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Effects of Presurgical Exercise Training on Cardiorespiratory Fitness Among Patients Undergoing Thoracic Surgery for Malignant Lung Lesions Lee W. Jones, PhD1 Carolyn J. Peddle, MS2 Neil D. Eves, PhD3 Mark J. Haykowsky, PhD4 Kerry S. Courneya, PhD2 John R. Mackey, MD5 Anil A. Joy, MD5 Vikaash Kumar, MD5 Timothy W. Winton, MD6 Tony Reiman, MD4
BACKGROUND. To determine the effects of preoperative exercise training on cardiorespiratory fitness in patients undergoing thoracic surgery for malignant lung lesions.
METHODS. Using a single-group design, 25 patients with suspected operable lung cancer were provided with structured exercise training until surgical resection. Exercise training consisted of 5 endurance cycle ergometry sessions per week at intensities varying from 60% to 100% of baseline peak oxygen consumption (VO2peak). Participants underwent cardiopulmonary exercise testing, 6-minute walk (6MW), and pulmonary function testing at baseline, immediately before, and 30 days after surgical resection.
RESULTS. Five patients were deemed ineligible before surgical resection and were 1
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
removed from the analysis. Of the remaining 20 patients follow-up assessments were obtained for 18 (90%) before resection and 13 (65%) patients postresection.
2 Faculty of Physical Education, University of Alberta, Edmonton, Alberta, Canada.
The overall adherence rate was 72%. Intention-to-treat analysis indicated that
3
Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada. 4
Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada. 5
Department of Oncology, University of Alberta, Edmonton, Alberta, Canada. 6
Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
mean VO2peak increased by 2.4 mL kg21 min21(95% confidence interval [CI], 1.0–3.8; P 5 .002) and 6MW distance increased 40m (95% CI, 16–64; P 5 .003) baseline to presurgery. Per protocol analyses indicated that patients who attended 80% of prescribed sessions increased VO2peak and 6MWD by 3.3 mL kg21 min21 (95% CI, 1.1–5.4; P 5 .006) and 49 meters (95% CI, 12–85; P 5 .013), respectively. Exploratory analyses indicated that presurgical exercise capacity decreased postsurgery, but did not decrease beyond baseline values.
CONCLUSIONS. Preoperative exercise training is a beneficial intervention to improve cardiorespiratory fitness in patients undergoing pulmonary resection. This benefit may have important implications for surgical outcome and postsurgical recovery in this population. Larger randomized controlled trials are warranted. Cancer 2007;110:590–8. 2007 American Cancer Society.
Supported by funds from the Alberta Cancer Board, Canada. Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, Georgia, June 2–6, 2006. We thank Tyson Kochan, BS, Susan Goruk, BS, and Chris Sellar, MS, for assistance in data collection and analysis. Address for reprints: Lee W. Jones, PhD, Box 3624, Department of Surgery, Duke University Medical Center, Durham, NC 27710; Fax: (919) 684-8203; E-mail:
[email protected] Received January 11, 2007; revision received March 13, 2007; accepted March 15, 2007.
ª 2007 American Cancer Society
KEYWORDS: exercise training, prehabilitation, surgery, lung cancer, cardiorespiratory fitness.
P
ulmonary resection is the treatment of choice for a variety of disorders including nonsmall-cell lung cancer (NSCLC), selected cases of oligometastatic disease (sarcoma, colorectal cancer, melanoma, etc) and some nonmalignant lesions. Despite significant advancements in surgical techniques and postoperative care, complications from pulmonary resection are considerable and largely depend on the extent of resection, the cardiopulmonary reserve of the patient, and the presence of comorbid disease.1,2 In recent years investigators have demonstrated the role of exercise-based assessments to evaluate medical operability of pulmonary resection patients because this simulates the stresses imposed on the cardio-
DOI 10.1002/cncr.22830 Published online 20 June 2007 in Wiley InterScience (www.interscience.wiley.com).
Exercise Before Lung Surgery/Jones et al.
pulmonary system by the operative procedure.1,3 Among the wide number of exercise-based assessments that are available cardiopulmonary exercise testing (CPET) that includes the measurement of peak oxygen consumption (VO2peak) has been shown to be the strongest independent predictor of surgical complication rate.1,4–6 Specifically, NSCLC patients with a preoperative VO2peak 15 mL kg21 min21are at comparatively low risk of complications, whereas patients with 15 mL kg21 min21 and 10 mL kg21 min21 are at increased and very high risk of complications, respectively.1,4–6 Given this evidence, interventions that can improve presurgical VO2peak may have considerable clinical benefit for NSCLC patients undergoing surgical resection. However, to our knowledge to, no reported study has examined the effects of presurgical exercise training in this clinical population. To this end, we conducted a prospective, single-arm feasibility study to examine the effects of presurgical exercise training on preoperative and postoperative markers of exercise capacity including VO2peak relative to body mass (mL kg21 min21), VO2peak percent predicted, 6minute walk distance (6MWD), and pulmonary function (PFT) outcomes. We hypothesized that presurgical exercise training would have a beneficial effect on measures of cardiorespiratory fitness before surgical resection.
MATERIALS AND METHODS
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at UAH. At the discretion of the thoracic surgeon, eligible patients were provided with a thorough review of the study by the study coordinator and asked if they were willing to participate. Interested participants were then scheduled for a baseline CPET, 6MWD, and a PFT. After the successful completion of the baseline assessments all participants were scheduled for immediate exercise training.
Exercise Training Intervention The exercise training program was individually tailored to each patient and aimed specifically at increasing VO2peak. All exercise training sessions were supervised by exercise specialists. Exercise training consisted of 5 endurance cycle ergometry (Lifestyle Fitness 9500HR; Life Fitness, Franklin Park, Ill) sessions per week on consecutive days until surgical resection. In Week 1, exercise intensity was initially set at 60% of baseline VO2peak for a duration of 20 minutes. Duration and/or intensity were subsequently increased throughout the first week up to 30 minutes at 65% VO2peak. In Weeks 2 and 3, exercise intensity varied between 60% to 65% VO2peak for a duration of 25 to 30 minutes for 4 sessions, in the remaining session patients cycled for 20 to 25 minutes at ventilatory threshold determined by a systematic increase in the VE/VO2 ratio, whereas VE/VCO2 remained constant.7 From the fourth week onwards patients performed 3 sessions at 60% to 65% VO2peak, 1 threshold workout for 20 to 30 minutes, and 1 interval workout. Interval workouts consisted of 30 seconds at peak VO2 followed by 60 seconds of active recovery for 10 to 15 intervals.8–10 All exercise sessions included a 5-minute warm-up and a 5-minute cool-down. Exercise training intensity and safety was monitored continuously via heart rate, blood pressure, and oxyhemoglobin saturation.
Setting and Patients The study was conducted at the University of Alberta Hospital (UAH), the University of Alberta, and Cross Cancer Institute, Alberta, Canada. Consecutive patients with suspected stage I-IIIA NSCLC, with or without preoperative histologic confirmation who were candidates for primary surgery for curative intent at the UAH were potentially eligible for this study. Patients were deemed not eligible if they had: 1) uncontrolled hypertension, 2) uncontrolled cardiac/pulmonary disease, 3) pulmonary function (forced expired volume [FEV] 1 \ 1.1L; diffusion capacity for carbon monoxide [DLCO] adj.) \70% predicted, or 4) contraindications to exercise training based on a cardiopulmonary exercise test. The Alberta Cancer Board and UAH approved the study and written informed consent was obtained from all participants before initiation of any study procedures.
Outcomes The primary outcome was change in VO2peak (mL kg21 min21) between baseline and immediately before pulmonary resection (presurgery). Secondary exercise capacity outcomes were VO2peak as a percentage of age and gender predicted and 6MWD. Secondary pulmonary function outcomes included FEV in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), single breath DLCO, and residual volume (RV).
Procedures Using a prospective, single-group design, potential participants were identified and screened for eligibility via medical record review of surgical candidates
Timing of Assessments Cardiopulmonary exercise testing, 6MWD, and PFTs were conducted at baseline, immediately presurgery, and postsurgery.
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FIGURE 1. Study flow. Outcome Assessments Peak oxygen consumption (VO2peak) To determine VO2peak, a physician-supervised CPET with 12-lead ECG monitoring (Mac 5000, GE Healthcare) was performed by an exercise physiologist. The specific protocol for this test has previously been reported in detail11 and followed ATS guidelines.12 In brief, tests were performed on an electronically braked cycle ergometer (Ergoline, Ergoselect 100, Bitz, Germany) with breath-by-breath expired gas analysis (Medgraphics, CPX/D system, St. Paul, Minn). Workloads were increased 5–20W/minute until volitional exhaustion or until a symptom limitation was achieved. All participants found the CPET to be feasible, with dry mouth as the only complaint. During exercise oxyhemoglobin saturation was monitored continuously using pulse oximetry (BCI, Hand-Held Pulse Oximeter, Waukesha, Wisc), whereas blood pressure was measured every 2 minutes. Exertional dyspnea and leg discomfort were evaluated at the end of each workload using the modified Borg Scale. All data were recorded as the highest 30-second value elicited during the CPET. Mean percentage of age- and sex-predicted VO2peak was calculated from the equation provided by Jones et al.13 Six-minute walk test The 6-minute walk test was conducted according to the guidelines of the ATS.14 Patients were instructed to cover the longest distance possible in 6 minutes under the supervision of an exercise physiologist. The distance walked was determined in a measured corridor, between 2 cones that were placed 30 meters
apart. The test was performed twice at each study timepoint with the average recorded. Age- and sexpredicted 6MWD was calculated from the equation of Gibbons et al.15
Pulmonary function test Spirometry (SensorMedics Vmax22, Yorba Linda, Calif), DLCO, and lung volumes determined by body plethysmograph (6200 Autobox; SensorMedics) were measured in the sitting position according to the ATS guidelines.16 Exercise adherence Exercise adherence was assessed directly by attendance to the intervention. Exercise performed outside of the program was assessed by self-report using the Godin Leisure Time Exercise Questionnaire (GLTEQ).17 Participants completed the GLTEQ at baseline, presurgery, and postsurgery. Medical characteristics Medical data (ie, age, sex, weight, height, smoking history, tumor stage, tumor pathology, and surgery type) was abstracted from medical records. Concurrent comorbid conditions were evaluated using the modified Charlson Index.18 Perioperative and postoperative complications were coded as an adverse event if they occurred within 30 days of pulmonary resection. Statistical Analysis Descriptive information was collated on the demographic and medical characteristics of participants
Exercise Before Lung Surgery/Jones et al.
and surgical complications. Our primary analysis used a repeated measures analysis of variance (RMANOVA) to compare changes in VO2peak from baseline to presurgery. Secondary analyses used RMANOVAs to compare changes in secondary outcomes from baseline to presurgery to postsurgery. The principal analysis of primary and secondary study outcomes used the intention-to-treat (ITT) approach. The ITT analysis included all participants recruited to the study (n 5 20) regardless of adherence to the intervention. We employed the last-observation-carried-forward procedure for participants who were lost-to-follow-up. In addition, because we also wanted to examine whether change in study outcomes was a function of exercise adherence, we conducted a protocol specified analysis using independent samples Student t tests to examine change in study outcomes based on adherence to the intervention ( .05).
Per Protocol Analysis Table 3 displays the changes in primary and secondary outcomes from baseline to presurgery by exercise adherence (\80% vs 80%). For patients who achieved 80% adherence (n 5 12), VO2peak increased 3.3 mL kg21 min21 (P 5 .006) and 6MWD increased 49 m (P 5 .013). Significant beneficial changes were also observed in predicted VO2peak (P < .001), VO2peak (L min21) (
