Pre- and Post-Operative Exercise Program in Upper Gastrointestinal Cancers

Study Overview
=================
Brief Summary
-----------------
Esophageal and gastric cancers are a considerable health burden. In the past 10 years the 5-year survival for both cancers has doubled. This is due to a number of factors including advances in neo adjuvant and adjuvant chemotherapy and radiotherapy. However, physical fitness significantly declines as a result of neo adjuvant an adjuvant therapy. From studies in other cancers it is known that peri operative training improves physical fitness, yet there is little research into its effects in those with upper gastrointestinal cancers. The aim of this study is to assess the effect of a pre-and post operative training program on patients with upper gastrointestinal cancers on their physical fitness and consequently their optimism, quality of life and post operative morbidity.

Detailed Description
-----------------
The comparator in this study will be standard oncological care. There patients will receive the exact same care as the intervention group patients but will receive no exercise training program. The primary goal of this multi-centre randomised controlled trial are to investigate the effects of peri-operative exercise training programmes on physical fitness, measured with a 6 minute walk test, in patients undergoing a major curative upper-GI resection for either oesophageal or gastric cancer. The secondary aims will look at the effect of peri-operative exercise training on patients quality of life, optimism and well being, post operative morbidity, nutritional status and blood markers of inflammation.

Official Title
-----------------
The Effect of a Pre- and Post- Operative Exercise Programme Versus Standard Care on Physical Fitness in People With Upper Gastrointestinal Cancers- Study Protocol for a Randomised Control Trial: The PERIOP-OG Trial.

Conditions
-----------------
Exercise Intervention

Intervention / Treatment
-----------------
* Behavioral: Standard Exercise Program


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be 18 years of age or above; Have confirmed Multi Disciplinary Team (MDT) evidence of adenocarcinoma or squamous cell cancer of the oesophagus, oesophago- gastric junction or stomach requiring neoadjuvant therapy and planned curative resection. Be referred by a multidisciplinary team meeting for neo adjuvant chemotherapy or neo adjuvant chemoradiotherapy prior to planned oesophagectomy or gastrectomy. Have measurement confirming (endoscopic or otherwise) that the tumour starts more than 5cm below cricopharyngeus; Be fit for pre-operative anaesthesia and surgery Be able to provide written informed consent. Exclusion Criteria: Inability to participate in the exercise program (unable to perform 6 Minute Walk Test, unable to attend for assessment of parameters at any time point). Patients with high grade dysplasia (squamous cell or adenocarcinoma); Patients who have or develop metastatic disease at time of enrolment or during their neoadjuvant therapy; Patients being referred for primary surgery without requirement for neoadjuvant treatment; Patients with squamous cell cancer of the oesophagus who the MDT recommends or who individually elect to undergo definitive chemoradiotherapy; Evidence of previous/concomitant malignancy that would interfere with this treatment protocol; Pregnancy; Patients participating in other trials that would interfere with the implementation of this protocol at a particular site.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group randomised 1:1 controlled multi centre trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Structured Exercise Intervention<br>The exercise training program was designed to improve physical fitness while the patients are receiving neoadjuvant treatment prior to surgery and for a 6 week period after surgery once patients are deemed fit to return to training. | Behavioral: Standard Exercise Program<br>* Standard Exercise Program- Participants will be invited to take part in a structured home, supervised, or both, exercise program while undergoing neo adjuvant therapy and for a six week period when deemed fit post surgery.<br>|
| No Intervention: Standard Oncological Care<br>This group will receive standard oncological care and will receive no formal education of exercise intervention. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Physical Fitness | The primary goal of this multi-centre randomised controlled trial is to investigate the effects of peri-operative exercise training programmes on physical fitness, defined as the distance covered in metres and centimetres during a 6 minute walk test, in patients undergoing a major curative upper-GI resection for either oesophageal or gastric cancer. To complete the Six Minute Walk Test, no warm up is permitted and participants rest in a seated position for 10 minutes prior to the test beginning. Participants walk up and down a 20m course marked by cones for 6 minutes under instruction to cover as much ground as possible. The number of laps completed is recorded. A standard set of instructions as well as encouragement is used. After 6 minutes, the participant stops and the distance covered in the final partial lap as measured and total distance covered is calculated. Change from baseline to post treatment difference between groups. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Strength - The Sit to Stand Test | Strength will be measured using two tests. the Sit to Stand Test . Participants will sit on a chair (height 43-45 cm) with arms crossed on their, and legs flat on the floor, parallel to each other, and approximately shoulder width apart. Participants will stand up and sit down 10 times as quickly as possible. Participants must not bounce off the chair when moving from a seated position to standing position. They must fully extend their legs on each stand. The time taken to perform 10 repetitions will be timed using a stopwatch. Participants will perform two trials and the best trial will be recorded as their score. Change from baseline to post treatment difference between groups. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 
| Change in Strength - The Handgrip Test | Strength will be measured using a hand dynamometer. The test will be conducted in a standing position with the upper arm tight against the participant's trunk and the forearm at a right angle to the upper arm. If this is not possible the participant may sit in an upright chair or use their free hand to rest the dynamometer on a table to support the arm. The gripping handle will be set to a comfortable width to ensure the patient can rest the middle piece of the fourfingers on the handle. The participant will be instructed to squeeze the handle with maximum force for a few seconds. The value on the scale will be recorded. The participant will complete two trials on each hand. The highest score will be accepted.Change from baseline to post treatment difference between groups. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 
| Change in Body Composition | Determined by body mass index (BMI). BMI will be calculated as weight in kilograms divided by height in meters squared. Height will be measured using a wall stadiometer to the nearest .1cm. Weight will be measured using an electronic scales to the nearest .1kg.Change from baseline to post treatment difference between groups. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 
| Change in Physical Activity - Accelerometer | This will be measured using two assessments: 3-day ActivPAL3 triaxial accelerometer. Participants will be instructed to wear the device on the midpoint of the anterior aspect of the right thigh and attach using a film adhesive frame dressing. They will continue to wear this for three days continuously. They cannot wear the ActivPAL3 triaxial accelerometer during water activity periods. Change from baseline to post treatment difference between groups. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 
| Change in Quality of Life measured using the EQ-5D Health Questionnaire | EQ-5D (Euro qual health questionnaire consists of 5 themes graded 1-5 and an overall score. The questionnaire is then converted to an index value using the Crosswalk value sets developed for the EQ-5D Health Questionnaire. There is a descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. The respondent is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions. The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labeled 'the best health you can imagine' and 'the worst health you can imagine. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 
| Change in Optimism | Optimism as an outcome is measured using the Life Orientation Test-Revised (LOT-R: Scheier, Carver, & Bridges, 1994) and consists of ten items assessing generalised expectancies for positive versus negative outcomes. This will be administered at baseline and pre-surgery only. The scale uses 10 questions on a 1-10. There are 4 filler questions. High scores indicate optimism. | Baseline, Change from baseline to one week before surgery | 
| Change in Well Being-The Functional Assessment of Cancer Therapy (FACT-E) questionnaire. | Functional Assessment of Cancer Therapy-Esophageal (FACT-E) questionnaire. This is an HRQOL instrument validated in patients with esophageal cancer. It is composed of a general component (FACT-G) and an esophageal cancer subscale (ECS). Patients will score a series of questions (0 = not at all; 4 = very much) in five sections (physical well-being; social/family well-being; emotional well-being; functional well-being; additional concerns) for the past 7 days. Higher scores will suggest better quality of life. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 
| Well Being - Semi-structured Interviews. | Semi-structured interviews will explore patients' perceptions of the surgical pathway. This will be analysed from interview transcripts through qualitative analysis using thematic content analysis. | One week before surgery | 
| Change in Well Being - Self-efficacy (General Self Efficacy Scale) | Self reported measure of Self-efficacy (General Self Efficacy Scale). 10 item questionnaire.Scored 1-4. 1 being not at all true, 4 being Exactly True. The total score is calculated by finding the sum of the all items. For the GSE, the total score ranges between 10 and 40, with a higher score indicating more self-efficacy. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 
| Change in Well Being - Mastery (Pearlin Mastery Scale). | Mastery (Pearlin Mastery Scale). This consists of seven items designed to assess one aspect of psychological coping resources (Mastery). Example items include, Sometimes I feel that I am being pushed here and there in life (reverse-scored) and What happens to me in the future mostly depends on me. Response options range from 1, strongly disagree, to 7, strongly agree. Score range from 7-28. Higher scores indicate greater mastery. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, six weeks after surgery, twelve weeks after surgery | 
| Fear of Surgery Questionnaire | The fear of surgery questionnaire is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences. Scoring range 0-100 with 0 being not afraid at all and 100 indicating very afraid. | One week before surgery | 
| Post Operative Morbidity - Post Operative Morbidity Score (POMS) | Post-operative Morbidity Outcomes: Assessed using the Post-operative Morbidity Score (POMS) at day 15. The POMS is an 18-item tool that addresses morbidity relevant to the post-surgical patient. The subcategories are Pulmonary, Infectious, Renal, Gastrointestinal, Cardiovascular, Neurological, Hematological, Wound and Pain. It is implemented as the morbidity either being present or absent. | Day 15 post surgery | 
| Post Operative Morbidity - Post Operative Morbidity Score (POMS) | Post-operative Morbidity Outcomes: Assessed using the Post-operative Morbidity Score (POMS) at day 15. The POMS is an 18-item tool that addresses morbidity relevant to the post-surgical patient. The subcategories are Pulmonary, Infectious, Renal, Gastrointestinal, Cardiovascular, Neurological, Hematological, Wound and Pain. It is implemented as the morbidity either being present or absent. | Day 30 post surgery | 
| Post Operative Morbidity -Clavien-Dindo Classification of Surgical Outcomes | The Clavien-Dindo classification of surgical complications, this consists of 5 grades that rank a post operative complication. grade one being any deviation form the usual post operative course and grade 5 being death. | Day 15 post surgery | 
| Post Operative Morbidity -Clavien-Dindo Classification of Surgical Outcomes | The Clavien-Dindo classification of surgical complications, this consists of 5 grades that rank a post operative complication. grade one being any deviation form the usual post operative course and grade 5 being death. | Day 30 post surgery | 
| Change in Nutritional Status -Assessed using Glasgow Prognostic Score | The Glasgow Prognostic Score Provides cancer prognosis based on serum biomarkers CRP and Albumin. It is calculated as follows: a score of 0 for normal C reactive protein and albumin levels, score 1 for either an abnormal C reactive protein or abnormal albumin level and score 2 for both abnormal C reactive protein and abnormal albumin levels. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery,15 days after surgery, 30 days after surgery, six weeks after surgery, twelve weeks after surgery | 
| Change in Nutritional Status -Assessed using Foodbook 24 | Foodbook24 is a Web-based, dietary tool consisting of a 24- hour dietary recall and food frequency questionnaire alongside supplementary questionnaires. | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, 15 days after surgery, 30 days after surgery, weeks after surgery, twelve weeks after surgery | 
| Change in concentration of blood markers of Inflammation- C-Reactive Protein | C-Reactive Protein will be assessed at each time point. A level greater that 15mmol/L | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, 15 days after surgery, 30 days after surgery, six weeks after surgery, twelve weeks after surgery | 
| Change in concentration of blood markers of Inflammation- White Cell Differential | White Cell Differential will be assessed at each time point. Normal range 3.5-10.5 x 109/L | Baseline, one week after completion of neo adjuvant treatment, one week before surgery, 15 days after surgery, 30 days after surgery, six weeks after surgery, twelve weeks after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Oesophageal Cancer, Gastric Cancer, Physical Fitness