Effects of Exercise Therapy Dosing Schedule on Impaired Cardiorespiratory Fitness in Patients With Primary Breast Cancer: A Randomized Controlled Trial.

BACKGROUND: Current exercise guidelines for clinical populations recommend an exercise therapy (ET) prescription of fixed intensity (moderate), duration (40-50 minutes per session), and volume (120-160 min/wk). A critical overarching element of exercise programming that has received minimal attention is dose scheduling. We investigated the tolerability and efficacy of 2 exercise training dose regimens on cardiorespiratory fitness and patient-reported outcomes in patients with posttreatment primary breast cancer. METHODS: Using a parallel-group randomized trial, we randomly allocated 174 postmenopausal patients (2.8 years after adjuvant therapy) with impaired peak oxygen consumption (VO2peak) to 1 of 2 supervised exercise training interventions delivered with a standard linear (LET) (fixed dose intensity per session for 160 min/wk) or nonlinear (NLET) (variable dose intensity per session for ≈120 min/wk) schedule compared with a stretching attention control group for 16 consecutive weeks. Stretching was matched to exercise dosing arms on the basis of location, frequency, duration, and treatment length. The primary end point was change in VO2peak (mL O2·kg-1·min-1) from baseline to after intervention. Secondary end points were patient-reported outcomes, tolerability, and safety. RESULTS: No serious adverse events were observed. Mean attendance was 64%, 75%, and 80% for attention control, LET, and NLET, respectively. In intention-to-treat analysis, VO2peak increased 0.6±1.7 mL O2·kg-1·min-1 (P=0.05) and 0.8±1.8 mL O2·kg-1·min-1 (P=0.07) in LET and NLET, respectively, compared with attention control. Change in VO2peak ranged from -2.7 to 4.1 mL O2·kg-1·min-1 and from -3.6 to 5.1 mL O2·kg-1·min-1 in LET and NLET, respectively. Approximately 40% of patients in both exercise dosing regimens were classified as VO2peak responders (ie, Δ ≥1.32 mL O2·kg-1·min-1). NLET improved all patient-reported outcomes compared with attention control. CONCLUSIONS: Short-term exercise training, independently of dosing schedule, is associated with modest improvements in cardiorespiratory fitness in patients previously treated for early-stage breast cancer. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01186367.

Validity of Estimated Cardiorespiratory Fitness in Patients With Primary Breast Cancer.

Background: Estimated peak oxygen consumption (Vo2peak) is widely used in oncology; however, estimated Vo2peak equations were developed in noncancer settings. Objectives: The aim of this study was to evaluate the validity of estimated Vo2peak in women with primary breast cancer and to develop oncology-specific estimated Vo2peak equations. Methods: Vo2peak was directly measured (TrueOne 2400, Parvo Medics) during 380 cardiopulmonary exercise tests in women previously treated for breast cancer (mean age: 59 ± 10 years; 3.1 ± 1.2 years post-therapy). The American College of Sports Medicine (ACSM), the Fitness Registry and the Importance of Exercise National Database (FRIEND), and heart failure (HF)-FRIEND equations were used to estimate Vo2peak. New equations were developed using patient and peak (Oncpeak) or submaximal (Oncsub) exercise test characteristics. Results: The median differences between measured and estimated Vo2peak were 7.0 mL O2·kg-1·min-1, 3.9 mL O2·kg-1·min-1, and -0.2 mL O2·kg-1·min-1 for ACSM, FRIEND, and HF-FRIEND, respectively. The number of estimated Vo2peak values within ±3.5 mL O2·kg-1·min-1 of the measured values was 70 (18%), 164 (43%), and 306 (81%) for ACSM, FRIEND, and HF-FRIEND, respectively. The Oncpeak and OncSub models included body mass index, age, a history of chemotherapy or radiation, the peak measured heart rate, and the treadmill grade and/or speed. The median differences between measured and estimated Vo2peak were 0.02 mL O2·kg-1·min-1 (Oncpeak) and -0.2 mL O2·kg-1·min-1 (Oncsub). Eighty-six percent (n = 325) and 76% (n = 283) estimated Vo2peak values were within ±3.5 mL O2·kg-1·min-1 of the measured Vo2peak values for Oncpeak and Oncsub, respectively. Conclusions: HF-FRIEND or oncology-specific equations could be applied to estimate Vo2peak in patients previously treated for breast cancer in settings where cardiopulmonary exercise tests are not available. (Trial Comparing the Effects of Linear Versus Nonlinear Aerobic Training in Women With Operable Breast Cancer [EXCITE]; NCT01186367.

Effects and tolerability of exercise therapy modality on cardiorespiratory fitness in lung cancer: a randomized controlled trial.

BACKGROUND: Poor cardiorespiratory fitness (CRF) is a cardinal feature of post-treatment primary lung cancer. The most effective exercise therapy regimen to improve CRF has not been determined. METHODS: In this parallel-group factorial randomized controlled trial, lung cancer survivors with poor CRF (below age-sex sedentary values) were randomly allocated to receive 48 consecutive supervised sessions thrice weekly of (i) aerobic training (AT)-cycle ergometry at 55% to >95% of peak oxygen consumption (VO2 peak); (ii) resistance training (RT)-lower and upper extremity exercises at 50-85% of maximal strength; (iii) combination training (CT)-AT plus RT; or (iv) stretching attention control (AC) for 16 weeks. The primary endpoint was change in CRF (VO2 peak, mL O2 ·kg-1 ·min-1 ). Secondary endpoints were body composition, muscle strength, patient-reported outcomes, tolerability (relative dose intensity of exercise), and safety. Analysis of covariance determined change in primary and secondary endpoints from baseline to post-intervention (Week 17) with adjustment for baseline values of the endpoint and other relevant clinical covariates. RESULTS: Ninety patients (65 ± 9 years; 66% female) were randomized (AT, n = 24; RT, n = 23; CT, n = 20; and AC, n = 23) of the planned n = 160. No serious adverse events were observed. For the overall cohort, the lost-to-follow-up rate was 10%. Mean attendance was ≥75% in all groups. In intention-to-treat analysis, VO2 peak increased 1.1 mL O2 ·kg-1 ·min-1 [95% confidence interval (CI): 0.0, 2.2, P = 0.04] and 1.4 mL O2 ·kg-1 ·min-1 (95% CI: 0.2, 2.5, P = 0.02) in AT and CT, respectively, compared with AC. There was no difference in VO2 peak change between RT and AC (-0.1 mL O2 ·kg-1 ·min-1 , 95% CI: -1.2, 1.0, P = 0.88). Favourable improvements in maximal strength and body composition were observed in RT and CT groups compared with AT and AC groups (Ps < 0.05). No between-group changes were observed for any patient-reported outcomes. Relative dose intensity of exercise was lower in RT and CT compared with AT (Ps < 0.05). CONCLUSIONS: In the context of a smaller than planned sample size, AT and CT significantly improved VO2 peak in lung cancer survivors; however, the tolerability-to-benefit ratio was superior for AT and hence may be the preferred modality to target impaired CRF in post-treatment lung cancer survivors.

Novel Methods for Reporting of Exercise Dose and Adherence: An Exploratory Analysis.

PURPOSE: The purpose of this study was to explore whether methods adapted from oncology pharmacological trials have utility in reporting adherence (tolerability) of exercise treatment in cancer. METHODS: Using a retrospective analysis of a randomized trial, 25 prostate cancer patients received an aerobic training regimen of 72 supervised treadmill walking sessions delivered thrice weekly between 55% and 100% of exercise capacity for 24 consecutive weeks. Treatment adherence (tolerability) was assessed using conventional (lost to follow-up and attendance) and exploratory (e.g., permanent discontinuation, dose modification, and relative dose intensity) outcomes. RESULTS: The mean total cumulative "planned" and "completed" dose was 200.7 ± 47.6 and 153.8 ± 68.8 MET·h, respectively, equating to a mean relative dose intensity of 77% ± 24%. Two patients (8%) were lost to follow-up, and mean attendance was 79%. A total of 6 (24%) of 25 patients permanently discontinued aerobic training before week 24. Aerobic training was interrupted (missing ≥3 consecutive sessions) or dose reduced in a total of 11 (44%) and 24 (96%) patients, respectively; a total 185 (10%) of 1800 training sessions required dose reduction owing to both health-related (all nonserious) and non-health-related adverse events. Eighteen (72%) patients required at least one session to be terminated early; a total of 59 (3%) sessions required early termination. CONCLUSIONS: Novel methods for the conduct and reporting of exercise treatment adherence and tolerability may provide important information beyond conventional metrics in patients with cancer.