Cardiac irradiation, anthracyclines linked to VHD risk in childhood cancer survivors

Higher doses of heart radiation therapy (RT) and anthracyclines contribute to an increased risk of valvular heart disease (VHD) in childhood cancer survivors, as suggested in a nested case-control study.

Researchers used data from the PanCareSurFup and ProCardio cohorts. They identified 225 childhood cancer survivors with symptomatic VHD (median age 7 years, 60.4 percent male) and 442 without VHD (control) (median age 7.5 years, 60.9 percent male). Cases and controls were matched based on sex, age at cancer diagnosis, and calendar year of initial diagnosis.

Doses were estimated by performing a whole-body dosimetric reconstruction using a voxel-based anthropomorphic phantom with more than 200 delineated anatomic structures or substructures. Cumulative dose of cytotoxic agents was also evaluated.

Results showed that the odds of VHD were higher among survivors who had received a mean heart RT dose of 5 to <15 Gy than among those who had not undergone a heart RT (odds ratio [OR], 4.7, 95 percent confidence CI, 2.1–10.7), with the risk even higher among those who had more than half of their heart exposed.

Of note, the likelihood of VHD associated with heart RT increased exponentially with the dose, with an OR of 104.1 (95 percent CI, 27.8–389.6) for mean heart dose of ≥30 Gy, as well as follow-up, with the OR rising from 6.0 (95 percent CI, 1.4–26.5) after 5–19 years to 71.4 (95 percent CI, 20.4–250.0) after ≥30 years.

Anthracycline doses also showed an exponential dose-response association with VHD, with an OR of 3.8 (95 percent CI, 1.4–10.3) for cumulative anthracycline doses of ≥400 mg/m².

The findings underscore a need for long-term cardiac surveillance, the researchers said.