REVOLUTION Surgery (REVOLUTION Surgery)

Recruiting

• Conditions: Colorectal Cancer; Gastric Cancer; Pancreatic Cancer; Cachexia; Oesophageal Cancer

• Registration Number: NCT05642819
• Lead Sponsor: University of Edinburgh

Brief Summary

Some people with cancer suffer from muscle wasting, lose weight and feel tired. This process, termed cachexia, is a significant problem and can lead to a reduction in both quality and quantity of life.

Cachexia is caused by interactions between the tumour and the patient. Historically, it was considered to be a purely end-stage phenomenon of advanced cancer, however, it is now known that early signs of cachexia can even influence the outcomes of patients with potentially curative pathology, including those planned for a surgical resection.

This study aims to collect information, from patients who are at risk of cachexia, about body composition, physical activity, quality of life and the body's immune response to cancer. Previously these measures have been most frequently studied in isolation, or at one single time-point, and are therefore likely to give an incomplete picture. A more holistic characterisation of surgical patients at risk of cancer cachexia, across their treatments, is currently lacking.

Participants with cancer will be recruited to the study from surgical services in the United Kingdom (UK). A small number of 'control' patients without cancer, who are undergoing surgery for a benign condition, will also be recruited for comparison. Those recruited will have their height and weight measured, answer questionnaires about quality of life, undergo assessment of their physical function and levels of activity, have blood taken to analyse markers of inflammation and have their body composition measured by a variety of methods. A subgroup of patients will also undergo an additional magnetic resonance imaging (MRI) scan of their abdomen and thighs. At the time of their operation, participants will also have small biopsies of muscle, fat, tumour and urine taken for biochemical analysis. Patients with cancer, will be asked to return for three follow up appointments during the year after their operation where these assessments will be repeated.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-15
• Study First Submitted QC: 2022-11-29
• Study First Posted: 2022-12-08
• Study Start: 2023-10-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-29
• Last Update Posted: 2024-12-04
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Inclusion Criteria (Cancer Resection)

• Patients with cancer (Clinical, histological, cytological or radiological evidence) planned for surgical resection of a malignancy of the oesophagus, stomach, pancreas, colon, or rectum
• Aged 18-years and over
• Able to give written informed consent

Inclusion Criteria (Healthy Controls)

• Patients identified at surgical clinic as being planned for an open abdominal operation for a non-inflammatory, benign condition (e.g. donor nephrectomy)
• Aged 18-years and over
• Able to give written informed consent

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Exclusion Criteria

• Any concomitant medical or psychiatric problems which, in the opinion of the investigator, would increase the risk of complication for the participant and/or investigator
• Presence of a concomitant inflammatory (e.g., rheumatoid arthritis, inflammatory bowel disease) or muscle wasting condition other than cancer
• Participants who are pregnant, suffer from claustrophobia or with implanted medical devices (e.g., cardiac pacemaker, metallic foreign bodies, aneurysm clip) would not be able to undergo the additional multiparametric magnetic resonance imaging (MRI)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Longitudinal changes in weight	Measured at baseline, following completion of any neo-adjuvant anti-cancer therapy, 6 (+/- 2) weeks, 6 (+/- 1) months and 12 (+/- 1) months following surgical resection	Longitudinal changes in weight (kg) - combined with height (m) to report body mass index (BMI) (kg/m2)
Longitudinal changes in computed tomography (CT) body composition (muscle quantity)	Measured at staging CT scan, at repeat scan following any neoadjuvant anti-cancer therapies and at follow-up scans following surgical resection / adjuvant anti-cancer therapies and other scans up to 1 year post surgical resection	Longitudinal changes in cross-sectional area (cm2) and volume (cm3) of skeletal muscle and radiodensity of skeletal muscle, subcutaneous fat, visceral fat and intra-muscular adipose tissue.
Longitudinal changes in CT body composition (fat quantity)	Measured at staging CT scan, at repeat scan following any neoadjuvant anti-cancer therapies and at follow-up scans following surgical resection / adjuvant anti-cancer therapies and other scans up to 1 year post surgical resection	Longitudinal changes in cross-sectional area (cm2) and volume (cm3) of subcutaneous and visceral adipose tissue
Longitudinal changes in physical activity	Measured at baseline, following completion of any neo-adjuvant anti-cancer therapy, 6 (+/- 2) weeks, 6 (+/- 1) months and 12 (+/- 1) months following surgical resection	A personal activity monitor (FitBit) will be worn for the next eight days to assess step count and time of physical activity
Longitudinal changes in CT body composition (muscle radiodensity)	Measured at staging CT scan, at repeat scan following any neoadjuvant anti-cancer therapies and at follow-up scans following surgical resection / adjuvant anti-cancer therapies and other scans up to 1 year post surgical resection	Longitudinal changes in radiodensity (HU - Hounsfield units) of skeletal muscle
Longitudinal changes in CT body composition (fat radiodensity)	Measured at staging CT scan, at repeat scan following any neoadjuvant anti-cancer therapies and at follow-up scans following surgical resection / adjuvant anti-cancer therapies and other scans up to 1 year post surgical resection	Longitudinal changes in radiodensity (HU - Hounsfield units) of subcutaneous and visceral adipose tissue
Longitudinal changes in systemic inflammation	Measured at baseline, following completion of any neo-adjuvant anti-cancer therapy, 6 (+/- 2) weeks, 6 (+/- 1) months and 12 (+/- 1) months following surgical resection	Longitudinal changes in serum levels of pro-inflammatory cytokines and other markers of systemic inflammation
Longitudinal changes in muscle function	Measured at baseline, following completion of any neo-adjuvant anti-cancer therapy, 6 (+/- 2) weeks, 6 (+/- 1) months and 12 (+/- 1) months following surgical resection	The 'timed up and go' test will be assessed for all participants as an estimate of lower limb muscle function
Longitudinal changes in muscle strength	Measured at baseline, following completion of any neo-adjuvant anti-cancer therapy, 6 (+/- 2) weeks, 6 (+/- 1) months and 12 (+/- 1) months following surgical resection	Isometric knee extension will be assessed for patients undergoing a multiparametric MRI as an estimate of quadriceps strength. This will be done using a hand-held dynamometer.
Longitudinal changes in risk of nutritional deficit	Measured at baseline, following completion of any neo-adjuvant anti-cancer therapy, 6 (+/- 2) weeks, 6 (+/- 1) months and 12 (+/- 1) months following surgical resection	Patient Generated Subjective Global Assessment Short Form ('PG-SGA-SF') questionnaires will be used to assess symptom burden and quality of life measures, specifically regarding nutritional risk in catabolic conditions
Longitudinal changes in quality of life (physical, psychological and social function in patients with cancer)	Measured at baseline, following completion of any neo-adjuvant anti-cancer therapy, 6 (+/- 2) weeks, 6 (+/- 1) months and 12 (+/- 1) months following surgical resection	European Organisation For Research And Treatment Of Cancer Quality of Life Questionnaire C30 ('EORTC-QLQ-C30') questionnaires will be used to assess symptom burden and general quality of life
Longitudinal changes in symptom burden, function and general quality of life in patients with anorexia / cachexia)	Measured at baseline, following completion of any neo-adjuvant anti-cancer therapy, 6 (+/- 2) weeks, 6 (+/- 1) months and 12 (+/- 1) months following surgical resection	Functional Assessment of Anorexia / Cachexia Therapy ('FAACT') questionnaires will be used to assess symptom burden, quality of life and function
Longitudinal tissue-level changes in fat content	Muscle biopsies will be taken at the time of surgical resection. Where participants are amenable, additional repeat needle biopsies of the quadriceps muscle will be performed at follow-up appointments 6 (+/- 1) months and 12 (+/- 1) months post surgery	Longitudinal changes in tissue level changes associated with cachexia, such as fat content of skeletal muscle
Longitudinal tissue-level changes in collagen content	Muscle biopsies will be taken at the time of surgical resection. Where participants are amenable, additional repeat needle biopsies of the quadriceps muscle will be performed at follow-up appointments 6 (+/- 1) months and 12 (+/- 1) months post surgery	Longitudinal changes in tissue level changes associated with cachexia, such as collagen content of skeletal muscle
Longitudinal tissue-level changes in protein content	Muscle biopsies will be taken at the time of surgical resection. Where participants are amenable, additional repeat needle biopsies of the quadriceps muscle will be performed at follow-up appointments 6 (+/- 1) months and 12 (+/- 1) months post surgery	Longitudinal changes in tissue level changes associated with cachexia, such as protein content of skeletal muscle
Evaluation of multiparametric magnetic resonance imaging (MRI) in cachexia	MRI scan performed pre-operatively	Evaluation of multiparametric MRI as a novel method for estimation of skeletal muscle mass and fat-infiltration across cachectic and weight-stable patients with cancer

Secondary Outcome Measures

Name	Time	Method
Correlation of multiparametric magnetic resonance imaging (MRI) and changes in physical function	MRI scan and assessments of physical function & muscle strength performed pre-operatively.	Evaluation of the relationship between physical function \& muscle strength (as assessed by personal activity monitor (FitBit), 'timed up and go' test and isometric knee extension using a hand-held dynamometer) and multiparametric MRI assessment of thigh muscle quantity.
Correlation of multiparametric magnetic resonance imaging (MRI) and tissue-level changes	MRI scan performed pre-operatively, tissue samples collected at the point of surgical resection.	Correlation of multiparametric MRI estimates of skeletal muscle mass and fat infiltration with CT image derived analyses and tissue level changes in fat, collagen and protein content of skeletal muscle.

Trial Locations

Locations (1)

University of Edinburgh; 🇬🇧 Edinburgh, United Kingdom