Circulating microRNAs and Cytokines as Prognostic Biomarkers for Doxorubicin-Induced Cardiac Injury and for Evaluating the Effectiveness of an Exercise Intervention.

PURPOSE: To define a set of biomarkers that can be used to identify patients at high risk of developing late doxorubicin (DOX)-induced cardiac morbidity with the goal of focused monitoring and early interventions. EXPERIMENTAL DESIGN: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 hours), cytokines (24 hours), and troponin (24 hours, 4 and 6 weeks). Cardiac function was evaluated using echocardiography before and 24 hours after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples were collected from mice treated with DOX or DOX + exercise. Plasma samples from 13 DOX-treated patients with sarcoma were also evaluated before and 24 hours after therapy. RESULTS: Elevations in plasma miRNA-1, miRNA-499 and IL1α, IL1ß, and IL6 were seen in DOX-treated mice with decreased ejection fraction and fractional shortening 24 hours after DOX therapy. Troponin levels were not elevated until 4 weeks after therapy. In mice treated with exercise during DOX, there was no elevation in these biomarkers and no change in cardiac function. Elevations in these biomarkers were seen in 12 of 13 patients with sarcoma treated with DOX. CONCLUSIONS: These findings define a potential set of biomarkers to identify and predict patients at risk for developing acute and late cardiovascular diseases with the goal of focused monitoring and early intervention. Further studies are needed to confirm the predictive value of these biomarkers in late cardiotoxicity.

Feasibility and Acceptability Findings of an Energy Balance Data Repository of Children, Adolescents, and Young Adults with Cancer.

Cancer patients suffer changes in energy balance (EB), the combination of energy intake (nutrition) and energy expenditure (physical activity (PA)), which may influence cancer-related morbidity, mortality, and quality of life. Significant gaps remain in our understanding of the frequency and magnitude of these EB changes. Herein, we report on the feasibility and acceptability of a longitudinal repository of EB outcomes in children, adolescents and young adults (AYA) with cancer along the cancer continuum to fill these gaps. This EB repository includes PA, nutrition, and physical function (PF) parameters. PA data were gathered through activity trackers. Nutritional data were gathered through food diaries and micronutrient labs. PF was assessed with validated objective and patient-reported measures. Feasibility was achieved with >50% enrollment of eligible patients (n = 80, Mage = 18.1 ± 7.5); 26 were children with cancer and 54 were AYAs with cancer. An 88.75% retention rate indicated acceptability. Despite COVID-19 disruptions, >50% of participants provided completed data for PA and micronutrient labs as of April 2020. Food diaries and PF data collection experienced disruptions. Methodological adaptations are in progress to minimize future disruptions. Overall, our findings demonstrate that prospective EB assessments are feasible and acceptable among children and AYAs with cancer.