Trial Information

Impact of Nutrition and Swallowing Function in a Randomized Controlled Trial of Head and Neck Cancer Patients During the Course of Treatment

Background: Multimodal treatment for advanced head and neck cancer (HNC) is associated with
acute toxicities including mucositis, xerostomia, and dysphagia and a high prevalence of
weight loss, requiring nutritional intervention. Currently, there is ongoing debate about
the best way to provide nutrition support while undergoing chemoradiation (CRT) therapy
after surgery for advanced head and neck cancer (HNC). Randomized controlled trials
comparing the nutritional benefits of feeding tubes over dietary counseling and/or
supplementation have not conclusively demonstrated a reduction in weight loss, unplanned
hospitalizations, treatment toxicities, or tumour control. Additionally, the relative
benefits of feeding tubes are controversial. Studies evaluating the efficacy of feeding
tubes report that patients with feeding tubes have increased risk of aspiration, feeding
tube dependence, a small but finite risk of tumour seeding, but more importantly long term
functional swallowing impairment. However, emerging data are reporting that swallowing
exercise programs that are designed to strengthen musculature throughout the course of
treatment may lead to improved return of functional swallowing. Thus, preservation of
functional swallowing may potentially improve return to oral nutrition.

Purpose: Our purpose of this study is to compare the efficacy of nutritional and swallowing
intervention with/out a percutaneous endoscopic gastrostomy (PEG) tube to that of ad lib
nutrition and swallowing counseling with/out a PEG tube in advanced HNC patients. Weight,
caloric intake, instrumental swallowing function, xerostomia, mucositis, pain, unplanned
treatment interruptions, unplanned hospital admissions, complications, duration of feeding
tube, tumour control, performance status, and quality of life (QOL) will be assessed before,
during, 3 and 6 months after CRT therapy to determine if there is any differences between
the intervention groups.

Study Design: A randomized controlled longitudinal design during the entire course of
treatment including surgery and CRT therapy will be conducted to investigate the efficacy of
nutritional and swallowing interventions in HNC patients at baseline, after each course of
consecutive course treatment and 3 and 6 month follow-up. Patients demonstrating a safe
functional swallow following surgery will be randomly assigned to one of four groups: Group
1 - patients will receive PEG tube/in-depth nutrition and swallowing intervention; Group 2 -
patients will receive PEG tube/ad lib nutrition and swallowing counseling; Group 3 -
patients will receive in-depth nutrition and swallowing intervention; or Group 4 - patients
will receive ad lib nutrition/Kaofeed tube nutrition and swallowing counseling.

Study Sample: Patients with diagnosis of HNC to the oral cavity, pharynx, and larynx
undergoing surgery and CRT therapy at the University of Alberta Hospital (UAH) and Cross
Cancer Institute (CCI) will be eligible for participation in the study.

Inclusion criteria are: ≥ 18 years of age; diagnosed with HNC to sites of the oral cavity,
oropharynx, and larynx; all histologic types of cancer; advanced tumour stages; all forms of
radiation therapy (RT) including standard or investigational for HNC; all forms of
chemotherapy (CT) including standard or investigational for HNC; alert and mentally
competent; English-speaking. Exclusion criteria are: unable to have safe swallow following
surgical intervention; allergy or intolerance to any enteral nutritional supplements in
current use; renal insufficiency. There are approximately 3-4 HNC patients scheduled for
surgery, and CRT therapy per week at UAH/CCI. With a significance level of 0.01 between
groups and a power of 0.85 (an effect size of 0.9) a minimum sample size of 41 patients is
required for this study. As a pilot study with 20 degrees of freedom, an adequate and
reasonable sample size would require 24 patients to be recruited to participate.

Data Collection: Patients will be informed of the study and consent obtained. Demographic
and clinical data will be collected at the time of recruitment. Patient's height and weight
will be recorded. Patients will be asked to complete the Patient Generated Subjective Global
Assessment, Head and Neck Symptom Checklist, Edmonton Symptom Assessment Score and
University of Washington Quality of Life Revised Questionnaire. Patients will be given
instructions on how to complete the 24h dietary recall, will have assessments for mucositis
and xerostomia and an appointment for modified barium swallow. After surgery, patient's who
have a verified safe swallow by a speech-language pathologist (SLP) and MBS will be
randomized into 1 of 4 groups. Patient randomized to Group 1 or 2 will have percutaneous
gastrostomy (PEG) tubes inserted as per gastroenterology PEG tube insertion protocol.
Patients randomized to Group 1 or 3 will have additional nutrition and swallowing
intervention. Patients randomized to Group 3 or 4 who have symptoms that prevent them from
swallowing or have a >5% weight loss during treatment will be offered a Kaofeed tube for
nutrition supplementation. Nutritional intervention as outlined in studies by Ravasco et al.
(2005) and Goncalves Dias et al (2005) will include individualized nutrition orientation to
therapeutic diet that will aid the patient in achieving a caloric and protein intake which
promotes approximately 40 kcal/kg/day. The nurse practitioner together with the patient will
meet on a daily basis to review their therapeutic diet and resolve issues of symptom
management that prevent dietary intake. Swallowing intervention will include evaluation of
functional swallowing by a SLP. The SLP together with the patient will meet on a daily basis
to review functional swallowing and will teach/aid the patient to adjust their swallowing to
meet their changing safe swallowing needs. All parameters and study measurement are outlined
in Table 1.

Data Analysis: Descriptive statistics will be used to generate a profile of the nutrition
status, caloric intake, nutrition impact symptoms, swallowing function, quality of life,
unplanned treatment interruptions, unplanned hospital admissions, and complications of HNC
patients at baseline, after each course of consecutive course treatment and 3 month
follow-up. Changes, as well as differences in nutrition status, caloric intake, nutrition
impact symptoms, quality of life and swallowing function before and after each course of
treatment, and 3 month follow-up will be examined using t-tests and analysis of variance
(ANOVA).

Significance of the Study: The high prevalence and negative consequences of weight loss,
primarily stemming from dysphagia in advanced HNC patients using the current multimodal
treatment regime supports the need to determine the most effective nutritional management of
this patient group. Additionally, this pilot study may establish the foundation for future
protocols and guidelines for nutritional care of HNC patients.