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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: S0, S1, S2, and S3. 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 (S0, S1, S2, and S3), our PHSI microscope system enhances the visualization of tumor cells and tumor microenvironment components, thus being beneficial for pathology and oncology. [ABSTRACT FROM AUTHOR]

Superselective neck dissection, defined as dissection of two or less contiguous neck levels, has recently been introduced to reduce surgical morbidity of neck dissection while maintaining favorable oncologic outcomes. The purpose of this review is to report the results of superselective neck dissection when applied to specific settings: the management of regional disease after chemoradiation, head and neck squamous cell carcinoma with clinical N0 necks, and high risk papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

For patients undergoing surgical cancer resection of squamous cell carcinoma (SCCa), cancer-free surgical margins are essential for good prognosis. We developed a method to use hyperspectral imaging (HSI), a noncontact optical imaging modality, and convolutional neural networks (CNNs) to perform an optical biopsy of ex-vivo, surgical gross-tissue specimens, collected from 21 patients undergoing surgical cancer resection. Using a cross-validation paradigm with data from different patients, the CNN can distinguish SCCa from normal aerodigestive tract tissues with an area under the receiver operator curve (AUC) of 0.82. Additionally, normal tissue from the upper aerodigestive tract can be subclassified into squamous epithelium, muscle, and gland with an average AUC of 0.94. After separately training on thyroid tissue, the CNN can differentiate between thyroid carcinoma and normal thyroid with an AUC of 0.95, 92% accuracy, 92% sensitivity, and 92% specificity. Moreover, the CNN can discriminate medullary thyroid carcinoma from benign multinodular goiter (MNG) with an AUC of 0.93. Classical-type papillary thyroid carcinoma is differentiated from MNG with an AUC of 0.91. Our preliminary results demonstrate that an HSI-based optical biopsy method using CNNs can provide multicategory diagnostic information for normal and cancerous head-and-neck tissue, and more patient data are needed to fully investigate the potential and reliability of the proposed technique. [ABSTRACT FROM AUTHOR]

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. In the current study, we used a larger sample size which incorporates multiple sub‐sites to address the role of peritumoral LVD and MVD in HNSCC metastasis and prognosis. It was found that peritumoral MVD was positively associated with metastasis, while LVD was 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. [ABSTRACT FROM AUTHOR]

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/m2 and then 250 mg/m2 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. Cancer 2014;120:3940-3951. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

The erratum corrects the name of the first author listed in a reference cited. [ABSTRACT FROM AUTHOR]

BACKGROUND Paranasal sinus squamous cell carcinomas (PNSSCC) account for 3% of all head and neck malignancies. There has been little information on the trends in incidence and survival, and no randomized trials have been conducted to guide therapy. METHODS Patients with PNSSCC reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1973 through 2009 were categorized by sex, age, year of diagnosis, primary site, stage, and treatment. The incidence and survival were then compared across different demographic and disease-related categories by calculating rate ratios (RRs) and mortality hazard ratios along with the corresponding 95% confidence intervals (CIs). RESULTS In total, 2553 patients with PNSSCC were identified. While incidence of PNSSCC showed a gradual decline, survival remained largely unchanged. The proportion of patients with advanced disease decreased from 14.7% during the period from 1983 to 1992 to 12.4% during 1993-2002 and to 9.5% during 2003-2009. Compared with whites, incidence was higher among African Americans (RR 1.63; 95% CI, 1.39, 1.90) and among all other racial groups (RR, 1.78; 95% CI: 1.53-2.07). After adjusting for age, sex, disease stage, tumor site, and treatment, mortality among African American patients also was increased (hazard ratio, 1.22; 95% CI, 1.04-1.43). Among patients with localized disease, the relation between race and mortality was no longer evident once the results were controlled for tumor classification. CONCLUSIONS The current findings point to racial disparities in the incidence of PNSSCC and, to a lesser extent, in the outcome of patients with PNSSCC. Although there has been a decline in the proportion of patients presenting with advanced PNSSCC, the overall survival remained stable over time. Cancer 2013;119:2602-2610. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Laryngeal preservation programs for patients with advanced laryngeal squamous cell carcinomas (SCC) have generally excluded patients with T4 disease. The accuracy of preoperative imaging in evaluating thyroid cartilage penetration and extralaryngeal spread (ELS) has previously been questioned. Clinically, SCC spread into noncartilaginous structures may have less of a functional impact when compared with thyroid cartilage penetration. The current study was designed to characterize and quantify the routes and frequency of ELS. METHODS: A total of 103 laryngectomy specimens with preoperative contrast-enhanced neck computed tomography scans were coded according to the observed extent of disease by pathological and radiological data. Previously irradiated tumors or those of pyriform sinus origin were omitted. Routes of spread were categorized as anterior (thyroid cartilage penetration), posterior (arytenoid cartilage destruction and thyroarytenoid space widening), inferior (conus elasticus penetration), and superior (base of tongue, thyrohyoid membrane or thyroid notch penetration involvement). RESULTS: Sixty-three cases of ELS were identified. Anterior spread by thyroid cartilage penetration occurred in 44% of all instances of ELS, followed by both inferior and posterior spread each representing 33% of ELS cases. Superior spread occurred with a frequency of 24%. CONCLUSIONS: Although thyroid cartilage penetration is a common route of ELS of glottic and supraglottic SCC, ELS into surrounding structures with thyroid cartilage penetration was found to occur in only 44% of the cases of ELS in the current study. As illustrated, advanced SCC spreads in a variety of pathways. Once these patterns are better understood and identified at the time of initial evaluation, subgroups of patients with ELS who may still be candidates for laryngeal preservation may be identified. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Surgical resection of head and neck (H and N) squamous cell carcinoma (SCC) may yield inadequate surgical cancer margins in 10 to 20% of cases. This study investigates the performance of label-free, reflectance-based hyperspectral imaging (HSI) and autofluorescence imaging for SCC detection at the cancer margin in excised tissue specimens from 102 patients and uses fluorescent dyes for comparison. Fresh surgical specimens (n = 293) were collected during H and N SCC resections (n = 102). The tissue specimens were imaged with reflectance-based HSI and autofluorescence imaging and afterwards with two fluorescent dyes for comparison. A histopathological ground truth was made. Deep learning tools were developed to detect SCC with new patient samples (inter-patient) and machine learning for intra-patient tissue samples. Area under the curve (AUC) of the receiver-operator characteristic was used as the main evaluation metric. Additionally, the performance was estimated in mm increments circumferentially from the tumor-normal margin. In intra-patient experiments, HSI classified conventional SCC with an AUC of 0.82 up to 3 mm from the cancer margin, which was more accurate than proflavin dye and autofluorescence (both p < 0.05). Intra-patient autofluorescence imaging detected human papilloma virus positive (HPV+) SCC with an AUC of 0.99 at 3 mm and greater accuracy than proflavin dye (p < 0.05). The inter-patient results showed that reflectance-based HSI and autofluorescence imaging outperformed proflavin dye and standard red, green, and blue (RGB) images (p < 0.05). In new patients, HSI detected conventional SCC in the larynx, oropharynx, and nasal cavity with 0.85–0.95 AUC score, and autofluorescence imaging detected HPV+ SCC in tonsillar tissue with 0.91 AUC score. This study demonstrates that label-free, reflectance-based HSI and autofluorescence imaging methods can accurately detect the cancer margin in ex-vivo specimens within minutes. This non-ionizing optical imaging modality could aid surgeons and reduce inadequate surgical margins during SCC resections. [ABSTRACT FROM AUTHOR]