What is the clinical evidence from this study?

Study design: Cohort. Population: Childhood cancer survivors (n=24214). Intervention: Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥50% of heart) vs. Survivors without cardiac radiotherapy exposure. Primary outcome: Severe to fatal (grade 3 to 5) cardiac disease (RR 1.6, 95% CI 1.1 to 2.3, p=0.02).

March 12, 2019Open Access

Therapy-Related Cardiac Risk in Childhood Cancer Survivors: An Analysis of the Childhood Cancer Survivor Study

Resultado clave

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.

Diseño del estudio

Tipo

Cohort (n=24,214)

Multicéntrico

Sí

PICO estructurado

Does radiotherapy dose/volume and anthracycline chemotherapy increase the risk of severe to fatal cardiac disease in childhood cancer survivors?

Población

24,214 5-year survivors of childhood cancer diagnosed before age 21, followed for a median of 20.3 years to assess therapy-related cardiac risk.

Exposición

Radiotherapy (varying doses and exposed cardiac volumes) and anthracycline chemotherapy

Comparador

Survivors without cardiac radiotherapy exposure or lower doses

Resultado

Severe to fatal cardiac diseasehard clinical

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.

Resultado numérico

Relative Risk: 1.6 (95% CI 1.1–2.3)

valor p: p=0.02

Limitaciones

Grade 3 to 4 cardiac outcomes were self-reported
Omitting grade 1 to 2 events likely underrepresents true cardiac risk
Cohort has a median age of just 27.5 years, when cardiac disease is uncommon in the general population
Specific cardiac RT exposures were reconstructed from medical records and modeled in age-appropriate phantoms rather than on individual patient anatomy

Resumen

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.

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