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

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

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

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

Incidental findings during the diagnostic work-up in the head and neck cancer pathway:Effects on treatment delay and survival

Objectives: As a result of the increasing number of diagnostic scans, incidental findings (IFs) are more frequently encountered during oncological work-up in patients with head and neck squamous cell carcinomas (HNSCC). IFs are unintentional discoveries found on diagnostic imaging. Relevant IFs implicate clinical consequences, resulting in delay in oncologic treatment initiation, which is associated with unfavorable outcomes. This study is the first to investigate the incidence and nature of IFs over the years and establish the effect of relevant IFs on delay. Material and methods: This retrospective study compared two time periods (2010 & ndash;2011 and 2016 & ndash;2017), described associations between relevant IFs and delay in carepathway interval (days between first visit and treatment initiation) and assessed the effect of relevant IFs on overall two-year survival. Results: In total, 592 patients were included. At least one IF was found in 61.5% of the patients, most frequently on chest-CT. In 128 patients (21.6%) a relevant IF was identified, resulting for the majority in radiologist recommendations (e.g. additional scanning). Presence of a relevant IF was an independent significant factor associated with delay in treatment initiation. The risk of dying was higher for patients with a relevant IF, although not significant in the multivariable model (HR: 1.46, p = 0.079). Conclusion: In diagnostic work-up for HNSCC patients, relevant IFs are frequently encountered. As the frequency of additional imaging rises over the years, the number of IFs increased simultaneously. These relevant IFs yield clinical implications and this study described that relevant IFs result in significant delay in treatment initiation

A comparison of the Thunderbeat and standard electrocautery devices in head and neck surgery:a prospective randomized controlled trial

PURPOSE: New energy-based sutureless vessel ligation devices, such as the Thunderbeat (Olympus Medical Systems Corp., Tokyo, Japan), could reduce operative time and limit blood loss in head and neck surgery; however, efficacy and safety in major head and neck surgery have not been investigated in a prospective, randomized study. METHODS: This prospective, double-arm, randomized controlled trial consisted of two parts: total laryngectomy (TL) and neck dissection (ND). Thirty patients planned for TL were randomized in two groups. For the ND part, forty-two operative sides were likewise randomized. In both parts, Thunderbeat was used in addition to the standard instrumentation in the intervention groups, while only standard instrumentation was used in the control groups. Primary outcome values were blood loss, operative time and complication rate. RESULTS: For the TL part there was no difference in mean blood loss (p = 0.062), operative time (p = 0.512) and complications (p = 0.662) between both hemostatic techniques. For the neck dissection part, there was a reduction in blood loss (mean 210 mL versus 431 mL, p = 0.046) and in operative time (median 101 (IQR 85-130) minutes versus 150 (IQR 130-199) minutes, p = 0.014) when Thunderbeat was used. There was no difference in complication rate between both hemostatic systems (p = 0.261). CONCLUSION: The Thunderbeat hemostatic device significantly reduces operative blood loss and operative time for neck dissections, without increase in complications. In TL, blood loss using Thunderbeat was comparable with the standard technique, but the operative time tended to be shorter. TRIAL REGISTRATION: UMCG Research Register, Reg. no. 201700041, date of registration: 18/1/2017

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/)

The Relation Between Histological, Tumor-Biological and Clinical Parameters in Deep and Superficial Leiomyosarcoma and Leiomyoma

Purpose: Leiomyosarcomas (LMS) of deep and superficial tissues were examined to identify prognostic markers explaining their different biological behaviour and to define differences between cutaneous and subcutaneous LMS. LMS and leiomyomas (LM) of the skin were compared to and consistent differences that could aid in the (sometimes difficult) diagnosis