Head and Neck 2020-12-19

Benign connective and soft‐tissue neoplasms of the oral and maxillofacial region: A cross‐sectional study of 1066 histopathological specimens

Adriana Aparecida Silva da Costa, Thalita Soares Tavares, Patrícia Carlos Caldeira, Natália Santos Barcelos, Maria Cássia Ferreira Aguiar

Publication date 19-12-2020


Abstract Background Benign connective and soft‐tissue neoplasms (CSTNs) are unusual in the head and neck region. The aim of the present study was to evaluate the demographic and clinicopathological features of these neoplasms.
MethodsA cross‐sectional study was conducted of cases diagnosed as benign CSTNs, with data collected from biopsy records. The chi‐square test was used. A p‐value <0.05 was considered indicative of statistical significance.
Results Among the 38 119 specimens, 1066 (2.79%) were benign CSTNs: 369 fibroblastic/myofibroblastic, 250 adipocytic, 179 vascular, 130 neural, 94 osseous/cartilaginous, 19 muscular, and two fibrohistiocytic. Most patients were female (62.8%) and white‐skinned (45.8%). Mean age was 42 years. The tongue (25.2%) was the most affected site for extraosseous neoplasms.
Conclusion This study had the largest sample of benign oral and maxillofacial CSTNs. Although these tumors have similar clinical features, the characterization and differentiation detailed here may help clinicians with regards to the correct diagnosis.

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Increased rate of recurrence and high rate of salvage in patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma with adverse features treated with primary surgery without recommended adjuvant therapy

"Ryan M. Carey, David Shimunov, Gregory S. Weinstein, Steven B. Cannady, John N. Lukens, Alexander Lin, Samuel Swisher‐McClure, Joshua M. Bauml, Charu Aggarwal, Roger B. Cohen, Jason G. Newman, Ara A. Chalian, Christopher H. Rassekh, Devraj Basu, Bert W. OMalley, Karthik Rajasekaran, Robert M. Brody"

Publication date 16-12-2020


Abstract Background Some patients with human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline‐recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS).
Methods Three‐hundred and sixty‐four patients with treatment‐naïve, HPV‐associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared.
Results The 3‐year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P < .001). Despite increased LRF, avoiding PORT was not associated with increased 3‐year distant metastasis rates (8% vs 4%, P = .56) or worse 3‐year survival (95% vs 98%, P = .34). Recurrences in the surgery alone cohort varied between local and regional sites and were often successfully salvaged.
Conclusions Patients with HPV‐associated OPSCC who do not receive indicated PORT have an increased risk of LRF but similar survival due to high salvage rates.

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Importance of dose in palliative treatment for incurable head and neck cancer with radiotherapy

María J. García‐Anaya, Rafael Ordoñez, María D. Toledo, Raquel C. Correa, Ana Otero, Alicia Román, Isabel García‐Ríos, José A. Medina, Jaime Gómez‐Millán

Publication date 15-12-2020


Abstract Purpose To identify predictors of palliation for head and neck cancer treated with the “Hypo Trial” hypofractionated radiation therapy regimen in a clinical setting.
Design/Method We retrospectively assessed 106 consecutive patients with incurable cancer, treated between January 2008 and December 2018. Regimen used was 30‐36Gy in 5‐6 biweekly fractions of 6Gy.
Results The prescription dose was 30Gy in 57 (53.8%) patients and 36Gy in 49 (46.2%) patients. 89.6% patients completed the prescribed treatment. With a median follow‐up of 6.92 months, 79.2% of the patients experienced clinical palliation. Palliation was correlated with the radiation therapy dose (P = 0.05). Median overall and progression‐free survival (OS, PFS) were 7 and 4.63 months, respectively. Achieving palliation was associated to OS (P = 0.01).
Conclusions This short palliative hypofractionated scheme resulted in a high rate of palliation, with excellent compliance and acceptable toxicity. Our results show that radiation dose is a predictive factor for palliation.

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Definitive intensity‐modulated radiotherapy or surgery for early oral cavity squamous cell carcinoma: Propensity‐score‐matched, nationwide, population‐based cohort study

Wen‐Chi Liu, Hsueh‐Erh Liu, Yi‐Wei Kao, Lei Qin, Kuan‐Chou Lin, Chih‐Yuan Fang, Lo‐Lin Tsai, Ben‐Chang Shia, Szu‐Yuan Wu

Publication date 12-12-2020


Abstract Background No evidence is currently available to estimate the outcomes of intensity‐modulated radiation therapy (IMRT) and surgery for patients with early oral cavity squamous cell carcinoma (E‐OCSCC).
Methods We recruited patients from the Taiwan Cancer Registry Database who had received a diagnosis of E‐OCSCC. Propensity score matching was performed, and Cox proportional hazards model was used to analyze all‐cause mortality.
Results In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) (95% confidence interval CI) for surgery compared with definitive IMRT, T2N0M0 compared with T1N0M0, and male patients compared with female patients were 0.303 (0.245, 0.375), 1.340 (1.077, 1.668), and 2.012 (1.432, 2.826), respectively. The aHRs (95% CIs) for age 61 to 70, 71 to 80, and ≧81 years compared with <40 years were 2.984 (1.43, 4.225), 3.353 (2.578, 4.112), and 4.277 (4.104, 5.679), respectively.
Conclusions For patients with E‐OCSCC, surgery may be considered the first option rather than definitive IMRT.

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Why are there different conclusions about thyroid cancer mortality?

Louise Davies

Publication date 12-12-2020


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In‐depth analysis of thyroid cancer mortality

Brandon LaBarge, Vonn Walter, Darrin V. Bann, David Goldenberg

Publication date 12-12-2020


Abstract Background There are reports of an increasing thyroid cancer mortality rate. This study aimed to analyze the latest trends in this rate over time and compare findings from different cancer registries.
Methods Thyroid cancer incidence‐based mortality (IBM) rates were obtained from the Surveillance, Epidemiology, and End Results (SEER) program, including SEER‐9, SEER‐13, and SEER‐18. The National Center for Health Statistics (NCHS) thyroid cancer mortality rate was acquired for comparison. Statistical analysis was performed using the Join Point software.
ResultsNCHS data revealed an overall annual percent change (APC) over 1987 to 2017 of 0.61 (P < .01), and the value was nearly four times greater for males compared to females. The overall IBM APC values for SEER‐9, SEER‐13, and SEER‐18 were also positive and statistically significant (P < .01).
Conclusions The increased thyroid cancer mortality rate observed in previous studies continues to be statistically significant based on updated NCHS and SEER IBM data.

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"Jatin Shahs Head and Neck Surgery and Oncology, 5th edition.Jatin Shah, Sneha Patel, Bhuvanesh Singh, Richard Wong Elsevier, New York, NY, 2020, 896 pp, $399.99"

Christopher M. K. L. Yao

Publication date 11-12-2020


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Proposal of a TNM classification–based staging system for esthesioneuroblastoma: More precise prediction of prognosis

Meng Sun, Kai Wang, Yuan Qu, Jianghu Zhang, Shiping Zhang, Xuesong Chen, Jingbo Wang, Runye Wu, Ye Zhang, Junlin Yi, Jianping Xiao, Guozhen Xu, Xiaodong Huang, Jingwei Luo

Publication date 10-12-2020


Abstract Background Esthesioneuroblastoma (ENB) is a rare malignant neoplasm. Currently, no consistent and universal staging system for ENB exists. The aim of this study is to propose a TNM‐based classification.
Subjects and methods Hundred and forty‐two patients from our institution, with ENB pathologically confirmed between July 1978 and December 2018, were reviewed. All patients were restaged according to the Kadish stage, Morita stage and American Joint Committee on Cancer (AJCC) T classification from clinical and radiological data. Multivariate Cox proportional hazard regression analyses were performed to determine the impact of various factors. The goodness‐of‐fit and predictive accuracy of the different staging systems were calculated using R software.
Results The median follow‐up time was 57 months (range: 4‐229 months). According to the Kadish system, the 5‐year overall survival (OS) for patients with stage A, B and C was 100%, 83.6% and 64.2%, respectively (P = .055). With respect to the Morita classification, 5‐year OS for stages A, B, C and D was 100%, 83.6%, 70.7% and 50.0%, respectively (P = .004). Analysis based on the proposed staging model demonstrated 5‐year OS for stage I, II, III and IV disease was 100%, 88.9%, 75.9% and 49.0%, respectively (P < .001). In separate multivariate Cox regression models, only the novel staging system exhibited independent effects on OS (P = .004); the Akaike information criterion and Harrells concordance index were also superior to those calculated for the Kadish or Morita systems.
Conclusions The proposed TNM‐based staging system offers an improved prognostic assessment for patients with ENB. Further verification and refinement from additional dataset application is required.

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Variations in the association of grade with survival across the head and neck cancer landscape

Eric M. Anderson, Michael Luu, Bonnie L. Balzer, Kevin S. Scher, Alain C. Mita, Diana J. Lu, Stephen L. Shiao, Jon Mallen‐St. Clair, Allen S. Ho, Zachary S. Zumsteg

Publication date 10-12-2020


Abstract Background Although pathologic tumor grade is a well‐established prognostic risk factor that impacts staging and treatment decisions across multiple cancer types, its role in head and neck squamous cell carcinoma (HNSCC) is less certain.
MethodsHNSCC patients diagnosed from 2010 to 2015 and undergoing primary surgery in the National Cancer Data Base were identified. Propensity score matching and multivariable Cox regression were performed.
Results Among 27 041 HNSCC patients, 13 941 had oral cavity cancers (OCC). Intermediate‐grade (hazard ratio HR 1.16, 95% CI 1.07‐1.26, P < .001) and high‐grade (HR 1.38, 95% CI 1.26‐1.52, P < .001) tumors had worse survival than low‐grade tumors. This magnitude was comparable to other well‐established prognostic factors, including margin positivity, extranodal extension, and lymphovascular invasion. By contrast, there was no association between grade and survival in larynx/hypopharynx or HPV(−) oropharynx cancer.
Conclusions The prognostic impact of pathologic grade is highly variable across head and neck subsites and is the strongest among OCC patients.

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Pretreatment serum vitamin level predicts severity of radiation‐induced oral mucositis in patients with nasopharyngeal carcinoma

Gaili Chen, Huangang Jiang, Dazhen Jiang, Qiuji Wu, Zheng Li, Xinying Hua, Xiaoyan Hu, Hongli Zhao, Xiaoyong Wang, Haijun Yu, Conghua Xie, Yahua Zhong

Publication date 10-12-2020


Abstract Background Radiation‐induced mucositis (RIOM) is a common radiotherapy toxicity. We aimed to evaluate the relationship of serum vitamin status with RIOM among nasopharyngeal carcinoma (NPC) patients who underwent radiotherapy.
MethodsNPC patients who underwent concurrent chemoradiotherapy with available pretreatment serum vitamin values were included. Serum vitamin levels and clinical characteristics were collected. Logistic regression analysis and receiver operating characteristic curves were conducted to explore the potential risk factors and corresponding cut‐off values for severe RIOM.
Results Two hundred and forty NPC patients were enrolled. Multivariate regression analysis showed that mean oral cavity radiation dose (OR = 2.042; 95% CI = 1.585‐2.630; P < .001), weekly concurrent chemotherapy (OR = 3.898; 95% CI = 1.085‐14.004; P = .037), lower serum level of vitamin B2 (OR = 0.951; 95% CI = 0.924‐0.978; P < .001), and vitamin C (OR = 0.455; 95% CI = 0.346‐0.598; P < .001) were independent risk factors for developing severe RIOM.
Conclusions The findings of this study revealed that serum vitamin status could predict the severity of RIOM, providing a theoretical basis for the prevention and treatment of RIOM.

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In reply to Kumar et al, Is TORS for oropharyngeal squamous cell carcinoma being done more often than actually indicated?

James E. Bates, Robert J. Amdur

Publication date 09-12-2020


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Is Transoral Robotic Surgery (TORS) for oropharyngeal squamous cell carcinoma being done more often than actually indicated?

Anuj Kumar, Sarbani Ghosh Laskar, Shivakumar Thiagarajan

Publication date 09-12-2020


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Reply to the letter to the Editior by Cantu

Xiaoli Mu, Xingchen Peng

Publication date 09-12-2020


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Letter to Editor

Giulio Cantù

Publication date 09-12-2020


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Metastatic thyroid carcinoma to the parapharyngeal and retropharyngeal spaces: Systematic review with seven newly reported cases describing an uncommon presentation of a common disease

Mykayla L. Sandler, Monica H. Xing, Juliana C. Levy, Raymond L. Chai, Azita S. Khorsandi, Camilo Gonzalez‐Velazquez, Mark L. Urken

Publication date 09-12-2020


Abstract Background Metastatic thyroid carcinoma to retropharyngeal and parapharyngeal (RP/PP) lymph nodes is rare. Literature suggests previous lateral neck dissection (LND) may alter patterns of lymphatic drainage in the neck, predisposing to these less common sites of spread.
MethodsPRISMA‐guided systematic search for all published cases detailing RP/PP metastases of well‐differentiated thyroid carcinoma from 1970 to 2019.
Results Seventy articles were identified and 44 were included, along with seven cases treated at our institution, totaling 239 cases. Cases represented both retropharyngeal (60.7%) and parapharyngeal (39.3%) metastases identified in the initial (27.6%) and recurrent (72.4%) setting.
ConclusionRP/PP metastases generally present in the recurrent setting. RP/PP metastases often represent high‐risk disease, and surgical treatment is recommended.

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Aspirin use predicts prolonged survival in patients with oropharyngeal cancer: Nationwide Veterans Affairs database study

Christine M. Clark, Annemarie C. Newark, Ali Fokar, Jessica H. Maxwell

Publication date 08-12-2020


Abstract Background Single‐institution studies suggest that aspirin reduces the risk of death in head and neck cancer. The aim of this study was to investigate the effect of aspirin use on overall survival (OS) in veterans with oropharyngeal cancer (OPC).
MethodsA total of 23 083 veterans with OPC were identified between 2005 and 2018 from the Veterans Health Administration Corporate Data Warehouse. Records were queried for clinical‐demographic data, aspirin prescriptions, and outcomes. Three‐year OS was estimated. A Cox model was used to estimate hazard ratios (HR) for aspirin use.
Results Among the 23 083 identified veterans, 17 206 veterans met inclusion criteria. 21.8% used aspirin. Three‐year OS was prolonged for aspirin users (66%) compared to nonaspirin users (54%; P < .001). Adjusted HR for death for nonaspirin users was 1.75 (95% confidence interval (CI) 1.60‐1.91). The average treatment effect of aspirin on survival using inverse probability weighting was 10% (95% CI 0.08‐0.11).
Conclusion Aspirin use following OPC diagnosis was independently associated with improved 3‐year OS among veterans nationwide.

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Endoscopic transoral nasopharyngectomy

Roberto M. Soriano, Rima S. Rindler, Samuel N. Helman, Gustavo Pradilla, C. Arturo Solares

Publication date 08-12-2020


Abstract BackgroundA minimal access technique for the management of nasopharyngeal tumors extending below the palatal plane and laterally beyond the pterygoid musculature is yet to be developed. In this study we demonstrate the feasibility of endoscopic transoral nasopharyngectomy (ETON) for resection of large nasopharyngeal lesions as a natural orifice alternative to traditional approaches.
MethodsETON was completed in three latex‐injected specimens. Surgical freedom (SF) and angles of attack (AoA) were calculated along the internal carotid artery (ICA).
Results An endoscopic transoral approach was successfully used to identify the parapharyngeal ICA and subsequently perform a complete nasopharyngeal resection. SF and AoA (sagittal) were found to be the greatest at the anterior genu of the ICA.
ConclusionsETON is feasible. It provides wide exposure of the skull base and proximal control of the ICA. It may be indicated for the management of nasopharyngeal tumors with inferolateral extension, involving the ICA.

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Association between external and internal lymphedema and chronic dysphagia following head and neck cancer treatment

Claire Jeans, Elizabeth C. Ward, Bena Brown, Anne E. Vertigan, Amanda E. Pigott, Jodie L. Nixon, Chris Wratten, May Boggess

Publication date 08-12-2020


Abstract Background To examine the relationship between chronic external and internal head and neck lymphedema (HNL) and swallowing function in patients following head and neck cancer (HNC) treatment.
Methods Seventy‐nine participants, 1‐3 years post treatment were assessed for external HNL using the MD Anderson Cancer Centre Lymphedema Rating Scale, and internal HNL using Pattersons Radiotherapy Edema Rating Scale. Swallowing was assessed via instrumental, clinical and patient‐reported outcome measures.
ResultsHNL presented as internal only (68%), combined external/internal (29%), and external only (1%). Laryngeal penetration/aspiration was confirmed in 20%. Stepwise multivariable regression models, that accounted for primary site, revealed that a higher severity of external HNL and internal HNL was associated with more severe penetration/aspiration (P < .004 and P = .006, respectively), diet modification (P < .001 both), and poorer patient‐reported outcomes (P = .037 and P = .014, respectively).
Conclusion Increased swallowing issues can be expected in patients presenting with more severe external HNL and/or internal HNL following HNC treatment.

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Image‐guided robotic radiosurgery for glomus jugulare tumors—Multicenter experience and review of the literature

Felix Ehret, Markus Kufeld, Christoph Fürweger, Alfred Haidenberger, Christian Schichor, Ralph Lehrke, Susanne Fichte, Carolin Senger, Martin Bleif, Daniel Rueß, Maximilian Ruge, Jörg‐Christian Tonn, Alexander Muacevic, John‐Martin Hempel

Publication date 08-12-2020


Abstract Background Glomus jugulare tumors (GJTs) are challenging to treat due to their vascularization and location. This analysis evaluates the effectiveness and safety of image‐guided robotic radiosurgery (RRS) for GJTs in a multicenter study and reviews the existing radiosurgical literature.
Methods We analyzed outcome data from 101 patients to evaluate local control (LC), changes in pretreatment deficits, and toxicity. Moreover, radiosurgical studies for GJTs have been reviewed.
Results After a median follow‐up of 35 months, the overall LC was 99%. Eighty‐eight patients were treated with a single dose, 13 received up to 5 fractions. The median tumor volume was 5.6 cc; the median treatment dose for single‐session treatments is 16 Gy, and for multisession treatments is 21 Gy. Fifty‐six percentage of patients experienced symptom improvement or recovered entirely.
ConclusionsRRS is an effective primary and secondary treatment option for GJTs. The available literature suggests that radiosurgery is a treatment option for most GJTs.

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Impact of greater auricular nerve sacrifice during parotidectomy on quality of life

Flora Yan, Vincent M. Desiato, Shaun A. Nguyen, Eric J. Lentsch

Publication date 08-12-2020


Abstract Background Greater auricular nerve (GAN) sacrifice can alter sensation; however, the impact on quality of life (QoL) is unclear.
Objective The aim of this study was to evaluate patients QoL following GAN sacrifice versus preservation.
Methods Patients who underwent parotidectomy from 2010 to 2019 at a single institution completed two QoL surveys. Results between GAN‐sacrificed versus preserved cohorts and short (≤ 1 year) versus long‐term (> 1 year) follow‐up were compared.
Results Of 404 patients, 67 with known GAN status completed the surveys. GAN‐sacrificed patients more frequently experienced sensation loss of the lobule and concha than GAN‐preserved patients (P = .042 and P = .041, respectively). Interference with daily activities or amount of regained sensation was not different based on GAN status. Short‐term follow‐up patients had a higher number of symptoms and affected areas than long‐term follow‐up patients (P = .014 and P = .002, respectively).
ConclusionGAN sacrifice leads to sensation loss of the lobule and concha; however, it does not significantly impair QoL.

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Evaluating compliance with process‐related quality metrics and survival in oral cavity squamous cell carcinoma: Multi‐institutional oral cavity collaboration study

Sara W. Liu, Neil M. Woody, Wei Wei, Swathi Appachi, Kevin J. Contrera, Jillian C. Tsai, Ahmed I. Ghanem, Brian Matia, Nikhil P. Joshi, Jessica L. Geiger, Jamie A. Ku, Brian B. Burkey, Joseph Scharpf, Brandon L. Prendes, Jimmy J. Caudell, Neal E. Dunlap, David J. Adelstein, Sandro Porceddu, Howard Liu, Farzan Siddiqui, Nancy Y. Lee, Shlomo Koyfman, Eric D. Lamarre

Publication date 08-12-2020


Abstract Background Process‐related measures have been proposed as quality metrics in head and neck cancer care. A recent single‐institution study identified four key metrics associated with increased survival. This study sought to validate the association of these quality metrics with survival in a multi‐institutional cohort.
Methods Multicenter retrospective study of patients with oral cavity squamous cell (1/2005‐1/2015). Baseline patient and disease characteristics and compliance with quality metrics was evaluated. Association between compliance with quality metrics with overall survival (OS), disease‐free survival (DFS), and disease‐specific survival (DSS) was evaluated using Cox proportional hazards models.
Results Failure to comply with two or more of the quality metrics was associated with worse OS, DFS, and DSS. Adherence to all or all but one of the quality metrics was found to be associated with improved survival.
Conclusions Process‐related quality metrics are associated with increased survival in patients with oral cavity squamous cell carcinoma in a multi‐institutional cohort.

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Population‐based analysis on the effect of nodal and distant metastases in sinonasal adenocarcinoma

Cynthia M. Chweya, Christopher M. Low, Jamie J. Van Gompel, Kathryn M. Van Abel, Janalee K. Stokken, Garret Choby

Publication date 08-12-2020


Abstract Background Minimal information has been reported on the effect of distant and nodal metastases at the time of diagnosis on survival in patients with sinonasal adenocarcinoma (SNAC).
Methods The Surveillance, Epidemiology, and End Results database was utilized to compare overall survival (OS) and disease‐specific survival (DSS).
Results Of the 325 patients with SNAC identified, 5‐year and 10‐year OS for all included patients was 64% and 58%, respectively. On multivariate analysis, the presence of distant metastases (P < .0001), maxillary and frontal sinus primary tumors (P = .0042, P = .0006), and increasing age (P = .007) were risk factors for worsened DSS. The presence of regional spread to multiple cervical nodal basins (OS RR 3.26, P = .002; DSS RR 2.51, P = .013) and a single nodal basin (DSS RR 2.19, P = .046) was associated with worsened survival compared to no regional spread.
Conclusion Survival in SNAC was significantly worsened with increasing age, tumor site of origin, and distant metastatic disease.

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Early fiberoptic endoscopic evaluation of swallow in transoral robotic surgery: Description of swallow function and recovery in the acute postoperative period for oropharyngeal squamous cell carcinoma

Emma K. Charters, Hans Bogaardt, Amy L. Freeman‐Sanderson, Kirrie J. Ballard, Sarah Davies, Justine Oates, Jonathan Clark

Publication date 08-12-2020


Abstract Background Transoral robotic surgery (TORS) is a minimally invasive approach for the treatment of oropharyngeal cancer. The effects on swallowing and speech need to be comprehensively evaluated to understand the associated morbidity.
MethodsA prospective cohort of 21 patients was recruited to undergo pre‐TORS and post‐TORS swallowing and communication assessment. Fiberoptic endoscopic evaluation of swallowing (FEES) was used in the first postoperative week.
Results Sixteen participants (76.2%) had penetration‐aspiration scores ≥3 or higher, seven (33.3%) aspirated on thin liquids, three (14.3%) did so silently. Prolonged recovery trajectory occurred for the majority of the cohort, particularly if TORS was followed by adjuvant radiotherapy. Swallowing and communication scores were significantly worse in base of tongue primary tumors and with advanced age.
Conclusion Early FEES demonstrates a significant decline in swallowing function, including increased secretion load, pharyngeal residue, laryngeal penetration, and aspiration. Silent aspiration occurred in 14% and thus highlights the necessity for instrumental assessment to ascertain aspiration risk.

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Bipedicled submental musculofascial “hammock” flap for salvage laryngectomy closure reinforcement

Richard E. Hayden, Brent A. Chang, David P. Mullin, Andrew K. Patel, Thomas H. Nagel, Brittany E. Howard, Michael L. Hinni, David G. Lott, Carrlene B. Donald

Publication date 08-12-2020


Abstract Background The aim of the study was to describe a novel technique for reinforcement of salvage laryngectomy closure using a bipedicled musculofascial submental flap.
MethodsA retrospective cohort study design identified patients who underwent salvage laryngectomy reinforcement with a bipedicled submental hammock flap between January 2008 and December 2016 were compared to salvage laryngectomy patients treated with primary closure of the neopharynx during the same time period. Pharyngocutaneous fistula rates were compared between groups.
Results Pharyngocutaneous fistula rate in the submental hammock group (2/31, 6.5%) was significantly lower compared to the primary closure group (14/45, 31%, P < .05).
Conclusion The bipedicled musculofascial submental hammock flap is a viable method for reinforcement of salvage laryngectomy defects. It has a favorable pharyngocutaneous fistula rate compared to primary closure alone and has unique advantages over conventional methods of reinforcement.

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Hybrid positron emission tomography imaging for initial staging of sinonasal tumors: Total lesion glycolysis as prognosticator of treatment response

Christian M. Meerwein, Alexander Maurer, Paul Stolzmann, Thomas M. Stadler, Michael B. Soyka, David Holzmann, Martin W. Hüllner

Publication date 08-12-2020


Abstract Background To assess hybrid positron emission tomography (PET) imaging in the initial staging and outcome prediction of sinonasal malignancies.
Methods Retrospective study on patients with sinonasal malignancies undergoing hybrid PET imaging for initial staging.
Results Complete remission (CR) was achieved in 45 of 65 patients (69.2%). Overall sensitivity for detection of primaries using 18F‐fluoro‐deoxy‐d‐glucose PET (FDG‐PET) was 95.4%, for lymph node metastases 100% and distant metastases (DM) 100%. On univariate analysis, PET parameter total lesion glycolysis (TLG) was associated with achieving CR after primary treatment (176.8 ± 157.2 vs 83.7 ± 110.8, P = .03). Multivariate logistic regression demonstrated that TLG adjusted for the T classification best predicted achievement of CR.
Conclusions Hybrid PET imaging yields an excellent sensitivity in detecting primary tumors, lymph node metastases and DM in sinonasal malignancies. TLG of the primary tumor is an independent prognostic factor for achieving CR after initial treatment.

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Human papillomavirus oropharynx carcinoma: Aggressive de‐escalation of adjuvant therapy

Eric J. Moore, Kathryn M. Van Abel, David M. Routman, Christine M. Lohse, Katharine A. R. Price, Michelle Neben‐Wittich, Ashish V. Chintakuntlawar, Daniel L. Price, Jan L. Kasperbauer, Joaquin J. Garcia, Michael L. Hinni, Samir H. Patel, Jeffrey R. Janus, Robert L. Foote, Dan J. Ma

Publication date 08-12-2020


Abstract Background Aggressive dose de‐escalated adjuvant radiation therapy (RT) in patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC).
Methods Patients with HPV(+)OPSCC on a phase II clinical trial of primary surgery and neck dissection followed by dose de‐escalated RT (N = 79) were compared with a cohort of patients who received standard adjuvant therapy (N = 115). Local recurrence‐free, regional recurrence‐free, distant metastases‐free survival, and progression‐free survival (PFS) were assessed.
Results Of 194 patients, 23 experienced progression at a median of 1.1 years following surgery (interquartile range IQR 0.7‐2.0; range 0.3‐5.4); 10 patients in the de‐escalated cohort and 13 patients in the standard cohort. The 3‐year PFS rate for the de‐escalated cohort was 87%, and in the standard cohort was 90% (hazard ratio HR 1.18, 95% confidence interval (CI) 0.50‐2.75).
Conclusion Patients with HPV(+)OPSCC who undergo surgical resection and neck dissection and meet criteria for adjuvant therapy can undergo aggressive dose de‐escalation of RT without increasing risk of progression locally, regionally or at distant sites.

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Rapid recurrence in head and neck cancer: Underappreciated problem with poor outcome

Douglas Y. Lee, Jesty Abraham, Eric Ross, John A. Ridge, Miriam N. Lango, Jeffrey C. Liu, Jessica R. Bauman, Vladimir Avkshtol, Thomas J. Galloway

Publication date 08-12-2020


Abstract 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).
MethodsCT simulation images in patients with HNC managed surgically with adjuvant therapy at a single center between 2010 and 2017 were retrospectively reviewed.
ResultsA 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.

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Prognostic nomogram for adenoid cystic carcinoma in different anatomic sites

Xiaoli Mu, Yan Li, Ling He, Hui Guan, Jingjing Wang, Zhigong Wei, Yan He, Zheran Liu, Ruidan Li, Xingchen Peng

Publication date 08-12-2020


Abstract Background Adenoid cystic carcinoma (ACC) is a relatively uncommon tumor. The existing prediction model is limited to the head and neck. We aim to construct a prognostic nomogram combined with the clinical features and treatment options of ACC to predict the disease‐specific survival (DSS) of patients diagnosed with ACC in different anatomic sites.
MethodsA novel predictive model was constructed using 1285 patients with ACC from the Surveillance, Epidemiology, and End Results (SEER) registry between 2010 and 2015. The performance of this model was externally validated using 118 patients with ACC in the West China Hospital, Sichuan University between 2010 and 2017.
Results The prognostic model demonstrated that age, primary site, lymph node metastasis, distant metastasis, radiotherapy and surgery were independent factors for DSS. The validation of the model using an external cohort proved its reliability.
Conclusion The developed novel predictive model is shown to provide accurate and efficient predictive information for patients with ACC for different anatomic sites.

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Decline in circulating viral and human tumor markers after resection of head and neck carcinoma

Erin M. Lopez, April Michelle Tanner, Eugenie Du, Samip N. Patel, Jared Weiss, Mark C. Weissler, Trevor Hackman, Gaorav P. Gupta, Jose Zevallos, Sandra Elmore, Renee Betancourt, Leigh Thorne, Siddharth Sheth, Margaret L. Gulley

Publication date 08-12-2020


Abstract BackgroundDNA sequencing panels can simultaneously quantify human and viral tumor markers in blood. We explored changes in levels of plasma tumor markers following surgical resection of head and neck carcinoma.
Methods In preresection and postresection plasmas, targeted DNA sequencing quantified variants in 28 human cancer genes and levels of oncogenic pathogens (human papillomavirus HPV, Epstein‐Barr virus EBV, Helicobacter pylori) from 21 patients with head and neck squamous cell carcinoma.
Results Preresection, 11 of 21 patients (52%) had detectable tumor markers in plasma, most commonly TP53 mutation or HPV genome. Several days postresection, levels fell to undetectable in 8 of 10 evaluable patients, while two high‐stage patients retained circulating tumor markers.
Conclusions Modern sequencing technology can simultaneously quantify human gene variants and oncogenic viral genomes in plasma. Falling levels of cancer‐specific markers upon resection can help identify viral and human markers to track at subsequent timepoints as a means to evaluate efficacy of interventions.

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Synergistic effects of combined treatment with ultrasound‐mediated cisplatin‐loaded microbubbles and atorvastatin on head and neck cancer

Ai‐Ho Liao, Wan‐Ting Lin, Hang‐Kang Chen, Cheng‐Ping Shih, Chih‐Hung Wang, Yueng‐Hsiang Chu

Publication date 08-12-2020


Abstract Background Previously, we used ultrasound (US)‐mediated cisplatin (CDDP)‐loaded microbubbles (CDDP‐MBs) to increase intratumoral CDDP level while decreasing systemic cytotoxicity. Statins have shown antitumorigenic properties. Our study investigated the effects of atorvastatin with CDDP‐MBs and US on head neck cancer.
Methods Cell viability analysis with CDDP‐MBs and atorvastatin combined with US in Fa Du cell line were tested. Cell proliferation and glutathione level were also evaluated.
Results Both CDDP and atorvastatin reduced cells viability. Coadministration of CDDP and atorvastatin resulted in synergistic inhibitory effect. After US sonication, cell viability with atorvastatin and CDDP was significantly reduced for CDDP combined with MBs (65.98% to 49.13%) and for CDDP‐MBs (86.17% to 50.15%). CDDP‐MBs combined with atorvastatin and US inhibited the proliferation of cells: 19.61% for CDDP‐MBs + atorvastatin + US, 36.28% for CDDP + atorvastatin, and 71.73% for atorvastatin alone. Also, CDDP‐MBs + atorvastatin + US induced apoptosis by decreasing cellular level of glutathione.
Conclusions Atorvastatin combined with MB‐conjugated CDDP exerts synergistic inhibitory effect on head neck cancer.

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Cost‐effectiveness of endoscopic endonasal vs transcranial approaches for olfactory groove meningioma

Terence S. Fu, Christopher M. K. L. Yao, Hedyeh Ziai, Eric Monteiro, Joao Paulo Almeida, Gelareh Zadeh, Fred Gentili, John R. Almeida

Publication date 08-12-2020


Abstract 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).
ConclusionEEA may be a cost‐effective alternative to transcranial approaches for selected OGM.

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Changes in treatment trends in the early glottic cancer population after the Affordable Care Act

Bharat Akhanda Panuganti, Emelia Stuart, Philip Weissbrod

Publication date 08-12-2020


Abstract Background The clinical impact of Medicaid expansion in otolaryngology is uncertain. Herein, we evaluate the impact of Medicaid expansion on treatment patterns (primary radiotherapy vs surgery) in the early glottic cancer population.
Methods Data regarding adults with Tis‐T2N0M0 glottic cancer that were treated with either surgery or radiotherapy between January 2010 and December 2016 were obtained from the Surveillance, Epidemiology, and End Results (SEER) cancer database. Changes in treatment trends and survival in the Medicaid expansion setting were discerned.
Results The proportion of patients undergoing radiotherapy decreased from 64.8% to 59% after the Patient Protection and Affordable Care Act (PPACA) was implemented. State Medicaid expansion status was associated with reduced odds of radiation therapy (odds ratio OR = 0.66). Patients were diagnosed more often with earlier stage disease (20.6% vs 17.0% T2 diagnoses) in the Medicaid expansion cohort.
Conclusion The implementation of the PPACA was associated with a significant increase in surgical therapy for and earlier diagnosis of glottic cancer.

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National trends in oropharyngeal cancer incidence and survival within the Veterans Affairs Health Care System

Jose P. Zevallos, Jennifer R. Kramer, Vlad C. Sandulache, Sean T. Massa, Christine M. Hartman, Angela L. Mazul, Benjamin M. Wahle, Sophie P. Gerndt, Erich M. Sturgis, Elizabeth Y. Chiao

Publication date 08-12-2020


Abstract Background Oropharyngeal squamous cell carcinoma (OPSCC) epidemiology has not been examined previously in the nationwide Veterans Affairs (VA) population.
Methods Joinpoint regression analysis was applied to OPSCC cases identified from VA administrative data from 2000 to 2012.
Results We identified 12 125 OPSCC cases (incidence: 12.2 of 100 000 persons). OPSCC incidence declined between 2000 and 2006 (annual percent change APC = −4.27, P < .05), then increased between 2006 and 2012 (APC = 7.02, P < .05). Significant incidence increases occurred among white (APC = 7.19, P < .05) and African American (APC = 4.87, P < .05) Veterans and across all age cohorts. The percentage of never‐smokers increased from 8% in 2000 to 15.7% in 2012 (P < .001), and 2‐year overall survival improved from 31.2% (95% confidence interval (CI) 30‐33.4) to 55.7% (95% CI 54.4‐57.1).
ConclusionsOPSCC incidence is increasing across all racial and age cohorts in the VA population. Smoking rates remain high among Veterans with OPSCC and gains in survival lag those reported in the general population.

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Prognostic potential of mid‐treatment nodal response in oropharyngeal squamous cell carcinoma

David J. Byun, Moses M. Tam, Adam S. Jacobson, Mark S. Persky, Theresa T. Tran, Babak Givi, Mark D. DeLacure, Zujun Li, Louis B. Harrison, Kenneth S. Hu

Publication date 08-12-2020


Abstract Background We examine the prognostic implications of mid‐course nodal response in oropharyngeal cancer (OPX) to radiation therapy.
Methods In 44 patients with node‐positive OPX undergoing concurrent chemoradiation, nodal volumes were measured on cone beam CTs from days 1, 10, 20, and 35. Nodal decrease (ND) was based on percent shrinkage from day 1.
Results At a median follow‐up of 17 months, the 2‐year disease‐free survival (DFS), locoregional control (LRC), distant metastasis‐free survival (DMFS), and overall survival (OS) were 87%, 92%, 89%, and 92%, respectively. Patients with ND ≥43% at D20 had improved LRC (100% vs 78.4%, P = .03) compared to D20 ND <43%. On multivariate analysis, D20 ≥43% was independently prognostic for LRC (HR 1.17, P = .05).
Conclusion Patients with low‐risk oropharynx cancer with ND of ≥43% by treatment day 20 had significantly improved LRC. The prognostic benefit of ND may assist in identifying candidates for treatment de‐escalation.

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Epidemiologic factors in patients with advanced head and neck cancer treated with radiation therapy

Michael T. Brennan, Nathaniel S. Treister, Thomas P. Sollecito, Brian L. Schmidt, Lauren L. Patton, Yi Yang, Alexander Lin, Linda S. Elting, James S. Hodges, Rajesh V. Lalla

Publication date 08-12-2020


Abstract Background Approximately 50% of patients with head and neck cancer (HNC) initially were seen with advanced disease. We aimed to evaluate the association of epidemiologic factors with advanced HNC at diagnosis.
Methods The Ora Rad multicenter prospective cohort study enrolled HNC patients receiving curative‐intent radiation therapy. Factors assessed for association with advanced HNC presentation at diagnosis included demographics, social and medical history, cancer characteristics, human papilloma virus (HPV) status, and dental disease measures.
Results We enrolled 572 participants; 77% male and mean (SD) age of 61.7 (11.2) years. Oropharyngeal squamous cell carcinomas (88% HPV‐related) were seen with smaller tumors, but more frequent nodal involvement. Private medical insurance and no Medicaid were associated with smaller tumors. A higher dental disease burden was associated with larger tumors.
Conclusions Insurance status, cancer type/location, and dental disease are associated with advanced HNC and may represent potentially modifiable factors or factors to be considered in the screening process of new lesions.

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A real‐world comparison of cisplatin vs cetuximab used concurrently with radiation in the treatment of locally advanced oropharyngeal carcinoma

Andrea S. Fung, Arfan Raheen Afzal, Robyn Banerjee, Brock Debenham, Desiree Hao

Publication date 08-12-2020


Abstract Background This population‐based retrospective study compares the efficacy of cisplatin (cis‐RT) vs cetuximab (cetux‐RT) with concurrent radiation as definitive treatment in patients with oropharyngeal carcinoma (OPC).
Methods Patients with OPC treated in Alberta with cis‐RT or cetux‐RT between 2006 and 2016 were evaluated. Median disease‐free survival (DFS) and overall survival (OS) were assessed using the Kaplan‐Meier method. Multivariable analysis (MVA) was completed with a Cox proportional hazards model.
Results Among 546 patients with OPC, 431 (78.9%) received cis‐RT and 115 (21.1%) cetux‐RT. Patients treated with cetux‐RT were more likely to develop a recurrence after treatment compared to cis‐RT (25% vs 15%, P = .01). On MVA, current smoking, human papillomavirus (HPV)‐negative status, higher Charlson comorbidity index (CCI), T‐stage, and cetux‐RT predicted for worse DFS and OS. Outcomes in older patients with a higher CCI still favored cis‐RT.
Conclusions Our data reaffirm results from randomized studies showing better survival outcomes with cis‐RT compared to cetux‐RT even among those who are >65 with CCI ≥3.

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Impact of age and comorbidity on survival among patients with oral cavity squamous cell carcinoma

Krupal B. Patel, Daniel Martin, Songzhu Zhao, Bhavna Kumar, Ricardo Carrau, Enver Ozer, Amit Agrawal, Stephen Kang, James W. Rocco, David Schuller, Theodoros Teknos, Guy Brock, Matthew Old

Publication date 08-12-2020


Abstract Objective To identify predictors of overall survival (OS) and to stratify patients according to significant prognostic variables.
MethodsA retrospective study of 274 consecutive patients with primary Oral Cavity Squamous Cell Carcinoma. Kaplan‐Meier, Cox proportional hazard models, and recursive partitioning analysis (RPA) were used for analysis of OS. These results were further validated using National Cancer Database cohort of 21 895 patients.
Results Median OS was 3.65 years. T‐classification and N‐classification, alcoholic beverages/week, age, and adjuvant treatment were significant predictors of OS. RPA identified high‐risk subpopulations: N0‐1 patients with CCI ≥ 4.5 and N2‐3 patients ordered by those not receiving adjuvant treatment, those with T3‐4 disease despite adjuvant therapy, and those having T1‐2 disease with adjuvant therapy.
Conclusions This study utilized significant prognostic indicators and RPA to highlight the importance of age, N‐classification, T‐classification, comorbidity, and adjuvant therapy in conjunction with American Joint Committee on Cancer staging to improve preoperative counseling.

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Transcervical endoscopic retropharyngeal lymph node (RPLN) dissection in nasopharyngeal carcinoma with RPLN recurrence

You‐Ping Liu, Shun‐Lan Wang, Xiong Zou, Rui You, Qi Yang, Meng‐Xia Zhang, Zhi‐Qiang Wang, Mei Lin, Yu‐Long Xie, Si‐Yuan Chen, Yan‐Feng Ouyang, Zi‐Kun Yu, Xue‐Kui Liu, Rui Sun, Yi‐Jun Hua, Pei‐Yu Huang, Hao Li, Ming‐Yuan Chen

Publication date 08-12-2020


Abstract Background Surgical access for retropharyngeal lymph node (RPLN) dissection is difficult. We aimed to examine the efficacy of transcervical endoscopic RPLN dissection (TSE‐RPLND) for recurrent RPLN in nasopharyngeal carcinoma (NPC).
Methods From April 2013 to February 2019, a total of 31 patients with NPC diagnosed with RPLN recurrence underwent TSE‐RPLND. The clinical characteristics, complications, and survival outcomes were retrospectively analyzed.
Results The mean duration of surgery, quantity of bleeding and postoperative hospitalization stay were 347.9 minutes, 107.7 mL, and 8.7 days, respectively. After a median follow‐up of 31.0 months, the 2‐year locoregional relapse‐free survival, distant metastasis‐free survival, progression‐free survival, and overall survival rates were 63.9%, 95.2%, 59.9%, and 83.3%, respectively. The long‐term incidences of swallowing problems, permanent nutrient tube, tongue atrophy, and shoulder problems were 6 (19.4%), 3 (9.7%), 3 (9.7%), and 3 (9.7%), respectively.
ConclusionsTSE‐RPLND is an effective method to treat RPLN recurrence in NPC, but nerve injury‐related complications should not be ignored.

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Mortality and cause of death in patients with tracheostomy: Longitudinal follow‐up study using a national sample cohort

Young Ju Jin, Seung Yoon Han, Bumjung Park, Il‐Seok Park, Jin‐Hwan Kim, Hyo Geun Choi

Publication date 08-12-2020


Abstract Background The purpose of this study was to evaluate the long‐term mortality and cause of death in patients with tracheostomy.
Methods Data from the Korean National Health Insurance Service‐Health Screening Cohort were collected from 2002 to 2013. A total of 2394 tracheostomy participants and 9536 control participants were included in this study. The crude and adjusted hazard ratios (HRs) for tracheostomy‐associated mortality were analyzed. Subgroup analysis according to age and cause of death was analyzed.
Results The tracheostomy group showed a significantly higher rate of death (69.1%) than the nontracheostomy group (13.3%). The adjusted HR for mortality was 13.5 in the tracheostomy group. The most common cause of death after tracheostomy was a circulatory disease, followed by neoplasm, respiratory disease, and trauma.
Conclusions Patients with tracheostomy had a significantly increased long‐term mortality rate compared with patients with nontracheostomy. The circulatory disease was the most common cause of death following tracheostomy.

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Prognostic value of immune‐related genes and immune cell infiltration analysis in the tumor microenvironment of head and neck squamous cell carcinoma

Zizhuo Wang, Huangbo Yuan, Jia Huang, Dianxing Hu, Xu Qin, Chaoyang Sun, Gang Chen, Beibei Wang

Publication date 08-12-2020


Abstract Background Head and neck squamous cell carcinoma (HNSCC) is one of the few malignant tumors that respond well to immunotherapy. We aimed to investigate the immune‐related genes and immune cell infiltration of HNSCC and construct a predictive model for its prognosis.
Methods We calculated the stromal/immune scores of patients with HNSCC from The Cancer Genome Atlas using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm and investigated the relationship between the scores and patients prognosis. Three machine learning algorithms (LASSO, Random Forest, and Rbsurv) were performed to screen key immune‐related genes and constructed a predictive model. The immune cell infiltrating was calculated by the Tumor Immune Estimation Resource algorithm.
Results The stromal and immune scores significantly correlated with prognosis. A 6‐gene signature was selected and displayed a robust predictive effect. The expressions of key genes were associated with immune infiltrating. GSE65858 validated the results.
Conclusion Our study comprehensively analyzed the tumor microenvironment of HNSCC and constructed a robust predictive model, providing a basis for further investigation of therapy.

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Postoperative radiotherapy is associated with improved overall survival for alveolar ridge squamous cell carcinoma with adverse pathologic features

Corbin D. Jacobs, Hannah Williamson, Ian Barak, Daniel J. Rocke, Russel R. Kahmke, Gita Suneja, Yvonne M. Mowery

Publication date 08-12-2020


Abstract Background Alveolar ridge squamous cell carcinoma (ARSCC) is poorly represented in randomized trials.
Methods Adults in the National Cancer Database diagnosed with ARSCC between 2010 and 2014 who should be considered for postoperative radiotherapy (PORT) based on National Comprehensive Cancer Network (NCCN)‐defined risk factors were identified.
Results Eight hundred forty‐five (58%) of 1457 patients meeting the inclusion criteria received PORT. PORT was associated with improved overall survival (OS) on unadjusted (hazard ratio HR 0.83, 95% confidence interval CI 0.70‐0.98, P = .02) and multivariable (HR 0.78, 95% CI 0.64‐0.94, P = .002) analyses. PORT was associated with significantly improved 5‐year OS for patients with 1 (68% vs 58%, P < .001), 2 (52% vs 31%, P < .001), and ≥3 (38% vs 24%, P < .001) NCCN‐defined risk factors. Prognostic variables significantly associated with worse OS on multivariable analysis included advanced age, primary tumor size ≥3 cm, high grade, positive margin(s), stage N2‐3, level IV/V nodal metastasis, and extranodal extension.
ConclusionPORT for resected ARSCC with adverse pathologic features is associated with significantly improved OS.

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Trends in chronic opioid therapy among survivors of head and neck cancer

Anuja Kriplani, Jessica A. Lavery, Akriti Mishra, Deborah Korenstein, Allison N. Lipitz‐Snyderman, Denise M. Boudreau, Natalie Moryl, Erin F. Gillespie, Talya Salz

Publication date 08-12-2020


Abstract Background Survivors of head and neck cancer (HNC) have increased risk of opioid misuse.
Methods Using Surveillance, Epidemiology and End‐Results‐Medicare data, we matched adults ≥66 years diagnosed with HNC 2008‐2015 with cancer‐free controls. We computed odds ratios (OR) for receipt of chronic opioid therapy (COT, claims for ≥90 consecutive days) for HNC survivors compared to controls each year after matching through 2016.
Results The cohort of HNC survivors declined from 5107 in the first year after diagnosis to 604 in the sixth year after diagnosis. For 5 years, rates of COT among HNC survivors exceeded that of controls. Differences between survivors and controls declined each year (ORs: year 1, 4.36; year 2, 2.60; year 3, 2.18; year 4, 1.85; and year 5, 1.35; all P‐values <.05).
Conclusions Among older HNC survivors, cancer‐associated opioid use in the first years after diagnosis suggests that the benefit of opioids must balance the risk of opioid misuse.

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Systematic review of postoperative therapy for resected squamous cell carcinoma of the head and neck: Executive summary of the American Radium Society appropriate use criteria

Danielle N. Margalit, Assuntina G. Sacco, Jay S. Cooper, John A. Ridge, Richard L. Bakst, Beth M. Beadle, Jonathan J. Beitler, Steven S. Chang, Allen M. Chen, Tom J. Galloway, Shlomo A. Koyfman, Carol Mita, Jared R. Robbins, C. Jillian Tsai, Minh T. Truong, Sue S. Yom, Farzan Siddiqui

Publication date 08-12-2020


Abstract Background The aims of this systematic review are to (a) evaluate the current literature on the impact of postoperative therapy for resected squamous cell carcinoma of the head and neck (SCCHN) on oncologic and non‐oncologic outcomes and (b) identify the optimal evidence‐based postoperative therapy recommendations for commonly encountered clinical scenarios.
Methods An analysis of the medical literature from peer‐reviewed journals was conducted using the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guideline. Prospective studies and methodology‐based systematic reviews and meta‐analyses of postoperative therapy for SCCHN were identified by searching Medline (OVID) and EMBASE (Elsevier) using controlled vocabulary terms (ie, National Library of Medicine Medical Subject Headings MeSH, EMTREE). Study screening and selection was performed with Covidence software and full‐text review. The RAND/UCLA appropriateness method was used by the expert panel to rate the appropriate use of postoperative therapy, and the modified Delphi method was used to come to consensus.
ResultsA total of 5660 studies were identified and screened using the title and abstract, leading to 201 studies assessed for relevance using full‐text review. After limitation to the eligibility criteria, 101 studies from 1977 to 2020 were identified, including 77 with oncologic endpoints and 24 with function and quality of life endpoints. All studies reported staging prior to the implementation of American Joint Committee on Cancer (AJCC‐8).
Conclusions Prospective clinical studies and systematic reviews identified through the PRISMA systematic review provided good evidence for consensus statements regarding the appropriate use of postoperative therapy for resected SCCHN. Further research is needed in domains where consensus by the expert panel could not be achieved for the appropriateness of specific postoperative therapeutic interventions.

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Ipsilateral radiation for squamous cell carcinoma of the tonsil: American Radium Society appropriate use criteria executive summary

C. Jillian Tsai, Thomas J. Galloway, Danielle N. Margalit, Richard L. Bakst, Beth M. Beadle, Jonathan J. Beitler, Steven Chang, Allen Chen, Jay Cooper, Shlomo A. Koyfman, John A. Ridge, Jared Robbins, Minh Tam Truong, Sue S. Yom, Farzan Siddiqui

Publication date 08-12-2020


Abstract Background We conducted the current systemic review to provide up‐to‐date literature summary and optimal evidence‐based recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil.
Methods We performed literature search of peer‐reviewed journals through Pub Med. The search strategy and subject‐specific keywords were developed based on the expert panels consensus. Articles published from January 2000 to May 2020 with full text available on Pub Med and restricted to the English language and human subjects were included. Several prespecified search terms were used to identify relevant publications and additional evidence published since the initial American College of Radiology Appropriateness Criteria Ipsilateral Tonsil Radiation recommendation was finalized in 2012. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.
Results The initial search and review returned 46 citations. The authors added three citations from bibliographies, websites, or books not found in the literature search. Of the 49 citations, 30 citations were retained for further detailed review, and 14 of them were added to the evidence table. Articles were removed from the bibliography if they were not relevant or generalizable to the topic, or focused on unknown primary disease. Several commonly encountered clinical case variants were created and panelists anonymously rated each treatment recommendation. The results were reviewed and disagreements discussed.
Conclusions The panel provided updated evidence and recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil in the setting of primary radiation‐based therapy and postoperative adjuvant radiotherapy. This committee did not reach agreements for some case variants due to a lack of strong evidence supporting specific treatment decisions, indicating a further need for research in these topics.

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Comprehensive in silico analysis for identification of novel candidate target genes, including DHX36, OPA1, and SENP2, located on chromosome 3q in head and neck cancers

Omer Faruk Karatas, Ozel Capik, Neslisah Barlak, Elanur Aydin Karatas

Publication date 08-12-2020


Abstract Background Major milestones of head and neck carcinogenesis have been associated with various genetic abnormalities; however, a clear picture of the molecular networks deregulated during the carcinogenesis of head and neck squamous cell carcinoma (HNSC) has not yet completely revealed.
Methods In this study, we used in silico tools and online data sets to evaluate the underlying reasons for the expressional changes of genes residing within the chromosome 3q and to help understanding their contributions to HNSC carcinogenesis.
Results We found that 13 of 20 most upregulated genes in HNSC are localized to 3q. Further analysis revealed a gene signature consisting of DHX36, OPA1, and SENP2, which showed significant correlation in HNSC samples and potentially be deregulated through similar mechanisms including DNA amplification, transcriptional, and posttranscriptional regulation.
Conclusions Considering our findings, we suggest DHX36, OPA1, and SENP2 genes as overexpressed in HNSC tumors and that might be concurrently involved in HNSC carcinogenesis, tumor progression, and induction of angiogenic pathways.

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Use of intraoperative neural monitoring for prognostication of recovery of vocal mobility and reduction of permanent vocal paralysis after thyroidectomy

Gerard Thong, Catherine Brophy, Patrick Sheahan

Publication date 08-12-2020


Abstract Introduction The benefits of intraoperative neural monitoring (IONM) of recurrent laryngeal nerve (RLN) on post‐thyroidectomy vocal cord palsy (VCP) rates are contentious. We wished to study impact of IONM on permanent VCP after thyroidectomy.
Methods Retrospective review of prospective series of 1011 (1539 nerves‐at‐risk) patients undergoing thyroidectomy without (418, group 1) and with (583, group 2) IONM.
Results There were three recognized nerve injuries in group 1, vs one in group 2 (P = .3). There were no differences in overall VCP rates. However, patients in group 2 with immediate postoperative VCP had higher likelihood of full recovery than patients in group 1 (55 of 56 vs 23 of 29 patients, P = .01), and lower incidence of total permanent VCP (2 of 917 vs 9 of 647 patients, P = .01).
Conclusion Among patients with immediate postoperative VCP after thyroidectomy, IONM is associated with a higher likelihood of regaining normal vocal function. This may be related to better identification of RLN branching in IONM cases.

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Untreated head and neck cancer: Natural history and associated factors

Paul Zolkind, Jake J. Lee, Ryan S. Jackson, Patrik Pipkorn, Sean T. Massa

Publication date 08-12-2020


Abstract Background This study aims to provide modern estimates of survival for untreated head and neck cancer (HNC) and to identify patient‐ and tumor‐specific factors associated with not receiving definitive treatment.
Methods Adults with mucosal HNC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Median overall survival of untreated patients was calculated and stratified by site and stage. Cause‐specific survival and factors associated with no treatment were investigated with advanced statistics.
Results The study cohort included 6477 patients who received no treatment. Overall, untreated patients had a median survival of 12 months, with significant variability by site and stage. Multivariable analysis identified advanced age, black race, unmarried status, and lack of private insurance as associated with no treatment.
Conclusions Survival of HNC without treatment is dismal, yet substantial variation exists by tumor site and stage. Higher rates of no treatment among the poor and racial minorities are potentially driven by disparities in care availability and provision.

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Islanded facial artery musculo‐mucosal flap for partial pharyngeal defect reconstruction after total laryngectomy: Case report

Nisha Rajrattansingh Akali, Arya Chandrababu Jaya, Deepak Balasubramanian, Subramania Iyer, Krishnakumar Thankappan

Publication date 08-12-2020


Abstract Background Partial pharyngeal defect reconstruction after total laryngectomy with regional and free fasciocutaneous flaps has been described. However, mucosal flaps for such defects have not been reported.
Methods An islanded facial artery musculo‐mucosal (FAMM) flap was used to reconstruct a partial pharyngeal defect after total laryngectomy. Surgical, swallowing, and speech outcomes were analyzed at 6 months postoperatively.
Results At 6 months, videofluoroscopy showed no post swallow residue, fistula, trachea‐esophageal puncture leak, or stricture. Perceptual analysis of recorded cold speech, native language passage sample, and the intelligibility analysis was good. The patient had normal mouth opening and marginal mandibular nerve function.
Conclusion Islanded FAMM flap is ideal for partial pharyngeal defects, which cannot be closed primarily. Speech and swallowing outcomes were good. It provided a robust and predictable blood supply and adequate reach. There was no significant donor site morbidity. The musculo‐mucosal flap replaced “like‐with‐like” tissue.

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Neoadjuvant selpercatinib for advanced medullary thyroid cancer

Yelda Jozaghi, Mark Zafereo, Michelle D. Williams, Maria K. Gule‐Monroe, Jennifer Wang, Elizabeth G. Grubbs, Ara Vaporciyan, Mimi I. Hu, Naifa Busaidy, Ramona Dadu, Steven G. Waguespack, Vivek Subbiah, Maria Cabanillas

Publication date 08-12-2020


Abstract Background Targeted kinase inhibitors have been increasingly utilized in the treatment of advanced medullary thyroid cancer (MTC) over the last decade. Recently, highly potent next generation selective RET inhibitors have been clinically validated, and selpercatinib was recently Food and Drug Administration (FDA)‐approved for advanced MTC. The advent of highly selective, potent RET inhibitors is broadening the treatment options for patients with RET‐mutated cancers.
Methods We report the first published case of neoadjuvant selpercatinib followed by surgery for a patient with initially unresectable, widely metastatic, RET‐mutated MTC who was treated on a single patient protocol.
Results After greater than 50% RECIST response, the patient underwent complete surgical resection followed by selpercatinib resumption. He remains locoregionally disease‐free 21 months after starting therapy with stable metastatic disease (after initial partial response); and calcitonin/CEA continue to decline.
Conclusion This novel treatment strategy for locoregionally advanced RET‐mutated MTC warrants further study in clinical trials.

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Issue Information

Publication date 08-12-2020


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Publication date 08-12-2020


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Transcervical arterial ligation for prevention of postoperative hemorrhage in transoral oropharyngectomy: Systematic review and meta‐analysis

Daniel D. Sharbel, Mary Abkemeier, James Sullivan, Zach Zimmerman, William G. Albergotti, Umamaheswar Duvvuri, James Kenneth Byrd

Publication date 08-12-2020


Abstract Background Transcervical arterial ligation has been studied as a useful procedure to prevent bleeding events after transoral robotic surgery (TORS).
MethodsA systematic review of English‐language literature on arterial ligation in TORS from 2005 to 2019 was conducted using Cochrane, Pub Med, Web of Science (WoS), and Science Direct databases. Studies evaluating ligation and rates of postoperative hemorrhage were included. Meta‐analysis of included studies was performed to assess impact of ligation on postoperative hemorrhage.
Results Five studies with 2008 patients were included. History of radiation (odds ratio OR = 2.26, P = .02) and advanced tumor stage (OR = 1.93, P = .02) were found to predispose patients to postoperative hemorrhage. Arterial ligation was protective against severe hemorrhage in the mixed primary surgical modality cohort (OR = 0.33, P = .03) and in the TORS‐only subgroup (OR = 0.21, P = .02), but did not significantly impact overall odds of postoperative hemorrhage.
Conclusion Transcervical arterial ligation offers protection against major/severe postoperative hemorrhage in patients undergoing TORS.
Level of EvidenceII.

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Radical external beam re‐irradiation in the treatment of recurrent head and neck cancer: Critical review

Michaela Svajdova, Pavol Dubinsky, Tomas Kazda

Publication date 08-12-2020


Abstract Management of patients with recurrent head and neck cancer remains a challenge for the surgeon as well as the treating radiation oncologist. Even in the era of modern radiotherapy, the rate of severe toxicity remains high with unsatisfactory treatment results. Intensity‐modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and heavy‐ion irradiation have all emerged as highly conformal and precise techniques that offer many radiobiological advantages in various clinical situations. Although re‐irradiation is now widespread in clinical practice, little is known about the differences in treatment response and toxicity using diverse re‐irradiation techniques. In this review, we provide a comprehensive overview of the role of radiation therapy in recurrent or second primary head and neck cancer including patient selection, therapeutic outcome, and risk using different re‐irradiation techniques. Critical review of published evidence on IMRT, SBRT, and heavy‐ion full‐dose re‐irradiation is presented including data on locoregional control, overall survival, and toxicity.

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Transoral endoscopic thyroidectomy vestibular approach vs conventional open thyroidectomy: Meta‐analysis

Yichao Wang, Shengliang Zhou, Xueting Liu, Shu Rui, Zhihui Li, Jingqiang Zhu, Tao Wei

Publication date 08-12-2020


Abstract Background To conduct a meta‐analysis to compare the safety and efficacy of transoral endoscopic thyroidectomy vestibular approach (TOETVA) with conventional open thyroidectomy (COT).
MethodsMEDLINE, EMBASE, Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials in the Cochrane Library from January 2007 to March 2020 were searched to identify studies comparing TOETVA and COT.
Results Six eligible nonrandomized studies involving 1151 patients were included. Meta‐analysis results revealed that TOETVA group had a significantly longer operative time (weighted mean difference WMD, 66.09; 95% confidence interval CI, 35.22‐96.96; P < .0001) and larger amount of drainage (WMD, 98; 95% CI, 20.14‐175.86; P = .01). There were no significant differences in terms of postoperative outcomes.
ConclusionTOETVA appears to be as feasible and safe as the COT for the treatment of patients with benign thyroid nodules and selected differential thyroid carcinomas.

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The effectiveness of radiotherapy in the treatment of head and neck mucosal melanoma: Systematic review and meta‐analysis

"Marc C. Grant‐Freemantle, Billy Lane ONeill, Anthony James P. Clover"

Publication date 08-12-2020


Abstract Introduction Mucosal melanoma (MM) is a rare condition with a poor prognosis. Surgery is the corner stone of treatment, however, radiotherapy has been commonly employed as a treatment strategy and recent studies suggesting that survival outcomes may be improving are emerging.
MethodsA systematic review and meta‐analysis comparing risk ratios of radiotherapy and surgery and radiotherapy (SRT) with surgery for 5‐year overall survival, local recurrence and distant metastasis in head and neck mucosal melanoma (HNMM).
ResultsSRT has a lower risk of death compared to surgery RR 0.93 95% CI = 0.87, 0.98 (P = .01) and a reduced risk of local recurrence RR 0.63 95% CI = 0.48, 0.82 (P = .005). SRT has no effect on distant metastasis. Radiotherapy has worse survival when compared to surgery RR 1.2 95% CI = 1.03, 1.33 (P = .0006).
ConclusionsSRT confers a moderate survival advantage in HNMM compared to surgery. This is most likely secondary to reduced local recurrence.

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Evidence for different molecular parameters in head and neck squamous cell carcinoma of nonsmokers and nondrinkers: Systematic review and meta‐analysis on HPV, p16, and TP53

Frans J. Mulder, Damiana D. C. G. Pierssens, Laura W. J. Baijens, Bernd Kremer, Ernst‐Jan M. Speel

Publication date 08-12-2020


Abstract Background The goal of this review was to present an overview of the currently identified molecular parameters in head and neck squamous cell carcinoma (HNSCC) of nonsmokers and nondrinkers (NSND).
Methods Following the PRISMA guidelines, a systematic search was performed using the electronic databases Pub Med, Embase, and Google Scholar.
Results Of the 902 analyzed unique studies, 74 were included in a quantitative synthesis and 24 in a meta‐analysis. Human papillomavirus (HPV) was reported as a molecular parameter in 38 studies, followed by p16 and TP53 (23 and 14 studies, respectively). The variety of other molecular parameters concerned sporadic findings in small numbers of NSND.
ConclusionsHNSCC in NSND is more often related to HPV and p16 overexpression compared to tumors of smokers‐drinkers. In a third of virus‐negative tumors, TP53 mutations were detected with a mutational profile associated with aging and ultraviolet light exposure rather than to tobacco consumption.

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Treatment tolerability and outcomes in elderly patients with head and neck cancer

Daniel R. Dickstein, Marc Egerman, Erica Monrose, Achintya Varma, Umut Ozbek, Sonam Sharma, Jerry T. Liu, Vishal Gupta, Marshall R. Posner, Krzysztof Misiukiewicz, Brett A. Miles, Eric Genden, Richard L. Bakst

Publication date 08-12-2020


Abstract Purpose The number of elderly patients with head and neck squamous cell carcinoma (HNSCC) continues to grow. Management of this cohort remains poorly defined. We investigated treatment tolerability and clinical outcomes in this underrepresented population.
Methods We identified patients aged ≥70 with nonrecurrent, nonmetastatic HNSCC treated curatively from 2007‐2018 and analyzed clinical covariates.
Results Two hundred and twenty patients with a median age of 75 (interquartile range:72‐80) were identified. Age and comorbidities were not correlated with toxicity (P ≥ .05). Patients who experienced a treatment interruption had significantly greater weight loss (P = .042) and worse overall survival (OS) (P < .001), but not worse disease‐specific survival (P = .45), or locoregional control (P = .21).
Conclusions Treatment interruptions were associated with weight loss and worse OS, but not disease related outcomes, suggesting an interruption in the elderly may be a surrogate for another issue. In sum, our data should guide clinical trial design to benefit this growing, neglected cohort.

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Adjustable breathing resistance for laryngectomized patients: Proof of principle in a novel heat and moisture exchanger cassette

Maartje Leemans, Sara H. Muller, Maarten J. A. Alphen, Wim Vallenduuk, Richard Dirven, Michiel W. M. Brekel

Publication date 08-12-2020


Abstract Background Due to the heat and moisture exchangers (HME) breathing resistance, laryngectomized patients cannot always use an (optimal) HME during physical exercise. We propose a novel HME cassette concept with adjustable “bypass,” to provide adjustment between different breathing resistances within one device.
Methods Under standardized conditions, the resistance and humidification performance of a high resistance/high humidification HME (XM) foam in a cassette with and without bypass were compared to a lower resistance/lesser humidification HME (XF) foam in a closed cassette.
Results With a bypass in the cassette, the resistance and humidification performance of XM foam were similar to those of XF foam in the closed cassette. Compared to XM foam in the closed cassette, introducing the bypass resulted in a 40% resistance decrease, whereas humidification performance was maintained at 80% of the original value.
Conclusions This HME cassette prototype allows adjustment between substantially different resistances while maintaining appropriate humidification performances.

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New approach to an overlooked flap: Technique to augment venous drainage of the infrahyoid myocutaneous flap

Xiaoming Lyu, Shuming Liu, Lei Zheng, Mingwei Huang, Jianguo Zhang, Jie Zhang

Publication date 07-12-2020


Abstract Background To describe a technique in which the anterior jugular vein is preserved in the infrahyoid myocutaneous flap (IHMCF) to augment skin paddle venous drainage.
Methods From April 2018 to December 2019, 14 patients with primary oral cancer underwent radical resection and IHMCF reconstruction. Three‐dimensional reconstruction of the anterior jugular vein was used to assess the venous drainage of the skin paddle preoperatively. The anterior jugular vein was preserved during dissection of the flap. Healing of the recipient and donor sites was observed.
Results Total flap necrosis occurred in one patient and marginal skin paddle necrosis occurred in one patient. No flap complications occurred in the other 12 patients.
Conclusion This new approach to augment venous drainage of the IHMCF appears to be effective for decreasing risk of flap necrosis.

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Risk factors for subsequent recurrence after surgical treatment of recurrent pleomorphic adenoma of the parotid gland

Steven A. Rooker, Kathryn M. Van Abel, Linda X. Yin, Alex A. Nagelschneider, Daniel L. Price, Kerry D. Olsen, Jeffrey R. Janus, Jan L. Kasperbauer, Eric J. Moore

Publication date 04-12-2020


Abstract Background Recurrent pleomorphic adenoma (PA) can be a lifelong disease, and rates of subsequent recurrence are high.
Methods Patients between 2000 and 2015 were identified. Primary outcome was subsequent recurrence after surgical salvage.
Results Twenty‐seven of 84 patients developed a subsequent recurrence. Risk factors for subsequent recurrence included a higher number of previous recurrences (P < .01), worse preoperative facial nerve function (P < .01), and deep parotid lesion(s) (P < .01). Interval since last surgery was protective (P < .01), specifically >10 years since last surgery (P < .01). For patients with a >10‐year interval since their last surgery, the subsequent recurrence‐free rate at 10 years follow‐up was 80.2% vs 31.8%.
Conclusions For patients presenting with a >10‐year interval since their last surgery, subsequent recurrence rates are low, which may allow for as needed surveillance recommendations. For patients presenting with recurrent PA and ≤10 years since their last surgery, a closer surveillance is warranted.

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Preliminary development and validation of a measure of fear of swallowing and swallowing‐related movement injury in head and neck cancer: Swallowing Kinesiophobia Scale

Giselle D. Carnaby, Karishma Chhabria

Publication date 02-12-2020


Abstract Background Fear is an under‐recognized issue in intervention adherence in head and neck cancer (HNC). We developed and validated a patient reported outcome for swallowing fear in HNC patients.
Methods Items were adapted from the Tampa Scale for Kinesiophobia to swallowing function. A beta version was completed by 51 HNC patients undergoing chemo +/− radiotherapy at baseline and post‐treatment. Psychometric and factor structure analyses were applied.
Results Swallowing Kinesiophobia Scale (SWKS) demonstrated strong face and content validity, internal consistency, and test‐retest reliability. Factor analysis revealed three‐factors: somatic factor, swallow avoidance, and fear of harm. Factors correlated positively with depression score, worry scale, and anxiety and pain scales. Score differences between patient subgroups (dysphagic vs nondysphagic) confirmed discriminative validity.
Conclusion The SWKS is a psychometrically valid tool to identify patients with fear of swallowing and swallowing‐related movement. It can help identify patients early in treatment who may need additional support.

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Limitations of preoperative cytology for medullary thyroid cancer: Proposal for improved preoperative diagnosis for optimal initial medullary thyroid carcinoma specific surgery

Alan D. Workman, Selen Soylu, Dipti Kamani, Anahita Nourmahnad, Natalia Kyriazidis, Ryan Saade, Yin Ren, Lori Wirth, William C. Faquin, Ayşe M. Onenerk, Yuri E. Nikiforov, Zaid Al‐Qurayshi, Emad Kandil, Richard T. Kloos, Leslie Eldeiry, Carrie Lubitz, Nikolaos Stathatos, Gregory W. Randolph

Publication date 02-12-2020


Abstract Background Preoperative diagnosis of medullary thyroid carcinoma (MTC) is often difficult, given the poor sensitivity of fine‐needle aspiration (FNA) cytology for MTC. This study investigates this issue and presents recommendations for improving preoperative diagnostic paradigms in MTC cases.
Design/Method Histopathologically confirmed MTC patients with preoperative cytologic assessment of index nodules were enrolled. FNA diagnosis, final pathology, and surgery details were collected.
Results Out of 71 patients, 49 (69%) were diagnosed by FNA as either definitive MTC (35, 49%) or suspected MTC (14, 20%) and 22 (31%) patients had no indication of MTC on FNA.
Conclusion In a tertiary‐care setting, one‐third of subjects had an FNA interpretation that did not suggest the possibility of MTC. The limitations of preoperative diagnosis are especially problematic for MTC as they can cause delayed or incomplete treatment. Additional testing is proposed to improve preoperative diagnosis and surgical care of MTC patients.

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Complication analysis of three different designs of temporary mandibulotomy in tongue cancer treatment

Ting‐Han Chiu, Filippo Marchi, Shiang‐Fu Huang, Chung‐Jan Kang, Chun‐Ta Liao, Shao‐Yu Hung, David Chon‐Fok Cheong, Chung‐Kan Tsao

Publication date 01-12-2020


Abstract Background Mandibulotomy helps access posterior oral cavity tumors. If osteotomy designs affect postoperative and postradiotherapy complications, needs to be tested clinically.
Methods Two hundred and eighteen patients who underwent midline mandibulotomy for primary tongue cancer wide excision and flap reconstruction at Chang Gung Memorial Hospital during 2014‐2019.
Results There were 114 straight, 54 notched, and 50 stair‐stepped osteotomy cases. Stair‐stepped osteotomy had less advanced tumor stages (P = .009) and notched osteotomy more common single‐plate fixations (P = .012). The former showed higher mandibular heights (P = .000) and more intact midline teeth (P = .011) than notched and straight ones. Straight osteotomy cases showed lower early infection rates (P = .039). Single‐plate fixation was related to more flap dehiscence (P = .001) and oro‐cutaneous fistulas (P = .035).
Conclusions Complex osteotomy does not offer long‐term benefits in midline mandibulotomies for primary tongue cancers and has higher early infections. Single‐plate fixation increases postoperative complications.

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Risk factors for the development of high‐grade dysplasia and carcinoma in patients with laryngeal squamous cell papillomas: Large retrospective cohort study

Daša Gluvajić, Lea Hošnjak, Vida Stegel, Srdjan Novaković, Nina Gale, Mario Poljak, Irena Hočevar Boltežar

Publication date 01-12-2020


Abstract Background The incidence and risk factors for the development of high‐grade dysplasia (HG‐D) and laryngeal squamous cell carcinoma (LSCC) were assessed in patients with laryngeal squamous cell papillomas (LSP).
Methods Clinical data, human papillomaviruses (HPV) typing, HPV E6/E7 mRNA in situ hybridization, and sequencing of host genes in LSP biopsies of 163 patients were analyzed.
Results Progression to HG‐D and LSCC was identified in 21.5% and 4.3% of LSP patients, respectively. A more advanced age at LSP onset and lack of HPV infection were detected as risk factors for the development of HG‐D and LSCC (P < .05). The identification of HG‐D was associated with its progression to LSCC (P < .05). Host gene mutations were identified in 3 of 7 patients with LSCC.
Conclusions The histological monitoring of LSP and HPV typing are necessary for early detection of epithelial changes. Further research is needed to elucidate the role of host gene mutations in LSCC transformation.

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Ambulatory thyroidectomy is safe and beneficial in papillary thyroid carcinoma: Randomized controlled trial

Zeyu Zhang, Fada Xia, Wenlong Wang, Bo Jiang, Lei Yao, Yun Huang, Xinying Li

Publication date 28-11-2020


Abstract Background Currently, no randomized controlled trial has been performed to investigate the safety profiles, economic benefit and mental health of ambulatory thyroidectomy in patients with papillary thyroid carcinoma (PTC).
Methods Patients diagnosed with PTC were enrolled in this study and were randomly assigned to ambulatory group and control group. The safety profiles, economic benefit and mental health were investigated.
Results Four hundred and eleven patients completed the study. There was no significant difference in demographic or tumor index. The incidence of complications was not significantly different (P = .631). The economic cost was significantly lower (P < .001) and hospitalization was significantly shorter (P < .001) in ambulatory group. No significant difference was shown in depression (P = .758) and stress disorder (P = .390). However, the ambulatory group showed a higher point of anxiety (P < .001).
Conclusion The ambulatory thyroidectomy is safe in patients with PTC, with significant benefits of economic cost and hospitalization.

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Not only gustatory sweating and flushing: Signs and symptoms associated to the Frey syndrome and the role of botulinum toxin A therapy

Maria Raffaella Marchese, Francesco Bussu, Stefano Settimi, Emanuele Scarano, Giovanni Almadori, Jacopo Galli

Publication date 28-11-2020


Abstract Background The classic symptoms of Frey syndrome are gustatory sweating and flushing. Aims of the study were to describe prevalenceand severity of typical and atypical presentations of the disorder and to assess the effects of botulinum neurotoxin A (BoNT‐A) therapy in patients with Frey syndrome after parotidectomy.
Methods In this prospective, observational study on 18 patients, we assessed symptom severity before therapy, after 15 days, 1, 3 and 6 months follow‐up with the sweating‐flushing‐itch‐paresthesia‐pain (SFIPP) Frey scale specifically designed by the authors themselves for this study.
Results Before BoNT‐A injection, all patients (100%) complained gustatory sweating, 80% paresthesia, 77% gustatory flushing, 60% pain and 60% gustatory itch. The SFIPP‐Frey overall score and the symptom‐specific ones decreased significantly at each post‐therapy control.
Conclusions The prevalence of “unusual” manifestations is not negligible. BoNT‐A improves symptoms severity. The SFIPP‐Frey scale may be useful to assess symptoms and to monitor post‐therapy outcomes.

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Circular RNA circ_0004507 contributes to laryngeal cancer progression and cisplatin resistance by sponging miR‐873 to upregulate multidrug resistance 1 and multidrug resistance protein 1

Xuehan Yi, Wei Chen, Chen Li, Xiaoqiang Chen, Qin Lin, Shuchun Lin, Desheng Wang

Publication date 28-11-2020


Abstract Background Circular RNAs (circRNAs) play critical roles in various types of cancer and chemosensitivity.
Methods The expression levels of circ_0004507 and microRNA‐873 (miR‐873) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). The interaction between circ_0004507 and miR‐873 was predicted by circinteractome and verified by dual‐luciferase reporter assay and RNA pull‐down assay. Xenograft tumor model was established to confirm the biological role of circ_0004507 in vivo.
Resultscirc_0004507 was highly expressed and miR‐873 was lowly expressed in laryngeal cancer tissues. circ_0004507 knockdown or miR‐873 overexpression inhibited cell proliferation, migration and invasion, and increased apoptosis and cisplatin sensitivity in laryngeal cancer cells. miR‐873 was identified as a direct target of circ_0004507. circ_0004507 interference inhibited tumor growth and promoted cisplatin sensitivity by upregulating miR‐873 in vivo.
Conclusion Knockdown of circ_0004507 inhibited laryngeal cancer progression and cisplatin resistance by sponging miR‐873, providing a potential target for laryngeal cancer therapy.

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Solid organ transplantation worsens the prognosis of patients with cutaneous squamous cell carcinoma of the head and neck region—Comparison between solid organ transplant recipients and immunocompetent patients

Amit Ritter, Samih Badir, Muhammad Mansour, Zvi Segal, Dean Ad‐El, Gideon Bachar, Thomas Shpitzer, Aron Popovtzer, Aviram Mizrachi

Publication date 27-11-2020


Abstract Background Cutaneous squamous cell carcinoma of the head and neck (CSCC‐HN) appears to behave more aggressively in immunosuppressed patients. We aimed to investigate this hypothesis by comparing solid organ transplant recipients (SOTR) with CSCC‐HN to immunocompetent patients.
MethodsA retrospective comparative study was conducted for SOTR and immunocompetent patients who were treated for CSCC‐HN.
ResultsA total of 177 SOTR and 157 immunocompetent patients with CSCC‐HN were included. Lymph node metastases were more common in the SOTR group (9% vs 3%), and distant metastases occurred only in SOTR (3% of patients). SOTR had a higher rate of recurrences (19% vs 10%), which were mostly regional (7%) and distant (3%). The 2‐year disease‐specific survival of SOTR was lower (93% vs 100%).
ConclusionsSOTR with CSCC‐HN has significantly worse outcomes compared to immunocompetent patients. Solid‐organ transplantation should be regarded as a negative prognostic factor in patients with CSCC‐HN.

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Parotid gland stem cells: Mini yet mighty

Sezin Yuce Sari, Melek Tugce Yilmaz, Aysenur Elmali, Fazli Yagiz Yedekci, Deniz Yuce, Gokhan Ozyigit, Mustafa Cengiz, Gozde Yazici

Publication date 27-11-2020


Abstract Background Our aim was to evaluate the correlation between the radiation doses to parotid gland (PG) stem cells and xerostomia.
Methods Patients diagnosed with head and neck cancer (HNC) were retrospectively evaluated, and xerostomia inventory (XI) was applied to these patients. PG stem cells were delineated on the treatment planning CT, and the mean doses to the PG stem cells calculated.
Results The total test score and mean doses to bilateral PGs were significantly correlated (r = .34, P = .001), and the mean doses to bilateral PG stem cell niches were significantly correlated with the total test score (r = .32, P = .002).
Conclusions In this study, we found that the mean dose to PG stem cells can predict dry mouth as much as the mean dose to the PG.

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Experimental investigation of esophageal reconstruction with electrospun polyurethane nanofiber and 3D printing polycaprolactone scaffolds using a rat model

Hanaro Park, In Gul Kim, Yanru Wu, Hana Cho, Jung‐Woog Shin, Su A Park, Eun‐Jae Chung

Publication date 26-11-2020


Abstract Background We evaluated the outcome of esophageal reconstructions using tissue‐engineered scaffolds.
Method Partial esophageal defects were reconstructed with the following scaffolds; animals were grouped (n = 7 per group) as follows: (a) normal rats; (b) rats implanted with three‐dimensional printing (3DP) polycaprolactone (PCL) scaffolds; (c) with human adipose‐derived mesenchymal stem cell (ADSC)‐seeded 3DP PCL scaffolds; (d) with polyurethane (PU)‐nanofiber(Nf) scaffolds; and (e) with ADSC‐seeded PU‐Nf scaffolds.
Results The esophageal defects were successfully repaired; however, muscle regeneration was greater in the 3DP PCL + ADSC groups than in the PU‐Nf + ADSC groups (P < .001). Regeneration of the epithelium was greater in PU‐Nf and PU‐Nf + ADSC groups than in the 3DP PCL and 3DP PCL + ADSC groups (P < .001).
ConclusionA tendency for more re‐epithelization was observed with the PU‐Nf scaffolds, while more muscle regeneration was achieved with the 3DP PCL scaffolds.

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Handheld reflectance confocal microscopy: Personalized and accurate presurgical delineation of lentigo maligna (melanoma)

Yannick S. Elshot, Biljana Zupan‐Kajcovski, William M. C. Klop, Marcel W. Bekkenk, Marianne B. Crijns, Menno A. Rie, Alfons J. M. Balm

Publication date 24-11-2020


Abstract Background The surgical treatment of lentigo maligna melanoma is associated with high rates of local recurrence. Handheld reflectance confocal microscopy (HH‐RCM) allows for in vivo presurgical detection of subclinical lentigo maligna (melanoma) (LM/LMM).
MethodsA single‐center retrospective study from December 2015 to July 2017. Frequency and extent of negative surgical margins, and the diagnostic accuracy of presurgical mapping by HH‐RCM was determined.
Results Twenty‐six consecutive patients with LM/LMM were included. In 45.8%, HH‐RCM detected subclinical LM with a sensitivity of 0.90 and specificity of 0.86. The management was changed in two (7.7%) patients. Of the 24 remaining lesions, 95.8% were excised with negative margins with a mean histological margin of 3.1 and 5.3 mm for LM and LMM, respectively. At a mean follow‐up of 36.7 months, there was one (4.8%) confirmed recurrence.
Conclusions Our method of presurgical delineation by HH‐RCM appears to provide a reliable method for the surgical treatment of LM/LMM with a limited rate of overtreatment.

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Evaluation of opioid prescription patterns among patients undergoing thyroid surgery

Hilary C. McCrary, Christopher I. Newberry, Geoffrey C. Casazza, Richard B. Cannon, Alexander L. Ramirez, Jeremy D. Meier

Publication date 23-11-2020


Abstract Background There is variability in opioid prescription patterns among surgeons performing thyroidectomy. Thus, the aim of this study is to evaluate opioid prescription rates and opioid use among hemithyroidectomy (HT) and total thyroidectomy (TT) patients.
Design/Method An electronic postoperative survey was distributed to assess opiate use among patients undergoing HT/TT. Groups were compared using t‐tests, chi‐square tests, and analysis of variance.
ResultsA total of 142 opiate naïve patients were included, of which 75 (52.8%) underwent HT and 67 (47.1%) underwent TT. The mean number of tablets prescribed was 21.3 (HT = 22.1, TT = 20.4; P = 0.3), with a mean of 14.1 tablets unused after surgery (HT = 13.2 tablets, TT = 15.0 tablets; P = 0.44). The mean morphine milligram equivalent (MME) prescribed was 150.1 mg (HT = 159.0 mg, TT = 140.2 mg; P = 0.3), with a mean of 98.2 MME unused after surgery (HT = 93.7 mg, TT = 103.2 mg; P = 0.6).
Conclusions Opioids are overprescribed after thyroid surgery. Avoidance of overprescribing is vital in mitigating the current opioid crisis.

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Rare case of metastatic liposarcoma to the thyroid gland and a review of the literature of metastatic sarcomas to the thyroid

Monica H. Xing, Neil Mundi, Aparna Govindan, Azita Khorsandi, Margaret Brandwein‐Weber, Ammar Matloob, Bobby Liaw, Mark L. Urken

Publication date 21-11-2020


Abstract Background Liposarcomas are the second most common type of soft tissue sarcomas. Typically, myxoid liposarcomas have a metastatic rate of 10%, usually involving the retroperitoneal space, abdomen, and spine. Metastasis to the thyroid is extremely rare.
Design/MethodA 62‐year‐old male with a history of metastatic myxoid liposarcoma in his right thigh presented to our clinic for evaluation of a thyroid nodule incidentally identified on a CT scan. A subsequent FNA biopsy was suggestive of a metastatic liposarcoma.
Results The patient underwent a left thyroid lobectomy and final pathology confirmed a grade II/III metastatic myxoid liposarcoma that measured 3.3 cm. The patient tolerated the procedure well.
Conclusions Our case highlights the role of a patients medical history when evaluating thyroid nodules to optimize accurate diagnosis, as liposarcomas do not typically metastasize to the thyroid. We also provide an updated review of the literature on all cases of metastatic sarcomas to the thyroid.

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Prior chemoradiotherapy and pathological perineural invasion predict the survival outcomes of salvage surgery in head and neck squamous cell carcinoma

Nisha Rajrattansingh Akali, Rahul Buggaveeti, Sheejamol Velickakathu Sukumaran, Deepak Balasubramanian, Subramania Iyer, Krishnakumar Thankappan

Publication date 21-11-2020


Abstract Background The purpose of the study was to evaluate the oncological outcomes of salvage surgery in squamous cell carcinoma of the head and neck (SCCHN).
Methods This is a retrospective analysis of all patients of SCCHN with recurrence or second primary, post‐treatment, who underwent salvage surgery. The outcomes were analyzed in terms of overall survival, overall survival postsalvage surgery and disease‐free survival (DFS) postsalvage surgery. Clinical and pathological predictors were considered.
Results Two hundred and forty‐one patients were included. The mean follow‐up was 56.33 months. Five‐year survival OS from date of initial diagnosis of the tumor was 61.2%. The 5‐year OS survival after salvage surgery was 47.1%. Five‐year DFS after salvage surgery was 28.1%. Prior chemoradiotherapy and pathological perineural invasion were independent predictors on multivariate analysis.
Conclusions Survival outcomes after appropriate salvage treatment are good. Prior chemoradiotherapy and perineural invasion on salvage pathology are predictors of poorer outcomes.

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Transoral robotic salvage oropharyngectomy with submental artery island flap reconstruction

Andrew J. Holcomb, Jeremy D. Richmon

Publication date 19-11-2020


Abstract Background Transoral robotic surgery (TORS) is an effective approach for select salvage oropharyngeal resections. Reconstruction in these scenarios is often necessary for vascular coverage and optimal functional outcomes but can be challenging. The submental artery island flap (SAIF) is well‐suited to this reconstruction.
Design/Method Two patients presented with recurrent oropharyngeal tumors after chemoradiation. Each tumor was resected using TORS, and the SAIF was utilized for reconstruction. Flap inset was completed using TORS in one case.
Results Both patients experienced uneventful recovery free from bleeding events or fistula formation and experienced no partial flap loss or donor site complications.
Conclusions The SAIF is a simple reconstructive option for TORS defects that may be inset using robotic assistance and avoids the need for free tissue transfer.

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AHNS endocrine surgery section consensus statement on nasopharyngolaryngoscopy and clinic reopening during COVID‐19: How to get back to optimal safe care

Benjamin Bleier, Alan Workman, Ciersten Burks, Alice Maxfield, Brendan C. Stack, Cherie‐Ann Nathan, Susan McCammon, Mark Varvares, Cecelia Schmalbach, Steven Wang, Joseph Califano, Yelizaveta Shnayder, Marion B. Gillespie, Danny Enepekides, Ian Witterick, Ivan El‐Sayed, Derrick Lin, Urjeet Patel, Dennis Kraus, Gregory Randolph

Publication date 17-11-2020


Abstract This article provides best practice guidelines regarding nasopharyngolaryngoscopy and OHNS clinic reopening during the COVID‐19 pandemic. The aim is to provide evidence‐based recommendations defining the risks of COVID‐19 in clinic, the importance of pre‐visit screening in addition to testing, along with ways to adhere to CDC guidelines for environmental, source, and engineering controls.

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Partial parotidectomy via periauricular incision: Retrospective cohort study and comparative analysis to alternative incisional approaches

C.Alessandra Colaianni, Allen L. Feng, Jeremy D. Richmon

Publication date 15-11-2020


Abstract Background We investigated a periauricular approach to the parotid and compared outcomes to alternative parotidectomy incisions.
Methods Retrospective chart review of patients (n = 97) undergoing partial parotidectomy for benign or malignant pathology by a single surgeon. After October 2017, most patients were approached via a periauricular incision (n = 59).
Results There was no significant difference in patient age, tumor location, length of hospital stay, postoperative complication, or pathology. Mean tumor diameter was significantly smaller in the periauricular group (2.1 cm) than in the traditional incision group (2.6 cm). No permanent injuries to facial nerve branches occurred in either group. Patients were followed for a median of 44 days after surgery.
Conclusions This is the largest study to date that demonstrates the periauricular incision is a safe and feasible approach for most parotid neoplasms. The cosmetic advantage of this approach is that the resulting scar is smaller and does not extend into the neck.

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ERRATUM

Publication date 15-11-2020


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Role of resection of torus tubarius to maximize the endonasal exposure of the inferior petrous apex and petroclival area

Lifeng Li, Nyall R. London, Daniel M. Prevedello, Ricardo L. Carrau

Publication date 10-11-2020


Abstract Endoscopic access to the petrous apex and petroclival region often requires sacrificing the Eustachian tube (ET). This study aimed to compare the maximum exposure of the petrous apex and petroclival region via an endonasal corridor when sparing or resecting the ET and its torus. Six cadaveric specimens (12 sides) were dissected through an endonasal transpterygoid approach. Endonasal exposure of the petroclival region was completed using techniques that included the preservation of the ET (group 1), resection of the torus tubarius (group 2), and resection of the ET (group 3) were sequentially performed on each side. The working distances from the anterior genu of the petrous internal carotid artery (ICA) to the inferior boundaries of each corridor were measured and compared. In group 1, the medial petrous apex and petroclival sulcus could be exposed with a working distance of 4.08 ± 0.67 mm. In group 2, the fossa of Rosenmüller, inferior petrous apex, and hypoglossal canal could be exposed, with a significantly increased working distance of 18.33 ± 0.89 mm (P = .001). In group 3, the exposure and ICA control was superior and offered a working distance of 20.67 ± 0.78 mm. No statistically significant difference derived from comparing groups 2 and 3 (P = .875). Resection of the torus tubarius can increase exposure of the petrous apex and petroclival region. It provides an alternative to resecting the ET, which might be beneficial for maintenance of middle ear function. ET resection, however, seems superior when ICA control is required.

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Prognostic role of intraparotid lymph node metastasis in primary parotid cancer: Systematic review

Orlando Guntinas‐Lichius, Jovanna Thielker, K. Thomas Robbins, Kerry D. Olsen, Ashok R. Shaha, Antti A. Mäkitie, Remco Bree, Vincent Vander Poorten, Miquel Quer, Alessandra Rinaldo, Luiz Paulo Kowalski, Juan Pablo Rodrigo, Marc Hamoir, Alfio Ferlito

Publication date 09-11-2020


Abstract Background The prognostic importance of intraparotid lymph node metastasis (P+) in patients with primary parotid gland carcinoma is unclear.
Methods Nineteen retrospective and noncomparative cohort studies, published between 1992 and 2020, met the inclusion criteria and included 2202 patients for this systematic review.
Results The pooled prevalence of the P in adult patients in the unselected studies was 24.10% (95% confidence interval = 17.95‐30.25). The number of P+ lymph nodes per patient was counted in only three studies and ranged from 1 to 11. The 5‐year recurrence‐free survival rate based on Kaplan‐Meier analysis varied from 83% to 88% in P− patients compared to 36% to 54% in P+ patients. The average hazard ratio for tumor recurrence in patients with P+ compared to P− was 2.67 ± 0.58.
ConclusionsP+ is an independent negative prognostic factor in primary parotid gland cancer and should be included into the treatment planning.

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Accuracy of fine‐needle aspiration cytology in detecting cervical node metastasis after radiotherapy: Systematic review and meta‐analysis

"Andrea Costantino, Giuseppe Mercante, Elisa DAscoli, Fabio Ferreli, Luca Di Tommaso, Ciro Franzese, Caterina Giannitto, Manuele Casale, Giuseppe Spriano, Armando De Virgilio"

Publication date 09-11-2020


Abstract Purpose To define the accuracy of fine‐needle aspiration cytology (FNAC) in diagnosing persistent or recurrent neck metastases in previously irradiated patients.
Methods The study was performed according to the PRISMA‐DTA guidelines.
ResultsA total of 382 FNACs were used for calculation of diagnostic accuracy parameters. The overall pooled sensitivity and specificity in detecting malignant nodes were 69.1% (95% CI: 56.3%‐80.7%; I2 = 79.5%) and 84.2% (95% CI: 71.8%‐93.5%; I2 = 87.0%), respectively. Cumulative diagnostic odds ratio (DOR) was 16.54 (95% CI: 4.89‐38.99; I2 = 65.8%), while cumulative positive and negative likelihood ratio (PLR and NLR) were 5.4 (95% CI: 2.3‐11.2) and 0.37 (95% CI: 0.22‐0.54), respectively.
ConclusionsFNAC alone could not guide the decision to perform a salvage neck dissection in previously irradiated patients, but its results should be assessed in relation to the specific clinical context.

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Institutional financial toxicity of failure to adhere to treatment guidelines for head and neck squamous cell carcinoma

James M. Jurica, Felixnando Rubio, David J. Hernandez, Vlad C. Sandulache

Publication date 09-11-2020


Abstract Background Delays in treatment of head and neck squamous cell carcinoma (HNSCC) are known to increase disease recurrence, generating the need for additional salvage treatment, often with immunotherapy.
Methods Three treatment metrics were identified: time from diagnosis to treatment initiation (TTI), time from surgery to postoperative radiotherapy (surg → PORT), and total treatment package time (TPT). Financial toxicity was calculated using hazard ratios, pembrolizumab cost, and dosing data for a Veterans Health Administration (VHA) institutional cohort (n = 338) and a standardized cohort (n = 100).
Results Estimated financial toxicity for the VHA cohort was $2 047 407, $316 545, and $1 114 101 for TTI, surg → PORT, and TPT, respectively. Estimated financial toxicity for the standardized patient cohort was $454 028, $544 576, and $1 879 628 for TTI, surg → PORT, and TPT, respectively.
Conclusions Failure to meet established HNSCC treatment metrics generates significant, yet avoidable, institutional financial toxicity which is particularly relevant to integrated single‐payer systems such as the VHA in the modern immunotherapy era.

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Role of intraoperative recurrent laryngeal nerve monitoring for pediatric thyroid surgery: Comparative analysis

Amit Ritter, Roy Hod, Yonatan Reuven, Thomas Shpitzer, Aviram Mizrachi, Eyal Raveh, Gideon Bachar

Publication date 09-11-2020


Abstract Background The data on the advantages of intraoperative nerve monitoring (IONM) during pediatric thyroid surgeries are limited. We aimed to study the role of IONM by comparing between children who underwent thyroid surgery with and without IONM.
MethodsA retrospective study of all children who underwent thyroid surgery between 2001 and 2019.
Results The study included 113 patients with 183 recurrent laryngeal nerve (RLN) at risk. Transient paralysis rate was more than 5‐fold lower in the IONM group compared to the control group (1.5% vs 8%; P = .114). Permanent paralysis was documented only in the control group (2.5% vs 0%; P = .552). Children <10 years and those who underwent central neck dissection had significantly higher rates of RLN injury.
ConclusionsIONM was associated with decreased rate of RLN injury during pediatric thyroid surgery and should be considered especially in children under 10 years of age and those undergoing concomitant central neck dissection.

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Therapeutic implications of immune‐profiling and EGFR expression in salivary gland carcinoma

Emily Guazzo, Caroline Cooper, Lisa Wilkinson, Sophie Feng, Brigid King, Fiona Simpson, Sandro Porceddu, Benedict Panizza, Jermaine I. G. Coward

Publication date 09-11-2020


Abstract Background Data relating to the efficacy of immune checkpoint inhibitors (ICI) for salivary gland carcinomas (SGC) is gradually evolving with responses varying among different histotypes. To address these disparities, this retrospective analysis examined the prevalence of recognized biomarkers of response to ICI; namely programmed death‐1 (PD‐1), programmed death‐ligand 1 (PD‐L1), combined positive score (CPS), epidermal growth factor receptor (EGFR), and microsatellite instability (MSI) in patients with SGC with an aim to determine any prognostic or survival benefits and stratify the use of ICI in this disease.
Patients and methods Of 52 patients with primary SGC eligible for this study, the most common histological types were adenoid cystic carcinoma (n = 17, 33%), salivary duct carcinoma (n = 14, 27%), mucoepidermoid carcinoma (n = 11, 21%), and acinic cell carcinoma (n = 6, 11%). Immunohistochemistry (IHC) was performed using the Ventana Discovery Ultra auto‐staining platform for EGFR, PD‐1, PD‐L1, and mismatch repair (MMR) proteins. CPS ≥1 defined PD‐L1 positive cases and log‐rank testing was performed to examine the relationship between PD‐L1 expression status and disease‐free survival (DFS) and overall survival (OS).
ResultsCPS positivity was seen in 9 (17.3%) patients, none of which were adenoid cystic carcinoma. All 52 (100%) cases expressed retained MMR proteins inferring microsatellite stability (MSS) and EGFR expression was identified in 45 of 52 (86.5%) patients. CPS positivity (score ≥1) was significantly associated with advanced pathological T status (P = .021), advanced pathological N status (P = .006), high histological tumor grade (P = .045), and positive histological margin (P = .023). Patients with PD‐L1 positivity in tumor cells did not have an inferior 3‐year OS (P = .93).
Conclusion The data from this retrospective study highlighting the uniform microsatellite stability alongside the low prevalence of CPS positivity suggests that only a minority of SGC patients may benefit from ICI therapy alone. The high rates of EGFR expression in SGC may be a target to augment immune checkpoint therapy response.

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microRNAs deregulation in head and neck squamous cell carcinoma

Juliana Carron, Caroline Torricelli, Janet K. Silva, Gabriela S. R. Queiroz, Manoela M. Ortega, Carmen S. P. Lima, Gustavo J. Lourenço

Publication date 06-11-2020


Abstract Head and neck (HN) squamous cell carcinoma (SCC) is the eighth most common human cancer worldwide. Besides tobacco and alcohol consumption, genetic and epigenetic alterations play an important role in HNSCC occurrence and progression. microRNAs (miRNAs) are small noncoding RNAs that regulate cell cycle, proliferation, development, differentiation, and apoptosis by interfering in gene expression. Expression profiling of miRNAs showed that some miRNAs are upregulated or downregulated in tumor cells when compared with the normal cells. The present review focuses on the role of miRNAs deregulations in HNSCC, enrolled in risk, development, outcome, and therapy sensitivity. Moreover, the influence of single nucleotide variants in miRNAs target sites, miRNAs seed sites, and miRNAs‐processing genes in HNSCC was also revised. Due to its potential for cancer diagnosis, progression, and as a therapeutic target, miRNAs may bring new perspectives in HNSCC understanding and therapy, especially for those patients with no or insufficient treatment options.

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Immune checkpoint expression in HNSCC patients before and after definitive chemoradiotherapy

Johannes Doescher, Peter Minkenberg, Simon Laban, Ulrike Kostezka, Adrian Witzleben, Thomas Karl Hoffmann, Patrick Johannes Schuler, Stephanie Ellen Weissinger

Publication date 06-11-2020


Abstract Background Primary platinum‐based chemoradiotherapy (CRT) remains the treatment of choice for nonresectable squamous cell carcinoma of the head and neck (HNSCC). Immune‐checkpoint modulators are used as palliative therapy and studied in combination with definitive CRT. However, the immunological changes by CRT need yet to be understood.
MethodsA cohort consisting of 67 paired tissue biopsies (N = 134) of HNSCC patients before and after CRT was created. The expression of PD‐1, PD‐L1, and CD27 of tumor and immune cells by immunohistochemistry was evaluated.
ResultsPD‐L1 expression on immune cells of non‐responders was significantly lower before CRT (P = .008). CD27 was expressed only on immune cells and not on cancer cells. A significant lower CD27‐expression score was observed following CRT (P = .019).
Conclusions Conventional CRT changes the expression of CD27 in the tumor microenvironment. Whether this is due to a loss of expression or a reduction of CD27+ cells must be evaluated in further analyses.

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HIF‐1a expression and differential effects on survival in patients with oral cavity, larynx, and oropharynx squamous cell carcinomas

Justin E. Swartz, Inge Wegner, Rob Noorlag, Pauline M. W. Kempen, Robert J. J. Es, Remco Bree, Stefan M. W. Willems

Publication date 05-11-2020


Abstract Background Hypoxia is a negative prognostic factor in head and neck squamous cell carcinomas. Under hypoxia, the hypoxia‐inducible factor (HIF)‐1a transcription factor is overexpressed. We investigated whether there were site differences in HIF‐1a expression and its effect on patient outcomes per subsite.
Design/MethodA total of 941 patients with HNSCC in the squamous cell carcinoma of the oropharynx (OPSCC, n = 302), oral cavity (OSCC, n = 391), or larynx (LSCC, n = 248) were included. Expression of HIF‐1a in tissue samples was investigated using immunohistochemistry. Overall survival (OS), disease‐free survival (DFS), and locoregional control (LRC) were analyzed.
ResultsHIF‐1a expression was higher in OSCC than in LSCC and OPSCC. High HIF‐1a expression led to worse prognosis in OPSCC (OS P = .029, DFS P = .085) and LSCC (OS P = .041, DFS P = .011) and better in OSCC (OS P = .055, DFS P = .012). There was no association between HIF‐1a and LRC.
Conclusions High HIF‐1a expression is related to poor outcome in OPSCC and LSCC and better outcome in OSCC.

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Regional disease control in sinonasal mucosal melanoma: Systematic review and meta‐analysis

Armando De Virgilio, Andrea Costantino, Federica Canzano, Remo Accorona, Giuseppe Mercante, Fabio Ferreli, Luca Malvezzi, Giovanni Colombo, Raul Pellini, Giuseppe Spriano

Publication date 05-11-2020


Abstract Purpose To systematically analyze the regional disease control after sinonasal mucosal melanoma (SNMM) primary treatment.
Methods The study was performed according to the PRISMA guidelines searching on Scopus, Pub Med/MEDLINE, Cochrane Library, and Google Scholar databases.
ResultsA total of 15 studies with 936 patients (median age: 68.0 years, IQR 65‐71) were included. Overall, the cumulative regional recurrence rate (RRR) was 18.4% (n = 917, 99% CI: 14.0%‐23.4%), with a median follow‐up of 30.0 months (n = 765, IQR 22.0‐37.0). The RRR in clinical node negative patients was 17.0% (99% CI: 12.2%‐22.5%), with a median follow‐up of 22.0 months (n = 327, IQR 21.5‐31.5).
Conclusions The RRR of SNMM after primary treatment is not to be neglected. Further prospective studies should be encouraged to clarify if elective treatment of the neck could be recommended at least in a subgroup of patients.

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Mock clinical testing in the validation of fluid‐phase biomarkers for head and neck carcinoma diagnosis: A Scoping review

John Adeoye, Chi Ching Joan Wan, Peter Thomson

Publication date 05-11-2020


Abstract This review sought to determine the range and nature of prospective‐sampling and blinding methods for validating nonviral biofluid markers diagnostic of head and neck carcinomas. Electronic database searching was conducted to identify studies published in English from January 1, 2009 to August 1, 2020. Sixteen studies from 17 articles published between 2011 and 2020 were included in this review. We found that about 3 out of 100 studies utilized at least one of the mock testing approaches for biomarker validation. Protein, mRNA, and metabolomic markers also represented the only groups whose validation has been attempted using these methods. Furthermore, studies that utilized both methods were found to have lower bias concerns on the quality assessment of diagnostic accuracy studies (QUADAS‐2) tool. Overall, there is a need to include these protocols in research endeavours verifying diagnostic biomarkers for head and neck carcinomas following the preliminary establishment of their classification accuracy.

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Analysis of palliative care treatment among head and neck patients with cancer: National perspective

Christopher Blake Sullivan, Zaid Al‐Qurayshi, Kristi Chang, Nitin A. Pagedar

Publication date 05-11-2020


Abstract Background To analyze the characteristics and survival patterns of patients with head and neck squamous cell carcinoma (SCC) who received palliative treatment during their first course of treatment.
Methods Cohort analysis utilizing the National Cancer Data Base (NCDB) of patients with a diagnosis of oral cavity/oropharyngeal, hypopharyngeal, and laryngeal SCC. Statistical analysis included multivariate logistic regression and Cox Hazard ratio modeling, and Kaplan‐Meier survival analysis.
Results165 081 patients were included, of which 2747 patients received palliative treatment. Patients who received palliative treatment tended to be ≥65 years old, black, Charlson/Deyo score ≥3, hypopharyngeal cancer, stage (III‐IV), with Medicaid insurance (P < .05). Patients were more likely to be treated with palliative intent if they underwent chemotherapy/radiotherapy and declined surgery (P < .001) compared to patients who underwent surgery and declined chemotherapy/radiotherapy (P = .006).
Conclusions Palliative care use in head and neck oncology is associated with older patients, non‐whites, Medicaid patients, and nonsurgically treated patients.

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Induction of interleukin‐6 by irradiation and its role in epithelial mesenchymal transition and radioresistance of nasopharyngeal carcinoma cells

Xun Yuan, Linli Zhang, Yu Huang, Dongbo Liu, Ping Peng, Shunfang Liu, Guoxian Long, Guangyuan Hu, Wei Sun

Publication date 05-11-2020


Abstract Background Epithelial mesenchymal transition (EMT) participates in the radioresistance of cancer cells. In this study, we evaluated whether interleukin‐6 (IL‐6) regulates EMT and subsequent radioresistance in nasopharyngeal carcinoma (NPC) cells.
Methods Western blot was used to analyze the expression of proteins. Immunofluorescent assay was performed to detect the position and content of specific proteins. Colony formation assay was applied to measure the proliferation ability of NPC cells. Flow cytometry was adopted to measure cell apoptosis.
ResultsNPC cells seen with typical morphological transition and unique proteins change of EMT when exposed to irradiation. IL‐6 and its downstream signal molecules elevated in irradiated cells. Blocking IL‐6 with anti‐IL‐6 receptor antibody hampered EMT and radioresistance. Cell radiosensitivity and apoptosis rates in irradiated NPC cells declined significantly upon IL‐6 stimulation.
Conclusion Irradiation could induce EMT and activate IL‐6 signaling in NPC cell lines. Blocking IL‐6 was able to inhibit EMT and cellular radioresistance.

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Clinical evaluation of the efficacy of materials used for primary reconstruction of orbital floor defects: Meta‐analysis

Maeva Bourry, Jean‐Benoit Hardouin, Fabien Fauvel, Pierre Corre, Pierre Lebranchu, Hélios Bertin

Publication date 04-11-2020


Abstract Background The aim of this network meta‐analysis (NMA) was to compare the clinical results obtained after primary reconstruction of orbital floor fractures (OFF) using different materials.
Methods Pub Med, Cochrane, and Google Scholar databases were screened from 1989 to 2019. For a study to be eligible, it had to evaluate two or more materials and report the following clinical parameters: diplopia and/or enophthalmos and/or other complications.
Results Nine studies involving 946 patients presenting with an OFF were included. After the surgical procedure, 105 patients (11%) had diplopia, while 43 patients (4.5%) suffered from enophthalmos. The NMA revealed that less postoperative diplopia and enophthalmos were obtained either by using polydioxanone (PDS), or a polymer of l‐lactic acid and dl‐lactic acid (PL/DLLA), or porous polyethylene, or titanium mesh compared with the use of autologous bone grafts.
ConclusionP(L/DL)LA and PDS seem to be the best options for small and intermediate defects, whereas the association of porous polyethylene and titanium should be preferred for larger defects.

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Machine learning models to predict length of stay and discharge destination in complex head and neck surgery

Khodayar Goshtasbi, Tyler M. Yasaka, Mehdi Zandi‐Toghani, Hamid R. Djalilian, William B. Armstrong, Tjoson Tjoa, Yarah M. Haidar, Mehdi Abouzari

Publication date 03-11-2020


Abstract Background This study develops machine learning (ML) algorithms that use preoperative‐only features to predict discharge‐to‐nonhome‐facility (DNHF) and length‐of‐stay (LOS) following complex head and neck surgeries.
Methods Patients undergoing laryngectomy or composite tissue excision followed by free tissue transfer were extracted from the 2005 to 2017 NSQIP database.
Results Among the 2786 included patients, DNHF and mean LOS were 421 (15.1%) and 11.7 ± 8.8 days. Four classification models for predicting DNHF with high specificities (range, 0.80‐0.84) were developed. The generalized linear and gradient boosting machine models performed best with receiver operating characteristic (ROC), accuracy, and negative predictive value (NPV) of 0.72‐0.73, 0.75‐0.76, and 0.88‐0.89. Four regression models for predicting LOS in days were developed, where all performed similarly with mean absolute error and root mean‐squared errors of 3.95‐3.98 and 5.14‐5.16. Both models were developed into an encrypted web‐based interface: https://uci-ent.shinyapps.io/head-neck/.
Conclusion Novel and proof‐of‐concept ML models to predict DNHF and LOS were developed and published as web‐based interfaces.

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2015 American Thyroid Association guidelines and thyroid‐stimulating hormone suppression after thyroid lobectomy

Robert Reed, Andrew Strumpf, Teresa G. Martz, Kaitlin J. Kavanagh, Katherine L. Fedder, Mark J. Jameson, David C. Shonka

Publication date 30-10-2020


Abstract Background2015 American Thyroid Association (ATA) guidelines recommended more conservative treatment in low‐risk well‐differentiated thyroid cancer (WDTC), stating that lobectomy alone may be sufficient. The guidelines further recommend mild thyroid‐stimulating hormone (TSH) level suppression (0.5‐2 mU/L) for this population. Our goal is to evaluate the natural history of patients undergoing lobectomy to determine the percentage that would require postoperative levothyroxine supplementation under these guidelines.
Methods Retrospective chart review of 168 patients that underwent lobectomy between 2010 and 2019 was performed. Preoperative and postoperative TSH values and the rate of patients prescribed levothyroxine were analyzed.
Results Thirty‐five percent of patients were prescribed levothyroxine postoperatively. At 6 weeks postoperatively, 66% had TSH value of >2; this increased to 76% by 6 to 12 months.
Conclusion To adhere to ATA guidelines for WDTC managed with lobectomy alone, the majority of patients (76%) would require postoperative levothyroxine supplementation. Low preoperative TSH was found to be the most significant predictor for postoperative TSH < 2.

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Prognostic value of the 8th edition American Joint Commission Cancer nodal staging system for patients with head and neck cutaneous squamous cell carcinoma: A multi‐institutional study

Peter P. Luk, Ardalan Ebrahimi, Michael J. Veness, Lachlan McDowell, Matthew Magarey, Kan Gao, Carsten E. Palme, Jonathan R. Clark, Ruta Gupta

Publication date 29-10-2020


Abstract Background The 8th edition American Joint Committee on Cancer staging manual (AJCC8) introduced a separate staging system for head and neck cutaneous squamous cell carcinoma (HNcSCC) which parallels mucosal SCC and incorporates extranodal extension (ENE). This study aims to evaluate its prognostic utility.
Methods Univariate analysis of 1146 patients with metastatic HNcSCC from four Australian cancer centers was performed according to both AJCC 7th (AJCC7) and the 8th editions.
ResultsAJCC8 increased classification of 924 (80.6%) patients to either pN2a or pN3b and 341 patients (29.8%) from stage III to IV compared to AJCC7. The disease‐specific survival (DSS) was not significantly different between pN1, pN2 or pN3a categories per AJCC8. Estimates of model performance for the AJCC8 pN staging revealed modest predictive capacity (Harrells C of 0.62 for DSS).
Conclusions The risk stratification according to pN classification of AJCC8 staging system performed poorly as a prognostic indicator.

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Combined endoscopic and transoral resection of a high‐staged juvenile nasopharyngeal angiofibroma: A pictorial essay

Wilson P. Lao, Kristelle J. Lagabon, Gabriel A. Arom, Paul C. Walker, Steve C. Lee

Publication date 28-10-2020


Abstract Juvenile nasopharyngeal angiofibromas (JNAs) are highly vascular and benign tumors that can expand into the skull base. Delay of treatment can result in intracranial invasion, requiring extensive open approaches such as a facial translocation, maxillary swing, or an orbitozygomatic craniotomy. We describe a single‐stage, combined endoscopic and transoral approach on a 14‐year‐old male with extensive high‐stage dumbbell‐shaped JNA involving the infratemporal fossa, orbit, buccal space, and intracranial extension into Meckels cave. Successful resection of the tumor and good postoperative outcome was achieved. A transoral approach allowed for greater access to the infratemporal fossa, where endonasal resection was not possible, allowing for improved visualization, greater traction, and dissection. In select highly staged JNAs with significant lateral extension and intracranial involvement, successful and complete resection may be accomplished with this combined approach. Utilization of this approach avoids the morbidity of more invasive open approaches.

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Development of a multiomics database for personalized prognostic forecasting in head and neck cancer: The Big Data to Decide EU Project

Stefano Cavalieri, Loris De Cecco, Ruud H. Brakenhoff, Mara Serena Serafini, Silvana Canevari, Silvia Rossi, Davide Lanfranco, Frank J. P. Hoebers, Frederik W. R. Wesseling, Simon Keek, Kathrin Scheckenbach, Davide Mattavelli, Thomas Hoffmann, Laura López Pérez, Giuseppe Fico, Marco Bologna, Irene Nauta, C. René Leemans, Annalisa Trama, Thomas Klausch, Johannes Hans Berkhof, Vasilis Tountopoulos, Ron Shefi, Luca Mainardi, Franco Mercalli, Tito Poli, Lisa Licitra, the BD2Decide Consortium

Publication date 27-10-2020


Abstract Background Despite advances in treatments, 30% to 50% of stage III‐IV head and neck squamous cell carcinoma (HNSCC) patients relapse within 2 years after treatment. The Big Data to Decide (BD2Decide) project aimed to build a database for prognostic prediction modeling.
Methods Stage III‐IV HNSCC patients with locoregionally advanced HNSCC treated with curative intent (1537) were included. Whole transcriptomics and radiomics analyses were performed using pretreatment tumor samples and computed tomography/magnetic resonance imaging scans, respectively.
Results The entire cohort was composed of 71% male (1097)and 29% female (440): oral cavity (429, 28%), oropharynx (624, 41%), larynx (314, 20%), and hypopharynx (170, 11%); median follow‐up 50.5 months. Transcriptomics and imaging data were available for 1284 (83%) and 1239 (80%) cases, respectively; 1047 (68%) patients shared both.
Conclusions This annotated database represents the HNSCC largest available repository and will enable to develop/validate a decision support system integrating multiscale data to explore through classical and machine learning models their prognostic role.

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Nodal disease burden and outcome of medullary thyroid carcinoma

Lindsey E. Moses, Jamie R. Oliver, Janine M. Rotsides, Qianhui Shao, Kepal N. Patel, Luc G. T. Morris, Babak Givi

Publication date 27-10-2020


Abstract Background Medullary thyroid carcinoma (MTC) is a rare malignancy with high incidence of cervical lymph node (CLN) metastasis. We investigated the impact of nodal disease burden on survival.
Methods We searched the National Cancer Database for MTC patients treated surgically. Impact of nodal metastasis on survival was analyzed using Cox univariable and multivariable regression.
Results We identified 2627 patients from 2004 to 2015. Positive CLNs were identified in 1433 (54.5%), and 542 (20.6%) had >10 CLN+. Overall survival was 94.5% and 89.6% at 3 and 5 years. Patients with 11 to 20 CLN+ had significantly worse survival than patients with 1 to 10 CLN+ in univariable and multivariable analyses (HR = 3.56 (2.31‐5.50) vs 2.26 (1.60‐3.20); P < .0001). The ratio of positive to dissected CLN was associated with overall survival.
Conclusions Higher burden of nodal disease is associated with worse survival in MTC. The number of positive nodes could be a valuable prognosticator in addition to the current staging system.

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Impact of early oral hydration on pharyngocutaneous fistula following total laryngectomy

Ovie Edafe

Publication date 26-10-2020


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Reply to the Letter to the Editor regarding “Early oral hydration protects against pharyngocutaneous fistula after total laryngectomy or total pharyngolaryngectomy”

Matthieu Le Flem, Laure Santini, Carole Boulze, Abdallah Alshukry, Antoine Giovanni, Patrick Dessi, Nicolas Fakhry

Publication date 26-10-2020


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Need for long‐term follow‐up in sinonasal inverted papilloma: A Single‐institution experience

Gregori H. A. Binz, Michael B. Soyka, David Holzmann, Christian M. Meerwein

Publication date 26-10-2020


Abstract Background Most studies on sinonasal inverted papillomas (SNIPs) regarding risk factors for recurrence, recurrence rates (RRs) and malignant transformation are biased by a significant proportion of revision cases.
Methods Retrospective study on patients with consecutive, treatment‐naïve SNIPs at a tertiary referral center between 1999 and 2019.
Results Overall, RR was 9.8% (10 of 102 patients), with 2 of 10 recurrences (20%) occurring after more than 5 years. Histopathological workup revealed synchronous malignancy in 2 of 102 patients (2%). Subgroup analysis revealed a significantly higher RR for SNIPs involving the frontal sinus (26.3% vs 6.0%, P = .02). No SNIPs primarily originating from the frontal sinus were observed.
Conclusion Overall, RR of treatment‐naïve SNIPs is comparably low; however, long‐term follow‐up is mandatory due to late recurrences. Secondary involvement of the frontal sinus was identified as risk factor for recurrence. No SNIPs primarily originating from frontal sinus were observed.

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