The Issue of Radiation-induced Cardiovascular Toxicity: Preclinical Highlights and Perspectives on Preventive Strategies

A bout one-half of all cancer patients will receive external beam radiation therapy in the course of their disease, either as neoadjuvant or as adjuvant or as exclusive therapy in case of locally advanced disease. Although the true incidence of radiation-induced vascular disease is uncertain, it is a significant concern in long-term survivors because it will potentially alleviate the survival benefit of radiation therapy. Based on the experience of adjuvant irradiation for breast cancer, numerous papers have investigated the impact of irradiation on heart coronaries. In a recent study published few weeks ago in the New England Journal of Medicine, Darby et al. provided meaningful insights on the risk of ischemic coronary heart disease in breast cancer patients receiving radiotherapy, based on dosimetric parameters. he authors incorporated systemic agents or individual risk factors at time of radiotherapy and established correlations between dose to the heart and the risk of coronary disease. They found that there was a linear correlation between the mean dose to the heart and the risk of coronary event, which increased by 7.4% per Gray (95% confidence interval: 2.9-14.5, p < 0.001). In this study, the estimated dose to the whole heart was 4.9 Gy (range, 0.03-27.72). Of interest, the authors did not evidence a threshold for cardiac toxicity, suggesting that even low doses can generate cardiovascular morbidity. The increase in coronary events began within the first 5 years after radiation therapy and continued into the third decade after completion of the treatment course. ctually, the physiopathology of cardiovascular toxicity is not fully understood. It is usually alleged that large vessels, such as the carotids, are relatively more resistant to ionizing radiation. Few data corroborate this assumption. Moreover, for patients with head and neck carcinoma, the dose delivered to the carotid is usually much higher, ranging from 50 to 70 Gy. Although the vascular remodeling after such high doses could be somewhat different, irradiation generates functional changes that are relatively common to most vessels. Early cardiovascular toxicity from radiotherapy results from direct cellular toxicity against endothelial cells through apoptosis and necrosis. These events increase vascular