Teske, Arco J.

Objective Animal data suggest that exercise during chemotherapy is cardioprotective, but clinical evidence to support this is limited. This study evaluated the effect of exercise during chemotherapy for breast cancer on long-term cardiovascular toxicity. Methods This is a follow-up study of two previously performed randomised trials in patients with breast cancer allocated to exercise during chemotherapy or non-exercise controls. Cardiac imaging parameters, including T1 mapping (native T1, extracellular volume fraction (ECV)), left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), cardiorespiratory fitness, and physical activity levels, were acquired 8.5 years post-treatment. Results In total, 185 breast cancer survivors were included (mean age 58.9±7.8 years), of whom 99% and 18% were treated with anthracyclines and trastuzumab, respectively. ECV and Native T1 were 25.3%±2.5% and 1026±51 ms in the control group, and 24.6%±2.8% and 1007±44 ms in the exercise group, respectively. LVEF was borderline normal in both groups, with an LVEF<50% prevalence of 22.5% (n=40/178) in all participants. Compared with control, native T1 was statistically significantly lower in the exercise group (β=−20.16, 95% CI −35.35 to −4.97). We found no effect of exercise on ECV (β=−0.69, 95% CI −1.62 to 0.25), LVEF (β=−1.36, 95% CI −3.45 to 0.73) or GLS (β=0.31, 95% CI −0.76 to 1.37). Higher self-reported physical activity levels during chemotherapy were significantly associated with better native T1 and ECV. Conclusions In long-term breast cancer survivors, exercise and being more physically active during chemotherapy were associated with better structural but not functional cardiac parameters. The high prevalence of cardiac dysfunction calls for additional research on cardioprotective measures, including alternative exercise regimens. Trial registration number NTR7247.

BACKGROUND: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry. METHODS: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative. RESULTS: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment. CONCLUSIONS: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.

12081 Background: A common conception is that exercise training is cardioprotective for patients with breast cancer receiving adjuvant chemotherapy, but evidence to support this assertion is limited. This study aims to evaluate the effect of exercise training during adjuvant chemotherapy for breast cancer on long-term structural and functional cardiac outcomes. Methods: This is a follow-up study of two previously performed randomized studies in breast cancer patients; the PACT (N = 204) and PACES (N = 230) study. Cardiac outcomes, including extracellular volume fraction (ECV), left ventricular ejection fraction (LVEF) on cardiac MRI and global longitudinal strain (GLS) on echocardiography, were evaluated in patients allocated to moderate-to high-intensity exercise and non-exercise controls using linear and logistic regression models, adjusted for relevant confounders. Additionally, we explored the influence of self-reported PA during chemotherapy on cardiac outcomes, regardless of treatment allocation. Results: In total, 185 breast cancer survivors were included (mean age 58.9±7.8 years, mean time since treatment 8.5±1.1 years). Mean ECV was 25.3±2.5 in the control group and 24.6±2.8 in the exercise group. Mean LVEF was borderline normal in both (54.6±4.9 and 53.0±7.8) with an LVEF < 50% of 17.1% and 27.8% in control and exercise group, respectively. Compared to control, no significant effect of exercise during chemotherapy on ECV (β = -0.61, 95%CI: -1.55;0.32) or on abnormal ECV (OR = 0.80, 95%CI: 0.26;2.45) was found. Native T1 was statistically significantly lower in the exercise group compared to control (β = -16.75%CI: -31.5 ;-1.93). The odds of having an abnormal native T1 appeared lower in the exercise group (OR 0.58, 95%CI: 0.28;1.17). We found no benefit of exercise for LVEF or GLS (β = -1.82, 95%CI: -4.06;0.42 and β = 0.21, 95%CI: -0.87;1.28), nor on the likelihood of having an abnormal LVEF or GLS (OR = 1.78, 95%CI: 0.79;4.16); OR = 1.21, 95%CI: 0.56;2.63), respectively. Higher self-reported physical activity levels during chemotherapy tended to be associated with better cardiac outcomes. Conclusions: Exercise training during chemotherapy was not associated with long-term cardioprotection in patients with early-stage breast cancer. The high prevalence of cardiac abnormalities years post-chemotherapy suggests the need to include cardiac assessment in long-term follow-up programs for breast cancer survivors and calls for more research on cardioprotective measures during adjuvant chemotherapy, including alternative exercise dosing regimens and pharmacological adjuncts. Clinical trial information: NTR7247.