Combined aerobic and resistance exercise training intervention programme (CARP) for lymphoma survivors following therapy

There is abundant evidence supporting the health benefits physical activity in cancer survival. Exercise per se is associated with positive physical and psychosocial benefits for survivors of solid tumours. There are limited available research data on blood borne cancers. Lymphoma is one such haematological cancer where survivors often experience decrements in psychosocial, physical functioning and quality of life (QoL) domains. A minority (~25%) of lymphoma survivors meet the recommended public guidelines for exercise. Further to this, the work of Bellizzi and colleagues (2009) indicates that QoL decrements often persist for years following treatment. Conventional wisdom dictates that exercise is likely to be an effective means of alleviating some adverse outcomes from blood borne cancers but this hypothesis is largely untested to date. Further to this, the theory of planned behaviour (TPB) has been shown to provide effectual model for predicting exercise behaviour amongst cancer survivors but known to differ by tumour type. Therefore, the aims of the present thesis were to determine the effects of 12-weeks of a combined aerobic and resistance training programme (CARP) on QoL and health related outcomes in Hodgkin's lymphoma (HL) and Non-Hodgkin's lymphoma (NHL) survivors. The thesis focused specifically on four main aims; Aim 1 the primary aim was to identify whether a 12-week CARP is effective at improving QoL in HL and NHL survivors. Secondary Aims were to; Aim 2 to determine whether a 12-week CARP is effective at improving standard measures of muscle function and cardio-respiratory fitness in HL and NHL survivors. Aim 3 to examine whether a 12-week CARP affects inflammatory environment and/or immune function in HL and NHL survivors. Aim 4 to identify whether theory of planned behaviour (TPB) may be an effectual model to predict exercise intention in HL and NHL survivors. In realising these aims, a parallel group randomised control exercise trial (RCT) was conducted with two components. Forty-one (n=41) HL and NHL survivors completed the trial at St George's hospital, London. Participants, who had completed chemotherapy or radiation treatment (<6 months), were stratified according to tumour type and randomly assigned to either control (CON; n=21) or intervention (INT; n=20). The intervention consisted of a combination of 12-weeks supervised aerobic and resistance training (CARP) whilst the control group received usual care. The first component consisted of three measurement phases; baseline (To; n=41), post-intervention (T1; n=41) for all measurements, and 12 months follow-up (T2; n=15) for qualitative measures. A representative sample (n=6) from the intervention group took part in a focus group to explore participant perception of the impact of the CARP. QoL was assessed using the previously validated European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30) questionnaire. Secondary outcome measures consisted of health-related quality of life (HRQoL) determined by Functional Assessment of Cancer Therapy in Lymphoma (FACT-Lym); Mood disturbance and fatigue were determined using Profile of Mood States (POMS) questionnaire; anxiety and depression were determined using Hospital Anxiety and Depression scale (HADS). Participant cardiorespiratory fitness was assessed using the Balke-ware treadmill test, muscle function assessed by grip strength and muscle endurance tests. Blood was sampled using the standard venepuncture method followed by radioimmunoassay to determine interleukin 6 (IL-6) and c-reactive protein (CRP) concentrations. In order to identify determinants of exercise intention and behaviour in HL and NHL survivors, a second component to the trial utilised a validated TPB questionnaire, assessed at baseline (To; n=41), and post-intervention (T1; n=41). Data were analysed using SPSS version 18.0 using appropriate statistical functions. Statistical significance was set at p<0.05. Data are presented as means i standard deviations (S.D.). Results demonstrate that study adherence between To and T1 was 87.2% (41/47) with a large accession rates at 12 months follow up (15/41). Linear mixed models analysis was used to examine subjectively reported outcomes. Clinically relevant improvements in QoL were achieved in both groups at T1. HRQoL, a domain of QoL, increased with exercise; the improvements were both clinically relevant and statistically significant. Subscales of QoL and HRQoL that significantly improved with exercise are social function (p=0.020), emotional well-being (p=0.029), and functional well-being (p=0.025), as well as functional lymphoma specific concerns (p=0.034). Mood disturbance was unchanged in either group, physical function improved only in the control group (p=0.049). Both groups showed improved (p<0.05) physical well-being, vigour, reduced fatigue, and increase in subjectively reported amount of physical activity (IPAQ) as time passed from the end of treatment. At follow-up, HRQoL, lymphoma concerns, fatigue, and the trial outcome index significantly improved in both groups (p<0.05) from baseline; anxiety significantly increased in the intervention and anxiety, physical well-being, and functional well-being improved in the control group. Both groups reduced physical activity at follow-up. Predicted aerobic capacity showed a trend towards an increase, whereas resting heart rate (p=0.041) abdominal muscle endurance (p=0.018) significantly improved in the [NT group with a concomitant trend for a decrease in the CON group. However, this did not reach a level of significance. Although both groups experienced worsening of pulmonary function post intervention, this only reached a level of significance in the ]NT group. No significant changes in either IL-6 or CRP were observed during the study. ANOVA and MANOVA were used to analyse physical outcomes. Regression analysis was used to determine the predictive value of the TPB variables upon intention to exercise, and TPB variables and intention upon actual behaviour. Simultaneous Multiple Regressions were used first to determine the equation for each model. Stepwise Multiple Regressions were used to examine the impact of each variable on the dependent variable to find the best model of prediction. At baseline (both INT and CON groups collapsed to one) the model predicts intention (68.6%), but prediction of variation in actual behaviour is low (36.2%); self- efficacy (13:0.495) and social support (13:0.469) predict intention to exercise among lymphoma survivors and self-efficacy (B=0.609) alone predicts actual behaviour at To. At T1, the model predicts 77.0% of the variation in intention amongst the CON group but only 14.7% of actual behaviour; attitude (B=0.864) predicted intention to behave. Amongst the exercising group, the model predicts 61.5% of the variation in intention, but only 19.2% of actual behaviour; social support (B=0.800) predicts intention to exercise. None of the determinants significantly predicted actual behaviour at T1. The current thesis presents the first data in examination of the impact of a CARP amongst post- treatment lymphoma survivors. The exercise training intervention significantly improved HRQOL and psychosocial well-being. This is noteworthy as lymphoma survivors are often burdened with reduced HRQOL and psychosocial morbidity. Although predicted aerobic fitness levels were statistically unchanged in INT following the intervention, the trend towards an improvement indicates that either an increase in exercise programme length or intensity of exercise sessions may achieve statistical improvement in future studies. The findings from this thesis indicate CARP to be effective in improving psychosocial outcomes in lymphoma survivors. At 12-month follow-up, reduced physical activity was associated with increased anxiety; functional and physical well-being did not improve despite increases seen in CON. Thus, future research should aim to increase long-term exercise behaviour in hopes to maintain the positive effects seen with exercise. Such interventions should focus on social support and self-efficacy as a means to encourage intention to exercise. Behaviour techniques should be designed to enhance self-efficacy and social support when devising an exercise programme for lymphoma survivors. Further to this, CARP is well tolerated and demonstrates high levels of adherence in HL and NHL survivors. However, the same participants display large accession rates in the 12 months following completion of the intervention. Results at 12 months follow up should cautiously owing to the risk of bias, particularly performance, detection, and attrition bias. As such, methods of promoting exercise adherence in the months following completion of an exercise intervention may be particularly important in HL and NHL survivors.