Transforming Growth Factor Alpha Stimulation of Mucosal Tissue Cultures from Head and Neck Squamous Cell Carcinoma Patients Increases Chemoresistance to Cisplatin

The monoclonal epidermal growth factor receptor ( EGFR) antibody cetuximab (Erbitux(TM)) was recently approved by the European Medicines Agency for the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) in combination with a platinum-based chemotherapy. Since the antibody has only a limited effect as a monotherapy, possible explanations for the synergistic effect with cisplatin are enhanced antibody-dependent cytoxicity and increased sensitivity to the drug. Most of our knowledge of EGFR biology in HNSCC is based on studies using EGFR inhibitors and/or antibodies. Our study was designed to evaluate the impact of EGFR stimulation on cisplatin-induced DNA damage. Therefore, tissue cultures were produced of tumor-free oropharyngeal mucosa biopsies of HNSCC patients and controls. In a previous study, overexpression of EGFR in tissue cultures from tumor patients compared to controls was confirmed by immunohistochemical staining. Twenty-four-hour stimulation of tissue cultures with transforming growth factor alpha (TGF-alpha), a specific EGFR ligand, resulted in a reduction of cisplatin-induced DNA damage by 35% in cases, whereas in controls TGF-alpha had no effect. This reflects a statistically significant increase in cellular chemoresistance to cisplatin following TGF-alpha stimulation and helps to further understand effects of EGFR antisense therapy in combination with chemotherapy. Copyright (C) 2010 S. Karger AG, Base

Assessment of functional outcomes in head and neck cancer

The goals of the present publication are (a) to identify standardised methods and tools applied in clinical trials and cohort studies to assess key functional aspects in HNC, using the Brief ICF Core Set for head and neck cancer (ICF-HNC) as a reference and (b) to propose a set of sound standardised methods and tools suitable to assess functional problems in HNC. This work contributed to the development of practical ICF-HNC based guidelines targeting the standardised measurement of functional outcomes in HNC follow-up and clinical research in Germany. A systematic review of randomised and clinical controlled trials, and observational studies in HNC were carried out to identify standardised methods and tools. Suitable methods and tools were then selected based on pre-defined criteria. 210 assessment methods and tools were identified in 136 studies: 146 patients reported outcomes (PRO) and 64 tools rated by health professionals. Altogether 59 tools were considered suitable to be included in guidelines: four side effects classifications, two performance status scales, 31 PROs, 10 assessment criteria for clinical examinations, seven assessment methods and tools for the evaluation of technical, equipment-based procedures and five technical, equipment-based procedures. It was possible to identify and select sound and standardised assessment methods and tools for almost all functioning areas defined in the ICF-HNC. Since no tool sufficiently covers support provision by immediate family and by health professionals as well as economic self-sufficiency, we recommend a corresponding update of existing tools

Priorities of head and neck cancer patients: a patient survey based on the brief ICF core set for HNC

The International Classification of Functioning, Disability and Health Core Set for Head and Neck Cancer (ICF-HNC) covers the typical spectrum of problems in functioning experienced by patients with head and neck cancer (HNC). The major goal of the present work was to evaluate patients' priorities using the brief ICF-HNC as a starting point. A priorities assessment checklist consisting of 15 statements was created based on the 14 validated categories of the brief ICF-HNC. In a cross-sectional study, patients were requested to select up to 5 items that were especially important to them. The checklist was sent by mail to 465 patients at different time points of cancer follow-up and handed out to 56 patients with recent HNC diagnosis. Altogether 300 (64.51 %) patients returned the checklist. The top priority of our sample was "I want to survive the cancer", followed by "I want that all the expenses for cancer treatment, cancer care and any additional follow-up treatments be covered by my health insurance or by the welfare system", "I want to be able to continue performing all daily life tasks well", "I want to have trusting relationships with my doctors, nurses and therapists" and "I want to be able to speak clearly". Although survival was, as expected, the top priority for patients enrolled in the study, we show that the weight given to survival and further symptoms or daily life activities meaningfully changes when the biopsychosocial perspective proposed in the ICF is adopte

DNA repair and mutagen sensitivity of epithelial cells and lymphocytes in oropharyngeal cancer

Tobacco-associated nitrosamines are known carcinogens causing DNA damage in epithelial cells of the head and neck. A matched case-control study was performed to evaluate the sensitivity of patients with squamous cell cancer (SCC) of the oropharynx, and controls to tobacco-associated nitrosamines. Quantitative DNA repair was evaluated following a period of 15 and 30 min. Fresh biopsies from 100 male donors of macroscopically healthy oropharyngeal cells and lymphocytes (50 SCC patients and 50 controls) were incubated with N-nitrosodiethylamine (NDEA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or N-nitrosonornicotine (NNN). DNA damage in epithelial cells and lymphocytes was assessed using the comet assay. Following incubation with NDEA, cells underwent a period of DNA repair. All of the nitrosamines caused equivalent genotoxic damage in mucosal cells and lymphocytes of the two groups. Lymphocyte DNA repair capacity in the control group (26.8 and 37.1% after 15 and 30 min) was comparable to the tumor group (23.6 and 40.6%). However, epithelial cell DNA repair capacity of carcinoma patients was significantly reduced to 17.1% (15 min) and 23% (30 min) compared to the DNA repair of the control group (36.2%, 15 min and 46.0%, 30 min). Mutagen sensitivity was comparable in patients and controls. Thus, reduced epithelial cell DNA repair capacity of tumor patients is a possible endogenous risk factor for the development of head and neck squamous cell cancer

Evaluating sequelae after head and neck cancer from the patient perspective with the help of the International Classification of Functioning, Disability and Health

Functioning is recognized increasingly as an important study outcome with head and neck cancer (HNC). The International Classification of Functioning, Disability and Health, as adopted by the World Health Organization in 2001, is based on a comprehensive bio-psycho-social view. The objective of this study was to evaluate functioning from the patient perspective and to classify the results using the comprehensive view of the ICF. Patients with HNC were interviewed on their problems in daily life using qualitative methodology. Sampling of patients followed the maximum variation strategy. Sample size was determined by saturation. All individual interviews were digitally recorded and transcribed verbatim. Interview texts were divided into meaning units and the concepts contained in the meaning units were linked to the ICF according to established linking rules. The transcribed data were analyzed and linked by a second health professional and the degree of consensus was calculated using kappa statistics. Concordance of identified ICF categories among different tumor locations was also measured with kappa statistics. Until saturation was reached, 18 patients were interviewed: seven patients with oral cancer, five with hypopharyngeal cancer and six with laryngeal cancer. Thousand four hundred and sixty-two (1,462) different concepts were translated into the ICF using 104 different, second-level ICF categories. These ICF categories are presented in detail. From the patient perspective, the ICF components (a) Body functions, (b) Activities and participation and (c) contextual Environmental factors are equally represented, while (d) Body structures show by far the least number of categories. The concordance between different tumor locations rages between 0.53 and 0.58 (confidence interval 0.42-0.70). The degree of consensus in the linking process was 0.58 (confidence interval 0.45-0.73). The ICF classification can display problems with functioning following HNC sufficiently. For patients with HNC Body functions, Activities and participation in every-day life and contextual Environmental factors are equally relevant. Therefore, rehabilitation of these patients must not confine itself to anatomical and (patho-) physiologic changes, but should move towards a more comprehensive view including the individual patient's demands on daily life and the given individual contextual circumstances