC) care delivery in ways that will likely persist long term. As we scan the horizon, this crisis has the potential to amplify preexisting racial/ethnic disparities for patients with HNC. Potential drivers of disparate HNC survival resulting from the pandemic include (a) differential access to telemedicine, timely diagnosis, and treatment; (b) implicit bias in initiatives to triage, prioritize, and schedule HNC‐directed therapy; and (c) the marked changes in employment, health insurance, and dependent care. We present four strategies to mitigate these disparities: (a) collect detailed data on access to care by race/ethnicity, income, education, and community; (b) raise awareness of HNC disparities; (c) engage stakeholders in developing culturally appropriate solutions; and (d) ensure that surgical prioritization protocols minimize risk of racial/ethnic bias. Collectively, these measures address social determinants of health and the moral imperative to provide equitable, high‐quality HNC care.

Background We sought to develop mapping functions that use EORTC responses to approximate health utility (HU) scores for patients with head and neck cancer (HNC). Methods In total, 209 outpatients with HNC completed the EORTC QLQ-C30 & QLQ-H&N35 (EORTC), EQ-5D-5L and the HUI-3. Results of the EORTC were mapped onto both EQ-5D-5L and HUI-3 scores using ordinary least squares regression and two-part models. Results The OLS model mapping EORTC onto the EQ-5D-5L performed best (adjusted R2 = .75, 10-fold cross-validation RMSE = 0.064, MAE 0.050). The HUI-3 model mapping onto EORTC through OLS was more limited (adjusted R2 = .5746, 10-fold cross cross-validation RMSE = 0.168, MAE 0.080). The EQ-5D-5L model was able to discriminate between certain clinical indices of disease severity on subgroup analysis. Conclusion The EORTC to EQ-5D-5L mapping algorithm has good predictive validity and may enable researchers to translate EORTC scores into HU scores for head and neck patients with cancer.

This study examines outcome heterogeneity and potential to refine the TNM-8 cN-classification using radiologic extranodal extension (rENE) in a contemporary HPV-positive (HPV+) oropharyngeal carcinoma (OPC) cohort.All HPV+ OPC treated with definitive IMRT from 2010-2015 were included. Pre-treatment CT/MR of cN+ cases were reviewed by a head-neck radiologist for rENE. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) vs rENE-negative (rENE-). Multivariable analysis (MVA) for OS confirmed the prognostic value of rENE. Refined cN-classifications for new TNM staging proposals were evaluated against TNM-8 using established criteria.A total of 517 cN+ (rENE+: 97; rENE-: 420) and 41 cN0 cases were identified. The rENE+ proportion increased with rising N-category (N1/N2/N3: 11%/19%/84%, p 0.001). Median follow-up was 5.1 years. Compared to rENE-, rENE+ patients had a lower 5-year OS (56% vs 85%) and DFS (46% vs 83%) overall, and in N1 (OS: 57% vs 89%; DFS: 51% vs 87%) and N2 subsets (OS: 45% and 76%; DFS: 33% vs 74%) (all p 0.001). MVA confirmed the prognostic value of rENE for OS (HR = 3.86, p 0.001) and DFS (HR = 3.89, p 0.001). We proposed two new cN-classifications: Schema1 reclassified any N_rENE+ as New_N3; Schema2 reclassified N1_rENE+ as New_N2 and N2_rENE+ as New_N3. Stage incorporating either Schema1 (ranked 1st) or Schema2 (ranked 2nd) cN-categories outperformed TNM-8.This study confirms that rENE is prognostically important and facilitates understanding of known outcome heterogeneity within TNM-8 in HPV+ OPC patients. rENE is a promising parameter to refine the TNM-8 cN-classifications.

Importance Skull base surgery requires precise preoperative assessment and intraoperative management of the patient. Surgical navigation is routinely used for complex skull base cases; however, the image guidance is commonly based on preoperative scans alone. Objective The primary objective of this study was to assess the image quality of intraoperative cone-beam computed tomography (CBCT) within anatomical landmarks used in sinus and skull base surgery. The secondary objective was to assess the registration error of a surgical navigation system based on intraoperative CBCT. Design Present study is a retrospective case series of image quality after intraoperative cone beam CT. Setting The study was conducted at Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto. Participants A total of 46 intraoperative scans (34 patients, 21 skull base, 13 head and neck) were studied. Main Outcome and Measures Thirty anatomical landmarks (vascular, soft tissue, and bony) within the sinuses and anterior skull base were evaluated for general image quality characteristics: (1) bony detail visualization; (2) soft-tissue visualization; (3) vascular visualization; and (4) freedom from artifacts (e.g., metal). Levels of intravenous (IV) contrast enhancement were quantified in Hounsfield's units (HU). Standard paired-point registration between imaging and tracker coordinates was performed using 6 to 8 skin fiducial markers and the corresponding fiducial registration error (FRE) was measured. Results Median score for bony detail on CBCT was 5, remaining at 5 after administration of IV contrast. Median soft-tissue score was 2 for both pre- and postcontrast. Median vascular score was 1 precontrast and 3 postcontrast. Median score for artifacts on CBCT were 2 for both pre-and postcontrast, and metal objects were noted to be the most significant source of artifact. Intraoperative CBCT allowed preresection images and immediate postresection images to be available to the skull base surgeon. There was a significant improvement in mean (standard deviation [SD]) CT intensity in the left carotid artery postcontrast 334 HU (67 HU) (p Conclusion Intraoperative CBCT in complex skull base procedures provides high-resolution bony detail allowing immediate assessment of complex resections. The use of IV contrast with CBCT improves the visualization of vasculature. Image-guidance based on CBCT yields registration errors consistent with standard techniques.

The extirpation of skull base malignancies may be associated with significant morbidity and can profoundly impact health related quality of life (HRQOL). In this review, we sought to provide an overview of HRQOL and the factors that influence it for patients with skull base malignancies. Narrative review. HRQOL tends to improve in the months to years following treatment and is profoundly impacted by both tumor location and treatment approach. Wherever possible, HRQOL should always be elicited from the patient directly. Several HRQOL instruments have been used in this population including generic, site-specific and disease specific measures. Given that HRQOL is a multidimensional concept with several important facets, validated disease-specific instruments are generally preferred.

Intensity-modulated radiation therapy (IMRT) has enabled risk-tailored approach to elective mucosal and nodal clinical target volumes (CTVs) in treatment of head and neck carcinoma of unknown primary (HNCUP). This study report outcomes following such approach.HNCUP patients treated with definitive IMRT between 2005 and 2018 were reviewed. Local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS) and grade ≥3 late toxicity (LT) were analyzed. Multivariable analysis (MVA) was used to identify OS predictors for entire cohort and cN2-3 subgroup.A total of 203 patients were eligible: cN1 (7%), cN2a (14%), cN2b (46%), cN2c (14%) and cN3 (19%). Among 118 patients with known HPV status (by p16 staining), 81 (68%) were positive. IMRT target volume spared contralateral tonsil (55%), bilateral or contralateral sides of hypopharynx (72%), nasopharynx (72%), larynx (87%) and contralateral uninvolved neck (21%). Median follow-up was 5 years. Five-year LF, RF, DM, OS, and LT were 3%, 14%, 10%, 79%, and 7% respectively. Four patients developed mucosal recurrence: 3 within and 1 at the margin of the elective mucosal CTV. None of ipsilateral neck irradiation patients failed in the contralateral uninvolved neck. MVA identified cN2c-N3, HPV-negative status and older age as predictors for inferior OS. Within cN2-3 subgroup (n = 189): cN2c-N3, HPV-negative status and older age predicted lower OS, while concurrent chemotherapy was associated with better OS.Definitive IMRT with risk-adaptive radiation volume de-escalation for HNCUP resulted in high probability of tumor control with acceptable rate of late toxicity.

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 ).

Positive margins have been reported up to 80% in advanced maxillary cancers. Intraoperative navigation (IN) aims to improve margins, but provides a two-dimensional view of a registered instrument without anticipating any cutting directions, and the information is displayed in monitors outside surgical field. Augmented Reality (AR) can delineate margins while addressing the gaze-toggling drawback of IN. In a preclinical setting, we implemented preoperative-planned osteotomies needed for maxillectomies and projected this information on the surgical field using AR. We aimed to improve negative margin rates while retaining the benefits of AR.Five maxillary tumor models were built. Five fellowship-trained surgeons completed virtual unguided and AR-guided maxillectomies. Comparisons in terms of intratumoral cuts, close, adequate, and excessive distances from the tumor were performed. Differences between "ideal" cutting-plan and the AR-guided virtual osteotomies was obtained. Workload questionnaires to evaluate the technology were completed.115 virtual osteotomies were analyzed. Intra-tumoral and "close" margins were lower for the AR-assisted osteotomies (0.0% vs 1.9% p 0.0001 and 0.8% vs 7.9% p 0.0001). Proportion of "adequate" margins were higher in the AR simulations (25.3% vs 18.6%, p = 0.018). The AR osteotomies had high similarity with the pre-planned with interclass correlation index close to 1 in "adequate" margins 0.893 (95% CI: 0.804-0.949). Workload scores were better for AR-guided simulations for the domains of mental demand, performance, effort and frustration.The projector-based AR method improved margin delineation, and preoperative planning was accurately translated to the simulations. Clinical translation will aim to consolidate our preclinical findings to improve outcomes.

ImportanceWhile several studies have documented a link between socioeconomic status and survival in head and neck cancer, nearly all have used ecologic, community-based measures. Studies using more granular patient-level data are lacking.ObjectiveTo determine the association of baseline annual household income with financial toxicity, health utility, and survival.Design, Setting, and ParticipantsThis was a prospective cohort of adult patients with head and neck cancer treated at a tertiary cancer center in Toronto, Ontario, between September 17, 2015, and December 19, 2019. Data analysis was performed from April to December 2021.ExposuresAnnual household income at time of diagnosis.Main Outcome and MeasuresThe primary outcome of interest was disease-free survival. Secondary outcomes included subjective financial toxicity, measured using the Financial Index of Toxicity (FIT) tool, and health utility, measured using the Health Utilities Index Mark 3. Cox proportional hazards models were used to estimate the association between household income and survival. Income was regressed onto log-transformed FIT scores using linear models. The association between income and health utility was explored using generalized linear models. Generalized estimating equations were used to account for patient-level clustering.ResultsThere were 555 patients (mean [SD] age, 62.7 [10.7] years; 109 [20%] women and 446 [80%] men) included in this cohort. Two-year disease-free survival was worse for patients in the bottom income quartile (Conclusions and RelevanceIn this cohort study, patients with head and neck cancer with a household income less than CAD$30 000 experienced worse financial toxicity, health status, and disease-free survival. Significant disparities exist for Ontario’s patients with head and neck cancer.