DENTOFACIAL-PBT Stage 2 - Feasibility Study

The overall aim is to ascertain if it is feasible to determine the prevalence of adverse effects to the teeth and jaws in the United Kingdom National Health Service cohort of childhood head and neck cancer survivors treated with proton beam therapy using a mixed methods study. This will involve data being collected both retrospectively and prospectively. This study is being hosted by Manchester University NHS Foundation Trust with the support of the Proton Clinical Outcomes Unit at The Christie NHS Foundation Trust.

RESEARCH QUESTIONS:

[RQ-1]: How often have adverse effects to the teeth and jaws occurred in UK childhood head and neck cancer patients treated with proton beam therapy at The Christie NHS Foundation Trust and overseas in the NHS Proton Overseas Programme? [RQ-2] Is it practical to collect data on side effects to the teeth and jaws in this group of patients? [RQ-3] Is it possible to reliably contour the maxilla, mandible and the teeth on treatment planning computed tomography images to extract the radiation dose to these structures? [RQ-4] How should dental outcomes in childhood head and neck cancer patients treated with proton beam therapy be monitored? [RQ-5] Is it possible to link side effects reported by patients to their treatment dose? [RQ-6] Do side effects reported by patients align with those reported by their dentist? [RQ-7] What is the effect of age at the time of treatment on dentofacial development? [RQ-8] What is the effect of radiation dose on dentofacial development? [RQ-9] Is the QoL in childhood head and neck cancer survivors different in those with and without reported / identified dentofacial toxicities?

STUDY DESIGN:

A mixed methods, cross-sectional, self-administered survey has been developed. This is to be completed once by an eligible study participant. The survey contains pre- and post-treatment questions focused on the teeth and jaws, as well as including select scales from the FACE-Q™ Craniofacial module to collect HRQoL data. Participants aged 16 years or older will be directed to complete the survey individually. For participants aged less than 16 years old at the time of survey distribution, an individual with parental responsibility will be directed to complete the survey alongside their child. At the end of the survey, participants will be asked if they would be interested in being involved in a feasibility study regardless of whether they have reported a dentofacial toxicity. If a survey respondent enrols in the feasibility study, their completed survey will be linked to the data collected in the feasibility study. If a survey respondent does not enrol in the feasibility study, no patient-identifiable data will be collected, therefore their survey answers will be anonymous.

This feasibility study will aim to retrospectively analyse paediatric HNC patients treated with PBT to determine the prevalence of dentofacial toxicities, the feasibility of correlating PROs to PBT dosimetric data to establish dose-effect relationships, and to determine if it is possible to compare PROs to those reported by dental professionals. Information on the development of a participant's teeth and jaws will be requested from their dentist (if applicable). Further insight into the beliefs and concerns of patients will be elicited through virtual semi-structured qualitative interviews, which will adopt a 'palette of methods' approach. Additionally, individuals residing in the Greater Manchester area who attend an annual review with an Oncologist will be offered the opportunity to have a dental assessment at their next scheduled visit (n = approximately 25 patients). This will not only provide an additional opportunity for study recruitment should an individual not already be enrolled, but it will allow additional data collection on dental outcomes in this cohort. There will be no randomisation, blinding or masking of recruited participants.

Once a participant has consented and is enrolled into the study, the research team will conduct the following steps:

(A) Notify the Proton Clinical Outcomes Unit of a participant's enrolment and request patient identifiable treatment planning data from the clinical system at The Christie. For example, this data will include, sex, age at treatment, diagnosis, subsite, treatment location, chemotherapy history, surgery history and follow-up time. This will include any data collected on select AEs/toxicities, specifically 'musculoskeletal deformity', 'dental development disorders', 'dental caries' and 'periodontal disease' as graded in the 'Common Terminology Criteria for Adverse Effects' (CTCAE) version 5.0 (2017).

(B) Details of the participant's dentist (if registered) will be requested directly from the participant at the start of the study. Once these details are available, a letter will be sent to a participant's dentist outlining the following about the study: its aims, source of funding, ethical approval status, information requests, timeframes, and plans for dissemination of findings. Only information on the development of the teeth and jaws will be requested. This will include requesting relevant radiographs (X-Rays) that show the patient's teeth before (if available) and after treatment.

(C) Assessment of dental radiographs and dental clinical photographs (if available) from the clinical system at The Christie or MFT.

(D) Qualitative Interviews on MS Teams: Further insight into CCS thoughts and experiences will be elicited through virtual semi-structured interviews with a purposeful sample of participants to enhance and enrich the quantitative data.To enable participants with a variety of different skill sets and confidence levels to participate, the researcher will offer a list of methods for the individual to opt into. It is recognised that children are key stakeholders in this study and that their perspectives on dentofacial toxicities need to be considered. Allowing alternative approaches to participation to a traditional one-to-one interview may empower participants, thus making the research more inclusive.

Participation in the interviews could occur in five ways:

1. Individual participation of a CCS now aged 16 years or older,
2. A CCS now aged 16 years or older alongside a friend or family member for moral support.
3. Individual participation of a person with parental responsibility for an eligible participant aged less than16 years,
4. Participation of a person with parental responsibility alongside an eligible participant aged less than 16 years.
5. Participation of a person with parental responsibility alongside a friend or family member for moral support (without CCS) [healthy volunteer/s]. (E) Dental assessment and collection of PROMs data on established Oncology clinics: 10% (n = approximately 25) of the eligible study cohort attend a follow-up clinic in Manchester to review any late treatment adverse effects once a year. These established clinics are held at The Royal Manchester Children's Hospital (RMCH) [for individuals <16 years old, known to patients as a "follow-up clinic"] and at The Christie NHS Foundation Trust [for individuals >16 years old, known to patients as a "late effects clinic"]. Prior to contacting eligible participants, the radiation plan will be checked to confirm that radiation dose to the maxilla, mandible and/or teeth was received. If radiation was not delivered to these structures, a participant will not be contacted. Eligible participants attending these clinics will be contacted with a separate PIS, outlining the opportunity to see a dentist at their next scheduled clinical visit and to have a dental assessment, which will include an orthopantomogram (OPT).