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TOPLINE:

Childhood cancer survivors who were exposed to heart radiation therapy or high cumulative anthracycline doses face increased risks for valvular heart disease. Greater exposure to platinum-based agents may be a risk factor as well.

METHODOLOGY:

• Long-term survival after childhood cancer has considerably improved over the past 25 years, but survivors are at risk for treatment-related chronic health conditions, including valvular heart disease. Data on the specific treatments and dose exposures linked to valvular heart disease risk have been lacking.
• To bridge this gap, researchers conducted a nested case-control study using two European cohorts, including 225 childhood cancer survivors with symptomatic valvular heart disease and 442 survivors matched for sex and age at cancer diagnosis. Among those with heart disease, 86.7% were diagnosed more than 20 years after their childhood cancer.
• Data on cumulative doses of chemotherapy and radiation therapy were collected until the date of cardiac diagnosis or corresponding follow-up time for control individuals. For those who received radiation therapy, individualized reconstruction of treatments and whole-body dosimetry were performed to estimate mean heart radiation doses and dose-volume metrics.

TAKEAWAY:

• Mean heart radiation dose showed an exponential association with the risk for valvular heart disease, with an odds ratio (OR) of 4.7 at 5 to < 15 Gy of radiation, 12.8 at 15 to < 30 Gy, and 104.1 at ≥ 30 Gy. Even average doses < 5 Gy were associated with an increased risk compared with no radiotherapy. The risk for valvular heart disease grew over time: Among survivors exposed to mean doses ≥ 30 Gy, the OR was 6.0 after 5-19 years but rose to 71.4 after 30 years.
• Cardiac volume exposed to radiation was also tied to heart disease risk. When more than 50% of the heart received ≥ 5 Gy of radiation, the OR for valvular heart disease was 15.9; at doses ≥ 15 Gy, the OR was 18.1.
• Cumulative anthracycline dose showed a nonlinear association with the risk for valvular disease, with doses of 400 mg/m² or higher linked to an increased risk (OR, 3.8). Most survivors who received such high anthracycline doses were treated between 1970 and 1989.
• Exposure to platinum-based agents was not associated with the risk for valvular heart disease, but there was suggestive evidence that higher cumulative doses were associated with an increased risk. No statistically significant associations were found with other chemotherapy agents.

IN PRACTICE:

“The major contribution of this study is the magnitude of the risks observed and the meaningful role of a [radiotherapy] dose of 1 Gy or higher, which to our knowledge had not been previously demonstrated,” the authors of the study wrote. These findings, they added, “could impact the development of new treatment protocols for childhood cancer and may also influence guidelines for cardiac disease surveillance.”

SOURCE:

The study, led by Rivalin Aho Glele, Radiation Epidemiology Group, INSERM, Unit 1018-CESP, Villejuif, France, was published online in JAMA Oncology.

LIMITATIONS:

Outcome data were collected from multiple sources with varying levels of clinical detail. The researchers lacked information on lifestyle and cardiovascular risk factors such as smoking, obesity, hypertension, and diabetes, which have been associated with the risk for valvular heart disease in previous studies of adult cancer survivors.

DISCLOSURES:

The study received support from the European Union’s Seventh Framework Programme, the Ligue Nationale Contre Le Cancer, the Institut pour la Recherche en Santé Publique, the French Agence Nationale pour la Recherché Scientifique, the ARC Foundation for Cancer Research, the Gustave Roussy Foundation, and others. Three authors reported receiving grants from the European Commission, and one author reported receiving grants from the Swiss Cancer Research during the conduct of the study. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.