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

Abstract

ObjectiveTo investigate the impact of modifications to contemporary cancer protocols, which minimize exposures to cardiotoxic treatments and preserve long term health, on serious cardiac outcomes among adult survivors of childhood cancer.DesignRetrospective cohort study.Setting27 institutions participating in the Childhood Cancer Survivor Study.Participants23 462 five year survivors (6193 (26.4%) treated in the 1970s, 9363 (39.9%) treated in the 1980s, and 7906 (33.6%) treated in the 1990s) of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft tissue sarcomas, and bone sarcomas diagnosed prior to age 21 years between 1 January 1970 and 31 December 1999. Median age at diagnosis was 6.1 years (range 0-20.9) and 27.7 years (8.2-58.3) at last follow-up. A comparison group of 5057 siblings of cancer survivors were also included.Main outcome measuresCumulative incidence and 95% confidence intervals of reported heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias by treatment decade. Events were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Multivariable subdistribution hazard models were used to estimate hazard ratios by decade, and mediation analysis examined risks with and without exposure to cardiotoxic treatments.ResultsThe 20 year cumulative incidence of heart failure (0.69% for those treated in the 1970s, 0.74% for those treated in the 1980s, 0.54% for those treated in the 1990s) and coronary artery disease (0.38%, 0.24%, 0.19%, respectively), decreased in more recent eras (P<0.01), though not for valvular disease (0.06%, 0.06%, 0.05%), pericardial disease (0.04%, 0.02%, 0.03%), or arrhythmias (0.08%, 0.09%, 0.13%). Compared with survivors with a diagnosis in the 1970s, the risk of heart failure, coronary artery disease, and valvular heart disease decreased in the 1980s and 1990s but only significantly for coronary artery disease (hazard ratio 0.65, 95% confidence interval 0.45 to 0.92 and 0.53, 0.36 to 0.77, respectively). The overall risk of coronary artery disease was attenuated by adjustment for cardiac radiation (0.90, 0.78 to 1.05), particularly among survivors of Hodgkin lymphoma (unadjusted for radiation: 0.77, 0.66 to 0.89; adjusted for radiation: 0.87, 0.69 to 1.10).ConclusionsHistorical reductions in exposure to cardiac radiation have been associated with a reduced risk of coronary artery disease among adult survivors of childhood cancer. Additional follow-up is needed to investigate risk reductions for other cardiac outcomes.Trial registrationClinicalTrials.gov NCT01120353.

Falling risk of heart disease among survivors of childhood cancer

“…This was principally due to a strong decline among survivors of Hodgkin lymphoma. They also report evidence suggesting a decline in the risk of heart failure among patients treated in the 1990s, although it was not statistically significant 5. Risk of the other cardiac outcomes remained unchanged after adjustment for confounding.…”

“…Importantly, Mulrooney and colleagues explored the joint effects of anticancer treatment and traditional cardiac risk factors, adjusting for all other available explanatory risk factors. Dyslipidaemia and hypertension remained strongly and independently associated with most cardiac outcomes, providing important insights to help inform preventative interventions for cancer survivors 5…”

“…Using data from the Childhood Cancer Survivor Study (CCSS), based in the United States and Canada, the authors explored whether changes in anticancer treatment have had a measurable impact on the risk of cardiac conditions among survivors 5. The CCSS is a hospital based retrospective cohort study including more than 23 000 participating survivors of the most common childhood cancers diagnosed before age 21, and treated in the 1970s, 1980s, or 1990s.…”

“…Cumulative anthracycline doses were abstracted from hospital records. Mean radiation dose to the heart was estimated by reconstructing individual radiotherapy treatments using age specific computerised phantoms 5…”

“…The investigators undertook a mediation analysis to determine whether there was evidence that any of the decline in risk could be attributable to changes in specific anticancer treatments received during the period between 1970 and 1999. Reductions in radiotherapy exposure appear to account for some of the decline 5…”