Mouth and Tooth Diseases

All Conditions

Neoplasms

Periodontal Diseases

Dental Caries

Head and Neck Neoplasms

Stomatognathic Diseases

Mouth Diseases

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

Rare Diseases

Xerostomia

Mouth Neoplasms

Oral Cancer

Lip and Oral Cavity Cancer

All Drugs and Chemicals

Anti-Infective Agents

Fluorides

Imidacloprid

Listerine

Sodium Fluoride

Protective Agents

Anti-Infective Agents, Local

Topical application of 38% silver diamine fluoride plus 5000 PPM fluoride gel 1 mo before and 1 and 3 months after radiation treatment

Placebo application of silver diamine fluoride plus 5000 PPM fluoride gel 1 mo before and 1 and 3 months after radiation treatment

Topical application to all surfaces of the teeth

silver diamine fluoride, 38%

Gel applied after application of silver diamine fluoride and dispensed for home use

Sodium fluoride gel, 5000 PPM

Amal Noureldin, DDS

The Texas A \& M College of Dentistry, with partner Texas Oncology-Baylor Charles A. Sammons Cancer-Center Radiation-Oncology, proposes to conduct a preliminary clinical study (NIH Stage 0) to pilot test a randomized clinical trial of the efficacy of professionally applied 38% silver diamine fluoride to prevent tooth decay in 60 patients who are being treated with radiation for life threatening head and neck cancer.

Head and neck cancer has increased in Texas over the last two decades. Radiation-induced tooth decay is a devastating yet potentially preventable side effect of the cancer treatment. Silver diamine fluoride, already the standard of care in children, is inexpensive, easy to apply, and safe. The objective of the research is to conduct a single site pilot RCT (NIH Stage 0) to determine feasibility and preliminarily assess the efficacy of 38% silver diamine fluoride and 5000 PPM fluoride gel for prevention of radiation-induced dental caries over 6 months. Eligible participants will be up to 60 head and neck cancer patients who are scheduled for radiotherapy. The proposed intervention will be applied within 1 m before and at 1- and 3-m post radiation. The primary outcome is dental caries surfaces at 6 months post-radiotherapy (DMFS).Secondary outcomes are The Gingival Index, Gingival Bleeding Index, MDASI-HN, and Oral Health Quality of Life score will be secondary outcomes.

Randomized Controlled Trial, Intention to Treat

Test and placebo drugs will be identical in appearance and labeled by the manufacturer as A and B. The biostatistician will generate an assignment list. Individual packets will be prepared, and the clinician will open the packet to determine which study drug to apply. The packets and the drug containers will be color coded to minimize error. In each case a second staff member will verify on site that the participant received the correct coded treatment. Blinding: Participants and the examiners will be blind to treatment.

SDF Application in Oral Cancer Patients to Prevent Dental Caries

Silver Diamine Fluoride: Novel Addition to the Prophylactic Bundle for Dental Management of Radiation-Induced Dental Caries in Oral and Pharyngeal Cancer Patients

Dental Caries Surfaces determined by intraoral inspection

Silness and Loe Gingival Index for assessment of gingival condition (0 to 3) determined clinically

Bleeding at 6 sites of each tooth determined clinically

University of Washington

Texas A & M University Baylor College Of Dentistry

Clinical Associate Professor

Symptoms and General Pathology

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Musculoskeletal Diseases

Eye Diseases

Skin and Connective Tissue Diseases

Immune System Diseases

Blood and Lymph Conditions

Diseases and Abnormalities at or Before Birth

Syndrome

Diabetes Mellitus

Sjogren's Syndrome

Sarcoidosis

Cystinosis

Lymphoproliferative Disorders

Lymphatic Diseases

Hypersensitivity

Hypersensitivity, Delayed

Lysosomal Storage Diseases

Metabolism, Inborn Errors

Genetic Diseases, Inborn

Metabolic Diseases

This study will examine saliva samples from healthy volunteers and patients with various diseases to learn more about how disease affects the mouth and salivary glands. It will use a method called salivary proteomics to identify multiple proteins in saliva and discover if there are protein patterns unique to specific diseases. The study will:

* Characterize the salivary proteome in patients with Sjogren's syndrome, graft-versus-host disease, diabetes, sarcoidosis, cystinosis, dental caries, and immunodeficiencies and in patients who have had head and neck radiation
* Evaluate the possible use of salivary proteomics for early diagnosis
* Evaluate the potential use of salivary proteomics for prognosis and treatment

Patients participating in NIH clinical studies who have Sjogren's syndrome, graft-versus-host disease, diabetes, sarcoidosis, cystinosis, dental caries, or an immunodeficiency, or patients undergoing head and neck radiation may be eligible for this study. Candidates are screened with a medical and dental history, head and neck examination, and photographs of any mouth sores or disease. Healthy volunteers also have blood drawn for routine laboratory testing.

Participants have saliva collected from the floor of the mouth, the parotid salivary glands in the cheek, and the submandibular and sublingual salivary glands under the tongue. Patients with certain diseases also provide a urine sample. Saliva samples are collected as follows:

* One time from healthy volunteers and patients with Sjogren's syndrome, diabetes, sarcoidosis, cystinosis and immunodeficiencies
* Five times from patients undergoing stem cell transplant: at baseline before transplant and about 1, 2, 3 and 6 months after transplant.
* Three times from patients undergoing head and neck radiation: at baseline before radiation and at 3 and 6 months after the conclusion of radiation.

The diagnostic potential of the proteomic methods has been explored by several groups in recent years. Saliva contains many proteins, some of which are altered in various disease states. In this study, saliva is to be sampled in patients with head and neck radiation, diabetes, hematopoietic stem cell transplant, Sjogren's syndrome, cystinuria, methylmalonic acidemia and other conditions. Various novel analytical and data-processing tools will be used to infer characteristic salivary protein and salivary analyte signatures of these disorders. In some cases, these data will be evaluated with data for the oral flora present in the saliva and plaque of these patient groups and relate the presence and levels of particular bacteria to the proteomic profile.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
SDF Application in Oral Cancer Patients to Prevent Dental Caries	NCT05403125	Dental Caries	silver diamine ... Sodium fluoride...	18 Years -	Texas A & M University Baylor College Of Dentistry
Salivary Proteins in Disease and Health	NCT00100204	Diabetes Mellit... Sarcoidosis Dental Caries Sjorgren's Synd... Cystinosis Head and Neck N...		-	National Institutes of Health Clinical Center (CC)
Salivary Proteins in Disease and Health	NCT00100204	Diabetes Mellit... Sarcoidosis Dental Caries Sjorgren's Synd... Cystinosis Head and Neck N...		-	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for dental caries