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Kaplan-Meier survival curves for T1/2 and T3/4 tumors stratified by the expression of (A) EGFR and (B) HER2. Based on AQUA-expression scores.

Correlation between marker expression intensity and sample collection year. Corr. = correlation coefficient, A.U. = arbitrary unites.

Supplementary Table S1 (Excel file). TCGA datasets; Supplementary Table S2. CART cutoff points for each marker and the number of samples (N) in each category; Supplementary Table S3. Adjusted survival analysis; Supplementary Table S4. TCGA p16 expression data for HPV- and HPV+ HNSCC.

(A) Western blots for the indicated protein markers after siRNA depletion, (B) representative high and low staining immunofluorescent microscopy images for each marker. CK = cytokeratin (epithelial tumor stain), DNA = DAPI stain, C = control siRNA (siGL2), IB = immunoblotting, scale bar = 100μm.

TCGA datasets.

(A and B) KM survival curves specimens with (A) high EGFR stratified by wild type (WT) or amplified (AMP) CCND1, or cases with (B) low EGFR stratified by p16 mRNA expression (TCGA cohort), (C) correlation between medium CDK6 (M) or high CDK6 (H) mRNA expression and CCND1 expression. m = slope. mRNA data for 243 HPV- HNSCC samples (6) were downloaded using cBioportal (26, 27). Please also see Figure 4.

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

The incidence of Merkel cell carcinoma (MCC) continues to increase. Understanding of MCC biology has advanced rapidly, with current staging providing valuable prognostic information. MCC treatment often is multidisciplinary. Surgery remains an important component in the staging and treatment, most commonly involving wide excision of the cancer and sentinel lymph node biopsy. Lymphadenectomy is used to treat nodal disease. Radiotherapy enhances locoregional control and possibly survival. Systemic therapies, in particular novel immunotherapies, may be promising in the treatment of advanced or recurrent and metastatic disease.

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

Author(s): MD Anderson Head and Neck Surgery Treatment Guidelines Consortium; Consortium members; Maniakas, Anastasios; Jozaghi, Yelda; Zafereo, Mark E; Sturgis, Erich M; Su, Shirley Y; Gillenwater, Ann M; Gidley, Paul W; Lewis, Carol M; Diaz, Eduardo; Goepfert, Ryan P; Kupferman, Michael E; Gross, Neil D; Hessel, Amy C; Pytynia, Kristen B; Nader, Marc-Elie; Wang, Jennifer R; Lango, Miriam N; Kiong, Kimberley L; Guo, Theresa; Zhao, Xiao; Yao, Christopher MKL; Appelbaum, Eric; Alpard, Jennifer; Garcia, Jose A; Terry, Shawn; Flynn, Jill E; Bauer, Sarah; Fournier, Danielle; Burgess, Courtlyn G; Wideman, Cayla; Johnston, Matthew; You, Chenxi; De Luna, Rolando; Joseph, Liza; Diersing, Julia; Prescott, Kaitlin; Heiberger, Katherine; Mugartegui, Lilian; Rodriguez, Jessica; Zendehdel, Sara; Sellers, Justin; Friddell, Rebekah A; Thomas, Ajay; Khanjae, Sonam J; Schwarzlose, Katherine B; Chambers, Mark S; Hofstede, Theresa M; Cardoso, Richard C; Wesson, Ruth Aponte; Won, Alex; Otun, Adegbenga O; Gombos, Dan S; Al-Zubidi, Nagham; Hutcheson, Katherine A; Gunn, G Brandon; Rosenthal, David I; Gillison, Maura L; Ferrarotto, Renata; Weber, Randal S; Hanna, Ehab Y; Myers, Jeffrey N; Lai, Stephen Y | Abstract: BackgroundCOVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel.MethodsThe MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular.RecommendationsEach subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred.ConclusionThese guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.

BACKGROUND: Tracheal dryness is a concern after total laryngectomy due to the potential for mucus plugs (MP). This study compared heat and moisture exchanger (HME) cassettes to external tracheal humidification (ETH) surrounding MP events. METHODS: A retrospective comparative cohort study comparing outcomes before/after implementation of a patient safety initiative utilizing HME during post-laryngectomy hospitalization. The number of MP events were compared with a pre-implementation control group using ETH. Patient characteristics were analyzed for correlation with MP. RESULTS: The rate of MP was significantly lower in the HME group than ETH (0.13 and 0.38 per 10 inpatient days, respectively, p=0.016). The proportion of patients with one or more MP events was also significantly reduced in the HME group (50% ETH and 11% HME, p=0.012). Method of humidification was the only significant variable associated with MP on logistic regression modeling (p=0.008). CONCLUSIONS: HMEs were superior to ETH for prevention of mucus plugging.

OBJECTIVE: Hospital-acquired aspiration pneumonia remains a rare but potentially devastating problem. The best means by which to prevent aspiration in a cancer hospital population has not been evaluated. The aim of this study was to evaluate the impact of dysphagia screening on aspiration pneumonia rates in an acute care oncology hospital. METHODS: A prospective single-institution quality-improvement dysphagia screening protocol at a comprehensive cancer center. Effect of dysphagia screening implemented in 2016 on hospital acquired aspiration pneumonia rates coded “aspiration pneumonitis due to food/vomitus” were compared with rates from 2014-15, prior to implementation. Screening compliance, screening outcomes, patient demographics, and medical data were reviewed as part of a post hoc analysis. RESULTS: Of 12,392 admissions in 2014-16, 97 patients developed aspiration pneumonia during their hospitalization. No significant change in aspiration pneumonia rate was seen during the dysphagia screening year when compared to prior years (baseline- 7.36 and screening year- 8.78 per 1000 discharges p=0.33). Sixty-eight of the cases (66%) were associated with emesis/gastrointestinal obstruction or perioperative aspiration and only 15 (15%) with oropharyngeal dysphagia. Multivariate analysis found that patients admitted to GI surgery had an aspiration risk equivalent to patients admitted to head and neck, thoracic and pulmonary services (OR 0.65, p= 0.2). DISCUSSION: Nursing-initiated dysphagia screening did not decrease aspiration pneumonia rates. The causes of aspiration-associated pneumonia were heterogeneous. Aspiration of intestinal contents is a more common source of hospital-acquired pneumonia than oropharyngeal dysphagia.

PURPOSE Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus–associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.

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

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

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

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

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

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

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

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

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

Objective: To report T1-2N0 tongue cancer recurrences initially treated with surgery alone. Methods: Between 1990 and 2010, 27 patients at tertiary hospital referral center institution were treated with curative intent for locoregional recurrence after initial glossectomy with or without neck dissection for T1-2N0 tongue cancer. None had received adjuvant postoperative radiation as a component of the original treatment. Results: Median time to locoregional recurrence was 12 months (range 5â39 months) and 78% of failures occurred in the first 2 years. Most treatment failures were local (63%). Salvage strategy was risk-adapted by individual patient. The 5-year disease specific survival (DSS) was 61%. Patients with local recurrences alone fared significantly better than those with regional recurrences (5-yr DSS: 86% vs. 22%, PÂ =Â 0.0018). Local recurrences were usually treated by surgery alone, while regional recurrences were more commonly treated with combined modality treatment (PÂ =Â 0.005). Conclusions: Recurrence of early stage oral tongue cancer can be successfully salvaged in a majority of cases. Patients developing regional recurrence have significantly worse prognosis than those with local failures. Keywords: Oral cancer, Head and neck cancer, Tongue neoplasms, Salvage therapy

OBJECTIVES To investigate the prognostic impact of primary tumor-specific growth rate (TSGR) on treatment outcomes after definitive radiation therapy (RT) for nonoropharyngeal squamous cell carcinoma (non-OPSCC). METHODS The diagnostic tumor and nodal volumes of 39 non-OPSCC patients were contoured and compared to corresponding RT planning scan volumes to determine TSGR. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were evaluated according to the Kaplan-Meier method; and hazard ratios (HR) were estimated using Cox regression. Based on the 75th percentile TSGR of 2.18%, we stratified patients into a high TSGR group (≥ 2.18% per day) and low TSGR group (

6010 Background: Definitive or postoperative chemoradiation (CRT) is highly curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a potential deintensification strategy, we studied primary transoral surgery (TOS) and, in intermediate pathologic risk patients, reduced dose postoperative RT (PORT). Methods: E3311 is a phase II trial with randomization to reduced- or standard-dose PORT for resected stage III-IVa (AJCC7) intermediate pathologic risk HPV+ OPC, stratified by smoking history. Primary endpoints have been reported; we now present updated 3-year PFS and patient-reported outcomes (PRO), including head and neck-cancer specific quality of life (FACT-H&N) and swallowing perception and performance (MDADI). Results: Of 519 enrolled patients, 495 underwent TOS. The primary oncologic endpoint was 2-year PFS for 50 Gy (Arm B) or 60Gy (Arm C). Among 360 eligible and treated patients (ETP), Arm A (observation, N = 38) enrolled 11%, Arms B (N = 100) or C (N = 109) randomized 58%, and Arm D (66Gy + weekly cisplatin, N = 113) enrolled 31%. With 35.1 months median follow-up, 3-year PFS Kaplan-Meier estimate is 96.9% (90% CI [91.9%, 100%]) for Arm A; 94.9% (90% CI [91.3%, 98.6%]) for Arm B; 93.5% (90% CI [89.4%, 97.9%]) for Arm C; and 90.7% (90% CI [86.2%, 95.4%]) for Arm D. Recurrences and death without recurrence were 4 and 1 in Arm B, and 5 and one in Arm C. Smokers ( > 10 pack-years) did not have worse 3-year PFS in Arms B or C. Treatment arm distribution and outcome for ineligible patients who started adjuvant therapy mirrored the 360 ETP. A comparison combining arms B/C versus arm D in the proportion of patients stable/improved in FACT-H&N total score, from baseline to 6 months post-treatment as a pre-specified endpoint, was 56% vs. 38% (p value = 0.011, one-sided Fisher’s exact test); however, underlying differences in treatment and risk may be confounding. An exploratory comparison between Arms B and C revealed improvement in FACT H&N (63% in Arm B vs. 49% in Arm C had a stable/improved score, p-value = 0.056). Conclusions: Primary TOS and reduced PORT retained outstanding oncologic outcome at 35 months follow up, with favorable QOL and functional outcomes, in intermediate risk HPV+ OPC. Clinical trial information: NCT 01898494.

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

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

Clinical decision making for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and anatomic location, with few validated biomarkers. The epidermal growth factor receptor (EGFR) is an important therapeutic target, but its value in guiding therapeutic decision making remains ambiguous. We integrated analysis of clinically annotated tissue microarrays with analysis of data available through the TCGA, to investigate the idea that expression signatures involving EGFR, proteins regulating EGFR function, and core cell-cycle modulators might serve as prognostic or drug response–predictive biomarkers. This work suggests that consideration of the expression of NSDHL and proteins that regulate EGFR recycling in combination with EGFR provides a useful prognostic biomarker set. In addition, inactivation of the tumor suppressor retinoblastoma 1 (RB1), reflected by CCND1/CDK6-inactivating phosphorylation of RB1 at T356, inversely correlated with expression of EGFR in patient HNSCC samples. Moreover, stratification of cases with high EGFR by expression levels of CCND1, CDK6, or the CCND1/CDK6-regulatory protein p16 (CDKN2A) identified groups with significant survival differences. To further explore the relationship between EGFR and RB1-associated cell-cycle activity, we evaluated simultaneous inhibition of RB1 phosphorylation with the CDK4/6 inhibitor palbociclib and of EGFR activity with lapatinib or afatinib. These drug combinations had synergistic inhibitory effects on the proliferation of HNSCC cells and strikingly limited ERK1/2 phosphorylation in contrast to either agent used alone. In summary, combinations of CDK and EGFR inhibitors may be particularly useful in EGFR and pT356RB1-expressing or CCND1/CDK6-overexpressing HPV-negative HNSCC. Mol Cancer Ther; 15(10); 2486–97. ©2016 AACR.

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

Objectives: Lymph node yields (LNYs) following neck dissection have been associated with differences in oral cavity cancer survival. The objective of this study was to evaluate temporal trends in LNYs in neck dissections for oral cavity carcinoma. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER 18) database. Inclusion criteria included diagnosis of malignant oral cavity cancer (tongue and floor of mouth) squamous cell carcinomas diagnosed from January 1, 2006-December 31, 2016. Patients with AJCC 6th Edition Stages 1-4a who underwent surgery were included. All-cause age-adjusted mortality for tongue and floor of mouth cancers during this period was assessed using SEER*Stat. Results: The median LNY among 8,580 patients in the sample was 25 LNs (Interquartile range 14-39). LNY statistically increased over time from 22 LNs in 2004 to 27 in 2014 (p < 0.0001). In contrast, there was no change in the median number of positive LNs during the same period (median 2 positive LNs in 2004 and 2014). There was no significant difference in lymph node yield based on sex, region, insurance status, or relative location to a metropolitan center. After adjusting for patient age, sex, race, marital status, regional income, and percent current smokers in the county of residence, tumor subsite and TNM stage, LNY less than 18 was independently associated with a 44% greater risk of death from any cause, compared with greater LNYs (HR 1.44, 95% CI 1.29-1.60, p=.0001). During this period, all-cause age-adjusted mortality declined from 469.7 per 100,000 (468.2-471.2) to 429.0/100,000 (428.2-430.8). Conclusion: LNY following neck dissection for oral tongue and floor of mouth cancers increased significantly over a decade, during which survival also improved. The cause of improved LNY is not known but may nevertheless be contributing to declining mortality in patients with oral tongue and floor of mouth cancers. Citation Format: Punam Patel, Suraj Kedarisetty, Miriam Lango. Trends in lymph node yield for neck dissection and oral cavity carcinoma survival [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B40.

6500 Background: ECOG-ACRIN 3311 examines reduced postoperative therapy in patients with “intermediate risk” p16+ oropharynx cancer (OPC) undergoing primary transoral surgical management. We report the primary endpoint of 2-year progression free survival (PFS) for patients randomized to 50Gy vs 60Gy without chemotherapy. Methods: Between December 2013 and July 2017, 82 credentialed surgeons performed transoral resection (TOS) for 519 OPC patients (cT1-2 stage III/IV AJCC7 without matted neck nodes); post-operative management was determined by pathologically assessed risk. Among 353 eligible and treated patients, Arm A enrolled 10% (N=37) for clear margins, 0-1 nodes, no extranodal extension (ENE)), Arms B (50Gy, N=102) or C (60Gy, N=104) randomized 58%, for clear/close margins, 2-4 + nodes, or ENE ≤1mm, while Arm D (N=110, 60-66Gy plus weekly cisplatin, 40 mg/m2, positive margin with any T stage, >4 + nodes, or >1mm ENE) enrolled 31%. Arm D assignment was based on >1mm ENE (76%), > 4 nodes (27%), and/or positive margins (11%). Intermediate-risk patients were stratified by smoking history (>10 pk-yr). Of the 80 pts (15%) deemed ineligible, 28 had scans/labs not done per protocol, however treatment arm distribution for all patients mirrored that for the 353 pts eligible and treated. Results: Median follow-up was 31.8 months. 2 yr PFS for Arms A, B and C were 93.9% (90% CI=87.3%, 100%), 95.0% (90% CI=91.4%, 98.6%) and 95.9% (90% CI=92.6%, 99.3%) respectively, while Arm D was 90.5% (90% CI=85.9%, 95.3%). The regimen of TOS + low-dose radiation is considered worthy of further study, since the primary endpoint of the upper bound of the 90% CI (in the intermediate risk group) exceeding 85% was met. Of 17 progression events, 7 were locoregional. There were 10 distant recurrences: Arm A=1, Arm B=2, Arm C=4, Arm D=3. Grade III/IV treatment-related AE rates were 15%/2% during surgery, 13%/2% for Arm B and 25%/0% for Arm C. There were 2 treatment-related deaths (one surgical and one Arm D). Conclusions: Transoral resection of p16+ OPC is safe and results in good oncologic outcome, presenting a promising deintensification approach. For patients with low-risk disease, 2-yr PFS is favorable without post-operative therapy. For those with uninvolved surgical margins

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

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

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

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

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

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

// Tim N. Beck 1,4,* , John Kaczmar 1,2,* , Elizabeth Handorf 1 , Anna Nikonova 1 , Cara Dubyk 1 , Suraj Peri 1 , Miriam Lango 3 , John A. Ridge 3 , Ilya G. Serebriiskii 1,6 , Barbara Burtness 5 , Erica A. Golemis 1,4 and Ranee Mehra 1,2 1 Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA, USA 2 Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA 3 Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA 4 Molecular and Cell Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA, USA 5 Department of Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA 6 Department of Biochemistry, Kazan Federal University, Kazan, Russia * These authors contributed equally to this work and should be considered Co-first authors Correspondence to: Ranee Mehra, email: // Keywords : biomarkers, RB1, CDK4/6, E2F, head and neck cancer Received : April 16, 2015 Accepted : May 22, 2015 Published : May 29, 2015 Abstract Locally advanced squamous cell carcinoma of the head and neck (SCCHN) that is not associated with human papillomavirus (HPV) has a poor prognosis in contrast to HPV-positive disease. To better understand the importance of RB1 activity in HPV-negative SCCHN, we investigated the prognostic value of inhibitory CDK4/6 phosphorylation of RB1 on threonine 356 (T 356 ) in archival HPV-negative tumor specimens from patients who underwent surgical resection and adjuvant radiation. We benchmarked p T356 RB1 to total RB1, Ki67, p T202/Y204 ERK1/2, and TP53, as quantified by automatic quantitative analysis (AQUA), and correlated protein expression with tumor stage and grade. High expression of p T356 RB1 but not total RB1 predicted reduced overall survival (OS; P = 0.0295), indicating the potential relevance of post-translational phosphorylation. Paired analysis of The Cancer Genome Atlas (TCGA) data for regulators of this RB1 phosphorylation identified loss or truncating mutation of negative regulator CDKN2A (p16) and elevated expression of the CDK4/6 activator CCND1 (cyclin D) as also predicting poor survival. Given that CDK4/6 inhibitors have been most effective in the context of functional RB1 and low expression or deletion of p16 in other tumor types, these data suggest such agents may merit evaluation in HPV-negative SCCHN, specifically in cases associated with high p T356 RB1.

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

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

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

Examine the relationship among the severity of patient-perceived voice impairment, perceptual dysphonia severity, occupational voice demand, and voice therapy adherence. Identify clinical predictors of increased risk for therapy nonadherence.A retrospective cohort study of patients presenting with a chief complaint of persistent dysphonia at an interdisciplinary voice center was done. The Voice Handicap Index-10 (VHI-10) and the Voice-Related Quality of Life (V-RQOL) survey scores, clinician rating of dysphonia severity using the Grade score from the Grade, Roughness Breathiness, Asthenia, and Strain scale, occupational voice demand, and patient demographics were tested for associations with therapy adherence, defined as completion of the treatment plan. Classification and Regression Tree (CART) analysis was performed to establish thresholds for nonadherence risk.Of 166 patients evaluated, 111 were recommended for voice therapy. The therapy nonadherence rate was 56%. Occupational voice demand category, VHI-10, and V-RQOL scores were the only factors significantly correlated with therapy adherence (P 0.0001, P = 0.018, and P = 0.008, respectively). CART analysis found that patients with low or no occupational voice demand are significantly more likely to be nonadherent with therapy than those with high occupational voice demand (P 0.001). Furthermore, a VHI-10 score of ≤29 or a V-RQOL score of40 is a significant cutoff point for predicting therapy nonadherence (P 0.011 and P 0.004, respectively).Occupational voice demand and patient perception of impairment are significantly and independently correlated with therapy adherence. A VHI-10 score of ≤9 or a V-RQOL score of40 is a significant cutoff point for predicting nonadherence risk.

Background The purpose of this study was to report associations between p16 status, clinicopathologic characteristics, and outcomes for head and neck squamous cell carcinoma of unknown primary (CUP). Methods Specimens of squamous cell CUP were reanalyzed. Human papillomavirus (HPV) status was determined by p16 stain. A tissue microarray (TMA) was constructed to evaluate biomarkers potentially prognostic in head and neck squamous cell carcinoma (HNSCC). Results A majority of the population (n = 26; 74%) was p16 positive (+). Prognostic factors benefiting survival were p16+ status (p

Background Psychosocial functioning is associated with vascular endothelial growth factor (VEGF) in various patient populations. This study examined whether psychosocial functioning in patients with head and neck squamous cell carcinoma (HNSCC) is associated with tumor VEGF expression, a protein that stimulates angiogenesis and is associated with poor prognosis. Methods Forty-two newly diagnosed patients completed assessments of psychosocial functioning (ie, depressive symptoms, perceived stress, anxiety, social support) before surgery. Tumor samples were obtained for VEGF analysis and human papillomavirus (HPV)-typing. Results Poorer psychosocial functioning was associated with greater VEGF expression controlling for disease stage (odds ratio [OR], 4.55; 95% confidence interval [CI], 1.72–12.0; p < .01). When examined by HPV status, the association between psychosocial functioning and VEGF remained significant among patients who were HPV negative (OR, 5.50; 95% CI, 1.68–17.3; p < .01), but not among patients who were HPV positive. Conclusion These findings inform our understanding of the biobehavioral pathways that may contribute to poor outcomes in non-HPV-associated HNSCCs. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1113–1119, 2014

Head/neck sarcomas are rare, accounting for about 1% of head/neck malignancies and 5% of sarcomas. Outcomes have historically been worse in this group, due to anatomic constraints leading to difficulty in completely excising tumors, with high rates of local recurrence. We retrospectively analyzed cases of head/neck soft tissue sarcomas (STS) and osteogenic sarcomas managed in a multi-disciplinary setting at Fox Chase Cancer Center from 1999-2009 to describe clinicopathologic characteristics, treatment, outcomes, and prognostic factors for disease control and survival. Thirty patients with STS and seven patients with osteogenic sarcoma were identified. Most STS were high grade (23) and almost all were localized at presentation (28). Common histologies were synovial cell (6), rhabdomyosarcoma (5), angiosarcoma (4), liposarcoma (4) and leiomyosarcoma (3). The type of primary therapy and disease outcomes were analyzed. Cox proportional hazards regression analysis was performed to identify predictors of disease-free survival (DFS) and overall survival (OS). The HR and 95% CI for Cox model and median DFS/OS analyzed by Kaplan-Meier curves were calculated.