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.

Head and neck squamous cell carcinoma (HNSCC) is an immunogenic cancer type, and tumor associated macrophages (TAMs) are a major component of the tumor microenvironment (TME). In this systematic review and meta-analysis, studies assessing tumor infiltration with CD68+, iNOS+, HLA-DR+, CD11b+, CD163+, CD206+, and CD204+TAMs were included, and correlation to survival hazard was studied. A low number of CD68+TAMs correlated to better overall survival (OS) in multivariate analysis (HR 1.36 95 %CI (1.07-1.72) P = .01). CD68+TAMs did not correlate to disease free survival (DFS), disease specific survival (DSS), progression free survival (PFS), or recurrence free survival (RFS). A low number of CD163+TAMs correlated to better OS in uni- and multivariate analysis (resp. HR 2.65 95 %CI (1.57-4.46) P = .01 and HR 2.42 95 %CI (1.72-3.41) P < .001). A low number of CD163+TAMs also correlated to better DFS and PFS, whereas a low number of CD204+TAMs only correlated to PFS. While IHC analysis of pan macrophage marker CD68 and M2-like marker CD163 both show prognostic utility in OS, CD163 is a stronger prognosticator, as indicated by multivariate meta-analysis. CD163+TAMs also correlate to DFS and PFS; outcomes that are more relevant to patients, thus showing promising results for future clinical implementation.

Objective In total laryngectomy, the neopharynx can be closed in several ways. It is suggested that a pseudo-diverticulum is seen more frequently in patients closed with vertical closure than with “T”-shaped closure, causing postoperative dysphagia. We report the results of patients treated with vertical closure and “T”-shaped closure with regard to the formation of a pseudo-diverticulum and postoperative dysphagia. Methods In our retrospective cohort study, we identified 117 consecutive laryngectomized patients treated in the VU University Medical Center of Amsterdam between March 2009 and December 2013. Evaluations with statistical analysis of postoperative outcome measures (the formation of a pseudo-diverticulum and dysphagia), qualitative and quantitative variables were conducted. Results Patient demographics were similar between the vertical-shaped closure and the “T”-shaped closure groups. In 84.6% of patients with vertical closure, a pseudo-diverticulum was seen compared to 18.5% with “T”-shaped closure (p < 0.001). Dysphagia was increasingly seen in patients with a pseudo-diverticulum (60.5%) compared to patients without a pseudo-diverticulum (39.5%) (p = 0.090). Conclusion Formation of a pseudo-diverticulum is more frequently seen in laryngectomy patients closed with vertical closure than in patients closed with “T”-shaped closure of the neopharynx. It is favorable to implement “T”-shaped closure in laryngectomy.

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). 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. Data of 14,114 patients were analyzed. Oral cavity cancer treatment did not change over time, while survival improved from 54% to 58% (p = 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. 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.

There is often a mismatch between the chronological and biological age of head and neck squamous cell carcinoma (HNSCC) patients. Treatment is based on chronological age, while biological age seems to be a better prognosticator for treatment toleration. This study investigated whether tumor characteristics are associated with chronological and biological age. The relation with survival was also assessed. Prospectively collected data from 164 newly diagnosed HNSCC patients enrolled in the OncoLifeS database were analyzed. Biological age was assessed by a multidomain geriatric assessment. Several immunological markers were tested by immunohistochemistry on tissue microarray sections from the tumor. Disease-free survival (DFS), adjusted for chronological- and biological age, was assessed by univariable and bivariable analyses. In biologically old patients, a lower infiltration of CD163+ macrophages (p = 0.036) as well as CD4+ (p = 0.019) and CD8+ (p = 0.026) lymphocytes was found in the tumor microenvironment. Chronological older patients showed significantly lower PD-L1 combined positive scores (p = 0.030). Advanced tumor stage and perineural growth were related to a worse DFS. None of the immunological markers showed a significant association with DFS. Biological age might have a stronger influence on tumor microenvironment than chronological age. These findings should initiate clinical studies investigating the response to specific treatment regimens (e.g., immunotherapy) according to the biological age.