Pre-Radiotherapy Dental Assessment of Head and Neck Oncology Patients: An Audit.

Objectives: Approximately 300 people are diagnosed with Head and Neck cancer annually in Northern Ireland. The management may include treatment by surgery or by chemotherapy and radiotherapy,
or a combination of modalities. Patients whose oral cavity, teeth, salivary glands and jaws that
will be affected by treatment, particularly radiotherapy should have a pre-treatment assessment. This should be done as early as possible to maximise the time available for dental management. However, this can be challenging owing to the complexities of cancer diagnosis, treatment planning and multidisciplinary management. At the Belfast Dental Hospital, a number of patients were referred post- radiotherapy with complications after not having received a pre-treatment assessment. The referrals for pre- treatment dental assessment were also late in patients’ multidisciplinary journey, limiting the time period
for dental input. The purpose of this audit was to examine the time period between dental assessment and commencement of radiotherapy and whether this was an adequate time frame for dental management. This audit will also examine the dental diseases present and the treatments required pre-radiotherapy. Methods: Data for this audit was collected over 4 months in 2012
by analysing the dental charts and referrals of new patients who were referred to and attended the dental head and neck oncology clinic. A standardised referral pro-forma was introduced from September 2013 to improve the referral process.
A re-audit was conducted over 4 months in 2014. Data was collected similarly as previous. The time period between dental assessment and commencement of radiotherapy was examined. The presence of dental disease and subsequent treatments required were also noted.
Results: 63 new patients were examined in the dental head and neck oncology clinic over 4 months in 2012. 48 (76.2%) were examined pre-radiotherapy. The average length of time between dental assessment and radiotherapy commencement was 11 days. A new standardised referral pro-forma was introduced in 2013. In the re-audit, 65 new patients were seen over 4 months in 2014.
60 (92.3%) patients were examined pre-radiotherapy. The average length of time between dental assessment and radiotherapy commencement was 18 days.
Conclusion: Given the high prevalence of pre-existing dental disease amongst head and neck cancer patients, prompt dental assessment and treatment is vital. Efforts aimed at improving the care pathway are on-going through the implementation of a mandatory referral pro-forma and a dedicated assessment clinic.

Experience of Managing Head and Neck Cancer Patients Amongst Specialty Trainees in Restorative Dentistry

Background: Upon completion of Specialty Training in Restorative Dentistry, trainees (StRs) should
be proficient in maxillofacial prosthodontics to meet the restorative needs of head and neck cancer patients (HANC), and in preparation for the Intercollegiate Specialty Fellowship Examination (ISFE).1,2
Objective: The aim of this study is to collate and compare data relating to the training of Restorative Dentistry Rs in the management of HANC patients across different geographical locations within the British Isles. Methods: Current trainees were invited to complete an online questionnaire by the Specialty Registrars in Restorative Dentistry Group (SRRDG). Participants were asked to rate their confidence and experience in assessing and planning treatment for HANC patients, attending theatre and manufacturing surgical obturators, and in providing implants for appropriate cases. Respondents were also asked to appraise clinical and didactic teaching within their unit, and to rate their confidence of passing oncology- based questions in a future ISFE. Results: Responses were obtained from 21 StRs (n=21) training in all five countries within the British Isles. Most respondents were based in England (76%). A third were in their 5th year of training. Less than half reported that they were confident
of independently assessing (48%) or treatment planning (38%) HANC patients. More than half of StRs (52%) indicated that they were not confident of attending theatres alone and manufacturing a surgical obturator. One third (33%) rated their experience of treating oncology patients with implants as poor or very poor, including three in their 5th year of training. Less than one third rated didactic teaching in maxillofacial prosthodontics at their unit as good or excellent. Only 4 respondents indicated that they were confident of answering an ISFE oncology question on management of healthcare delivery. Six StRs expressed concerns over a lack of case-based exposure.
Conclusion: Experience and training in maxillofacial prosthodontics is inconsistent for StRs across the British Isles with many lacking in clinical exposure.

Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 a population-based study.

BACKGROUND: Head and neck (H&N) cancers are a heterogeneous group of malignancies, affecting various sites, with different prognoses. The aims of this study are to analyse survival for patients with H&N cancers in relation to tumour location, to assess the change in survival between European countries, and to investigate whether survival improved over time.
METHODS: We analysed about 250,000 H&N cancer cases from 86 cancer registries (CRs). Relative survival (RS) was estimated by sex, age, country and stage. We described survival time trends over 1999-2007, using the period approach. Model based survival estimates of relative excess risks (RERs) of death were also provided by country, after adjusting for sex, age and sub-site.
RESULTS: Five-year RS was the poorest for hypopharynx (25%) and the highest for larynx (59%). Outcome was significantly better in female than in male patients. In Europe, age-standardised 5-year survival remained stable from 1999-2001 to 2005-2007 for laryngeal cancer, while it increased for all the other H&N cancers. Five-year age-standardised RS was low in Eastern countries, 47% for larynx and 28% for all the other H&N cancers combined, and high in Ireland and the United Kingdom (UK), and Northern Europe (62% and 46%). Adjustment for sub-site narrowed the difference between countries. Fifty-four percent of patients was diagnosed at advanced stage (regional or metastatic). Five-year RS for localised cases ranged between 42% (hypopharynx) and 74% (larynx).
CONCLUSIONS: This study shows survival progresses during the study period. However, slightly more than half of patients were diagnosed with regional or metastatic disease at diagnosis. Early diagnosis and timely start of treatment are crucial to reduce the European gap to further improve H&N cancers outcome.

Impact of Referral Protocols on the Dental Management of Patients Undergoing Treatment for Head and Neck Oncology in Northern Ireland

Objective: To evaluate the handling, by a group of practice-based researchers, of a recently introduced bulk fill resin-based composite restorative material, Filtek Bulk Fill Restorative (3M ESPE).

Methods: The twelve selected evaluators were sent explanatory letters, a pack of the material under investigation to use for 8 weeks, and a questionnaire.

Results: The evaluators rated the ease of use of the bulk fill restorative the same as the previously used posterior composite material. The provision of one shade only for evaluation may have compromised the score for aesthetic quality. No post-operative sensitivity was reported.

Conclusions: The bulk fill material was well received as indicated by the high number of evaluators who would both purchase the material and recommend it to colleagues.

Clinical relevance: A recently introduced bulk fill restorative material achieved a rating for handling which was similar to the evaluators’ previously used resin composite, although there were some concerns regarding the translucency of the material.

Oral Health Status of Patients Undergoing Treatment for Head and Neck Oncology in Northern Ireland

This study aimed to collect data on the oral health status of patients undergoing treatment for head and neck oncology across Northern Ireland. Data were collected on all patients referred to the Northern Ireland Multidisciplinary Head and Neck Oncology Team for discussion and treatment planning. Each patient underwent pre-treatment dental assessment in the Centre for Dentistry, Queen’s University Belfast, between June 2013 and November 2014. Data were collected from clinical oral examinations supplemented with intra-oral radiographs. During the course of the study 96 patients were assessed and the levels of dental disease observed in this cohort were high. On clinical examination
43% were diagnosed with caries and 46% with periodontal disease. Ten patients were completely edentate. The disease profile of this patient group presents significant challenges to dental services tasked with rendering patients dentally fit prior to undergoing oncology treatment.

Specialty Registrars’ Experience of Managing Head and Neck Cancer Patients

Objective The aim of this study was to collate and compare data on the training of Specialty Registrars in Restorative Dentistry (StRs) in the management of head and neck cancer (HANC) patients across different training units within the UK and Ireland. Methods Current trainees were invited to complete an online questionnaire by the Specialty Registrars in Restorative Dentistry Group (SRRDG). Participants were asked to rate their confidence and experience of assessing and planning treatment for HANC patients, attending theatre alone and manufacturing surgical obturators, and providing implants for appropriate cases. Respondents were also asked to appraise clinical and didactic teaching at their unit, and to rate their confidence of passing a future Intercollegiate Specialty Fellowship Examination (ISFE)-station assessing knowledge of head and neck cancer. Results Responses were obtained from 21 StRs (n=21) training within all five countries of the British Isles. Most respondents were based in England (76%), with one StR in each of Scotland, Wales, Northern Ireland and the Republic of Ireland. A third (33%) were in their 5th year of training. Almost half of the StRs indicated that they were confident of independently assessing (48%) new patients with HANC, with fewer numbers reporting confidence in treatment planning (38%). The majority (52%) of respondents indicated that they were not confident of attending theatre alone and manufacturing a surgical obturator. A third (33%) rated their experience of treating HANC patients with implants as ‘poor’ or ‘very poor’, including three StRs in their 5th year of training. Less than one third (<33%) rated didactic teaching in maxillofacial prosthodontics at their unit as ‘good’ or ‘excellent’, and only 7 StRs indicated that they were confident of passing an ISFE-station focused on HANC. Conclusion Experience and training regarding patients with head and neck cancer is inconsistent for StRs across the UK and Ireland with a number of trainees reporting a lack of clinical exposure.

Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.

BACKGROUND: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. METHODS: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old ('older adults', 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults. CONCLUSIONS: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.

O6-Methylguanine-DNA-Methyltransferase methylation: prevalence and predictive value in head and neck squamous cell carcinoma

Introduction: Le gène O6-méthylguanine-ADN méthyltransferase (MGMT) code pour une enzyme spécifique réparatrice de l’ADN qui protège les cellules de la toxicité des agents alkylants. Ainsi, l’activité du MGMT est un mécanisme majeur de résistance aux agents alkylants. Il a été démontré qu’une diminution de l’expression du gène MGMT par une hyperméthylation du promoteur résulte en une amélioration de la survie chez les patients avec certains types de tumeurs qui sont traitées avec des agents chimiothérapeuthique alkylants. Objectifs: Déterminer la prévalence de la méthylation du gène MGMT chez des patients avec des cancers épidermoïdes localement avancés de la sphère ORL traités avec chimioradiothérapie et évaluer l’impact de cette méthylation sur la survie. Méthodes: Sur 428 patients consécutifs, traités avec chimioradiothérapie à notre institution et suivis pour un période médiane de 37 mois, 199 spécimens chirurgicaux paraffinés ont été récupérés. L’ADN était extrait et modifié par le traitement au bisulfite. Une réaction en chaîne de la polymérase, spécifique à la méthylation était entreprise pour évaluer l’état de méthylation du promoteur du gène du MGMT. Les résultats de laboratoire étaient corrélés avec la réponse clinique. L’analyse statistique était exécutée à l’aide du test de Fisher pour les données catégoriques et à l’aide des courbes de Kaplan-Meier pour les échecs au traitement. Résultats : Des 199 extraits d’ADN initiaux, 173 (87%) étaient modifiés au bisulfite avec succès. Des ces spécimens modifiés, 71 (41%) ont démontré une hyperméthylation du MGMT. Pour les cas de méthylation et nonméthylation du MGMT, les caractéristiques des patients n’étaient pas significativement différentes. Les taux de réponse étaient 71 et 73% (p=NS) respectivement. Le contrôle locorégional était respectivement 87 et 77% (p=0.26), la survie sans maladie était 80 et 60% (p=0.38), la survie sans métastase à distance était 92 et 78% (p=0.08) et la survie globale était 64 et 62% (p=0.99) à 3 ans. Conclusions : L’état de méthylation du MGMT est fortement prévalent (41%) et semble avoir un possible impact bénéfique sur la survie quand la chimioradiothérapie est administrée aux patients avec des stades avancés de cancers tête et cou.

Quality-of-life measurement in patients undergoing radiation therapy for head and neck cancer: a Hong Kong experience

The aims of this study are (1) to establish a reliable and valid quality-of-life (QOL) questionnaire for Chinese patients with head and neck (H&N) cancer who are treated with radiation therapy and (2) to evaluate the impact of the immediate side effects of treatment on the QOL of these patients. The 39-item "Quality of Life Radiation Therapy Instrument with Head and Neck Companion Module" (QOL-RTI/H&N) was translated into Chinese. In the reliability evaluation phase (study module 1), the questionnaire was administered twice to 56 H&N cancer patients, 7 days apart, during the second and third week of radiation therapy. In the validity evaluation phase (study module 2), 138 patients completed the QOL-RTI/H&N before starting and at the end of radiation therapy. Sixty-nine of these 138 patients also completed the QOL-RTI/H&N during the second week of their radiation therapy, at the same time as completing the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire. Cronbach alpha coefficients were 0.88 for the general-tool QOL-RTI and 0.90 for the H&N subscale. Test-retest reliability was satisfactory with intraclass correlation coefficients of 0.89 for the general-tool QOL-RTI and 0.75 for the H&N subscale. The instrument can discriminate between patients with stage I or II disease and those with stage III or IV disease (P < .05). Concurrent validity was established by the good agreement with the FACT-H&N (r = 0.86, P < .001). A highly significant deterioration was in the QOL from the baseline to the end of treatment (mean difference for general tool = 1.95, P < .001; mean difference for H&N subscale = 4.85, P < .001). The Chinese QOL-RTI/H&N is a reliable and valid tool for determining the QOL in H&N cancer patients receiving radiation therapy. The immediate side effects of treatment had a significantly negative impact on the patients' QOL. The impact was relatively large for the functional and treatment-site aspects.

A microfluidic system for testing the responses of head and neck squamous cell carcinoma tissue biopsies to treatment with chemotherapy drugs

Tumors are heterogeneous masses of cells characterized pathologically by their size and spread. Their chaotic biology makes treatment of malignancies hard to generalize. We present a robust and reproducible glass microfluidic system, for the maintenance and “interrogation” of head and neck squamous cell carcinoma (HNSCC) tumor biopsies, which enables continuous media perfusion and waste removal, recreating in vivo laminar flow and diffusion-driven conditions. Primary HNSCC or metastatic lymph samples were subsequently treated with 5-fluorouracil and cisplatin, alone and in combination, and were monitored for viability and apoptotic biomarker release ‘off-chip’ over 7 days. The concentration of lactate dehydrogenase was initially high but rapidly dropped to minimally detectable levels in all tumor samples; conversely, effluent concentration of WST-1 (cell proliferation) increased over 7 days: both factors demonstrating cell viability. Addition of cell lysis reagent resulted in increased cell death and reduction in cell proliferation. An apoptotic biomarker, cytochrome c, was analyzed and all the treated samples showed higher levels than the control, with the combination therapy showing the greatest effect. Hematoxylin- and Eosin-stained sections from the biopsy, before and after maintenance, demonstrated the preservation of tissue architecture. This device offers a novel method of studying the tumor environment, and offers a pre-clinical model for creating personalized treatment regimens.