Increasing Adherence to Prophylactic Swallowing Exercises During Head and Neck Radiotherapy: The Multicenter, Randomized Controlled PRESTO-Trial

The PRophylactic Swallowing Exercise Therapy program for patients with Oropharyngeal cancer (PRESTO) was a multicenter, open-label randomized controlled trial. Patients were enrolled at four Belgian hospitals (University Hospitals of Antwerp, Ghent and Leuven and General Hospital Sint-Jan Bruges).

Patients with a stage III or IVA-B (TNM7) newly diagnosed squamous cell carcinoma of the oropharynx were prospectively recruited for this study. Candidates for enrollment were both men and woman older than 18 years, with no cognitive or language deficits that might interfere with the correct implementation of the swallowing therapy protocol. Patients were treated with 6–7 weeks fractionated RT/CRT with or without induction chemotherapy. Exclusion criteria were the presence of a recurrent carcinoma or metastasis from a non-HNC carcinoma and previous RT/CRT or surgery in the head-neck region with possible impact on swallowing function. Written informed consent was obtained from all participants.

The minimization program QMinim was used to randomly assign all participants with a 1:1:1 allocation to one of the three exercise groups: diary-supported PSE (paper group), app-supported PSE (app group) and therapist-supported PSE (therapist group). The minimization factors were age (20–60 vs. ≥ 60 years old), treating center, presence of baseline dysphagia and treatment (radiotherapy or concomitant chemoradiotherapy). The three groups differed in degree and kind of adherence-improving measures. All patients performed the same PSE program 5 times a week during the first 4 weeks of RT/CRT. Limiting the therapy program to the first 4 weeks of RT/CRT was a general measure to maximize adherence since acute toxicity typically peaks during week 5 of radiotherapy treatment [25, 26]. The PSE comprised 2 evidence-based exercises, alternating daily and targeting the main muscle groups involved in swallowing. First, tongue strengthening exercises (TSE) were done since tongue strength is the main bolus-driving force. Furthermore, reduced tongue strength can cause oral and pharyngeal residue and aspiration [27]. The TSE were performed using the Iowa Oral Performance Instrument (IOPI, model 3.2, IOPI Medical LLC, Woodinville, WA, USA) (Fig. 1) and consisted of 120 tongue presses per session, divided into 12 sets of 10 repetitions. Patients were instructed to pause for 30 s between every set. Second, chin-tuck against resistance (CTAR) exercises were used since they have a significant impact on the suprahyoid muscles [28]. The exercises were done using the Swallowing Exercise Aid (SEA) [28] (Fig. 2) and one session consisted of 30 sets of 5 repetitions for a total of 150 chin-tucks per day. Fifteen seconds of rest was provided between sets. The fifth repetition was a combination of a chin-tuck with an effortful swallow since this exercise has been shown to improve tongue-base posterior motion and tongue-base pharyngeal wall pressures [29]. Patients practiced at 60–80% of their 1repetition maximum (1RM), which was recalculated every week [30]. We practiced following the overload principle and took into account a high intensity [31].

The degree of adherence was expressed as the percentage of completed repetitions per week (%reps) and by means of 4 different categories, defined by Wall et al., including negligible practice (< 25%reps), low practice (25–50%reps), moderate practice (50–75%) and high practice (> 75%) [19]. At the end of the session, all patients, regardless of their group, were questioned about the degree of difficulty they had in completing the task, about the factors contributing to this difficulty and if they had any concerns or suggestions.

The paper group performed the first exercise session under supervision of the SLP. After this first session, the IOPI and SEA were given home, patients received a logbook with written instructions and they continued practicing at home. They were asked to register in their logbook how many exercise repetitions they performed each day and whether these repetitions were successful or not. Adherence was then calculated based on the patients’ record.

Once a week, an appointment with the SLP was scheduled to recalculate the target level, based on their new 1RM.

Similar to the paper group, the app group performed the first exercise session together with the SLP. During this first session, participants were coached in the use of the tablet and app. Both the tablet and exercise devices were then given home so that further practice could be done at home. The app allowed registering all repetitions and whether they were successful or not. Each week, an appointment with the SLP was scheduled to recalculate the target level and to read data from the tablet. Adherence was calculated based on this data.

The application was developed in collaboration with the 3D animation, app and game studio Cyborn, Antwerp, Belgium (https://​www.​cyborn.​be). It was provided to patients on a SAMSUNG GALAXY TAB A6 and practicing at home didn’t require internet connection. Every week, the SLP connected the tablet with Wi-Fi to enable synchronization and data upload to the server.

The app consisted of instructional videos and images for both exercises. Patients could watch them as many times as needed to fully understand the exercise. The app uses gamification, i.e. using game elements in a non-game environment, with the aim of making a difficult task easier and more pleasant [32]. By means of gamification, it was expected that the app would help, support and motivate patients during practice. The aim of the game was to help a squid to make her underwater world more beautiful. Every time the patient practiced, he/she could win plants, flowers, stones and fish to brighten up the squids’ coral reef. Figure 3 shows screenshots of the application. The number of exercises and repetitions the patients completed, were saved.

Every week, patients in the app group were questioned about their experiences with the tablet and application using visual analogue scales (VAS). These scales were added in a later phase of the study, meaning that only a subset of patients systematically completed these questions. The VAS were 100 mm lines on which the patients were asked to place a vertical mark to indicate to what extent they agreed with the statement. The distance to the vertical mark was then measured to create a score. Table 1 shows an overview of the all scales concerning the tablet and app.

The patients in the therapist group were given face-to-face therapy for 5 days/week. Each session, clear and repeated instructions were given and patients received continuous feedback on their performance by the SLP. The therapist kept a logbook and registered the number of exercise repetitions the patients performed each day, and whether these repetitions were successful or not. Adherence was calculated based on therapist data.

The full study protocol has been published previously [33].

One hundred and fifty patients were recruited for this study. In one patient, baseline measurements were never taken due to an acute life-threatening hospitalization. Another patient was excluded due to a change in the study protocol, namely by adding the exclusion criteria of having a tracheotomy influencing the execution of the CTAR exercise. This leaves us with a total cohort of 148 patients. Patients, disease and treatment characteristics of the whole cohort and separate groups can be found in Table 2. One patient had multiple primary tumors, here the larger T-stage was taken into account in the calculations.

Patients who immediately dropped out after baseline measures (paper group: n = 1, app group: n = 3, therapist group: n = 1) were not included in the adherence analyses, giving a final number of 48 patients in the paper group, 46 in the app group, and 49 in the therapist group. Table 3 shows an overview of all drop-outs with the timing of drop-out and reason for drop-out. During the exercise weeks, there were 9 drop-outs in the paper group, 8 drop-outs in the app group and 4 drop-outs in the therapist group. As shown in Table 3, a total of 18 patients refused further participation in the study. The most common reasons were pain, general weakness and the additional burden the exercises put during the RT/CRT. One patient refused further participation because of disbelief in the exercises.

Linear mixed-effects models showed significant effects of group (F_{(2, 119)} = 20.194, p < 0.001), time (F_{(3, 342)} = 43.988, p < 0.001) and group by time interaction (F_{(6, 342)} = 4.546, p < 0.001). These effects were confirmed by the additional GEE analysis. Adherence rates decreased in all 3 groups during the 4 training weeks, but with significant differences between groups. The highest decline was found in the app group and the smallest decline in the therapist group. During all 4 weeks, the therapist group achieved the highest adherence rates (Fig. 4). Between week 1 and 4, adherence rates decreased significantly in the paper group from 77%reps to 55%reps; from 72%reps to 27%reps in the app group and from 92%reps to 73%reps in the therapist group. Post hoc analyses, adjusted by means of Bonferroni-Holm correction, were performed and are shown in Table 4. Adherence rates during week 1 and 2 were already significantly lower in the app group compared to the therapist group and during week 2 the paper group reached significantly higher adherence rates than the app group. During week 3 and 4, there was a significant difference between each of the three groups: adherence was significantly higher in the paper group compared to the app group and patients in the therapist group achieved significantly higher adherence rates than patients in the other 2 groups.

Wall and colleagues [19] defined 4 levels of adherence to PSE, including negligible practice (< 25%reps), low practice (25–50%reps), moderate practice (50–75%) and high practice (> 75%). In Fig. 4, we applied those levels of adherence on current results. The adherence in the therapist group can be labeled as high during the first 3 weeks and moderate during week 4 (73%). The paper group reached high adherence rates during week 1 and 2 and moderate rates during week 3 and 4, whereas the app group had moderate (week 1 and 2) to low (week 3 and 4) adherence rates.

When dividing the app group into two age groups, < 60 years old and > 60 years old, no significant differences were found in adherence rates (F_{(1, 135)} = 1.712, p < 0.193). Moreover, there was no impact of the degree of experience the patients had with tablets/mobile apps on patients’ adherence (F_{(2, 135)} = 0.049, p = 0.952).

In 13 of the 46 patients in the app group, the attitudes towards the tablet and app were systematically questioned. Table 5 gives an overview of the results of the visual analogue scales. Overall, the tablet and app were judged to be user-friendly, the app startup was found easy and the app was found to be very clear and useful. However, the added value of the game element and its adequacy concerning age, gender, etc. were scored less strong.