Aarti A. Kenjale

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.

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.

Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training

AIMS To determine if type 2 diabetes mellitus (T2D) differentiates endothelial function and plasma nitrite response (a marker of nitric oxide bioavailability) during exercise in peripheral arterial disease (PAD) subjects prior to and following 3 months supervised exercise training (SET). METHODS In subjects with T2D+PAD (n = 13) and PAD-only (n = 14), endothelial function was measured using brachial artery flow-mediated dilation. On a separate day, venous blood draws were performed at rest and 10 min following a symptom-limited graded treadmill test (SL-GXT). Plasma samples were snap-frozen for analysis of nitrite by reductive chemiluminescence. All testing was repeated following 3 months of SET. RESULTS Prior to training both groups demonstrated endothelial dysfunction, which was correlated with a net decrease in plasma nitrite following a SL-GXT (p ≤ 0.05). Following SET, the PAD-only group demonstrated an improvement in endothelial function (p ≤ 0.05) and COT (p ≤ 0.05), which was related to a net increase in plasma nitrite following the SL-GXT (both p ≤ 0.05). The T2D+PAD group had none of these increases. CONCLUSIONS T2D in the presence of PAD attenuated improvements in endothelial function, net plasma nitrite, and COT following SET. This suggests that T2D maybe associated with an inability to endogenously increase vascular NO bioavailability to SET.

Potential mechanisms for reduced delivery of nitric oxide to peripheral tissues in diabetes mellitus.

Nitric oxide (NO) bioavailability is crucial for normal vascular endothelial function and health. Recent studies have demonstrated an endocrine role for NO equivalents that may be transported in the blood to peripheral tissue beds, where under hypoxic conditions they can liberate NO and cause vasodilation. Exercise training improves endothelial function but its effect on NO bioavailability in peripheral tissues during acute exercise stress in CVD is unclear. This paper will present evidence and discuss possible mechanisms by which NO delivery to peripheral tissues may be dysfunctional in diabetic subjects.

Reliability of maximal cardiopulmonary exercise testing in men with prostate cancer.

PURPOSE To accurately assess exercise interventions and to evaluate acute and chronic cardiovascular effects in patients with early-stage cancer, consistently reliable functional outcome measures must be obtained. An incremental cardiopulmonary exercise test (CPET) with gas exchange measurement to assess peak oxygen consumption (V˙O2peak) provides the gold standard outcome of cardiorespiratory fitness. METHODS In the context of a randomized controlled trial, 40 patients with prostate cancer (mean age, 59 ± 7 yr) after radical prostatectomy performed two maximal CPET within 5.6 ± 5.5 d of each other. Incremental treadmill tests were performed in the morning under identical laboratory conditions. Reliability and within-subject variability from test 1 to test 2 for peak and submaximal variables were assessed by correlation coefficients, intraclass correlations (ICC), Bland-Altman plots, coefficient of variation, and paired t-tests. RESULTS There was high reliability between CPET for V˙O2peak (r = 0.92; P < 0.001; ICC, 0.900), ventilatory threshold (r = 0.88; P < 0.001; ICC, 0.927), minute ventilation-carbon dioxide production relation (V˙E/V˙CO2) (r = 0.86; P < 0.001; ICC, 0.850), and peak heart rate (r = 0.95; P < 0.001; ICC, 0.944). However, high within-subject variability was observed for all CPET parameters (mean coefficient of variation, 4.7%). Compared with those for test 1, significantly higher mean values were observed for V˙O2peak (27.0 ± 5.6 vs 28.1 ± 5.3 mL·kg·min, P < 0.05), ventilatory threshold (1.91 ± 0.5 vs 1.97 ± 0.4 L·min, P < 0.05), and V˙E/V˙CO2 (31.3 ± 5.8 vs 32.8 ± 3.4, P < 0.05) in test 2. CONCLUSIONS These findings indicate the presence of significant, and potentially clinically important, variability in CPET procedures in men with clinically localized prostate cancer and have important implications for the application and use of CPET to evaluate the efficacy of interventions to improve aerobic capacity in the oncology setting.

Prognostic Validation of the Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index in Inoperable Non–Small-Cell Lung Cancer

Introduction: To investigate the prognostic utility of the body mass index, severity of airflow obstruction, measures of exertional dyspnea, and exercise capacity (BODE) index in patients with inoperable non–small-cell lung cancer (NSCLC). Methods: One hundred consecutive patients with inoperable NSCLC and performance status 0 to 3 completed pulmonary function testing, the modified Medical Research Council dyspnea scale, a 6-minute walk test, and body mass index—the multidimensional 10-point BODE index. Cox proportional models were used to estimate the risk of all-cause mortality according to the BODE index with or without adjustment for traditional prognostic factors. Results: Median follow-up was 31.5 months; 61 deaths (61%) were reported during this period. There was a significant univariate association between the BODE index score and mortality (adjusted ptrend = 0.027). Compared with patients with a BODE index of 0, the adjusted hazard ratio for risk of death was 1.37 (95% confidence interval [CI], 0.74–2.55) for a BODE index of 1, 1.22 (95% CI, 0.45–3.25) for a BODE index of 2, and 2.44 (95% CI, 1.19–4.99) for a BODE index more than 2. The BODE index provided incremental prognostic information beyond that provided traditional markers of prognosis (adjusted ptrend = 0.051). Every one-point increase in the BODE index, the risk of death increased by 25% (hazard ratio = 1.25; 95% CI, 1.27–4.64). Conclusions: The BODE index is a strong independent predictor of survival in inoperable NSCLC beyond traditional risk factors. Use of this multidimensional tool may improve risk stratification and prognostication in NSCLC.