M.W.M. van den Brekel

Modern imaging techniques and ultrasound-guided aspiration cytology for the assessment of neck node metastases: a prospective comparative study

SummaryAlthough palpation has proved to be an unreliable staging procedure, the indications for and the implications of more reliable radiologic staging methods for the neck in patients with a primary squamous cell carcinoma of the head and neck remain controversial. Only a very accurate imaging technique can replace neck dissection in clinical NO disease. This study compares the value of palpation with computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US) with or without guided aspiration cytology for neck node staging. One hundred and thirty-two patients with squamous cell carcinoma of the head and neck were examined radiologically before undergoing a total of 180 neck dissections as part of their treatment. CT, US and MRI proved to be significantly more accurate than palpation for cervical lymph node staging. The accuracy of US-guided aspiration cytology was significantly better than of any other technique used in this study. Modern imaging techniques are essential for appropriate assessment of neck node metastases. In view of advances in the accuracy of contemporary imaging, the need for elective treatment of the neck requires reappraisal.

The surgical dilemma of 'functional inoperability' in oral and oropharyngeal cancer: current consensus on operability with regard to functional results.

Objectives:  If surgical resection of a tumour results in an unacceptable loss of function, this is defined as ‘functional inoperability’. The current survey aims to define the borders of functional inoperability in oral and oropharyngeal carcinoma and evaluate its current use by obtaining opinions from the experts in the field.

Sentinel Node Detection in Head and Neck Malignancies: Innovations in Radioguided Surgery

Sentinel node mapping is becoming a routine procedure for staging of various malignancies, because it can determine lymph node status more precisely. Due to anatomical problems, localizing sentinel nodes in the head and neck region on the basis of conventional images can be difficult. New diagnostic tools can provide better visualization of sentinel nodes. In an attempt to keep up with possible scientific progress, this article reviews new and innovative tools for sentinel node localization in this specific area. The overview comprises a short introduction of the sentinel node procedure as well as indications in the head and neck region. Then the results of SPECT/CT for sentinel node detection are described. Finally, a portable gamma camera to enable intraoperative real-time imaging with improved sentinel node detection is described.

Human papillomavirus status in young patients with head and neck squamous cell carcinoma

The role of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) development has been recognized only in the last decade. Although younger patients develop HNSCC associated with HPV, the incidence in young patients has not been studied. Forty‐five young HNSCC patients (<40 years) were tested for HPV and the expression of p16ink4a and p53 in tumor biopsies. The presence of HPV was correlated with the absence and presence of alcohol and tobacco exposure. Paraffin‐embedded, archival biopsy materials from HNSCC of 45 patients younger than 40 years were analyzed. HPV subtypes were identified by PCR followed by genotyping. Expression of p16ink4a and p53 were determined by immunohistochemistry. Fourteen (31%) of the HNSCC specimens from 45 patients unequivocally exhibited HPV16 positivity. Sixty percentage of the oropharyngeal tumors and 5% of the oral cavity tumors were HPV16 positive. P16ink4a overexpression was detected in 93% of the HPV16‐positive tumors. None of the HPV16 tumors showed p53 overexpression. There was no association of HPV positivity with (lack of) exposure to alcohol and smoking. HPV association was not exclusively detected in nonsmoking, nondrinking young HNSCC patients. The presence of p16ink4a accumulation and the absence of p53 overexpression are good surrogate markers for HPV‐associated HNSCC.

Evaluation of long term (10-years+) dysphagia and trismus in patients treated with concurrent chemo-radiotherapy for advanced head and neck cancer.

OBJECTIVES Assessment of long term (10-years+) swallowing function, mouth opening, and quality of life (QoL) in head and neck cancer (HNC) patients treated with chemo-radiotherapy (CRT) for advanced stage IV disease. MATERIALS AND METHODS Twenty-two disease-free survivors, participating in a multicenter randomized clinical trial for inoperable HNC (1999-2004), were evaluated to assess long-term morbidity. The prospective assessment protocol consisted of videofluoroscopy (VFS) for obtaining Penetration Aspiration Scale (PAS) and presence of residue scores, Functional Oral Intake Scale (FOIS) scores, maximum mouth opening measurements, and (SWAL-QOL and study-specific) questionnaires. RESULTS At a median follow-up of 11-years, 22 patients were evaluable for analysis. Ten patients (46%) were able to consume a normal oral diet without restrictions (FOIS score 7), whereas 12 patients (54%) had moderate to serious swallowing issues, of whom 3 (14%) were feeding tube dependent. VFS evaluation showed 15/22 patients (68%) with penetration and/or aspiration (PAS⩾3). Fifty-five percent of patients (12/22) had developed trismus (mouth opening⩽35mm), which was significantly associated with aspiration (p=.011). Subjective swallowing function (SWAL-QOL score) was impaired across almost all QoL domains in the majority of patients. Patients treated with IMRT showed significantly less aspiration (p=.011), less trismus (p=.035), and less subjective swallowing problems than those treated with conventional radiotherapy. CONCLUSION Functional swallowing and mouth opening problems are substantial in this patient cohort more than 10-years after organ-preservation CRT. Patients treated with IMRT had less impairment than those treated with conventional radiotherapy.

Current assessment and treatment strategies of dysphagia in head and neck cancer patients: a systematic review of the 2012/13 literature.

Purpose of reviewDysphagia, or swallowing impairment, is a serious sequel of head and neck cancer (HNC) and its treatment. This review focuses on the rapidly growing literature published during the past 2 years about the current assessment and treatment strategies of dysphagia in HNC patients. Recent findingsFunctional swallowing assessment has become standard of care in many HNC centers, to prevent or identify (silent) aspiration, to optimize functional outcomes, and to determine the appropriate rehabilitation strategy. Also preventive swallowing exercises are considered more and more in the pretreatment setting with promising results on (pharyngeal) swallowing function. However, there is a lack of consensus regarding type, frequency, or intensity of the exercises. Furthermore, long-term follow-up of swallowing function might be necessary, given the potential for long-term sequels following HNC treatment. SummaryRegarding dysphagia evaluation, there is still a lack of a uniform ‘gold-standard’ for both assessment and treatment strategies. More high-quality data, adequately controlled, adequately powered and randomized, on prophylactic and therapeutic swallowing exercises are needed, with longer follow-up and better adherence to treatment, for better understanding the effects of chemo and radiotherapy dosage, and of frequency, timing and duration of treatment, to improve swallowing function and optimize quality of life.

T3‐T4 laryngeal cancer in The Netherlands Cancer Institute; 10‐year results of the consistent application of an organ‐preserving/‐sacrificing protocol

Both organ‐preserving concurrent (chemo)radiotherapy ((C)RT) and organ‐sacrificing surgery (total laryngectomy) are used for treatment of advanced laryngeal cancer. The purpose of this study was to present the assessment of our treatment protocol for T3 (C)RT and T4 disease (total laryngectomy + postoperative RT).

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells, and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biologic processes that could be targeted to overcome intrinsic resistance. Experimental Design: We analyzed both microRNA and mRNA expression in a large panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of patients with laryngeal cancer. Results: miRs, mRNAs, and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial-to-mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of patients with laryngeal cancer. Conclusions: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pretreatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors. Clin Cancer Res; 21(24); 5630–8. ©2015 AACR.

Computed tomography for the detection of neck node metastases in melanoma patients

AIMS To assess the value of CT scanning for detection of lymph node metastases in the neck. METHODS The appearance and site of the metastases was studied, as well as the sensitivity and specificity of CT. RESULTS Nodal metastases did not always show a high contrast uptake and nodal density therefore cannot be used as a criterion for metastasis. Irregular contrast enhancement was seen in seven of the 21 tumour-positive necks. Frequently, metastases in the parotids, superficial nodes in the neck and in the posterior triangle were seen. The sensitivity and specificity of palpation and CT scanning were 87 and 100%, respectively. CONCLUSIONS However, because small, clinically occult, melanoma metastases were frequently overlooked on CT, the role of this imaging modality in assessing occult metastases remains limited. Based on recent data from literature it is reasonable to speculate that ultrasound guided fine needle aspiration cytology (FNAC) will prove to be more effective than a non-invasive staging procedure of the neck in melanoma patients.

Differential diagnosis of pulmonary carcinoma following head and neck cancer by genetic analysis.

Purpose: Patients with head and neck cancer often develop a lung tumor that can be diagnosed as distant metastasis (DM) or second primary tumor (SPT). In this study, we use TP53 mutation analysis for validation of an allelic loss marker panel and a decision algorithm for distinguishing between DM and SPT. Experimental Design: Tumor pairs of 39 patients were analyzed for TP53 mutations, for patterns of allelic loss and immunohistochemical analysis of p53 expression. Results of these three analyses were compared, using mutation analysis as gold standard. Results: Loss of heterozygosity (LOH) analysis indicated DM in 15 and SPT in 23 cases (one inconclusive). TP53 mutation analysis was informative in 15 cases. Based on the p53 mutation status alone, nine tumors were diagnosed as SPT and six as DM. In all 15 cases the LOH analysis was in concordance with the TP53 mutation analysis. Immunostaining for p53 showed promise as a first scan to diagnose lung tumors as SPT but cannot be used to diagnose DM. Conclusion: The TP53 mutation data validate the suitability of the LOH marker panel and decision algorithm for differential diagnosis of DM and SPT in the lung. LOH analysis can theoretically be exploited in almost all cases and is less laborious than TP53 mutation analysis.