Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥50% of the heart) increased the rate of severe to fatal cardiac disease (RR 1.6) compared with no cardiac radiotherapy.
Cohort (n=24,214)
Yes
Does radiotherapy dose/volume and anthracycline chemotherapy increase the risk of severe to fatal cardiac disease in childhood cancer survivors?
In childhood cancer survivors, both low-to-moderate radiotherapy doses to large cardiac volumes and high doses to small volumes, as well as anthracycline use, significantly increase the risk of late-onset severe to fatal cardiac disease.
Relative Risk: 1.6 (95% CI 1.1–2.3)
p-value: p=0.02
PURPOSE: The impacts of radiotherapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk for late-onset cardiac disease in survivors of childhood cancer remain unresolved. PATIENTS AND METHODS: We determined the rates of severe to fatal cardiac disease in 24,214 5-year survivors in the Childhood Cancer Survivor Study diagnosed between 1970 and 1999 at a median age of 7.0 years (range, 0 to 20.9 years), with a median attained age of 27.5 years (range, 5.6 to 58.9 years). Using piecewise exponential models, we evaluated the association between cardiac disease rates and demographic and treatment characteristics. RESULTS: The cumulative incidence of cardiac disease 30 years from diagnosis was 4.8% (95% CI, 4.3 to 5.2). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥ 50% of heart) were associated with an increased rate of cardiac disease (relative rate, 1.6; 95% CI, 1.1 to 2.3) compared with survivors without cardiac radiotherapy exposure. Similarly, high doses (≥ 20 Gy) to small cardiac volumes (0.1% to 29.9%) were associated with an elevated rate (relative rate, 2.4; 95% CI, 1.4 to 4.2). A dose-response relationship was observed between anthracycline chemotherapy and heart failure with younger children (age ≤ 13 years) at the greatest risk for heart failure after comparable dosing. CONCLUSION: These observations support advances in radiation field design and delivery technology to reduce cardiac dose/volume and should guide future treatment protocols. They also inform clinical practice guidelines for post-therapy surveillance and risk-reducing strategies.
Bates et al. (2019) conducted a cohort in Childhood cancer survivors (n=24,214). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥50% of heart) vs. Survivors without cardiac radiotherapy exposure was evaluated on Severe to fatal (grade 3 to 5) cardiac disease (RR 1.6, 95% CI 1.1 to 2.3, p=0.02). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥50% of the heart) increased the rate of severe to fatal cardiac disease (RR 1.6) compared with no cardiac radiotherapy.