Discussion
The co-primary endpoints of this pilot and feasibility study of physical activity for older adults with metastatic GI cancer were met. Twenty participants were recruited within 12 months and at least 50% of participants adhered to at least 50% of the prescribed physical activity programme. In addition, the accelerometer-measured light-intensity and moderate-intensity to vigorous-intensity physical activity increased by 307 and 25 min per week, respectively. No unexpected or serious safety signals were identified, and no participants died during the 12-week intervention. This pilot and feasibility study provides critical foundational data to inform a randomised trial designed to evaluate the efficacy of physical activity on an objectively measured physical function endpoint.
The population of older adults with metastatic GI cancer face dual challenges: (1) the decline in physiological reserve due to both metastatic cancer and ageing; and (2) the toxicities from treatment.40 41 The unfavourable synergy from ageing with cancer and chemotherapy—a double hit to key physiological systems—manifests as accelerated declines in function.42 43 We hypothesise that the deterioration of physical function in patients with cancer is from age-related and cancer treatment-accelerated declines in aerobic capacity,11 ambulatory activity,12 13 and muscle strength and mass.14 15 Supporting this hypothesis is the observation that patients with cancer have a lower aerobic capacity,44 ambulatory activity,45 muscle strength46 and muscle mass,47 compared with matched control participants who do not have a history of cancer.
Examining the feasibility of a structured physical activity programme in older adults with metastatic GI cancer was motivated by the observation that participation in physical activity is one of the strongest predictors of physical function among older adults without cancer.48 49 Physical functions, such as walking or locomotion, have been a primary emphasis of natural selection throughout human evolution.50 This has resulted in redundant sets of physiological systems—including the cardiovascular, pulmonary, neurological and musculoskeletal—that work in conjunction to enable physical function. When one physiological system becomes compromised, other systems compensate.51 Consequently, declines in physical function become clinically evident only when this extensive network of physiological reserves becomes depleted, and other compensatory systems have failed.52 This decline in physical function erodes quality of life,5 increases the likelihood of experiencing chemotherapy toxicities,6 7 which constrains opportunities to receive additional life-sustaining therapies and consequently increases the risk of death.8 We have proposed physical function as a biomarker that synchronously describes the performance and coordination of various physiological systems that may be impaired because of ageing and cancer treatment.53
The increase of 307 min per week light-intensity physical activity and 25 min per week of moderate-intensity to vigorous-intensity physical activity may be clinically valuable. Higher volumes of light-intensity physical activity are associated with a reduced risk of developing mobility disability among older adults.54 Moderate-intensity to vigorous-intensity physical activity is associated with dose-dependent changes in the SPPB and gait speed, and relatively small increases (~48 min per week) in moderate-intensity to vigorous-intensity physical activity are associated with meaningful reductions in the risk of major mobility disability.55 In a meta-analysis of 11 studies, higher volumes of light-intensity physical activity were associated with a lower risk of death, independently of the volume of moderate-intensity and vigorous-intensity physical activity.56 It is important to recognise that accelerometer-defined light-intensity physical activity may be consistent with the energy expenditure of moderate or vigorous-intensity physical activity in older adults.57
Recently introduced treatment options for patients with metastatic GI cancers have significantly extended overall survival. Among patients with metastatic colorectal cancer, overall survival has improved threefold in the past 20 years.58 Among patients with metastatic pancreatic cancer, a chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil and leucovorin compared with gemcitabine as first-line therapy improves overall survival by 40%.59 Among patients with metastatic gastric cancer, a combination of nivolumab and chemotherapy compared with chemotherapy alone as first-line therapy improves overall survival by 30%.60 This has created an opportunity to develop interventions that prevent the loss of physical function to maximise quality of life while patients receive life-prolonging therapy.61
There are limitations to this study. The principal limitation is the small sample size of recruited participants from a single cancer centre. It is possible that the participants who chose to enrol in this study were not like patients who did not enrol. The intervention length was limited to 12 weeks, which precludes our ability to comment on the ability of participants to adhere to this programme over a longer time horizon. Our study was not designed with the intent of conducting extensive null hypothesis significance testing on study outcome measures.
There are strengths to this study. This study successfully recruited older adults, who are often under-represented in clinical trials. Moreover, study participants had a variety of GI malignancies, such as pancreatic cancer, which are less commonly studied in the context of lifestyle modification trials. This study used an evidence-based physical activity programme that has been proven efficacious in preventing a functional decline in healthy older adults.16 17 The physical activity programme was tailored to the unique needs of patients with metastatic cancer. The physical activity programme required minimal equipment and was predominately home based in a manner that could be broadly disseminated in a nationwide trial. Moreover, during the COVID-19 pandemic, virtual physical functioning assessments were validated for cancer survivors,62 and the implementation of these methods may improve the accessibility of clinical trials to older adults.63