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

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

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

The effect of three-dimensional visualisation on performance in endoscopic sinus surgery:A clinical training study using surgical navigation for movement analysis in a randomised crossover design

Objectives: Endoscopic imaging techniques and endoscopic endonasal surgery (EES) expertise have evolved rapidly. Only few studies have assessed the effect of three-dimensional (3D) endoscopy on endoscopic sinus surgery (ESS). The present study aimed to objectively and subjectively assess the additional value of 3D high-definition (HD) endoscopy in ESS. Design: A randomized crossover study of endoscopic surgery performance, using five ESS tasks of varying complexity, performed on Thiel embalmed human specimens. Setting: Simulated surgical environment. Participants: Thirty participants, inexperienced in ESS. Main outcome measures: Performance was assessed using video imaging, surgical navigation and questionnaires. Main outcome measures were as follows: efficiency (defined by time to task completion), distance covered inside the nose, average velocity towards target, accuracy (measured by error rate), and subjective assessment of endoscope characteristics. Results: During ESS tasks, both efficiency and accuracy did not differ significantly between 2D HD and 3D HD endoscopy. Subjectively, imaging characteristics of the 3D HD endoscope were rated significantly better. Conclusions: ESS performance of inexperienced participants was not significantly improved by the use of 3D HD endoscopy during ESS tasks, although imaging characteristics of the 3D HD endoscope were rated significantly better. Surgical field characteristics and surgical techniques are likely to influence any additional value of 3D HD endoscopy

Acute symptoms during the course of head and neck radiotherapy or chemoradiation are strong predictors of late dysphagia

AbstractPurposeTo determine if acute symptoms during definitive radiotherapy (RT) or chemoradiation (CHRT) are prognostic factors for late dysphagia in head and neck cancer (HNC).Material and methodsThis prospective cohort study consisted of 260 HNC patients who received definitive RT or CHRT. The primary endpoint was grade 2–4 swallowing dysfunction at 6months after completing RT (SWALM6). During treatment, acute symptoms, including oral mucositis, xerostomia and dysphagia, were scored, and the scores were accumulated weekly and entered into an existing reference model for SWALM6 that consisted of dose–volume variables only.ResultsBoth acute xerostomia and dysphagia were strong prognostic factors for SWALM6. When acute scores were added as variables to the reference model, model performance increased as the course of treatment progressed: the AUC rose from 0.78 at the baseline to 0.85 in week 6. New models built for weeks 3–6 were significantly better able to identify patients with and without late dysphagia.ConclusionAcute xerostomia and dysphagia during the course of RT are strong prognostic factors for late dysphagia. Including accumulated acute symptom scores on a weekly basis in prediction models for late dysphagia significantly improves the identification of high-risk and low-risk patients at an early stage during treatment and might facilitate individualized treatment adaptation

Standardised Ki-67 proliferation index assessment in early-stage laryngeal squamous cell carcinoma in relation to local control and survival after primary radiotherapy

ObjectivesAmbiguous results have been reported on the predictive value of the Ki-67 proliferation index (Ki-67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early-stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut-off values are attributing factors. Our aim was to elucidate the predictive value of the Ki-67 PI for LC and disease-specific survival (DSS) using a well-defined series of T1-T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA). MethodsA consecutive and well-defined cohort of 208 patients with T1-T2 LSCC treated with primary RT was selected. The Ki-67 PI was determined using DIA. Mann-Whitney U-tests, logistic and Cox regression analyses were performed to assess associations between Ki-67 PI, clinicopathological variables, LC and DSS. ResultsIn multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06-4.59, P = .04) and alcohol use (HR 2.84, 95% CI 1.20-6.71; P = .02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16-8.64; P = .03). Ki-67 PI was not associated with LC (HR 1.59; 95% CI 0.89-2.81; P = .11) or DSS (HR 0.98; 95% CI 0.57-1.66; P = .97). In addition, continuous Ki-67 PI was not associated with LC (HR 2.03; 95% CI 0.37-11.14, P = .42) or DSS (HR 0.62; 95% CI 0.05-8.28; P = .72). ConclusionThe Ki-67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment-related decision-making for LSCC

High DNMT1 Is Associated With Worse Local Control in Early-Stage Laryngeal Squamous Cell Carcinoma

OBJECTIVES/HYPOTHESIS: Early-stage laryngeal squamous cell carcinoma (LSCC) has yielded local control rates of 75% after radiotherapy. DNA methylation, in which DNA methyltransferases play an important role, has influence on tumorigenesis. In this study, we investigated the association between the expression of DNA methyltransferase 1 (DNMT1) and local control in early-stage LSCC treated with radiotherapy. STUDY DESIGN: Retrospective cohort study. METHODS: We analyzed a well-defined homogeneous series of 125 LSCC patients treated with radiotherapy with curative intent. The association of immunohistochemical expression of DNMT1 with local control was evaluated using Cox proportional hazard regression models. RESULTS: With a median follow-up of 58 months, 29 local recurrences (23%) were observed. On univariate analysis, worse local control was associated with high DNMT1 expression (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.10-6.01). Also, higher T-stage (HR 2.48, 95% CI 1.06-5.80) and positive N-status (HR 2.62, 95% CI 1.06-6.47) were associated with worse local control. Multivariate Cox regression demonstrated that high DNMT1 (HR 2.81; 95% CI 1.20-6.58) was independently associated with worse local control. CONCLUSIONS: We found an association between high DNMT1 expression and worse local control in a homogeneous well-defined cohort of early-stage LSCC patients treated with definitive radiotherapy. The association between DNA methylation status as determined by DNMT1 expression and local control suggests that DNMT1 acts as a potential prognostic tumor marker in treatment decision-making in early-stage laryngeal carcinoma. LEVEL OF EVIDENCE: NA Laryngoscope, 2021

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

Cortactin expression assessment improves patient selection for a watchful waiting strategy in pT1cN0-staged oral squamous cell carcinomas with a tumor infiltration depth below 4 mm

BACKGROUND: In this feasibility study we aimed to evaluate the value of previously reported molecular tumor biomarkers associated with lymph node metastasis in oral squamous cell carcinoma (OSCC) to optimize neck strategy selection criteria. METHODS: The association between expression of cortactin, cyclin D1, FADD, RAB25, and S100A9 and sentinel lymph node status was evaluated in a series of 87 (cT1‐2N0) patients with OSCC treated with primary resection and SLNB procedure. RESULTS: Tumor infiltration depth and tumor pattern of invasion were independent prognostic markers for SLN status, while none of the tumor makers showed a better prognostic value to replace SLNB as neck staging technique in the total cohort. However, in the subgroup of patients with pT1N0 OSCC, cortactin expression (OR 16.0, 95%CI 2.0–127.9) was associated with SLN classification. CONCLUSIONS: Expression of cortactin is a promising immunohistochemical tumor marker to identify patients at low risk that may not benefit from SLNB or END

The impact of acoustic neuroma on long-term quality-of-life outcomes in the United Kingdom

To quantify the impact of acoustic neuroma on the quality-of-life (QOL) patients in the United Kingdom. Online questionnaire survey. Members of the British Acoustic Neuroma Association received PANQOL questionnaires. Of the 880 BANA members contacted, 397 (45.1%) responded, although only 359 had complete datasets for analysis. Composite QOL scores were as follows: for microsurgery 58 (SD 35), for radiotherapy 56 (SD18), for combination of surgery and radiotherapy 49 (SD 14), and for the observation group 54 (SD 20). No statistical significance with ANOVA (p = 0.532). Mean (SD) composite QOL scores were as follows: for follow-up 10 years 65 (SD 45). Overall, these values were significantly different compared by ANOVA (p 10 years) QOL outcomes show no significant differences between the different treatment groups