Amy R. Lane

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.

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.

Exercise and the Regulation of Endocrine Hormones.

The endocrine system has profound regulatory effects within the human body and thus the ability to control and maintain appropriate function within many physiological systems (i.e., homeostasis). The hormones associated with the endocrine system utilize autocrine, paracrine, or endocrine actions on the cells of their target tissues within these physiologic systems to adjust homeostasis. The introduction of exercise as a stressor to disrupt homeostasis can greatly amplify and impact the actions of these hormones. To that end, the endocrine response to an acute exercise session occurs in a progression of phases with the magnitude of the response being relative to the exercise work intensity or volume. Various physiologic mechanisms are considered responsible for these responses, although not all are completely understood or elucidated. Chronic exercise training does not eliminate the acute exercise response but may attenuate the overall effect of the responsiveness as the body adapts in a positive fashion to the training stimulus. Regrettably, an excessive intensity and/or volume of training may lead to maladaptation and is associated with inappropriate endocrine hormonal responses. The mechanisms leading to a deleterious maladaptive state are not well understood and require additional research for elucidation.

Quantitative Measures of Physical Functioning After Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Feasibility Study

BACKGROUND The safety and feasibility of the symptom-limited cardiopulmonary exercise test (CPET) and the 6-minute walk test (6MWT) has not been rigorously tested in patients with multiple myeloma (MM) after high-dose chemotherapy with autologous stem cell transplantation (ASCT), nor have correlations with patient-reported outcomes (PROs) been explored. PATIENTS AND METHODS We undertook CPET, 6MWT, and PRO assessments using standardized measurements and questionnaires in patients with MM in remission after ASCT. RESULTS A total of 22 patients who were a median of 17 months after ASCT underwent assessment. No severe adverse events were observed. Exercise capacity, measured during CPET as the peak oxygen consumption, was 17.5 ± 5.9 mL/kg/min, the equivalent of 38% ± 18% less than that for age- and sex-predicted sedentary normative values. During the 6MWT, the mean 6-minute walk distance was 500 m, or 25% ± 13% less than the predicted values. Additional analysis using Pearsons correlation revealed no significant univariate associations between exercise or functional capacity and any PROs. CONCLUSION Patients with MM have marked and significant reductions in quantitative measures of physical function for years after the initial therapy, although that did not correlate with PROs in the present pilot study. Larger prospective studies are required to determine the clinical ramifications of these findings and to mechanistically dissect them, as well to test interventions aimed at mitigating them.

Relationship Between Salivary and Serum Testosterone Levels In Response To Different Exercise Intensities

The anabolic hormone testosterone (T) continues to be researched extensively in exercise studies, with blood serum or plasma samples collected routinely. This method is considered both valid and reliable; however, the collection process can be invasive and difficult during exercise. For this reason, non-invasive sampling, such as saliva collections, is increasing in popularity. PURPOSE: To investigate the association between salivary and serum T before and after various intensities of exercise to assess the validity of saliva collection for T measurement. METHODS: 12 endurance-trained males (Mean±SD; VO2max 58.2±6.4 ml/kg/min, 22±4.6 years, BMI 21.6±1.9) completed three 30-minute exercise (cycling) sessions at 40% (Low), 60% (Moderate), and 80% (High) of VO2max as well as a 30-minute resting Control session on four separate days. Salivary (s) and serum (S) samples were assessed for T prior to (Pre), immediately post (Post), and 30 minutes post (30 Min Post) each session. RESULTS: Low exercise caused a significant (p<0.05) increase in ST, but not sT, while Moderate and High exercise caused an increase (p<0.01) in both ST and sT. A strong positive correlation (Spearman [rs]) existed between sT and ST in the Moderate (rs=0.912 [p<0.001; n=36; 12 subjects x 3 measurement times-samples]), and High (rs=0.898 [p<0.001]) sessions, but not as strong for the Low (rs=0.517 fp=0.001]) session. CONCLUSIONS: These results suggest that sT and ST levels are strongly associated to exercise. However, the exercise-related sT and ST responses-changes were more closely aligned at Moderate and High intensities, suggesting a greater validity between the saliva and serum responses to higher intensity exercise.

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.

Assessing biological maturity: chronological age and the pubertal development scale predict free testosterone in adolescent males

Abstract Background: Pubertal development status has implications for development of physical characteristics, performance, and injury risk in school-aged athletes. Objective: The objective of this study was to evaluate the ability of non-invasive measures of biological maturity to predict salivary free testosterone. Participants: A total of 61 physically active males (ages 6–16) participated in this study. Methods: Participants had their anthropometrics measured, completed the Pubertal Development Scale (PDS), and reported their birthdays and the heights of their biological parents. Exact chronological age and percent of predicted height were calculated. Resting salivary samples were collected and assessed for free testosterone levels using enzyme-linked immunosorbent assay procedures. Variables were entered into a stepwise linear regression to predict free testosterone. Results: The regression model was statistically significant (R2=0.716, F2,61=74.2, p<0.005) with chronological age (β=0.66, t60=7.587, p<0.005) and PDS (β=0.26, t60=3.02, p=0.004) remaining as significant predictors of free testosterone. Conclusions: Chronological age and PDS adequately predict salivary free testosterone levels in school-aged males and may be an appropriate tool to evaluate physical maturity in school-aged males quickly, cheaply, and accurately.

Exercise augments the nocturnal prolactin rise in exercise-trained men

Objective: The objective of this study was to profile over a 24 h period the prolactin responses of exercise-trained men on a day involving rest with no exercise in comparison to a day involving exercise training sessions. Methods: This is a quasi-experimental design study using repeated measures determination of 24 h prolactin responses in exercise-trained men (n = 16; age = 27.3± 3.3 years (mean ± standard deviation)). Blood samples were taken hourly over a 24 h period on a day involving two intensive exercise training sessions (ED), and on a separate control day (CD) with no exercise activity. The order of the ED and CD was randomized. Physical activity and diet were controlled and replicated for the ED and CD. Blood specimens were handled, prepared and analyzed utilizing appropriate standard clinical practices. The data were analyzed with the Friedman analysis of variance and Nemenyi post hoc statistical procedure for repeated measures. Results: On the CD, prolactin displayed a typical circadian rhythm with daytime values of the hormone being less than the nocturnal rise once sleep had begun (p < 0.05; 16:00–20:00 h > all other times). On the ED, prolactin responses were noticeably different from those of the CD. The morning and afternoon exercise sessions included significant increases in prolactin immediately at the end of the exercise sessions, being greater than corresponding CD time points (p < 0.01; 01:00 h and 10:00 h); also for the second hour (2 h) following the morning exercise session. On the ED there was a displayed circadian nocturnal response in the hormone with 16:00–24:00 h being elevated above the all nonexercise effected values for that specific day (p < 0.01). Finally, the ED nocturnal elevation for prolactin for 16:00–24:00 h was significantly greater than the same respective hours on the CD (p < 0.05). Conclusion: Findings clearly demonstrated that nocturnal prolactin responses are augmented in exercise-trained men on days when they perform exercise. The mechanisms inducing this adaptive response are unclear but warrant further investigation.

Exercise training biomarkers: Influence of short-term diet modification on the blood lactate to rating of perceived exertion (La:RPE) ratio

This study examined the effect of dietary consumption of carbohydrates (CHO) on the blood lactate to rating of perceived exertion (La:RPE) ratio during an intense micro-cycle of exercise training. This ratio is a proposed biomarker of exercise training stress and potential indicator for under- or overtraining in athletes. Sixteen male athletes were randomly assigned into two groups; high CHO (H-CHO; 60% of daily caloric intake) and low CHO (L-CHO; 30% of daily caloric intake). Diets were controlled the day before and for the three days of the micro-cycle. The micro-cycle consisted of three successive days of 60 minutes of intense cycling (∼70% of VO2peak). Blood samples were obtained immediately before and after exercise (post) on each day of exercise training (D1, D2, D3) and were analyzed for blood lactate. Rating of perceived exertion (RPE) scores were taken at the end of each exercise session and combined with the post exercise lactate value to form the La:RPE ratio. An analysis of variance (ANOVA) showed a significant difference between the La:RPE ratio for the H-CHO and L-CHO groups at D3 even though the exercise intensity was not significantly different between the groups. Specifically, the ratio was significantly (p < 0.02) lower on D3 in the L-CHO group (∼31% lower) than in the H-CHO group. From these findings it is recommended that diet needs to be monitored when using the La:RPE ratio as an exercise training biomarker to determine whether an athlete is truly under-training or overtraining. Athletes or coaches that use the La:RPE ratio as a training biomarker, but do not monitor dietary CHO intake need to interpreted their findings carefully.