The Wessex Fit-4-Cancer Surgery Trial

University Hospital Southampton NHS Foundation Trust1,560 enrolled

Overview

Trial Phase: Phase III: A multi-centre efficacy pragmatic factorial design randomised controlled trial with patient informed development and process evaluation Indication: Patients undergoing major electively resectable intra - cavity cancer surgery with or without neoadjuvant cancer treatments (including chemotherapy (NAC), chemoradiotherapy (CRT), or immunotherapy). Objective: To investigate the efficacy of a community based Structured Responsive Exercise-training Programme (SRETP) ± psychological support on surgical outcome by reducing postoperative length of stay (LOS) and complications. Secondary Objective: To investigate the efficacy of a community based Structured Responsive Exercise-training Programme (SRETP) ± psychological support to improve disease-free overall survival. Cardiopulmonary Exercise test (CPET) variables, physical activity, morbidity, radiological markers of sarcopenia, toxicity, tumour down-staging, tumour regression, disability adjusted survival (WHODAS) overall survival and quality of life (QoL).

Rationale: Fitter patients have better surgical outcomes. Poor physical fitness measured objectively using cardiopulmonary exercise testing has been associated with increased LOS, increased morbidity and mortality in many patient cohorts undergoing major cancer surgery. Chemotherapy and radiotherapy have detrimental effects on physical fitness, which may in turn have a detrimental effect on the patients' ability to withstand surgery. Research suggests psychological factors including depression and self-efficacy (confidence to manage cancer-related problems) prior to surgery predict recovery trajectories in health-related quality of life up to 2 years after major surgery for colorectal cancer. The aim is to investigate whether SRETP (Prehabilitation) ± psychological support prior to and during cancer treatment before major elective surgery reduces LOS, increases survival and improves their ability to self manage. Additionally, we aim to see if this intervention can bring about long-term behavioural change in relation to physical activity. Trial Design: Phase III: A pragmatic factorial design randomised controlled to assess the effectiveness of a prehabilitation programme delivered prior to cancer treatments and/or major cancer surgery in patients undergoing elective intra-cavity major cancer surgery in Wessex. Sample size: 1560 Intervention: 1. An in-hospital transition to a community based Structured Responsive Exercise-Training Programme (SRETP) ± psychological support (delivered in community/ council gyms or Cancer Support Centers). The intervention/s will be delivered before surgery. Patients receiving neoadjuvant cancer treatments prior to surgery will receive the intervention during and after these treatments. 2. Control: Standard care with extra monitoring

Interventions

SRETPBEHAVIORAL

SRETP will involve short periods of exercise at a high intensity interspersed with short periods of exercise at a moderate intensity (aerobic interval training). We will also include resistance training in each session. Exercise intensities during the interval exercise-training program are specific to each patient and derived from CPET. Moderate intensity exercise is below the anaerobic threshold (AT). Patients will exercise at 80% of oxygen uptake (VO2) obtained at the anaerobic threshold (80%AT) for moderate intensity exercise - 3 minutes. Severe exercise intensity is recognised as 50% of the difference between the VO2 AT and VO2 Peak (50%∆) - 2 minutes.

Psychological supportBEHAVIORAL

Support sessions will be patient-centred, giving the patient an opportunity to raise any issues/concerns they are having, this may include (but will not be limited to) ways of coping with their reactions to cancer, family and relationship issues, exploring personal issues and dealing with practical issues. Patients will have access to other resources available at the cancer centres including but not restricted to further information about their condition and how to access financial support. These processes reflect the best practice currently being delivered by cancer support centre staff in the Wessex region. Any patient deemed at risk (i.e. from suicidal ideation or self harm) will be reported to their GP, followed up by a letter.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female patients * aged over 18 years old * scheduled to have major intra-cavity cancer surgery with a curative intent, defined as thoracic, colorectal, oesophagogastric, urological and hepatobiliary (inc. pancreatic). * surgery alone (unimodal) * surgery combined (multimodal) with cancer treatments (neoadjuvant chemotherapy, chemoradiotherapy or immunotherapies). * All patients deemed by the MDT as potentially curable or undergoing neoadjuvant cancer treatments prior to restaging and surgery. Exclusion Criteria: * Patients will be excluded if under the age of 18 years, * if their tumour is considered surgically non- resectable, * having absolute or relative contraindications to completing a CPET, * patients are unable to perform CPET due to other coexisting acute illness or conditions (e.g. lower limb dysfunction), * patients decline surgery, * if their weight exceeds 145kg * patients unable to give informed consent. * Patients having \>2 mm ST depression if symptomatic or 4 mm if asymptomatic or \>1 mm ST elevation during any CPET will need to be withdrawn from study.

Outcomes

Primary Outcomes

Post-operative length of hospital stay

Date of hospital admission minus date of discharge would equal length of post-operative stay (LOS).

Time frame: up to 1 year

Secondary Outcomes

Change in objectively measured cardiopulmonary exercise testing variables - Oxygen uptake at anaerobic threshold (ml/kg/min) and oxygen uptake at peak exercise (ml/kg/min)

Change in cardiopulmonary exercise variables i.e. oxygen uptake (VO2) at anaerobic threshold (AT) and at peak exercise. A clinically significant difference in physical fitness is defined as ≥ 2ml/min/kg VO2 at AT.

Time frame: up to 15 weeks

Overall survival - 1

Overall survival at 1 year post surgery

Time frame: 1 year post-operatively

Overall survival -2

Overall survival at 5 year post surgery

Time frame: 5 years post-operatively

Disease free survival

Clinical or radiologically measured disease free survival

Time frame: 1 year post-operatively

Post-operative morbidity -1

Patients post-operative morbidity survey (POMS) will be characterised on day 3, 5, 7 and 15. The POMS 18-item survey will be used to address nine domains of postoperative morbidity (pulmonary, infectious, renal, gastrointestinal, cardiovascular, neurological, wound complication, haematological and pain).

Time frame: POMS at day 3,5,7 and 15.

Post-operative morbidity -2

On day of discharge, patient's surgical complications (if any) will be graded using the Clavien-Dindo classification of surgical complications This classification is used to assess overall hospital morbidity following surgical procedures. Patients are graded as 0 (no complications) or Grade I-V based on the level of complication, including the number of organ system involvement. Grade V is defined as death of a patient. A record of the Comprehensive Complication Index (CCI) - an update of the Clavien-Dindo classification will also be collected

Time frame: up to 1 year

Physical activity -1

Number of steps while active using a triaxial accelerometer eg. Senseware