Exposure to anthracyclines reduced LVEF by 0.83% per 100 mg/m² and male sex reduced LVEF by 1.37% compared to females; 7.2% of childhood cancer survivors had reduced LVEF with no significant change over 4.3 years follow-up.
Cohort (n=487)
Yes
Does exposure to specific anticancer treatments (anthracyclines, radiotherapy) reduce LVEF in adult childhood cancer survivors compared to other systemic therapies?
In adult survivors of childhood cancer, reduced LVEF is present in 7.2% and is strongly associated with cumulative anthracycline dose, though cardiac function appears stable over a medium-term 4-year follow-up.
Effect estimate: β coefficient -0.83 per 100 mg/m² cumulative anthracycline dose; β coefficient -1.37 for male sex (95% CI 95% CI -1.20 to -0.45 for anthracycline dose; 95% CI -2.36 to -0.37 for male sex)
Absolute Event Rate: 7.2% vs 6.1%
p-value: p=<0.001 for anthracycline; 0.01 for male sex
Childhood cancer survivors (CCS) are at risk for cardiac late effects. Echocardiographic assessment of cardiac function by left ventricular ejection fraction (LVEF) is recommended for survivors treated with known cardiotoxic treatments (anthracyclines; heart-relevant radiotherapy). The evidence on cardiotoxicity of other systemic anticancer therapies is conflicting and longitudinal changes in heart function are understudied. We assessed cardiac function in CCS; factors associated with LVEF and longitudinal changes in LVEF. In this ongoing prospective, multicenter cohort study, we invited CCS aged ≥ 18 years, diagnosed < 21 years, survived ≥ 5 years, and received any systemic anticancer therapy or heart-relevant radiotherapy between 1976 and 2019. We invited them for an echocardiographic assessment including 2-dimensional LVEF (reduced LVEF: <54% for females; <52% for males). We stratified CCS in anthracyclines only, heart-relevant radiotherapy only, both, and a standard risk group exposed to any other systemic anticancer treatment and compared groups using ANOVA- and t-tests. We performed multivariable linear regression to investigate sociodemographic, treatment-, and lifestyle-related factors (hypertension, smoking, dyslipidemia, diabetes, overweight/obesity), and multilevel modelling to assess LVEF changes over time. We assessed 487 CCS (median age: 32 years, IQR: 24–39) with a median time since diagnosis of 24 years (IQR 17‒31). Overall prevalence of reduced LVEF was 7.2% (35/487), 7.3% (19/260) for anthracyclines only, 3.6% (1/28) for heart-relevant radiotherapy only, 9.4% (8/85) for both, and 6.1% (7/114) for the standard risk group. Male CCS were at risk for reduced LVEF β coefficient for male sex = -1.37; 95%CI -2.36, -0.37, and higher cumulative anthracycline dose (per 100 mg/m²) was associated with reduced LVEF (β − 0.83; 95%CI − 1.20, − 0.45). Heart-relevant radiotherapy, other systemic anticancer treatments, and lifestyle were not associated with LVEF. We found a slight annual improvement of LVEF 0.24% among 140 participants followed up for a median of 4.3 years, however, there was no indication of statistical significance (p = 0.12). This first Swiss study found that a substantial proportion of survivors had reduced LVEF, especially males and those treated with anthracyclines. While cardiac function appeared stable over a four-year period, long-term changes remain uncertain, emphasizing the importance of ongoing cardiac surveillance in this vulnerable population.
Fankhauser et al. (Tue,) conducted a cohort in Adult childhood cancer survivors aged ≥18 years, diagnosed before age 21, survived ≥5 years, treated with systemic anticancer therapy and/or heart-relevant radiotherapy (n=487). Exposure to anthracyclines and/or heart-relevant radiotherapy and other systemic anticancer treatments vs. Standard risk group treated with other systemic anticancer treatments excluding anthracyclines and heart-relevant radiotherapy was evaluated on Prevalence and longitudinal change of reduced left ventricular ejection fraction (LVEF), defined as <54% for females and <52% for males (β coefficient -0.83 per 100 mg/m² cumulative anthracycline dose; β coefficient -1.37 for male sex, 95% CI 95% CI -1.20 to -0.45 for anthracycline dose; 95% CI -2.36 to -0.37 for male sex, p=<0.001 for anthracycline; 0.01 for male sex). Exposure to anthracyclines reduced LVEF by 0.83% per 100 mg/m² and male sex reduced LVEF by 1.37% compared to females; 7.2% of childhood cancer survivors had reduced LVEF with no significant change over 4.3 years follow-up.