Miranda J. West

Safety and Feasibility of Aerobic Training on Cardiopulmonary Function and Quality of Life in Postsurgical Nonsmall Cell Lung Cancer Patients A Pilot Study

A feasibility study examining the effects of supervised aerobic exercise training on cardiopulmonary and quality of life (QOL) endpoints among postsurgical nonsmall cell lung cancer (NSCLC) patients was conducted.

Prognostic significance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer

BACKGROUND To investigate the prognostic importance of functional capacity and exercise behavior in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Using a prospective design, 118 consecutive participants with histologically confirmed metastatic (inoperable) NSCLC and Eastern Cooperative Oncology group (ECOG) 0-3 completed a six-minute walk test to assess functional capacity and questionnaire that assessed self-reported exercise behavior. Cox proportional models were used to estimate the risk of all-cause mortality according to six-minute walk distance (6MWD) (<358.5m, 358.5-450 m, ≥450 m) and exercise behavior (MET-hrswk(-1)) categories with adjustment for important covariates. RESULTS Median follow-up was 26.6 months; 77 deaths were reported during this period. Functional capacity was an independent predictor of survival (P(trend)=0.003) and added incremental prognostic value beyond that provided by PS plus other traditional markers of prognosis (P(trend)=0.025). Compared with patients achieving a 6MWD <358.5m, the adjusted hazard ratio (HR) for all-cause mortality was 0.61 (95% CI, 0.34-1.07) for a 6MWD of 358.5-450 m, and 0.48 (95% CI, 0.24-0.93) for a 6MWD >450 m. In unadjusted analysis, there was a borderline significant effect of exercise behavior on survival (p=0.052). Median survival was 12.89 months (95% CI, 9.11-21.05 months) for those reporting <9MET-hrswk(-1) compared with 25.63 months (95% CI, 11.28 to ∞ months) for those reporting ≥9MET-hrswk(-1). CONCLUSIONS Functional capacity is a strong independent predictor of survival in advanced NSCLC that adds to the prediction of survival beyond traditional risk factors. This parameter may improve risk stratification and prognostication in NSCLC.

Safety and efficacy of aerobic training in operable breast cancer patients receiving neoadjuvant chemotherapy: A phase II randomized trial

Abstract Background. To evaluate the safety and efficacy of moderate-to-high intensity aerobic training in breast cancer patients receiving neoadjuvant chemotherapy. Methods. Twenty patients with stage IIB–IIIC operable breast cancer were randomly assigned to receive doxorubicin plus cyclophosphamide (AC) or AC in combination with aerobic training (AC + AET) (n = 10/group) for 12 weeks. The AC+ AET group performed three supervised aerobic cycle ergometry sessions per week at 60%–100% of exercise capacity (VO2peak). Safety outcomes included exercise testing as well as treatment- and exercise training-related adverse events (AEs), whereas efficacy outcomes included cardiopulmonary function and patient-reported outcomes (PROs) as measured by a cardiopulmonary exercise test (CPET) and Functional Assessment of Cancer Therapy-Breast (FACT-B) scale. Results. Twelve non-significant ECG abnormalities and three non-life threatening events occurred during CPET procedures. One AE was reported during aerobic training. There were no significant between group differences for clinician-documented events (e.g. pain, nausea) or hematological parameters (ps > 0.05). Attendance and adherence rates to aerobic training were 82% and 66%, respectively. Intention-to-treat analysis indicated that VO2peak increased by 2.6 ± 3.5 ml/kg/min (+ 13.3%) in the AC + AET group and decreased by 1.5 ± 2.2 ml/kg/min (−8.6%) in the AC group (between group difference, p = 0.001). FACT-B increased 11.1 points in the AC + AET group compared to a 1.5 point decrease in the AC group (between group difference, p = 0.685). Conclusion. Moderate-to-high intensity aerobic training when conducted with one-on-one supervision is a safe adjunct therapy associated with improvements in cardiopulmonary function and select PROs during neoadjuvant chemotherapy.

Exercise Behavior, Functional Capacity, and Survival in Adults With Malignant Recurrent Glioma

PURPOSE Identifying strong markers of prognosis are critical to optimize treatment and survival outcomes in patients with malignant recurrent glioma. We investigated the prognostic significance of exercise behavior and functional capacity in this population. PATIENTS AND METHODS Using a prospective design, 243 patients with WHO grades 3 to 4 recurrent malignant glioma and Karnofsky performance status (KPS) ≥ 70 completed a self-administered questionnaire that assessed exercise behavior and performed a 6-minute walk test (6MWT) to assess functional capacity. Cox proportional models were used to estimate the risk of all-cause mortality according to 6MWT distance (6MWD; < 390 meters, 390-489 meters, > 489 meters) and exercise behavior (metabolic equivalent [MET] -h/wk) adjusted for KPS and other important clinical factors. RESULTS Median follow-up was 27.43 months. During this period, 149 deaths were recorded (61% of the total sample). Exercise behavior was an independent predictor of survival (P = .0081). Median survival was 13.03 months for patients reporting < 9 MET-h/wk relative to 21.84 months for those reporting ≥ 9 MET-h/wk. Exercise behavior added incremental prognostic value beyond that provided by KPS, age, sex, grade, and number of prior progressions (P < .001). Compared with patients reporting < 9 MET-h/wk, the adjusted hazard ratio for mortality was 0.64 (95% CI, 0.46 to 0.91) for patients reporting ≥ 9 MET-h/wk. Functional capacity was not an independent predictor of prognosis. CONCLUSION Exercise behavior is a strong independent predictor of survival that provides incremental prognostic value to KPS as well as traditional markers of prognosis in malignant recurrent glioma.

Modulation of Circulating Angiogenic Factors and Tumor Biology by Aerobic Training in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Aerobic exercise training (AET) is an effective adjunct therapy to attenuate the adverse side-effects of adjuvant chemotherapy in women with early breast cancer. Whether AET interacts with the antitumor efficacy of chemotherapy has received scant attention. We carried out a pilot study to explore the effects of AET in combination with neoadjuvant doxorubicin–cyclophosphamide (AC+AET), relative to AC alone, on: (i) host physiology [exercise capacity (VO2 peak), brachial artery flow-mediated dilation (BA-FMD)], (ii) host-related circulating factors [circulating endothelial progenitor cells (CEP) cytokines and angiogenic factors (CAF)], and (iii) tumor phenotype [tumor blood flow (15O–water PET), tissue markers (hypoxia and proliferation), and gene expression] in 20 women with operable breast cancer. AET consisted of three supervised cycle ergometry sessions/week at 60% to 100% of VO2 peak, 30 to 45 min/session, for 12 weeks. There was significant time × group interactions for VO2 peak and BA-FMD, favoring the AC+AET group (P < 0.001 and P = 0.07, respectively). These changes were accompanied by significant time × group interactions in CEPs and select CAFs [placenta growth factor, interleukin (IL)-1β, and IL-2], also favoring the AC+AET group (P < 0.05). 15O–water positron emission tomography (PET) imaging revealed a 38% decrease in tumor blood flow in the AC+AET group. There were no differences in any tumor tissue markers (P > 0.05). Whole-genome microarray tumor analysis revealed significant differential modulation of 57 pathways (P < 0.01), including many that converge on NF-κB. Data from this exploratory study provide initial evidence that AET can modulate several host- and tumor-related pathways during standard chemotherapy. The biologic and clinical implications remain to be determined. Cancer Prev Res; 6(9); 925–37. ©2013 AACR.

Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma

The study was undertaken to evaluate cardiorespiratory fitness, skeletal muscle function, and body composition of patients with newly diagnosed and untreated, postsurgical primary malignant glioma.

Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function Following Radical Prostatectomy for Clinically Localized Prostate Cancer

UNLABELLED Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n=25 per group) after RP. AT consisted of five walking sessions per week at 55-100% of peak oxygen uptake (VO2peak) for 30-60 min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow-mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤ 21) decreased by 20% in the AT group and by 24% in the UC group (difference: p=0.406). There were no significant between-group differences in any erectile function subscale (p>0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT00620932.

Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility study

The feasibility of symptom-limited cardiopulmonary exercise testing (CPET) prior to allo-SCT was assessed in addition to the prognostic value of CPET-derived measures. CPET was performed prospectively on 21 patients with hematologic malignancies, with assessments of peak (for example, peak oxygen consumption, VO2peak) and submaximal (for example, ventilatory threshold (VT)) measures of cardiopulmonary function. No serious adverse events were observed during CPET procedures, with 95% of patients achieving criteria for a peak test. Mean VO2peak was 24.7±6.4 mL kg−1 min−1 (range: 10.9–35.5), equivalent to 29%±17% below that of age-matched healthy controls. All patients proceeded with the conditioning regimen followed by allo-SCT. Median follow-up was 25 months. During this period, 11 (52.4%) patients died (n=6, relapsed disease; n=5, non-relapse mortality (NRM)); 9 patients (43%) developed pulmonary toxicity. In univariate analyses, both peak and submaximal markers of cardiopulmonary function were predictors of OS, pulmonary toxicity and NRM. For OS, the HR for VO2peak and VT were 0.89 (95% CI, 0.8–0.99, P=0.04) and 0.84 (95% CI, 0.71–0.98, P=0.03), respectively. In conclusion, CPET is safe and feasible prior to allo-SCT. Patients have marked impairments in cardiopulmonary function prior to allo-SCT. CPET-derived metrics may complement conventional measures to improve risk stratification.

Changes in Functional Performance Measures in Adults Undergoing Chemoradiation for Primary Malignant Glioma: A Feasibility Study

PURPOSE To investigate the feasibility of longitudinal assessment of functional performance measures in newly diagnosed postsurgical malignant glioma patients. METHODS Patients with histologically confirmed, clinically stable, postsurgical, and previously untreated high-grade glioma (HGG) or low-grade glioma (LGG) were studied. Using a prospective design, all participants performed a cardiopulmonary exercise test with expired gas analysis to assess cardiorespiratory function (VO(2peak)) immediately following surgical resection (mean, 10 days). Additional functional outcomes were skeletal muscle cross-sectional area (CSA) via magnetic resonance imaging, isokinetic muscle strength (isokinetic dynamometry), and body composition (air displacement plethysmography). Quality of life (QOL) was assessed by the Functional Assessment of Cancer Therapy-Brain scale. All study assessments were repeated at 6 and 24 weeks following surgery. RESULTS Thirty-five patients (HGG, n = 25; LGG, n = 10) completed baseline assessments. Of these, 20 HGG (80%) and nine LGG (90%) and 15 HGG (60%) and nine LGG (90%) patients completed study assessments at 6 weeks and 24 weeks, respectively. Intention-to-treat analyses indicated several significant time-by-group interactions, with favorable improvements in functional and QOL endpoints from baseline to 24 weeks in the LGG cohort and unfavorable changes in the HGG cohort. Per-protocol analyses including participants assessed at all three study timepoints indicated significant improvements in VO(2peak) and fatigue from baseline to 24 weeks in the HGG cohort; peak workload, body composition, and muscle strength improved from baseline to 6 weeks (all p-values < .05). CONCLUSIONS Longitudinal quantitative functional assessments are safe and feasible among select patients undergoing chemoradiation for primary malignant glioma. Large prospective studies investigating the clinical importance of these measures appear warranted.

Effect of aerobic exercise training on cardiorespiratory fitness and quality of life in postsurgical non-small cell lung cancer patients

7577 Background: The effects of standard NSCLC adjuvant therapy (i.e., pulmonary resection, adjuvant chemotherapy) together with deconditioning secondary to treatment has a profound negative impact...