A Comprehensive Review of Radiotherapy-Induced Coronary Artery Disease-Epidemiology, Biological Mechanisms, and Preventive Strategies

Abstract

Radiation-induced cardiac toxicity is a recognized complication in patients undergoing thoracic radiotherapy. A crucial manifestation of this toxicity is the damage caused to coronary arteries, which can result in accelerated atherosclerosis that may remain undetected for many years. As cancer survival rates continue to improve, the incidence of radiation-induced coronary artery disease (RICAD) is increasing, making it one of the leading causes of morbidity and mortality among patients treated with radiotherapy for mediastinal cancers. The pathophysiology of RICAD involves a complex interplay of cellular mechanisms, including endothelial dysfunction, inflammation, and fibrosis. These processes are related to several molecular insults such as DNA damage, telomere erosion, and mitochondrial dysfunction. However, to fully understand the initiation and progression of the disease, further research is critical to uncover additional contributing factors. Different strategies for preventing cardiovascular complications in cancer patients are gaining significant attention. Recent advancements in radiotherapy, particularly the new FLASH radiotherapy technique, show promise in reducing the incidence of these complications. This review focuses on the effects of radiotherapy on coronary artery disease, exploring the underlying cellular and molecular mechanisms, as well as potential strategies to prevent RICAD.

Keywords: cellular and molecular mechanisms; coronary artery disease; radiation-induced coronary artery disease; radiotherapy.

Figure 1

Molecular mechanisms of radiation-induced damage. Infographic showing ROS generation, nuclear vs. mitochondrial DNA damage, telomere erosion, and the activation of cellular repair/apoptosis pathways, as well as their role in radiation-induced coronary artery disease.

Figure 2

Schematic representation of the biological mechanisms (in red) underlying RICAD, as well as potential preventive strategies (in green). The biological mechanisms include the molecular and cellular processes involved. The preventive strategies encompass radiotherapy techniques and pharmacological interventions aimed at reducing RICAD. 3DCRT: three-dimensional conformal radiation therapy; IMRT: intensity-modulated radiation therapy; DIHB: deep inspiration breath hold; VMAT: volumetric modulated arc therapy.