Risk and Temporal Changes of Heart Failure Among 5‐Year Childhood Cancer Survivors: a DCOG‐LATER Study

Abstract

Background Heart failure is one of the most important late effects after treatment for cancer in childhood. The goals of this study were to evaluate the risk of heart failure, temporal changes by treatment periods, and the risk factors for heart failure in childhood cancer survivors ( CCS ). Methods and Results The DCOG‐LATER (Dutch Childhood Oncology Group–Long‐Term Effects After Childhood Cancer) cohort includes 6,165 5‐year CCS diagnosed between 1963 and 2002. Details on prior cancer diagnosis and treatment were collected for this nationwide cohort. Cause‐specific cumulative incidences and risk factors of heart failure were obtained. Cardiac follow‐up was complete for 5,845 CCS (94.8%). After a median follow‐up of 19.8 years and at a median attained age of 27.3 years, 116 survivors developed symptomatic heart failure. The cumulative incidence of developing heart failure 40 years after childhood cancer diagnosis was 4.4% (3.4%–5.5%) among all CCS. The cumulative incidence of heart failure grade ≥3 among survivors treated in the more recent treatment periods was higher compared with survivors treated earlier (Gray test, P =0.05). Mortality due to heart failure decreased in the more recent treatment periods (Gray test, P =0.02). In multivariable analysis, survivors treated with a higher dose of mitoxantrone or cyclophosphamide had a higher risk of heart failure than survivors who were exposed to lower doses. Conclusions CCS treated with mitoxantrone, cyclophosphamide, anthracyclines, or radiotherapy involving the heart are at a high risk for severe, life‐threatening or fatal heart failure at a young age. Although mortality decreased, the incidence of severe or life‐threatening heart failure increased with more recent treatment periods.

Major cardiac events for adult survivors of childhood cancer diagnosed between 1970 and 1999: report from the Childhood Cancer Survivor Study cohort

“…Notably, the risk for heart failure was observed to further decrease from the 1980s into the 1990s, suggesting a favorable trend. In contrast, Dutch investigators recently reported that survivors from the 1970s had a lower cumulative incidence of heart failure compared with those treated in the 1980s and 1990s 22. However, the temporal pattern of reduction in exposure to radiotherapy (defined as maximum prescribed heart dose) in Dutch survivors was of a smaller magnitude (with no chest radiotherapy ranging from 65.6% in the 1970s to 82.2% in the 1990s) than in the Childhood Cancer Survivor Study cohort (ranging from 23% to 60%) utilizing detailed heart dosimetry measurements.…”

The support of genetic evidence for cardiovascular risk induced by antineoplastic drugs

“…In addition to the above global evaluations, we also illustrated some of our predictions for well-established and frequently used antineoplastic drugs with known cardiovascular side effects. As the most common chemotherapy approach, anthracycline-involved treatment improves overall survival but may induce severe or life-threatening heart failure in some individuals ( 5 , 60 ). Mechanistically, anthracycline can cause dose-dependent cardiotoxicity by redox cycling and free-radical formation mediated by topoisomerase-IIβ ( 6 , 7 ).…”

5 years of experience with DIBH (Deep inspiration breath-hold) combined with SGRT (Surface-Guided Radiation Therapy) in left-sided breast cancer

“…The common clinical complications are asymptomatic pericarditis, congestive heart failure, and heart infarction. Even though clinicians have to give particular attention to these complications, anthracycline treatment [60][61][62]) is an additional major risk factor for additional cardiotoxicity during radiotherapy with a synergistic effect. However, the use of anthracycline, other cardiotoxic chemotherapies, immunotherapy [63][64][65] and targeted therapies [66,67] should only be used with great caution and only after carrying out a careful treatment plan and optimization [1,30,40].…”