Baseline Characteristics of Individuals with Metastatic Cancer Enrolled in the Alberta Cancer Exercise Study and 12-Week Findings for Symptom-Related and Physical Fitness Measures.

1. Introduction

Advanced cancers, including metastatic cancers, typically involve cancer spread and require long-term therapies for cancer control and symptom palliation [ 1 ]. Although survival rates are improving due to progress in treatment options, people diagnosed with advanced cancers frequently face diverse cancer-specific and treatment-related challenges. These include, but are not limited to, uncertain prognosis, high symptom burden, decreased physical function, and psychosocial concerns [ 2 , 3 , 4 , 5 ]. As such, there is a tremendous impact of advanced cancer upon daily functioning and quality of life [ 4 , 6 , 7 , 8 ].

Exercise has been found to be safe, feasible, and associated with important health benefits for people with advanced cancer [ 9 , 10 , 11 , 12 , 13 , 14 ]. Structured exercise interventions can help improve quality of life, alleviate cancer-related symptoms (e.g., fatigue, dyspnea, insomnia), and enhance physical function in these individuals [ 9 , 10 , 13 , 15 ]. However, people with advanced cancer often experience barriers to exercise participation. Reported challenges include symptoms of fatigue, pain, and shortness of breath, apprehensions about injury, limited professional guidance, and lack of accessible, suitable settings [ 2 , 16 , 17 , 18 , 19 , 20 , 21 ]. Current exercise oncology research remains limited in applicability to the advanced cancer population [ 10 , 22 , 23 , 24 ]. There is a need for larger, well-designed studies examining evidence-based exercise interventions that can be tailored to different cancer populations, that focus on reducing burden (e.g., travel) and optimizing adherence, and that can be successfully implemented in accessible, real-world settings [ 9 , 10 , 13 , 15 , 21 ].

The Alberta Cancer Exercise (ACE) study is a hybrid effectiveness–implementation study, designed to investigate the effectiveness of a 12-week exercise program for cancer survivors and to examine real-world implementation outcomes [ 25 , 26 ]. To address gaps in cancer care services, further work is needed to investigate how best to adapt and implement evidence-based exercise programs specifically for people with advanced cancer within cancer institutions and community settings across Canada. While exercise has generally been found to be safe and feasible in the advanced cancer population, it has not been well explored within the context of community-based settings. In studies of community- and home-based walking programs, there have been challenges identified with recruiting and retaining participants [ 27 , 28 ]. Given the heterogeneity of the advanced cancer population and the diverse challenges experienced by individuals, there is a need for large-scale research specifically related to community-based exercise, with consideration given to outcomes that are important to this population, particularly cancer-related symptoms and functional ability [ 29 ]. Findings from the ACE study can help elucidate the characteristics of people with metastatic cancer who choose to participate and are able to complete the program, and the relative benefit from exercise participation. Thus, the ACE study provides the opportunity to further examine the feasibility and effectiveness of evidence-based community-based exercise programs among individuals with metastatic disease.

Objectives: The primary objective of this study is to describe the baseline characteristics of individuals with metastatic cancer who enrolled in the 12-week community-based ACE program. Secondary objectives are to examine the feasibility of the program (i.e., safety, completion, and attendance) and to evaluate 12-week changes in physical activity behavior, symptoms, quality of life, and physical fitness measures.

2. Materials and Methods

2.1. Study Design and Participants

The ACE study is a hybrid effectiveness–implementation trial evaluating a 12-week cancer-specific, community-based exercise program delivered in Alberta, Canada. The ACE trial commenced in January 2017 and closed to recruitment in February 2023. The methods and initial findings of the ACE study have been previously reported in detail [ 25 , 26 ]. Participants enrolled in the ACE study include adults with any type and stage of cancer, at different points along the cancer trajectory (up to three years following completion of cancer treatment).

The current study consists of a secondary analysis of baseline and 12-week data for a subgroup of participants with metastatic cancer enrolled in the ACE study. Participants were identified if they self-reported disease spread on their pre-exercise screening form. Metastatic disease was confirmed through the medical clearance process or on medical chart review. For the present analyses, participants with primary bone cancer or multiple myeloma were excluded.

2.2. Screening Process

Due to the implementation focus of the ACE study, the study procedures were adapted and refined overtime to improve participant screening, enhance study feasibility, and reduce participant burden [ 25 ]. The screening process also helped inform the type of group-based exercise training that was recommended for each participant (i.e., in-person circuit training, virtual circuit training, or personal training). There were four key steps in the screening and triage of ACE participants:

Pre-screening to identify participants with high-risk cancers (e.g., lung, neurological, pancreatic) and/or metastatic disease spread.

Cancer intake form and Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) to identify specific cancer-related concerns and other health conditions potentially impacting physical activity participation.

In-person or telephone interview with a clinical exercise physiologist to review screening findings and to determine need for medical clearance and/or specialized support.

Physical fitness assessment to evaluate physical function and mobility and to identify participants with underlying issues requiring medical clearance and/or specialized support.

2.3. Program Characteristics

The ACE program involves full-body, group-based circuit training or personal training, with a combination of aerobic, resistance, balance, and flexibility exercises. Exercise sessions consist of ≥60 min of mild- to moderate-intensity exercise, offered twice a week for 12 weeks. Prior to COVID-19, sessions were delivered and supervised by ACE-trained exercise specialists at 18 urban sites across the province of Alberta, Canada, including three academic institutions, six YMCA locations, three Wellspring Alberta locations, and six municipal fitness centers. With the onset of the COVID-19 pandemic in March 2020, exercise programming was delivered in a virtual format. In-person assessments and exercise sessions gradually resumed starting in September 2021 with 13 in-person sites restored, and virtual sessions continued to be offered for the remainder of the ACE study. Program details have been outlined in detail in a previous paper [ 26 ].

2.4. Data Collection

The main study outcomes include physical activity level, physical fitness, cancer-related symptoms, and health-related quality of life. Outcomes are evaluated at baseline, at 12 weeks (immediately post-program), and at one year. Data from the ACE study are stored securely in a REDCap database housed in the Faculty of Medicine and Dentistry at the University of Alberta.

2.5. Participant Characteristics

To better understand the profile of the ACE participants with metastatic cancer, we extracted data on the following baseline characteristics that were collected across all participants over the study duration:

Sociodemographic factors: Age, biological sex, gender identity, ethnicity, marital status, education level, income, employment status, smoking status, drinking status

Anthropometric measures: Body mass index

Medical and cancer history: Number of comorbidities, primary cancer type, number and location of metastases, treatment status, current and completed treatments

Exercise-related outcomes: Physical Activity Stages of Change, Godin-Shephard Leisure-Time Physical Activity Questionnaire (to calculate physical activity minutes per week [ 30 ])

Symptom-related and quality of life measures: Functional Assessment of Cancer Therapy-Fatigue (FACT-F; also referred to as FACIT-F) scale (higher FACT scores indicate better quality of life), Edmonton Symptom Assessment Scale (ESAS; higher ESAS scores indicate higher symptom burden), 5-level EQ-5D (EQ-5D-5L; higher levels on EQ-5D-5L dimensions indicate more severe problems), EQ visual analogue scale (EQ VAS; higher EQ VAS scores indicate better health)

Physical fitness measures: 30 s timed sit-to-stand (in-person and virtual assessments), one-legged stance (in-person and virtual assessments), 6-Minute Walk Test (6MWT) (in-person assessments only; discontinued during the COVID-19 pandemic), 2 min step test (included in virtual assessments to replace the 6MWT during the COVID-19 pandemic), active shoulder flexion range of motion (in-person and virtual assessments)

We also extracted 12-week data for physical activity minutes per week, symptom-related and quality of life measures, as well as physical fitness measures.

2.6. Data Analysis

Descriptive statistics were used to report sociodemographic, cancer-related, and exercise-related characteristics, symptom-related measures, and physical fitness measures of the ACE participants with metastatic cancer at baseline. Prior to analysis, we explored missing data and outliers and examined test assumptions of normality. To check for normality in the distribution of the study data, we used the Kolmogorov–Smirnov statistical test for large sample sizes and graphed the data for each study outcome [ 31 ].

The primary self-reported outcome measure was the FACT-F questionnaire, which was examined as total FACT-F scale and FACT Trial Outcome Index (TOI) scores. In particular, the TOI measure has been used to assess health-related quality of life in people with cancer and incorporates measures of physical wellbeing, functional wellbeing, and cancer-specific symptoms (i.e., fatigue) [ 32 ]. The TOI has been found to be associated with progression-free survival in a large cohort of individuals with advanced cancer [ 33 ]. For this analysis, we also examined the FACT-G scale and FACT-Fatigue subscale scores. To explore symptom burden in the participants, we descriptively analyzed ESAS scores as: (a) individual symptom scores (0–10); (b) total symptom distress scores (0–90); (c) physical scores, (0–60); and (d) emotional scores (0–20) [ 34 ]. We also categorized the severity of individual symptoms using the following ESAS score categories: (a) no/mild symptoms (score 0–3); (b) moderate symptoms (score 4–6); and (c) severe symptoms (score 7–10) [ 34 , 35 ]. Similarly, we descriptively analyzed the EQ-5D-5L data for each dimension according to problem severity category: (a) no problems (Level 1); (b) slight problems (Level 2); (c) moderate problems (Level 3); (d) severe problems (Level 4); and (e) extreme problems (Level 5) [ 36 ]. To further explore physical fitness levels, baseline participant data for the 30 s sit-to-stand, one-legged stance, and strength measures were compared to age- and sex-matched norms [ 37 , 38 , 39 , 40 ].

For study feasibility, we determined the overall study enrollment and 12-week completion rates for the participants with metastatic cancer in the ACE study. Comparisons of baseline characteristics between participants who remained in the study vs. participants who dropped out (including those who withdrew from the study and those who were lost to follow-up prior to the 12-week study time point) were conducted using independent samples t-tests and Mann–Whitney U tests for continuous data, and chi-squared tests for categorical data. Implementation feasibility of the ACE program was examined through calculating rates of attendance in the exercise program (number of exercise sessions attended/number of sessions offered in program) for all participants included in the analysis [ 41 ]. Based on the previous literature examining supervised exercise programs with cancer and older adult populations [ 10 , 11 , 42 , 43 , 44 ], the target attendance rate for this study was defined as participation in at least 70% of the sessions over the 12-week exercise program. The feasibility of the community-based ACE program was considered acceptable if at least 60% of the participants with metastatic cancer met the study target rate of 70% for exercise program attendance. Safety of the ACE program was examined by reporting the number and severity of exercise-related adverse events that occurred in the participants during the 12-week program. The severity of any adverse event was rated according to Common Terminology Criteria for Adverse Events system [ 45 ]. A very low rate (<1%) of adverse events was considered acceptable for the ACE program. The rates for safety and feasibility were established a priori in the study protocol [ 25 ].

Effects of exercise participation: Paired Student’s t-tests and Wilcoxon signed-rank tests for non-parametric data were used to analyze short-term (12-week) changes in physical activity, symptoms, quality of life, and physical fitness measures following participation in the ACE program. We also explored participant outcomes by subgroups of biological sex, current chemotherapy status, and exercise training type (in-person personal vs. in-person circuit vs. virtual circuit training).

Clinically meaningful improvements for selected patient-reported outcomes and physical fitness measures were analyzed based on the following minimal important differences (MIDs): 5–6 points on the FACT TOI, 3 points on the FACT Fatigue subscale, and 3–5 points on the FACT-G scale, corresponding to an estimated 6- to 8-point MID for the combined total FACT-F scale score (FACT-G scale plus Fatigue subscale items) [ 32 , 46 , 47 ]; 3 points, 2 points, and 3 points on the ESAS physical, emotional, and total symptom distress scores, respectively, and 1 point on the ESAS wellbeing item score [ 48 , 49 ]; and 5 points on the EQ VAS score [ 50 ]. A 10% increase was used for physical activity minutes per week [ 25 ]. For physical fitness measures, established MIDs were 2 repetitions for the 30 s sit-to-stand test [ 51 , 52 ]; 24 s for one-legged stance [ 53 ]; 30 m for the 6 min walk test [ 54 ]; 10% increase for the 2 min step test [ 55 , 56 ]; and 14 degrees for shoulder range of motion [ 57 ].

3. Results

3.1. Participant Flow

Of 2966 participants referred to the ACE program between 2017 and 2023, 306 participants (10.3%) enrolled in the study had confirmed presence of metastatic cancer and were included in this secondary analysis ( Figure 1 ). Of 306 participants with metastatic cancer, 274 (89.5%) completed the 12-week ACE study. Reasons for dropout in 32 participants included cancer progression/recurrence (n = 14), difficulty with attending program due to symptoms, commute, or family responsibilities (n = 3), other health illness (n = 3), or no response/reason given (n = 12). Due to the COVID-19 initial lockdown in March 2020 and lack of staff access to research and clinical sites, in-person post-intervention study assessments were not conducted for all participants completing the Winter 2020 session (n = 30). This contributed to missing data in physical fitness measures, before virtual study assessments were implemented for participants joining after May 2020.

The study completion rates by region were 92.1% for Calgary, 87.7% for Edmonton, 85.7% for the North Zone, and 86.7% for the South Zone. For female and male participants, the rates were 90.5% and 87.7%, respectively. By age group, the study completion rates were 87.0% for young adults, 88.5% for middle-aged adults, and 92.4% for older adults. The completion rates by exercise training type were 87.2% for in-person circuit training, 89.0% for in-person personal training, and 94.5% for virtual circuit training.

3.2. Baseline Characteristics

Baseline sociodemographic and cancer-related characteristics of the participants are provided in Table 1 and Table 2 . Briefly, many ACE participants were female (65.4%), middle-aged (62.4%), married or common-law (73.9%), of European descent (75.8%), and diagnosed with at least one comorbidity (71.9%). The most common primary cancer types were breast (33.7%), genitourinary (16.7%), digestive (15.0%), and lung (10.8%). Frequent sites of metastases included bone (44.8%), liver (28.8%), lung (25.8%), and other (20.3%). Most participants (74.8%) were on active cancer treatment at the time of their enrolment in the ACE program, with chemotherapy (35.9%) and hormone therapy (28.4%) being the most common current therapies. Reasons for the 77 participants being off treatment included: surveillance (45.5%), remission (50.6%), no further treatment (1.3%), and treatment stopped due to side effects (2.3%).

Exercise-related characteristics of the ACE participants with metastatic cancer are provided in Table 3 . At baseline, the participants were engaging in a mean of 90.2 min of physical activity per week. About half of the participants (49.3%) were classified as sedentary in terms of their physical activity level, and over half were in the contemplation (23.2%) or preparation (31.4%) stages of physical activity behavior change.

Baseline symptom and physical fitness measures are provided in Supplementary File S1 . Approximately half of the participants (49.0%) were below age- and sex-matched norms for the one-legged stance measure, while 79.4% were below norms for the 30 s sit-to-stand measure. Mean scores for individual ESAS items ( Supplementary File S2 ) ranged from 0.6 to 3.5, with better scores for nausea, appetite, and shortness of breath (mean scores: 0.6, 1.1, and 1.2, respectively), and worse scores for tiredness and wellbeing (mean scores: 3.5 for both). Most participants (99.0%) reported no or slight problems with self-care on the EQ-5D-5L ( Supplementary File S3 ). Activity was identified as most troublesome on the EQ-5D-5L with almost 30% of participants indicating moderate, severe, or extreme problems.

Comparisons by study completion: Baseline characteristics by study completion status are also presented in Table 1 , Table 2 and Table 3 and Supplementary File S1 . Statistical comparisons of baseline characteristics demonstrated that participants who dropped out of the ACE study were more likely to be receiving current chemotherapy ( p = 0.011) and had higher rates of lung metastasis ( p = 0.043). Moreover, study dropouts had lower rates of college or university level education ( p = 0.035) and of being in the action/maintenance stages of physical activity change ( p = 0.032) than those who completed the 12-week study. Study completers were more likely to be receiving hormone therapy ( p = 0.035) and have other types of comorbidities ( p = 0.032), and also had better baseline scores on the FACT-G scale ( p = 0.001), FACT TOI ( p = 0.009), FACT Fatigue subscale ( p = 0.027), FACT-F scale ( p = 0.003), ESAS physical ( p = 0.004), ESAS total ( p = 0.009), and EQ VAS ( p < 0.001) compared to dropouts. There were no differences in physical activity minutes per week ( p = 0.580) or physical fitness measures ( p > 0.05) at baseline.

3.3. Program Feasibility and Safety

Exercise location and type: The ACE participants included in this analysis enrolled in exercise classes at the following study locations: Edmonton (n = 130, 42.5%), Calgary (n = 140, 45.8%), North Zone (Fort McMurray: n = 2, 0.7%; Grand Prairie: n = 8, 2.6%; Red Deer, n = 11, 3.6%), and South Zone (Lethbridge: n = 6, 2.0%; Medicine Hat: n = 9, 2.9%). The types of group-based exercise classes attended by the participants included in-person circuit training (n = 133, 43.5%), in-person personal training (n = 100, 32.7%), and virtual circuit training (n = 73, 23.9%).

Exercise session attendance: The mean percentage of exercise sessions attended by the participants over the 12-week ACE program was 73.7% (based on n = 301; missing data for n = 5 participants in the North Zone). By location, the 12-week program attendance rates were 71.0% for Calgary, 76.5% for Edmonton, 71.6% for the North Zone (Fort McMurray: N/A; missing data for 2 participants; Grand Prairie: 78.8%; missing data for 3 participants; Red Deer: 68.3%), and 75.8% for the South Zone (Lethbridge: 81.8%; Medicine Hat: 71.7%). Mean program attendance rates by biological sex and by age group were 72.3% in female participants, 76.3% in male participants, 67.1% in young adults, 72.3% in middle-aged adults, and 78.0% in older adults. By exercise training type, attendance rates were 69.8% for in-person circuit training, 77.1% for in-person personal training, and 75.7% for virtual circuit training. Of the 301 participants with data on exercise attendance, 65.1% met the target rate of 70% attendance.

Adverse events: There were two adverse events which occurred during participation in the ACE program, resulting in a rate of adverse events of 0.65%. The incidents consist of one exercise-related event (CTCAE Grade 1: nervous system disorder) and one minor non-exercise-related event (CTCAE Grade 1: injury). The first event involved a participant with brain metastases who experienced an absence seizure while resting (seated) between exercise sets at a community site. The event lasted a short duration (<10 s) and resolved on site. The participant was immediately taken to the hospital for further investigation. It was later determined that the participant had progression of brain metastases, and they were withdrawn from ACE by their oncology care team. The second case was a participant with brain metastases who experienced a fall resulting in a hit to the head. The fall occurred prior to start of the exercise session in another location of the community-based site. The participant was taken to the hospital for further investigation and was cleared with no resulting injuries.

3.4. Changes in Symptom-Related, Quality of Life, and Physical Fitness Measures

Baseline and 12-week scores for the symptom-related, quality of life, and physical fitness measures are presented in Table 4 . On the FACT measure, there were statistically significant improvements on the TOI, Fatigue subscale, and FACT-F scale scores in the ACE participants who completed the 12-week study ( p < 0.001), and a significant but weaker effect on the FACT-G scale score ( p = 0.010). No significant changes were found on the ESAS scores in the participants, but statistically and clinically significant improvements were found for the EQ VAS score at 12 weeks ( p < 0.001). Physical activity minutes per week increased significantly ( p < 0.001) and clinically from baseline to 12 weeks. In terms of physical fitness measures, there were significant improvements for all measures from baseline to 12 weeks ( p < 0.001), with clinically significant improvements on the 30 s sit-to-stand test, 6MWT, and 2 min step test. The proportions of responses by level of severity on the EQ-5D-5L dimensions for the ACE participants who completed the 12-week study are presented in Supplementary File S4 .

Subgroup analyses: Pre–post program changes in the symptom-related and physical fitness measures for subgroups by biological sex and chemotherapy status are presented in Supplementary Files S5 and S6 . Male participants with metastatic cancer demonstrated statistically and clinically significant improvements over 12 weeks on the FACT TOI and Fatigue subscale (all p < 0.001) and statistically significant improvement on the FACT-G ( p = 0.018) and FACT-F ( p < 0.001) scores. Female participants showed significant benefits for the FACT Fatigue subscale ( p < 0.001), TOI ( p = 0.002) and FACT-F ( p = 0.006) scores, but these changes did not meet clinically significant levels. ESAS scores did not change in either group over 12 weeks, but there was statistically and clinically significant improvement of the EQ VAS score in both groups ( p < 0.001). Statistically and clinically meaningful benefits were found in both groups for physical activity minutes per week, 30 s sit-to-stand, 6MWT, and 2 min step test ( p < 0.001), while statistically significant benefits were seen for the one-legged stance ( p < 0.001) and bilateral shoulder range of motion ( p < 0.001 to p = 0.036) tests.

With regard to chemotherapy status, participants who were off chemotherapy treatment demonstrated significant improvements at 12 weeks on the FACT and EQ VAS scores ( p < 0.001), with both statistically and clinically meaningful improvements on the FACT Fatigue subscale and EQ VAS scores. For those receiving chemotherapy, there were no statistical or clinical improvements on symptom-related and quality of life measures. There were no changes on ESAS scores in those who were off chemotherapy. ESAS physical and total symptom distress scores statistically worsened in participants on chemotherapy ( p = 0.036 and p = 0.031), but these changes did not reach clinically significant levels. Participants both on and off chemotherapy showed significant and clinically meaningful increases in weekly minutes of physical activity ( p < 0.001). Measures of physical fitness improved significantly in the participants who were not receiving chemotherapy ( p < 0.001), with clinical improvements in 30 s sit-to-stand, 6MWT, and 2 min step test. Participants receiving current chemotherapy improved significantly on the 30 s sit-to-stand, one-legged stance, and 6MWT at 12 weeks ( p < 0.001), with clinical improvements seen in the 30 s sit-to-stand and 6MWT.

Changes in the symptom-related and physical fitness measures by exercise training type are presented in Supplementary File S7 . ACE participants taking part in in-person personal and virtual circuit training improved statistically on all FACT measures ( p < 0.001 to p = 0.046), while those in in-person circuit training improved statistically on the Fatigue subscale measure only ( p = 0.022). Clinically meaningful improvement was seen on the FACT TOI score for in-person personal training participants. There were no significant changes on the ESAS scores for any of the three groups, except that in-person circuit training participants had worse ESAS physical scores ( p = 0.039) and in-person personal training participants had better ESAS physical scores ( p = 0.031) at 12 weeks. EQ VAS, physical activity minutes per week, 30 s sit-to-stand test, and left shoulder range statistically improved in all three groups. Participants in the two in-person groups significantly improved on the one-legged stance and 6MWT measures ( p < 0.001; *note: 6MWT was measured only in virtual participants able to attend in-person testing). Virtual group participants showed improvements for the 2 min step test ( p < 0.001; *note: 2 min step test was not part of the test battery for in-person participants). Left shoulder range of motion improved significantly in all three groups ( p = 0.007 to p = 0.034), while right shoulder improved in virtual circuit participants only ( p = 0.002).

4. Discussion

This study provides insight on the effectiveness and implementation of community-based exercise programming for individuals with metastatic cancer. The findings demonstrate that many people diagnosed with advanced cancers were willing and able to access, successfully participate in, and benefit from the exercise program. To our knowledge, this analysis from the ACE study represents one of the largest study cohorts of people with metastatic cancer in the exercise oncology literature to date [ 9 , 13 , 15 , 24 ]. Individuals with confirmed metastatic cancer at study entry made up close to 12% of the total ACE study cohort [ 26 ]. The high completion and attendance rates of ACE participants with metastatic cancer support the overall feasibility of a community-based exercise program model of care. Moreover, exercise participation resulted in significant improvements in physical activity, symptoms, quality of life, and physical fitness measures, supporting the benefit of exercise. Individuals with metastatic cancer commonly face barriers to exercise, such as cancer-related symptoms and concerns, as well as lack of accessible information and support [ 18 , 19 , 20 , 21 ]. Key features of the ACE program, including the community-based in-person and virtual offerings, option for self-referral, and tailored exercise support, likely contributed to addressing some of these barriers and supporting access to exercise programming for these individuals. Given the rising prevalence of people living with metastatic cancer and the complex challenges they experience, tailored and accessible exercise programs, as well as other supportive care services, are needed to meet the unique needs of this population [ 1 , 58 , 59 ].

Consistent with the full ACE cohort at baseline [ 26 ], breast cancer was the most common diagnosis in 34% of the subgroup of participants with metastatic cancer. However, this percentage of breast cancer was lower than the full ACE cohort (45%). Moreover, our sample included over 200 participants (66.3%) with a non-breast cancer diagnosis. A recent estimation of the number of individuals living with metastatic cancer in the U.S. indicated high prevalence rates for lung, breast, colorectal, and prostate cancers [ 58 ]. In a Canadian study of 1366 individuals with metastatic cancer referred to an out-patient palliative care clinic, gastrointestinal cancer was the most common cancer type [ 60 ]. These diagnoses are consistent with the characteristics of the ACE metastatic subgroup which showed breast, genitourinary (e.g., prostate), digestive (e.g., gastrointestinal), and lung cancer as the most common cancer types. Due to the heterogeneity of the metastatic cancer population in terms of cancer types and treatment regimens, people diagnosed at this stage of disease experience varying prognostic estimates, physical impairments, and symptom-related issues [ 1 , 4 ]. However, there is increasing evidence of exercise benefits for a variety of advanced and metastatic cancers including breast, lung, prostate, and colorectal cancers [ 15 ]. These findings further highlight the need for community-based programming that can support exercise participation in people with both these common as well as less common types of metastatic cancer.

While the ACE study was feasible for a large, diverse group of individuals with metastatic cancer, our analysis revealed that other cancer-related factors were related to study completion status and changes in study outcomes. Participants who dropped out of the study were more likely to have lung metastases and be undergoing chemotherapy at the time of enrollment. These findings suggest individuals with specific disease characteristics may require further tailored support to sustain participation in exercise programs. A key finding of our study is that ACE participants receiving chemotherapy who remained in the study improved their physical activity levels and physical fitness measures without a negative impact on many of the self-reported measures of quality of life and fatigue. Although they did not experience the improvements seen in participants who were off chemotherapy, particularly for the ESAS physical and total symptom scores, the results show that overall, their wellbeing and symptoms did not worsen to a clinically significant extent with exercise. Observational studies in advanced cancer have demonstrated that physical function and patient-reported outcomes often deteriorate rapidly during cancer treatment [ 61 , 62 , 63 ]. Our findings suggest that exercise may help to attenuate the impact of treatment on symptom levels, while enhancing physical fitness, even in those receiving active chemotherapy. Furthermore, higher levels of physical functioning (e.g., performance status and mobility) have been associated with improved treatment tolerance in some cancer populations [ 64 , 65 ]. These results support consideration of exercise for individuals undergoing treatment for metastatic disease, with potential benefits for symptom control, physical fitness, and treatment outcomes.

Our analysis provides additional findings related to symptom status in the participants with metastatic cancer. The ESAS scores of the ACE participants were generally low compared to other datasets [ 60 , 66 ], suggesting those opting to participate in the ACE program may have had a lower symptom burden than typically seen. Moreover, while benefits were found for other patient-reported outcomes (i.e., FACT, EQ VAS), no significant changes were found in ESAS scores following the 12-week exercise program. One explanation is that the ESAS may lack sensitivity to improvement in patients with stable disease presenting with low symptom burden. In ACE, we also note the small proportion of participants who dropped out of the study had worse symptom scores at baseline than those who completed the study. Cancer-related symptoms, particularly fatigue, have been commonly identified as key barriers to exercise participation in individuals with advanced cancer [ 16 , 18 , 19 , 20 , 21 ]. These findings further reinforce the need for symptom assessment and tailored exercise support, as well as interdisciplinary support for comprehensive symptom management, particularly for those with high symptom burden [ 67 ].

The high study completion and exercise attendance rates in this analysis support feasibility and effectiveness of community-based exercise programming for the subgroup of ACE participants with metastatic cancer. It is important to note the low rate of adverse events among these participants in the ACE study. Previous reviews have demonstrated similarly low rates of adverse events in individuals with advanced disease participating in structured exercise trials [ 11 , 13 , 68 ]. However, our understanding of adverse events related to exercise is limited due to absent or insufficient reporting of exercise-related harms in the exercise oncology literature, as well as limited representation of diverse and advanced cancer types [ 13 , 69 , 70 ]. The risk of adverse events in participants with metastatic cancer is anticipated given the high potential for disease progression and unpredictable symptom burden in this population. However, the overall risk remains quite low, particularly in comparison to the potential for benefit from exercise in these individuals. Consideration of these known risks is crucial when designing and implementing exercise programming in oncology. Key practices to address the risk of adverse events include comprehensive screening and routine monitoring, tailored exercise support (e.g., medical supervision) and modifications, and training of exercise professionals in adverse event identification, management and reporting [ 71 , 72 , 73 ].

Finally, our exploratory analyses yield interesting results regarding subgroup findings according to exercise training type. Improvements on the FACT measure were strongest for participants who were engaging in the in-person group personal training, followed closely by those in the virtual circuit training. These findings suggest that exercise-related factors may influence the degree and type of benefits obtained by participants. The delivery of the ACE program took place in real-world settings and conditions, including virtual formats following the initial lockdown due to COVID-19. Though the ACE program was delivered at most sites as a full-body circuit training program, participants were shown modifications for each exercise to suit individual needs and capabilities. Selected sites also offered group-based personal training options for participants requiring more tailored exercise support. Thus, flexibility in exercise prescription and delivery may be an important consideration to support engagement and optimize the benefits to participants.

5. Limitations

Limitations in the study population include the high percentage of breast cancer compared to other cancer types, as well as the relatively low symptom burden of the participants. However, the study had considerable representation of individuals with non-breast cancer types and with higher symptom burden, allowing generalizability of these findings to a heterogenous population of metastatic cancer. ACE participants were mainly of European ethnic origin, and there were low proportions of individuals of visible minorities and Indigenous populations [ 74 ]. Personal factors, such as cultural and ethnic origin, race, and gender identity, require important consideration as they may influence disparities in physical activity engagement and access to exercise-related information and support [ 75 , 76 , 77 ]. Future exercise oncology research should consider more deliberate identification and representation of diverse participant profiles, and investigation of factors influencing key outcomes. Another study limitation is the use of the ESAS measure to assess cancer-related symptoms. Though this measure has strong clinical use [ 34 ], it may be limited as a tool to capture changes in symptom burden over time. The use of other self-reported and objective measures strengthened the findings of the ACE study. Finally, there were high rates of missing data for the physical fitness measures during the COVID-19 lockdown. However, a key learning from the ACE study is how to adapt and implement study assessments and exercise programming for individuals with metastatic cancer under real-world conditions.

6. Conclusions

The ACE study highlights the feasibility and benefit of cancer-specific community-based exercise programming for individuals diagnosed with different types of metastatic cancer. Due to the large sample size of the ACE study, we have the opportunity to further explore factors associated with adherence and response to exercise across different cancer types and stages to help inform clinical programming recommendations.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/curroncol32100560/s1 . File S1: Baseline symptom-related and physical fitness measures of participants with metastatic cancer enrolled in the Alberta Cancer Exercise study (N = 306); File S2: Baseline ESAS item scores for participants with metastatic cancer enrolled in the Alberta Cancer Exercise study (N = 306) *; File S3: Proportion of responses by level of severity on EQ-5D-5L at baseline for participants with metastatic cancer enrolled in the Alberta Cancer Exercise study (N = 306); File S4: Proportion of responses by level of severity on EQ-5D-5L dimensions at baseline and at 12 weeks for Alberta Cancer Exercise participants with metastatic cancer who completed 12-week study (n = 274) *; File S5: Baseline scores and associated changes at 12 weeks for Alberta Cancer Exercise participants with metastatic cancer who completed 12-week study, by biological sex (female: n = 181; male: n = 93); File S6: Baseline scores and associated changes at 12 weeks for Alberta Cancer Exercise participants with metastatic cancer who completed 12-week study, by chemotherapy treatment status (on current chemotherapy: n = 92; off chemotherapy: n = 182); File S7: Baseline symptom and physical fitness measures and associated changes at 12 weeks for Alberta Cancer Exercise participants with metastatic cancer who completed 12-week study, by exercise training type (in-person circuit training: n = 116, in-person personal training: n = 89; virtual circuit training: n = 69).

Author Contributions

Conceptualization, S.M.S., M.L.M., S.N.C.-R., K.S.C., A.A.J., H.L., J.C.E., M.A. and E.P.; methodology, S.M.S., M.L.M., S.N.C.-R., T.W., C.S., K.S.C. and E.P.; validation, C.S., T.W. and S.M.S.; formal analysis, M.L.M. and S.M.S.; investigation, all authors; resources, M.L.M. and S.N.C.-R.; data curation, T.W. and C.S.; writing—original draft preparation, S.M.S. and M.L.M.; writing—review and editing, all authors; supervision, M.L.M. and S.N.C.-R.; project administration, M.L.M., C.S. and T.W.; funding acquisition, M.L.M., S.N.C.-R., A.A.J., K.S.C., H.L. and J.C.E. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Health Research Ethics Board of Alberta Cancer Committee (code: HREBA.CC-16-0905) on 23 December 2016.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The original contributions presented in this study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors have no conflicts of interest to declare.

Funding Statement

The ACE study was funded through grants from the Alberta Innovates Cancer Prevention Research Opportunity (CPRO) and the Alberta Cancer Foundation.

Footnotes

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

References

1. Hart N.H., Nekhlyudov L., Smith T.J., Yee J., Fitch M.I., Crawford G.B., Koczwara B., Ashbury F.D., Lustberg M.B., Mollica M., et al. Survivorship care for people affected by advanced or metastatic cancer: MASCC-ASCO standards and practice recommendations. Support Care Cancer. 2024;20:1160–1172. doi: 10.1007/s00520-024-08465-8.

2. Cheville A.L., Troxel A.B., Basford J.R., Kornblith A.B. Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer. J. Clin. Oncol. 2008;26:2621–2629. doi: 10.1200/JCO.2007.12.3075.

3. Dunn J., Watson M., Aitken J.F., Hyde M.K. Systematic review of psychosocial outcomes for patients with advanced melanoma. Psycho-Oncology. 2017;26:1722–1731. doi: 10.1002/pon.4290.

4. Hart N.H., Crawford-Williams F., Crichton M., Yee J., Smith T.J., Koczwara B., Fitch M.I., Crawford G.B., Mukhopadhyay S., Mahony J., et al. Unmet supportive care needs of people with advanced cancer and their caregivers: A systematic scoping review. Crit. Rev. Oncol. Hematol. 2022;176:103728. doi: 10.1016/j.critrevonc.2022.103728.

5. Rojas-Concha L., Hansen M.B., Petersen M.A., Groenvold M. Symptoms of advanced cancer in palliative medicine: A longitudinal study. BMJ Support. Palliat. Care. 2023;13:e415–e427. doi: 10.1136/bmjspcare-2021-002999.

6. Cardoso F., Harbeck N., Mertz S., Fenech D. Evolving psychosocial, emotional, functional, and support needs of women with advanced breast cancer: Results from the Count Us, Know Us, Join Us and Here & Now surveys. Breast. 2016;28:5–12. doi: 10.1016/j.breast.2016.04.004.

7. Cheville A.L., Beck L.A., Petersen T.L., Marks R.S., Gamble G.L. The detection and treatment of cancer-related functional problems in an outpatient setting. Support. Care Cancer. 2009;17:61–67. doi: 10.1007/s00520-008-0461-x.

8. Di Lascio S., Pagani O. Is it time to address survivorship in advanced breast cancer? A review article. Breast. 2017;31:167–172. doi: 10.1016/j.breast.2016.10.022.

9. Chen Y., Li X., Ma H., Zhang X., Wang B., Guo T., Xiao Y., Bing Z., Ge L., Yang K., et al. Exercise training for improving patient-reported outcomes in patients with advanced-stage cancer: A systematic review and meta-analysis. J. Pain Symptom Manag. 2020;59:734–749.e10. doi: 10.1016/j.jpainsymman.2019.09.010.

10. De Lazzari N., Niels T., Tewes M., Götte M. A Systematic review of the safety, feasibility and benefits of exercise for patients with advanced cancer. Cancers. 2021;13:4478. doi: 10.3390/cancers13174478.

11. Heywood R., McCarthy A.L., Skinner T.L. Safety and feasibility of exercise interventions in patients with advanced cancer: A systematic review. Support. Care Cancer. 2017;25:3031–3050. doi: 10.1007/s00520-017-3827-0.

12. Heywood R., McCarthy A.L., Skinner T.L. Efficacy of exercise interventions in patients with advanced cancer: A systematic review. Arch. Phys. Med. Rehabil. 2018;99:2595–2620. doi: 10.1016/j.apmr.2018.04.008.

13. Nadler M.B., Desnoyers A., Langelier D.M., Amir E. The effect of exercise on quality of life, fatigue, physical function, and safety in advanced solid tumor cancers: A meta-analysis of randomized control trials. J. Pain Symptom Manag. 2019;58:899–908.e7. doi: 10.1016/j.jpainsymman.2019.07.005.

14. Turner K., Tookman A., Bristowe K., Maddocks M. ‘I am actually doing something to keep well. That feels really good’: Experiences of exercise within hospice care. Prog. Palliat. Care. 2016;24:204–212. doi: 10.1080/09699260.2015.1123441.

15. Rodríguez-Cañamero S., Cobo-Cuenca A.I., Carmona-Torres J.M., Pozuelo-Carrascosa D.P., Santacruz-Salas E., Rabanales-Sotos J.A., Cuesta-Mateos T., Laredo-Aguilera J.A. Impact of physical exercise in advanced-stage cancer patients: Systematic review and meta-analysis. Cancer Med. 2022;11:3714–3727. doi: 10.1002/cam4.4746.

16. Burke S., Utley A., Belchamber C., McDowall L. Physical activity in hospice care: A social ecological perspective to inform policy and practice. Res. Q. Exerc. Sport. 2020;91:500–513. doi: 10.1080/02701367.2019.1687808.

17. Cheville A.L., Dose A.M., Basford J.R., Rhudy L.M. Insights into the reluctance of patients with late-stage cancer to adopt exercise as a means to reduce their symptoms and improve their function. J. Pain Symptom Manag. 2012;44:84–94. doi: 10.1016/j.jpainsymman.2011.08.009.

18. Frikkel J., Götte M., Beckmann M., Kasper S., Hense J., Teufel M., Schuler M., Tewes M. Fatigue, barriers to physical activity and predictors for motivation to exercise in advanced cancer patients. BMC Palliat Care. 2020;19:43. doi: 10.1186/s12904-020-00542-z.

19. Mikkelsen M.K., Nielsen D.L., Vinther A., Lund C.M., Jarden M. Attitudes towards physical activity and exercise in older patients with advanced cancer during oncological treatment—A qualitative interview study. Eur. J. Oncol. Nurs. 2019;41:16–23. doi: 10.1016/j.ejon.2019.04.005.

20. Sheill G., Guinan E., Neill L.O., Hevey D., Hussey J. The views of patients with metastatic prostate cancer towards physical activity: A qualitative exploration. Support. Care Cancer. 2018;26:1747–1754. doi: 10.1007/s00520-017-4008-x.

21. Shallwani S.M., Thomas R., King J., Toupin-April K., Poitras S. Perspectives and experiences of leisure-time physical activity in adults with stage 4 cancer: A qualitative interpretive-description study. Disabil. Rehabil. 2024;46:1515–1526. doi: 10.1080/09638288.2023.2200037.

22. Campbell K.L., Winters-Stone K.M., Wiskemann J., May A.M., Schwartz A.L., Courneya K.S., Zucker D.S., Matthews C.E., Ligibel J.A., Gerber L.H., et al. Exercise guidelines for cancer survivors: Consensus statement from international multidisciplinary roundtable. Med. Sci. Sports Exerc. 2019;51:2375–2390. doi: 10.1249/MSS.0000000000002116.

23. Shallwani S.M., King J., Thomas R., Thevenot O., De Angelis G., Aburub A.S., Brosseau L. Methodological quality of clinical practice guidelines with physical activity recommendations for people diagnosed with cancer: A systematic critical appraisal using the AGREE II tool. PLoS ONE. 2019;14:e0214846. doi: 10.1371/journal.pone.0214846.

24. Shallwani S.M., Ranger M.-C., Thomas R., Brosseau L., Poitras S., Sikora L., King J. A scoping review of studies exploring leisure-time physical activity in adults diagnosed with advanced cancer. Palliat. Support. Care. 2021;19:615–630. doi: 10.1017/S1478951520001327.

25. McNeely M.L., Sellar C., Williamson T., Shea-Budgell M., Joy A.A., Lau H.Y., Easaw J.C., Murtha A.D., Vallance J., Courneya K., et al. Community-based exercise for health promotion and secondary cancer prevention in Canada: Protocol for a hybrid effectiveness-implementation study. BMJ Open. 2019;9:e029975. doi: 10.1136/bmjopen-2019-029975.

26. McNeely M.L., Shallwani S.M., Williamson T., Sellar C., Gobeil E., Joy A.A., Lau H., Easaw J., Sexsmith J., Courneya K.S., et al. Baseline characteristics of participants in the Alberta Cancer Exercise hybrid effectiveness–implementation study: A wake-up call for action. Cancers. 2025;17:772. doi: 10.3390/cancers17050772.

27. Lowe S.S., Watanabe S.M., Baracos V.E., Courneya K.S. Home-based functional walking program for advanced cancer patients receiving palliative care: A case series. BMC Palliat. Care. 2013;12:22. doi: 10.1186/1472-684X-12-22.

28. Tsianakas V., Harris J., Ream E., Van Hemelrijck M., Purushotham A., Mucci L., Green J.S.A., Fewster J., Armes J. CanWalk: A feasibility study with embedded randomised controlled trial pilot of a walking intervention for people with recurrent or metastatic cancer. BMJ Open. 2017;7:e013719. doi: 10.1136/bmjopen-2016-013719.

29. Wang T., Molassiotis A., Chung B.P.M., Tan J.-Y. Unmet care needs of advanced cancer patients and their informal caregivers: A systematic review. BMC Palliat. Care. 2018;17:96. doi: 10.1186/s12904-018-0346-9.

30. Trinh L., Plotnikoff R.C., Rhodes R.E., North S., Courneya K.S. Associations between physical activity and quality of life in a population-based sample of kidney cancer survivors. Cancer Epidemiol. Biomark. Prev. 2011;20:859–868. doi: 10.1158/1055-9965.EPI-10-1319.

31. Mishra P., Pandey C., Singh U., Gupta A., Sahu C., Keshri A. Descriptive statistics and normality tests for statistical data. Ann. Card. Anaesth. 2019;22:67–72. doi: 10.4103/aca.aca_157_18.

32. Cella D., Eton D.T., Lai J.-S., Peterman A.H., Merkel D.E. Combining anchor and distribution-based methods to derive minimal clinically important differences on the Functional Assessment of Cancer Therapy (FACT) anemia and fatigue scales. J. Pain Symptom Manag. 2002;24:547–561. doi: 10.1016/S0885-3924(02)00529-8.

33. Hui D., Darke A.K., Guthrie K.A., Subbiah I.M., Unger J.M., Hershman D.L., Krouse R.S., Bakitas M., O’Rourke M.A. Association between health-related quality of life and progression-free survival in patients with advanced cancer: A secondary analysis of SWOG clinical trials. JCO Oncol. Pract. 2022;18:e442–e451. doi: 10.1200/OP.21.00407.

34. Hui D., Bruera E. The Edmonton Symptom Assessment System 25 years later: Past, present, and future developments. J. Pain Symptom Manag. 2017;53:630–643. doi: 10.1016/j.jpainsymman.2016.10.370.

35. Selby D., Cascella A., Gardiner K., Do R., Moravan V., Myers J., Chow E. A single set of numerical cutpoints to define moderate and severe symptoms for the Edmonton Symptom Assessment System. J. Pain Symptom Manag. 2010;39:241–249. doi: 10.1016/j.jpainsymman.2009.06.010.

36. EuroQol Research Foundation . EQ-5D-5L User Guide. EuroQol Research Foundation; 2019. [(accessed on 28 May 2025)]. Available online: https://euroqol.org/publications/user-guides .

37. McKay M.J., Baldwin J.N., Ferreira P., Simic M., Vanicek N., Burns J., For the 1000 Norms Project Consortium. 1000 Norms Project Consortium. Baldwin J., McKay M., et al. Reference values for developing responsive functional outcome measures across the lifespan. Neurology. 2017;88:1512–1519. doi: 10.1212/WNL.0000000000003847.

38. Rikli R.E., Jones C.J. Functional fitness normative scores for community-residing older adults, ages 60–94. J. Aging Phys. Act. 1999;7:162–181. doi: 10.1123/japa.7.2.162.

39. Rikli R.E., Jones C.J. Development and validation of criterion-referenced clinically relevant fitness standards for maintaining physical independence in later years. Gerontologist. 2013;53:255–267. doi: 10.1093/geront/gns071.

40. Springer B.A., Marin R., Cyhan T., Roberts H., Gill N.W. Normative values for the unipedal stance test with eyes open and closed. J. Geriatr. Phys. Ther. 2007;30:8–15. doi: 10.1519/00139143-200704000-00003.

41. Hawley-Hague H., Horne M., Skelton D.A., Todd C. Review of how we should define (and measure) adherence in studies examining older adults’ participation in exercise classes. BMJ Open. 2016;6:e011560. doi: 10.1136/bmjopen-2016-011560.

42. Bullard T., Ji M., An R., Trinh L., Mackenzie M., Mullen S.P. A systematic review and meta-analysis of adherence to physical activity interventions among three chronic conditions: Cancer, cardiovascular disease, and diabetes. BMC Public Health. 2019;19:636. doi: 10.1186/s12889-019-6877-z.

43. Rivera-Torres S., Fahey T.D., Rivera M.A. Adherence to exercise programs in older adults: Informative report. Gerontol. Geriatr. Med. 2019;5:2333721418823604. doi: 10.1177/2333721418823604.

44. Sheill G., Guinan E., Brady L., Hevey D., Hussey J. Exercise interventions for patients with advanced cancer: A systematic review of recruitment, attrition, and exercise adherence rates. Palliat. Support. Care. 2019;17:686–696. doi: 10.1017/S1478951519000312.

45. U.S. Department of Health and Human Services . Common Terminology Criteria for Adverse Events (CTCAE) National Cancer Institute; 2017. [(accessed on 17 June 2025)]. Version 5.0. Available online: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf .

46. Jayadevappa R., Cook R., Chhatre S. Minimal important difference to infer changes in health-related quality of life-a systematic review. J. Clin. Epidemiol. 2017;89:188–198. doi: 10.1016/j.jclinepi.2017.06.009.

47. Webster K., Cella D., Yost K. The Functional Assessment of Chronic Illness Therapy (FACIT) measurement system: Properties, applications, and interpretation. Health Qual. Life Outcomes. 2003;1:79. doi: 10.1186/1477-7525-1-79.

48. Hui D., Shamieh O., Paiva C.E., Perez-Cruz P.E., Kwon J.H., Muckaden M.A., Park M., Yennu S., Kang J.H., Bruera E. Minimal clinically important differences in the Edmonton Symptom Assessment Scale in cancer patients: A prospective, multicenter study. Cancer. 2015;121:3027–3035. doi: 10.1002/cncr.29437.

49. Hui D., Shamieh O., Paiva C.E., Khamash O., Perez-Cruz P.E., Kwon J.H., Muckaden M.A., Park M., Arthur J., Bruera E. Minimal clinically important difference in the physical, emotional, and total symptom distress scores of the Edmonton Symptom Assessment System. J. Pain Symptom Manag. 2016;51:262–269. doi: 10.1016/j.jpainsymman.2015.10.004.

50. Bourke S., Bennett B., Oluboyede Y., Li T., Longworth L., O’Sullivan S.B., Braverman J., Soare I.-A., Shaw J.W. Estimating the minimally important difference for the EQ-5D-5L and EORTC QLQ-C30 in cancer. Health Qual. Life Outcomes. 2024;22:81. doi: 10.1186/s12955-024-02294-3.

51. Wright A.A., Cook C.E., Baxter G.D., Dockerty J.D., Abbott J.H. A comparison of 3 methodological approaches to defining major clinically important improvement of 4 performance measures in patients with hip osteoarthritis. J. Orthop. Sports Phys. Ther. 2011;41:319–327. doi: 10.2519/jospt.2011.3515.

52. Zanini A., Crisafulli E., D’Andria M., Gregorini C., Cherubino F., Zampogna E., Azzola A., Spanevello A., Schiavone N., Chetta A. Minimum clinically important difference in 30-s sit-to-stand test after pulmonary rehabilitation in subjects with COPD. Respir. Care. 2019;64:1261–1269. doi: 10.4187/respcare.06694.

53. Goldberg A., Casby A., Wasielewski M. Minimum detectable change for single-leg-stance-time in older adults. Gait Posture. 2011;33:737–739. doi: 10.1016/j.gaitpost.2011.02.020.

54. Bohannon R.W., Crouch R. Minimal clinically important difference for change in 6-minute walk test distance of adults with pathology: A systematic review. J. Eval. Clin. Pract. 2017;23:377–381. doi: 10.1111/jep.12629.

55. Perera S., Mody S.H., Woodman R.C., Studenski S.A. Meaningful change and responsiveness in common physical performance measures in older adults. J Am. Geriatr. Soc. 2006;54:743–749. doi: 10.1111/j.1532-5415.2006.00701.x.

56. Kwon S., Perera S., Pahor M., Katula J.A., King A.C., Groessl E.J., Studenski S.A. What is a meaningful change in physical performance? Findings from a clinical trial in older adults (the LIFE-P study) J. Nutr. Health Aging. 2009;13:538–544. doi: 10.1007/s12603-009-0104-z.

57. Muir S.W., Corea C.L., Beaupre L. Evaluating change in clinical status: Reliability and measures of agreement for the assessment of glenohumeral range of motion. N. Am. J. Sports Phys. Ther. 2010;5:98–110.

58. Gallicchio L., Devasia T.P., Tonorezos E., Mollica M.A., Mariotto A. Estimation of the number of individuals living with metastatic cancer in the United States. JNCI J. Natl. Cancer Inst. 2022;114:1476–1483. doi: 10.1093/jnci/djac158.

59. Lai-Kwon J., Heynemann S., Hart N.H., Chan R.J., Smith T.J., Nekhlyudov L., Jefford M. Evolving landscape of metastatic cancer survivorship: Reconsidering clinical care, policy, and research priorities for the modern era. J. Clin. Oncol. 2023;41:3304–3310. doi: 10.1200/JCO.22.02212.

60. Cheung W.Y., Le L.W., Zimmermann C. Symptom clusters in patients with advanced cancers. Support. Care Cancer. 2009;17:1223–1230. doi: 10.1007/s00520-009-0577-7.

61. Shallwani S.M., Simmonds M.J., Kasymjanova G., Spahija J. Quality of life, symptom status and physical performance in patients with advanced non-small cell lung cancer undergoing chemotherapy: An exploratory analysis of secondary data. Lung Cancer. 2016;99:69–75. doi: 10.1016/j.lungcan.2016.06.018.

62. Vistad I., Cvancarova M., Astrup G.L., Rustøen T., Liavaag A.H. Symptom experience and self-rated physical functioning in patients with ovarian cancer receiving chemotherapy. Int. J. Gynecol. Cancer. 2018;28:1167–1175. doi: 10.1097/IGC.0000000000001287.

63. Silver H.J., Dietrich M.S., Murphy B.A. Changes in body mass, energy balance, physical function, and inflammatory state in patients with locally advanced head and neck cancer treated with concurrent chemoradiation after low-dose induction chemotherapy. Head Neck. 2007;29:893–900. doi: 10.1002/hed.20607.

64. Van Abbema D.L., Van Den Akker M., Janssen-Heijnen M.L., Van Den Berkmortel F., Hoeben A., De Vos-Geelen J., Buntinx F., Kleijnen J., Tjan-Heijnen V.C.G. Patient- and tumor-related predictors of chemotherapy intolerance in older patients with cancer: A systematic review. J. Geriatr. Oncol. 2019;10:31–41. doi: 10.1016/j.jgo.2018.04.001.

65. Groen W.G., Naaktgeboren W.R., van Harten W.H., van Vulpen J.K., Kool N., Sonke G.S., Van Der Wall E., Velthuis M.J., Aaronson N.K., May A.M., et al. Physical fitness and chemotherapy tolerance in patients with early-stage breast cancer. [(accessed on 16 July 2025)];Med. Sci. Sports Exerc. 2022 54:537–542. doi: 10.1249/MSS.0000000000002828. Available online: https://journals.lww.com/acsm-msse/fulltext/2022/04000/physical_fitness_and_chemotherapy_tolerance_in.1.aspx .

66. Barbera L., Seow H., Howell D., Sutradhar R., Earle C., Liu Y., Stitt A., Husain A., Sussman J., Dudgeon D. Symptom burden and performance status in a population-based cohort of ambulatory cancer patients. Cancer. 2010;116:5767–5776. doi: 10.1002/cncr.25681.

67. Stout N.L., Brown J.C., Schwartz A.L., Marshall T.F., Campbell A.M., Nekhlyudov L., Zucker D.S., Basen-Engquist K.M., Campbell G., Meyerhardt J., et al. An exercise oncology clinical pathway: Screening and referral for personalized interventions. Cancer. 2020;126:2750–2758. doi: 10.1002/cncr.32860.

68. Weller S., Hart N.H., Bolam K.A., Mansfield S., Santa Mina D., Winters-Stone K.M., Campbell A., Rosenberger F., Wiskemann J., Quist M., et al. Exercise for individuals with bone metastases: A systematic review. Crit. Rev. Oncol. Hematol. 2021;166:103433. doi: 10.1016/j.critrevonc.2021.103433.

69. Dunn R.M., Hayes S.C., Sandler C.X., Spence R.R. Adverse event assessment and reporting in exercise oncology: A review. [(accessed on 9 June 2025)];Exerc. Sport Mov. 2023 1:1–7. doi: 10.1249/ESM.0000000000000014. Available online: https://journals.lww.com/acsm-esm/fulltext/2023/09000/adverse_event_assessment_and_reporting_in_exercise.2.aspx .

70. Thomsen S.N., Lahart I.M., Thomsen L.M., Fridh M.K., Larsen A., Mau-Sørensen M., Bolam K.A., Fairman C.M., Christensen J.F., Simonsen C. Harms of exercise training in patients with cancer undergoing systemic treatment: A systematic review and meta-analysis of published and unpublished controlled trials. eClinicalMedicine. 2023;59:101937. doi: 10.1016/j.eclinm.2023.101937.

71. Campbell K.L., Cormie P., Weller S., Alibhai S.M.H., Bolam K.A., Campbell A., Cheville A.L., Dalzell M.-A., Hart N.H., Higano C.S., et al. Exercise recommendation for people with bone metastases: Expert consensus for health care providers and exercise professionals. JCO Oncol. Pract. 2022;18:e697–e709. doi: 10.1200/OP.21.00454.

72. Jones L.W. Evidence-based risk assessment and recommendations for physical activity clearance. Appl. Physiol. Nutr. Metab. 2011;36:S101–S112. doi: 10.1139/h11-043.

73. Spence R.R., Sandler C.X., Jones T.L., McDonald N., Dunn R.M., Hayes S.C. Practical suggestions for harms reporting in exercise oncology: The Exercise Harms Reporting Method (ExHaRM) BMJ Open. 2022;12:e067998. doi: 10.1136/bmjopen-2022-067998.

74. Statistics Canada 2021 Census of Population. [(accessed on 1 July 2025)];2023 Available online: https://www12.statcan.gc.ca/census-recensement/2021/dp-pd/prof/index.cfm?Lang=E.

75. Norris M.K., Fox F.S., Lee C., Wang E., Green K., Yan H., Dieli-Conwright C.M. Narrowing the Gap for Minority Cancer Survivors: Exercise Oncology in the Past, Present, and Future. J. Clin. Exerc. Physiol. 2020;9:155–170. doi: 10.31189/2165-7629-9.4.155.

76. Schmitz K.H., Demanelis K., Crisafio M.E., Kennedy M.A., Schwartz A.L., Campbell A., Gorzelitz J., Wood K.C., Wilson C.M., Scalise R.L., et al. Proximity to cancer rehabilitation and exercise oncology by geography, race, and socioeconomic status. Cancer. 2025;131:e35515. doi: 10.1002/cncr.35515.

77. Wojcik K.M., Wilson O.W.A., Shiels M.S., Sheppard V.B., Jayasekera J. Racial, ethnic, and socioeconomic disparities in meeting physical activity guidelines among female breast cancer survivors in the United States. Cancer Epidemiol. Biomark. Prev. 2024;33:1610–1622. doi: 10.1158/1055-9965.EPI-24-0650.

Associated Data

Supplementary Materials

Data Availability Statement

The original contributions presented in this study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.