Preoperative Physical Activity Intervention in Patients Before Planned Liver Resection for Cancer (APACHE)

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to assess the impact of preoperative physical activity on physical capacities of patients undergoing liver resection for primary or secondary liver cancer.

Detailed Description
-----------------
The purpose of this study is to investigate the effects of a preoperative exercise program in patients with primary or secondary liver cancer undergoing hepatectomy. Preoperative exercise programs have been shown to be effective in other cancer populations, but have been poorly studied in patients with liver cancer. For these patients, it remains unclear what the optimal composition of such programs should be and how they should be delivered. Outcome measures in this study will include preoperative outcomes (oxygen consumption, quality of life, fatigue and physical activity level, anthropometric measures, plasma concentrations of hepatokines) and postoperative outcomes (length of hospital stay and postoperative complications). After the study is explained and consent obtained, subjects will be tested on a submaximal exercise on cycloergometer with gas exchanges analysis and with pre and post blood test. Then, they will answer various questionnaires assessing physical activity, quality of life and fatigue. Patients scheduled for liver resection will be randomized to one of two groups. The first group (experimental group) will be subdivided into two groups: interval training 1 and interval training 2, which differentiate themselves by two different intensities.The second group (control group) will receive standard care. The prehabilitation program will last 6 weeks with 3 sessions per week and will consist in two interval training programs on a cycloergometer with two different intensities. One month after surgery, peri and postoperative complications will be noted.

Official Title
-----------------
Preoperative Physical Activity Intervention in Patients Before Planned Liver Resection for Cancer

Conditions
-----------------
Primary Liver Cancer, Secondary Liver Cancer, Liver Metastases

Intervention / Treatment
-----------------
* Behavioral: Interval training
* Other: Standard Oncologic care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged >18 years old. Patients with primary liver cancer, biliary tract cancer, liver metastasis endorsed in the University Hospital of Besancon No opposition of patients Join a French social security or receiving such a scheme Exclusion Criteria: Legal incapacity or limited legal capacity Patients being in the disqualification of another study or under the national register of volunteers Patients unlikely to cooperate or anticipated low cooperation Patients with a maximal oxygen consumption above 35 ml/min/kg

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br> | Other: Standard Oncologic care<br>* Patients in control group will follow the standard oncologic care. They will perform only 2 sub-maximal exercises.<br>|
| Experimental: Interval training 1<br> | Behavioral: Interval training<br>* Patients in experimental group will perform a 6 weeks' physical activity program with 3 sessions per week. Physical activity intervention will consist in 2 different interval training programs on cycloergometer: Interval training 1 and Interval training 2, with a difference in exercise intensities.<br>|
| Experimental: Interval training 2<br> | Behavioral: Interval training<br>* Patients in experimental group will perform a 6 weeks' physical activity program with 3 sessions per week. Physical activity intervention will consist in 2 different interval training programs on cycloergometer: Interval training 1 and Interval training 2, with a difference in exercise intensities.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Oxgen consumption at anaerobic threshold : | Oxygen consumption at anaerobic threshold will be assessed at baseline and at the end of the 6 weeks' program with a submaximal exercise performed on cycloergometer | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complications with the Dindo Clavien classification : | Postoperative complications will be assessed using the Dindo Clavien classification which consists in a 7 grades classification (I, II, IIIa, IIIb, IVa, IVb and V). | One month after surgery | 
| Intensive care stay : | Postoperative intensive care stay will be evaluated (number of days). | One month after surgery | 
| Changes of Hepatokines plasmatic concentrations : | Fetuin A (ng/mL) concentrations will be analyzed. | Comparison between plasmatic concentrations pre-exercise (day 1), post exercise (day 1) and at 6 weeks | 
| Hepatokines plasmatic concentrations : | Fibroblast Growth Factor 21 (FGF21) (pg/mL) concentrations will be analyzed. | Comparison between plasmatic concentrations pre-exercise (day 1), post exercise (day 1) and at 6 weeks | 
| Changes in Physical activity level : | Physical activity level will be measured using the long-form of the International Physical Activity Questionnaire (IPAQ). It consist in a description of the physical activity level by assessing 5 activity domains during the 7 last days. Physical activity level is expressed in Metabolic Equivalent Tasks (METs). It enables to classify patients in 3 categories : low physical activity level, moderate physical activity level and high physical activity level. | Comparison between baseline, after the 6 weeks' program | 
| Changes in Quality of life : | Health related quality of life will be measured with the EORTC Quality of Life Questionnaire QLQ-C30 which is a cancer specific questionnaire. It consists in 30 items to measure 15 dimensions of quality of life. It generates a score between 0 and 100. A higher score means a higher quality of life level. | Comparison between baseline, after the 6 weeks' program | 
| Changes in Fatigue : | Fatigue will be measured with the Quality of Life Questionnaire QLQ-FA12 which enables to assess cancer related fatigue. It consists in 12 items to measure 5 dimension go health related fatigue. It generates a score between 0 and 100. A higher score means a higher fatigue level. | Comparison between baseline, after the 6 weeks' program | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exercise, Adapted physical activity, preoperative, liver resection, hepatectomy