Title: A pilot study to investigate improvements in physical fitness and quality of life resulting from a 9 week structured responsive endurance training programme (SRETP) following neoadjuvant chemoradiotherapy prior to elective rectal cancer surgery
Funder: Department of Health (England)

Abstract: BACKGROUND Neoadjuvant chemoradiotherapy (NACRT) for advanced rectal cancer is associated with better local disease control, with minimal impact on survival (4,5). Exercise improves bowel cancer outcome. Stated by the BBC (August 2011) “The risk of dying from bowel cancer can be reduced if physically activity” (11,12). Cancer and chemotherapy are known to cause fatigue via oxidative stress, leading to muscle weakness and poor quality of life (6). Moreover, aerobic exercise, decreases oxidative stress (14). We have pilot data showing that NACRT reduces physical fitness in upper and lower GI cancer surgery (8,9). The literature shows that low fitness (high-risk patients) is associated with a higher risk of adverse outcome (death and serious complication) after major surgery (13-16,21,22). Exercise training improves HRQL, reduces complications and is safe in elderly cancer patients (15-20).We have feasibility data showing that the reduction fitness caused by NACRT can be improved. AIMS This proposal therefore outlines a study to explore: PRIMARY HYPOTHESIS A 9-week SRETP compared with a control group (no training) will result in a clinically significant difference in physical fitness (2.0ml/kg/min VO2 at LT) in patients who have had NACRT prior to cancer surgery. SECONDARY OUTCOMES A 9-week SRETP compared with a control group (no training) will result in a clinically significant difference in physical fitness (2.0ml/kg/min VO2 Peak) post NACRT prior to cancer surgery SRETP following NACRT and prior to cancer surgery will provide psychological health benefits and improve patient’s HRQL (assessed by semi-structured interviews and questionnaires -EORTC QLQ-30 and EQ-5D). EXPLORATORY OUTCOMES 1. To investigate whether SRETP following NACRT and prior to cancer surgery is associated with a change in physical activity (assessed by the number of steps while active using an accelerometer) 2. To investigate whether there is a change in the day 7 surgical morbidity (using POMS) and mortality. 3. The effect of SRETP on cancer downstaging post-NACRT (TNM staging). PLAN OF INVESTIGATION (See Annex 1) We propose a prospective, parallel group, RCT using a 9-week SRETP in patients undergoing NACRT prior to cancer resection in two NHS hospitals. Physiological data will be analysed by an investigator blinded to study group allocation. Physical fitness before and at intervals (0, 3, 6, 9 and 14 weeks) after NACRT measured using CPET. Block randomization by centre carried out post-NACRT to an exercise (SRETP) and control group (no training) in a 1:1 distribution. The SRETP will have 3 sessions per week for 9 weeks, whilst the negative control group will be given general exercise advice. At week 9, both groups will undergo standard care cancer staging scans and a CPET. CPET is also performed at weeks 14. Activity monitors (SenseWear Pro Accelerometer) will be fitted pre-, during and post-NACRT (week 3 and 9) to measure change in physical activity. HRQL questionnaires (EORTC-QLQc30v3, EQ-5D) will also be carried out on activity monitoring sessions as above, as well as 6 weeks post-operatively. HRQL semi-structured interviews will be carried out by a psychologist at the end of the SRETP. Postoperative outcomes will be objectively recorded using POMS (Day, 5, 7 and 14). PATIENT BENEFIT If the hypotheses are supported by the study results, patients: - Will improve baseline fitness and regain control of their pre-operative management. - Reduce post-NACRT fatigue levels, - Improve HRQL, - Instigate behavioural changes in the short term, with potential long-term benefit. - Improve surgical outcomes (longer survival, fewer post-operative complications) - Improve cancer downstaging post-NACRT (Tumour, Node and Metastasis Staging – TNM). - Reduce hospital resources (reduction in patient length of stay, reduced demand for post-operative high dependency care and associate health economic benefits).


Research activity codes: 6.4 SURGERY;6.7 PHYSICAL
Health categories: CANCER AND NEOPLASMS