Malcolm A. West

Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study

BACKGROUND Patients requiring surgery for locally advanced rectal cancer often additionally undergo neoadjuvant chemoradiotherapy (NACRT), of which the effects on physical fitness are unknown. The aim of this feasibility and pilot study was to investigate the effects of NACRT and a 6 week structured responsive exercise training programme (SRETP) on oxygen uptake [Formula: see text] at lactate threshold ([Formula: see text]) in such patients. METHODS We prospectively studied 39 consecutive subjects (27 males) with T3-4/N+ resection margin threatened rectal cancer who completed standardized NACRT. Subjects underwent cardiopulmonary exercise testing at baseline (pre-NACRT), at week 0 (post-NACRT), and week 6 (post-SRETP). Twenty-two subjects undertook a 6 week SRETP on a training bike (three sessions per week) between week 0 and week 6 (exercise group). These were compared with 17 contemporaneous non-randomized subjects (control group). Changes in [Formula: see text] at [Formula: see text] over time and between the groups were compared using a compound symmetry covariance linear mixed model. RESULTS Of 39 recruited subjects, 22 out of 22 (exercise) and 13 out of 17 (control) completed the study. There were differences between the exercise and control groups at baseline [age, ASA score physical status, World Health Organisation performance status, and Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) predicted mortality]. In all subjects, [Formula: see text] at [Formula: see text] significantly reduced between baseline and week 0 [-1.9 ml kg(-1) min(-1); 95% confidence interval (CI) -1.3, -2.6; P<0.0001]. In the exercise group, [Formula: see text] at [Formula: see text] significantly improved between week 0 and week 6 (+2.1 ml kg(-1) min(-1); 95% CI +1.3, +2.9; P<0.0001), whereas the control group values were unchanged (-0.7 ml kg(-1) min(-1); 95% CI -1.66, +0.37; P=0.204). CONCLUSIONS NACRT before rectal cancer surgery reduces physical fitness. A structured exercise intervention is feasible post-NACRT and returns fitness to baseline levels within 6 weeks. CLINICAL TRIAL REGISTRATION NCT 01325909.

Preoperative aerobic exercise training in elective intra-cavity surgery: a systematic review

Reduced physical fitness is associated with increased risk of complications after intra-cavity surgery. Aerobic exercise training interventions improve physical fitness in clinical populations. However, it is unclear whether implementing a preoperative aerobic exercise training intervention improves outcome after intra-cavity surgery. We conducted a systematic review (Embase and PubMed, to April 2011) to address the question: does preoperative aerobic exercise training in intra-cavity surgery result in improved postoperative clinical outcomes? Secondary objectives were to describe the effect of such an intervention on physical fitness and health-related quality of life (HRQL) and report feasibility, safety, and cost-effectiveness. Ten studies were identified from 2443 candidate abstracts. Eight studies were small (<100 patients) and all were single centre. Seven studies reported clinical outcomes. Two studies were controlled trials and two used a sham intervention group. One study in cardiac surgery demonstrated reduced postoperative hospital and intensive care length of stay in the intervention group. Eight studies showed improvement in ≥ 1 measure of physical fitness after the intervention. HRQL was reported in five studies; three showed improved HRQL after the intervention. The frequency, duration, and intensities of the exercise interventions varied across the studies. Adherence to exercise interventions was good. Two exercise-related adverse events (transient hypotension) were reported. Evidence for improved postoperative clinical outcome after preoperative aerobic exercise training interventions is limited. However, preoperative aerobic exercise training seems to be generally effective in improving physical fitness in patients awaiting intra-cavity surgery and appears to be feasible and safe.

The effect of neoadjuvant chemotherapy on physical fitness and survival in patients undergoing oesophagogastric cancer surgery

BACKGROUND Neoadjuvant chemotherapy (NAC) followed by surgery for resectable oesophageal or gastric cancer improves outcome when compared with surgery alone. However NAC has adverse effects. We assess here whether NAC adversely affects physical fitness and whether such an effect is associated with impaired survival following surgery. METHODS We prospectively studied 116 patients with oesophageal or gastric cancer to assess the effect of NAC on physical fitness, of whom 89 underwent cardiopulmonary exercise testing (CPET) before NAC and proceeded to surgery. 39 patients were tested after all cycles of NAC but prior to surgery. Physical fitness was assessed by measuring oxygen uptake (VO₂ in ml kg(-1) min(-1)) at the estimated lactate threshold (θL) and at peak exercise (VO₂ peak in ml kg(-1) min(-1)). RESULTS VO₂ at θL and at peak were significantly lower after NAC compared to pre-NAC values: VO₂ at θL 14.5 ± 3.8 (baseline) vs. 12.3 ± 3.0 (post-NAC) ml kg(-1) min(-1); p ≤ 0.001; VO₂ peak 20.8 ± 6.0 vs. 18.3 ± 5.1 ml kg(-1) min(-1); p ≤ 0.001; absolute VO₂ (ml min(-1)) at θL and peak were also lower post-NAC; p ≤ 0.001. Decreased baseline VO₂ at θL and peak were associated with increased one year mortality in patients who completed a full course of NAC and had surgery; p = 0.014. CONCLUSION NAC before cancer surgery significantly reduced physical fitness in the overall cohort. Lower baseline fitness was associated with reduced one-year-survival in patients completing NAC and surgery, but not in patients who did not complete NAC. It is possible that in some patients the harms of NAC may outweigh the benefits. Trials Registry Number: NCT01335555.

The effects of neoadjuvant chemoradiotherapy on physical fitness and morbidity in rectal cancer surgery patients

BACKGROUND Neoadjuvant chemoradiotherapy (NACRT) followed by surgery for resectable locally advanced rectal cancer improves outcome compared with surgery alone. Our primary hypothesis was that NACRT impairs objectively-measured physical fitness. We also wished to explore the relationship between fitness and postoperative outcome. METHOD In an observational study, we prospectively studied 27 consecutive patients, of whom 25 undertook cardiopulmonary exercise testing (CPET) 2 weeks before and 7 weeks after standardized NACRT, then underwent surgery. In-hospital post-operative morbidity and mortality were recorded. Patients were followed up to 1 year for mortality. Data was analysed blind to clinical details. Receiver-operating characteristic (ROC) analysis defined the predictive value of CPET for in-hospital morbidity at day 5. RESULTS Oxygen uptake ( [Formula: see text] in ml kg(-1) min(-1)) at estimated lactate threshold (θˆL) and at peak exercise ( [Formula: see text] at peak in ml kg(-1) min(-1)) both significantly decreased post-NACRT: [Formula: see text] at θˆL 12.1 (pre-NACRT) vs. 10.6 (post-NACRT), p < 0.001 (95%CI -1.7, -1.2); [Formula: see text] at peak 18.1 vs. 16.7, p < 0.001 (95%CI -3.1, -1.0). Optimal [Formula: see text] at θˆL and peak pre-NACRT for predicting postoperative morbidity were 12.0 and 18.1 ( [Formula: see text] at θˆL - AUC = 0.71, 77% sensitive and 75% specific; [Formula: see text] at peak - AUC = 0.75, 78% sensitive and 76% specific). Optimal [Formula: see text] at θˆL and peak post-NACRT for predicting postoperative morbidity were 10.7 and 16.7 ( [Formula: see text] at θˆL - AUC = 0.72, 77% sensitive and 83% specific; [Formula: see text] at peak - AUC = 0.80, 85% sensitive and 83% specific). CONCLUSION NACRT before major rectal cancer surgery significantly decreased physical fitness as assessed by CPET. TRIALS REGISTRY NUMBER NCT01334593.

Exercise intervention in people with cancer undergoing adjuvant cancer treatment following surgery: A systematic review.

BACKGROUND Remaining physically active during and after cancer treatment is known to improve associated adverse effects, improve overall survival and reduce the probability of relapse. This systematic review addresses the question: is an exercise training programme beneficial in people with cancer undergoing adjuvant cancer treatment following surgery. METHODS A systematic database search of Embase, Ovid, Medline without Revisions, SPORTDiscus, Web of Science, Cochrane Library and ClinicalTrials.gov for any randomised controlled trials (RCT) or non-RCT addressing the effect of an exercise training programme in those having adjuvant cancer treatment following surgery was conducted. RESULTS The database search yielded 6489 candidate abstracts of which 94 references included the required terms. A total of 17 articles were included in this review. Exercise training is safe and feasible in the adjuvant setting and furthermore may improve measures of physical fitness and health related quality of life (HRQoL). CONCLUSION This is the first systematic review on exercise training interventions in people with cancer undergoing adjuvant cancer treatment following surgery. Due to the lack of adequately powered RCTs in this area, it remains unclear whether exercise training in this context improves clinical outcomes other physical fitness and HRQoL. It remains unclear what is the optimal timing of initiation of an exercise programme and what are the best combinations of elements within an exercise training programme to optimise training efficacy. Furthermore, it is unclear if initiating such exercise programmes at cancer diagnosis may have a long-lasting effect on physically activity throughout the subsequent life course.

Validation of preoperative cardiopulmonary exercise testing-derived variables to predict in-hospital morbidity after major colorectal surgery.

In single‐centre studies, postoperative complications are associated with reduced fitness. This study explored the relationship between cardiorespiratory fitness variables derived by cardiopulmonary exercise testing (CPET) and in‐hospital morbidity after major elective colorectal surgery.

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

Comparison of oxygen uptake during arm or leg cardiopulmonary exercise testing in vascular surgery patients and control subjects

BACKGROUND Cardiopulmonary exercise testing by cycle ergometry (CPET(leg)) is an established assessment tool of perioperative physical fitness. CPET utilizing arm ergometry (CPET(arm)) is an attractive alternative in patients with lower limb dysfunction. We aimed to determine whether oxygen uptake obtained by CPET(leg) could be predicted by using CPET(arm) alone and whether CPET(arm) could be used in perioperative risk stratification. METHODS Subjects underwent CPET(arm) and CPET(leg). To evaluate the ability of VO₂ obtained from CPET(arm) to predict VO₂ from CPET(leg), we calculated prediction intervals (PIs) at lactate threshold θ(L) and peak exercise in both groups. Receiver operating characteristic (ROC) curves were used to risk stratify patients into high and low categories based on published criteria. RESULTS We recruited 20 vascular surgery patients (17 males and three females) and 20 healthy volunteers (10 males and 10 females). In both groups, PIs for at and peak were wider than clinically acceptable (patient group - VO₂ at θ(L) CPET(arm) ranged from 55% to 108% of CPET(leg) and from 54% to 105% at peak; healthy volunteers - 37-77% and 41-79%, respectively). The area under the ROC for CPET(arm) VO₂ in patients was 0.84 [95% confidence interval (CI): 0.66, 1.0] at θ(L), and 0.76 (95% CI: 0.54, 0.99) at peak. CONCLUSIONS Although a relationship exists between VO₂ values for CPET(arm) and CPET(leg), this is insufficient for accurate prediction using CPET(arm) alone. This however does not necessarily preclude the use of CPET(arm) in perioperative risk stratification.

Prehabilitation and Nutritional Support to Improve Perioperative Outcomes

Purpose of ReviewThe purpose of this study is to evaluate the role of physical exercise and nutrition interventions in adult patients before elective major surgery.Recent FindingsExercise training before elective adult major surgery is feasible, safe, and efficacious, but the clinical effectiveness remains uncertain. Early data suggests a reduction in morbidity, length of stay, and quality of life, but the results of larger definitive studies are awaited. Nutritional interventions are less well evaluated and when they are, it is often in combination with exercise interventions as part of a prehabilitation package.SummaryStudies evaluating exercise and nutrition interventions before elective major surgery in adults are producing encouraging early results, but definitive clinical evidence is currently very limited. Future research should focus on refining interventions, exploring mechanism, and evaluating the interactions between therapies and large-scale clinical effectiveness studies.

Physical activity and quality of life in cancer survivors: A meta-synthesis of qualitative research

Qualitative research on the impact of physical activity on quality of life (QoL) in adults diagnosed with cancer is accumulating. However, the field of physical activity and cancer survivorship lack a synthesis of this research to reliably understand the implications for future research and practice. The aim of this meta-synthesis was to identify, appraise, and synthesize qualitative research on cancer survivors’ perspectives of the impact of physical activity on their QoL. Seven electronic databases were searched for original studies published in English, and reference lists of relevant studies were hand-searched to identify additional studies. Forty studies met eligibility criteria and were included in this meta-synthesis. Study characteristics and major findings were extracted, and findings were summarized, compared, and synthesized. Themes identified in this review revealed that physical activity positively impacted four dimensions of cancer survivors’ QoL: physical (e.g., managing the physical consequences of cancer and its treatment), psychological (e.g., evoking positive self-perceptions), social (e.g., feeling understood by others), and spiritual (e.g., redefining life purpose). This meta-synthesis corroborates conclusions from reviews of quantitative research and illustrates that physical activity can be used to improve QoL in adult cancer survivors, regardless of diagnosis (i.e., stage, cancer type) and treatment status. It also provides detailed insight into specific aspects within each dimension of QoL impacted by physical activity from cancer survivors’ perspectives, which is important for understanding the meaning and utility of physical activity for them. However, more research is needed to further develop the qualitative evidence base in order to better understand how physical activity impacts on QoL experiences in men, young adults, and adults diagnosed with less common types of cancer at different points along cancer trajectory (i.e., diagnosis, treatment, post-treatment, palliation).