The effect of a pre- and post-operative exercise program versus standard care on physical activity and sedentary behavior of patients with esophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (the PERIOP-OG Trial): a randomized controlled trial†.

Neoadjuvant cancer treatment (NCT) reduces both physical fitness and physical activity (PA) levels, which can increase the risk of adverse outcomes in cancer patients. This study aims to determine the effect of exercise prehabilitation on PA and sedentary behavior (SB) in patients undergoing NCT and surgery for esophagogastric malignancies. This study is a randomized pragmatic controlled multi-center trial conducted across three Irish hospitals. Participants were aged ≥18 years scheduled for esophagectomy or gastrectomy and were planned for NCT and surgery. Participants were randomized to an exercise prehabilitation group (EX) that commenced following cancer diagnosis, continued to the point of surgery, and resumed following recovery from surgery for 6 weeks or to usual care (UC) who received routine treatment. The primary outcome measures were PA and SB. Between March 2019 and December 2020, 71 participants were recruited: EX (n = 36) or UC (n = 35). No significant differences were found between the EX group and UC group on levels of PA or SBs across all measured timepoints. Significant decreases in moderate-vigorous physical activity levels (MVPAs) were found between baseline and post-surgery (P = 0.028), pre-surgery and post-surgery (P = 0.001) and pre-surgery and 6-week follow-up (P = 0.022) for all participants. Step count also significantly decreased between pre-surgery and post-surgery (P < 0.001). Baseline aerobic fitness was positively associated to PA levels and negatively associated with SB. Esophagogastric cancer patients have lower than recommended levels of PA at the time of diagnosis and this decreased further following completion of NCT. An optional home- or group-based exercise intervention was not effective in improving PA levels or behaviors across the cancer treatment journey.

A two-arm non-randomised trial of MedEx IMPACT: a community-based, physical activity behaviour change intervention for survivors of cancer.

PURPOSE: This two-arm non-randomised trial examined the short- and long-term effects of a usual care (UC) community-based exercise programme (MedEx Move On (MMO)), and UC combined with a physical activity (PA) behaviour change (BC) intervention (MedEx IMproved PA after Cancer Treatement (MedEx IMPACT)) on PA levels, cardiorespiratory fitness (CRF) and quality of life (QoL) among survivors of cancer. METHODS: Cancer survivors referred to MMO were recruited (n = 191; mean age (± SD) 56 (± 10y), 73% female). Eighty-seven participants were assigned to UC, and 104 participants were assigned to the MedEx IMPACT intervention group (MI). UC and MI both received twice-weekly supervised exercise classes for 12-weeks. MI also received an independent PA programme, 4 PA information sessions and a 1:1 exercise consultation during the 12-week programme. Assessments of physical and psycho-social health, including 6-day accelerometry, the 6-min time trial and the Functional Assessment of Cancer Therapy-General QoL questionnaire, were conducted at baseline (T1), post-intervention (T2) and 3 months following programme completion (T3). RESULTS: Linear mixed-model analyses of variance demonstrated significant main effects for time for both groups from T1 to T2 with increases in objectively measured daily steps (p < 0.05), CRF (p < .001) and QoL (p < .01), which were maintained for CRF (p < .001) at T3. MI participants also maintained increases achieved at T2, in steps and QoL, at T3 (p < 0.01). CONCLUSION: Twelve weeks of twice-weekly supervised exercise was effective in increasing PA, CRF and QoL among survivors of cancer. MI resulted in the maintenance of all improvements achieved 3 months following programme completion.

The impact of prehabilitation interventions on affective and functional outcomes for young to midlife adult cancer patients: A systematic review.

OBJECTIVE: Cancer remains one of the most enduring health crises of the modern world. Prehabilitation is a relatively new intervention aimed at preparing individuals for the stresses associated with treatment from diagnosis. Prehabilitation can include exercise, psychological and nutrition-based interventions. The present systematic review aimed to assess the efficacy of prehabilitation on affective and functional outcomes for young to midlife adult cancer patients (18-55 years). Outcomes of interest included prehabilitation programme composition, duration, mode of delivery and measures used to determine impact on affective and functional outcomes. METHODS: The following databases were searched with controlled and free text vocabulary; Psychological Information database (PsychINFO), Culmunated Index to Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE) and Public MEDLINE (PubMed). Abstract and full-text screening was conducted with a secondary reviewer and final texts were subject to risk of bias analysis. RESULTS: Thirteen texts were included at full-text. These included data of 797 prehabilitation participants (mean age 53 years) and a large representation of female participants (71% average). Evidence was found for the efficacy of psychological prehabilitation for anxiety reduction. Prehabilitation did not significantly affect health related quality of life. Findings moderately supported the therapeutic validity of exercise prehabilitation for functional outcomes, both in terms of clinical and experimental improvement with respect to the quality of evidence. Variation between all prehabilitation types was observed. There was insufficient evidence to support the efficacy of psychological prehabilitation on stress, distress or depression. CONCLUSION: Implications for future research are highlighted and then discussed with respect to this young to midlife age group.

Study protocol for the investigation of the clinical effectiveness of a physical activity behaviour change intervention for individuals living with and beyond cancer.

Most individuals living with and beyond cancer are not sufficiently active to achieve the health benefits associated with regular physical activity (PA). The purpose of this study was to describe the study protocol for a two-arm non-randomised comparison trial conducted within a community-based setting, which aimed to investigate the clinical effectiveness of a cancer-specific PA behaviour change (BC) intervention, namely MedEx IMPACT (IMprove Physical Activity after Cancer Treatment), compared to a general exercise rehabilitation programme, among survivors of cancer. Individuals who had completed active-cancer treatment who were referred to a community-based exercise rehabilitation programme were invited to participate in the trial. Participants in the control group (CG) attended twice-weekly supervised exercise classes for 12 weeks. Classes were delivered as part of a chronic illness exercise rehabilitation programme. Participants in the MedEx IMPACT intervention group (IG) also attended the twice-weekly supervised exercise classes for 12 weeks and received cancer-specific materials, namely an independent PA programme, 4 PA information sessions and a 1:1 exercise consultation. The primary outcome was PA levels measured by 6-day accelerometry and self-report PA. Secondary outcomes included cardiorespiratory fitness (CRF), quality of life (QoL) and sedentary behaviour. Outcomes were measured at baseline and months 3, 6 and 12. Few effective PA BC interventions for individuals living with and beyond cancer have been identified. The results of this study will have implications for the planning and provision of community-based exercise oncology rehabilitation programmes for individuals living with and beyond cancer.

The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients: a randomised controlled trial (The EMPOWER Trial).

BACKGROUND: The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health. METHODS: Between October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Patients underwent cardiopulmonary exercise testing (CPET) and completed HRQoL questionnaires (EORTC-QLQ-C30 and EQ-5D-5L) pre-NCRT and post-NCRT (week 0/baseline). At week 0, patients were randomised to exercise prehabilitation or usual care (no intervention). CPET and HRQoL questionnaires were assessed at week 0, 3, 6 and 9, whilst semi-structured interviews were assessed at week 0 and week 9. Changes in oxygen uptake at anaerobic threshold (VO2 at AT (ml kg-1 min-1)) between groups were compared using linear mixed modelling. RESULTS: Thirty-eight patients were recruited, mean age 64 (10.4) years. Of the 38 patients, 33 were randomised: 16 to usual care and 17 to exercise prehabilitation (26 males and 7 females). Exercise prehabilitation significantly improved VO2 at AT at week 9 compared to the usual care. The change from baseline to week 9, when adjusted for baseline, between the randomised groups was + 2.9 ml kg -1 min -1; (95% CI 0.8 to 5.1), p = 0.011. CONCLUSION: A 9-week exercise prehabilitation programme significantly improved fitness following NCRT. These findings have informed the WesFit trial (NCT03509428) which is investigating the effects of community-based multimodal prehabilitation before cancer surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT01914068 . Registered 1 August 2013.

Perceptions of wellbeing and quality of life following participation in a community-based pre-operative exercise programme in men with newly diagnosed prostate cancer: A qualitative pilot study.

BACKGROUND: Men with a newly diagnosed prostate cancer are often treated by surgery. The time window between cancer diagnosis and surgery causes high levels of uncertainty and stress, which negatively impact quality of life (QoL). We previously reported a larger intervention pilot study which demonstrated that participation in a community-based pre-operative exercise programme significantly improved physical fitness and health-related quality of life in men with prostate cancer prior to surgery. The aim of the current pilot study was to get an insight into men's perceptions of wellbeing and QoL following completion of the pre-operative exercise programme. METHODS: From November 2017 to June 2018, men scheduled for prostate cancer surgery were recruited and took part in a prescribed community-based pre-operative exercise programme in the time available between referral and surgery. Following completion of the pre-operative exercise programme (within 1 week before surgery), participants took part in one semi-structured interview which explored four broad QoL domains: physical, psychological, social, and spiritual wellbeing. Data were analysed using thematic analysis (a bottom up/inductive analysis). RESULTS: Eleven men were recruited: mean standard deviation (SD) age was 60 ± 7 years. Data supported four main themes. Participation in the community-based pre-operative exercise training programme (over a mean (SD) of 4 ± 2 weeks) provided participants with: 1) a teachable moment; 2) a journey of preparation; 3) a sense of optimism; and 4) social connectedness prior to surgery. CONCLUSION: This study provides an insight into how the exercise programme impacted wellbeing and QoL in men preparing for prostate cancer surgery. These findings highlight the important role that exercise prehabilitation plays for men preparing for prostate cancer surgery. Such exercise programmes can be easily implemented into standard cancer pathways by establishing relationships between hospital teams and community exercise programmes.

The effects of cancer therapies on physical fitness before oesophagogastric cancer surgery: a prospective, blinded, multi-centre, observational, cohort study.

Background: Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. Methods: Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). Results: In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg -1.min -1 (-1.80 to -0.69) and -3.02ml.kg -1.min -1 (-3.85 to -2.20); p<0.0001). Baseline chemo/chemoradiotherapy anaerobic threshold and peak were associated with one-year mortality (HR=0.72, 95%CI 0.59 to 0.88; p=0.001 and HR=0.85, 0.76 to 0.95; p=0.005). The change in physical fitness was not associated with one-year mortality. Conclusions: Chemo/chemoradiotherapy prior to oesophagogastric cancer surgery reduced physical fitness. Lower baseline fitness was associated with reduced overall survival at one-year. Careful consideration of fitness prior to chemo/chemoradiotherapy and surgery is urgently needed.

BACKGROUND: Cancer treatments such as chemotherapy and radiotherapy given to people with oesophageal and gastric cancer (also known as cancer of the food pipe/stomach) before surgery can improve survival. However, the impact such treatments have on fitness and recovery after surgery is unclear. The aim of this research was to understand the impact cancer treatments has on fitness and any complications after surgery. METHODS: Patients with oesophageal and gastric cancer (also known as cancer of the food pipe/stomach) who were being treated by cancer treatment and surgery were recruited from different hospitals in the UK. All participants were asked to undertake an exercise test to measure fitness and fill out questionnaires to measure quality of life before and after cancer treatment. Complications patients experienced after surgery, the number of patients who had to be readmitted to hospital 30 days after surgery and one-year survival was recorded. RESULTS: A total of 160 consented to participate in this study and 159 were included in the study (72% male, average age 65 years). In total, 132 patients (83%) had cancer treatment, 109 (71%) had cancer treatment and the two exercise tests and 100 (63%) had surgery and were followed-up after surgery. Study findings show that fitness reduced after cancer treatment. Patient's fitness levels at the start of the study (or before cancer treatment) were linked to one-year survival. The fall in fitness after cancer treatment was not linked to death at the one-year follow-up. CONCLUSION: Cancer treatments before oesophageal and gastric cancer reduce fitness. Patients with a lower fitness level before cancer treatment had a reduced overall survival at one-year. Careful consideration of fitness prior to such cancer treatments and surgery is urgently needed.

Physical, psychological and nutritional outcomes in a cohort of Irish patients with metastatic peritoneal malignancy scheduled for cytoreductive surgery (CRS) and heated intrapertioneal chemotherapy (HIPEC): An exploratory pilot study.

BACKGROUND: Treatment for peritoneal malignancy (PM) can include cytoreductive surgery (CRS) and heated intrapertioneal chemotherapy (HIPEC) and is associated with morbidity and mortality. Physical, psychological and nutritional outcomes are important pre-operatively. The aim of this pilot study was to investigate these outcomes in patients with PM before and after CRS-HIPEC. METHODS: Between June 2018 and November 2019, participants were recruited to a single-centre study. Primary outcome was cardiopulmonary exercise testing (CPET) variables oxygen uptake (VO2) at anaerobic threshold (AT) and at peak. Secondary outcome measures were upper and lower body strength, health related quality of life (HRQoL) and the surgical fear questionnaire. Exploratory outcomes included body mass index, nutrient intake and post-operative outcome. All participants were asked to undertake assessments pre CRS-HIPEC and 12 weeks following the procedure. RESULTS: Thirty-nine patients were screened, 38 were eligible and 16 were recruited. Ten female and 6 male, median (IQR) age 53 (42-63) years. Of the 16 patients recruited, 14 proceeded with CRS-HIPEC and 10 competed the follow up assessment at week 12. Pre-operative VO2 at AT and peak was 16.8 (13.7-18) ml.kg-1.min-1 and 22.2 (19.3-25.3) ml.kg-1.min-1, upper body strength was 25.9 (20.3-41.5) kg, lower body strength was 14 (10.4-20.3) sec, HRQoL (overall health status) was 72.5 (46.3-80) % whilst overall surgical fear was 39 (30.5-51). The VO2 at AT decreased significantly (p = 0.05) and HRQoL improved (p = 0.04) between pre and post- CRS-HIPEC. There were no significant differences for any of the other outcome measures. CONCLUSION: This pilot study showed a significant decrease in VO2 at AT and an improvement in overall HRQoL at the 12 week follow up. The findings will inform a larger study design to investigate a prehabilitation and rehabilitation cancer survivorship programme.

The effect of a pre- and post-operative exercise programme versus standard care on physical fitness of patients with oesophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (The PERIOP-OG Trial): Study protocol for a randomised controlled trial.

BACKGROUND: Advances in peri-operative oncological treatment, surgery and peri-operative care have improved survival for patients with oesophagogastric cancers. Neoadjuvant cancer treatment (NCT) reduces physical fitness, which may reduce both compliance and tolerance of NCT as well as compromising post-operative outcomes. This is particularly detrimental in a patient group where malnutrition is common and surgery is demanding. The aim of this trial is to assess the effect on physical fitness and clinical outcomes of a comprehensive exercise training programme in patients undergoing NCT and surgical resection for oesophagogastric malignancies. METHODS: The PERIOP-OG trial is a pragmatic, multi-centre, randomised controlled trial comparing a peri-operative exercise programme with standard care in patients with oesophagogastric cancers treated with NCT and surgery. The intervention group undergo a formal exercise training programme and the usual care group receive standard clinical care (no formal exercise advice). The training programme is initiated at cancer diagnosis, continued during NCT, between NCT and surgery, and resumes after surgery. All participants undergo assessments at baseline, post-NCT, pre-surgery and at 4 and 10 weeks after surgery. The primary endpoint is cardiorespiratory fitness measured by demonstration of a 15% difference in the 6-min walk test assessed at the pre-surgery timepoint. Secondary endpoints include measures of physical health (upper and lower body strength tests), body mass index, frailty, activity behaviour, psychological and health-related quality of life outcomes. Exploratory endpoints include a health economics analysis, assessment of clinical health by post-operative morbidity scores, hospital length of stay, nutritional status, immune and inflammatory markers, and response to NCT. Rates of NCT toxicity, tolerance and compliance will also be assessed. DISCUSSION: The PERIOP-OG trial will determine whether, when compared to usual care, exercise training initiated at diagnosis and continued during NCT, between NCT and surgery and then during recovery, can maintain or improve cardiorespiratory fitness and other physical, psychological and clinical health outcomes. This trial will inform both the prescription of exercise regimes as well as the design of a larger prehabilitation and rehabilitation trial to investigate whether exercise in combination with nutritional and psychological interventions elicit greater benefits. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03807518 . Registered on 1 January 2019.

The effect of participating in MedEx Wellness, a community-based chronic disease exercise rehabilitation programme, on physical, clinical and psychological health: A study protocol for a cohort trial.

BACKGROUND: Community-based exercise rehabilitation programmes for chronic disease are an effective alternative to traditional hospital-based programmes. MedEx Wellness is a novel community-based exercise rehabilitation programme that integrates a range of chronic diseases. The aim of this trial was to investigate the effect of participating in MedEx Wellness on physical, clinical and psychological health. METHODS: A prospective cohort study was conducted. Participants were recruited at induction to the MedEx Wellness programme following referral from healthcare professionals. Participants underwent a baseline assessment before commencing the exercise programme and repeat assessments at 3, 6 and 12 months. The primary outcome was cardiorespiratory fitness (6 minute- time trial) at 12 months. Secondary outcomes included health-related quality of life (EuroQoL-5D, Satisfaction with Life Scale, Warwick Edinburgh Mental Wellbeing Scale, Patient Health Questionnaire8, Functional Assessment of Cancer Therapy Questionnaire), free living activity behavior (accelerometer) and healthcare utilization (recall questionnaire). Tertiary outcomes included blood pressure (24 h), biomarkers (lipids, glucose and C-reactive protein), other components of physical fitness, including strength (handgrip test, sit-to-stand test), flexibility (sit-and-reach test), body composition (body mass index and waist-to-hip ratio), and falls risk (timed up and go test), and claudication time (incremental treadmill walking test), cognitive function, including attention (Attention Network Task), memory (Luck & Vogel Visual Working Memory Task) and cognitive reserve. Exploratory outcomes included psychosocial determinants of physical activity (self-efficacy, social support, intentions). DISCUSSION: This trial will evaluate whether participation in the MedEx Wellness programme has positive effects on physical, clinical and psychological health in individuals with a range of chronic diseases. TRIAL REGISTRATION: ISRCTN Registry ISRCTN10351412.

Physical Activity Across the Cancer Journey: Experiences and Recommendations From People Living With and Beyond Cancer.

BACKGROUND: The majority of individuals living with and beyond cancer are not sufficiently active to achieve health benefits. OBJECTIVE: The aim of this study was to explore individuals' experiences of physical activity (PA) behavior across the cancer journey and to ask individuals living with and beyond cancer to identify strategies to support habitual PA. DESIGN: An exploratory, descriptive, qualitative design was used. METHODS: Purposive sampling methods were used to recruit individuals living with and beyond cancer who had been referred to, and/or participated in, a community-based exercise program or were attending a cancer support center. The focus group discussions were audio recorded, transcribed verbatim, and analyzed using a thematic analysis approach. RESULTS: Seven focus groups were conducted with 41 participants. Many individuals reported that regular PA provided a vehicle for recovery that created a sense of "self-power," defined as taking ownership and control of one's health to increase well-being. Barriers to PA participation included environmental-, patient-, and treatment-related challenges. Recommendations to support long-term adherence to PA included completion of fitness assessments at regular intervals and provision of a home exercise program. LIMITATIONS: The benefits and barriers to PA participation for individuals diagnosed with cancers that were not represented may not have been identified. The strategies recommended to support habitual PA may be salient only to individuals whose cancer diagnoses were represented. CONCLUSIONS: Exercise is seen as a vehicle for recovery from cancer but long-term adherence for individuals is complex. The findings from this study can inform the development of exercise oncology rehabilitation programs and could support a greater likelihood of program success, thereby optimizing the health, well-being, and quality of life of survivors of cancer.

Compliance, adherence and effectiveness of a community-based pre-operative exercise programme: a pilot study.

BACKGROUND: Pre-operative exercise training improves HR components of fitness and HRQoL following hospital-based programmes. OBJECTIVE: To assess compliance and adherence of a pragmatic community-based preoperative exercise programme and its effect on health-related (HR) components of fitness and health-related quality of life (HRQoL). METHODS: Thirty-two surgical oncological participants (15 prostate cancer and 17 colorectal cancer (CRC)) were recruited and assessed to measure HR components of fitness (strength and functional exercise capacity) and HRQoL. An exercise programme was prescribed in the time available prior to surgery with repeat assessments pre-operatively. RESULTS: Twenty-four participants (14 prostate cancer and 10 CRC) completed the full study (75% compliance). Exercise training was delivered over a median interquartile range (IQR) of 4 (3-4) weeks and 2 (1-3) weeks for the prostate cancer and CRC participants, with > 80% adherence. From baseline to post-exercise intervention, there were significant improvements in lower body strength in the prostate cancer group (p = 0.045), the CRC group (p = 0.001), and in both groups overall (p = .001). Additionally, there were statistically significant improvements in HRQoL: global health status for CRC group (p = 0.025) and for both groups overall (p = 0.023); emotional health subscale for the prostate cancer group (p = 0.048) and for both groups overall (p = 0.027); nausea/vomiting/pain subscale for the CRC group (p = 0.005) and for both groups overall (p = 0.030); and for health scale status for the prostate cancer group (p = 0.019) and for both groups overall (p = 0.006). CONCLUSION: This community-based pre-operative exercise programme showed acceptable compliance and adherence rates, and significantly increased upper and lower body strength and HRQoL. Pre-operative exercise training should be considered as early as possible in the surgical-oncology pathway and respected within patient scheduling.

Perioperative prehabilitation and rehabilitation in esophagogastric malignancies: a systematic review.

Cancers of the esophagus and stomach are challenging to treat. With the advent of neoadjuvant therapies, patients frequently have a preoperative window with potential to optimize their status before major resectional surgery. It is unclear as to whether a prehabilitation or optimization program can affect surgical outcomes. This systematic review appraises the current evidence for prehabilitation and rehabilitation in esophagogastric malignancy. A literature search was performed according to PRISMA guidelines using PubMed, EMBASE, Cochrane Library, Google Scholar, and Scopus. Studies including patients undergoing esophagectomy or gastrectomy were included. Studies reporting on at least one of aerobic capacity, muscle strength, quality of life, morbidity, and mortality were included. Twelve studies were identified for inclusion, comprising a total of 937 patients. There was significant heterogeneity between studies, with a variety of interventions, timelines, and outcome measures reported. Inspiratory muscle training (IMT) consistently showed improvements in functional status preoperatively, with three studies showing improvements in respiratory complications with IMT. Postoperative rehabilitation was associated with improved clinical outcomes. There may be a role for prehabilitation among patients undergoing major resectional surgery in esophagogastric malignancy. A large randomized controlled trial is warranted to investigate this further.

Exercise interventions for people undergoing multimodal cancer treatment that includes surgery.

BACKGROUND: People undergoing multimodal cancer treatment are at an increased risk of adverse events. Physical fitness significantly reduces following cancer treatment, which is related to poor postoperative outcome. Exercise training can stimulate skeletal muscle adaptations, such as increased mitochondrial content and improved oxygen uptake capacity may contribute to improved physical fitness. OBJECTIVES: To determine the effects of exercise interventions for people undergoing multimodal treatment for cancer, including surgery, on physical fitness, safety, health-related quality of life (HRQoL), fatigue, and postoperative outcomes. SEARCH METHODS: We searched electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, SPORTDiscus, and trial registries up to October 2018. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared the effects of exercise training with usual care, on physical fitness, safety, HRQoL, fatigue, and postoperative outcomes in people undergoing multimodal cancer treatment, including surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, performed the data extraction, assessed the risk of bias, and rated the quality of the studies using Grading of Recommendation Assessment, Development, and Evaluation (GRADE) criteria. We pooled data for meta-analyses, where possible, and reported these as mean differences using the random-effects model. MAIN RESULTS: Eleven RCTs were identified involving 1067 participants; 568 were randomly allocated to an exercise intervention and 499 to a usual care control group. The majority of participants received treatment for breast cancer (73%). Due to the nature of the intervention, it was not possible to blind the participants or personnel delivering the intervention. The risk of detection bias was either high or unclear in some cases, whilst most other domains were rated as low risk. The included studies were of moderate to very low-certainty evidence. Pooled data demonstrated that exercise training may have little or no difference on physical fitness (VO2 max) compared to usual care (mean difference (MD) 0.05 L/min-1, 95% confidence interval (CI) -0.03 to 0.13; I2 = 0%; 2 studies, 381 participants; low-certainty evidence). Included studies also showed in terms of adverse effects (safety), that it may be of benefit to exercise (8 studies, 507 participants; low-certainty evidence). Furthermore, exercise training probably made little or no difference on HRQoL (EORTC global health status subscale) compared to usual care (MD 2.29, 95% CI -1.06 to 5.65; I2 = 0%; 3 studies, 472 participants; moderate-certainty evidence). However, exercise training probably reduces fatigue (multidimensional fatigue inventory) compared to usual care (MD -1.05, 95% CI -1.83 to -0.28; I2 = 0%; 3 studies, 449 participants moderate-certainty evidence). No studies reported postoperative outcomes. AUTHORS' CONCLUSIONS: The findings should be interpreted with caution in view of the low number of studies, the overall low-certainty of the combined evidence, and the variation in included cancer types (mainly people with breast cancer), treatments, exercise interventions, and outcomes. Exercise training may, or may not, confer modest benefit on physical fitness and HRQoL. Limited evidence suggests that exercise training is probably not harmful and probably reduces fatigue. These findings highlight the need for more RCTs, particularly in the neoadjuvant setting.

Physical activity levels in locally advanced rectal cancer patients following neoadjuvant chemoradiotherapy and an exercise training programme before surgery: a pilot study.

BACKGROUND: The aim of this pilot study was to measure changes in physical activity level (PAL) variables, as well as sleep duration and efficiency in people with locally advanced rectal cancer (1) before and after neoadjuvant chemoradiotherapy (CRT) and (2) after participating in a pre-operative 6-week in-hospital exercise training programme, following neoadjuvant CRT prior to major surgery, compared to a usual care control group. METHODS: We prospectively studied 39 consecutive participants (27 males). All participants completed standardised neoadjuvant CRT: 23 undertook a 6-week in-hospital exercise training programme following neoadjuvant CRT. These were compared to 16 contemporaneous non-randomised participants (usual care control group). All participants underwent a continuous 72-h period of PA monitoring by SenseWear biaxial accelerometer at baseline, immediately following neoadjuvant CRT (week 0), and at week 6 (following the exercise training programme). RESULTS: Of 39 recruited participants, 23 out of 23 (exercise) and 10 out of 16 (usual care control) completed the study. In all participants (n = 33), there was a significant reduction from baseline (pre-CRT) to week 0 (post-CRT) in daily step count: median (IQR) 4966 (4435) vs. 3044 (3265); p < 0.0001, active energy expenditure (EE) (kcal): 264 (471) vs. 154 (164); p = 0.003, and metabolic equivalent (MET) (1.3 (0.6) vs. 1.2 (0.3); p = 0.010). There was a significant improvement in sleep efficiency (%) between week 0 and week 6 in the exercise group compared to the usual care control group (80 (13) vs. 78 (15) compared to (69 ((24) vs. 76 (20); p = 0.022), as well as in sleep duration and lying down time (p < 0.05) while those in active EE (kcal) (152 (154) vs. 434 (658) compared to (244 (198) vs. 392 (701) or in MET (1.3 (0.4) vs. 1.5 (0.5) compared to (1.1 (0.2) vs. 1.5 (0.5) were also of importance but did not reach statistical significance (p > 0.05). An apparent improvement in daily step count and overall PAL in the exercise group was not statistically significant. CONCLUSIONS: PAL variables, daily step count, EE and MET significantly reduced following neoadjuvant CRT in all participants. A 6-week pre-operative in-hospital exercise training programme improved sleep efficiency, sleep duration and lying down time when compared to participants receiving usual care. TRIAL REGISTRATION: Clinicaltrials.gov NCT01325909.

The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients (The EMPOWER Trial): study protocol for a randomised controlled trial.

BACKGROUND: The standard treatment pathway for locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Neoadjuvant CRT has been shown to decrease physical fitness, and this decrease is associated with increased post-operative morbidity. Exercise training can stimulate skeletal muscle adaptations such as increased mitochondrial content and improved oxygen uptake capacity, both of which are contributors to physical fitness. The aims of the EMPOWER trial are to assess the effects of neoadjuvant CRT and an in-hospital exercise training programme on physical fitness, health-related quality of life (HRQoL), and physical activity levels, as well as post-operative morbidity and cancer staging. METHODS/DESIGN: The EMPOWER Trial is a randomised controlled trial with a planned recruitment of 46 patients with locally advanced rectal cancer and who are undergoing neoadjuvant CRT and surgery. Following completion of the neoadjuvant CRT (week 0) prior to surgery, patients are randomised to an in-hospital exercise training programme (aerobic interval training for 6 to 9 weeks) or a usual care control group (usual care and no formal exercise training). The primary endpoint is oxygen uptake at lactate threshold ([Formula: see text] at [Formula: see text]) measured using cardiopulmonary exercise testing assessed over several time points throughout the study. Secondary endpoints include HRQoL, assessed using semi-structured interviews and questionnaires, and physical activity levels assessed using activity monitors. Exploratory endpoints include post-operative morbidity, assessed using the Post-Operative Morbidity Survey (POMS), and cancer staging, assessed by using magnetic resonance tumour regression grading. DISCUSSION: The EMPOWER trial is the first randomised controlled trial comparing an in-hospital exercise training group with a usual care control group in patients with locally advanced rectal cancer. This trial will allow us to determine whether exercise training following neoadjuvant CRT can improve physical fitness and activity levels, as well as other important clinical outcome measures such as HRQoL and post-operative morbidity. These results will aid the design of a large, multi-centre trial to determine whether an increase in physical fitness improves clinically relevant post-operative outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01914068 (received: 7 June 2013). SPONSOR: University Hospital Southampton NHS Foundation Trust.

The effect of neoadjuvant chemoradiotherapy on whole-body physical fitness and skeletal muscle mitochondrial oxidative phosphorylation in vivo in locally advanced rectal cancer patients--an observational pilot study.

BACKGROUND: In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness. METHODS: We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg-1.min-1), and the post-exercise phosphocreatine recovery rate constant (min-1), a measure of muscle mitochondrial capacity in vivo. RESULTS: Median age was 67 years (IQR 64-75). Differences (95%CI) in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold -2.4 ml.kg-1.min-1 (-3.8, -0.9), p = 0.004; Oxygen uptake at Peak -4.0 ml.kg-1.min-1 (-6.8, -1.1), p = 0.011; and post-exercise phosphocreatine recovery rate constant -0.34 min-1 (-0.51, -0.17), p<0.001. CONCLUSION: The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery. TRIAL REGISTRATION: Clinicaltrials.gov registration NCT01859442.