RT to Heart, Anthracyclines Increased CVD in Hodgkin Survivors

In Hodgkin lymphoma survivors, both mean heart radiation dose and cumulative dose of anthracyclines significantly predicted cardiovascular disease, according to an analysis of EORTC-LYSA trials published recently in Lancet Haematology.

Researchers led by Maja V. Maraldo, PhD, of the department of oncology, Rigshospitalet, Copenhagen, Denmark, found that both mean heart radiation dose per 1 Gy increase (hazard ratio [HR], 1.015 [95% confidence interval (CI), 1.006–1.024]) and the dose of anthracyclines per 50 mg/m² increase in cumulative dose (HR, 1.077 [95% CI, 1.021–1.137]) significantly predicted cardiovascular disease among these survivors. However, no effect was found for cumulative dose of vinblastine, vincristine, and mean radiation dose to the left or right internal carotid artery.

“Clearly, to minimize the risk of cardiovascular disease, doses of both radiation to the heart and anthracyclines should be kept as low as possible without jeopardizing the patients’ chance of cure,” wrote Maraldo and colleagues. “Use of the quantitative risk estimates from the present study will allow the optimal combination of systemic therapy and modern, individualized radiotherapy to be estimated for each individual patient with respect to cardiovascular risk.”

In the study, the researchers used data on late-effect cardiovascular disease taken from nine EORTC-LYSA randomized trials conducted from 1964 to 2004 including data from a 2009 to 2010 Life Situation Questionnaire given to survivors. The questionnaire assessed late-onset effect of treatment for Hodgkin lymphoma. Data were available for 6,039 patients with a median follow-up of 9 years; 1,919 patients responded to the questionnaire.

The median age of patients at treatment was 30 years. Including both survey respondents and non-respondents, 67% of patients were treated with anthracyclines, 65% were treated with vinblastine, and 46% received vincristine. Almost 90% of patients had their heart exposed to radiation during their treatment. 

Using both trial data and the questionnaire, 1,238 cardiovascular events were reported in 703 patients. Patients had a median age of 45 at the time of the first cardiovascular event. The most commonly reported events were ischemic heart disease (19%), congestive heart failure (12%), arrhythmia (16%), and valvular disease (11%).

In an editorial that accompanied the article Serhan Kupeli, of Çukurova University, Adana, Turkey, wrote that these results emphasized “the importance of avoiding cardiotoxicity and designation of treatment in a manner that is tailored to the individual.”

“With these findings, Maraldo and colleagues have contributed to the quantification of cardiovascular disease risk in relation to doses of radiotherapy and anthracyclines. Studies dealing with risk counseling and screening of cardiac functions of these patients are particularly important because there are no generally accepted schema or principles for the risk counseling,” he wrote.