Potential imaging targets in primary head and neck squamous cell carcinoma and lymph node metastases.

PURPOSE: To investigate glycoprotein nonmetastatic melanoma protein B (GPNMB) and vascular endothelial growth factor (VEGF) as potential fluorescent imaging markers by comparing their protein expression to epidermal growth factor receptor (EGFR). MATERIALS AND METHODS: Thirty-eight paired samples of untreated head and neck squamous cell carcinoma (HNSCC) primary tumours (PT) and corresponding synchronous lymph node metastases (LNM) were selected. After immunohistochemical staining, expression was assessed and compared by the percentage of positive tumour cells. Data were analysed using the Mann-Whitney test, effect sizes (ESr) and Spearman's correlation coefficient (r). RESULTS: GPNMB expression was observed in 100 % of PT, and median 80 % (range 5-100 %) of tumour cells, VEGF in 92 % and 60 % (0-100 %), EGFR in 87 % and 60 % (0-100 %) respectively. In corresponding LNM, GPNMB expression was observed in 100 % of LNM and median 90 % (20-100 %) of tumour cells, VEGF in 87 % and 65 % (0-100 %), and EGFR in 84 % and 35 % (0-100 %). A positive correlation was found between expression in PT and LNM for GPNMB (r = 0.548) and EGFR (r = 0.618) (p < 0.001), but not for VEGF (r = -0.020; p = 0.905). GPNMB expression was present in a higher percentage of tumour cells compared to EGFR in PT (p = 0.015, ESr = -0.320) and in LNM (p < 0.001, ESr = -0.478), while VEGF was not (p = 1.00, ESr = -0.109 and - 0.152, respectively). CONCLUSION: GPNMB expression is higher than EGFR in untreated HNSCC PT and corresponding LNM, while VEGF expression is comparable to EGFR. GPNMB is a promising target for fluorescent imaging in HNSCC.

Narrow band imaging reveals field cancerisation undetected by conventional white light: Optical diagnosis versus histopathology.

OBJECTIVE: To assess whether narrow band imaging (NBI) detects fields of cancerisation around suspicious lesions in the upper aerodigestive tract, which were undetected by white light imaging (WLI). METHODS: In 96 patients with laryngeal and pharyngeal lesions suspicious for malignancy, 206 biopsies were taken during laryngoscopy: 96 biopsies of suspicious lesions detected by both WLI and NBI (WLI+/NBI+), 60 biopsies adjacent mucosa only suspicious with NBI (WLI-/NBI+), and 46 biopsies of NBI and WLI unsuspicious mucosa (WLI-/NBI-) as negative controls. Optical diagnosis according to the Ni-classification was compared with histopathology. RESULTS: Signs of (pre)malignancy were found in 88% of WLI+/NBI+ biopsies, 32% of WLI-/NBI+ biopsies and 0% in WLI-/NBI- (p < .001). In 58% of the WLI-/NBI+ mucosa any form of dysplasia or carcinoma was detected. CONCLUSION: The use of additional NBI led to the detection of (pre)malignancy in 32% of the cases, that would have otherwise remained undetected with WLI alone. This highlights the potential of NBI as a valuable adjunct to WLI in the identification of suspicious lesions in the upper aerodigestive tract.

Influence of Frailty and Life Expectancy on Guideline Adherence and Outcomes in Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Prospective Pilot Study.

BACKGROUND: Cutaneous squamous cell carcinoma is the second most common malignancy of the skin, often occurring in older patients and in the head and neck area (cSCCHN). Age, life expectancy, and frailty are not taken into consideration by current guidelines. OBJECTIVES: The objective of this study was to evaluate the influence of frailty and life expectancy on guideline deviation, treatment outcomes, and quality of life (QoL) after treatment in patients with cSCCHN. METHODS: Patients with cSCCHN were prospectively included. A geriatric assessment was performed, including the Geriatric 8 (G8), Groningen Frailty Indicator, and Timed Up and Go test (TUG). The Lee index was used to predict a limited life expectancy, and the Adult Comorbidity Evaluation-27 was used as a comorbidity index. QoL was assessed by the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire at three time points. RESULTS: Seventy-seven patients with cSCCHN were included. Frail patients had significantly more high-risk tumours. Guideline deviation occurred in 7.8% and was more common in patients who were frail (G8), with high-risk tumours (≥T2), with a limited life expectancy or an increased TUG. Guideline deviation did not lead more often to progression of disease in our study. No predictors for post-operative complications were found. BaSQoL subscores were very low at each time point and did not change significantly with time in the total group. Frail patients reported more fear of recurrence or new tumours 3 months after treatment, and less concern about other people's skin 6 months after treatment, compared to non-frail patients. Complication rate, gender, or guideline deviation did not affect any subscale scores. CONCLUSIONS: Assessment of frailty and life expectancy can guide physicians and patients in treatment decisions. Deviation from guidelines towards less aggressive treatment schedules can be considered in frail patients with a limited life expectancy, since it did not negatively affect short-term outcomes or QoL in patients with cSCCHN in our study. However, these results should be confirmed by other, larger prospective studies with a longer follow-up period.

Age-related Differences in Tumour Characteristics and Prognostic Factors for Disease Progression in Cutaneous Squamous Cell Carcinoma of the Head and Neck.

Guidelines for cutaneous squamous cell carcinoma of the head and neck do not take the age of the patient into account, but instead assume equal tumour characteristics and prognostic factors for poor outcome in younger and elderly patients. The aim of this study was to compare tumour characteristics of younger (< 75 years) and elderly (≥ 75 years) patients and identify age-specific risk factors for progression of disease, comprising local recurrence, nodal metastasis and distant metastasis. Patient and tumour characteristics were compared using χ2 or Fisher's exact tests. Multivariable competing risk analyses were performed to compare risk factors for progression of disease, incorporating the risk of dying before developing progression of disease. A total of 672 patients with primary cutaneous squamous cell carcinoma of the head and neck were retrospectively included. Larger tumour diameter, worse differentiation grade and deeper invasion were observed in older patients. In elderly patients, but not in younger patients, tumour diameter ≥ 40 mm, moderate differentiation grade and an invasion depth ≥ 2 mm were independent risk factors for progression of disease.

The effect of treatment delay on quality of life and overall survival in head and neck cancer patients.

OBJECTIVE: Head and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of delay on health-related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival. METHODS: Patients with mucosal HNSCC were prospectively included. HRQOL and 2-year overall survival were analysed using linear mixed-model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation. RESULTS: Median CPI was 39 days for the 173 patients included. A trend towards higher HRQOL-scores (indicating better HRQOL) during 2-year follow-up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score-ß: 2.62, 95% CI: 0.57-4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65-15.76, p = 0.005) and stage-IV tumours (HR: 12.37, 95% CI: 2.81-54.39, p = 0.001). Delay was not associated with worse overall survival. CONCLUSION: Timely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL-scores or decreased overall survival during 2-year follow-up.

Determinants of delay in the head and neck oncology care pathway: The next step in value-based health care.

OBJECTIVE: Head and neck squamous cell carcinomas (HNSCC) are relatively fast-growing tumours, and delay of treatment is associated with tumour progression and adverse outcomes. The aim of this study is to identify determinants of delay in a head and neck oncology centre. METHODS: This cohort study with prospectively collected data investigated associations between patient (including geriatric assessment at first consultation), tumour and treatment characteristics and treatment delay. Two quality indicator intervals assessing value-based healthcare were studied: care pathway interval (CPI, interval between first visit in an HNOC and treatment initiation) and time-to-treatment initiation (TTI, interval between histopathological confirmation of HNSCC and treatment initiation), using regression analyses. RESULTS: Stage-IV tumours and initial radiotherapy were independent predictors of delay in CPI. Initial radiotherapy was associated with delay in TTI. Overall, 37% of the patients started treatment within 30 days after first consultation (67% in case of initial surgical treatment and 11.5% if treated with (chemo)radiation, p < 0.001). Geriatric assessment outcomes were not associated with delay. Indicators for delay in initial surgery patients were stage-IV tumours (CPI). CONCLUSION: The majority of HNSCC patients encounter delay in treatment initiation, specifically in patients with advanced-stage tumours or when radiotherapy is indicated.

High-definition videolaryngoscopy is superior to fiberoptic laryngoscopy: a 111 multi-observer study.

PURPOSE: This study aims to analyse differences in fiberoptic laryngoscopy (FOL) versus high definition laryngoscopy (HDL) by examining videolaryngoscopy images by a large group of observers with different levels of clinical expertise in ear, nose and throat (ENT) medicine. METHODS: This study is a 111 observer paired analysis of laryngoscopy videos during an interactive presentation. During a National Meeting of the Dutch Society of ENT/Head and Neck Surgery, observers assessed both FOL and HDL videos of nine cases with additional clinical information. Observers included 41 ENT consultants (36.9%), 34 ENT residents (30.6%), 22 researchers with Head and Neck interest (19.8%) and 14 with unspecified clinical expertise (12.6%). For both laryngoscopic techniques, sensitivity, specificity, positive and negative predictive value and diagnostic accuracy were determined for identifying a normal glottis, hyperkeratosis, radiotherapy adverse effects and squamous cell carcinoma. The sensitivities for FOL and HDL were analysed with regard to the different levels of clinical expertise. RESULTS: The overall sensitivity for correctly identifying the specific histological entity was higher in HDL (FOL 61% vs HDL 66.3%, p < 0.05). HDL was superior to FOL in identifying a normal glottis (FOL 68.1% vs HDL 91.6%, p < 0.01) and squamous cell carcinoma (FOL 70.86% vs HDL 79.41%, p = 0.02). Residents and researchers with Head and Neck interest diagnosed laryngeal lesions more correctly with HDL (p < 0.05). CONCLUSIONS: In a large population of observers with different levels of clinical expertise, HDL is superior to FOL in identifying laryngeal lesions.

Predictors for distant metastasis in head and neck cancer, with emphasis on age.

PURPOSE: Distant metastasis (DM) in patients with head and neck squamous cell carcinoma (HNSCC) is uncommon, but strongly deteriorates prognosis. Controversy exists regarding age as a predictor for the presence and development of DM. The aim of this study was to investigate age and other predictors for DM in HNSCC patients. METHODS: From 1413 patients diagnosed with a primary HNSCC between 1999 and 2010 in a tertiary referral centre, patient, disease and pathological characteristics were extracted from patient files. Uni- and multivariable Cox regression analyses were performed to identify risk factors for DM as primary outcome. RESULTS: DM occurred in 131 (9.3%) patients, of which 27 (1.9%) were diagnosed simultaneously with the primary tumour, 27 (1.9%) were diagnosed synchronous, and 77 (5.4%) were diagnosed metachronous. The most common site of DM was lung (51.1%), followed by bone (19.1%) and liver (11.5%). Multivariable analysis identified male gender (HR = 1.95, 95% CI 1.23-3.10) hypopharyngeal tumours (HR = 3.28, 95% CI 1.75-6.14), advanced T-stage (HR = 1.61, 95% CI 1.09-2.38), poor differentiation grade (HR = 2.49, 95% CI 1.07-5.78), regional lymph node metastasis (HR = 5.35, 95% CI 3.25-8.79) and extranodal extension of regional lymph nodes metastasis (HR = 3.06, 95% CI 1.39-6.72) as independent prognostic factors for the presence or development of DM. No relation with age was found. CONCLUSION: Age is not related to the presence or development of DM. This study emphasizes the importance of screening for DM, especially in males, patients with hypopharyngeal tumours, advanced T-stage, histopathological poor differentiation grade, regional lymph node metastasis and extranodal extension.

Effect of Patient Characteristics on Treatment Decisions Regarding Keratinocyte Carcinoma in Elderly Patients: A Review of the Current Literature.

There are straightforward guidelines for treatment of keratinocyte carcinoma (formerly known as non-melanoma skin cancer); however, there are no clear recommendations specifically for elderly patients. The aim of this review was to provide an overview of the current literature about the effect of patient characteristics, specifically life expectancy, frailty and comorbidity, on treatment decisions in elderly patients with keratinocyte carcinoma, by searching PubMed database. It was found that the literature is limited and based mostly on small retrospective studies. Therefore, it is difficult to give firm recommendations about how to treat elderly people who have keratinocyte carcinoma. A "one-size-fits-all" approach to this population is not sufficient: life expectancy and frailty need to be considered in the decision-making process regarding treatment for elderly people with keratinocyte carcinoma. Among the comorbidity scores, Adult-Comorbidity-Evaluation-27-index seems to have the best prognostic value. Prospective studies are needed to generate more individualized recommendations for this increasing and often vulnerable group.

Differences in the diagnostic value between fiberoptic and high definition laryngoscopy for the characterisation of pharyngeal and laryngeal lesions: A multi-observer paired analysis of videos.

OBJECTIVES: High definition laryngoscopy (HDL) could lead to better interpretation of the pharyngeal and laryngeal mucosa than regularly used fiberoptic laryngoscopy (FOL). The primary aim of this study is to quantify the diagnostic advantage of HDL over FOL in detecting mucosal anomalies in general, in differentiating malignant from benign lesions and in predicting specific histological entities. The secondary aim is to analyse image quality of both laryngoscopes. DESIGN: Retrospective paired analysis with multiple observers evaluating endoscopic videos simulating daily clinical practice. SETTING: A tertiary referral hospital. PARTICIPANTS: In 36 patients, both FOL and HDL videos were obtained. Six observers were provided with additional clinical information, and 36 FOL and HDL videos were evaluated in a randomised order. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of observers using both flexible laryngoscopes were calculated for detection of mucosal lesions in general and uncovering malignant lesions. Sensitivities were calculated for prediction of specific histological entities. Image quality (scale 1-10) was assessed for both flexible laryngoscopes. RESULTS: HDL reached higher sensitivity compared to FOL for detection of mucosal abnormalities in general (96.0% vs 90.4%; P = .03), differentiating malignant from benign lesions (91.7% vs 79.8%; P = .03) and prediction of specific histological entities (59.7% vs 47.2%; P < .01). Image quality was judged better with HDL in comparison with FOL (mean: 8.4 vs 5.4, P < .01). CONCLUSIONS: HDL is superior to FOL in detecting mucosal anomalies in general, malignancies and specific histological entities. Image quality is considered as superior using HDL compared to FOL.

Detection of high-grade dysplasia, carcinoma in situ and squamous cell carcinoma in the upper aerodigestive tract: Recommendations for optimal use and interpretation of narrow-band imaging.

OBJECTIVES: The primary goal was to study the diagnostic potential of narrow-band imaging (NBI), and the secondary goal was to evaluate the most common mistakes when using and interpreting NBI. DESIGN: Retrospective study. SETTING: University Medical Center Groningen, tertiary referral hospital, the Netherlands. PARTICIPANTS: Three hundred and seventy patients who underwent rigid endoscopy of the upper aerodigestive tract. Two observers assessed all lesions. Twelve observers assessed a selection of 100 lesions. All observers were provided with both white light imaging and NBI. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and reasons for insufficient photograph quality. RESULTS: When using NBI, the sensitivity, specificity, PPV, NPV and accuracy for detecting invasive carcinoma, carcinoma in situ or high-grade dysplasia were 92%, 68%, 61%, 94% and 77%, respectively. In multiple-observer analysis, values were 76%, 58%, 53%, 83% and 65% with the evaluation strictly based on type V patterns of Ni's classification, vs 83%, 68%, 64%, 85% and 74% when evaluation was also based on lesion-specific clinical characteristics. Lesions that caused misinterpretations were leukoplakia, papillomas and mucosal lesions after irradiation. In total, 185 photographs were assessed to be of suboptimal quality due to blurring (36%), bleeding (6%), insufficient zooming (15%) and/or insufficient lighting (17%). CONCLUSION: NBI is a relatively reliable screening method for detecting malignancy. Evaluation based on Ni's classification alone is not sufficient. To optimise NBI photograph quality, we recommend sufficient zooming and prevention of bleeding, blurring and inadequate lighting.

Predictive factors for pharyngocutaneous fistulization after total laryngectomy: a Dutch Head and Neck Society audit.

BACKGROUND: Incidences of pharyngocutaneous fistulization (PCF) after total laryngectomy (TL) reported in the literature vary widely, ranging from 2.6 to 65.5%. Comparison between different centers might identify risk factors, but also might enable improvements in quality of care. To enable this on a national level, an audit in the 8 principle Dutch Head and Neck Centers (DHNC) was initiated. METHODS: A retrospective chart review of all 324 patients undergoing laryngectomy in a 2-year (2012 and 2013) period was performed. Overall PCF%, PCF% per center and factors predictive for PCF were identified. Furthermore, a prognostic model predicting the PCF% per center was developed. To provide additional data, a survey among the head and neck surgeons of the participating centers was carried out. RESULTS: Overall PCF% was 25.9. The multivariable prediction model revealed that previous treatment with (chemo)radiotherapy in combination with a long interval between primary treatment and TL, previous tracheotomy, near total pharyngectomy, neck dissection, and BMI < 18 were the best predictors for PCF. Early oral intake did not influence PCF rate. PCF% varied quite widely between centers, but for a large extend this could be explained with the prediction model. PCF performance rate (difference between the PCF% and the predicted PCF%) per DHNC, though, shows that not all differences are explained by factors established in the prediction model. However, these factors explain enough of the differences that, compensating for these factors, hospital is no longer independently predictive for PCF. CONCLUSIONS: This nationwide audit has provided valid comparative PCF data confirming the known risk factors from the literature which are important for counseling on PCF risks. Data show that variations in PCF% in the DHNCs (in part) are explainable by the variations in these predictive factors. Since elective neck dissection is a major risk factor for PCF, it only should be performed on well funded indication.

Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The current knowledge about potential risk factors for lymph node (LN) metastasis in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) is primarily based on studies that lack adjustment for confounding variables. OBJECTIVES: We sought to identify independent risk factors for LN metastasis in patients with HNcSCC and to evaluate the impact of LN metastasis on prognosis. METHODS: Patients with primary HNcSCC were retrospectively included. Potential risk factors were analyzed by univariate and multivariate Cox regression models. Survival was compared using the Kaplan-Meier method. RESULTS: Three hundred thirty-six patients with 545 primary HNcSCCs were included. The median follow-up period was 43 months (range, 1-176 months). LN metastasis occurred in 55 patients (16.4%). The following independent risk factors of HNcSCC for the development of LN metastasis were identified: location on the ear, tumor diameter >50 mm, moderate and poor differentiation, and tumor thickness >2 mm. There was a significant decline in disease-specific survival and overall survival in patients with LN metastasis compared to patients without LN metastasis. LIMITATIONS: The retrospective study design. CONCLUSION: LN metastases from HNcSCC are common with diminished survival rates. This study confirmed some well-known risk factors, but also found moderate differentiation as an independent risk factor for LN metastasis.

Distal chip versus fiberoptic laryngoscopy using endoscopic sheaths: diagnostic accuracy and image quality.

Laryngeal visualization is the hallmark in the diagnostic approach of laryngeal disease. In addition to fiberoptic techniques, digital distal chip technology has been developed to improve visualization. Endoscopic sheaths are used in daily clinical practice to prevent cross-contamination. The objective of the study was to evaluate diagnostic accuracy, image quality and interrater reliability of both flexible distal chip laryngoscopy (DCL) and flexible fiberoptic laryngoscopy (FOL) using contamination preventing endoscopic sheaths. In 53 cases both DCL and FOL images were collected during routine examination using endoscopic sheaths. All images were randomly shown to four experts in the field of laryngology and head and neck oncology. Observers were asked to choose a diagnosis, express their confidence level of that diagnosis and validate image quality: in this way 420 observations (four observers using two techniques) were analyzed. Accuracy in detecting laryngeal disease was 78 % (both DCL and FOL). Confidence level of diagnosis tended to be higher in DCL (p = 0.05). Image quality was validated better in DCL as compared to FOL (p < 0.05). Interrater agreement in identifying laryngeal disease was 1.5 times higher in DCL (κ = 0.44) as compared to FOL (κ = 0.29). In this study, reflecting daily clinical setting using sheathed endoscopes, DCL is identical to FOL regarding diagnostic accuracy, but DCL is superior to FOL in image quality and interrater reliability.

The effect of endoscopic sheaths on visualization in distal chip and fiberoptic laryngoscopy.

Endoscopic sheaths covering the laryngoscope are advised to prevent cross contamination, but might hamper visualization as the most important tool in the diagnostic approach of laryngeal disease. We evaluated whether endoscopic sheaths change image quality and diagnostic accuracy of flexible distal chip laryngoscopy (DCL) and flexible fiberoptic laryngoscopy (FOL). Twelve healthy volunteers underwent a flexible laryngoscopy using a distal chip and a fiberoptic laryngoscope with and without endoscopic sheaths, and in this way 48 images were collected. To determine diagnostic accuracy, the 48 images were mixed with images of 40 patients. All images were randomly shown to four experts in the field of laryngology and head and neck oncology. Observers were asked to validate image quality, choose a diagnosis, and express their confidence level of that diagnosis. Image quality was validated better in DCL as compared to FOL (p < 0.05) both with or without endoscopic sheaths. Endoscopic sheaths worsened image quality in DCL (p < 0.05) but not in FOL. No differences were observed between DCL and FOL with or without endoscopic sheaths in diagnostic accuracy (79-89%). Confidence levels (7.7-8.1) were comparable in DCL and FOL and not influenced by endoscopic sheaths. Image quality in DCL is superior to FOL, but significantly hampered by the use of endoscopic sheaths. In FOL the image quality is already low and not further diminished by endoscopic sheaths.

The influence of clinical experience on reliable evaluation of pharyngeal and laryngeal lesions: comparison of high-definition laryngoscopy using narrow band imaging with fibre-optic laryngoscopy.

BACKGROUND: Fibre-optic laryngoscopy is still widely used in daily clinical practice; however, high-definition laryngoscopy using narrow band imaging could be more reliable in characterising pharyngeal and laryngeal lesions. METHODS: Endoscopic videos were assessed in a tertiary referral hospital by 12 observers with different levels of clinical experience. Thirty pairs of high-definition laryngoscopy with narrow band imaging and fibre-optic laryngoscopy videos were judged twice, with an interval of two to four weeks, in a random order. Inter- and intra-observer reliability, sensitivity and specificity were calculated in terms of detecting a malignant lesion and a specific histological entity, for beginners, trained observers and experts. RESULTS: Using high-definition laryngoscopy with narrow band imaging, inter-observer reliability for detecting malignant lesions increased from moderate to substantial in trained observers and experts (high-definition laryngoscopy with narrow band imaging κ = 0.66 and κ = 0.77 vs fibre-optic laryngoscopy κ = 0.51 and κ = 0.56, for trained observers and experts respectively) and sensitivity increased by 16 per cent. CONCLUSION: Inter-observer reliability increased with the level of clinical experience, especially when using high-definition laryngoscopy with narrow band imaging.

Oncological and functional outcomes in T3 and T4 laryngeal cancer patients: choice for larynx preservation or total laryngectomy based on expected laryngeal function.

OBJECTIVE: To determine oncological and functional outcomes in patients with T3 and T4 laryngeal carcinoma, in which choice of treatment was based on expected laryngeal function and not T classification. METHODS: Oncological outcomes (disease-specific survival and overall survival) as well as functional outcomes (larynx preservation and functional larynx preservation) were analysed. RESULTS: In 130 T3 and 59 T4 patients, there was no difference in disease-specific survival or overall survival rates after radiotherapy (RT) (107 patients), chemoradiotherapy (36 patients) and total laryngectomy (46 patients). The five-year disease-specific survival rates were 83 per cent after RT, 78 per cent after chemoradiotherapy and 69 per cent after total laryngectomy, whereas overall survival rates were 62, 54 and 60 per cent, respectively. Five-year larynx preservation and functional larynx preservation rates were comparable for RT (79 and 66 per cent, respectively) and chemoradiotherapy (86 and 62 per cent, respectively). CONCLUSION: There is no difference in oncological outcome after (chemo)radiotherapy or total laryngectomy in T3 and T4 laryngeal carcinoma patients whose choice of treatment was based on expected laryngeal function.

Identification of new head and neck squamous cell carcinoma molecular imaging targets.

OBJECTIVES: Intraoperative fluorescence imaging (FI) of head and neck squamous cell carcinoma (HNSCC) is performed to identify tumour-positive surgical margins, currently using epidermal growth factor receptor (EGFR) as imaging target. EGFR, not exclusively present in HNSCC, may result in non-specific tracer accumulation in normal tissues. We aimed to identify new potential HNSCC FI targets. MATERIALS AND METHODS: Publicly available transcriptomic data were collected, and a biostatistical method (Transcriptional Adaptation to Copy Number Alterations (TACNA)-profiling) was applied. TACNA-profiling captures downstream effects of CNAs on mRNA levels, which may translate to protein-level overexpression. Overexpressed genes were identified by comparing HNSCC versus healthy oral mucosa. Potential targets, selected based on overexpression and plasma membrane expression, were immunohistochemically stained. Expression was compared to EGFR on paired biopsies of HNSCC, adjacent macroscopically suspicious mucosa, and healthy mucosa. RESULTS: TACNA-profiling was applied on 111 healthy oral mucosa and 410 HNSCC samples, comparing expression levels of 19,635 genes. The newly identified targets were glucose transporter-1 (GLUT-1), placental cadherin (P-cadherin), monocarboxylate transporter-1 (MCT-1), and neural/glial antigen-2 (NG2), and were evaluated by IHC on samples of 31 patients. GLUT-1 was expressed in 100 % (median; range: 60-100 %) of tumour cells, P-cadherin in 100 % (50-100 %), EGFR in 70 % (0-100 %), MCT-1 in 30 % (0-100 %), and NG2 in 10 % (0-70 %). GLUT-1 and P-cadherin showed higher expression than EGFR (p < 0.001 and p = 0.015). CONCLUSIONS: The immunohistochemical confirmation of TACNA-profiling results showed significantly higher GLUT-1 and P-cadherin expression than EGFR, warranting further investigation as HNSCC FI targets.