Rehabilitation in inoperable lung cancer

Abstract

Worldwide lung cancer is the second most frequently diagnosed cancer. In Australia it is the leading cause of cancer burden and death. The overwhelming majority of people are diagnosed once the disease has spread beyond the primary site. Lung cancer is associated with high levels of poorly controlled symptoms, a decline in physical function, low physical activity (PA) levels and poor health-related quality of life (HRQoL) compared to the healthy population. For people with operable non-small cell lung cancer (NSCLC) increased PA levels are associated with improvements in HRQoL, exercise capacity, fatigue, and psychological distress. Increased exercise capacity at diagnosis of inoperable NSCLC is associated with improved survival. Further research regarding the effects of exercise interventions is required in populations with inoperable NSCLC as the majority of studies conducted to date in this population have either been single-group studies or small randomised controlled trials which are frequently subject to high rates of attrition and lack longer-term follow-up of outcomes.

The first aim of this thesis was to conduct a systematic review of outcome measures that have been utilised to assess PA levels in lung cancer and report on the psychometric properties of included measures. The second aim of this thesis was to conduct a randomised controlled trial (RCT) to determine the effects of home-based multi-disciplinary rehabilitation both during and following treatment for inoperable NSCLC and report on quantitative and qualitative outcomes.

The systematic review identified significant variation in the measurement of PA in lung cancer; 34 articles utilising 21 different outcome measures were included in the review. Seventeen (50%) studies used performance-based measures, such as accelerometers or pedometers, to quantify PA and the remaining studies used patient self-report measures, such as the Godin Leisure Time Exercise (GLTEQ) or the International Physical Activity (IPAQ) questionnaires. Only two studies used both performance-based and self-reported methods of PA measurement. Eighteen (53%) studies reported on the psychometric properties of the outcomes used to measure PA in lung cancer and the quality of those that did was commonly rated as ‘fair’ or ‘poor’. Reflective of the increased research activity and interest in this area, an update of this systematic review performed in 2018 identified an additional 31 articles measuring PA in lung cancer. Updated findings were consistent with the original review with 14 articles (45%) reporting utilisation of performance-based outcome measures and 19 (61%) including patient-reported outcomes. Again, only two articles measured PA using both methods of measurement. For articles retrieved in the updated review, the IPAQ was the most frequently used questionnaire, this is in contrast to the published review where the GLTEQ was most commonly used.

The RCT assessed the efficacy of home-based multi-disciplinary rehabilitation both during and following treatment for inoperable NSCLC. Participants randomised to the intervention group received an eight-week rehabilitation package of care, delivered by a combination of home-visits and telephone calls, involving exercise (aerobic and resistance), behaviour change techniques to support increased exercise and PA and early initiation of patient-centred symptom self-management support. Following the initial eight-week program intervention participants received reduced frequency telephone contact to support exercise behaviours until trial completion at six months. Quantitative outcomes were measured at baseline (prior to randomisation), nine weeks and six months post-baseline and included: exercise capacity (six-minute walk distance (6MWD), the primary outcome), PA levels (performance-based using accelerometers and patient self-report), muscle strength (quadriceps and handgrip), patient reported outcomes (symptom severity and distress, HRQoL, mood, exercise motivation, exercise self-efficacy and resilience) and survival. Ninety-two participants were recruited and 78 (all participants who provided data for at least one follow-up measure) were included in modified intention-to-treat analyses. Adherence to the aerobic component of the exercise program was 65%. There were no significant between-group differences for measures of physical function, mood, self-efficacy or resilience at either follow-up time point. However, a significant interaction effect was demonstrated between group allocation and time across the three study timepoints for the 6MWD; indicating that the temporal pattern of 6MWD results was significantly different between the groups. This difference may be in part due to the timing of exercise with respect to treatment for lung cancer, with less decline in 6MWD observed for the intervention group in the long-term (between baseline and six months) than during the initial treatment phase (between baseline and nine weeks). At six-month follow-up statistically and clinically significant between-group differences favouring the intervention group were found for symptom severity levels, HRQoL and exercise motivation. The intervention group survival benefit at censoring for data analyses was not statistically significant, however at a median of 230 days greater than the usual care group, is of likely clinical importance for those with inoperable disease.

Following the initial eight weeks of the program 25 intervention group participants completed semi-structured interviews regarding their views and experiences of program involvement. The majority of participants found the program acceptable and reported multiple physical and mental health benefits including improved strength and fitness, motivation and prevention of boredom. Program enablers included: having supportive family and friends; advice and support from expert health professionals; the perception that the exercise program had been individually tailored to be achievable; having ongoing program monitoring and modification as required by the program physiotherapists; and having a program which consisted of exercise that participants found familiar and enjoyable. Barriers to exercise program completion were symptom exacerbations and poor weather. Adherence to exercise was reportedly increased by use of simple activity trackers and exercise diaries and receiving weekday exercise text message reminders. Few participants watched the study DVD of resistance exercises that was provided to them; most feeling it was not required or reporting they did not have the technology to watch the DVD.

Recommendations for future research to improve outcomes for people with lung cancer include greater consensus regarding utilisation of a core set of validated outcomes to measure PA. Where possible to employ both patient-reported and performance-based methods of PA measurement. The findings from the RCT support the benefits of the rehabilitation package of care delivered both during and following treatment for inoperable NSCLC. However, the significant interaction between time and group allocation for the 6MWD indicates the need to consider the timing of exercise in relation to lung cancer treatment. Routine self-monitoring of symptoms should be embedded into lung cancer care pathways; electronic self-reported data could be used to trigger an alert for clinician follow-up of symptoms above a given threshold. Future studies should implement strategies to improve exercise adherence and ensure target training intensities are met. This could involve remote monitoring of exercise sessions or the use of online ‘virtual’ exercise groups, formulating alternative indoor exercise plans and implementing flexible program designs incorporating largely home-based exercise with supervised hospital or community-based sessions as needed.