BACKGROUND AND AIMS
Almost two-thirds of the 35,000 children diagnosed with cancer in Europe each year are treated with anthracycline chemotherapy.1 Despite improved survival rates, this therapy is responsible for symptomatic heart failure in up to 10% of patients decades after treatment.2 Furthermore, emerging evidence suggests that the late effects of the drug extend beyond systolic impairment.3,4
MATERIALS AND METHODS
Queen’s University Belfast, UK, conducted a study of 86 adult survivors of childhood cancer who were treated with over 100 mg/m2 doxorubicin equivalent. Each participant completed a 36-Item Short Form Health Survey (SF36) questionnaire to assess quality of life compared with Irish normative data.5,6 A 6-minute walk test (6MWT) was performed, and per cent predicted values were calculated, adjusted for age, sex, weight, and height.7,8 Cardiac biomarker analysis (wide-range C-reactive protein [wrCRP], N-terminal prohormone of brain natriuretic peptide, and troponin T), and cardiac imaging with echocardiography and MRI were performed.
Of the 86 survivors of childhood cancer studied, 55% were male, with an average age of 28 years (range: 18–53 years). The average anthracycline dose administered was 270 mg/m2 (108–705 mg/m2).
Echocardiography demonstrated that 16% had an ejection fraction of <53%, and 29% had a global longitudinal strain of <-18%. A noteworthy 70% of these survivors achieved the National Health Service (NHS) exercise benchmarks.9
Cardiorespiratory fitness, as measured by 6MWT, was below the lower limit of normal (<80% predicted) in 40% (34) of patients. In terms of quality of life, survivors of childhood cancer consistently underperformed against the standard, especially in general health (abnormal in 20% of participants), mental health (16%), and physical functioning (13%). Wide range C-reactive protein fell within the low cardiovascular risk category (<1 mg/L) in 31 patients, medium risk (1–3 mg/L) in 27 patients, and high risk (>3 mg/L) in 28 of the 86 patients.10
RESULTS
Outcomes varied by exercise habit. Inactive survivors of childhood cancer displayed abnormal wrCRP levels (p=0.002), underperformed in the 6MWT (p=0.002), and showed diminished indexed stroke volumes in MRI results (p=0.015) compared with participants who undertook regular exercise. A positive relationship was observed between the amount of exercise (measured in minutes per week) and improved 6MWT, fractional shortening, and septal E/e’ (all p<0.05). Those engaging in intense physical activity exhibited improved outcomes in 6MWT and quality of life metrics, as well as reduced frailty, wrCRP, N-terminal prohormone of brain natriuretic peptide, and global longitudinal strain (all p<0.05).
CONCLUSION
In conclusion, anthracycline chemotherapy treatment for childhood cancer is associated with abnormal cardiac imaging, but also an increased prevalence of impaired cardiorespiratory fitness, inflammation, and impaired quality of life in every domain. It remains uncertain whether sedentary behaviour results from cardiotoxicity, or if exercise counteracts its effects. This field warrants further exploration.
