Mouth and Tooth Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Rare Diseases

Periodontal Diseases

Leukoplakia

Mouth Diseases

Stomatognathic Diseases

Precancerous Conditions

Pathological Conditions, Anatomical

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Ketorolac

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Ketorolac Rinse

In Phase II trials, treatment with ketorolac tromethamine oral rinse has been shown to block periodontal disease progression even in the absence of standard clinical intervention such as scaling and root planing which is routinely done to reduce the periodontal pathogen load that is driving the local destructive host inflammatory response. Resolution of periodontal disease has a favorable effect on normalizing the cellular and biochemical indices of inflammation as reflected by histological changes as well as the levels of prostaglandin E2 (PGE2) and interleukin I beta (IL-1beta). In this trial, we will prospectively evaluate if eliminating the inflammatory process (via inhibition of PGE2 biosynthesis) in the oral cavity has a favorable impact on reversing oropharyngeal leukoplakia. To test this hypothesis, up to 57 prospectively identified individuals with objective findings of oropharyngeal leukoplakia will be randomized to receive either a mouth rinse containing ketorolac or placebo. Ketorolac is a 7-fold selective inhibitor of cyclooxygenase-2 (Cox-2), which has been designed for local delivery to maximize the drug exposure to critical oral target tissues while minimizing gastric and systemic exposure to the drug. All responses will be determined at the three month completion of trial using the response criteria developed at MD Anderson Cancer Center. The drug will be given for three months and then all the patients will be followed for one additional month off all oral treatment to observe for late side effects. Based on the analysis of oral exam and photographically documented change in the pretreatment area of leukoplakia, the response of all patients will be determined.

The evaluation of the outcome will include a measurable secondary endpoint consisting of an assessment of histological change as determined by serial punch biopsies of the oral cavity. In addition, a panel of carcinogenesis and inflammatory markers will be serially measured at baseline, at one month follow up or at study conclusion. In the residual tissue, other bioassays will be evaluated to determine their suitability as intermediate endpoint markers. The purpose of this study is a preliminary evaluation of the effectiveness of ketorolac as a potential chemoprevention agent for oropharyngeal cancer. If ketorolac administration in this preliminary Phase IIB trial is associated with reversal of leukoplakia, then a definitive Phase III chemoprevention trial with a cancer reduction endpoint (most likely in a cooperative group-type setting) may be the next validation step.

Randomized, Double Blind, Placebo-Controlled, Phase IIB Trial of Ketorolac Mouth Rinse Evaluating the Effect of Cyclooxygenase Inhibition on Oropharyngeal Leukoplakia: Collaborative Study of the NCI, NIDCD and the NIDCR

National Cancer Institute (NCI)

Dental Caries

Head and Neck Neoplasms

Tooth Demineralization

Tooth Diseases

Curative intent radiotherapy for head and neck cancer. Doses will be prescribed by an independent Clinical Oncology team. There will be no alteration or experimentation of radiotherapy dosage

Radiotherapy (curative) for head and neck cancer

Ciaran E Moore, BDS (Hons)

Gerry McKenna, BDS

Gerry McKenna, PhD, BDS, FDS

Background Post-radiotherapy head and neck cancer (HANC) patients are at increased risk of dental caries and periodontal disease due to radiation-related damage to the teeth and salivary glands. Currently the exact aetiology of post-radiotherapy dental disease, and variation in its incidence and severity based on tumour location and radiotherapy dose, is poorly understood. Consequently there is a lack of clear guidance on how HANC patients should be dentally managed both before and after their radiotherapy.

Aim The aim of this study is to quantify the relationship between dental radiation dose, 'spared' parotid gland radiation dose, tumour location, and post-radiotherapy dental disease.

Methods A prospective cohort study will be undertaken in HANC patients treated with radiotherapy. A total of 215 patients will be recruited over a period of 2.5 years. Participants will be assessed and rendered dentally fit prior to radiotherapy in the School of Dentistry, Belfast. All patients will be followed-up at 6, 12, and 24-months post-radiotherapy. Data to be collected at each visit will include: total number of carious teeth, periodontal disease indices, salivary flow rates, diet, oral hygiene, mouth opening, xerostomia and oral health-related quality of life.

Radiotherapy, including individual tissue-dose exposures, will be prescribed by the Clinical Oncology team as per current practice. Doses to the teeth and 'spared' parotid gland will be determined using radiotherapy research software (Non-Clinical Eclipse System sold by Varian Medical Systems UK Ltd).

Using appropriate statistical tests, data analysis will determine the relationship between dental disease, radiation dose, and tumour location.

Anticipated variation in the incidence and severity of post-radiotherapy dental disease based on the radiotherapy dose and tumour location, will inform the development of a clinical risk-assessment tool that will allow dentists to categorise patients as 'high' or 'low' risk of future disease. Guidelines regarding pre-radiotherapy dental extractions and post-radiotherapy preventative strategies will also be developed and will advise clinicians based on this risk assessment.

A micro-costings study will be undertaken to evaluate patient and healthcare costs associated with the diagnosis and management of pre- and post-radiotherapy dental disease.

Plan of investigation

Clinical hypothesis The primary hypothesis of the study is that increased mean radiation dose to the teeth and to the 'spared' parotid gland is associated with an increase in the mean number of carious teeth and in the proportion with periodontal disease 2 years post-radiotherapy.

Study design: Prospective cohort study.

* Pre-radiotherapy assessment at baseline and patients rendered dentally fit.
* Post-radiotherapy follow-up assessments at 6 months, 12 months, and 24 months.

Pre-radiotherapy assessment:

In line with current practice, the Multidisciplinary Head and Neck Cancer Team (Royal Victoria Hospital, Belfast) will continue to refer head and neck cancer patients for pre-radiotherapy dental assessment to the School of Dentistry, Belfast. Referred patients will be assessed in the existing 'Head and Neck Clinic' in the School of Dentistry. All potentially eligible patients will be informed of the research study and invited to participate. Each recruited patient will be assessed by a trained and calibrated dentist (examiner). Examiners will undergo pre-study training and calibration to ensure consistent clinical measurements. Inter-examiner consistency will be calculated using the Kappa statistic. A structured protocol will be followed. Radiographs may be requested provided specific criteria have been fulfilled. The same examiner(s) will interpret and record data from all radiographs.

The following measurements will be collected:

* Dental caries: The presence or absence of dental caries on each tooth will be determined using the World Health Organization's criteria and coding system and ICDAS-II, and recorded in a modified version of the Oral Health Assessment Form for Adults, 2013. Radiographic evidence of secondary caries or caries into dentine will also be recorded.
* Periodontal disease: A six-point periodontal charting will be performed for all patients. Clinical attachment loss and probing pocket depths will be measured using a Williams Periodontal Probe and recorded for six sites on each tooth. The 'Centers for Disease Control and Prevention (CDC)', in partnership with the 'American Academy of Periodontology (AAP)' workgroup definition of periodontitis will be used to identify those with active periodontal disease: 2 or more interproximal sites with attachment loss ≥3 mm, and 2 or more interproximal sites with pocket depths ≥4 mm (not on same tooth) or one site with pocket depth ≥5 mm.
* Stimulated salivary flow rate using paraffin pellets.
* Ruler measurement of mouth opening.
* Oral hygiene practice and dietary assessment using the World Health Organization's Oral Health Questionnaire for Adults.
* Subjective assessment of quality of life and experience of xerostomia using questionnaire booklets containing the European Organization for Research and Treatment of Cancer (EORTC) QLQC30 quality-of-life instrument, the associated head and neck specific module HN35, the Oral Health Impact Profile, and the modified Xerostomia Questionnaire.

All patients will receive standardised oral hygiene and dietary advice. A dental treatment plan will be formulated for each patient to ensure adequate dental fitness prior to radiotherapy. Dental treatment required pre-radiotherapy (e.g. restorations and extractions) will be co-ordinated by the School of Dentistry in line with current practice.

Post-radiotherapy assessments:

Participants will be followed-up at 6 months, 12 months, and 24 months post-radiotherapy.

At each follow-up visit, patients will undergo dental assessment in the School of Dentistry, Belfast. The following measurements will be collected (using the same methods and examiners outlined above): charting of dental caries, 6-point clinical attachment loss and probing pocket depth charting, stimulated salivary flow rate, mouth opening, oral hygiene practice, dietary assessment, quality of life, and xerostomia. A structured protocol will be followed. Radiographs may be requested provided specific criteria have been fulfilled. At each visit, patients will receive standardised oral hygiene and dietary advice. Consultants will oversee treatment plans for the restoration of dental health. Required treatment will be co-ordinated by the School of Dentistry in line with current practice.

Radiation dose and tumour location determination Patients will receive radiotherapy as prescribed by their Consultant Clinical Oncologist. The Clinical Oncologist will also plan individual tissue exposures in line with current practice. Using additional research software, doses to the teeth and to the 'spared' parotid gland will be calculated after the teeth and parotid glands have been contoured on each patient's radiotherapy planning CT scan. The Clinical Oncologist will contour the parotid glands in line with current practice. A dentist will contour the teeth on patient-anonymised CT scans. Tumour location will be determined from the initial referral letter sent by the Head and Neck Cancer Multidisciplinary Team.

Sample size Simplified sample size calculations were conducted based upon an independent samples t-test and correlation coefficient. Assuming the standard deviation of the number of carious teeth in post-radiotherapy head and neck cancer patients is 4.0 (based upon the results of a 10-year School of Dentistry audit) and comparing patients receiving over 20 Gray to the 'spared' parotid gland with those receiving under 20 Gray (based upon a 80%/20% distribution seen in a Cancer Centre radiation dose audit), the investigators would require a total sample of 150 patients with available data to have over 80% power to detect a difference of 3.0 in the mean number of carious teeth between the under 20 Gy and over 20 Gy groups as statistically significant at the 5% level. Furthermore, a sample size of 150 patients would allow 80% power to detect, as significant at the 5% level, a correlation coefficient of 0.22 for the association between radiation dose to the 'spared' parotid gland (Gy) and the number of carious teeth. Assuming 30% dropout the investigators would therefore need to recruit 215 patients.

Statistical analysis Primary outcome measures to be analysed include: (1) the number of carious teeth and (2) the presence of periodontal disease.

1. Initial comparisons between the radiation dose to the 'spared' parotid gland and the number of carious teeth will be performed using independent t-tests (categorising radiation dose as \<20Gy and \>20Gy) and ANOVA (categorising radiation dose as \<20Gy, 20-30Gy, 30-40Gy, and \>40Gy) as appropriate. Adjusted analysis will be performed using multiple linear regression, with the number of carious teeth as the outcome variable, radiation dose to the 'spared' parotid gland as an explanatory variable (categorised as above) along with potential confounding variables: dental radiation dose, oral hygiene practice, diet, and mouth opening. Without categorising radiation dose, a separate analysis will be conducted using linear regression with the number of carious teeth as the outcome variable and radiation dose to the 'spared' parotid gland (Gy) as the explanatory variable to give the increase in the number of carious teeth per 10 unit increase in Gray. If the number of carious teeth is not normally distributed transformations will be used prior to analysis or equivalent non-parametric techniques will be used.
2. Initial comparisons of the association between radiation dose to the 'spared' parotid gland (categorised as above) and the presence of periodontal disease (Yes/No) will be performed using chi-square tests. Adjusted analysis will be performed using logistic regression with presence of periodontal disease as the outcome variable, radiation dose to the 'spared' parotid gland as the explanatory variable and dental radiation dose, oral hygiene practice, diet, smoking, medical history, and mouth opening as potential confounders. Similar analyses will be undertaken to determine the effects of dental radiation dose and tumour location on the number of carious teeth and the presence of periodontal disease in post-radiotherapy head and neck cancer patients.

Secondary outcomes to be analysed include: quality of life, salivary flow rate, diet, oral hygiene practice, mouth opening, xerostomia (all change from baseline); tooth loss, and denture wear. Dichotomous outcomes will be analysed using chi-square tests and logistic regression as above. Continuous outcomes will be analysed as above, apart from variables with baseline measurements, for which ANCOVA will be used to compare outcome measurements adjusting for baseline. Adjusted analyses will use multiple linear regression models as above but with baseline measurements as an additional explanatory variable.

A micro-costings study will also be undertaken to evaluate patient and healthcare costs in relation to the diagnosis and treatment of pre- and post-radiotherapy dental disease.

* Patient costs to be evaluated include: cost of travel to dental appointments, time off work to attend for dental treatment, cost of dental treatment incurred pre and post-radiotherapy (general or private practice), out-of-pocket expenses (e.g. pain-relief medications).
* Healthcare costs to be evaluated include: clinical and administration staff costs for pre- and post-radiotherapy dental assessments and treatment, equipment, general overheads, remuneration of primary care dental practitioners.

Cost savings due to improved treatment planning of patients will also be hypothesised.

Post-radiation Dental Disease Amongst Head and Neck Cancer Patients

The Effect of Dental and Salivary Gland Radiation Dose on the Occurrence of Post-radiotherapy Dental Disease in Patients With Head and Neck Cancer

The mean number of carious teeth amongst head and neck cancer patients post-radiotherapy

The proportion of head and neck cancer patients with periodontal disease post-radiotherapy.

Change from baseline. Range of scores from 0 (no xerostomia) to 90 (worst xerostomia)

Change from baseline. 14 oral health problems presented - patients asked to score how often they are personally encountered (very often, fairly often, occasionally, hardly ever, never, don't know)

Change from baseline. Respondents asked to detail how often they consume e.g. sugar buns

Change from baseline. Patients asked to indicate e.g. how often do you brush your teeth

Queen's University, Belfast

Belfast Health and Social Care Trust

Necrosis

Anti-Infective Agents

Endothelial Growth Factors

Mitogens

the same patients in group 2 after they had been treated with scaling and root planing (SRP) were considered as Group 3.

Non-surgical periodontal therapy is an anti-infective therapy which includes both mechanical and chemotherapeutic approaches to minimize or eliminate microbial biofilm, the primary etiology of gingivitis and periodontitis

Non-surgical periodontal treatment

ÇİĞDEM COŞKUN TÜRER

The primer aim of the study was to determine serum and gingival crevicular fluid (GCF) endocan levels in periodontal diseases pathogenesis supported with vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) levels.

The study consist of three groups: periodontally healthy individuals (group 1; n = 20), individuals with generalized chronic periodontitis (group 2; n = 20), the same patients with chronic periodontitis after they had been treated with scaling and root planing (SRP) were considered as Group 3. Clinical measurements were recorded; GCF and serum samples were obtained from each participant before and 6 weeks after therapy. Endocan, VEGF-A and TNF-α levels were measured by enzyme-linked immunosorbent assay.

Endocan, VEGF and TNF-alpha Levels in Periodontal Disease and After Treatment

Effect of Non-surgical Periodontal Treatment on Gingival Crevicular Fluid and Serum Endocan, Vascular Endothelial Growth Factor-A and Tumor Necrosis Factor Alpha Levels

Bulent Ecevit University

Skin and Connective Tissue Diseases

Behaviors and Mental Disorders

Breast Neoplasms

Quality of Life

Antineoplastic Agents

Anastrozole

Aromatase Inhibitors

Postmenopausal women with breast cancer taking Arimidex, Aromasin, or Femara

Healthy volunteer postmenopausal women not taking Aromatase Inhibitors

L. Susan Taichman, RDH MPH PhD

The purpose of this study is to determine how aromatase inhibitors (AIs) such as Arimidex, Aromasin or Femara affect a woman's oral health and oral health related quality of life. Patients, dental professionals and medical oncologists will benefit from a greater understanding of the best oral care follow up practices of breast cancer survivors using aromatase inhibitors.

OBJECTIVES:

Primary

This cross-sectional prevalence study seeks to investigate the incidence and severity of oral health changes, specifically of periodontal conditions, among breast cancer survivors and the ways in which these outcomes affect their quality of life.

Secondary

* To determine the prevalence and severity of oral conditions in postmenopausal women with early stage breast cancer using adjuvant AI therapy as compared to postmenopausal women not using adjuvant AI therapy.
* To determine if adjuvant AI therapy use is associated with greater alveolar bone loss or increased levels of bone turnover biomarkers in postmenopausal women with cancer undergoing adjuvant AI therapy compared to postmenopausal women not receiving AI therapy.
* To determine the oral health-related quality of life among postmenopausal women with early stage breast cancer who are receiving adjuvant AI therapy.

Each patient will have 5ml of blood collected at the visit. Saliva, and urine will also be collected at the study visit.

Oral Health in Breast Cancer Survivors on Aromatase Inhibitors

National Institute of Dental and Craniofacial Research (NIDCR)

University of Michigan

Principal Investigator

periodontal pocket samples

The treatment of otolaryngology (OLR) cancer is based on surgery, radiation, sometimes used in combination with chemotherapy. Patients treated with radiotherapy have multiple oral diseases: mucositis, hyposalivation, tissue fibrosis, exacerbation of periodontitis. Over 70% of patients with head and neck cancers treated with radiotherapy have a lower level of dental clinical attachment and 92% have loose teeth or missing. The management of these oral complications is a priority in OLR oncology. The aim is to improve the oral health of patients to achieve a comfortable life acceptable and necessary for healing.

This project proposes to deepen the investigation with two main objectives:

1. To study in vivo the effect of radiation treatment on the evolution of the viral flora of the periodontium in a cohort of patients and matched controls.
2. To study in vitro the effects of irradiation on the replication EBV (herpesvirus) in producing websites lymphoepithelial tonsillar, and atypical dendritic cells associated with EBV that existence were recently discovered.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Randomized, Double Blind, Placebo-Controlled, Phase IIB Trial of Ketorolac Mouth Rinse Evaluating the Effect of Cyclooxygenase Inhibition on Oropharyngeal Leukoplakia: Collaborative Study of the NCI, NIDCD and the NIDCR	NCT00001698	Leukoplakia Periodontal Dis...	Ketorolac Rinse	-	National Institutes of Health Clinical Center (CC)
Post-radiation Dental Disease Amongst Head and Neck Cancer Patients	NCT03703648	Head and Neck C... Caries, Dental Periodontal Dis... Radiotherapy Si...	Radiotherapy (c...	18 Years -	Belfast Health and Social Care Trust
Endocan, VEGF and TNF-alpha Levels in Periodontal Disease and After Treatment	NCT02750956	Periodontal Dis...	Non-surgical pe...	25 Years - 49 Years	Bulent Ecevit University
Oral Health in Breast Cancer Survivors on Aromatase Inhibitors	NCT01693731	Periodontal Dis... Quality of Life		-	University of Michigan
Towards a Viral Etiology of Periodontal Disease in Relation to Radiotherapy Treatment of Head and Neck Cancers	NCT02180932	Periodontal Dis...	periodontal poc...	18 Years - 80 Years	Centre Hospitalier Universitaire de Nice

Spots Global Cancer Trial Database for periodontal disease