In a European study reported in the Journal of Clinical Oncology, de Baat et al identified heart exposure to radiotherapy and cumulative anthracycline doses as factors associated with increased risk of heart failure in survivors of childhood cancers. Survivors who received a mean heart radiotherapy dose of ≥ 5 Gy were found to have an increased risk of heart failure; the risk associated with radiotherapy increased with larger volumes exposed. Survivors who received ≥ 100 mg/m2 of total cumulative anthracyclines had a substantially increased risk of heart failure, whereas survivors treated with a lower dose showed no significantly increased risk.
Study Details
The study included data from 42,361 patients in the PanCareSurFup and ProCardio cohort of survivors of childhood cancers diagnosed between 1940 and 2009 in seven European countries who survived for at least 5 years. A nested case-control study including 500 heart failure cases and 500 controls without heart failure was conducted to identify risk associated with heart radiotherapy and anthracycline exposure.
Key Findings
In the entire cohort, the cumulative incidence of heart failure was 2% (95% confidence interval [CI] = 1.7%–2.2%) by age 50 years.
In the case-control study, compared with no heart radiotherapy, risk of heart failure was not significantly increased with a mean heart radiotherapy dose of > 0 to < 5 Gy (odds ratio [OR] = 1.3, 95% CI = 0.8–2.0), whereas risk was increased with mean doses of 5 to < 15 Gy (OR = 5.5, 95% CI = 2.5–12.3), 15 to < 35 Gy (OR = 9.0, 95% CI = 4.6–17.6), and ≥ 35 Gy (OR = 22.6, 95% CI = 4.9–102.8). At doses of 5 to < 15 Gy, risk of heart failure significantly increased if ≥ 50% of the heart was exposed.
In the case-control study, compared with no anthracycline use, risk of heart failure was not significantly increased at total cumulative anthracycline doses of > 0 to < 100 mg/m2 (OR = 2.3, 95% CI = 0.7–7.1), whereas risk was significantly increased at total cumulative doses of 100 to < 250 mg/m2 (OR = 5.8, 95% CI = 2.9–11.3) and ≥ 250 mg/m2 (OR = 21.2, 95% CI = 11.4–39.2).
The investigators concluded: “Survivors who received a mean heart radiotherapy dose of ≥ 5 Gy have an increased risk of heart failure. The risk associated with radiotherapy increases with larger volumes exposed. Survivors treated with < 100 mg/m2 total cumulative anthracycline dose have no significantly increased risk of heart failure. These new findings might have consequences for new treatment protocols for children with cancer and for cardiomyopathy surveillance guidelines.”
Esmée C. de Baat, MD, of the Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the European Union’s Seventh Framework Programme for research, technological development, and demonstration; Dutch Cancer Society; Swiss Paediatric Oncology Group; and others. For full disclosures of the study authors, visit ascopubs.org.
