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Importance: Extranodal extension (pENE) is a critical prognostic factor in oropharyngeal cancer (OPC) that drives therapeutic disposition. Determination of pENE from radiological imaging has been associated with high inter-observer variability. However, the impact of clinician specialty on human observer performance of imaging-detected extranodal extension (iENE) remains poorly understood., Objective: To characterize the impact of clinician specialty on the accuracy of pre-operative iENE in human papillomavirus-positive (HPV+) OPC using computed tomography (CT) images., Design Setting and Participants: This prospective observational human performance study analyzed pre-therapy CT images from 24 HPV+ OPC patients, with duplication of 6 scans (n=30) of which 21 were pathologically confirmed pENE. Thirty-four expert observers, including 11 radiologists, 12 surgeons, and 11 radiation oncologists, independently assessed these scans for iENE and reported human-detected radiologic criteria and observer confidence., Main Outcomes and Measures: The primary outcomes included accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and Brier score for each physician, compared to ground-truth pENE. The significance of radiographic signs for prediction of pENE were determined through logistic regression analysis. Fleiss' kappa measured interobserver agreement, and Hanley-MacNeil AUC discrimination testing., Results: Median accuracy across all specialties was 0.57 (95%CI 0.39 to 0.73), with no specialty showing discriminate performance greater than random estimation (median AUC 0.64, 95%CI 0.44 to 0.83). Significant differences between radiologists and surgeons in Brier scores (0.33 vs. 0.26, p < 0.01), radiation oncologists and surgeons in sensitivity (0.48 vs. 0.69, p > 0.1), and radiation oncologists and radiologists/surgeons in specificity (0.89 vs. 0.56, p > 0.1). Indistinct capsular contour and nodal necrosis were significant predictors of correct pENE status among all specialties. Interobserver agreement was weak for all the radiographic criteria, regardless of specialty ( κ <0.6)., Conclusions and Relevance: Multiobserver testing shows physician discrimination of HPV+OPC pENE on pre-operative CT remains non-different than blind guessing, with high interrater variability and low diagnostic accuracy, regardless of clinician specialty. While minor differences in diagnostic performance among specialties are noted, they do not significantly affect the overall poor agreement and discrimination rates observed. The findings underscore the need for further research into automated detection systems or enhanced imaging techniques to improve the accuracy and reliability of iENE assessments in clinical practice., Competing Interests: Conflict of Interest Statement: Dr. Fuller has received unrelated direct industry grant/in-kind support, honoraria, and travel funding from Elekta AB; honoraria, and travel funding from Philips Medical Systems; and honoraria, and travel funding from Varian/Siemens Healthineers. Dr. Fuller has unrelated licensing/royalties from Kallisio, Inc. Dr. Sandulache is a consultant for, and equity holder in, Femtovox Inc (unrelated to current work).

Objective: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients., Study Design: Retrospective analysis of prospective cohort from 2015 to 2021., Setting: Single-institution NCI-Designated Comprehensive Cancer Center., Methods: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during transoral robotic surgery (TORS). Tube duration was censored at last disease-free follow-up. Multivariate regression was performed for G-tube placement (odds ratio [OR] [95% confidence interval [CI]) and removal (Cox hazard ratio, hazard ratio [HR] [95% CI])., Results: Of 924 patients, most had stage I to II (81%), p16+ (89%), node-positive (88%) disease. Median follow-up was 2.6 years (interquartile range 1.5-3.9). Most (91%) received radiation/chemoradiation, and 16% received TORS. G-tube rate was 27% (5% after TORS). G-tube risk was increased with chemoradiation (OR 2.78 [1.87-4.22]) and decreased with TORS (OR 0.31 [0.15-0.57]) and PSSHN-Diet score ≥60 (OR 0.26 [0.15-0.45]). G-tube removal probability over time was lower for T3 to T4 tumors (HR 0.52 [0.38-0.71]) and higher for PSSHN-Diet score ≥60 (HR 1.65 [1.03-2.66])., Conclusions: In this modern cohort of patients treated for OPC, 27% received G-tubes-50% less than institutional rates 10 years ago. Patients with preserved baseline swallowing and/or those eligible for TORS may have lower G-tube risk and duration., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Cancer centers are regionalizing care to expand patient access, but the effects on patient volume are unknown. This study aimed to compare patient volumes before and after the establishment of head and neck regional care centers (HNRCCs)., Methods: This study analyzed 35,394 unique new patient visits at MD Anderson Cancer Center (MDACC) before and after the creation of HNRCCs. Univariate regression estimated the rate of increase in new patient appointments. Geospatial analysis evaluated patient origin and distribution., Results: The mean new patients per year in 2006-2011 versus 2012-2017 was 2735 ± 156 patients versus 3155 ± 207 patients, including 464 ± 78 patients at HNRCCs, reflecting a 38.4 % increase in overall patient volumes. The rate of increase in new patient appointments did not differ significantly before and after HNRCCs (121.9 vs 95.8 patients/year; P = 0.519). The patients from counties near HNRCCs, showed a 210.8 % increase in appointments overall, 33.8 % of which were at an HNRCC. At the main campus exclusively, the shift in regional patients to HNRCCs coincided with a lower rate of increase in patients from the MDACC service area (33.7 vs. 11.0 patients/year; P = 0.035), but the trend was toward a greater increase in out-of-state patients (25.7 vs. 40.3 patients/year; P = 0.299)., Conclusions: The creation of HNRCCs coincided with stable increases in new patient volume, and a sizeable minority of patients sought care at regional centers. Regional patients shifted to the HNRCCs, and out-of-state patient volume increased at the main campus, optimizing access for both local and out-of-state patients., (© 2022. Society of Surgical Oncology.)

Importance: Counseling prior to thyroid cancer (TC) treatment is an essential component of informed consent. An informed patient affects treatment-related expectations and patient engagement, factors that contribute significantly to patient-reported quality-of-life outcomes., Objective: To describe experiences with pretreatment counseling among survivors of TC and to test factors associated with self-reported treatment meeting expectations., Design, Setting, and Participants: A cross-sectional survey was administered between October 18, 2019, and February 8, 2020, to members of ThyCa: Thyroid Cancer Survivors' Association Inc, and to individuals accessing the public-facing ThyCa website. Survey respondents were asked 55 questions, including 4 free-text questions and 2 multiple-choice questions about pretreatment counseling., Main Outcomes and Measures: Respondents self-reported (1) their unmet information needs, (2) rates of treatment meeting expectations, and (3) rates of treatment understanding. A mixed-methods analysis was performed, including qualitative content analysis of free-text responses and multivariable logistic regression of factors associated with self-reported levels of treatment meeting expectations., Results: Of the 1412 survey respondents, 1249 were women (88.4%). The median age at diagnosis was 48 years (range, 18-85 years), and the median age at the time of survey completion was 60 years (range, 18-87 years). A total of 1259 respondents (89.2%) provided free-text responses to the question, "What would you tell someone newly diagnosed with your same condition?" Of these individuals, 526 (37.2%) reported inadequate pretreatment plan understanding and 578 (40.9%) reported that their treatment experience did not meet their expectations. Treatment met expectations for only 95 respondents (18.1%) reporting an inadequate pretreatment plan understanding. Of the 526 survivors of TC reporting a lack of understanding, 473 (90.0%) provided additional textual comments, most commonly in the categories of postoperative treatment, surveillance, and treatment effects. On multivariable logistic regression, self-reported failure to have an understanding of TC treatment was independently associated with failure of treatment to meet expectations (odds ratio, 5.1 [95% CI, 3.7-6.9]). Patients reporting a full understanding of their treatment plan were 5-fold more likely to indicate that their initial treatment experience was on par with expectations, independent of reported postoperative complications, age, sex, and other potential confounders., Conclusions and Relevance: In this survey study, a substantial proportion of survivors of TC reported inadequate pretreatment understanding. This gap in understanding was associated with high levels of self-reported failure of treatment to meet expectations, which in turn is associated in other studies with poorer patient-reported quality-of-life outcomes. These outcomes may be improved by addressing gaps in patient understanding so expectations more closely match TC diagnosis and treatment pathways.

The utilization of sentinel lymph node (SLN) biopsy has transformed the workup and staging of intermediate-thickness cutaneous melanomas. SLN biopsy, performed at the time of primary tumor excision, accurately maps lymph nodes at risk of harboring occult metastatic deposits from head and neck cutaneous melanomas and represents the current standard of care. Completion lymphadenectomy identifies additional tumor in 12% to 24% of SLN biopsy positive cases but does not affect melanoma-specific survival., Competing Interests: Disclosure No commercial or financial conflicts of interest for any authors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC., Methods: E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index., Results: Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented., Conclusion: Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC., Competing Interests: Robert L. FerrisThis 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.Stock and Other Ownership Interests: NovasentaConsulting or Advisory Role: Merck, Pfizer, EMD Serono, Numab, Macrogenics, Aduro Biotech, Novasenta, Sanofi, Zymeworks, Bristol Myers SquibbResearch Funding: Bristol Myers Squibb, AstraZeneca/MedImmune, Merck, Tesaro, Novasenta Gregory S. WeinsteinPatents, Royalties, Other Intellectual Property: Olympus Shuli LiEmployment: TakedaStock and Other Ownership Interests: Takeda Harry QuonEmployment: Johns Hopkins HospitalLeadership: Pistevo HealthStock and Other Ownership Interests: Oncospace, Pistevo HealthHonoraria: Sanofi/RegeneronConsulting or Advisory Role: Pinnacle Biologics, Tactile MedicalResearch Funding: Toshiba, Vibrent HealthPatents, Royalties, Other Intellectual Property: Filed under Hopkins, we have several patents related to mobile informatics solutionsOther Relationship: EPIC Ranee MehraStock and Other Ownership Interests: GlaxoSmithKline (I)Consulting or Advisory Role: Bayer, Rakuten MedicalResearch Funding: AstraZeneca, Merck Christine H. ChungConsulting or Advisory Role: Bristol Myers Squibb, CUE Biopharma, Mirati Therapeutics, Sanofi/Regeneron, ExelixisResearch Funding: AstraZeneca, Bristol Myers Squibb, Lilly, Merck, Regeneron, Ignyta, Pfizer, Brooklyn ImmunoTherapeutics, Iovance BiotherapeuticsTravel, Accommodations, Expenses: AstraZeneca, Mirati Therapeutics Maura L. GillisonConsulting or Advisory Role: Bristol Myers Squibb, Merck, EMD Serono, Kura Oncology, BioNTech, Shattuck Labs, Bayer, Debiopharm Group¸ Ipsen, Gilead Sciences¸ Bicara Therapeutics, Nektar¸ Istari, LLX Solutions, OncLive, Seagen, Kura Oncology, Mirati Therapeutics, Sensei BiotherapeuticsResearch Funding: Bristol Myers Squibb, Genocea Biosciences, Cullinan Oncology, Genentech, Agenus, Kura Oncology Umamaheswar DuvvuriConsulting or Advisory Role: ACTIVARTIS BiotechResearch Funding: Kolltan Pharmaceuticals, Medrobotics Bert W. O'Malley JrPatents, Royalties, Other Intellectual Property: Receive royalties from University of Pennsylvania via a licensed technology to Olympus Inc Neil D. GrossHonoraria: Intuitive SurgicalConsulting or Advisory Role: PDS Biotechnology, Verb Surgical, Sanofi/Regeneron, Shattuck LabsResearch Funding: Regeneron, MedImmune, GenentechPatents, Royalties, Other Intellectual Property: UpToDate R. Bryan BellHonoraria: Merck, RegeneronConsulting or Advisory Role: MacrogenicsSpeakers' Bureau: Merck, RegeneronResearch Funding: Bristol Myers Squibb/Celgene Nabil F. SabaHonoraria: Merck, CUE Biopharma, BioNTech AG, GlaxoSmithKlineResearch Funding: Bristol-Myers Squibb, ExelixisTravel, Accommodations, Expenses: Merck, Pfizer, Blueprint Medicines Barbara BurtnessConsulting or Advisory Role: Merck, Debiopharm Group, CUE Biopharma, Maverick Therapeutics, Rakuten Medical, Nanobiotix, Macrogenics, ALX Oncology, IO Biotech, Ipsen, Genentech/Roche, Kura Oncology, Merck KGaA, PPD Global, ExelixisResearch Funding: Merck (Inst), Aduro Biotech (Inst), Formation Biologics (Inst), Bristol Myers (Inst), CUE Biopharma (Inst)Travel, Accommodations, Expenses: Merck, Debiopharm GroupNo other potential conflicts of interest were reported.

Objectives: To develop nomograms predicting overall survival (OS), freedom from locoregional recurrence (FFLR), and freedom from distant metastasis (FFDM) for patients receiving chemoradiation for laryngeal squamous cell carcinoma (LSCC)., Material and Methods: Clinical and treatment data for patients with LSCC enrolled on NRG Oncology/RTOG 0129 and 0522 were extracted from the RTOG database. The dataset was partitioned into 70% training and 30% independent validation datasets. Significant predictors of OS, FFLR, and FFDM were obtained using univariate analysis on the training dataset. Nomograms were built using multivariate analysis with four a priori variables (age, gender, T-stage, and N-stage) and significant predictors from the univariate analyses. These nomograms were internally and externally validated using c-statistics (c) on the training and validation datasets, respectively., Results: The OS nomogram included age, gender, T stage, N stage, and number of cisplatin cycles. The FFLR nomogram included age, gender, T-stage, N-stage, and time-equivalent biologically effective dose. The FFDM nomogram included age, gender, N-stage, and number of cisplatin cycles. Internal validation of the OS nomogram, FFLR nomogram, and FFDM nomogram yielded c = 0.66, c = 0.66 and c = 0.73, respectively. External validation of these nomograms yielded c = 0.59, c = 0.70, and c = 0.73, respectively. Using nomogram score cutoffs, three risk groups were separated for each outcome., Conclusions: We have developed and validated easy-to-use nomograms for LSCC outcomes using prospective cooperative group trial data., (Copyright © 2021. Published by Elsevier Ltd.)

The incidence of Merkel cell carcinoma (MCC) continues to increase. Understanding of MCC biology has advanced rapidly, with current staging providing valuable prognostic information. MCC treatment often is multidisciplinary. Surgery remains an important component in the staging and treatment, most commonly involving wide excision of the cancer and sentinel lymph node biopsy. Lymphadenectomy is used to treat nodal disease. Radiotherapy enhances locoregional control and possibly survival. Systemic therapies, in particular novel immunotherapies, may be promising in the treatment of advanced or recurrent and metastatic disease., Competing Interests: Disclosures None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Prognostic factors and optimal treatment approaches for Merkel cell carcinoma (MCC) remain uncertain. This study evaluated the influences of sentinel lymph node (SLN) biopsy and lymphovascular invasion (LVI) on treatment planning and prognosis., Study Design: Retrospective cohort study., Methods: Stage 1 to 3 MCC patients treated 2005 to 2018. Predictors of nodal radiation were tested using logistic regression. Predictors of recurrence-free, disease-specific, and overall survival were tested in Cox proportional hazard models., Results: Of 122 patients, 99 were without clinically apparent nodal metastases. Of these, 76 (77%) underwent excision and SLN biopsy; 29% had metastasis in SLNs, including 20% of MCCs 1 cm or less. Primary tumor diameter, site, patient age, gender, and immunosuppressed status were not significantly associated with an involved SLN. Among patients who underwent SLN biopsy, 13 of 21 (62%) MCCs with LVI had cancer in SLNs compared with 14 of 44 (25.5%) without LVI (P = .003). Although local radiation was common, nodal radiation was infrequently employed in SLN negative (pathologic N0) patients (21.8% vs. 76.2% for patients with SLN metastases, P = .0001). Survival of patients with positive SLNs was unfavorable, regardless of completion lymphadenectomy and/or adjuvant radiation. After accounting for tumor (T) and node (N) classification, age, immunosuppression, and primary site, a positive SLN and LVI were independently associated with worse survival (LVI/recurrence-free survival [RFS]: hazard ratio [HR] 2.3 (1.04-5, P = .04; LVI/disease-specific survival [DSS]: HR 5.2 (1.8-15, P = .007); N1a vs. pN0/RFS HR 3.6 (1.42-9.3, P = .007); DSS HR5.0 (1.3-19, P = .17)., Conclusion: SLN biopsy assists in risk stratification and radiation treatment planning in MCC. LVI and disease in SLNs, independently associated with worse survival, constitute markers of high-risk disease warranting consideration for investigational studies., Level of Evidence: III Laryngoscope, 131:E828-E835, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Survivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival., Methods: We measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes., Results: Using the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p = 0.013), cytoplasmic (p = 0.018) and total compartments (p = 0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p = 0.0264) and total compartments (p = 0.0264), but not in the nucleus (p = 0.0729)., Conclusions: Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Rapid recurrence, defined as gross tumor recurrence after primary operation but prior to initiating postoperative radiation therapy (PORT), is underappreciated in head and neck cancer (HNC)., Methods: CT simulation images in patients with HNC managed surgically with adjuvant therapy at a single center between 2010 and 2017 were retrospectively reviewed., Results: A total of 194 patients with HNC were included. Rapid recurrence occurred in 39 patients (20%) with a median time from operation to CT simulation of 37 days. On multivariable analysis (MVA), extranodal extension (ENE) was the only predictor of rapid recurrence (P = .03). While rapid recurrence, ENE, and perineural invasion were all associated with poor overall survival (OS) on MVA, rapid recurrence was the strongest predictor (hazard ratio [HR] 5.47)., Conclusion: Rapid recurrence occurs at an underappreciated rate and is associated with poor survival outcomes. Patients with ENE are at highest risk and may benefit from diagnostic imaging evaluations immediately prior to PORT., (© 2020 Wiley Periodicals LLC.)

Objectives: To investigate the prognostic impact of primary tumor-specific growth rate (TSGR) on treatment outcomes after definitive radiation therapy (RT) for nonoropharyngeal squamous cell carcinoma (non-OPSCC)., Methods: The diagnostic tumor and nodal volumes of 39 non-OPSCC patients were contoured and compared to corresponding RT planning scan volumes to determine TSGR. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were evaluated according to the Kaplan-Meier method; and hazard ratios (HR) were estimated using Cox regression. Based on the 75th percentile TSGR of 2.18%, we stratified patients into a high TSGR group (≥ 2.18% per day) and low TSGR group (< 2.18% per day)., Results: The median follow-up was 22 months (range: 1-86 months) and median time between diagnostic and simulation computed tomography scans was 22 days (range: 7-170 days). Median RT dose was 70 Gy (range: 60-79.2 Gy). Based on the 75th percentile TSGR, OS at median follow-up was 50.0% for the high TSGR group compared to 92.5% for the low TSGR group (HR [95% confidence interval (CI)] = 2.12[1.16-11.42], P = 0.018). There was a trend toward worse DFS at median follow-up for the high versus low TSGR groups, at 55.6% and 82.3%, respectively (HR [95% CI] = 2.29[0.82-6.38], P = 0.103)., Conclusion: Our study contributes to growing literature on TSGR as a temporal biomarker in patients with non-OPSCC. Patients with high TSGR ≥2.18% per day have significantly worse OS compared to those with TSGR below this threshold. Efforts to address treatment initiation delays may benefit patients with particularly aggressive and rapidly growing tumors., Level of Evidence: 4 Laryngoscope, 130:2378-2384, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To survey a large cohort of thyroid cancer survivors from ThyCa on information needs and expectations of their treatment to better understand the pretreatment counseling, information, and support needs of this population., Methods: Anonymous survey of thyroid cancer survivors., Results: One thousand one hundred twenty-four patients with thyroid cancer participated in the survey. Three hundred sixty-two (37.44%) reported not having had a full understanding of their treatment plan and 407 (46.41%) reported that their thyroid cancer treatment did not conform to expectations. Patients diagnosed at younger ages were significantly more likely to report inadequate understanding of the treatment, failure of treatment to meet expectations, and call for greater attention to psychological well-being. Older patients were more likely to report unexpected effects on speech and swallowing. Regardless of age, patients most frequently called for greater attention to management of energy levels (endorsed by 61% of respondents), psychological well-being (50%), and weight changes (48%)., Conclusions: Improvements are needed in age-specific communication of thyroid cancer diagnosis and treatment., (© 2020 Wiley Periodicals, Inc.)

Background: Tracheal dryness is a concern after total laryngectomy due to the potential for mucus plugs (MP). This study compared heat and moisture exchanger (HME) cassettes to external tracheal humidification (ETH) surrounding MP events., Methods: A retrospective comparative cohort study comparing outcomes before/after implementation of a patient safety initiative utilizing HME during post laryngectomy hospitalization. The number of MP events were compared with a pre-implementation control group using ETH. Patient characteristics were analyzed for correlation with MP., Results: The rate of MP was significantly lower in the HME group than ETH (0.13 and 0.38 per 10 inpatient days, respectively, P = .02). The proportion of patients with one or more MP events was also significantly reduced in the HME group (50% ETH and 11% HME, P = .01). Method of humidification was the only significant variable associated with MP on logistic regression modeling (P = .008)., Conclusions: HMEs were superior to ETH for prevention of MP., (© 2020 Wiley Periodicals, Inc.)

The COVID-19 epidemic was not the first coronavirus epidemic of this century and represents one of the increasing number of zoonoses from wildlife to impact global health. SARS CoV-2, the virus causing the COVID-19 epidemic is distinct from, but closely resembles SARS CoV-1, which was responsible for the severe acute respiratory syndrome (SARS) outbreak in 2002. SARS CoV-1 and 2 share almost 80% of genetic sequences and use the same host cell receptor to initiate viral infection. However, SARS predominantly affected individuals in close contact with infected animals and health care workers. In contrast, CoV-2 exhibits robust person to person spread, most likely by means of asymptomatic carriers, which has resulted in greater spread of disease, overall morbidity and mortality, despite its lesser virulence. We review recent coronavirus-related epidemics and distinguish clinical and molecular features of CoV-2, the causative agent for COVID-19, and review the current status of vaccine trials., (© 2020 Wiley Periodicals, Inc.)

Background: COVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel., Methods: The MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular., Recommendations: Each subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred., Conclusion: These guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability., (© 2020 Wiley Periodicals, Inc.)

Objective: Hospital-acquired aspiration pneumonia remains a rare but potentially devastating problem. The best means by which to prevent aspiration in a cancer hospital population has not been evaluated. The aim of this study was to evaluate the impact of dysphagia screening on aspiration pneumonia rates in an acute care oncology hospital., Methods: A prospective single-institution quality improvement dysphagia screening protocol at a comprehensive cancer center. Effect of dysphagia screening implemented in 2016 on hospital-acquired aspiration pneumonia rates coded "aspiration pneumonitis due to food/vomitus" was compared with rates from 2014 to 2015 prior to implementation. Screening compliance, screening outcomes, patient demographics, and medical data were reviewed as part of a post hoc analysis., Results: Of 12,392 admissions in 2014 to 2016, 97 patients developed aspiration pneumonia during their hospitalization. No significant change in aspiration pneumonia rate was seen during the dysphagia screening year when compared to prior years (baseline, 7.36; screening year, 8.78 per 1000 discharges; P = .33). Sixty-eight of the cases (66%) were associated with emesis/gastrointestinal obstruction or perioperative aspiration and only 15 (15%) with oropharyngeal dysphagia. Multivariate analysis found that patients admitted to gastrointestinal surgery had an aspiration risk equivalent to patients admitted to head and neck, thoracic, and pulmonary services (odds ratio, 0.65; P = .2)., Discussion: Nursing-initiated dysphagia screening did not decrease aspiration pneumonia rates. The causes of aspiration-associated pneumonia were heterogeneous. Aspiration of intestinal contents is a more common source of hospital-acquired pneumonia than oropharyngeal dysphagia.

Background: The objective of this study was to compare the cosmesis and recurrence rates of conventional excision (CE), Mohs micrographic surgery (MMS), external-beam radiation therapy (EBRT), or brachytherapy (BT), for basal cell carcinoma and squamous cell carcinoma of the skin., Methods: Population, Intervention, Control, Outcome, Study Design (PICOS), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Meta-Analyses of Observational Studies in Epidemiology (MOOSE) methods were used to identify studies on PubMed (from 1985 to 2018), including patients with American Joint Committee on Cancer (AJCC) T1-T2N0 basal cell carcinomas and squamous cell carcinomas and ≥10 months follow-up who received CE, MMS, EBRT, or BT. The primary endpoint was cosmesis, classified as "good," "fair," or "poor." The secondary endpoint was 1-year recurrence. Fixed-effects and random-effects meta-analyses were performed to evaluate primary and secondary outcomes with respect to treatment modality., Results: In total, 18,095 studies met initial search criteria. There were 24 CE, 13 MMS, 19 EBRT, and 7 BT studies included with a total of 21,371 patients. The summary effect size for "good" cosmesis was 81% (95% CI, 70.6%-89.6%), 74.6% (95% CI, 63%-84.6%), and 97.6% (95% CI, 91.3%-100%) for CE, EBRT, and BT, respectively. Good cosmesis was 96.0% in the only MMS study that reported cosmesis. BT had improved "good" cosmesis over EBRT (P = .0025) and was similar to CE and MMS. No significant differences were seen for "fair" or "poor" cosmesis. One-year recurrence rates were low throughout at 0.8% (95% CI, 0.3%-1.6%), 0.2% (95% CI, 0%-0.6%), 2% (95% CI, 1.3%-2.7%), and 0% (95% CI, 0%-0.5%) for CE, MMS, EBRT, and BT, respectively., Conclusions: For T1-T2N0 skin cancers, BT and MMS have improved cosmesis over EBRT and CE. It is unclear whether this is because of treatment superiority or selection and reporting bias. Local control is similar among all modalities at 1 year., (© 2019 American Cancer Society.)

Objectives: To characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment., Materials and Methods: We retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥ 10 years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportional hazards modeling was used for univariable analysis (UVA) and multivariable analysis (MVA) for time to CNP after completion of radiation., Results: We identified 112 patients with no evidence of disease and follow-up ≥ 10 years (median 12.2). Sixteen (14%) patients developed at least one CNP. The median time to CNP was 7.7 years (range 0.6-10.6 years). Most common was CN XII deficit in eight patients (7%), followed by CN X deficit in seven patients (6%). Others included CN V deficit in three, and CN XI deficit in two. Eight of the thirteen patients with a CN X and/or CN XII deficit required a permanent gastrostomy tube. On UVA, site of primary disease, post-radiation neck dissection, chemotherapy, and radiation dose were significantly associated with increased risk of CNP., Conclusion: Iatrogenic CNP may develop years after head and neck cancer treatment and often leads to swallowing dysfunction. Long-term follow up is essential for these patients receiving head and neck radiation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Health care consumer organizations and insurance companies increasingly are scrutinizing value when considering reimbursement policies for medical interventions. Recently, members of several American Academy of Otolaryngology-Head & Neck Surgery (AAO-HNS) committees worked closely with one insurance company to refine reimbursement policies for preoperative localization imaging in patients undergoing surgery for primary hyperparathyroidism. This endeavor led to an AAO-HNS parathyroid imaging consensus statement (https://www.entnet.org/content/parathyroid-imaging). The American Head and Neck Society Endocrine Surgery Section gathered an expert panel of authors to delineate imaging options for preoperative evaluation of surgical candidates with primary hyperparathyroidism. We review herein the current literature for preoperative parathyroid localization imaging, with discussion of efficacy, cost, and overall value. We recommend that planar sestamibi imaging, single photon emission computed tomography (SPECT), SPECT/CT, CT neck/mediastinum with contrast, MRI, and four dimensional CT (4D-CT) may be used in conjunction with high-resolution neck ultrasound to preoperatively localize pathologic parathyroid glands. PubMed literature on parathyroid imaging was reviewed through February 1, 2019., (© 2019 Wiley Periodicals, Inc.)

Objective: Oropharynx cancer incidence trends in low socioeconomic (SES) regions of the United States (US) have not been well described. Our objective was to describe tonsil cancer incidence trends in low SES regions, and compare observed trends with those for larynx cancer., Materials and Methods: Age-adjusted incidence rates and trends for tonsil and larynx squamous cell carcinomas (2000-14) from Surveillance, Epidemiology, and End Results (SEER 18) were evaluated using SEER*Stat and Joinpoint 4.5.0.1. Annual percentage changes (APCs) were compared between low and high SES counties. The laryngeal cancer cohort was included as a comparator reflecting a tobacco-related malignancy., Results: Tonsil cancer incidence trends increased at least as much in low SES as in high SES counties (APC/AAPC 4.4, 95%CI 2.4-6.4 versus APC/AAPC 2.9, 95%CI 2.4-3.3). Pairwise comparison confirmed no differences between incidence trends across SES quintiles for tonsil cancer incidence rates. In contrast, age-adjusted incidence rates of larynx cancer decreased in high SES counties (APC/AAPC -2.4, 95%CI -2.4 to -2.0, p < 0.001) and were stable in low SES counties (APC/AAPC -0.9, 95%CI -1.9 to 0.2, p = 0.10). Compared with larynx cancer patients, tonsil cancer patients in low SES regions were significantly more likely to be younger and white., Conclusion: In low SES US counties, tonsil cancer incidence rates increased from 2000 to 2014, while larynx cancer rates did not change, reflecting diverging trends for larynx and tonsil cancers. Tonsil cancer incidence rates are increasing in most US regions regardless of regional socioeconomic status. Prevention efforts should take these findings into account., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to examine the relationships among patient occupation, laryngeal diagnosis, perceptual dysphonia severity, and patient-perceived voice impairment., Methods: Adult patients presenting with a chief complaint of dysphonia over a 20-month period at a tertiary care, interdisciplinary voice center were included in this retrospective cohort study. Patients were categorized by profession: vocal performers, high occupational voice demand, low or no occupational voice demand, and retired. Associations between professional voice demand and clinician rating of dysphonia severity using the "Grade" score from the Grade, Roughness, Breathiness, Asthenia, and Strain scale and patient ratings of voice impairment using the Voice Handicap Index-10 (VHI-10) were tested using standard descriptive statistical methods., Results: One hundred and sixty-three patients with a presenting complaint of dysphonia were evaluated. Significant associations were found on univariate and multivariable analysis among a patient's occupational voice demand, Grade, Roughness, Breathiness, Asthenia, and Strain grade, and VHI-10 score (P = 0.007 and P < 0.001, respectively). Patients subject to greater vocal demands as a result of their occupation had a greater perception of impairment, regardless of acoustic-perceptual severity, when compared with those with low or no occupational voice demand. Although voice diagnosis was significantly associated with VHI-10 score on univariate analysis, it failed to reach significance on multivariable analysis. Demographic measures such as gender and age also did not correlate with perceived vocal impairment., Conclusion: Patient-perception of voice impairment is influenced by occupational demand, independent of acoustic-perceptual dysphonia. Performers and people with high occupational voice needs demonstrate a unique sensitivity to subtle voice changes., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The association between regional breast cancer diagnostic rates, treatments, and outcomes is unclear. We sought to investigate the management and survival of women with invasive ductal carcinoma (IDC) from geographic regions with variable rates of diagnosis., Methods: Data on women diagnosed with IDC years 2009-2010 were obtained from the Surveillance, Epidemiology, and End Results database. Patients were divided into quartiles based on the IDC diagnostic rate within their county of residence. Chi-square and one-way analysis of variance (ANOVA) analyses tested the association between patient and clinical characteristics and the diagnostic rate quartiles. Cox regression analyses compared survival between the quartiles., Results: Among the 83,375 patients included, the mean age was 60.8 y and 70.9% were white. Patients residing in counties with the highest diagnostic rates were more frequently white, employed, educated, and wealthier and more often received adjuvant radiation following both partial mastectomy for localized disease and complete mastectomy for advanced disease compared to patients in counties with the lowest diagnostic rates. The highest diagnostic rate quartile had 10% decreased odds of death compared to the lower quartile (hazard ratio: 0.897; 95% confidence interval: 0.832-0.966). However, after adjustment for socioeconomic variables, survival was comparable (hazard ratio: 0.916; 95% confidence interval: 0.835-1.003)., Conclusions: Regional variation in IDC diagnostic rates is associated with differences in socioeconomic status, grade, stage, and treatment. Patients from regions with the highest rates of diagnosis may have improved access to evidence-based care and resultant superior survival. Enhancing access to care may improve outcomes of patients residing in regions where breast cancer is diagnosed less frequently., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: Investigate the impact of rural geography on larynx cancer incidence and survival., Study Design: Surveillance, Epidemiology, and End Results (SEER) database study., Methods: Incidence and survival rates by Rural-Urban Continuum codes for larynx squamous cell carcinoma patients diagnosed from 2004 to 2012 were evaluated using SEER statistical software and Cox proportional hazards survival analysis., Results: The lowest age-adjusted incidence rates for larynx cancer were seen in densely populated urban regions, with mean rates of 2.8 per 100,000 person years (95% confidence interval [CI]: 2.7-2.8); the highest were in the most rural areas, with mean rates of 5.3 per 100,000 person years (95% CI: 4.7-5.9). Nevertheless, of 23,659 larynx cancer patients diagnosed over this period, 19,556 (82.7%) arose in urban residents, compared with 1,428 or 6% from rural areas. Urban larynx cancer patients more likely lived in counties with an American College of Surgeons-approved cancer center and/or a fourfold greater otolaryngology physician supply. Nevertheless, frequency of advanced stage at initial presentation was similar. Cause-specific and overall survival were no different, both on univariable and multivariable analyses., Conclusions: Compared with urban populations, Rural populations are at greater risk of developing larynx cancer, but initial stage and survival after diagnosis are comparable. Priority should be given to prevention strategies to decrease incidence rates., Level of Evidence: 4 Laryngoscope, 1874-1880, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

In North America, underserved and vulnerable populations experience poorer health outcomes despite greater per capita health care expenditures. Biologic, behavioral, and socioeconomic factors lead to more advanced disease presentation that may necessitate disparate treatment. Additionally, vulnerable populations are more likely to obtain care from low-volume providers, and are more likely to receive inappropriate care. Disparities in care are exacerbated by the distribution of the physician workforce and limited participation by physicians in the care of vulnerable populations. Multipronged strategies are needed to ameliorate observed disparities in care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Examine the relationship among the severity of patient-perceived voice impairment, perceptual dysphonia severity, occupational voice demand, and voice therapy adherence. Identify clinical predictors of increased risk for therapy nonadherence., Methods: A retrospective cohort study of patients presenting with a chief complaint of persistent dysphonia at an interdisciplinary voice center was done. The Voice Handicap Index-10 (VHI-10) and the Voice-Related Quality of Life (V-RQOL) survey scores, clinician rating of dysphonia severity using the Grade score from the Grade, Roughness Breathiness, Asthenia, and Strain scale, occupational voice demand, and patient demographics were tested for associations with therapy adherence, defined as completion of the treatment plan. Classification and Regression Tree (CART) analysis was performed to establish thresholds for nonadherence risk., Results: Of 166 patients evaluated, 111 were recommended for voice therapy. The therapy nonadherence rate was 56%. Occupational voice demand category, VHI-10, and V-RQOL scores were the only factors significantly correlated with therapy adherence (P < 0.0001, P = 0.018, and P = 0.008, respectively). CART analysis found that patients with low or no occupational voice demand are significantly more likely to be nonadherent with therapy than those with high occupational voice demand (P < 0.001). Furthermore, a VHI-10 score of ≤29 or a V-RQOL score of >40 is a significant cutoff point for predicting therapy nonadherence (P < 0.011 and P < 0.004, respectively)., Conclusion: Occupational voice demand and patient perception of impairment are significantly and independently correlated with therapy adherence. A VHI-10 score of ≤9 or a V-RQOL score of >40 is a significant cutoff point for predicting nonadherence risk., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

The following article is part of a series in an initiative by the American Head and Neck Society's Education Committee and will review clinical practice guidelines for head and neck oncology. The primary goal is to increase awareness of current best practices pertaining to head and neck surgery and oncology. This manuscript is a review of current knowledge in laryngeal cancer with a focus on anatomy, epidemiology, diagnosis, evaluation, and treatment., (© 2017 Wiley Periodicals, Inc.)

Objectives: To characterize the recognized but poorly understood long-term toxicities of radiation therapy (RT) for head and neck cancer (HNC)., Materials and Methods: We retrospectively evaluated patients treated with curative-intent RT for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥10years. Long-term toxicities of the upper aerodigestive tract were recorded and assigned to two broad categories: pharyngeal-laryngeal and oral cavity toxicity. Kaplan-Meier estimates and Chi-square tests were used for univariable analysis (UVA). Cox model and logistic regression were used for multivariable analysis (MVA)., Results: We identified 112 patients with follow-up ≥10years (median 12.2). The primary tumor sites were pharynx (42%), oral cavity (34%), larynx (13%), and other (11%). Forty-four percent received postoperative RT, 24% had post-RT neck dissection, and 47% received chemotherapy. Twenty-eight (25%) patients developed pharyngeal-laryngeal toxicity, including 23 (21%) requiring permanent G-tube placed at median of 5.6years (0-20.3) post-RT. Fifty-three (47%) developed oral cavity toxicity, including osteoradionecrosis in 25 (22%) at a median of 7.2years (0.5-15.3) post-RT. On MVA, pharyngeal-laryngeal toxicity was significantly associated with chemotherapy (HR 3.24, CI 1.10-9.49) and age (HR 1.04, CI 1.00-1.08); oral cavity toxicity was significantly associated with chemotherapy (OR 4.40, CI 1.51-12.9), oral cavity primary (OR 5.03, CI 1.57-16.1), and age (OR 0.96, CI 0.92-1.00)., Conclusion: Among irradiated HNC patients, pharyngeal-laryngeal and oral cavity toxicity commonly occur years after radiation, especially in those treated with chemotherapy. Follow-up for more than five years is essential because these significant problems afflict patients who have been cured., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Locoregionally advanced nonmelanoma skin cancer (NMSC) has an aggressive clinical course characterized by high rates of treatment failure and poor survival compared with localized skin cancers. Our goal was to investigate multimodal therapy for lymph-node-positive NMSC. Data from patients with lymph-node-positive NMSC who underwent surgery and adjuvant therapy at a single tertiary center from 2002 to 2012 were retrospectively reviewed. Median follow-up was 1.8 years (range: 0.5 to 8.5). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The chi-square test and logistic regression were used to determine the association between locoregional control (LRC) and the following variables: evidence of extracapsular extension, number of lymph nodes positive, largest involved lymph node, presence of a positive margin, and use of concurrent chemoradiation (CRT). Forty-six patients were evaluated, 13 (28%) of whom received adjuvant CRT. CRT patients were younger (p < 0.001) and had a significantly greater number of positive lymph nodes (p = 0.016) than patients who received adjuvant radiation alone. At 5 years, LRC was 76%, PFS was 65%, and OS was 49%. Univariate analysis demonstrated that CRT (p = 0.006), largest lymph node measurement (p = 0.039), and ≥3 involved lymph nodes (p = 0.001) predicted local recurrence. CRT (p = 0.035, odds ratio [OR] 0.20 [95% confidence interval 0.05 to 0.90]) and ≥3 involved lymph nodes (p = 0.017, OR 0.07 [95% confidence interval 0.01 to 0.62]) remained significant on multivariate analysis. CRT was well tolerated. No grade ≥3 toxicities were observed except for 1 asymptomatic grade-4 thrombocytopenia. Patients with lymph-node-positive NMSC do poorly. Patient selection for intensification of adjuvant therapy needs clarification.

Objective: To describe geographic variation in spending and evaluate regional Medicare expenditures for otolaryngologist services with population- and beneficiary-related factors, physician supply, and hospital system factors., Study Design: Cross-sectional study., Methods: The average regional expenditures for otolaryngology physician services were defined as the total work relative value units (wRVUs) collected by otolaryngologists in a hospital referral region (HRR) per thousand Medicare beneficiaries in the HRR. A multivariable linear regression model tested associations with regional sociodemographics (age, sex, race, income, education), the physician and hospital bed supply, and the presence of an otolaryngology residency program., Results: In 2012, the mean Medicare expenditure for otolaryngology provider services across HRRs was 224 wRVUs per thousand Medicare beneficiaries (standard deviation [SD] 104), ranging from 31 to 604 wRVUs per thousand Medicare beneficiaries. In 2013, the average Medicare expenditures for each HRR was highly correlated with expenditures collected in 2012 (Pearson correlation coefficient .997, P = .0001). Regional Medicare expenditures were independently and positively associated with otolaryngology, medical specialist, and hospital bed supply in the region, and were negatively associated with the supply of primary care physicians and presence of an otolaryngology residency program after adjusting for other factors. The magnitude of associations with physician supply and hospital factors was stronger than any population or Medicare beneficiary factor., Conclusion: Wide variations in regional Medicare expenditures for otolaryngology physician services, highly stable over 2 years, were strongly associated with regional health system factors. Changes in health policy for otolaryngology care may require coordination with other physician specialties and integrated hospital systems., Level of Evidence: NA. Laryngoscope, 127:1312-1317, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To describe the deployment of otolaryngologists and evaluate factors associated with the geographic distribution of otolaryngologists in the United States., Study Design: Cross-sectional study., Methods: The otolaryngology physician supply was defined as the number of otolaryngologists per 100,000 in the hospital referral region (HRR). The otolaryngology physician supply was derived from the American Medical Association Masterfile or from the Medicare Enrollment and Provider Utilization Files. Multiple linear regression tested the association of population, physician, and hospital factors on the supply of Medicare-enrolled otolaryngologists/HRR., Results: Two methods of measuring the otolaryngology workforce were moderately correlated across hospital referral regions (Pearson coefficient 0.513, P = .0001); regardless, the supply of otolaryngology providers varies greatly over different geographic regions. Otolaryngologists concentrate in regions with many other physicians, particularly specialist physicians. The otolaryngology supply also increases with regional population income and education levels. Using AMA-derived data, there was no association between the supply of otolaryngologists and staffed acute-care hospital beds and the presence of an otolaryngology residency-training program. In contrast, the supply of otolaryngology providers enrolled in Medicare independently increases for each HRR by 0.8 per 100,000 for each unit increase in supply of hospital beds (P < .0001) and by 0.49 per 100,000 in regions with an otolaryngology residency-training program (P = .006), accounting for all other factors., Conclusion: Irrespective of methodology, the supply of otolaryngologists varies widely across geographic regions in the United States. For Medicare beneficiaries, regional hospital factors-including the presence of an otolaryngology residency program-may improve access to otolaryngology services., Level of Evidence: NA Laryngoscope, 127:95-101, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

We conducted a retrospective study to determine the incidence and treatment outcomes of neck metastases in patients with squamous cell carcinoma (SCC) of the hard palate and/or maxillary alveolus after surgical excision of the primary tumor. We also sought to identify any risk factors for recurrence. Our study population was made up of 20 patients-9 men and 11 women, aged 46 to 88 years (mean: 72.6)-who had undergone excision of an SCC of the hard palate and/or maxillary alveolus at a tertiary care cancer center over a 7-year period. Half of all patients were former tobacco users. Of the 20 tumors, 10 involved the maxillary alveolus, 4 involved the hard palate, and 6 involved both sites. Three patients were clinically categorized as T1, 9 as T2, 6 as T3, and 2 as T4; pathologically, 8 tumors were categorized as T4a. In addition to maxillectomy, a neck dissection was performed in 7 patients-4 therapeutically and 3 electively. Eight of 20 patients experienced a recurrence: 4 local, 6 regional, and 2 distant (several patients had a recurrence at more than one site). Univariate analysis identified perineural invasion (p = 0.04) as a statistically significant risk factor for recurrence. Of 14 patients with a clinicopathologically negative neck, 5 (36%) developed a cervical recurrence, and 4 of them died of their disease. An advanced stage (T4 vs.

Clinical decision making for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and anatomic location, with few validated biomarkers. The epidermal growth factor receptor (EGFR) is an important therapeutic target, but its value in guiding therapeutic decision making remains ambiguous. We integrated analysis of clinically annotated tissue microarrays with analysis of data available through the TCGA, to investigate the idea that expression signatures involving EGFR, proteins regulating EGFR function, and core cell-cycle modulators might serve as prognostic or drug response-predictive biomarkers. This work suggests that consideration of the expression of NSDHL and proteins that regulate EGFR recycling in combination with EGFR provides a useful prognostic biomarker set. In addition, inactivation of the tumor suppressor retinoblastoma 1 (RB1), reflected by CCND1/CDK6-inactivating phosphorylation of RB1 at T356, inversely correlated with expression of EGFR in patient HNSCC samples. Moreover, stratification of cases with high EGFR by expression levels of CCND1, CDK6, or the CCND1/CDK6-regulatory protein p16 (CDKN2A) identified groups with significant survival differences. To further explore the relationship between EGFR and RB1-associated cell-cycle activity, we evaluated simultaneous inhibition of RB1 phosphorylation with the CDK4/6 inhibitor palbociclib and of EGFR activity with lapatinib or afatinib. These drug combinations had synergistic inhibitory effects on the proliferation of HNSCC cells and strikingly limited ERK1/2 phosphorylation in contrast to either agent used alone. In summary, combinations of CDK and EGFR inhibitors may be particularly useful in EGFR and p T356 RB1-expressing or CCND1/CDK6-overexpressing HPV-negative HNSCC. Mol Cancer Ther; 15(10); 2486-97. ©2016 AACR., (©2016 American Association for Cancer Research.)

Given the marked difference in clinical presentation and treatment response based on human papilloma virus (HPV) status, HPV-associated oropharyngeal squamous cell carcinoma is now viewed as a distinct biologic and clinical entity. HPV-associated oropharyngeal squamous cell carcinoma has increased by nearly 7.5 % per year, from approximately 16 % in the early 1980's to nearly 70 % today, and is believed will continue to increase dramatically in the coming years. Currently, a myriad of treatment options exist for these patients as many active clinical trials are underway which aim to identify the most appropriate interventions for this unique group of patients. This review aims to provide considerations between surgical and non-surgical management for HPV-associated oropharyngeal squamous cell carcinoma., Competing Interests: The authors declare that they have no competing interests.

Objective: To report T1-2N0 tongue cancer recurrences initially treated with surgery alone., Methods: Between 1990 and 2010, 27 patients at tertiary hospital referral center institution were treated with curative intent for locoregional recurrence after initial glossectomy with or without neck dissection for T1-2N0 tongue cancer. None had received adjuvant postoperative radiation as a component of the original treatment., Results: Median time to locoregional recurrence was 12 months (range 5-39 months) and 78% of failures occurred in the first 2 years. Most treatment failures were local (63%). Salvage strategy was risk-adapted by individual patient. The 5-year disease specific survival (DSS) was 61%. Patients with local recurrences alone fared significantly better than those with regional recurrences (5-yr DSS: 86% vs . 22%, P  = 0.0018). Local recurrences were usually treated by surgery alone, while regional recurrences were more commonly treated with combined modality treatment ( P  = 0.005)., Conclusions: Recurrence of early stage oral tongue cancer can be successfully salvaged in a majority of cases. Patients developing regional recurrence have significantly worse prognosis than those with local failures.

The free fibula flap is the preferred reconstructive method for oncologic defects of the mandible. Arterial inflow of the extremity is routinely evaluated with several modalities; however, venous screening is rarely performed. Patients with cancer are at elevated risk of occult deep venous thrombosis (DVT). An asymptomatic thrombus encountered during free fibula reconstruction is a serious concern. Although such cases have been reported, we suspect the incidence of DVT during fibula free flap harvest is underappreciated. This monograph uses a case example to review risk factors for occult DVT, present a strategy for preoperative assessment, and provide a reconstructive algorithm to for mandibular reconstruction in such instances.

Background: Dysphagia-related symptoms in patients with head and neck cancer are common before treatment. We hypothesized greater self-reported baseline dysphagia would predict gastrostomy placement during primary radiation., Methods: Swallowing-specific/general surveys (SwalQOL/EuroQOL) collected prospectively before definitive radiation were analyzed for associations with gastrostomy placement. Prophylactic gastrostomy was recommended at the discretion of a multidisciplinary team blinded to the surveys., Results: Of 84 patients in the cohort, 42 patients (50%) received feeding tubes. Eleven patients (13%) who underwent prophylactic feeding tube placement reported the greatest pretreatment dysphagia, whereas those who avoided gastrostomies reported the least. Prophylactic gastrostomy was more strongly associated with patient-reported measures than other clinical criteria. Controlling for stage IV, T3 to T4 classification, smoking, chemotherapy, and pretreatment weight loss, baseline dysphagia remained an independent predictor of feeding tube placement (odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.05-0.55; p = .01). Patients without gastrostomies during treatment avoided persistent gastrostomy dependence., Conclusion: Baseline dysphagia-related symptoms before radiation are independent predictors of gastrostomy placement. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1318-E1324, 2016., (© 2015 Wiley Periodicals, Inc.)

Vocal cord paralysis after administration of the chemotherapeutic agent vincristine is a rare occurrence. Most occurrences are bilateral. Of the 24 cases referenced in this article, 19 are children. In all the reported cases, symptoms have occurred after multiple doses of vincristine have been administered. The authors report a case of a 39-year-old woman with unilateral vocal cord motion impairment occurring 3 days after the administration of the first dose of vincristine. This is the first case of vocal cord motion impairment reported after the administration of only 1 dose of this drug.

Cavernous hemangiomas of the submandibular gland are rare. Signs and symptoms typically resemble those of sialolithiasis and chronic sialadenitis. If a lesion extends into the parapharyngeal space, otalgia and sore throat can result. Spontaneous regression is not a characteristic of cavernous hemangiomas. Surgical excision is a management option. We report the case of an adult with a submandibular gland cavernous hemangioma with parapharyngeal extension.

Locally advanced squamous cell carcinoma of the head and neck (SCCHN) that is not associated with human papillomavirus (HPV) has a poor prognosis in contrast to HPV-positive disease. To better understand the importance of RB1 activity in HPV-negative SCCHN, we investigated the prognostic value of inhibitory CDK4/6 phosphorylation of RB1 on threonine 356 (T356) in archival HPV-negative tumor specimens from patients who underwent surgical resection and adjuvant radiation. We benchmarked pT356RB1 to total RB1, Ki67, pT202/Y204ERK1/2, and TP53, as quantified by automatic quantitative analysis (AQUA), and correlated protein expression with tumor stage and grade. High expression of pT356RB1 but not total RB1 predicted reduced overall survival (OS; P = 0.0295), indicating the potential relevance of post-translational phosphorylation. Paired analysis of The Cancer Genome Atlas (TCGA) data for regulators of this RB1 phosphorylation identified loss or truncating mutation of negative regulator CDKN2A (p16) and elevated expression of the CDK4/6 activator CCND1 (cyclin D) as also predicting poor survival. Given that CDK4/6 inhibitors have been most effective in the context of functional RB1 and low expression or deletion of p16 in other tumor types, these data suggest such agents may merit evaluation in HPV-negative SCCHN, specifically in cases associated with high pT356RB1.

Objective: Medicare Part B physician payment indicates a cost to Medicare beneficiaries for a physician service and connotes physician clinical productivity. The objective of this study was to determine whether there was an association between practice arrangement and Medicare physician payment., Study Design: Cross-sectional study., Setting: Medicare provider utilization and payment data., Subjects and Methods: Otolaryngologists from 1 metropolitan area were included as part of a pilot study. A generalized linear model was used to determine the effect of practice-specific variables including patient volumes on physician payment., Results: Of 67 otolaryngologists included, 23 (34%) provided services through an independent practice, while others were employed by 1 of 3 local academic centers. Median payment was $58,895 per physician for the year, although some physicians received substantially higher payments. Reimbursements to faculty at 1 academic department were higher than to those at other institutions or to independent practitioners. After adjustments were made for patient volumes, physician subspecialty, and gender, payments to each faculty at Hospital C were 2 times higher than to those at Hospital A (relative ratio [RR] 2.03; 95% CI, 1.27-3.27; P = .003); 2 times higher than to faculty at Hospital B (RR 2.04; 95% CI, 1.4-2.7; P = .0001); and 1.6 times higher than to independent practitioners (RR 1.6; 95% CI, 1.04-2.7; P = .03). Payments to physicians in the other groups were not significantly different. Differences in reimbursement corresponded to an emphasis on procedures over office visits but not Medicare case mix adjustments for patient discharges from associated institutions., Conclusions: Variation in the cost of academic otolaryngology care may be subject in part to institutional factors., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Background: The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP)., Methods: Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC)., Results: A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p < .0001), absence of macroscopic extracapsular extension (ECE; p = .004), younger age (p = .01), and higher grade (p = 0.007). The prognostic implication of worse overall survival (OS) with macroscopic ECE (p = .009) remained significant when limited to patients who were p16+ (p = .002). Exploratory TMA between unknown primary and controls suggested a biomolecular difference between squamous cell CUP and known-primary cancer., Conclusion: The majority of patients with squamous cell CUP were p16+, indicative of HPV association. P16 staining and ECE seem to be the most prognostic features in squamous cell CUP., (© 2014 Wiley Periodicals, Inc.)

Background: Psychosocial functioning is associated with vascular endothelial growth factor (VEGF) in various patient populations. This study examined whether psychosocial functioning in patients with head and neck squamous cell carcinoma (HNSCC) is associated with tumor VEGF expression, a protein that stimulates angiogenesis and is associated with poor prognosis., Methods: Forty-two newly diagnosed patients completed assessments of psychosocial functioning (ie, depressive symptoms, perceived stress, anxiety, social support) before surgery. Tumor samples were obtained for VEGF analysis and human papillomavirus (HPV)-typing., Results: Poorer psychosocial functioning was associated with greater VEGF expression controlling for disease stage (odds ratio [OR], 4.55; 95% confidence interval [CI], 1.72-12.0; p < .01). When examined by HPV status, the association between psychosocial functioning and VEGF remained significant among patients who were HPV negative (OR, 5.50; 95% CI, 1.68-17.3; p < .01), but not among patients who were HPV positive., Conclusion: These findings inform our understanding of the biobehavioral pathways that may contribute to poor outcomes in non-HPV-associated HNSCCs., (Copyright © 2013 Wiley Periodicals, Inc.)

Carcinoma of an unknown primary (CUP) encompasses a heterogeneous group of tumors for which no primary site can be detected following a thorough history, physical examination, and noninvasive and invasive testing. CUP presenting with metastasis to the neck (metastatic cervical carcinoma from an unknown primary [MCCUP]) has been an enigma since von Volkmann first described it in 1882 as a cancer arising in a branchial cleft cyst. Genetic studies have shed some light on this unusual entity. In most cases, clinical features, imaging studies, and a meticulous assessment of the upper aerodigestive tract should assist in identifying the source of disease. Molecular testing of cytologic specimens for Epstein-Barr virus and human papillomavirus (HPV) can facilitate identification of the primary site in the nasopharynx and oropharynx. At least 25% of MCCUPs are directly attributable to HPV-related malignancies, and this number can be expected to increase. Minimally invasive transoral mucosal sampling can identify an otherwise clinically and radiologically occult cancer. We performed a literature review with the objective of discussing the history, epidemiology, clinical presentation, diagnostic workup, and management of MCCUP.

Background: In head and neck cancer patients prior to treatment, dysphagia noted by patients is more common than aspiration on formal swallow studies. The authors hypothesized that patient-reported dysphagia impacts multiple domains of quality of life (QOL) and predicts disease recurrence and disease-related death., Methods: The Swal-QOL, a dysphagia-specific, swallowing-related, QOL measure, and the EuroQOL-5D-3L were administered to 159 patients before treatment with curative intent in this prospective cohort study. Logistic regression analysis evaluated associations among clinical and subjective measures. Multivariable competing risk regression tested the impact of clinical, tumor, and patient-reported measures on survival., Results: Baseline dysphagia, pain, and diminished patient-reported health state were found to be closely associated with weight loss before treatment and advanced T classification. However, only 58% of patients (23 of 40 patients) reporting dysphagia experienced > 5% weight loss. Dysphagia was found to be associated with pain and/or diminished patient-reported health state, independent of weight loss. Female patients were more likely to report pain and dysphagia, whereas male patients reported dysphagia alone. Dysphagia was found to be predictive of disease recurrence and disease-related death, adjusting for T and N classifications, ECOG performance status, smoking status, and weight loss, and accounting for competing risks of death (recurrence-free survival: hazards ratio, 3.8 [95% confidence interval, 1.7-8.4; P = .001] and disease-related death: hazards ratio, 4.2 [95% confidence interval, 1.04-5; P = .004])., Conclusions: Baseline dysphagia affects multiple domains of QOL and general health perceptions in patients with head and neck cancer prior to treatment. A dysphagia measure captures the effort of maintaining nutrition, and identifies patients predisposed to disease recurrence and disease-related death., (© 2013 American Cancer Society.)

Purpose: Multimodality treatment of squamous cell carcinoma of the head and neck (SCCHN) often involves radiotherapy and cisplatin-based therapy. Elevated activity of DNA repair mechanisms, such as the nucleotide excision repair (NER) pathway, of which ERCC1 is a rate-limiting element, are associated with cisplatin and possibly RT resistance. We have determined excision repair cross-complementing group 1 (ERCC1) expression in human papillomavirus (HPV)-negative SCCHN treated with surgery [± adjuvant radiotherapy/chemoradiation (CRT)]., Experimental Design: We assessed ERCC1 protein expression in archival tumors using immunofluorescence staining and automatic quantitative analysis (AQUA) with three antibodies to ERCC1 (8F1, FL297, and HPA029773). Analysis with Classification and Regression Tree (CART) methods ascertained the cutoff points between high/low ERCC1 expression. Multivariable analysis adjusted for age, T, and N stage. Kaplan-Meier curves determined median survival. ERCC1 expression at initial tumor presentation and in recurrent disease were compared. Performance characteristics of antibodies were assessed., Results: ERCC1 low/high groups were defined on the basis of AQUA analysis with 8F1/2009, FL297, and HPA029773. Among patients treated with surgery plus adjuvant radiotherapy/CRT, longer median survival was observed in ERCC1-low versus ERCC1-high tumors (64 vs. 29 months; P = 0.02; HPA029773). Data obtained with HPA029773 indicated no survival difference among patients treated only with surgery. Recurrent cancers had lower ERCC1 AQUA scores than tumors from initial presentation. Extensive characterization indicated optimal specificity and performance by the HPA029773 antibody., Conclusions: Using AQUA, with the specific ERCC1 antibody HPA029773, we found a statistical difference in survival among high/low-ERCC1 tumors from patients treated with surgery and adjuvant radiotherapy., (©2013 AACR.)

Unlabelled: (18)F-CP-18, or (18S,21S,24S,27S,30S)-27-(2-carboxyethyl)-21-(carboxymethyl)-30-((2S,3R,4R,5R,6S)-6-((2-(4-(3-F18-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)-24-isopropyl-18-methyl-17,20,23,26,29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28-pentaazadotriacontane-1,32-dioic acid, is being evaluated as a tissue apoptosis marker for PET imaging. The purpose of this study was to determine the biodistribution and estimate the normal-organ radiation-absorbed doses and effective dose from (18)F-CP-18., Methods: Successive whole-body PET/CT scans were obtained at approximately 7, 45, 90, 130, and 170 min after intravenous injection of (18)F-CP-18 in 7 healthy human volunteers. Blood samples and urine were collected between the PET/CT scans, and the biostability of (18)F-CP-18 was assessed using high-performance liquid chromatography. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on the biodistribution of the tracer., Results: (18)F-CP-18 was 54% intact in human blood at 135 min after injection. The tracer cleared rapidly from the blood pool with a half-life of approximately 30 min. Relatively high (18)F-CP-18 uptake was observed in the kidneys and bladder, with diffuse uptake in the liver and heart. The mean standardized uptake values (SUVs) in the bladder, kidneys, heart, and liver at around 50 min after injection were approximately 65, 6, 1.5, and 1.5, respectively. The calculated effective dose was 38 ± 4 μSv/MBq, with the urinary bladder wall having the highest absorbed dose at 536 ± 61 μGy/MBq using a 4.8-h bladder-voiding interval for the male phantom. For a 1-h voiding interval, these doses were reduced to 15 ± 2 μSv/MBq and 142 ± 15 μGy/MBq, respectively. For a typical injected activity of 555 MBq, the effective dose would be 21.1 ± 2.2 mSv for the 4.8-h interval, reduced to 8.3 ± 1.1 mSv for the 1-h interval., Conclusion: (18)F-CP-18 cleared rapidly through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both the effective dose and the bladder dose can be reduced by frequent voiding. From the radiation dosimetry perspective, the apoptosis imaging agent (18)F-CP-18 is suitable for human use.

Purpose: This is a retrospective analysis of the impact of moderate dysplasia at the resection margin for early stage cancer of the oral tongue., Materials and Methods: Patients with T1-2N0 oral tongue cancer treated with surgery alone at Fox Chase Cancer Center (FCCC) from 1990 to 2010 were reviewed. Tumor and margin characteristics were abstracted from the pathology report. Overall survival (OS), disease-free survival (DFS) and local control (LC) were calculated using the Kaplan Meier method. Predictors of LC, OS and DFS were analyzed., Results: 126 Patients met the inclusion criteria. Dysplasia was present at the final margin in 36% of the cases (severe: 9%, moderate: 15%, mild: 12%). Median follow-up was 52 months. 3 and 5-year actuarial LC for the entire cohort was 77% and 73%, respectively. Actuarial 5-year LC and DFS were significantly worse for patients with moderate or severe dysplasia at the margin vs. none or mild dysplasia at the margin (49% vs 82%, p=0.005 and 49% vs 80%, p=0.008, respectively); 3-year comparisons were not significant. When analyzed separately, the detrimental local effect of moderate dysplasia at the margin persisted (p=0.02) and the effect of severe dysplasia at the margin was approaching significance (p=0.1). Mild dysplasia at the margin did not significantly impair LC or DFS. Multivariate analysis demonstrated worse LC (HR: 2.99, p=0.006) and DFS (HR: 2.84, p=0.008) associated with severe or moderate dysplasia at the margin., Conclusions: Both severe and moderate dysplasia at the margin appear to be correlated with inferior LC and DFS. Additional therapy may be justified, despite added morbidity., (Copyright © 2013. Published by Elsevier Ltd.)

Background: The impact of extranodal extension (ENE) of metastatic papillary thyroid carcinoma (PTC) on short- and long-term clinical outcomes, including biochemical testing, has not been reported., Methods: This single-institution National Cancer Institute-designated Comprehensive Cancer Center cohort study included patients with macroscopic metastases and excluded patients with gross residual disease after surgery, distant disease, or poorly differentiated papillary carcinoma. A suppressed or stimulated thyroglobulin (Tg) < 1 ng/mL, without suspicious imaging or anti-thyroglobulin antibodies, after radioactive iodine (RAI) treatment was termed an excellent or "complete biochemical response" (CR)., Results: Of 89 subjects included, 60 previously untreated patients underwent total thyroidectomy and therapeutic neck dissection; 29 additional patients underwent a neck dissection for persistence or recurrence after prior surgery and RAI administration. ENE, identified in 29 patients (33%), was associated with T4 classification (p = 0.02) and involvement of a greater number of nodes (median 11 vs. 5, p = 0.03). ENE was associated with a 20% increased risk of nodal persistence necessitating additional surgery (p = 0.02). In a multivariable analysis, ENE, T4 classification, and recurrence/persistence proved to be independent predictors of systemic disease progression (ENE: hazard ratio [HR] 4.3 [95% confidence interval (CI) 1.2-15], p = 0.02; T4 classification: HR 4.2 [CI 1.3-14], p = 0.01; recurrent/persistent status: HR 3.6 [CI 1.1-12], p = 0.035). Nodal or systemic disease progression was rare after a biochemical CR; in contrast, in previously untreated patients, stimulated Tg levels (sTg) > 50 ng/mL prior to initial RAI administration, heralded the progression of nodal disease, and also predicted the eventual development of systemic disease (p = 0.0001). Of those with a sTg > 50 ng/mL, over 70% underwent surgery for nodal persistence within five years. The presence of ENE diminished the odds of a biochemical CR (odds ratio 3.5% [CI 1.3-10], p = 0.02), and increased the probability that the sTg levels after surgery will exceed 50 ng/mL (odds ratio 5 [CI 1.2-21], p = 0.03). Following surgery for tumor persistence, 25% of those with ENE were rendered biochemically free of disease., Conclusions: ENE diminishes the probability of a biochemical CR after treatment for regional metastatic PTC, and increases the probability of tumor persistence after initial resection, likely from abundant metastasis. ENE and nodal persistence independently predict eventual systemic disease progression.