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.

Raman spectroscopy for cancer detection and cancer surgery guidance: translation to the clinics.

Oncological applications of Raman spectroscopy have been contemplated, pursued, and developed at academic level for at least 25 years. Published studies aim to detect pre-malignant lesions, detect cancer in less invasive stages, reduce the number of unnecessary biopsies and guide surgery towards the complete removal of the tumour with adequate tumour resection margins. This review summarizes actual clinical needs in oncology that can be addressed by spontaneous Raman spectroscopy and it provides an overview over the results that have been published between 2007 and 2017. An analysis is made of the current status of translation of these results into clinical practice. Despite many promising results, most of the applications addressed in scientific studies are still far from clinical adoption and commercialization. The main hurdles are identified, which need to be overcome to ensure that in the near future we will see the first Raman spectroscopy-based solutions being used in routine oncologic diagnostic and surgical procedures.

The influence of closure technique in total laryngectomy on the development of a pseudo-diverticulum and dysphagia.

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.

Addition of tumor microenvironment immune cell composition to improve the performance of a predictive model for oral squamous cell carcinoma.

BACKGROUND: Conventional clinicopathological characteristics insufficiently predict prognosis in oral squamous cell carcinoma (OSCC). We aimed to assess the added predictive value of tumor microenvironment immune cell composition (TMICC) in addition to conventional clinicopathological characteristics. METHODS: Primary tumor samples of 290 OSCC patients were immunohistochemically stained for CD4, CD8, CD20, CD68, CD163, CD57, FoxP3 and Programmed cell Death Ligand 1. Additionally, clinicopathological characteristics were obtained from patients' medical files. Predictive models were trained and validated by conducting Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses with cross-validation. To quantify the added predictive power of TMICC within models, receiver operating characteristic (ROC) analyses were used. RESULTS: Recurrence occurred in 74 patients (25.5%). Conventional clinicopathological characteristics (tumor localization, pathological T-stage, pathological N-stage, extracapsular spread, resection margin, differentiation grade, perineural invasion, lymphovascular invasion) and treatment modality, were used to build a LASSO logistic regression-based predictive model. Addition of TMICC to the model resulted in a comparable AUC of respectively 0.79 (±0.01) and 0.76 (±0.1) in the training and test sets. The model indicated that high numbers of CD4+ T cells protected against recurrence. Lymph node metastasis, extracapsular spread, perineural invasion, positive surgical margins and reception of adjuvant treatment were associated with increased risk for recurrence. CONCLUSIONS: The TMICC, specifically the number of CD4+ T cells, is an independent predictor , however, addition to conventional clinicopathological characteristics does not improve the performance of a predictive model for recurrence in OSCC.

The prognostic role of tumor associated macrophages in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis.

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.

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 = 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.

Relocation of inadequate resection margins in the wound bed during oral cavity oncological surgery: A feasibility study.

BACKGROUND: Specimen-driven intraoperative assessment of the resection margins provides immediate feedback if an additional excision is needed. However, relocation of an inadequate margin in the wound bed has shown to be difficult. The objective of this study is to assess a reliable method for accurate relocation of inadequate tumor resection margins in the wound bed after intraoperative assessment of the specimen. METHODS: During oral cavity cancer surgery, the surgeon placed numbered tags on both sides of the resection line in a pair-wise manner. After resection, one tag of each pair remained on the specimen and the other tag in the wound bed. Upon detection of an inadequate margin in the specimen, the tags were used to relocate this margin in the wound bed. RESULTS: The method was applied during 80 resections for oral cavity cancer. In 31 resections an inadequate margin was detected, and based on the paired tagging an accurate additional resection was achieved. CONCLUSION: Paired tagging facilitates a reliable relocation of inadequate margins, enabling an accurate additional resection during the initial surgery.