Dose Delays, Dose Reductions, and Relative Total Dose Intensity in Patients With Advanced Cancer Who Exercised During Neoadjuvant Chemotherapy Treatment.

BACKGROUND: When it comes to chemotherapy, maintaining the dose and schedule of treatment are of vital importance, as clinical evidence suggests that dose intensity is associated with optimal treatment outcomes for various tumors. Yet, reduced dose intensity is a common method of mitigating the chemotherapy-induced side effects. Exercise has been shown to attenuate chemotherapy-related symptoms that frequently cluster together. Understanding this, we conducted a retrospective analysis in patients with advanced disease treated with adjuvant or neoadjuvant chemotherapy regimens and who completed exercise training during treatment. METHODS: Data were collected retrospectively in a chart review of 184 patients, aged 18 years or older and treated for Stage IIIA-IV cancer. Data collection included baseline patient demographics and clinical characteristics, including age at diagnosis, cancer stage at initial diagnosis, chemotherapy regimen, and planned dose and schedule. Cancer types included brain (6.5%), breast (35.9%), colorectal (8.7%), non-Hodgkin's lymphoma (7.6%), Hodgkin's lymphoma (11.4%), non-small cell lung (16.8%), ovarian (10.9%), and pancreatic (2.2%). All patients completed at least 12 weeks of prescribed, individualized exercise. Each program included cardiovascular, resistance training, and flexibility components, under the supervision of a certified exercise oncology trainer once a week. RESULTS: RDI was measured for each myelosuppressive agent in a regimen over the entire chemotherapy course and then averaged across the myelosuppressive agents in a regimen. An RDI of less than 85% was designated as the clinically meaningful threshold for reduction in RDI based on previously published studies. CONCLUSIONS: A considerable proportion of patients across regimens had dose delays (18.3%-74.3%) and dose reductions (18.1%-84.6%). Between 12% and 83.9% of patients missed at least 1 dose of a myelosuppressive agent that was part of their standard regimen. Overall, 50.8% of patients received less than 85% of the RDI. In short, patients with advanced cancer and an exercise adherence above 84.3% saw fewer chemotherapy dose delays and dose reductions. These delays and reductions occurred significantly less frequently compared to the published norms in the sedentary population (P < .05).

Patient Comments on a Hospital- and University-Based Exercise Oncology Program.

The purpose of this study was to identify referral source and patient-reported factors that promoted follow-through and participation in exercise oncology rehabilitation programs. A three question open-ended survey was administered to patients enrolled in trainer-supervised, hospital-based (n = 101), or university-based (n = 17) cancer rehabilitation program that provided 12 weeks of individualized one on one aerobic and resistance training 1-3 days per week. Significant themes for each question were as follows: Question #1. Who referred you to the program/facility? Oncology team (Χ2 = 145.814 P ≤ 0.001); Question #2. What convinced you to follow through with the referral? Health, fatigue, and need for supervision (Χ2 = 74.814 P ≤ 0.001); and Question #3. What motivates you to continue in the program? Personal results, getting healthy, and the trainer (Χ2 = 108.729 P ≤ 0.001). In this study, oncology team referral confirms previous work. Patient follow-through and continuation appear largely self-motivated as patients' health and the attainment of health through personal results are primary motivators for continuation in the program. Question #3 responses note the importance of the trainer in maintaining continuation in an exercise oncology rehabilitation program.

Cost-Savings Analysis of an Individualized Exercise Oncology Program in Early-Stage Breast Cancer Survivors: A Randomized Clinical Control Trial.

PURPOSE: In an attempt to promote the integration of exercise oncology as a standard part of clinical practice, economic evaluations are warranted. Thus, the purpose of this study was to prospectively analyze cost savings of an individualized exercise oncology program when patients were randomly assigned. METHODS: For this open-label, randomized, prospective, comparative clinical trial, patients with early-stage breast cancer (stage I-II) were randomly assigned into two groups: the control group (CG, n = 120) and the exercise training group (EX, n = 123). Patients in the exercise intervention group completed 12 weeks of prescribed, individualized exercise that aligned with ACSM exercise guidelines for cancer survivors. The CG received the current standard of care, which includes a resource guide with various options available to the cancer survivor. RESULTS: In the EX group, all physical fitness measures significantly improved compared with baseline (P < .001), while remaining unchanged for the CG (P > .05). Patients in the CG had the highest total mean health care utilization across all measures (CG: $8,598 US dollars, compared with EX: $6,356 US dollars) for emergency visits, outpatient visits, and office-base visits that were not a part of their treatment plan. At baseline, the mean Eastern Cooperative Oncology Group (ECOG) scores did not significantly differ (P > .05); however, at follow-up, a larger proportion of the EX group had ECOG scores of 0 or 1, compared with the CG (P < .05). Finally, patient-reported outcomes were significantly higher in the exercise group, compared with the CG at the 12-week follow-up (P < .001). CONCLUSION: A supervised, individualized 12-week exercise intervention led to significant improvements in fitness parameters and ECOG scores, as well as a decrease in unplanned health care utilization among early-stage breast cancer survivors.

Measuring the Feasibility and Effectiveness of an Individualized Exercise Program Delivered Virtually to Cancer Survivors.

ABSTRACT: In the spring of 2020, we faced a global pandemic that resulted in social distancing limitations not previously experienced, forcing practitioners to adapt exercise programming to a virtual model. The purpose of this investigation was to measure the effectiveness of a virtual exercise oncology program in 491 participants undergoing antineoplastic therapy between March and June 2020. Each session was completed virtually with a certified exercise oncology trainer. Fitness and psychological parameters were measured preexercise and postexercise intervention. Overall, participants completed 4949 of 5892 prescribed exercise sessions. Patients saw increases in cardiovascular endurance (15.2%, P < 0.05), muscular endurance (18.2%, P < 0.05), flexibility (31.9%, P < 0.05), feelings of support (58.7%, P < 0.05), and quality of life (32.2%, P < 0.05), as well as decreases in loneliness (54%, P < 0.05) and fatigue (48.7%, P < 0.05). In light of our findings, we assert that virtual exercise training is a viable option in circumstances where in-person, individualized exercise training is not possible.

Cost Savings Analysis of Individualized Exercise Oncology Programs.

BACKGROUND: The physical and economic toll of cancer make it a high health priority. The rising cost of cancer care is now a primary focus for patients, payers, and providers. Escalating costs of clinical trials and national drug regulations have led the median monthly costs of cancer drugs to rise from less than $100 in 1965 to 1969, to more than $5000 in 2005 to 2009, stressing the importance of finding innovative ways to reduce cost burden. In the present study, we report the economic evaluation of an individualized exercise oncology program beginning early after diagnosis. METHODS: An independent research group, ASCEND Innovations, retrospectively analyzed patient records to statistically demonstrate the impact of exercise oncology during cancer treatment. All patients completed 12 weeks of prescribed, individualized exercise that included cardiovascular, strength training, and flexibility components. The 3 primary hospital measures leveraged for statistical comparison before and after supportive care enrollment were number of encounters, number of readmissions, and average total charges, as well as emergency room visits and length of hospital stay ( P < .05). RESULTS: The resulting dataset consisted of 1493 total hospital encounters for 147 unique patients. The results statistically demonstrate a positive effect of exercise oncology during cancer care, in terms of reductions in overall cost per patient pre- to post-intervention. CONCLUSIONS: Individualized exercise oncology programs should be employed as part of the national standard of care for individuals battling cancer, in order to improve patient outcome and reduce cost burden.

Concise review on the safety of exercise on symptoms of lymphedema.

Lymphedema is an atypical accumulation of high-protein fluid located just beneath the skin, which often occurs in the arm or leg. Exercising with lymphedema was traditionally considered to be unsafe. However, recent research indicates that exercise may be beneficial to individuals with lymphedema. Studies indicate that exercise can improve the range of motion and strength of the afflicted limb(s), as well as overall fitness and functional quality of life, and can be performed without exacerbating symptoms of lymphedema.

Ten Weeks of Home-Based Exercise Attenuates Symptoms of Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer Patients.

The purpose of this investigation was to determine if a structured, home-based exercise program was beneficial to reduce symptoms of chemotherapy-induced peripheral neuropathy and improve quality of life (QOL). A total of 50 women who are breast cancer survivors and are listed in the Breast Cancer Registry of Greater Cincinnati database were recruited by mail. Participants were initially asked to complete the McGill QOL questionnaire and the Leeds Assessment of Neuropathic Symptoms and Signs, before beginning a 10-week home-based exercise program. At the completion of the exercise program, subjects were asked again to complete the same two questionnaires. Pre- and post-intervention data were analyzed using a repeated measures ANOVA, at a significance level of α<0.05. Six individuals completed the investigation. Prior to the 10-week exercise program, participants described their pain as unpleasant skin sensations (Pre-HBEx, N=6), abnormally sensitive to touch (Pre-HBEx, N=6), and coming on suddenly in bursts for no apparent reason (Pre-HBEx, N=5). Following 10-weeks of exercise, participants reported experiencing less of these symptoms (Post-HBEx, N=3, 1, and 4 respectively; P=0.05). It was also determined that troublesome symptoms were significantly reduced after 10-weeks of home-based exercise (P=0.05).

Voluntary wheel running in rats receiving doxorubicin: effects on running activity and cardiac myosin heavy chain.

BACKGROUND: The clinical use of the highly effective chemotherapeutic agent doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. This cardiotoxicity is associated with a cardiac myosin heavy chain (MHC) isoform shift from the alpha isoform to the beta isoform. Exercise prior to DOX treatment has been shown to attenuate the MHC shift associated with DOX, but little is known about the cardioprotective nature of exercise during DOX treatment. MATERIALS AND METHODS: DOX-treated rats were assigned to normal cage activity (sedentary, SED+DOX) or 24-hour voluntary wheel running access (WR+DOX). All animals received weekly 2.5 mg/kg DOX injections for 6 weeks (15 mg/kg cumulative) and hearts were subsequently excised for determination of MHC isoform expression using sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: At baseline, WR+DOX rats on average ran 62+/-4 km, and at week 6 ran 30+/-5 km, which was significantly lower than baseline (p<0.05). SED+DOX hearts expressed 57+/-7% of MHC as the alpha-MHC isoform and 43+/-7% as the beta-MHC isoform. WR+DOX hearts expressed 76+/-4% as the alpha-MHC and 24+/-4% as the beta-MHC isoform, which was significantly different from that of SED+DOX (p<0.05). CONCLUSION: DOX treatment significantly reduced wheel running activity, but this reduced running distance deemed to be cardioprotective as hearts from WR+DOX rats contained significantly greater levels of the favorable alpha-MHC isoform than SED+DOX.

Endurance exercise training preserves cardiac function in rats receiving doxorubicin and the HER-2 inhibitor GW2974.

PURPOSE: To determine if endurance exercise training performed prior to administration of the anticancer drugs DOX and GW2974 would be cardioprotective. METHODS: Rats remained sedentary or exercise trained for 10 weeks. Following the exercise or sedentary period, rats were randomly assigned to treatment groups. Rats in sedentary and exercise groups received saline or a combination of 10 mg/kg DOX and 30 mg/kg GW2974. Cardiac function was assessed 2, 5, or 10 days following treatments. RESULTS: Sedentary animals receiving DOX/GW2974 experienced significant cardiac dysfunction. At 2-, 5-, and 10-days post, cardiac function in trained, drug-treated animals was significantly preserved. Additionally, animals exercised prior to DOX/GW2974 injections had significantly lower levels of myocardial lipid peroxidation and caspase-3 and -8 activities compared to their sedentary counterparts. CONCLUSIONS: Exercise training protected against the cardiac dysfunction associated with DOX/GW2974 administration and may be related to an inhibition in apoptotic signaling.

Trastuzumab and doxorubicin-related cardiotoxicity and the cardioprotective role of exercise.

Women diagnosed with breast cancer typically undergo a multimodal approach to treating their disease. The treatments used often result in sequelae such as fatigue, hair loss, nausea and vomiting, and functional impairment. Many of these sequelae can be controlled or eliminated with pharmacological, physical, or social interventions. However, 2 effective cytotoxic agents, doxorubicin and trastuzumab, are associated with a potentially life-threatening sequela, cardiotoxicity. Currently, these agents are dosage and duration limited to circumvent cardiac damage. Exercise prior to and during the administration of these agents is emerging as a possible cardioprotective intervention based on the findings of animal model studies. Incorporating exercise into the breast cancer treatment trajectory may eliminate the dosage and duration restrictions of these antineoplastic agents and ultimately affect survival and quality of life. The authors present the pharmacological mechanism for each agent and the exciting results of animal model studies that lay the groundwork for future clinical trials.

Acute exercise protects against doxorubicin cardiotoxicity.

UNLABELLED: Numerous methods have been used to minimize the cardiotoxic effects of the chemotherapeutic agent doxorubicin (DOX), and most have had limited success. Chronic endurance exercise has been shown to protect against DOX cardiotoxicity, but little is known regarding the effects of acute exercise on DOX-induced cardiac dysfunction. PURPOSE: The purpose of this study was to determine the effects of a single bout of acute endurance exercise on the cardiac dysfunction associated with DOX treatment. METHODS: Male Sprague-Dawley rats either performed an acute exercise bout on a motorized treadmill for 60 minutes at a maximal speed of 25 m/min with a 5% grade (EX) or remained sedentary (SED) 24 hours before receiving either a 15-mg/kg DOX bolus dose or saline (SAL). Cardiac function was then analyzed 5 days post injection using a Langendorff isolated perfused heart model. In addition, myocardial lipid peroxidation was analyzed as an indicator of oxidative stress. RESULTS: Doxorubicin treatment alone (SED+DOX) promoted a significant decline in end-systolic pressure (-35%), left ventricular developed pressure (-59%), and the maximal rate of left ventricular pressure development (-43%) as well as a 45% increase in lipid peroxidation products when compared with SED+SAL (P<.05). Acute exercise 24 hours before DOX treatment, however, had a cardioprotective effect, as end-systolic pressure, left ventricular developed pressure, and the maximal rate of left ventricular pressure development were significantly higher in EX+DOX compared with SED+DOX (P<.05) and EX+DOX had similar levels of lipid peroxidation products as SED+SAL CONCLUSIONS: An acute exercise bout performed 24 hours before DOX treatment protected against cardiac dysfunction, and this exercise-induced cardioprotection may partly be explained by a reduction in the generation of reactive oxygen species.

Time-course of changes in cardiac function during recovery after acute exercise.

Exercise-induced cardiac dysfunction (EICD) has been observed immediately following exhaustive exercise in trained individuals, but limited and conflicting data are available regarding EICD in a previously untrained population days after an exhaustive exercise bout. The purpose of this study was to examine the effects of a single bout of acute exercise on cardiac function during the 72 h after exercise and identify potential contributing mechanisms. After completing an acute exercise bout on a motorized treadmill (25 m/min, 5% grade, 60 min), rats were sacrificed immediately, 24 h, 48 h, or 72 h after the exercise bout. At the scheduled time of sacrifice, hearts were isolated and perfused for determination of ex vivo cardiac function, and examined for malondialdehyde (MDA), a lipid peroxidation index, and antioxidant potential (AOP). During the 48 h post exercise, left ventricular developed pressure decreased by 30%, dP/dtmax declined by 37%, and dP/dtmin showed a 34% decrease (p<0.05). By 72 h, cardiac function had returned to control levels. MDA was increased immediately after the exercise bout and at the 24 and 48 h intervals (p<0.05). Conversely, AOP progressively decreased at the 24 and 48 h intervals. As with cardiac function, MDA and AOP had returned to control levels by 72 h post-exercise. These data indicate that a single bout of prolonged, moderately intense exercise performed by previously sedentary rats impaired cardiac function for up to 48 h. This decrement in cardiac function was associated with increased lipid peroxidation and decreased antioxidant potential.