Onset of hypothyroidism after total laryngectomy:Effects of thyroid gland surgery and preoperative and postoperative radiotherapy

Background: To determine time of onset and risk of hypothyroidism after total laryngectomy (TL) with and without (hemi)thyroidectomy in relation to treatment regimen, that is, preoperative radiotherapy (RT-TL), postoperative radiotherapy (TL-RT), and postoperative re-irradiation (RT-TL-RT). Methods: Retrospective review of 128 patients treated by RT-TL (51 patients), TL-RT (55 patients), and RT-TL-RT (22 patients). Risk of hypothyroidism was determined by multivariable Cox regression analysis and euthyroid survival was calculated using Kaplan-Meier method. Results: Hypothyroidism developed in 69 (54%) patients. The median onset of hypothyroidism was later (P <.01) and the risk of hypothyroidism was lower (hazard ratio 0.49; P =.014) in the TL-RT group compared to both other treatment regimens. Euthyroid survival did not differ between the treatment regimens. Two years euthyroid survival was 24% with and 61% without (hemi)thyroidectomy (P <.001). Conclusions: Patients treated with TL-RT have later onset of hypothyroidism. Higher risk for hypothyroidism is associated with salvage TL after radiotherapy and (hemi)thyroidectomy

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

Evaluating Laryngopharyngeal Tumor Extension Using Narrow Band Imaging Versus Conventional White Light Imaging

OBJECTIVE/HYPOTHESIS: Comparing detection and extension of malignant tumors by flexible laryngoscopy in the outpatient setting with laryngoscopy under general anesthesia using both White Light Imaging (WLI) and Narrow Band Imaging (NBI). STUDY DESIGN: Prospective randomized controlled trial. METHODS: Two hundred and thirty-three patients with laryngeal and pharyngeal lesions underwent flexible and rigid laryngoscopy, with both WLI and NBI. Extension of malignant lesions (n = 132) was compared between both techniques in detail. RESULTS: Sensitivity of NBI during flexible endoscopy (92%), was comparable with that of WLI during rigid endoscopy (91%). The correlation of tumor extension between flexible and rigid laryngoscopy was high (rs = 0.852-0.893). The observed tumor extension was significantly larger when using NBI in both settings. The use of NBI during flexible laryngoscopy leads to upstaging (12%) and downstaging (2%) of the T classification. CONCLUSIONS: NBI during flexible laryngoscopy could be an alternative to WLI rigid endoscopy. NBI improves visualization of tumor extension and accuracy of T staging. LEVEL OF EVIDENCE: 3 Laryngoscope, 2021

To what extent has the last two decades seen significant progress in the management of older patients with head and neck cancer?

Introduction: Life expectancy is rising and consequently also the number of older patients with head and neck cancer. Different treatment regimens are often applied for older patients. The aim of this study is to investigate how treatment patterns and survival rates have changed over the past 20 years in older patients with head and neck squamous cell carcinoma (HNSCC). Materials: Patient and tumour characteristics, treatment and 5-year survival data from the Netherlands Cancer Registry of patients aged >60 years diagnosed with HNSCC in 1990-1995 and 2010-2015 were compared using chi-square test and relative survival analysis. Results: Data of 14,114 patients were analyzed. Oral cavity cancer treatment did not change over time, while survival improved from 54% to 58% (p 1/4 0.03). Oropharyngeal and hypopharyngeal cancer treatment shifted towards non-surgical, with survival improving from 31% to 51% (p < 0.01) and 26% to 34% (p < 0.01), respectively. Laryngeal cancer treatment changed towards surgery in stage I and non-surgical treatment in stage III and IV disease. Survival in laryngeal cancer stage I remained stable and favorable at a relative survival rate of around 90%. Survival non-significantly changed from 54% to 49% for stage III disease and from 37% to 33% for disease. Conclusion: Relative survival increased for all head and neck cancer sites in older patients, except for laryngeal cancer. For oropharyngeal, hypopharyngeal and advanced laryngeal cancer, a shift towards non-surgical treatment modalities was observed. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY licens

Determinants of delay and association with outcome in head and neck cancer:A systematic review

Introduction: Head and neck cancers (HNC) are relatively fast-growing tumours, and delay in treatment initiation is associated with tumour progression and adverse outcome. An overview of factors contributing to delay can provide critical insights on necessary adjustments to optimize care pathways. This systematic review aims to identify factors associated with delay and summarize the effect of delay on oncological outcome measures. Methods: A search strategy was conducted according to PRISMA guidelines to search electronic data-bases for studies assessing the carepathway interval (days between first visit in head and neck oncology center and treatment initiation) and/or time-to-treatment-initiation interval (days between histological diagnosis and treatment initiation) and 1) determinants of delay and/or 2) effect of delay on outcome within these timeframes. Due to heterogeneity between included studies, a meta-analysis was not possible. Results: Fifty-two studies were eligible for quantitative analysis. Non-Caucasian race, academic setting, Medicaid/no insurance and radiotherapy as primary treatment were associated with delay. Advanced tumour stage was related to increased time-to-treatment initiation in the four common sites combined (oral cavity, oropharynx, hypopharynx, larynx). Separate determinants for delay in different tumour locations were identified. In laryngeal, oral cavity cancer and the four common HNC sites combined, delay in start of treatment is associated with decreased overall survival, although no cut-off time point could be determined. Conclusion: Race, facility type, type of insurance and radiotherapy as primary treatment were associated with delay and subsequent inferior survival in the four common sites combined. (C) 2021 The Authors. Published by Elsevier Ltd

The effect of delayed primary treatment initiation on adverse events and recurrence in older head and neck cancer patients

Background and purpose: As a result of rapid tumor growth in head and neck squamous cell carcinoma (HNSCC), delay in treatment initiation can result in tumor progression and inferior outcome. Especially older and frail patients are prone to develop adverse events. The aim of this study was to assess the effect of delay on development of adverse events and recurrence in older HNSCC patients. Materials and methods: This cohort study with prospectively collected data included all newly diagnosed, curatively treated HNSCC patients (>60 years) between 2015 and 2017. Time-to-treatment interval and geriatric domains were assessed. Adverse events were defined as postoperative complications (ClavienDindo classification) and acute radiation-induced toxicity (Common Terminology Criteria of Adverse Events). Multivariable regression models were performed, using adverse events and recurrence as outcome variables. Results: A total of 245 patients were included. Median time-to-treatment was 26 days for surgery patients and 40 days for radiotherapy patients (p < 0.001). Delayed treatment initiation was not associated with postoperative complications or acute radiation-induced toxicity. Delay was significantly associated with recurrence risk within two years after treatment initiation in a model adjusted for stage and tumor location in patients treated with initial surgery (HR:4.1, 95%CI:1.2- 14.0, p = 0.024). For patients treated with radiotherapy, delay was not significantly associated with recurrence risk. Conclusion: Delayed treatment initiation was independently associated with increased recurrence risk in patients treated with initial surgery. Delay was not associated with short-term adverse events. These findings highlight the importance of establishing fast-track care pathways to minimize delays and improve especially long-term outcome. (c) 2022 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 173 (2022) 154-162 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Meta-analysis of 701 published cases of sinonasal neuroendocrine carcinoma:The importance of differentiation grade in determining treatment strategy

AbstractThe aim of this meta-analysis was to provide treatment guidelines for sinonasal neuroendocrine carcinoma (SNC) by combining all available data in the literature.A literature search for all studies concerning SNC was performed against the MEDLINE and EMBASE databases. Available clinical data was normalized, pooled, and statistically analyzed.A total of 701 cases of SNC were available for analysis, comprising 127 well or moderately differentiated sinonasal neuroendocrine carcinomas (SNEC), 459 sinonasal undifferentiated carcinoma (SNUC) and 115 sinonasal small cell carcinoma (SmCC). Tumor type was the most important predictor of survival, with a 5-year disease-specific survival (DSS) of 70.2% for SNEC, 35.9% for SNUC and 46.1% for SmCC. Tumor stage on presentation was of limited value in predicting survival or response to treatment. Overall, the application of surgery yielded significantly better results (5-year DSS 52.2% versus 30.1%, p<0.001). In SNUC, radiotherapy was a beneficial supplement to surgery (5-year DSS 54.7% versus 15.7%, p=0.027), while radiotherapy as monotherapy performed poorly (5-year DSS 17.9%). Chemotherapy did not appear to contribute to survival.Based on these findings, we can conclude that the most important predictors of survival in SNC are differentiation grade and the associated choice of treatment modality. In contrast to other head and neck cancers, tumor staging appears of limited value in predicting survival or deciding on a treatment strategy. Surgery should be the cornerstone of treatment, supplemented by radiotherapy in poorly differentiated subtypes (SNUC, SmCC). Chemotherapy does not appear to contribute to survival

Glycoprotein Nonmetastatic Melanoma Protein B as Potential Imaging Marker in Posttherapeutic Metastatic Head and Neck Cancer

OBJECTIVE: To evaluate expression of potential molecular imaging targets epidermal growth factor receptor (EGFR), glycoprotein nonmetastatic melanoma protein B (GPNMB), and vascular endothelial growth factor (VEGF) in lymph nodes (LNs) with or without head and neck squamous cell carcinoma (HNSCC) metastases after (chemo)radiation. STUDY DESIGN: Retrospective study comparing receptor expression in paired lymph nodes after initial treatment. SETTING: A tertiary referral hospital. SUBJECTS AND METHODS: Salvage neck dissection specimens of 40 patients treated with (chemo)radiation were selected. LNs that contained viable tumor, reactive changes after initial treatment, and normal LNs were analyzed using immunohistochemically determined H-scores and by calculating sensitivity and specificity rates and positive/negative predictive values (PPVs/NPVs). RESULTS: EGFR expression was found in 86% and GPNMB expression in 100% of the LNs with viable tumor. VEGF expression was present in all lymph node types. For EGFR, the sensitivity rate was 86%, and specificity rate was 81%. For GPNMB, these were 100% and 75%, respectively. PPV of EGFR was 61.8% and NPV was 98.2%. These were 56.4% and 100% for GPNMB, respectively. CONCLUSION: In residual or recurrent HNSCC lymph node metastases, both EGFR and GPNMB show tumor-specific expression in immunohistochemistry, which may prove useful in future molecular imaging in salvage neck dissections. Immunohistochemically detected VEGF expression indicates that this target is not feasible for imaging purposes in salvage surgery. Therefore, GPNMB could be a new potential imaging target showing comparable results to EGFR in immunohistochemistry

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

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