Tolerance and Benefits of Mandibular Advanced Device for Snoring and Sleep Apnea in Oropharyngeal Cancer

The department of stomatology of the CHUM (Centre Hospitalier Universit├⌐ de Montreal)mandate is to ensure oral management of patients with oropharyngeal cancers (OPC),including papillomavirus (HPV), treated with radiotherapy (RTH), surgery andchemotherapy. At CHUM clinic, several patients who have had RTH treatments (with orwithout surgery or/and chemotherapy) complain of snoring and respiratory arrest duringsleep. HPV‐associated OPC, squamous cell carcinoma, has had a net increasing incidencefor more than 20 years in North America (4.6/100,000) and male mortality has increased by3.1% per year since 2001. In Quebec, the incidence is almost 26 cases per million.Worldwide, it is ranked to be the 13 most common cancer in male aged 25‐39 years; themale/female ratio is 2.5 (female have more HPV cervix related cancer) ‐ Global oralhealth status report: towards universal health coverage for oral health by 2030‐ (Geneva:World Health Organization; 2022).Snoring occurs in nearly 40% of the general population, increases with age and can be oneof the telltale signs of sleep apnea (brief and repetitive breathing stops at risk ofmortality if left untreated). Snoring can be associated with poor sleep quality andproduces a loud disturbing noise for the sleeping partner. Obstructive sleep apnea (OSA)is reported by 2‐4% of the general population and by almost 30% of the elderly mainlyrelated to obesity and heart disorders. The risk factors associated with these conditionsare lost of airway muscle tone during sleep, retrognathia, deep/narrow palate, obesityand age. Fatigue and drowsiness are markers of OSA. Following RTH, there may beoropharyngeal tissue fibrosis that may contribute to snoring and sleep apnea.Sleep disordered breathing are known in individuals with OPC. Our first results of theongoing survey seem to indicate that severe snoring, causing drowsiness or fatigue, wouldbe present in 47% of patients with OPC. A recently published literature review, from ourteam, also found a snoring self‐reports prevalence from 33% to 82%. A polygraphic sleeprecording study found that 65% of individuals with head and neck cancer (including OPC)have snoring, a value that increases to 92% when OSA is concomitant. On the other hand,OSA seem to be present in over 70% of OPC patients, before and after treatment. However,causality remains to be demonstrated; these sleep disorders are often pre‐existing andcan worsen as a result of RTH.In adults, snoring is mainly controlled by devices correcting the dorsal position ofsleep as well as with mandibular advanced device (MAD). Regarding apnea, positivepressure vessels (PPC or CPAP) are the most effective. The MAD is indicated for mild tomoderate OSA or for low CPAP tolerance. To date, following RTH, there are no studiesconducted under strict conditions. Some 'suggestions' in favour of standard treatments,PPC or MAD, were made. In addition, no studies have estimated the nasal discomfort anddryness associated with these treatments in the OPC population. Intuitively, nylon MAD,thin and with little contact on the mucous membranes, could be indicated in the presenceof OPC. To date, only one study, based on 2 cases, suggests the use of MAD in thepresence of OPC. There is therefore a gap of evidences in the literature as to whetherpatients treated for OPC presenting snoring and OSA would be able to tolerate and benefitfrom MAD.Objectives: Conduct a pilot study, with a mixed quantitative and qualitative design, toreduce snoring or sleep apnea using an MAD, and improve the quality of life and sleep.Hypotheses: Individuals who have received RTH as part of a treatment for OPC and who havesnoring or OSA, can 1) tolerate and 2) benefit from treatment with MAD.Experimental method and approach. ‐ Study design: Pilot trial, mixed and sequential design, randomized with active MADvs. non‐active MAD (control) and single‐blind condition analyses for theparticipant. The D‐SAD nylon MAD is marketed by Panthera Dental (Quebec) andprovided free of charge as part of this project. The study includes a total of 8visits to CHUM: 5 for clinical appointments and 3 nights of home sleep datacollection. The 3 nights of sleep recordings will be spaced 4‐5 weeks apart foradaptation to MAD. Night 1 will be for basal level, and nights 2 and 3 forrecordings with active MAD or control. This will be done under the supervision ofsleep lab director of CHUM, collaborator for over 25 years and residents. ‐‐ ‐Population: Adult patients (+18 years, female or male; ratio of 1/4 toward men;female is a rare phenotype of OSA pre‐menopause) who received RTH in the Departmentof Radiation Oncology, with snoring‐respiratory complaints during sleep, andfollow‐up in Stomatology at CHUM for OPC. Exclusions: Pregnant or breastfeedingwoman; edentation preventing retention of the MAD; taking opioid‐type medications;history of major depression, uncontrolled hypertension, stroke; under treatment withCPAP for sleep apnea; regular and intense orofacial pain; under pharmacologicaltreatment for insomnia; excessive alcohol or drug use (e.g., cannabis, opioid).Recruitment: With the help of CHUM radiation oncology and dental staff (dentist anddental hygienist, resident). An informed consent will be completed. ‐ Sample size: It is expected that 24 participants (risk of 2‐4 dropouts based on ourexperience) will be recuited. A 30% reduction in snoring and apnea/h is expected;this based on publications and an estimate of sample size. Indeed, a statistician,estimated that for a 30% decrease in snoring/night time (base at 8.9%/night, SD3.4%) 15 participants are required for an effect size (ES) of 0.79; forapnea‐hypopnea index/h (base at 11.5, SD 5)19 participants are required for a ES of0.7. For subjective reports of snoring intensity (9 participants are required; ES of1.11), however, an article reported significant results with 18 subjects. [20] Afinal sample of 20‐22 subjects is targeted. These estimates are comparable to thosein our previous orthotic studies of bruxism and OSA populations done by our groupmembers. ‐ Types of data and collection: After completing the consent, the participant will beasked to complete demographic, sleep and basic medical information. It will be builtfrom validated questionnaires estimating quality of life (SF‐12), sleep (PSQI),sleepiness (Epworth), risk of apnea (Stop Bang), fatigue (Chalder), and orofacialpain. The data will be entered via WEB (REDCap) and saved on the CHUM/CITADELLEserver. Following the 3 home sleep recordings, paticipants will assess onquestionnaire their perception of change in sleep quality based on the validatedscales used in our previous studies on apnea and MAD. In addition, the comfort ofMAD (tolerance) and the perception of the spouse will also be estimated as in ourprevious studies. The quantitative home sleep data, namely duration and snoringindexes, apnea‐hypopnea, instability and sleep duration, will be calculated, asalready published, by the measurements obtained (breathing, oxygen saturation, sleepposition, pulse, snoring) with the ambulatory recording instruments (Alice TM,Philips, USA) from CHUM sleep laboratory and analyzed by qualified technical staff.Qualitative data on MAD treatment expectations and oral health experiences relatedto POC (chewing, pain) will be estimated in a subgroup of participants (n=15),before and after MAD treatment. This will be done by a semi‐structured interview. ‐ Statistics and design for analysis: Like sleep analyses, the results will beanalyzed blindly with the following tests: 1) parametric tests such as: t‐test forinter‐group comparisons, linear mixed models and linear mixed models for repeatedmeasurements, followed by contrasts for post‐hoc comparisons where appropriate usingthe Tukey method (SPSS software); 2) nonparametric tests such as chi‐square,Mann‐Whitney and non‐parametric ANOVA for repeated measurements followed bycontrasts for post‐hoc comparisons where appropriate using the Tukey method (forcategory data and/or when the data distribution does not correspond to a normaldistribution); 3) correlation tests, such as Pearson's or Spearman's correlationcoefficient, if applicable. A biostatistician will oversee the analyses. Qualitativedata will be analyzed to extract recurring themes from transcripts of verbatimsusing software, N*VIVO. The collection of themes will be done until saturation. Thesoftware allows data coding and categorization for final analysis .