Prehabilitation of Patients With oEsophageal Malignancy Undergoing Peri-operative Treatment

Study Overview
=================
Brief Summary
-----------------
'Pre-EMPT' - A cohort-controlled, interventional study to assess the effects of a pre-emptive exercise programme, or 'prehabilitation', in patients undergoing peri-operative chemotherapy for adenocarcinoma of the lower oesophagus and gastro-oesophageal junction.

Detailed Description
-----------------
Oesophageal cancer has the fastest rising incidence of any solid tumour in the western world with the UK, and London, having particularly high rates of the disease. Those patients being considered for cure will benefit from pre-operative/neo-adjuvant chemotherapy (NAC), which is known to have a deleterious effect on fitness and is associated with increased post-operative morbidity. Post-operative morbidity is also associated with reduced survival. Reduction in fitness is compounded by major surgery and significantly reduces the numbers of patients who commence or complete the standard treatment of post-operative chemotherapy to around 40%. Chemotherapy and surgery for oesophageal cancer both represent significant physiological insults that may have detrimental effects on physical activity and outcomes after surgery. Cardiopulmonary exercise (CPEX) testing has been effectively used in numerous tumour groups to predict outcome after surgery, although its role in oesophageal cancer patients remains uncertain owing to conflicting data from institutional series. Advanced exercise programmes, sometimes termed 'prehabilitation', directed by experienced multidisciplinary teams are increasingly being used to mitigate the secondary effects of cancer treatment. 'Prehabilitation' has been shown to reduce postoperative morbidity and mortality in thoracic patients undergoing elective high-risk surgery. In addition, results of studies examining physical exercise and cancer recurrence/survival which effect immune system function in cancer survivors suggest that physical exercise training may improve a number of immune system parameters that may be important in cancer defence. The investigators believe that optimising patient fitness through a structured and expert-devised exercise programme of 'prehabilitation' during neo-adjuvant chemotherapy and prior to surgery will mitigate the effects of chemotherapy and improve patient outcomes after surgery. The investigators intend to assess the feasibility of a 'prehabilitation' programme and quantify the resultant effects primarily using CPEX testing. In addition, changes in hospital 'length of stay' will be documented with a number of additional parameters.

Official Title
-----------------
'Pre-EMPT' - An Interventional Study to Assess the Effects of Pre-emptive Exercise , or 'Prehabilitation', in Patients Undergoing Peri-operative Treatment for Adenocarcinoma of the Oesophagus and Gastro-oesophageal Junction

Conditions
-----------------
Surgery, Oesophageal Adenocarcinoma, Chemotherapy Effect

Intervention / Treatment
-----------------
* Behavioral: Exercise prehabilitation during chemotherapy before surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be diagnosed with operable oesophageal and gastro-oesophageal adenocarcinoma and scheduled to undergo standard neo-adjuvant chemotherapy and oesophago-gastric surgery as recommended by the Multidisciplinary Meeting decision. 18+ </=79 (patients above this age may be included in studies after the feasibility study has been completed) Participants must be able to understand and independently consent to participation in the study. Participants must be able to understand and complete the questionnaires. Participants must be willing to undergo all the standard assessments and interventions included in this study - CPEX testing, blood sampling, questionnaires and exercise intervention where appropriate. Participants must be willing to wear the Fibit monitoring device and agree with its use Participants must be ASA 1-3 and fit for surgical resection Patients should have a Body Mass Index (BMI) equal to or above 18.5 with less than 10% self-reported unintentional weight loss at diagnosis. Exclusion Criteria: Participants will be excluded if they: Are not considered medically fit for surgery at diagnosis, as decided by the Multidisciplinary team Will undergo primary or palliative chemotherapy Are recommended to have chemoradiotherapy Are under 18 years old Are over 79 years old Are unable to undergo CPEX testing Do not wish to take part in selected aspects of the study Cannot or do not wish to attend the CHHP for assessment and/or advice on exercise Cannot understand and give informed consent to the study Cannot understand and complete the questionnaires Do not wish to wear a Fitbit monitoring device ASA 4+ Patients with BMI of less than 18.5 with self-reported unintentional weight loss of 10% or more at diagnosis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cohort-controlled
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional<br>Participants will be given a monitored exercise program during their treatment starting before chemotherapy | Behavioral: Exercise prehabilitation during chemotherapy before surgery<br>* Monitored exercise training in patients with a new diagnosis of oesophageal adenocarcinoma<br>|
| No Intervention: Non-interventional<br>Patients will have standard care. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiopulmonary fitness | Cardiopulmonary exercise test on bicycle ergometer | Baseline to 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative complications | Clavien-Dindo; ECCG- Esophageal Complications Consensus Group | Date of surgery to date of discharge, up to 45 days post-surgery | 
| Post-operative length of hospital stay | Number of in-hospital days from date of surgery | Date of surgery to date of discharge, up to 45 days post-surgery | 
| Lean body mass | Computerised tomography assessment of lean body mass | Baseline to 5 months | 
| Daily activity levels | Steps per day measured by Fitbit | Baseline to 5 months | 
| Sleep quality assessment | Sleep data from Fitbit | Baseline to 5 months | 
| Change in Health-related Quality of Life: Oesophageal cancer-specific questionnaire | EORTC QLQ-OES18 | Baseline to 12 months post-surgery | 
| Change in Health-related Quality of Life: Cancer questionniare | EORTC QLQ-C30 | Baseline to 12 months post-surgery | 
| Change in Well-being | SWEMWEBS questionnaire | Baseline to 12 months post-surgery | 
| Disease recurrence | Pathological or radiological confirmation of recurrent disease | Date of surgery to date of recurrence, up to 12 months post-surgery | 
| Post-operative mortality | In-patient, 30-day, 90-day, 1-year | Date of surgery to date of death, up to 12 months post-surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prehabilitation, Exercise, Cancer, Neo-adjuvant chemotherapy