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T lymphocytes expressing CD57 and lacking costimulatory receptors CD27/CD28 have been reported to accumulate with aging, chronic infection, and cancer. These cells are described as senescent, with inability to proliferate but enhanced cytolytic and cytokine-producing capacity. However, robust functional studies on these cells taken directly from cancer patients are lacking. We isolated these T cells and their CD27/28+ counterparts from blood and tumor samples of 50 patients with previously untreated head and neck cancer. Functional studies confirmed that these cells have enhanced ability to degranulate and produce IFN-γ. They also retain the ability to proliferate, thus are not senescent. These data suggest that CD27/28-CD57+ CD8+ T cells are a subset of highly differentiated, CD45RA+ effector memory (T EMRA ) cells with retained proliferative capacity. Patients with > 34% of these cells among CD8+ T cells in the blood had a higher rate of locoregional disease relapse, suggesting these cells may have prognostic significance., Competing Interests: NCS discloses consulting fees from Sensorion, Regeneron, and GeoVax in addition to research funding from Astex Pharmaceuticals. The authors have no conflicting financial interests related to this work., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Significance: Polarized hyperspectral microscopes with the capability of full Stokes vector imaging have potential for many biological and medical applications., Aim: The aim of this study is to investigate polarized hyperspectral imaging (PHSI) for improving the visualization of collagen fibers, which is an important biomarker related to tumor development, and improving the differentiation of normal and tumor cells on pathologic slides., Approach: We customized a polarized hyperspectral microscopic imaging system comprising an upright microscope with a motorized stage, two linear polarizers, two liquid crystal variable retarders (LCVRs), and a compact SnapScan hyperspectral camera. The polarizers and LCVRs worked in tandem with the hyperspectral camera to acquire polarized hyperspectral images, which were further used to calculate four Stokes vectors: S 0 , S 1 , S 2 , and S 3 . Synthetic RGB images of the Stokes vectors were generated for the visualization of cellular components in PHSI images. Regions of interest of collagen, normal cells, and tumor cells in the synthetic RGB images were selected, and spectral signatures of the selected components were extracted for comparison. Specifically, we qualitatively and quantitatively investigated the enhanced visualization and spectral characteristics of dense fibers and sparse fibers in normal stroma tissue, fibers accumulated within tumors, and fibers accumulated around tumors., Results: By employing our customized polarized hyperspectral microscope, we extract the spectral signatures of Stokes vector parameters of collagen as well as of tumor and normal cells. The measurement of Stokes vector parameters increased the image contrast of collagen fibers and cells in the slides., Conclusions: With the spatial and spectral information from the Stokes vector data cubes ( S 0 , S 1 , S 2 , and S 3 ), our PHSI microscope system enhances the visualization of tumor cells and tumor microenvironment components, thus being beneficial for pathology and oncology., (© 2024 The Authors.)

Significance: Automatic, fast, and accurate identification of cancer on histologic slides has many applications in oncologic pathology., Aim: The purpose of this study is to investigate hyperspectral imaging (HSI) for automatic detection of head and neck cancer nuclei in histologic slides, as well as cancer region identification based on nuclei detection., Approach: A customized hyperspectral microscopic imaging system was developed and used to scan histologic slides from 20 patients with squamous cell carcinoma (SCC). Hyperspectral images and red, green, and blue (RGB) images of the histologic slides with the same field of view were obtained and registered. A principal component analysis-based nuclei segmentation method was developed to extract nuclei patches from the hyperspectral images and the coregistered RGB images. Spectra-based support vector machine and patch-based convolutional neural networks (CNNs) were implemented for nuclei classification. The CNNs were trained with RGB patches (RGB-CNN) and hyperspectral patches (HSI-CNN) of the segmented nuclei and the utility of the extra spectral information provided by HSI was evaluated. Furthermore, cancer region identification was implemented by image-wise classification based on the percentage of cancerous nuclei detected in each image., Results: RGB-CNN, which mainly used the spatial information of nuclei, resulted in a 0.81 validation accuracy and 0.74 testing accuracy. HSI-CNN, which utilized the spatial and spectral features of the nuclei, showed significant improvement in classification performance and achieved 0.89 validation accuracy as well as 0.82 testing accuracy. Furthermore, the image-wise cancer region identification based on nuclei detection could generally improve the cancer detection rate., Conclusions: We demonstrated that the morphological and spectral information contribute to SCC nuclei differentiation and that the spectral information within hyperspectral images could improve classification performance.

Purpose: On the basis of synergistic effects between green tea polyphenon E (PPE) and EGFR-tyrosine kinase inhibitor in preclinical studies, we conducted a phase Ib study of the PPE and erlotinib combination in patients with advanced premalignant lesions (APL) of the oral cavity and larynx., Patients and Methods: Patients were treated with a fixed dose of PPE (200 mg three times a day) and dose escalation of erlotinib (50, 75, 100 mg daily) for 6 months with tissue biopsy at baseline and 6 months. Primary endpoints were safety and toxicity; secondary endpoints were evaluation of pathologic response, cancer-free survival (CFS), overall survival (OS), and biomarker modulation., Results: Among 21 enrolled patients, 19 began treatment and 17 completed 6 months of treatment with PPE and erlotinib. Main characteristics of treated patients: 15 severe dysplasia or carcinoma in situ and 17 oral cavity. Only skin rash was associated with dose-limiting toxicity and MTD. Recommended doses for phase II studies are PPE 600 mg daily plus erlotinib 100 mg daily for 6 months. Pathologic responses in 17 evaluable patients: pathologic complete response (47%) and pathologic partial response (18%). The 5-year CFS and OS were 66.3% and 93%, respectively. Among tested biomarkers, only phosphorylated ERK was correlated with response to treatment., Conclusions: Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early-stage head and neck cancer., (©2020 American Association for Cancer Research.)

Primary management for head and neck cancers, including squamous cell carcinoma (SCC), involves surgical resection with negative cancer margins. Pathologists guide surgeons during these operations by detecting cancer in histology slides made from the excised tissue. In this study, 381 digitized, histological whole-slide images (WSI) from 156 patients with head and neck cancer were used to train, validate, and test an inception-v4 convolutional neural network. The proposed method is able to detect and localize primary head and neck SCC on WSI with an AUC of 0.916 for patients in the SCC testing group and 0.954 for patients in the thyroid carcinoma testing group. Moreover, the proposed method is able to diagnose WSI with cancer versus normal slides with an AUC of 0.944 and 0.995 for the SCC and thyroid carcinoma testing groups, respectively. For comparison, we tested the proposed, diagnostic method on an open-source dataset of WSI from sentinel lymph nodes with breast cancer metastases, CAMELYON 2016, to obtain patch-based cancer localization and slide-level cancer diagnoses. The experimental design yields a robust method with potential to help create a tool to increase efficiency and accuracy of pathologists detecting head and neck cancers in histological images.

Background: There is conflicting evidence regarding the role of peritumoral lymphatic vessel density (LVD) and blood microvessel density (MVD) in the metastasis and prognosis of head and neck squamous cell carcinoma (HNSCC). Existing studies are limited to one or two head and neck subsites and/or small sample sizes. A larger study incorporating multiple sub-sites is needed to address the role of peritumoral LVD and MVD in HNSCC metastasis and prognosis., Methods: Tissue samples from 200 HNSCC cases were stained simultaneously using immunohistochemistry (IHC) for markers of peritumoral LVD (lymphatic vessel marker D240) and MVD (blood vessel marker CD31). Of the stained slides, 166 and 167 were evaluable for LVD and MVD, respectively. The results were then correlated with clinicopathologic features and patient outcomes., Results: Patients with metastatic disease were more likely to have high peritumoral MVD. Through multivariable analyses, MVD was not significantly related to DFS and OS, while low LVD was related to higher risk of disease progression and poor survival., Conclusions: Peritumoral MVD was found to be positively associated with metastasis, while LVD was found to be inversely related to both metastasis and progression of HNSCC. These findings may suggest a prognostic role of both peritumoral LVD and MVD in patients with HNSCC., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Head and neck malignancies comprise a heterogeneous group of malignancies that cause significant morbidity to those affected. These malignancies are associated with specific risk factors and exposures, some of which impact prognosis. The most common risk factors for developing head and neck cancers are tobacco and alcohol use. Marijuana and e-cigarettes, occupational exposures, and use of topical substances have also been linked to head and neck cancers. Human papilloma virus has been associated with oropharyngeal cancer. Such measures as oral hygiene, screening, smoking cessation, and vaccination are measures taken to decrease the incidence and morbidity of head and neck cancers., (Published by Elsevier Inc.)

Purpose: Previous studies revealed diverging results regarding the role of survivin in squamous cell carcinoma of the head and neck (SCCHN). This study aimed to evaluate the clinical significance of survivin expression in SCCHN; the function of survivin in DNA-damage repair following ionizing radiation therapy (RT) in SCCHN cells; and the potential of honokiol to enhance RT through downregulation of survivin. Experimental Design: Expression of survivin in SCCHN patient primary tumor tissues ( n = 100) was analyzed and correlated with clinical parameters. SCCHN cell lines were used to evaluate the function of survivin and the effects of honokiol on survivin expression in vitro and in vivo Results: Overexpression of survivin was significantly associated with lymph nodes' metastatic status ( P = 0.025), worse overall survival (OS), and disease-free survival (DFS) in patients receiving RT ( n = 65, OS: P = 0.024, DFS: P = 0.006) and in all patients with SCCHN ( n = 100, OS: P = 0.002, DFS: P = 0.003). In SCCHN cells, depletion of survivin led to increased DNA damage and cell death following RT, whereas overexpression of survivin increased clonogenic survival. RT induced nuclear accumulation of survivin and its molecular interaction with γ-H2AX and DNA-PKCs. Survivin specifically bound to DNA DSB sites induced by I-SceI endonuclease. Honokiol (which downregulates survivin expression) in combination with RT significantly augmented cytotoxicity in SCCHN cells with acquired radioresistance and inhibited growth in SCCHN xenograft tumors. Conclusions: Survivin is a negative prognostic factor and is involved in DNA-damage repair induced by RT. Targeting survivin using honokiol in combination with RT may provide novel therapeutic opportunities. Clin Cancer Res; 24(4); 858-69. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: We examined the prognostic value of a panel of biomarkers in patients with squamous cell carcinoma of the head and neck (SCCHN) who were human immunodeficiency virus (HIV) positive (HIV-positive head and neck cancer) and HIV negative (HIV-negative head and neck cancer)., Methods: Tissue microarrays (TMAs) were constructed using tumors from 41 disease site-matched and age-matched HIV-positive head and neck cancer cases and 44 HIV-negative head and neck cancer controls. Expression of tumor biomarkers was assessed by immunohistochemistry (IHC) and correlations examined with clinical variables., Results: Expression levels of the studied oncogenic and inflammatory tumor biomarkers were not differentially regulated by HIV status. Among patients with HIV-positive head and neck cancer, laryngeal disease site (P = .003) and Clavien-Dindo classification IV (CD4) counts <200 cells/μL (P = .01) were associated with poor prognosis. Multivariate analysis showed that p16 positivity was associated with improved overall survival (OS; P < .001) whereas increased expression of transforming growth factor-beta (TGF-β) was associated with poor clinical outcome (P = .001)., Conclusion: Disease site has significant effect on the expression of biomarkers. Expression of tumor TGF-β could be a valuable addition to the conventional risk stratification equation for improving head and neck cancer disease management strategies., (© 2017 Wiley Periodicals, Inc.)

Purpose: This study intends to investigate the feasibility of using hyperspectral imaging (HSI) to detect and delineate cancers in fresh, surgical specimens of patients with head and neck cancers. Experimental Design: A clinical study was conducted in order to collect and image fresh, surgical specimens from patients ( N = 36) with head and neck cancers undergoing surgical resection. A set of machine-learning tools were developed to quantify hyperspectral images of the resected tissue in order to detect and delineate cancerous regions which were validated by histopathologic diagnosis. More than two million reflectance spectral signatures were obtained by HSI and analyzed using machine-learning methods. The detection results of HSI were compared with autofluorescence imaging and fluorescence imaging of two vital-dyes of the same specimens. Results: Quantitative HSI differentiated cancerous tissue from normal tissue in ex vivo surgical specimens with a sensitivity and specificity of 91% and 91%, respectively, and which was more accurate than autofluorescence imaging ( P < 0.05) or fluorescence imaging of 2-NBDG ( P < 0.05) and proflavine ( P < 0.05). The proposed quantification tools also generated cancer probability maps with the tumor border demarcated and which could provide real-time guidance for surgeons regarding optimal tumor resection. Conclusions: This study highlights the feasibility of using quantitative HSI as a diagnostic tool to delineate the cancer boundaries in surgical specimens, and which could be translated into the clinic application with the hope of improving clinical outcomes in the future. Clin Cancer Res; 23(18); 5426-36. ©2017 AACR ., (©2017 American Association for Cancer Research.)

A label-free, hyperspectral imaging (HSI) approach has been proposed for tumor margin assessment. HSI data, i.e., hypercube (x,y,λ), consist of a series of high-resolution images of the same field of view that are acquired at different wavelengths. Every pixel on an HSI image has an optical spectrum. In this pilot clinical study, a pipeline of a machine-learning-based quantification method for HSI data was implemented and evaluated in patient specimens. Spectral features from HSI data were used for the classification of cancer and normal tissue. Surgical tissue specimens were collected from 16 human patients who underwent head and neck (H&N) cancer surgery. HSI, autofluorescence images, and fluorescence images with 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) and proflavine were acquired from each specimen. Digitized histologic slides were examined by an H&N pathologist. The HSI and classification method were able to distinguish between cancer and normal tissue from the oral cavity with an average accuracy of 90%±8%, sensitivity of 89%±9%, and specificity of 91%±6%. For tissue specimens from the thyroid, the method achieved an average accuracy of 94%±6%, sensitivity of 94%±6%, and specificity of 95%±6%. HSI outperformed autofluorescence imaging or fluorescence imaging with vital dye (2-NBDG or proflavine). This study demonstrated the feasibility of label-free, HSI for tumor margin assessment in surgical tissue specimens of H&N cancer patients. Further development of the HSI technology is warranted for its application in image-guided surgery., ((2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Surgical cancer resection requires an accurate and timely diagnosis of the cancer margins in order to achieve successful patient remission. Hyperspectral imaging (HSI) has emerged as a useful, noncontact technique for acquiring spectral and optical properties of tissue. A convolutional neural network (CNN) classifier is developed to classify excised, squamous-cell carcinoma, thyroid cancer, and normal head and neck tissue samples using HSI. The CNN classification was validated by the manual annotation of a pathologist specialized in head and neck cancer. The preliminary results of 50 patients indicate the potential of HSI and deep learning for automatic tissue-labeling of surgical specimens of head and neck patients.

An estimated 200,000 deaths each year worldwide are due to cancer of the head and neck, mostly mucosal squamous cell carcinoma and nonmelanoma skin cancer. The status of surgical margins is important for prognosis and need for adjuvant therapy. We will discuss how margin status impacts outcomes and therapy, and the conundrum of determining margin status., (© 2015 Wiley Periodicals, Inc.)

Importance: Cost containment is at the forefront of responsible health care delivery. One way to decrease costs is to decrease hospital length of stay (LOS). Data are lacking on factors contributing to LOS in patients with head and neck cancer (HNC) undergoing fibular free-tissue reconstruction (FFTR) of head and neck defects., Objective: To identify factors contributing to increased LOS following FFTR of head and neck defects in patients with HNC using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) methodology., Design: Retrospective medical record review, with reference to the ACS NSQIP form, of 30 consecutive patients with HNC undergoing FFTR of head and neck defects in a single tertiary academic institution from July 2013 through June 2014. Data were collected on demographic and tumor characteristics, preoperative risk factors, operative variables, and postoperative adverse events., Main Outcomes and Measures: Factors associated with increased hospital LOS., Results: Median LOS was 10 days (range, 8-31 days), and patients were divided into 2 groups (LOS, ≤ 10 days [n = 16]; and LOS, >10 days [n = 14]). There were no significant differences in demographics, tumor characteristics, or preoperative medical comorbidities between the 2 groups. Univariate analysis demonstrated that operative time, ventilator dependence, wound event, and altered mental status were associated with longer LOS. Multivariate analysis revealed significant association with LOS greater than 10 days for operative time of longer than 11 hours (odds ratio [OR], 7.26; 95% CI, 1.12-47.29; P = .04) and ventilator dependence for more than 48 hours postoperatively (OR, 12.05; 95% CI, 1.06-137.43; P = .045)., Conclusions and Relevance: Evaluated by the ACS NSQIP criteria, FFTR of head and neck defects in patients with HNC was associated with LOS longer than 10 days for procedures lasting longer than 11 hours and for patients who are ventilator dependent for more than 48 hours.

Background: The purpose of this study was to determine if lymph node ratio is associated with locoregional recurrence for patients with oral cavity or laryngeal cancer treated with initial surgical management., Methods: The study included 350 patients with oral cavity (73%) or laryngeal cancer (27%) who underwent initial surgery. All analyses were multivariable, adjusting for primary site, pathologic prognostic factors, and adjuvant therapy., Results: Lymph node ratio was significantly associated with locoregional recurrence, in which each 1% increase in lymph node ratio had an adjusted hazard ratio (HR) for locoregional recurrence of 1.02 (95% confidence interval [CI], 1.002-1.042; p = .05). Lymph node ratio was also associated with OS, in which each 1% increase in lymph node ratio had an adjusted HR for death of 1.028 (95% CI, 1.012-1.045; p = .001)., Conclusion: Adjusting for pathologic factors and adjuvant therapy, lymph node ratio was found to be an independent prognostic factor for locoregional recurrence and overall survival (OS). Patients with lymph node ratio ≥20% are at high risk of locoregional recurrence and death, and may be considered for adjuvant chemoradiation., (© 2014 Wiley Periodicals, Inc.)

Background: Platinum-based therapy combined with cetuximab is standard first-line therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Preclinical studies have suggested that mammalian target of rapamycin inhibitors may overcome resistance to epidermal growth factor receptor blockers and may augment cetuximab antitumor activity. We conducted a phase 1b trial of carboplatin, cetuximab, and everolimus for untreated RMSCCHN., Methods: Patients received carboplatin (area under the curve = 2 mg/ml/min; 3 weeks on, 1 week off), cetuximab (with a loading dose of 400 mg/m(2) and then 250 mg/m(2) weekly), and dose-escalating everolimus (2.5, 5.0, 7.5, and 10 mg/day) with a 3+3 design. After 4 cycles, patients without progression continued cetuximab/everolimus until progression or intolerable toxicity. Patients (age ≥ 18 years) had previously untreated, unresectable RMSCCHN not amenable to radiotherapy and an Eastern Cooperative Oncology Group performance status of 0 to 2., Results: The study enrolled 20 patients (male/female = 18/2) with RMSCCHN; the median age was 65 years (44-75 years). Thirteen patients received everolimus (male/female = 92%). Two of 6 patients receiving 2.5 mg/day experienced dose-limiting toxicity (DLT) with grade 3 hyponatremia and nausea. In 7 patients receiving de-escalated everolimus (2.5 mg every other day), grade 3 hyperglycemia produced DLT in 1 of 6 patients. The objective response rate (RR) was 61.5% (all partial responses). Progression-free survival (PFS) was 8.15 months. The pharmacokinetics of everolimus was described with a 2-compartment mixed-effects model. There was a significant correlation between tumor p-p44/42 staining and response (P = .044) and a marginally significant correlation between phosphorylated mammalian target of rapamycin and overall survival., Conclusions: The maximum tolerated dose of everolimus with cetuximab and carboplatin was 2.5 mg every other day. The regimen was associated with an encouraging RR and PFS, and this suggested possible clinical efficacy in a select group of patients with squamous cell carcinoma of the head and neck., (© 2014 American Cancer Society.)

Head and neck cancer is a heterogenous group of cancers involving the upper aerodigestive tract. In this review article, the most common sites will be discussed, including the oral cavity, oropharynx, hypopharynx, and larynx. Etiology and epidemiology will be discussed followed by staging, treatment, and survival., (© 2014 Wiley Periodicals, Inc.)

Epidermal growth factor receptor (EGFR) and COX-2 inhibitors synergistically inhibit head and neck squamous cell carcinoma tumorigenesis in preclinical studies. We conducted a phase I and pharmacokinetic study with the erlotinib and celecoxib combination in patients with advanced premalignant lesions. Thirty-six subjects with oral leukoplakia, mild, moderate, or severe dysplasia, or carcinoma in situ were screened for study participation; 12 consented and received therapy for a median of 5.38 months. Erlotinib was escalated following a standard 3+3 design at 50, 75, and 100 mg orally daily and celecoxib was fixed at 400 mg twice daily for 6 months. Biopsy of lesions and cytobrush of normal mucosa were performed at baseline, 3, 6, and 12 months. Erlotinib pharmacokinetics were analyzed in 10 subjects. The maximum tolerated dose of erlotinib with celecoxib 400 mg BID was 50 mg per day with skin rash being the main observed toxicity. Overall histologic response rate was 63% (complete response, 43%; partial response, 14%; stable disease, 29%; and disease progression, 14%). With median follow-up of 36 months, mean time to progression to higher-grade dysplasia or carcinoma was 25.4 months. Downregulation of EGFR and p-ERK in follow-up biopsies correlated with response to treatment. Larger average erlotinib V/F (approximately 308 L) and CL/F (8.3 L/h) compared with previous studies may be related to relatively large average bodyweights. Average erlotinib t1/2 was 25.6 hours. Encouraging responses to the celecoxib and erlotinib combination correlated with EGFR pathway inhibition. Although erlotinib-related rash was the main limitation to dose escalation, the intervention was well tolerated.

Acetylated tubulin (AT) expression has been proposed as a marker for sensitivity to taxane chemotherapy. We wanted to explore AT as a prognostic marker in squamous cell carcinoma of the head and neck (SCCHN). We assessed AT expression in archival tissue from our institutional tissue bank of primary SCCHN specimens. We also examined AT expression on pre-therapy tissues of patients with SCCHN receiving induction chemotherapy with docetaxel, cisplatin and 5FU (TPF IC). AT expression was assessed on archival cases of SCCHN with (N = 63) and without (N = 82) locoregional lymph node metastases (LNM). The predominant tumor site was oral cavity (52 %). Immunohistochemistry staining was based on staining intensity and percentage of tumor cells stained to create a weighted index (WI). A total of nine patients who received TPF IC were evaluable for response by RECIST and also had pre-therapy tissues available. A significant independent correlation between AT and tumor grade (p = 0.001) and primary location (p = 0.008) was noted. There was a trend of higher AT in patients with presence of LNM (p = 0.052) and a trend in improved OS for patients with an AT WI below the median compared to those above the median for patients with no LNM (p = 0.054). For patients treated with induction TPF, we observed an inverse correlation between AT expression and response to TPF IC (p = 0.0071). AT expression is correlated with tumor grade and primary site. There was an observed trend correlating AT with presence nodal metastases. The observed inverse correlation with response to taxane based chemotherapy needs validation in a larger sample size.

Analysis of quality of life (QOL) has revealed that preservation of swallowing, speech, and breathing functions has a direct impact on QOL and that these functions are important patient-reported outcomes. The purposes of this study were to adapt and culturally validate the M.D. Anderson Dysphagia Inventory (MDADI) to the Brazilian Portuguese language and to evaluate QOL related to dysphagia in patients treated for head and neck cancer. This was a cross-sectional study that included 72 adult patients with a mean age of 63 years who were treated for head and neck cancer. Construct validity and reliability analyses were performed through the comparison of the MDADI with three other health-related QOL questionnaires administered at the time of enrollment and MDADI application 2 weeks thereafter, respectively. Reliability was established by assuring both internal consistency (Cronbach's α) and test-retest reliability (intraclass correlation coefficient, ICC). Test-retest reliability for the total score in the MDADI had an ICC greater than 0.795 (p < 0.001). The MDADI had significant statistical correlations with the other questionnaires. Patients treated for head and neck cancer had a mean total score of 83 on the MDADI, which is indicative of minimal limitation in overall QOL. In conclusion, the present study validates the adaptation of the MDADI to the Brazilian Portuguese language and provides another tool to evaluate the impact of dysphagia on the QOL of head and neck cancer patients.

Purpose: We investigated the efficacy and underlying molecular mechanism of a novel chemopreventive strategy combining EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) with cyclooxygenase-2 inhibitor (COX-2I)., Experimental Design: We examined the inhibition of tumor cell growth by combined EGFR-TKI (erlotinib) and COX-2I (celecoxib) treatment using head and neck cancer cell lines and a preventive xenograft model. We studied the antiangiogenic activity of these agents and examined the affected signaling pathways by immunoblotting analysis in tumor cell lysates and immunohistochemistry (IHC) and enzyme immunoassay (EIA) analyses on the mouse xenograft tissues and blood, respectively. Biomarkers in these signaling pathways were studied by IHC, EIA, and an antibody array analysis in samples collected from participants in a phase I chemoprevention trial of erlotinib and celecoxib., Results: The combined treatment inhibited head and neck cancer cell growth significantly more potently than either single agent alone in cell line and xenograft models, and resulted in greater inhibition of cell-cycle progression at G1 phase than either single drug. The combined treatment modulated the EGFR and mTOR signaling pathways. A phase I chemoprevention trial of combined erlotinib and celecoxib revealed an overall pathologic response rate of 71% at time of data analysis. Analysis of tissue samples from participants consistently showed downregulation of EGFR, pERK, and pS6 levels after treatment, which correlated with clinical response., Conclusion: Treatment with erlotinib combined with celecoxib offers an effective chemopreventive approach through inhibition of EGFR and mTOR pathways, which may serve as potential biomarkers to monitor the intervention of this combination in the clinic. Clin Cancer Res; 19(5); 1244-56. ©2013 AACR., (©2013 AACR.)

Background: Adenoid cystic carcinoma (ACC) of the head and neck (ACCHN) is a rare tumor of minor salivary, parotid, and submandibular glands. The biologic behavior of the disease is poorly understood, and nonsurgical treatment strategies have yet to be standardized. The long-term prognosis continues to be guarded, with an estimated 10-year survival of <60%. Population-based studies examining ACC are scarce. The authors aimed to analyze incidence rates and survival outcomes for patients diagnosed with ACCHN using national population-based data., Methods: Data were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Newly diagnosed ACCHN cases reported to SEER from 1973 through 2007 were categorized according to their sex, race, age, year of diagnosis, marital status, treatment interventions, primary tumor site, and disease stage. Incidence of ACCHN and postdiagnosis survival were examined over time and compared across different demographic and disease-related categories., Results: The authors identified 3026 patients with ACCHN. The mean age at diagnosis among those cases was 57.4 years (range, 11-99 years). Analyses of incidence data demonstrated a decline in ACCHN rates between 1973 and 2007, noted across all sexes and races with no detectable inflexion points. The overall 5-year, 10-year, and 15-year survival outcomes for ACCHN patients were 90.3%, 79.9%, and 69.2%, respectively. Females, patients with localized disease, and younger patients were found to have significantly better survival across all time periods (all comparison-specific log-rank P values <0.001). Multivariate analyses revealed better prognosis among women compared with men (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65-0.82), among married compared with unmarried individuals (HR, 0.81; 95% CI, 0.71-0.91), with certain sites of origin and stage of disease (HR, 2.788; 95% CI, 2.36-3.29), and in those who had surgery of the primary tumor site (HR, 0.45; 95% CI, 0.37-0.54)., Conclusions: The overall incidence of ACC is declining. The noted differences in survival based on sex, marital status, site of origin, and treatment intervention require further investigation., (Copyright © 2012 American Cancer Society.)

Background: Results of a pooled analysis of case-control studies show a higher risk of head and neck cancer (HNC) associated with a low body mass index (BMI) and a lower risk associated with being overweight or obese compared with being normal weight. However, these results are prone to bias due to residual confounding by smoking, a strong risk factor, and possible weight loss prior to diagnosis. Using prospectively collected data from the Cancer Prevention Study-II cohort and the Nutrition cohort, we examined the association of BMI with HNC mortality and incidence, overall and by smoking status., Methods: Mortality analyses included 1,383 cases among 1,059,153 participants; incidence analyses included 340 cases among 150,262 participants. Multivariable Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI) for the association of BMI with HNC incidence and mortality., Results: Overall, compared with the category of BMI 22.5-24.9 kg/m(2), the categories of BMI 25.0-29.9 kg/m(2) and ≥ 30.0 kg/m(2) were associated with a lower risk of HNC mortality but not incidence. In never smokers, there were no associations of BMI with HNC incidence or mortality. In smokers, BMI < 22.5 kg/m(2) was associated with a higher risk of HNC mortality (HR = 1.42, 95% CI, 1.20-1.67)., Conclusions: In this prospective cohort, there was no association between BMI and HNC incidence, although BMI was inversely associated with HNC mortality in smokers., Impact: These suggest that there is no etiologic relationship between BMI and HNC., (©2012 AACR.)

Achieving optimal oncologic outcomes is always the priority for care of our head and neck cancer patients. Preserving functional status is equally important. Traditional surgical approaches to the oropharynx were extensive and unappealing to patients. This led to a surge in the use of chemoradiation for these patients. However, these nonsurgical treatments often left the patients with long-term gastrostomy tubes and tracheotomies, and thus they did not achieve the goal of preserving functional status. TORS is a new approach to tried and true oncologic resections and has demonstrated comparable to improved oncologic and functional outcomes. Adding TORS to the multidisciplinary care of head and neck cancer patients, particularly those with oropharynx and larynx primaries, may allow our patients to achieve a cancer-free and highly functional life.

A growing national health care initiative is gathering momentum to improve the quality of care for all Americans. Efforts to establish, monitor, and reward quality care have therefore been extensive. The Institute of Medicine has established that a large proportion of individuals do not receive recommended cancer care for their stage of disease, and that quality of care metrics should be established to decrease inappropriate care (overuse, under use, or wrong use). The American Head and Neck Society has been instrumental in developing quality measures for two of the most common head and neck cancers and in promoting adherence to these measures to improve quality of care for all patients.

Background: There is a perception that a total laryngectomy has a devastating effect on patients and their families, but only a few studies have addressed long-term quality of life (QOL) after laryngectomy., Methods: A cross-sectional study of 49 patients more than 2 years since laryngectomy was performed with a general health status instrument (Short Form-12, version 2 [SF-12 v2.]) and a disease-specific QOL instrument (University of Washington Quality of Life questionnaire, version 4 [UW-QOL v4.]) in a national meeting of laryngectomy survivors., Results: As measured by the UW-QOL, patients identified speech, appearance, and activity as the most important problems after total laryngectomy, but surprisingly, no correlation was seen between speech and overall QOL. Age was a predictor of appearance and anxiety, women were more likely to report difficulties swallowing, irradiated patients reported more difficulties with speech and anxiety, and patients who received chemotherapy were more likely to report difficulties with mood. The SF-12 captured no differences between normal subjects and laryngectomees in the physical summary domain (p = .21); however, laryngectomees scored better in the mental domain (p = .004). Laryngectomees had lower scores in physical function (p = .005) and role physical (p = .036)., Conclusions: Long-term QOL is not decreased after total laryngectomy when it is measured with general health instruments and compared with the normal population, but impairment in physical scales is found when disease-specific questionnaires or subscale scores are included. Age, sex, radiation therapy, and chemotherapy are independent predictors of UW-QOL subscales. Voice handicap is identified as a problem but is not predictive of overall QOL. A strong relationship exists between UW-QOL and SF-12., (Copyright 2005 Wiley Periodicals, Inc.)

In this review, the authors outline the epidemiology, genetic factors, treatment and outcomes of head and neck cancer.