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Impact of a walking intervention on cardiorespiratory fitness, self-reported physical function, and pain in patients undergoing treatment for solid tumors†
Article first published online: 27 JUL 2009
Copyright © 2009 American Cancer Society
Volume 115, Issue 20, pages 4874–4884, 15 October 2009
How to Cite
Griffith, K., Wenzel, J., Shang, J., Thompson, C., Stewart, K. and Mock, V. (2009), Impact of a walking intervention on cardiorespiratory fitness, self-reported physical function, and pain in patients undergoing treatment for solid tumors. Cancer, 115: 4874–4884. doi: 10.1002/cncr.24551
- Issue published online: 5 OCT 2009
- Article first published online: 27 JUL 2009
- Manuscript Accepted: 6 APR 2009
- Manuscript Revised: 3 APR 2009
- Manuscript Received: 19 DEC 2008
Vol. 119, Issue 9, 1762, Article first published online: 18 JAN 2013
Cancer treatment is associated with decline in measured and self-reported physical function and increased pain. In the current study, the authors evaluated the impact of a walking intervention on these outcomes during chemotherapy/radiation.
Patients with breast, prostate, and other cancers (N=126) were randomized to a home-based walking intervention (exercise) or usual care (control). Exercise dose during the intervention was assessed using a 5-item Physical Activity Questionnaire. Outcome measures were cardiorespiratory fitness, expressed as peak oxygen uptake (VO2) measured during treadmill testing (n = 85) or estimated by 12-minute walk (n = 27), and self-reported physical function, role limitations, and pain derived from Medical Outcomes Study Short Form 36. Linear regression was used to evaluate pre-to-post intervention change outcomes between groups.
The mean (standard deviation) age of the patients was 60.2 (10.6) years. Diagnoses included prostate (55.6%) and breast (32.5%) cancer. Treatment included external beam radiotherapy (52.3%) and chemotherapy (34.9%). Exercise patients reported worsening Medical Outcomes Study physical function role limitations by the end of cancer treatment (P = .037). Younger age was associated with improved Medical Outcomes Study physical function (P = .048). In all patients, increased exercise dose was associated with decreased Medical Outcomes Study pain (P = .046), regardless of diagnosis. The percent change of VO2 between prostate and nonprostate cancer patients when adjusted for baseline VO2 and Physical Activity Questionnaire values was 17.45% (P = .008), with better VO2 maintenance in the prostate group.
Exercise during cancer treatment improves cardiorespiratory fitness and self-reported physical function in prostate cancer patients and in younger patients, regardless of diagnosis, and may attenuate loss of those capacities in patients undergoing chemotherapy. Exercise also reduces the pain experience. Cancer 2009. © 2009 American Cancer Society.
Although advances in cancer treatment with chemotherapy and radiation have contributed to better survival, they are associated with several side effects, including fatigue, anorexia, and emotional distress. Many chemotherapy regimens have become increasingly dose-dense and dose-intense and are often administered in combination with radiotherapy, which may intensify treatment-related symptoms. Furthermore, these symptoms can lead to a marked decrease in physical activity, which may result in reduced strength, muscle and bone mass, and cardiorespiratory fitness, as well as increased pain. As treatment progresses, the accompanying physical deconditioning may result in treatment delay or drug dose reductions.1
Population-based studies suggest that physical limitations exacerbated during cancer treatment continue beyond treatment completion if no actions are taken to counteract their effects.2, 3 Several trials have shown that individualized exercise programs are helpful in preserving or improving physical and cardiovascular fitness either during or after cancer treatment.4-10 These studies were limited because of focus on a single diagnosis, such as breast cancer,7, 8, 10, 11 small numbers of patients,11-13 or the requirement that patients exercise under supervision at a healthcare facility, which is often a barrier to exercise adherence.11, 14 In this randomized controlled trial it was hypothesized that a home-based walking program would increase cardiorespiratory fitness and physical function and decrease pain in patients undergoing curative treatment for a variety of cancer diagnoses.
MATERIALS AND METHODS
Setting and Subjects
Study patients were recruited from a university teaching hospital and a community cancer center in Baltimore, Maryland. The study target population was individuals aged ≥21 years with diagnoses of stage I to III cancer who were scheduled to receive chemotherapy, radiotherapy, or both. Exclusion criteria included comorbidities such as cardiovascular disease, cognitive dysfunction, metastatic cancer, hematologic malignancies, and other conditions that could preclude the advisability or safety of a moderate-intensity walking program. Individuals who were already exercising more than 120 minutes per week were ineligible for the study.
Recruitment and Enrollment
Potential patients were identified from patient lists in radiation oncology and medical oncology clinics and were screened by telephone interview. A total of 5439 patients were assessed for eligibility, 620 were eligible, and 138 signed informed consent and were randomized to either the intervention or control arm (Fig. 1). After enrollment and randomization, 12 patients withdrew, leaving 126 patients in the analytic sample, 68 of whom were in the walking intervention. Reasons for study dropouts in the walking intervention group (Fig. 1) included feeling overwhelmed (n = 2), becoming too sick (n = 1), change in cancer treatment plan (n = 1), and refusal to be followed (n = 1). In the control group, reasons reported for dropout included change in cancer diagnosis to stage IV after study enrollment (n = 2), medical complications (n = 1), psychologic issues (n = 2), and objection to study group assignment (n = 1).
Subjects who completed the study were compared with dropouts with regard to age, weight, cancer diagnosis, cancer stage, cancer treatment, race, and highest education level. Those who dropped out had a lower mean (standard deviation [SD]) educational level of 14.77 years (3.52) versus 16.69 (2.74; P = .029) versus those who completed the study. A higher proportion of ethnic minorities dropped from the study (18.1%) versus Caucasians (5.6%) (P = .024). Fitness was expressed as peak oxygen uptake (VO2), either directly measured by treadmill testing or estimated from the 12-minute walk test. Subjects were given a choice of test to be administered. The treadmill test was performed on a SensorMedics Vmax 229 Metabolic and ECG System; SensorMedics Corporation, Yorba Linda, Calif). Electrocardiographic and cardiorespiratory responses were continuously monitored. Subjects performed a modified Balke Protocol beginning at 3 miles per hour (mph), 0% grade, which increased by 2.5% grade each 3 minutes. The rating of perceived exertion (RPE) using the Borg 6 to 20 scale15 was obtained during each stage. The test was stopped at volitional fatigue. Subjects were encouraged to reach an RPE of at least 18. The respiratory exchange ratio was also monitored and patients were encouraged to reach a value of 1.1 as another indicator of maximal effort. The highest oxygen uptake reached was considered VO2. For patients who did not perform the treadmill test because of constraints (ie, unwillingness to travel to a separate location where testing was performed), a 12-minute walk test was administered,16 during which patients were instructed to walk for 12 minutes as far as possible along a premeasured route, and the distance walked was measured. The distance walked was used to estimate VO2.17
Self-reported physical function status was measured by 2 subscales of the Medical Outcomes Survey Short Form 36: 1) the Physical Functioning subscale, a 10-item measure sensitive to perceived losses in functioning, which included limitations for vigorous activities, moderate activities, carrying groceries, climbing several flights of stairs, bending/kneeling/stooping, walking more than a mile, walking several blocks, walking 1 block, and bathing or dressing oneself; and b) the Role Limitations Due to Physical Health subscale, a 4-item measure reflecting diminishment of health-related daily activities within the preceding 4 weeks, including cutting back on work/activities, accomplishing less than desired, limitations in usual types of work/activities, and difficulty performing work/activities. Pain level was assessed using the 2-item self-report Pain subscale, which reflects bodily pain and work interference caused by pain in the preceding 4 weeks.
The exercise dose was measured using a 5-item subscale of the Cooper Aerobics Center Longitudinal Study Physical Activity Questionnaire, a 15-item scale that assesses the degree of participation over the previous month in normal daily activities as well as in moderate or vigorous exercise activities.18 The questionnaire assigns metabolic equivalent (MET) values to the reported activities to derive MET hours expended per week. The 5 items chosen to reflect aerobic activity were walking, jogging, running, swimming, and biking. Although the focus of the study was on walking, which was the basis of the exercise prescription for those assigned to the exercise group, some patients performed other aerobic activities such as cycling either as a substitute for or as a supplement to walking. As such, these activities were included as components of the Physical Activity Questionnaire score.
The directly measured or estimated VO2, the Medical Outcomes Study Physical Functioning, Role Limitations Due to Physical Health, and Pain subscales, and the Physical Activity Questionnaire were administered before chemotherapy or radiotherapy (pretest) and after the completion of cancer treatment (post-test). After the pretest, which established baseline habitual activity, the 2 groups began their assigned programs, which then continued throughout their cancer treatment.
The prescribed exercise intervention consisted of an individualized walking prescription based on American College of Sports Medicine guidelines, which encourages moderate intensity exercise that corresponds to approximately 50% to 70% of the maximum heart rate and is consistent with exercise recommendations for populations with chronic disease.19, 20 The exercise prescription was a brisk 20- to 30-minute walk followed by 5 minutes of slower walking (cool down), 5 times per week. Exercisers were telephoned biweekly by a study nurse to assess walking progress, to answer questions, and to offer support, such as listening to cancer treatment concerns. Subjects in the control group received biweekly telephone calls and were encouraged to maintain their current levels of activity, but no specific exercise advice was offered. Individuals in both groups received usual healthcare provided by their own oncology team. Adherence to the exercise prescription was defined as walking at least a total of 60 minutes over the course of at least 3 sessions weekly for >⅔ of the total number of weeks of each subject's cancer treatment. These criteria are in accordance with guidelines of the American College of Sports Medicine and the Centers for Disease Control and Prevention.21 Among controls, if patients walked >60 minutes for >2/3 of their treatment weeks, they were considered nonadherent to their study assignment.
Sample Size Calculation and Statistical Analyses
Based on expected medium to large effect sizes reported from baseline to exercise completion for a study with similar outcomes,5 our study was powered at ≥0.80 (α = .05) with a sample size of 60 for each study group to show group differences for fitness, physical function, and pain. Descriptive statistics were calculated among those who completed the study, and for those who withdrew. Group comparisons were performed using chi-square or Student t test analysis, as appropriate. Distributions of outcome measures were reviewed using histograms and box plots; reliability coefficients were calculated for the Medical Outcomes Study subscales.
The primary analysis was based on intent to treat; group comparisons were made regardless of the degree of adherence to the assigned group. This approach is an effectiveness analysis that not only considers the efficacy of the treatment but is also influenced by whether patients actually perform the intervention. The secondary analysis was a dose-response analysis, which evaluated outcomes based on the actual amount of exercise performed according to the Physical Activity Questionnaire, regardless of group assignment. This secondary analysis was necessitated by the finding that, contrary to study instructions, 22.4% of the control patients performed exercise at a level at least equivalent to what was assigned for the exercise group. Pretest group comparisons were evaluated with Student t tests. Regression analyses using post-/pretest change scores as outcomes, and demographics and relevant pretest scores as covariates, were performed under both statistical approaches. Covariates included pretest outcome scores, pretest and net (post-test minus pretest) Physical Activity Questionnaire scores, and demographic variables. Data were analyzed using STATA statistical software (version 10.0; StataCorp, College Station, Tex). Each subject provided written informed consent, and the study was approved by the Western Institutional Review Board.
Baseline Characteristics of Exercise and Control Groups
The final sample consisted of 126 patients, who had a mean age of 60.2 (SD, 10.6) years and were predominantly Caucasian (78.6%), men (61.1%), and partnered (84.9%). The most common diagnoses were prostate (55.6%) and breast cancer (32.5%). For the entire sample, 12 (10%) had stage I disease, 89 (70%) patients had stage II disease, and 25 (20%) had stage III disease. Although there was no difference in stage of disease between exercise and control groups, the nonprostate group was more heavily represented by patients with stage III disease (29%) than the prostate group (13%; P = .013). All breast cancer patients were women. Patients were undergoing treatment with external beam radiation therapy (52.4%), chemotherapy (34.9%), combination chemotherapy and radiotherapy (7.1%), or brachytherapy alone (5.6%). For the entire sample, the mean (SD) number of cancer treatment weeks was 12.83 (5.15) with a range of 5 to 35 weeks. The mean (SD) total weeks of cancer treatment was 15.8 (5.89) for nonprostate and 10.44 (2.73) for prostate cancer patients. Patient characteristics are listed in Table 1. No significant differences were noted between groups except for education, in which a higher percentage of exercisers versus controls had college experience or higher. Weight loss occurred in 85 (67.46%) participants during the exercise study, with more stage III patients experiencing weight loss (76%) than either stage I (67%) or II (65%) patients.
|Total, N=126||Study Groups||P*|
|Exercise, n=68||Control, n=58|
|Mean age, median y (SD)||60.2 (10.6)||59.8 (10.8)||60.6 (10.8)||.70|
|No. (%)||No. (%)||No. (%)|
|Men||49 (38.9)||27 (39.7)||22 (37.9)|
|Women||77 (61.1)||41 (60.3)||36 (62.1)|
|Partnered||107 (84.9)||61 (89.7))||46 (79.3)|
|Unpartnered||19 (15.1)||7 (10.3)||12 (20.7)|
|High school||15 (11.9)||7 (10.3)||8 (13.8)|
|College||52 (41.3)||35 (51.5)||17 (29.3)|
|Grad school||59 (46.8)||26 (38.2)||33 (56.9)|
|Full time||60 (55.1)||31 (54.4)||29 (55.8)|
|Part time||11 (10.1)||5 (8.8)||6 (11.5)|
|Resigned||30 (27.5)||15 (26.3)||15 (28.9)|
|Disabled||8 (3.9)||6 (10.5)||2 (3.9)|
|Leave of absence||4 (3.17)||1 (1.7)||3 (4.4)|
|Other||13 (10.3)||8 (11.8)||5 (8.6)|
|American Indian||1 (0.8)||0 (0.0)||1 (1.7)|
|Asian/Pacific Islander||2 (1.6)||0 (0.0)||2 (3.4)|
|Black non-Hispanic||20 (15.8)||9 (13.2)||11 (19.0)|
|White non-Hispanic||99 (78.6)||57 (83.8)||42 (72.5)|
|Hispanic||3 (2.4)||1 (1.5)||2 (3.4)|
|Other||1 (0.8)||1 (1.5)||0 (0.0)|
|Breast||41 (32.5)||23 (33.8)||18 (31.0)|
|Colorectal||7 (5.6)||2 (2.9)||5 (8.6)|
|Prostate||70 (55.6)||38 (55.9)||32 (55.2)|
|Other||8 (6.4)||5 (7.4)||3 (5.2)|
|XRT||66 (52.4)||38 (55.9)||28 (48.3)|
|Chemotherapy||44 (34.9)||24 (35.3)||20 (34.5)|
|Both||9 (7.1)||4 (5.9)||5 (8.6)|
|Brachytherapy||7 (5.6)||2 (2.9)||5 (8.6)|
A total of 112 patients completed a baseline and post-test treadmill or 12-minute walking test. Data from 126 patients were available for analyses of physical function and pain. Subjects completing both pretest and post-test evaluations (n = 112) in the treadmill (n = 85) and 12-minute walk (n = 27) groups were compared with regard to cancer treatment type, diagnosis, randomization, and sex. No statistically significant differences were noted (data not shown). Adherence to the walking intervention was 67.6% in the exercise group, with an average walking time of 117 (SD = 105) minutes per week. Among controls, adherence to their assignment was 77.6%, whereas 22% of these patients exercised >60 minutes during 3 sessions a week.
Patients completing both the pretest and post-test (n = 112) and those who did not (n = 14) were compared with regard to group assignment, cancer diagnosis, cancer treatment type, and sex. Significant differences between the groups were noted on all of the variables (P < .002) except exercise group assignment (data not shown). Of the 14 patients not completing both tests, 71.4% had a diagnosis of breast cancer, and 14.3% had colorectal cancer. These individuals were predominantly women (78.6%) and receiving chemotherapy (78.6%). Furthermore, 1 of those missing the pretest and 7 of those missing the post-test were breast cancer patients. Of the 4 patients missing both tests, 2 had breast cancer and 2 had colorectal cancer.
Baseline outcome measures between assigned groups were not statistically different. Because the number of prostate cancer patients in the study (n = 70) was relatively large, comparisons of baseline outcome measures were also performed between patients with a diagnosis of prostate and nonprostate cancers. Significant differences between these groups included higher baseline pain and role limitation related to physical function in patients with nonprostate diagnoses (breast, colorectal) (Table 2).
Reliability Analysis of Measures
Cronbach alpha for subscale reliability was estimated at .77 for Medical Outcomes Study Physical Functioning, .91 for Role Limitations Due to Physical Health, and .86 for Pain, indicating acceptable reliability of the measures among patients in the study.
Changes in Cardiorespiratory Fitness
The intent-to-treat analysis demonstrated an average 2.9% decrease in post-pre change of VO2 among exercisers, and a 5.6% increase among controls. However, the difference in change (−8.4%) between exercisers and controls was not significant (P = .26). In the dose-response analysis, there was a significant difference (P = .008) of 17.45% in the percentage change of VO2 (post-pre) between prostate and nonprostate patients when adjusted for baseline VO2 test, and baseline and change of Physical Activity Questionnaire scores (Table 3). Because percentage change in VO2 was the primary outcome, its association with Physical Activity Questionnaire score was ascertained by including change in Physical Activity Questionnaire as a covariate. In addition, because level of change in Physical Activity Questionnaire and VO2 were potentially influenced by the pretest measures, these values were also included in the regression model. On average, prostate patients experienced a nearly 8% increase, whereas those in the nonprostate group suffered a >9% loss (percentages are adjusted for covariates in the model). A similar analysis including type of VO2 test administered showed that individuals taking the 12-minute walk test had an average decrease of 17% change in VO2 (standard error, 9.9; P = .85) compared with those taking the treadmill test (data not shown).
|Other Cancer, n=44, Mean (SE)||Prostate Cancer, n=68, Mean (SE)||Total, N=112, Mean (SE)|
|Pretest VO2 score||13.13 (0.59)||13.73 (0.54)||13.50 (0.40)|
|Post-test VO2 score||12.04 (0.69)||13.33 (0.56)||12.83 (0.44)|
|Percent change* VO2 score unadjusted||−7.11 (5.08)||6.45 (6.44)||1.12 (4.42)|
|Percent change VO2 score adjusted†||−9.47 (5.51)||7.98 (4.84)||1.12 (4.03)|
In intent-to-treat analysis, patients assigned to exercise had greater limitations in physical role (Medical Outcomes Study Role Limitations Due to Physical Health) from pre- to post-test versus controls (P = .037) (Table 4), when adjusting for baseline Role Limitations Due to Physical Health, age, cancer diagnosis, and cancer diagnosis and treatment group. Prostate cancer diagnosis was predictive of a larger increase in physical functioning compared with nonprostate cancer diagnosis when controlling for exercise group assignment and baseline Medical Outcomes Study Physical Functioning (P = .19) (Table 5). Age was inversely associated with a change in level of physical functioning (P = .048).
|Usual Care, n=58, Mean (SE)||Exercise, n=68, Mean (SE)||Total, N=126, Mean (SE)|
|Pretest MOS- RLPS score||64.22 (5.64)||59.19 (5.24)||61.51 (3.83)|
|Post-test MOS- RLPS score||53.45 (5.41)||39.71 (5.19)||46.03 (3.78)|
|Net MOS-RLPS score unadjusted||−10.78 (6.03)||−19.49 (6.26)||−15.48 (4.37)|
|Net MOS-RLPS score adjusted†||−8.41 (5.08)||−21.55 (4.69)||−15.48 (3.45)|
|Other Cancer, n=56, Mean (SE)||Prostate Cancer, n=70, Mean (SE)||Total, N=126, Mean (SE)|
|Pretest MOS- PFS score||82.90 (2.03)||87.69 (1.62)||85.56 (1.29)|
|Post-test MOS- PFS score||70.27 (3.18)||85.32 (1.89)||78.63 (1.85)|
|Net MOS-PFS score unadjusted||−12.63 (2.73)||−2.37 (1.58)||−6.93 (1.56)|
|Net MOS-PFS score adjusted†||−15.71 (3.10)||0.07 (1.64)||−6.93 (1.45)|
An intent-to-treat analysis of change in pain level (Medical Outcomes Study Pain), controlling for pretest pain, age, cancer diagnosis, and interaction of treatment group and cancer diagnosis, indicated no significant difference between the change in pain scores of the exercise and usual care groups (P = .55). In dose-response models including change in Physical Activity Questionnaire and either treatment group, cancer diagnosis, or both with interaction, the only significant and consistent relationship with a change in pain was the change in Physical Activity Questionnaire. For example, an average increase in Physical Activity Questionnaire was associated with a decrease in reported pain at the end of cancer treatment (P = .046), with adjustment for age, cancer diagnosis, and baseline pain and physical functioning (Table 6). Furthermore, an increase in reported pain was associated with an increase in physical role limitations (Medical Outcomes Study Role Limitations Due to Physical Health) (P < .01), when controlling for exercise group assignment, cancer diagnosis, baseline pain scores, and age (data not shown).
|Total, N=126, Mean (SE)|
|Pretest MOS-Pain score||78.13 (1.88)|
|Post-test MOS-Pain score||76.45 (1.93)|
|Net MOS-Pain score unadjusted||−1.68 (2.30)|
|Net MOS-Pain score adjusted at 50th percentile net PAQ† (2.28)‡||−2.49 (2.01)|
|Net MOS-Pain score adjusted at 99th percentile net PAQ (30.67)‡||10.63 (5.88)|
The key findings from this study suggest that patients who exercise during cancer treatment maintain or increase cardiorespiratory fitness and self-reported physical function and experience less pain than those who are sedentary. Regarding fitness, individuals who were undergoing treatment for prostate cancer improved fitness levels from baseline compared with those with other cancers, who declined in their fitness levels. Patients with prostate cancer primarily received radiotherapy, often in association with androgen deprivation therapy, in which treatment and treatment-related side effects are typically more easily tolerated than treatment with chemotherapy with or without radiation.22 The ability to adhere to an exercise regimen because of relatively minimal treatment toxicity may, in part, explain these findings. The 17% difference between prostate and nonprostate patients in net V02 function from the beginning to the end of the study does not indicate a meaningful clinical improvement in the prostate patients, but does suggest a relative and potentially meaningful clinical loss of cardiorespiratory fitness for nonprostate patients, nearly all of whom were receiving chemotherapy. Thus, it is possible that differences between prostate and nonprostate patients related to the outcome of fitness improvement may be a proxy for treatment duration and intensity.
Not surprisingly, all patients who dropped out early were receiving chemotherapy, providing further evidence for the physical and other strains that are experienced with this mode of treatment. Anemia, infections, nausea, and peripheral neuropathy are among chemotherapy-related toxic effects that may interfere with ability to exercise. It is also possible that patients receiving chemotherapy who do not benefit from exercise during active treatment, such as those with severe gastrointestinal side effects, may have problems with maintaining adequate nutrition. Evidence of weight loss in more than 66% of patients in this study suggests that inadequate nutrition was a factor in reduced exercise, either as a result of inadequate caloric intake to allow for exercise participation, or as an indicator of reduced overall function. Future work implementing and evaluating exercise interventions that begin when chemotherapy is completed should be considered. Although length of treatment for cancer was not estimated for the exercise and control groups, there were no significant group differences for cancer site, diagnostic stage, or cancer treatment type. Attention to length of time for each cancer treatment type, and correspondingly the length of exercise regimen duration, however, will allow for ascertainment of fitness, physical function, and other outcomes specific to each cancer treatment type. It is well established that chemotherapy involves the greatest time to completion and often includes delays because of low blood counts or other problems. Thus, chemotherapy patients are most likely to be heterogeneous in terms of exercise regularity and may merit separate study to identify exercise regimen components that could enhance activity benefit.
Increased doses of exercise were associated with decreased pain at the end of cancer treatment. Pain etiology (somatic, visceral, or neuropathic), causation (directly from malignancy or from treatment side effects), and impact on daily function were not the primary focus of this study, but these data suggest that exercise decreases the pain experienced by patients undergoing cancer treatment. Additional study of exercise and its impact on specific types of cancer and cancer treatment-related pain will add important information to this understudied yet important clinical issue. Individuals with prostate cancer reported lower baseline pain levels than those with other diagnoses, and therefore our results should be interpreted cautiously, as some types of pain may be more amenable to exercise than others. Exercise has been shown to aid in management of postradiation breast cancer pain,23 in alleviating musculoskeletal pain in the elderly,24 and in decreasing perceptions of non–cancer-related pain in healthy adults.25 However, to our knowledge, the relation between exercise and pain has been little studied.26 The role of exercise in cancer patients with acute or chronic pain represents a rich area for future study.
In the current study, younger age was associated with better maintenance of physical function when adjusted for treatment group and cancer diagnosis. This finding, although not entirely unexpected, suggests that more work needs to be done with older patients who are at risk for physical decline even before a cancer diagnosis occurs. Older patients who are better conditioned at the onset of serious illness may be more likely to maintain that condition than those with poor levels of fitness, who are also experiencing a cancer diagnosis and subsequent treatment. Aging is a risk factor for malignancy, with nearly 60% of all newly diagnosed cancers in this age group.27 The associated increased risk for cancer emphasizes the need to identify effective, low-cost, easily implemented physical activities that patients can use to maintain functional status during and after cancer treatment, especially in older patients. Low-impact exercise programs such as walking may be a feasible approach to maintaining function, and more study of walking programs focused on older cancer patients is warranted.
Adherence to the assigned group was lower than expected, especially in the intervention group, but our experience is not dissimilar from other studies that involved exercise.6, 28 Although randomized controlled trials are the gold standard for testing any intervention, this study demonstrates the difficulty in maintaining the group assignment given the mounting public knowledge and increasing promotion about the benefits of exercise for treating and managing chronic health conditions. Despite the high crossover in this study, pooling patients and analyzing results based on actual exercise performed provides important information regarding the value of exercise on study outcomes. Given that those who crossed over were minimally different at baseline, the study has considerable internal validity.
Intent-to-treat analysis yielded only a few significant findings. This can largely be attributed to the crossover effect in both groups, in which 32.4% of patients assigned to exercise “dropped out,” and 22% of controls “dropped in” to exercise. The finding that group assignment to exercise was associated with an increased limitation in physical role by the end of treatment compared with controls may suggest that walkers were engaging in fewer other activities because of the time committed to walking. Alternatively, walkers may have experienced more fatigue related to increased energy expenditure during walking exercise. Energy conservation has been suggested for reducing fatigue during cancer treatment, but more recently exercise has been found to be helpful in managing these cancer- and treatment-related conditions.6-8 The finding that exercise in this study yielded improvement in some subscales of the Medical Outcomes Study instrument, a quality of life measure, is consistent with other studies, in which regular exercise has been associated with improved quality of life for patients receiving cancer treatment.9, 10
The recruitment of patients who were exercising up to 120 minutes per week may have allowed individuals with meaningful pretreatment levels of fitness into the study, thereby obscuring baseline to follow-up changes in fitness among individuals who were not similarly active upon study entry. Dropping the baseline exercise level ceiling for study inclusion, although it may slow time to accrual completion, will help to alleviate this potential confounding issue in future research.
Strengths of this trial included an intent-to-treat analysis to evaluate an at-home exercise intervention that can be replicated by patients independently as well as in subsequent intervention studies. Although the literature supporting the benefits of exercise is considerable and continues to grow, much of it addresses its use in patients with breast cancer exclusively.8-13, 29-33 Thus, the broad findings from published studies may not be applicable to individuals experiencing other types of cancer and their associated treatments. The present study included patients with a variety of cancer diagnoses and showed that exercise benefits are attainable for all patients in terms of pain and for maintaining physical function status among younger patients.
Although the study was designed to include >1 patients with a variety of cancer diagnoses, the final sample size limited statistical power for subset analysis by cancer diagnosis and other variables. Another limitation was allowing the patient a choice of test for cardiorespiratory fitness assessment. This choice was made because the treadmill testing was done at a facility approximately 10 miles from the main study site and required a separate visit and travel, whereas the 12-minute walk could be done at the main study site. The use of 2 methodologies for the assessment of this primary variable may have obscured study results. Offering the treadmill test at the site where patients receive treatment may preserve enrollment and allow for greater consistency in administering outcome assessments, thereby improving data integrity.
An important goal of exercise during cancer treatment should be to preserve or improve fitness and physical function, and to reduce pain.8-10, 12-14, 33, 34 Future intervention studies among patients receiving cancer treatment should focus on developing more specific exercise guidelines based on age, treatment type, and possibly cancer diagnosis. Although a brisk walking program is well tolerated by prostate cancer patients and younger individuals undergoing any type of treatment, older patients receiving chemotherapy may benefit from an exercise program that is milder, such as more leisurely walking, possibly combined with strength training, which may enhance fitness and function, and reduce pain.
Conflict of Interest Disclosures
Supported by National Institutes of Health (NIH) Grant 1 R01 NRO 4991 (Victoria Mock, PI) and Grant No. UL1 RR 025,005 from the National Center for Research Resources, a component of the NIH, and NIH Roadmap for Medical Research.
- 19American College of Surgeons. ACSM's Exercise Management for Persons with Chronic Diseases and Disabilities. Champagane, IL: Human Kinetics; 1997.
- 20American College of Surgeons. ACSM's Guidelines for Exercise Testing and Prescription. 6th ed. Baltimore: Williams & Wilkins; 2000.
- 27SEER Cancer Statistics Review: Age Distribution (%) of Incidence Cases by Site, 1997-2001. Bethesda, Md: National Cancer Institute; 2004., , , et al.