Study: 4% of childhood cancer survivors develop heart failure within 40 years

Although childhood cancer survival has improved markedly over the past few decades, a new study out of the Netherlands suggests a greater proportion of those survivors are at risk of developing heart failure at young ages, due in part to cardiotoxic treatments.

“As a result of better survival over the years, the survivor population continues to grow in size,” lead author E. A. M. Feijen, PhD, with the University of Amsterdam, and colleagues wrote in the Journal of the American Heart Association. “It is known that 75% of CCS (childhood cancer survivors) will develop at least a chronic health condition, and among those aged 45 years, 80.5% of survivors will have a serious/disabling or life‐threatening health condition.”

Previous studies have shown the cumulative incidence of symptomatic heart failure 30 years after a childhood cancer diagnosis to range from 2.7 to 4.1 percent, while another found 27 percent of survivors treated with cardiotoxic agents had asymptomatic heart failure 15 years after their cancer diagnosis.

To examine how the risk of CCS developing heart failure has changed over time—as well as the risk associated with specific treatments—Feijen et al. analyzed a Dutch cohort of five-year childhood cancer survivors who were diagnosed between 1963 and 2001. The researchers followed 5,845 CCS for a median of 19.8 years until they were about 27 years old on average.

A total of 116 patients—or 2 percent—developed symptomatic heart failure during follow-up, but Feijen and colleagues also constructed models estimating the incidence of heart failure 40 years after a childhood cancer diagnosis, adjusted for the patient’s sex and age at diagnosis as well as the year of diagnosis.

The estimated incidence of heart failure 40 years postdiagnosis was 4.4 percent, with the cumulative incidence of heart failure grade 3 or worse growing in more recent treatment periods.

The authors said the increased use of anthracyclines and mitoxantrone could explain why CCS diagnosed at a later date showed a greater risk of developing heart failure. But they also said clinicians may have become more precise in recent eras in diagnosing and documenting CCS with heart failure.

Treatment with anthracyclines and mitoxantrone, in particular, was associated with higher risks for developing heart failure, and a dose-response relationship was observed with the latter chemotherapy drug as well as cyclophosphamide.

“Our results showed no safe dose for anthracyclines,” Feijen and coauthors wrote. “This finding and the statistically significant association and dose‐response relationship of mitoxantrone with symptomatic heart failure underscore the need for primary prevention (such as avoiding cardiotoxic treatment), the use of lower doses of cardiotoxic treatments in children with cancer, and considering alternatives to mitoxantrone in new treatment protocols for children with cancer.”

Radiotherapy involving the heart was associated with double the risk of developing heart failure, but the authors noted the correlation was even stronger for chemotherapy than radiotherapy. Feijen et al. called for physicians to be especially vigilant in monitoring CCS for signs of heart failure, even at relatively young ages, and suggested guidelines be updated to help clinicians manage patients who have already been treated with these cardiotoxic therapies.