Cardiovascular disease

Delayed pericarditis, which can present abruptly or as a chronic pericardial effusion.

Pancarditis that includes pericardial and myocardial fibrosis, with or without endocardial fibroelastosis.

Cardiomyopathy (in the absence of significant pericardial disease), which can occur even without anthracycline exposure.

Ischemic heart disease.

Functional valve injury, often aortic.

Conduction defects.

Individual radiation fraction size.

Volume of the heart that is exposed to radiation.[19,51]

Total radiation dose.

Total radiation dose.

Various studies have demonstrated a substantially increased risk of these outcomes with higher radiation doses, particularly doses to the heart exceeding 35 Gy.[10,12,18,19,28]

Total radiation dose.

At higher radiation doses, rates of heart failure, pericardial disease, and valvular disease have been reported to exceed 10% after 20 to 30 years. Although some studies suggest that doses less than 5 Gy may be associated with an increased risk of cardiovascular disease, the relative risk is small (i.e., 2.5) and the 95% CI is large (i.e., 0.2–41.5); moreover, the dosimetric analyses are generally estimations of incidental cardiac exposure.[10,18,28]

Total radiation dose.

Low to moderate doses of radiation therapy (5.0–19.9 Gy) to large cardiac volumes (>50% of the heart) are associated with an increased rate of cardiac disease (i.e., 1.6-fold) compared with survivors who did not have any cardiac radiation therapy exposure.[19]

Total radiation dose.

High doses of radiation (>20 Gy) to small cardiac volumes (0.1%–29.9%) are associated with an elevated rate of cardiac disease (relative rate, 2.4).[19,52]

Total radiation dose.

Additional confirmatory data are needed for an accurate assessment of risk at very low cardiac doses.

Total radiation dose.

Similar to anthracyclines, manifestation of these late effects may take years, if not decades, to present.

In a cohort study of 2,563 patients with Hodgkin lymphoma treated in four consecutive COG clinical trials between 2002 and 2022 (AHOD0031, AHOD0831, AHOD1331, S1826), the cumulative incidence of grades 3 to 5 cardiac disease was estimated to decrease, from 10% in the first trial to 6% in the last trial.

All patients received doxorubicin, 1,362 received mediastinal radiation therapy, and 307 received the cardioprotectant dexrazoxane (80% of children in the S1826 study). Radiation therapy was substantially reduced and refined, whereas the anthracycline doses were increased.

Based on modeling used as part of this study, survivors treated in the recent high-risk Hodgkin lymphoma trial (S1826), the 30-year risk of serious cardiac morbidity will be increased less than 2% above the expected rate in an untreated population (5%). Reductions in the proportion of children receiving mediastinal radiation therapy and increases in dexrazoxane use were estimated to offset the increased doxorubicin dose, producing a net reduction in late cardiac disease.

These results suggest that cardiac toxic effects are estimated to decrease from older to newer Hodgkin lymphoma trials, even in females aged 12 years and younger, who are most susceptible to anthracycline-induced heart failure.