Background
Squamous head and neck cancer (HNC) has high incidence in developed countries. HNC is categorized according to the area of the head or neck in which it occurs, with greater incidence in the larynx, followed by the oropharynx, oral cavity, and hypopharynx. At the time of diagnosis, 1% of all patients have a distant metastasis, with the highest rate (4%) observed in the nasopharynx and earlier-stage tumors located in the larynx and the oral cavity. Tobacco and alcohol use and human papilloma virus (HPV) infection are the most important risk factors [
1].
Although chemo-radiation therapy (CRT) protocols have been designed to preserve swallowing function and essential speech organs, dysphagia is a frequent symptom in these patients and the primary adverse effects are usually associated with acute or late swallowing disturbances [
2‐
6]. Preservation of underlying anatomical structures does not guarantee normal function. CRT affects target areas and may result in lack of coordination of swallowing phases, lack of swallow coordination with respiratory function, reduced elevation of larynx, delayed laryngeal closure, loss of tongue strength, and prolonged oral and pharyngeal time in swallowing [
6‐
9]. Radiation-induced dysphagia pathogenesis includes an initial process of acute inflammation with the appearance of edema, which may be followed by fibrosis of the soft tissues resulting in neurological alteration and muscle damage. Xerostomia, pain, and pharynx obliteration are the key elements of acute-phase dysphagia. At 3 months, many patients have regained swallowing function. In later stages, with the appearance of diffuse fibrosis of the connective tissue and skin in the irradiated area, changes are observed in the efficacy and safety of swallowing. It is believed that hypoxia and chronic oxidative stress could perpetuate tissue damage even long after the end of treatment, which would explain the appearance of dysphagia in the chronic phase [
10]. These side effects contribute to higher rates of malnourishment, weight loss, and bronchoaspiration [
6,
11], resulting in a need for alternative or supplementary methods for feeding and hydration, both early and long-term [
8].
For years, delays have been reported in referring HNC patients undergoing CRT to rehabilitation departments. Patients were only referred when they presented with obvious swallow deficits or the consequent malnourishment, weight loss, changes in voice characteristics, etc., often months or years post-CRT [
12]. The greater the delay, the worse is the patient’s detrimental muscle disuse and swallow dysfunction [
13,
14].
In recent years, there has been a growing interest in swallowing interventions. Potential benefits of prophylactic exercises conducted during [
15‐
17], soon after [
18], or before the CRT intervention [
19] have been described, and improvements in functional swallow outcomes and quality of life parameters after respiratory therapy (RT) intervention have been reported [
14]. Nevertheless, supportive care for earlier dysphagia management in rehabilitation departments continues to play a secondary role in HNC diagnosis in most health systems [
9,
12].
New ways to treat HNC dysphagia in an early intervention are now being explored, using inspiratory and expiratory muscle training (IEMT), a technique initially developed for patients with chronic respiratory diseases [
20] that has shown its usefulness in patients with dysphagia [
21‐
25]. Designed to improve respiratory muscle strength, IEMT also trains muscles involved in coughing, speech, and swallowing [
26]. The hypothesis of the ongoing Redyor (Rehabilitation Dysphagia Oropharyngeal Cancer) study is that improvement of the swallowing function is due to the strengthening of the suprahyoid muscle (anterior portion of the digastric, mylohyoid, and geniohyoid). The suprahyoid/submental muscles participate in the pharyngeal phase of swallowing. Their weakness or lack of coordination can decrease the amplitude of the hyoid, causing an inadequate opening of the upper esophageal sphincter that exposes the airway to the passage of the bolus. Some authors have evaluated the effect of IEMT on the swallow muscles by videofluoroscopy swallow studies (VFSS), noting that the amplitude of the hyoid movements increase during training, both in the oral (jaw and tongue) and pharyngeal phases [
27]. The usefulness of IEMT to train respiratory, cough, speech, and swallowing muscles is well established in pathologies other than chronic obstructive pulmonary disease, such as stroke-related dysphagia [
28], but the most recent neurophysiological findings suggest the capacity for improving motor recruitment of the suprahyoid musculature, the activity of pharyngeal musculature, and the palate, as well as an increase in the amplitude of the movements of the hyoid [
29,
30], could be considered and included as a new therapeutic tool for the treatment of HNC swallowing disturbances in the acute stage after diagnosis.
Available data suggest that pre-habilitation exercises could further improve these results [
18,
19]. The Redyor study is based on the hypothesis that an early intervention could contribute to preserve swallow function and quality of life. The main objective of this study is to determine the effectiveness of 21-week IEMT added to standard swallowing exercises performed before or immediately after CRT (early or late intervention, respectively) to preserve swallow function in patients with HNC receiving radiotherapy in a randomized clinical trial. Secondary objectives of this study include assessing changes in quality of life, comparing the effectiveness of the VFSS and Volume-Viscosity Swallow Test (V-VST) for screening dysphagia, and evaluating the effect of IEMT added to standard swallow exercises in a home-based dysphagia rehabilitation program in patients with HNC undergoing CRT.
Discussion
Rehabilitation intervention in acute HNC patients is currently limited in Spain. Swallow disturbances are considered a side-effect during CRT, and early swallowing and speech intervention is not systematically considered. Acute side-effects are considered “normal” in the development of the illness and during treatment, and the Rehabilitation Department becomes involved only when a patient demands a referral or a clinician requests an evaluation; decision protocols have not yet been developed. On the other hand, there is increased interest in facing this problem, first by developing a good screening method to determine which patients require evaluation, and then evaluating new treatment techniques, including home-based training interventions. A challenge when dealing with dysphagia related to HNC is determining the clinical profile of patients who might benefit from rehabilitation interventions (e.g., IEMT). Research is urgently needed to identify the usefulness of various dysphagia screening methods and therapeutic interventions such as IEMT.
Strengths and limitations of the study
The study has several potential limitations that must be considered. First, losses to follow-up are common in cancer studies; to address this concern, sample size estimation assumed a loss of about 20% of patients (higher than the usual 10–15% used in previous studies). We presume that these losses will affect both study arms equally. Second, the study lacks a control group; however, this design is justified by the available evidence of the benefits of swallow and speech therapy in patients with HNC-related dysphagia.
Repercussions of the Redyor study
Interventions to help patients confront, manage, and treat dysphagia are urgently needed. The lack of randomized controlled trials in the early diagnosis of HNC and the high number of patients lost to follow-up due to CRT side effects highlight the potential scientific contributions of this study.
Trial status
Protocol version number: Redyor_2
Begin recruitment: 03/25/2015
End recruitment: 08/21/2018
End data collection: 04/29/2019
Trial status: Enrollment is in progress; final data collection will end May 2019
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