Of 371 invited HNC patients we enrolled 240 randomizing 118 to the control group and 122 to the intervention program. Three participants were randomized by mistake and another two were excluded due to change in treatment plan leaving a total 235 participants. Seven baseline questionnaires went missing. Nineteen participants (8%) had dropped out, 12 (5%) died and 2 (0.9%) were terminal at 12-month follow-up, and another 26 (11%) were lost to follow-up for other reasons. For the intervention group most dropouts occurred during intervention, mainly due to disliking the PRT. Figure 3 shows the flow of participants through the study.
Table 1 indicates a well-balanced randomization with equally distributed baseline characteristics except for total radiotherapy dose where the intervention group received less total Gy. Mean age at inclusion was 63 years [range 38–88]. Most participants (60%) had oropharynx cancer and received concurrent chemo-radiotherapy (54%). Eight percent had primary surgery. It appears as if non-participants (n = 17) are older and more likely to be female, p16-negative and current smoker and to have oral cancer and primary surgery, but differences were not tested for significance.
The overall results did not show differences between groups for the primary outcome (PAS), nor secondary outcomes with few exceptions. Participants in the intervention group had significantly better mouth opening (observed and experienced) and reported better social functioning, less pain on NRS, less anxiety, nausea & vomiting, appetite loss, constipation, and coughing at end-of-treatment, and less nausea and vomiting and senses problems 2 months after treatment. Conversely, the control group scored better on the MDADI functional domain at 2 and 6 months and had less pharyngeal residue 2 months after treatment (Table 2). The control group had better odds for normal gargle 1 year after treatment (online resource 2). Detailed tables of all binary outcomes can be found in online resource 2. Nasogastric tube placement was more frequent in the control group (55%) than in the intervention group (48%). Mean duration of tube dependence was 55 days (range 1–243) with no difference between groups (p = 0.63) (data not shown).
Due to the differing control groups at the two hospitals, we performed post hoc analyses each hospital separately; one analysis on the hospital with the non-active control group (n = 128) and one analysis on the hospital with an active control group (n = 107). For the hospital with the non-active control group, more outcomes showed significant differences between groups and several with significant differences at 1-year follow-up in favour on intervention group for mouth opening, depression, anxiety, pain on NRS and EORTC H&N35, insomnia and use of pain killers (Table 3). Analysing the hospital with an active control group, fewer outcomes showed significant differences between groups compared to the analyses on the full sample. Some differences between intervention and control group remained, however, although mainly at end-of-treatment (Table 4).
At baseline 15 (6%) participants presented with decreased swallow safety for liquid (PAS > 2), 21 (9%) had trismus, 66 (28%) was limited in their oral diet (FOIS ≤ 6), 7 (3%) dependent on tube feeding, 31 (13%) had impaired gargle function, 35 (15%) could not whistle and 23 (10%) had symptoms of depression (MDI ≥ 20). Figure 4 provides an overview of the development of impairment for both groups at all follow-ups. An elaborate table can be found in online resource 3. Raw data graphs on all outcomes and in four groups; intervention groups and control groups at each hospital, respectively, are provided in online resource 4.
There were no adverse events related to the swallowing intervention, and only few adverse events during or immediately after PRT: dyspnoea (n = 2), flare-up of old injury (n = 2), nausea and vomiting (n = 2), nerve- and muscle pain (n = 1), dizziness (n = 1), joint pain (n = 1).
Adherence to swallowing intervention was analysed on a sub-sample (n = 45) in another study . Participants were prescribed an average of 6.5 unique exercises [range 4–14], and median adherence to self-administered exercise was 78%. Median attendance to supervised sessions was 100% (range 53–100%) .
Fourteen participants provided comments in the questionnaires related to their satisfaction with the trial. Comments were divided into (1) improved motivation, (2) better coping with treatment, (3) a sense of limited late effects, (4) gratefulness for social and emotional support pointing to the benefits of the intervention outside the a priori decided outcomes.