Pre-habilitation of Patients With Head and Neck Cancer

Study Overview
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Brief Summary
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The purpose of this study is to explore whether early initiated physical exercise concurrent with a swallowing and mouth opening exercise program will have a positive effect on swallowing function and other quality of life aspects in patients treated with radiotherapy for head and neck cancer. The investigators hypothesize that patients who complete the program will have improved swallowing function and physical function one year after completing their treatment compared to patients who do not participate in the training program.

Detailed Description
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Although the potential negative impact of head and neck cancer (HNC) and its treatment on eating ability and quality of life is well documented there is no evidence based and standardized rehabilitation program available for Danish patients affected by HNC while going through radiotherapy (with or without concurrent chemotherapy). This study proposal is based on a thorough literature review on HNC treatment and late effects, and interventions targeting dysphagia and physical functioning. Traditionally, rehabilitation is initiated when loss of function is already established. Emerging evidence suggests, however, that it can be of benefit to the patient to initiate an early rehabilitation process (prehabilitation) starting before initiation of treatment and during treatment. Prehabilitation aims to enhance pre-treatment functional capacity for better tolerance of treatment, facilitate general recovery, and prevent development of functional impairment or reduce the extent of these problems in a long-term perspective. HNC patients have a unique set of functional challenges such as pre- and post-treatment dysphagia, pain, and weight loss and often also high baseline levels of alcohol and tobacco consumption. In addition, studies have shown that only 31 % and 9 % of HNC patients are meeting public health guidelines for physical activity before and after diagnosis, respectively, and that weight loss in HNC patients treated with chemoradiation begin after only 1 week of therapy. Most of the weight loss was lean body mass (LBM) rather than fat loss. Loss of LBM is significantly associated with physical performance and increased functional dependence. The level of physical activity typically decreases significantly during treatment. Dysphagia is considered the most prominent complication to HNC and its treatment, affecting physical function and quality of life. Post treatment dysphagia occurs in a significant proportion of patients and results from multiple factors such as xerostomia, taste loss, decreased sensory function, fibrosis and trismus. Disuse of swallowing muscles due to acute radiation effects or tube feeding can contribute to decline in swallowing function. Often, difficulties in swallowing and mouth opening are presenting features of HNC even at the time of diagnosis. To reduce these problems, patients may do a series of exercises before and during treatment to promote strength, mobility, and endurance of base of tongue, pharyngeal constrictors, and suprahyoid strap muscles. Although no definitive trials have yet been carried out, small randomized controlled trials (RCTs) and observational studies investigating pre-treatment swallowing and/or mouth opening exercise programs show promising benefits. Further, the few studies of resistance and cardio training on functional capacity in HNC patients are generally promising with medium to large effects on fatigue and physical function measures. For weight loss it seems as if progressive resistance training (PRT) is able to almost reverse the loss of LBM in HNC patients. Generally studies on swallowing therapy for HNC patients have relied greatly on self-practice, and thus report low compliance. In view of this knowledge the investigators determine that there is a need for studies that include patients with HNC undergoing (chemo)radiation therapy focusing on i) prevention of dysphagia and loss of muscle strength and ii) improvement of compliance to mouth opening and swallowing exercises. The purpose of the SYNK study is a randomized design to test the effect of theory based intervention on eating dysfunctions secondary to radiation treatment for HNC. The SYNK intervention consists of: i) individual instructions in swallowing and mouth opening exercises 3 days per week by occupational therapist throughout radiotherapy, ii) progressive resistance training twice weekly by physiotherapist, either individually or group based, throughout radiotherapy, iii) daily home-based swallowing and mouth opening exercises from beginning of treatment until 2 months after end-of-treatment (self-practice), and iv) weekly follow-up phone contacts with occupational therapists from end-of-treatment and 2 months onwards. The investigators will enroll patients from the Oncological Department Rigshospitalet and randomize 240 patients. Patients will be randomized (1:1) to standard care plus the SYNK intervention and to standard care (control group). The proposed study has the potential to support the general health status of HNC patients as well as to minimize adverse late effects of treatment (i.e. swallowing and mouth opening difficulties, general physical deterioration due to physical inactivity and problems with eating, and reduced QoL). The design of the intervention, being early, intensive and bimodal adds a new dimension to research in the prevention of devastating late effects in this particularly vulnerable patient group. The investigators hypothesize that the SYNK intervention will: Improve swallowing function Improve physical function to stop the loss of muscle strength Improve quality of life and lessen the symptoms of anxiety and depression

Official Title
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Bimodal Pre-habilitation Program to Improve Symptom Control After Treatment for Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Behavioral: Swallowing therapy & resistance training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological proven cancer in one or more of the following areas: larynx, hypopharynx, oropharynx, cavi oris, or unknown primary tumor Set to curative radiotherapy with or without concurrent chemotherapy for treatment of cancer in the head and neck region in accordance with the Danish Head and Neck Cancer Group (DAHANCA) guidelines Fully self-reliant Danish skills, oral and written Informed consent Exclusion Criteria: Previously received treatment for head and neck cancer (radiotherapy, chemotherapy and/or surgery). Pregnancy ECOG performance status > 2 Presence of psychological-, family-, sociological- or geographical issues that could prevent the patient from completing the intervention Simultaneous or previous illness or conditions that could prevent the patient's ability to complete the intervention.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Swallowing therapy & resistance training<br>Mouth opening and swallowing exercise intervention by occupational therapist for half an hour 3 times a week for 5-6 weeks during radiotherapy. Progressive resistance training by physiotherapist for 1 hour twice weekly for 5-6 weeks during radiotherapy. | Behavioral: Swallowing therapy & resistance training<br>* i) Individual instructions in swallowing and mouth opening exercises 3 days per week by occupational therapist throughout radiotherapy, ii) Progressive resistance training twice weekly by physiotherapist, either individually or group based, throughout radiotherapy, iii) Daily home-based swallowing and mouth opening exercises from beginning of treatment until 2 months after end-of-treatment. iv) Weekly follow-up phone contacts with occupational therapists from end-of-treatment and 2 months onwards.<br>|
| No Intervention: Standard Care<br>Patients in this arm are randomized to usual care / control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Swallowing function measured by penetration aspiration scale (PAS) during a Fiber Endoscopic Evaluation of Swallowing (FEES). | To investigate the change in swallowing function among patients in intervention- and the control group from baseline to 14 and 58 weeks follow up and the difference in change between intervention - and the control group. | Baseline, 14 weeks and 58 weeks. Participants will be followed up till 12 months after they finalize their radiotherapy, an expected average of 58 weeks from baseline. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of fatigue by the EORCT QLQ-C30 3-point fatigue subscale. | To investigate the change in fatigue among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Maximal Interincisal Distance (MID) by Therabite Range of Motion (ROM) scale | To investigate the change in mouth opening and the development of trismus (defined as MID ≤ 35mm) among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Dysphagia related quality of life by M.D. Anderson Dysphagia Inventory (MDADI) | To investigate the change in patient reported quality of life related to dysphagia among patients in intervention- and the control group from baseline to 6, 14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. We will also use this outcome to evaluate correlation or deviations in patient vs observer rated outcomes by comparing the MDADI to the PAS score (primary outcome). | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Health related quality of Life by the European Organisation for Research and Treatment of Cancer (EORCT) Quality if Life Questionnaire (QLQ)-30 and EORCT QLQ - H&N35 | To investigate the change in health related quality of life among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Level of oral intake by Functional Oral Intake Scale (FOIS) | To investigate the change in oral intake and tube dependency among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Weight loss by body weight | To investigate the change in weight loss among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Physical strength by 30 seconds Sit to Stand (STS) test. | To investigate the change in lower extremities' strength as an expression of the overall physical strength among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Pain by numerical rating scale (NRS) | To investigate the change in pain among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Depression by Major Depression Inventory (MDI) | To investigate the change in depressive symptoms among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Anxiety by Symptom Check List (SCL-92) Anxiety subscale | To investigate the change in anxiety among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Performance Status by Eastern Cooperative Oncology Group (ECOG) performance scale | To investigate the change in performance status among patients in intervention- and the control group from baseline to 6,14, 28 and 58 weeks follow up and the difference in change between intervention - and the control group. | baseline, 6 weeks, 14 weeks, 28 weeks and 58 weeks. | 
| Subjective symptoms of dysphagia by Eating Assessment Tool (EAT-10) | EAT-10 is a questionnaire screening tool used to evaluate patient-experienced symptoms of dysphagia and measures the level of ten specific difficulties related to swallowing. We will measure this outcome at the same time as our primary outcome to analyze the correlation between the subjective and objective measures of oropharyngeal dysphagia. | Participants will be followed up till 12 months after they finalize their radiotherapy, an expected average of 58 weeks from baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, Intervention, Rehabilitation, Late Effects, Dysphagia