An in vitro study showing the three-dimensional microenvironment influence over the behavior of head and neck squamous cell carcinoma

Objectives: The Head and Neck Squamous Cell Carcinoma (HNSCC) ranks sixth worldwide. The mechanisms of growth, invasion and metastasis of this pathology are extensively studied and generally related to specific variations in signaling pathways like the PI3K-Akt; however most of these competent studies have been performed bidimensionally, which may hide important questions. This study sought to analyze the influence of the microenvironment upon the behavior of HNSCC. Study Design: The status of pAkt, NF-kappa B and Cyclin D1 proteins was accessed through immunofluorescence and western blot methods in HNSCC cell lines originating from tongue, pharynx and metastatic lymph node when submitted to a three-dimensional culture model utilizing a matrix system. A bidimensional culture model (monolayer) was used as control. Results: The HNSCC cell lines cultured three-dimensionally exhibited a growth pattern characterized by small isolated islands, different from the control group. When the three-dimensional model was applied, two of the studied cell lines showed the same expression pattern as the bidimensional model regarding nuclear or cytoplasmatic localization, as well as reduction of all protein levels; however, the cell line originated from tongue, which specially has the epidermal growth factor receptor constitutively activated, demonstrated nuclear translocation of pAkt and also an increase in the levels of Cyclin D1. Conclusions: The results suggest the influence of the microenvironment upon the behavior of HNSCC cells due to the changed expression of proteins related to tumor growth and cellular invasion. Furthermore, intrinsically genetic conditions also played important roles over the cells, despite the culture model employed.

Depression, fatigue, and health-related quality of life in head and neck cancer patients: a prospective pilot study

To assess the prevalence of depression and fatigue symptoms in head and neck cancer patients during radiotherapy treatment and relate them symptoms with these patients' quality of life. This is a prospective study. The Beck Depression Inventory (BDI), Piper Fatigue Scale-revised and Functional Assessment Cancer Therapy Head and Neck (FACT-H&N) were applied to 41 head and neck cancer patients at three times: at the start of treatment (T1), approximately 15 days after the start of treatment (T2) and at the end of treatment (T3), approximately 30 days after the start of the radiotherapy. The mean BDI and PIPER increased during the radiotherapy treatment. BDI scores did not demonstrate the presence of depression, although the number of symptoms increased, and the presence of fatigue rose as treatment advanced. The mean FACT H&N decreased in the middle and at the end of treatment, indicating worsening in these patients' Quality of Life. Depression and fatigue symptoms increased during radiotherapy treatment, while QoL levels decreased. This demonstrates that these symptoms are strongly correlated and that their presence negatively influenced QoL. At the start of treatment, nurses need to advise patients and plan care, offering interventions to decrease these symptoms and improve QoL.

DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors

Aims: To evaluate the associations of excision repair cross complementing-group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Methods and results: The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2-19.7, P = 0.027], which was also high in patients with advanced stage (OR= 5.04, 95% CI: 1.07-23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40-33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07-23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months). Conclusion: Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.

Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer.

Methylating agents are involved in carcinogenesis, and the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) removes methyl group from O(6)-methylguanine. Genetic variation in DNA repair genes has been shown to contribute to susceptibility to squamous cell carcinoma of the head and neck (SCCHN). We hypothesize that MGMT polymorphisms are associated with risk of SCCHN. In a hospital-based case-control study of 721 patients with SCCHN and 1234 cancer-free controls frequency-matched by age, sex and ethnicity, we genotyped four MGMT polymorphisms, two in exon 3, 16195C>T and 16286C>T and two in the promoter region, 45996G>T and 46346C>A. We found that none of these polymorphisms alone had a significant effect on risk of SCCHN. However, when these four polymorphisms were evaluated together by the number of putative risk genotypes (i.e. 16195CC, 16286CC, 45996GT+TT, and 46346CA+AA), a statistically significantly increased risk of SCCHN was associated with the combined genotypes with three to four risk genotypes, compared with those with zero to two risk genotypes (adjusted odds ratio (OR)=1.27; 95% confidence interval (CI)=1.05-1.53). This increased risk was also more pronounced among young subjects (OR=1.81; 95% CI=1.11-2.96), men (OR=1.24; 95% CI=1.00-1.55), ever smokers (OR=1.25; 95%=1.01-1.56), ever drinkers (OR=1.29; 95% CI=1.04-1.60), patients with oropharyngeal cancer (OR=1.45; 95% CI=1.12-1.87), and oropharyngeal cancer with regional lymph node metastasis (OR=1.52; 95% CI=1.16-1.89). In conclusion, our results suggest that any one of MGMT variants may not have a substantial effect on SCCHN risk, but a joint effect of several MGMT variants may contribute to risk and progression of SCCHN, particularly for oropharyngeal cancer, in non-Hispanic whites.

CAREGIVING FOR A FAMILY MEMBER WITH HEAD AND NECK CANCER

Objective: To know the perception of informal caregivers regarding the care for a family member with head and neck cancer. Methods: Qualitative study conducted between March and May 2014 in the radiotherapy outpatient center of the Centro de Alta Complexidade em Oncologia – CACON (Oncology High Complexity Center) of the Hospital Universitário de Brasília – HUB (University Hospital of Brasília) using semi-structured interviews with nine caregivers about the experience of caring for family members. Data underwent Content Analysis and four units of meaning were identified: “Representation of cancer in the Family”, “The care as debt, individual reward or reconstruction of family ties”, “Repercussions of cancer on the caregiver’s personal life” and “Social support and network used by caregivers”. Results: Feelings of sadness and surprise at the moment of diagnosis were attributed to cancer, as well as the idea of punishment. The care was seen as personal satisfaction, accomplishment and opportunity for family rapprochement. Work overload and change in routine were altered functions. Religiosity, exchange of experience in the waiting room and institutional support appeared as coping strategies. Conclusion: The experience of caring for family members with head and neck cancer directly interferes in the lives of caregivers. Pointing out the institutional embracement as a strategy within the social network reinforces the importance of integrating the caregivers as a significant part of the health care plan developed by the health team.

Chromosome 22q a frequent site of allele loss in head and neck carcinoma

Background. Loss of heterozygosity (LOH) correlates with inactivated tumor suppressor genes. LOH at chromosome arm 22q has been found in a variety of human neoplasms, suggesting that this region contains a tumor suppressor gene(s) other than NF2 important to tumorigenesis. The aim of this study was to evaluate the presence of LOH on chromosome 22q11.2-13 and determine whether there was a relationship between loss in this genomic region and tumor histologic parameters, anatomic site, and survival in patients with squamous cell carcinoma of the head and neck (HNSCC).Methods. Fifty matched blood and HNSCC tumor samples taken at the time of surgical treatment were evaluated for LOH by use of four microsatellite markers mapping to 22q11.2-q13. Clinical information was available for all patients. The frequency and distribution of LOH was correlated with clinical (age, sex, use of tobacco and alcohol, site of primary tumor, clinical stage, adjuvant therapy and overall survival) and histologic parameters (histopathologic stage, tumor differentiation).Results. LOH at 22q was found in 19 of 50 (38%) informative tumors. The respective incidence of allelic loss for the patients was as follows: 28% at D22S421, 10% at D22S277, 8% at D22S44S, and 4% at D22S280. No statistical differences were apparent with a mean follow-up of 30 months. Laryngeal tumors showed a higher incidence of LOH compared with oral tumors.Conclusions. These results suggest that the D22S277 locus may be closely linked to a tumor suppressor gene (TSG) and involved in upper aerodigestive tract carcinogenesis. In particular, laryngeal tumors may harbor another putative TSG on 22q11.2-q12.3 that may play a role in aggressive stage III/IV disease. (C) 2000 John Wiley & Sons, Inc.

Aspirin and other non-steroidal anti-inflammatory drug prescriptions and survival after the diagnosis of head and neck and oesophageal cancer

Peer reviewed

Esophageal and head and neck cancer

Clinical Nutrition for Oncology Patients provides clinicians with the information they need to help cancer survivors and patients make informed choices about their nutrition and improve their short-term and long-term health. This comprehensive resource outlines nutritional management recommendations for care prior to, during, and after treatment and addresses specific nutritional needs and complementary therapies that may be of help to a patient. This book is written by a variety of clinicians who not only care for cancer survivors and their caregivers but are also experts in the field of nutritional oncology.

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

Background Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Methods Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Results Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. Conclusion For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further.

Quality-of-life among head and neck cancer survivors at one year after treatment – A systematic review

Abstract Background: The importance of quality-of-life (QoL) research has been recognised over the past two decades in patients with head and neck (H&N) cancer. The aims of this systematic review are to evaluate the QoL status of H&N cancer survivors one year after treatment and to identify the determinants affecting their QoL. Methods: Pubmed, Medline, Scopus, Sciencedirect and CINAHL (2000–2011) were searched for relevant studies, and two of the present authors assessed their methodological quality. The characteristics and main findings of the studies were extracted and reported. Results: Thirty-seven studies met the inclusion criteria, and the methodological quality of the majority was moderate to high. While patients of the group in question recover their global QoL by 12 months after treatment, a number of outstanding issues persist – deterioration in physical functioning, fatigue, xerostomia and sticky saliva. Age, cancer site, stage of disease, social support, smoking, feeding tube placement and alcohol consumption are the significant determinants of QoL at 12 months, while gender has little or no influence. Conclusions: Regular assessments should be carried out to monitor physical functioning,degree of fatigue, xerostomia and sticky saliva. Further research is required to develop appropriate and effective interventions to deal with these issues, and thus to promote the patients’ QoL.

Monte Carlo evaluation of collapsed-cone convolution calculations in head and neck radiotherapy treatment plans

The presence of air and bone interfaces makes the dose distribution for head and neck cancer treatments difficult to accurately predict. This study compared planning system dose calculations using the collapsed-cone convolution algorithm with EGSnrcMonte Carlo simulation results obtained using the Monte Carlo DICOMToolKit software, for one oropharynx, two paranasal sinus and three nodal treatment plans. The difference between median doses obtained from the treatment planning and Monte Carlo calculations was found to be greatest in two bilateral treatments: 4.8%for a retropharyngeal node irradiation and 6.7% for an ethmoid paranasal sinus treatment. These deviations in median dose were smaller for two unilateral treatments: 0.8% for an infraclavicular node irradiation and 2.8% for a cervical node treatment. Examination of isodose distributions indicated that the largest deviations between Monte Carlo simulation and collapsed-cone convolution calculations were seen in the bilateral treatments, where the increase in calculated dose beyond air cavities was most significant.