ve To 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. Design Retrospective cohort study. Setting 27 institutions participating in the Childhood Cancer Survivor Study. Participants 23 462 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 measures Cumulative 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. Results The 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). Conclusions Historical 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 registration ClinicalTrials.gov NCT01120353.
Bibliographical noteFunding Information:
Funding: The Childhood Cancer Survivor Study is supported by the National Cancer Institute grant CA55727 (to GTA, principal investigator), the Cancer Center Support (CORE) grant (CA21765) to St Jude Children’s Research Hospital (to CW Roberts, principal investigator) and the American Lebanese Syrian Associated Charities (ALSAC), Memphis, TN. The funders of the study had no role in the study design; data collection, analysis, or interpretation; or in writing of the report; and in the decision to submit the article for publication. All authors had independence from funders and full access to the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and accuracy of the data analysis. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare support from the National Cancer Institute (CA55727, to GTA, principal investigator) for the Childhood Cancer Survivor Study; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: The Childhood Cancer Survivor Study is approved by the St Jude Children’s Research Hospital Human Research Protection Program as well as the human subjects committees at each participating institution. Data sharing: Data are available per the Childhood Cancer Survivor Study resource sharing plan. Public access data tables are posted on the Childhood Cancer Survivor Study website (https://ccss.stjude.org/ data-and-analysis/public-access-data-tables).
© Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.