A review of randomized controlled trials by a panel of clinical and research experts confirmed that during and after cancer treatment, exercise is safe and beneficial for reducing many common sequelae of cancer treatment, such as fatigue, increased body weight, health-related physical fitness, and health-related quality of life (HRQoL).1 Although results of the effectiveness of community-based exercise programs have recently been published,2–8 effective translation of this research into clinical oncology practice remains to be demonstrated and is a top research question in the field.9 Very little is known about the effectiveness of outpatient exercise rehabilitation programs for cancer survivors in “real-world” settings, where the stringent eligibility requirements and expectations typical for research trials are removed, the program is embedded within existing healthcare infrastructure, and delivery of the program is by nonresearch staff.9
The purpose of this study was to evaluate the effectiveness of a cancer rehabilitation program implemented using evidence-based guidelines within an existing clinical care setting. The primary aim was to describe the changes in health and physical function that occurred with the completion of this hospital-based, individualized cancer rehabilitation program. The secondary aim was to determine whether demographics, cancer variables, and baseline health habits moderated the effect of the rehabilitation program.
Patients and Methods
Design and Setting
This study was a retrospective chart review of assessments routinely performed for the Strides to Strength Cancer Rehabilitation Program, which took place in an outpatient facility dedicated to cancer rehabilitation at the Novant Health Presbyterian Medical Center in Charlotte, North Carolina. Participants pay $300 for the program, but approximately 50% received scholarships to attend. The hospital's research ethics board approved this study.
Patients
This study includes a consecutive sample of cancer survivors who enrolled in the program between 2008 and 2012. Any adult with a history of cancer could enroll during or after any cancer therapy. Patients were referred by oncologists or other staff, or were self-referred via word of mouth or advertisements. Approval from the treating physician was received.
Exercise Program
The program consisted of supervised exercise sessions Tuesdays and Thursdays for 12 weeks (24 sessions), and optional education classes every Thursday. Exercise classes were supervised by 2 exercise physiologists and a registered dietician or nurse with oncology-specific certifications.10–13 Education classes on symptom management, nutrition, stress, home exercise, sexuality, and genetics were led by content experts.
The exercise program was developed in line with the available guidelines for cancer survivors at the time, which included moderate-to-vigorous intensity aerobic exercise, low-to-moderate intensity resistance exercise, and flexibility exercises.1,14,15 Generally, sessions lasted 60 minutes, including a 10-minute warm-up, 20 to 30 minutes of aerobic exercise, 15 to 25 minutes of functional and/or resistance machine strength training, 5 minutes of flexibility exercises, and 5 minutes of relaxation (eg, progressive relaxation or guided imagery). The exercise program was individualized based on needs, goals, and limitations of each participant.1 Modifications to this general format and the specific exercises included in each participant's program were made as needed.
The aerobic exercise intensity prescription was adapted to treatment timing as follows: 40% to 60% of age-predicted heart rate reserve (HRR) for ongoing chemotherapy treatment, 50% to 70% HRR for up to 3 months postchemotherapy or current radiation treatment, and 60% to 80% HRR for 3 or more months posttreatment. Although the American Cancer Society suggests that a lower intensity may be required during chemotherapy or radiation treatment,14 there was no evidence-based prescription for specific intensity levels during different times of the treatment trajectory at the time. Therefore, the exercise physiologists (P.D., T.B.) developed this approach based on experience. Aerobic exercise modes included treadmill, recumbent cycle ergometer, arm ergometer, elliptical, or NuStep.
A group-based strength-training circuit was performed that included biceps curls, triceps extensions, and vertical press on Tuesdays, and squats and hamstring curls on Thursdays. Participants who were posttreatment also completed chest press, rows, leg extension, seated leg curl, leg press, and latissimus pull-down exercises on a Nautilus system. Initially, participants would perform one set of 8 to 12 repetitions15 with a weight that felt challenging at 10 repetitions, and would progress every 2 to 3 weeks as tolerated by adding sets (up to 3 maximum)15 and then weight. A goal rating of perceived exertion of 11 to 14 on the 6 to 20 Borg scale16 was encouraged for all aerobic and resistance exercises.
Outcome Measures
At baseline, participants completed questionnaires and an assessment of physical fitness with an exercise physiologist. After each participant completed all 24 sessions, an identical assessment was performed. Whenever possible, the same exercise physiologist performed both assessments on a given participant, and they were blinded to baseline values at the follow-up assessment.
Patient-Reported Outcomes: The baseline questionnaire included questions about demographics, cancer diagnosis and treatment, and health habits, including smoking, alcohol consumption, and exercise frequency. Established questionnaires included the Functional Assessment of Cancer Therapy (FACT)-General, FACT-Fatigue, and Duke Activity Status Index (DASI). The FACT-General is a cancer-specific assessment of HRQoL, and the FACT-Fatigue includes an additional 13 questions related to fatigue; both are reliable and validated.17 The DASI is a 12-item general self-assessment of functional capacity.18 A higher score on the DASI and FACT questionnaires indicates better health.
Physical Fitness: Components of health-related physical fitness include body size and composition, aerobic fitness, muscular endurance, and flexibility.15 These components were assessed because they are known to be negatively affected by some cancer therapies.15,19–25 Resting heart rate (HRrest) and blood pressure (BP) were measured after several minutes of quiet, seated rest. Height and weight were measured using a stadiometer and physician's beam scale. Waist circumference was measured around the narrowest portion of the waist.15 Percent body fat was estimated by using the sum of 3 skinfolds (triceps, supra iliac, abdomen)15 using Lange Skinfold Calipers (Beta Technology, Santa Cruz, CA). Functional capacity was measured by distance walked during a 6-minute walk test (6MWT) using a 261-foot circular track and standardized instructions.26 Absolute muscular endurance of the abdominal and upper body muscle groups were tested using the curl-up and YMCA bench press tests, respectively.15 The curl-up test was performed without a metronome and the goal was to perform as many as possible in 60 seconds.15 The bench press test goal was maximum repetitions performed with proper technique to volitional fatigue with a standardized weight (35 lbs for women, 80 lbs for men).15 Flexibility for the upper and lower body was measured by forward shoulder flexion in the supine position with a goniometer and with the sit and reach test following standardized instructions,15 respectively.
Statistics
Baseline characteristics were compared between the total group that enrolled in the program and the group of participants with a completed follow-up assessment who are included in the analyses in this study, using chi-square and independent t tests. Paired sample t tests were performed with a Sidak correction to a P value of 0.05 for multiple comparisons on baseline and follow-up measurements. For variables with published minimally clinically important differences (MCIDs), the percentage of participants with an improvement that equaled or exceeded them was calculated.
An exploratory analysis was performed to determine the moderating effect of demographics, cancer variables (ie, diagnosis and treatment characteristics), and health habits on the impact of the exercise program on change in functional capacity (6MWT) and HRQoL (FACT-General). Individual multiple regressions were performed with the follow-up value of 6MWT/FACT-General as the dependent variable, and the respective baseline value as a covariate in the model to account for the influence of baseline values. The predictors tested in the models included the variables listed in Table 1, plus baseline measures of FACT-General, DASI score, 6MWT distance, and body mass index (BMI). Categorical variables were dummy coded using the most positive outcome (eg, no treatment, exerciser) as the reference against which all other levels were compared. The Tukey honest significant difference test was used to test pairwise differences among categorical predictors with more than 2 levels. Predictors and pairwise differences with P values of 0.10 or less are reported for this exploratory analysis.
Results
A total of 299 patients enrolled in the program, and 163 (55%) completed the program (ie, attended all 24 exercise sessions); 31 of these did not complete the follow-up assessment, leaving 132 patients with cancer with both assessments completed. Table 1 describes the demographics, baseline health habits, and diagnosis/treatment characteristics of both groups; those with a follow-up assessment were not different from the total group who enrolled.
The study participants were predominantly middle-aged (55.1 ± 11.8 years), female (83%), Caucasian (76%), and married (64%), and enrolled in the program 1.4 years postdiagnosis on average. The most common cancer type was breast, and most had early-stage cancer. Most participants had surgery (83%), half had completed chemotherapy and/or radiation therapy (41% and 36%, respectively), and one-quarter had chemotherapy and/or radiation therapy ongoing or planned (20% and 19%, respectively).
Patient Characteristics
Both HRrest and BP did not change significantly (Table 2). There was a significant mean improvement in the 6MWT, indicating improved functional capacity, as well as significant improvements in the tests of muscular endurance, upper and lower body flexibility, and all patient-reported outcome measures (Table 2). There were no statistically significant changes in body composition measures (Table 2).
Despite no significant change in systolic BP, 55% achieved a decrease equal to or greater than the MCID of 2 mm Hg27 (Table 3). Although the average improvement in 6MWT distance was 45 meters, 39% achieved the MCID of 54 meters28 (Table 3). This objective measure of functional capacity was similar to the subjective assessment (DASI), wherein 35% achieved the MCID29 (Table 3). The average improvements in the FACT-General and FACT-Fatigue exceeded the MCID's, and in approximately two-thirds (60% and 67%, respectively) of participants.17 For body weight reduction from baseline, only 4% of participants achieved the MCID of a 5% reduction30 (Table 3). Overall, 88% of the participants with a completed follow-up assessment experienced a clinically meaningful improvement in one or more of these measures.
Predictors of the 6MWT performance after completion of the program included marital status, age, pre-diagnosis exercise frequency, and postradiation versus no radiation (Table 4). In post hoc comparison, postradiation patients walked 79 meters less than those currently receiving treatment (P=.087), and 69 meters less than those who did not receive radiation (P=.100).
Predictors of FACT-General following completion of the program included age, exercise frequency prediagnosis, current versus never-smoker, and occasional versus no alcohol consumption (Table 4). There were no significant differences with alcohol consumption frequency, although current smokers had a 10.3-point higher FACT-General score than former smokers (P=.043).
Discussion
Program Effectiveness
The primary study purpose was to evaluate the changes in HRQoL and fitness in cancer survivors who completed a hospital-based cancer rehabilitation program. There were significant improvements in both objective and self-reported measures of functional capacity, as well as HRQoL, fatigue, flexibility,
Change in Outcomes After Program Completion
In an effort to translate research to practice, data from exercise programs implemented in clinical or community settings are emerging. Two small pilot studies have demonstrated improvements in the 6MWT31 and HRQoL32 in cancer survivors who have completed outpatient pulmonary rehabilitation or cancer-specific programming. Cancer rehabilitation programs delivered at community centers have also reported significant improvements in the 6MWT, HRQoL, flexibility, and strength.3–7 The effect on fatigue of exercise programs conducted outside of a research setting is inconsistent. Our study demonstrated statistically significant and clinically meaningful reductions in patient-reported fatigue, thereby strengthening the available evidence regarding the effectiveness of exercise treatment of fatigue. To our knowledge, this is the first study to assess and report an improvement in self-reported functional capacity (DASI) in cancer survivors, a predictor of all-cause and cardiovascular disease–related mortality and events.29 This program did not result in statistically significant changes in body composition or resting cardiovascular function. The lack of change in measures of body size or composition is consistent with findings of other studies,4,33,34 and not surprising given the short duration of the program. The mean change in HRrest and BP are similar to those reported by community-based programs for cancer survivors with similar exercise prescriptions.4,34 A program with increased exercise frequency (ie, 3 vs 2 one-hour sessions/week) resulted in larger improvements, perhaps suggesting an exercise dose–response relationship.
Moderation of Effectiveness
The second study aim was to determine whether demographics, cancer variables, and baseline health habits moderate the effect of the rehabilitation program. A number of these variables were significant predictors of changes in functional capacity and HRQoL, demonstrating that these variables should be measured before program initiation, and considered in designing individualized programs and when assessing the effect of the program.
The proposition that cancer variables moderate the exercise response is fundamental to the field of cancer and exercise research.35 Radiation treatment
Participants Whose Improvements Exceeded MCID or Meaningful Clinical Threshold
In healthy individuals, the trainability of aerobic fitness is not affected by age.37 However in the current study, age was a significant predictor of functional capacity after program completion, wherein every 10-year increase was associated with 30 more meters in 6MWT distance. Two studies have assessed the moderating effect of cancer survivor age on peak oxygen consumption, which is moderately correlated with 6MWT distance.38 In breast cancer survivors receiving chemotherapy, a differential response to exercise dose occurred between those in the aerobic training and the usual care groups in younger (≤50 years) but not older participants,39 and all age groups exhibited the same response in patients with lymphoma exercising during or after chemotherapy treatment.40
Age also predicted the effect of the program on HRQoL. Specifically, for every 10-year increase, the FACT-General score was 2 points lower, indicating that the program had a larger effect on HRQoL in younger individuals. This is a new finding, as 3 previous studies have reported that cancer survivor age did not moderate the effect of exercise training on HRQoL.39–41 The reason for this discrepancy could be that previous studies dichotomized age as older and younger than 50 years, rather than using it as a continuous variable such as in our study.
Performing 30 minutes of exercise at least once per week prediagnosis was associated with a greater improvement
Predictors of 6-Minute Walk Test Distance and FACT-General Score Following Program Completion
Smoking is associated with poorer HRQoL in noncancer populations.43 In the current study, smokers experienced a significantly greater FACT-General score than never-smokers or former smokers, even when adjusted for baseline values. Alcohol consumption also moderated the effect of the exercise program on FACT-General score, where occasional drinkers had a higher HRQoL after the program than those who never drank. This is in line with the positive psychological benefits reported with low and moderate alcohol consumption.44
Although baseline BMI has previously been reported to be a moderator of change in aerobic fitness41 and HRQoL40 with exercise training interventions in cancer populations, BMI was not a predictor of any exercise responses in the current study.
To our knowledge, this study is the largest report of a hospital-based cancer rehabilitation program. Furthermore, the sample size and baseline characteristics allowed for exploration of the moderating effect of a number of variables, producing new findings and confirming others previously reported. Although the retrospective design allowed assessment of a real-world clinical program in a nonresearch setting, it also incorporates some limitations to interpretation. First, the 55% program completion rate could introduce positive bias; however, our comparison of baseline characteristics showed that those with completed follow-up assessment were representative of the total population enrolled. Further, the potential for bias with self-referral to an exercise program may be offset by oncologic staff referrals. The study results are only generalizable to those who complete a rehabilitation program, but within that context, external validity of the study is strong due to the varied population and lack of stringent eligibility criteria. Although assessments not performed for research purposes may lack protocol fidelity, program staff used several practices to ensure precision and accuracy, including following published guidelines, using the same assessor for baseline and follow-up assessments, and blinded follow-up assessments.
Conclusions
A 24-session, hospital-based, individualized, and supervised rehabilitation program was effective at improving functional capacity, HRQoL, fatigue, muscular endurance, and flexibility in cancer survivors with mixed diagnoses both during and after treatment. A longer program duration or greater weekly frequency of sessions may be required for an effect on resting cardiovascular function and body composition. Most participants experienced one or more improvements that met or exceeded established MCIDs. Overall, these results demonstrate the effective translation of cancer and physical activity research to clinical practice. Adoption of evidence-based cancer rehabilitation programming as a part of standard oncologic care is likely to improve the health and well-being of cancer survivors.
Ms. Ballard and Mr. Downey were Novant Health employees and developed the program and collected the data described in the manuscript. They provided revisions and approval of the manuscript, but were not involved in data analysis or interpretation. Dr. Kirkham is supported by a Canadian Institutes of Health Research Postdoctoral Fellowship and an Alberta Innovates – Health Solutions Clinician Fellowship. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
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